Monday, 31 August 2009

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1 Monday, 31 August 2009

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3 Improving prevention and management of coronary artery disease 303 IMPROVING PREVENTION AND MANAGEMENT OF CORONARY ARTERY DISEASE 1795 EUROASPIRE III: Risk factor and therapeutic management in people at high risk of developing cardiovascular disease from 12 European countries K. Kotseva 1, C. Jennings 1,G.DeBacker 2, D. De Bacquer 2, P. Amouyel 3,D.Gaita 4,U.Keil 5,A.Pajak 6, Z. Reiner 7, D. Wood 1 on behalf of EUROASPIRE Study Group. 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom; 2 University of Ghent, Ghent, Belgium; 3 Institut Pasteur de Lille, Lille, France; 4 Institute of Cardiovascular Disease, Timisoara, Romania; 5 Institute of Epidemiology and Social Medicine, Munster, Germany; 6 Institute of Clinical Epidemiology and Population Studies, Krakow, Poland; 7 University Hospital Rebro, Zagreb, Croatia Objectives: EUROASPIRE III surveyed people in general practice at high risk of developing cardiovascular disease. The aim was to determine whether the 2003 Joint European Societies guidelines on cardiovascular disease prevention for high risk individuals are being followed in clinical practice. Methods: This survey was undertaken in selected geographical areas and general practices in 12 European countries: Belgium, Bulgaria, Croatia, Finland, Germany, Italy, Latvia, Poland, Romania, Slovenia, Spain and the UK. Consecutive patients, men and women <80 years of age, without a history of coronary or other atherosclerotic disease, but treated with antihypertensive and/or lipid lowering and/or anti-diabetes treatments, were identified retrospectively. Data collection was based on a review of patient s medical notes and a prospective interview and examination at least six months after the start of drug treatment. Results: 4366 high risk individuals (57.7% females) were interviewed (participation rate 76.7%). Overall 70.8% had a blood pressure 140/90 mm Hg ( 130/80 in people with diabetes mellitus), 78.9% had a total cholesterol 4.5 mmol/l and 30.2% reported a history of diabetes. Only 26.3% of patients using antihypertensive medication achieved the blood pressure goal, 30.6% of patients on lipidlowering medication achieved the total cholesterol goal and 52.9% of patients with self-reported diabetes had a HbA1c < 6.5%. The use of cardioprotective medication was: aspirin or other anti-platelets 22.0%; beta-blockers 31.2%; ACE inhibitors/arb 55.7%; calcium channel blockers 24.0%; and statins 39.9%. Conclusions: The EUROASPIRE III survey shows that risk factor management in patients being treated as high cardiovascular risk is a major cause for concern. Blood pressure, lipid and glucose control are completely inadequate with a large majority of patients not achieving the targets defined in the prevention guidelines. Primary prevention needs a systematic, comprehensive, multidisciplinary approach, which addresses lifestyle, risk factor and therapeutic management, and a health care system which invests in prevention. (33.6%) was obese (BMI>30 kg/m 2 ) and 65.0% had a metabolic syndrome (IDF definition). Conclusion: Persistent dyslipidemia is highly prevalent in statin-treated patients in Europe and Canada with high proportions of patients not at LDL-C goals and/or with low HDL-C and elevated triglycerides. A more intensive and comprehensive lipid management in this high-risk population, in line with current guidelines, would decrease the prevalence of lipid abnormalities and might contribute to further decrease the CV risk of these patients Trends in acute coronary syndrome management and early mortality: Myocardial Ischaemia National Audit Project (MINAP) 2004 to 2007 C.P. Gale 1, B.A. Cattle 1, A.D. Simms 1, P.D. Baxter 1,T.Munyombe 1, T.H. West 1, D.C. Greenwood 1, K.A.A. Fox 2,R.M.West 1. 1 University of Leeds, Leeds, United Kingdom; 2 The University of Edinburgh, Edinburgh, United Kingdom Purpose: Evidence from international registries suggests ACS mortality has declined and this is associated with increased use of evidence-based therapies. Not all countries demonstrate similar concordance with recommendations for care. In light of contemporary ACS guidelines, we characterised changes in ACS management and early mortality across England and Wales from 01/01/04 to 31/12/07. Methods: Using MINAP, we studied 340,983 ACS events from 228 hospitals. Data were smoothed using splines and in-patient and 30-day mortality rates adjusted for the proportion of admissions corresponding to in-patient and 30-day death respectively. Seasonal trends were investigated by time series structural decomposition. Results: Rates of NSTEACS were consistently greater than those of STEMI. Acute aspirin therapy increased for AMIs, but was lower for NSTEACS than for STEMIs. Chronic aspirin use for NSTEACS was greater than that for STEMI. Rates of recording of evidence-based secondary preventative medication at discharge reduced. There was an increase in the rate of recording of clopidogrel use. The total rates of revascularisation for STEMI increased (Figure 1). There was a reduction in the rate of thrombolysis and increase in the rate of primary PCI. Rates of in-patient and 30-day mortality for STEMI and NSTEACS declined in parallel. Early morality rates were higher for NSTEACS than for STEMI High prevalence of dyslipidemia in 18,574 patients treated with statins in Europe and Canada: Results of the dyslipidemia international study A.K. Gitt 1, J.P.P. Kastelein 2 on behalf of DYSIS Study Group. 1 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Academic Medical Center, Amsterdam, Netherlands Background: Although statins are the cornerstone of cardiovascular (CV) prevention, patients treated with statins remain at substantial risk of CV events. Persistent lipid abnormalities are likely to contribute to this residual CV risk. The objective of the study was to assess the prevalence of dyslipidemia in patients receiving statin therapy. Methods: This cross-sectional study was conducted by 2,929 primary care physicians, cardiologists, endocrinologists and internists in 12 countries (Europe, Canada). Patients were consecutive outpatients 45 years-old, on statin therapy for 3 months with available lipid values. A clinical examination and the recording of the latest lipid values on statin were performed in all patients. Results: 18,574 patients (mean age 65.8±9.8 years old; 58.4% male) have been enrolled since April, Of these patients, 74.6% had hypertension, 39.7% diabetes, 28.9% a family history of premature CV disease and 15.0% were current smokers. CHD was present in 36.8% of patients, cerebrovascular disease in 9.5% and peripheral arterial disease in 10.5%. One third of the study population Table 1 Patients with CHD or Diabetes Patients with or SCORE risk 5% SCORE risk <5% N=14,929 (80.4%) N=3,645 (19.6%) LDL-C not at goal [ 2.5/2.0 mmol/l (high risk); 3.0 mmol/l (low risk)] 47.1%/70.9% 55.7% TC not at goal [ 4.5/4.0 mmol/l (high risk); 5 (low risk)] 51.5%/70.6% 62.9% Low HDL-C [<1.0 mmol/l (male); <1.2 mmol/l (female)] 28.2% 18.7% Elevated TG [>1.7 mmol/l] 39.2% 34.4% LDL-C not at goal and low HDL-C and/or high TG 24.6%/35.5% 23.9% No residual lipid abnormalities 26.4%/13.5% 25.9% CHD = coronary heart disease; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; HDL-C = high-density lipoprotein cholesterol; TG = triglycerides. Figure 1. Pharmacological and invasive revascularisation rates for STEMI 2004 to 2007 adjusted for STEMI admission rate (with time series decomposition graphs for thrombolysis (above right) and primary PCI (below right)); first row: raw data, second row: effect of season, third row: decomposed trend, fourth row: extracted noice. Conclusions: These data demonstrate significant changes in ACS performance and improvement in early mortality for STEMI and NSTEACS. Although early mortality rates have improved, NSTEACS have higher early mortality rates, and lower rates of acute aspirin use than those with STEMI. Despite a reduction in thrombolysis rates, total STEMI revascularisation rates improved and were associated with increased primary PCI rates Persistence with beta-blockers in coronary heart disease patients in UK primary care E. Setakis 1,C.Morley 2,S.Cockle 3, T.P. Van Staa 1, G. Kassianos 4. 1 GPRD Division, MHRA, London, United Kingdom; 2 Bradford Royal Infirmary, Bradford, United Kingdom; 3 Servier Laboratories Limited, Slough, United Kingdom; 4 Birch Hall Medical Centre, Bracknell, United Kingdom Purpose: To investigate persistence with beta-blocker therapy in CHD patients treated in UK primary care. Methods: Retrospective cohort study (UK General Practice Research Database (GPRD)). Patients were included if they had a 1st ever diagnosis of CHD (angina, heart failure, previous MI) after 1st April 2004 and a 1st ever prescription for a beta-blocker on or after that CHD diagnosis. Patients with a history of hypertrophic (obstructive) cardiomyopathy were excluded. Kaplan-Meier life tables analysis was used to estimate the persistence with treatment. Treatment was considered continuous if a new prescription was given within 3 months of the expected end of the current prescription. Patients were followed from index date until the earliest of date of death, transfer out of practice or last collection date.

4 304 Improving prevention and management of coronary artery disease / Diabetes prevention, treatment and control Results: 12,493 patients (68.0% male; mean age 58.0 years (s.d years)) were included. Overall, 27% of patients had discontinued treatment by 1 year, rising to 39% by 2 years and 50% by 3 years after initiation of beta-blockers. Persistence was greater for males than females (discontinued at 1 year: 25% versus 31%; 2 years 37% versus 44%; 3 years: 47% versus 57%) and for patients with a history of MI, compared to those with angina or heart failure (discontinued at 1 year: 21%, 32% and 29%; 2 years: 32%, 44% and 45%; 3 years: 43%, 55% and 56%, respectively). Continuation with beta-blockers Conclusions: Around a quarter of patients have discontinued beta-blocker therapy within 1 year of initiation, rising to half of patients at 3 years. Persistence is greater in those with a history of MI compared to those with heart failure or angina. Adverse events are commonly associated with beta-blockers and this may contribute to the lack of persistence with treatment Identification of patients with impaired outcome on ACE-inhibitor therapy J. Brugts 1, E. Boersma 1,A.Isaacs 2, W. Remme 3, M. Bertrand 4, K. Fox 5,R.Ferrari 6, M. De Maat 2, A. Danser 2, M.L. Simoons 1 on behalf of EUROPA-trial investigators. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Erasmus MC, Rotterdam, Netherlands; 3 STICARES, Rhoon, Netherlands; 4 Hopital Cardiologique CHRU de Lille, Lille, France; 5 Royal Brompton Hospital, London, United Kingdom; 6 Azienda Ospedaliera Di Ferrara (Arcispedale S. Anna), Ferrara, Italy Background: The efficacy of ACE-inhibitors in stable CAD may be increased by targeting therapy to those patients who are most likely to benefit. However, these patients cannot be identified based on clinical characteristics. Genetic profiling could be a new approach to identify patients who do, or do not respond to therapy. Objective: To investigate whether genetic polymorphisms in the reninangiotensin-system (RAAS) and bradykinin pathways modify the treatment benefit of the ACE-inhibitor perindopril. Methods: In 8907 stable coronary artery disease patients from the randomized placebo-controlled EUROPA-trial, we analyzed 52 haploytpe-tagging SNP s in 12 genes within the pharmacodynamic pathways of ACE-inhibitors. The primary outcome was the reduction in cardiovascular mortality, non-fatal MI and resuscitated cardiac arrest during four years of follow-up. Cox regression was performed with correction for multiple testing by permutation analysis. Our genetic findings were verified in the PROGRESS trial. In addition, the genetic variation was related to plasma measurements of RAAS hormones. Findings: Three polymorphisms in the angiotensin-ii receptor type I and bradykinin receptor type I genes significantly modified the treatment benefit of perindopril. We identified a pharmacogenetic profile, which defined a group of patients (73.5%), who experienced a more pronounced treatment effect (HR 0.68; 95% CI ) and a group of patients (26.5%), who did not benefit from treatment with perindopril (HR 1.26; 95% CI ) with significant interaction (P for interaction = ). Pharmacogenet. profile of ACE-i therapy Interpretation This unique pharmacogenetic analysis identified genetic determinants of treatment benefit of ACE-inhibitor therapy by perindopril Impact of non steroidal anti-inflammatory drugs (NSAIDs) on CV outcomes in atherothrombotic patients: insights from the European REACH registry O. Barthelemy 1,J.P.Collet 1,G.Cayla 1, T. Chastre 1,U.Zeymer 2, P.G. Steg 3,D.L.Bhatt 4, G. Montalescot 1 on behalf of the REACH Registry investigators. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 4 Cleveland Clinic, Cleveland, United States of America Aim: We analysed whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable atherothrombotic patients. Methods: We analysed 21,253 patients of the European REACH Registry performed in 18 European countries between 2003 and ,406 (86.6%) patients had established atherothrombotic disease and 2,847 (13.4%) were selected on the basis of multiple risk factors but had no prior history of vascular disease. The use of aspirin (ASA) and/or NSAIDs was determined at enrolment and ischemic events were recorded over two years of follow-up. MACCE was defined as the composite of death, MI or stroke. The composite of MACCE and re-hospitalization (MACCE/H) was also evaluated. Results: The mean age was 67.1±9.7 years, and 68.5% were male. Four groups were defined: 1) no ASA no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs + ASA with 6,814 patients (32.1%), 13,043 (61.4%), 544 (2.6%) and 852 (4.0%) patients in these groups, respectively. In patients not taking ASA, the prescription of NSAIDs was associated with non-significant trends for an excess of MACCE, death, stroke or bleeding (see figure). In patients on chronic aspirin treatment, the use of NSAIDs was associated with a significant excess of MACCE and stroke; the trends for more death, MI or bleeding were not significant (see figure). The composite of MACCE/H was significantly higher in NSAIDs users, without (26.3% vs 18.5%) or with (27.8% vs 20.6%) concomitant ASA, p< for both. Figure 1 Conclusions: With or without concomitant ASA use, the use of NSAIDs appears to be associated with a modest increase of ischemic risk. This excess of risk is particularly clear in patients taking ASA which identifies the subset of patients with a prior history of vascular event. DIABETES PREVENTION, TREATMENT AND CONTROL 1821 Risk of death differs according to type of oral glucose-lowering therapy in patients with diabetes and a previous myocardial infarction: a nationwide study T.K. Schramm 1,G.H.Gislason 1, M.L. Norgaard 2, J.N. Rasmussen 3, F. Folke 2, M.L. Hansen 2, C.H. Jorgensen 2, A. Vaag 3, L. Kober 1, C. Torp-Pedersen 2. 1 Rigshospitalet (The Heart Centre), Copenhagen, Denmark; 2 Gentofte University Hospital (Dept. of Cardiology), Hellerup, Denmark; 3 Steno Diabetes Center, Gentofte, Denmark Purpose: The potential risk of individual oral glucose-lowering agents is largely unknown. We conducted a nationwide analysis of risk of death associated to different oral glucose-lowering drugs used as monotherapy in diabetes patients with a previous myocardial infarction (MI). Methods: All residents in Denmark 20 years of age with a previous MI who initiated monotheraphy with oral glucose-lowering therapy during 1997 to 2006 were included. The population was followed by individual-level-linkage of nationwide registers up till 9 years. The use of oral glucose-lowering drugs was identified by prescription claims. The risk of death associated with use of individual oral glucose-lowering drugs with metformin as the reference, was estimated by multivariable, time-dependent Cox proportional-hazard analyses, adjusted for age, gender, comorbidity, socioeconomic status and concomitant cardiovascular medication. By entering drug use as time-dependent variables, risk assessment of single drug use only was ensured. Results: A total of 8,220 subjects were included. The distribution of drugs was: metformin 2,758 (33.6%), glimeperide 3,651 (44.4%), gliclazide 487 (5.9%), glibenclamide 1,132 (13.8%), glipizide 642 (7.8%), tolbutamide 485 (5.9%), repaglinide 178 (2.2%) and acarbose 34 (0.4%), respectively. During the study period 1,377 (16.4%) died. An increased risk of death was associated to treatment with glimeperide, glibenclamide, glipizide, and tolbutamide when compared with

5 Diabetes prevention, treatment and control 305 metformin, whereas no significant difference was found for gliclazide, repaglinide and acarbose deaths from any cause during approximately person-years of follow-up. HbA1c was 1.0% lower among those randomized to intensive glucose control over an average of 5 years. Intensive therapy resulted in a 16% reduction in non-fatal MI (RR 0.84, 95% CI ) and a 15% reduction in CHD (RR 0.85, 95% CI ). No significant effect on stroke was observed (RR 0.90, 95% CI ) or all-cause mortality (RR 1.02, 95% CI ). In absolute terms 2 non-fatal MIs or 3 CHD events were avoided for every 200 patients treated for 5 years Conclusion: We provide robust evidence that a reduction in HbA1c of 1% over 5 years significantly reduced coronary events without an excess risk of death. Total Death Conclusion: Individual oral glucose-lowering drugs carry a difference in the risk of death. Gliclazide and repaglinide, being as safe as metformin, whereas other commonly used sulfonylureas were associated with higher risk of death Do angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent the incidence of diabetes? A meta-analysis of more than 100,000 patients M. Al-Mallah, S. Siddiqui, M. Sinno, A. Abu Samra. Henry Ford Health System, Detroit, United States of America Background: The prevalence of diabetes mellitus (DM) increased exponentially over the past years, with 100 million people expected to develop diabetes in the coming 15 years. The impact of medical therapy on the incidence of new onset DM is not clear. We performed a systematic review and meta analysis to study the impact of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on the incidence of new onset DM. Methods: MEDLINE, EMBASE, BIOSIS, Cochrane databases from inception till February 2009 for randomized controlled trials (RCT) that reported new incident DM with ACEI or ARB therapy. A total of 18 RCT are included in this meta analysis. A random-effect model was used and between-studies heterogeneity was estimated with I2. Results: There were patients randomized to ACEI or ARB and patients randomized to other therapies. ACEI/ARB use was associated with a decrease in new onset DM (RR 0.78, 95% CI , p=0.003 for ACEI and RR 0.8, 95% CI , p< for ARB) (figure 1). Treating 100 patients with ACEI or 50 patients with ARB prevents one case of new onset DM. Forest Plot Conclusions: The cumulative evidence suggests that the use of ACEI/ARB prevents the incidence of diabetes mellitus. This may be of special clinical benefit in patients with pre-diabetes or metabolic syndrome Does more intensive control of glucose reduce cardiovascular events in type 2 diabetes? K.K. Ray, S.R.K. Sheshasai, S. Wijesuriya, R. Sivakumaran, S. Nethercott, D. Preiss, S. Erqou, N. Sattar. University of Cambridge, Cambridge, United Kingdom Background: It remains unclear whether intensive control of glucose reduces cardiovascular events among individuals with type 2 diabetes mellitus. Methods: We conducted a meta-analysis of randomized controlled outcome trials to assess the impact of intensive v.s. standard glucose control on death and cardiovascular outcomes. Rates of non-fatal myocardial infarctions (MI), fatal and non-fatal coronary heart disease (CHD), strokes and all-cause mortality were calculated from relevant publications. We conducted a random effects meta-analysis of the rate ratio in intensive vs standard therapy groups. Results: 5 trials involving participants fulfilling the eligibility criteria were included. There were 1497 non-fatal MIs, 2318 CHD events, 1127 strokes and 1824 Does tighter glycemic control improve macrovascular outcomes in people with type II diabetes mellitus? A meta-analysis of patients in randomised controlled trials K.Y. Ooi 1, B. Billah 2,H.Krum 2. 1 The Alfred Hospital, Melbourne, Australia; 2 Monash University, Melbourne, Australia Background: There remains considerable uncertainty regarding the relationship between long-term glycemic control in people with type II diabetes mellitus (DM) and the risk of developing macrovascular disease. Methods: We therefore performed a meta-analysis of randomised controlled trials (RCTs) that compared tighter glycemic control in people with type II DM versus those receiving standard DM therapy. RCTs were identified by systematic search of manuscripts, abstracts and databases. Only studies with populations of greater than 500 subjects were included. Major endpoints that could be meta-analysed included all-cause mortality, cardiovascular mortality and the incidence of acute myocardial infarction (AMI), stroke and peripheral vascular disease (PVD). Results: Data was able to be extracted from 5 RCTs contributing patients. This is summarised in the table. Outcome # of Patients Risk Ratio (95% CI) p-value for significance All cause mortality ( ) Cardiovascular mortality ( ) AMI ( ) Stroke ( ) PVD ( ) Conclusions: This meta-analysis suggests no significant survival benefit or reduction in major cardiovascular events with tighter glycemic control in people with type II DM, with the exception of a decrease in the risk of AMI. Therefore, a focus on other modifiable cardiovascular risk factors may be of more importance in reducing the risk of type II DM associated macrovascular disease Diabetes is the strongest independent predictor of mortality in acute cerebrovascular disease R. Margato 1, H. Ribeiro 1,S.Carvalho 1, C. Ferreira 1, J. Gabriel 2, A. Velon 2, P. Guimaraes 2, P. Mateus 1, P. Fontes 1, I. Moreira 1. 1 Centro Hospitalar de Trás os Montes e Alto Douro, Cardiology Department, Vila Real, Portugal; 2 Centro Hospitalar de Trás os Montes e Alto Douro, Neurology Department, Vila Real, Portugal Purpose: Cerebrovascular disease is the leading cause of dead in Portugal. There are few studies that report the underlying prevalence of preventable cardiovascular (CV) risk factors and there respective impact on prognosis. Methods: We did a retrospective study of patients (pts) consecutively admitted to a Cerebrovascular Disease Unit with the diagnosis of stroke or transient ischemic attack (TIA) over a period of 5 years. Demographic data, CV risk factors, clinical parameters and in- hospital mortality were analyzed. In statistical analysis, X2 and Student s t test were used; logistic regression was performed for multivariate analysis. Results: 3508 pts were studied, with a mean age of 73±11.51 years and 52.3% male; 55.2% of pts had hypertension, 19% diabetes, 14% dyslipidemia, 5% obesity and 2.5% smoking. On admission 8.4% of pts presented with TIA, 15.8% with hemorrhagic stroke and 75.8% with ischemic stroke. Mean hospital stay was 7.1±6.7 days and in-hospital mortality was 15.4%. Multivariate analysis that adjusted for age, sex, cardiovascular risk factors and type of stroke identified hypertension (OR= 1.49; IC95% ; p=0. 02), diabetes (OR=2.5; IC95% ; p=0.01) and hemorrhagic stroke (OR= 1.9; IC95% ; p= 0,032) as independent predictors of in-hospital mortality. Conclusions: In this large cohort of patients admitted for acute cerebrovascular accident, hypertension was the most prevalent cardiovascular risk factor and diabetes the strongest independent predictor of in-hospital mortality.

6 306 Diabetes prevention, treatment and control / Predictors of outcome in cardiac resynchronisation therapy 1826 Effect of multifactorial comprehensive cardiac rehabilitation on risk factor control and mortality in type 2 diabetes - three years results of the randomized DANSUK study A.M.B. Soja 1, A.D.O. Zwisler 1,S.Rasmussen 2,T.M.Melchior 3, E. Hommel 4, J. Fischer Hansen 5, M. Madsen 2 on behalf of The DANREHAB Study Group. 1 The Heart Centre, Rigshospitalet, Department of cardiology, Copenhagen University Hospital, Copenhagen, Denmark; 2 National Institute of Public Health, Copenhagen, Denmark; 3 Department of cardiology, Roskilde, Denmark; 4 Steno Diabetes Centre, Gentofte, Denmark; 5 Bispebjerg University Hospital, Department of cardiology, Copenhagen, Denmark Bagground and aims: The Steno 2 study has shown beneficial effect of multifactorial intervention in patients with type 2 diabetes (T2DM) and microalbuminuria although results from the ACCORD study have given rise to some dispute according to the antihyperglycemic treatment. In a randomized clinical trial on comprehensive cardiac rehabilitation (CR) we found improvement in lifestyle and risk factors after 12 months of intervention compared to usual care (UC) among patients with T2DM. We now report if these effects are translated into clinical endpoints after 3 years. Materials and methods: We used a centrally randomized clinical trial comparing CR with UC. Of 1614 eligible patients, 770 (47%) were randomized in ways of 390 patients receiving UC and 380 patients CR. A total of 151 patients (20%) had known T2DM at randomization and 75 patients were allocated to CR and 76 patients to UC. Patients randomized to CR received 12 weeks of individually tailored, multi-disciplinary programme and clinical control after 3, 6 and 12 months. A composite blinded administrative register-based primary outcome measure included total mortality, myocardial infarction or first acute re-admissions due to heart disease. For secondary outcomes we used acute re-admissions and acute length of stay. We used Cox-regression for analysing time-to-event and Poisson regression for analysing length of stay and number of re-admissions. The follow-up time was 3 years after randomization. Results: Significantly differences in traditionally cardiovascular risk factors were obtained at the end of study period (p<0.05). More patients in the CR group received cardio protective agents compared to UC (p<0.05). There was no significant difference in the composite outcome (CR vs. UC; Hazard ratio: %CI: ) or when looking separately at the components in the primary outcome. Amongst the CR and UC patients, 57% and 62% were acute re-admitted at least once (p=0.80). There were 238 and 355 acute re-admissions for CR patients and UC patients (p=0.17) with a mean length of stay of 5.8 days and 7.7 days, respectively (p<0.05). Conclusion: Although the DANSUK trial find significantly greater reduction in blood pressure and improvement in glycemic control in patients with T2DM receiving CR compared to UC, these effects do not yet translate into the primary clinical endpoint at 3 years follow-up. A marginally significant reduction in acute length of stay in patients receiving CR was obtained. Shortness of intervention or follow-up period or a small sample size could explain some of the results that failed to appear. vs 75 years). The use of CRT-D declined with advancing age (48 vs 43 vs 29%; p<0.05 for <65 vs 75 years and for vs 75 years). At the 6-months evaluation, the prevalence of responders to CRT was similar in the three groups (58 vs 60 vs 62%, p>0.5). At the 12-months evaluation, LVEF (34±11%, 34±11%, 37±12%) and NYHA Class (2.0±0.7, 2.1±0.7, 2.2±0.7) significantly and similarly improved at all ages (p<0.05 vs baseline for all groups). During the follow-up (length: 19±13 months), all-cause mortality was higher only when comparing the 75 vs the <65 years patients (Kaplan-Meier analysis, p=0.005). In all groups, mortality was significantly associated with the non responder condition. Conclusions: CRT significantly improves left ventricular performance and functional capacity also in selected elderly patients. Mortality seems to be determined by the non responder condition. Specifically designed controlled clinical trials will have to verify and, eventually, generalize the results we have obtained Differences in dyssynchrony and response to cardiac resynchronization therapy between native LBBB and pacing-induced LBBB T. Arita, K. Ando, Y. Soga, M. Goya, H. Yokoi, M. Iwabuchi, M. Nobuyoshi. Kokura Memorial Hospital, Kitakyushu, Japan Background: Cardiac resynchronization therapy (CRT) improves global cardiac function through exerting more coordinated contraction/relaxation among segments. Although most of patients with heart failure and LBBB well respond to CRT, there still remains unclear whether effects of CRT are comparable between patients with native LBBB (Group: nl) and pacing-induced LBBB (Group: pl). Methods: Twentry-four patients in group nl and 12 patients in group pl underwent CRT due to conventional indications. At pre and 3-6 month post CRT, echocardiography was performed by which left ventricular volumes, functions and dyssynchrony parameters were obtained. In this study, global discoordination (spatial nonuniformity) index (GDI=ISR/(GSR+ISR), where ISR (internal strain rate)= ( S (n) - S (n) )dt)/2, GSR=global strain rate) was calculated in addition to conventional dyssynchrony (temporal nonuniformity) parameters. Results: LVESV were significantly different between two groups (p<0.01, 38.0±19.8ml (nl) vs 15.5±19.2ml (pl)), however, EF, MR area were not significantly different (9.7±8.2% vs 4.9±6.3%, 0.10±0.20 vs 0.065±0.13, respectively). Tissue Doppler derived longitudinal dyssynchrony parameters showed no difference (42.4±13.9ms vs 36.5±12.0ms), however, SPMWD showed significant difference (p<0.01, 268.9±84.6ms vs 155.2±94.7ms). More circumferential discoordination were observed throughout the cardiac cycle. However, no significant difference was observed as regards longitudinal discoordination. PREDICTORS OF OUTCOME IN CARDIAC RESYNCHRONISATION THERAPY 1899 Cardiac resynchronisation therapy is effective in elderly patients. The results of the InSync registry S. Fumagalli 1, M. Gasparini 2, M. Lunati 3,M.Santini 4, M. Landolina 5, A. Achilli 6, F. Tronconi 7, S. Valsecchi 7, N. Marchionni 1, L. Padeletti 8. 1 ICU, Geriatric Cardiology and Medicine Unit, AOU Careggi and University, Florence, Italy; 2 Istituto Clinico Humanitas, Rozzano, Italy; 3 Niguarda Hospital, Milano, Italy; 4 Ospedale San Filippo Neri, Rome, Italy; 5 Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 6 Belcolle Hospital, Viterbo, Italy; 7 Medtronic Italia, Milan, Italy; 8 Internal Medicine and Cardiology Unit, AOU Careggi and University, Florence, Italy Purpose: The aging process of population arises some important issues about the usefulness in elderly subjects of medical interventions essential in younger patients. Aim of this study was to assess the influence of age on the effectiveness of cardiac resynchronisation therapy, alone (CRT) or in combination with an ICD (CRT-D). Chronic heart failure (CHF) is, in fact, one of the most important syndromes in elderly patients, associated with an increased incidence of disability and hospital admissions, and with a worsened health-related quality of life and a greater mortality. Methods: We evaluated the 1787 consecutive patients admitted for CRT or CRT- D in the eight Italian Centers taking part in the InSync Registry between 1999 and Accordingly to the endpoint of the present study, patients were divided into three age-groups (<65 years, n=571, age: 57±7; years, n=740, age: 70±3; 75 years, n=476, age: 78±3). Results will be presented following this stratification criterion. Results: Male gender (p<0.001) and the prevalence of coronary artery disease (p<0.001) increased with age. COPD, diabetes and renal insufficiency reached the highest prevalence in the years group. Left ventricular ejection fraction (LVEF) did not differ by age (26±8 vs 26±7 vs 27±8%, p>0.5), while NYHA Class worsened in elderly patients (2.9±0.6 vs 3.0±0.6 vs 3.0±0.6; p=0.017 <65 Global discoordination index Conclusion: In comparison to heart failure with pacing-induced LBBB, those with native LBBB have more dyssynchrony/discoordination especially in circumferential direction which might result in more reverse remodeling after CRT Outcome of chronic heart failure patients after device implantation is highly dependent on concomitant medical treatment regimen C. Adlbrecht, M. Huelsmann, M. Gwechenberger, C. Khazen, F. Wiesbauer, M. Ehlenitzky, S. Neuhold, T. Binder, I.M. Lang, R. Pacher. Medical University of Vienna, Vienna, Austria Background: Device implantation in chronic heart failure (CHF) for cardiac resynchronization therapy (CRT) with or without implantable cardioverter/defibrillator (ICD) is an established treatment option for symptomatic patients under medical baseline therapy. However, in the real world, medical therapy is not always up-titrated to the desirable dosages. This provides the opportunity to evaluate the impact of optimizing medical therapy in patients who had received a device therapy with proven effectiveness. Aim: This observational cohort study assessed the real life - effect of CRT compared to CRT/ICD therapy and the impact of concomitant pharmacotherapy on outcome. Results: Mean follow-up for the 205 CHF patients (95 CRT and 110 CRT/ICD) was 16.8±12.4months. In the total study cohort 83 (41%) reached the combined primary endpoint of all-cause death or cardiac hospitalization (CRT group: 25 (26%), CRT/ICD group: 58 (52.7%), p<0.001). Cox regression analysis revealed non-optimized medical therapy at follow-up (HR=2.080 [ ], p=0.013) and CRT/ICD versus CRT (HR=2.504 [ ], p 0.001) as significant predictors of the primary endpoint.

7 Predictors of outcome in cardiac resynchronisation therapy / ICD therapy: patient and device monitoring 307 Conclusion: Our data stress the importance of professional monitoring and titration of pharmacotherapy not only in medically treated CHF patients but also in patients under device therapy by a heart failure unit or a specialized cardiologist Effect of heart failure history on CRT patient survival D. Gras 1,C.Muto 2, T. Maounis 3, A. Schuchert 4, M.-G. Bongiorni 5, R. Frank 6, T. Vesterlund 7, E. Boulogne 8, L. Padeletti 9 on behalf of the MASCOT Investigators. 1 NCN, Nantes, France; 2 Ospedale Loreto Mare, Naples, Italy; 3 Onassis Cardiac Surgery Center, Athens, Greece; 4 Friedrich-Ebert-Krankenhaus, Neumuenster, Germany; 5 Ospedale Cisanello, Pisa, Italy; 6 Hopital Pitié-Salpetrière, Paris, France; 7 Aalborg Hospital, Aalborg, Denmark; 8 St. Jude Medical, Zaventem, Belgium; 9 Ospedale Careggi, Florence, Italy Purpose: Patients candidate for Cardiac Resynchronization Therapy (CRT) often have a long history of Heart Failure (HF) having required numerous hospitalizations for their heart disease. We investigated whether the time since the first diagnosis of HF and the number of hospitalizations for HF in the 6 months preceding the implantation of the CRT device, had any effect on patient survival. Methods: The MASCOT study enrolled patients candidate for CRT and followed them for 2 years. Information on the patients heart failure history was collected at baseline. Post-hoc survival analyses were performed on the 393 randomized patients to investigate the effect of time since HF diagnosis (above vs. below median) and the number of HF hospitalizations in the 6 months preceding the CRT device implant (none vs. 1 vs. 2 or more) on the 2 year patient survival. Results: The median duration since the diagnosis of heart failure was 31.2 months. 43% of patients had no HF hospitalization, 32% had 1 hospitalization only, and 25% of patients had at least 2 hospitalizations in the 6 months preceding CRT device implant. Both a longer history of Heart Failure (p=0.04) and an increasing number of hospitalizations for Heart Failure in the 6 months preceding CRT implantation (p< Figure 1) were significantly associated with decreased survival over a 2-year follow-up period. Reverse remodeling, defined as at least a 10% decrease in LVESV, was less in the older group (26% vs 46%; p=0.03). Moreover, there was no difference between two groups neither in the time to first occurrence of Atrial Fibrillation (AF) nor in the time of occurrence of permanent AF. Parameters <70 (n=202) 70 (n=207) P-value Age (years) 60±7 75±4 NYHA Class III/IV (%) 87/13 86/ Ischemic Cardiomyopathy Diabetes (%) QRS width (ms) 165±31 162± CRT-P/CRT-D (%) 42/58 46/ ACE/ARB (%) Beta Blocker (%) Diuretics (%) Amiodarone (%) Spironolactone (%) Quality of life 45±21 45± LVEF (%) 24±6 26± Conclusions: Pts >70 yrs benefited as well as pts <70 yrs from CRT, in terms of symptoms, cardiac function, mortality and HF hospitalization. Reverse remodeling was observed more frequently in pts <70 years Heart disease and QRS duration predict hyperresponse to cardiac resynchronization therapy L. Koutbi, F. Franceschi, J. Mancini, E. Bastard, G. Habib, J.C. Deharo. AP-HM - Hopital de la Timone, Marseille, France Purpose: After cardiac resynchronization therapy (CRT), some patients experience a remission of heart failure symptoms. They have been qualified as hyperresponders (HR) to CRT. Little is known about this population. The aim of this study was to determine the incidence and predictive factors of hyperresponse to CRT. Methods: We performed a single-center study of patients successfully implanted with CRT devices at our institution from 2004 to At implantation, all patients had a III NYHA functional status and a left ventricular ejection fraction (LVEF) 35%. Clinical and echographic data were prospectively collected before implantation and at 6 months. Patients were considered as HR when LVEF was above 45% and NYHA functional class was II at 6 months. Results: Out of 175 consecutive patients who succesfully received a CRT device, 18 (10.3%) were HR at 6 months. In HR, non-ischemic cardiomyopathy (NICM) was more frequent than in non-hr (72.2% vs 41.4%; p=0.013), baseline LVEF was less depressed (28.8±5% vs 24.7±5%; p=0.003), baseline QRS duration was higher (180±25 ms vs 164±30 ms; p=0.03), and QRS narrowing after CRT was more important (-51±28 ms vs -32±29 ms; p=0.013). No difference was found in age, sex and medical therapy. Conclusion: Hyperresponse to CRT occurred in 10.3% of our patients at 6 months. HR were more likely to occur in case of NICM, less depressed LVEF, wider baseline QRS and a higher shortening of the QRS after CRT. Figure 1 Conclusions: HF patients who are typically candidate for CRT, could potentially benefit from earlier consideration for device implantation, in terms of further improvement in survival and hospitalization. These preliminary findings should, however, be confirmed by a controlled study Old age does not influence cardiac resyncronization therapy effects A. Vicentini 1,S.DeFeo 1,C.Muto 2, T. Maounis 3, A. Schuchert 4, C. Gazzola 5, E. Boulogne 6, L. Pedeletti 7. 1 Casa di Cura Dott. Pederzoli, Peschiera del garda, Italy; 2 Ospedale Loreto Mare, Naples, Italy; 3 Onassis Cardiac Surgery Center, Athens, Greece; 4 Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; 5 St. Jude Medical, Milan, Italy; 6 St. Jude Medical, Zaventem, Belgium; 7 Ospedale Careggi, Firenze, Italy Purpose: Cardiac resynchronization therapy (CRT) has been demonstrated to improve symptoms, cardiac function and survival in pts with systolic heart failure and electrical dyssynchrony. Whether age negatively affects the response to CRT is unclear. Methods: The MASCOT study enrolled 409 pts candidate for CRT, with no exclusion criteria on upper age limit. We performed post-hoc analyses on pts either > or <70 yrs old at the time of device implantation. Results: Pts >70 yrs has more often an ischemic cardiomyopathy, were less on b-blockers and spironolactone, had a slightly better cardiac function than pts < 70 yrs (Table 1). After 12 months of CRT, pts > 70 yrs derived significant improvements in NYHA Class, Quality of Life, LVEF, with similar degree to pts < 70 yrs. Mortality (12% vs. 9%) and HF hospitalizations (15% of pts vs. 16% of pts) were no different. IMPLANTABLE-CARDIOVERTER DEFIBRILLATOR THERAPY: PATIENT AND DEVICE MONITORING 1909 Event notifications by remote monitoring systems performing automatic daily checks: load, characteristics and clinical utility N. Varma 1,A.Epstein 2,A.Irimpen 3,L.Gibson 4,C.Love 5. 1 Cleveland Clinic, Cleveland, United States of America; 2 University of Alabama Medical Center, Birmingham, United States of America; 3 Tulane University Medical Center, New Orleans, United States of America; 4 BIOTRONIK, Inc., Lake Oswego, United States of America; 5 Davis Heart & Lung Research Institute, Columbus, United States of America Purpose: Remote Monitoring technology (RMT) may facilitate data access but this has not been tested. RMT systems that automatically (w/o patient or physician interaction) perform daily surveillance may best detect important events but there is concern that this mode risks data overload, potentially increasing office visits (OVs). The TRUST multicenter trial tested this hypothesis. Methods: 1,312 patients implanted with ICDs with RMT were randomized 2:1 to remote monitoring (RM) or conventional (C) groups. In RM, follow up OVs occurred at 3 and 15 months. In between, RMT updated device status daily and triggered event notifications (EN) for conditions listed in Table. Evaluation of EN by RMT and ENs prompting OVs were tracked. C patients were evaluated with OVs every 3 months. Results: RM was a typical ICD population (63±13 yrs; 72% male; NYHA class II 56%; LVEF 29±11%; CAD 65%; amiodarone 14%; 1 prevention indication 72%; and DDD 58%). During a possible 372,011 transmission days, 5715 ENs were received (1.5%). 409 of 843 (48.5%) RM patients generated 1 EN (median 6 EN/patient). Most ENs were due to arrhythmias. Median time from onset to evaluation of VT/VF

8 308 Implantable-cardioverter defibrillator therapy: patient and device monitoring events in RM patient was < 2days,vs.> 30 days in C. EN evaluation resulted in management decision made remotely in 89%. Of 11% resulting in OV, 51% required significant reprogramming or anti-arrhythmic medication change (compared to 29% of OV in C). Event Notification Type Total ENs # Pts Mean per pt ± SD Median per pt VT and/or VF detection (32.8%) 8.01± Duration of mode switching or Atrial burden > 10% (2.5 h) (8.3%) 30.8± SVT detection (10.0%) 8.87± Shock impedance <25 or > (0.5%) 12.2± Ventricular lead impedance <250 or > (0.5%) 7.6± VT/VF and 30 J shock ineffective (2.2%) 1.24± Atrial lead impedance <250 or > (0.4%) 6± VT/VF detection programmed to OFF 1 1 (0.1%) N/A N/A Conclusions: Event notifications generated by RMT systems with automatic daily surveillance occur infrequently, without overburdening clinic resources, and provide rapid detection and notification of important events Early detection of heart failure decompensation by Optivol fluid status monitoring R. Bover Freire 1, I. Fernandez Lozano 2, J. Fernandez De La Concha 3, X. Beiras Torrado 4, V. Monivas Palomero 2, J.J. Garcia Guerrero 3, E. Garcia Campo 4, J. Perez-Villacastin 1. 1 Cardiology Department, Hospital Clinico San Carlos, Madrid, Spain; 2 Cardiology Department, Hospital Puerta de Hierro, Madrid, Spain; 3 Cardiology Department, Hospital Infanta Cristina, Badajoz, Spain; 4 Cardiology Department, Hospital Xeral de Vigo, Vigo, Spain Introduction: Up to 90% of heart failure decompensations present progressive pulmonary congestion. Intrathoracic impedance monitoring (Optivol feature, Medtronic) may alert of progressive heart failure patient deterioration. The diagnostic accuracy of Optivol monitoring is not well established. Methods: We performed a multicentre prospective observational trial in four hospitals in Spain. All patients had a Medtronic ICD or ICD/CRT device with Optivol capability. Heart failure decompensations (defined by worsening of heart failure signs and symptoms) and Optivol alerts were recorded during the study. Results: 100 patients were included in the study protocol. 89% were male, and the mean age was 65.0±11.55 years. 60.8% had an ICD and 39.2% an ICD/CRT device. Etiologies were more frequently ischemic (64.6%) or idiopathic (26.4%) myocardiopathy. 60.7% had a heart failure diagnosis, 21.6% were in NYHA functional class II, and 56.9% in NYHA III. Mean ejection fraction was 31.0±13.3%, and the mean BNP value at study entry was pg/ml. 74.2% were on beta blockers, 95% on ACEIs or ARBs. During the follow-up were performed 140 device interrogations. There were 20 events of new-onset or decompensated heart failure (13 with preceding Optivol alert) and 40 Optivol sound alerts (27 without posterior clinical changes) during a mean follow-up of 52 months. The Optivol alert detected clinical heart failure deterioration with 65% sensitivity, 77.5% specificity, 32.5% positive predictive value, and with a negative predictive value of 93%. Multivariate analysis showed BNP values (p=0.001), patient age (p=0.049) and left ventricular ejection fraction (p=0.059) at baseline as predictors of heart failure decompensation preceded by Optivol alert (true positive events). There was no difference in Optivol diagnostic capability stratified by type of device (ICD vs. ICD/CRT) or patient medication (beta blockers and/or ACEIs/ARBs). Conclusions: A device-based algorithm that alerts patients in case of decreasing intrathoracic impedance may facilitate the detection of heart failure decompensation. In our prospective study, despite an acceptable sensitivity, the positive predictive value was too low. Adequate patient selection before implanting a device with Optivol capability could be crucial for improving diagnostic accuracy Implantable cardioverter defibrillator recipients: comparison of primary and secondary indicated patients during long-term follow-up C.J.W. Borleffs, G.H. Van Welsenes, L. Van Erven, R.J. Van Bommel, E.T. Van Der Velde, F.R. Rosendaal, E.E. Van Der Wall, J.J. Bax, M.J. Schalij. Leiden University Medical Center, Leiden, Netherlands Background: Large trials have shown the beneficial effect of an implantable cardioverter defibrillator (ICD) for secondary, as well as primary prevention of sudden death. The aim of this study was to assess the long-term follow-up of ICD recipients and to compare patients with a primary to those with a secondary indication. Methods: A total of 1870 consecutive patients (1519 male, age 63±12 years) were evaluated at ICD implantation. Seven-hundred-eighty-seven patients (42%) received an ICD for secondary prevention: after a ventricular arrhythmia lasting longer than 30 seconds or with hemodynamic consequences. The remaining 1083 had a primary indication. During follow-up, all events triggering appropriate device therapy and death were noted. Results: During a mean follow-up of 39±31 months, a total of 323 (17%) patients died. Appropriate device therapy was noted in 590 (32%) patients, consisting of 2.3±5.3 shocks and 24.8±148.0 ATP. Cumulative event rate (Figure) for death after six years was 28% for primary prevention and 26% for secondary prevention (p=0.2). Calculated cumulative rate of appropriate therapy at six years was 34% for primary prevention and 52% for secondary prevention (p<0.001). Conclusions: In a large cohort of ICD-recipients, comparison of the long-term follow-up in patients with a primary or a secondary indication shows major differences in the occurrence of ventricular arrhythmias, causing ICD therapy. Survival is not significantly different between the two groups Hypertrophic Cardiomyopathy: Single-center experience with ICD implantation & follow-up L. Valtuille, N. Galizio, J.L. Gonzalez, M. Ramirez, A. Fernandez, J.H. Casabe, E. Guevara, F. Landeta, M. Diez, L. Favaloro. Favaloro Foundation - University Hospital, Buenos Aires, Argentina Introduction: Implantable cardioverter defibrillator (ICD) implantation in survivors of sudden cardiac death (SCD) and/or sustained VT in hypertrophic cardiomyopathy (HCM) is widely accepted. However, experts recommendations regarding primary prevention (PP) patients (pts) is not uniform. Prospective registries could offer additional information in clinical decision-making. Objectives: To describe a group of pts with HCM undergoing ICD implantation at our institution, to analyze implantation characteristics and to describe the outcomes of this population. Methods: Between 1994 and 2009, from a prospectively followed HCM group of 349 pts, 45 (12.8%) received an ICD. Pts were divided according to primary (PP) or secondary prevention (SP) of SCD. A high defibrillator threshold (DFT) was defined as >20 J for VF reversion. Follow-up analysis was performed with the Kaplan Meier method. Baseline characteristics: age 35.5 yr (range 4-81 yr), 27 males (60%), NYHA II-IV 29.6%, mean LVEF 54.1% (9 pts LVEF<50%). Results: Thirty-six pts underwent ICD implantation for PP and nine for SP. Among PP pts, 10 (27.8%) presented one major risk factor for SCD and 24 (66.7%) two or more major risk factors. The remaining 2 pts (5.6%) presented either LVEF <30% or NYHA III with left ventricular tract obstruction. ICD implantation: most devices were unicameral (66.7%). Nine out of 41 pts (22%) had a high DFT. Follow-up was longer in SP pts than in PP pts (87.6 vs 22.5 months, p 0.01). Appropriate shocks: Six pts (13.3%) had shocks due to VT/VF. Mean time to shock was 20.9 months (range 15 days to 68.2 months). The SP group had a higher proportion of pts receiving shocks (n=3, 33.3%) compared to the PP group (n=3, 8.3%) However, there were no differences in survival free of shocks between these two groups (log rank=0.56). Inappropriate shocks: In the PP group, 9 pts (25%) received shocks (7 SVT, 2 noise). In the SP group, two pts (22.2%) received shocks (AF and noise). Four pts (8.8%) underwent heart transplantation. Death occurred in 3 pts (8.3%), all of them in the SP group. Mean time to death was 59.3 months (range months). Cause of death was either sudden or presumed to be sudden. Conclusions: In our study population, most pts presented two or more risk factors for SCD. Rate of ICD implantation was 12.8%. One-fifth of pts presented high DFTs. A higher proportion of pts in the SP group received shocks due to VT/VF; however, event free survival was not different between SP and PP groups. PP pts presented more than three times the incidence of inappropriate shocks compared to the incidence of shocks due to VT Longevity of ICD pulse generators: 10-year multicenter experience L.M. Kallinen, R. Hauser on behalf of Multicenter Registry Investigators. Minneapolis Heart Institute Foundation, Minneapolis, United States of America Purpose: Despite their widespread use the clinical performance of ICD pulse generators (IPG) is poorly characterized. The aim of this prospective multicenter study was to assess IPG battery longevity, and causes of other IPG failures and replacements. Methods: Data for IPGs that were removed from service at 9 centers were entered into the Multicenter Registry. Information included manufacturer, model, dates of implant and failure, signs of battery depletion or failure, and cause of failure. Results: From 1998 to 2008, 2,320 IPGs were removed from service for normal battery depletion, electronic or housing defects, and for manufacturers advisories (Table). Overall, there was no difference in longevity between manufacturers (p=0.053). However, Medtronic single and dual chamber IPGs exhibited longer battery life than Boston-Scientific or St. Jude Medical IPGs (p>0001). ICD- CRT IPGs exhibited shorter battery longevity for all manufacturers compared to single or dual chamber IPGs (p>0.0001). The incidence of electronic and housing defects was significantly different between manufacturers (p>0.01).

9 Implantable-cardioverter defibrillator therapy: patient and device monitoring / Antibradycardia pacing: from stimulation to function 309 Reason for removal from service and average implant times for IPG type and manufacturer All ICD Pulse Boston Medtronic St. Jude Generators Scientific Medical No. ICD Pulse Generators 2,320 1,022 1, No. Removed for Battery Depletion 2,161 (93%) 973 (95%) 912 (91%) 276 (93%) No. Removed for Electronic, Housing, or Other Failure 91 (4%) 33 (3%) 42 (4%) 16 (5%) No Removed for Advisory 68 (3%) 16 (2%) 47 (5%) 5 (2%) Average Implant Times (months ± SD) All Pulse Generators 51±20 52±17 51±23 49±18 ICD Pulse Generators Removed for Normal Battery Depletion Single Chamber PG 60±17 59±15 67±18 53±18 n=1,021 n=502 n=314 n=205 Dual Chamber PG 54±15 52±12 57±17 46±14 n=658 n=321 n=279 n=58 ICD-CRT PG 41±12 38±10 42±12 42±10 n=235 n=58 n=169 n=8 Conclusion: Short ICD-CRT battery longevity, electronic and housing defects, and manufacturers advisories have had a negative impact on ICD pulse generator performance Lead dislodgement and lead related cardiac perforation in ICD patients G.M. Nair, J.S. Healey, L. Long, J. Dean, S. Divakaramenon, S.C. Ribas, C.A. Morillo, S.J. Connolly. McMaster University, Hamilton, Canada Introduction: Lead related issues following ICD implantation in published literature range from 1% to as high as 8% and necessitate repeat surgical procedures. Methods: A retrospective analysis of ICD implants between April, 2005 and October, 2008 at our institution was performed. Results: A total of 1339 patients received ICDs with active fixation RV leads. 125 (9.3%) lead related issues were identified of which 47 (3.5%) were attributed to lead dislodgements and 7 (0.5%) to lead related cardiac perforation. A statistically significant difference in lead dislodgement rates between the three major vendors was not noted. ICD leads from vendor 1 (see table) was associated with a higher rate of cardiac perforation compared to leads from the other vendors- 5cases (0.88%; p <0.001). This was close to the lower end of published lead perforation rates for leads of similar design. There were no deaths related to repeat procedures. 3 (0.22%) patients needed more than 1 procedure for lead repositioning. 2 (0.15%) patients developed device infection following intervention for lead dislodgement. ICD Manufacturer Total No of Devices - Right Ventricular Right Ventricular From April 2005 Active Fixation Active Fixation to October 2008 Lead Dislodgement Lead Perforation (N) N (%) N (%) Vendor (5.07) 5 (0.88) Vendor (2.86) 1 (0.24) Vendor (1.72) 1 (0.29) P value for Test of Two P value for Test of Two Proportions - Dislodgement Proportions - Perforation Vendor 1 vs (NS) <0.001 Vendor 1 vs (NS) <0.001 Vendor 2 vs (NS) 0.9 (NS) Conclusions: Lead dislodgement and lead related cardiac perforation are responsible for repeat interventions in ICD patients. ANTIBRADYCARDIA PACING: FROM STIMULATION TO FUNCTION 1920 The relationship between left ventricular dyssynchrony and left atrial function in right ventricular pacing D. Leong, A. Mitchell, H. Lim, H. Dimitri, B. John, M. Stiles, M. Alasady, D. Lau, P. Sanders, G. Young. University of Adelaide, Adelaide, Australia Purpose: Right ventricular (RV) pacing may be associated with deleterious effects on cardiac function and left ventricular (LV) synchrony. The effect of RV pacing and LV dyssynchrony on left atrial (LA) structure and function are unknown, however. We hypothesised that LA function is impaired by 1) RV pacing and 2) LV dyssynchrony. Methods: Fifty subjects (mean age 73±13 years) and left ventricular ejection fraction (60±9%) were studied: 40 with permanent RV pacing over a 28±8-month period, and 10 free of cardiac disease, hypertension, and diabetes mellitus (controls). During transthoracic echocardiography, M-mode images were acquired in the parasternal short axis view at the level of papillary muscles, and grey-scale and tissue velocity images were acquired in 3 apical views. LV synchrony was measured by 1) standard deviation of values for time-to-peak systolic tissue velocity on a 12-segment model (tissue Doppler DI), 2) standard deviation of values for time-to-peak systolic longitudinal 2D strain on an 18-segment model (2D DI), and 3) septal-posterior wall motion delay (SPWMD). LA strain was measured using speckle tracking: a region of interest was marked on the left atrium in apical 4- and 2-chamber views and longitudinal strain values were averaged. Septal A was measured as the peak tissue velocity at the septal mitral annulus in late diastole on tissue velocity imaging. LA volume wasmeasured using biplane method of discs. Results: RV pacing was associated with greater LV dyssynchrony than controls; tissue Doppler DI 41.7±3.4 v. 17.3±5ms (p =0.003), 2D DI 69.6±3.4 v. 37.5±5.2ms (p<0.001). Longitudinal LA strain and septal A were significantly greater among controls than paced subjects (24.8±9.3 v. 15.3±6.2%, p = and 8.5±1.2 v. 6.6±1.9cm/s, p = 0.01 respectively). There was a significant linear association between longitudinal LA strain and both tissue Doppler DI (r = 0.34, p = 0.03) and 2D DI (r =0.39,p =0.01). There was a trend towards a linear relationship between LA strain and SPWMD (r =0.37, p = 0.07). There was a significant linear association between septal A and tissue Doppler DI (r =0.42, p =0.002), 2D DI (r =0.3,p =0.04), and SPWMD (r =0.37, p =0.03). LA volume indexed to body surface area increased in a linear fashion with the duration paced (r =0.45, p =0.005). Conclusions: There is a consistent association between different indices of LV dyssynchrony and LA contractile function in patients undergoing permanent RV pacing. The LV dyssynchrony induced by RV pacing may impair LA function,resulting in adverse LA remodelling. LA volume increases with the duration paced Long term results of patients with AV-block randomized to biventricular pacing versus DDD(R)-pacing A.E. Albertsen, P.T. Mortensen, H. Egeblad, J.C. Nielsen. Aarhus University Hospital, Aarhus, Denmark Introduction: Experimental studies and clinical trials indicate that single site right ventricular pacing causes left ventricular (LV) dyssynchrony and dysfunction increasing the risk of congestive heart failure. We investigate if biventricular (BIV) pacing can preserve LV ejection fraction (LVEF) as compared with standard dual chamber DDD(R)-pacing in patients with high grade AV-block referred for conventional pacemaker implantation. Methods: Twenty nine consecutive patients with high-grade AV-block were randomized to permanent DDD(R) (n=15) or BIV pacing (n=14). All patients had bipolar active fixation leads implanted in the right atrium and in the right ventricular septum connected to a BIV pacemaker. In the BIV-group, a dedicated LV-lead was implanted in a lateral coronary sinus tributary. Endpoints were: LVEF measured by 3-D echocardiography and 6 minutes walk test, all estimated the day after pacemaker implantation (baseline) and after one and 3 years of follow-up. Mean±SD are reported. Results: Mean age was 75 (range 25-90) years. At three years of follow-up, LVEF decreased in the DDD(R)-group from 60.0±4% at baseline to 53.2±11% (p=0.06) and remained unchanged in the BIV-group 54.5±8% and 56.6±11%, (p=0.50). No difference in LVEF was observed between groups at the end of follw-up (DDD(R)-group 53.2±11% vs. BIV-group 56.6±11%, p=0.44). Walking distance was unchanged in the DDD(R)-group after 36 months of pacing (baseline 480±46m, 36 months 485±70m; p=0.74) but increased significantly in the BIV-group (baseline 469±70m, 36 months 509±66m; p<0.001). Conclusions: In patients with high-grade AV-block, BIV-pacing preserves LVEF and increases walking distance as compared to DDD(R)-pacing. These results indicate that BIV-pacing may prevent pacing induced heart failure in patients with AV-block who need ventricular pacing LV apex and LV septal pacing for long term preservation of mechanical coordination and ventricular contractility F.W. Prinzen 1, R.W. Mills 1,L.M.Mulligan 2, N. Skadsberg 2, R.N. Cornelussen 1, F. Van Wijk 3. 1 Cardiovascular Research Institute, Maastricht, Netherlands; 2 Medtronic, Minneapolis, United States of America; 3 Bakken Research Institute Medtronic, Maastricht, Netherlands Objective: Conventional right ventricular (RV) apex pacing is associated with asynchronous activation and reduced left ventricular (LV) pump function. Previous studies have shown acute hemodynamic benefits over RV apex pacing by LV septal or LV apex pacing. We investigated whether this improvement translates into a long-term benefit and how acute LV function during single site LV pacing compares to biventricular pacing. Methods: After AV-nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex (RVa, n = 9), RV septum (RVs, n=7), LV apex (LVa, n = 7), or LV septum (LVs, n = 8; trans-ventricular septal approach). LV contractility (dp/dtmax/pinstantaneous) was measured during normal ventricular conduction from atrial pacing (AP) and during ventricular pacing 1-3 hours and 16 weeks after implant. At 16 weeks, contractility was also measured after an acute switch from the implant site (IS) to the non-implanted apex (both for LV septal group) and to RV apex + LV lateral (BiV) pacing. Results: While acute and chronic RVa and RVs apex pacing significantly reduced contractility (Figure a; mean ± SD, *p<0.05 contrasted to 100%), LVs and LVa pacing maintained contractility near AP levels. After 16 weeks of RVa pacing, switching to LVa pacing (but not BiV pacing) increased contractility (Figure

10 310 Antibradycardia pacing: from stimulation to function / Predictors of cardiovascular events: lessons from large databases b). After 16 weeks of LV pacing, switching to RV apex pacing decreased contractility. Collectively, acute LV apex pacing enhanced contractility over acute BiV (p<0.001). synchronisn > 94%. Pts were divided in two groups on the basis of RVSP and RVEF: Group I (RVSP < 40 mmhg and RVEF > 50%) and Group II (RVSP>40 mmhg and RVEF<50%).After 48 months there was statistical significant variation in LVEF,LVDD and MPI in both groups (p<0.001).however the Kaplan Meier curve demonstrated that only in group II there was a significant increase in the overall morbidity and/or hospitalization for HF during time as compared to pts of group I (p<0.05). Conclusion: right systolic pressure and function contribute to identify pts with baseline abnormal LVEF who develop a worse clinical course after permanent RVAp in long term follow-up. Therefore such parameters allow detecting pts in whom avoid RVAp and who need alternative and/or integrated modality of pacing. Figure 1 Conclusions: Chronic LVa and LVs pacing maintain contractility near normal levels, and at a higher level than RVa and RVs pacing. Acutely, LV apex pacing improves contractility compared to BiV pacing Adeno-associated virus-mediated HCN4 gene transfer increases spontaneous ventricular escape beats in canine model of AV block N. Murakoshi 1, R. Kamimura 2,K.Setoyama 2,D.Xu 1, M. Igarashi 1, K. Yoshida 1, K. Tanoue 2, Y. Sekiguchi 1, I. Yamaguchi 1,K.Aonuma 1. 1 University of Tsukuba, Tsukuba, Japan; 2 Kagoshima University, Kagoshima, Japan Purpose: Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels, carrying an inward current termed If, were encoded by four subtypes of HCN genes. HCN4 is the predominant HCN transcript in the adult sinoatrial node, and plays an important role in the generation of cardiac pacemaker potentials. In this study, we investigated whether the HCN4 gene therapy using an adeno-associated virus (AAV) vector was effective and safe for canine model of atrioventricular (AV) block. Methods: Canine model of AV block was generated by catheter ablation to AV node. Electronic pacemaker was implanted, and pacing rate was set at 40 bpm in each group. AAV-HCN4 was injected around the right bundle of the heart (AAV- HCN4 group). As control, AAV-EGFP was transferred likewise (AAV-EGFP group). We checked the percentage of electronically paced beats and sensed beats in both groups once a week for 8 weeks. Four weeks after gene transfer, we investigated the conduction sequence in the right ventricle using CALTO system, and the response of HR to an infusion of isoprotelenol (ISP). Results: In AAV-EGFP group, approximately all of the ventricular rhythm was originated from electronic pacemaker, and spontaneous ventricular escape beats were rare. In AAV-HCN4 group, spontaneous ventricular escape beats accounted for 23% of all ventricular beats at 2 weeks, 14% at 4 weeks, and 16% at 8 weeks. No arrhythmias such as sustained ventricular tachycardia were observed in both groups. The HR increased by 171% in response to an infusion of ISP in AAV- HCN4 group, whereas HR increased by 146% in AAV-EGFP group. The CALTO system showed that the initiation of the conduction sequence was around the injected points in all animals of the AAV-HCN4 group. GFP-positive cells were focally detected in the right ventricular septum of AAV-EGFP group. Conclusions: AAV-mediated HCN4 gene transfer has a therapeutic potential as a partial alternative to electronic pacemakers. However, it appears that the therapeutic strategy cannot sufficiently compensate for the decreased HR, further development of approach will be needed for the clinical application Assessment of right ventricular function can predict the long term clinical evolution of patients with permanent conventional dual-chamber pace-maker E.Moro,C.Marcon,E.Marras,G.Allocca,N.Sitta,P.Delise. Conegliano General Hospital, Conegliano, Italy Introduction: the negative haemodynamics effects of permanent dual-chamber right ventricular apical pacing (RVAp) on cardiac performance are well known, however which patients (pts) are at risk of heart failure (HF) and/or worse clinical outcome is still not exactly established. Aim: identify which parameters of cardiac function predict negative long term clinical evolution in pts with permanent RVAp and reduced left ventricular ejection fraction (LVEF) but who have not indication to cardiac resynchronization therapy (CRT). Population: we studied 38 pts (22 M, 16 F, mean age 74 years) with advanced atrio-ventricular block and clinical indication to permanent cardiac pacing. All pts had basal LVEF 50% and absent indication to CRT. Methods: pacemaker interrogation, clinical and Echo/Doppler follow-ups were performed at post-implantation and after 12, 24, 36 and 48 months. The following parameters were collected: LVEF, left ventricular end-diastolic diameter (LVDD), myocardial performance index (MPI), right ventricular systolic pressure (RVSP), right ventricular ejection fraction (RVEF) and HF morbidity/hospitalization. Results: the percentage of ventricular pacing was > 95% and of atrio-ventricular 1925 Left ventricular electromechanical dyssynchrony after long-term ventricular pacing in patients with acquired atrioventricular block R. Costa, M.I.P. Leao, R.F. Mori, G. Giannini, K.R. Silva, R.T. Silva, C.E.B. Lima, S.P.L. Costa, I.M. Penteado. Associação para Estudo e Desenvolvimento da Eletroterapia Cardíaca, Sao Paulo, Brazil Background: Right ventricular pacing (RVP) may lead patients with impaired left ventricular (LV) function to dyssynchrony and heart failure. The effects of RVP in patients with normal LV function remain unclear. Purpose: To evaluate the effects of long-term RVP on ventricular synchrony in patients with normal LV function. Methods: Electromechanical delay was accessed by Tissue Doppler in 36 consecutive patients with acquired AV block and normal LV function at first implant. LV dyssynchrony was measured by the time interval between the shortest and longest electromechanical delays in the five LV segments. It was established by a delay greater than 65ms. LV ejection fraction was estimated by Simpson. Patients were divided in two groups according to the LV dyssynchrony occurrence and assessed under clinical, demographic and echocardiographic aspects. Student s t- test, Qui-square test and Person s coefficient were performed. Results: After 8.4±6.4 years of RVP 25 patients (69.9%) were in NYHA FC I. LV dyssynchrony was detected in 14 (38.9%) pts. Electromechanical delay was 125.8±40.5 ms and 34.2±17.2 ms in patients with and without dyssynchrony, respectively. No significant difference was observed between both groups of patients (Table). The correlation between the studied variables and LV dyssynchrony was not significant. Variables LV Dyssynchrony absent LV Dyssynchrony present N 22 (61.1%) 14 (38.9%) Male 59.1% 50.0% Age at PM implantation (y.o.) 68.0± ±12.1 Time under pacing (years) 8.2± ±7.1 NYHA FC I 59.1% 67.7% LVEF 0.54± ±0.09 Conclusion: Although LV dyssynchrony were frequent after long-term RV pacing, no correlation was found with clinical or cardiac functional performance. PREDICTORS OF CARDIOVASCULAR EVENTS: LESSONS FROM LARGE DATABASES 1950 The eight independent predictors of elevated resting heart rate among 8922 patients with stable coronary artery disease L. Lorgis 1, M. Zeller 2, P. Jourdain 3, J. Beaune 4, J.P. Cambou 5, B. Vaisse 6, B. Chamontin 5,Y.Cottin 1 on behalf of LHYCORNE. 1 Centre Hospitalier Universitaire de Dijon, Dijon, France; 2 LPPCE,IFR 100, University of Burgundy, Dijon, France; 3 Centre Hospitalier Rene Dubos, Pontoise, France; 4 Centre Hospitalier Universitaire, Lyon, France; 5 Centre Hospitalier Universitaire, Toulouse, France; 6 Centre Hospitalier Universitaire, Marseille, France Background: Heart rate (HR) is a key determinant of both myocardial ischemia and prognosis in patients with coronary disease. Reducing HR is known to relieve ischemia and improve cardiovascular prognosis. However, there is currently no information about HR distribution and predictors of high heart rate in patients with stable coronary artery disease (CAD). Method: The LHYCORNE cohort was a prospective, observational study primary care physicians included consecutive stable CAD patients with treated hypertension. 98% of patients were also followed by cardiologists. Only patients with atrial fibrillation were excluded from the analysis. In these patients, we analysed HR distribution, and factors independently associated with HR above the mean cohort HR. Results: 8922 stable CAD patients in sinus rhythm (76% of males, 66±11 years, BP:141/82 mmhg, 26% diabetes). Mean resting HR was 70±6 bpm and the distribution was: <60 bpm (7%); bpm (38%); bpm (38%); bpm (14%); >90 bpm (2%). Sixty-two percent of patients were on beta-blockers and had a mean 69±8 bpm resting HR versus 73±8 bpm without beta-blockers

11 Predictors of cardiovascular events: lessons from large databases 311 (p<0.001). In multivariate analysis we identified 8 independent predictors of HR over 70 bpm (figure). Conclusion: This large cohort shows that in the real life, over 50% of stable coronary patients have a HR>70 bpm, presenting a particularly high-risk profile. These data underline the need to measure and analyse HR in stable coronary patients taking into account its therapeutic and prognostic role. Methods: The CHADS2 score was calculated in 18,888 patients without AF included in the European REACH registry in 18 European countries between 2003 and ,254 (86%) patients had established cardiovascular disease ( symptomatic patients) and 2,634 (14%) were included on the basis of multiple risk factors with no prior vascular disease ( asymptomatic patients). Ischemic events wererecordedduringa2yearsfollow-upperiod.maccewasdefinedasthe composite of CV Death, MI or Stroke. Results: The mean age of the population was 66.6±9.7 years. 69% of patients were male and 32.5% diabetic. A CHADS2 score of 0, 1, 2, 3, 4, 5 and 6 was found in 1,911 (10.1%), 5,323 (28.2%), 5,478 (29%), 3,623 (19.2%), 1,930 (10.2%), 527 (2.8%), and 96 (0.5%) patients, respectively. CHADS2 score levels were associated with a stepwise increase in rates of death and MACCE (p< for both) (Figure). The correlation between CHADS2 score and events was stronger in symptomatic patients. Among symptomatic patients (without AF) the CHADS2 score was also predictive of the occurrence of non fatal stroke (5.5% for CHADS2 3 vs 1.5% for CHADS2 <3; p< ) Prognostic value of resting heart rate in a general population of patients with stable coronary artery disease: a prospective, single center, cohort study M. Ruiz Ortiz, E. Romo Penas, C. Ogayar Luque, D. Mesa Rubio, M. Delgado Ortega, J.C. Castillo Dominguez, M. Anguita Sanchez, A. Lopez Granados, J.M. Arizon Del Prado, J. Suarez De Lezo. Hospital Universitario Reina Sofia, Cordoba, Spain Purpose: Resting heart rate (RHR) has proven to be an adverse prognostic factor in selected populations of patients with stable coronary artery disease (CAD), referred for coronary angiography or participants in clinical trials. Our aim is to assess the prognostic value of RHR in a general, non-selected, population of patients with stable CAD. Methods: From February 1, 2000 to January 31, 2004, all patients with stable CAD attended at two outpatient cardiology clinics were included in the study and followed for major events (total mortality, acute coronary syndrome ACS, coronary revascularization, stroke and hospitalization for heart failure). The association of RHR ( 70 beats per minute -bpm- versus <70 bpm) with major events and total mortality was assessed. Results: We included 1264 patients, with a mean age of 67±10 years, followed for 26±16 months. Follow-up was complete in 99.45% of cases. RHR was 70 bpm in 645 patients (51%) and <70 bpm in 619 (49%). Probability of events at mean follow-up was 17.99% if RHR 70 bpm and 17.91% if RHR <70 bpm (p=0.32) and total mortality, 2.32% and 2.82%, respectively (p=0.56). Baseline features of both groups are shown in the table. After adjusting for them all, no significant association between RHR and major events was found (Hazard Ratio HR- 1.01, CI , p=0.94). Neither association was found for women (n=338), patients with previous ACS (n=1043) or patients with ejection fraction <0.40 (n=128). In patients aged 75 years (n=275), RHR was a protective factor (HR 0.50, CI , p=0.037). There was not significant association between RHR and total mortality in the entire series or any of the subgroups. Conclusion: RHR was not an adverse prognostic factor in this general, nonselected, low-risk population of patients with stable CAD. Prognostic relevance of RHR in clinical practice can be low in this setting The CHADS2 score predicts adverse cardiovascular outcome in atherothrombotic patients without atrial fibrillation: Insights from the European REACH registry O. Barthelemy 1,F.Beygui 1,J.Silvain 1, A. Bellemain-Appaix 1, U. Zeymer 2, D.L. Bhatt 3, P.G. Steg 4, G. Montalescot 1 on behalf of the REACH Registry investigators. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Cleveland Clinic, Cleveland, United States of America; 4 Bichat-Claude Bernard Hospital (AP-HP), Paris, France Aim: The CHADS2 score is a reliable, easy-to-use, and popular bedside score to assess the risk of stroke in patients with atrial fibrillation (AF). The items of the score are all key determinants of prognosis in vascular patients. We hypothesized that the CHADS2 score would adequately assess the risk of death and major events in stable atherothrombotic patients in absence of AF Figure 1 Conclusions: In stable atherothrombotic patients without AF, the CHADS2 score appears to adequately evaluate the 2 years risk of death, stroke or MACCE. This score is simple, does not require computerized calculation and is commonly used by cardiologists in the setting of AF Pharmacogenetic of Acenocoumarol in patients with extreme requirements V. Perez-Andreu 1, V. Roldan-Schilling 1, M.F. Lopez 2, A.I. Anton 1, I. Alberca 3,J.Corral 1,J.Hermida 4, F. Espana 5, V. Vicente 1, R. Gonzalez-Conejero 1. 1 Centro Regional de Hemodonacion. Universidad de Murcia, Murcia, Spain; 2 Hospital Juan Canalejo, A Coruna, Spain; 3 Hospital Universitario, Salamanca, Spain; 4 CIMA. Navarra, Pamplona, Spain; 5 Hospital La Fe, Valencia, Spain It is well known that common polymorphisms (SNPs) in CYP2C9 and in VKORC1 determine coumarin dose requirements and together with environmental factors can explain about 40% of the total variance in such dose. SNPs in new genes could also explain modest percentages in interpersonal variability, and hence be involved in the risk of therapy. Due to patients are treated by traditional trial-anderror dosing, those with extreme dose requirements to achieve a steady coagulation are also those with the higher risk at starting therapy. Aim: To better define these additional candidate genes, we investigated the pharmacogenetic of acenocoumarol in patients who need extreme doses for reaching a therapeutic INR level. Patients and Methods: We reviewed patients with a steady anticoagulation from 5 Spanish hospitals. We make a statistical approach about acenocoumarol dose requirements in our population, establishing the minimum dose requirement as 5 mg/week (corresponding percentile 5) and the maximum dose as 30 mg/week (p95). For each patient, we selected a control subject taking 13,5mg/week (p50), adjusted by sex and age. Patients older than 75 years or taking any medication known to interfere with acenocoumarol were excluded. Finally, 80 patients in p5 group, 196 in p95 and their respective controls (n=80+196) were included. Genotyping included: VKORC1 C1173T, calumenin A29809G, FVII - 323Ins/Del, GGCX R325Q, CYP2C9 and CYP4F2 V433M. Results: Patients in p5 were older than patients in p95 (71 vs 61 years, p<0.001). Multivariate analysis showed that only the alleles VKORC1 1173T and CYP2C9*3 were significantly more frequent in patients in p5 vs their controls (p=0.004 and p=0.001, respectively). In p95 group, VKORC1 1173C, CYP2C9*no-3 and, interestingly, CYP4F2 433M variants were also overrepresented vs their controls (multivariate analysis all p 0.001). Conclusions: Our results confirm that VKORC1 C1173T and CYP2C9 play a significant role in patients taking extreme acenocoumarol dose. Moreover, we provide new information about the pharmacogenetics of acenocoumarol, as the CYP4F2 V433M polymorphism might play a relevant role in the higher dose requirements. Abstract 1951 Table 1 Age (years) Male sex DM SBP (mmhg) DBP (mmhg) SR LVEF Statins Antiplatelets BB ACEI/ARA RHR 70 bpm 67±11 71% 36% 131±15 75±9 93% 0.55± % 88% 57% 52% RHR < 70 bpm 66±10 76% 26% 128±16 73±9 96% 0.58± % 96% 71% 43% p value <0.001 < <0.001 < ACEI/ARA, angiotensin converting enzyme inhibitors/angiotensin receptor antagonists; BB, beta-blockers; DPB, diastolic blood pressure; DM, diabetes mellitus, LVEF, left ventricular ejection fraction, RHR, resting heart rate, SBP, systolic blood pressure, SR, sinus rhythm.

12 312 Predictors of cardiovascular events: lessons from large databases / Update on risk assessment in acute coronary syndromes 1954 D-dimer testing, thrombophilia screening and recurrences in patients with venous thromboembolism: a 6-year follow-up J. Conard 1, E. Ombandza-Moussa 1,M.M.Samama 1, A.G. Turpie 2, M.H. Horellou 1,I.Elalamy 1. 1 AP-HP - Hopital Hotel-Dieu, Paris, France; 2 McMaster University, Hamilton, Canada Purpose: The clinical relevance of D-dimers (D-di) measurement and thrombophilia screening in the follow-up of patients with history of a venous thromboembolism (VTE) event remains uncertain. Methods: We studied retrospectively 149 patients referred for thrombophilia screening following at least one VTE episode. 9 patients were lost to 6 year followup. D-di were measured by ELFA (Vidas BioMérieux) at first assessment. Results: At first assessment, 63 patients (group A) were without oral anticoagulant treatment (OAT) and 77 patients (group B) were still on OAT. Hereditary thrombophilia was present in 48% of group A and 65% of group B (p<0.02). D-di were significantly lower in patients on OAT (194±130 vs 399±242 ng/ml) (p<0.001). The prevalence of VTE recurrences during follow-up was higher in group A (10 patients, 16%, including 7 with a hereditary thrombophilia), than in group B (one patient with homozygous FV Leiden mutation, 1.3%) (p<0.001). In group A, D-di were higher in the 10 patients with recurrence (512±244 ng/ml) as compared with the 53 without (328±202 ng/ml) (p<0.001). Of the 77 patients on OAT, 24 discontinued OAT during follow-up and 8 (33%) had a recurrent VTE episode after an average interval of 11±9 months (extremes 2 to 38 months); D-di levels were significantly higher than in the 16 without recurrence (p<0.05). Among these 24 patients, hereditary thrombophilia was more frequent in those with a recurrent thrombosis: 75% (6/8) than in those without recurrence: 37% (6/16); p<0.05. D-di level at first assessment was predictive of recurrent VTE, independently of OAT intake (36% patients with D-di over 500 μg/l versus 9% patients with D-di below 500 μg/l, RR=3.90, 95% CI: ). Conclusions: Increased D-di level is a marker of hypercoagulation which could facilitate prediction of recurrent thromboembolic episodes. The efficiency of OAT in patients with symptomatic thrombophilia was demonstrated. After discontinuation of OAT, recurrence was more frequent in patients with thrombophilia. This suggests that thrombophilia is a risk factor for recurrence. UPDATE ON RISK ASSESSMENT IN ACUTE CORONARY SYNDROMES 1956 The HEART score for chest pain patients at the emergency room B.E. Backus 1,A.J.Six 2, J.C. Kelder 1,T.P.Mast 3, F. Van Den Akker 3, P.A. Doevendans 3. 1 St Antonius Hospital, Nieuwegein, Netherlands; 2 Zuwe Hofpoort Ziekenhuis, Woerden, Netherlands; 3 University Medical Center Utrecht, Utrecht, Netherlands Purpose: Chest pain is a common reason for presentation at the emergency room. The diagnosis of Acute Coronary Syndrome without ST elevation (Non ST-ACS) causes uncertainty, as absolute criteria for Non ST-ACS are lacking. Arguments are: suspicious patient History, typical ECG changes, higher Age, Risk factors for atherosclerotic diseases and elevated serum levels of Troponin. Each can be scored with zero, one or two points, depending on the severity. The HEART score is the sum of these five. The purpose of the current study is to validate the HEART score. Methods: A total of 2161 cardiology patients presented at the emergency rooms of the four participating hospitals during January-March 2006, of which 910 (42%) patients due to chest pain. Patients with ST elevation myocardial infarction were not evaluated as they went straight to the catheterization laboratory. End points were acute myocardial infarction (AMI), Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG) or death, occurring within 6 weeks after presentation. Results: An AMI was diagnosed in 92 (10.45%) patients, 82 (9.32%) underwent PCI and 36 (4.09%) CABG and 13 (1.48%) died. The HEART scores in the patients with and without an end point were 7.2±1.7 and 3.8±1.9 respectively (p<0.0001). The percentage of patients with an endpoint in the various HEART groups is given in figure Evaluation of the TIMI and GRACE scores in developing countries: insights from the ACCESS registry J.C. Nicolau 1, G. Montalescot 2, C. Martinez-Sanchez 3, N. Antepara 4, A. Escobar 5,S.Alam 6, M. Sobhy 7,A.Leizorowicz 8 on behalf of The ACCESS Investigators Group. 1 Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil; 2 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 3 Instituto Nacional de Cardiologia Ignacio Chaves, Mexico City, Mexico; 4 Hospital Universitário, Caracas, Venezuela; 5 Clinica Medellin, Medellin, Colombia; 6 American University, Beirut, Lebanon; 7 Alexandria University, Alexandria, Egypt; 8 Univ. Claude Bernard, Lyon, France Purpose: Various risk scores have been proposed to risk stratify patients presenting with non-st-elevation acute coronary syndromes (NSTEACS). However, little is known on the performance of these scores specifically in developing countries. Methods: The ACCESS (ACute Coronary Events a multinational Survey of current management Strategies) is a registry from developing countries that included patients hospitalized with suspected acute coronary syndromes. From these, 6320 (mean age 61±11.9 y.o., 67.2% males) had NSTEACS, being 2055 from Africa (Algeria, Egypt, Morocco, South Africa and Tunisia), 2562 from Latin America (Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Guatemala, Mexico and Venezuela) and 1703 from Middle East (Iran, Jordan, Koweit, Lebanon, Saudi Arabia and United Arab Emirates). Two score performances (TIMI and GRACE) were analyzed for the whole population and for each region; ROC curves considering in-hospital death and death or recurrent ischemia were constructed and the area under the curves (AUC) were compared in the different scenarios. For the GRACE score, cardiac arrest at admission was not considered (information not retrieved). Results: 1) The mean ± SD GRACE score for Africa (AF), Latin America (LA) and Middle East (ME) were 119.6±35, 125.9±35.5 and 120.8±35.5 (P<0.001), respectively; for the TIMI score, the numbers were 3.1±1.4, 3.4±1.4 and 3.3±1.4 (P<0.001); 2) The mortality rates for AF, LA and ME were 1.4%, 2.0%, and 0.9% (P=0.014); the rates of death or recurrent ischemia were 12.3%, 9.1%, and 10.6% (P=0.002). 3) The AUC ± SE for the GRACE and TIMI scores taking into account death were, respectively, 0.81±0.02 vs. 0.65±0.03 for the whole population (P<0.001), 0.81±0.04 vs. 0.57±0.06 (P=0.001) for AF, 0.78±0.03 vs. 0.65±0.04 for LA (P=0.009), and 0.83±0.06 vs. 0.78±0.05 for the ME (P=0.570). 3) Taking into account death or recurrent ischemia the AUC were, respectively, 0.60±0.01 vs. 0.61±0.01 for the whole population (P=0.855), 0.60±0.02 vs. 0.64±0.02 for AF (P=0.139), 0.63±0.02 vs. 0.60±0.02 for LA (P=0.253), and 0.58±0.02 vs. 0.58±0.02 (P=0.853) for the ME. Conclusions: 1) There are significant differences among the different developing regions in terms of clinical outcome, the highest risk patients and higher mortality rates being seen in Latin America. 2) The GRACE score performed significantly better than the TIMI score to predict mortality globally, and also for AF and LA. The two scores were less accurate, but fared similarly, when considering death or recurrent ischemia. Figure 1 Conclusions: A HEART score of 0-3 points holds a risk < 0.9% for an endpoint and supports early discharge. With a risk of 12% a HEART score of 4-6 points implies admission for clinical observation. A HEART score 7 points, with a mean risk of 65%, supports early invasive strategies. The HEART score helps to make accurate diagnostic and therapeutic choices and facilitates communications Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors and clinical implications (analysis from the ACUITY Trial) E. Nikolsky 1, R. Mehran 1,A.J.Kirtane 1,A.J.Lansky 1,A.M.Lincoff 2, A. Caixeta 1,M.Fahy 1, J.W. Moses 1, E.M. Ohman 3, G.W. Stone 1. 1 The Columbia University Medical Center and the Cardiovascular Research Foundation, New York, Ny, United States of America; 2 The Cleveland Clinic Cleveland, Ohio, United States of America; 3 Duke University, Durham, Nc, United States of America Objective: Gastrointestinal bleeding (GIB) is one of the sources of hemorrhage in patients (pts) with acute coronary syndromes (ACS) undergoing early invasive management. The data are scarce, however, regarding the implications of GIB in pts with ACS whose contemporary management includes composite antithrombotic and antiplatelet therapy. Our aim was to assess the incidence, predictors and outcomes of GIB in intermediate- to high-risk pts with ACS. Methods: The study represents post hoc analysis of pts with moderateand high risk ACS in the randomized Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial who were enrolled in 17 countries between August 2003 and December Pts were randomized to the open-label use of 1 of 3 antithrombin regimens started prior to angiography (heparin+gp IIb/IIIa inhibitors [H+GPI], bivalirudin+gpi, or bivalirudin monotherapy), and based on angiography were triaged to PCI, CABG or medical management. Results: GIB within 30 days of randomization occurred in 178 (1.3%) pts. In the entire study population, older age, baseline anemia and smoking were identified as independent predictors of GIB. In pts triaged to medical management, randomization to bivalirudin monotherapy decreased the likelihood of GIB compared with randomization to H+GPI (OR 0.22 [0.07, 0.67], P=0.007). At 1-year F/U pts with

13 Update on risk assessment in acute coronary syndromes 313 vs. without GIB had remarkably worse clinical outcomes (Table). On multivariable analysis, GIB independently predicted 1-year all-cause mortality (HR 3.95 [2.62, 5.96]), cardiac mortality (HR 3.70 [2.10, 6.52]), and composite ischemia (HR 1.86 [1.34, 2.60]) (all P<0.0001). Clinical outcomes at 1 year follow-up GIB (+) n=178 GIB ( ) n=13641 P value All-cause death 21.9% 3.9% < Cardiac death 13.2% 2.3% < Myocardial infarction 15.8% 7.3% < Unplanned revascularization 12.3% 9.0% 0.12 Composite ischemic outcome* 34.7% 16.3% < Stent thrombosis 5.8% 2.4% *All cause death, myocardial infarction and unplanned revascularization, By Academic Research Consortium definition. Conclusions: GIB is a devastating condition in the scenario of ACS. Future trials are warranted to determine effective measures to prevent GIB in high-risk populations Four times higher hospital mortality due to major bleeding complications in NSTE-ACS in clinical practice: lessons from the Euro Heart Survey ACS registry A.K. Gitt 1, H. Bueno 2,W.Wojakowski 3, M. Tendera 3,H.Katus 4, M. Gierlotka 5, M. Tubaro 6,Y.Hasin 7,F.Schiele 8, J.P. Bassand 8 on behalf of ACS Registry. 1 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Hospital General Universitario Gregorio Maranon, Madrid, Spain; 3 Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland; 4 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 5 Slaskie Centrum Chorob Serca, Zabrze, Poland; 6 Ospedale San Filippo Neri, Rome, Italy; 7 Poria Medical Centre, Tiberias, Israel; 8 CHU de Besancon - Hopital Jean Minjoz, Besancon, France Background: Data from recent randomised trials of antithrombotic treatment for ACS have highlighted the influence of bleeding complications on outcome. Little is known about the prevalence of major bleeding complications in NSTE-ACS in clinical practice. Methods: Between Oct 2006 to Oct 2008, 21,582 consecutive patients with ACS were enrolled into the ACS-Registry of the Euro Heart Survey Programme to document treatment and hospital outcome. We examined the impact of major bleeding complications (bleeding with drop of haemoglobin >5g/dl or hematocrit > 15%) on hospital outcome of NSTE-ACS. Results: Of 12,850 patients with NSTE-ACS, 270 (2.1%) had major bleeding complications. Patients with major bleedings were older, more often female and did receive treatment with GP IIb/IIIa blockers and heparins more frequently. Hospital mortality was significantly higher in patients with major bleeding even after correction for differences in patient characteristics, kind of NSTE-ACS and treatment (OR 4.22, 95% CI ). Major bleeding (n=270) No major bleed (n=12,580) p-value Age [years] < 0.01 Female Gender 47.0% 36.4% <0.01 Prior MI 32.3% 29.6% ns Prior PCI 18.2% 17.8% ns Prior Bypass 10.4% 6.8% <0.05 Prior Stroke 11.1% 6.4% <0.01 Diabetes mellitus 33.0% 29.9% ns Renal Failure 16.7% 7.9% <0.01 PCI 60.2% 42.6% <0.01 GP IIb/IIIa 22.2% 11.7% <0.01 ASA 93.3% 93.3% ns Clopidogrel 79.3% 80.8% ns LMW-Heparin 54.7% 53.6% ns Unfr. Heparin 65.2% 55.4% <0.05 Hospital Mortality 11.1% 3.1% <0.01 Conclusion: The incidence of major bleeding complication in NSTE-ACS in clinical practice in Europe was 2.1%. Major bleeding complications were associated with 4-fold increased hospital mortality ST2 and IL33 have independent prognostic value in patients with acute coronary syndromes compared with GRACE score and N-terminal pro-b-type natriuretic peptide O.S. Dhillon, S.Q. Khan, H. Narayan, N.G. Kh, M. Noor, Q. Pa, I.B. Squire, J.E. Davies, L.L. Ng. University of Leicester, Leicester, United Kingdom Purpose: ST2, a member of the interleukin-1 receptor family is up-regulated after applying mechanical strain to cardiac myocytes. In study populations with STelevation myocardial infarction (STEMI) ST2 has demonstrated prognostic value but interleukin 33 (IL33), its natural ligand, has not been investigated in ACS. We assessed the prognostic value of ST2 and IL33 in unselected patients with both STEMI and nonstemi for death/heart failure (HF) combined and death, HF or MI separately. Comparison was made with N-terminal pro-b-type natriuretic (NTproBNP) and GRACE Score. Methods: In this prospective single centre study we recruited 1254 ACS patients (902 men, mean age 66.4 SD 12.6 yrs, 672 STEMI) with mean follow up 797 days [range ]. A single blood test was taken 3-5 days after admission for ST2, IL33 and NTproBNP. Results: In a Cox regression model containing baseline characteristics we discovered IL33 was associated with increased risk of late mortality in patients with STEMI only (HR 1.33 p=0.001 along with age, egfr) which remained after adjustment for GRACE score and NTproBNP. Kaplan-Meier analysis revealed that STEMI patients with both IL33 and NTproBNP levels above median had the highest mortality rates (log rank p<0.001). No significant association between IL33 and HF or MI was found in either STEMI or NSTEMI. ST2 levels were predictive of death/hf combined (HR 2.25 p=0.001) as were age, KillipClass>1 and egfr. The association of ST2 with mortality was stronger than for HF (HR 2.39 p<0.001 vs HR 1.87 p=0.028) and particularly evident for early mortality in STEMI. A 1-SD increase in ST2 levels was associated with 9.30-fold rise in the hazard of death at 30 days p<0.001 and is also highly discriminatory C-statistic 0.82 p<0.001 compared with NSTEMI HR 6.07 p=0.009, C-statistic 0.73 p< After addition of NTproBNP and GRACE score to the model ST2 remained associated with death and MI (HR 0.12 p=0.002) but not with HF. C- statistic increased to 0.90 p<0.001 for death at 30 days in STEMI using a model combining GRACE, NTproBNP and ST2. In patients with high GRACE scores or NTproBNP levels further stratification by ST2 identified those at highest risk of death/hf (log rank and respectively both p<0.001). Conclusions: This is the first report identifying IL33 as a novel prognostic marker of mortality in STEMI patients beyond clinical factors, GRACE score and NTproBNP levels. ST2 is an independent predictor of cardiac events in ACS which is particularly evident for early events in the STEMI population. Knowledge of biomarker levels improves risk stratification beyond GRACE scoring alone Performance of the GRACE risk score in acute coronary syndromes: impact of patient-related variables and of variables associated with the acute event P. Carmo, J. Ferreira, C. Aguiar, P. Goncalves, R. Gomes, S. Lima, J. Brito. Hospital de Santa Cruz, Carnaxide, Portugal Purpose: The GRACE risk score, recommended as the preferred multi-factorial tool for predicting outcome on admission in acute coronary syndromes (ACS), incorporates 8 variables, of which 6 are associated with event severity (heart rate, systolic blood pressure, Killip class, ST-segment deviation, elevated cardiac markers, and cardiac arrest), and 2 with the patient (Pt) (age and creatinine).the aim of our study was to evaluate the prognostic performance of the global GRACE risk score and of each of it s 2 subsets of variables variables associated with event severity and patient-related variables for outcomes before and after the first 30 days. Methods: We studied 460 Pts with non-st-elevation ACS (age 63±11 years, 22% female, and 57% with elevated troponin). For each patient we calculated the global GRACE risk score (Global S), the sum of points attributed to variables associated with acute event severity (Event S), and the sum of points attributed to the 2 patient-related variables (Patient S).ROC curve analyses were performed to assess the prognostic accuracy of the Global S, the Event S, and the Patient S, for incidence of death (D) and myocardial infarction (MI) at 30 days after admission and between 30 days and 1 year.the best discriminatory value for each Score was used to calculate the risk of events during follow-up (Hazard Ratio, HR). Results: The incidence of D/MI was 7,6% at 30 days and 15% at 1 year.the prognostic accuracies of the Global S, Event S, and Patient S are shown on the Table.The Global S had a good performance at 30 days (Global S>148, HR=4.53, 95% CI, ) as well as between day 30 and 1 year (Global S>128, HR=5.13, 95% CI, ). The Event S but not the Patient S predicted outcome at day 30. Between day 30 and 1 year, both the Event S and the Patient S were associated with risk of D/MI, but the Patient S showed the best performance. Table 1 Partial Score Incidence of D/MI 0-30 days Incidence of D/MI days Event Score Score >88: 17%; Score 88: 6% Score <47: 10%; Score 47: 5% HR=2.93 ( ) P=0.003 HR=2.53 ( ) P=0.027 Patient Score Score >63: 9%; Score 63.3: 6% Score >63: 12%; Score 63: 2% HR=0.72 ( ) P=0.369 HR=7.05 ( ) P=0.001 Conclusion: In a real-world population of non-st-elevation ACS, the excellent performance of the GRACE risk score at 30 days was essentially due to variables associated with the acute event severity, whereas for outcomes between day 30 and 1 year it was strongly explained by patient-related variables.

14 314 Update on risk assessment in acute coronary syndromes / Long-term problems in patients with coarctation of the aorta 1961 Serial assessment of MPO in patients with ACS provides independent prognostic information M. Weber, H. Nef, H. Moellmann, C. Liebetrau, M. Woelken, C. Hamm. Kerckhoff Klinik GmbH, Bad Nauheim, Germany Background: Decision on the therapeutical strategy in patients presenting with acute coronary syndromes is mainly based on the individual risk. Besides clinical factors biomarkers, namely cardiac troponins have become the cornerstone for risk stratification. However, there is an ongoing search for new biomarkers enabling improved risk stratification. In the present study we investigate the predictive value of serial assessment of myeloperoxidase in consecutive patients with an ACS. Methods and results: From April 2005 until November 2006 all consecutive patients (n=762, 29% females, aged 65 (IQR 55-75) years) admitted to our center because of an ACS with an episode of chest pain within the last 48 hours were included. Admission diagnosis was STEMI in 54% of the patients and NSTE-ACS in 46%. Clinical follow up after 6 months (175±48 days) was available for almost all patients; only 8 patients were lost to follow up. During this period 55 (7.2%) patients died. From baseline (n=699) and day 1 (n=555) EDTA plasma samples BNP, TnI and MPO were measured. MPO levels on admission were highly elevated with a strong relation to the time interval from onset of symptoms until blood drawing. However, no difference between those who survived and those who deceased was observed (858 pg/ml vs. 804 pg/ml; p=0.412). In contrast, MPO plasma levels assessed on day 1 were highly predictive for subsequent death (Log Rank 8.33; p=0.039) and remained a significant prognosticator even after adjusting for clinical factors, egfr, TnI and BNP (HR 3.3, 95%CI ; p=0.015). Conclusion: MPO is highly elevated in patients with an ACS. Assessed on day 1 it provides incremental and independent information beyond that derived from traditional clinical risk factors and established biomarkers. LONG-TERM PROBLEMS IN PATIENTS WITH COARCTATION OF THE AORTA 1999 A novel approach to assess vascular function using aortic wall tissue Doppler imaging. Study of repaired aortic coarctations versus normal subjects M. Serban, M. Iancu, I. Ghiorghiu, I. Craciunescu, C. Ginghina. Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania Background: Tissue Doppler imaging (TDI) has recently emerged as a new technique for the evaluation of aortic wall velocities and superior to standards measurements of arterial function. Aortic coarctation (CoA) is associated with increased morbidity, even after correction. Impaired vascular function of precoarctational arterial bed may be related to long term prognosis of this patients. Purpose: The aim of the study was to investigate the potential clinical application of TDI for the assessment of aortic elastic properties in patients with repaired CoA. Methods: Study groups were composed of 23 patients with repaired CoA (mean age 28,65±9,98 years) and 20 age and sex-matched healthy subjects. Aortic stiffness was assessed using M-mode evaluation of systolic (ASD) and diastolic (ADD) aortic diameters, parasternal long-axis view, 3 cm above the aortic valve. The following indexes of aortic elasticity were calculated using accepted formulae: aortic strain (Ao Strain), aortic distensibility (Ao Dis), aortic stiffness index (Ao SI). Using TDI, at the same point as in M-mode, systolic maximum wall expansion velocity (SW) and early and late wall contraction (EW, AW) diastolic velocities were determined online. Results: CoA patients had highly statistically significant reduced aortic wall velocities comparing with control subjects for SW (7,54±2,24 vs 11,70±2,30 cm/s, p<0,001) and EW (8,47±2,80 vs. 11,26±2,94 cm/s, p=0,005). SW was positively related to Ao Dis and Strain and negatively related to ADD and Ao SI, with high statistical significance; EW had also a high statistically significant positive correlation with Ao Dis and Strain and a negative one with Ao SI. Correlation coefficients are shown in the table. ADD ASD Ao Dis Ao Strain Ao SI SW -0,402** -0,163 0,554** 0,578** -0,494** EW -0,287-0,124 0,347* 0,426** -0,367* AW - 0,086-0,083 0,031 0,045-0,03 *p<0,05, **p<0,01. Conclusions: Systolic and early diastolic velocities of aortic wall were decreased in patients with repaired aortic coarctation versus normal subjects, in correlation with aortic dilatation and altered M-mode derived aortic stiffness parameters. TDI assessment of aortic wall velocities is a very feasible and useful tool in the evaluation of vascular function Late expansion of an implanted stent in growing patients with coarctation of aorta J. Suarez De Lezo 1,M.Pan 1,M.Romero 1, J. Segura 1,D.J.Pavlovic 1, S. Ojeda 1, A. Gamez 1, I. Tejero 1, M. Lafuente 1, A. Medina 2. 1 Hospital Universitario Reina Sofia, Cordoba, Spain; 2 Hospital Universitario Dr Negrin, Las Palmas, Spain Objectives: Stent repair of severe coarctation of the aorta seems to be an effective and definitive treatment in adult patients. However, the use of stents at early ages has not been recommended due to the absence of growth capacity in the stented segment throughout the child s life, leading to relative stenosis at adulthood. In this study, we assess the feasibility of late stent re-expansion in growing children with stent-treated coarctation of the aorta. Methods: From Novenber 1993 to December 2008, 123 patients with coarctation of the aorta were treated at our institution by stent implantation. From them, we studied 10 patients who were treated under the age of 6 years. All 10 patients had late stent re-expansion at a mean of 11±4 years after the original procedure. Results: The mean age at stent implantation was 2±1.5 years. Reasons for stenting at an early age included life-threatening conditions (n=2), failure of previous treatment (n=4), and extreme hypoplasia (n=10). The implanted stent diameter at the first procedure was 8.8±1.2 mm and the minimal lumen diameter of the aorta changed from 2.3±0.3 mm pre-implant to 9.6±1.2 mm post-procedure. Two patients also underwent coil obliteration of an aneurysm. For the re-expansion procedure a surgical subclavian approach was used in 3 patients and a conventional femoral puncture in the remaining 7. The balloon diameter used for re-expansion was 15±1.3 mm. After balloon dilatation, the minimal lumen diameter of the stented segment rose from 9±2 to13±2 mm and the stent shortened from 37±11 to 32±9 mm. Minor fractures (detachment of 1-2 struts) of the stent occurred after re-expansion in 6 patients; 4 patients required one additional stent to improve the immediate result. The peak gradient across the coarctation changed as follows: baseline 53±17 mmhg, post-stent 5±4 mmhg, follow-up 30±12 mmhg, and post re-expansion 5±5 mmhg. There were no complications associated with balloon dilation of the stent or damage to the aorta. All patients remain symptom-free without hypertension 29±33 months later. Conclusions: Balloon re-expansion of a stent implanted in the aorta in small children is feasible, although a second stent may be required to improve the outcome of the procedure. This final treatment may be delayed for years, until the target stent diameter can be accommodated to the final growth of the aorta in a single additional procedure Aortic growth late after coarctation repair R.J. Franken 1, P. Luijendijk 2, B.J. Bouma 2, M. Groenink 2, A.M. Spijkerboer 2, B.J.M. Mulder 2. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Academic Medical Center, Amsterdam, Netherlands Purpose: Long-term outcome of repaired aortic coarctation (CoA) may be complicated by dilatation of the thoracic aorta. Aim of the study was to demonstrate the presence and progression of aortic dilatation late after coarctation repair. Methods: We analyzed retrospective data of adult post-coarctectomy patients, who had serial Magnetic Resonance Images (MRI) performed at least 3 years apart, on the presence and progression the thoracic aorta dilatation. Determinants for the presence and progression of ascending aorta dilatation were identified. Results: Forty-five patients (mean age 31±9.3 years, male 53%) had a mean MRI follow-up of 5.5±1.3 years. The mean maximum diameter of the aorta at baseline was 30.4 mm ± 5.7 (range mm), at the end of follow-up 32.4±6.1 (range mm). Dilatation ( 35 mm) of the ascending aorta was present in 8% of the patients at baseline and in 15% at the end of follow up. Determinants for a dilated aortic baseline diameter were older age (R = 0,562 P = < 0.001) and a bicuspid aortic valve (R= 0,450, P = 0.002). Although growth was found in all segments of the thoracic aorta, it was most prominent in the ascending aorta with 2 mm/5 yrs (range mm/5yrs). Compared to other surgical modalities, end-to-end anastomosis was associated with increased ascending aorta growth rates (R = 0,321, P = 0.03). Conclusions: Aortic dilatation is a significant problem in coarctation patients late after repair. Older age and a bicuspid aortic valve are predictors for ascending aortic dilatation. Corrective surgery by end-to-end anastomosis is associated with increased growth of the ascending aorta Complications of aortic coarctation repair assessed using cardiovascular magnetic resonance S.S.M. Chen, R.H. Mohiaddin. Royal Brompton Hospital, London, United Kingdom Purpose: Surgical repair for coarctation of the aorta (CoA) has been the main form of treatment and more recently, aortic stenting. We used cardiovascular magnetic resonance (CMR) to assess the long-term success of repair of CoA with respect to structural complications and residual stenosis. Methods: CMR studies between were reviewed. Details of age at,

15 Long-term problems in patients with coarctation of the aorta / Atrial septal defect closure Unresolved issues 315 date and type of repair were obtained from medical notes. Multi-slice HASTE, cine and turbo-spine echo T2 images, and aortic in-plane and through-plane flow studies were analysed for complications (aneurysmal dilatation, false aneurysm, dissection) and residual stenosis. Aneurysmal dilatation was defined as widening at the repair site in comparison to the diameter of the pre- and post-aortic segments. Residual stenosis was defined as constriction at the repair site with flow acceleration on in-plane flow analysis, ±peak recorded velocity on through-plane measurement of >2.5m/s. Results: 281 studies were analysed (167 males, 114 females, aged 31±9 years). Average time between surgery and balloon dilatation, and CMR imaging 18±7 years, and in aortic stenting 4±0.8 years. Types of repair: resection+end-to-end anastomosis (n=94), subclavian flap repair (n=62), aortic stenting (n=43), interposition graft repair (n=31), balloon dilatation (n=24), dacron patch repair (n=19), and bypass graft (n=8). Structural complications were found in patch repair (15/19 aneurysmal dilatation of the patch, 2/19 suture line false aneurysms, 2/19 residual stenosis), and subclavian flap repair (38/62 aneurysmal dilatation of the flap, 2/62 suture line false aneurysms, and 2/62 residual stenosis). Residual stenosis was the main complication in resection+end-to-end anastomosis. (57/94). Balloon dilatation had 17/24 residual stenosis and mild aneurysmal dilatation in 4/24. Aortic stenting had less residual stenosis (6/43), with minimal structural complications (no dissection, but 1/43 displacement of the stent, 1/43 aneurysm). Graft repairs had good long term results: interposition grafts (3/31 suture line false aneurysms, 4/31 residual stenosis at arch-graft anastomosis) and bypass grafts (no residual stenosis, and 2/8 suture line false aneurysm). Conclusion: Patch and flap aneurysms are frequent complications of patch and subclavian flap repairs, and residual stenosis was high in resection+end-to-end anastomosis. Balloon dilatation had frequent residual stenosis. Graft and bypass graft repair are the most favourable surgical repairs with limited complications and residual stenosis. Aortic stenting appears quite successful but long term follow-up is not yet available Comparison between a beta-adrenergic receptor blocker and angiotensin II receptor antagonist for the treatment of hypertension in repaired aortic coarctation E. Moltzer 1, F.U.S. Mattace Raso 2, Y. Karamermer 3,E.Boersma 3, G. Webb 4, M.L. Simoons 3, A.H.J. Danser 5, A.H. Van Den Meiracker 5, J.W. Roos-Hesselink 3. 1 Dept of Cardiology, Thoraxcenter and Division of Pharmacology, Dept of Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 2 Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 3 Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, Netherlands; 4 Philadelphia Adult Congenital Heart Center, University of Pennsylvania, Philadelphia, United States of America; 5 Division of Pharmacology and Vascular and Metabolic Diseases, Dept of Internal Medicine, Erasmus MC, Rotterdam, Netherlands Purpose: To compare effects on 24-hour blood pressure, large artery stiffness and neurohormonal status of metoprolol (beta-adrenergic receptor blockade) versus candesartan (angiotensin II type 1 receptor blockade) in hypertensive patients after repaired aortic coarctation. Methods: In an open label randomised crossover pilot study, hypertensive adult post-coarctectomy patients were treated with metoprolol 100 mg and candesartan 8 mg. Treatment effects were assessed with 24-hour ambulatory blood pressure monitoring, measurements of large artery stiffness by Pulse Wave Velocity (PWV) and carotid stiffness and neurohormonal plasma levels at baseline and after eight weeks of either treatment. Patients with current use of antihypertensive medication were enrolled after a washout period of three weeks. In case hypertension persisted after four weeks of treatment, medication dose was doubled. Results: Sixteen patients (mean age 36.9±12.3 years, 25.7±14.7 years after repair, 62.5% male) completed the study. Twenty-four hour mean arterial pressure (MAP) at baseline was 97.7±6.2 mmhg. Metoprolol (mean dose 162.5±50.0 mg daily) decreased MAP more than candesartan (mean dose 13.0±4.0 mg daily, resp. 7.0±4.2 and 4.1±3.6 mmhg, p=0.018). Daytime systolic blood pressure (BP) at baseline was 148.6±6.7 mmhg and daytime diastolic BP 82.9±8.2 mmhg. Metoprolol reduced both systolic (10.1±1.7 mmhg, p=0.008) and diastolic (8.8±1.2 mmhg, p=0.032) BP more than candesartan (resp. 4.4±2.0 mmhg and 4.6±1.2 mmhg), Large artery stiffness did not change on either treatment. With metoprolol, plasma B-type natriuretic peptide increased (p<0.05), whereas plasma renin decreased (p=0.008). With candesartan, plasma renin and noradrenaline increased (resp. p=0.002 and p=0.022), whereas aldosteron levels decreased (p=0.031). Conclusion: In hypertensive adult post-coarctectomy patients, metoprolol had more antihypertensive effect than candesartan. An 8-week treatment had no measurable effect on large artery stiffness Do we need to screen all patients with coarctation of the aorta for intracranial aneurysms? S.L. Curtis 1, M. Bradley 2, P. Wilde 1,J.Aw 1, S. Chakrabarti 1, M. Hamilton 1,R.P.Martin 1, M.S. Turner 1, A.G. Stuart 1. 1 Bristol Congenital Heart Centre, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, Bristol, United Kingdom; 2 Department of Neuroradiology, Frenchay Hospital, Frenchay Park Road, Bristol BS16 1UU, Bristol, United Kingdom Purpose: Intracranial aneurysms ( IAs ) are found in approximately 2.3% of adults with a mean age at detection of 52 years. IAs<7mm are at low risk of rupture. Older studies have suggested that 10-50% of patients with coarctation of the aorta have IAs and that 5% total deaths in the early surgical era were due to haemorrhagic stroke. Screening recommendations for detecting IAs in patients with coarctation of the aorta are variable. We questioned the current prevalence of IAs in coarctation and the necessity for screening. We also sought to investigate the association between hypertension and IAs. Methods: Consecutive patients over 16 years with coarctation of the aorta undergoing MRA of the brain between May 1999 and October 2007 were included. MRA was performed using a Siemens Avanto 1.5 Tesla scanner using a 3D time of flight protocol. Scans were independently double-reported by a neuroradiologist. IAs were described in terms of site and size. Statistics are described as mean±s.d. and median±range. Continuous variables were compared using the student t-test and the Mann-Whitney U test. Categorical variables were compared using Fisher s Exact test. Results: 122 scans were retrieved and 116 were available for double-reporting. Median age of the patients was 28±11 years (range years). IAs were found in 11 patients (9.5%). The mean diameter of the aneurysms was 3.9mm (range mm). The patients with aneurysms (IA) were older than those without (no IA) (IA-median 35 years, range years; no IA-median 27 years, range years; Z=-1.730; p=0.08). Hypertension affected almost half of patients (45%), and was significantly more common in the aneurysm group (IA-82% v no IA - 41%; p=0.024). 29 patients fulfilled criteria for hypertension but were neither diagnosed as such nor receiving treatment. More patients in the IA group had aortic aneurysms but this was not statistically significant (IA-18%, no IA-9%, p=0.32). There was no association between ascending aortopathy, bicuspid aortic valves and IAs. Conclusion: Patients with coarctation of the aorta have a higher prevalence of IAs and they occur at a much earlier age than in population studies. However the aneurysms are small and thus at low risk of rupture. Elective endovascular repair of IAs has a morbidity/mortality rate of 3-5% and therefore the benefits of treating small unruptured aneurysms are finely balanced against conservative management. This study suggests that routine screening of aneurysms may not be necessary. Hypertension is likely to be an important pathophysiological factor and should be treated aggressively. ATRIAL SEPTAL DEFECT CLOSURE UNRESOLVED ISSUES 2005 Closure of the atrial septal defect in the elderly patients M. Pieculewicz, P. Podolec, T. Przewlocki, L. Tomkiewicz-Pajak, M. Hlawaty, P. Wilkolek, W. Tracz. Department of Cardiac and Vasculare Disease Collegium Medicum Jagiellonian Univercity, John Paul II, Krakow, Poland Objective: Closure of the atrial septal defect in the elderly patients is controversial. The aim of the study was to evaluate the outcomes of transcatheter closure of secundum atrial septal defect (ASD) in elderly patients. Methods: From a total of 281 pts with ASD who underwent transcatheter closure 42 pts over 60 years (30 F, 12 M) with a mean age of 65.3±15.7 (60-75) were analyzed. All patients had an isolated secundum ASD with a mean Qp:Qs: 2.69±1.6 ( ). A symptom-limited treadmill exercise tests with respiratory gas exchange analysis and transthoracic color Doppler echocardiographic study as well as Quality of life (QoL) measured using the SF36 questionnaire (SF36q) were repeated in all pts before procedure and after 12 months of follow-up. Results: The ASO device was successfully implanted in all pts (procedure time 37.7±4.5 (13-59) minutes, fluoroscopy time 11.2±9.9 (6-40) minutes). There were no major complications. The defect echo diameter was 17.7±5.8 (12-30) mm. The mean balloon stretched diameter of ASD was 22.4±7.9 (14-34) mm. The diameter of the implanted devices ranged mm. After 12 months of ASD closure, all the pts showed a significant improvement of exercise capacity parameters. 7 QoL parameters (except mental health) improved at 6 months follow up compared to their baseline data. The mean SF36q scale increased signifi- Table 1 Before ASD closure 12 months after ASD closure p value Time of exercise (min) 9.1± ±5.1 <0.001 VO2peak (ml/kg/min) 8.2± ±5.1 <0.001 SF36q scale ± ±22.7 < The right atrial area (cm 2 ) 24,8±1,3 17.2±1,2 < The right ventricular area (cm 2 ) 19,5±1,37 12±1,3 <0.0001

16 316 Atrial septal defect closure Unresolved issues cantly in 22 (88%) pts of mean 46.2±19,1 (5-69). The right ventricular dimension decreased in 20 pts (80%) (Table 1). Conclusions: Closure of ASD in elderly patients caused a significant clinical and hemodynamic improvement after percutaneous treatment, which is maintained to long-term follow-up what justified this procedure in old age Real time three dimensional transoesophageal echocardiography improves anatomical analysis before and during device transcatheter closure of atrial septal defects E. Brochet, P. Aubry, J.M. Juliard, L. Lepage, D. Detaint, D. Messika Zeitoun, A. Vahanian. Bichat-Claude Bernard Hospital (AP-HP), Paris, France Objectives: to compare the value of real time 3D (RT3D) and bi-dimensional (2D) transoesophageal echocardiography (TEE) in the assessment of atrial septal anatomy before and during transcatheter closure of atrial septal defects (TCASD) Methods: 2Dand RT3DTEE were performed in 27 consecutive patients (age 42±15 yrs) undergoing TCASD using a matrix array TEE transducer (X7-2, Philips imaging). Multiplane 2D and 3D en face views of ASDs were used to assess the shape, location, size and number of defects. Maximal ASD diameter (Max D) was measured on line by 2Dand off line by RT3DTEE after adequate choice of section planes within a 3D volume data set (QLab, Philips). 2D and RT3DTEE were compared before and during intervention. Results: RT3D en face views provided excellent visualization of the shape and location of ASD in all patients. In pts with multifenestrated ASD (n=4) RT3D identified a higher number of defects (n=11) than 2D (n=7)(p=0.002) Overall, Max D was significantly higher with RT3D than with 2DTEE (18±6vs16±6 mm p=0.02). This difference was observed in non circular ASD (n=16) but not in circular ASD (n=7). Differences between balloon stretched diameter and Max D were lower with RT3D (7±3 mm) than with 2DTEE (8.5±3mm) (p=0.003). During the procedure RT3D was superior to 2DTEE to monitor adequate crossing of the defect, especially in multiple defects, defect sizing and device s deployment monitoring. Finally, RT3D was superior to 2DTEE in identifying the final shape and position of the device before release. p<0.0001, respectively) and almost returned to previous value (Fib = 253±49 mg/dl; TAT = 2.1±1.2, respectively) at 1 month after TCO-ASD. TAT at 5 days significantly positively correlated with age (r=0.39, p<0.002), Qp to Qs ratio (r=0.27, p<0.03), fluoroscopic time (r=0.51, p<0.0001) and device size (r=0.45, p<0.0001). 50(+) showed significantly higher TAT and Fib than 50( ) at any time point except for pretreatment Fib and no 50(+) complained neurological symptom but 12 of 65 (18.5%) in 50( ) complained neurological symptom at 5 days to 3 weeks after TCO-ASD (ns). In 50( ), H(+) showed significantly higher TAT than H( ) before (5.2±5.6 vs. 2.0±3.7, p<0.02) and at 5 days after TCO-ASD (10.2±6.5 vs. 6.5±3.4, p<0.01). Conclusions: Coagulation activity transiently increased after TCO-ASD and this increase was pronounced in older patients 50 years old. In patients < 50 years old, this increased coagulation activity may be associated with transient neurological symptoms after TCO-ASD One year efficacy of patent foramen ovale closure using the new bioabsorbable septal repair implant B. Van Den Branden, M.C. Post, H.W.M. Plokker, J.M. Ten Berg, M.J. Suttorp. St Antonius Hospital, Nieuwegein, Netherlands Background: A high rate of residual shunting is present at short-term follow up, using the new bioabsorbable device for patent foramen ovale (PFO) closure. We report the efficacy of PFO closure with the bioabsorbable device at one year follow up. Methods: All consecutive patients, undergoing a percutaneous closure of a symptomatic PFO using the bioabsorbable closure device between November 2007 and January 2009, were included. The efficacy was based on residual shunting and graded as minimal, moderate or severe, using contrast transthoracic echocardiography (ctte) with the Valsalva manoeuvre. Results: In total 62 patients were included (55% female, mean age 47.2±11.8 years). The implantation was successful in 97%. In hospital (IH), one day after closure (n=60), a residual shunt was present in 60% of patients (minimal 32%, moderate 20%, large 8%). A residual shunt at one month (n=56) was present in 39% (minimal 27%, moderate 9%, large 4%, p=0.002 compared to IH), at six month (n=37) in 27% (minimal 16%, moderate 11%, p=0.004 compared to IH), and at one year follow up (n=19) in 21% (all minimal, p=0.004 compared to IH). A moderate or large shunt was present in 28%, 13%, 11%, and 0% at 1 day, 1, 6, and 12 months follow up, respectively. A predictor for residual shunt could not be identified. Conclusion: There is a significant decrease in the residual shunt rate during the first year after PFO closure with the new bioabsorbable device. However, there is still residual shunting 1 year after closure in 21% of the examined patients. Therefore, we will perform further echocardiographic follow-up to assess longterm efficacy more accurately. Conclusion: RT3DTEE improves anatomical analysis before and during transcatheter closure of ASD. In addition, RT3D facilitates the monitoring of ASD closure Therefore, RT3DTEE should become the preferred echocardiographic method during percutaneous ASD closure Transient hypercoagulable state and neurological symptom after transcatheter occlusion of atrial septal defect using amplatzer septal occluder K. Suda 1,Y.Kudo 1,S.Itoh 2, Y. Tananari 2,H.Nishino 1,H.Ishii 1, M. Iemura 1, Y. Maeno 1, H. Yasunaga 2,T.Matsuishi 1. 1 Kurume University School of Medicine, Kurume, Japan; 2 St. Mary s Hospital, Kurume, Japan Background: Although transcatheter occlusion of atrial septal defect using Amplatzer septal occluder (TCO-ASD) became popular, there was little information about the change in coagulation profile. Objective: To determine change in coagulation activity and its association with headache after TCO-ASD. Material and Methods: Subjects were 73 patients who underwent TCO-ASD. Prospectively blood samples were obtained before, at 5 days, and 1 month after TCO-ASD and fibrinogen (Fib) and thrombin-antithrombiniii complex (TAT) were measured. Also, we determined if they had neurological symptoms such as headache and nausea [H(+) or H( )] within a month. Then the patients were divided into 2 groups; 50 years old [50(+), n=8] and <50 years old [50( ), n=65] because generally older patients showed higher TAT. Coagulation activity was compared among 3 time points; before, at 5 days, and 1 month after TCO-ASD and the time course of TAT was compared between 50(+) and 50( ). Correlation of the maximum TAT and demographic data were determined and the maximum TAT was compared between (H+) and (H ). Results: Both Fib and TAT increased significantly at 5 days (Fib = 235±55 before vs. 311±66 mg/dl at 5 days, p<0.0001; TAT = 3.2±6.4 before vs. 8.4±8.0, 2009 Cardiac troponin I release after transcatheter closure of the atrial septal defect M. Pieculewicz, P. Podolec, T. Przewlocki, P. Wilkolek, L. Tomkiewicz- Pajak, E. Suchon, M. Hlawaty, M. Olszowska, W. Tracz. Department of Cardiac and Vasculare Disease Collegium Medicum Jagiellonian Univercity, John Paul II, Krakow, Poland Cardiac troponin-i (ctni) is a very specific and sensitive marker of myocardial injury. A significant increase of ctni levels after percutaneous atrial septal defect (ASD) closure has been reported. The aim of the study was to identify ctni rise after percutaneous ASD closure, to determine its prognostic significance and to assess the relationship between supraventricular ectopy (SVE) in early follow-up and procedural increase of cardiac markers. Methods: Consecutive 281 patients (161 F, 120 M) with a mean age of 47.2±17.2 (15-74) with ASD who underwent transcatheter closure, were analyzed. The troponin I (TnI) and CK-MB level was measured at 0, 8, 16 and 24 hours after procedure. Holter monitoring was performed on all pts before procedure, 1 and 6 months of follow-up. Results: The ASO device was successfully implanted in all patients (procedure time 39.1±4.2 (11-52) minutes, fluoroscopy time 11.0±7.0 (4-41) minutes). A significant increase in number of SVE premature beats/24 hours was noted 1 month after procedure: 1020,9±431 ( ) compared to baseline data 54,5±43 (0-560) (p<0,0001), after 6 month SVE decreased to 61,8±51 (4-701). In none of the pts ctni was elevated before the procedure. Periprocedurally, the increase of cardiac markers: TnI over 50% beyond reference level was observed in 57,2% of pts, and two-folded increase of CK-MB levels in 2.2%. There was a significant correlation between SVE premature beats/24 hours 1 month after procedure and periprocedural increase of TnI (p<0,0001 r =95921). In addition, ctni rise was significantly related with the procedure time (p<0,001), fluoroscopy time (p<0,001), and the device size (p<0,001). In multivariable analizes (including 12 clinical, procedural and anatomical factors) number of SVE ectopy 1 month afrer ASD closure, procedural time and device size were independent risk factors for TnI rise. Conclusions: The significant increase of ctni is noted frequently after the transcatheter closure of ASD not connected with myocardial infarction symptoms or other serious clinical complications. The independent risk factors for ctni rise are:

17 Atrial septal defect closure Unresolved issues / Science Hot Line 317 number of the peri-procedural supraventricular ectopy, elongated time of procedure and larger device size Symptomatic tachy- and bradyarhythmias after transcatheter closure of interatrial communications with Amplatzer devices M. Szkutnik, J. Bialkowski. Silesian Center for Heart Diseases, Zabrze, Poland Introduction: Transcatheter closure of interatrial communications (ASD) with Amplatzer occluders (ASO) became standard treatment in many centers. We analyzed the incidence of cardiac arrhythmias after such treatment. Methods: The group of 759 patients (pts) after transcatheter closure of ASD with ASO were retrospectively analyzed. Only pts with a new and symptomatic arrhythmias were included to the study. All pts, who had arrhythmias prior to ASD closure, were excluded. Results: New tachy- and bradyarhtymias after implantation of ASO were observed in 11 pts (1,5%). There were 9 pts (mean age 36,7 y) with atrial tachyarhythmias (AF in 8 and SVT in 1 pt), which appeared between 1 day and 3 months after implantation. Seven pts were treated initially by pharmacotherapy; in 2 of them sinus rhythm returned just after cardioversion. In another 2 cardioversion was performed as initial therapy. In non but one recurrence of tachycardia was observed, however 7 of them had prolonged (till one) year pharmacotherapy. In 2 pts aged 15 and 16 years complete a-v block appeared 4,3 and 1,5 year after ASO implantation respectively. In the first one intermittent II degree a-v block (Mobitz II) was observed before ASD closure. DDDR pacemaker was implanted in both pts. Conclusions: Transcatheter closure of ASD with ASO is associated with the risk of new atrial tachyarythmias (usually early after the procedure and in older patients). The risk of complete heart block is low, but it can appear in late follow-up. Thence close long term follow-up of all patients is obligatory. SCIENCE HOT LINE 2015 Focal adhesion kinase regulates load-induced PGC-1a expression and mitochondrial biogenesis in mice left ventricle T. Tornatore, C. Clemente, C. Judice, S. Rocco, T. Theizen, A.H. Macedo, A.P. Dalla Costa, M. de Oliveira, J. de Lima, K. Franchini. University of Campinas, Department of Internal Medicine, Faculty of Medical Sciences, Campinas, Brazil Aims: Mechanical stress invokes mitochondrial biogenesis and shifts of the substrate metabolism of myocardium. These processes are mostly drive by NRF-1 and Tfam transcription factors, which are coordinately regulated by transcriptional co-activator PGC-1a. The molecular mechanisms involved in the activation of PGC-1a by the mechanical stimuli are not known. Herein, we examined whether signaling mediated by FAK (Focal Adhesion Kinase) plays a role in the activation of PGC-1a and mitochondrial biogenesis induced by pressure overload in mice left ventricle (LV). Methods: Knockdown of FAK in mice LV was obtained by administering sirna targeted to FAK (sirnafak) through the jugular vein. Pressure overload of LV was induced by transverse aortic constriction (TAC). The levels of FAK and ANP transcripts were obtained by quantitative RT-PCR (qrt-pcr). Western blotting was used to detect the protein levels of FAK, phosphofak-tyr397, PGC-1a and NFR-1. Mitochondrial biogenesis was assessed by the mtdna/ndna ratio obtained by qrt-pcr of D-Loop and 18S genes. Myocardial AMP and ATP levels were obtained by a chromatographic method. Results: sirnafak reduced myocardial FAK transcript and protein by 50, 25 and 20% after 1, 7 and 15 days of TAC, respectively. FAK depletion markedly attenuated the hypertrophic growth and the increases of myocardial ANP transcript in TAC mice, in respect to TAC mice treated with sirnagfp. TAC enhanced the myocardial PGC1a and NRF-1 and FAK knockdown attenuated this increase. Pressure overload lasting 7 and 15 days markedly increased the mtdna/ndna ratio in the LV. Depletion of FAK attenuated the rises in the mtdna/ndna ratio induced by aortic banding. The AMP/ATP ratio was show to remain unchanged in the myocardium of 1 day but it was progressively reduced in 7 and 15 day TAC in respect to SO mice Connexin 43 is fundamental for cytoprotective signal transduction on mitochondrial KATP channels U. Hoppe, D. Rottlaender, M. Wolny, M. Guido, J. Endres-Becker, K. Boengler, R. Schulz, G. Heusch. University of Cologne, Cologne, Germany Background: Potassium (K + ) channels of the inner mitochondrial membrane influence cell function and survival. Multiple signaling pathways and pharmacological actions converge on mitochondrial adenosine triphosphate-sensitive K + (mitokatp) channels and protein kinase C (PKC) as pivotal components of cytoprotection against necrotic and apoptotic cell injury. However, the molecular structure of mitokatp channels remains unresolved and no mitochondrial phosphoprotein has yet been identified that may mediate cytoprotection by these kinases. Methods and Results: We show that mitochondrial connexin 43 is essential for drug- and PKC-mediated mitokatp channel activation, which is restricted to a specific mitochondrial subpopulation. By patch-clamping the inner membrane of subsarcolemmal murine cardiac mitochondria, we found that mitokatp channel activity is significantly increased by the epsilon isoform of PKC (PKCε). Baseline mitokatp channel properties are similar in wildtype and connexin 43 deficient (Cx43+/-) mice. However, genetic connexin 43 deficiency or pharmacological connexin inhibition by carbenoxolone significantly reduce drug- and PKCmediated stimulation of mitokatp channels, explaining loss of cytoprotection in Cx43+/- mice in vivo. Connexin 43 and PKCε associate in mitochondrial protein complexes. Furthermore, mitokatp channels of interfibrillar mitochondria, which do not contain any detectable connexin 43, are completely drug- and PKCinsensitive, (i) confirming the fundamental role of connexin 43 for mitokatp channel stimulation and (ii) indicating compartimentation of mitochondria in cell signaling. Conclusion: Our results define a novel molecular function of mitochondrial connexin 43 and provide a link between cytoprotective stimuli and mitokatp channel opening. Thus, mitochondrial connexin 43 is a major target for drug development against cell injury Myocardial ischemia/reperfusion injury is mediated by leukocytic TLR2 and reduced by systemic administration of a novel anti-tlr2 antibody F. Arslan 1, M. Smeets 1, L.A.J. O Neill 2, B. Keogh 3,P.McGuirk 3, L. Timmers 1, I.E. Hoefer1, P.A. Doevendans 1, G. Pasterkamp 1, D. De Kleijn 1. 1 University Medical Center Utrecht, Utrecht, Netherlands; 2 Trinity College Dublin, Dublin, Ireland; 3 Opsona Therapeutics Ltd. Background: Reperfusion therapy for myocardial infarction is hampered by detrimental inflammatory responses partly via Toll-like receptor (TLR) activation. Targeting TLR signaling may optimize reperfusion therapy and enhance cell survival and heart function after myocardial infarction. Here we evaluated the role of TLR2 as a therapeutic target using a novel monoclonal anti-tlr2 antibody. Method and Results: Mice underwent 30 minutes ischemia, followed by reperfusion. Antibody and controls were administered 5 minutes prior to reperfusion. Cardiac function and dimensions were assessed at baseline and 28 days postinfarction, using 9.4T mouse-mri. Saline and IgG isotype treatment resulted in 34.5±3.3% and 31.4±2.7% infarction, respectively. Bone marrow transplantation experiments between wild-type and TLR2null mice revealed that final infarct size is determined by circulating TLR2 expression. A single intravenous bolus injection of anti-tlr2 antibody reduced infarct size to 18.9±2.2% (p=0.001). Compared to saline, anti-tlr2 treated mice exhibited less expansive remodeling (end-diastolic volume: 68.2±2.5 μl versus 76.8±3.5 μl; p=0.046), and preserved systolic performance (ejection fraction: 51.0±2.1% vs. 39.9±2.2%, p=0.009; systolic wall thickening: 3.3±6.0 versus 22.0±4.4%, p=0.038). Anti-TLR2 treatment significantly reduced neutrophil and macrophage infiltration. Furthermore, TNFα, IL1α, GM-CSF and IL-10 were significantly reduced as were phosphorylated-c-jnk and phosphorylated-p38-mapk levels. Conclusions: Circulating TLR2 expression mediates myocardial I/R injury. Antagonizing TLR2 5 minutes prior to reperfusion reduces infarct size and preserves cardiac function and geometry. Anti-TLR2 therapy exerts its action by reducing leukocyte influx, cytokine production and pro-apoptotic signaling. Hence, monoclonal anti-tlr2 antibody is a potential candidate as an adjunctive for reperfusion therapy in patients with myocardial infarction Exosomes are the active cardioprotective component in MSC secretion D. De Kleijn 1,R.C.Lai 2,F.Arslan 1,L.M.May 3,S.K.Sze 4, L. Timmers 1,A.Choo 3,G.Pasterkamp 1, C.N. Lee 5,S.K.Lim 2. 1 UMC Utrecht, Experimental Cardiology, Utrecht, Netherlands; 2 IMB, Singapore, 3 BTI, Singapore, 4 NTU, Singapore, 5 NUH, Singapore, Secretion from Human ESC-derived mesenchymal stem cells (MSCs) has shown to reduce infarct size for 60% in a mouse and porcine model after reperfusion and provides an off-the-shelf MSC-based therapeutic option. The cardioprotective effect was associated with large complexes in the secretion of nm in diameter. It is, however, unknown how MSC secretion exerts its therapeutic effect. Here we demonstrate that these complexes in MSC secretion contain small RNAs and exosome associated proteins CD9, CD81, and Alix. Flotation density analyses revealed that these proteins were located in detergent-sensitive phospholipid vesicles. In addition, we identified exosomes as a homogenous population in MSC-CM with a particle size of rh=45-55 ηm using High Performance Liquid Chromatography. This exosome fraction separated from MSC secretion also reduced infarct size for 60% in a mouse myocardial ischemia/reperfusion injury model. These findings identifies exosomes, for the first time, as the biologically active cardioprotective component in MSC secretion that can be used as a therapeutic compound for the treatment of myocardial infarction. Due to the affordable costs, excellent quality control and consistency and potential vehicle properties that can cross membranes, exosomes have the potential to be used in a broad therapeutic range in cardiovascular disease.

18 318 Science Hot Line / You want prognosis? Do echo 2019 Focal C-reactive protein and all cause mortality B.G. Nordestgaard, J. Zacho, A. Tybjærg-Hansen. Copenhagen University Hospital, Herlev Hospital, Herlev, Denmark Context: Elevated levels of C-reactive protein (CRP) associate with increased risk of all cause mortality. Objective: We tested whether this is a robust and causal association. Design: We studied 10,388 white persons from the general population, the Copenhagen City Heart Study. During 12 years 2754 persons died. We measured baseline high-sensitivity CRP and fibrinogen levels, and genotyped for 4 CRP polymorphisms. Results: Levels of CRP >3 mg/l, compared with levels <1 mg/l, associated with a multifactorially adjusted 2-fold increased risk of all cause mortality. Stratifying CRP into tertiles, quintiles or octiles resulted in step-by-step increased risk of all cause mortality (all trend, p<0.0001). Excluding those who died within 2 years after CRP measurement resulted in similar but slightly attenuated risk increases (all trend, p<0.0001). After adjustment for fibrinogen levels the association between CRP and all cause mortality attenuated further, but persisted. Genotype combinations of the 4 CRP polymorphisms associated with up to a 49% increase in CRP levels, resulting in a theoretically predicted increased risk of up to 16% for all cause mortality. However, these genotype combinations did not associate with increased risk of all cause or cardiovascular mortality. Conclusions: A single CRP measurement robustly associates with increased risk of all cause mortality. However, adjustment for fibrinogen levels largely attenuated this association and genetically elevated CRP levels did not associate with increased mortality. Therefore, elevated CRP levels do not appear to cause early death but more likely is a marker of hidden inflammatory disease possibly leading to death Chronic, low dose epoetin-β treatment following PCI significantly improves left ventricular ejection fraction in ischemic heart failure M. Bergmann 1, F. Knobelsdorff-Brenckhahn 2, R. Wassmuth 2, H. Mehling 2, A. Busjahn 3, J. Schulz-Menger 2,R.Dietz 2. 1 ASKLEPIOS Clinic St. Georg, Hamburg, Germany; 2 Charite Campus Buch, Berlin, Germany; 3 HealthTwist, Berlin, Germany Background: Experimentally, low doses of epoetin-β not affecting hemoglobin levels were shown to be beneficial for left ventricular both concerning cardiomyocyte protection as well as angiogenesis. The latter effect is due to enhanced mobilization of endothelial progenitor cells. However, chronic low dose epoetin treatment has not been tested previously in the clinical setting. Here, we analysed the effects of epoetin-β over 6 months on left ventricular cardiac remodeling following succesful percutaneous coronary intervention (PCI). Study design: We performed an investigator-initiated, randomized, placebocontrolled, double-blind, single-center study in patients with symtomatic ischemic cardiomyopathy following PCI (NCT ). Inclusion criteria were reduced ejection fraction and succesful revascularization by PCI within the last 14 days. Major exclusion criteria were hemoglobin higher than 16mg/dl and contraindications for cardiac MRI. Patients were treated according to current guidelines. Echocardiography, cardiac MRI, exercise capacity and brain natriuretic peptide levels were measured at baseline and after 6 months; data analysis was finalised in a double-blind fashion. Results: At the end of the study, follow up data for 28 patients were complete; data are reported as mean ± SEM. Both between groups as well as in-group differences were statistically analysed. Serum erythropoetin levels were significantly higher but in the normal range at the 6 months final visit in the EPO group. Hemoglobin levels and exercise capacity increased and bnp levels decreased in both groups during the 6 months follow up without significant differences. Five patients had to be re-admitted to the hospital during the 6months study course, all events were judged unrelated to the treatment. Specifically, no target vessel revascularization had to be performed. Epoetin-β treatment significantly improved global ejection fraction as measured by echocardiography (EPO EF 5.2±2.0%, p<0.05; placebo EF 0.3±1.6% p=ns) and cardiac MRI ( EF 3.1±1.6%, p<0.05; placebo -1.9±1,2, p=ns). Summary: To our knowledge, this pilot trial has examined for the first time the effectiveness of low dose epoetin-β treatment in patients with ischemic cardiomyopathy following PCI and normal hemoglobin levels. The treatment proved to be safe. Analysis of ejection fraction by two independent methods, namely echocardiography and cardiac MRI, suggest the treament to be effective regarding global left ventricular ejection fraction. This approach warrants further mechanistic studies as well as larger trials to confirm effectiveness. YOU WANT PROGNOSIS? DO ECHO 2043 Left atrial enlargement and dysfunction - a new marker of long-term poor proognosis in dilated cardiomyopathy E. Michalak 1, Z.T. Bilinska 1, J.M. Michalak 2, J. Grzybowski 1, W. Ruzyllo 1,P.Hoffman 1. 1 Institute of Cardiology, Warsaw, Poland; 2 Central Clinical Hospital of the MSWiA (Ministry of Interior & Administr. of the Republic of Poland), Warsaw, Poland Coexistence of systolic and diastolic dysfunction is frequent in heart failure. Pts with dilated left ventricle and EF<30% had a poor prognosis. Left atrial (LA) enlargement and dysfunction indices could be additional markers of poor long-term prognosis in this disease. M-mode, 2-dimesional, pulse and color Doppler echocardiography were performed in 165 pts with non-coronary dilated cardiomyopathy (mean age 40,6±12,6yrs, 24F). LA diameters and volumes: maximal (LAVmax, LADmax), pre-systolic (LAVpreP, LADpreP, ECG P wave) and minimal (LAVmin, LADmin) and left ventricular diastolic (LVVD) and systolic volumes (LVVS) were assessed using 2D acoustic quantification method with modified Simpson s rule in apical 4-chamber view. The following parameters were evaluated: LA and LV diameter and volume indices, LA total emptying fraction (LAV TE%=[LAVmax-LAVmin]*100/LAVmax), LA active emptying fraction (LAV AE%= [LAVpreP-LAVmin]*100/LAVpreP),LA vcf [LADpreP-LADmin]/[LAD*tA], LVEF%, Emax/Amax, t dece, mitral regurgitant fraction (MR%), mean CWP. 61pts had significant mitral regurgitation fraction MR%>30%. During follow-up 7,1±2,6yrs (13,3-1,4yrs) 68 pts died. Multifactor regression analysis revealed that all parameters except MR%, Emax/Amax, LAV TE% and LV EF% were significant independent predictive factors of survival (p<0,001). Kaplan_Meier estimates of survival showed that pts with LAV TE% >21,6% had better survival than those with LAV TE%<21,6%. Kaplan-Meier estimate of survival Conclusion: LA maximal, presystolic and minimal volumes and diametres, active emptying fraction and LA vcf were additional valuable factors of poor long-term prognosis in dilated cardiomyopahty Prediction of life-threatening ventricular tachyarrhythmias and death in patients with previous myocardial infarction by left ventricular longitudinal strain analysis C.T.A. Ng 1,M.Bertini 1, J.W. Borleffs 1, V. Delgado 1,G.Nucifora 1, G. Boriani 2, D.Y. Leung 3, M.J. Schalij 1,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Univ. di Bologna - Istituto di Cardiology, Bologna, Italy; 3 The University of New South Wales, Sydney, Australia Purpose: Impaired left ventricular (LV) ejection fraction (EF) is an important clinical criterion for insertion of implantable cardioverter-defibrillators (ICD) in patients with previous myocardial infarctions. However, better risk stratification is needed as most patients with ICD do not experience appropriate therapy. Therefore, the aim of this study was to risk stratify patients with previous myocardial infarction

19 You want prognosis? Do echo 319 and ICD implantation by assessing segmental longitudinal strains in the infarct, peri-infarct and remote LV zones. Methods: Echocardiographic 2-dimensional speckle tracking longitudinal strain analysis using a 17-segment LV model was performed in 148 patients with previous myocardial infarction and ICD implantation for primary prevention. An infarct segment was defined as a longitudinal strain value of -5%. A peri-infarct segment was defined as immediately adjacent to an infarct segment. A remote segment was defined as any segment that is not an infarct or peri-infarct segment. Mean longitudinal strains of the infarct, peri-infarct and remote zones were calculated. All patients were followed up for combined endpoint of occurrence of life-threatening ventricular tachyarrhythmias treated with appropriate ICD therapy and death. Results: The mean age was 65±11 years, 127 men. 74 (50%) patients had cardiac resynchronization therapy (CRT). Mean LVEF was 28±6%. Mean longitudinal strains of the infarct, peri-infarct and remote zones were -0.9±2.5%, -10.5±2.0%, and -14.1±3.4% respectively, p< After a mean follow-up period of 23±19 months, 46 (31%) patients experienced the combined endpoint. Patients with the combined endpoint had no significant differences in LVEF (24±6 vs. 26±7%, p=0.09) but had higher wall motion score index (2.04±0.30 vs.1.90±0.39, p=0.010). Similarly, mean longitudinal strain in the peri-infarct zone was more impaired in patients who experienced the combined endpoint as compared to others (-9.5±1.5 vs ±2.1%, p<0.001), but there were no significant differences in mean longitudinal strains of the infarct and remote zones. Only mean longitudinal strain in the peri-infarct zone (hazard ratio 1.4, 95% confidence interval , p=0.012) and CRT (hazard ratio 0.5, 95% confidence interval , p=0.040) were independent predictors of the combined endpoint during follow-up on multivariate Cox regression analysis. Conclusions: Longitudinal strain of the peri-infarct zone may be a useful risk stratification parameter for patients with previous myocardial infarction who are candidates for ICD implantation for primary prevention Global longitudinal strain is superior to ejection fraction and wall motion scoring for the prediction of mortality T. Stanton, R. Leano, T.H. Marwick. The University of Queensland, Brisbane, Australia Purpose: Global LV systolic function is an important determinant of mortality, usually measured by ejection fraction (EF) which has some technical limitations. Global longitudinal strain (GLS) is an automated technique for measurement of long-axis function. The aim of this study was to compare GLS with EF and wall motion scoring (WMS) for the prediction of mortality. Methods: We followed 546 consecutive individuals (64% male, mean age 60.9±11.9 years) undergoing echocardiography for all-cause mortality over 5.2±1.5 years. EF was calculated using Simpson s biplane. WMS was determined by 2 experienced readers. GLS was calculated using 2D speckle tracking as the mean GLS from 3 standard apical views. Significant univariate predictors of mortality were identified using Cox Models. Nested models of significant baseline variables followed by the separate addition of EF, WMS and GLS were then undertaken. Results: Means were EF 57.6±12.1%, WMS 1.3±0.4 and GLS -16.6±4.3%. There were 91 deaths. Clinical factors associated with outcome (model chisquare=20.2) were age (HR 1.5, 95%CI , p<0.01), diabetes (HR 1.8, 95%CI , p=0.01) and hypertension (HR 1.6, 95%CI , p<0.05). 3 separate models were used to evaluate the additional prognostic information obtained from imaging (Figure). Although addition of EF (HR 1.2, 95%CI , p<0.05) or WMS (HR 1.3, 95%CI , p<0.01) added to the predictive power of clinical variables, the addition of GLS (HR 1.5, 95%CI , p<0.001) caused the greatest increment in model power (chi square=33.7, p<0.001, figure) Speckle tracking echocardigraphy for the prognosis of patients with systolic and diastolic heart failure H. Dokainish, M. Alam, J. Nguyen, N. Lakkis, M. Stampehl. Baylor College of Medicine, Houston, United States of America Background: There are no published data on the utility of speckle strain echocardiography for the prediction of outcome in patients with heart failure (HF). Methods: Patients who fit the Framingham criteria for HF underwent comprehensive echocardiography and were followed prospectively for events. In the 3 apical views, speckle-based automated functional imaging (AFI) was utilized to obtain average global systolic strain (GSS) using General Electric EchoPAC software. Optimum cut-off values for the prediction of outcome were generated from receiver operating characteristic curves, and Kaplan-Meier survival curves were generated using log rank statistics. The primary endpoint was cardiac death or rehospitalization for heart failure requiring intravenous therapy. Results: 177 patients had >/=90 day follow-up. The mean age was 56.5±8.9 years, 60/118 (51%) were female, 103 (87%) hypertensive, 47/118 (40%) diabetic, and 59/118 (50%) had coronary artery disease. The mean left ventricular ejection fraction (LVEF) was 36.4±16.7%, with 52/177 (30%) of patients with LVEF>/=45%. There were 41 primary outcomes (23%) at a mean of 104±46 days follow-up: 4 cardiac deaths and 37 HF rehospitalizations. The optimal cut-off to predict the primary endpoint was AFI GSS<13%, which was a significant predictor of event-free survival (log rank statistic=7.4, p=0.007), while LVEF was not a significant predictor of outcome (Figure, 35% p=0.08). Conclusion: Global longitudinal strain is a superior predictor of outcome compared to either ejection fraction or wall motion scoring and is now the optimal method for assessment of global left ventricular systolic function Prognostic value of peak treadmill exercise echocardiography in patients with normal post-exercise treadmill echocardiography J. Peteiro, A. Bouzas-Mosquera, A. Campos, P. Pazos, P. Pinon, A. Castro-Beiras. University of A Coruna, A Coruna, Spain Background and purpose: American and European practice guidelines state that treadmill exercise echocardiography (EE) relies on post-exercise imaging. Although peak treadmill EE may have higher sensitivity for the detection of coronary artery disease (CAD), its prognostic value remains to be determined. Our aim was to assess the value of peak treadmill EE for predicting outcome in patients with known or suspected CAD and negative post-exercise echocardiography. Methods: We studied 2527 consecutive patients who underwent treadmill EE and had normal results at post-exercise imaging. Wall motion score index and left ventricular ejection fraction were evaluated at rest, peak and post-exercise (45 secs). Ischemia was defined as the development of new or worsening wall motion abnormalities with exercise. The end-points were all-cause mortality and major cardiac events. Figure 1 Conclusions: In a HF population consisting of preserved and depressed LVEF, AFI GSS was a significant predictor of cardiac death or rehospitalization for HF, more so than LVEF. This may connote a more comprehensive LV function assessment by GSS compared to LVEF in this population. Survival (%) according to peak ischemia

20 320 You want prognosis? Do echo / Diastology: jump into the future? Results: Overall, 124 patients (4.9%) developed new or worsening wall motion abnormalities. During a follow-up of 2.9±1.8 years, 104 patients died. The 5-year mortality rate was 3.5% in patients without ischemia vs. 15.3% in those with ischemia (p <0.001). In the multivariate analysis, ischemia at peak exercise was an independent predictor of mortality (hazard ratio [HR] 1.90, 95% confidence interval [CI] , p=0.014) and major cardiac events (HR 2.25, 98% CI , p=0.017). The addition of the peak EE results to clinical and exercise variables provided significant incremental prognostic information for predicting mortality (p=0.025) and major cardiac events (p=0.021). Conclusion: Peak treadmill exercise echocardiography provides significant prognostic information for predicting mortality and major cardiac events in patients with known or suspected CAD and negative post-exercise echocardiography Prognostic implication of stress echocardiography result in hypertensives and normotensives. A study on 10,054 patients L. Cortigiani 1,R.Sicari 2,R.Bigi 3, F. Bovenzi 1, E. Picano 2. 1 Ospedale Civile, Lucca, Italy; 2 Fondazione G Monasterio, Pisa, Italy; 3 Universita di Milano, Milan, Italy Background: The relative prognostic meaning of stress echocardiography (SE) result in hypertensives (H) and normotensives (N) remains to be addressed. Aim. To compare the prognostic implication of SE in a large cohort of H and N with known or suspected coronary artery disease (CAD). Methods: The study group was formed by 10,054 patients (5,355 H and 4,699 N) who underwent exercise (n=536), dobutamine (n=2,007) or dipyridamole (n=7,511) SE for evaluation of known (n=4,075) or suspected (n=5,979) CAD. Patients were followed-up for a median of 24.4 months. Results: Ischemia at SE was assessed in 2,873 patients. During follow-up, 1,391 events (782 deaths, 609 infarctions) occurred. Independent prognostic indicators were ischemia at SE (HR 2.67, CI , p<0.0001), resting wall motion abnormality (RWMA) (HR 1.41, CI , p<0.0001), diabetes (HR 1.55, CI , p<0.0001), age (HR 1.03, CI , p<0.0001), male sex (HR 1.26, CI , p=0.003), left bundle branch block (HR 1.55, CI , p=0.006), and prior angioplasty (HR 1.26, CI , p=0.02) in H, and ischemia at SE (HR 1.41, CI , p<0.0001), peak wall motion score index (HR 2.57, CI , p<0.0001), diabetes (HR 1.84, CI , p<0.0001), age (HR 1.04, CI , p<0.0001), RWMA (HR 1.36, CI , p=0.007), and male sex (HR 1.27, CI , p=0.01) in N. Annual event rate was markedly higher in H than in N with no ischemia and no RWMA (2.6% and 1.6%, p<0.0001): figure. Moreover, event-rate associated to ischemic SE was similar (p=0.97) in H with and without RWMA, but lower (p=0.006) in N without RWMA (Figure). Conclusions: SE result allows effective prognostication in H and N. However, a non ischemic test predicts better survival in N than in H with no RWMA. DIASTOLOGY: JUMP INTO THE FUTURE? 2049 Normal values for diastolic strain rate from combined speckle tracking and Doppler tissue imaging. Preliminary data from the HUNT3-study H.D. Dalen, A. Thorstensen, C.B. Ingul, S.A. Aase, A. Stoylen. Norwegian university of science and technology, Trondheim, Norway Purpose: Strain rate imaging is becoming a widely published method for quantifying both systolic and diastolic left ventricular (LV) function. The aim of the study is to establish normal values for global diastolic strain rate. Methods: 1296 persons aged 20 to 89 which participated in the HUNT 3 study was randomised to echocardiographic examination which included colour tissue Doppler imaging Personell were eligible for inclution if they were without known heart diseases, diabetes or treated hypertension. 31 were excluded after echocardiographic examination. Post-prosessing analysis was performed with a semi-automatic software with segmentation of the myocardium and tracking along ultrasound beam with tissue Doppler and tracking perpendicular to the ultrasound beam with speckle tracking. Segments with poor data quality were discarded manually. An 18 segment LV model was used segments were analysed. Global diastolic strain rate was calculated as the average of accepted segments for E and A respectively. 98,9% had segments accepted for global strain rate measurement. Results: The over all longitudinal diastolic strain rate E and A (s -1 ) was (SD) 1,29 (0,29) and 0,98 (0,23). Participants were divided into 3 age groups: <40, and >60 years. In females longitudinal diastolic strain rate E (s -1 ) was (SD) 1,56 (0,24), 1,36 (0,25) and 1,08 (0,20) respectively and in males 1,41 (0,23), 1,21 (0,22) and 1,03 (0,23). There was a very highly significant decrease of strain rate E with increasing age with p<0,0001 between all adjacent age groups. Mean strain rate E was higher in female groups than in male and the significance of difference between genders was very highly significant with p<0,0001. Longitudinal strain rate A (s -1 ) in females was 0,83 (0,17), 0,98 (0,22) and 1,37 (0,29) respectively. The increase in mean strain rate A with increasing age was very highly significant with p<0,0001 between adjacent age groups, but there was no significant difference between genders. Conclusions: The study presents preliminary normal values for global diastolic strain rate E and A for both genders. Mean strain rate E decreases significantly with increasing age and is significant higher in females than in males. Mean strain rate A increases significantly with increasing age but there is no significant difference between genders. In all age groups there is a significant variability for both diastolic strain rate E and A which has to be taken into account in individual clinical decision making. Abbreviations: LV - Left ventricle SD - Standard deviation 2050 Are E/Ea and E/(Ea x Sa) ratios reliable predictors of left ventricular diastolic pressures in an unselected population? E. Chieffo, M. Previtali, A. Repetto, M. Ferrario, C. Klersy. IRCCS Pol. S.Matteo Università di Pavia, Pavia, Italy Background: E/Ea and E/(Ea x Sa) ratios are considered reliable non-invasive predictors of LV diastolic pressures (LVDP), but recent studies in pts with heart failure have shown a lack of correlation between these parameters and invasively measured LVDP. Aim of this study was to: 1) assess the correlation between E/Ea and E/(Ea x Sa) with LVDP in an unselected population; 2) evaluate the influence of LV systolic function and end-diastolic volumes (EDV) on this relationship; 3) define sensitivity (SE) and specificity (SP) of E/Ea in predicting normal or increased LVDP. Methods: 100 pts (81 men and 19 women, aged 63±11) 43% with EF 50%, 50% with LV dilation (LVEDV >75 ml/m 2 ) in sinus rhythm and no significant valvular regugitation, underwent hemodynamic study with measurement of pre-a LVDP and LVEDP with fluid-filled catheters and complete echo-doppler evaluation in the same day; septal (S), lateral (L) and average (Av) E/Ea and E/(Ea x Sa) were calculated. Results: In the overall population a statistically significant correlation was found between pre-a LVDP and S E/Ea (r =0.29 P=0.004), Av E/Ea (r =0.25 P=0.01), S E/(Ea x Sa) (r =0.31 P=0.002), L E/(Ea x Sa) (r =0.29 P=0.004) and Av E/(Ea x Sa) (r =0.31,P=0.002); the strongest correlation was found for S E/Ea (r=0.48, p=0.0002) and E/(Ea x Sa) (r=0.45, P=0.001) in the subgroup with normal LVEDV. A significant correlation with LVEDP was found only for L E/(Ea x Sa) (r=0.41, P=0.01) in the subgroups with EF 50% and for S E/(Ea x Sa) (p=0.003, r=0.40) in the subgroup with normal LVEDV. Pts with normal ( 15 mmhg) or increased LVEDP showed no significant difference in S (11.6 vs 12.6), L (13.8 vs 14.9) and Av E/Ea (12.4 vs 13.1). Moreover, LVEDP was not significantly different in the 3 subgroups with E/Ea 8, between 8-15 and 15, while a significant difference in pre-a LVDP between the 3 subgroups was found only for S E/Ea (P=0.0005). An E/Ea 8 had a low sensitivity (S 11, L 41 and Av 20%) but high specificity (S 89, L 66, AV 88%) for identifying normal LVEDP; a E/Ea 15 had a low sensitivity (S 47, L 26 and Av 29%) but high specificity (S 68, L 83, AV 74%) for LVEDP >15mmHg. Conclusions: 1) In an unselected population E/Ea and E/(EaxSa) show a statistically significant but weak correlation with pre-a LVDP, while a significant correlation with LVEDP is found only in pts with systolic LV dysfunction or normal LVEDV. 2) The E/Ea cut-off values for normal or increased LVEDP have a good specificity but a low sensitivity for predicting normal and increased LVEDP and are therefore of limited clinical value for predicting LVEDP in the individual pt Long term endurance training does not prevent the age related decline in left and right ventricular diastolic function assessed by Doppler echocardiography A.J. Teske 1,N.H.Prakken 2,B.W.DeBoeck 1, B.K. Velthuis 2, P.A. Doevendans 1,M.J.Cramer 1. 1 University Medical Center Utrecht, Department of Cardiology, Utrecht, Netherlands; 2 University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands Purpose: 1) to evaluate the effect of long term endurance training on LV and RV diastolic function and 2) whether the normal aging effect on diastolic function is impeded due to endurance training. Methods: A total of 289 healthy individuals were prospectively enrolled for echocardiographic evaluation. Groups were defined based on age and athletic

21 Diastology: jump into the future? 321 activities: 1) young non-athletes (18-40 y, n=62), 2) old non-athletes (>40y, n=53), 3) young regular (9-18 h/sp/wk, n=58), 4) young professional (>18h/sp/wk, n=63) and 5) old athletes (>40 y, >9 h/sp/wk, n=53). LV and RV pulsed wave Doppler indices for diastolic function were obtained in rest. Differences were calculated using ANOVA-Bonferroni. Correlations were evaluated using Pearson. Results: No significant differences were found between the young controls, regular- and professional athletes in LV (MV E/A-ratio 2.08±0.5 vs. 2.12±0.5 vs. 2.30±0.7, E/E 5.24±0.9 vs. 5.36±0.9 vs. 5.01±0.8, respectively, p=ns) and RV (TV E/A-ratio 2.35±0.6 vs. 2.40±0.6 vs. 2.56±0.6, E/E 4.25±0.9 vs. 4.11±1.0 vs. 4.44±1.0, respectively, p=ns) diastolic parameters. These were also comparable between controls and athletes >40y (MV E/A-ratio 1.68±0.4 vs. 1.52±0.4, E/E 6.22±1.5 vs. 5.90±1.1, TV E/A-ratio 2.02±0.6 vs. 2.04±0.5, E/E 4.00±0.7 vs. 4.20±1.2, p=ns). In both the athletes and controls, similar and significant correlations were found between age and diastolic parameters (figure). In all parameters, age was the most important determinant in multivariate analysis while the influence of training was <2% of the observed variance. Methods: 214 consecutive patients (aged 58±11 years, 64% male) with preserved ejection fraction ( 50%) undergoing exercise stress echocardiography were followed over 2.7±1.7 years. Left ventricular (LV) filling pressure was estimated as the ratio of early diastolic transmitral flow (E-velocity) and early diastolic tissue velocity (septal E ), with E/E >15 at exercise considered raised. Ischaemia was identified by inducible regional wall motion abnormalities. Deaths and cardiovascular hospitalisations were recorded, and analysed by the Kaplan Meier and Cox regression methods. Results: 69 patients developed ischaemia with stress and 19 had a raised E/E. There were 63 events (7 deaths, 56 cardiovascular hospitalisations). Event-free survival (see Figure) in patients with raised exercise E/E and no ischaemia was comparable to patients with ischaemia alone (p=0.84). The combination of raised exercise E/E and ischaemia yielded a significantly worse survival curve than patients with normal exercise E/E with or without ischaemia (P<0.05). Independent, significant predictors of outcome by Cox regression analysis were; exercise E/E >15 (HR=2.052; p=0.041), ischaemia (HR=1.814; p=0.021) and peak heart rate (HR=1.014; p=0.014). Conclusion: The amount of endurance training does not alter diastolic properties in either ventricle. The decrease in diastolic function observed in healthy, nonathletic individuals with age is also observed in the aging athletes heart A new global tissue Doppler index: correlation with left ventricular end-diastolic pressure in patients with severe mitral regurgitation C. Mornos, D. Cozma, A. Ionac, L. Petrescu, D. Dragulescu, S. Pescariu, D. Maximov, D. Popa, S.I. Dragulescu. Institute of Cardiovascular Diseases, Timisoara, Romania The ratio between early diastolic transmitral velocity and early mitral annular diastolic velocity (E/Ea) reflects left ventricular (LV) filling pressure in a variety of cardiac diseases. We belive that combining the index of diastolic function (E/Ea) and a parameter that explores LV systolic performance (Sa, peak systolic velocity of mitral annulus) provides a close prediction of left ventricular end-diastolic pressure (LVEDP). Aim: to assess the relationship between a new parameter, E/(Ea Sa), and LVEDP in patients with severe mitral regurgitation. Methods: We screened 67 consecutive patients with severe mitral regurgitation, in sinus rhythm, referred for LV cathetherism. Patients with inadequate echocardiographic image, paced rhythm, mitral prosthesis, severe mitral annular calcification, pericardial disease, acute coronary syndrome or coronary artery by-pass within 72 hours were excluded. The remaining 55 patients formed our study group. Echocardiography was performed simultaneously with LVEDP measurement. E/Ea and E/(Ea Sa) were calculated; the average of the velocities of septal and lateral mitral annulus was used. LVEDP were obtained with micromanometertipped catheters. Results: Simple regression analysis demonstrated a significant linear correlation between E/(Ea Sa) and LVEDP (r=0.81, p<0.001). Significant but weaker correlations were found between LVEDP and E/Ea (r=0.73, p<0.001), Sa (r=-0.59, p=0,004), pulmonary artery systolic pressure (r=0.57, p=0.007), E wave (r=0.45, p=0.009), Ea (r=-0.31, p=0.01), left atrial volume (r= 0.28, p=0.02). We couldn t demonstrate significant relationships between LVEDP and LV ejection fraction. The area under the receiver-operating characteristic curve (ROC) for prediction of LVEDP>15 mmhg was greatest for E/(Ea Sa) (AUC=0.87, p<0.001) followed by E/Ea ratio (AUC=0.81, p<0.001). A statistical comparison of the ROC curves provides that E/(Ea Sa) was more accurate than E/Ea (p=0.02). The optimal E/(Ea Sa) cut-off to predict a LVEDP level >15 mmhg was 1.95 (sensitivity of 85% and specificity of 83%). Conclusions: E/(Ea Sa) correlates strongly with LVEDP and can be a simple and accurate echocardiographic index for the estimation of LVEDP in patients with severe mitral regurgitation, in sinus rhythm Role of exercise E/E and ischaemia in predicting outcome in patients undergoing exercise echocardiography D.J. Holland, S.B. Prasad, T.H. Marwick. The University of Queensland, Brisbane, Australia Background: Raised LV filling pressure after exercise may be accurately measured from exercise E/E. We sought to define the relative contribution of raised exercise E/E and ischaemia to outcomes. Conclusion: An elevated E/E response to exercise holds similar prognostic outcomes as inducible ischaemia, implicating the importance of measuring E/E during stress echocardiography Incremental prognostic value of the novel diastolic indices for prediction of clinical outcome in patients with ST elevation myocardial infarction M. Shanks, A.C.T. Ng, N.R.L. Van Der Veire, L.M. Antoni, S.A. Mollema, M.J. Schalij, E.E. Van Der Wall, J.J. Bax. Leiden University Medical Center, Leiden, Netherlands Purpose: Echocardiographic predictors of outcome after acute ST-elevation myocardial infarction (STEMI) include left ventricular (LV) ejection fraction (EF), endsystolic volume index (ESVI), and mitral insufficiency. Prognostic value of newer diastolic function indices by 2-dimensional speckle tracking (2DST) after STEMI is unknown. Methods: Echocardiograms were performed within 48 hours of admission in 371 consecutive, first STEMI patients (mean age 62.6±11.7 years, 77.6% male). Indices of diastolic function including mean strain rate during isovolumic relaxation (SRIVR), mean early diastolic strain rate (SRE) and mean diastolic strain at peak transmitral E wave (DSE) by 2DST were obtained from the 3 apical views. Mean Em from 4 basal segments by color-coded tissue Doppler imaging was also measured. Indices of diastolic filling including E/SRIVR, E/SRE, E/DSE, and E/Em were calculated. Primary endpoint was a composite of death, hospitalization for heart failure, repeat myocardial infarction and repeat revascularization. Results: Primary endpoint occurred in 84 patients (22.6%) during a mean follow-up of 16.8±11.9 months. Patients with clinical events had lower baseline LVEF (39.7±8.2 vs 45.7±7.7%, p<0.001), ESVI (36.1±16.8 vs 28.4±9.2 ml/m 2, p=0.045), higher troponin (13.0±11.2 vs. 6.5±5.0 μg/l, p=0.002) and more likely to have multivessel disease (68.6 vs 38.7%, p<0.001). Similarly, these patients had higher E/Em (15.6±8.3 vs 12.3±4.9, p=0.003) and E/SRIVR (481.4±458.8 vs 391.2±517.1, p<0.001), and more impaired Em (5.09±1.95 vs 5.96±2.02 cm/s, p=0.001), SRIVR (0.20±0.12 vs 0.31±0.21 s -1,p<0.001) and DSE (7.71±2.88 vs 8.78±2.63%, p=0.030). Mean SRIVR (p<0.001), number of stenosed vessels (p<0.001) and LVEF (p=0.011) were independent predictors of the combined endpoint on Cox regression analysis. When the patient population was dichotomized based on the median SRIVR, patients with SRIVR 0.24 s -1 post-stemi had significantly higher event rates than others (HR 2.74, 95% CI , p<0.001). Conclusion: After acute STEMI, mean SRIVR, LVEF and number of stenosed vessels were independent predictors of the combined endpoint. Evaluation of LV diastolic function by mean SRIVR after STEMI may be useful in identifying high risk patients.

22 322 Diastology: jump into the future? / Coronary artery surgery: miscellaneous POSTER SESSION 3 MODERATED POSTERS 1 CORONARY ARTERY SURGERY: MISCELLANEOUS P2065 DNA enzyme targeting transcription factor c-jun reduces intimal hyperplasia in human saphenous vein explants and inhibits Vein Graft stenosis in rabbits J. Ni, A. Waldman, L. Khachigian. The University of New South Wales, Sydney, Australia Background: Previous studies from our group using DNAzymes (catalytic oligodeoxynucleotides) have demonstrated that the bzip transcription factor c- Jun is required for inducible smooth muscle cell (SMC) proliferation and migration. DNAzymes (Dz13) targeting c-jun inhibit intimal thickening in ligated rat carotid arteries and balloon-injured rabbit carotid arteries. The present study was designed to validate the hypothesis that Dz13 may reduce intimal hyperplasia in human saphenous veins ex vivo, and in an animal model of vein graft transplantation. Methods/Results: By immunohistochemical staining, we found that c-jun is expressed together with PCNA in alpha-sm actin+ cells in failed human coronary artery bypass saphenous vein graft segments. c-jun levels increase after SMC exposure to fluid shear stress (10 dynes/cm 2 ), which was inhibited by DNAzyme Dz13 (34 nucleotides length, with a 3-3 -linked inverted T) and ERK and JNK inhibitors, but not Dz13scr (scrambled arm counterpart of Dz13). We generated an adenovirus vector overexpressing c-jun using the padeasy system. SMCs were transduced/transfected with adeno-c-jun, adeno-c-jun/dz13 or adeno-c- Jun/Dz13scr. Western blotting and RT-PCR verified the induction of c-jun, and the activation of c-jun inducible genes, such as MMP-2. Overexpression of c-jun increased SMC proliferation, whereas Dz13 inhibited adeno-c-jun inducible SMC growth. Using an in vitro scratch assay, SMC transduced with adeno-c-jun underwent accelerated wound repair, which was inhibited by Dz13 but not Dz13scr. Intimal hyperplasia in human saphenous veins ex vivo was attenuated by Dz13, but not Dz13scr. Moreover, Dz13 delivery to the jugular veins of rabbits immediately prior to end-to-side autologous transplantation into carotid arteries inhibited intimal thickening after 4 weeks. On the other hand, overexpression of c-jun by adenovirus in this model lead to accelerated neointimal hyperplasia. Conclusions: These studies indicate that c-jun is expressed in failed human coronary artery bypass saphenous veins and in jugular veins after carotid artery transplant in rabbits. Dz13 inhibits vein graft failure, whereas c-jun overexpression stimulates this process. Targeting c-jun may therefore be useful to reduce the incidence of coronary bypass graft failure. P2066 Appraise a Customized strategy for left main revascularization. The Customize study D. Capodanno 1,M.E.DiSalvo 1, A. Caggegi 1, D. Tomasello 1, G. Cincotta 1,M.Miano 1, S. Tolaro 2, L. Patane 2, A.M. Calafiore 1, C. Tamburino 1 on behalf of CUSTOMIZE. 1 University of Catania, Catania, Italy; 2 Centro Cuore Morgagni, Cardiac Catheterization Laboratory, Pedara, Italy Purpose: Current guidelines strictly recommend coronary artery bypass grafting (CABG) as the first choice of revascularization for patients with left main coronary artery (LMCA) disease. However, the SYNTAX trial has recently suggested the utility of a tailor-made strategy of revascularization for treating patients with LMCA disease by using clinical tool as the Syntax score. We tested the hypothesis that a non-guideline driven approach using percutaneous coronary intervention (PCI) as the first choice and demanding CABG if strictly mandatory may be as safe as the traditional guideline-driven approach. Methods: Between January 2002 and January 2008, PCI have been used as a default strategy for LMCA revascularization in Center 1 (non guidelinedriven group), whereas CABG has been used as a default strategy in Center 2 (guideline-driven group). We compared clinical outcomes of these two populations using extensive adjustment with a non parsimonious model of variables including Syntax score, EuroSCORE and percentage of complete revascularization. Primary endpoint was the long term rate of MACE, defined as the composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR). Results: PCI was performed in 390 patients (60%) of Center 1 and 41 patients of Center 2 (14%), whereas CABG was performed in 257 patients of Center 1 (40%) and 242 patients of Center 2 (86%). Syntax score was 29±12 in the non guideline-driven group and 31 in the guideline-driven group (p = 0.03). At long-term follow up (787±652 days), no differences were observed between non guideline-driven group vs the guideline-drive group with regards to MACE (HR 1.35, 95% CI , p = 0.143). A trend towards lower rates of cardiac death was in favour of non-guideline driven group (HR 0.55, 95% CI , p = 0.057), whereas TVR were more likely to be performed in the non guideline-driven group (HR 2.70, 95% CI , p = 0.003). Conclusions: A tailor-made strategy of PCI as a default option for LMCA revascularization gives similar results when compared with the traditional strategy based on current guidelines. P2067 Assessment of repolarization features after coronary artery bypass grafting A. Ben Halima, M. Ben Halima, A. Ben Youssef, S. Bouraoui, S. Ouerghi, K. Mzoughi, Z. Ibn El Hadj, T. Mestiri, T. Kilani, S. Kachboura. Abderrahmane Mami University Hospital, Ariana, Tunisia Introduction: Imbalances in autonomic nervous system and impaired myocardial repolarization have been shown to increase the risk for arrhythmias in patients with coronary artery disease. Purpose: Study of the effect of on-pump and off-pump coronary artery bypass grafting (CABG) on QT intervals Methods: The study group consisted of 100 consecutive patients (mean age 62±10 years) with coronary artery disease who underwent elective CABG. Fifty two patients underwent on-pump CABG (group 1) and 48 patients underwent offpump CABG (group 2). The 2 groups were comparable regarding clinical and postoperative characteristics. All patients had 12 lead ECG before surgery and 1 day after CABG. We measured QT end intervals (max and min) and QT apex intervals (max and min) corrected according to Bazett Formulae and calculated their dispersion (QT max QT min) Results: In group 1, we noticed a significant increase of QT apex et QT end intervals after surgery compared to baseline. In group 2, there was no significant variation of QT intervals. Results are summerized in the following table Comparison of QT interval before and after CABG Group 1 on-pump Group 2 off-pump Before surgery After surgery p Before surgery After surgery p RR 937± ±128 < ± ±155 NS QT apex min 313±44 342± ±44 334±34 NS QT apex max 344±39 382± ±51 342±36 NS QT apex dispersion 31±20 40±30 NS 13±8 12±8 NS QT end min 402±55 450± ±39 419±41 NS QT end max 438±51 495±57 < ±48 432±45 NS QT end Dispersion 37±20 48±29 NS 13±8 12±9 NS Conclusion: On-pump CABG is associated with a non-uniform recovery of repolarization compared with off-pump CABG. This may be explained by loss of liquids and problems of myocardial protection during on-pump CABG. These results suggest that off-pump CABG may be associated with a lower risk of ventricular arrhythmia P2068 Randomized comparison of Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) surgery versus sirolimus-eluting stenting in isolated proximal LAD-stenosis H. Thiele, P. Neumann-Schniedewind, S. Jacobs, E. Boudriot, T. Walther, F.W. Mohr, G. Schuler, V. Falk. Herzzentrum der Universitaet Leipzig, Leipzig, Germany Background: Bare-metal stenting is inferior to minimally invasive direct coronary artery bypass grafting (MIDCAB) in patients with isolated proximal left anterior descending (LAD) lesions due to a higher reintervention rate with similar results for mortality and reinfarction. Sirolimus-eluting stents (SES) are effective in restenosis reduction. The purpose of this randomized study was to compare PCI using SES with MIDCAB for patients with isolated proximal LAD coronary artery disease. Methods: A total of 130 patients with significant proximal LAD stenosis were randomized to either SES (n=65) or surgery (n=65). The combined clinical endpoint was freedom from major adverse cardiac events (MACE), such as death from cardiac causes, myocardial infarction, and the need for target vessel revascularization (TVR) within 12 months. Clinical symptoms were assessed by the CCS-classification. Results: Follow-up was completed for all patients. MACE occurred in 7.7% of patients after stenting, as compared with 7.7% after surgery (P=0.03 for noninferiority). The individual components of the combined endpoint revealed mixed results. While non-inferiority was revealed for the difference in death and myocardial infarction (1.5% versus 7.7%, non-inferiority P<0.001), non-inferiority was not established for the difference in target vessel revascularization (6.2% versus 0, non-inferiority P=0.21). Clinical symptoms improved significantly in both treatment groups in comparison to baseline and the percentage of patients free from angina after 12 months was 81% versus 74% (p=0.49). Conclusions: In isolated proximal LAD disease, PCI using SES is non-inferior to MIDCAB surgery at 12-month follow-up with respect to MACE at a similar relief in clinical symptoms and less periprocedural complications.

23 Coronary artery surgery: miscellaneous / Creating alternative image 323 P2069 Influence of on-pump versus off-pump cardiac surgery on completeness of revascularization in patients with stable coronary artery disease - MASS III trial N.H. Lopes, E.G. Lima, R.D. Vieira, C.L. Garzillo, L.A.M. Cezar, A. Hueb, L.A.O. Dallan, F.S. Paulitsch, J.A.F. Ramires, W.A. Hueb. Heart Institute of University of Sao Paulo, Sao Paulo, Brazil Background: Coronary Artery Bypass Surgery (CABG) with use of Cardiopulmonary Bypass (CPB) is a routine and safe procedure with low mortality in elective patients. Recent data in performing CABG on Off-pump (OPCAB) suggest reduced morbidity. However, comparisons of selected patients undergoing offpump versus conventional on-pump CABG have yielded inconsistent results and raised concerns about completeness of revascularization in off-pump CABG, as well in its influence on five-year survival. Methods: In a single center randomized trial, patients undergoing myocardial revascularization were randomly assigned OPCAB or On-pump (ONCAB) technique. Both surgical and anesthetic techniques were standardized. Primary composite end-points were freedom from overall death, myocardial infarction further revascularization (surgery or angioplasty) and stroke. Besides, they were stratified considering completeness of revascularization. Results: Of 308 patients randomized to CABG, 153 underwent on-pump and 155 underwent off-pump surgery. Baseline characteristics were similar among patients. In the OPCAB group 71 and 82 patients had received complete and incomplete revascularization respectively. On the other hand, in the ONCAB group 89 had complete and 66 incomplete revascularization. Comparing two techniques we observed a tendency of more complete revascularization in ONCAB group (p=0,053). But, in five-year follow up, the composite event free probability rates were: 82,5% for complete and 77,7% for incomplete revascularization (p=0.219). Conclusion: Although there was a tendency of more complete revascularization in ONCAB group, incomplete revascularization was associated with similar outcomes compared to complete revascularization during five years follow-up regardless the technique of CABG. P2070 C-reactive protein is not predictive of atrial fibrillation following coronary artery bypass surgery A. Kourliouros, O. Valencia, A. Tsiouris, M. Tavakkoli Hosseini, A. Kiotsekoglou, A.J. Camm, M. Jahangiri. St George s Healthcare NHS Trust, London, United Kingdom Purpose: Atrial fibrillation (AF) is the commonest arrhythmia following cardiac surgery. Inflammation has been implicated in the pathogenesis of postoperative AF, however, the predictive value of inflammatory cytokines in its occurrence remains controversial. We set out to examine the association of baseline and postoperative C-reactive protein levels (CRP) with AF following CABG. Methods: 316 consecutive patients undergoing first-time CABG with the use of cardiopulmonary bypass and no history of AF were included. Heart rhythm was assessed with continuous tele-monitoring for 72 hours postoperatively, 6- hourly clinical examinations and daily electrocardiograms thereafter. CRP measurements were performed prior to surgery and on a minimum of two occasions during hospital stay. Results: Baseline CRP was not significantly different between patients who developed postoperative AF (n=80, 25.3%) and those who remained in sinus rhythm (SR) (p=0.61). Multivariate logistic regression analysis with the inclusion of baseline CRP as an independent variable, revealed non-use of statins as the only independent risk factor associated with postoperative AF (p=0.043). Peak incidence of AF was observed on the second postoperative day (39%) followed by postoperative day 3 (31%). Peak CRP levels were observed on day 3, but did not differ significantly between the AF and SR groups (median, 231 vs. 238mg/L, p=0.68). There was a trend for increased CRP levels in the AF group when compared to the SR group on postoperative days 4, 5 and 6, which, however, remained nonsignificant (p=0.14). P2071 Impact of on-pump and off-pump coronary artery bypass surgery in incidence of early postoperative atrial fibrillation E.G. Lima, R.D. Vieira, H.B. Ribeiro, C.L. Garzillo, F.S. Paulitsch, A. Hueb, L.A.O. Dallan, J.A.F. Ramires, N.H. Lopes, W.A. Hueb. Heart Institute of University of Sao Paulo, Sao Paulo, Brazil Background: The incidence of atrial fibrillation (AF) may reach 40% of the patients submitted to coronary artery bypass graft (CABG) surgery. Moreover, there are few prospective and randomized studies comparing the occurrence of AF in the on-pump versus the off-pump CABG. It is unclear, whether the development of inflammatory systemic response, secondary to the extracorporeal circuit, might contribute to the physiopathology of AF. Methods: Between 2002 and 2008, patients with multivessel coronary artery disease, stable angina, and preserved ventricular function, according to surgeon s agreement that revascularization could be attained by either strategies, were randomly assigned to on or off-pump CABG. The primary end-points were cardiovascular death, stroke, and unstable angina requiring additional revascularization along five years of follow-up. Continuous electrocardiograph monitoring, and clinical symptoms during hospitalization were used to the diagnostic of AF. Results: In MASS III study 308 subjects were randomly assigned to intervention: 153 to the on-pump group and 155 to the off-pump group. AF occurred in 29 subjects (15%) in the off-pump group vs. 6 (4%) in the on-pump group (p=0,001). Baseline characteristics were similar among groups, except for patients presented AF were older (p=0.027). The incidence of primary end-points was similar among both groups. Nonetheless, patients presented AF had longer ICU (p<0,001) and hospitalization stay (p<0,001). Conclusion: Off-pump surgery was associated with higher incidence of AF compared with on-pump procedure. AF after CABG contributed to prolonged ICU and hospitalization stay. Even though, there is no difference on mortality and primary end-points at late follow-up. P2072 Low cardiopulmonary bypass perfusion temperature is an independent risk factor for acute kidney injury after coronary artery bypass surgery A. Kourliouros, O. Valencia, S.D. Phillips, P.O. Collinson, J.P. Van Besouw, M. Jahangiri. St George s Healthcare NHS Trust, London, United Kingdom Purpose: Acute kidney injury (AKI) is a common complication after coronary artery bypass surgery (CABG). The role of hypothermia in postoperative renal function remains controversial. We set out to examine the effect of varying cardiopulmonary bypass (CPB) temperatures on early postoperative renal function. Methods: Patients undergoing first time CABG between 2002 and 2006 and without evidence of preoperative renal insufficiency (estimated creatinine clearance 50 ml/min, calculated by Cockcroft-Gault formula) were studied. Medical history and intraoperative variables, including nasopharyngeal and arterial line CPB perfusion temperatures, were collected prospectively. Primary endpoint was the development of early postoperative AKI (defined as creatinine clearance <50 ml/min), which was assessed using multivariate and propensity score analyses. Results: 1072 patients were included. Acute kidney injury occurred in 175 (16%). Univariate analysis demonstrated that lower CPB perfusion temperatures (and not nasopharyngeal ones), were significantly associated with renal dysfunction following CABG. Multivariate regression analysis identified reduced CPB perfusion temperature as an independent risk factor for AKI (OR 0.92, 95% CI 0.86 to 0.98, p=0.012), along with age (OR 1.07, 95% CI 1.04 to 1.10, p<0.001) and depressed preoperative creatinine clearance (OR 0.89, 95% CI 0.87 to 0.91, p<0.001). Propensity score adjustment confirmed that lower CPB perfusion temperatures (<27 C) were associated with postoperative AKI (OR 1.66, 95% CI 1.16 to 2.39, p=0.0056). Conclusions: Lower CPB perfusion temperatures are significantly associated with AKI following CABG. In addition to the known age-related decline in renal function, it appears that hypothermia and/or the rewarming process contribute to renal injury during cardiac surgery. MODERATED POSTERS 2 CREATING ALTERNATIVE IMAGE Conclusions: Baseline CRP levels were not predictive of AF after on-pump CABG. Increased CRP coincided with the occurrence of postoperative AF but its plasma concentrations were not significantly different between the AF and SR groups. P2074 Cardiac MSCT as an alternative to coronary angiography in the pre operative assessment of coronary disease before aortic valve surgery J.-C. Cornily, M. Gilard, V. Jan, P.Y. Pennec, G. Le Gal, J. Boschat. CHU de Brest - Hopital de la Cavale Blanche, Brest, France Purpose: In patients with severe aortic valve disease, conventional coronary angiography (C-CAG) is still recommended before surgery. A preliminary study suggests that, when compared to C-CAG, MSCT-Coronary Angiography (MSCT- CAG) was able to rule out coronary artery disease (CAD) in many of these patients. Our objective was to prospectively assess the safety of ruling out CAD solely on the basis of a normal MSCT-CAG.

24 324 Creating alternative image Methods: We included all consecutive patients scheduled for C-CAG before aortic valve surgery. We first estimated calcium scoring (Agatston score equivalent (ASE)). Patients underwent injected MSCT if ASE was < C-CAG was cancelled when MSCT-CAG quality was sufficient and showed no significant coronary artery stenosis. Patients benefited from C-CAG in case of calcium scoring 1000, bad quality of the MSCT images or evidence of CAD. Our primary endpoint was to assess the occurrence of per- and post-operative myocardial infarction defined by the apparition of a Q wave on the ECG or an abnormal post operative troponin Ic elevation (>20 ng/ml) in these patients who underwent surgery with no prior C-CAG. Results: Between Aug 1st 2005 and Aug 30th 2008, we included 199 patients: 118 men (58%); aged 69±12 years; valvular disease: Aortic stenosis: n = 164, aortic regurgitation: n = 29, annuloaortic ectasia: n = 6. A total of 63 patients went directly through C-CAG because of a 1000 ASE. MSCT-CAG was performed in 136 patients. We performed both C-CAG and MSCT-CAG on 30 patients because of abnormal MSCT (n = 18) or bad quality MSCT (n = 12). Finally,106 patients benefited from surgery without previous C-CAG. A single patient over 106 (0.9%) suffered a per surgery myocardial infarction after a sub-normal MSCT. The post surgery C-CAG confirmed the occlusion of a small diagonal artery that had been detected on MSCT but considered <50% stenosis. This <1% ischemic event after normal MSCT-CAG is close to the published data about valve surgery after normal C-CAG. Conclusion: When ASE<1000, MSCT was performed and allowed us to avoid C-CAG in 106/136 patients (78%) with good clinical outcome. MSCT is safe in this particular indication and might be recommended first instead of C-CAG when ASE<1000. P2075 Predictive Value of Multi-Slice Computed Tomography (MSCT) for ischemia on myocardial perfusion imaging J.E. Van Velzen 1,J.D.Schuijf 1, J.M. Van Werkhoven 1,E.Boersma 2, F.R. De Graaf 1, M.P. Stokkel 1, P. Kaufmann 3, J.W. Jukema 1, E.E. Van Der Wall 1,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 3 University Hospital Zurich, Zurich, Switzerland Purpose: Previous studies have shown a large discrepancy between the presence of stenosis on MSCT angiography and the presence of ischemia. Therefore, identification of high risk features on MSCT for ischemia may improve guidance of the clinician in their decision for further diagnostic and/or therapeutic options. The purpose of this study was to identify variables on MSCT angiography that may indicate a higher likelihood for ischemia. Methods: Both MSCT and myocardial perfusion imaging (MPI) by means of SPECTwere performed in 616 patients (59% male, age 60±11 years) with known or suspected coronary artery disease (CAD). Based on MSCT angiography, the presence, extent and degree of stenosis ( 50% luminal narrowing or not) were determined. Lesions were classified as non-calcified, mixed and calcified. Ischemia on MPI was defined as a SSS >4. Results: Ischemia was observed in 28% (n=168) of patients. Multivariate analysis showed that extent of disease ( 3 diseased segments) was a significant independent predictor of ischemia (OR 1.6, p =0.03). Also degree of stenosis (presence of >50% stenosis) was a strong independent predictor for ischemia (OR 3.4, p<0.0001). Interestingly, plaque composition was identified as predictive for ischemia as well with the presence of 3 mixed plaques in particular (OR 2.9, p<0.0001). Chi-square analysis showed that MSCT variables had significant incremental value over clinical risk stratification for the prediction of abnormal MPI. Conclusions: More advanced and severe atherosclerosis on MSCT is predictive for ischemia on MPI. MSCT variables (describing extent, degree and composition) have significant incremental value over clinical risk stratification for the prediction of abnormal MPI. P2076 Effect of glucose lowering on carotid intima-media thickness, coronary artery calcification and coronary circulatory function in type 2 diabetes mellitus T.H. Schindler 1,A.D.Facta 2, J. Cadenas 2,J.Sayre 2,J.Goldin 2, H.R. Schelbert 2. 1 University Hospitals of Geneva, Cardiovascular Center, Geneva, Switzerland; 2 Department of Molecular and Medical Pharmacology at UCLA, Los Angeles, United States of America Objective: To determine the effect of plasma glucose lowering on coronary circulatory function, carotid intima-media thickness (IMT) and coronary artery calcification (CAC). Methods: In twenty-two patients with type 2 diabetes, and in 17 healthy controls coronary circulatory function was determined with positron-emission-tomography (PET) measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine-stimulated hyperemia, while structural alterations of the carotid IMT were assessed with high resolution vascular ultrasound and CAC with electron beam tomography (EBT). In diabetic patients, measurements were repeated again after a 1 year follow-up of glucose-lowering therapy with glyburide and metformin and also in healthy controls. Results: At baseline, the endothelium-related MBF increase to CPT ( MBF- CPT) and to adenosine-stimulation ( MBF-ADO) were less in diabetic patients than in controls (0.09±0.09 vs. 0.25±0.12 and 1.08±0.31 vs. 1.37±0.41 ml/g/min, p<0.05; respectively), while carotid IMT and CAC were abnormally increased diabetic patients (0.83±0.19 vs. 0.68±0.11 mm 2 and 35.28±68 vs. 4.25±9HU,p<0.05; respectively). Treatment with glyburide and metformin significantly decreased plasma glucose concentrations from 205±72 to 160±44 mg/dl. This decrease in plasma glucose resulted in a significant increase in MBF to CPT and a non-significantly to ADO, respectively (0.09±0.09 vs. 0.19±0.17 and 1.19±0.51 ml/g/min), while a further abnormal mild increase in carotid IMT and CAC was observed (0.86±0.18mm 2 and 59.88±102 HU). The decrease in plasma glucose levels correlated with an improvement in MBF to CPT and to ADO, respectively (r=0.46, p and r=0.36, p 0.056) and, also with a lower progression of carotid IMT and CAC, respectively (r=0.46, p and r=0.48, p 0.036). Further, on multivariate analysis, the improvement in endotheliumdependent coronary artery function was an independent predictor of the slowed progression of CAC (p by ANOVA). Conclusions: The close association between the decrease in plasma glucose concentrations and its beneficial effects on functional and structural abormalities of the arterial wall denotes direct adverse effects of hyperglycemia on diabetesrelated vasculopathy. An improvement of coronary endothelial function in type 2 diabetes mellitus may mediate, at least in part, direct preventive effects on the progression of structural epicardial disease. P2077 Evaluation of arterial healing after stent implantation by optical frequency domain (OFDI) imaging: an in vivo comparison with histology in a pig coronary artery model C. Templin 1,M.Meyer 1, M. Mueller 1, P. Kronen 2, K. Weber 3, D. Paunovic 4,S.Hoerstrup 1,R.Corti 1, T.F. Luescher 1, U. Landmesser 1. 1 University Hospital Zurich, Zurich, Switzerland; 2 Vetsuisse Faculty, Zurich, Switzerland; 3 Harlan Laboratories, Itingen, Switzerland; 4 Terumo Europe, Leuven, Belgium Background: Optical frequency domain imaging (OFDI), a second-generation form of optical coherence tomography (OCT), is capable of acquiring images of histological resolution at a markedly higher speed (pullbacks of up to 40mm/s) and willsubstantially facilitateuse of coronary optical imaging, given that coronary arteries have to be flushed for light imaging for blood removal. We present the first validation study of OFDI for in vivo examination of stent healing. Methods: Twenty stents were implanted in coronary arteries of Landrace Large White Duroc pigs (bare-metal-stents, BMS, and Biolimus A9 drug-eluting stents, DES, Nobori). After 1, 3, 10, 14 and 28 days the animals underwent follow-up angiography with coronary OFDI (Terumo-OFDI). A comparison between OFDI and light microscopic (histology) and electron microscopic images (SEM) is performed. Results: Neointima thickness increased from day 10/14 to day 28 (BMS 0.085±0.07 mm vs ±0.07 mm, p<0.0001; DES 0.038±0.04 mm vs ±0.06 mm, p<0.0001); however, to a lesser extent with DES (p<0.0001). Furthermore, struts with a thrombosis-like pattern (Class V) were visible at the early time points (i.e. day ±15.3%), but disappeared after day 10. Stent Strut classification

25 Creating alternative image 325 strut coverage could be clearly detected and number of uncovered struts was reduced over time (0-3 vs days: 72.75±19.94% vs. 2.28±2.30%, p<0.001). Conclusions: Our results suggest that OFDI provides valuable information and represents a viable method for coronary in vivo imaging of arterial healing after stent implantation. Given its ability to provide microscopic information at high speed, this technology may represent an excellent tool for examination of stent healing, detection of smaller stent-strut associated thrombosis and neointima proliferation patterns. P2078 Optimal acquisition time for myocardial perfusion imaging using an ultrafast cardiac gamma camera with a novel detector technique R. Buechel, B. Herzog, V. Treyer, R. Katz, L. Husmann, I. Burger, A. Pazhenkottil, I. Valenta, O. Gaemperli, P. Kaufmann. University Hospital Zurich, Zurich, Switzerland Purpose: To establish the optimal scan time for a novel ultrafast cardiac gamma camera with cadmium zinc telluride (CZT) solid-state detectors for myocardial perfusion SPECT imaging. Methods: Twenty patients (17 males, age range years, BMI range kg/m 2 ) underwent a one-day 99mTc-tetrofosmin adenosine-stress (325MBq)/rest (913MBq) imaging protocol (15 minutes per scan) on a standard dual-detector SPECT camera (Ventri, GE Healthcare). Each scan was immediately repeated on a ultra fast camera (Discovery NM 530c, GE Healthcare) with 9 (low dose) and 6 minutes (high dose) scan time and reconstructed using list mode to obtain scan durations of 1 minute, 2 minutes etc. up to a maximum of 9 minutes for low and 6 minutes for high dose. Percent uptake from the Discovery NM 530c (20 segment model) for each scan duration was compared for each patient to Ventri data for low and high dose using Pearson coefficient. For the scan duration above which no further correlation improvement was observed, Bland- Altman (BA) limits of agreement were obtained for the uptake in the five main anatomical left ventricular regions (apex, anterior, septal, lateral, and inferior). Results: Maximum correlation of quantitative uptake was achieved after 3 minutes with low dose and at 2 minutes with high dose. BA limits were -13.2% to 14.4% for low dose and -11.6% to 16.4% for high dose at 3 and 2 minutes, respectively, yielding 97.5% clinical agreement with the Ventri images. Correlation of quantitative uptake Conclusions: Discovery NM 530c with new CZT solid-state detectors allows substantial reduction in acquisition time for SPECT myocardial perfusion imaging. Alternatively, this may allow reduction in radiation dose. P2079 Can ventricular dyssynchrony during exercise predict response to resynchronization therapy? A radionuclide angiography study C. Valzania 1,F.Fallani 1,G.Gavaruzzi 2,M.Biffi 1, C. Martignani 1, I. Diemberger 1,M.Bertini 1, G. Domenichini 1,C.Rapezzi 1, G. Boriani 1. 1 Institute of Cardiology, Univ. of Bologna, Bologna, Italy; 2 Department of Nuclear Medicine, Policlinico S.Orsola-Malpighi, Bologna, Italy The aim of the study was to evaluate the possibility to predict the response to cardiac resynchronization therapy (CRT) at mid-term follow up by radionuclide angiography with Fourier phase analysis, performed both at rest and during exercise. Methods: Twenty-one consecutive heart failure patients (76% men, 65±9 yrs) with idiopathic dilated cardiomyopathy, NYHA class III, and left ventricular (LV) dysfunction, were enrolled into the study. All patients underwent equilibrium Tc99 radionuclide angiography with bicycle exercise at 3 times: during spontaneous rhythm, immediately after CRT activation, and after 3 months of CRT. Ejection fraction (EF) and Fourier phase analysis were evaluated in both ventricles. Interventricular dyssynchrony was expressed as the difference between LV and right ventricular (RV) mean phases. Intraventricular dyssynchrony was assessed by the standard deviation of the mean phase in each ventricle. Results: At baseline, immediately after CRT activation, 10/11 (91%) among midterm responders had a decrease in LV dyssynchrony during exercise, compared to only 4/10 (40%) among mid-term non-responders (p=0.03). Overall, a decrease in LV dyssynchony vs. spontaneous rhythm was observed at 3-month follow-up, both at rest (from 52±26 to 34±22 ms, p=0.002), and during exercise (from 52±25 to 42±23 ms, p=0.03). Moreover, LVEF improved at 3 months at rest (32±12 vs. 26±9%, p<0.001), as well as during exercise (32±13 vs. 26±9%, p=0.002), and a correlation was observed between LVEF and LV dyssynchrony (r= at rest and r= during exercise, p<0.05). No significant variations in RV dyssynchrony or RVEF were observed during CRT, either acutely or during follow-up. Interventricular dyssynchrony decreased at 3 months only during exercise (p=0.012 vs. spontaneous rhythm). Conclusions: These data suggest that a decrease in LV dyssynchrony during exercise immediately after CRT activation may be predictive of mid-term response to CRT. Further efforts to optimize CRT programming during follow-up might be focused on patients without an acute decrease in exercise LV dyssynchrony. P2080 Different patterns of myocardial iron overload by T2* Cardiovascular MR as markers of risk for cardiac complication in thalassemia major A. Pepe 1, A. Meloni 1, V. Positano 1,G.Rossi 2, P. Pepe 2, M.C. Galati 3,A.Zuccarelli 4,G.Restaino 5,G.Valeri 6, M. Lombardi 1. 1 MRI Lab, Institute of Clinical Physiology, G Monasterio Foundation, Pisa, Italy; 2 Epidemiology and Biostatistics Unit, Institute of Clinical Physiology, CNR, Pisa, Italy; 3 UOS Talassemie A.O. Pugliese-Ciaccio, Catanzaro, Italy; 4 Centro di microcitemia Ospedale civile, Olbia, Italy; 5 Radiology Department, Università Cattolica del Sacro, Campobasso, Italy; 6 Radiology Department, Ospedali Riuniti, Ancona, Italy Purpose: Cardiac complications mainly related to myocardial iron overload (MIO) remain the main cause of mortality in thalassemia major (TM). Thalassemia cardiomyopathy is treatable and reversible if appropriate chelation therapy is instituted in time. The validated multislice multiecho T2* CMR technique has permitted to quantify segmental and global myocardial iron burden detecting different patterns of iron overload. Aim of our study was to verify the risk of cardiac complications (heart failure, arrhythmias and pulmonary hypertension) related to different patterns of MIO in a large cohort of TM patients. Methods: Within the MIOT (myocardial iron overload) project we consecutively studied 568 TM patients using the multislice multiecho T2* CMR technique to quantify segmental and global MIO. The MIOT project is a previously validated network of six CMR centres and 56 thalassemia centres sharing a common clinical-instrumental database. Three short-axis views (basal, medium, apical) of the left ventricle were acquired using a multislice multiecho T2* sequence. Using a previously validated software the 16 segmental T2* values and the mean global heart T2* value were provided. A conservative cut off of 20 ms was considered the limit of normal for the segmental and global T2* values. Results: We identified 4 groups of patients: group I (23%) with homogeneous MIO (all segments with T2* values < 20 ms), group II (12%) with heterogeneous MIO and global heart T2* < 20 ms (the majority of segments with T2* values < 20 ms); group III (25%) with heterogeneous MIO and global heart T2* > 20 ms (the majority of segments with T2* values > 20 ms); group IV (39%) with no MIO (all segments with T2* values > 20 ms).the percentage of patients with cardiac complications was significantly different in the 4 groups (group I 36% vs group II 14% vs group III 17% vs group IV 3.2%; P=0.001). In particular, the percentage of patients with heart failure was significantly different in the 4 groups (group I 18% vs group II 14% vs group III 5% vs group IV7%; P=0.001). No significant differences were found among groups in the percentage of arrhythmias and pulmonary hypertension. Odds Ratio for cardiac complications was 2.4 ( OR 95%CI; P= ) for patients with homogeneous MIO vs patients with no MIO. Conclusions: Cardiac complications (in particular heart failure) are correlated with MIO distribution increasing from the patients with no MIO to the patients with homogeneous MIO. Homogeneous MIO predicts a significantly higher risk to develop cardiac complications suggesting an intensive chelation therapy in this group of patients. P2081 Aortic dilatation and reduced elasticity after surgical repair of tetralogy of fallot - assessment by magnetic resonance imaging A. Silva Ferreira 1,E.Rizzo 2, M. Ladouceur 2, A. Redheuil 2, M. Bensalah 2,A.Azarine 2, Y. Boudjemline 2, E. Mousseaux 2. 1 Hospital dos Lusiadas, Lisbon, Portugal; 2 European Hospital George Pompidou (AP-HP), Paris, France Purpose: Despite anatomically successful repair of tetralogy of Fallot (TOF), a significant proportion of survivors develop late dilatation of the proximal aorta, possibly as a consequence of intrinsic histological abnormalities. This study sought to assess aortic elasticity in patients with surgically corrected TOF, and its relationships to aortic dimensions, aortic valve competence and left ventricular (LV) function. Methods: Magnetic Resonance Imaging (MRI) was performed on 71 patients with successfully repaired TOF (mean age 28±12 years, 20±9 years after corrective surgery) and 30 healthy controls (mean age 29±8 years). Aortic diameters were measured at five levels: sinuses of Valsalva, sinotubular junction, tubular aorta, aortic arch and descending aorta. Steady-state free precession and velocity-encoded MRI sequences were used to assess LV ejection fraction, aortic regurgitation (AR) fraction, and two indices of aortic elasticity: pulse wave velocity (PWV) and aortic distensibility.

26 326 Creating alternative image / Thrombosis and anti-thrombotic therapy Results : Compared to healthy subjects, repaired TOF patients showed reduced aortic elasticity as indicated by increased PWV (7.4±5.9 m/s vs. 4.4±1.2 m/s, p <0.001) and reduced aortic distensibility (3.9± mmhg -1 vs. 5.6± mmhg -1, p=0.002). Patients with repaired TOF also had higher aortic diameters in all the predefined levels (p<0.001) except the descending aorta (p=ns). Mild or moderate degrees of AR were present in 10 patients (median AR fraction 3% vs. 1% in controls; p<0.001). The mean LV ejection fraction was significantly lower in corrected TOF patients (58%±9 vs. 65%±3, p<0.001). An increased PWV correlated with aortic regurgitation fraction (r=0.21, p=0.037) and also with dilatation of the aortic sinuses, sinotubular junction, tubular aorta and aortic arch (r=0.23 to 0.30, p 0.034). Aortic distensibility correlated with LV ejection fraction (r=0.35, p=0.001) and aortic regurgitation fraction (r=-0.34, p=0.001). Conclusion : Reduced aortic elasticity and dilatation of the proximal aorta are frequently present in patients with corrected TOF. Reduced aortic elasticity correlates with and may contribute to progressive aortic dilatation, aortic regurgitation and LV dysfunction. THROMBOSIS AND ANTI-THROMBOTIC THERAPY P2083 Slow response to clopidogrel predicts low response A. Bellemain, J. Silvain, J.-P. Collet, F. Beygui, O. Barthelemy, R. Choussat, N. Vignolles, D. Brugier, B. Bertin, G. Montalescot. Pitie-Salpetriere Hospital (AP-HP), Paris, France Aim: The fast onset of inhibition of platelet aggregation may be relevant in the setting of acute coronary syndromes and percutaneous coronary intervention, but its relation to the final degree of inhibition is not well established. Low clopidogrel response and high post-treatment platelet reactivity are known to be associated with poor clinical outcome. We performed a post-hoc analysis of the ALBION randomized study to determine if the slow response to clopidogrel loading dose predicts clopidogrel low response and high post-treatment platelet reactivity. Methods: ALBION included 103 NSTEACS low to intermediate risk patients, randomised to receive 300, 600 or 900mg LD of clopidogrel. Early kinetic profile of delta Maximal Platelet Aggregation (deltampa, ADP 20 μmol/l) and MPA were studied (with baseline sample as reference), with 8 time points within the 24 hours postloading. Low response was defined as deltampa < 10% over the first 24 hours, fast response was defined as a deltampa 10% within the first hour after loading (the other patients were slow responders), and high post-treatment platelet reactivity as MPA 56.56% (threshold of the fourth quartile). Inflammatory markers (PAC1 and P-selectin) were also evaluated according to the type of response. Results: 55% of patients were slow responders. Slow response was a reliable marker of low response to clopidogrel, whatever the LD group (figure). Low and slow response were both associated with high post-treatment platelet reactivity. Faster onset of action was more frequent with higher clopidogrel LD. Slow responders had also less decrease in inflammatory markers. Figure 1 Conclusion: Slow response to clopidogrel is a marker of low response at 24 hours and high post-treatment platelet reactivity. The clinical relevance of this finding remains to be shown. P2084 Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications V.L. Serebruany 1,S.Rao 2,M.Siva 3, J.L. Donovan 3, A.O. Kannan 3, L.M. Makarov 1,S.Goto 4,D.Atar 5. 1 Johns Hopkins University, Towson, United States of America; 2 Duke Clinical Research Institute, Durham, United States of America; 3 University of Massachusetts, Worcester, United States of America; 4 University of Tokai, Kanagawa, Japan; 5 Akers University, Oslo, Norway Background: Data from ACS trials and registries suggest a link between increased risk of bleeding and cardiovascular mortality. However, the potential association of bleeding risk and the inhibition of platelet aggregation (IPA) is not established. It may play a critical role for the safety of more aggressive platelet inhibition, or/and individual tailoring of antiplatelet strategies. We correlated (IPA) with bleeding events assessed by TIMI-, GUSTO-, and BleedScore scales in a large cohort of patients with coronary artery disease (CAD) and ischemic stroke (IS) treated with chronic low dose aspirin plus clopidogrel. Methods: We conducted secondary post-hoc analyses of 5μM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore scales in a dataset consisting of patients with documented CAD (n=246) and previous IS (n=117). Results: Demographic characteristic differ substantially dependent on the underlying vascular disease, however IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious hemorrhagic events, where the TIMI scale was the most exclusive, while BleedScore was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during 2-3 distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. IPA above 50% strongly predicts minor (r2 =0.583), but not severe (r2 =0.109) bleeding events. Conclusion: Chronic oral combination antiplatelet regimens are associated with a very high ( %) prevalence of superficial bleeding episodes. We postulate that in trials and registries, these hemorrhages are grossly underestimated. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. While IPA is well suited for defining the risk of minor complications, more serious bleeding events cannot be predicted. P2085 The clopidogrel patient information card significantly improves knowledge and adherence to anti-platelet therapy S. Bhattacharyya, H. Madani, S. Myers, R. Rakhit. Royal Free Hospital, London, United Kingdom Background: Stent thrombosis is a serious and sometimes fatal complication of drug eluting stent (DES) implantation. Premature anti-platelet therapy discontinuation is a major predictor of both early and late stent thrombosis. Patient education level is an independent risk factor associated with discontinuation of antiplatelet therapy. The clopidogrel warning card has been suggested as possible mechanism to improve patient education and possible adherence. The card was introduced into clinical practice at our institution in We sought to investigate the effect of the introduction of a clopidogrel card on patient knowledge base. Methods: 100 consecutive patients undergoing percutaneous coronary intervention (PCI) with DES implantation were identified over a 6 month period. Group 1 consisted of 50 patients recruited prior to introduction of the clopidogrel card (March May 2006). Group 2 consisted of 50 patients after the introduction of the clopidogrel card (May 2006-July 2006). Patients in group 1 did not receive a clopidogrel card. Patients in group 2 received a clopidogrel card. 6 months post PCI all patients were seen in clinic. Knowledge in four categories was documented: (1) Indication for clopidogrel (2) Minimum duration of clopidogrel therapy (3) Side effects of clopidogrel and (4) Medical advice sought prior to temporary interruption/early cessation of clopidogrel. Results: The percentage of patients who knew the correct answer for each category are listed below. (1)Indication for clopidogrel: 44% of patients in group 1 versus 76% of patients in group 2 (Odd ratio 4, 95% Confidence Interval (CI) ( ), p=0.002). (2)Minimum Duration of Clopidogrel: 30% of patients in group 1 versus 90% of patients in group 2 (Odd ratio 21, 95% CI (7-63), p<0.0001). (3)Side Effects of Clopidogrel: 24% of patients in group 1 versus 12% of patients in group 2 (Odd ratio 0.4, 95% CI ( ), p=0.19). (4)Medical advice sought prior to discontinuation of clopidogrel: 84% of patients in group 1 versus 98% of patients in group 2 (Odd ratio 5.4, 95% CI ( ), p=0.2). Conclusion: The introduction of the clopidogrel card may have significantly improved patient knowledge of the indication for clopidogrel and the minimum duration of clopidogrel therapy. No difference was noted in knowledge of side effect profile. By improving patient knowledge the clopidogrel card may potentially improve adherence to therapy. This has important implications for minimizing the risk of stent thrombosis associated with anti-platelet withdrawal. P2086 The effect of duration of Clopidogrel treatment on outcome in following coronary stent implantation D. Zahger, H. Gilutz, C. Cafri, R. Ilia, A. Porat. Soroka University Medical Center, Beer Sheva, Israel Background: Dual anti platelet therapy for 9-12 months is superior to 1 month only following coronary stenting. Whether an intermediate treatment period might be sufficient, while reducing the risk and cost of clopidogrel treatment, is unknown. Objectives: To examine the continuous relation between the duration of clopidogrel use during the first year following coronary stenting and outcome. Methods: We studied all patients who underwent coronary stenting at our center between 6/03 8/05 and performed a landmark analysis of patients who were event free (death or non-fatal AMI) 1, 3, 6, 9 and 12 months following stenting.

27 Thrombosis and anti-thrombotic therapy 327 Each cohort was followed for one year; the occurrence of death and of death or non-fatal AMI was compared between clopidogrel users and non-users at the beginning of each time point. The effect of clopidogrel on outcome was assessed in a multivariate model. Results: Demographic and clinical data were available for 1154 patients. 974 were treated with bare-metal stents (BMS). Within this group multivariate analysis at the various time points showed a significant reduction of mortality: 6 months: 4.4% vs. 1.7%, OR: , 9 months: 3.1% vs. 0.9%, OR: and 12 months: 3.2% vs. 1.3%, OR: The composite of mortality or non-fatal AMI was also independently reduced by clopidogrel at all time points: 6 months: 9.5% vs. 6%, OR: , 9 months: 8.5% vs. 2.7%, OR: and 12 months: 7.8% vs. 2%, OR: No statistically significant differences were shown among DES users. Conclusions: In an observational study of 1154 consecutive patients we found that clopidogrel treatment for 12 months after coronary stenting is associated with a lower risk of death or the composite of death or non-fatal AMI in patients treated with BMS. These findings suggest that shorter treatment periods are not sufficient. The apparent lack of benefit in DES recipients was probably due to the very high rate of clopidogrel utilization among these patients. P2087 The variable response of PCI subjects with apparent Clopidogrel resistance to re-loading with 600mg A.S.P. Sharp, R.T. Gerber, C. Godino, A. Latib, M. Ferraro, A. Colombo. San Raffaele Hospital, Milan, Italy Background and methods: It is increasingly recognized that subjects undergoing PCI may exhibit a variable response to clopidogrel pretreatment. When platelet inhibition is measured using the VerifyNow assay, a high platelet P2Y12 reactive units score (PRU>240), reflecting a relatively impaired response to clopidogrel, has been associated with an increased risk of clinical events. However, it is unclear whether a high residual PRU represents a patient who is simply under-treated, or a patient who truly is resistant to the effects of clopidogrel. We ran a prospective study to assess the response of those with a high PRU at the time of their PCI (despite the recommended Clopidogrel and aspirin pre-pci regimens) to re-loading with 600mg clopidogrel and subsequently re-assessed their PRU 24 hours post-procedure so see if platelet activity was now within a more favourable range. Results: Of 106 patients tested, 23 patients had a PRU value 240 at the time of their PCI. Of these, 19 patients had their first exposure to clopidogrel within a month prior to their PCI, whilst the remaining four were taking clopidogrel for more than one year. Mean age, sex and renal function did not differ between the two response groups, but diabetes was more prevalent in subjects with a high PRU (30.4% vs. 14.4%; p=0.08). Overall, of the 23 patients who exhibited a sub-optimal PRU (>240) at the time of their PCI, 14 of these patients achieved a PRU<240 after an additional 600mg loading dose of clopidogrel (mean drop in PRU in these subjects 161 ± SD 57). However, nine subjects continued to show a PRU of>240 despite the extra 600mg on top of their standard treatment and exhibited only a small change in their baseline PRU (mean drop in PRU 32±49). There were no bleeding sequelae in any of the patients given additional clopidogrel. Conclusion: In this cohort of patients, 61% of those subjects with an apparently sub-optimal response to standard clopidogrel loading had a large fall in their PRU after re-loading, suggesting these patients were either under-treated or partially resistant. This could be easily rectified with an additional loading dose. However, 39% of patients with a sub-optimal PRU after traditional loading regimes exhibited little response to an additional 600mg loading dose and may represent truly resistant subjects. These two groups may require different strategies to ensure appropriate inhibition of platelets, with consideration given to the merits of an alternate anti-platelet drug in those with a poor response to clopidogrel re-loading. P2088 The frequency and intra-individual variation of clopidogrel non-responsiveness over time as measured by VerifyNow in patients with stable coronary heart disease A.A. Pettersen, H. Arnesen, I.U. Njerve, M.T. Kase, I. Seljeflot. Dept. of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway Evaluation of in vitro treatment effect of clopidogrel has lately been given large attention, and different laboratory methods are now available for this purpose. Aims and Methods: We investigated the frequency and stability of clopidogrel non-responsiveness in patients with stable coronary heart disease by use of the VerifyNow P2Y12 method. The method gives results both in platelet reaction units (PRU) and as %-inhibition. Patients on chronic single aspirin treatment (160 mg/d) were randomized to continue on aspirin or change to clopidogrel 75 mg/d. Followup time for laboratory assessements were 1 month and 1 year. All blood samples were drawn in fasting condition 24 hour after the last intake of medication. The cut-off for response was defined as the 95%/5% percentile of all patients tested when being on aspirin (n=227, mean age 62 yrs, 78% male), giving PRU value 170 and %-inhibition 24% to be non-responders. Results: After 1 month on clopidogrel (n=89) the mean PRU-level was 144 (SD 69) and %-inhibition 43 (SD 25). After 1 year blood samples from 70 patients on clopidogrel were available and the mean PRU-level was 154 (SD 79) and %- inhibition 35 (SD 28), significantly different from 1 month (p=0.050 and p=0.013, respectively). The frequency of non-responders defined with PRU and % inhibition was 35% and 28%, respectively at 1 month and 43% and 41% respectively at 1 year. To evaluate the intra-individual variation of non-responsiveness over time we performed an agreement calculation, which shows an agreement of 67% when using the PRU with kappa =0.321 (p=0.001) and 77% with kappa =0.504 (p<0.001) when using the % inhibition, judged to be fair or moderate. In conclusion, the frequency of clopidogrel non-responsiveness evaluated by the VerfyNow P2Y12 method is considerable, in agreement with data obtained with other methods. The intra-individual variation over time, although significant agreement, indicate that precaution has to be taken when judging the individual response. The concequences for clinical outcome is under investigation. P2089 The presence of the CYP p450 C19*2 allele is associated with impaired response to clopidogrel as measured by the verifynow P2Y12 near-patient testing device in patients undergoing coronary angiography A. Worrall 1, A. Armesilla 2,M.Norell 1, S. Khogali 1,M.Cusack 1, A. Smallwood 1, J. Cotton 1. 1 Heart and Lung Centre, Wolverhampton, United Kingdom; 2 University of Wolverhampton, Wolverhampton, United Kingdom Objectives: To investigate the effect of the presence of the cytochrome (CYP) p450 C19*2 loss-of-function allele on the response to clopidogrel, as measured by a near-patient testing device, in a cohort of patients with acute coronary syndrome (ACS). Background: Recent studies have linked the common polymorphism CYP p450 C19*2 to impaired clopidogrel response in certain patients. We sought to relate the presence of the polymorphism to clopidogrel response as measured by a wellvalidated near-patient testing device in a real-world cohort of high-risk patients. Methods: 259 consecutive patients admitted with high-risk acute coronary syndromes were enrolled in the study. All patients were able to take dual anti-platelet therapy and received loading and maintenance doses of both aspirin and clopidogrel according to our local protocol. The study was approved by the local research and ethics committee and informed consent gained from all patients. Angiography was performed and a management plan of angioplasty, CABG or medical therapy was pursued. Clinical follow up was recorded to 1 year. Whole blood was taken for determination of clopidogrel response in P2Y12 reaction units (PRU) using a VerifyNow near patient testing device (Accumetrics). A second sample was stored at -80 C for later genotypic analysis. Results: 193/259 (74.5%, CI 69-80%) patients were found to be homozygous wild-type (*1/*1) and 66/259 (25.5%, CI 21 31%) had at least one copy of the *2 polymorphism (*1/*2 or *2/*2). Significantly higher P2Y12 activity was observed in the *2 group (Mean PRU 222.5, SD ±96.6 vs 283.8, SD ±80.7; P<0.0001). This finding was replicated in the 135 patients retested at 30 days (Mean PRU 189.2, SD ±98.0 vs 256.3, SD ±76.8; P=0.003). In patients undergoing PCI for their ACS, the 12 month MACCE events were numerically higher in the group with the *2 allele, but this did not reach statistical significance 6/80 (7.5%, CI 3 16%) events vs 4/24 (16.7%, CI %) events P=0.17. Conclusions: The results confirm that presence of the cytochrome p450 C19*2 polymorphism is an important determinant of response to clopidogrel in patients with acute coronary syndromes, and that this effect may be measured with a widely available near-patient testing device in a real-world population. This effect is evident both early after loading and at 30 days. Near-patient testing is likely to play an important role in tailoring anti-platelet treatment to reduce adverse events in patients with impaired clopidogrel response. P2090 The relative contribution of the CYP2C19*2 polymorphism in the low responsiveness to clopidogrel in the VASP-02 study B. Aleil 1,F.DePoli 2, M. Zaehringer 1, J.P. Collet 3, G. Montalescot 3, C. Leon 4, J.P. Cazenave 4,M.C.Dickele 2, J.P. Monassier 5, C. Gachet 4. 1 Clinique de l Orangerie, Strasbourg, France; 2 Service de Cardiologie, Centre Hospitalier Général, Haguenau, France; 3 Institut de Cardiologie and INSERM U856, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France; 4 UMR_S 949 INSERM, Université de Strasbourg, Etablissement Français du Sang-Alsace, Strasbourg, France; 5 Service de Cardiologie, Hôpital Emile Muller, Mulhouse, France Purpose: The CYP2C19*2 genetic variant is known to contribute to low responsiveness to clopidogrel treatment, leading to a higher rate of cardiovascular events. Systematic identification of the 2C19*2 carriers to predict the individual patient s response to clopidogrel is a matter of debate. Methods: Data of the VASP-02 study comparing patients responsiveness to 75 and 150 mg/day maintenance dose of clopidogrel were reanalyzed by determining the 2C19*2 carrier status of the patients. Platelet reactivity index (PRI) was determined using the VASP method. A PRI>69% defines low responsiveness to clopidogrel. Results: In the 37 non responder patients, 42.4% were 2C19*2 carriers versus 22.0% in the responder patients (p=0.022). After multivariate analysis, 2C19*2

28 328 Thrombosis and anti-thrombotic therapy polymorphism and high body weight were two independent predictors of high PRI (odds ratio [95% confidence interval] 3.39 [ ] p=0.039 and 3.14 [ ] p=0.021) respectively. Increasing the maintenance dose of clopidogrel from 75 to 150 mg/day in non responder patients resulted in a significant decrease of PRI from 76.4±4.6 to 62.8±10.4% (p<0.01) in 2C19*2 carriers and from 76.1±5.3 to 60.8±13.4% (p<0.01) in non carriers. The mean decrease of PRI after doubling the dose was not significantly different between carriers and non carriers of the genetic variant (-13.6±9.3 and -15.3±11.8% p=0.39, respectively). Conclusions: CYP2C19*2 is an important determinant of the responsiveness to clopidogrel while other independent factors such as body weight also are involved. Hyporesponsiveness in 2C19*2 carriers can be easily overcome by doubling the maintenance dose of clopidogrel. Thus, combined functional pharmacodynamic monitoring and genetic determination of CYP profile should help improve patient s responsiveness to clopidogrel. P2091 The significance of clopidogrel low-responsiveness assessed by a point-of-care assay in acute coronary syndrome patients undergoing coronary stenting K.H. Lee, S.H. Lee, J.W. Lee, J.K. Sung, H.S. Wang, Y.J. Youn, N.S. Lee, J.Y. Kim, J.H. Yoon, K.H. Choe. Wonju Christian Hospital, Wonju, Korea, Republic of Perpose: To prevent atherothrombotic events, clopidogrel and aspirin is currently routinely used in treatment of patients undergoing percutaneous coronary intervention (PCI). Despite clopidogrel therapy, patients undergoing PCI are at risk of recurrent coronary events. Therefore, we sought to prospectively evaluate the death and myocardial infarction (MI) of acute coronary syndrome patients and their responsiveness to clopidogrel. Methods: We enrolled consecutive 610 patients (pts, 160 males, 65.2±10.3 years) who received percutaneous coronary intervention (PCI) with acute coronary syndrome (Unstable angina, non-st elevation MI and ST elevation MI) from Jan to Jun Endpoint was defined by cardiac death and stent thrombosis (ST) by definitions of the Academic Research Consortium (ARC). Aspirin and clopidogrel responsiveness were evaluated by VerifyNow tests (Accumetrics Inc, CA). Clopidogrel low-responsiveness was defined as the less than 20%.inhibition of P2Y12 receptor. Results: Baseline demographic characteristics were similar between normal group (370 pts) and low responsiveness group (240 pts) of clopidogrel. Cardiac death occurred in 7 pts (1.9%) of normal group and 14 pts (5.8%) in low group (p=0.009). Stent thrombosis occurred in 5 pts of normal group (0.7%, 4 definit and 1 probable) and 10 pts of low group (4.2%, 7 definite, 2 probable and 1 possible)(p=0.028). The associations between cardiac death and clopidogrel low-responsiveness were evaluated with multivariable logistic regression models adjusted for age and sex. The adjusted Odds ratio for cardiac death was (p=0.013, 95%CI; ) Conclusions: The low-responsiveness of clopidogrel measured with a point-ofcare assay is an independent predictor of cardiac death and stent thrombosis in acute coronary syndrome patients undergoing PCI. P2092 Adverse events associated with high clopidogrel loading doses after acute coronary syndrome C. Pizzi 1, M. Dorobantu 2, G. Tatu-Chitoiu 2,L.Calmac 2, O. Manfrini 1, M. Udeanu 1,E.Craiu 3, C. Macarie 4, R. Bugiardini 1. 1 University of Bologna, Bologna, Italy; 2 Emergency Hospital of Bucharest/Spitalul Clinic de Urgenta Bucuresti (Floreasca), Bucharest, Romania; 3 Hospital of Constanta, Constanta, Romania; 4 Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania Background: In clinical practice, the use of standard or higher than standard clopidogrel loading doses is becoming more common even in those patients not receiving percutaneous coronary intervention (PCI). However, there is no clinical evidence to support such a strategy. Objective: We sought to assess whether patients with acute coronary syndromes (ACS) not undergoing PCI would receive additional benefit from 2 clopidogrel loading dose strategies (standard: 300 mg, and high: >300 mg) versus a noloading regimen with a single daily dose of 75 mg. Methods: We performed a retrospective analysis of outcomes in 763 patients with ACS not undergoing PCI who received standard-loading dose (n=361) or high-loading dose (n=105) versus no-loading dose (n=297) clopidogrel, in 14 study hospitals (International Registry for Acute Coronary Syndrome in Transitional Countries, IRACS-TC) between January 2006 and December All patients received a maintenance daily dose of clopidogrel 75 mg and aspirin 175 mg all throughout the study period. The primary efficacy end point was in-hospital cardiovascular death and recurrent ischemia. The key safety end point was major bleeding. Results: The rate of the combined endpoint of in-hospital cardiovascular death and recurrent ischemia was higher in the high-loading dose compared with the no-loading dose group (59.0% vs. 42.9%; p <0.0001). After adjustment for any clinical confounder (age, sex, risk factors, heart rate, systolic blood pressure, prior AMI, Killip class, ST-elevation myocardial infarction, and in-hospital acute medications) the odds ratio for high-loading dose versus no-loading dose was 3.28 (95% CI ; p=0.001). There was no benefit for the use of 300 mg loading dose over no-loading dose clopidogrel (odds ratio for the combined endpoint 1.59; 95% CI ; p=0.11). Bleeding event rates did not significantly differ (p=0.26) among no-loading dose (0.70%), standard-loading (1.1%) or high-loading dose (1.9%) groups. Conclusions: The use of clopidogrel loading doses is not associated with additional clinical benefit in patients with ACS not undergoing PCI. It may harm them if doses are >300 mg. P2093 Anti-thrombotic effects of an anti-von willebrand factor a1 domain aptamer in blood from patients under aspirin and clopidogrel therapy D. Arzamendi Aizpurua, F. Dandachli, G. Ducrocq, J.F. Theoret, W. Mourad, J. Gilbert, J. Gilbert, R. Schaub, Y. Merhi, J.F. Tanguay. Montreal Heart Institute, Montreal, Canada Background: Anti-thrombotic therapy, together with coronary intervention, is the base of treatment of acute coronary syndromes (ACS). Different anti-platelet therapies have shown a reduction in myocardial infarction and mortality, but with the cost of increasing bleeding. Platelets adhere to damaged arteries via binding of GPIb to the A1 domain of von Willebrand Factor (VWF), under high shear. The anti-vwf, ARC1779, is considered to be active on damaged sites under shear, without systemic effects on platelets and bleeding. Aim: To determine the anti-thrombotic effects of ARC1779 in an ex-vivo model with blood from patients on double anti-platelet therapy. Methods: Venous blood from 27 patients under aspirin and clopidogrel and 5 normal volunteers was labeled with 111In-autologous platelets and perfused over injured porcine aortic segments in Badimon chambers at high shear rate. Blood was treated with nm ARC1779, 100 nm Reopro or placebo, 5 min before beginning the perfusion (therapy) or 10 min after (rescue). Platelet adhesion and aggregation, thrombus mass and P-selectin expression were measured by gamma counter, impedance aggregation, SEM and flow cytometry, respectively. Results: Under therapy, we observed a significant reduction in platelet adhesion (106/cm 2 ) for ARC1779 at 75 and 250 nm and for Reopro vs. placebo (4.8, 3.8 and 2.9 vs. 7.2, p <0.05). Lower thrombus mass was confirmed by SEM. Rescue treatments had no effects on adhesion. ARC1779 did not affect P-selectin expression compared to placebo (2.2% vs. 2.5%) neither platelet aggregation in response to TRAP-1 (10.5 vs. 11.8). Conclusion: ARC1779 achieves anti-thrombotic potency comparable to Reopro, without any systemic effects on platelet activation and aggregation. These properties make ARC1779 suitable for clinical development as a new anti-platelet agent. P2094 Prevalence and predictors of bleeding in patients on prolonged dual oral antiplatelet therapy undergoing DES implantation R. Rossini 1, G. Musumeci 1, C. Lettieri 2, N. Lortkipanidze 1, M. Romano 2, T. Nijaradze 1,A.Izzo 2, G. Biondi Zoccai 3, A. Gavazzi 1, D.J. Angiolillo 4. 1 Ospedali Riuniti di Bergamo, Bergamo, Italy; 2 Ospedale Carlo Poma, Mantova, Italy; 3 Division of Cardiology, University of Turin, Torino, Italy; 4 University of Florida-Shands Jacksonville, Jacksonville, United States of America Purpose: Bleeding has emerged as a predictor of early and late mortality after percutaneous coronary interventions. Although dual oral antiplatelet therapy with aspirin and clopidogrel is associated with a higher risk of bleeding, the prevalence and predictors of bleeding events in patients on prolonged (12 months) treatment after drug-eluting stent (DES) implantation has been poorly explored. Methods: All consecutive patients (n=579) undergoing DES implantation and discharged on dual antiplatelet therapy with aspirin and clopidogrel for 12 months at our Institution were included in this study. Patients were followed-up for 12 months and the prevalence and predictors of in-hospital and long-term bleeding events were evaluated. The impact of bleeding events on all cause death, major adverse cardiac events (MACE), definite stent thrombosis, and premature discontinuation of antiplatelet therapy were also assessed. Results: The incidence of in-hospital major and minor/nuisance bleeding was 1.2% and 3.7%, respectively. The incidence of cumulative long-term major and minor/nuisance bleeding was 1.9% and 6.7%, respectively. Multivariable analysis showed that in-hospital bleeding was predicted by previous peptic ulcer disease (odds ratio [OR]=7.55, p=0.040) and long-term bleeding was associated with female gender (OR=2.04, p=0.014), previous peptic ulcer disease (OR=2.21, p=0.037), and previous myocardial infarction (OR=2.10, p=0.012). The incidence of overall mortality and MACE was significantly higher in patients who experienced a major bleeding (11.4% vs 2.2%, p<0.001). Patients who had any bleeding event were more likely to prematurely discontinue antiplatelet therapy (73.7% vs 14.2%, p<0.001) and had a higher risk of definite stent thrombosis (7.1% vs 1.3%; p=0.023). Conclusions: In DES treated patients on long-term dual antiplatelet therapy bleeding events are more common in females and in patients with a prior history of peptic ulcer disease and myocardial infarction. Patients experiencing a bleeding event are more likely to discontinue prematurely antiplatelet therapy and have stent thrombosis.

29 Thrombosis and anti-thrombotic therapy 329 P2095 High-risk patients for GI bleeding on dual antiplatelet therapy in Spain are more like to receive PPI therapy than their American peers A. Lanas 1,L.Guastello 2, R. Casado 1, D. Saini 2, M. Polo-Tomas 1, J. Scheiman 2,A.DelRio 1. 1 Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain; 2 University of Michigan Medical Center, Ann Arbor, United States of America Background: Proton-pumpinhibitor (PPIs) therapy is now recommended for the prevention of upper GI complications (UGIC) in patients on antiplatelet therapywith > 1 risk factors. Patients undergoing percutaneous coronaryintervention (PCI) require aggressive dual antiplatelet therapy. No study has determined whether PPIs are being used appropriately to reduce GI bleeding risk in such patients and whether there are different prescription habits between countries. Methods: We have performed a parallel retrospective cross-sectional study of medical records at the University in USA and University in Spain. Patients admitted to the hospital for PCI in 2006 and 2007 were included. Data were extracted on: (1) patient demographics; (2)medications used; (3)indication for PPI use; and, (4)risk factors for GI bleeding (age 70; history of peptic ulcer disease; concurrent warfarin,corticosteroids 10 mg daily, or daily NSAIDs). Patients with 1 risk factor were defined as high-risk (HR) for GI bleeding. The proportion of patients discharged on PPI therapy was calculated and stratified by GI bleeding risk. OR were calculated using Chi squared test. Results: 612 patients were included. Patients from Spain were older than those from USA (67.3±9.1 vs. 62.5±11.6; p < 0.001); the proportion of HR patients for GI bleeding was different (Table). However, HR patients from Spain had a higher probability of receiving PPI therapy at hospital discharge (OR: 2.90; 95%CI: ; p = ) than their American peers. Variable USA patients (n=199) Spain patients (n=413) p-value High-risk patients (HR) 40% 51% PPI at admission 30% 31% PPI at discharge 41% 75% HR patients on PPI at admission 48% 58% HR patients on PPI at discharge 58% 80% Low-risk patients on PPI at discharge 30% 71% Conclusions: There are important differences regarding PPI prescription habits among cardiologists from two different centers in the USA and Spain when managing PCI patients on dual antiplatelet therapy. HR patients for GI bleeding from Spain had a significantly higher probability of receiving PPI therapy at hospital discharge than their American peers. P2096 Age-related differences in the antithrombotic therapy in patients with PCI. Results from the ALKK-PCI Registry A.K. Schwarz 1,R.Zahn 1, M. Hochadel 2, S. Kerber 3, K.E. Hauptmann 4, H. Mudra 5,H.Darius 6, J. Senges 2,U.Zeymer 1. 1 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Klinik für Kardiologie, Herz- und Gefäß-Klinik GmbH, Bad Neustadt, Germany; 4 Krankenhaus der Barmherzigen Brüder Trier, Trier, Germany; 5 Klinik für Kardiologie, Pneumologie und Intern. Intensivmedizin, Klinikum Neuperlach, Städt. Klinik., München, Germany; 6 Klinik für Innere Medizin - Kardiologie, Vivantes Klinikum Neukölln, Berlin, Germany Purpose: Antithrombotic therapy plays a crucial role in the therapy of patients with CAD. With increasing life expectancy, the number of elderly (>75 years) coronary patients is constantly increasing. This analysis examines possible agerelated differences in the antithrombotic therapy in patients with Acute Coronary Syndrome and elective PCI. Methods: We analyzed data of unselected patients with ST-elevation myocardial infarction (STEMI), Non-ST-elevation myocardial infarction (NSTEMI), unstable Angina (UA) and elective PCI from the ALKK-PCI Registry Results: In 2006, a total of consecutive patients with PCI were enrolled in 42 hospitals. Thereof, 33,7% (n=6762) were and 66,3% (n=20033) were < 75 years. Patients 75 with NSTEMI and STEMI received significantly less often a clopidogrel loading dose of 600 mg (NSTEMI: 40,1% vs. 47,6%, p<0,001; STEMI: 55,6% vs. 60,9%, p<0,01). Furthermore, elderly patients with UA, NSTEMI and STEMI were significantly less often treated with aspirin i.v. (UA: 30,3% vs. 35,3%, p=0,026; NSTEMI: 42,3% vs. 47,6%, p<0,01; STEMI: 64,0% vs. 69,1%, p<0,01). There was no difference found in clopidogrel loading dose and aspirin i.v. in pa- tients with elective PCI. The frequency of the administration of GPIIb/IIIa antagonists is shown in the table below. Conclusion: Elderly patients ( 75) with ACS receive significantly less intensive antithrombotic treatment with aspirin i.v., 600 mg clopidogrel loading dose as well as GPIIb/IIIa antagonists, while there is no difference in elective PCI. P2097 The in vitro effects of E5555, a PAR-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease V.L. Serebruany 1, M. Kogushi 2, D. Dastros-Pitei 3,M.Flather 4, D.L. Bhatt 5. 1 Johns Hopkins University, Towson, United States of America; 2 Eisai, LTD, Tsukuba, Japan; 3 Eisai, London, United Kingdom; 4 Royal Brompton Hospital, London, United Kingdom; 5 Brigham and Women s Hospital, Boston, United States of America Background: E5555 is a potent protease activated receptor (PAR-1) antagonist targeting the G-coupled receptor and modulating thrombin-platelet-endothelial interactions. The drug is currently being tested in Phase II trials in patients with coronary artery disease (CAD) with potential antithrombotic and antiinflammatory benefits. We investigated the in vitro effects of E5555 on platelet function beyond PAR-1 blockade in healthy volunteers and CAD patients treated with aspirin (ASA) with or without clopidogrel. Methods: Conventional aggregation induced by 5 μm ADP, 1 μg/ml collagen, 10 μm TRAP, whole blood aggregation with 1 μg/ml collagen, and expression of 14 intact, and TRAP-stimulated receptors by flow cytometry were utilized to assess platelet activity after preincubation with escalating concentrations of E5555 (20 ng/ml,50 ng/ml, and 100 ng/ml) in healthy volunteers, CAD patients treated with ASA, and CAD patients treated with ASA and clopidogrel combination (n=10, for each group). Results: E5555 inhibited a number of platelet biomarkers. Platelet inhibition was usually moderate, present already at 20 ng/ml, and was not seemingly dose-dependent without TRAP stimulation. E5555 caused 10-15% inhibition of ADP- and collagen-induced platelet aggregation in plasma, but not in whole blood. TRAP-induced aggregation was inhibited almost completely. PECAM-1, GP IIb/IIIa antigen, and activity withpac-1, GPIb, thrombospondin, vitronectin receptor expression, and formation ofplatelet-monocyte aggregates was also significantly reduced by E5555. TRAP stimulation caused dose-dependent effects between 20 and 50 ng/ml E5555 doses. P selectin, LAMP-1, LAMP,and CD40- ligand were not affected by E5555. Conclusion: E5555 in vitro moderately but significantly inhibits platelet activity beyond PAR-1 blockade. Antiplatelet potency of ASA alone, and the combination of ASA and clopidogrel are enhanced by E5555 providing rationale for their synergistic use. Selective blockade ofplatelet receptors suggests unique antiplatelet properties of E5555 as a potential addition to the current antithrombotic regimens. P2098 Thrombin generation curve in patients submitted to angioplasty with a combination of antiplatelet agents, fondaparinux and unfractionated heparin F. Schiele, E. Racadot, N. Meneveau, M.F. Seronde, V. Descotes- Genon, R. Chopard, J. Dutheil, J.P. Bassand. University hospital, Besancon, France Rationale: The thrombin generation curve (TGC) allows a dynamic measure of the thrombin generation, sensitive to platelet and coagulation activity. We compared TGC variables in patients pre treated with combinations of antiplatelet, Fondaparinux and unfractionated heparin (UFH). Methods: TGC was performed in 30 healthy volunteers (group 1) and in 141 patients treated according to their clinical situation: stable patients with aspirin and Clopidogrel (group 2), unstable patients with additional 2.5 mg Fondaparinux (group 3), with additional Tirofiban (group 4) and with 50U/kg of UFH (group 5). TGC was performed in platelet rich plasma by fluorimetry technique. The TGC parameters were: Endogenous Thrombin Potential (ETP= area under the curve), latence (time to initiation of thrombin), maximal concentration of thrombin (Cmax), time to reach this peak (T max) and maximal rising slope (slope). Results: Aspirin and Clopidogrel induced a 32% reduction in ETP (1 vs 2). When Fondaparinux was added, there was no change in ETP despite a decrease in slope and in Cmax (2 vs 3). When Tirofiban was added there was a 22% decrease Age GPIIb/IIIa antagonist p value Elective 75 6,9% n.s. <75 7,7% UA 75 14,9% <0,01 <75 20,8% NSTEMI 75 32,1% <0,00001 <75 43,0% STEMI 75 56,9% <0,0001 <75 64,2% n.s. = not significant. ETP, slope and Tmax in the 5 groups

30 330 Thrombosis and anti-thrombotic therapy in ETP, in Cmax and in slope (3, vs 4). After a bolus of 50U/kg UFH, no thrombin formation could be detected by TGC. There was no effect of Fondaparinux in coagulation times (comparable latence and Tmax between groups 2 and 3), but a significant decrease in Cmax and slope (figure). The modest reduction in ETG (50%) after Fondaparinux, even with double or triple antiplatelet therapy might explain the catheter thrombus formation and the need of additional bolus of UFH during PCI. Conclusions: TCG provide important information of the efficacy of antiplatelet and anticoagulant agents, particularly in patients treated with Fondaparinux and could be helpful for monitoring in the setting of PCI P2099 Elevated residual platelet reactivity to adenosine diphosphate and arachidonic acid in patients after myocardial infarction compared to patients after elective coronary stenting T.F. Althoff 1,M.Fischer 2, F. Knebel 1, E. Langer 3,S.Ziemer 3, G. Baumann 1. 1 Charite - Universitätsmedizin Berlin, Campus Mitte, Klinik für Kardiologie und Angiologie, Berlin, Germany; 2 Vivantes Klinikum im Friedrichshain, Department of Cardiology, Berlin, Germany; 3 Charite - Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin und Pathobiochemie, Berlin, Germany Purpose: Elevated residual platelet reactivity despite treatment with clopidogrel and acetyl salicylic acid (ASA) is associated with ischemic events after coronary stenting. For patients who have undergone coronary stenting for myocardial infarction, standard antiplatelet therapy equals that recommended for patients after elective coronary stenting for a minimum of four weeks. We sought to demonstrate that there is a persistent enhancement of residual platelet reactivity after myocardial infarction requiring a continued intensified antiplatelet regime. Methods: This study prospectively enrolled subjects after coronary stenting for myocardial infarction (STEMI or NSTEMI) and control subjects after elective coronary stenting. Platelet function testing was performed 48 hours and 30 days after coronary stenting. We assessed residual platelet reactivity with lighttransmittance aggregometry (LTA) using adenosine-5 -diphosphate (ADP, 5μM and 2,5μM) and arachidonic acid (AA) as agonists. Moreover we performed multiple electrode aggregometry (MEA), a point-of-care test recently developed, using ADP, ADP + prostaglandin E1 (PG) and AA as agonists. Results: A total of 66 patients were included. Fourty-eight hours after coronary stenting all measures of residual platelet reactivity were significantly elevated in the infarction group (Figure). Residual platelet reactivity to ADP was still consistently elevated at the 30 day follow up - albeit statistically not significant. Contrarily, residual platelet reactivity to AA significantly decreased over time in the infarction group. Early stent thrombosis (within 30 days) was documented in 91 (38%) patients, late stent thrombosis (from 31 to 365 days) in 39 (16%) patients and very late stent thrombosis (later than 365 days) in 107 patients (45%). Late stent thrombosis occurred steadily at a constant rate of % per year up to 5 years after stent implantation. Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2.75, 95% CI ), diabetes (2.08, ) and age (0.96, ). Conclusion: Up to 5 years after DES implantation, we observed a steady increase in the cumulative incidence of late stent thrombosis. P2101 Differential proteomic profiling of coronary stent thrombosis versus atherothrombosis K. Distelmaier, M. Kubicek, B. Redwan, C. Adlbrecht, O. Wagner, I.M. Lang. Medical University of Vienna, Vienna, Austria Purpose: Coronary stent implantation is reducing the risk of major adverse cardiac events. However, the occurrence of stent thrombosis (ST) remains a severe complication that results in abrupt coronary artery closure and acute myocardial infarction (AMI). The underlying molecular and cellular mechanisms of ST are not fully understood. Methods: We compared thrombus aspirated from the site of plaque rupture of 34 patients with ST and 39 patients with AMI due to atherosclerotic occlusion within a native coronary artery (time from first medical contact to balloon inflation 89±12 versus 81±16 minutes) by proteomic profiling. Results: While leukocytes were low at the culprit site in ST (-0.48±2.45 G/L), they accumulated at the site of atherosclerotic plaque rupture (1.71±4.41 G/L, p=0.019). In contrast to native thrombus, stent thrombus was characterized by high levels of von Willebrand factor, and platelet specific proteins e.g., Platelet glycoprotein I beta and Platelet glycoprotein IX and Platelet factor IV. Local complement activation was not detected in ST, with low levels of C-reactive protein, serum amyloid P, cell adhesion molecules, and low levels of other mediators of inflammation. Conclusion: Our results demonstrate different proteomic patterns in stent thrombus compared with native coronary artery thrombus, displaying proteins involved in platelet aggregation rather than inflammation. Platelet reactivity 48 h after stenting Conclusion: In patients undergoing coronary stenting for acute myocardial infarction, residual platelet reactivity remains elevated for at least 48 hours, indicating a need for a continued intensified antiplatelet therapy. P2100 Incidence of late stent thrombosis up to 5 years after implantation of drug-eluting stent in routine practice Y. Onuma 1, P. Wenaweser 2, J. Daemen 1, G. Hellige 2, K. Tsuchida 1, P. Juni 2,R.VanDomburg 1,P.W.Serruys 1, S. Windecker 2. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Department of cardiology, university of Bern, Bern, Switzerland Background: Stent thrombosis (ST) has been a safety concern of drug-eluting stents. Late ST was reported to occur at an annual rate of % up to 4 years after drug-eluting stent (DES) implantation. Little is known, however, about occurrence of ST more than 4 year after implantation of DES. Methods: Between April 2002, and December 2005, 8,146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3,823) or paclitaxel-eluting stents (PES; n=4,323) at two academic hospitals. We investigated the incidence and time course of stent thrombosis up to 5 years. Results: Angiographically documented stent thrombosis occurred in 237 patients of 8,146 patients with an incidence density of 0.78 per 100 person-years and a cumulative incidence at 5 years of 3.5%. Kaplan-meier survival estimate is presented in the figure. P2102 Fibrin clot structure/fibrinolysis and relationship to ischaemic heart disease and metabolic factors in older individuals with type 2 diabetes: the Edinburgh Type2DiabetesStudy R.A. Ajjan 1,K.A.Hess 1,A.M.Carter 1, A. Trehan 1, K.S. Standeven 1, P.J. Grant 1, R.M. Williamson 2, R.M. Reynolds 3,J.F.Price 3, M.W.J. Strachan 2. 1 University of Leeds, Leeds, United Kingdom; 2 Metabolic Unit, Western General Hospital, Edinburgh, United Kingdom; 3 The University of Edinburgh, Edinburgh, United Kingdom Thrombus formation represents the final step in the atherothrombotic process and studies have shown that fibrin clot structure predicts predisposition to cardiovascular events. This study assessed the relationship between clot structure/fibrinolysis and cardiac ischaemia as well as metabolic parameters in older individuals with type 2 diabetes (T2DM). Fibrin clot structure and fibrinolysis were assessed ex vivo in 255 T2DM patients [mean age 68.9 ( ); male=158] using a validated turbidimetric assay. Clot maximum absorbance (MA), a measure of clot density, and time from full clot formation to 50% lysis were recorded. Ischaemic heart disease (IHD) was defined as a history of myocardial infarction or symptoms of angina and/or medical treatment for this condition with or without ECG changes. After controlling for age and sex, MA correlated with a history of IHD (r=0.48, p=0.002), and lysis time correlated with plasma glucose and triglyceride levels (r=0.47, p=0.002 and r=0.42, p=0.007, respectively). Neither MA nor lysis time correlated with HbA1c, total cholesterol or cholesterol subfractions. Individuals with IHD (n=106) had higher MA at 0.338±0.01 as compared with those without an ischaemic history [0.307±0.01 au; p=0.02], whereas lysis time was not affected [781±37 and 755±37 seconds, respectively; p=0.62]. In a logistic regression model including MA, lysis time, age, sex and body mass index (BMI), only MA was an independent predictor of cardiac ischaemia with odds ratio of 1.40 (1.03, 1.92; p=0.03). In conclusion, an increase in clot MA is associated with a higher risk of myocardial

31 Thrombosis and anti-thrombotic therapy 331 ischemia in older individuals with T2DM. The correlation between lysis time and plasma glucose, but not HbA1c, suggests that fluctuation in glucose levels is more important at determining fibrinolysis potential than long term glycaemic control. Further clinical studies are warranted to fully elucidate the role of clot structure in predisposition to cardiac events in this group of individuals. P2103 The novel synthetic cyclic peptide (S,S) PSRCDCR- NH2, inhibits carotid artery thrombosis in rabbits V. Roussa 1, E.M. Stathopoulou 2, K. Egglezopoulos 3, N.D. Papamichael 1,V.Mousis 2, V. Tsikaris 2, C.S. Katsouras 1, K.K. Naka 1,A.D.Tselepis 2, L.K. Michalis 1. 1 University Hospital of Ioannina, Cardiology Department, Ioannina, Greece; 2 University of Ioannina, Department of Chemistry, Ioannina, Greece; 3 Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece Purpose: Platelet activation and aggregation, which play a key role in the pathogenesis of acute coronary syndromes, are primarily mediated by GPIIb/IIIareceptors binding to their ligands, through the RGD (Arg-Gly-Asp) sequence. GPIIb/IIIa inhibitors used in clinical practice compete to fibrinogen for the binding to the GPIIb/IIIa receptor through RGD-mediated interactions. We have recently synthesized a constraint cyclic peptide, (S,S) PSRCDCR-NH2, that exhibits potent non-rgd antiplatelet activity in vitro, possibly interacting with the ligand rather than the receptor. We studied the peptide s effect on a rabbit experimental thrombosis model. Methods: Three groups (n=5 in each group) were studied, receiving intravenously a. normal saline, 6ml/kg/h (control group), b. (S,S) PSRCDCR-NH2, 6 mg/kg bolus plus 2.4 mg/kg/h, c. eptifibatide, 900 μg/kg bolus plus 10 μg/kg/h. Carotid artery thrombus formation was induced by electrical stimulation, under continuous blood flow monitoring. Ex vivo platelet aggregation to 20 μm ADP and 500 μm AA in platelet rich plasma (PRP) was determined before (baseline) and at 60 min after the initiation of drug administration (instantly prior to electrical stimulation). Ninety minutes after electrical stimulation the carotid thrombus was removed and weighed. Blood loss was calculated by the amount of blood, gathered on a pre-weighed gauze, positioned on a standardized incision, performed on the anterior abdominal wall. Results: In the control group, carotid artery was totally occluded within 23.3±3.2 min after electrical stimulation. By contrast, in the (S,S) PSRCDCR-NH2 and eptifibatide groups, carotid artery blood flow at 90 min after electrical stimulation, was reduced to 45.9±1.5% and 35.3±2.0% respectively (p<0.001 vs control). Thrombus weight was significantly reduced in animals receiving (S,S) PSRCDCR-NH2 or eptifibatide vs control (1.5±0.3mg or 2.1±1.1mg vs 5.7±0.8mg, respectively, p<0.008 vs control). Platelet maximum aggregation to ADP and AA in the control group was not altered compared to baseline 60 min after electrical stimulation, whereas was significantly inhibited in the (S,S) PSRCDCR-NH2 and eptifibatide groups by 42.1±3.1 and 38.3±11.0% to ADP (p<0.005 vs control), and 75.6±12.0 and 40.0±11.1%, to AA (p<0.007 vs control). There was no significant increase of blood loss observed in (S,S) PSRCDCR-NH2 and eptifibatide groups compared to control. Conclusions: (S,S) PSRCDCR-NH2, a non-rgd novel cyclic peptide, reduces experimental thrombus formation in rabbits by inhibiting platelet aggregation, without affecting bleeding assays. P2104 A proinflammatory and prothrombotic environment in young individuals with type 1 diabetes: the effects of glycaemic control K.A. Hess, M. Mathai, T. Koko, K.F. Standeven, P. Holland, A.M. Carter, F. Phoenix, P.J. Grant, R.A. Ajjan. University of Leeds, Leeds, United Kingdom C-reactive protein (CRP) and complement C3 are both predictors of cardiovascular events, and the latter is possibly a better indicator of arteriosclerotic burden. In addition to inflammatory molecules, fibrin clot structure has been linked to cardiovascular disease, as compact clots are associated with premature and more severe atherothrombotic conditions. Although the atherosclerotic process starts at an early age, little is known about CRP and C3 plasma levels in younger individuals with type 1 diabetes (T1DM). Also, studies investigating blood clot structure in this cohort are still lacking. The present work analyses CRP and C3 plasma levels and evaluates fibrin clot structure in children with T1DM and investigates the effects of improving glycaemic control in young adults with this condition. ELISA was used to determine CRP and C3 plasma levels in 30 Type 1 DM children [14 yrs (range 11-17)] and 17 age matched controls, whereas fibrin clot structure was studied using a validated turbidimetric assay. The above parameters were further assessed in 18 young adults [23 yrs (range 18-26)], before and after improving glycaemic control. T1DM children had higher C3 levels (mean±sem) compared with controls (1.13±0.24 versus 0.83±0.24 mg/ml respectively; p<0.001), whereas the difference in CRP levels failed to reach statistical significance (0.85±1.36 versus 0.5±1.21 mg/l respectively; p=0.06). Clot final turbidity (FT), an indicator of clot density, was higher in diabetes children at 0.38±0.01, compared with controls (0.31±0.02;p<0.01). In young adults with T1DM, a reduction of HbA1c from 10.5% to 9.2% (p<0.05) was associated with a decrease in C3 levels from 1.09±0.05 mg/ml to 0.96±0.05 mg/ml (p<0.05) but had no effect on plasma CRP levels. Improving glycaemic control was associated with a reduction in FT from 0.30±0.02 to 0.26±0.02 (p<0.05), demonstrating the formation of less compact clots. Analysing all diabetes individuals together, clot FT correlated positively with C3 plasma levels (r=0.39, p<0.01) but not CRP, suggesting an interaction between C3 and clot structure. This is the first report describing a denser ex vivo clot structure and elevated C3 levels in children with T1DM, further confirming that the vascular inflammatory/thrombotic process starts at a young age in individuals at risk. Moreover, the drop in clot FT and C3 plasma levels after improving glucose control, suggests that early glycaemic intervention is important to prevent long term cardiovascular complications, a concept backed by clinical outcome studies. P2105 Effect of edoxaban (DU-176b) on thrombin generation and platelet activation in shed and venous blood with fondaparinux as active comparator M.M. Samama 1,M.Wolzt 2,K.Ogata 3, J. Mendell 4, S. Kunitada 4. 1 Hotel Dieu University Hospital, Paris, France; 2 Medical University of Vienna, Vienna, Austria; 3 Daiichi Sankyo Co., Ltd., Tokyo, Japan; 4 Daiichi Sankyo Pharma Development, Edison, United States of America Purpose: The shed blood model allows for the study of activated coagulation at a site of standardized tissue injury due to local release of tissue factor which may add insight into pathophysiological states. Edoxaban is an oral, direct factor Xa (FXa) inhibitor in development for stroke prevention in atrial fibrillation patients. The aim of this study was to investigate the effect of 3 doses of edoxaban on markers of coagulation in shed and venous blood compared with placebo and fondaparinux, an active comparator. Methods: Healthy, male subjects (n = 100) were randomized to either single doses of edoxaban (30, 60 and 120 mg PO), placebo or fondaparinux (2.5 mg SC). Primary objective was comparison of various assays for coagulation including prothrombin fragment 1+2 (F1+2), thrombin-anti-thrombin (TAT) and platelet activation [β-thromboglobulin (β-tg)] in venous and shed blood, obtained after percutaneous incision, for edoxaban, placebo and fondaparinux. Secondary objectives included pharmacokinetics, blood volume and safety of edoxaban. Results: There was a rapid and sustained reduction in F1+2, TAT and β-tg following edoxaban mg in both venous and shed blood. Reductions after fondaparinux were significantly less marked. Baseline-corrected F1+2, TAT, and β-tg values remained decreased for edoxaban up to 24 hours for shed blood but were less pronounced in venous blood. The treatments were well tolerated with a few cases of mild bleeding distributed across the 4 active treatment arms. Conclusions: Edoxaban at single doses up to 120 mg causes rapid and sustained inhibition of coagulation up to 24 hours as demonstrated by decreased F1+2, TAT and β-tg in the shed blood model which approximates a procoagulant pathophysiological state. P2106 Concomitant administration of low-dose rivaroxaban - an oral, direct Factor Xa inhibitor - with clopidogrel and acetylsalicylic acid enhances antithrombotic efficacy in rats E. Perzborn, E. Fischer, U. Lange, M. Harwardt. Global Drug Discovery, Cardiology Research, Bayer Schering Pharma, Wuppertal, Germany Purpose: Rivaroxaban an oral, direct Factor Xa inhibitor is currently undergoing phase III studies for the secondary prevention of acute coronary syndromes in patients receiving acetylsalicylic acid (ASA) or ASA and a thienopyridine (ATLAS2 TIMI51). The present study assessed the effects of low doses of rivaroxaban, the thienopyridine clopidogrel, ASA, or their combinations, on arterial thrombosis and haemostasis in a rat arteriovenous (AV)-shunt model. Methods: The effects of intravenous rivaroxaban (0.01, 0.03, and 0.1 mg/kg; study A, B and C, respectively), oral clopidogrel 1 mg/kg, oral ASA 3 mg/kg and their combinations on thrombosis were investigated in a rat AV-shunt model. The shunt was located between the right common carotid artery and the left jugular vein. Bleeding times were measured in a rat tail-transection model. Results: Rivaroxaban dose dependently reduced thrombus formation, with an ED 50 of 0.33 mg/kg. Thrombus formation was not significantly inhibited by low doses of rivaroxaban (0.01 and 0.03 mg/kg) or ASA alone, but was moderately inhibited by clopidogrel (28 35%). Addition of either ASA or low doses rivaroxaban to clopidogrel did not enhance its antithrombotic effects. However, the combinations of either low dose of rivaroxaban (0.01 and 0.03 mg/kg) with ASA resulted in a significant reduction of thrombus formation (24%, p<0.05; and 37%, p<0.001, respectively). Addition of these same two low doses of rivaroxaban to the com-

32 332 Thrombosis and anti-thrombotic therapy bination of clopidogrel and ASA resulted in a slight further increase (43%) in the antithrombotic effect. Combining an effective dose of rivaroxaban (0.1 mg/kg) to either ASA or clopidogrel, or to the combination of ASA and clopidogrel, increased the antithrombotic effect to 39, 52 and 51%, respectively (p<0.001 vs control). The antithrombotic efficacy of the combination of rivaroxaban and ASA was similar to that of the combination of ASA and clopidogrel (37%, p<0.001 vs control). Rivaroxaban or ASA alone did not affect bleeding times, but there was a slight, non-significant increase in bleeding time with clopidogrel alone ( fold vs control). Addition of rivaroxaban (either 0.03 or 0.1 mg/kg) to the combination of clopidogrel and ASA slightly increased bleeding time beyond the increase observed with clopidogrel alone, but this effect did not reach statistical significance (2.8- and 2.5-fold vs control, respectively). Conclusion: These results suggest that low doses of rivaroxaban co-administered with either ASA or the combination of clopidogrel and ASA may have greater antithrombotic effect than the individual treatments. P2107 High Density Lipoprotein (HDL) from healthy subjects, but not from patients with coronary artery disease, exerts anti-thrombotic effects on human endothelial cells E.W. Holy 1,C.Besler 1,G.G.Camici 2, T.F. Luescher 1, U. Landmesser 1, F.C. Tanner 1. 1 University Hospital Zurich, Zurich, Switzerland; 2 Inst. of Physiology, University of Zurich-Irchel, Zurich, Switzerland Background: Arterial thrombus formation is determined by the balance between pro- thrombotic mediators such as tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1), and anti-thrombotic factors like tissue factor pathway inhibitor (TFPI) or tissue plasminogen activator (tpa). Native HDL from healthy subjects (HS) has anti-thrombotic properties; however, it remains unknown whether this is the case for HDL from patients with stable coronary disease (CAD) or acute coronary syndrome (ACS). Methods: HDL was isolated by sequential ultracentrifugation from HS and patients with CAD and ACD. The effects of HDL (50 μg/ml) on TF, TFPI, and PAI-1 expression in human endothelial cells were determined by Western blot analysis; tpa release was measured by ELISA. Results: HDL from HS impaired thrombin-induced TF expression (-45±5%, p<0.05, n=16) and activity (-33±8%, p<0.05, n=7); in contrast, HDL from CAD and ACS patients did not (p=ns, n=12 and n=8). Similarly, HDL from HS increased TFPI expression by 2-fold (p<0.01, n=8), while HDL from CAD and ACS patients had no effect (p=ns). HDL from HS enhanced tpa release (+26±3%; p=0.05, n=8); in contrast, HDL from CAD and ACS patients did not (p=ns, n=6). Furthermore, HDL from HS did not affect PAI-1 expression, while HDL from CAD patients enhanced PAI-1 expression by 62% (p<0.05 vs. healthy, n=12) and HDL from ACS patients by 2 fold (p<0.05 vs. control and p<0.05 vs. healthy, n=8). Pretreatment with the inhibitor of NO formation, L-NAME (100 μm), abolished the anti-thrombotic effects of HDL from HS on TF, TFPI, and tpa expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of HDL from HS on TF, TFPI, and tpa. Conclusion: This study demonstrates that HDL from healthy subjects exerts antithrombotic effects on endothelial cells. In contrast, HDL from CAD and ACS patients loses these antithrombotic properties and instead enhances PAI-1 expression, thereby becoming pro-thrombotic. This observation might be highly relevant for HDL-targeted therapies. P2108 Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism is associated with atherothrombotic complication after drug-eluting stent implantation J.-W. Suh 1,H.-S.Kim 2,J.-S.Park 2, H.-J. Kang 2, I.-H. Chae 1, D.-J. Choi 1. 1 Seoul National University Bundang Hospital, Seongnam, Korea, Republic of; 2 Seoul National University, Seoul, Korea, Republic of Background: Single nucleotide polymorphisms (SNPs) of vitamin K epoxide reductase complex subunit 1 (VKORC1) was reported to have association with arterial vascular disease. We investigated whether SNP of VKORC is associated with clinical outcomes among patients who underwent drug-eluting stent (DES) implantation. Methods: We prospectively collected genomic DNA in patients who underwent DES deployment from Sep 2003 to Dec 2006 and compared clinical outcomes according to their VKORC1 genotype at the locus (rs ). The primary end-point was composite of atherothrombotic events [cardiac death, myocardial infarction, and non-hemorrhagic stroke]. Results: Mean follow-up duration was 631±251 days. Genotyping was completed in 764 cases (TT genotype (n=640, 83.8%) vs. non-tt (CC or CT) genotype (n=124, 16.2%)). Non-TT group showed more composite events than TT group (7.3% vs. 3.0%, p=0.032). In the Cox regression analysis, non-tt genotype of VKORC gene was a significant predictor of atherothrombotic events (Hazard ratio 2.56, 95% confidence interval ). In the event-free survival analysis, non-tt group also showed significantly poorer cardiovascular events-free survival rate than TT group (p=0.02). Conclusions: VKORC1 genotype is associated with cardiovascular events in patients with DES implantation, suggesting the role of coagulation system. P2109 The impact of the genetic polymorphism G455A on the b-chain fibrinogen gene on thrombotic process in patients with coronary artery disease D. Tousoulis, N. Papageorgiou, C. Antoniades, G. Hatzis, A. Miliou, A. Giolis, A. Antonopoulos, C. Tentolouris, C. Toutouzas, C. Stefanadis. 1st Cardiology Unit Hippokration Hospital Athens, Athens, Greece Purpose: Evidence suggests that fibrinogen plays a critical role in atherosclerosis. A genetic polymorphism on fibrinogen chain B, the G455A, has been associated with fibrinogen levels in healthy individuals, but its effect on thrombotic process in patients with coronary artery disease (CAD) is unclear. In the present study we examined the effect of this polymorphism on prothrombotic profile of patients with CAD. Methods: The study population consisted of 243 individuals, 191 of which with angiographically documented CAD and the rest with angiographically documented absence of any significant coronary stenoses. The G455A polymorphism was detected by polymerase chain reaction (PCR) and appropriate restriction enzymes. Fibrinogen levels were measured by immunonephelometry, while other factors of thrombosis such as plasma levels of d-dimers, factors V and X, plasminogen and thrombin time were measured by standard coagulometry techniques. Results: The genotype distribution was GG: 48.2%, AG: 40.3%, AA: 11.5% and GG: 50.0%, AG: 34.6%, AA: 15.3% for CAD patients and healthy individuals respectively. Among CAD patients AA patients had significantly higher levels of fibrinogen than GA patients. There was no difference among other genotypes (AA: 517.5±144.0, AG: 434.0±132.2, GG: 443.0±121.0 mg/dl p<0.05 for AAvsGA, p=ns for AAvsGG, GAvsGG). Plasma plasminogen levels did not differ across the three genotypes GG (106.3±19.1u/ml) compared to GA (112.5±20.0 u/ml) and AA (115.8±11.5u/ml), p=ns for all. Moreover, there was no significant difference in plasma levels of factor X (AA: 94.1±20.3 vs GA: 91.6±26.1 vs GG: 101.2±23.2%, p=ns for all), factor V (AA: 124.9±28.4 vs AG: 125.7±34.4 vs GG: 122.0±32.2%, p=ns for all), thrombin time (AA: 19.5±3.2 vs GG: 20.8±18.4 vs GA: 19.0±1.7 sec, p=ns) and D-dimers (AA: 551.7±321.5 vs GA: 511.4±526.7 vs GG: 616.3±817.4 mg/l p=ns). Conclusions: Genetic polymorphism G455A on fibrinogen b-chain gene affects fibrinogen levels, but has no effect on other thrombotic markers. These findings indicate that this polymorphism may play important role in the process of atherothrombosis by affecting only fibrinogen levels, but not other thrombotic parameters. P2110 Effects of direct thrombin or factor Xa inhibition on clot thrombogenicity in vitro: Comparison of dabigatran with rivaroxaban and apixaban J. Van Ryn, M. Kink-Eiband, I. Kuritsch, W. Wienen. Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany A thrombus can remain active for hours to days, mostly due to surface-bound activated clotting factors that are protected from inhibition by heparin therapy. In contrast, the new, small molecule inhibitors of either thrombin (dabigatran) or factor Xa (rivaroxaban and apixaban) can inhibit clot-bound thrombin or factor Xa, respectively. However, it is unknown if this direct inhibition results in reduced clot thrombogenicity as measured by the ability of the thrombus to convert fibrinogen into fibrin. This study investigated the ability of dabigatran, a direct inhibitor of thrombin, or rivaroxaban and apixaban, direct inhibitors of factor Xa to reduce the thrombogenicity of a clot, measured as inhibition of FPA generation in human plasma in vitro. Clots were generated in human platelet rich plasma supplemented with Ca 2+, and then extensively washed in buffer to remove all trapped FPA. Clots were then transferred to 0.5 ml plasma containing either dabigatran, rivaroxaban or apixaban and further incubated for 1 hr at 37 C. Clots were then removed and the reaction was stopped using bentonite. Fibrin formation was measured as FPA release using ELISA. In separate experiments, prothrombin fragment 1+2 (F1+2) was measured as an indices of thrombin generation to directly assess effectiveness of factor Xa inhibitors in the clot. In untreated plasma containing a thrombus, there was an average of 30±5 ng/ml of FPA generation (mean ± SE, n=8). In plasma containing increasing concentrations of dabigatran (1nM-10 μm), there was a concentration-dependent inhibition of FPA, with an IC50 of 127 nm, n=4/conc. Apixaban and rivaroxaban had no effect on FPA release when tested at concentrations up to 10 μm. FPA release with both inhibitors was similar to control, untreated plasma containing a clot, resulting in generation of ng/ml FPA. Prothrombin F1+2 generation was not elevated when the thrombus was added to plasma, even in the absence of treatment. Only when clots were placed in a buffer system with factor Va and prothrombin supplementation, could an elevation of prothrombin F1+2 be measured. In this purified system, the factor Xa inhibitors were shown to inhibit prothrombin F1+2. This study demonstrates that a thrombus alone is thrombogenic when added to plasma and can induce fibrin formation and that thrombin in an existing clot plays a key role in thrombus propagation. Dabigatran could inhibit this thrombogenicity by directly binding thrombin in the clot, this occurred at clinically relevant concen-

33 Thrombosis and anti-thrombotic therapy / Controversial issues in the management of acute coronary syndromes 333 trations. The factor Xa inhibitors, rivaroxaban and apixaban had no effect in this experimental setting. P2111 Heparin induced thrombocytopenia after cardiac surgery and the tale of complications A. Neykova, B.T. Tzvetkov, M.K. Kirsch. AP-HP - Hopital Henri Mondor, Creteil, France Heparin-induced thrombocytopenia (HIT) occurs in 1 to 3% of patients after cardiac surgery. HIT induces a prothrombotic state which may adversely affect postoperative outcomes. It may be complicated in 30 75% of cases by a paradoxical thrombotic syndrome (HITT), either arterial or venous. The aim of the present study was to evaluate the rate of thrombosis and other complications hemorrhagia and infections in case of HIT after cardiac surgery and and compare with other patients with thrombocytopenia. In this study we included 29 patients with HIT after cardiac surgery and 70 patients after cardiac surgery with thrombocytopenia without HIT (control group). Those are all 29 patients with HIT in our clinic in the period HITT is present in 7 patients (22.2%), and three of them are with multiple sites of thrombosis. Three patients of the control group present a thrombosis event. All patients are treated with non fractioned heparin and almost all (except 2 patients) of HIT cases are treated by danaparoid as alternative anticoagulation. The data from HIT patients and the control group were compared using t-test and chi-square test for continuous and categorical variables, respectively. The mean time of HIT diagnosis is on day 8 after the surgery. We observed a very low incidence of thrombosis in our HIT group, 22.2%. The p value comparing the rate of thrombosis in the two groups is on the limit of significance, N=97, p=0.04. There are no significant differences between groups comparing the rate of hemorrhagia and infections, N=97, p=1 and p=0.36. The rate of all complications is significantly higher in HIT group χ 2 =12.10, df=1, N=97,p= HIT is a serous disease, witch favored clinically important events in the postoperative setting of cardiac surgery. P2112 Patient s clinical characteristics according to clopidogrel and aspirin response tested in the cath lab during coronary stenting: data from the Verifynow french registry (Verifrenchy) C. Thuaire 1, G. Range 1, M. Kerkeni 2,R.Berthier 3, E. Teiger 4, J.P. Claudel 5, N. Delarche 6, P. Brunel 7, F. Albert 1, J.P. Collet 8. 1 Hopitaux de Chartres, Chartres, France; 2 Clinique Saint-Hilaire, Rouen, France; 3 Hôpital de Corbeil, Corbeil, France; 4 AP-HP - Hopital Henri Mondor, Creteil, France; 5 Infirmerie Prostestante, Lyon, France; 6 Hôpital de Pau, Pau, France; 7 Nouvelles Cliniques Nantaises, Nantes, France; 8 Pitie-Salpetriere Hospital (AP-HP), Paris, France Purpose: An impaired response to anti-platelet treatment is associated with an increased risk of adverse events after PCI. We prospectively evaluated clinical factors influencing clopidogrel and aspirin response in patients included in the Verifynow French Registry (Verifrenchy). Methods: Verifrenchy is a large prospective multicentric registry of 1001 patients undergoing coronary stenting in 20 French centers evaluating the aspirin and clopidogrel response tested with point-of-care method (Verifynow/Accumetric) in the cath lab. Non clopidogrel response was defined as P2Y12 platelet inhibition < 15%. Non aspirin response was defined as ARU 550. Results: In this cohort, 36% were clopidogrel non responder and 8.6% were aspirin non responder Significant Patients characteristics according to Clopidogrel and Aspirin response are listed below. Clinical factors/antiplatelet response Variable Total Clopidogrel Clopidogrel p-value cohort non responder responder n=1001 n=360 n=641 Age (years) 66,5 68,3 65,5 <0,001 BMI, kg/m 2 26,5 27,2 26,2 <0,001 Diabetes, n (%) 181 (18,1) 127 (35,3) 134 (20,9) <0,001 Current smoker, n (%) 181 (18,1) 49 (13,6) 132 (20,6) 0,02 Clopidogrel pretratment > one week, n (%) 534 (53,4) 152 (42,2) 383 (59,8) < 0,001 Clopidogrel loading dose (mg) 441,7 423,5 454,1 0,04 Aspirin non response, n (%) 84 (8,6) 47 (13,6) 37 (5,9) <0,001 Variable Total Aspirin Aspirin p-value cohort non responder responder n=972 n=84 n=888 Male gender, n (%) 807 (83,3) 78 (92,9) 729 (82,1) 0,03 Clearance creatinin (μmol/ml/mn) 81,6 88, Aspirin pre-treatment > one week, n (%) 660 (68) 47 (56) 613 (69,1) 0,02 ACE-inhibitor, n (%) 524 (53,9) 34 (40,5) 490 (55,2) 0,01 Beta-blocker, n (%) 699 (71,9)) 52 (61,9) 647 (72,9) 0,03 Statin, n (%) 783 (80,6) 59 (70,2) 724 (81,5) 0,01 Clopidogrel non response, n (%) 345 (35,5) 47 (56) 298 (33,6) <0,001 Conclusions: Despite the differences in clinical characteristics influencing these antiplatelet responses, there is a significant link between aspirin and clopidogrel non response suggesting an in vivo antiplatelet interaction. CONTROVERSIAL ISSUES IN THE MANAGEMENT OF ACUTE CORONARY SYNDROMES P2113 Metoprolol administration pre-reperfusion reduces infarct size by diminishing myocardial reperfusion injury B. Ibanez 1,G.Cimmino 1, S. Prat-Gonzalez 1, G. Vilahur 2, R. Hutter 1,M.J.Garcia 1,V.Fuster 1,J.Sanz 1,L.Badimon 2, J.J. Badimon 1. 1 Mount Sinai Hospital, New York, United States of America; 2 Hospital de Sant Pau, Barcelona, Spain The administration of metoprolol (MET) prior to coronary reperfusion has been shown to reduce myocardial infarction (MI) size; however the mechanisms of action remain elusive. In addition whether the oral post-reperfusion MET administration, as the current guidelines recommend, exert similar cardioprotective effect is unknown. Recent evidences suggest that myocardial reperfusion injury significantly contributes to the final size of MI The aims of the present work were 1) to study the effect of MET administration on myocardial reperfusion injury and 2) to assess whether early oral post-reperfusion administration results in similar cardioprotective effect than the i.v. pre-reperfusion administration Methods: Yorkshire pigs (n=30) underwent a MI by 90 min LAD coronary occlusion. Animals were randomized to one of the following 3 strategies: prereperfusion MET (7.5mg i.v. 60 pre-reperfusion followed by 50mg/12h oral), postreperfusion MET (placebo i.v. plus 50mg/12h oral), or non-met (placebo i.v. and no further medication). 12 animals (4/group) were sacrificed at 24h for reperfusion injury analysis (neutrophil infiltration, myocardial apoptosis, and degree of salvage kinases activation). The remaining pigs underwent a Magnetic Resonance Imaging (MRI) at 3d for area at risk (AAR, % of LV on T2-weighted images) and infarct size (% of AAR showing delayed enhancement after gadolinium) Results: Despite similar AAR on MRI in the 3 groups, MI size was significantly smaller in the pre-reperfusion MET group (69±4% of AAR) than in the postreperfusion MET (87±6%, p=0.036 vs. the pre-reperfusion) and the non-met (93±4%, p=0.002 vs. the pre-reperfusion and p=0.4 vs. the post-reperfusion). Neutrophil infiltration was significantly (p<0.05) lower in the pre- than in the postand the non-met groups (0.27, 0.56 and 0.54 MPO units). Myocardial apoptosis (cleaved caspase-3 by western blot) was significantly (p<0.05) lower in the pre- than in the post- and the non-met groups (114, 153, and 140 arbitrary units respectively). Salvage kinases activation (phosph-akt by western blot) was significantly (p<0.05) higher in the pre- than in the post- and the non-met groups (118, 91, and 96 arbitrary untis respectively). Conclusions: In a large animal model of MI, the pre-reperfusion i.v. metoprolol administration resulted in significantly smaller MI size than the post-reperfusion oral administration. The smaller MI size was observed along with a significant reduction in myocardial reperfusion injury. Our results suggest that circulating levels of metoprolol at the time of reperfusion are necessary in order to attain cardioprotection. P2114 Lower rate of invasive revascularisation in acute coronary syndrome patients with significant stenosis on coronary angiography when angiography is performed on a diagnostics only hospital A. Hvelplund 1, S. Galatius 2, M. Madsen 3, J.N. Rasmussen 1, S. Rasmussen 1, J.K. Madsen 2, S.Z. Abildstrom 4 on behalf of The DANAMICS group. 1 National Institute of Public Health, Copenhagen, Denmark; 2 Gentofte Hospital, Hellerup, Denmark; 3 University of Copenhagen, Inst. of Public Health, Copenhagen, Denmark; 4 Glostrup University Hospital, Glostrup, Denmark Purpose: We studied the population of all acute coronary syndrome (ACS) patients with a significant stenosis on their coronary angiography (CAG) in order to evaluate differences in invasive revascularisation rate related to type of hospital where CAG was performed. Denmark (population 5.5 million) has a universal health insurance coverage system and uniform national guidelines for the treatment of ACS. In Denmark there are 5 hospitals with tertiary invasive centres performing both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). An additional 8 hospitals perform diagnostic coronary angiographies and a further 36 hospitals without these facilities receive patients with ACS. Methods: All patients hospitalised with a first ACS from January 2005 to December 2007 were identified in the National Patient Register. We included those patients who were found to have significant stenosis on their CAG, which was recorded in the Danish Heart Registry along with subsequent revascularisation. Information on comorbidity was also recorded. Information on education, personal income and vital status and previous medication was obtained from Statistics Denmark on an individual basis. Cox proportional-hazard models, with revascularisation within 60 days as outcome, was used to estimate the difference in revascularisation related to type of CAG hospital. Results: Of patients with first ACS in the period, were examined with CAG.

34 334 Controversial issues in the management of acute coronary syndromes Of 2207 patients having significant stenosis in one or more vessels from the diagnostics only hospitals there were 78% receiving revascularisation vs. 91% of the patients from the invasive hospitals. Adjusting for known differences between the groups such as gender, age, number of stenotic vessels and the other variables mentioned, there was a hazard ratio (HR) of 0.37 (95% CI , p < ) of receiving revascularisation for the patients examined with CAG in the diagnostics only hospitals in comparison to those examined in the invasive centres. Excluding the acute CAGs (day 0-1) we found 2070 patients having significant stenosis from the diagnostics only hospitals and 78% received revascularisation vs. 84% of the 4661 patients from the invasive hospitals. This gave a HR of 0.55 (95% CI , p < ). Conclusion: Patients hospitalised with a first ACS who have significant stenosis on their CAG are treated with a less aggressive invasive approach if the CAG is performed in a hospital with only diagnostic CAG facilities. The difference persists when excluding the acute CAGs which are more often performed in the invasive centres. P2115 Primary PCI with a new drug eluting stent: mid term results of multicentre NOBORI STEMI study F. Fath-Ordoubadi 1,A.Serra 2,Z.Xu-Ming 3, P. Laanmets 4, N. Jagic 5, J. Monsegu 6, D. Hildick-Smith 7, J. Guarinos 8, S. Hoffmann 9, G.B. Dnazi 10 on behalf of NOBORI STEMI study group. 1 Manchester Royal Infirmary, Manchester, United Kingdom; 2 Hospital del Mar, Barcelona, Spain; 3 Kiang Wu Hospital, Macau, Macau SAR, People s Republic of China; 4 North-Estonia Regional Hospital, Tallinn, Estonia; 5 Clinical Centre Kragujevac, Kragujevac, Serbia; 6 Val de Grace, Paris, France; 7 Sussex Cardiac Centre, Brighton, United Kingdom; 8 Hospital Joan XXIII, Taragona, Taragona, Spain; 9 Vivantes Netzwerk für Gezundheit GmbH, Berlin, Germany; 10 Ospedale Maggiore Policlinico, Milan, Italy Purpose: Use of drug eluting stents (DES) in patients presenting with ST elevation myocardial infarction (STEMI) is still controversial, despite their efficacy in reducing restenosis. Our aim was to study safety of a new DES, in this vulnerable population. Nobori stent employs biodegradable polymer and Biolimus A9 applied only abluminally. Once polymer is degraded and the drug is completely released this stent is expected to behave similarly to BMS. Therefore it is hypothesized that besides its proven efficacy this stent could have very good safety profile. Methods: NOBORI 2 is a multicentre study involving 125 centres across Europe and Asia. Out of the first 1000 consecutive patients treated with Nobori stent in this registry study 234 had STEMI while 524 had stable angina or silent ischemia (SA). Data were entered electronically and source data verification is planned for all patients. Primary endpoint is MACE (composite of death, MI, and TLR), at 6 and 12 months; secondary endpoints include rate of death/mi, stent thrombosis, TVR at 1, 6 and 12 months and yearly up to 5 years. Results: In the STEMI group, compared to the SA group, mean age (63±12 vs 64±10 years), sex (male: 79% vs 82%), proportion of diabetics (25.1 vs 31.1%), smokers (58 vs 51.1%), average number of lesions (1.37±0.64 vs 1.4±0.74), and stents per patients (1.65±1.18 vs 1.72±1.13) were comparable. However, patients with STEMI were less likely to have hypertension (53.9 vs 70%, p<0.001), dyslipidemia (56.4 vs 74.2%, p<0.001) and previous revascularisation (25.1 vs 44.8%, p<0.001). At 1 month follow-up hierarchical MACE rate was low in both groups (1.65 in STEMI vs 1.15% in SA). One patient (0.4%) died in the STEMI group, 3 patients (1.2%) had reinfarction and 1 patient (0.4%) underwent TLR. There were 5 MIs (0.9%) and 4 TLRs (0.8%) in the SA group. By the time of the presentation complete 6 months follow-up will be available, including adjudicated events and stent thrombosis. Conclusion: These preliminary data show a favourable outcome trend for Nobori stent in patients treated for STEMI. Longer term data will be available at the time of presentation. P2116 Procedural characteristics of radial versus femoral arterial access during primary percutaneous coronary intervention in STEMI patients W. Dorniak 1, G.D. Pinna 2, J. Klaudel 1,Z.Lajkowski 1, K. Pawlowski 1, W. Krasowski 1, G. Raczak 3. 1 St Wojciech-Adalbertus Hospital, Gdansk, Poland; 2 Fondazione S. Maugeri Clinica Del Lavoro e della Riabilizatione, Montescano, Italy; 3 Medical University of Gdansk, Gdansk, Poland Background: Primary percutaneous coronary intervention (PCI) in STEMI patients is usually performed via femoral artery. There are data suggesting that the hemorrhagic risk of the procedure can be significantly reduced if the radial artery approach is chosen. Safety and effectiveness of this approach are well documented for elective procedures, but concerns persist on the potential reperfusion delay when it is applied to STEMI pts. Aim: To assess the immediate angiographic results and duration of primary PCI for STEMI, performed via radial vs. femoral arterial access. Methods: 223 consecutive STEMI patients with <12 hour anginal pain, admitted to hospital between and , randomized to either femoral (n=107) or radial artery (n=116)approach. Patients randomized to radial approach were switched to femoral approach if arterial arch patency (Allen s test) proved abnormal. Results: Good immediate angiographic result (TIMI3) was achieved in 94% and 95% of patients in radial and femoral group, respectively ( p=0.99). Total procedural time and time to first balloon inflation [min] following the femoral or radial approach, were [median (interquartile range)] 37 (32-44) and 39 (32-45) (p=0.93), and 22 (19-25) and 22 (20-24) (p=0.92), respectively. Total cannulation time (patient lying on the table to arterial access) [min] was 7.8 ( ) and 8.2 ( ) in the femoral and radial group, respectively (p=0.40). Fluoroscopy time during angiography [min] was 0.9 ( ) and 1.2 ( ) for the femoral and radial approach, respectively (p< ). Total fluoroscopy time [min] was 5.9 ( ) and 6.1 ( ) for the femoral and radial approach, respectively (p= 0.75). The amount of contrast media [ml] used in both groups was very similar: 150 ( ) and 140 ( ); p= Betweengroup switch rate was 3% in initially femoral and 4% in initially radial group. Conclusion: These results show that radial approach is equally effective in terms of reperfusion rates and is not related to reperfusion delay as compared to femoral approach in STEMI patients treated by primary PCI. P2117 Longer distance from home to invasive centre is associated with lower rate of coronary angiographies following acute coronary syndrome A. Hvelplund 1, S. Galatius 2, M. Madsen 3, J.N. Rasmussen 1, S. Rasmussen 1, J.K. Madsen 2,S.Z.Abildstrom 4 on behalf of The DANAMICS group. 1 National Institute of Public Health, Copenhagen, Denmark; 2 Gentofte Hospital, Hellerup, Denmark; 3 University of Copenhagen - Institute of Public Health, Copenhagen, Denmark; 4 Glostrup University Hospital, Glostrup, Denmark Purpose: We studied the unselected population of all acute coronary syndrome (ACS) patients of an entire nation in order to evaluate differences in coronary angiography (CAG) rate. Denmark (population 5.5 million) has a universal health insurance coverage system and uniform national guidelines for the treatment of ACS. There are 5 tertiary invasive centres performing CAG, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), 8 hospitals with diagnostic units performing CAG only, and a further 36 hospitals without these facilities receiving patients with ACS. We investigated if there was a difference in the rate of CAG after admission with ACS depending on distance between place of residence and invasive centre. Methods: All patients, hospitalised with a first ACS from January 2005 to December 2007, were included from the National Patient Register. Age, gender and information on co-morbidity were recorded for each patient. Information on distance from each patients place of residence to the nearest invasive centre was obtained from Statistics Denmark along with information on education, family income, previous medicine use and vital status. Patients were grouped in tertiles according to distance to centre. Outcome was CAG within 60 days identified in the Danish Heart Registry. Cox proportional-hazard models were used to estimate the difference in the rate of CAG related to distance when adjusting for explanatory variables. Results: Of patients with first ACS 33% lived less than 21 km from one of the 5 invasive centres, 33% lived between km, and 33% >64 km away. Longer distance to an invasive centre was associated with less invasive examination after the event. The cumulative incidence of CAG was 77% for the third living closest to a centre vs. 68% for those living farthest away. When adjusting for patient characteristics such as gender, age, income, education, admission year, previous revascularisation, co-morbidity and medicine use there was a hazard ratio (HR) of 0.79 (95% CI , p < ) of receiving CAG for the patients living farthest away in comparison to those living closest to the centres. Conclusion: Despite uniform national guidelines, patients hospitalised with a first acute ACS are treated with a less aggressive invasive diagnostic approach the farther away they live from an invasive centre. When planning the management of ACS patients it is imperative that all parts of the healthcare system perform equally well so patients can rely on the same optimal treatment regardless of their place of residence. P2118 In-hospital management and outcome of Acute Coronary Syndromes (ACS) in developing countries: results of the ACCESS registry G. Montalescot 1, M. Sobhy 2,S.Alam 3, C. Martinez-Sanchez 4, A. Escobar 5, N. Antepara 6, J.C. Nicolau 7, P. Blondin 8, A. Leizorowicz 9. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Alexandria University, Alexandria, Egypt; 3 American University, Beirut, Lebanon; 4 National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico; 5 Clinica Medellin, Medellin, Colombia; 6 Hospital Universitario, Caracas, Venezuela; 7 Heart Institute (InCor) - University of Sao Paulo Medical School, Sao Paulo, Brazil; 8 Medical Affairs Department Sanofi Aventis Intercontinental, Paris, France; 9 Universite Claude Bernard, Lyon, France Purpose: Randomized studies and registries in ACS are usually performed in

35 Controversial issues in the management of acute coronary syndromes 335 developed countries which have substantial health care resources. ACCESS is the first large international ACS registry performed in developing countries. Methods and Results: 19 countries (Algeria, Argentina, Brazil, Colombia, Dominican Republic, Ecuador, Egypt, Guatemala, Iran, Jordan, Kuwait, Lebanon, Mexico, Morocco, Saudi Arabia, South Africa, Tunisia, United Arab Emirates, Venezuela) enrolled ACS patients, 6320 with non-st elevation ACS (NSTE-ACS) and 5411 with ST elevation myocardial infarction (STEMI). Mean age was 59.6 years, 75% were males and 74% were non-caucasians. Risk factors were dominated by active smoking (n=4730, 41%) and diabetes (n=4208, 36%) while 57% had hypertension, 42% dyslipidemia and 28% a BMI>30. Prior MI (22%), heart failure (5%), peripheral vascular disease (5%) and stroke (4%) were the most frequently found in medical history. Health insurance coverage was governmental in 51% but 25% patients had no insurance coverage at all. At admission, an ECG was performed in 99.2% but 7.3% had no necrosis biomarker measured neither at admission nor during hospitalization. In STEMI, fibrinolysis was used in 2127 patients (39.3%), predominantly streptokinase (n=1517, 71.7%); 26% of the STEMI patients had primary or rescue PCI within the first 24 hours. In NSTE-ACS, a coronary angiogram was performed during hospitalization in 59% of patients, a PCI in 31% and CABG in 7%. In PCI patients, 94% received at least one stent, 44% being drug-eluting stents. Aspirin (94%), clopidogrel (81%), beta-blockers (78%), statins (91%), ACE-inhibitors (68%) were largely prescribed. In contrast, GPIIbIIIa inhibitors (17%), bivalirudin (0.1%) and fondaparinux (0.1%) were rarely used. The in-hospital mortality rate was 2.6% (3.9% in STEMI, 1.5% in NSTEACS, p<0.0001). After multivariable analysis, the factors most strongly associated with death were age, high heart rate, low blood pressure, high killip class, type of ACS (STEMI), non-use of betablockers or ACE inhibitors, use of amiodarone or insulin. Conclusion: ACS in developing countries seem to occur at a younger age with higher rates of smokers and diabetics than in western countries. Management is somewhat more conservative with low intervention rates, use of less expensive drugs but higher use of DES than expected, with finally low in-hospital mortality. Statins and antiplatelet agents were widely prescribed. Betablockers, thienopyridines and ACE inhibitors were associated with improved survival. P2120 Intramyocardial percutaneous stem cell injection guided by endocardial mapping in patients early after acute myocardial infarction K. Krause, K. Jaquet, C. Schneider, B. Koektuerk, K.-H. Kuck. Asklepios Clinic St. Georg, Hamburg, Germany Background: Intramyocardial cell injection has been demonstated to have superior effects on cell distribution and tissue retention compared to the intracoronary approach in preclinical studies. This first-in-man study aims to implement PICI in patients early after acute myocardial infarction (AMI). Methods: On day 10.5±5 after AMI and PCI (culprit lesion: 18 LCA, 2 RCA) 20 patients (mean 60.4±11.4 years) received bone marrow derived mononuclear cells in the vital low voltage region of the infarction area using left ventricular electromechanical mapping (EMM). We injected 2.0± cells including 1.0± CD45-/CD34+ stem cells in each patient. In a subgroup of 15 patients EMM was performed at 6-month follow-up. Echocardiography, laboratory data and clinical assessment (6-month and 12-month follow-up) were performed in all 20 patients. Results: None of the patients showed periprocedural complications or major adverse events related to the PICI during the 12-month follow-up. Baseline normalized unipolar voltage UV improved from 45.5±14.3% to 59.3±19.2% in the infarction area (p=0.002) and reduction of the low voltage area from 28.7±12% to 20.3±13.5% (p=0.016) in 15 patients with EMM follow-up after 6 months. Endocardial electrogram fragmentation showed no increase in the area of injection. There was no sustained ventricular tachycardia documented in the Holter-ECG s. During the 12-month follow-up in all 20 patients LVEF improved from 40.8±6.8% to 47,0±10,5%. P2119 Distal protection with thrombectomy reduced death and onset of heart failure at chronic state in patients with reperfused anterior myocardial infarction S. Hosokawa, Y. Hiasa, S. Miyazaki, R. Ogura, T. Takahashi, K. Kishi. Tokushima Red Cross hopital, Komatsushima, Japan Background: Studies have found conflicting results regarding the efficacy of distal protection with thrombectomy. Objective: We sought to determine the effect of distal protection on heart failure for patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Methods and Results: We performed 2D echocardiographic assessment 2 weeks (predischarge: baseline) and 6 months (chronic stage) after the onset of MI in consecutive 333 patients (114 patients with the distal protection: group DP, 219 without: group non-dp). Intravenous myocardial contrast echocardiography was underwent 2 weeks after PCI. Contrast defect was calculated as contrast defect area/myocardial area. All patients were followed for 4.25±0.7 years, and major adverse cardiac events (MACEs: death, re-hospitalization caused by heart failure) were found in 33 patients (10%). There are no significant differences between two groups in maximum CPK, ejection fraction and WMSI at baseline and 6month after PCI. However contrast defect of group non-dp was larger than that of group DP (15±11 vs 11±9, P=0.0034). Multivariate logistic analysis demonstrated that DP is independent negative predictor of MACEs after STEMI [RR (95%CI ), p=0.02]. Figure 1 Conclusions: These findings suggest that distal protection reduced death and onset of heart failure with reperfused anterior myocardial infarction. Distal protection preserves microvascular integrity; thus, it may represent a useful adjunct to pharmacotherapy EMM: injection points (dark spots) Conclusion: Intramyocardial percutaneous cell injection and left ventricular mapping in patients early after AMI was shown to be a safe procedure and is associated with improved electromechanical parameters and increased LVEF during a 12-month-follow-up. P2121 Proton Pump inhibitors and clopidogrel response on cardiovascular major events in patients after acute myocardial infarction. Data from the FAST-MI registry of the french society of cardiology T. Simon 1, P.H. Quandalle 2, J. Machecourt 3, R. Sader 4, L. Ledain 5, V. Bataille 6, P.H. Brunel 7,P.Djiane 8, J.M. Julliard 9, N. Danchin 10 on behalf of FAST-MI investigators. 1 APHP, Saint Antoine Hospital; UPMC-Paris 06, Paris, France; 2 Department of Cardiology, Roubaix, France; 3 Centre Hospitalier Universitaire de Grenoble, Grenoble, France; 4 Department of Cardiology, Laon, France; 5 Department of Cardiology, La Rochelle, France; 6 INSERM, Toulouse, France; 7 Nouvelles Cliniques Nantaises, Nantes, France; 8 AP-HM - Hopital de la Timone, Marseille, France; 9 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 10 European Hospital George Pompidou (AP-HP), Paris, France Background: Proton pump inhibitors (PPIs) are frequently administered in patients after AMI. Studies have suggested that co-prescription of PPIs with clopidogrel decreases the effect of clopidogrel on platelet activation due to a potential drug-drug interaction at the CYP 2C19 level. Aim: To assess in-hospital death and clinical major events at one year followup according to the use of PPIs alone or associated with clopidogrel in patients admitted for AMI. Methods: We analyzed data on the prescription of PPIs within 48 hours of admission and in-hospital death in 3059 patients enrolled in the French registry of Acute ST-elevation and non-st-elevation Myocardial Infarction (FAST-MI). Use of PPIs at hospital discharge and 1-year clinical outcomes were also analyzed among hospital survivors receiving clopidogrel. Results: PPIs were prescribed in 1922 (63%) of the patients (omeprazole (n= 1346), other PPIs (n= 576)) of whom 88% received also clopidogrel. Early use of PPIs was not a correlate of in-hospital death in patients with or without clopidogrel (OR =0.91; 95% CI: ). Among hospital-survivors, 2178 patients received clopidogrel of whom 1289 patients (59%) received PPIs at hospital dis-

36 336 Controversial issues in the management of acute coronary syndromes charge. At one year, death occurred in 6.6% and 5.1% of patients with or without PPIs, respectively. After adjustment, prescription of PPIs at discharge was not an independent correlate of events. Similarly, the rate of death, recurrent MI, stroke and hospitalization for bleeding did not differ with regard to the use of PPIs (10.6% vs 8.4% with or without PPIs respectively, p=0.34). No difference was observed between patients on omeprazole and those on other PPIs for the risk of in-hospital or one-year mortality. Conclusion: The use of PPIs in AMI patients had no effect on the clinical response to clopidogrel with regard to in-hospital death or death and major cardiovascular events at one year follow-up. P2122 Effect of thrombolysis with immediate transport to PCI vs. thrombolysis with ischemia-guided strategy on left ventricular function in ST-elevation myocardial infarction N. Mistry 1, E. Bohmer 2,P.Hoffmann 3, R. Bjornerheim 1, S.E. Kjeldsen 1, S. Halvorsen 1. 1 Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway; 2 Department of Medicine, Innlandet Hospital Trust, Lillehammer, Lillehammer, Norway; 3 Department of Radiology, Oslo University Hospital, Ullevål, Oslo, Norway Objectives: Treatment of acute ST-elevation myocardial infarction (STEMI) with prehospital or in-hospital thrombolysis is widely used in rural areas with long transfer delays to invasive centers. In this setting it is unclear which treatment strategy that best preserves left ventricular function. In the NORDISTEMI study (NORwegian Study on DIstrict Treatment of ST-Elevation Myocardial Infarction) we aimed to test the hypothesis that thrombolysis with immediate transport to percutaneous coronary intervention (PCI) results in better preserved left ventricular function compared to a more conservative, ischemia-guided strategy. Methods: 266 patients with STEMI of less than 6 hours duration and more than 90 minutes time delay to PCI were randomized to thrombolysis followed by PCI or thrombolysis followed by concervative strategy. Ejection fraction (EF), end systolic volume (ESV) and end diastolic volume (EDV) in the two treatment strategies were assessed by echocardiography, magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) when clinically feasible, three months after the myocardial infarction. Results: EF ranged from 55 to 65% with the three different methods, but was literally identical in the two treatment strategies (table). ESV and EDV were also the same in the two treatment stategies. The median EDV (ml) in the conservative and in the early invasive strategy measured with echocardiography, MRI and SPECT was 108 vs. 106 (p=0.76), 157 vs. 162 (p=0.41) and 101 vs. 104 (p=0.34), respectively. Purposes: Pharmacological modulation of Monocytes activities represents an important strategy for the prevention and treatment of atherosclerosis. The study performed to analysis the possible anti-inflammatory mechanism of pioglitazone. Methods: A total of 97 subjects with ACS were entrolled into 12-week, prospective, open-label,double-blind, controlled clinical study. They were randomized to receive either pioglitazone (30mg QD) (n=42) or placebo (n=55) in addition to standard therapy. 21 subjects with non-chd chest pain and 20 healthy subjects also were observed. Clinical characteristics (age, heart rate, lipid profile, fasting glucose, blood pressure, etc.), inflammatory markers (high-sensitivity C- reactive protein,monocyte chemoattractant protein-1, tumour-necrosis factor-α, interleukin-6, soluble CXCL-16, soluble CD40 ligand, MMP-9) in plasm and expressions of CCR2 and TLR-4 on circulating monocytes were measured at baseline and after 12 weeks. Results: Levels of hs-crp, MMP-9, scxcl-16, IL-6,TNF-α, scd40l and MCP- 1 in patients with ACS were significantly higher than those in the two control groups (P<0.01). The frequencies of CCR2 or TLR-4 and both of CCR2 and TLR- 4 on CD14+ monocytes in patients with ACS were significantly higher than that in healthy and non-chd chest pain subjects,and expression of CCR2 is directly correlated with expression of TLR-4 on monocytes (r=0.229, P=0.027). Real-time PCR analysis showed that mrna expression of CCR2 and TLR-4 on monocytes in patients with ACS was higher than that of non-chd chest pain groups (P<0.01). Pioglitazone could decrease circulating leucocyte count, TG and plasm levels of hs-crp than placebo (P<0.05), and decreased levels of scd40l, MMP- 9, scxcl-16 and MCP-1 in plasm (P<0.05). Pioglitazone could lower expression of CCR2 and TLR-4 on monocytes (P<0.01), and only inhibit mrna expression of CCR2 on monocytes (P<0.01). Conclusions: Pioglitazone significantly reduces biomarkers of monocytes activation and levels of acute-phase reactants in ACS patients. Potential underlying mechanisms include direct modification of transcription within the monocytes. P2124 Pharmacologic inhibition of MyD88 ameliorates adverse cardiac remodeling and apoptosis after experimental acute myocardial infarction B. Van Tassell, F.N. Salloum, L. Smithson, A. Varma, N.H. Hoke, I.M. Seropian, C. Gelwix, V. Chau, A. Abbate. Virginia Commonwealth University, Richmond, United States of America Purpose: Myocardial ischemia activates an inflammation, apoptosis, and ventricular remodeling. Myeloid differentiation factor 88 (MyD88) coordinates the inflammatory response from Toll-like receptor and interleukin-1 (IL-1) receptor agonists. We evaluated the effects of pharmacologic MyD88 inhibition on left ventricular remodeling and cardiomyocyte apoptosis after experimental myocardial infarction (MI). Methods: ICR mice (male, n=21) were randomized to daily intraperitoneal injections with a IMG2005 (1 mg/kg, n=10) or saline (n=11) for 14 days following permanent coronary artery ligation. A second experimental group of ICR mice were randomized to pre-treatment with MyD88 small interfering RNA (sirna, 0.45 mg/g, n=3) or IL-1 receptor associated kinase inhibitor (IRAK, 0.1 mg/kg, n=3) for 7 days after the same infarction protocol. Echocardiography was performed at baseline, 7 days, and 14 days after surgery. Animals were then sacrificed for histologic evaluation of infarct size and cardiomyocyte apoptosis. Results: MyD88 inhibition, IRAK inhibition, and MyD88 sirna all reduced LV end-systolic and end-diastolic diameter. MyD88 inhibition also reduced cardiomyocyte apoptosis in the peri-infarct myocardium (0.3±0.1%) versus saline (1.4±0.4%, P<0.05). There was no difference in infarct size with treatment and a trend toward improved survival at 14 days after MI. Table. Ejection Fraction after 3 months Ejection Fraction Conservative strategy Early invasive strategy p-value Echocardiography (n=191) 55 ( ) 55 (49-62) 0.70 MRI (n=178) 57 (53-63) 57 (49-65) 0.87 SPECT (n=241) 65 (55-71) 63 (51-70) 0.41 Conclusion: Ejection fraction and left ventricular volumes assessed with echocardiography, MRI and SPECT three months post-myocardial infarction did not differ between the two treatment strategies. Our data suggest that, in patients with STEMI, an early invasive strategy following thrombolysis does not preserve left ventricular function better than a conservative strategy. P2123 The effects of pioglitazone treatment on inflammatory activity of monocytes in patients with acute coronary syndrome W.P. Zhang, Y. Wu, Y. Liu, Z.Y. Yuan. Department of Cardiology, the First Affiliated Hospital of Medical School, Xi an JIAOTONG University, Xi an, China, People s Republic of Conclusion: Pharmacologic MyD88 inhibition attenuates pathologic ventricular remodeling and cardiomyocyte apoptosis after MI without altering infarct scar formation, and may represent a novel translational approach for the prevention of heart failure after MI. P2125 Follow-up results after interventional treatment of infarct related saphenous vein graft occlusion R. Hoffmann, G. Nitendo, V. Deserno, M. Kelm, U. Adamu. Universitaetsklinikum Aachen, Medizinische Fakultaet der RWTH, Aachen, Germany Acute occlusion of saphenous vein grafts resulting in acute coronary syndromes may be treated by interventional revascularization. There are little data on intermediate and long term results after revascularization of acute saphenous vein graft occlusion. Methods: 50 patients (67±10 years, 47 male) with troponin positive acute coronary syndrome due to acute total or subtotal occlusion (TIMI flow 0=39, TIMI 1=8, TIMI 2=3) of one saphenous vein graft (12.0±5.3 years after surgery, 3.6±0.9 grafts) were treated by percutaneous coronary intervention (39 patients using bare metal stents, 11 patients using drug eluting stents). Clinical follow-up was obtained in all patients. Angiographic 6 month follow-up was performed in 35 patients (70%). Results: Acute revascularization of the infarct related saphenous vein graft (lesion length 17.6±10.3 mm, reference diameter 3.1±0.8 mm) was possible in 94% of patients. After a mean follow-up of 32.5±17.4 months 13 patients (26%) died, 13 patients (26%) had recurrent myocardial infarction and 20 patients (40%) had recurrent coronary revascularization (PCI or CABG). Angiographic follow-up demonstrated reocclusion of the vein graft in 3 cases (9%). 21% of lesions were found to be restenotic. Conclusion: Acute revascularization of an infarct related saphenous vein graft is possible in the majority of cases. Angiography demonstrates a high patency rate at 6 months follow-up. Still, the clinical prognosis of patients with revascularized infarct related saphenous vein graft is quite poor.

37 Controversial issues in the management of acute coronary syndromes 337 P2126 Long-term effects of music therapy on patients with acute myocardial infarction and previous revascularization; 7-year experience P.M. Mitrovic, B. Stefanovic, Z. Vasiljevic, M. Radovanovic, N. Radovanovic, G. Krljanac, D. Rajic, G. Matic, A. Novakovic, M. Ostojic. University Institute for Cardiovasculari Diseases, CCS, School of Medicine, Unversity of Belgrade, Belgrade, Serbia Unrelieved anxiety can produce an increase in sympathetic nervous system activity leading to an increase in cardiac workload. The purpose of this study was to evaluate the effectiveness of music therapy for reduction of new coronary events in patients with acute myocardial infarction (AMI) and previous revascularization. Methods: 740 patients (males 82.4%, mean age 58.9±7.2 yrs) with AMI after previous revascularization have been selected from the patients consecutively submitted from April 1990 to January The patients with early perioperative AMI were excluded from the study. The average time interval from CABS to AMI was 92.6±14 months. The average number of grafts was 3.2 grafts/pts. All patients were randomized and divided in 2 groups: Study group of 370 patients treated with music therapy and Control group of 370 patients with no music therapy. Each patient in study group underwent two sessions of medical therapy (12 minutes) in a day. Both groups were similar in baselines, post-ami characteristics and post-ami medical therapy. Results: Comparing parameters of Study and Control group of patients in 7-year follow-up period, Study group had lower anxiety score (r=-0.22, p=0.15) with statistically significant reduction in systolic blood pressure (p=0.0009), diastolic blood pressure (p=0.0008), heart rate (p=0.0046), heart failure expression (p=0.0014), angina (p=0.0048), reinfarction (p=0.0146), sudden deaths (p=0.0456) and reoperation (p=0.0028). Conclusion: This study provides support for the use of musical therapy in patients with AMI and previous revascularization to reduce blood pressure, heart rate and new coronary events expression. These effects of music therapy are probably because of decreasing in sympathetic nervous system activity. P2127 The effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with type 2 diabetes mellitus after myocardial infarction H. Yokoe 1, F. Yuasa 1, T. Sugiura 2,T.Iwasaka 1. 1 kansai medical university, Osaka, Japan; 2 kochi medical university, Kochi, Japan Background: Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal cardiovascular events in type2 diabetes mellitus (DM) after myocardial infarction (MI). However the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on the sympathetic and baroreflex function in the type2 DM patient after MI. Methods: Thirty patients with type2 DM after MI were assigned to a pioglitazone group (n=15) or control group (n=15). Baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) (microneurography at peroneal nerve) were measured at rest and during baroreceptor stimulation (phenylephirine infusion) and baroreceptor deactivation (nitroglycerin infusion). Insulin resistance and plasma adiponectin were measured. Insulin resistance was evaluated using the homeostasis model assessment insulin resistance (HOMA-IR). These measurement were performed at baseline and after 3 months. Results: Resting MSNA reduced significantly (from 37±7 to 25±8 burst/min; p=0.007) and BRS improved significantly (from 6.7±3.0 to 9.9±3.2 msec/mmhg; p=0.01) after pioglitazone. MSNA response to baroreceptor activation (change of integrated MSNA from -26±13 to-45±11%; p=0.001) and baroreceptor deactivation (change of integrated MSNA from 115±14 to 153±23%; p=0.01) improved significantly after pioglitazone. Adiponectin (6.9±3.3 to 12.2±7.1μg/ml; p=0.01) and HOMA-IR (4.0±2.7 to 2.1±0.9; p=0.006) improved significantly after pioglitazone. The change in resting MSNA was related significantly to the changes in HOMA-IR (r=0.6; p<0.05) and plasma adiponectin (r=0.7; p<0.05) after pioglitazone. However, there were no significant changes in measured variables in the control group. Conclusion: Pioglitazone treatment increased arterial BRS and decreased sympathetic nerve traffic through the improvement of insulin resistance and adiponectin in the patients with type2dm after MI, which indicate that the sympathoinhibitory effects of this agent may contribute to the benefical effects of pioglitazone in type 2 DM after MI. P2128 Implementation of the ESC guidelines on the management of AMI in community hospitals J. Ferrieres 1, J.B. Ruidavets 1, D. Arveiler 2, J. Dallongeville 3, B. Haas 2,M.Montaye 3, A. Bingham 4, V. Bongard 1, P. Ducimetiere 4. 1 Department of Cardiology B and Department of Epidemiology, INSERM U558, Toulouse University Hospital, Toulouse, France; 2 Department of Epidemiology and Public Health, Louis Pasteur University, Medical Faculty, EA 1801, Strasbourg, France; 3 Department of Epidemiology and Public Health, INSERM U744, Pasteur Institute of Lille, Lille, France; 4 IFR69, Paul Brousse Hospital, Villejuif, France Background: Guidelines should help physicians to make decisions in daily practice. However, discrepancies may exist between guidelines and their implementation in daily practice. So, ongoing audits are needed to ensure the appropriate implementation of guidelines. The aim of this study was to analyze management of acute myocardial infarction (AMI) in three population registries. Methods: In three areas of France (North, North-East, Southwest), we registered in 2006 all acute coronary syndromes (ACS) aged years, without any previous history of coronary heart disease, in the 3 former MONICA Registries of Lille, Strasbourg and Toulouse. We obtained precise data before, during and after hospitalization for all consecutive cases of ACS hospitalized in all hospitals covered by the 3 registries. In order to compare with the 2008 ESC guidelines on management of AMI, we restricted our analysis in patients (pts) with a discharge diagnosis of incident AMI. Results: Among 2018 incident ACS hospitalized in 2006, 1212 (60%) were discharged with a diagnosis of incident AMI. Mean age was 57.2±10.3, and 79.2% were men. The delay between symptom onset and first medical contact was <1 h in 25%, <2 h in 45% and <4 h in 59% of pts. The first medical contact was a physician-manned ambulance for 48% of pts. The delay between symptom onset and hospitalization was <1 hin8%,<2 h in 26% and <4 h in 53% of pts. Pre-hospital care included pre-hospital fibrinolysis in 10.6%, aspirin in 35.5% and clopidogrel in 15.1% of pts. Among all AMI, 74% were hospitalized in a percutaneous coronary intervention (PCI)-capable hospital and 53% had a primary angioplasty. During the first 24 h of hospitalization, 60.7% had PCI, 5.0% inhospital fibrinolysis, 89.2% aspirin, 86.2% clopidogrel, 66.0% β-blockers, 60.7% angiotensin-converting enzyme (ACE) inhibitors and 42.2% statins. Among all pts treated with PCI, 95.2% had stents and 28.4% drug-eluting stents. An impaired ejection fraction (<40%) was recorded in 9.8% of pts. Among discharged pts, 93.7% had aspirin, 86.3% clopidogrel, 87.0% β-blockers, 75.6% ACE inhibitors and 90.8% had statins. One month mortality was 6.0%. Conclusion: The management of AMI including emergency medical system, ambulance service, pre-hospital fibrinolysis, hospitalization in PCI-capable hospital, rate of PCI, discharge preventive drugs has greatly improved in France. However, the first medical contact often remains a general practitioner and about half of the pts are admitted at hospital more than 4 hours after symptom onset. Surveys of real-life daily practice are highly needed. P2129 Emergency department bypass reduces the time to reperfusion therapy V. Gomes, J. Trigo, P. Gago, J. Mimoso, R. Faria, N. Marques, W. Santos, V. Brandao. Hospital Central de Faro, Faro, Portugal Purpose: In patients (pts) with ST elevation myocardial infarction (STEMI) the reperfusion therapy (RT) is associated with better survival. The delay to RT remains too long. The pre-hospital emergency system- Green Way AMI (GWAMI)- with pre-hospital ECG, STEMI triage, emergency department (ED) bypass and direct admission to the Cardiology Department- aims to reduce the time to RT in STEMI. We evaluated the reduction of the time to RT in the pts admitted with STEMI through the GWAMI during 5 consecutive years ( ). Methods: We studied 1073 pts admitted with STEMI between 01/01/2004 and 30/11/2008.The pts were allocated in 2 groups according the admission: Group A (GA): Admitted through the GWAMI-390 pts (36%); Group B (GB): Admitted through the ED-683 pts (64%). The pts of the 2 groups were compared in the following parameters: age, sex, cardiovascular (CV) risk factors, CV event history, pre-hospital delay (PHD), in-hospital delay (IHD), RT and time door-toneedle/balloon (TD-N/B). We also consider the rate of pts who underwent RT in the recommended times: below 30 min to TD-N; bellow 90 min to TD-B. Results: The rate of pts admitted through the GWAMI was 11% in 2004, 13% in 2005, 30% in 2006 and 51% in 2007 and 64% in The mean age of the pts studied was 66±14 years, being 799 pts (74,5%) male. 69,9% of the pts were submitted to RT (fibrinolysis: 25,9% and primary angioplasty: 74,1%) with higher rate in GA (85,9% vs 60,8%, p< 0,0005). Significant reductions of the PHD, IHD and TD-NB were seen in GA. The rate of RT within the recommended times was significantly higher in GA (table). Group A Group B p PHD: median (Q25-75) 3h30 (2h17-5h47) 4h02 (2h03-10h03) <0,0005 TD-N: median (Q25-75) 0h14 (0h06-0h31) 1h07 (0h42-2h00) <0,0005 TD-B: median (Q25-75) 0h20 (0h15-0h33) 1h31 (1h03-2h26) <0,0005 TD-N<30 min (%) <0,0005 TD-B<90 min (%) <0,0005 Conclusion: The rate of pts admitted through GWAMI is increasing in this region. The GWAMI has had a very significant impact in the reduction of the pre-hospital delay, in-hospital delay and in the door-to-needle/balloon times, allowing increasing numbers of pts to be treated with early reperfusion therapy according to the recommendations.

38 338 Controversial issues in the management of acute coronary syndromes P2130 The effect of prehospital remote ischemic perconditioning on left ventricular function in STEMI patients treated with primary angioplasty: a randomised study K. Munk, N.H. Andersen, M.R. Schmidt, S.S. Nielsen, C.J. Terkelsen, E. Sloth, H.E. Botker, T.T. Nielsen, S.H. Poulsen. Aarhus University Hospital, Aarhus, Denmark Purpose: We have found that remote ischemic perconditioning (rperc) - i.e. episodes of nonlethal ischemia in a distant organ while the heart suffers lethal ischemia - administrated as an adjunct to primary percutaneous coronary intervention (ppci) - increases myocardial salvage in patients with acute STEMI. In the present study we assessed the effects of rperc on left ventricular function and remodeling. Methods: Among 260 patients with ongoing first STEMI randomized to rperc (5 periods of 5 minutes upper limb ischemia) during transfer to ppci versus ppci alone, early and/or late echocardiographic evaluation of LV function was performed in 227. Echocardiographic outcome measures were global systolic longitudinal strain of left ventricle (GLS, %) by speckle tracking, ejection fraction and LV volumes. Results: The two groups had similar baseline characteristics. For all patients, no difference in echocardiographic indexes of LV function early after ppci and after 1 month follow up was found. In high risk patients with first time LAD STEMI and no procedural and follow up adverse cardiac events (N=91) LV ejection fraction after 30 days was higher in the group of rperc vs. ppci alone (55.1±7.7%; 50.9±10.1%, respectively (p=0.049)). GLS showed borderline improvement in rperc treated patients (-16.4±2.9%) compared with patients treated with ppci alone (-14.9±3.4%) (p=0.055) after 30 days. P2132 Mortality reduction in acute myocardial infarction following organization of a regional network in a population of 1 million inhabitants with low-adherence to European guidelines I.S. Benedek, M. Chitu, I. Kovacs, A. Sarbu, M. Kurtinecz, C. Matei, S.Z. Madaras, G. Kozma, I. Benedek, T. Benedek. University Emergency Hospital Targu-Mures, Targu Mures, Romania Purpose: We followed the evolution of mortality in Acute Coronary Syndromes (ACS) in a period of 4 years during which all the cases recorded in a territory of 1 million inhabitants with low-adherence to european guide-lines were included in Regional Registry of ACS in Romania. Methods: The registry included 13 hospitals, having the closest interventional center at a maximum distance of 200 km. Population groups: gr.1 pts. presented at the territorial hospitals, without PCI facilities, gr. 2- pts. presented directly to the interventional center. Results: The registry included a total number of patients with ACS, out of which Acute Myocardial Infarction and Unstable Angina. The percentage of reperfusion therapy (primary PCI + thrombolysis) in gr.1 was 9.15% in 2004, increasing up to 17.16% in Only 0.3% of these patients were sent for primary PCI in the first year, this percentage increasing to 5.6% in the last year. In gr.2, reperfusion therapy was possible in 99.39% of cases, consisting in primary PCI in 76.96% cases, facilitated PCI in 15.75% cases and thrombolysis in 6.6% cases. Mortality rates in gr.1 showed a continuous decrease, from 20.77% in 2004 to 14.2% in 2008, correlated with the increase of reperfusion therapy (p=0.001). In group 2 global mortality was 6.6% for patients arrived in time for PCI, compared with 17.65% for patients with late arrival (>12 hours) (p<0.001). Conclusions: We succeeded to decrease the mortality rates in AMI in a territory of 1 million inhabitants from 20.77% to 14.2%, representing a 31.6% reduction in mortality for AMI patients presented in territorial hospitals without PCI facilities. This was mainly due to a complex educational and organizational activity which resulted in more than double rates of patients receiving reperfusion therapy and 18 times higher percentage sent to interventional center in 2008 compared with Still, the percentage of reperfusion therapy in the territorial hospitals remain very low in this region of Romania with very low adherence to european guidelines, reflected in high mortality rates. Left ventricular function - 30 days Conclusion: In this echocardiographic study, adjunctive treatment to ppci with prehospital rperc, improved LV function and remodeling after 1 month in high risk patients with first LAD STEMI. P2131 The radial approach reduces bleeding complications in STEMI patients without increasing the time to revascularization D. Arzamendi Aizpurua, J.F. Tanguay, H.Q. Ly, P. Lavoie-L allier, R. Ibrahim, Y. Reyna, R. Gallo, P. Deguise, G. Gosselin, S. Doucet on behalf of Group of Research in Interventional Cardiology from the Montreal Heart Institute. Montreal Heart Institute, Montreal, Canada Background: In the current era of reperfusion therapy, primary percutaneous coronary intervention (PPCI) combined with adjunctive antithrombotic therapy performed in a timely fashion has become the mainstay for ST elevation myocardial infarction (STEMI). Nevertheless, bleeding remains one of the major complications of these therapies and might be associated with an increase in mortality. Aim: To analyze the clinical impact of the radial approach on both the rate of bleeding and the time to revascularization in patients with STEMI undergoing PPCI. Methods: From April 2007 to March 2008, demographic, clinical and procedural data on all patients with STEMI referred for PPCI to the Montreal Heart Institute s cardiac catheterization laboratories were analyzed. Data were compared between each study group of patients undergoing PPCI either from a radial or a femoral approach. Results: Of the 488 patients included in the study, 236 (48.4%) patients underwent PPCI using the radial approach and the femoral approach was used in 252 patients (51.6%). No differences were found in baseline characteristics in terms of age, gender and cardiovascular risk factors. ST segment deviation, TIMI flow preprocedure and hemodynamic values at admission were comparable between both groups. Time from patients arrival to the cath-lab to puncture was of 8.15±4.5 minutes for the radial approach vs. 8.8±5.8 minutes for the femoral approach (p=0.15). Access site major bleeding was significantly higher in the femoral group vs. the radial group, 13.5% vs. 2.9% respectively (p<0.001). Using multivariable analysis, the femoral approach showed to be the main variable associated with an increased risk of bleeding with a HR of 5.86 (CI 95% ). Conclusions: In the setting of PPCI and adjunctive pharmacological therapies for STEMI, the radial approach was associated with a significantly lower incidence of major bleeding compared to the femoral approach, without compromising time to reperfusion. P2133 RADIal vs femoral approach with the usage StarClose for PCI for patients with Acute Myocardial Infarction. The RADIAMI II study, prospective, randomized, single center trial P. Chodor, T. Kurek, A. Kowalczuk, M. Swierad, T. Was, G. Honisz, A. Swiatkowski, W. Streb, Z. Kalarus. Silesian Center for Heart Diseases,Medical University of Silesia, Zabrze, Poland Background: The transradial approach for percutaneous coronary intervention (PCI) is associated with lower number of puncture site and bleeding complications, faster rehabilitation and better quality of life. These advantages were also identified for same available closure devices like StarClose clip. There is limited data of comparing transradial approach vs. transfemoral approach with the useage of closure device for PCI in acute myocardial infarction (MI). Methods: 108 patients with acute MI, symptoms <12hour, age <75 years, I and II Kilip-Kimbale class were randomly assigned to transradial approach (group I; n=49) or transfemoral approach with use of closure device at the end of the procedure (group II; n=59). We compare the timing of the procedure, angiographic results, serious cardiac events (MACE necessity of repeating the revascularization procedure in the infarct-related artery, a necessity of aortocoronary by-pass grafting, new onset of MI, death from any cause and stroke), bleeding complication, puncture site complications, time period of patient partial and full mobilization. Results: 108 patients were included in the study, 63.9% male, aged 59.6±10.04 years. Transfemoral approach was used in 2 (4.08%) patients belonging to group I and there was no need to use transradial approach in patients belonging to group II. Time intervals between patient s admission to hospital and artery puncture, balloon inflation, and total procedure timing in group I and group II were: 51.±22.1min vs. 40.4±16.3min (P=0.005); 67.4±17.1 vs. 58.0±17,4 (P0.015); 87.0±24.9min vs. 80.5±21.4min (P=0.163). TIMI 3 flow was achieved in 49 (100%) of patients in group I and 58 (98.3%) of group II. There were no significant differences in serious cardiac events (group I n=1 (2.1%) vs. group II n=1 (1.7%); P=NS) and bleeding complications (group I n=2 (4.2%) vs. group II n=2 (3.4%); P=NS). The mean period of time to partial and full mobilization in group I was 25.9±16.8 h. and 4.26±1.30 days vs 24.3±11.9 h. and 4.37±1.35 days in group II (both P=NS). Conclusions: The transradial approach compared to transfemoral approach for PCI in acute MI is associated with significantly increased of door to needle and door to balloon time. There were no differences in major cardiac events between both groups. The usage of StarClose clip after PCI allows to reduce the number of bleeding complication in this group as well as enables earlier initiation of rehabilitation comparable to transradial group.

39 Controversial issues in the management of acute coronary syndromes 339 P2134 Early versus late invasive strategy in successful thrombolysis reperfused acute myocardial infarction S. Champagne 1, D. Pongas 1, E. Aptecar 2, P. Dupouy 2, R. Cohen 3, S. Elhadad 3, J.L. Dubois-Rande 1, E. Teiger 1. 1 AP-HP - Hopital Henri Mondor, Creteil, France; 2 clinique les fontaines, Melun, France; 3 Centre Hospitalier General de Lagny-Marne-la-Vallee, Lagny/Marne, France New ESC guidelines recommend to perform angiography 3 to 24 hours after successful fibrinolytic therapy. However few convincing data exist about the optimal timing of PCI following successful reperfusion by thrombolysis. The aim of this study was to assess the prognosis of those patients in regard of the delay of PCI following successful thrombolysis. Methods: 204 consecutive patients were admitted in intensive care unit for definite reperfused acute myocardial infarction from 3 institutions. Two groups were defined according the delay of PCI from thrombolysis: early (<24 hours; n= 132) versus late (>24 hours; n=72). End point of the study was the rate of in hospital MACCE, defined as death, Congestive heart failure (CHF), haemorrhagic stroke and Re infarction (Re MI). Results: Baseline clinical and angiographic characteristics were similar between two groups.there was a non significant trend of 12.5% MACCE in the early group versus 9% in the late group (p= 0.13). Re MI occurred more significantly in the early group (6.7%) than in the delay (1.4%); p< In hospital Death was 1.6% in the early group and 0% in the delay group (p = 0.6). CHF occurred in 10.6% in the early group and in 7.5% in the delay (p= 0.6). No haemorrhagic stroke was noted. See table. Clinical characteristics and outcomes Early PCI (n=132) Delay PCI (n=72) p Age, yr 56.4± ± Previous MI 7% 12% 0.2 Time from PCI, day 0 6.3±9.6 Death 1.6% Re MI 6.7% 1.4% < CHF 10.6% 7.5% 0.6 Haemorrhagic strokes 0 0 MACCE 12.5% 9% 0.1 Data are expressed as seam ± SD or as number (percentage) except as indicated. Conclusion: Early PCI (<24 hours) in successful thrombolysis reperfused acute myocardial infarction seems to be harmful even in the delay recommend by the new ESC guidelines because of increased re infarction. It might be safer to postpone PCI more than 24 hours after the thrombolysis when the pro thrombotic status related to fibrinolysis is over. P2135 Efficacy of statin therapy in patients with acute myocardial infarction is determined by polymorphism of enos gene promoter Y.A. Lutay 1, A.N. Parkhomenko 1, V.E. Dosenko 2, A.A. Moibenko 2. 1 NSC The M.D. Strazhesko Institute of Cardiology, Kiev, Ukraine; 2 Institute of Physiology, Kiev, Ukraine The benefits of statins have been demonstrated in patients with stable coronary artery disease and non ST elevation acute coronary syndromes (ACS). These benefits, however, have not been well documented in patients with ST-segment elevation acute myocardial infarction (STEMI). The aim of this study was to analyze the impact of early statin therapy upon hospital complications in patients with STEMI depending on genotypes of enos gene promoter. 162 patients with recent ST elevation MI were investigated. The enos gene polymorphism has been analyzed by PCR-RFLP analysis. 70 patients were treated with statins (atorvastatin 20 mg or simvastatin 40 mg) in addition to standard treatment since the first hours of ACS and 92 patients did not received statins until discharge. Genotype distributions of enos TT, TC and CC genotypes in promoter region were 0.40 (N =28), 0.46 (N = 32) and 0.14 (N = 10) in statin group and 0.46 (N =42), 0.44 (N = 40) and 0.11 (N = 10) in controls, respectively. Groups were similar regarding baseline characteristics and concomitant treatment. -786TT genotype of enos gene promoter was associated with decreased risk of recurrent ischemic events (myocardial infarction and post-mi angina) and acute heart failure during the period of hospitalization in statin treated patients. While there were no benefits of early statin treatment in patients with TC, CC and both (TC+CC) genotypes. Patients with -786TT genotype of enos gene promoter should be the target for early statin therapy after acute ST elevation MI. P2136 Early statin treatment prior to primary PCI for acute myocardial infarction: a randomized placebo controlled trial S. Post 1,M.C.Post 2, F.D. Eefting 2, M.J. Goumans 3, M.A. Bosschaert 2, P.R. Stella 3,F.H.DeMan 3,B.J.Rensing 2, P.A. Doevendans 3. 1 St Antonius Hospital Nieuwegein and University Medical Centre, Utrecht, Netherlands; 2 St Antonius Hospital, Nieuwegein, Netherlands; 3 University Medical Center Utrecht, Utrecht, Netherlands Purpose: Early statin therapy might reduce reperfusion injury, which develops after primary percutaneous coronary intervention (PCI) following acute myocardial infarction (AMI). The aim of this study was to determine whether early atorvastatin treatment will reduce left ventricle (LV) remodelling, infarct size and improve microvascular perfusion. Methods: Forty-two consecutive patients (82% male, mean age 61.2±9.8) who underwent a primary PCI for a first ST-elevated AMI were randomized for pretreatment with atorvastatin 80 mg (n=20) or placebo (n=22), continued for one week. All patients received atorvastatin 80 mg once daily seven days after primary PCI. The LV function and infarct size were measured by MRI (1.5 T Philips ) within 1 day, after 1 week and at 3 months follow up. The primary endpoint was the end-systolic volume index (ESVI) at 3 months. Secondary endpoints were global LV function measurements, myocardial infarct size, biochemical markers, TIMI flow and ST-T elevation resolution. Results: ESVI three months after AMI was 25.0 ml/m 2 in the atorvastatin arm and 25.0 ml/m 2 in the placebo arm (p=0.84). Overall, the differences in change from baseline to 3 months follow up, in global LV function and myocardial infarct size did not differ between both treatment arms. Furthermore, biochemical markers, TIMI flow and ST-T elevation resolution did not differ between atorvastatin and placebo arm. Conclusion: Pre-treatment with atorvastatin in an acute myocardial infarction does not result in an improved cardiac function, microvascular perfusion or decreased myocardial infarct size. P2137 Germany Reperfusion hemorrhage: a new therapeutic target in ST-elevation myocardial infarction A. Kumar 1,J.D.Green 1, V. Sabhaney 1, S. Poeschko 2,R.Dietz 2, M.G. Friedrich 1. 1 University of Calgary, Calgary, Canada; 2 Charite - Campus Buch, Franz-Volhard-klinik, HELIOS Klinikum, Berlin, Introduction: Reperfusion injury in myocardial infarction leads to microvascular obstruction, which can occur with or without hemorrhage. The incidence and implications of reperfusion hemorrhage are not well investigated. Purpose: We performed an in vivo study in patients with acute reperfused STEMI to assess the relationship of hemorrhage to microvascular obstruction, infarct size and functional parameters using cardiovascular magnetic resonance. Methods: 19 patients (age 56±11years, 3 female) with ST-elevation myocardial infarction were recruited in a tertial referral centre, and a comprehensive CMR study was performed to assess tissue injury on day 6±4 post reperfusion therapy using a protocol to quantify LV functional parameters (cine SSFP CMR), hemorrhage (T2*w-CMR), microvascular obstruction (early post-contrast CMR) and infarct size (late enhancement). Results: From 19 patients with STEMI, 10 had microvascular obstruction with hemorrhage (MO+H+ group), 3 had microvascular obstruction without hemorrhage (group MO+H ), and 6 had myocardial infarction not complicated by microvascular injury (group MO ). These groups were not different for major clinical parameters including TIMI risk score and time to reperfusion. There were no patients with hemorrhage but without MO. In patients with hemorrhagic infarction (MO+H+), hemorrhage was smaller than the amount of MO (7.3±6.4g of hemorrhage vs. 12.2±6.9g of MO), and hemorrhage was located in the subendocardium of the MO zone, occupying a mean of 58.6±31.2% of the MO zone. Hemorrhage occurred in the largest infarcts of this study only, and infarct size in the hemorrhage group was larger than in both other groups (infarct size MO+H+ 61.9±24.6g, MO+H 14.9±8.6g, MO- 12.6±4.4g, p<0.05 for MO+H+ vs. both other groups). Hemorrhagic infarcts had a larger MO zone than infarcts with MO but without hemorrhage (amount MO MO+H+ 12.2±6.9g vs. MO+H 2.2±2.1g, p<0.05). Overall, hemorrhage was observed exclusively in patients who had infarction involving more than 25g of myocardial necrosis and more than 5g of microvascular obstruction. This was also reflected in significantly worse functional parameters (LV ejection fraction and LV end-systolic volume) in the hemorrhage group compared to both other groups MO+H and MO. Conclusion: Reperfusion hemorrhage is associated with larger infarct size, larger amount of microvascular obstruction and worse functional parameters. Hemorrhage should therefore be considered a new therapeutic target in acute STelevation myocardial infarction. P2138 Early vs. late referral for coronary angiography after thrombolysis for STEMI G. Almpanis, P. Davlouros, G. Vagenakis, Z. Kopsida, K. Sheffneux, M. Papathanasiou, G. Hahalis, A. Mazarakis, J. Chiladakis, D. Alexopoulos. University of Patras, Patras, Greece Purpose: To investigate any difference in outcome between patients with STelevation myocardial infarction (STEMI) subjected to coronary angiography (CAG) early (within 24 hours post-thrombolysis) vs. late (> 24 hours), within a health network serving approximately 1.5 million people in western Greece. Methods: Retrospective analysis and telephone follow-up of all thombolysed STEMI patients referred for CAG to our hospital from January 2005 till June Results: OUt of 437 thrombolysed STEMI patients referred for CAG, 127 (29.1%), (Group-A), were refered within 24 hours post-thrombolysis and 310 (70.9%), (Group-B), >24 hours post-thrombolysis (6.91±5.2days). Group-A pa-

40 340 Controversial issues in the management of acute coronary syndromes / Echocardiography in cardiomyopathy tients were younger (57.95±12 vs ±11 years, p=0.006), had less frequently non significant CAD (3.9% vs 10% p=0.036), more frequently one vessel disease (60.6% vs 45%, p=0.006), and were subjected to PCI more frequently (85% vs 69.2%, p <0.001) compared to group-b. The latter were more frequently treated conservatively (7% vs 15.5%, p=0.018). Coronary risk factors were similar between the two groups. Telephonic follow-up regarding MACE (major coronary events: death, myocardial infarction, revascularisation, reinfarction), was conducted at 30.3±11.8 months. Death occured in 7.8% of Group-A patients vs 5.8 group-b patients (p=0.273), reinfarction in 1.5% vs 1.9% (p=0.576), revascularisation with PCI in 4.7% vs 3.8% (p=0.430), revascularisation with coronary bypass-grafting in 5.5% vs 1.9% p=0.051, CAG without intervention in 2.3% vs 2.2% (p=0.594) and the combined MACE occurred in 23.6% vs 18% (p=0.117). Conclusion: Despite the ESC guidelines for early referral for CAG postthrombolysis, this practice was applied infrequently in our area in the past four years. However early vs. late CAG referral groups did not differ in mortality, or major cardiovascular events. P2139 ECHOCARDIOGRAPHY IN CARDIOMYOPATHY Prognostic implications of left ventricular dyssynchrony early after non-st elevation myocardial infarction without congestive heart failure C.T.A. Ng, D.T. Tran, C. Allman, J. Vidaic, D.Y. Leung. The University of New South Wales, Sydney, Australia Purpose: To determine the independent predictors of left ventricular (LV) dyssynchrony after non-st elevation myocardial infarction (NSTEMI), and predictive value of dyssynchrony for long term LV dysfunction. Methods: LV dyssynchrony was performed in 100 NSTEMI patients (age 60.0±11.8 years, 71 men) using 4 dyssynchrony parameters at baseline. Coronary angiography was performed in 97 patients with 70% diameter stenosis defined as significant. Repeat echocardiography was performed at 6 and 12 months. Results: Early LV dyssynchrony was independently predicted by presence of significant proximal left circumflex artery stenosis and global systolic function. LV end-diastolic volume index decreased with time (47.1±14.2 vs 46.4±13.6 vs 43.1±12.8 ml/m 2,p<0.001) and was independently predicted by lower number of diseased vessels and absence of early dyssynchrony. LV end-systolic volume index decreased with time (23.5±12.3 vs 22.1±10.9 vs 20.2±10.2 ml/m 2, p<0.001), and was independently predicted by absence of early dyssynchrony, lower number of diseased vessels and revascularization. LVEF increased with time (52.1±11.0 vs 53.8±10.2 vs 54.8±9.7%, p=0.014), and was independently predicted by absence of early dyssynchrony, lower number of diseased vessels and revascularization. Figure Conclusions: After NSTEMI, proximal left circumflex artery stenosis independently predicted LV dyssynchrony. Early LV dyssynchrony independently predicted persistent lower LVEF and larger LV end-systolic volume index at baseline and follow-up. P2140 Early detection of functional abnormalities in asymptomatic arrhythmogenic right ventricular cardiomyopathy gene carriers using echocardiographic deformation imaging A.J. Teske, M.G. Cox, B.W. De Boeck, P.A. Doevendans, R.N. Hauer, M.J. Cramer. University Medical Center Utrecht, Department of Cardiology, Utrecht, Netherlands Purpose: The first presentation of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often potentially lethal ventricular arrhythmias originating from the right ventricle (RV), typically at a young age. This emphasizes the importance of an early recognition of this disease, for instance in ARVC- family members. The aim of this study is to evaluate the value of tissue deformation imaging to detect subclinical RV functional abnormalities in asymptomatic genotyped carriers of ARVC. Methods: A total of 43 asymptomatic first degree family members of ARVC probands (not fulfilling the diagnosis of ARVC according to the task-force criteria (TF-c)) were prospectively enrolled for echocardiographic examination. In a total of 14 (38.0±13.2 years), a genetic mutation (PKP2) could be identified (others had no mutation or genetic screening). All individuals were age-matched with 4 controls (n=56, 38.2±12.7 years) undergoing the same echocardiographic evaluation (dimensions, global systolic parameters, visual assessment, and deformation imaging of the RV free wall). Echocardiographic evaluation was performed blinded. Deformation analysis was analyzed blinded to group and findings from the conventional echocardiogram. A peak systolic strain >-18% and/or postsystolic shortening (post-systolic index >15%) in any segment was considered abnormal. Results: No significant differences in baseline characteristics were seen between the groups. RV dimensions in the family group were similar to the controls (RVOT 15.4±2.9 vs. 14.4±1.9 mm/m 2, RVIT 18.6±2.6 vs. 19.1±2.6 mm/m 2,p=NS). Global systolic parameters were moderately reduced in the family group (TVI-syst 9.1±1.6 vs. 11.1±1.7 cm/s, TAPSE 20.0±3.2 vs. 23.9±2.8 mm, p<0.001). On visual assessment (according to the TF-c), a major criterion was scored in 4 (20%) and 3 (5%), and a minor in 4 (20%) and 13 (23%) of family members and controls, respectively. Mean TDI and 2D-strain deformation (-rate) values were reduced in the ARVC family members in the basal and mid RV segment. A peak systolic strain of >-18% was seen in 6 family members (43%) and post systolic strain in 10 (71%). Either abnormality was observed in 11 (79%), almost exclusively in the basal segment, and in non of the controls. 2D-strain showed abnormal segments in 8 (57%) of family members and 5 (9%) controls. Conclusion: Echocardiographic deformation imaging detects functional abnormalities in the basal RV segment in almost 80% of asymptomatic ARVC gene carriers. Furthermore, false positive findings in visual assessment (28%) could be prevented since all showed normal deformation values and patterns. P2141 Identification and characterization of super-responders to cardiac resynchronization therapy: an echocardiographic study A. Zaroui 1, P. Reant 1, E. Donal 2, A. Deplagne 1, A. Mignot 1, P. Bordachar 1, A. Solnon 2, C. Leclercq 2, R. Roudaut 1, S. Lafitte 1. 1 Hopital Cardiologique Haut-Leveque, Bordeaux, France; 2 CHU de Rennes - Hopital de Pontchaillou, Rennes, France Background: In some patients, cardiac resynchronization therapy (CRT) has been recently shown to induce a spectacular effect on left ventricular (LV) function and inverted remodelling with nearby normalization of LV contraction. Objectives: To analyze and characterize super-responders (CRTSR) by echocardiography before CRT using conventional and dedicated tools for contractility assessment such as strain techniques. Methods: 186 patients have been investigated in 2 French specialized centers before and 6 months after implantation of a CRT device accordingly to ESC guidelines. Echocardiographies including measurements of LV dimensions, function and contraction by 2-dimensional strain, right ventricular function and pressure assessment, mitral valve analysis were performed at baseline and at 6 months by an independent core-center lab. CRTSR were defined as a reduction of endsystolic volume of at least 15% and an ejection fraction (EF)>50% and were compared to conventional responder patients (CRTCR, patients with a reduction of end-systolic volume of at least 15% but an EF<50%). Results: 18/186 patients (9.7%) were identified as CRTSR, only 2/18 patients had ischemic cardiomyopathy (p<0.01). No difference was observed regarding NYHA status, EKG duration or EF between CRTSR and CRTCR at baseline. CRTSR presented with significant lower end-diastolic and end-systolic diameters (64±8mm vs 70±8mm (p<0.01) and 54±7mm vs 59±9mm (p<0.01), respectively), and end-diastolic and end-systolic volumes (149±46ml vs 182±68ml (p<0.02) and 117±42ml vs 137±59ml (p<0.01)), lower left atrial volume (50.4±28 vs 77±41.5, p<0.001), and higher LV dp/dtmax (796±312mmHg s -1 vs 688±256 mmhg s -1 (p<0.05)). Regarding strain analysis, CRTSR had significantly higher longitudinal values than CRTCR (-12.8±3% vs -9±2.6%, p<0.001) whereas no difference was observed for other components (p ns). ROC curves identified global longitudinal strain as the best parameter for predicting CRTSR with cut-off values of -12% (Se=71%, Spe=85%, AUC=0.87, p<0.0001). The multiparametric logistic regression identified global longitudinal strain >-12% and left atrial volume <50mL as independent predictors of CRTSR (OR: 14.1; CI at 95%:3.8; 25.3; p<0.004 and OR: 1.3, CI at 95%:1.1; 2.8; p<0.01, respectively). Conclusion: In a large multicenter study, CRT super-responders (EF>50%) were observed in 9.7% of the population and were associated with less-depressed LV function as determined by strain analysis. Global longitudinal strain appears to be the best predictor of CRTSR. P2142 Use of tissue Doppler velocity as an index of global myocardial function in atrial fibrillation with preserved left ventricular ejection fraction H.J. Yoon, H. Kim, C.D. Han, H.S. Park, H.T. Kim, Y.K. Cho, C.W. Nam, S.H. Hur, Y.N. Kim, K.B. Kim. Keimyung University DongSan Hospital, Daegu, Korea, Republic of Background: Although atrial fibrillation (AF) has been reported to be a risk factor

41 Echocardiography in cardiomyopathy 341 in cardiovascular adverse event, the relationship of AF to the prognosis of AF with preserved ejection fraction is still uncertain. We evaluated the relationship between tissue Doppler-derived index including conventional echocardiographic parameters and clinical outcomes of AF by retrospectively cross-sectional study. Methods: One hundred forty eight patients with permanent AF who had preserved ejection fraction were included in this study. Clinical data were obtained and echocardiographic study was performed. Development of clinical events was defined as the composite of cardiovascular death, readmission of heart failure and ischemic stroke. Results: During the mean follow-up time of 2.2 years, there were 35 clinical events (2 deaths, 22 heart failures, and 11 ischemic strokes). In univariate analyses, age, ejection fraction, systolic mitral annular velocity (Sm), early diastolic annular velocity (Em) and left atrial dimension were correlated to clinical events. Multivariate regression analyses identified three significant parameters: patients with events demonstrated significantly lower Sm, Em and larger left atrial dimension as compared to those without events. Furthermore, patients with both Sm > 5 cm/s and Em > 7cm/s were significantly free of clinical endpoint (odds ratio=2.63, 95% CI , p=0.001). Kaplan-Meier Survival Curve Conclusions: In AF with preserved ejection fraction, tissue Doppler indexes, reflected by Sm and Em, were found to be the most powerful predictor of cardiovascular events. P2143 Strain ST-T change on the electrocardiogram reflects subendocardial dysfunction: Demonstration using 2D speckle tracking echocardiography M. Takeuchi 1, T. Nishikage 1,H.Nakai 1,V.Mor-Avi 2, R.M. Lang 2, Y. Otsuji 1. 1 University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan; 2 The University of Chicago Medical Center, Chicago, United States of America Purpose: Strain ST-T change on the surface ECG might reflect subsendocardial dysfunction. 2D speckle tracking echocardiography has the potential for the assessment of left ventricular (LV) strain and twist profile. We hypothesized that strain ST-T change is associated with (1) the preferential reduction of longitudinal strain and (2) the reduction of both clockwise twist at early systole and untwisting during early diastole and (3) the paradoxical augmentation of peak twist due to subendocardial dysfunction. Methods: 3 levels of LV short axis views and 3 LV apical views were acquired in 46 hypertensive patients with LV hypertrophy diagnosed by 2D echocardiography and 23 age-matched control subjects. Using 2D strain software, longitudinal, radial and circumferential strain was measured. Time domain LV twist curve was generated from the basal and the apical short-axis views, from which clockwise twist at early systole, end-systolic twist and untwisting values at early diastole was determined. Patients were divided into two groups according to the presence (n=18) or absence (n=28) of strain ST-T change on the 12-lead ECG. Results: No significant differences of LV ejection fraction were noted among the three groups. Longitudinal strain was significantly reduced in patients with strain ST-T change (-13.4±3.2) compared to those without strain ST-T change (-17.4±3.4, p<0.001) or control subjects (-19.9±2.0, p<0.001). Radial and circumferential strain was also significantly lower in patients with strain ST-T change compared to control subjects. Although LV twist at end-systole was similar between patients with strain ST-T change and those without ST-T change (16.2±6.7 degree vs. 15.1±4.1 degree), clockwise LV twist at early systole (0.03±0.91 degree vs ±1.01 degree, p<0.0167) and LV untwisting (10% of diastole: 3.0±11.0% vs. 14.7±17.8%, p<0.0167, 20% of diastole: 26.1±31.1% vs. 47.5±25.6%, p<0.0167) was significantly depressed in strain ST-T change group compared to no ST-T change group. Conclusions: The reduction of longitudinal strain, early systolic clockwise twist and LV untwisting variables in patients with strain ST-T change reflect subendocardial dysfunction, which can be assessed by 2D speckle tracking echocardiography. P2144 Attenuated coronary flow reserve is associated with subtle changes in left ventricular diastolic function among healthy individuals P. Kamvrogiannis 1, E. Alexandridis 1, G. Karayannis 1, G. Giamouzis 2, H. Parissis 1, A. Chamaidi 1, G. Sitafidis 1, J. Skoularigis 1,J.Butler 2, F. Triposkiadis 1. 1 Department of Cardiology, Larissa University Hospital, Larissa, Greece; 2 Emory University Hospital, Atlanta, United States of America Background: Coronary flow reserve (CFR) may be reduced in healthy individuals in the presence of major cardiovascular risk factors. The purpose of this study was to examine whether depressed CFR is associated with sub-clinical LV diastolic dysfunction in this population. Methods: A total of 101 consecutive asymptomatic individuals (age 52.5±13.2 years; 68% male; election fraction 62±6%) with normal resting ECG and at least one major risk factor formed the study population. Transthoracic two-dimensional and Doppler echocardiography was performed on all individuals. To evaluate left ventricular (LV) diastolic function the following parameters were determined: mitral E/A ratio, deceleration time, E/E average ratio of septal and lateral annular velocities, isovolumic relaxation time (IVRT), and left atrial volume index (assessed with the biplane area-length method). Phasic coronary flow velocities were obtained in the left anterior descending coronary artery at rest and during hyperemia (0.15 mg/kg/min adenosine triphosphate infusion IV). CFR was estimated from the ratio of hyperemic/baseline diastolic velocity. Based on CFR values, patients were divided into three groups: normal CFR (group A, CFR 2.5, n=60), borderline CFR (group B, 2.5>CFR 2.00, n=26), and abnormal CFR (group C, CFR<2.00, n=15). Diastolic function indices were compared in the three groups with one-way analysis of variance. Results: See Table. Parameter Group A Group B Group C E/A 1.13± ± ±0.53 Deceleration time, msec 205±46 205±38 195±56 Isovolumic relaxation time, msec 85±11 88±15 94±12* E/E average 8.4± ± ±3.1 Left atrial volume index, cm 3 /m ± ± ±7.0 *p<0.05 vs. A; p<0.01 vs. A; p<0.05 vs. B/ Conclusions: CFR is often impaired in healthy individuals in the presence of major cardiovascular risk factors and is associated with sub-clinical LV diastolic dysfunction, characterized by prolongation of IVRT and increased left atrial size. These findings suggest that more aggressive risk factor treatment in this group may delay onset of clinical HF. P2145 Echocardiographic assessment of left ventricular diastolic pressures validated using an implantable pressure sensor T.C. Poerner, B. Goebel, E. Luthardt, C. Schmidt-Winter, S. Otto, J. Gummert, H.R. Figulla. Universitaetsklinikum Jena, Jena, Germany Background: Noninvasive assessment of left ventricular (LV) diastolic pressures in patients with heart failure is essential for clinical decision making and adjustment of therapy. Aim of the study was to evaluate the accuracy of echocardiographic estimation of LV mean diastolic (LVMDP) and end-diastolic (LVEDP) pressures against intraventricular pressure measurements from an implantable manometer. Methods: Permanent LV pressure sensors (Transoma LVP-1000) were implanted in 5 patients with poor LV function, who underwent cardiac surgery. All devices were verified again 6 months later using Millar catheters and showed no measurement errors. In this time interval patients were followed-up several times, performing a total of 21 simultaneous echocardiographic examinations and pressure readings from the Transoma device. Results: Results are summarized in Table 1. Early mitral velocity E enabled a slightly better estimation of LVMDP compared to the indices E/E and E/A. Values of E >85 cm/s predicted LVMDP >12 mmhg with a sensitivity of 83% and specificity of 87%, respectively. On the other hand, the ratio E/A was the best predictor of elevated LVEDP (E/A >1: 71% sensitivity and 83% specificity for LVEDP >15 mmhg). Table 1 Parameter Echocardiographic Echocardiographic assessment of LVMDP assessment of LVEDP Linear Prediction of Linear Prediction of Correlation LVMDP > 12 mmhg Correlation LVEDP > 15 mmhg E r=0.60; p=0.003 AUC=0.927; p=0.002 r=0.48; p=0.016 AUC=0.821; p=0.026 E/A r=0.56; p=0.005 AUC=0.901; p=0.003 r=0,45; p=0.025 AUC=0.839; p=0.019 E/Eprop r=0.169; p=n.s. AUC=0.604; p=n.s. r=0.26; p=n.s. AUC=0.714; p=n.s. PVr-A r=0.64; p=0.012 AUC=0.667; p=n.s. r=0.58; p=0.024 AUC=0.565; p=n.s. E/E r=0.23; p=n.s. AUC=0.875; p=0.005 r=0.36; p=n.s. AUC=0.786; p=0.048 AUC: area under ROC-Curve, E: early mitral inflow velocity (cm/s), A: late mitral inflow velocity (cm/s), E : early diastolic mitral annulus velocity (cm/s), PVr-A: difference in duration between pulmonary venous regurgitation and mitral A wave (ms), Eprop: propagation velocity of early mitral inflow (cm/s).

42 342 Echocardiography in cardiomyopathy Conclusions: In patients with systolic heart failure conventional Doppler parameters of mitral inflow proved to be robust enough for a quick and noninvasive assessment of elevated filling pressures. P2146 Echocardiographic predictors of global systolic strain in patients with heart failure H. Dokainish, J. Nguyen, M. Alam, N. Lakkis, M. Stampehl. Baylor College of Medicine, Houston, United States of America Background: There are few data on the echocardiographic correlates of left ventricular speckle-based global systolic strain (GSS) in patients with heart failure (HF), and whether GSS can be depressed in patients with preserved LVEF. Methods: Patients with HF underwent comprehensive echocardiography. In the 3 apical views, speckle-based automated functional imaging (AFI) was utilized to obtain GSS using General Electric EchoPAC software. Univariate and multivariate predictors were determined using linear regression analysis. Results: 177 patients were studied, with mean age of 56.5±8.9 years; 60/118 (51%) were female, 103 (87%) were hypertensive, 47/118 (40%) were diabetic, and 59/118 (50%) had known coronary artery disease. The mean left ventricular ejection fraction (LVEF) was 36.4±16.7%. Fifty-two (30%) of patients had LVEF 45%, of whom 27/52 (52%) had GSS<16% (previously published lower limit of normal). In the entire population, the best echocardiographic correlates of GSS were LVEF (R=0.66), followed by mitral annular systolic velocity (Sa, R=0.63), mitral annular late diastolic velocity (Aa, R=0.51), LV mass (R=0.45), LV end-diastolic dimension (R-0.45), mitral annular early diastolic velocity (Ea, R=0.44), E/Ea (R=0.33, p<0.001), and left atrial volume (R=0.28, Figure). In a multivariate model, independent predictors of GSS (R=0.76 for combined model) were LVEF (p<0.001), Aa (p<0.001), Ea (P=0.002), and LV mass (0.005). Figure 1. Correlation of GSS with LVEF Conclusions: In patients with HF, global systolic strain (GSS) is depressed in a significant proportion who have preserved LVEF. Among all patients, independent predictors of GSS were systolic, diastolic and morphologic variables. These data suggest that GSS may provide information on myocardial systolic performance beyond that provided by LVEF. P2147 Semi-automated left ventricular function assessment by real-time three-dimensional echocardiography is ready for prime time O.I.I. Soliman 1,B.M.VanDalen 1,M.L.Geleijnse 1, W.B. Vletter 1, A.M. Al-Amin 2, F.J. Ten Cate 1. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Al-Azhar University, Cairo, Egypt Objectives: To investigate the inter-observer agreements of real-time threedimensional echocardiography (RT3DE) assessment of the left ventricular (LV) function in real-world practice. Background: RT3DE provides accurate LV function with a good variability between two expert observers. However, the variability between several observers with varying degrees of experience, a real-world practice, is yet to be determined. Methods: Twenty patients (mean age 50±15 years, 13 men) in sinus rhythm with a wide range of LV function (from normal to severe heart failure) underwent RT3DE full-volume acquisition of LV. Ten blinded observers performed off-line 3DE LV function analysis with varying degrees of experience in RT3DE. Eight observers analysed all datasets twice after limited early experience (< 20 cases of acquisition and analysis) and after advanced learning (>50 cases of acquisition and analysis). Two experts with several hundred cases of acquisition and analysis analysed all datasets twice within 12 weeks. Semi-automated border detection with bi-plane projections was performed using semi-automated software with a minimal manual interference according to a standard protocol. Inter- and intra-observer variability among non-experts was calculated as coefficient of variation and as percentage of absolute difference from average measurement. Linear regression was used to test interclass correlation between non-experts and experts. Results: The volume rate of 3DE datasets ranged from 30 to 37 Hz (mean 35 Hz). Mean global LV end-diastolic volume, LV end-systolic volume, and the LV ejection fraction were 169 ml, 103 ml, and 40%, respectively. Experts interand intra-observer variability was 5%, 3% for LV end-diastolic volume, 6%, 4% for LV end-systolic volume, and 7%, 5% for the LV ejection fraction, respectively. Experts interclass correlation was 0.98, 0.97, 0.96 for LV end-diastolic volume, LV end-systolic volume, and the LV ejection fraction, respectively. Coefficient of variation among non-experts was 5±6% vs. 3±1% for global LV end-diastolic volume, 8±7% vs. 5±2% for LV end-systolic volume, and 11±13% vs. 5±3% for the LV ejection fraction during early and late experience, respectively. Linear correlations (R2 = 0.89, 0.88 and 0.87 vs. 0.95, 0.94 and 0.93) between experts and non-experts improved during advanced experience for global LV end-diastolic volume, end-systolic volume and ejection fraction, respectively. Conclusions: RT3DE provides, fast, simple, reproducible assessment of LV function after a short learning curve. P2148 Strain rate imaging demonstrates impaired regional right ventricular deformation in adult unoperated patients with Marfan syndrome A. Kiotsekoglou 1, G.R. Sutherland 1, J.C. Moggridge 1, V. Kapetanakis 1, B.H. Bijnens 2, M.J. Mullen 3, N. Bunce 1, D.K. Nassiri 1,A.J.Camm 1, A.H. Child 1. 1 St. George s University of London, London, United Kingdom; 2 Catholic University Leuven, Leuven, Belgium; 3 Royal Brompton Hospital, London, United Kingdom Introduction: Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder caused by mutations in the fibrillin-1gene that encodes for the protein fibrillin-1. Fibrillin-1 has been identified as a regulator of transforming growth factor-β (TGF-β) bioactivity in the extracellular matrix. TGF- β dysregulation has been linked to reduced left ventricular (LV) stroke volume in the MFS mouse model. LV dysfunction has also been demonstrated in humans but little attention has been paid to the right ventricle (RV). We aimed to assess RV function in adult unoperated patients with MFS. Methods: Forty-three patients with MFS (mean age 30±12 years, 25 men and 18 women) and 49 normal controls without significant differences in age, sex and body surface area from the patient group were examined. No patient had more than mild valvular disease. All subjects underwent an echocardiographic examination at rest. Dp/Dt was measured for all patients. 2D colour Doppler data was recorded using a 4-chamber apical view to evaluate longitudinal systolic strain/strain rate (εsys/srsys) in the RV free lateral wall. Diastolic strain rate was also assessed in the same region. Measurements were averaged over 3 consecutive cardiac cycles. Results: Values are presented as mean ± SD. Dp/Dt values were significantly lower in patients with MFS compared to normal controls (746.79± mmhg vs ± mmhg, p < 0.001). Both longitudinal εsys and SRsys were significantly reduced in the basal, mid- and apical segments of RV free lateral wall in patients with MFS when compared to normal controls (p < 0.001). Diastolic strain rate values were also significantly lower in the MFS group (p < 0.001). In a multiple regression analysis including age, sex, heart rate and pulmonary systolic pressure, MFS was negatively associated with reduced RV free lateral wall regional deformation (p < 0.001). Conclusion: These findings suggest reduced regional RV systolic and diastolic deformation in patients with MFS. This could be attributed to fibrillin-1 deficiency in the cardiac extracellular matrix. Treatment may need to be tailored to prevent further deterioration by supporting RV function. P2149 Global strain, functional capacity and outcome in patients with dilated cardiomyopathy G. Karatasakis, A. Dimopoulos, E. Leontiadis, E. Andreanides, G. Athanasopoulos, S. Polymeros, D.V. Cokkinos. Onassis Cardiac Surgery Center, Athens, Greece Introduction: Global strain (GS) and strain rate (GSR) of the left (LV) and right (RV) ventricle offer new possibilities for the evaluation of ventricular function. The relation of these new indices to functional capacity and patients outcome has not been elucidated. Methods: We studied 34 pts (age years) with previously diagnosed dilated cardiomyopathy (DCM) with LVEF< 40%. They all underwent complete echocardiographic and TDI study for the evaluation LV ejection fraction by the Simpson s rule, longitudinal GS and GSR of the LV and RV and circumferential strain (CS) of the LV. They also underwent cardiopulmonary exercise test for the evaluation of O2 consumption (VO2). Study end- points (EP) were defined as: 1. cardiac death, 2. heart transplantation (TX) and 3. ventricular assist device (LVAD) implantation. Pts were followed up for 28±8 months. Results: During follow up 6 pts had LVAD implantation 2 orthotopic cardiac TX and 2 pts died. Two of the LVAD pts had subsequent cardiac Tx. Pts that reached EP during follow up had lower VO2 (12.±3.6 vs 22±4.6 ml/kg/min p=0.0001), LVEF (23±11 vs 35±10%, p=0.0001), GS of the LV (-4.2±3.8 vs -11.7±5.1%, p=0.0001), GSR of the LV (-019±0.29 vs -0.65±0.26 1/s, p=0.0001), GS of the RV (-16.4±7 vs -26.2±9%, p=0.0001), GSR of the RV (-1.1±0.6 vs -1.5±0.3 1/s, p=0.001) and CS (-4.8±2.2 vs 8.3±3.7%, p=0.001). Overall VO2 was related to GSLV (r=0,64, p=0.0001), GSRLV (r=0.52, p=0.001), GSRV (r=0.52, p=0.002), GSRRV (r=0.047, p=0.000), and CS (r=0.56, p=0.003). and Str (r=0.58, p=0.001). By stepwise logistic regression, among univariate predictors of endpoints, Str was the only independent predictor of pts outcome (p=0.021)

43 Echocardiography in cardiomyopathy 343 Conclusion: In pts with DCM and compromised ventricular function, global longitudinal and circumferential strain are lower in pts that are going to die or need TX and LVAD implantation during F/U. Functional capacity expressed by VO2 is related to longitudinal and circumferential global strain of both ventricles. GSLV (p=0.047) and GSRV (p=0.035) were the only independent predictors of outcome while EF had no prognostic value. Aims: Accurate quantification of left ventricular (LV) volumes and ejection fraction (EF) is of critical importance. MRI is considered as the reference and then we sought to compare standard two-dimensional echocardiography (2DE), threedimensional echocardiography (3DE) and left ventricular angiography for LV volumes and EF assessment, relative to cardiac magnetic resonance imaging (MRI) in heart failure patients. Methods: We studied 24 patients (17 men, age 58±15 years) with history of heart failure who underwent echocardiographic assessment of LV volumes and function as well as cardiac catheterisation. All patients underwent 2DE followed by 3DE (Full volume real-time 3DE images were acquired from apical views with the ie33 ultrasound system (Philips Medical system), and analyzed using a QLAB workstation with a semi-automated endocardial border detection software), LV angiography and MRI in a 48-hour delay. No patient was excluded from the study due to poor image quality. Results/Discussion: The heart failure etiology was: 41,7% (n=10) ischemic cardiomyopathy, 50% (n=12) dilated idiopathic cardiomyopathy and 8,3% (n=2) of patients suffered from heart failure with preserved EF. The mean LV end-diastolic volume (LVEDV) evaluated by MRI was 208±108mL (121±64 ml/m 2 ), mean EF 31±13% and mean LV end-systolic volume (LVESV) was 149±97 ml. LVEDV was underestimated by 3DE (mean LVEDV 153±49 ml) and left ventricular angiography (mean LVEDV 157±52mL). 3DE data sets highly correlated with MRI, especially concerning EF (r: 0.86, 0.88, and 0.96 for LVEDV, LVESV, and EF, respectively) with small biases (-55 ml, -44 ml, 1,1%) and acceptable limits of agreement. 2DE measurements correlated less well with MRI (r: 0.70, 0.82, 0.84), which correlated well with LV volume evaluation on angiography. The 3DE-derived LV volumes are underestimated in most of our patients with severe LV dysfunction, and 3DE data sets do not correlate as well as expected. We didn t exclude patients with poor echocardiographic windows, sometimes with LV not totally accommodated within the pyramidal volume of acquisition. We then determined that with a LVEDV below 240 ml, 3D was more accurate for volumes and EF evaluation. We can therefore apply our results in the everyday life of heart failure, with real patients. Conclusion: Compared with MRI, 3DE is a good method to evaluate LVEF, but it appears to underestimate significantly LV volumes (especially when LVEDV 240mL) with the problem of foreshortened apical views in heart failure patients: as LVEDV increase, 3D accuracy simultaneously decrease. P2150 Myocardial tissue Doppler echocardiography and atorvastatin in heart failure M. Correale, M. Ceglia, N.D. Brunetti, A. Libertazzi, R. Ieva, M. Di Biase. University of Foggia, Foggia, Italy Background: Observational studies, prospective studies and posthoc analyses of randomised clinical trials have suggested that statins could be beneficial in patients with chronic heart failure. Statins have pleiotropic effects beyond reducing the low-density lipoprotein-cholesterol concentration. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure. In these conditions, myocardial mitral annular (S ) systolic and early diastolic (E ) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced S or E values of <3cm/s have a very poor prognosis. In heart failure noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/E ) is a strong prognosticator, especially when E/E is > or =15. This study sought to determine whether treatment with atorvastatin affects left ventricular dysfunction in patients with chronic heart failure, using newly developed ultrasonic tissue Doppler imaging. Methods and Results: A total of 236 patients (aged 68,24±12,87 years; 152 were male) with chronic heart failure were randomized to either administration of atorvastatin (118 patients: aged 67,36±11,58; male 79%; LVEF: 37,59±11,70%) or no atorvastatin therapy (118 patients: aged 63,65±16,56; male 80%; LVEF: 41,30±13,07%) for 12 months. Conventional echocardiography Doppler was used to assess left ventricular (LV) ejection fraction, peak velocities of transmitral early and late diastolic LV filling, the ratio of transmitral early to late LV filling velocity, and E-deceleration time. TDI measurements recorded at the mitral annulus included systolic velocity (S ), early (E ) and late (A ) diastolic velocities, and the ratio of early to late diastolic velocity (E /A ). The transmitral to mitral annular early diastolic velocity ratio (E/E ) was calculated. Results: During the follow-up period (12±2 months), patients in the atorvastatin group showed lower E/E ratio (13,62±8,33 vs 20,95±7,91, P < 0,05), and higher early (E ) diastolic TDI velocity of the mitral annulus at septal annulus (P < 0,05), compared with the no atorvastatin group. Conclusions: One year of atorvastatin treatment improved LV function in patients with chronic heart failure. Tissue Doppler Imaging has the potential to become a sensitive tool for detecting the effects of early medical intervention on myocardial dysfunction in this patient population. P2151 Assessment of left ventricular function in heart failure: limits of real-time three-dimensional echocardiography in real life P.Moceri,D.Bertora,P.Gibelin.CHU de Nice - Hopital Pasteur, Nice, France P2152 Correlation of Doppler echocardiographic parameters and N-terminal B-type Natriuretic Peptide (NT-BNP) levels in elderly patients with systolic heart failure A. Bernheim 1,S.Y.Min 1, M. Wachter 1, D. Jenny 2, M. Neuhaus 2, P. Mussio 3,L.Joerg 4,M.Pfisterer 1, H.P. Brunner-La Rocca 1, P. Buser 1 on behalf of TIME-CHF investigators. 1 University Hospital Basel, Basel, Switzerland; 2 Kantonsspital Baden, Baden, Switzerland; 3 Spital Bülach, Bülach, Switzerland; 4 Kantonsspital St. Gallen, St. Gallen, Switzerland Purpose: Doppler echocardiography and brain-type natriuretic peptide (BNP) have been proposed for the non-invasive estimation of intracardiac filling pressures and the assessment of cardiac performance. Little is known about the correlation between Doppler echocardiography and BNP in patients shortly after stabilization for decompensated systolic heart failure (SHF). Methods: NT-BNP levels and echocardiographic parameters were assessed at baseline in 391 patients (mean age, 76±8 years) with SHF (left ventricular ejection fraction [LVEF] 45%). Estimation of LV filling pressures was derived from the ratios of the early transmitral inflow velocity (E) to the mitral annular velocity of the septal (E/e septal) or the lateral (E/e lateral) annulus. Systolic right ventricular to atrial pressure gradients (RVPG) were measured as an estimate of systolic pulmonary artery pressures. Tricuspid annular motion (TAM) served as a marker of RV function. Results: Median values of NT-BNP and Doppler echocardiographic data are presented in Table 1. NT-BNP showed a significant, but weak association with E/e septal (r=0.17, p=0.009). For E/e lateral (r=0.11, p=0.1) and LVEF (r=-0.07, p=0.21), no correlation with NT-BNP was observed. NT-BNP and E/e septal exhibited a similar correlation with RVPG (NT-BNP: r=0.29, p<0.0001; E/e septal: r=0.28, p<0.0001) and an inverse relation to TAM (NT-BNP: r=-0.19, p=0.0002; E/e septal: r=-0.16, p=0.01). Table 1 NT-BNP (median, interquartile range), pg/ml 4406 ( ) LVEF, % 30±8 E/e septal 20±11 E/e lateral 16±12 TAM, mm 15±5 RVPG, mmhg 34±11 Abbreviations as indicated in text. Conclusions: E/e septal showed a significant relation to NT-BNP. Moreover, both parameters were linked to increased pulmonary artery pressures and decreased RV function. However, the correlation between Doppler echocardiographic parameters and NT-BNP levels was unexpectedly weak. This implies that in elderly patients with SHF, the noninvasive assessment of the cardiac filling state may be less accurate than previously thought and factors other than cardiac performance are likely to importantly influence NT-BNP levels. P2153 Usefulness of 2D speckle tracking echocardiography in carcinoid heart disease N. Mansencal, E. Mitry, P. Rougier, O. Dubourg. APHP - Hopital Ambroise Pare, Boulogne, France Background: Carcinoid heart disease (CHD), which is mainly defined as a valvular heart disease, may occur in patients presenting with digestive endocrine tumor and carcinoid syndrome. The most frequent presentation of CHD is a right-sided CHD and may be associated with right ventricular enlargement. Velocity vector imaging (VVI) is a new echocardiographic technology that measures myocardial velocity and deformation using 2D speckle tracking. The aim of this study was to compare the pattern of VVI in pts with CHD and in healthy pts. Methods: We prospectively studied 60 pts divided in 2 groups: 30 pts with CHD (group 1) and an age- and sex-matched control group (n=30, group 2). All pts with CHD had histologically proven digestive endocrine tumor and carcinoid syndrome. Quantification of CHD severity was performed according to a previous validated scoring system (score between 0 and 20). We systematically performed transthoracic echocardiography in all patients, with the use of VVI technology, allowing to measure systolic peak velocity (V), peak strain (S) and peak strain rate (SR) in basal, mid and apical right ventricular free wall in apical 4-chamber view. Right ventricular systolic function was also assessed by the right ventricular fractional area change (FAC) measured in apical 4-chamber view. Results: Values of V, S and SR in basal, mid and apical right ventricular free wall (FW) were significantly lower in group 1 as compared to control group (p<0.02 for basal FW and p<0.01 for mid and apical FW). Mean CHD score of severity was 10.7±4.6. In patients with lowest tertile of CHD score, no significant difference occurred between group 1 and group 2, concerning global values of V, S and SR, whereas patients with highest tertile of CHD score presented with the most

44 344 Echocardiography in cardiomyopathy important right ventricular systolic dysfunction. Strong correlation was found between CHD score of severity and global values of V (r=0.90, p<0.0001), whereas correlation between CHD score and FAC was weak (r=0.42, p=0.04). Conclusion: Our study suggests that VVI could be of interest in patients with CHD, allowing to quantify right ventricular systolic function. Right ventricular systolic dysfunction in CHD is related to the degree of valvular severity. P2154 Characterization of myocardial deformation in hypertrophic cardiomyopathy using speckle tracking: a comparison with physiological hypertrophy H. Badran 1, M. Saber 2, A. El-Sherif 2, A. Farhan 2,Y.Nassar 2, S. Moktar 2, M. Yacoub 3. 1 Menoufiya University, Shebin, Egypt; 2 Cairo University, Cairo, Egypt; 3 Imperial College London, London, United Kingdom Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder that is characterized not only by the growth of cardiomyocytes, but also by changes in cardiac architecture and cellular metabolism and, finally, by myocardial dysfunction. strain (ε)/strain rate (SR) imaging, using speckle tracking, has been shown to be a more sensitive technique for quantifying regional myocardial deformation (RMD). Objective: This study was designed to characterize global and regional myocardial deformation using 2-dimensional strain and SR imaging in HCM and compare it to physiological hypertrophy in athletes. Methods: The study population comprised 21 patients with HCM (mean age 26.2±6 years) with asymmetric septal hypertrophy (IVS = mm) and 34 age matched athletes with IVS >12 mm. Apical four -chamber view was displayed; 2D RMD using speckle tracking was used to measure longitudinal peak systolic strain (εsys), peak systolic SR [SRsys], time to peak (ε) [TTP], post systolic strain (εpss) and intra-ventricular systolic delay (intra-v delay). These parameters were quantified in basal, mid and apical segments of septal and lateral walls of the left ventricle. Results: RMD of LV segments was significantly reduced in HCM patients in comparison to corresponding segments in athletes, (p <0.001). (εsys) and SRsys of the basal (-8.5±5.5%, -0.7±0.5 sec-1) and mid (-4.8±7.5%,-0.57±0.5 sec-1) segments were significantly lower than apical septal (21.6±21%, 1.62±0.6 sec-1) and all lateral segments [-14.4±6.9%, -1.1±0.4 sec-1, -11.7±5%, -0.77±4.2 sec- 1, 12.3±6.4%, -0.75±0.5 sec-1 respectively (p <0.001) in HCM patients, while myocardial deformation was normal and almost homogenous in athletes. εpss was detected in more than one segment in 67% of HCM patients but not in athletes. The latter showed homogeneous systolic activation of the ventricular walls. Furthermore, HCM group, showed significant increase of the intra-v systolic delay between segments which is more prominent in septal than in lateral wall. The standard deviations (SD) of intra-v delay obtained from septal segments were greater in HCM compared to athletes (42±12 versus 7±3 ms in septal segments and 51±10 versus 3±2 ms, in lateral segments respectively, p <0.001). Conclusion: The non uniform distribution and magnitude of LV hypertrophy in patients with HCM, is associated with disorganized contraction and regional heterogeneity of myocardial systolic function. Deformation analysis using speckle tracking is a novel ultrasonic technique that helps to differentiate mechanical dysfunction in HCM from myocardial adaptation in physiologic hypertrophy. P2155 Usefulness of contrast echocardiography in Tako-Tsubo cardiomyopathy N. Mansencal, A. Lamar, A. Beauchet, R. El Mahmoud, R. Pilliere, O. Dubourg. APHP - Hopital Ambroise Pare, Boulogne, France Background: Assessment of left ventricular (LV) dysfunction in Tako- Tsubo cardiomyopathy (TTC) is of importance. Biplane LV angiography wellcharacterizes this dysfunction, but is invasive. The aim of this prospective study was to assess the reliability of contract echocardiography in TTC. Methods: We prospectively studied 50 women divided into 2 groups: 25 consecutive patients with TTC (group 1) and 25 patients with proved coronary artery disease (CAD) (group 2). Groups 2 was age- and sex-matched with group 1. All patients underwent coronary arteriography, biplane LV angiography, conventional transthoracic echocardiography and contrast transthoracic echocardiography less than 24 hours after the onset of symptoms. Gold standard for LV systolic function assessment was LV angiography. Results: Mean age of patients with TTC was 73±11 years. Mean angiographic LVEF was 38±9%. LV segments were well-classified as having (or not) wall motion abnormalities in 70% and 88% by observer 1 using conventional and contrast echocardiography, respectively (p < ), and in 91% and 99% by observer 2 using conventional and contrast echocardiography, respectively (p < ). In patients with TTC, LVEF was 42±11% assessed by conventional echocardiography (versus 38±9% by LV angiography, p < ) and 38.2±8.5% using contrast agent (p = 0.42, as compared to LV angiography). Sensitivities and specificities for the diagnosis of TTC by observer 1 were respectively 56% and 64% using conventional echo versus 88% and 84% using contrast agent. Sensitivities and specificities for observer 2 were respectively 72% and 88% using conventional echo versus 96% and 96% using contrast agent. Accuracy for the diagnosis of TTC was significantly improved using contrast echocardiography for both observers, whereas interobserver agreement was excellent using contrast agent (kappa = 0.85 versus 0.34 using conventional echocardiography). Conclusion: We demonstrated that contrast echocardiography is an accurate imaging method for a non-invasive assessment of left ventricular systolic function in TTC. P2156 Incremental value of subclinical left ventricular systolic dysfunction for the identification of patients with obstructive coronary artery disease G. Nucifora, J.D. Schuijf, M. Bertini, V. Delgado, A.J.H.A. Scholte, J.M. Van Werkhoven, J.W. Jukema, E.R. Holman, E.E. Van Der Wall, J.J. Bax. Leiden University Medical Center, Leiden, Netherlands Purpose: Diastolic and subclinical systolic dysfunction may indicate coronary artery disease (CAD) even in asymptomatic patients. However, whether these characteristics can improve prediction of obstructive CAD is still unknown. Methods: A total of 182 consecutive outpatients (54±10 years, 59% males) without known CAD and with LV ejection fraction 50% underwent 64-slice MSCT coronary angiography and echocardiography. MSCT angiograms showing atherosclerosis were classified as showing obstructive ( 50% luminal narrowing) CAD or not. Conventional echocardiographic parameters of LV systolic and diastolic function were obtained; in addition, speckle tracking echocardiography was performed to assess LV global longitudinal strain (GLS). The relation between this parameter of LV systolic function and obstructive CAD was explored using multivariate and ROC analyses. Results: Based on MSCT, 32% patients were classified as having no CAD, whereas 33% showed non-obstructive CAD and the remaining 35% had obstructive CAD. Multivariate analysis of clinical and echocardiographic characteristics showed that only high pre-test likelihood of CAD (OR 3.21, 95% , p=0.046), GLS (OR 1.97, 95% CI , p<0.001), and diastolic dysfunction (OR 3.72, 95% CI , p=0.006) were associated with obstructive CAD. A value of GLS yielded high sensitivity and specificity in identifying patients with obstructive CAD (83% and 77%, respectively), providing a significant incremental value over pre-test likelihood of CAD and diastolic dysfunction (Figure). Incremental value of GLS Conclusions: GLS impairment in patients without overt LV systolic dysfunction, expressing subclinical LV dysfunction, aids detection of patients with obstructive CAD. This information may be useful for selection of appropriate further diagnostic tests. P2157 Effects of cardiac resynchronization therapy on subepicardial and subendocardial left ventricular twist M. Bertini 1, N. Ajmone Marsan 1, G. Nucifora 1, V. Delgado 1,R.J.Van Bommel 1, C.J.W. Borleffs 1, G. Boriani 2,M.Biffi 2, M.J. Schalij 1, J.J. Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 Univ. di Bologna - Istituto di Cardiology, Bologna, Italy Purpose: Subepicardial and subendocardial layers have different orientation of myofibers: right and left hand orientation, respectively. Subepicardial layer leads the direction of left ventricular (LV) twist, having larger radius of rotation. Minimal data are available on subepicardial and subendocardial LV twist and cardiac resynchronization therapy (CRT) in heart failure (HF) patients. The aim of the study was to explore the effects of CRT on LV twist in both layers. Methods: A total of 75 HF patients scheduled for CRT were included. Realtime three-dimensional echocardiography was performed and repeated within 48 hours after CRT, to assess LV volumes, LV ejection fraction (EF) and systolic dyssynchrony index (SDI). Speckle tracking analysis was applied to LV basal and apical short axis images to assess subepicardial and subendocardial LV apical and basal rotation. LV twist was defined as the net difference at isochronal time point between apical and basal rotation. Consequently, subepicardial and subendocardial LV twist were calculated at baseline and within 48 hours after CRT (immediately after CRT). Results: The mean age was 65±10 years, 49 men. Ischemic aetiology of HF was present in 38 (51%) patients. At baseline LVEF was 26±6% and improved to 31±7% immediately after CRT (p<0.001). At baseline SDI was 7.6±2.4% and improved to 5.8±2.3% immediately after CRT (p<0.001). Peak subepicardial LV twist increased from 2.3±1.9 to 3.4±2.1 (p=0.001) and peak subendocardial LV

45 Echocardiography in cardiomyopathy 345 twist from 4.5±3 to 5.5±3.2 (p=0.003). The acute change ( ) of LVEF was significantly related to LV end-systolic volume, SDI, SDI, subepicardial LV twist, subepicardial LV twist, subendocardial LV twist and subendocardial LV twist. At multivariable linear regression analysis the strongest determinant of LV systolic improvement immediately after CRT was subepicardial LV twist (β=0.54, p<0.001). Conclusions: An immediate improvement of subepicardial LV twist after CRT is the best reflector of the positive effect of CRT on LV systolic function P2158 Two-dimensional speckle tracking strain echocardiography in heart transplant patients B. Syeda, P. Hoefer, P. Pichler, M. Vertesich, S. Roedler, S. Mahr, S. Graf, J. Bergler-Klein, D. Glogar, T. Binder. Medical University of Vienna, Vienna, Austria Background: Longitudinal strain determined by 2 dimensional speckle tracking is a sensitive parameter to detect early systolic left ventricular dysfunction. However, it is unclear if heart transplant (HTX) patients exhibit reduced longitudinal strain compared to healthy individuals. Methods: Transthoracic echocardiography (TTE) and multidetector computed tomographic angiography (MDCT, dual source 2x32x0.6mm, Siemens Definition) was performed in 31 HTX patients (126.8±67.6 months [10.6 years] post transplantation) and in 42 asymptomatic healthy subjects. Grey-scale apical 2-, 3- and 4-chamber views were recorded and stored for automated offline speckle tracking for longitudinal strain analysis (EchoPAC 7.0, GE). The presence of coronary artery disease (CAD) and left ventricular ejection fraction (LVEF%) was assessed by MDCT. Results: Nine of the 31 transplant patients had significant allograft CAD. Mean global longitudinal peak systolic strain (GLPSS) was significantly lower in the transplant recipients than in the healthy population (-13.9±4.2% vs ±5.8%, respectively, p<0.01). This was still the case after excluding the 9 transplant patients with CAD (-14.1±4.4% vs ±5.8%, respectively, p<0.02). LVEF% was 60.7±10.1% in transplant recipients vs. 64.8±6.4% in the healthy population (p=ns). There was no significant age difference within the two groups 62.9±10.7 years vs. 60.4±11.6 years, respectively (p=ns). Conclusion: GLPSS is reduced in heart transplant recipients compared to healthy subjects despite equal LVEF%. This difference is independent of age. Longitudinal strain analysis could allow the early detection of subclinical left ventricular dysfunction in heart transplant recipients. P2159 Differences in the cardiomyopathy progression of female and male fabry patients. implications for monitoring and treatment M. Niemann 1, S. Herrmann 1, F. Breunig 1,M.Beer 2, C. Wanner 1, W. Voelker 1,G.Ertl 1, F. Weidemann 1. 1 Medizinische Klinik I, Wuerzburg, Germany; 2 Radiologische Klinik, Wuerzburg, Germany Background: The established disease model for the Fabry cardiomyopathy is based mainly on data from male patients. In this model the cardiomyopathy progression starts with left ventricular hypertrophy and reduced regional myocardial function and progresses towards myocardial fibrosis. Whether it is similar in female patients was never systematically investigated. Methods: 115 patients with genetically proven Fabry disease (64 females and 51 males) were investigated with standard echocardiography (for the assessment of left ventricular hypertrophy), strain rate imaging (for regional myocardial deformation) and magnetic resonance imaging (MRI) using the late enhancement (LE) technique for the detection of fibrosis. Results: Female Fabry patients (n=64; age 43±10 years, range from 10 to 83 years) had a left ventricular wall thickness (LVWT) range from 5 to 16 mm. Thirtyfour percent of the female patients (n=22) had at least one LE positive segment. LE was first seen at a LVWT of 9 mm. In the female patients being non hypertrophic (LVWT < 13 mm) 11 patients had already LE positive segments. Above 13 mm LVWT all females showed LE in MRI. In the 51 male Fabrys (age 43±7 years, range from 7 to 66 years) the LVWT ranged from 6 to 20 mm. Forty-nine percent of the male patients (n=25) had at least one LE positive segment. LE occurred first at 12mm LVWT. All male patients having a LVWT of more than 16 mm (n=6) showed at least one LE positive segment. The youngest female with LE was 36 and the youngest male patient with LE was 23 years old. The presence of LE was associated with low strain rate values in male and female patients. In female patients showing LE the reduction of strain rate values were independent of left ventricular wall thickness (peak systolic strain rate lateral in hypertrophic patients with LE = -0.7±0.2 s -1 ; in non hypertrophic patients with LE = -0.7±0.2 s -1 ;p>0.05). Conclusion: In contrast to male patients, the loss of function and the development of fibrosis in female Fabry patients do not necessarily require hypertrophy. Thus, the cardiomyopathy progression in female and male Fabry patients is different which should have implications for monitoring and treatment of Fabry female patients. P2161 Regional distribution of entity of strain and time to peak strain of right ventricle in normal individuals and in heart failure patients A. Meris 1,C.Conca 1,C.Klersy 2, A. Evangelista 1, J. Klimusina 1, M. Averaimo 1, A. Auricchio 1, F. Faletra 1. 1 Fondazione Cardiocentro Ticino, Lugano, Switzerland; 2 Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Purpose: Assessment of right ventricular (RV) function is of paramount importance in many cardiovascular diseases. RV strain by using 2D speckle tracking has been used to a limited extent in the evaluation of RV function. Methods: We prospectively enrolled 100 normal subjects and 76 patients with RV dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) < 2 cm. Longitudinal peak strain (LPS), defined as percentage of maximum shortening in systole (negative values) for 6 RV segments (basal, mid, and apical segments of the RV free wall and septum), global RV strain (GS), defined as the average of LPS in the 6 segments, and time-to-peak strain (TPS) defined as the time from the beginning of QRS to LPS, were measured from 4-chamber apical view. Results: LPS and GS in normal subjects and in patients with RV dysfunction are shown in the Figure. Normal subjects have a significantly (p <0.05) higher LPS and GS and a shorter TPS than patients with RV dysfunction. A significant correlation between LPS and TAPSE (r = -0.83, p <0.001) was found. Considering TAPSE as the reference parameter, the ROC curve showed that the highest sensitivity/specificity cut-off to identify normal LPS is -19% [sensitivity of 95% (95%CI 87% to 98%) and a specificity of 85% (95%CI 77% to 91%)]. Conclusions: 2D speckle tracking may be a useful tool to evaluate global and regional RV function. Greater differences are noted in the regional distribution of the amount of mechanical dyssynchrony rather than in the timing. P2162 Left ventricular dysfunction during right ventricular pacing: volumetric analysis with real-time three-dimensional echocardiography T. Wolber, C. Brunckhorst, F. Duru. University Hospital Zurich, Zurich, Switzerland Background: Chronic right ventricular apical (RVA) pacing has been associated with increased risk of heart failure and adverse outcome. RVA pacing induces abnormal electrical activation patterns of the left ventricle. However, few data exist on the acute effects of RVA pacing on three-dimensional ventricular function. We performed three-dimensional (3D) echocardiography with volumetric analysis to assess global and regional left ventricular function during RVA pacing. Methods: 26 patients with implanted cardiac devices and normal intrinsic atrioventricular conduction were included in the study. Three-dimensional echocardiography was performed during intrinsic sinus rhythm and during RVA pacing. Time-volume analysis of 16 myocardial segments was performed offline. A systolic dyssynchrony index (SDI) was calculated to assess regional variation in systolic function. Longitudinal function was assessed by sequential time-volume analysis of apical, mid-ventricular and basal segments. Results: During RVA pacing, a reversed apical-to-basal longitudinal contraction sequence was observed in 58% of all patients. RVA pacing was associated with 3D echo contraction front mapping

46 346 Echocardiography in cardiomyopathy increased LV dyssynchrony and reduced LV ejection fraction (LVEF). SDI increased from 4.4±2.2 to 6.3±2.4 percent (P=0.001).Three-dimensional left ventricular ejection fraction (LVEF) declined from 53±13 to 47±14 percent (P=0.05). Conclusion: RT3DE volumetric assessment of left ventricular function provides evidence that pacing from the RVA results in acute alterations in LV contraction sequence and increased LV dyssynchrony. Further studies are warranted to assess the potential of RT3DE to identify patients who might be at increased risk of pacing-induced heart failure or who might benefit from alternate-site or multisite pacing. P2163 Contrast enhancement has no additional value in RV volumetric measurements with real-time 3D echocardiography D.H.F. Gommans 1, A.P.J. Van Dijk 2, M.A. Brouwer 2,M.J.Van Der Vlugt 2. 1 Radboud University Medical Centre, Nijmegen, Netherlands; 2 Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands Purpose: Real-time 3D echocardiography (RT3DE) has the potential to substitute cardiac MRI for RV volumes. The purpose of this study was to assess accuracy and reproducibility of RT3DE for RV volumes with and without the use of contrast. Methods: RT3DE images (IE-33, Philips) were obtained from the apical view before and after contrast agent-injection (Sonovue) in 40 healthy males. Using on board software (Qlab 5, GI view) RV and LV volumes were divided into 7 shortaxis and 7 long-axis slices. Endocardial contours were manually traced for enddiastolic and end-systolic volumes. Accuracy for LV measurement was confirmed by comparison to a validated standard (Qlab 5, CV view, 3DQ ADV). Accuracy of RT3DE RV measurement was determined by comparison of LV SV with RV SV. Volumes were traced twice and compared to obtain intraobserver variability. Results: Obtained with RT3DE, mean LV EDV and ESV were 127.5±21.4 and 50.5±12.7 ml, LVEF was 60.4±7.7% with excellent comparison to the standard (mean difference -0.02, p=0.99). Mean RV EDV and ESV were 108.7±21.8 and 44.6±14.5 ml, RVEF was 59.3±8.0%. In the short-axis view with and without contrast the mean difference between RV and LV SV was -7.4±17.6 ml, p<0.05 and -11.2±11.4 ml, p<0.05. In the long-axis view with and without contrast mean difference between RV and LV SV was -5.0±17.1 ml, p<0.07 and -10.6±12.5 ml, p<0.05 (Figure). In short-axis view Pearson correlations between RV and LV SV with and without contrast were 0.50 and 0.77, p< In the long-axis view correlations with and without contrast were 0.51 and 0.75, p< Reproducibility was good (r = 0.971, SEE = 10.1). Conclusion: RT3DE underestimates RV volumes, but it is a feasible and reproducible method. Contrast has no additional value for volumetric measurements. P2164 Assessment of right ventricular systolic function: validation of six echocardiographic methods versus cardiac magnetic resonance imaging M. Pavlicek, A. Wahl, K. Wustmann, F. Praz, S. De Marchi, M. Schwerzmann, T. Rutz, C. Eigenmann, B. Meier, C. Seiler. Inselspital Bern, Berne, Switzerland Purpose: Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Numerous parameters are routinely employed, namely peak systolic tricuspid annular velocity by Doppler tissue imaging (DTItv), tricuspid myocardial acceleration during isovolumetric contraction (IVA), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI) and fractional length and area change (FAC), without knowing the most accurate one for systolic RV function assessment. We prospectively compared these parameters with cardiac magnetic resonance (CMR) as reference method. Methods: 72 patients underwent both CMR and transthoracic echocardiography within 11±32 days. The RV was imaged by CMR from the base towards the apex during short end-expiratory breath-holds using contiguous short axis slices in 8mm increments. Volumes were calculated from the area within the manually traced contours and the slice thickness (disk summation). Echocardiographic values were obtained by 2D-, M-Mode-, Doppler-echocardiography, and pulsed wave DTI. Results: 17 (24%) patients showed normal biventricular systolic function, 32 (44%) predominant left ventricular dysfunction, 14 (19%) predominant RV dysfunction and 9 (13%) pulmonary hypertension. RV ejection fraction (EF) as determined by CMR ranged from 25 to 80%. It correlated with DTItv (r=0.42, p<0.0001), TAPSE (r=0.42, p<0.0001), IVA (r=0.31, p=0.009), fractional length change (r=0.34, p=0.03), FAC (r=0.32, p=0.007) and MPI (r=-0.25, p=0.04). The accuracy of the methods for the detection of RVEF<50% is shown in the table. Table 1 p-value Area under the curve Sensitivity, Specificity, Cut off value % % DTItv, cm/s < TAPSE, mm < FAC, % IVA, m/s RV length change, % MPI, no unit Conclusions: The echocardiographic methods most accurately detecting impaired RV ejection fraction <50% are those measuring tricuspid annular free wall motion in the long axis. P2165 Right ventricular function in asymptomatic patients with systemic sclerosis C. Dumitrascu, A. Dumitrascu, C. Draghici, M. Grigore, C.M. Tanaseanu. Sf Pantelimon Emergency Hospital, Bucharest, Romania Cardiopulmonary involvement in patients with systemic sclerosis (SSc) carries a poor prognosis, mainly due to pulmonary hypertension and rightheart failure. Subclinical cardiac involvement has a higher frequency. Aim Of The Study: to assess the right ventricular (RV) myocardial function in patients with systemic sclerosis and related the findings to the clinical features of the disease. Methods: Twenty-six patients with SSc (mean age, 56±15 years [± SD]) and 25 healthy, age-matched control subjects were studied. The patient underwent clinical exam, routine lab tests, determination of anti SCL and anti centromere antibodies, Doppler echocardiography. Results: Compared with control subjects, RV free wall thickness (5.6±1.4 mm vs 3.9±1.2 mm, p < 0.001) and end-diastolic dimensions were increased in patients with SSc, The mean value of Tr E/A in SSc was lower than in controls (0.9±0.2 vs. 1.2±0.2, p=0.03). The mean value of Tei index for the RV was higher in SSc patients than in controls (0.34±0.08 vs. 0.29±0.02, p <0.001) The isovolumic relaxation time corrected to RR interval was increased (6.5±2.9 versus 4.5±2.5%). TAPSE measurements were significantly different between SSc and control patients (2.4±0.43 vs. 1.9±0.39 cm with P < ). LVEF was similar, but RVEF was lower in the SSc group (RVEF: 49.6±6.8 vs. 39.2±6.7% with P < ). Contrary to expectation, pulmonary artery systolic pressure (PASP) did not correlate well with RV function (r = 0.260, r2= 0.063, P = 0.015). Conclusions: In progressive systemic sclerosis, RV systolic dysfunction is common and appears to be a result of pulmonary hypertension, disturbance of myocardial microcirculation, and myocardial fibrosis. Pulmonary hypertension was not well correlated with RV dysfunction; it suggested pulmonary hypertension was not the only cause of RV failure. Primary right heart involvement was the other possible cause. In evaluation of the patients with SSc echo appeared to be the most useful among the noninvasive tests, mainly due to the high specificity. P2166 Left ventricular untwisting in restrictive and pseudo-restrictive left ventricular filling; novel insights into diastology B.M. Van Dalen, O.I.I. Soliman, W.B. Vletter, F.J. Ten Cate, M.L. Geleijnse. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Objectives: Conceptually, an ideal therapeutic agent should target the underlying mechanisms that cause left ventricular (LV) diastolic dysfunction. The objective of our study was to gain further insight into the mechanics of diastology by comparison of LV untwisting measured by speckle tracking echocardiography (STE) in young healthy adults with normal and pseudo-restrictive LV filling, and dilated cardiomyopathy (DCM) patients with true restrictive LV filling. Methods: The study comprised 20 healthy volunteers with a Doppler LV-inflow pattern compatible with restrictive LV filling but an E/Em ratio <8 ( pseudorestrictive ), 20 for age and gender matched healthy volunteers with normal LV filling and an E/Em ratio <8, and 10 DCM patients with true restrictive LV filling and an E/Em ratio >15. LV untwisting parameters were determined by STE.

47 Echocardiography in cardiomyopathy 347 Results: Compared to healthy subjects, DCM patients had decreased peak diastolic untwisting velocity (-62±33 degrees/s vs. -113±25 degrees/s, P <0.01) and untwisting rate (-15±9 degrees/s vs. -51±24 degrees/s, P <0.01) (Figure 1). Compared to healthy subjects with normal LV filling, healthy subjects with pseudo-restrictive LV filling had increased peak diastolic untwisting velocity (- 123±25 degrees/s vs. -104±30 degrees/s, P <0.05) and untwisting rate (-59±23 degrees/s vs. -44±22 degrees/s, P <0.05) (Figure 1). Conclusion: Faster LV untwisting plays a pivotal role in the rapid early diastolic fillingoccasionally seen in young healthy individuals. In contrast, in DCM patients untwisting is severely delayed and this impairment to utilize suction may reduce LV filling. P2168 Noninvasive estimation of left ventricular filling pressure in patients with heart failure independent of systolic function F.L. Dini 1, P. Ballo 2, L. Badano 3, P. Barbier 4, M. Galderisi 5,S.Ghio 6, A. Rossi 7, P.L. Temporelli 8. 1 Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy; 2 Sant Andrea Hospital, La Spezia, Italy; 3 Santa Maria della Misericordia Hospital, Udine, Italy; 4 Centro Cardiologico Monzino, Milan, Italy; 5 Azienda Ospedaliera Universitaria Federico II, Naples, Italy; 6 Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 7 University of Verona, Verona, Italy; 8 Istituto Scientifico - Fondazione Salvatore Maugeri IRCCS, Veruno, Italy Background: Using Classification And Regression Tree (CART) analysis, we sought a noninvasive estimation of left ventricular (LV) filling pressure in patients with heart failure (HF) by decision models based on single or combined echo- Doppler parameters. Methods and Results: HF patients (n=258) with a wide range of LV ejection fraction (EF= 43±16%) underwent echo-doppler and hemodynamic evaluation. Elevated LV filling pressure was defined by a pulmonary capillary wedge pressure >15 mmhg. Patients were classified according to: E wave deceleration time (EDT) <150 ms, mitral-to-myocardial early velocities (E/e ) >15, 15 >E/e >8, left atrial (LA) volume index >40 ml/m 2, E wave-to-color M-mode propagation velocity >2, difference in duration of pulmonary vein flow and mitral velocities at atrial contraction >30 ms. A classification tree was developed using CART analysis (derivation cohort: n=178). Using this model, E/e >15 or EDT <150 ms as a first decisional node allowed identification of presence of elevated LV filling pressure in 71 patients. As further steps, 15 >E/e >8 as a second node followed by one of the remaining criteria as a third node permitted prediction of raised filling pressure in 79 more patients (92% sensitivity, 74% specificity). Models were validated in a testing group of 80 patients. With respect to standard criteria, the best performance of CART analysis was found in patients with EF >50%, with a 9.5% relative increase in accuracy. P2167 Can 3D echocardiography be used to investigate the dynamics of cardiac function? A functional data analysis K.K. Poppe, G.A. Whalley, R.N. Doughty, C.M. Triggs. The University of Auckland, Auckland, New Zealand Background: Cardiac motion is a continuum, depending on the relationship between systolic and diastolic phases. Real-time 3-dimensional echocardiography (RT3DE) allows left ventricular volumes (LVVs) to be calculated for each frame of an imaging sequence. By converting the repeated volume measurements to a function of time, functional data analysis techniques can be applied. We explore the representation of LV dynamics using the 1st and 2nd derivatives of LVV throughout the cardiac cycle. Method: RT3DE loops (Philips ie33) were captured from 15 normal and 15 postacute coronary syndrome (ACS) subjects. For each subject, LVVs (proportional to end-diastolic volume) were converted to a function of time (R software). The 1st derivative of the function is the velocity (vel) of volume change; the 2nd derivative is acceleration (acc). Plots showing 2 dynamic dimensions (LVV vs vel, and vel vs acc) and 3 dimensions (LVV vs vel vs acc) were created. Results: Normal/ACS subjects: 60%/80% male, median age 24/64yrs, median ejection fraction (LVEF) 60%/36%. In all subjects, LVV vs vel and vel vs acc plots evolved closed curves that frequently crossed themselves, suggesting the 2D plot was an inadequate summary of LV dynamics. The apparent loops on the 2D plots were unravelled in the 3D plots, revealing the changing directions of vel and acc through the cardiac cycle. While the appearance of curves was similar across subjects, the area within the curve appears reduced with low LVEF. a) LVV vs time, b) 2D plot, c) 3D plot Conclusion: This pilot study graphically displayed the dynamics of LVV through the cardiac cycle. As motion is assessed throughout systole and diastole, the area within the curve may prove a more sensitive measure of function than LVEF. Further evaluation of the technique is required and should involve 3D not 2D curves. CART Analysis Conclusions: These classification rules may be used to build up ease-of-use pathways for predicting elevated LV filling pressure in patients with HF. P2169 Arterial stiffness and coronary flow reserve are independent determinants of LV untwisting in untreated patients with essential hypertension. A speckle tracking echocardiography study I. Ikonomidis, C. Papadopoulos, J. Lekakis, I. Paraskevaidis, H. Triantafyllidi, S. Tzortzis, C. Tsitlakidis, P. Trivilou, D.T. Kremastinos. University of Athens, Athens, Greece LV utwisting is a novel marker of myocardial relaxation and LV diastolic suction. Arterial stiffness and impaired coronary microcirculation may determine left ventricular (LV) function. We investigated the association of the above parameters with LV twisting and untwisting. Methods: We studied 60 untreated consecutive patients (mean age: 54±11 years), with newly diagnosed essential hypertension (clinic blood pressure >140/90 mmhg and >125/80mmHg in 24hour ambulatory BP monitoring) and 30 healthy controls matched for atherosclerotic factors. Exclusion criteria were diabetes, familiar hyperlipidemia, CAD, and pulmonary disease. We measured a) Carotid to femoral artery pulse wave velocity (PWV) b) Coronary flow reserve (CFR) after adenosine infusion. c) Peak Twisting (ptw-deg) and Untwisting (Utw) at mitral valve opening (UtwMVO) and at the end of LV early filling defined as the end of the mitral inflow E wave (UtwE-deg) using speckle tracking imaging. We calculated the percentage difference between Peak twisting and untwisting at MVO [%difference (ptw UtwMVO)] and end of mitral E wave [%difference (ptw UtwE)] and the corresponding untwisting rates. Results: Patients had higher PWV (10.5±1.8 vs 8.2±1.5, p<0.01) and lower CFR, (2.5±0.6 vs 3.2±0.6, p<0.01) than normals. Compared to controls, hypertensives had increased peak twisting (15.7±3.6 vs.13.8±4.3 deg p<0.05) and decreased %difference ptw-utwmvo (29±8 vs. 38±7%, p<0.05) %difference ptw-utwe 67±9 vs. 73±8%, p<0.05), untwisting rate at MVO (0.34±0.1 vs. 0.55±0.1 deg/sec p<0.05) and end of mitral E wave (0.19±0.1 vs. 0.24±0.1 deg/sec p<0.05)). Increasing PWV and decreasing CFR were related to reduced %difference ptw-utwmvo (r=-0.48 and r=0.43, p<0.01), %difference ptw-utwe (r=-0.37, r=0.47, p<0.01), untwisting rate at MVO (r=-0.64 and r=0.43, p<0.01) and end of LV early filling (r=-0.38 and r=0.42, p<0.01). By regression analysis,

48 348 Echocardiography in cardiomyopathy the above relations remained significant after adjustment for age, sex, BMI, LV mass and blood pressure (p<0.01). By ROC analysis a PWV>10.5 and CFR<2.5 were significant predictors of an untwisting rate at MVO >0.30%/sec (median of the study population) [AUC=82%, 95% CI: 70-90% p<0.01 and AUC=71%, 95% CI: 56-87% p=0.013]. Conclusions: Increased arterial stiffness and abnormal coronary microcirculation are independent determinants of impaired LV untwisting in never-treated patients with essential hypertension. patients with normal glucose tolerance. Using logistic regression model adjusting for age, gender, site and size of AMI, and blood pressure, newly diagnosed DM (odds ratio 3.0) and a history of DM (odds ratio 9.0) remained significant predictors of CFVR < 2 whereas impaired glucose tolerance (IGT) was not. Conclusions: The study shows that CFVR is decreased in patients with known or newly diagnosed DM even after adjustment of possible confounders, whereas patients with IGT have preserved CFVR compared to those with normal glucose metabolism. P2170 Intima media-thickness of the common carotid artery in major vascular surgery patients: a predictor of postoperative and late cardiovascular events W.J. Flu 1,J.P.VanKuijk 1, S.E. Hoeks 1,R.Kuijper 2, O. Schouten 2, D. Goei 2,T.Winkel 2,Y.VanGestel 2,J.J.Bax 3, D. Poldermans 4. 1 Erasmus MC, Rotterdam, Netherlands; 2 Erasmus, Rotterdam, Netherlands; 3 Leiden University Medical Center, Leiden, Netherlands; 4 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Purpose: Cardiovascular complications are the leading cause of postoperative and late morbidity and mortality in vascular surgery patients. The Revised Cardiac Risk (RCR) Index is commonly used for preoperative risk stratification. This study evaluated the incremental prognostic value of the common carotid artery intima media-thickness (CCA-IMT) in predicting cardiovascular events, next to the prognostic value of the RCR Index. Methods: In 508 vascular surgery patients the following risk factors were recorded; ischemic heart disease, heart failure, stroke, diabetes mellitus and renal dysfunction. Troponin T measurements and ECG s were performed postoperatively on day 1, 3 and 7. The CCA-IMT was analysed using high-resolution B- mode ultrasonography. The study endpoint was the composite of 30-day cardiac ischemia and late cardiovascular mortality. The optimal predictive value of CCA- IMT was calculated using ROC curve analysis. Multivariable regression analyses were used to assess the additional value of CCA-IMT to predict cardiac events. Results: 30-day cardiac ischemia and late cardiovascular mortality was noted in 117 (23%) and 81 patients (16%), respectively. The optimal predictive value of CCA-IMT was 1.25mm (sens.70%, spec.80%). Multivariable analysis showed that the RCR Index was predictive for 30-day cardiac ischemia (OR=2.6 95%CI ) and late cardiovascular mortality (HR %CI ). An increased CCA-IMT on top of the RCR Index was independently associated with 30-day cardiac ischemia (OR 2.5, 95%CI ) and late cardiovascular mortality (HR %CI ) (Figure). P2172 Implication of dynamic variation of left ventricular vortex flow morphology on left ventricular function: a quantitative vorticity imaging study using contrast echocardiography G.R. Hong, I.W. Song, S.H. Lee, J.S. Park, D.G. Shin, Y.J. Kim, J.H. Chio. Yeungnam University, Daegu, Korea, Republic of Background: We hypothesized that the dynamic changes of LV vortex flow morphology optimizes LV fillingand ejection. The aim ofthisstudy wastocharacterize dynamic changes in LV vortex flow morphology during cardiac cycle in normals and patients with systolic (SHF) and diastolic heart failure (DHF). Methods: 17 normals and 20 patients (13 with SHF and 7 with DHF) underwent 2-D contrast echocardiography. LV vorticity was estimated by particle image velocimetry. We measured maximal and minimal vortex flow size (TVS,%) and phasic variation in the vortex flow size (PV-TVS,%) and time to maximum vortex formation (t-mv). Results: Max-TVS was significantly larger in normals than SHF (p<0.001) but there was no significant difference between normals and DHF. Min-TVS was significantly larger in normals than in patients with SHF and DHF (p<0.001). PV-TVS was greater in normals than SHF (p<0.01) but there was no significant difference between normals and DHF. T-MV during diastole was significantly longer in DHF than normal and SHF (p<0.001). Quantitative LV vortex size Max-TVS (%) Min-TVS (%) PV-TVS (%) t-mv (ms) Normal 86±12 32±11 57±25 89±27 SHF 50±14 12±7 35±19 95±35 DHF 78±18 8±5 61±31 185±56 TVS, total vortex size; PV, phasic variation; t-mv, time to maximal vortex size; SHF, systolic heart failure; DHF, diastolic heart failure. Cumulative Long Term Survival Conclusions: The present study shows that an increased CCA-IMT has prognostic value in vascular surgery patients to predict cardiovascular events, incremental to the prognostic value of the RCR Index. P2171 Influence of abnormal glucose metabolism, on coronary microvascular function after a recent myocardial infarction B.B. Loegstrup 1, D.E. Hoefsten 1, T.B. Christophersen 1, J.E. Moeller 2, H.E. Boetker 3, P.A. Pellikka 4,K.Egstrup 1. 1 Svendborg Hospital, Svendborg, Denmark; 2 Department of Cardiology, Copenhagen, Denmark; 3 Aarhus University Hospital, Aarhus, Denmark; 4 Mayo Clinic Division of Cardiovascular Diseases, Rochester, United States of America Objectives: To assess the association between abnormal glucose metabolism and depressed coronary flow velocity reserve (CFVR) in patients with acute myocardial infarction (AMI). Background: Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism independent of other risk factors. Methods: Study population consisted of 183 patients with a first AMI. 161 patients with no history of diabetes mellitus (DM) performed an oral glucose tolerance test. After coronary angiography and revascularization a transthoracic echocardiography and non-invasive assessment of CFVR was performed. CFVR was assessed in the distal part of left descending artery. Adenosine was administered by intravenous infusion (140 μg/kg/min) to obtain the hyperaemic flow profiles. The CFVR was the ratio of hyperaemic to baseline peak diastolic coronary flow velocities. Results: Median CFVR was 1.9; 109 patients (60%) had a CFVR 2. CFVR was depressed in 22 patients with a history of DM, and in 39 patients with newly diagnosed DM, whereas CFVR did not differ in 58 patients with abnormal and 62 Conclusion: Phasic changes in vortex flow morphology correlates with global LV function and maybe a sensitive indicator of intracardiac hemodynamics in SHF and DHF P2173 Comparative effects of levosimendan and dobutamine on left ventricular diasolic function and brain natriuretic peptide in patients with decompansated advanced heart failure D. Duman, F. Palit, E. Simsek, O. Yildiz. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey Background: In this randomized prospective trial, we we compared the effects of levosimendan and dobutamine on left ventricular diastolic cardiac modifications and brain natriuretic peptide in patients with decompansated advanced heart failure (AHF).

49 Echocardiography in cardiomyopathy 349 Methods: Sixty-three patients (mean age 65±9.0 yrs) refractory to conventional theraphy with left venicular (LV) ejection fraction (EF) 0.35 and diastolic LV dysfunction due to idiopathic or ischemic cardiomyopathy were enrolled and were randomized to levosimendan (n= 33) or dobutamine (n= 30). All patients were in sinus rhythm and had pseudonormal (21%) or restrictive filling (79%) pattern by echo Doppler method. Conventional echo Doppler was used to assess LV EF, LV volumes, peak velocities of transmitral early (E) and late (A) diastolic LV filling, the ratio of transmitral early to late LV filling velocity (E/A), and deceleration time of E (DT). The E/e ratio was also evaluated using the tissue Doppler imaging together with plasma B-type natriuretic peptide (BNP) levels measurements before and after drug infusion. Results: The improvement of LV EF and LV volumes were smilar in both levosimendan and dobutamine groups. However, levosimendan but not dobutamine group showed a significant increase of A wave (p<0.05), DT (p<0.005), and a significant reduction of E wave (P< ), E/A (P< ) and E/e ratio (P<0.001). The levosimendan group had also a greater decrease in BNP at 24 hours compared with dobutamine group (p<0.005). The percent change of BNP in levosimendan group was significantly correlated with the percent change of E/e and DT (r=-0.42, p<0.01 and r=0.58, p<0.005, respectively). Conclusions: In patients with decompansated AHF, levosimendan and dobutamine both improve LV systolic function. However, levosimendan also improves LV diastolic function which was associated with a greater decrease of neurohormonal activation in these patients. P2174 Cardiovascular risk factors and early left ventricular longitudinal systolic dysfunction assessed by TDI in asymptomatic subjects with normal ejection fraction G. Di Salvo, S. Carerj, A. Salustri, F. Antonini-Canterin, S. La Carrubba, L. Cossu, P. Caso, A. Pezzano, R. Calabro, V. Di Bello on behalf of SIEC Italian Society of Cardiovascular Echography. Italian Society of Cardiovascular Echography (SIEC), Milan, Italy Background: In asymptomatic subjects with cardiovascular (CV) risk factors early diagnosis of left ventricular (LV) dysfunction is still a major challenge. Tissue Doppler imaging (TDI) is an important tool with a demonstrated clinical relevance in several cardiac diseases. Aim of this study were: 1. To evaluate the ability of TDI in detecting early longitudinal ventricular dysfunction; 2. To study the relationship between TDI and CV risk factors; 3. To assess the prognostic ability of TDI in a large group of asymptomatic subjects with preserved LV systolic function and normal diastolic function. Methods: A total of 1371 subjects (median age 60 years, 595 males) formed our study population: Controls, 265 healthy subjects; Group I, 434 subjects with one CV risk factor; Group II, 401 subjects with two CV risk factors; Group III, 271 subjects with 3 CV risk factors. A comprehensive standard echo-doppler evaluation, including PW-TDI study was performed in all patients. Follow up data were available on 554 subjects (mean age 55±13 years, 39% men). Results: Diastolic parameters (such as E/A, A wave, Em/Am; E/Em) were able to discriminate the number of CV risk factors. LV global longitudinal systolic function (Sm) was the only systolic parameter inversely related with the number of CV risk factors (p<0.0001). At multivariate analysis, Sm confirmed as the only functional parameter able to predict the increasing number of CV risk factors (p<0.001). Upon follow-up (mean 28±16 months), 18 individuals (3.2%) developed a first overt CVD event. The presence of an Sm value <7.5 cm sec showed a significant additional predictive value compared to the presence of CV risk factors. Conclusions: TDI is able to identify early longitudinal LV systolic abnormalities in presence of apparently normal systolic and diastolic function and progressively impairs with increasing CV risk factors, demonstrating a significant additional prognostic value compared to the simple presence of coexisting CV risk factors. P2175 Myocardial ejection velocities and strain underestimate electrical dyssynchrony during left bundle branch block (LBBB) K. Russell 1, A. Opdahl 1,O.Gjesdal 1,E.W.Remme 2,H.Skulstad 1, E. Kongsgaard 1, T. Edvardsen 1, O.A. Smiseth 1. 1 Rikshospitalet University Hospital, Oslo, Norway; 2 Institute of Surgical Research, Oslo, Norway Background: The clinical value of assessing LV intraventricular dyssynchrony prior to cardiac resynchronization therapy is controversial. This study investigated if peak myocardial ejection velocity (S), peak systolic strain (εs) and peak strain including post systole (ε) reflect electrical conduction delay in LBBB. Methods: In 5 anaesthetized dogs with LV micromanometers we measured myocardial segment lengths by sonomicrometry and intramyocardial-emgs (IM- EMG) by implanted electrodes. Onset of R in IM-EMG defined onset of regional electrical activation, and reference method for onset of true mechanical activation was first sign of active force generation (AFG) by LV pressure-segment length loop analysis. Time delay for lateral wall with respect to septum was quantified for each index during LBBB induced by RF-ablation. Results: During LBBB there was marked delay in electrical activation of the lateral wall by 50±7 ms (mean±sd) and similar delay in mechanical activation measured as onset AFG by 51±13 ms (p=ns). Mechanical activation measured as Figure 1 S, εs and ε, however, showed time delays of -30±25, 26±38 and -38±26 ms, respectively, indicating that these indices underestimated electrical dyssynchrony (Figure 1). Furthermore, peak S and peak εs suggested erroneously that the lateral wall was activated prior to septum. Similar finding were found by echocardiography. Conclusions: As predicted, LBBB was associated with marked delay in electrical activation between the LV lateral wall and septum and similar delay in true mechanical activation. Velocity and strain indices, however, were inaccurate measures of electrical delay, suggesting that these indices may lead to erroneous conclusions regarding magnitude of electrical delay and direction of the electrical activation sequence in LBBB. P2176 Apical untwist: an integral component of early diastolic left ventricular function U. Gustafsson, P. Lindqvist, M.Y. Henein, A. Waldenstrom. Heart center, Umeå University Hospital, Umeå, Sweden Background: Cavity twist is proven to be an important contributor to systolic left ventricular (LV) function and untwist to its filling. We aimed in this study to assess the exact relationship between LV apical untwist and early diastolic events of the cardiac cycle. Method: Short axis images of LV cavity at apical and basal levels were studied using echo speckle tracking in 43 healthy subjects, all in sinus rhythm, mean age 63 years, 22 females. Degrees of untwist were measured at 4 time points during early diastole (aortic valve closure, mid isovolumic relaxation, mitral valve opening and peak E velocity) at each level as well as globally. Peak LV E wave velocities were measured using conventional spectral Doppler. Studied individuals were divided into two groups according to the degree of apical untwist occurring during early filling (>2.5 degrees and <2.5 degrees). Results: The group with apical untwist >2.5 degrees in the early filling phase had significantly higher peak E velocities, 0.68m/s vs 0.58m/s (p=0.015), and significantly later onset of apical untwist with respect to AVC (p=0.05). The degree of global untwist during the isovolumic relaxation period inversely correlated with peak E wave velocity (R=-0.3 p=0.05), whereas that occurring during early filling phase directly correlated with peak E wave velocity (R=0.5 p<0.001). Conclusion: Global and especially apical untwist is an important integral component of early diastolic left ventricular function. The inverse relationship between the degree of global untwist during isovolumic relaxation and early diastolic filling velocities is in agreement with the known knowledge of shape change during this period. These findings highlight the important role of LV apical diastolic function in maintaining overall cavity performance. P2177 2D echo speckle tracking-assessed left ventricular torsion in healthy volunteers is gender but not age dependent C.J. Finn, L. Zhong, L.K. Tan, L.H. Chua, Z.P. Ding. National Heart Centre, Singapore, Singapore Background & Aim: Left ventricular (LV) torsion plays an important role in LV performance. However, the impact of age and gender on this measurement has not been extensively studied. We aimed to study the relationship between LV torsion, other conventional echo parameters, and age and gender. Methods: We performed echo studies (IE33, Philips) on normal healthy volunteers. LV torsion - defined as the instantaneous net difference of LV basal and apical rotations - was measured by off-line 2D echo speckle tracking analysis (QLab software) of LV basal and apical short-axis slices. Results: There were 69 healthy volunteers (mean age 42±11 years, range 26 to 72 years). ANOVA analysis revealed that there was no significant difference for LV torsion and rotation parameters among the age categories (table). Independent sample t-test revealed that females (n=36) had significantly greater values of peak LV torsion/diastolic length (1.9±0.7 degree/cm versus 1.5±0.4 degree/cm, P<0.001), untwisting rate (74.2±40.7 degree/sec versus 58±22.4 degree/sec, P<0.001) and peak diastolic untwisting velocity (-154±77 degree/sec versus - 115±46 degree/sec, P<0.001) than males (n=33). There was significant correlation between LV ejection fraction and LV torsion (r=0.23, P<0.05) but not for peak apical rotation (P=0.07) and peak basal rotation (P=0.16). Conclusion: The magnitude of LV torsion was independent of age in healthy volunteers. Peak LV torsion normalized to diastolic length, untwisting rate and

50 350 Echocardiography in cardiomyopathy LV rotation & torsion in normals by age Age (years) < >60 (n=13) (n=20) (n=13) (n=19) (n=4) P Value Peak LV torsion (degree) 14.8± ± ± ± ± Peak apical rotation (degree) 11.5± ± ± ± ± Peak basal rotation (degree) -4.0± ± ± ± ± Twist rate (degree/sec) 54.8± ± ± ± ± Untwist rate (degree/sec) 81.3± ± ± ± ± Peak systolic twisting velocity (degree/sec) 99.4± ± ± ± ± Peak diastolic untwisting velocity (degree/sec) -161± ± ±36-140±77-114± Peak LV torsion/diastolic length (degree/cm) 1.9± ± ± ± ± peak diastolic untwisting velocity were significantly higher in females compared to males. P2178 Sub-clinical and clinical high altitude pulmonary edema: an ultrasound lung comets study L. Pratali 1, M. Cavana 2,R.Sicari 1, E. Picano 1. 1 Fondazione G Monasterio, Pisa, Italy; 2 UB Rianimazione e Ambulatorio medicina di montagna, Aosta, Italy Background: The Ultrasound Lung Comets (ULCs) detected by chest sonography are a simple, non invasive, semiquantitative sign of increased extravascular lung water. High altitude pulmonary edema (HAPE)may occur in climbers,withan estimated frequency at %. Aim: to correlate the occurrence of HAPE with ULCs in a group of recreational climbers Methods: We evaluated 18 healthy subjects (mean age 45±10 years, 10 males) participating to a high altitude trekking in Nepal. We performed chest and cardiac sonography in all subjects, at sea level and at different altitudes during the ascent. ULCs were evaluated on anterior chest at 28 pre-defined scanning sites. Results: At individual patient analysis ULCs during ascent appeared in 15/18 subjects (83%) at 3440 height m s.l. and in 18/18 subjects (100%) at 4790 m s.l. in presence of normal left and right ventricular function and pulmonary artery systolic pressure rise (sea level= 24±5 mmhg vs peak ascent= 42±11 mmhg, p<0.001). The mean values of ULCs is shown in the figure. An ULCs score showed a negative correlation with O2 saturation (R=-0.7; p<0.0001). Conclusions: In recreational climbers, chest sonography reveals a high prevalence of clinically silent pulmonary edema, mirrored by reduction of O2 saturation and increase in pulmonary artery systolic pressure. P2179 Evaluation of non-invasive parameters for estimation of left ventricular filling pressures in heart failure patients after restrictive mitral annuloplasty and surgical ventricular restoration E.A. Ten Brinke, M. Bertini, R.J. Klautz, M.L. Antoni, J.J. Bax, P. Steendijk. Leiden University Medical Center, Leiden, Netherlands Purpose: Doppler echocardiography including tissue Doppler imaging (TDI) is widely used to assess diastolic left ventricular (LV) function. In particular, E/E is used as a non-invasive estimate of LV filling pressures. However, it is not established whether E/E is a good index for LV filling pressures in heart failure patients after extensive cardiac surgery and especially after restrictive mitral annuloplasty (RMA) and surgical ventricular restoration (SVR). Global diastolic strain rate during isovolumic relaxation (SRIVR) obtained with 2-dimensional speckle tracking analysis was recently proposed as an alternative approach to estimate LV filling pressures. Methods: We analyzed heart failure patients 6 months after RMA and/or SVR. Diastolic function was assessed invasively in the catheterization room. In addition, echocardiography including TDI and speckle tracking analysis was performed. Invasively measured indices included relaxation time constant Tau, dp/dtmin, and LV end-diastolic pressure (LVEDP). Invasive indices were correlated with a range of echocardiographic indices including E/A, IVRT, DT, E/E, SRIVR, and E/SRIVR. Results: A total of 23 heart failure patients were analyzed (RMA+SVR, n=11; RMA, n=8; SVR, n=4).the strongest correlation with invasive indices, in particular LVEDP, was found for SRIVR (r=-0.76, p<0.001). E/E did not correlate significantly with any of the invasively obtained diastolic indices (see Table). Correlations (r) tau -dp/dtmin LVEDP Mitral flow doppler E/A r 0.38 (p = 0.07) (p = 0.04) 0.65 (p < 0.001) IVRT r 0.33 (p = 0.12) (p = 0.18) 0.18 (p = 0.42) DT r (p = 0.70) 0.35 (p = 0.10) (p = 0.01) Tissue Doppler E/E r (p = 0.76) 0.08 (p = 0.71) (p = 0.58) Speckle tracking SRIVR r (p = 0.07) 0.46 (p = 0.03) (p < 0.001) E/SRIVR r 0.47 (p = 0.02) (p = 0.09) 0.46 (p = 0.03) Conclusions: In heart failure patients investigated 6 months after RMA and/or SVR, E/E correlated poorly with invasively obtained diastolic indexes. Global SRIVR, however, correlated well with LVEDP and dp/dtmin. Our data suggest that global SRIVR is a promising non-invasive index to assess left ventricular filling pressures in patients after extensive cardiac surgery. P2180 Can feature tracking correctly detect motion patterns as they occur in blood inside heart chambers? Validation of Echocardiographic Particle Image Velocimetry using moving phantoms R. Faludi 1,A.Walker 2,G.Pedrizzetti 3, J. Engvall 4, J.U. Voigt 5. 1 Heart Institute, University of Pecs, Pecs, Hungary; 2 Department of Clinical Physiology, Central Hospital, Vasteras, Sweden; 3 Dipartimento di Ingegneria Civile, University of Trieste, Trieste, Italy; 4 Department of Clinical Physiology, University Hospital, Linköping, Sweden; 5 Department of Cardiology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium Background: Echo Particle Image Velocimetry (PIV) is a new, feature tracking based approach to visualize and quantify blood flow patterns in heart chambers. In vivo, the flow velocity and direction of contrast enhanced blood is estimated by echocardiographic feature tracking algorithms and motion patterns, like vortices, are quantified. In this study we validated this new technique in moving phantoms. Methods: A linearly moving string phantom and a rotating agar phantom with graphite scatterers, both moving according to different, computer controlled speed patterns (range cm/s), were imaged at varying insonation angels (0-90 ) and frame rates (60-200/s). Over 80 different ultrasound image loops were analyzed for motion velocity and direction as well as for motion patterns of the scatterers in the phantoms using a dedicated prototype software. Measurement results were post-processed and analyzed with dedicated, custom made, MATLAB based tools and compared to the true values. Results: The new algorithm was able to estimate motion velocity with high accuracy (r=0.98, mean difference 1.6±1.9cm/s). Already at very low velocities, estimates became stable. Maximally detectable velocity was dependent on frame rate (r=0.65, p<0.001) and insonation angle (r=0.58, p<0.01) and reached 39 cm/s under optimal conditions. At higher velocities, estimates became random. Direction estimates were highly accurate in 80-90% of the samples (mean diff 1.4, n.s.). Interestingly, the accuracy of the direction estimate did not depend on motion velocity. Motion patterns (vortex size and position) were correctly identified. Conclusion: The new method of Echo-PIV appears feasible. Velocity estimates are accurate, the maximally detectable velocity, however, depends on imaging settings. Motion direction estimation works well, even at high velocities. We conclude, that Echo PIV may be used as a tool to analyze flow inside the heart, particularly if flow patterns are investigated. P2181 Intraoperative real-time 3D transesophageal echocardiography reliably assess left ventriuclar stroke volume: Direct comparison with thermodilution technique H. Yoshitani 1, M. Takeuchi 1,H.Nakai 1, K. Otani 1, N. Haruki 1, K. Kaku 1,Y.Nishimura 1, G. Ohara 1, R.M. Lang 2,Y.Ostuji 1. 1 University of Occupational and Environmental health, Kitakyushu, Japan; 2 The University of Chicago Medical Center, Chicago, United States of America Purpose: Accurate assessment of left ventricular (LV) volume by 2D transesophageal echocardiography (TEE) is often difficult, because imaging plane does not cut true apex. Although intraoperative assessment of LV volume is usually estimated stroke volume (SV) by thermodilution, we hypothesized that full volume datasets obtained from real-time 3DTEE could encompass whole part of the LV, thus allowing accurate determination of LV volume and SV in the operating room. Methods: To validate this hypothesis, we performed following 2 protocols. In protocol 1, full-volume datasets of 3D transthoracic echocardiography (3DTTE), as a reference standard, were acquired either before or after 3DTEE examination in 28 patients. LV volume was compared between two methods using quantitative software (QLab). In protocol 2, volumetric measurement of 3DTEE and 2DTEE were performed in 28 patients during cardiac surgery at different loading conditions. The values of SV obtained by 3DTEE (SV3D) and 2DTEE (biplane Simpson s

51 Echocardiography in cardiomyopathy 351 methods; SV2D) were compared to SV simultaneously acquired by thermodilution (SVT). Results: In protocol 1, excellent correlation of LV volumes (EDV: r=0.99, ESV: r=0.99). In protocol 2, a total of 53 datasets were obtained. Correlation between SV3D and SVT (r=0.73) was better compared to that between SV2D and SVT (r=0.35). 95% limits of agreement were lower in 3DTEE (±11 ml) compared to 2DTEE (±33 ml). SV2D (34±13 ml) was significantly smaller compared to SV3D (52±14 ml, p<0.001) and SVT (55±16 ml, p<0.001). Long-axis diameter from the mitral annulus to the LV apex was also significantly longer in 3DTEE compared to 2DTEE. Conclusions: Real-time 3DTEE allows accurate assessment of LV volume status, and could be another alternative for the determination of stroke volume during cardiac surgery. P2182 Routine performance of 3-dimensional transesophageal echocardiography: is there incremental value over 2-dimensional transesophageal echocardiography? S. Kort, B. Pulipati, D.L. Brown. Stony Brook University Medical Center, Stony Brook, United States of America Purpose: Three-dimensional transesophageal echocardiography (3D TEE) can provide additional information to that obtained by 2D TEE for specific indications. However, incremental value of 3D TEE over 2D TEE for routine use regardless of the indication has not been evaluated and is the aim of this study. Methods: We compared the data obtained from 3D and 2D TEE studies of 66 consecutive patients performed for various indications by the same operator. The time required for completion of 3D and 2D image acquisition and 3D reconstruction was compared to the time required for 2D acquisition performed alone for similar indications. Results: 3D TEE provided additional information to that obtained by 2D TEE in 55% of patients. 3D TEE revealed more detailed anatomy of the mitral valve and prosthetic valves in the mitral and aortic positions, offered enhanced visualization of the entire length of intracardiac catheters and was therefore most helpful in the assessment of valvular heart disease, evaluation of endocarditis involving native, prosthetic valves and intracardiac wires, delineation of complications related to endocarditis and guidance of percutaneous procedures. 3D TEE also provided additional information for other indications (exclusion of cardiac source of emboli and assessment prior to cardioversion). Adding 3D acquisitions and reconstructions to the routine 2D TEE protocol significantly prolonged the procedure time (41.28±17.58 vs 24.31±13.3 minutes, p<0.01). Conclusion: 3D TEE provides additional information to that obtained by conventional 2D TEE in the majority of patients regardless of the indication for the study. Because the additional imaging and reconstructions prolong the procedure time, development of specific protocols for efficient integration of 2D and 3D imaging is indicated before recommending this modality for routine clinical use. P2183 Does ventriculo-arterial coupling change during the course of normal pregnancy? An echocardiographic study R.O. Jurcut 1,O.R.Savu 1,S.Giusca 1,I.L.Gussi 2, R. Enache 1, B.A. Popescu 1, J. D Hooge 3, J. Deprest 3, J.U. Voigt 3, C. Ginghina 1. 1 Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania; 2 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 3 Catholic University of Leuven (KULeuven), Leuven, Belgium Purpose: Pregnancy is a physiologic condition associated with significant intravascular volume expansion and progressively decreased systemic vascular resistance due to the low impedance utero-placental circulation as well as associated vasodilatation. The aim of the study was to assess the evolution of ventriculoarterial coupling during the course of normal pregnancy. Methods: Twenty-seven pregnant women (30.7±2.9 years) and 14 age and sexmatched non-pregnant controls (30.2±4.4 years) were included. Echocardiography with conventional 2D and Doppler was performed longitudinally at 11-14, and 32 weeks during pregnancy, and at inclusion for the control group. Total vascular resistance (TVR), aortic distensibility (ADis) and arterial elastance (Ea) were calculated to characterize vascular adaptation. Left ventricular (LV) endsystolic wall stress (ESWS) and end-systolic elastance (Ees) were calculated. Ventriculo-arterial coupling index was derived as the arterial to end-systolic ventricular elastance ratio, as previously reported. Repeated measurements ANOVA was used to assess parameters evolution during pregnancy, and t-test was used for comparisons with the non-pregnant controls. Results: During pregnancy we found a progressive increase in LV end-diastolic volume (93.8±7.0 vs 88.8±6.0 ml in 3rd vs 1st trimester, p<0.01) and stroke volume (78.7±14.8 vs 68.7±12.5 ml, p<0.05), associated to a decreased TVR (982.7±284 vs ±158 dyne.s/cm5, P<0.05), which was significantly lower than in controls (1372.9±212 dyne.s/cm5, p<0.01). Aortic distensibility increased during pregnancy, reaching its peak during 3rd trimester (7.55±2.5 vs 6.25±2.1 mmhg -1,p<0.05). This change was present even after adjusting for maternal age (p<0.01), heart rate (p<0.01), and mean arterial pressure (p<0.01), known determinants of ADis. End-systolic wall stress was lower than in controls, and decreased significantly during pregnancy with a nadir at 3rd trimester (29.4±5.6 vs 41.9±9.6 g/cm 2,p<0.01). With a non-significant trend for increase of both Ea and LV Ees, the ventriculo-arterial coupling index was stable throughout pregnancy (0.79±0.11 vs 0.75±0.11, NS). Conclusions: Pregnancy is an increased preload state associated with progressively decreased total vascular resistance and increased aortic compliance, decreased end-systolic wall stress and increased cardiac output, leading to preserved ventriculo-arterial coupling P2184 Comparison between arterial wave intensity and arterial elastance to end-systolic ventricular elastance ratio as indices of ventricular-arterial coupling F. Antonini-Canterin 1, R. Caruso 2, R. Enache 3, B.A. Popescu 4, C. Ginghina 4,O.Vriz 5,D.Pavan 6, E. Leiballi 1, S. Carerj 2, G.L. Nicolosi 1. 1 Azienda Ospedaliera S. Maria Degli Angeli, Pordenone, Italy; 2 Policlinico Universitario, Messina, Italy; 3 Institute of Cardiovasc.Diseases C.C.Iliescu/Inst. De Boli CV, Bucharest, Romania; 4 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 5 Cardiology, San Daniele Del Friuli, Italy; 6 Cardiology, San Vito Al Tagliamento, Italy Background: The ventricular arterial coupling is a key determinant of cardiovascular performance. One reliable index of this coupling is the ratio of arterial elastance (Ea) to end-systolic ventricular elastance (Ees). Recently, carotid artery wave intensity (WI) has been used as a new index which provides information Abstract P2182 Table 1 Indication # of Patients # of Patients with Additional Information Provided by 3D MTEE Additional Data by 3D MTEE Pre-cardioversion 17 8 (47.1%) LAA thrombus excluded in technically difficult studies, malcoaptation of MV leaflets with central regurgitant orifice, mild P2 prolapse, incidental mobile fibroelastoma attached to the atrial surface of A2, better delineation of MV annular ring, better delineation of LAA clot, tethering of MV leaflets, excluded MV prolapse, retained MV chordae Source of Cardiac Emboli 16 6 (37.5%) LAA thrombus excluded in technically difficult studies, malcoaptation of the MV leaflets, MV anterior leaflet thickening with no prolapse, Lambl s excrescence, mobile atheroma in mid aortic arch, better definition of an LV thrombus with multiple extensions, better visualization of bioprosthetic MV and AV leaflets and struts, exclusion of paravalvular leak in the presence of eccentric AI, incidental torn chordae Endocarditis 12 6 (50%) Precise localization of MV leaflet perforation and attachment of vegetations, retained MV chordae, delineation of MV anatomy and extent of vegetations, excellent delineation of pacing leads for exclusion of vegetations, better visualization of AV struts Mitral Valve (78.6%) A2 and P2 prolapse, central malcoaptation and tethering, precise localization of partially dehisced prosthetic MV, retained posteromedial papillary muscle and chordae, better delineation of a partially ruptured papillary muscle and a torn chordae, better visualization of flail and partially flail MV Aortic Valve 5 3 (60%) Better visualization of prosthetic valve, residual VSD post AVR and VSD repair, incidental A2 prolapse ASD/PFO closure 2 2 (100%) Better delineation of ASD location and size, visualizing deployment of both arms of Ampulatzer device in the LA, better delineation of relationship between device and other structures, fenestrated septum identified

52 352 Echocardiography in cardiomyopathy / New or improved: angiogenesis and remodeling about the interaction of the heart and vascular system, as the first peak (W1) represents the forward compression wave and reflects left ventricle (LV) contractile function. We aimed to compare these two indices of ventricular-arterial coupling and to assess their correlations with parameters of LV function. Methods: We enrolled 77 consecutive patients (pts) without significant aortic or mitral valve disease referred to our echocardiographic laboratory. An echocardiographic and carotid ultrasound study (using a Prosound Alfa 10 Aloka machine) was performed, assessing LV function and ventricular-arterial coupling. The Ea/Ees ratio was determined, where Ea was calculated from stroke volume (SV) and end-systolic pressure as Systolic BP 0.9/SV and Ees was calculated by a modified single-beat method, as previously described, using an estimated normalized ventricular elastance at arterial end-diastole (ENd): Ees = [Diastolic BP (ENd(est) Systolic BP 0.9)]/(ENd(est) x SV). We determined WI as (dp/dt) (du/dt) at the level of right common carotid artery. A cut-off value for Ea/Ees ratio of >1.3 was considered for a pathologic ventricular-arterial coupling. Results: The clinical characteristics of pts were: mean age 64±15 years; 51 men. Hypertension was present in 33.3% of pts, coronary heart disease in 35.1%, non-ischemic dilated cardiomyopathy in 10.4%. Mean LV ejection fraction was 52±14%. Mean value of Ea/Ees was 1.43±0.72 and of W1 was 14130±9940 mmhg m/s3. Ea/Ees ratio and W1 showed a statistically significant negative correlation (r = -0.43, p <0.001). Considering the cut-off value of 1.3 for Ea/Ees ratio, W1 was significantly lower in patients with an Ea/Ees ratio >1.3 as compared with those with a normal ratio (10160±6500 vs 16800±11100 mmhg m/s3, p =0.002). Ea/Ees ratio and W1 were significantly correlated with parameters of LV systolic function: LV ejection fraction (r = and 0.56 respectively) and systolic mitral annular velocity, S-wave (r = and 0.66 respectively) (all p <0.001). Conclusions: The arterial WI significantly correlates with Ea/Ees ratio, a previously validated index of ventricular-arterial coupling. Both indices are strongly correlated with echocardiographic parameters of LV systolic function. The clinical value of these findings remains to be determined. Purpose: Non-ischemic diabetic cardiomyopathy may be due to myocardial steatosis. We evaluated left ventricular (LV) multidirectional strain/strain rate (SR) using 2D speckle tracking in patients with truly uncomplicated type 2 diabetes mellitus (DM) and documented myocardial steatosis on magnetic resonance spectroscopy. Methods: One hundred male subjects (47 with and 53 without DM) were recruited. Exclusion criteria for DM patients included HbA1c >8.5%, known cardiovascular disease or DM related complications, hyperlipidemia, blood pressure >150/85 mmhg. Myocardial ischemia was excluded by a negative dobutamine stress test. Healthy controls were matched for age, body mass index and body surface area. Results: Mean age was 57±6yrs. Median DM diagnosis duration was 4yrs, and mean HbA1c was 6.4±0.7%. There were no differences in LV end-diastolic volume index (41±9 vs44±8ml/m 2, p=ns), end-systolic volume index (16±5 vs 18±4mL/m 2, p=ns) and ejection fractions (61±6 vs60±5%, p=ns). Transmitral E/A (0.95±0.21 vs 1.12±0.32, p=0.007) and pulmonary S/D ratios (1.45±0.28 vs 1.25±0.27, p=0.001) were more impaired in diabetics. Diabetic patients had impaired longitudinal but preserved circumferential and radial functions (Table). Presence of DM was an independent predictor for longitudinal strain, systolic SR and early diastolic SR on multiple linear regressions (all p<0.001). Table 1. Strain and Strain Rate Parameters Between Patients with Diabetes Mellitus and Healthy Subjects Variable DM Patients (n=47) Controls (n=53) p value Mean global longitudinal strain (%) -18.3± ±1.9 < Mean global longitudinal systolic SR (s -1 ) -0.99± ± Mean global longitudinal early diastolic SR (s -1 ) 1.04± ±0.26 < Global circumferential strain (%) -22.7± ±3.2 NS Global circumferential systolic SR (s -1 ) -1.40± ±0.23 NS Global circumferential early diastolic SR (s -1 ) 1.79± ±0.61 NS Mean radial strain (%) 40.6± ±12.1 NS Mean radial systolic SR (s -1 ) 1.71± ±0.48 NS Mean radial early diastolic SR (s -1 ) -1.98± ±0.70 NS DM: diabetes mellitus; SR: strain rate; NS: not significant. Conclusions: In uncomplicated type 2 DM patients with documented myocardial steatosis, LV longitudinal systolic and diastolic functions were impaired but circumferential and radial functions were preserved. P2185 Uric acid level is an independent marker of left ventricular hypertrophy and impaired early diastolic relaxation in never treated hypertensives P. Xaplanteris, C. Vlachopoulos, K. Aznaouridis, A. Bratsas, I. Dima, K. Baou, G. Vyssoulis, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Background: Elevated levels of serum uric acid (UA) have emerged as a risk factor for cardiovascular disease in patients with essential hypertension (HT). We investigated the relationship between UA level and echocardiography indices in never treated subjects with essential HT. Methods: The study included 1100 newly diagnosed, never treated hypertensives (651 males, mean age 52.7±11.8 years, mean systolic blood pressure 164.8±9.1 mmhg, mean diastolic blood pressure 100.6±7.4 mmhg) naive to anti-ht medications. Left ventricular function was assessed by means of echocardiography, as part of the initial diagnostic work up; left ventricular mass index (LVMI), ejection fraction (EF), peak E- and A- velocity, E/A ratio, Tei index and left ventricular midwall fractional shortening (MWFS) were accordingly calculated.the relations between UA and echocardiographic indices were assessed using Pearson s correlation coefficient and univariate linear regression analysis, after adjusting for age, smoking, systolic/diastolic blood pressure, body mass index, fasting glucose and total cholesterol. Results: In our study population mean UA level was 5.3±1.7 mg/dl, LVMI 115.2±13.1 g/m 2, EF 64.9±4.9%, peak E-velocity 0.69±0.12 m/s, peak A- velocity 0.73±0.14 m/s, E/A ratio 0.96±0.22, Tei index 0.61±0.06, MWFS 21.7±3%. UA was correlated with LVMI (r=0.26, P<0.01), EF (r=-0.14, P<0.01), peak E-velocity (r=-0.132, P<0.01), E/A ratio (r=-0.07, P<0.05) and Tei index (r=0.113, P<0.01) but not with peak A-velocity or MWFS. In univariate linear regression analysis, UA emerged as as independent predictor of LVMI (β=0.574, P<0.05, adjusted R2 change 0.003) and E/A ratio (β=-0.008, P<0.05, adjusted R2 change 0.003). Conclusion: UA levels independently predict left ventricular hypertrophy and impaired early diastolic relaxation, as assessed by LVMI and E/A ratio in never treated HT. The mechanism responsible for the detrimental effect of uric acid on myocardial performance in hypertensives requires further investigation. P2186 Differential effects of type 2 diabetes mellitus with intensive glucose control on left ventricular myocardial functions C.T.A. Ng 1, V. Delgado 1, R.W. Van Deer Meer 1,M.Bertini 1, G. Nucifora 1, D.Y. Leung 2,N.R.VanDeVeire 1,H.J.Lamb 1, M.J. Schalij 1,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 The University of New South Wales, Sydney, Australia NEW OR IMPROVED: ANGIOGENESIS AND REMODELING P2187 Whole genome expression analysis in patients with chronic total coronary occlusion confirms negative correlation of interferon-beta with coronary collateralization S.H. Schirmer 1, A.M. Van Der Laan 2, J.O. Fledderus 3, O.L. Volger 4, M. Boehm 1, A.J.G. Horrevoets 4,J.J.Piek 2,N.VanRoyen 2. 1 Universitaetsklinikum der Saarlandes, Homburg, Germany; 2 Academic Medical Center, Amsterdam, Netherlands; 3 University Medical Center Utrecht, Utrecht, Netherlands; 4 VU University Medical Center, Amsterdam, Netherlands Purpose: Recently, we reported increased interferon (IFN)-beta signaling in patients with single vessel subtotal coronary stenosis and insufficient coronary collateral artery development, and showed that IFNbeta attenuated arteriogenesis in mice. Here, we investigated whole genome RNA expression analysis of stimulated monocytes from patients with chronic total occlusion (CTO) of a coronary artery and different degrees of collateralization. This patient group would benefit most from a pro-arteriogenic therapy as both the primary intervention as well as long-term results show lower rates of success than in patients with non-total coronary narrowings. Methods: 50 patients with CTO scheduled for elective PCI underwent intracoronary wedge-pressure measurements and assessment of pressure-derived collateral flow index (CFI). Monocytes were isolated from peripheral blood by negative isolation, and stimulated with 10 ng/ml lipopolysaccharide (LPS) for 3h. From 10 patients with highest and 10 with lowest CFI, RNA was isolated, amplified and hybridized to whole-genome bead-chip arrays (Illumina ). After normalization, differential expression was analyzed and Gene Set Enrichment Analysis (GSEA) was performed. Real-time RT-PCR was performed to validate gene expression in the whole patient group (n=50). Results: Baseline characteristics did not differ between patients with high (0.27±0.06) or low (0.47±0.08) CFI. After correcting for multiple testing, 120 genes were found to be differentially expressed in the LPS-stimulated monocytes between patients with low and patients with high CFI, of which 65 genes were more strongly induced in the group with a low CFI. Pathway analysis (GSEA) showed a highly significant enrichment of several interferon-related pathways in patients with a low CFI. Individual genes of these pathways were upregulated, and analysis of their promoter sequences confirmed the strong enrichment for IFNbeta response elements. Real-time RT-PCR analysis of the whole patient group (n=50) confirmed increased expression of IFNbeta regulated genes in stimulated monocytes from patients with low CFI, showing significant negative correlations of CFI with expression of the IFNbeta-regulated genes CXCL11, CCL8, IL27 and IL15RA. Conclusion: We provide evidence of increased IFNbeta signaling in a patient group with chronic total coronary artery occlusion and a hampered arteriogenic response. The data suggest inhibition of anti-arteriogenic IFNbeta-signaling as a potential therapeutic option for the stimulation of arteriogenesis in a patient group that would particularly benefit from pro-arteriogenic strategies.

53 New or improved: angiogenesis and remodeling 353 P2188 Endothelial microparticles and endothelial repair: identification of biological pathways in microparticle-mediated endothelial repair N. Werner, N. Heiermann, G. Nickenig. Universitaetsklinikum Bonn, Bonn, Germany Background: Apoptosis of endothelial cells leads to the development of endothelial dysfunction, which itself is one of the earliest pathophysiological correlates of atherosclerosis and strongly associated with an impaired cardiovascular prognosis. Endothelial cell apoptosis can be quantified using flow-cytometry based enumeration of the circulating endothelial cell-derived microparticles (EMP) within peripheral blood. Bone marrow derived endothelial progenitor cells (EPC) are an important cellular risk predictor. The vasculoprotective action of EPC seem to be mediated by an enhanced reendothelialization process after endothelial cell damage e.g. in endothelial dysfunction. We postulate that the apoptotic endothelial cell interact with the circulating EPC via EMP. Methods and Results: EMP were obtained from human coronary arterial endothelial cells (HCAEC) after serum starvation and isolated using ultracentrifugation. Flow cytometric analyses confirmed that EMP were positive for annexin V, CD31 (PECAM), CD49e (Integrin α5), CD51 (Integrin αv), CD51/61 (Integrin αvβ3), CXCR2, and CXCR4. Co-cultivation experiments demonstrated that cultivated HCAEC co-cultured with fluorescent-labelled EMP incorporate these membrane vesicles. Incubation of cultured mononuclear cells with EMP lead to an enhanced conversion of mononuclear cells into acdi-ldl/lectin positive EPC-like cells, co-cultivation of EPC with EMP prevented TNF-alpha induced cell apoptosis, and migration of EPC was enhanced in response to EMP. Proteomic analysis confirmed that several proteins involved in apoptosis, proliferation, and migration are carried by EMP. Finally, we measured EPC liberation from bone marrow into peripheral blood in C57bl6 mice. Intravenous treatment of mice with EMP enhanced the number of circulating sca-1/flk-1 positive EPC within peripheral blood compared to vehicle treated mice. The number of circulating CD31+/Annexin+ EMP and CD34+/KDR+ EPC was determined in 40 patients with coronary artery disease using flow cytometry. The number of circulating EMP correlated with EPC function (p<0.001, r=0.601). Conclusion: EMP and circulating EPC seem to substantially interact in rodents and humans. EMP influence conversion, migration, and apoptosis of EPC in vitro. EMP mobilize EPC in vivo after intravenous treatment of wildtype mice with EMP. We speculate that the described interaction of EMP with EPC enhance the homing process of EPC within the area of endothelial cell damage. Further studies will elucidate the underlying molecular mechanisms of the interaction between apoptotic and regenerating cells. P2189 The neuropeptide catestatin acts as angiogenic cytokine in vitro and in vivo M. Theurl 1, W. Schgoer 1, P. Schratzberger 1, M. Egger 1, A. Beer 1, D. Vasiljevic 1, J. Patsch 1, S. Mahata 2, R. Kirchmair 1. 1 University Hospital for Internal Medicine I, Innsbruck, Austria; 2 University of California, San Diego, United States of America Introduction: Catestatin (Cat), a biologically active fragment of Chromogranin A was initially described as a nicotinic antagonist inhibiting catecholamine release from adrenal medulla. Recently, also other biological effects for this peptide were described like release of histamine or activation during cutaneous wounds. We found that Cat induces chemotaxis on a variety of cells including endothelial cells (EC) and therefore hypothesized that Cat might act as a novel angiogenic cytokine. Results: To investigate the effect of Cat on EC differentiation into vascular structures in vitro, we performed a matrigel tube formation assay in the absence or presence of different concentrations of Cat. Cat at a concentration of 10-9M was most effective in promoting tube formation (1.77±0.079 vs. ctr.; n=4, P<0.01). This effect could be blocked by a Cat antibody (Ab) (0.87±0.1 vs. ctr; n=4, P<0.01 vs. Cat). The migratory response of ECs toward Cat was measured with a modified boyden chemotaxis chamber. Cat dose-dependently induced chemotaxis of EC (max. 10-9M: 1.67±0.034 vs. ctr; n=6, P<0.01). Additionally, Cat specifically induced proliferation of EC as measured by cell numbers of starved EC (1.86±0.13 vs. ctr., n=4, P<0.01; Cat-Ab 0.97±0.06 vs. ctr; n=4, P<0.05 vs. Cat). Western blot analysis revealed stimulation of ERK by 10-9M Cat indicating activation of this signal transduction pathway by Cat. We tested for angiogenic effects in vivo by using 2 different mouse models. In the mouse cornea neovascularization model Cat induced significant growth of new blood vessels. In the unilateral limb ischemia model injection of Cat (10 μg every other day for 2 weeks) into adductor muscles increased capillary (475±31 vs. 303±28/mm 2 ; n=7, P=0.003) and arteriole (10.1±0.8 vs. 5.2±1.0/mm 2 ;n=7, P=0.001) density, and accelerated perfusion recovery as shown by LDPI (LDPI ratio ischemic/control leg after 28 days of ischemia) 0.94 vs. 0.74; n=10, P= Conclusion: Our observations demonstrate that the neuropeptide Cat induces angiogenesis in vitro and in vivo inducing direct effects on EC. Beneficial effects in the limb ischemia model indicate that Cat might be a useful agent inducing therapeutic angiogenesis. P2190 Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle S. Zbinden 1,J.Wang 2, M. Adenike 2,H.Morsli 2,S.E.Epstein 2, M.S. Burnett 2. 1 Inselspital Bern, Berne, Switzerland; 2 Washington Hospital Center, Washington, United States of America Introduction: Metallothionein (MT)is a potent immunomodulatory molecule known to play a protective role incardiac and cerebral ischemia. Previously, we have shown that MT is highly upregulated following the induction of acute hindlimb ischemia in a mousemodel. The objectives of this study were to determine if MT is important incollateral development, and to investigate the mechanisms by which MTcontributes to flow recovery following the induction of acute hindlimb ischemia. Methods: Laser Doppler perfusion imaging andmatrigel plug assays were used to assess both collateral flow recovery andangiogenesis in MT knockout mice, compared to wildtype animals. Smooth muscle cells (SMCs) were isolated from MT knockout mice, and proliferation, migration and invasion assays were performed. Geneexpression of MMP9, PDGFR, VEGF in SMCs were measured by real time PCR. CD11b+ cells were isolated from MT knockout and wildtype animals and tested for invasiveness using an ECISassay. Results: We found that blood flow recovery (arteriogenesis) measured by Laser Dopplerwas reduced in MT KO mice (p=0.017). Furthermore, angiogenesis was impaired in MT knockout micewith significantly fewer vessels in the matrigel plugs from the MTKO animals compared to the plugs from the wildtype mice (6.19±0.916 vs 0.333±0.161, p=0.004). MTKO SMCs showed impaired proliferation using an MTT assay (p<0.05). Migratory capacity ofaortic SMCs from MTKO mice was significantly impaired compared to wildtype SMCs (O.D. units, 2.38±0.02 vs. 2.76±0.06, p=0.004). A similar pattern was observed in the invasion assay, with reduced invasiveness in the MTKO vs.wildtype cells (O.D. units, 0.700±0.02 vs ±0.05, p=0.008). MTKO SMCs had significantly lower expression levels of matrix metalloproteinase-9 (MMP9), (2% of wildtype, p=0.006). Likewise, MMP9 protein levels were decreased in MTKO cells, as demonstrated by ELISA. VEGF mrna levels were significantly lower in MTKO SMCs, (43% of wildtype, p=0.0006), as were VEGF-(p=0.015) and PDGF protein levels (54% of wildtype, p=0.005). CD11b+ cells from MT knockout mice were more invasive than wildtype cells (p<0.05). Conclusion: Both collateral flow recovery and angiogenesis are impaired in MTknockout mice. Possible mechanisms contributing to these deficiencies includeendothelial, SMC, and macrophage dysfunction in the MT knockout animals. P2191 Beta 2 adrenergic receptor improves the endothelial progenitor cells angiogenic function R. De Rosa, G. Galasso, F. Piscione, G. Santulli, A. Pierri, D. Sorriento, G. Iaccarino, B. Trimarco, M. Chiariello. Azienda Ospedaliera Universitaria Federico II, Naples, Italy Background: Endothelial progenitor cells (EPC) are present in the systemic circulation and home to sites of ischemic injury where promote neo-angiogenesis. We recently showed that β2 Adrenergic Receptors (β2ar) play a critical role in vascular tone regulation and neo-angiogenesis. To date, no data are available on the role of β2ar on EPC biology. Aim: To evaluate the role of β2ar on EPC angiogenic function. Methods: β2ar deficient mice (KO) and wild type (WT) mice in a C57/BL6 background, subjected to unilateral hindlimb ischemic surgery were used for this study. Circulating mouse EPC were harvested 5 days after ischemic hindlimb surgery and cultured according to previously described techniques. Fluorescence-activated cell sorter (FACS) analysis was used to detect the cell surface expression of the endothelial cell antigen Flk-1 on cultured EPC. β2ar expression on EPC was evaluated by Western blot (WB) analysis. EPC migration was performed using a modified Boyden chamber assay, while vascular network formation was assessed with an in vitro matrigel assay. To evaluate in vivo the EPC angiogenic function mice hindlimb blood flow was measured using a Doppler flow analyzer immediately before surgery and up to 3 weeks. Results: WB showed the expression of β2ar on EPC derived from WT mice. Stimulation of EPC derived from WT mice with isoproterenol (ISO), a potent β2ar agonist, induced a 4fold increase of Flk-1 expression on EPCs as assessed by FACS (p<0.05 vs basal condition) indicating a role of β2ar on EPC differentiation. Furthermore, ISO stimulation of WT derived EPC induced a 3fold increase mobilization (p<0.05 vs basal condition) and significantly increased EPC related vascular network formation as confirmed by tubules formation on matrigel assay (60±5 ISOvs10±3, p<0.05). Since KO mice are compromised in hindlimb reperfusion after ischemia, we investigated EPC levels after culture in WT and KO mice. Five days after the induction of ischemia, the number of EPC derived from WT mice increased 3fold compared to KO in response to ischemic surgery (p<0.05 vs EPC derived from KO mice), while no differences were noted before surgery. Finally, rescue experiments were performed comparing WT and KO EPCs. Interestingly, the impairment in limb reperfusion in KO mice was rescued by intravenous infusion of WT EPCs but not of KO EPCs as confirmed by Doppler analysis. Conclusion: The present study provides the first evidence that β2ar stimulation improves the in vivo and in vitro EPC angiogenic function.

54 354 New or improved: angiogenesis and remodeling P2192 Stimulation of transmural capillary endothelialization of small-diameter synthetic vascular grafts through local overexpression of a novel recombinant VEGFR2-ligand VEGF-A109 J. Hytonen 1, O. Leppanen 1, P. Korpisalo 1, S. Laidinen 1, D. Bergqvist 2, K. Alitalo 3, T.T. Rissanen 1, S. Yla-Herttuala 1. 1 A.I.Virtanen- Institute, University of Kuopio, Kuopio, Finland; 2 Uppsala University Hospital, Uppsala, Sweden; 3 University of Helsinki, Helsinki, Finland Background: Endothelialization of prosthetic vascular conduits through transmural capillarization is a theoretically appealing way to increase biocompatibility and ultimately improve the currently dismal patency rates of small-diameter prosthetic bypass grafts. However, in sharp contrast to non-human primates, in which highporosity PTFE vascular grafts are consistently endothelialized through transmural capillarization, human results have been discouraging, which may be caused by inadequacy of angiogenesis. Recently, we have shown in normal and ischemic skeletal muscle that transient overexpression of VEGF-A promotes capillary arterialization and sprouting angiogenesis, and induces supraphysiological blood flow. We hypothetized that transfection of perigraft tissues at the time of graft implantation would augment transmural capillarization and luminal endothelialization of high-porosity PTFE grafts. Methods: 52 NZW rabbits received 87 eptfe (30mm, 2.0mm ID, 60μm internodal distance) carotid end-to-end interposition grafts, and were randomized to local therapy with adenoviruses (Ad) encoding 1) VEGF-A165; 2) novel recombinant VEGF-A109 with identical ligand-induced VEGF-receptor-2 dimerization properties; or 3) control protein (nuclear-targeted β-galactosidase [LacZ]). At 6 or 28d after surgery contrast-enhanced CPS Doppler ultrasound data were obtained from target area and vessels were explanted for histology and expression studies. Results: AdVEGF-A165 and AdVEGF-A109 dramatically increased perfusion in perigraft tissues at 6d, a time point close to peak transgene expression (14.2±3.6 or 16.7±2.6 fold increase vs. baseline, P<0.01). At 28d the effect was attenuated but still significantly higher than baseline (2.9±1.0 or 3.6±1.3 fold increase, P<0.05). At 6d no luminal endothelial cells were observed in any of the groups. Three weeks later, at 28d, animals that had received AdVEGF-A165 or AdVEGF- A109 displayed an increase in luminal endothelialization through transgraft growth (9.8±3.3% or 7.9±3.4% luminal endothelial coverage at mid-graft vs. 0% in controls, P<0.01). No signs of increased pannus formation at anastomotic regions or luminal stenosis were observed in the treatment groups as compared to LacZ controls. Conclusions: This study suggests that local delivery of AdVEGF-A165 or AdVEGF-A109 introduced to the surgical wound at the time graft implantation - with no additional delay or morbidity associated with procedures such as autologous cell harvest - is a promising novel strategy to increase endothelialization of high-porosity synthetic vascular grafts. P2193 Angiopoietin-like 2 is a pro-angiogenic factor with potent vasodilator and hypotensive activity in mice N. Farhat, N. Thorin-Trescases, A. Drouin, B. Allen, A. Mamarbachi, M.A. Guillis, E. Thorin. Montreal Heart Institute, Montreal, Canada Angiopoietin-like 2 (Angptl2) is an orphan circulating 57 kda protein with predicted vascular activity. Our objectives were to study the pro-angiogenic activity of Angptl2 and its effect on vasomotor tone and blood pressure regulation in mice. We purified an Angptl2-GST fusion protein from the media of stably transfected HEK 293 cells by affinity chromatography on glutathione Sepharose. Migration and tube-like structure formation of cultured human umbilical vein endothelial cell (HUVEC) was studied in the presence of Angptl2 (250 nm). Migration was increased 5 times by Angptl2 (P<0.05), while tube-like structure formation was increased in Matrigel from 16±4 tubes to 67±13 (n=3, P<0.05). For comparison, VEGF (26 nm) increased tube formation to 72±14. In vitro, exogenous addition of purified Angptl2 (1 nm) induced 64±7% relaxation (n=10) of preconstricted (U46619, 30 nm; thromboxane A2 analog) isolated mesenteric arteries from C57BL6 mice. This response was endothelium-independent (62±13%; n=4), while acetylcholine-induced relaxation was abolished in denuded arteries (P<0.05). In intact arteries, while the nitric oxide synthase inhibitor N-nitro-Larginine (L-NNA, 100 μm) magnified Angptl2-induced relaxation to 82±5% (n=9, P<0.05), this response was fully prevented by ODQ (1 μm; n=4, P<0.05), an inhibitor of the soluble guanylate cyclase. In vivo intra-carotid injection of Angptl2 (6 μg/kg, 200 μl bolus) induced a rapid drop in systolic blood pressure from 89±3 (n=9) to 70±3 mmhg(p<0.05). The time to recover 50% of the pre-injection blood pressure (t50%) value was 250±63 sec. In the presence of L-NNA (5 mg/kg) baseline blood pressure increased (P<0.05) from 86±1 to111±3 mm Hg, but was unaffected by ODQ (1 mg/kg; 87±7 mm Hg); the hypotensive effect of Angptl2 (-19±2 mm Hg) was potentiated (P<0.05) by L-NNA (-33±3 mm Hg), but prevented by ODQ (-2±2 mmhg; P<0.05). In conclusion, Angptl2 is a pro-angiogenic factor with new vasodilatory and hypotensive activities. P2194 Tissue factor gene silencing contributes to inastabilization of neo-vessels formation G. Arderiu, E. Pena, L. Badimon. Barcelona Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Purpose: Accumulating evidence has transformed our view of tissue factor (TF) from a protease coreceptor triggering coagulation and thrombus formation into a multi functional transmembrane signaling receptor involved in angiogenesis and inflammation. Since atherosclerotic plaques seem to increase their risk in association to its neovascularization, we sought to investigate whether TF could trigger neovessel formation and confer risk to atherosclerotic plaques. Methods: We have used a three-dimensional co-culture system with human microvascular endothelial (HMEC-1), human vascular smooth muscle cells (HVSMC) and an in vivo model of xenograft implantation in mouse. HVSMC obtained by the explant technique from coronary arteries of heart explants during transplantation surgery and HMEC-1 were mixed and then plated together onto basement membrane-like gel (Matrigel). To discriminate each cell type, cells were labeled with two different fluorescent membrane dyes, PKH2 and PKH26. Analysis of capillary-like network formation was performed by time lapse video microscopy (Leica TCS SP2-AOBS). Chemotactic migration was measured in a modified Boyden chamber. Low expression of TF was induced with sirna, the delivery of TFsiRNA into the cells was done by a Nucleofactor device. For the in vivo studies cells were injected with the matrigel plugs subcutaneously in the dorsal midline region of nude mice. After seven days post injection, mice were euthanized and tumor tissue was analyzed. Results: We observed by confocal microscopy, that direct contact between HMEC-1 and HVSMC promoted branching morphogenesis in 3D BM cultures. VSMC localize around endothelial cells promoting migration (74±7.3 vs 23±5.4) of endothelial cells. The induction of this mechanism of formation of complex tubelike structures was inhibited by the inhibition of TF expression (sirna). Low levels of TF (75%±6.5 inhibition vs control) in HMEC-1 resulted in reduced cellular migration as well as upregulation of HAND2 (three folds up), and downregulation of CCL2 (four folds down) gene expression. Importantly, inhibition of TF expression in either HMEC-1 or HVSMC decreases their shared ability to form new capillaries in vivo ±15.70 pixels main tub HMEC-1, ±20.45 pixels main tub HVSMC vs ±15 pixels control). Conclusion: Our results demonstrate that TF has a key role in coordinating the formation of stable neovessels. These results indicate that TF, in addition to triggering intraluminal thrombosis, may contribute to atherosclerotic plaque complication by inducing medial neovascularization. Funded by SAF2006/10091, Fundacion Jesus Serra P2195 Evidence of novel vasculoangiogenic effect of cilostazol T.-H. Chao 1, S.-Y. Tseng 1,Y.-H.Li 1,P.-Y.Liu 1,G.-Y.Shi 1, H.-L. Wu 1,C.-L.Cho 2, J.-H. Chen 1. 1 National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan; 2 National Sun Yat-Sen University, Kaohsiung, Taiwan Background: Cilostazol is an antiplatelet agent with vasodilating effect working through increasing intracellular cyclic adenosine monophosphate (camp) levels. It has been recently reported to have some cellular effects, suggesting that it may promote angiogenesis. In this study, we investigated the in-vitro and in-vivo effects of cilostazol in promoting angiogenesis and vasculogenesis. Methods: Colony-forming units of early human endothelial progenitor cells (EPC) treated with cilostazol were counted 7 days after isolation. Cell proliferation, chemotactic motility and capillary-like tube formation in human umbilical vein endothelial cells (HUVEC) were examined. Eight-week-old male ICR mice were treated intraperitoneally with cilostazol (1, 5, 10 mg/kg) and saline 2 times per day since day 1 to day 7 after hindlimb ischemia and flow recovery in ischemic limb was measured by a Laser Doppler perfusion image analyzer. Quantification of circulating stem cells was performed and capillary density over ischemic limb was examined by counting anti-mouse CD31+ capillaries. Assays of endothelial NO synthase (enos) and Akt phosphorylation and vascular endothelial growth factor (VEGF) in ischemic muscle were performed by immunoblotting. Results: Colony-forming units of EPC were significantly increased with cilostazol, an effect mediated through camp/protein kinase A-dependent pathway. Cilostazol stimulated proliferation, chemotactic motility and capillary-like tube formation in HUVEC as a NO-mediated downstream event through activation of camp/protein kinase A and phosphatidylinositol 3-kinase/Akt-dependent pathways. Cilostazol also stimulated endothelial cell expression of matrix metalloproteinase, which mediated extracellular proteolysis, leading to endothelial cell invasion and migration during angiogenesis. Blood flow ratio (ipsilateral/contralateral) recovery and capillary density after 14 days in the ischemic hindlimb were significantly improved in cilostazol-treated mice (10mg/kg) than vehicle control, which were attenuated by L-NAME. Circulating CD34+ cells was also significantly higher in cilostazoltreated mice. Cilostazol increased VEGF protein levels, and up-regulated enos phosphorylation and Akt phosphorylation in ischemic muscle. Conclusions: Cilostazol enhanced the vasculo-angiogenic response in vitro and in vivo, providing a unique mechanism for beneficial effect of this drug in limb ischemia, partly mediated by activation of enos and VEGF. Accordingly, further

55 New or improved: angiogenesis and remodeling 355 preclinical and clinical studies of cilostazol on the other ischemic situations such as myocardial infarction will be justified. P2196 Impact of erythroblasts in bone marrow cells on limb salvage after cell implantation in patients with critical limb ischemia Y. Iso 1, T. Soda 1,T.Sato 1,R.Sato 1, T. Kusuyama 1,Y.Omori 1, M. Shoji 1, S. Koba 1, Y. Kobayashi 1, H. Suzuki 2. 1 Showa Univ. Hospital, Tokyo, Japan; 2 Showa Univ. Fujigaoka Hospital, Yokohama, Japan Objective: Therapeutic angiogenesis with bone marrow mononuclear cells (BMCs) has recently been developed as a less invasive intervention for patients with chronic critical limb ischemia (CLI). There have been no earlier findings, however, on which factors affect the long-term outcome after BMC implantation (BMI). The aim of this study is to identify which factors influence limb salvage after BMI. Methods: Fifteen no-option CLI patients treated with BMI were enrolled in the present study. Limb ischemia was assessed with the use of the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), and rest pain score. The cell populations among the implanted cells were determined by May-Giemsa staining and flow cytometry. Results: The limb salvage rate after BMI was approximately 53% (n= 7 in the amputation group and n= 8 in the salvage group). There were no significant differences between the groups in clinical characteristics, or in the ABI, TcO2 level, or rest pain score before implantation. The number of implanted BMCs was the same in the two groups. In the cytological studies, the percentages of erythroblasts and neutrophils in the salvage group were significantly higher and significantly lower, respectively, than those in the amputation group (p= 0.02, p= 0.03, respectively). There were no significant differences, however, in the percentages of myeloblasts, myelocytes, monocyte, or lymphocytes. The calculated erythroblast count was significantly higher in the salvage group than in the amputation group (p= 0.03), and the number of CD34-positive cells was somewhat greater in the salvage group than in the amputation group (p= 0.06). Logistic regression analysis revealed that the percentage of erythroblasts was significantly associated with limb salvage (95%CI , p= 0.03). In vitro angiogenesis assay demonstrated that CD235a (erythroid marker)-positive cells from BMCs significantly promote endothelial proliferation compared with the CD235a-negative cells (p< 0.05). Conclusions: The cellular composition of the BMCs injected into the ischemic limbs may contribute more to long-term limb outcome after the implantation than the severity of limb ischemia or background factors. The favorable effects of BMI appear to reflect the impact of the erythroblast doses. P2197 The initial down-regulation of collateral shear force allows perivascular macrophage accumulation and enhances collateral proliferation H. Sager, H. Schunkert, W.D. Ito, J. Weil. Universitaet zu Luebeck, Luebeck, Germany Purpose: Elevated shear force (SF) and increased perivascular macrophage accumulation are believed to be hallmarks of collateral growth (arteriogenesis). NOS expressions and activations are SF dependent. Endothelial monocyte/macrophage adhesion, however, is counteracted by increased NO availability and has been observed under low SF conditions. Methods: In order to resolve this paradox we first investigated the time course of SF and NOS expressions in growing rat collateral vessels after femoral artery occlusion. Secondly we examined the interdependency of SF, macrophage recruitment and collateral proliferation 1) after increasing collateral blood flow using peripheral nitroglycerin (GTN) infusions and 2) after enhancing macrophage recruitment under NO depletion (oral L-NAME). Results: (values are given as mean ± SEM, * p<0.05): SF was significantly down-regulated post occlusion (SF in dyn/cm 2 :pre-20±2.5 vs. post-occlusion 14±3.7*; n=10) correlating to reduced inos and enos expression (12 h after occlusion). Acute peripheral application of GTN led to a rise of collateral SF to pre-occlusion levels (SF in dyn/cm 2 :pre-20±2.5 vs. post-occlusion + GTN 22±2.8; n=10). Ongoing low SF conditions (continuous peripheral GTN infusion) reduced collateral macrophage recruitment (macrophages per collateral section: post- 42.5±4.4 vs. post-occlusion + GTN 26.3±1.9*; n=10) and diminished collateral proliferation (proliferative index: post- 0.54±0.04 vs. post-occlusion + GTN 0.19±0.08*; n=10) 3 days after occlusion. Chronic NO depletion led to a significant increase in pericollateral macrophage amounts (macrophages per collateral section: post ±7.3 vs. post-occlusion + L-NAME 164.6±14.7*; n=19) but not in proliferation (proliferative index: post- 0.6±0.06 vs. post-occlusion + L-NAME 0.59±0.08; n=19) 7 days after occlusion. Conclusions: Based on these results we propose following resolution of the Monocyte/NO Paradox : An initial phase characterized by low SF conditions allows the recruitment of circulating cells that are locally activated during a second phase of elevated hemodynamic forces. P2198 Fibrin improves human peripheral blood endothelial progenitor cells stemness and paracrine function A. Magera 1, R. Di Stefano 1,C.Armani 1,M.C.Barsotti 1, F. Chiellini 2, A. Minnocci 3, M. Alderighi 4, R. Solaro 4, G. Soldani 5, A. Balbarini 1. 1 Cardiac, Thoracic and Vascular Department, University of Pisa, Pisa, Italy; 2 BIOLab-Dept. of Chemistry and Industrial Chemistry,University of Pisa, Pisa, Italy; 3 BIO Labs-Polo S.Anna Valdera-SSSUP S.Anna, Pisa, Italy; 4 Dept. of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy; 5 Laboratory for Biomaterials and Graft Technology-Inst. of Clinical Physiology, CNR, Massa, Italy Purpose: Fibrin is a natural biopolymer appealing for cell-based regenerative therapies, supporting growth, migration and differentiation of several cell types. Endothelial progenitor cells (EPC) can be easily isolated from peripheral blood, eliminating donor morbidity and used to promote in vivo angiogenesis. Aim of this study was to investigate if fibrin is a good alternative to traditional matrices for EPC growth and function. Methods: Fibrin was obtained from fibrinogen (9 mg/ml) and thrombin (25 U/ml). Ultrastructure was investigated by scanning electron microscopy (SEM), cryogenic SEM (CRYO-SEM) and atomic force microscopy (AFM). EPC were obtained from peripheral blood and cultured on fibrin ( cell/cm 2 ) for 7-14 days. Fibronectin was used as a control. Metabolic activity was assessed by WST1 assay and viability by confocal microscopy (calcein incorporation). The expression of endothelial (CD31, KDR, vwf, Ve-Cadherin) and embryonic stem cell markers (nanog, oct-4) was assessed by flow cytometry, confocal microscopy and Real Time RT-PCR. For NANOG gene oligos unable to recognize the sequences encoded by pseudogenes were used. Angiogenesis was assessed on matrigel by incorporation of EPC into HUVEC tubules. Finally, the release of 50 cytokines was evaluated by a multiplexable bead system. Results: SEM and AFM revealed a nanometric fibrous structure, with mean fiber diameter of 165±4 nm and mean density of 95.9±0.2%, while CRYO-SEM showed micropores of different size ( μm).wst1 assay showed an increased metabolic activity of EPC cultured on fibrin as compared to fibronectin (fibrin: 0.519±0.06 a.u. vs. fibronectin: 0.243±0.06, n=5, p 0.01), up to 14 days. Flow cytometry showed no difference on the expression of endothelial markers (CD31=24±9%; vwf=28±11%; KDR=57±20%; VE-Cadherin=24±7%) as compared to fibronectin. Interestingly the culture on fibrin elicited a marked induction of Oct 4 and Nanog mrna levels, being 5.5±1.3 and 20.5±3.1 fold enriched on fibrin than fibronectin, p< Angiogenesis assay revealed no significant difference between EPC grown on fibrin or fibronectin. Finally, a significative release of the following cytokines: IP-10, PDGF-bb, IL-8, IL-16, MIG, MIF, SDF-1 α, GRO-α, MCP-1, M-CSF and HGF was detected only from EPC grown on fibrin. Conclusions: Fibrin is a suitable scaffold for EPC growth, viability and differentiation. The paracrine release of cytokines involved in cell recruitment suggests that EPC grown on fibrin might accelerate blood vessel formation. The stemness more expressed by EPC grown on fibrin adds a surplus value to EPC-based therapies. P2199 Composite scaffolds for a controlled delivery of bioactive pro-angiogenetic growth factors E. Briganti 1, D. Spiller 1, C. Mirtelli 1,P.Losi 1,S.Kull 1, S. Tonlorenzi 1, R. Di Stefano 2, G. Soldani 1. 1 IFC CNR - Ospedale Pasquinucci, Massa, Italy; 2 Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy Purpose: The aim of this study was to develop a novel composite scaffold that, combining good mechanical properties with a controlled and sustained release of bioactive pro-angiogenetic growth factors, should be useful for regenerative medicine applications in which a significant tissue distensibility is necessary, such as myocardial infarction. Methods: The scaffold, constituted by a synthetic biocompatible material, the polyetherurethane-polydimethylsiloxane (PEtU-PDMS), and a biological polymer, the fibrin, was fabricated by spray phase inversion in an original way. In brief, the thrombin solution was sprayed simultaneously to the PEtU-PDMS solution and then incubated overnight at 37 C with the fibrinogen solution at 10 or 20mg/ml, to reach a deep permeation of fibrin into wall thickness. During the fibrin polymerization vascular endothelial growth factors-165 (VEGF165), basic fibroblast growth factors (bfgf), and 5 or 10μg of heparin were incorporated in the fibrin layer. Structural-mechanical properties of scaffolds and the effect of fibrinogen and heparin concentration on growth factors release were evaluated. The in vitro VEGF and bfgf bioactivity was assessed using HUVEC culture. Finally, mrna expression of IL-8, L-SEL, LFA-1 and inos in human monocytes was measured to determine the immune response induced by scaffolds. Results: Morphological analysis of scaffolds surface showed an homogeneus fibrin layer, constituted by a network of randomly oriented nanofibers, firmly adherent onto the synthetic material. Tensile tests highlighted isotropy, handling and elasticity of the scaffolds. The rate of growth factors release from scaffolds was controlled by the fibrinogen concentration (20mg/ml of fibrinogen determined the slowest release rate), whereas it was not affected by heparin concentration; in addition, bfgf was retained for a longer time than VEGF and thus delivered more slowly. The biological activity of the released growth factors was maintained. Finally, scaffolds induced a slight immune response in vitro as showed by low mrna expression levels of inflammatory markers. Conclusion: The results of the present work suggest that the new developed composite scaffold once implanted, providing a co-localization and temporal dis-

56 356 New or improved: angiogenesis and remodeling tribution of bioactive VEGF and bfgf in addition to handling and elasticity, may be able to stimulate new vessels formation in the target tissue. Implants of composite scaffolds in ischemic hindlimb and in the dorsal subcutaneous tissue of Wistar rats are under investigation to assess their potential to induce angiogenesis. P2200 The impact of erythropoietin on local balance of angiopoietins and VEGF in a murine model of hind-limb ischemia G. Vogiatzi, D. Tousoulis, A. Briassoulis, A. Valatsou, C. Antoniades, D. Perrea, N. Papageorgiou, K. Marinou, D. Konstantinidis, C. Stefanadis. University of Athens, Athens, Greece Purpose: Angiopoietin (Ang) -1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) regulate angiogenesis and may be important in myocardial collateral development. Ang-2 and VEGF act synergistically to produce a stable and functional microvasculature while Ang-1 can also be antiangiogenic, offsetting VEGF-induced angiogenesis. We investigated whether erythropoietin (EPO) alters the local balance of the angiopoietins and VEGF in a murine model of hind limb ischemia. Methods: Wild type C57BL/6 male mice were anesthetized and underwent surgically induced unilateral hind-limb ischemia with ligation and excision of the left femoral artery. Mice were divided in a randomised blinded manner in two groups and received either EPO (400IU/kg for 5 days in 0.2ml solution, IM) or normal saline (0.2ml for 5 days, IM). At day 28 they were sacrificed and muscle tissues from the both limbs were snap frozen in liquid N2 for RNA extraction. Mice underwent laser Doppler perfusion imaging after surgery on days 1, 7 and 28 for the estimation of the bilateral hind-limb perfusion. Quantitative real time RT-PCR was performed to analyze the differential gene expression between these two models of several angiogenic factors such as VEGF, Ang-1 and Ang-2. Results: There was no significant difference in the expression of Ang-1 and VEGF between the ischemic (13.2±1.0 and 8.4±0.6 RLU) and non-ischemic (13.4±2.39 and 8.0±0.8 RLU, p=ns for both) limb of control animals. However, the ischemic limb expressed significantly lower Ang-2 (9.1±1.5 RLU) compared to the non-ischemic limb (11.6±1.5RLU, p=0.004) in the control animals. On the contrary, EPO induced a significant elevation of VEGF expression in the nonischemic limb (10.4±1.0 RLU) compared to the ischemic limb (7.6±1.1 RLU, p=0.008). Importantly, erythropoietin prevented the elevation of Ang-2 in the nonischemic limb (6.0±1.9RLU) compared to the ischemic (7.6±3.1RLU, p=ns) limb. The expression of Ang-1 was still not significantly different between the two limbs in the erythropoietin-treated animals (12.5±2.3 RLU in ischemic vs 11.3±1.0 RLU in the non-ischemic limb). Conclusion: Erythropoietin treatment increases VEGF and decreases Ang-2 expression at the non-ischaemic limb in animals with unilateral limb ischaemia. This finding suggests that erythropoietin may play a critical role in neoangiogenesis by interfering in the mechanisms regulating remote post-conditioning. P2201 Development of a 3D nanostructured scaffold with angiogenic potential in cardiovascular applications R. Di Stefano 1, A. Magera 1, E. Briganti 2,C.Ristori 1, M.C. Barsotti 1, D. Spiller 2, C. Mirtelli 2, P. Losi 2, G. Soldani 2, A. Balbarini 1. 1 Cardiac, Thoracic and Vascular Department, University of Pisa, Pisa, Italy; 2 IFC CNR - Ospedale Pasquinucci, Massa, Italy Purpose: Medical devices realized with a biocompatible polymer, the poly(ether)urethane-polydimetilsiloxane (PEtU-PDMS), may have important cardiovascular applications such as vascular prostheses or cardiac patches. Fibrin is an optimal matrix to promote the in situ release and maintaining of cells widely used in tissue engineering. Endothelial progenitor cells (EPC) are bone marrow cells able to contribute to the vascular repair. Aim of this work was to realize a nanocomposite 3D scaffold composed by PEtU-PDMS, coated with fibrin, able to support EPC growth and differentiation and to promote in vivo angiogenesis. Methods: Scaffolds were fabricated by spray-phase inversion technique (Advanced Spray Machine Technology). Surface morphology was analysed by stereo-microscopy (Ponceau Red staining) and scanning electron microscopy (SEM). EPC obtained from peripheral blood of healthy donors were cultured on scaffold (1x106 cell/cm 2 ) in endothelial culture medium containing 5% FBS and specific growth factors. Fibronectin coating was used as control. Cell viability (Calcein-AM incorporation) and endothelial markers expression was assessed by confocal microscopy. VEGF and bfgf release was evaluated by Elisa assay. Four types of scaffolds (A: PEtU-PDMS, B: PEtU-PDMS and fibrin, C: PEtU-PDMS, fibrin and growth factors, D: PEtU-PDMS, fibrin and EPC) were implanted subcutaneously in the dorsal right and left side (angiogenesis model) or in the unilateral hindlimb (ischemia model) of female nude rats for up 14 days. In vivo neo-angiogenesis was evaluated by histology and immunohistochemistry (CD31 staining) and by Laser Doppler imaging. Results: Pounceau staining showed that fibrin coating was homogeneous and tightly bound to the synthetic polymer surface. SEM showed a well organized layer of fibrin fibres in a nanometric scale (mean diameter 140 nm). EPC viability and the endothelial markers expression was as high as on fibronectin. VEGF and bfgf release was maintained until 14 days. The histological analysis of implanted scaffolds revealed a well organized network of neovessels around the scaffolds C and D as compared with controls (A and B). In the hindlimb ischemic model Laser Doppler blood perfusion was significantly higher with scaffold C implantation. Conclusions: The spray technology can realize a nanostructured 3D scaffold made of a biocompatible polymer and fibrin as matrix to allows EPC adhesion and differentiation. This new biodegradable support has the potential of an angiogenic sticker able to promote neo vessels formation in vivo. P2202 In vivo characterization of the angiogenic properties of T-cadherin D. Pfaff 1,M.Philippova 1,M.B.Joshi 1, E. Kyriakakis 1,P.Erne 2, T.J. Resink 1. 1 University Hospital Basel, Basel, Switzerland; 2 Kantonspital, Luzern, Switzerland Purpose: T-cadherin (T-cad) is an atypical GPI-anchored member of the cadherin superfamily which is upregulated in endothelial cells of vasa vasorum in atherosclerotic lesions and in endothelial cells of tumor-derived blood vessels. Pro-angiogenic properties for T-cad have been demonstrated in vitro using the endothelial cell spheroid model and the Nicosia heart model. Myoblast-mediated delivery of soluble T-cad to mouse skeletal muscle in vivo was shown to facilitate VEGF-induced angiogenesis, and T-cad gene ablation in a mouse mammary tumor model was shown to limit tumor angiogenesis. The effects of T-cad on angiogenesis in vivo remain poorly characterized. In this study we aim to exploit two in vivo models to further investigate and characterize the angiogenic potency of T-cad expressed on endothelial cells. Methods: We have generated an array of lentiviral vectors to overexpress native T-cad protein, to express different domain-deletion mutants of T-cad protein, and to downregulate T-cad protein. The first in vivo angiogenesis model constitutes a human vasculature in mice engineered by implanting primary human endothelial cells as spheroids embedded within a matrigel-fibrin matrix. In this model endothelial cells are transduced with lentivirii prior to preparation of spheroids. The second in vivo model is the shell-less chick embryo chorioallantoic membrane and here the vasculature is directly infected with lentivirii. Results: All engineered lentiviral vectors have been tested for efficient and reproducible modulation of T-cad protein in primary endothelial cells (EC s) and a variety of cell lines (endothelial cells, keratinocytes, squamous cell carcinoma cells, melanoma cells). Spheroids composed of T-cad overexpressing EC s or T-cadsilenced EC s (and corresponding control EC s) have been implanted into mice and the relevance of T-cad to building a new vasculature in mice is under analysis. Spheroids composed of EC s transduced with domain-deletion mutants of T-cad have been analysed for sprout outgrowth in vitro. Domains relevant to the ability of T-cad to either stimulate angiogenesis or inhibit angiogenesis in a dominant negative manner) have been identified and investigations on their relevance to vessel development in vivo are under way. Conclusion: Different in vivo models are being successfully used to characterize the angiogenic impact of T-cad expressed on endothelial cells. This underestimated molecule might be of use as a potential future target for several therapeutic approaches, e.g. during tumor angiogenesis. P2203 Gene therapy with AdPDGF-C and -D induces proliferation of fibroblasts and impairs cardiac function P. Korpisalo 1, H. Karvinen 1, M. Ryhanen 1, M. Merentie 1, J. Huusko 1, M. Hedman 2, S. Laidinen 1, J. Kilpijoki 1, U. Eriksson 3, S. Yla-Herttuala 1. 1 Department of Molecular Medicine, A.I. Virtanen Institute, Kuopio, Finland; 2 Department of Cardiology, Kuopio University Hospital, Kuopio, Finland; 3 Ludwig Institute for Cancer Research, Stockholm, Sweden Platelet derived growth factors (PDGFs) are a family of proteins that regulate pericyte proliferation and stabilisation of vessels. Recently two new members of the family PDGF-C and PDGF-D were identified and reported to have angiogenic potential. Thus, they might be useful in revascularisation of ischemic tissues with gene therapy. We have created adenoviruses encoding PDGF-C and PDGF-D, and tested the angiogenic potential of these growth factors in rabbit skeletal muscle and mouse myocardium. An AdLacZ marker-gene was used as a control. An ischemia model consisting of the ligation of the superficial femoral artery was used in rabbit hindlimb. Closed-chest, trans-thoracic myocardial injections were used in mice. High resolution CPS-ultrasound was used to evaluate changes in blood flow noninvasively in both models. High frequency ultrasound was used to quantify ejection fraction and other cardiac measures in mice. Histology was used in both models for the assessment of microvascular changes. AdPDGF-C and PDGF-D were found to induce proliferation of fibroblasts and inflammatory cells in the rabbit hindlimb six days after gene transfer. In mice myocardium a similar expression of the growth factors was found to impair cardiac function, such as ejection faction and fractional shortening. Additionally, an increase in the left-ventricular inner-volume was detected implicating possible cardiac insufficiency. The angiogenic changes induced by the growth factors in either model were quite modest compared to the fibrotic and inflammatory changes and functional defects. In conclusion, PDGF-C and PDGF-D have angiogenic potential in some models but hinder the function of target tissues after gene therapy in mice and rabbits. In

57 New or improved: angiogenesis and remodeling / Markers and monitors of endothelial function 357 the light of these results, the potential of AdPDGF-C and -D for therapeutic agents in tissues where impaired function can be life-threatening seems to be limited. P2204 Collateral vessel formation in patients with documented coronary occlusion: role of gender, smoking and of their combination F. Mouquet 1, F.J. Cuilleret 1,S.Susen 1, P.V. Ennezat 1, T. Letourneau 1, P.A.M. Doevendans 2, J. Dallongeville 3, M.E. Bertrand 1,B.Jude 1,E.VanBelle 1. 1 Hopital Cardiologique CHRU de Lille, Lille, France; 2 UMCU - Cardiology Department, Utrecht, Netherlands; 3 Institut Pasteur de Lille, Lille, France In case of coronary occlusion, development of coronary collaterals is an important adaptive mechanism: it can reduce the size of myocardial infarction (MI), preserve left ventricular function, and reduce the risk of death. Women and smokers have an increased risk of cardiovascular events after MI. Preclinical studies have suggested that these patients might exhibit a less developed collateral circulation. The present study was designed to evaluate the impact of gender, smoking and their combination on collateral circulation development in the clinical setting. 387 consecutive patients with at least one coronary occlusion of a major coronary vessel at diagnostic angiography were prospectively enrolled. The duration of coronary occlusion was recorded. Collateral development was graded with a previously validated angiographic method. In the population, 19% were women and 75% were smokers. Smoking was less frequent in women (23%) than in men (88%, p=0.0001). Multivariable analysis adjusted for age, cholesterol level, diabetes, severity of coronary artery disease, and duration of coronary occlusion, found that female gender (p=0.003) and smoking (p=0.003) were independently associated with a less developed collateral circulation (Figure). Among the 4 smoking/gender combination groups, smoking/women was the group with the least developed collateral circulation (CFG=1.84±0.55) while non-smoking/men was the group with the most developed collateral circulation (CFG=3.04±0.29, p=0.0001, Figure). Conclusion: In patients with coronary occlusion, collateral circulation is less developed in women and in smokers. The combination of female gender and smoking is particularly detrimental. This could partly explain the worse cardiovascular prognosis observed in these groups of patients after MI. P2205 Effects of endogenous NO and of NO-donors in arteriogenesis K. Troidl 1,S.Tribulova 1, H. Wustrack 2, I. Eitenmueller 1, W. Schierling 1,W.J.Cai 3,C.Troidl 1, W. Schaper 1. 1 Max-Planck- Institut fuer Herz und Lungenforschung, Bad Nauheim, Germany; 2 Klinikum der J.W. Goethe Universitaet, Frankfurt am Main, Germany; 3 Dept. of Anatomy, Central South Univ. Changsha, Xiansha, China, People s Republic of Purpose: Previous studies showed that targeted enos disruption in mice with femoral artery occlusion does not impede and transgenic enos overexpression does not stimulate collateral artery growth following femoral artery occlusion (FAL), suggesting that NO from enos does not play a role in arteriogenesis. However, pharmacological NOS inhibition with L-NAME markedly blocks arteriogenesis, suggestive of an important role of NO. Methods: In order to solve the paradox we studied targeted deletion of inos as well as enos (n=12 each) with respect to collateral growth. A subset of mice lacking enos received additionally L-NIL to block all sources of NO (n=5). Next we quantified time course of mrna expression of different NOS isoforms in a high fluid shear stress arteriogenesis model in rats (n=3 for each time point). Finally we evaluated the therapeutic effect of NO donors on arteriogenesis by determination of collateral conductances and by immunohistological investigations in rabbits (n=6). Results: We found that only inos knockout could partially inhibit arteriogenesis. However, the combination of enos knockout plus treatment with the inos inhibitor L-NIL completely abolished arteriogenesis. This resulted in severe consequences: Two animals had to be sacrificed because of pedal self-amputation, two died from ischemia provoked necrosis (gangrene), and only one animal survived the observation period. enos and especially inos (but not nnos) become up-regulated in shear stress-stimulated rat collateral vessels. This was strengthened by the observation that the NO-donor DETA NONOate strongly stimulated collateral artery growth, activated perivascular monocytes and increased proliferation markers. This resulted in a significantly increased collateral conductance of 235±31 ml/min/100mmhg (control FAL 133±12 ml/min/100mmhg). Conclusion: NO is necessary for arteriogenesis but inos plays an important part. P2206 Calcium-dependent gene regulation plays a critical role during shear stress induced arteriogenesis C. Troidl 1,H.Nef 1,S.Voss 1,A.Schilp 1,S.Kostin 2,K.Troidl 2, T. Schmitz-Rixen 3,C.W.Hamm 1,A.Elsaesser 4, H. Moellmann 1. 1 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 2 Max-Planck- Institut fuer Herz und Lungenforschung, Bad Nauheim, Germany; 3 Klinikum der J.W. Goethe Universitaet, Frankfurt am Main, Germany; 4 Klinikum Oldenburg, Oldenburg, Germany Purpose: Recently we could show that an activation of the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is an early and important event during fluid shear stress (FSS) induced arteriogenesis. The aim of the present study was to investigate calcium-dependent transcriptional regulation using a clinical relevant animal model in the hind limb of pigs, to uncover possible molecular mechanisms of collateral growth. Methods: Domestic pigs (n=18, 40±1 kg) were assigned to the following groups (each n=6): (1) sham operated pig served as controls, (2) ligature of the A. femoralis, (3) ligature of the A. femoralis combined with an arterio-venous shunt distal to the occlusion, which leads to chronically increased FSS. Pigs were euthanized after 7 days. Collateral arteries and muscle tissue of the M. quadriceps were isolated and analysed using quantitative real-time PCR, Western Blot analysis and immunohistochemistry. Investigations were carried out with special focus on Kv channel interacting protein 3, (KCNIP3), camp responsive element binding protein 1 (CREB1), nuclear factor of activated T-cells, cytoplasmic, calcineurindependent 1 (NFATC1), C-JUN protein (c-jun) and myocyte enhancer factor 2C (MEF2C). Results: In shunt treated pigs a strong growth of collateral arteries results in an increased collateral flow index. Western Blot analysis showed increased protein levels of KCNIP3 in the cytoplasmic fraction after shunt treatment. This was confirmed by immunohistochemical staining. Increased phosphorylation was found for NFATC1 after shunt treatment using Western Blot analysis. Accordingly, immunohistochemistry showed decreased cytoplasmic fluorescence signals of NFATC1. CREB- as well as c-jun-positive nuclei were increased in shunt treated pigs. For MEF2C no significant changes were observed between ligature and shunt treatment. Conclusion: Western Blot results showed that of the three most important calcium-dependent transcription factors (KCNIP3; NFATC1 and MEF2C) two are activated after shunt treatment. This was confirmed by immunohistochemistry and mrna abundance. In addition the increased expression of CREB and c-jun, which are also indirectly activated by calcium point towards the pivotal role of TRPV4-triggerd increase of cytosolic calcium during arteriogenesis. Our results demonstrate the important role of calcium as a central mediator of FSS-induced arteriogenesis by activation of the mechanosensitive Ca 2+ -channel TRPV4. MARKERS AND MONITORS OF ENDOTHELIAL FUNCTION P2207 A multicenter study to assess flow-mediated dilation variability L. Ghiadoni 1,F.Faita 2,L.DeSiati 3,A.Biggi 4,G.Ambrosio 5, G.A. Lanza 6, M.L. Muiesan 7,M.Volpe 3, S. Taddei 1, F. Cosentino 3 on behalf of the Working Group on Peripheral Circulation of the Italian Society of Cardiology. 1 Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy; 2 CNR Istituto di Fisiologia Clinica, Pisa, Italy; 3 2nd Faculty of Medicine, University La Sapienza, Rome, Italy; 4 Azienda Ospedaliero Universitaria di Parma, Parma, Italy; 5 Università di Perugia, Ospedale Silvestrini, Perugia, Italy; 6 Catholic University of the Sacred Heart, Rome, Italy; 7 University of Brescia, Brescia, Italy Purpose: Endothelial dysfunction is associated to cardiovascular risk factors and plays a pivotal role in prediction of cardiovascular events. Endothelial vasomotor testing may be performed non-invasively by assessment of flow-mediated dilation (FMD). Despite large efforts to standardize the technique, there are technical limitations related to its reproducibility.the aim of this multicentre study was to standardize the procedure for FMD assessment among different research centres and evaluate FMD variability over time in healthy volunteers. Methods: Seventy-five healthy subjects (aged 20-60years) were recruited in 6 italian university hospitals. FMD was assessed as dilation of the brachial artery secondary to 5 minutes wrist ischemia by trained operators using a clamp to held the ultrasound probe. Sequences of B-mode images of the brachial artery were VCR recorded for baseline FMD (time0) and repeated 1 hour after maintaining the probe in the same position (time1). A third sequence was obtained 1 month apart (time 2). Endothelium-independent vasodilation to glyceril trinitrate (25 mcg,

58 358 Markers and monitors of endothelial function sublingual) was also evaluated at time 1 and 2. FMD and response to GTN were measured blindly as percentage changes in brachial artery diameter by an automatic edge detection system at the coordinating centre. The intra- (time 0 versus 1) and inter-session (time 0 versus 2) coefficients of variation were calculated for the 6 different research centres and overall to assess FMD and GTN variability over time. Results: All recordings were suitable for analysis. FMD was 7.5±3.2% at time 0, 7.3.±3.3% at time 1 and 7.4±2.9% at time 2. Overall, the intra-session FMD variability was 10.2±12.1% ranging from 7.1 to 10.9% in the different centres. Inter-session FMD variability was 13.0±8.9%, ranging from 12.2% to 13.8% in the different centres. GTN response was 13.9±4.1% at time 0 and 12.8±4.8% at time 2. Overall inter-session variability of GTN response was 12.9±9.8%, ranging from 10.1% to 17.1% Conclusions: This multicenter study shows that intersession FMD coefficient of variation (1 month apart) results to be similar to the intra-session one (1 hour apart), which would represent the intrinsic variability in the endothelial response. Thus, a standardized procedure including operator training, defined experimental settings and automatic brachial artery measurements, ensures an adequate FMD reproducibility over time and it can be routinely used for the assessment of endothelial function in clinical studies. P2208 Endothelium function and intima-media thickness (IMT) changes in hypertensive patients under the influence of pharmacogenetically determined treatment in relation to five genes polymorphisms L. Sydorchuk 1,K.M.Amosova 2, V.P. Pishak 1, R.I. Sydorchuk 1, I.I. Sydorchuk 1. 1 Bukovinian State Medical University, Chernivtsi, Ukraine; 2 National State Medical University, Kyiv, Ukraine Objective: To evaluate endothelium function (EF) and IMT changes in patients with essential arterial hypertension (EAH) under influence of antihypertensive treatment during 9-12 months depending on I/D polymorphism in ACE gene, A1166C; in AGTR1 gene, T894G in enos gene, Pro12Ala in PPAR-γ2, Arg389Gly in ADRβ1 gene. Design/Methods: 249 patients (EAH I 26.5%; EAH II 45.8%; EAH III 27.7%; women 48.2%, men 51.8%, mean age 50.5±10.4 yrs) underwent combination therapy depending on genes polymorphism ((hydrochlorothiazide (HCTZ)+angiotensin II receptor (ARB) blocker), HCTZ+β1- blockers (BB), HCTZ+ACE inhibitors (ACEI), calcium antagonists (CA)+ARB, CA+BB, CA+ACEI). EF evaluated by Flow mediated brachial artery dilation Celermajer-test (FMD). Carotid artery IMT by Ultrasound. Efficacy criteria of treatment were FMD >10.0%, IMT <0.9mm (ESC/ESH 2007). Results: Number of patients with target IMT (<0.9mm) and FMD (>10.0%) increased by 15.9% and 29.3% after treatment, p< HCTZ+ARB increased percentage by 13.3% and 23.3%, p<0.001: reliable in ACE gene II-genotype (p 0.002), AGTR1 gene A-allele (0.001 p 0.05), enos gene G-allele carriers (0.006 p 0.023), PPARγ2 gene Pro-allele (0.005 p 0.028) and ADRβ1 gene Arg-allele (0.003 p 0.028). HCTZ+BB combo caused an 8.8% IMT increase (p=0.007): reliable in ID-genotype of ACE gene and TG-genotype of enos gene (p=0.045), without significant changes of FMD. Target IMT and FMD patients increased under HCTZ+ACEI by 18.0% and 36.0%, p<0.001: reliable in ACE gene ID-genotype (p<0.001), enos gene G-allele (0.001 p 0.046), PPARγ2 gene Pro-allele and ADRβ1 gene Arg-allele (0.001 p 0.014). 13.3% and 33.3% increase under CA+ARB, p<0.001, certainly in DD-genotype of ACE gene. CA+BB associated increase by 20.0% (p=0.011) and 53.3% (p<0.001): reliable in DDgenotype of ACE gene (p 0.011), independent on genotypes of AGTR1 gene (p 0.024), TG-genotype of enos gene, ProPro-genotypes of PPARγ2 gene and Gly-allele of ADRβ1 gene (p<0.001). CA+ACEI combo caused increase by 25.9% and 33.3%, p<0.001, certainly in DD-genotype carriers of ACE gene (p<0.001), A-allele of AGTR1 gene, G-allele of enos gene, Pro-allele of PPARγ2 gene and Arg-allele carriers of ADRβ1 gene (0.001>p 0.023). Conclusions: The reliable advantage in endothelial function improvement observed in all combinations of CA (better CA+ACEI), than with HCTZ (p<0.05) in D-allele carriers of ACE gene. Combos of CA+ARB and CA+ACEI are better than HCTZ+BB (p<0.05) in D-allele of ACE gene. P2209 Arterial wave reflections and determinants of endothelial function in erectile dysfunction patients: a hypothesis based on peripheral mode of action D. Terentes-Printzios, C. Vlachopoulos, N. Ioakeimidis, K. Baou, K. Aznaouridis, G. Antoniou, K. Rokkas, A. Askitis, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: Erectile dysfunction (ED) is associated with endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase is a determinant of endothelial dysfunction and C-type natriuretic peptide (CNP) which is highly expressed in the vascular endothelium is likely to exert a strong antiatherogenic activity that might be a key in compensating for deficiencies in NO. A possible interplay between ADMA and CNP with functional changes in penile and peripheral arteries was examined. Methods: ADMA and N-terminal fragment CNP (NT-proCNP) levels were measured in 85 ED patients and 37 subjects with normal erectile function matched for age and risk factors. Peak systolic velocity (PSV) of penile arteries below 25 cm/sec was considered to indicate severe arterial insufficiency (SAI). Augmentation Index (AIx) was measured as an index of wave reflections. Results: Patients with SAI (n=21) had significantly increased AIx (31 vs 23 vs 24%, P<0.001) and decreased NT-proCNP levels (left plot) as compared to subjects without SAI (PSV>25cm/s) and to controls. ADMA levels in patients with SAI were similar to those of men without SAI and significantly higher as compared to controls (middle plot). In ED patients, AIx exhibited a significant correlation with NT-proCNP (r=-0.19, P<0.05) and ADMA levels (r=0.17, P<0.05). Furthermore, CNP was inversely associated with ADMA (right plot). ADMA, CNP and penile arterial function Conclusions: Our data indicate that higher ADMA and lower CNP levels are unfavourably associated with a significantly decrease in penile vascular inflow and an increase in arterial wave reflections, most likely due to a markedly impaired NO and CNP activity in small arteries and arterioles. P2210 Dynamic reactivity of micro-circulation is less pronounced in type 2 diabetic subjects than in BMI and aged matched controls following a glucose challenge: potential implications for future CVD M.S.V. Chittari Macharotu, P.G. McTernan, N. Bawazeer, K. Lois, P.J. O Hare, M. Ciotola, S. Kumar, A. Ceriello. University of Warwick, Coventry, United Kingdom Purpose: Post meal hyperglycemia is an independent risk factor for retinopathy, macro vascular disease and cardiovascular disease (CVD). As limited data are available on the effects of post meal hyperglycemia on micro vascular reactivity, the aim of this study is to assess the effect of post meal hyperglycemia on both macro vascular and micro vascular reactivity simultaneously using flow mediated dilatation of brachial artery (FMD) and retinal vessel analysis (RVA) using a retinal vessel analyser. Methods: Subjects with type 2 diabetes (T2DM: Age: (mean±sd) 9.74 yrs; BMI: (mean±sd) 5.07 kg/m 2 ; n=22) and without type 2 Diabetes (ND: Age: 41.58±9.85 yrs and BMI: 30.11±4.96 kg/m 2 ; n=22) were recruited into this study, using strict criteria. Ethical approval was obtained from the Local Research Ethics Committee and all patients gave written consent. After overnight fast, a baseline FMD measurement of the right brachial artery and a measure of RVA as well as baseline blood markers were obtained. Subjects consumed 75 grams of glucose (OGTT) and plasma and serum markers, FMD and RVA were recorded every hour for 3 hrs. Results: OGTT confirmed ND and T2DM status. FMD and RVA analysis identified significant changes over time with both ND and T2DM subjects. Sub-cohort analysis determined that baseline arterial reactivity was significantly lower in T2DM subjects compared with ND subjects (P<0.05). In ND subjects, glucose challenge produced a gradual reduction of the FMD, reaching significance by 2 hr (P<0.01), no change was noted with RVA analysis. In T2DM subjects, hyperglycemia had a significant effect on FMD, (at an earlier time of 1hr) than noted in the ND subjects (P<0.05). Micro vascular reactivity in the T2DM subjects also showed a significantly different trend. Retinal arterial reactivity seems to increase initially due to rising blood glucose levels before showing reduced activity at a later stage. The dynamic range in the reactivity appears to be blunted compared with ND group, with statistically significant changes noted both at 1 and 2 hrs post glucose load (P<0.05). Conclusion: These novel data highlight that an acute increase in blood glucose can affect the arterial reactivity both at micro vascular as well as macro vascular level in T2DM patients. The blunted change in the micro circulation in T2DM could be due to either impaired auto regulation or impaired endothelial function or both. In conclusion, these findings may help to explain why postprandial hyperglycemia seems to be a risk factor for both CVD and retinopathy, indicating a possible link between CVD and retinopathy in T2DM. P2211 Non-invasiv measurement of local, regional and systemic arterial function in assessment of cardiovascular risk B. Gaszner 1, L. Priegl 1,I.Horvath 1, M. Illyes 2,A.Cziraki 1. 1 University of Pecs, Heart Institute, Pecs, Hungary; 2 TensioMed, Budapest, Hungary Purpose: Arterial stiffness parameters are commonly used to determine the development of atherosclerosis. The aim of our study was to compare local, regional and systemic arterial functional parameters measured by different non-invasiv examination methods for the assessment of cardiovascular risk.

59 Markers and monitors of endothelial function 359 Methods: The regional velocity of the pulse wave (PWVao), which shows the flexibility of the aortic wall, the local PWVcar at carotid artery measured by Doppler ultrasound, and the augmentation index (AIx), which varies proportionately with the resistance of the small arteries, were used for this purpose. Specification of the above mentioned parameters in healthy volunteers (control, n=99), in patients with either type II diabetes mellitus (DM, n=51), or ischemic heart disease (IHD, n=115) underwent diagnostic coronary angiography were performed. Measurements were simultaneously done using combined carotis Doppler echo-tracking system (Aloka SSD-5500) and oscillometric TensioClinic Arteriograph equipment. Results: The oscillometric AIx and PWVao values in control group (-39,3±31,9% and 8,5±1,6 m/s) significantly (p<0,05) increased in IHD and DM groups (Aix: -8,4±31,3% and -4,3±29,1%; PWVao: 10,2±2,3 m/s and 9,9±2,2 m/s). Echotracking PWVcar data showed similar significant tendency (PWVco 6,3±1.5 m/s; PWVIHD 7,5±1,6 m/s; PWVDM 7,4±1,3 m/s; p<0,05). Changes in echo-tracking Aix values were notable, but not significant. As a result of simultaneously conducted oscillometric and echo-tracking measurements a strong correlation of Aix, PWVcar and PWVao parameters (RAix=0,68 és RPVW=0,70) were found. Conclusions: According to the ESC 2007 guidelines in assessment of cardiovascular risk the arterial stiffness parameters were determined as part of the prognostic factors. Our results show that the increased cardiovascular risk could be assessed by the same extent with the local, regional and systemic arterial stiffness parameters using userfriendly oscillometric and echo-tracking methods. P2212 The role of asymmetric dimethylarginine in lighten the links between low-grade inflammation, endothelial and cardiorenal dysfunction in essential hypertension K. Dimitriadis, C. Tsioufis, C. Thomopoulos, D. Syrseloudis, E. Andrikou, I. Andrikou, V. Tzamou, D. Tousoulis, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, emerges as a marker of cardiovascular risk. Microalbuminuria, hypoadiponectinemia and subclinical inflammation are associated with atherosclerosis progression. We investigated the relationships of urinary albumin excretion, expressed as the albumin to creatinine ratio (ACR), with high-sensitivity C-reactive protein (hs-crp), adiponectin and ADMA in essential hypertensives. Methods: Our population consisted of 158 newly diagnosed untreated nondiabetic patients with stage I to II essential hypertension [106 men, mean age=49 years, office blood pressure (BP)=151/97 mmhg]. According to the ACR values determined as the mean of two non-consecutive morning spot urine samples, the study population was divided into microalbuminurics (n=32) (mean ACR= mg/g) and normoalbuminurics (n=126) (mean ACR<30 mg/g). Moreover, in all patients venous blood sampling was performed for estimation of lipid profile and hs-crp, adiponectin and ADMA concentrations. Results: Microalbuminurics compared to normoalbuminurics were older (53±7 vs 49±6 years, p<0.05), had higher 24-h systolic BP (144±11 vs 133±12 mmhg, p=0.001), while did not differ regarding sex, smoking status and metabolic profile (p=ns for all). Moreover, microalbuminurics compared to normoalbuminurics exhibited higher levels of ADMA (0.61±0.04 vs 0.55±0.03 μmol/l, p=0.001) and hs-crp (4.5±1.7 vs 2±1.1 mg/l, p<0.0001), whereas had lower adiponectin values (5.8±1.5 vs 9±2.6 μg/ml, p=0.019). In the total population, ACR was positively related to body mass index (r=0.319, p<0.0001), 24-h systolic BP (r=0.263, p<0.0001), ADMA (r=0.366, p<0.0001), hs-crp (r=0.318, p<0.0001) and negatively related to adiponectin (r=-0.169, p=0.004). Regarding ADMA, it was associated with 24-h pulse pressure (r=0.404, p<0.0001), hs-crp (r=0.221, p<0.0001) and adiponectin (r=-0.222, p<0.0001). Multiple regression analysis revealed that 24-h systolic BP, hs-crp and ADMA were the independent predictors of ACR (R2=0.58, p<0.0001). Furthermore, analysis of covariance showed that ADMA, adiponectin and hs-crp values were significantly different between groups even after adjustment for confounders (p<0.05). Conclusion: Microalbuminuric hypertensives exhibit pronounced inflammatory activation, endothelial dysregulation and hypoadiponectinemia. Moreover, the close association of ADMA with hs-crp and adiponectin, further establishes endothelial dysfunction as an integrative factor in the interpretation of ACR-related risk. P2213 Exercise induced gene-expression of DDAH-1 improves retinal microcirculation in obesity H. Hanssen 1,T.Nickel 2,V.Drexel 1,G.Hertel 1, I. Emslander 2, A. Schmidt-Trucksaess 1,M.Weiss 2,M.Halle 1. 1 Department of Prevention and Sports Medicine, Technische Universitaet Muenchen, Munich, Germany; 2 Department of Cardiology, Ludwig-Maximilians-Universitaet, Munich, Germany Purpose: Endothelial dysfunction is involved in the development of retinal microvascular changes in metabolic disorders. Retinal arteriolar narrowing and venular dilatation are associated with long-term risk of cardiovascular disease. ADMA (asymmetric dimethylarginine), a NO inhibitor, is metabolized by DDAH (dimethylarginine dimethylaminohydrolase). This study aimed to investigate the effect of regular endurance exercise on the arteriolar to venular diameter ratio (AVR) and the impact of the ADMA/DDAH-pathway. Methods: 46 male marathon runners aged were divided into the following groups: 15 obese (OR) (waist >102 cm, training distance/week (TD) 40km) and 14 lean runners (LR) (TD 40km) were compared to 17 lean athletes (LA) (TD 70km). AVR was assessed with a static vessel analyzer and blood samples were collected before and after a 10 week training program. Peripheral mononuclear cells (PBMC) were isolated by ficol gradient. DDAH-1-gene-expression in PBMC was analyzed by real time PCR. ADMA serum levels were detected by ELISA. Results: At baseline, AVR in obese runners was impaired (0.81). Endurance training improved AVR significantly in all groups (post-training: OR 0.86, LR 0.91, LA 0.96; p<0.001 for all). Training induced arteriolar dilatation was most pronounced in OR. Baseline ADMA-levels in OR were higher compared to lean subjects and decreased significantly during training (p<0.05; baseline 0.57 pg/ml to 0.46 pg/ml post-training). Associated with the ADMA decrease, we found an increase in DDAH-1 gene-expression in PBMC in OR (+220%; p<0.01). ADMA levels and DDAH gene expression were not altered in lean subjects compared to baseline. Conclusion: Obesity is associated with an impairment of the retinal microcirculation. Intensified endurance training normalizes AVR in obese runners. The amelioration of AVR in obese subjects seems to be caused by an exercise-induced improvement of endothelial function in retinal arterioles. The associated decrease in systemic ADMA levels is most probably induced by an enhanced DDAH expression. Our data suggest that endurance training improves endothelial microvascular function through modulation of the nitric oxide synthase pathway, generated by alterations of ADMA/DDAH signalling. P2214 Asymmetric dimethylarginine regulates endothelial progenitor and endothelial function via the vasodilator stimulated phosphoprotein VASP protein family F. Fleissner, J. Fiedler, J. Widder, G. Ertl, J. Bauersachs, T. Thum. Julius-Maximilians University, Wurzburg, Germany NO plays a vital role in endothelial vessel homeostasis. The NO synthase inhibitor asymmetric dimethylarginine (ADMA) reduces endothelial progenitor cell (EPC) number, differentiation and function. Migration assays using modified Boyden chambers revealed a significant reduction in migratory capacity of EPCs after treatment with increasing doses of ADMA. This effect could be rescued by adding the non-enzymatic NO donator pentaerythrithyltrinitrate (PETriN). Microarray analysis revealed deregulation of a variety genes involved in the regulation of NO bioavailability, such as vasodilator activated phosphoprotein (VASP). At the leading edge of lamellipodia and the tips of filopodia, VASP localizes to regions with dynamic actin reorganization and therefore plays an important role in cell migration. We therefore investigated the influence of ADMA on VASP expression and phosphorylation in EPC. Western Blots showed a significant reduction in VASP phosphorylation at the Ser239 site, whereas total VASP remained unchanged. Treatment with PETriN significantly increased phosphorylated VASP. Confocal imaging revealed a similar reduction in VASP phsophorylation. Interestingly, animal experiments using VASP-/- knockout mice showed improved nachrelated relaxation in organ bath experiments. Accordingly, an aortic sprouting assay showed significantly improved endothelial sprouting as well as increased numbers of circulating EPC in VASP-/- mice (90.2% increase in VASP-/- vs. wt, p<0.001). We therefore demonstrate improved endothelial function in VASP- /- mice suggesting possible compensative effects of other VASP protein family members. Indeed, the Ena/Vasp like protein (ENA) was upregulated in VASP-/- mice. SiRNA-mediated functional knockdown of ENA but not VASP in endothelial cells significantly attenuated migration capacity. Thus, ENA, a member of the VASP protein family is involved in the ADMAmediated impairment of vascular function. P2215 An optimized protocol for analysis of circulating angiogenic monocytes and endothelial progenitor cells by flow cytometry M. Hristov 1,S.Schmitz 1, T. Leyendecker 2, C. Schuhmann 3, P. Von Hundelshausen 1,F.Kroetz 3, H.Y. Sohn 3, F. Nauwelaers 4, C. Weber 1. 1 RWTH Aachen University, IMCAR, Aachen, Germany; 2 RWTH Aachen University, Department of Cardiology, Aachen, Germany; 3 LMU Munich, Department of Cardiology, Munich, Germany; 4 BD Biosciences Europe, Erembodegem, Belgium Purpose: Circulating adult endothelial progenitor cells (EPCs) have been shown to differentiate into mature endothelial cells, thus contributing to vascular homeostasis. Resident CD14dimCD16+ monocytes expressing the angiopoietin-1 receptor Tie2 functionally differ from classical inflammatory CD14bright monocytes and have also been implicated in angiogenesis. However, clinically applicable protocols for flow cytometric quantification of EPCs and Tie2+ monocytes in peripheral blood and a consensus on reference values remain elusive. Methods: The number of Tie2+CD14lowCD16+ proangiogenic monocytes and CD34+VEGFR2+CD45dim EPCs was assessed in peripheral venous blood of 58 consecutive patients (48 male, 10 female; mean age 66±11 years) with angiographically documented stable coronary artery disease by three-color flow cytometry using specific monoclonal antibodies conjugated to PerCP, PE, PE-Cy7,

60 360 Markers and monitors of endothelial function APC and APC-Cy7. Strict exclusion criteria (ACS within the last 6 months, current inflammation, autoimmune disease, ongoing or recidivated malignant disease, renal insufficiency with indication for dialysis, severe peripheral arterial occlusive disease with rest pain, atrial fibrillation and LVEF 45%) were applied to avoid confusing co-morbidity. In case of scheduled cardiac catheterization blood was drawn before the catheter intervention. Acquisition and analysis were performed on digital flow cytometers. Double- and back-gating was used to dissect complex mononuclear cell populations including a variety of overlapping phenotypes. This assessment was further refined by matching bright fluorochromes (PE-Cy7, PE) with dimly expressed markers (CD34, VEGFR2) and by automatic compensation to minimize fluorescence spillover. Results: Presuming a Gaussian distribution, we obtained average values (mean±sd) of 2.7±0.4% for Tie2+CD14lowCD16+ monocytes (range: %, CV: 14.6%) and 0.008±0.001% for CD34+VEGFR2+CD45dim EPCs (range: 0.006%-0.011%, CV: 15.8%). The intra- and inter-assay variability was 2.5% and 9.8%, respectively. Conclusions: We have developed a fast, highly sensitive and optimized assay for the flow cytometric quantification of circulating proangiogenic monocytes and EPCs in cardiovascular medicine. This protocol may represent a basis for standardized analysis and monitoring of these cell subsets to define their normal range and prognostic/diagnostic value in clinical use. P2216 Endothelial dysfunction after percutaneous coronary intervention -Is it different according to the kind of stent?- H. Teragawa, K. Nishioka, N. Mitsuba, S. Mikami, Y. Fujii, J. Soga, N. Fujimura, Y. Higashi, Y. Kihara. Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan Background: Several reports have shown that endothelial function is an important index of long-term prognosis, even in patients with coronary artery disease (CAD). However, it has not been fully elucidated how the kind of stent affects endothelial function in the long term. Therefore, we investigated endothelial function of the brachial artery before and 6 months after PCI in patients with CAD. Methods: The subjects were 160 patients (122 men, mean age 66 y) with CAD who underwent successful PCI for stenotic lesions. In each patient, brachial artery diameter responses to hyperemic flow (flow-mediated dilatation, FMD) and nitroglycerin (NTG) spray were measured by high-resolution ultrasonography just before and 6 months after stenting. Angiographic restenosis was defined as >50% diameter reduction at follow-up coronary angiography. Results: Seventy-eight patients were treated with bare metal stents (BMS), and 82 with drug-eluting stents (DES; 57 sirolimus-eluting stents, [SES] and 25 paclitaxel-eluting stents [PES]). The characteristics of the patients did not differ in the two groups except for the presence of diabetes mellitus (BMS, 27%; DES, 44%; p<0.05). The restenosis rate was significantly lower in patients with DES (BMS, 41%; DES, 10%; p < ). Brachial artery diameter at baseline and the percent increase in blood flow did not differ in the two groups before and after stenting. Before stenting, FMD (BMS, 3.7±0.4%; DES, 3.6±0.4%) and NTGinduced dilatation (BMS, 13.7±0.7%; DES, 13.7±0.6%) did not differ significantly in the two groups. Six months after stenting, the change in FMD was different in the two groups (BMS, 1.0±0.5%; DES; 1.3±0.5%; p<0.001), whereas the difference in NTG-induced dilatation was not significant in the two groups (BMS, 1.6±0.8%; DES, 0.4±0.7%; NS). The difference in FMD was similar in patients with SES ( 1.6±0.5%) and PES ( 0.9±0.8%; NS). Multivariate analysis demonstrated that DES (p<0.001, t = 3.68) affected FMD after PCI. Conclusions: These results suggest that endothelial function had deteriorated 6 months after implantation of a DES compared with PCI using a BMS, although the use of a DES markedly reduced restenosis. This finding may confirm the need for careful follow-up of patients with CAD, especially after implantation of a DES. P2217 Assessment of endothelial function in patients with Takayasu s arteritis by flow mediated vasodilatation and reactive nitrogen intermediates N. Senguttuvan, S. Jain, V. Dhawan, N. Khandelwal, A. Bahl, S. Verma. Post Graduate Institute of Medical Education and Research, Chandigarh, India Introduction: Takayasu s arteritis (TA) is among the commonest causes of renovascular hypertension in young. Endothelial function can be assessed by flow mediated vasodilatation (FMD) of the brachial artery. The dual role of nitric oxide (NO) has been well described in the pathogenesis of diseases like SLE, RA etc. The purpose of our study was to assess the endothelial function in patients with TA. To the best of our knowledge, there is no study that has been conducted to assess the endothelial function in patients with TA. Methods: We studied 20 patients with TA and 20 age and sex matched controls. After getting their informed consent, a detailed clinical examination and appropriate laboratory investigations were done to assess disease activity (active and inactive groups as per ACR criteria), FMD (measured as per the guidelines) and reactive nitrogen intermediates (RNI) levels (measured by the Green LC method). Those with hypertensive crisis and those who had undergone angioplasty and vascular surgery were excluded. Results: We used Mann Whitney U test, Fisher exact test and Kruskal Wallis test with posthoc pairwise analysis appropriately (p<0.05 was considered as significant). Mean (95% CI) of RNI level of patients with TA was 22.54μM ( ), which was significantly higher than that of controls 5.53μM ( ) (p<0.0001). It was also found that mean RNI level was significantly higher in patients with active TA 26.97±17.43μM ( ) when compared to patients with inactive TA 12.21±11.82μM ( ) or controls 5.53±5.42μM ( ). However, the posthoc analysis of RNI levels did not demonstrate any statistically significant difference between patients with inactive disease and controls (p=0.36). The mean flow mediated vasodilatation (95% CI) in patients with TA was found to be 25.72% ( ) as compared to 24.83% ( ) in controls (p>0.05). Similarly, no statistically significant difference was seen between patients with active TA and those with inactive TA. We further analyzed the effect of RNI levels in patients with TA in relation to FMD and found that all the subjects belonging to the abnormal category of FMD belonged to patients with TA irrespective of their RNI levels. Conclusion: The endothelial function, as measured by FMD, showed no difference between patients with TA and controls while mean RNI level was significantly elevated in patients with TA.Patients with active TA had significantly higher RNI levels than those with inactive disease. Hence, we put forth that RNI levels can be used to identify the disease activity levels in patients with TA. P2219 Correlations between the cardiovascular risk and disease activity in rheumatoid arthritis on the arterial stiffness in hypertensive patients R. Musetescu 1,E.Belu 1, A.E. Musetescu 2, D.-D. Ionescu 1. 1 Cardiology Center, Craiova, Romania; 2 University of Medicine, Craiova, Romania Background: Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease and accelerated atherosclerosis. Chronic inflammation may impair arterial function and lead to the increase of their stiffness reflected by Augmentation Index (AIx) changes. However, it is unknown the degree of impairment of the arterial stiffness in hypertensive patients with RA and the relationship with the disease activity. Objective: The aim of this study was to assess the vascular status of hypertensive patients with RA using the arteriographic method and to evaluate the relationship with the disease activity. Methods: We examined 78 hypertensive patients with RA (mean age 43.2±12.4 years), and 62 controls (mean age 45.6±11.5 years). All patients underwent standard clinical and biological (CRP, ESR) evaluation, with disease activity quantification by DAS28,4v. Augmentation index (AIx) was measured using Sphygmocor (AtCorMedical) device after standardised blood pressure measurement. The augmentation index was measured using applanation tonometry methods from radial artery. The study population was devided into two groups, the first group included patients with low disease activity (DAS28<3.2, n=21), meanwhile the second group included patients with moderate and high disease activity (DAS28>3.2, n=57). Results: study group analysis and comparison of means have shown that AIx was significantly higher in hypertensive RA patients compared to controls (28.64±10.16 vs ±2.46, p <0.001), as well as between the two study groups, in patients with moderate and high disease activity scores (26.32±8.26 vs ±2.84, p <0.001). Multiple regression analysis has also revealed that the presence of RA is an independent predictor for AIx (R2=0.716, p<0.001). Conclusions: The study revealed an increased augumentation index in hypertensive patients with RA especially in those with high disease activity scores. RA is associated with early increase of arterial stiffness and can be considered as an independent risk factor for cardiovascular morbidity. If these data are confirmed, aggressive prevention strategies for reducing the cardiovascular risk should be tested for persons with rheumatoid arthritis. P2220 Association of endothelial function and nitrooxidative stress with speckle tracking myocardial deformation in patients with rheumatoid arthritis. Effects of chronic inhibition of interleukin-1 I. Ikonomidis, S. Tzortzis, J. Lekakis, I. Paraskevaidis, I. Andreadou, M. Nikolaou, T. Kaplanoglou, G. Skarantavos, P. Soukakos, D.T. Kremastinos. University of Athens, Athens, Greece Inhibition of Interleukin-1 activity improves nitrooxidative stress, endothelial and coronary function. We investigated a) the association of nitrooxidative stress and endothelial function with myocardial deformation b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in rheumatoid arthritis (RA) patients. Methods: We compared 42 RA patients to 23 normal controls. 23 patients received anakinra (150mg s.c. o.d) and 19 patients prednisolone for 30 days. At baseline and post-treatment we assessed a) the LV longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography b) the coronary flow reserve (CFR) c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and d) nitrotyrosine (NT) blood levels. Results: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). Baseline CFR and NT were related with longitudinal strain (r=0.436, r=0.359), systolic strain rate (r=0.487, r=0.479) and early diastolic

61 Markers and monitors of endothelial function 361 strain rate (r=-0.367, r=-0.384), circumferential strain (r=0.439) and systolic strain rate (r=0.452) (p<0.05). FMD was related with longitudinal and circumferential diastolic strain rate (r=0.554, r=0.547, p<0.01). Compared to baseline, anakinratreated patients increased the longitudinal strain, systolic and early diastolic strain rate and circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients. There was a parallel improvement in FMD (5.3±3.0%, vs. 10.5±4.1%, p<0.01), CFR (2.4±0.6 vs. 3.08±0.5, p<0.01) and NT (median 787 vs. 388 nm p<0.05) after 30 days of anakinra treatment. Table 1. Chronic effects of anakinra on Longitudinal LV deformation parameters versus prednisolone-treated patients Anakinra (n=23) Prednisolone (n=19) P Baseline 30-days Baseline* 30-days Long. strain (%) -17.8± ± ± ± Long. systolic sr (1/s) -1.02± ± ± ± Long. early diastolic sr (1/s) 0.96± ± ± ± Conclusions: Myocardial deformation is impaired in RA patients and is related with nitrooxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitrooxidative stress. P2221 Regulation of endothelial thrombogenic activity under static and dynamic conditions by modulating alternative Splicing of tissue factor U. Rauch, A. Eisenreich, A. Zakrzewicz, A. Pries, H.-P. Schultheiss. Charite - Campus Benjamin Franklin, Berlin, Germany Background: The regulation of alternative splicing provides a powerful mechanism to control the protein diversity. The Cdc2-like kinases (Clk) and DNA topoisomerase I (DNA topo I) control alternative splicing by regulating the phosphorylation of serine/arginine-rich (SR) proteins. We recently showed Clks and DNA topo I to regulate alternative splicing of human tissue factor (TF) and cellular TF activity of TNF-α-induced HUVEC. This study investigated the impact of the SR proteins SRp75 and SF2/ASF on TF isoform expression and the regulation of thrombogenicity; and the role of Clks and DNA topo I in regulating the endothelial thrombogenicity under pro-inflammatory and dynamic conditions. Methods: HUVEC were pre-incubated with inhibitors of Clks and DNA topo I or sirnas against SRp75 or SF2/ASF before stimulation with TNF-α. TF expression was determined by Real-Time PCR and Western blotting and the thrombogenicity was measured by a chromogenic TF activity assay and a FXa generation assay. Results: Stimulation of HUVEC with TNF-α led to a 6-fold increased expression of alternatively spliced human (ash)tf and full length (fl)tf 1 h post induction (p<0.0001, n=5). Inhibition of SF2/ASF by specific sirnas led to a 2.5-fold increased in ashtf expression (p<0.05). The fltf mrna was reduced by 70% (p<0.0001). Combined inhibition of SRp75 and SF2/ASF by sirnas reduced the ashtf expression by 50% (p<0.0001) and fltf by 60% (p<0.01) in this static system (n=5). Moreover, we showed TNF-α to 5-fold increase the TF activity (p<0.0001, n=5). Inhibition of SF2/ASF reduced the TF activity by 50% and inhibition of SRp75 reduced the TF activity by 40% in HUVEC (p<0.01, n=5) 8h post TNF-α stimulation. These data demonstrate SF2/ASF and SRp75 to influence the regulation of TF isoform expression and cellular thrombogenicity under static conditions. Under dynamic flow conditions we found TNF-α to 3-fold increase the FXa generation in HUVEC (p<0.0001) 10 as well as 15 min post perfusion start (n=6). Inhibition of Clks significantly reduced the TNF-α-induced increase in FXa by 25% (p<0.0001) 10 and 15 min post perfusion start. Inhibition of DNA topo I led to a reduction of FXa generation by 70% 10 min (p< 0.001) and by 55% 15 min post perfusion start (p<0.0001). These data correspond to the expression of fltf, the main contributor to TF activity in HUVEC under the same conditions. Conclusion: These observations indicated that modulating alternative splicing of TF by the inhibition of SR proteins and the corresponding kinases influences the thrombogenicity under static and dynamic conditions in TNF-α-stimulated HU- VEC. P2222 Effect of nitric oxide on the AT-2 receptor expression in-vivo V.T. Dao, T. Suvorava, O. Kocgirli, S. Agouri, M. Oppermann, V. Balz, G. Kojda. Heinrich Heine University, Institute of Pharmacology and Clinical Pharmacology, Duesseldorf, Germany Purpose: We hypothesized that pentaerythritol tetranitrate (PETN) and endothelial nitric oxide (NO) might impact on the expression of angiotensin (AT) type 1 (AT-1) and type 2 (AT-2) receptors. Methods: We generated mice with an endothelial-specific overexpression of endothelial NO -synthase (enos) using the Tie-2 promotor and backcrossed these mice to the C57BL/6 background. Two of these lines were characterized by enos-western blot analyses and blood pressure measurements in comparison to transgene negative littermates. In addition, C57Bl/6 mice were fed with either 6 or 60 mg PETN/kg body weight/day for 4 weeks. Results: Analysis of line 1 of transgenic enos mice (1-eNOS++) showed a 2.3±0.15 fold higher aortic expression of enos and a reduction of blood pressure to 109.6±2.0 mmhg (P<0.01, n=4-6). Analysis of line 2 of transgenic enos mice (2-eNOS++) showed a 3.3±0.3 fold higher aortic expression of enos and a reduction of blood pressure to 105.0±3.0 mmhg (n=6, p<0.01). Treatment of 2- enos++ with the NOS-inhibitor L-nitroarginine (L-NAME) for 30 days completely inhibited the difference in blood pressure suggesting that the reduction of blood pressure in transgenic mice was caused by an increased bioavailability of endogenous NO. In lungs and left ventricular myocardium of 2-eNOS++ the expression of AT-1-receptors was similar to transgene negative littermates (P>0.05, n=8). In striking contrast, the expression of AT-2 receptors was increased by endothelial overexpression of enos in a gene-dose-dependent manner in the myocardium. In 1-eNOS++ and 2-eNOS++ this increase was significantly higher vs. control (P<0.05 and P<0.01, respectively). In lung tissue the AT-2 receptor expression was significantly increased in both lines vs. control (P<0.05). In addition the AT-2 receptor expression of L-NAME-fed mice was decreased in heart tissue of enos transgenic mice (n=4, P<0.05). Furthermore, in-vitro studies with the NO-Donor S-Nitroso-N-Acetyl-D,L-Penicillamin incubated porcine aortic endothelial cells resulted in significant higher expression levels of the AT-2 receptor (P<0.05). Preliminary experiments with PETN-fed mice showed a significant increase in AT-2-receptor expression in myocardial tissue (P<0.05) whereas the expression of the AT-1 receptors did not change (P>0.05) neither in myocardial nor in aortic tissue. Conclusion: These results show that endogenous NO and NO-Donors can upregulate vascular AT-2 receptor in-vivo. This newly discovered regulation might contribute to vasoprotective effects of NO. P2223 Humoral changes, expression of endothelial selection ligands and bubble grade following SCUBA (self contained underwater breathing apparatus) dive D. Glavas 1,A.Markotic 1,Z.Valic 1,N.Kovacic 2, I. Palada 1, R. Martinic 1,T.Breskovic 1,D.Bakovic 1, A.O. Brubakk 3, Z. Dujic 1. 1 Split University Hospital, Split, Croatia; 2 University of Zagreb-School of Medicine, Zagreb, Croatia; 3 Norwegian University of Science and Technology, Trondheim, Norway SCUBA (S) diving has diverse risk to health. The decompression sickness (DCS) is initiated by gas bubbles. Since CD15 and CD15s are leukocytes antigens recognised as ligands by endothelial selectins, we assumed they could be markers for impaired vasodilatation following diving. Aim: To evaluate humoral changes, expression of endothelial selection ligands (CD15 and CD15s on leukocytes) and formation of gas bubbles following open sea S dive. Methods: We performed an analysis of peripheral blood samples to detect the leukocytes that carries CD15 and CD15s and flow cytometry analysis of CD15 and CD15s to estimate any alteration in the membrane expression of those markers. The blood samples of 8 divers were collected 30 mins before and 50 mins after a dive to 54 m for 20 mins bottom time. The number of gas bubbles in the heart was monitored by ultrasound (according to Eftedal-Brubakk method). Results: Gas bubbles were observed in the right side of the heart in all 8 divers. The maximal mean bubble grade was 1.9±1.9 bubbles/cm 2. There was a significant increase in total white blood cells after the dive (before 6.4±1.6:after 8.0±1.9 (x10 9/l) and neutrophils (3.8±1.4:5.7±1.9), the monocytes slightly but not significantly increased (0.3±0.2:0.4±0.2), while lymphocytes significantly decreased (2.3±0.5:1.8±0.6). There were no significant changes in the red blood cells and platelet counts. There was a significant increase in LDH (175.3±39.5: 206.1±44.8 (IU/l)), CK (158.0±55.1:242.3±75.4), CKMB fraction (4.0±2.1:11.3±2.1), Na (137±1.0:139.5±1.1 (μm)) and decrease in K (4.8±0.2:4.3±0.3). There were no significant changes in glucose, laktate, CRP and troponin. The proportion of CD15+monocyte increased significantly after the dive (before dive 38.4±19.3 (mean±sd):after 67±34.2 (P<0.01; t-test) as well as the CD15s monocyte (CD15s high) (3.2±1.4:6.7±4.0 (P<0.05; t-test). The expression of the CD15 and CD15s was continously low on lymphocites (CD3+CD19+).There were no correlation between CD15+monocyte expression and average bubble formation (r=-0.56; P=0.17), as well as with CD15s+monocytes (r=0.43;p=0.29). Conclusion: The study suggests that biochemical changes, induced by SCUBA diving, primarily activate existing monocytes, rather that increase their number. The significant change of CD15+ monocytes and CD15s+high monocytes is not critical for bubble formation but may be involved in endothelial dysfunction. In addition, there were signs of muscle injury what supports the idea that inflammation may be part of decompression injury. The specific mechanisms involved in bubble formation await further examination.

62 362 Endothelial dysfunction: clinical studies ENDOTHELIAL DYSFUNCTION: CLINICAL STUDIES P2224 The incremental effect of sleep apnea on sub-clinical inflammation and asymmetric dimethyl-arginine levels in hypertensives: a nighttime partner of cardiovascular risk C. Thomopoulos, C. Tsioufis, A. Kasiakogias, D. Tsiachris, V. Tzamou, A. Mazaraki, I. Andrikou, I. Darladimas, T. Makris, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Objectives: Apart from the established role of high sensitivity C-reactive protein (hs-crp), diverse cytokines like IL-6, IL-18 and TNF-α promote a wide range of atherogenic effects in various domains of the vasculature. Asymmetric dimethyl arginine (ADMA) has been recognized as a marker of endothelial dysfunction in diverse clinical settings. In the present study, we investigated the possible associations of sleep apnea (SA) with the above mentioned serological markers in hypertensives. Methods: We studied 62 untreated hypertensives with SA documented by positive polysomnography (aged 48±7 years, 79% men, office systolic/diastolic blood pressure: 150±8/97±7mmHg), and 70 hypertensives without SA (negative polysomnography), matched for age, sex, smoking status, body mass index and 24 hour pulse pressure. All subjects underwent polysomnography, 24 hour ambulatory blood pressure monitoring, echocardiographic examination, while routine metabolic profile and serological markers were estimated in a single morning venous sample. Results: Hypertensives with SA compared to those without SA did not differ regarding waist circumference (0.92±0.1 vs. 0.92±0.1, p=ns) and 24h systolic BP (140±9 vs. 138±7 p=ns) while 24h diastolic BP was higher in hypertensives with SA (87.22±6.88 vs ±7.18mmHg, p=0.034). Furthermore, the former group with respect to the latter had significantly increased levels of log hs-crp by 28%, log TNF-α by 69%, logil-6 by 75% and logil-18 by 26% (p< for all cases). Similarly ADMA was increased in SA hypertensives by 13% (p<0.0001). Metabolic profile and left ventricle mass index resulted similar between the groups (p=ns, in all cases). In diverse ANCOVA study models, these differences remained statistically significant even after adjustment for confounders (p< for all cases). In the total study population all studied inflammatory markers plus ADMA were correlated with logahi and minsato2 (p< in all cases), while body mass index and 24 hour pulse pressure with all studied serological markers (p<0.05 in all cases). Conclusions: Hypertensive subjects with SA demonstrated increased levels of hs-crp, IL-6, IL-18, TNF-α and ADMA independently of confounders, including body size and 24h pulsatile load. The close association of apnea severity indexes with these serological markers further supports the incremental effect of SA on the cardiovascular risk duet of subclinical inflammation and endothelial dysfunction. P2225 The relation between endothelial dependent flow mediated dilation of the brachial artery and coronary collateral development A. Ongun 1, S. Gulec 1,N.Uslu 2, C. Tulunay Kaya 1, C. Ozdol 1, S. Turhan 1,Y.Atmaca 1,T.Altin 1,C.Erol 1. 1 Ankara University School of Medicine, Ankara, Turkey; 2 Baskent University Faculty of Medicine, Ankara, Turkey Background: Endothelial dysfunction is thought to be a potential mechanism for the decreased presence of coronary collaterals. The aim of the study was to investigate the association between endothelial function and the extent of coronary collaterals. Methods and Results: We investigated the association between endothelial function assessed via flow mediated dilation (FMD) following reactive hyperemia and the extent of coronary collaterals graded from 0 to 3 according to Rentrop classification in a cohort of 171 patients who had high grade coronary stenosis or occlusion on their angiograms. Mean age was 61 years and 75% were males. Of the 171 patients 88 (51%) had well developed collaterals (grades 2 or 3) whereas 83 (49%) had impaired collateral development (grades 0 or 1). Patients with poor collaterals were significantly more likely to have diabetes (p=0.001), but less likely to have used statins (p=0.083). FMD measurements were not different among good and poor collateral groups (11.5±5.6% vs. 10.4±6.2% respectively, p=0.214). Conclusions: No significant association was found between the extent of angiographically visible coronary collaterals and systemic endothelial function assessed by FMD. Table 1. Characteristics of the subjects Variables Poor collateral (n=83) Goodcollateral (n=88) pvalue Age (years) 61±10 61± Gender, males (%) 65 (78) 64 (73) Diabetesmellitus (%) 46 (55) 27 (31) Hypertension (%) 49 (59) 56 (64) Current smokers (%) 41 (49) 39 (44) Previous MI (%) 55 (66) 53 (60) LDL-C, mg/dl 109±34 107± Triglycerides, mg/dl 152±91 165± Ejectionfraction, % 46±13 49± Aspirin 72 (87) 74 (84) Beta-blockers 57 (69) 56 (64) Calcium channel blockers 5 (6) 11 (13) ACE-Is or ARBs 57 (69) 62 (71) Nitrates 28 (34) 35 (40) Statins 50 (60) 64 (73) nisms for the increased risk are poorly known. In this study we assessed whether children of pts with p-ami had abnormalities in plt and endothelial function. Methods: We studied 21 children (16±3 yrs, 9 M) of pts with p-ami ( 50 yrs old; Group 1) and 18 age and sex-matched children of healthy subjects (15±3 yrs, 9 M; Group 2). Blood samples were collected at rest and at peak treadmill exercise stress test (EST). Plt reactivity was assessed by monocyte-plt aggregates (MPA) and CD41 and PAC1 plt expression by flow cytometry with and without ADP stimulation (10-7 M). Peripheral vascular function was assessed by measuring brachial artery dilation during post-ischemic forearm hyperemia (flow mediated dilation, FMD) and after 25 μg of sublingual nitrates (nitrate-mediated dilation, NMD). Results: There were no differences in basal cytometry variables between groups. ADP and EST induced a higher percentage increase of flow cytometry markers in Group 1 compared to Group 2 (Table). FMD was significantly reduced in GROUP-1 compared GROUP-2 (7.7±3.0% vs 11.1±7.7% respectively; p=0.002), whereas no difference was found in NMD between the two groups (13.4±4.5% vs 15.2±3.5%; p=0.21). Children Children p of AMI patients of healthy subjects MPA pre/mpa at peak (%)* 9.5± ± MPA at peak/mpa at peak ADP (%)* 12.1± ± MPA preadp/mpa at peak ADP (%)* 10.6± ±4.9 <0.001 CD41 pre/cd41 at peak (%)* 5.5± ±3.6 <0.001 CD41 at peak/cd41 at peak ADP (%)* 14± ±5.5 <0.001 CD41 pre ADP/CD41 at peak ADP (%)* 10.1± ±1.1 <0.001 PAC1 pre/pac1 at peak (%)* 24.7± ±6 <0.001 PAC1 at peak/pac1 at peak ADP (%)* 154.4± ± PAC1 pre ADP/PAC1 at peak ADP (%)* 158.3± ±4.9 <0.001 *Data were expressed as pertentage variation of platelet indexes before (pre) and at peak of EST. CT = closure time, MPA = monocyte-platelet aggregates. Conclusions: Our results show that both plt and endothelial function have a less favourable profile in children of young AMI pts compared to controls. The pathophysiologic and clinical implications of these findings deserve appropriate investigations. P2227 Vascular endothelial function predicts mortality risk in patients with advanced ischemic chronic heart failure M. Shechter, S. Matetzky, M. Arad, M.S. Feinberg, D. Freimark. Chaim Sheba Medical Center, Tel Hashomer, Israel Background: Endothelial function is impaired in advanced chronic heart failure (CHF) patients. Aims: To explore the association between endothelial function and subsequent mortality risk in advanced CHF (ACHF). Methods and Results: We prospectively assessed brachial flow-mediated dilation (FMD) in 82 consecutive New York Heart Association (NYHA) class IV ischemic ACHF patients with left ventricular ejection fraction (LVEF) 22±3%. Following overnight fasting and discontinuation of all medications for 12 hours, percent improvement in FMD (%FMD) and nitroglycerin-mediated vasodilation (%NTG) were assessed using linear array ultrasound. All patients were followed for 14±2 months for pre-specified combined adverse cardiovascular events, including death, hospitalization for CHF exacerbation or myocardial infarction. Subjects were divided into 2 groups: (n=41) and > (n=41) the median %FMD of P2226 Platelet reactivity and endothelial function in children of patients with premature acute myocardial infarction L. Barone, G. Scalone, I. Coviello, A. Delogu, A. De Nisco, A. Di Monaco, R. Nerla, F. Infusino, G.A. Lanza, F. Crea. Catholic University of the Sacred Heart, Rome, Italy Background: Family history of premature acute myocardial infarction (p-ami) is associated with an increased risk of AMI in first degree relatives. The mecha- Kaplan-Meier Survival Plot

63 Endothelial dysfunction: clinical studies %. Both groups were comparable regarding cardiovascular risk factors, LVEF and concomitant medications. During follow-up 22 (53.6%) patients with FMD had composite adverse cardiovascular events compared with only 8 (19.5%) with FMD > the median (p<0.01). Furthermore, 5 deaths (12.1%) occurred in patients with FMD, compared with no deaths in FMD > the median (p<0.03) (Figure). Cox regression analyses revealed that FMD was an independent predictor for these events. Conclusion: Brachial artery FMD is associated with increased mortality risk in ischemic NYHA class IV ACHF patients. P2228 Smoking induces lipoprotein-associated Phospholipase A2 (Lp-PLA2) in cardiovascular disease free adults: the ATTICA study D. Panagiotakos 1, A. Tselepis 2,C.Pitsavos 3, C. Tellis 2, C. Chrysohoou 3, J. Skoumas 3, C. Stefanadis 3. 1 Harokopio University, Athens, Greece; 2 University of Ioannina, Ioannina, Greece; 3 University of Athens, Athens, Greece Background: Data from large Caucasian population studies have demonstrated an independent association between plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) and the risk of future cardiovascular events. We studied the association of smoking habits on Lp-PLA2 levels, in a sample of CVD free adults. Methods: During we randomly enrolled 3042 men and women (18-89 years) from the Attica region, Greece. Several socio-demographic, lifestyle (including current, former smoking or passive smoking), clinical and biological factors, were assessed in all participants. Lp-PLA2 activity in total plasma and in apob-depleted plasma, after the sedimentation of all apo B-containing lipoproteins with dextran sulfate-magnesium chloride (HDL-Lp-PLA2 activity), was determined by the trichloroacetic acid precipitation procedure using [3H]-PAF (100 μmol/l final concentration) as a substrate. Results: The total plasma Lp-PLA2 activity and mass were higher in current smokers compared to non-current smokers (p<0.05); similarly people reported exposed to second-hand smoke had also higher levels of Lp-PLA2 activity and mass compared to those who were not exposed to others cigarette smoke (p<0.05). Importantly, the molar ratio of Lp-PLA2 mass to apo B is higher in active smokers as compared to non-current smokers (2.8±1.4 vs. 2.0±1.1, p=0.03), and higher in secondhand smokers compared to non-current smokers (2.7±1.1 vs. 2.0±1.1, p=0.05). Moreover, Lp-PLA2 activity was positively associated with current or passive smoking (all p-values < 0.05) and this association was independent of various potential confounders. Conclusion: The present study shows for the first time that the plasma Lp-PLA2 activity or mass is strongly positively associated with active or secondhand smoking among healthy individuals. expression. This novel cytoprotective mechanism provides a mechanistic explanation how aspirin prevents acute coronary events at low plasma concentrations not related to its antiplatelet activity. P2230 Improved vasoreactivity following spironolactone therapy in chronic haemodialysis patients P. Flevari, S. Kalogeropoulou, D. Leftheriotis, F. Panou, S. Katsoudas, D. Bacharaki, D. Vlahakos, D. Kremastinos. Athens University Hospital Attikon, Athens, Greece Purpose: Cardiovascular mortality is the major cause of death in haemodialysis (HD) patients (pts). Endothelial dysfunction is commonly observed and precedes cardiovascular complications, including arrhythmias and sudden death. Although aldosterone directly affects endothelial function, the impact of its inhibition on HD pts has not yet been fully appreciated. Therefore, our goal was to study the vasoactive effect of spironolactone in HD pts, as evidenced by forearm venous occlusion plethysmography. Methods: Fourteen stable HD pts were studied, 9 male/5 female, mean aged 62±3 years. Pts with predialysis K + >6 meq/l were excluded. After an initial 4- month period of placebo treatment, all pts received spironolactone (25 mg thrice weekly) after each HD session for the next 4 months. Systemic blood pressure (BP), heart rate, and parameters of endothelial function were collected at baseline, after placebo administration, and following spironolactone treatment. We assessed forearm blood flow (FBF) i) at rest (baseline), ii) during reactive hyperaemia. Hyperaemic FBF corresponded to the mean value of the first 4 measurements observed after arterial occlusion release. The max % difference in reactive FBF (relative to baseline) was assessed. The duration of hyperaemia was the time (sec) at which FBF returned to 50% of its maximal increase relative to baseline flow. ANOVA for repeated measures was used for statistical analysis. Data are expressed as mean±se. Results: All patients completed the study without serious side effects. None of the above mentioned parameters were significantly changed during placebo administration. Following spironolactone treatment, predialysis K + increased from 4.4±0.2 to5.5±0.3 meq/l (p<0.01), while BP decreased [systolic BP from 148±4 to 122±3 mmhg(p<0.01) and diastolic BP from 74±3 to66±5 mmhg(p<0.01)]. After spironolactone administration, no significant differences were observed in baseline FBF values, while a significant increase was noted regarding the % difference in reactive FBF (from 51±12 to 152±46%, p<0.05). The duration of hyperaemia was also increased by treatment (from 35±8 to48±5 sec,p<0.01). Conclusion: In clinically stable HD pts, spironolactone administration is associated by favorable endothelial responses. Further studies are required in order to elucidate the pathophysiologic mechanism(s) and evaluate the clinical relevance of such treatment. P2229 Low-dose aspirin protects against coronary endothelial damage by inhibiting LOX-1-dependent uptake of electronegative L5 in acute myocardial infarction P.-Y. Chang, S.-C. Lu, J.-K. Lee, Y.-J. Chen, Y.-T. Lee. National Taiwan University Hospital, Taipei, Taiwan Purpose: Patients with coronary heart disease benefit from low-dose aspirin therapy through uncharacterized cytoprotective mechanisms independent of aspirin s antiplatelet effect. The electronegative low-density lipoprotein (LDL), named L5, is a naturally-occurring oxidized-ldl which exhibits a spectrum of atherogenic effects on cultured vascular cells. We hypothesized that low-dose aspirin protects against L5-induced coronary cell damage by inhibiting uptake of L5 through lectin-like oxidized LDL receptor-1 (LOX-1). Methods: Plasma LDL was isolated from patients with acute ST-elevation myocardial infarction and divided by ion-exchange chromatography into 5 subfractions, L1 L5, with increasing electronegativity. Cell proliferation was assessed by trypan blue exclusion and 3H-thymidine incorporation in human coronary artery endothelial cells (HCAECs) treated with each LDL subfractions. Fibroblast growth factor 2 (FGF2) expression was analyzed by ELISA and real-time PCR. Transcriptional regulation of FGF2 promoter was investigated using Luciferase reporter gene assay. The uptake of L5 by HCAECs was directly visualized by DiI fluorescence. LOX-1 expression was detected by immunochemical staining. Results: Aspirin had a biphasic effect on cell proliferation and intracellular FGF2 expression in HCAECs: a modest increase in both when aspirin concentrations were less than 0.2mmol/l (low-dose) and a concentration-dependent decrease when aspirin concentrations were higher than 0.2 mmol/l. The L5 specimens isolated from patients with acute myocardial infarction were able to induce HCAEC apoptosis and inhibit EC proliferation by down-regulating FGF2 expression. In contrast, L1-L4 hadno effects. Co-incubation of the cells with 50 ug/ml L5 and low-dose aspirin 0.2 mmol/l resulted in a significant attenuation of the inhibitory effects of L5. Imaging studies showed that the entry of DiI-labeled L5 into HCAECs was selectively inhibited by monoclonal antibody against LOX-1. Addition of lowdose aspirin decreased cellular LOX-1 expression, prevented DiI-L5 uptake and improved DNA synthesis. These changes were accompanied by maintenance of FGF2 gene promoter activity which was transcriptionally repressed by L5. Conclusions: This study showed that low-dose aspirin improved coronary cell survival by inhibiting L5 uptake through LOX-1 and maintained intracellular FGF2 P2231 Relation of digital vascular function and endothelial function by flow-mediated dilation with carotid atherosclerosis in hypertension A. Tatasciore, R. Tommasi, F. Santarelli, M. Zimarino, G. Renda, S. Gallina, R. De Caterina. Universita G. D Annunzio, Chieti, Italy Background and Aim: Systolic blood pressure (BP) has been related to arterial stiffness and the wave reflection phenomenon, in turn leading to atherosclerosis. We hypothesized that endothelial dysfunction, as assessed by flow-mediated dilation (FMD), might be a key mediator of this relationship. Here we tested the relationship of new tools to assess vascular function - the digital pulse amplitude augmentation (PAT) and the PulsePen - to assess arterial stiffness, with carotid artery intima-media thickness (IMT), as an index of atherosclerosis. Methods: In a cohort of 134 hypertensive patients we evaluated the relationship of several parameters assessing vascular function, including the peripheral vasodilatory function in response to hyperemia through the PAT, the pulse wave velocity (PWV, using the PulsePen) and FMD (by echo of the brachial artery, to assess endothelial dysfunction) with carotid artery IMT as a marker of atherosclerosis. Results: Systolic (S) BP, SBP variability, and all the 3 techniques assessing vascular function here studied had some relation with IMT at univariable regression analysis. At multivariable regression analysis, however, only PAT and PWV remained significantly related to IMT (Table), indicating that changes in vascular function explored by these techniques traduce the detrimental effects of SBP and SBP variability. Variables IMT Univariable Analysis, P (r) Multivariable Analysis, P SBP (mmhg) (0.203) NS SBP variability (mmhg) (0.202) NS FMD % (-0.211) PWV (0.219) PAT (0.380) Conclusions: Digital vascular dysfunction, assessed by the PAT hyperemic response, and arterial stiffness, evaluated as PWV, are directly and - at least in part - independently related to vascular atherosclerotic damage in hypertensive patients.

64 364 Endothelial dysfunction: clinical studies P2232 Graded association of arterial stiffness with asymmetric dimethylarginine, endothelin-1 and osteoprotegerin levels in essential hypertensive patients K. Dimitriadis, C. Tsioufis, E. Andrikou, D. Syrseloudis, C. Thomopoulos, I. Andrikou, A. Mazaraki, D. Tousoulis, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Arterial stiffening is a marker of atherosclerosis, whereas increased levels of asymmetric dimethylarginine (ADMA), osteoprotegerin (OPG) and endothelin-1 (ET-1) are associated with endothelial dysfunction states. In this study we examined the relationships of arterial stiffness with ET-1, OPG and ADMA levels in essential hypertensive patients. Methods: One hundred sixty-five newly diagnosed untreated non-diabetic patients with stage I to II essential hypertension [110 men, mean age=49 years, office blood pressure (BP)=151/97 mmhg] were divided into three groups according to carotid to femoral pulse wave velocity (PWV) values, assessed by means of a computerized method (Complior SP): Group A (PWV<7.4 m/sec), group B (PWV= m/sec) and group C (PWV>8.7 m/sec). Additionally, venous blood samples were drawn for estimation of lipid profile, ET-1, OPG and ADMA concentrations. Results: Patients in group A (n=61) compared to subjects in group B (n=53) and C (n=51) had lower office systolic BP (147±12 vs 150±14 vs 158±13 mmhg, respectively; p<0.05 for all cases) and left ventricular mass index (101.4±13 vs 115.2±15 vs 121.2±12 g/m 2, respectively; p<0.05 for all), while did not differ regarding metabolic profile (p=ns). Moreover, patients in group C compared to group B and A, exhibited higher levels of ADMA (0.63±0.04 vs 0.57±0.04 vs 0.52±0.03 μmol/l, respectively; p<0.05 for all), OPG (5.8±0.3 vs 4.3±0.5 vs 3.8±0.4 pmol/l, respectively; p<0.05 for all) and ET-1 (1.13±0.28 vs 0.65±0.17 vs 0.45±0.19 fmol/ml, respectively; p<0.05 for all). In the entire population, PWV was related to age (r=0.279, p<0.0001), office systolic BP (r=0.314, p<0.0001), ET-1 (r=0.236, p<0.05), OPG (r=0.314, p=0.03) and ADMA (r=0.193, p<0.05). Regarding ADMA, it was correlated with waist to hip ratio (r=0.209, p<0.05), office systolic BP (r=0.430, p<0.0001), whereas ET-1 exhibited a positive relationship with office systolic BP (r=0.214, p<0.05) and OPG (r=0.229, p<0.05). By multiple regression analysis it was revealed that age, office systolic BP, OPG and ADMA were independent predictors of aortic stiffness (R 2 =0.49, p<0.0001). Furthermore, analysis of covariance showed that ET-1, OPG and ADMA values remained significantly different between groups after adjustment for confounders (p<0.05). Conclusions: In essential hypertensives, aortic stiffness is gradually related to ET-1, OPG and ADMA levels, advocating common pathophysiological pathways of endothelial dysfunction and progressive atherosclerosis. Moreover, these findings further support the role of PWV as a tool to estimate vascular status in hypertension. P2233 Low 25-hydroxyvitamin D levels are associated with elevated plasma ADMA and C-reactive protein concentrations: nexus with cardiovascular disease D.T.M. Ngo 1,A.L.Sverdlov 1, J.J. Mcneil 2,J.D.Horowitz 1. 1 University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 2 Monash University, Melbourne, Victoria, Australia Background: Low plasma vitamin D concentrations are associated with significant increases in incidence of obesity, hypertension, diabetes; myocardial infarction; cardiovascular and all-cause mortality. However, the mechanism(s) underlying association between vitamin D status and cardiovascular risk remains uncertain. In the current study, we evaluated possible relationships between vitamin D status, endothelial dysfunction and inflammation. Methods: Studies were performed in a normal population cohort (n=253) aged 51 to 77 years (mean 63.4±6 years). Plasma concentrations of 25-hydroxyvitamin D3 (25(OH)D3) were determined by radioimmunoassay after extraction. Plasma concentrations of asymmetric dimethylarginine (ADMA), a marker/mediator of endothelial dysfunction, were determined by HPLC. High-sensitivity C-reactive protein (hs-crp) levels were utilized as a marker of inflammatory activation. Putative correlations were evaluated by univariate and multivariate analyses. Results: On univariate analyses, low 25(OH)D3 levels were inversely correlated with ADMA concentrations, hs-crp levels; and body mass index. Presence of hypertension, and treatment with an ACEi/ARB were also associated with low 25(OH)D3 levels. On backward multiple linear analyses, both ADMA (β=-0.19, p=0.003) and hs-crp (β=-0.14, p=0.03) concentrations were inverse correlates of plasma 25(OH)D3 concentrations; other significant correlates were: male gender (β=0.19, p=0.003, calcium levels (β=0.14, p=0.03), and use of angiotensinconverting enzyme inhibitor (β=-0.17, p=0.007). Table 1. Variables independently associated with high 25(OH)D3 levels β coefficient P value Male gender Calcium levels (mmol/l) Presence of ACEi/Ang IIi Hs-CRP (mmol/l) ADMA concentrations (μm) Conclusions: In this ageing population cohort, plasma 25(OH)D3 concentrations are inversely related to markers of endothelial dysfunction and inflammation. It remains to be determined whether this represents the mechanism(s) underlying the association between vitamin D status and cardiovascular risk. P2234 Exercise-training restores endothelium-dependent vasorelaxation and reverses endothelial NOsynthase uncoupling in Spontaneously Hypertensive Rats S. Thioub 1, C. Goanvec 1, F. Guerrero 1, J.-C. Cornily 2, J. Mansourati 2. 1 EA 4324, Université de Bretagne Occidentale, Brest, France; 2 University Hospital of Brest, Université de Bretagne Occidentale, Brest, France Many cardiovascular diseases are associated with oxidant stress involving uncoupling of endothelial nitric oxide synthase (enos). We sought to evaluate the effect of exercise training on enos coupling/uncoupling in Spontaneously Hypertensive Rats (SHR). Male SHR and Wistar-Kyoto (WKY) rats were divided into sedentary (n=20) and exercise (n=20) groups. Exercise group was submitted to a treadmill training protocol (20m/min, 60 min/day, 5 days/week, 9 weeks and 10 incline). Systolic Blood Pressure (SBP) was measured before training, 6 h (acute effects) and 72 h (chronic effects) after the last exercise bout. Responses to vasoactive compounds were examined in vitro in rings prepared from femoral artery. Dose-response curves to ACh (10-9 to 10-4 mol/l) alone or in the presence of either Nω-nitro-Larginine methyl esther (L-NAME, mol/l) or tetrahydrobiopterin (BH4, 10-5 mol/l), a cofactor for enos activity, were studied in rings precontracted with PE (10-7 mol/l). Sedentary life-style and training exercise did not alter SBP in WKY. In SHR, SBP increased significantly 6 h and 72 h (158±6 vs 184±4 mmhg and 184±4 mmhg) post-sedentary life-style (p= ). In trained SHR, SBP was significantly reduced 6 h post-exercise as compared to reference value (140±3 vs 161±3 mm Hg; p = 0.002). SBP was also decreased 72 h post-exercise as compared to postsedentary life-style (166±3 vs 184±4 mm Hg; p = 0.023). Results on femoral artery rings are summarized in the table. Emax (maximal relaxation) and EC50 (half-maximal effective dose) in response to ACh alone or in presence of BH4 ACh ACh+BH4 Emax (%) EC50 (μm) Emax (%) EC50 (μm) SHR sedentary (n=10) 33.60± ±0.54* 26.81± ±0.06 WKY sedentary (n=10) 48.50± ± ± ±0.15 SHR exercise (n=10) 95.68± ± ± ±0.06 WKY exercise (n=10) 86.87± ± ± ±0.05 Percent relaxation = percent reduction in force from PE. Training has acute and chronic hypotensive effects in SHR. Endothelial dysfunction associated with hypertension involves enos uncoupling. Endotheliumdependent vasorelaxation is improved by exercise training in normotensive rats. In hypertensive animals, exercise training restored ACh-induced vasorelaxation by coupling enos. P2235 Relevance of homocycteine on brachial flow-mediated vasodilation and carotid and femoral intima media thickness in sibling of hypertensive patients M.F. Elnoamany, H. Badran, H. Ebraheem, A. Reda, N. Elsheekh. Menoufyia Faculty of Medicine, Shebeen Elkom, Menoufyia, Egypt Background: Mild hyperhomocysteinaemia, a risk factor for vascular disease, is common in the general population. Offspring of hypertensive parents, have been reported to have endothelial dysfunction compared with the offspring of normotensive parents. This does not occur simply as a consequence of increased blood pressure but may rather be a cause of the condition. Carotid intima-media thickness (CIMT) is the second valid marker of generalized atherosclerosis. Aim of the work: We studied the relation of sonographically determined carotid & femoral intima-media wall thickness and enothelial function to serum homocysteine (Hcy) concentrations in offsprings of hypertensive parents. Methods: Plasma homocysteine levels were measured in normotensive siblings for hypertensive patients (n=78) and normotensive controls (n=30). All the subjects were non-diabetic, had no past history of myocardial infarction, stroke or peripheral vascular disease and had normal renal functions. Brachial artery flow-mediated (FMD) and nitroglcerine mediated vasodilatation (NTGMD) were measured to assess endothelial function. Also carotid and femoral intima-media thickness that reflect vascular disease were examined. Results: Hcy level were found to be significantly higher in normotensive siblings when compared to controls {13.7±4.5 versus 7.8±2.7 micromol/l (p<0.001)}. CIMT and femoral IMT were significantly increased in siblings in comparison to control (0.72±0.1 versus 0.59±0.1 and 0.71±0.1 versus 0.58±0.1 mm P<0.01) respectively. FMD and FMD% that reflect endothelial dysfunction but not NT- GMD & NTGMD% were significantly lower in siblings compared with control (0.7±0.1 versus 1.6±0.1mm and 20% versus 55%, P<0.001). Conclusion: Plasma homocysteine levels are significantly elevated in normotensive siblings for parents with essential hypertension. Increased carotid and

65 Endothelial dysfunction: clinical studies 365 femoral IMT in addition to endothelial dysfunction may serve as results of hyperhomocysteinaemia that create the potential cardiovascular risk. P2236 Intermittent airway obstruction and atherogenesis in hypertension. Risk stratification depends on disease severity A. Kasiakogias, C. Tsioufis, C. Thomopoulos, A. Mazaraki, P. Tolis, E. Andrikou, I. Andrikou, V. Tzamou, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: The adverse effect of obstructive sleep apnea (OSA) on the cardiovascular system may be partially explained by the action of inflammatory and atherogenic mediators. The aim of our study was to investigate the effect of disease severity on markers of atherosclerosis in hypertensive patients. Methods: 91 consecutive subjects with stage I-II hypertension and OSA confirmed by polysomnography were divided into two groups- of moderate (N=36) and severe disease (N=55) respectively- according to their apnea hypopneas index (AHI) (cut-off value= 30 episodes/hour). All patients underwent ambulatory blood pressure monitoring, while blood sampling was performed for routine laboratory testing and measurement of asymmetric dimethyl arginine (ADMA) and interleukin-18 (IL-18) levels. The albumin to creatinine ratio (ACR) was determined on two non-consecutive urine morning samples. Results: The two groups exhibited similar 24hr systolic and diastolic BP values (141±11 vs 140±7, 88±6 vs. 86±7mmHg, p=ns for both). There were also no significant differences regarding the body mass index, the metabolic profile and GFR. The severe OSA group exhibited higher levels of logadma (-0.23±0.1 vs ±0.08μmolŁ, p=0.02), logil-18 (2.5±0.13pg/ml vs. 2.4±0.109pg/ml, p=0.001) and logacr (1.13±0.31 vs. 0.97±0.28mg/g, p=0.032). In the entire population, the AHI was correlated with the logacr (r=0.23, p=0.05), logil-18 (r=0.32, p=0.003) and logadma (r=0.356, p=0.001). In a model of multiple regression analysis (adjusted r 2 =0.21), the AHI was independently predicted by the logil-18 (p=0.05) and the logadma (p=0.02). Inversely, in another model (adjusted R 2 =0.18) logadma was independently predicted by minimum O2 saturation during sleep (b=-0.29, p=0.017). Conclusions: OSA is accompanied by raised biomarkers of atherogenesis reflecting a condition of diffuse vascular damage. Apnea severity should be considered when estimating the cardiovascular risk profile in patients with concurrent hypertension. P2237 Coronary flow reserve is impaired in patients with migraine G. Kaynar, L.E. Sade, B. Yetis, H. Bozbas, S. Eroglu, B. Pirat, V. Simsek, B. Ozin, H. Muderrisoglu. Baskent University Faculty of Medicine, Ankara, Turkey Purpose: Migraine is a common neurovascular disorder characterized by attacks of severe headache, autonomic and neurological symptoms. To test the hypothesis that migraine can be associated with systemic endothelial and microvascular dysfunction we investigated coronary flow reserve (CFR) as a means of coronary microvascular function in patients with migraine. Methods: Sixty one patients (35 with migraine and 26 healthy controls) without coronary artery disease, hypertension or diabetes mellitus were included. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.56 mg/kg/4 minutes). CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. CFR 2 was considered normal. Results: Patients with migraine were younger than controls (Mean age: 30±7,5 vs 36±7,9 years; P=0,002). There were no significant differences regarding other clinical characteristics. Left ventricular systolic function was decreased in patients with migraine as compared with controls (Ejection fraction: 56,8±4,5% vs 60,4±3,2%; P < 0,001, mean mitral annular systolic velocity: 10,2±2.0cm/s vs 13.0±1.9cm/s; P<0.0001). Mean diastolic peak velocities at baseline and during hyperemia were 31,1±5,9 and 60,3±8,7 cm/s for migraine, 27±2,8 and 78,4±15,5 cm/s for healty controls. CFR values were significantly lower in subjects with migraine than in the control group (1,98±0,38 versus 2,96±0,62; P<0,001). Impaired CFR was observed in 45,7% of migraine patients as compared with 0% of healthy controls (P<0.0001) Conclusions: CFR which reflects coronary microvascular dysfunctions is impaired in a considerable proportion of patients with migraine suggesting subclinical atherosclerosis and increased cardiovascular risk in these patients. P2238 Pentaerithrityltetranitrate enhances reactive hyperemia in patients with coronary artery disease. A subanalysis of the randomized, double-blind, clinical PENTA study M.A. Ostad, B. Schnorbus, R. Schiewe, C. Medler, D. Wachtlin, T. Munzel, A. Warnholtz. University Medical Center, Mainz, Germany Purpose: Chronic treatment with nitroglycerin is characterized by the induction of tolerance and deterioration of endothelial dysfunction. Pentaerithrityltetranitrate (PETN) differs from nitroglycerin by the lack of tolerance induction and by antioxidative properties. Previously, we have reported the results of the PENTA study which revealed no deterioration of endothelial dysfunction in conduit arteries in patients with coronary artery disease (CAD). Reactive hyperemia depends on microvascular dilation in response to ischemia. Recent data from a clinical study have identified an association of lower reactive hyperemia with increased cardiovascular risk in patients with peripheral arterial disease. Yet it is unknown whether PETN has an impact on reactive hyperemia. Therefore we have analysed the hyperemic response to ischemia in the PENTA study. Methods: In a prospective, double-blind trial, 80 patients with CAD were randomly assigned to treatment for 8 weeks with oral PETN 80mg t.i.d. (PETN) or placebo (C), respectively. Brachial arterial endothelial function was measured as flow-mediated dilation before and after treatment. Peak reactive hyperemia was evaluated by pulsed doppler analysis of blood flow volume and mean shear stress within the first 5 seconds upon cuff release. Heart rate, blood pressure and hematokrit were monitored at all visits. Data monitoring and statistic analysis were independently performed by the coordination centre of clinical trials (KKS), Mainz. The trial was registered as ISRCTN Results: Both treatment groups were comparable regarding age, gender, distribution of cardiovascular risk factors, concomitant medication, baseline arterial diameter, hematokrit and hemodynamic status. Peak increases in blood flow volume and mean shear stress upon 5 minutes of ischemia were comparable at baseline. After treatment, the peak increases in blood flow volume (mean±sd: PETN: +173±420%; C: -8±503%, p=0.04) and mean shear stress (mean±sd: PETN: +123±374%; C: -71±462%, p=0.01) were significantly enhanced in the PETN group vs. C compatible with enhanced reactive hyperemia. Changes in peak reactive hyperemia did not correlate with changes in FMD. Conclusions: We conclude from our data that chronic PETN treatment of patients with CAD improves microvascular function. With respect to the prognostic significance of an enhanced reactive hyperemia the results of our study generate the hypothesis that chronic PETN treatment lowers the cardiovascular event rate in patients with atherosclerosis. This hypothesis should be prospectively investigated in a randomized trial. P2239 Early therapy with n-3 Polyunsaturated Fatty Acids improve endothelial function ultrasound parameters and diastolic function index in patients with acute myocardial infarction M. Haberka, K. Mizia Stec, M. Mizia, K. Gieszczyk, A. Chmiel, Z. Gasior. Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland Body of evidence suggests pleiotropic effects of n-3 Polyunsaturated Fatty Acids (n-3 PUFA) on several clinical endpoints in patients with acute myocardial infarction (AMI). Purpose: Our aim was to assess influence of early n-3 PUFA therapy on vascular function and left ventricular (LV) diastolic function in patients with AMI. Methods: Forty consecutive patients with AMI and successful coronary stent implantation were randomized to the study group (n=20; F/M=4/16; age=58±8; STEMI=70%; TIMI 3=100%; standard therapy + Omacor 1g daily) and the control group (n=20; F/M=4/16; age=62±10; STEMI=65%; TIMI 3=100%; standard therapy). All the patients were given pharmacotherapy according to the actual ESC recommendations. The study group patients were given n-3 PUFA therapy (Omacor 1g daily) starting from the 3rd day of AMI. The following non-invasive imaging methods were performed in the 3rd and 30th day after AMI: transthoracic echocardiography (TTE) and high-resolution ultrasound to measure: flow mediated dilatation (FMD), nitroglycerin-mediated vasodilatation (NMD) and intima-media thickness (IMT). Results: Baseline patients characteristics (standard laboratory parameters, MI localization, clinical risk factors, concomitant diseases and drugs therapy), ultrasound vascular parameters and TTE parameters did not differ significantly between both groups. Mean FMD (8.4±7.2 to 15.3±10.6%; p=0.019), but not NMD (26.9±12.1 to 30.2±14.0%;p=ns) values increased significantly after 1- month therapy with PUFA. FMD and NMD values did not change significantly among control patients (FMD: 9.9±6.4 to 10.2±9.0%; NMD: 25.1±11.4 to 25.8±14.0%;p=ns). Evaluation of TTE baseline and control parameters revealed significant decrease of E/E (E early diastolic maximal mitral ring movement velocity) index (12,1±3,6 to 10,7±2,7;p=0.02) in the PUFA group patients without significant changes in other diastolic function parameters (E and A wave, E/A ratio, E and A wave, isovolumetric relaxation time, deceleration time) and no significant changes in control patients. We found no correlation between FMD and E/E index values. Conclusions: Patients with AMI benefit from an early introduction of n-3 PUFA therapy revealing improvement in vascular function parameters and sensitive diastolic LV function index (E/E ) evaluated after one-month therapy.

66 366 Endothelial dysfunction: clinical studies / Lipids and statins P2240 Effect of long-term L-thyroxine treatment on endothelial function and carotid intima media thickness in young adults with congenital hypothyroidism M. Arcopinto, A.M. Marra, T. Lettiero, V. Apuzzi, G. Bosso, A. Valvano, F. Calabrese, M.C. Salerno, U. Oliviero, A. Cittadini. Azienda Ospedaliera Universitaria Federico II, Naples, Italy Background: Overt and subclinical hypothyroidism are associated with increased risk for atherosclerotic cardiovascular disease. Patients with Congenital Hypothyroidism (CH) display subtle abnormalities of the cardiovascular system that appear to be related to non physiological fluctuations of TSH levels and occur despite careful replacement therapy. Objective: Aim of the present case-control study was to assess arterial carotid intima-media thickness (CIMT) in conjunction with endothelial function by flowmediated vasodilation (FMD) in patients with CH in order to evaluate the effects of long-term levothyroxine (L-T4) replacement therapy. Patients and methods: Thirty young adults with CH aged 18.1±0.2 years and 30 age and sex-matched controls underwent IMT measurement by carotid Doppler ultrasound and brachial artery reactivity evaluation by flow-mediated dilatation (FMD) at the time of the study. Hypothyroidism was diagnosed by neonatal screening and L-T4 treatment was initiated within the first month of life and adjusted to maintain TSH levels in the normal range and free thyroxine in the highnormal range. Results: see table below. Stepwise regression analysis revealed that pubertal and total mean TSH was an independent determinant of FMD (p<0.0001) and IMT (p<0.0001), respectively. In addition, the number of episodes of subclinical hypothyroidism (TSH>5.0 mu/l with normal FT4) during puberty (r=-0.53, p< 0.003) was an additional risk factor for endothelial dysfunction. FMD and IMT values in CH and Controls Controls CH p FMD (%) 14.5± ±0.9 < NMD (%) 22.1± ±1.3 n.s. Mean CCA-IMT (mm) 0.62± ±0.003 < Mean ICA-IMT (mm) 0.61± ±0.004 < Mean ECA-IMT (mm) 0.63± ±0.003 < Data are expressed as mean ± SEM; FMD: flow mediated dilation; NMD: nitroglycerin mediated dilation; IMT, intima-media thickness. Conclusions: Young adults with CH, treated with long-term L-T4 replacement therapy, display endothelial dysfunction and increased CIMT predicted by indexes of L-T4 under-treatment. Therefore, long-term L-T4 therapy may induce increased risk of atherosclerosis and of acute cardiovascular events. P2241 Vascular dysfunction in HIV infected patients receiving highly active antiretroviral therapy I. Ikonomidis 1,J.Palios 1, J. Lekakis 1, L. Rallidis 2, S. Tsiodras 2, G. Poulakou 2, P. Panagopoulos 2, A. Papadopoulos 2, H. Giamarellou 2, D.T. Kremastinos nd Cardiology Department, Attikon Hospital, University of Athens Athens, Greece; 2 University of Athens, Athens, Greece Background: A high risk of atherosclerosis and cardiovascular disease has been described in HIV-1 positive individuals receiving highly active antiretroviral therapy (HAART). Reactive hyperemia is an endothelial dependant vascular reaction to ischemia in order to prevent tissue damage. We investigated whether HIV-1 positive individuals receiving HAART and patients who where naïve to medication had differences in their vascular function. Methods: We compared measurements of forearm reactive hyperemia using venous occlusion strain gauge plethysmograrhy (Hokanson AI6 Arterial Inflow System) in HIV individuals receiving HAART with patients naïve to treatment with similar risk factors. Mean carotid imtima media thickness of the right, left common carotids and carotid bulbs was measured in all subjects using B-mode ultrasonography Results: Forty four (N=44) HIV patients receiving HAART were compared to twenty six (N=26) naïve to therapy HIV patients with similar clinical characteristics. Patients exposed to treatment had worse reactive hyperemia results since they had lower % change in the blood flow between the maximum hyperemic blood flow and the baseline blood flow at rest (690±256 vs. 903±320, p<0,01). The maximum hyperemic flow in HAART receiving patients was lower comparing to HAART naïve patients (37,7±11,1 vs. 31,9±11,0, p<0.05). The baseline flow was similar between the two groups. In multivariate analysis the % change in the forearm blood flow during maximum hyperemia was independently correlated with treatment with HAART (p<0.01), total cholesterol (p<0.05), triglycerides (p<0.05), carotid IMT (p<0.05), a marker of subclinical atherosclerosis (p<0,05 respectively) among blood pressure, glucose levels, smoking, BMI, age, disease duration, viral load and CD4 lymphocyte count. Conclusions: Patients with HIV infection receiving HAART present functional abnormalities of arterial microcirculation as assessed by the reactive hyperemia parameters in comparison with naïve patients. This vascular dysfunction is determined by HAART treatment and metabolic parameters, is related with the carotid atherosclerosis and may thus increase the risk of cardiovascular events in these subjects P2242 Endothelial dysfunction in diabetic patients with myocardial perfusion abnormalities in absence of obstructive epicardial coronary disease R. Djaberi, J.D. Schuijf, J. Op T Roodt, A.J. Scholte, T.J. Rabelink, E. De Koning, E.E. Van Der Wall, J.J. Bax, J.W. Jukema. Leiden University Medical Center, Leiden, Netherlands Purpose: In patients with diabetes mellitus (DM) myocardial perfusion defects are often observed in absence of significant epicardial coronary artery stenosis. We hypothesized that these perfusion abnormalities may be explained by endothelial dysfunction. Methods: Prospectively, a total of 135 asymptomatic patients with DM (mean age 51±13yrs, 68 men), underwent cardiovascular screening by multi-slice computed tomography (MSCT) coronary angiography and myocardial perfusion imaging (MPI) by SPECT at rest and during adenosine stress. MSCT images were evaluated for the presence of significant coronary artery stenosis ( 50% luminal narrowing). To quantify size and severity of perfusion defects on SPECT images, the summed stress score (SSS) based on a 17 segment, 5 point model, was determined for each patient. Presence of any myocardial perfusion defect was defined as SSS>2. In all patients, flow mediated dilation (FMD) of the brachial artery, a marker of endothelial function, was determined using ultrasonography. Results: In 35 (27%) patients, significant coronary artery stenosis was observed on MSCT and these patients were excluded from further analysis. In the remaining 95 patients, abnormal myocardial perfusion was observed in 30 (32%) of patients. FMD was significantly lower in patients with myocardial perfusion defects (3.6±2.4), as compared to those without perfusion defects (6.4±2.6) (p<0.001) (Figure 1). Importantly, after correction for age and other cardiovascular risk factors, FMD remained the only predictor of the presence of abnormal myocardial perfusion (p<0.001). Conclusions: In patients with DM, myocardial perfusion abnormalities in absence of significant epicardial coronary artery stenosis are associated with endothelial dysfunction. LIPIDS AND STATINS P2243 The influence of statins on late cancer mortality in vascular surgery patients with chronic obstructive pulmonary disease Y.R.B.M. Van Gestel 1,S.E.Hoeks 1,D.D.Sin 2,V.Huzeir 1,H.Stam 1, F.W. Mertens 1,J.J.Bax 3, H.J.M. Verhagen 1,R.T.VanDomburg 1, D. Poldermans 1. 1 Erasmus Medical Center, Rotterdam, Netherlands; 2 University of British Columbia & The James Hogg icapture Center, St. Paul s Hospital, Vancouver, Canada; 3 Leiden University Medical Center, Leiden, Netherlands Purpose: Chronic obstructive pulmonary disease (COPD) is associated with an increased incidence of lung cancer, independently of smoking. Since at least 20 to 25% of the patients with COPD die from cardiovascular disease, medical treatments that confer cardiovascular risk reduction such as statins may reduce mortality in these patients. However, contradictory results exist regarding the effect of statins on cancer. Consequently, we investigated the association between COPD and cancer mortality and whether the use of statins modified this relationship. Methods: The study included 3371 patients with peripheral arterial disease who underwent vascular surgery between 1990 and The diagnosis of COPD was made according to the guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The endpoints were 10-year total cancer mortality, lung cancer mortality and extra-pulmonary cancer mortality. Results: COPD was associated with increased risk of total cancer mortality (Hazard Ratio, HR 1.61; 95%CI ). The risks for lung cancer (HR 2.06; 95%CI ) and extra-pulmonary cancer deaths (HR 1.43; 95%CI ) were both elevated in patients with COPD. The excess risk was mostly driven by patients with moderate and severe COPD. There was a trend towards lower cancer mortality risk among COPD patients who used statins (HR 0.57; 95%CI ). Interestingly, statins were significantly associated with reduced cancer mortality from sites other than the lungs (HR 0.49; 95% CI ).

67 Lipids and statins 367 Statins and cancer in COPD patients Conclusions: COPD was associated with increased lung and extra-pulmonary cancer mortality in this large cohort of peripheral arterial disease patients. Furthermore, statin may reduce the risk for (extra-pulmonary) cancer mortality in patients with COPD. P2244 Colesevelam added to a stable combination of a maximally tolerated statin and ezetimibe in patients with heterozygous familial hypercholesterolemia; the TRIPLE trial R. Huijgen 1,M.D.Trip 1, E. Bruckert 2, A.F.H. Stalenhoef 3, B.P.M. Imholz 4, P.N. Durrington 5, M. Eriksson 1, F.L.J. Visseren 6, J.R. Schaefer 7, J.J. Kastelein 1 on behalf of TRIPLE investigators. 1 Karolinski University Hospital, Huddinge, Sweden; 2 Hôpital Pitié-Salpêtrière, Paris, France; 3 Department of Internal Medicine, University Medical Centre Nijmegen, Nijmegen, Netherlands; 4 Department of Internal Medicine,Tweesteden Ziekenhuis, Waalwijk, Netherlands; 5 The University of Manchester, Manchester, United Kingdom; 6 Vascular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands; 7 Philipps University Hospital Marburg, Marburg, Germany Objectives: Guidelines for treatment of patients with familial hypercholesterolemia (FH) advise to reduce LDL-C levels below 100 mg/dl. However, a considerable proportion of FH patients are not at goal despite potent combination therapy. We studied if adding Colesevelam (COL) 3.75 g/day to a stable combination therapy is safe and can effectively reduce LDL-C. Methods: Heterozygous FH patients on maximally tolerated statin and ezetimibe 10 mg for at least 3 months with LDL-C >100 mg/dl and LDL-C variability 10% over 4 weeks were eligible. Patients continued their statin and ezetimibe and were randomized to COL or placebo (PBO) as add-on therapy for a 12 week double blind period and continued for another 40 weeks on open label active treatment. Results: Between August 2007 and September 2008 in 8 lipid clinics in 5 European countries 138 patients were screened. 52 Patients were excluded; 6 (4%) LDL-C below target, 31 (22%) too high (>10%) LDL-C variability, 15 (11%) excluded for other reasons. 86 (62%) Patients were randomized, 41 on PBO and 45 on COL. LDL-C at baseline was 3.7 mmol/l (PBO) and 3.9 mmol/l (COL). Changes in lipid parameters for patients having at least one lipid assessment (ITT) are given in the table. A LDL-C reduction from baseline of 15% or more was seen in 14 patients (33%) on COL and in 0 on PBO (P<0.0001). COL was well tolerated. Percentage change in Lipid parameters Least Square mean % change Placebo Colesevelam Treatment from baseline (N=39) (N=43) Difference (95% CI) LDL-C 6 weeks (-25.7, -11.8)* LDL-C 12 weeks (-17.7, -6.0)* Tot-Chol 12 weeks (-12.2, -2.5)* HDL-C 12 weeks (-3.0, 8.6) Triglycerides 12 weeks (-10.0, 16.9) ApoB/ApoA1 ratio 12 weeks (-19.2, -3.0)* *P< CI = Confidence Interval, LDL-C = Low Density Lipoprotein Cholesterol, Tot-Chol = Total Cholesterol, HDL-C = High Density Lipoprotein Cholesterol. Least square mean % change from baseline, based on ANOVA with site and treatment as co-factor. Conclusions: The 6 week primary endpoint was met, with a mean TD for LDL- C of up to 18.7%. In hefh patients not at goal, COL added to a combination of maximal tolerated statin and ezetimibe, significantly improved LDL-C, Tot-Chol and ApoB/ApoA1 ratio s. P2245 The role of conventional risk factors in explaining residual risk in statin-treated post myocardial infarction patients. Results from the IDEAL study A.G. Olsson 1, C. Lindahl 2,R.Fayyad 3,I.Holme 4 on behalf of IDEAL Investigators and Steering Committee. 1 University Hospital, Linköping, Linköping, Sweden; 2 Pfizer Sweden, Sollentuna, Sweden; 3 Pfizer Inc, New York, United States of America; 4 Ullevaal University Hospital, Oslo, Norway Background: We have previously described significant relations between Apolipoprotein B (apob), apob/apoa1 ratio and non-hdl-cholesterol and cardiovascular events (CVE) in statin-treated patients reaching the goals of 2.0 and 2.5 mmol/l in the IDEAL study. Methods: Patients were allocated to either 20 to 40 mg of simvastatin (n=4449) or atorvastatin 80 mg (n=4439) daily for 5 years. The study had an open-label randomized design (PROBE) and had no run-in phase. In this post-hoc subanalysis, for subjects who reached the LDL-C goals of 2.5 mmol/l or 2.0 mmol/l at 3 and 6 months, risk factors for CVE were investigated by Cox regression analysis including sex, age, systolic blood pressure, coronary heart failure at baseline, hypertension, diabetes, smoking, and prior statin use, and each of mean apob, mean apob/apoa1 and mean non-hdl at months 3 and 6. In addition, net reclassification analysis (NRI) was performed by logistic regression with cross-classification of CVE risk into 4 groups based on a model including apob/apoa-1 and excluding it over and above the adjustment factors defined above. A similar analysis was performed by comparing the model with and without smoking. Results: For subjects who reached LDL goals of <2.5 mmol/l, apob, apob/apoa1 and non-hdl-c significantly predicted CVE risk. The hazard ratios (HR) and 95% confidence intervals of 1 standard deviation increase in apob, apob/apoa1 and non-hdl were: 1.13 ( ), 1.16 ( ), and 1.11 ( ), respectively. Neither inclusion of the apob/apoa1 ratio or inclusion of smoking over and above the standard factors had much influence on the NRI for CVE. For apob/apoa-1, the index was 2.6% for goal <2.5 mmol/l, and 2.0% for goal <2.0 mmol/l. Similar numbers for smoking were 2.3% and 1.9%. Conclusion: For subjects who reached LDL goal, even though there are are still significant relations between conventional risk factors and outcome in post myocardial infarction patients, on-study apob/apoa1 did not provide further prediction of CVEmeasured by NRI. This does not diminish the need of paying attention to these factors in long term cardiovascular prevention. The causes of the residual risk in statin treated patients in a 5-year perspective may be related to more short-term factors such as thrombogenic and inflammatory factors or to other lipoproteins e.g. HDL. P2246 Combination niacin extended-release and simvastatin treatment causes greater reduction in atherogenic particles compared to atorvastatin monotherapy W. Insull Jr 1,P.P.Toth 2, H.R. Superko 3,R.Thakkar 4, P. Jiang 4, R. Parreno 4, R.J. Padley 4. 1 Baylor College of Medicine and Methodist Hospital, Houston, United States of America; 2 University of Illinois School of Medicine, Peoria, United States of America; 3 St. Joseph s Research Institute, Atlanta, United States of America; 4 Abbott, Abbott Park, United States of America The numbers of lipoprotein particles, in addition to their cholesterol content, may be of importance in determining cardiovascular risk. Previous studies have shown that statins can reduce LDL-particle numbers, but have little effect on LDL size. The purpose of this study was to compare the effects of a once-daily combination tablet of niacin extended-release (NER, Niaspan, Abbott) and simvastatin (NER/S, Simcor, Abbott) vs atorvastatin monotherapy on lipid particle sizes and total numbers in patients with dyslipidemia from the SUPREME study. Patients with dyslipidemia who were either not previously receiving statin therapy, or who discontinued any lipid-altering treatment for 4-5 weeks prior to the study, received 1000/40-mg/d NER/S for 4 weeks, followed by 2000/40-mg/d for 8 weeks; or atorvastatin 40-mg/d monotherapy for 12 weeks. Changes in nuclear magnetic resonance (NMR) lipoprotein subclasses from baseline to week 12 were compared using Wilcoxon rank-sum test and proportion of patients were compared using Fisher s exact test. The median percent changes in particle number and size from baseline to week 12 were calculated from 137 patients in the modified intentto-treat (mitt) population (NER/S treatment, n=74; atorvastatin monotherapy, n=63). There was no significant difference in LDL-cholesterol (LDL-C) levels in response to treatment with NER/S vs. atorvastatin monotherapy. However, NER/S treatment resulted in greater percent reductions in calculated particle numbers for LDL (51.6% vs. 42.7%; p=0.022), small LDL (55.0% vs. 44.7%; p=0.011), very low-density lipoprotein (VLDL) and chylomicrons (63.4% vs. 39.2%; p<0.001), compared to atorvastatin monotherapy, respectively. A greater proportion of patients in the NER/S group achieved an LDL-particle number of less than 1000 nmol/l (46% vs. 21%; p=0.002). NER/S treatment also resulted in greater increases in particle size for LDL (2.7% vs. 1.0%; p=0.007) and VLDL (9.3% vs. 0.1%; p<0.001), compared to atorvastatin monotherapy, respectively. Compared to atorvastatin monotherapy, NER/S treatment resulted in a greater reduction in the number of small LDL particles, VLDL and chylomicron particles were reduced, and the mean size of LDL and VLDL particles increased. This suggests that NER/S treatment may result in a shift towards a less atherogenic population of lipoprotein subclasses despite similar effects on total LDL-C levels.

68 368 Lipids and statins P2247 Reduction in cardiovascular events and associated cost after treatment initiation with niacin extended-release plus simvastatin combination therapy versus simvastatin plus ezetimibe fixed dose therapy R. Simko 1,R.Quimbo 2, M.J. Cziraky 2,S.Balu 1. 1 Abbott Laboratories, Abbott Park, United States of America; 2 HealthCore, Inc., Wilmington, United States of America Purpose: To compare annual cardiovascular disease (CVD) event risk and attributable-health care costs between patients initiating niacin extended-release (NER) plus simvastatin (NER/S) and simvastatin plus ezetimibe (S/E) fixed-dose therapy among patients with prior CVD. Methods: A retrospective analysis of patients aged 18 years newly initiating S/E or NER/S therapy (initial therapy of NER added to existing simvastatin therapy) between 1/1/2001 and 6/30/2006 (index date) was performed using a the HealthCore Integrated Research Database. Patients with a minimum of 12 months pre- and post-index date follow-up and CVD during the12 months prior to index date were included. CVD event risk was estimated using Kaplan-Meier survival analysis while adjusted post-index date mean annual CVD-attributable total health care costs [sum of inpatient, emergency room, and outpatient visit costs] were compared through a multivariate generalized linear model. Model covariates included treatment group, age, gender, pre-index CVD costs, Deyo-Charlson comorbidity index (DCI), and prior type 2 diabetes and hypertension. Results: A total of 7,065 study patients were identified initiating S/E (n=6,513) or NER/S (n=552). NER/S patients were significantly younger (58.5±9.2 years vs. 61.3±10.2 years; p<0.0001) and more likely to be male (85.1% vs. 67.9%; p<0.0001) compared to S/E patients. Pre-index date comorbidity burden (1.3±1.3 vs. 1.4±1.6; p=0.1018) was similar between the two groups. Patients initiating NER/S therapy were 32% [Hazard Ratio (HR): 0.68 ( )] less likely to experience a post-index CVD event versus S/E patients. Multivariate analysis demonstrated a 25% ($568, 95% CI: $443-$730 vs. $760, 95% CI: $710-$815; p=0.0289) reduction in mean annual CVD costs among NER/S patients compared to S/E patients. Conclusion: High risk patients with prior CVD treated with NER/S were associated with lower CVD event risk and total annual CVD-attributable costs compared to S/E patients. Higher utilization and early initiation of NER/S therapy which emphasizes the reduction of residual risk would seem to be beneficial as compared to an LDL-C centric treatment strategy. P2248 Increased cholesterol absorption in patients treated with strong statins M. Eto, M. Akishita, T. Akiyoshi, H. Ota, K. Nomura, K. Yamaguchi, S. Ogawa, K. Iijima, Y. Ouchi. Department of Geriatric Medicine, University of Tokyo, Tokyo, Japan Serum cholesterol levels are determined by both synthesis and absorption. Administration of statins effectively reduces serum cholesterol levels through inhibition of its synthesis and subsequent LDL receptor upregulation in liver, but compensatory increase in cholesterol absorption from small intestine might limit statin s beneficial effect. At present, mechanisms underlying cholesterol absorption remain largely unknown. Therefore, we conducted this cross-sectional study to clarify predictive factors for cholesterol absorption, especially focusing on types of statins. In this study, 141 patients were enrolled from our ambulatory clinic (73.7±9.4 yo., yo., 59 menand 82 women). Twenty-nine (21%) patients had a history of coronary artery disease and 39 (28%) had a history of ischemic stroke. Ninety-six (68%) patients had hypertension, 53 (38%) had diabetes, 71 (50%) were receiving strong statins and 34 (24%) were receiving standard statins. No patient received any cholesterol absorption inhibitors. Serum sitosterol and lathosterol levels were measured for an absorption marker and a synthesis marker, respectively. As expected, sitoserol levels were significantly higher (2.68±0.14 vs 1.78±0.15micro-g/mL, p<0.01) and lathosterol levels were lower (0.8±0.04 vs 1.56±0.17 micro-g/ml, p<0.01) in patients receiving any types of statins compared with those in patients not receiving statins. Interestingly, strong stain group had significant higher sitoserol levels (2.90±0.18 vs 2.23±0.19 micro-g/ml, p<0.01) and lower lathosterol levels (0.67±0.05 vs 1.08±0.15 microg/ml, p<0.01), although serum total cholesterol levels were comparable between these 2 groups. Multiple regression analysis using age, sex, risk factor profile, history of ischemic disorders and types of statins as variables, demonstrated that treatment with strong statins was the only one independent predictive factor for cholesterol absorption (p<0.01). In conclusion, cholesterol absorption is enhanced in patients treated with strong statins. These results provide clinical implications for cholesterol management to prevent atherosclerotic vascular disease. P2249 Cardiovascular event reduction after treatment initiation with simvastatin plus niacin extendedrelease combination therapy versus statin monotherapy among managed care dyslipidemia patients R. Simko 1,R.Quimbo 2,M.Cziraky 2,S.Balu 1. 1 Abbott Laboratories, Abbott Park, United States of America; 2 HealthCore, Inc., Wilmington, United States of America Purpose: To compare annual cardiovascular disease (CVD) event risk between patients initiating any statin monotherapy (SM) and niacin extended-release [NER] + simvastatin (NER/S) combination therapy among patients with dyslipidemia in a managed care setting. Methods: A retrospective analysis of patients aged 18 years newly initiatingsm or NER/S therapy (initial therapy of NER added to existing simvastatin therapy) between 1/1/2001 and 6/30/2006 (index date) was performed using the Health- Core Integrated Research Database. Patients with a minimum of 12 months preand post-index date follow-up and prior cardiovascular disease 12 months prior to initiation of therapy were included. Unadjusted and adjusted annual CVD event risk was estimated using Kaplan-Meier survival analysis and Cox proportional hazards model, respectively. Model covariates included treatment group, age, gender, Deyo-Charlson comorbidity index (DCI), and prior type 2 diabetes and hypertension. Results: A total of 26,051 study patients were identified initiating SM (n=25,499) or NER/S (n=552). NER/S patients were significantly younger (58.5±9.2 years vs. 60.4±11.8 years; p<0.0001) and more likely to be male (85.1% vs. 60.1%; p<0.0001) as compared to SM patients. NER/S patients were healthier at baseline than SM patients (pre-index DCI score: 1.3±1.3 vs. 1.5±1.6; p=0.001), though a higher percent of NER/S patients had hypertension (88.6% vs. 73.7%; p<0.0001). Patients initiating NER/S therapy were 39% [Hazard Ratio (HR): 0.61 ( ); p=0.0005] less likely to experience a post-index CVD event versus SM patients, while the adjusted rate was 32% [HR: 0.68 ( ); p=0.0078]. Conclusion: Treatment with NER/S among dyslipidemia patients was associated with lower CVD event risk compared to SM treated patients. Early initiation of NER/S therapy emphasizing reduction of residual risk would seem to be beneficial as compared to an LDL-C only focused treatment strategy. Further research on the impact of the individual lipid parameters on clinical outcomes in a real-world population is warranted. P2250 Attainment of normal lipid levels in french patients receiving er niacin/laropiprant added to statin therapy B. Ambegaonkar 1,G.Davies 2, H. Phatak 1, T. Souchet 3, V. Sazonov 1. 1 Merck and Co., Inc., Whitehouse Station, Nj, United States of America; 2 Merck and Co., Inc., Upper Gwynedd, Pa, United States of America; 3 MSD France, Paris, France Purpose: To project attainment of goal/normal levels of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and triglycerides (TG) following addition of ER niacin/laropiprant (ERN/LRPT) to ongoing statin therapy vs. continuation of current statin therapy in French patients at high risk for coronary heart disease (CHD). Methods: A model based on an iterative process used patient-level data from a French cohort identified from BKL-THALES database and individual patient lipid responses from a clinical trial of ERN/LRPT (2 g), to estimate normal lipid level attainment based on current European Society of Cardiology guidelines on Cardiovascular Disease Prevention in Clinical Practice. This process utilized the empirical response data from the trial that accounted for individual variability in treatment responses and correlation between treatment responses for the 3 lipid parameters. Gender-stratified analyses were conducted for high-risk groups, including CHD or CHD risk equivalents, with LDL-C>2.5 mmol/l. Results: Among 238 high-risk patients, mean age was 65 years; 77% were male; mean LDL-C, HDL-C, and TG levels (mmol/l) were 3.64, 1.21, and 2.27 respectively. Among women receiving ERN/LRPT added to statin vs. statin only, 38.4% vs. 3.0% reached LDL-C goal, 39.1% vs. 10.6% achieved 2 normal lipid levels, and 18.2% vs. 0.3% attained all 3 normal lipid levels. Similar patterns for goal/normal level attainment were observed in men with ERN/ LRPT added to statin vs. statin only: 31% vs. 4.6% for LDL-C, 40.4% vs. 17.7% for 2 lipids, 16.4% vs. 0.5% for all 3 lipids. Conclusions: In this projection of goal/normal lipid level attainment in French clinical practice, addition of ERN/LRPT to statin in high risk patients not at optimal lipid levels allows an additional 25% male patients and about one-third more female patients to achieve LDL-C goal. Among those with ERN/LRPT added to statin compared to statin only, additional 25% and up to 18% more patients attain 2 and all 3 normal lipid levels respectively. P2251 Beneficial effect of statin treatment on carotid atherosclerosis in patients with stable coronary artery disease stratified by renal function T. Ishizu, Y. Seo, N. Murakoshi, S. Watanabe, K. Aonuma. University of Tsukuba, Tsukuba, Japan Background: Chronic kidney disease (CKD) is common in patients with coronary

69 Lipids and statins 369 artery disease (CAD), and such patients have adverse outcomes. The purpose of the present study was to investigate the efficacy of cholesterol lowering treatment with a statin in modifying carotid atherosclerosis in patients with stable CAD stratified by glomerular filtration rate (GFR). Methods: One-hundred eleven patients with stable coronary artery disease were stratified into 3 baseline GFR groups: normal or increased ( 90 ml/min/1.73m 2 ; n=41 patients), mild reduction (60 to 89 ml/min/1.73m 2 ; n=58 patients), and moderate or severe reduction (<60 ml/min/1.73m 2 ; n=14 patients). Patients underwent carotid ultrasonography at baseline, 1-year and 2-year after statin treatment, and mean intima-media thickness (IMT) of the distal common carotid artery was measured using manual tracing software by a single sonographer blinded to patient clinical background. Results: LDL cholesterol and CRP levels were similar in the three groups at baseline and after statin treatment. Compared with patients with normal GFR, significant reductions in mean IMT were observed in moderate or severe CKD at 1-year (p=0.014) and in mild CKD at 2-year follow up (p=0.009) after adjustment for LDL cholesterol reduction. Conclusion: Among stable CAD patients, those with CKD benefited more from statin treatment than did patients without CKD. However, this benefit may not be attributed to the reduction of LDL cholesterol by statin treatment. P2252 Evidence of myocardial adrenergic innervation abnormalities in hyperlipidemic subjects: the beneficial effect of statins E.A. Zacharis 1,M.E.Marketou 1, S.I. Koukouraki 2, V.K. Prassopoulos 2,I.Karalis 1,G.F.Diakakis 1, F.I. Parthenakis 1, N.S. Karkavitsas 2, P.E. Vardas 1. 1 Cardiology Dept. Heraklion University Hospital, Heraklion, Greece; 2 Dept. of Nuclear Medicine, Heraklion, Greece Purpose: Hyperlipidemia results in endothelial dysfunction and myocardial perfusion abnormalities even in the absence of any organic heart disease. We investigated the association of dyslipidemia with myocardial adrenergic innervation disturbances using 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) and assessed the effect of statin therapy thereupon. Methods: We examined 30 hyperlipidemic subjects (20 men, aged 57±10 years, total cholesterol >240 mg/dl, LDL-C >16 0mg/dl), while 19 healthy volunteers served as a control group. None had any disease that may have affected myocardial adrenergic innervation. All subjects underwent a planar and a SPECT myocardial imaging of the heart after an intravenous infusion of 5mCi 123 I-MIBG. Heart to mediastinum ratio (H/M) was used for quantitative assessment of adrenergic innervation, 10 minutes and 4 hours after drug infusion, while SPECT scintigraphy evaluated the regional distribution of adrenergic activity. Twenty of the hyperlipidemic subjects received 20 mg/day rosuvastatin for 6 months, while the remaining ten received placebo. An 123 I-MIBG study was repeated at 6 months. Results: Total cholesterol and LDL-C levels were significantly reduced (from 312±135 mg/dl and 184±79 mg/dl to 195±72 mg/dl and 98±37 mg/dl respectively, p<0.05). The H/M ratio in hyperlipidemics at 10 min and 4 hours was 1.80±0.22 and 1.73±0.26 respectively; significantly lower than that in normals (2.30±0.9 and 2.14±0.10 respectively, p<0.05 for both) and was improved under rosuvastatin treatment (1.98±0.8 and 1.95±0.25 respectively, p<0.05). During SPECT scintigraphy, 19 hyperlipidemic subjects (68%) showed defects in the inferior wall, nine (32%) displayed additional regional disturbances in myocardial adrenergic activity in the anterior wall and ten subjects (33%) in the apex. These defects were ameliorated mostly in the inferior and anterior wall on re-evaluation, but only in those receiving rosuvastatin. No regional disturbances were detected in healthy subjects. Conclusions: This is the first study to show a high prevalence of myocardial adrenergic innervation disturbances in hyperlipidemic subjects, while the rosuvastatin further intensifies the cardioprotective effect of statins. Background: The majority of patients with dyslipidemia in Germany are treated with a statin. However, many patients do not achieve recommended lipid targets. Methods: DYSIS enrolled consecutive outpatients 45 years-old, on statin therapy for 3 months with available lipid values. We investigated whether in Germany patients with sedentary lifestyle (SL) differ in cardiovascular disease risk factor profile and LDL-C target achievement from patients without SL. Results: Patients with SL had a higher prevalence of cardiovascular risk factors, heart failure, cerebrovascular disease, and peripheral artery disease, compared to those without SL. There was no difference between both groups with regards to coronary heart disease. Logistic regression analysis adjusting for patient characteristics, heart failure and lipid lowering therapy identified SL as independent predictor of LDL not at goal (OR 1.25, 95%-CI ). Patients with SL Patients without SL P-value* n=1,822 (42.9%) n=2,422 (57.1%) Age (years, ±SD) 67.4± ± Female [%] BMI 30 mg/m 2 [%] < Hypertension [%] < Diabetes mellitus [%] < Metabolic syndrome (ATP III) [%] < Ischemic heart disease [%] Cerebrovascular disease [%] < Heart failure [%] < mg/day Simvastatin equivalent [%] mg/day Simvastatin equivalent [%] Ezetimibe [%] LDL-C not at goal [%] < LDL-C = low-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol /70 mg/dl (CHD/CHD equivalent), 130 mg/dl (2+ RF), 160 mg/dl (0-1 RF). Conclusion: SL was an independent determinant for not being at recommended lipid targets for secondary prevention in patients already treated with statins. These results demonstrate the urgent need for life style changes and a more intensive and comprehensive lipid management in these patients. P2254 Comparative efficacy of ezetimibe added to atorvastatin vs uptitration of atorvastatin in attainment of recommended lipid targets in patients at high risk of coronary heart disease (CHD) L. Leiter 1,H.Bays 2, S. Conard 3,J.Lin 4, M. Hanson 4,A.Shah 4, A.M. Tershakovec 4. 1 University of Toronto, Toronto, Canada; 2 Louisville Metabolic and Atherosclerosis Research Center, Louisville, Ky, United States of America; 3 University of Texas Southwestern Medical School, Dallas, Tx, United States of America; 4 Merck & Co, Inc, North Wales, Pa, United States of America Purpose: LDL-C has been identified by European and Canadian treatment guidelines as a major target for treatment of patients at high risk of CHD. Some guidelines also identify total C, total C/HDL-C ratio and Apo B as additional targets, and hs-crp as a potentially useful risk indicator. The purpose of this post hoc analysis was to compare the efficacy of ezetimibe 10 mg (E) added to atorvastatin (A) 40 mg to uptitration of A 80 mg on attainment of various lipid targets and hs-crp levels. Methods: After stabilization of A 40 mg therapy, patients with hypercholesterolemia at high risk of CHD were randomized to receive A 40 mg + E (n=288) or uptitration to A80 mg (n=291) for 6 weeks. This analysis assessed the attainment of various lipid and hs-crp targets set for the purpose of this study. Results: At baseline mean LDL-C was 2.3 mmol/l, mean total C was 4.3 mmol/l, mean Apo B was 1.0 g/l, and mean hs-crp was 1.7 mg/dl in both treatment groups. Mean total C/HDL-C ratio was 3.6 and 3.7 in the A 40 + E and A80 groups, respectively. Compared with doubling the dose of A to 80 mg, patients had greater odds of achieving LDL-C<2 mmol/l, total C<4.0 mmol/l, total C/HDL-C ratio<4.0, or Apo B<0.85g/L when treated with E added to A. In addition, patients achieving LDL-C<2 mmol/l had greater odds of also achieving total C<4.0, total C/HDL-C ratio<4.0 mmol/l, Apo B<0.85 g/l, or hs-crp<1 mg/dl with E added to A treatment compared with patients whose A dose was doubled to 80 mg (Figure). P2253 High prevalence of persistent lipid abnormalities in patients with sedentary lifestyle treated with statins in Germany: results of the dyslipidemia international study A.K. Gitt 1, C. Juenger 1, K. Bestehorn 2, F. Chazelle 3,W.Smolka 2, J. Senges 1, J.P.P. Kastelein 4 on behalf of DYSIS Study Group. 1 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Merck Sharp & Dohme, Haar, Germany; 3 Merck, Paris, France; 4 Academic Medical Center, Amsterdam, Netherlands Conclusions: Adding E to A 40 mg was more effective at reducing LDL-C, Apo B, total-c, total C/HDL-C ratio, and hs-crp levels than doubling the dose of A to 80 mg (the highest recommended dose) in statin-treated patients with hypercholesterolemia at high risk of CHD. The relative clinical outcomes benefits await further study. P2255 Influence of coenzyme Q10 supplementation in statin treated patients on left ventricular diastolic dysfunction. Results of randomised double-blind clinical study J. Fedacko, D. Pella, R. Rybar. Kosice University Medical School, Kosice, Slovak Republic Inhibition of HMG-CoA reductase by statins leads to decreased synthesis of

70 370 Lipids and statins cholesterol and coenzyme Q10 (CoQ10), because they share the same biosynthetic pathway. Background of our double-blind randomized, single centre prospective 3-months study (CoQ10 200mg/day vs. placebo) administered to statin treated patients was to evaluate possible benefits of coenzyme Q10 supplementation on left ventricular diastolic dysfunction. Methods: Sixty eligible patients were enrolled in the study. All patients underwent physical, laboratory, and echocardiographic examinations at the beginning and at the end of the study. Physical and laboratory examinations were performed also after 1 month. Results: Two of three observed parameters of the diastolic dysfunction were significantly improved in the CoQ10 treated patients - peak E/A ratio increased from 0.818±0.20 to 1.034±0.21 (p=0,0001) and isovolumetric relaxation time decreased from ±16.35ms to 86.40±13.53 ms (p=0.0001) while the third one remained statistically unchanged - deceleration time at baseline ±51.21 ms compared with final visit ±34.49 ms (p=0.2629). In the placebo group of patients the E/A ratio decreased from 1.175±0.37 to 1.107±0,34 (mild worsening, although the value 1.107±0.34 is still in reference values of E/A ratio, but this worsenig was close to achieving statistical significance (p=0.0857) statin therapy was continuous in all study patients during the whole study period. Isovolumic relaxation time remained nearly unchanged. The value moved from 84.79±16.42 to 88.91±20.49 (p=0.2747). Deceleration time also did not change significantly (from ±39.60 to172.00±39.27; p=0.2805). In conclusion, our results showed that supplementation of statin treated patients with coenzyme Q10 may improve left ventricular dysfunction. More randomised clinical studies are needed to address this issue to confirm this possible benefit. Purpose: Decreased 24-h heart rate variability (HRV) is associated with increased risk of cardiovascular morbidity and mortality. The objective of this study is to examine the relation between plasma lipids and HRV in hypercholesterolaemic subjects without coronary artery disease (CAD) before and after treatment with 10 mg rosuvastatin. Methods: We included 48 hyperlipidaemic subjects (32 men, aged 59±10 years). Inclusion criteria were hypercholesterolaemia (TCHOL >240 mg/dl) and low density lipoprotein (LDL-C) cholesterol>160 mg/dl. All had a normal echocardiogram and no signs of coronary artery disease. Holter recording and fasting blood samples were performed in all subjects. The subjects were randomized to receive 10 mg/day rosuvastatin (n=35 or placebo n=13) for 1 year and reevaluated. Results: Total cholesterol and LDL-C levels were significantly reduced (from 289±101 mg/dl and 172±67 mg/dl to 192±64mg/dl and 97±26mg/dl respectively, p<0.05). Heart rate variability indices at baseline and after 12 months of treatment with 10 mg/day of rosuvastatin in hypercholesterolaemic patients are showed in Table 1. Rosuvastatin placebo before 1 year before 1 year SDNN 51.32±14.7* 63.84± ±14.8** 51.14±13.1 SDANN ±19.3* 170.8± ±15.6** ±14.5 PNN ±1.8* 9.6± ±1.4** 7.46±1.7 RMSSD 28.67±12.7* 49.67± ±12.4** 29.32±13.5 *P<0.05 before vs 1 year, **P<0.05 vs patients before treatment. Conclusions: Treatment with rosuvastatin is associated with an increased 24-h HRV in hypercholesterolaemic patients without coronary artery disease. P2256 Understanding the awareness of hypercholesterolemia and the adherence to lipid-lowering treatment in Brazil: the CORE project A.C. Sposito, J.E. Dos Santos, F.A. Fonseca, J.R. Faria-Neto, R.D. Santos, J.A.F. Ramires, M.C. Bertolami, O.R. Coelho, E. Tutihashi, F.H.Y. Cesena on behalf of CLACC - Latin-American Council for Cardiovascular Care. CLACC, Sao Paulo, Brazil Purposes: to evaluate the proportion of adults with measured blood cholesterol, the prevalence of self-reported hypercholesterolemia (HCHOL), the rate of adherence to lipid-lowering treatment, and factors associated with non-adherence in Brazil. Methods: Part 1: 2000 individuals were interviewed in 70 cities. The sample was representative of the voting population. The margin of error of the survey was 3% at a 95% confidence interval. Part 2: 35 to 65 year-old patients (pts) from the two upper economic classes with self-reported HCHOL were interviewed. They were considered adherent (n=418) if on statins for more than one year, and nonadherent (n=417) if had withdrawn statins in the previous 12 months, without medical counselling. A segmentation analysis was performed to classify the pts into mutually exclusive groups, according to their attitudes. The chi-square test was used for statistical analyses. Results: Part 1: 53% of the interviewed individuals informed to have never had their blood cholesterol determined. Among those with measured blood cholesterol, 22% said that the level was high, meaning a prevalence of self-reported HCHOL of 10%. Among the individuals with presumed HCHOL, 33% informed to be on treatment and had always treated, 17% said that they had not been on treatment but started treating, 23% reported that they had treated but quitted, and 28% informed that they had never treated the HCHOL. Part 2: compared to the adherent pts, the non-adherent group reported a lower prevalence of arterial hypertension (39% vs. 29%, p=0.002) and diabetes mellitus (14% vs. 7%, p=0.001); a higher rate of smoking (27% vs. 36%, p=0.005); shorter, less detailed appointments; a lower level of trust in the physician; to be aware of HCHOL for a shorter time; to consider HCHOL less severe; to search information about HCHOL less frequently (54% vs. 40%, p <0.001) and alternative treatments more often (35% vs. 59%, p <0.001). Three behavioural profiles were characterized: undisciplined, misinformed/pleased, and worried (16%, 29%, and 55% of the sample, respectively). Adherence rates were 28%, 34%, and 65% in these groups, respectively (p <0.001). Conclusions: based on the prevalence of self-reported HCHOL (10%), the high proportion of non-measured blood cholesterol, and the low adherence to lipidlowering treatment, it is mandatory to improve the strategies targeting detection of HCHOL and treatment compliance. Among multiple factors that contribute to treatment non-adherence, behavioural patterns may be identified in the pts and help establish specific measurements to overcome barriers to adherence. P2257 Heart rate variability and plasma lipids before and after treatment with rosuvastatin in hypercholesterolaemic patients without coronary artery disease E.A. Zacharis 1, M.E. Marketou 1, E.I. Skalidis 1,I.Karalis 1, A.P. Patrianakos 1,K.Stokkos 1, E. Ganotakis 2, F.I. Parthenakis 1, P.E. Vardas 1. 1 Cardiology Dept. Heraklion University Hospital, Heraklion, Greece; 2 Dept. of Internal Medicine, Heraklion, Greece P2258 Sex differences in the effect of hypertension on lipid profiles in Chinese patients X. Fan, Y. Wang, K. Sun, H. Wang, X. Song, W. Song, W. Zhang, H. Wu, X. Zhou, R. Hui. Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medi, Beijing, China, People s Republic of Purpose: Differences in blood pressure and lipid profiles are well known between sexes. However, little is known about whether hypertension influences the sexrelated differences in serum lipid and lipoprotein levels. The present study aimed to examine the effect of hypertension on sex-related differences in lipid profiles in Chinese. Methods: We conducted a community-based cross-section study composed of 5389 hypertensive patients (3555 women and 1834 men) and 1285 normotensives (833 women and 452 men), aged years, from 7 rural communities in China. Dyslipidemia (including high- triglycerides, high- total cholesterol, highlow-density lipoproteins, and low- high-density lipoproteins) were diagnosed according to Adult Treatment Panel III guideline. Results: After adjustment for body mass index and fasting blood glucose, women showed higher levels of high-density lipoproteins than men before and after 55 years of age in either normotensives or hypertensive patients, while total cholesterol and low-density lipoproteins rose in women with aging and exceeded men significantly after 55 years of age. The level of triglycerides was lower in hypertensive or normotensive women than in men before 55 years of age. However, hypertensive women over 55 years of age showed significantly higher triglycerides level than did men (mean differences: 20.2 mg/dl, P<0.001), but no sexdifferences in triglycerides level were found in normotensives (mean differences: 2.4 mg/dl, P>0.05). Dyslipidemia was more common in men than in women in either normotensives (28.7% vs. 22.2%, P=0.042) or hypertensives (40.6% vs. 35.1%, P=0.027) before 55 years of age. However, this sex-related difference in dyslipidemia disappeared in normotensives (24.3% vs. 31.6%, P>0.05) and reversed in hypertensive patients (30.0% vs. 42.4%, P<0.001) after 55 years of age. Central obesity was more common in women than in men throughout the age span, and no effect of hypertension was found on this sex-related difference. Conclusions: Sex-related differences in lipid profiles can be influenced by age and hypertension. P2259 Beneficial modulation of heart rate variability indices after rosuvastatin treatment in type 2 diabetic patients E.A. Zacharis 1, M.E. Marketou 1, E.I. Skalidis 1,I.Karalis 1, K. Stokkos 1, A.P. Patrianakos 1, G.F. Diakakis 1, E. Ganotakis 2, F.I. Parthenakis 1, P.E. Vardas 1. 1 Cardiology Dept. Heraklion University Hospital, Heraklion, Greece; 2 Dept. of Internal Medicine, Heraklion, Greece Purpose: Diabetic autonomic neuropathy is a frequent and serious complication of diabetes mellitus (DM). The reduction in parameters of heart rate variability (HRV) seems not only to carry negative prognostic value in patients with diabetes but also to precede the clinical expression of autonomic neuropathy. The objective of this study was to examine the effect of rosuvastatin treatment on HRV indices in patients with type 2 DM. Methods: We included 52 subjects with type 2 DM (18men, aged 65±10 years) with low density lipoprotein (LDL-C) cholesterol<130 mg/dl. All had a normal echocardiogram and no signs of coronary artery disease. Holter recording and fasting blood samples were performed in all subjects. The subjects were random-

71 Lipids and statins / Other topics 371 ized to receive 10 mg/day rosuvastatin (n=28) or placebo (n=24) for 6 months and were reevaluated. Results: LDL-C levels was significantly reduced (from 108±52 mg/dl to 89±34mg/dl, p<0.05). Heart rate variability indices at baseline and after 6 months of treatment are showed in Table 1. Table 1 Rosuvastatin Placebo before 6 months before 6 months SDNN 48.3± ±17.6* 45.6± ±18.9 SDANN ± ±16.5* 115.9± ±16.5 pnn ± ±5.7* 6.93± ±4.7 rmssd 32.4± ±9.5* 35.4± ±2.5 *p<0.05 compared to baseline. Conclusions: Treatment with rosuvastatin is associated with an increased 24- h HRV in type 2 diabetic patients. The clinical significance of this finding needs further investigation. OTHER TOPICS P2261 Identification of an electronegative LDL as potential novel biomarker for acute coronary syndrome P.-Y. Chang 1, J.-K. Lee 1, Y.-J. Chen 1,S.-C.Lu 1, Y.-T. Lee 1, K.-C. Chang 2,P.-Y.Pai 2, C.-H. Chen 3. 1 National Taiwan University Hospital, Taipei, Taiwan; 2 China Medical University, Taichung, Taiwan; 3 Baylor College of Medicine, Houston, United States of America Purpose: L5, a highly electronegative LDL originally isolated from hypercholesterolemic human plasma, exhibits a spectrum of atherogenic effects on cultured vascular cells. To evaluate its clinical implication, we assess its prevalence in patients with acute coronary syndrome (ACS), coronary artery disease (CAD) or CAD risk factors in comparison with subjects without these risk factors. Methods: Fasting blood samples were collected from adult patients with angiographically evidenced (coronary artery stenosis 50%) ACS (n=20) or stable angina (n=20), asymptomatic hypercholesterolemia (LDL cholesterol 160 mg/dl; n=20), type 2 diabetes mellitus (HbA1c 8.0; n=20), history of chronic smoking (n=20), and healthy subjects without these risk factors (n=20). Plasma LDL was divided by ion-exchange chromatography and all detectable LDL subfractions were collected. The most electronegative LDL subfraction, L5, was quantitated and the ratio of L5 to total LDL was calculated. Significant elevation of plasma L5 levels was defined as a percentage ratio of L5/LDL higher than 1.0%. Results: Plasma LDL was divided by ion-exchange chromatography into 5 subfractions, L1 L5, with increasing electronegativity, in all hypercholesterolemic samples (n=20/20;l5/ldl= %). In contrast, ion-exchange chromatography failed to yield L5 in any of the healthy subjects without CAD risk factors. Irrespective of the plasma cholesterol concentrations, L5 was found in all ACS patients (n=20/20; L5/LDL= %) and most CAD patients with stable angina (n=14/20; L5/LDL= %). L5 was also found in most diabetic (n=16/20;l5/ldl= %) and most chronic smokers (n=14/20; L5/LDL= %). Patients with ACS had significantly higher L5/LDL ratio than patients with stable angina (5.9±2.2 vs. 1.8±1.3, p<0.05). Regardless of their origins, all L5 specimens were able to induce human coronary arterial endothelial cell apoptosis and inhibit EC proliferation by inhibiting fibroblast growth factor-2 expression. L1-L4 had no effects. Conclusions: We have identified a naturally-occurring oxidized LDL in human plasma named L5 as potential biomarker for ACS. The significant presence of L5 in patients with ACS, CAD or CAD risk factors but not in risk-free healthy subjects implicates a clinical correlation. Large-scale epidemiological survey and prospective investigations are warranted to confirm L5 s atherogenic role and hence identifying it as a novel therapeutic target. P2262 Significant impact of chromosomal locus 1p13.3 on serum LDL cholesterol and on angiographically characterized coronary atherosclerosis A. Muendlein 1, S. Rhomberg 1,C.H.Saely 1, T. Winder 2, G. Sonderegger 1,P.Rein 1,S.Beer 1, A. Vonbank 1,H.Drexel 1. 1 VIVIT Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein Objectives: Recently, a significant impact of a new locus on chromosome 1p13.3 on serum LDL cholesterol and clinical events of coronary artery disease (CAD) was described. Potential associations between variants on this locus and angiographically characterized coronary atherosclerosis are unknown. We therefore aimed at investigating the association of variants of locus 1p13.3 with coronary atherosclerosis. Methods: We performed genotyping of variants rs599839, rs646776, and rs on chromosome 1p13.3 in a large cohort of 1610 consecutive Caucasian patients undergoing coronary angiography, where lesions of 50% or more were classified as significant. Results: Compared to the homozygous common allele the rare alleles of variants rs599839, rs646776, and rs were significantly associated with decreased serum LDL cholesterol (132±40 vs. 125±36 mg/dl, p = 0.003, 132±40 vs. 124±36 mg/dl, p <0.001, and 131±40 vs. 125±37 mg/dl, p = 0.005, respectively). Further, carriers of the rare alleles of variants rs and rs were at a significantly lower risk of significant coronary stenoses than subjects who were homozygous for the frequent allele, with odds ratios (OR) of 0.78 [ ]; p = and 0.74 [ ]; p = 0.004, respectively. After multivariate adjustment including LDL cholesterol, the protective effect of the rare allele of variant rs646776, but not of variant rs599839, on CAD risk remained significant (OR = 0.77 [ ], p = 0.034). Conclusion: We conclude that chromosomal locus 1p13.3 is significantly associated with both, serum LDL cholesterol and coronary atherosclerotic lesions. P2263 Relationships between modulation of functional characteristics of plasma lipoproteins and changes in their size and composition by short-term exercise in patients with metabolic syndrome A.C.F. Casella-Filho, F.H.Y. Cesena, I.C. Trombetta, V. Monteiro- Silva, C. Denardi, C.C. Magalhaes, C.E. Negrao, R.C. Maranhao, P.L. Daluz, A.C.P. Chagas. Heart Institute (InCor) HC.FMUSP, Sao Paulo, Brazil Purpose: To verify whether modulation of functional properties of lipoproteins by short-term exercise training (ExT) is associated with changes in size and composition of LDL and HDL subfractions in patients with metabolic syndrome (MetS). Methods: Forty sedentary persons (30 with MetS, 10 controls) were evaluated. Twenty of those with MetS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer. LDL and HDL subfractions were obtained by plasma ultracentrifugation before and after ExT, and their compositions were analysed. HDL particle size was determined by laser-light scattering method. In vitro resistance of LDL to oxidation with CuSO4 was determined. In another assay, LDL from control subjects was incubated with HDL2a or 3b from MetS patients (before and after ExT) and the resistance to oxidation was verified. Results: ExT did not alter plasma levels of total cholesterol (TC), LDL-c, HDL-c, apoa1 and apob, but significantly decreased the concentration of triglycerides (TG). LDL resistance to oxidation markedly increased (+91%) after ExT, which was associated with a significant decrease in the content of apob (-16%) and TG (-14%), but not of TC, free cholesterol, cholesterol ester, total protein or phospholipids, in the LDL particle. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MetS after ExT, compared with coincubation with HDL2a or 3b from these patients before ExT (-23% for HDL2a and -18% for HDL3b). This was associated with a significant decrease in the content of TC and TG in HDL3b (-7% and -12%, respectively) and HDL3c (-13% and -15%, respectively). ExT did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a, and total protein content was unchanged in all HDL subfractions. HDL particle size did not change with ExT (10.23±1.10 vs 10.26±1.09 μm before and after ExT, respectively, p >0.05). Conclusions: in subjects with MetS, short-term ExT does not change plasma LDL-c concentration but reduces LDL vulnerability to oxidation, associated with a significant decrease in lipid (TG) and protein (apob) content in LDL, indicating a change from small, dense to larger, less dense particles. ExT does not change HDL size and plasma HDL-c concentration, but promotes early enhancement of anti-oxidative properties of HDL subfractions, associated with a decrease in TC and TG content in the smallest subfractions. P2264 Low HDL - high inflammatory markers in heart failure induced by high frequency pacing in minipigs B. Pennato 1, V. Lionetti 1, F. Bigazzi 2, M. Puntoni 3, A. Simioniuc 1, M. Campan 1, F.A. Recchia 1, T. Sampietro 3. 1 Scuola Superiore Sant Anna, Pisa, Italy; 2 Fondazione Toscana Gabriele Monasterio, Pisa, Italy; 3 CNR Istituto di Fisiologia Clinica, Pisa, Italy Background: Clinical, experimental and in vitro studies suggest a major role for high-density lipoproteins (HDL) in the vascular homeostasis regulation, not necessarily related to pro- or anti-atherosclerotic mechanisms. Low HDL, together with a pro-inflammatory state, seem to be associated with left ventricular dysfunction in the absence of coronary atherosclerotic lesions, as occurs in idiopathic dilated cardiomyopathy. Aim: To test possible correlations between the development of non-ischemic cardiac failure and altered levels of HDL and ApoAI, inflammatory markers C3, alpha- 2-macroglubulin and ceruplasmin, in a pig model of pacing-induced dilated cardiomyopathy. Material and Methods: 8 adult male minipigs were chronically instrumented with a pacemaker connected to the left ventricular (LV) wall. Blood samples were collected at baseline, i.e. before starting the pacing protocol, and after three weeks of pacing at 180 beats/min, when LV ejection fraction was <35% and end-diastolic pressure was >18 mmhg. Statistical analysis was performed with paired Student s t-test. Results: After three weeks of pacing there were no significant changes in total cholesterol and triglycerides compared to baseline (57±7.50 vs 53.88±13.79 mg/dl and 23.67±9.31 vs 28.43±4.50 mg/dl respectively). Conversely, HDL and

72 372 Other topics ApoAI levels were dramatically decreased (21.63±2.45 vs 9.63±3.62 mg/dl, p=0.0004, and 16.86±0.97 vs 9.76±3.41 mg/dl, p=0.002, respectively). Among the inflammatory markers, alpha-2-macroglubulin and ceruplasmin levels were significantly increased (107.14±15.65 vs ±26.04 mg/dl, p=0.0314, and 26.51±3.37 vs 36.45±5.92 mg/dl, p=0.0096, respectively), while C3 levels were not significantly changed (14.66±4.59 vs 17.88±8.30 mg/dl). Conclusion: Our results suggest a novel association between development of cardiac dysfunction and decrease in circulating HDL, even in the absence of other co-morbidities and alterations of total cholesterol and triglycerides. P2265 The role of lipoprotein-a on major cardiovascular events in patients with familial combined hyperlipidemia and metabolic syndrome C. Masoura, I. Skoumas, C. Pitsavos, K. Aznaouridis, V. Metaxa, L. Papadimitriou, F. Platsouka, T. Tsokanis, N. Giotsas, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: To evaluate the role of lipoprotein-a (Lp-a) on cardiovascular risk in familial combined hyperlipidemia (FCH) patients with metabolic syndrome (MetS). Methods: We studied prospectively 323 FCH patients with MetS (mean age 51 y, 208 males) for 9.8±3.4 years. Demographic and biochemical parameters were recorded at enrolment. Diagnosis of MetS was made according to the modified ATPIII criteria. Hard cardiovascular end-points, like acute myocardial infarction (AMI) and cardiovascular death, were recorded. Results: Overall 9% of the patients (29 patients, 10.6% males vs. 6.1% females, P=0.17) presented with outcomes. We observed no difference (P=NS) between patients with and without cardiovascular endpoints, in regard to total cholesterol (289±51 vs. 287±57 mg/dl), LDL-cholesterol (194±55 vs.189±58 mg/dl), triglycerides (317±140 vs. 340±176 mg/dl), HDL-cholesterol (37±8 vs. 38±9 mg/dl), apolipoprotein-a1 (137±20 vs.139±25 mg/dl) and apolipoprotein-b levels (180±41 vs. 172±41 mg/dl). In contrast patients with AMI and/or cardiovascular death were older (55.8±8.3 vs. 50.3±10.3 years, P=0.006) and they had higher waist/hip (0.942±0.084 vs ±0.066, P=0.069) and higher Lp-a levels (40.3±44.9 vs. 28.2±29.6 mg/dl,p=0.049) at enrolment. After Cox regression analysis, Lp-a at enrolment and age were the significant predictors for AMI and/or death (hazard ratio per 1 mg/dl-increase of Lp-a, 95% CI , P=0.011). Conclusions: Lp-a level represents an independent predictor of major cardiovascular events in FCH patients with metabolic syndrome. P2266 Characterization and validation of a combined oral triglyceride and glucose tolerance test in patients with coronary artery disease C.M. Werner, A. Filmer, M. Fritsch, S. Groenewold, M. Boehm, U. Laufs. Universitätsklinikum des Saarlandes - Klinik für Innere Medizin III, Homburg, Germany Background: Retrospective analyses of epidemiologic studies suggest an association of postprandial TG levels with the risk of cardiovascular events, whereas fasting TG levels may be less predictive. The aim of our study was to develop a combined oral triglyceride and glucose tolerance test (OTT/OGT) in order to measure postprandial triglyceride and glucose tolerance at the same time. Methods and Results: Pilot experiments in 25 healthy volunteers and cross-over studies in patients with CAD and metabolic syndrome showed that a sequential test protocol with a 75g fat load test applied 3 hours prior to a glucose tolerance test showed no significant differences in the triglyceride kinetics compared to the OTT alone. N = 300 consecutive patients with stable coronary artery disease (CAD) were subjected to the OTT->OGT protocol, patients with diabetes received the OTT alone (mean age 66 y.). In addition, 40 age-matched subjects without CAD were examined. Within the CAD patients, individuals without metabolic syndrome (MS) and normal glucose tolerance (n=54) showed the lowest triglyceride values (fasting TG 103±5 mg/dl, TG at maximum 183±11 mg/dl). Patients with CAD and metabolic syndrome and impaired glucose tolerance (IGT) or diabetes mellitus (DM) had the highest triglyceride values (n=132, fasting 198±11 mg/dl, at maximum 335±17 mg/dl). CAD patients with MS but no IGT/DM (n=57, fasting 130±7 mg/dl, at maximum 248±5 mg/dl) and patients with IGT/DM but no MS (n=57, fasting 122±7 mg/dl, at maximum 233±16 mg/dl) showed a significantly lower postprandial TG increase. The group of IGT/DM patients was the only group to show a further TG increase between 4 and 5 hours post OTT, suggesting a delayed triglyceride clearance in diabetic CAD patients. The triglyceride maximum did not significantly differ between CAD patients without MS and IGT/DM and control subjects without CAD. Interestingly, in all patient groups with CAD, the relative TG increase did not correlate to the absolute TG increase. Conclusions: TG tolerance and glucose tolerance can be simultaneously measured in CAD patients using a simple sequential test protocol. As expected, patients with metabolic syndrome and diabetes exhibit elevated fasting and postprandial TG. However, CAD patients show striking differences between their absolute and relative postprandial triglyceride increase. Follow-up examinations in over 500 patients will be performed to elucidate whether the postprandial triglyceride kinetics correlate with future cardiovascular events and whether this test protocol identifies patients with TG-associated cardiovasular risk. P2268 Postprandial lipemia in familial combined hyperlipidemia, familial hypercholesterolemia and healthy subjects A. Pavlidis, G. Kolovou, K. Anagnostopoulou, P. Petrou, K. Sorodila, A. Valaora, K. Salpea, D. Cokkinos. Onassis Cardiac Surgery Center, Athens, Greece Purpose: Familial combined hyperlipidemia (FCH) is the most common familial dyslipidemia among patients who suffer early myocardial infarction. Familial hypercholesterolemia (FH) is a monogenic disorder of lipid metabolism secondary to low density lipoprotein receptor mutations that has been strongly linked to premature coronary artery disease (CAD). Postprandial hypertriglyceridemia is also associated with CAD. The purpose of this study was to evaluate postprandial lipemia after an oral fat tolerance test (OFTT) in men with FCH and compare them to FH and healthy subjects. Methods: The study population consisted of 83 subjects. OFTT was given to 34 men with FCH, 29 men with FH and 20 healthy men. The FCH and FH groups were further divided according to the lipid phenotype, on the basis of Fredrickson s classification, into five subgroups: FCH IIA (n=13), FCH IIB (n=10), FCH IV (n=11), FH IIA (n=21) and FH IIB (n=8). TG concentrations were measured before, 2, 4, 6 and 8 h after OFTT and the postprandial response was evaluated by the areas under the curve (AUC) for TG concentrations. Results: The TG levels after OFTT were significantly higher in FCH compared to FH and healthy groups (AUC in mg/dl/h; 2678±1415 vs. 1503±1147 and 1011±652 respectively, p<0.001). The postprandial TG levels were significantly increased in FCH IV and FCH IIB groups compared to FCH IIA at 2h (p=0.002 and p=0.001 respectively), 4h (p=0.004 and p<0.001 respectively), 6h (p=0.002 and p<0.001 respectively) and 8h (p<0.001 and p<0.001 respectively). There were no significant differences between FCH IV and FCH IIB groups and among FH and FCH subgroups with the same lipid phenotype (FH IIA vs FCH IIA and FH IIB vs FCH IIB). Fasting TG levels were the only significant predictor of the AUC (Spearman s rank correlation; r = 0.907, p < 0.001). Conclusions: Fasting TG concentration is the main determinant of postprandial lipemia. FCH and FH patients demonstrate an exaggerated postprandial response that could partially contribute to the high cardiovascular risk. This abnormal response is even more pronounced in FCH subjects with a prevalent hypertriglyceridemic phenotype. These patients should be identified and treated promptly with the appropriate hypolipidemic regime. P2269 Improvement in the control of hypercholesterolemia in coronary heart disease patients over the decade from 1997 to 2007 S. Surowiec 1, P. Jankowski 1, R. Wolfshaut 2,M.Loster 1,K.Batko 2, A. Pajak 2, K. Kawecka-Jaszcz 1. 1 I Department of Cardiology and Hypertension Jagiellonian University Collegium Medicum, Krakow, Poland; 2 Faculty of Health Sciences Jagiellonian University Collegium Medicum, Krakow, Poland Background: Effective treatment of hypercholesterolemia improve prognosis in coronary heart disease patients. However, the control of hypercholesterolemia was found insufficient. Purpose of the present analysis was to assess changes in effectiveness of the hypercholesterolemia treatment in coronary patients under care of general practitioners (GP) and cardiologists in hospital outpatient clinics (HO). Methods: Consecutive patients after hospitalization due to myocardial infarction, unstable angina, PCI or CABG at age years, residents of Cracow province (1.2 mln. inhabitants), were examined 6-18 months after discharge in Cracovian Program of Secondary Prevention Ischemic Heart Disease ( ) and in Polish component of Euroaspire III ( ). Results: There were 365patients (188 treated in HO and 177 treated by GPs) examined in and 363 patients (228 and 135 respectively) examined in No significant differences in age and sex distribution were found between the studied groups. The use of the lipid lowering drugs was 18,6% in in patients treated by GPs and 48,9% in patients treated in HO (p<0,0001). After ten years the rates increased to 88,2% and 86,8% respectively. At baseline cholesterol concentration <4.5 mmol/l was found in 9,0% patients treated by GPs and 19.5% patients treated in HO (p<0,001) and at the end of the study in 52,3% and 52% of patients respectively. In LDL-Cholesterol <2,5 mmol was found in 8.3% patients treated by GPs and 18,8% treated in HO (p<0,001) and in in 59.9% of patients in both groups. At baseline HDL-cholesterol >1.0 mmol/l (men) or >1.2mmol/l (women) was found in over 80% of patients in both sites at baseline and at the end of the study Triglycerides concentration <1,7 mmol/l was found in 54,6% patients treated by GPs and in 59,0% patients treated in HO at baseline and at the end of the study in 71.9% and 60,9%, respectively (p<0.05). Conclusion: Differences in the lipid lowering treatment between patients treated in GPs and in HO found in , were no longer observed ten years after. Improvement e was achieved in both sites but it was more pronounced in patients treated by GPs.

73 Other topics 373 P2270 Postprandial triglycerides and postprandial inflammation are significantly reduced by eight weeks of eccentric endurance exercise P. Rein 1, C.H. Saely 2, A. Vonbank 1, S. Beer 1,V.Kiene 1,S.Aczel 1, T. Bochdansky 3,H.Drexel 1. 1 VIVIT-Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein; 3 Rankweil State Hospital, Rankweil, Austria Purpose: Postprandial triglyceridemia is considered to be a substantial risk factor for cardiovascular disease. The atherogenicity of postprandial hypertriglyceridemia may in part be driven by inflammatory mechanisms. We hypothesised that eccentric endurance exercise lowers both, postprandial triglyceride excursions and the postprandial inflammatory response. Methods: Over a training period of 8 weeks, 51 healthy non-diabetic subjects (16 men and 35 women, mean age 50.7 years) 3 to 5 times per week performed eccentric endurance exercise by hiking downhill a path in the Austrian alps covering a difference in altitude of 540 meters; for the upward way a cable car was used, where compliance was measured electronically. The area under the triglyceride curve according to Patsch was measured after a standardized oral fat load; together with postprandial trigylcerides also postprandial leukocytes were measured. Results: Both postprandial triglyceridemia (from 1762±880 mg*dl 1h 1at baseline to 1417±664 mg*dl 1h 1; p <0.001) and postprandial leukocytes (from 68.8±11.6 G*L 1h 1 to 66.5±13.6 G*L 1h 1; p = 0.023) were reduced significantly with 8 weeks of eccentric endurance exercise. Conclusions: Eight weeks of modestly strenuous eccentric endurance exercise significantly reduce postprandial triglyceridemia and postprandial inflammation. P2271 Coronary obstruction detected by computerized tomography angiography in familial hypercholesterolemia is associated with Achilles tendon xanthomata and coronary artery calcification M.H. Miname, J. Parga, J. Avila, A.P. Chacra, W. Salgado, C.E. Rochitte, R.D. Santos. Heart Institute InCor University of Sao Paulo, Sao Paulo, Brazil Familial hypercholesterolemia (FH) is characterized by early coronary heart disease (CHD) onset. Multidetector computed tomography (MDCT) angiography has been proposed as a non-invasive test to determine asymptomatic coronary obstruction presence and might be useful as a screening tool in this population at high risk of CHD. However, MDCT use is implicated with elevated cost, high radiation and contrast exposures. On the other hand, coronary artery calcification (CAC) quantification, an accepted measure of plaque burden and a marker of CHD events, can be easily obtained by computerized tomography with no contrast injection, low radiation exposure and at a lower cost. Our objective was to evaluate determinants of coronary obstruction assed by MDCT angiography in asymptomatic FH subjects. Seventy-nine FH subjects (38% men) underwent routine clinical, laboratory and 64-slice MDCT angiography evaluations. Achilles tendon xanthomas were found by clinical examination in 19% of subjects. The presence of CAC determined by Agatston s method (CAC socres > 0) and stenosis defined as 50% obstruction of vessel lumen were found respectively in 42% and in 16% of study subjects. There were no differences between the groups regarding: age (47±12 vs. 44±14 years, p=0.43), male gender (56% vs. 50%, p=0.15), LDL-C (295±47 vs. 279±52 mg/dl, p=0.24), cholesterol-year score (17.721±5.187 vs ±6.298, p= 0.26), HDL-C (46±8 vs. 47±11mg/dL, p=0.78), Lipoprotein(a) (median: 42 vs. 54 mg/dl, p= 0.58), and C reactive protein levels (median: 1.7 vs. 1.6 mg/l, p=0.14) in those presenting or not stenosis respectively. No differences were also found in those with or without stenosis respectively in the prevalence of smoking (0% vs. 14%, p=0.19), hypertension (31% vs. 32%, p=0.97), previous statin use (31% vs. 30%, p= 0.96) and in the presence of the metabolic syndrome (25% vs. 40%, p=0.39). However, those with stenosis had a greater CAC prevalence 100% vs. 32%, p<0.0001, and higher median CAC scores 49 vs. 0, p< The presence of Achilles tendon xanthomas was also more frequent in those with stenosis (47% vs. 13%, p=0.0084). In conclusion the presence of Achilles tendon xanthomata and CAC were associated with coronary stenosis. The presence of either CAC and Achilles tendon xanthomata might be useful in determining in whom MDCT angiography might be used as a screening tool to detect luminal obstruction in FH. Prospective data are necessary to evaluate the role of MDCT angiography in predicting CHD events in these subjects. Background and objective: In spite of statin therapy, the incidence of cardiovascular (CV) events is high. Whilst LDL-C goal is sometimes not reached, other lipid abnormalities can also contribute to CV risk. The objective of DYSIS study was to assess the prevalence of lipid abnormalities (LDL-C, HDL-C and triglycerides) in patients treated with statins. Methods: Analysis of 3721 Spanish patients included in DYSIS, a cross-sectional study carried out in Europe and Canada on 20,916 patients 45 years-old treated with statins for at least 3 months. Data were recorded from patient s clinical charts. We used the ATP-III recommendations to define patient risk, LDL-C goal and the normality or not of the HDL-C and triglycerides. Results: In 3721 patients (median age 65 year-old, 47.3% women, 61.2% highrisk patients), LDL-C was not at goal in 50.4% (men:51.4%, women: 49.1%, p=0.19). Lack of goal attainment was more frequent in high (58.8% [goal<100 mg/dl], 89.8% considering <70 mg/dl) and moderate risk (48.9% [goal <130 mg/dl]) vs low risk patients (21.3% [goal <160 mg/dl] p<0.001). Low HDL was present in 29.8% of the patients (men:25.0% [<40 mg/dl], women: 35.1% [<50 mg/dl], p<0.001) and in respectively, 34.8%, 37.1% and 2.1% of those at high, moderate and low CV risk. Triglycerides were 150 mg/dl in 37.6% (men: 41.4%, women: 33.8%, p<0.001), and respectively, in 40.7%, 42.0% and 20.8% (high, moderate or low CV risk). 36.8% had two or more abnormalities (6.4% abnormal LDL-C + low HDL-C, 13.1% abnormal LDL-C + triglycerides and 9.7% had abnormal values of the three parameters). Only 28.4% of patients had the three lipids within the recommended range or the range considered normal in the NCEP APT III guideline. Conclusions: Despite statin therapy, a large amount of patients show lipid abnormalities, not only abnormal LDL-C but also low HDL-C and/or abnormal triglycerides, especially those at higher CV risk. An integrated approach to the treatment of dyslipidaemia may be of interest in order to reduce the risk of CV complications even further in patients treated with statins. P2273 Controlling lipids in a high risk population with documented coronary artery disease for secondary prevention: are we doing enough? M. Singh 1,S.Chin 2,P.Giles 2, D. Carothers 2, K. Al-Allaf 2, J. Khan 2. 1 Rosalind Franklin University of Medicine & Science, Chicago Medical School, Illinois., North Chicago, United States of America; 2 Walsall Hospitals NHS Trust, Walsall, West Midlands., Walsall, United Kingdom Purpose: Prevalence of low HDL-C in patients who have achieved LDL-C targets in the current era of universal statin therapy for secondary prevention remains unknown. We conducted a study to determine the prevalence of low HDL-C in patients with documented coronary artery disease, and the lipid lowering treatment patterns in secondary prevention of CAD. Methods: In this retrospective cohort analysis, data were captured from 1999 to The Joint British Society 2 criteria were used for defining low HDL-C as <1.0 in males and <1.2 in females. We compared the prevalence of low HDL-C across the following categories of LDL-C: < 2 mmol/l, mmol/l, and > 2.5 mmol/l. Table 1 Variables LDL-C < 2 LDL-C: LDL-C > 2.5 No of patients Age 65.23± ± ±11.54 TC 3.38± ± ±0.78 HDL 1.16± ± ±0.33 LDL 1.50± ± ±0.63 P2272 Percentage lipid abnormalities in statin treated patients. The dyslipidemia international survey study (DYSIS-SPAIN) J.R. Gonzalez-Juanatey 1, J. Millan 2,C.Guijarro 3, E. Alegria 4, J.V. Lozano 5, V. Inaraja 6,G.Vitale 6,L.Cea-Calvo 6 on behalf of Spanish DYSIS investigators. 1 Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, 2 Hospital General Universitario Gregorio Maranon, Madrid, 3 Hospital Fundación Alcorcón, Madrid, 4 Clinica Universitaria de Navarra, Pamplona, 5 Centro de Salud Serrería 2, Valencia, 6 Clinical Research Department, Merck Sharp & Dohme, Madrid, Spain Results: 2087 patients with a mean age of 64.34±11.94 years constituted the study sample. 36.6% of patients in this study were found to have low HDL-C. Irrespective of gender, low HDL-C was prevalent across all levels of LDL-C, but interestingly most prevalent in patients with a LDL-C <2 mmol/l (43.06%). There was no correlation between the LDL-C and HDL-C levels implying their independent relationship and, thus, the need to treat them independently.

74 374 Other topics P2274 Body mass index independently predicts the variation in plasma levels of triglycerides and the triglycerides/hdl-cholesterol ratio after short-term red wine consumption F.H.Y. Cesena, A.C.M. Andrade, S.R. Coimbra, A.M. Benjo, P.L. Da Luz. Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil Purpose: To determine predictive factors of variations in plasma levels of triglycerides (TG), TG/HDL-c ratio, and plasma glucose after short-term red wine consumption. Methods: 42 individuals (64% men, 46±9 years) were given red wine (250 ml/day) for 14 days. Plasma concentration of lipids and glucose were measured before and after red wine consumption. Paired t test, analysis of variance and linear regression were used for statistical analyses. Results: Baseline characteristics included body mass index (BMI) 25.13±2.76 kg/m 2, LDL-c 156±39 mg/dl, and HDL-c 53±14 mg/dl. Red wine increased plasma levels of TG from 105±42 mg/dl to 120±56 mg/dl (p=0.001) and the TG/HDL-c ratio from 2.16±1.10 to 2.50±1.66 (p=0.014). In a linear regression model adjusted for age, gender, baseline BMI, blood pressure, lipids, and glucose, only BMI was independently predictive of the variation in plasma TG after red wine (beta coefficient 0.593, p <0.001). Similar results were found for the correlation between BMI and the variation in TG/HDL-c ratio (beta coefficient 0.529, p <0.001, adjusted model). When individuals were divided into 3 categories, according to their BMI, the average percent variation in TG after red wine was 4%, 17%, and 33% in the lower, intermediate, and higher quartiles, respectively (p=0.001). The respective numbers for the variation in the TG/HDL-c ratio were 5%, 18%, and 32% (p=0.007). The table shows the mean plasma levels of TG and TG/HDL-c ratio, according to BMI quartiles (Q), before and after red wine intake. Red wine also increased the plasma concentration of glucose from 92±9 mg/dl to 96±9 mg/dl (p=0.002). This variation was inversely correlated to baseline plasma glucose (beta coefficient 0.437, p=0.006) in a linear regression model adjusted for age, gender, baseline BMI, blood pressure and lipids. Q1 (n=14) Q2 (n=14) Q3 (n=14) BMI kg/m 2 BMI kg/m 2 BMI kg/m 2 Before After Before After Before After TG (mg/dl) 100±41 97±47 107±41 124±53 108±46 139±63 TG/HDL-c 1.91± ± ± ± ± ±1.93 Conclusions: Individuals with higher BMI are at greater risk for adverse metabolic effects of short-term red wine consumption, regarding elevation in plasma TG levels and the TG/HDL-c ratio. P2275 Cholesterol metabolism and hepatic function in cardiovascular patients aged 75 years and older T. Strandberg 1, M.H. Hovinen 2, K.H. Pitkala 2,T.A.Miettinen 2, R.S. Tilvis 2. 1 University of Oulu, Oulu, Finland; 2 University of Helsinki, Helsinki, Finland Purpose: One of the paradoxes in old age is that low serum cholesterol is often associated with better survival in epidemiological studies. We investigated hepatic function and cholesterol metabolism in a group of patients with stable cardiovascular disease (CVD) aged 75 years and older and related these to 7-year mortality Methods: In the DEBATE study mailed questionnaires, sent to a random sample of individuals aged 75 and over, were used to retrieve 400 home-living CVD patients. At baseline in 2000, they underwent clinical examinations and laboratory testing. 15D score was used to measure general function. Serum alanine aminotransferase (ALT, divided in quartiles) level was taken to reflect hepatic function, cholesterol metabolism was assessed with serum noncholesterol sterols (assessed in 374 individuals) of which lathosterol reflects hepatic cholesterol synthesis and cholestanol and plant sterols (campesterol, sitosterol) reflect cholesterol absorption. Total mortality up to 2006 was collected from national registers. Results: Average age at baseline was 80 years and 65.3% (n= 261) were women. Of the patients, 80.8% (n= 323), 36.5% (n=146) and 13.8% (n=55) had a history of coronary heart disease, cerebrovascular disorders, or peripheral artery disease, respectively. Median BMI was 26.1 kg/m 2 (interquartile range ). Median ALT level was 19 IU/L, (interquartile range 14-25; max 131). Although baseline 15D score was not significantly different between ALT quartiles, 7-year mortality (n=151, 40.4%) was inversely related to ALT quartile (mortality 51.1, 44.2, and 30.1% from the lowest to highest quartile, P=0.0007). Baseline comparisons were adjusted for age, sex and statin use. Both BMI and glucose were significantly higher with increasing ALT, while serum lipids including LDL-cholesterol were more inconsistent. However, marker of cholesterol synthesis significantly decreased (P=0.001) and markers of absorption significantly increased (P=0.04) with decreasing ALT quartiles. Conclusions: Lower ALT concentration and lower cholesterol synthesis reflected poorer prognosis in older CVD patients. LDL-cholesterol remained unaltered probably because cholesterol absorption still was reciprocally increased in these home-living inviduals with stable condition. P2276 Familial hypercholesterolaemia - an oportunity for preventive medicine A.M. Medeiros, A.C. Alves, V. Francisco, S. Silva, M. Bourbon on behalf of on behalf of the investigators of the Portuguese FH Study. Instituto Nacional de Saude Dr Ricardo Jorge, Lisbon, Portugal Cholesterol is a well known cardiovascular risk factor. Individuals with genetic disorders of lipid metabolism have an increased cardiovascular risk. Patients with Familial Hypercholesterolaemia (FH) have a 100 times greater risk of developing premature CHD than the population in general. OMS estimates that Portugal should have about cases of FH, but this disorder is severely under diagnosed in our country. It is essential that these patients are identified at a young age, so they can receive counseling and treatment according their condition. This is the main aim of Portuguese FH Study. The present study analyses the cardiovascular events, fatal and non fatal, on this population that could be avoided if these patients had been identified and treated at young age. Since 1999, a total of 302 index patients and 676 relatives have been received at our lab, from all over country, for the molecular study of FH. The molecular analysis identified 314 definite FH patients (index and relatives) which correspond to 1,6% of all cases estimated to exist in Portugal. Only 43% of the clinical diagnosed index patients had their diagnosis confirmed. About 16% (21/129) of the index cases and 9% (17/185) of the relatives genetically identified, already had a cardiovascular event (age index/years 45,31±12,89 and age relatives/years 44,23±11,04). In these 129 familes 45 premature deaths occurred (age/years 55,73±13,99). About 12% (21/175) of the index cases with clinical diagnosis of FH but in whom no mutation was found, also presented premature CHD (age/years 46,86±13,40) what seems to indicate that another gene defect, not yet known, must be the cause of such a severe phenotype. Clinical identification is possible but only the genetic diagnosis correctly identifies the pathway affected. This is important for disease prevention allowing for a more personalized counseling and treatment in order to decrease the elevated cardiovascular risk in these patients. Efforts must concentrate in the early identification of these patients so they can adopt a healthier life style and receive counseling and pharmacological treatment to prevent an early death, as already happen in so many families. These deaths could probably been avoided in these patients had been identified and treated at young age. Genetic identification allows the early diagnosis of this disorder, what is especially important for the prognosis of children and adolescents. The future must be centered in prevention and not in the treatment of the serious cardiovascular complications associated to this disorder. P2277 The correlation of the long pentraxin 3 (PTX3) to lipids in patients hospitalized with acute chest pain T. Brugger-Andersen 1,V.Ponitz 1,F.Kontny 2,H.Staines 3, H. Grundt 4,K.Miyamoto 5,C.Miyazawa 5, T. Matsuura 5, M. Sagara 5, D.W.T. Nilsen 1. 1 Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; 2 Department of Cardiology, Volvat Medical Center, Oslo, Norway; 3 Sigma Statistical Services, Balmullo, United Kingdom; 4 Department of Medicine, Stavanger University Hospital, Stavanger, Norway; 5 Perseus Proteomics Inc., Tokyo, Japan Background: The long pentraxin 3 (PTX3) is a recently identified member of the pentraxin protein family that also includes C-reactive protein. PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli, and elevated plasma levels are found in the acute coronary syndromes (ACS). However, currently available clinical data on the relation of PTX3 to lipids in a population hospitalized with acute chest pain is sparse. The aim of this study was to assess these variables. Methods: PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in EDTA plasma in admission samples from 795 patients. The patients were followed for 24 months for clinical outcome. A multiple regression model was fitted for the total population. Results: PTX3 was related to total cholesterol but not to high-density lipoprotein cholesterol or triglycerides for the total population (r= 0.213, p<0.001) (Table I). Table 1. The relationship between PTX3 and lipids for patients hospitalized with acute chest pain B (p-value) R Multiple regression Groups Total cholesterol HDL cholesterol Triglycerides model p-value All patients (n=795) (<0.001) 0.67 (0.304) (0.066) <0.001 HDL cholesterol, high-density lipoprotein cholesterol. Conclusion: In patients with acute chest pain PTX3 is correlated with total cholesterol. P2278 Cigarette smoking blocks the protective expression of Nrf2/ARE pathway in blood cells of young heavy smokers favouring inflammation: relation to endothelial function and carotid intima-media thickness C. Mozzini, A. Fratta Pasini, U. Garbin, A. Pasini, S. Manfro, C. Stranieri, L. Cominacini. University of Verona, Verona, Italy Purpose: Cigarette smoking constitutes a major risk factor for atherosclerotic

75 Other topics 375 vascular disease. Since cigarette smoking promotes oxidative stress and oxidative stress is an inductor of inflammation through activation of the redox-sensitive transcription factor NF-kB, as well as of the counteracting protective NF-E2- related factor 2 (Nrf2)/antioxidant related elements (ARE) pathway, this study was aimed to evaluate: 1) the balance between these two inducible elements in peripheral blood mononuclear cells (PBMC) derived from young healthy smokers and 2) the relationship with systemic indexes of oxidative stress, inflammation, endothelial function and carotid intima media thickness (IMT). Methods: 124 healthy volunteers (aged 26±4 years, 74/50 males/females) participated in the study. Smokers were described as individuals who smoked 5 10 (light smokers: LS) or (heavy smokers: HS) cigarettes per day for at least 3 years, whilst non-smokers (C) included those who had never smoked or those who had not smoked for at least 3 years. In PBMC were evaluated: NFkB activation (ELISA), Nrf2/ARE gene expression (Real time PCR and Western blotting), membrane oxidized phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero- 3-phosphorylcholine (ox-papc), (HPLC/mass spectrometry) and GSH (HPLC). Morever high-sensitivity C reactive (hs-crp), carotid IMT and flow-mediated vasodilation (FMD) of the brachial artery in response to hyperemia were measured. Results: LS showed significantly higher expression of Nrf2/ARE genes than HS and C in PBMC(p<0.001). On the contrary nuclear NF-kB activation in PBMC was significantly higher in HS than in LS and C (p<0.001).activation of NF-kB positively correlated (p<0.001), while the expression of the Nrf2/ARE negatively correlated with the degree of oxidative stress, as evaluated by membrane ox- PAPC and GSH in PBMC. Hs-CRP was significantly higher in HS than in LS and C (p<0.001) and was directly correlated with NF-kB activation in PBMC (p<0.001). FMD resulted significantly impaired in HS and LS than in C (p<0.01). Moreover FMD was significantly impaired in HS than in LS (p<0.01). Similarly there was an increased carotid IMT in both HS and LS when compared with C (p<0.001), but carotid IMT was higher in HS than in LS (p<0.001). Conclusions: Excessive oxidative stress induced by cigarette smoking abolishes the protective antioxidant response of the Nrf2/ARE pathway in PBMC of healthy young HS, favouring the activation of NF-kB and the systemic inflammation. These findings are associated with an impairment of FMD and an increase of carotid IMT. P2279 Genetic variant rs C>T in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 significantly predicts smoking severity in coronary artery disease patients C.H. Saely 1, A. Muendlein 1, A. Vonbank 1,P.Rein 2,S.Beer 1, J. Breuss 1, B. Gaensbacher 1,H.Drexel 1. 1 VIVIT Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein Objectives: Smoking is a major cause of preventable premature death, mainly due to its strong and dose-dependent impact on coronary artery disease (CAD). Recently, genetic determinants of nicotine dependence (which correlates with the amount of smoked cigarettes rather than with the smoker status per se) have been suggested. No data are available for patients already affected by CAD. Methods: We genotyped variant rs C>T in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 in a large cohort of 1303 consecutive Caucasian patients with angiographically proven CAD. Results: From our patients, 62.1% had a history of smoking (n = 809; 226 current and 581 past smokers). Genotype distributions of variant rs were not significantly different between patients with a history of smoking and those who had never smoked (ptrend across genotypes = 0.471). However, the variant among smokers proved strongly predictive for the average amount of cigarettes smoked per day (24/d, 23/d, and 30/d for subjects with the AA, the AT, and the TT genotypes; p <0.001 for those with the TT genotype vs. carriers of the A allele). This association remained significant after adjustment for age and gender (F = 12.4; p <0.001). Conclusions: Genetic variant rs C>T in the nicotinic acetylcholine receptor gene cluster significantly predicts smoking severity in patients with angiographically proven CAD. P2280 Synergistic effect of smoking and early-stage pulmonary dysfunction on abnormal pressure wave reflection in men K. Shiina, H. Tomiyama, C. Matsumoto, M. Odaira, M. Yoshida, A. Yamashina. Tokyo Medical University, Tokyo, Japan Objective: This cross-sectional study was conducted to clarify whether pressure wave reflection, as assessed by the augmentation index (AI), might be increased in the presence of early-stage pulmonary dysfunction and, if so, whether smoking modifies this relationship. Methods: In 6112 clinically healthy Japanese subjects {i.e., forced expiratory volume at 1 second/forced vital capacity (FEV1.0/FVC) ratio >70%, with no known history of pulmonary disease or cardiovascular disease}, pulmonary function, the radial augmentation index (rai) and second peak of radial systolic pressure wave form (SBP2), a surrogate marker of central systolic pressure, were measured. Results: The FEV1.0/FVC ratio and smoking status were found to show significant correlation with the augmentation index (AI) as assessed by radial pressure wave analysis with significant interaction between the two {B (95% confidence interval = ( ), t-value = -2.01, p = 0.03} in the 3351 men (49±9 years old), but not the 2761 women (46±10 years old) in this study. In men, the adjusted values of radial AI, SBP2 and the prevalence rate of subjects with elevated plasma levels of CRP were significantly higher in current smokers with early-stage pulmonary dysfunction than in the other 3 categories (Figure). AI, SBP2 and CRP in four groups Conclusion: In men, early-stage pulmonary dysfunction and current smoking may synergistically increase micro-vascular dysfunction and the increase in CV risk related to pressure wave reflection, and inflammation may contribute, at least in part, to such synergistic effects. P2281 Smokers benefit more from early invasive treatment of acute myocardial infarction than non-smokers E. Aune 1, J. Hjelmesaeth 1, K. Endresen 2, J.E. Otterstad 1. 1 Vestfold Hospital Trust, Toensberg, Norway; 2 Rikshospitalet University Hospital, Oslo, Norway Purpose: The aim of this study was to investigate whether a previously shown survival benefit of early invasive treatment of acute myocardial infarction (AMI) may differ according to smoking status. Methods: Prospective observational cohort study on consecutive patients admitted for AMI in 2003 (conservative cohort) (n = 311) and 2006 (invasive cohort) (n = 307). Patients were subdivided into current smokers at admission, including those who stopped within the last 3 months, and non-smokers (including ex-smokers). Statistics: Cox proportional hazards regression analysis. Results: A total of 27% (invasive cohort) and 32% (conservative cohort) of the patients were categorized as current smokers, respectively. Current smokers had a 72% increased risk (HR 1.72, 95% CI , p = 0.021) for death after one year, adjusted for treatment cohort, age, gender, prior AMI, prior stroke, and diabetes. Smokers and non-smokers in the invasive cohort had a 70% and 30% lower one-year mortality compared with the conservative cohort, respectively (Kaplan-Meier plots are presented in the figure). Non-smokers were significantly older than smokers both in the conservative (median age 77 vs. 60 years, p<0.001) and invasive cohort (median age 79 vs. 58 years, p = 0.001). We found a significant interaction (p = 0.039) between treatment cohort and smoking status supporting a larger survival benefit in smokers. Survival according to smoking status Conclusions: The survival benefit following introduction of early invasive management of unselected AMI patients was higher among smokers than nonsmokers. P2282 Smoking cessation increases serum adiponectin levels in an apparently healthy greek population S. Efstathiou 1, I. Skeva 1,C.Dimas 2, A. Panagiotou 2,K.Parisi 2, L. Janoumis 1, A. Kafouri 1, K. Bakratsas 1, T. Mountokalakis 1. 1 Hygeias Melathron, Athens, Greece; 2 Athens University Hospital Attikon, Athens, Greece Purpose: Smoking has been associated with low serum levels of adiponectin, an adipocytokine with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. However, no data are available so far in regard to the short-term impact of smoking cessation on serum adiponectin concentration. The objective of this study was to assess the early effect on serum adiponectin levels of smoking cessation supported by bupropion, a well-established pharmaceutical aid.

76 376 Other topics Methods: Apparently healthy smokers of both sexes with no additional cardiovascular risk factors were administered 150 mg sustained-release bupropion twice daily for 9 weeks. Quitters constituted the active group and non-quitters the control group. Sandwich enzyme-linked immunosorbent assays were employed for the measurement of serum adiponectin and serum cotinine, the major proximate metabolite of nicotine, which is widely used as a biomarker of tobacco exposure. Participants self-reported abstinence was confirmed by a serum cotinine level below 15 ng/ml. Results: Among the 106 Greeks of Caucasian origin who completed the study (mean age 44.5±11.3 years, 57 females, body mass index [BMI] 26.7±4.9 kg/m 2, daily cigarettes 27.1±10.6, Fagestrom score 7.4±1.8, Brinkman index 512.2±98.4, basal adiponectin 7.2±1.5 μg/ml, basal cotinine 381.4±191.1 ng/ml), 45 (42.5%) had quitted smoking at week 9. Quitters did not differ from non-quitters in terms of baseline characteristics. Quitters post-cessation adiponectin levels were significantly increased (mean difference from baseline 1.9±0.8 μg/ml [95% CI 1.2, 2.3], p < 0.001), while non-quitters adiponectin concentration remained unaltered (mean difference from baseline 0.1±0.4 μg/ml [95% CI -0.2, 0.3], p = 0.164). Cotinine levels at week 9 were lower in quitters (3.8±3.4 ng/ml) as compared to non-quitters (211.2±96.5 ng/ml; p < 0.001). Weight gain was non-significant in quitters (1.7±1.0 kg [95% CI -1.6, 2.4], p = 0.511) as well as in non-quitters (1.5±1.2 kg [95% CI -1.9, 2.5], p = 0.598). A multiple regression model including female gender (standardized β coefficient = 0.480, p = 0.002), age (0.355, p = 0.003), BMI (-0.308, p = 0.005), waist circumference (-0.276, p = 0.008), smoking status (-0.255, p = 0.010), and cotinine levels (-0.233, p = 0.021) explained about two thirds of the variation in adiponectin levels (adjusted R 2 = 0.656). Conclusions: Serum adiponectin levels appear to increase considerably within two months after smoking cessation. This finding may provide further insight into the mechanisms related to the detrimental effects of smoking and the benefits of quitting. P2283 Passive smoking is associated with masked hypertension in clinically normotensive non-smokers: cross-sectional results in a smoke-filled environment C. Thomopoulos, D.P. Papadopoulos, S. Massias, E. Michalopoulou, A. Bratsas, O. Papazachou, T.H. Makris. Department of Cardiology, Elena Venizelou General & Maternity Hospital, Athens, Greece Purpose: Clinical and experimental data indicate that passive smoking exerts detrimental effects on vascular homeostasis; however, its association with blood pressure (BP) levels especially in the clinically non-hypertensive range is still lacking. We investigated ambulatory BP levels among clinically normotensive nonsmokers exposed (PS) and not exposed (SF) to passive smoking aiming to evaluate the relative prevalence of masked hypertension (MH). Methods: From 790 consecutive never treated subjects who were referred to an outpatient hypertensive clinic, we excluded active smokers, nonsmokers not exposed to workplace smoking and those having a mean clinic BP>140/90mmHg (mean BP of three separate measurements with elapsing time of one week). In the remaining population echocardiographic examination and metabolic profile assessment was performed while all the clinically normotensives eligible to participate (112 PS and 100 SF) underwent to ambulatory BP monitoring. In all participants haemodynamic reaction to standing was assessed, while by appropriate questionnaires salt intake, type of followed diet, coffee and alcohol consumption and physical activity were registered; lastly, in the PS group the daily and overtime exposure to passive smoking were entered in our analysis. Results: SF with respect to PS group resulted older by 3±5 years, followed a more hygienic diet and consumed less alcohol (p<0.05 for all). PS with respect to SF group demonstrated higher 24h systolic BP and clinic heart rate (125±4 vs. 122±5mmHg, p<0.001 and 79±4 vs. 73±4 beats/min, p=0.009, respectively), while the prevalence of MH was higher in the former group (n=18, 16%) with respect to the latter (n=8, 8%), p=0.02. In a logistic multivariable regression model (R 2 adjusted=0.28, p=0.001) determinants (adjusted odds ratio, 95% confidence interval) of MH were passive smoking (1.22, ), daily (1.34, ) and over-time (1.34, ) duration of smoke exposure, male gender (1.32, ), younger age (0.64, ), adverse lifestyle attitudes, mean clinic systolic/diastolic BP (1.17, /1.21, ) and both standing diastolic BP and heart rate (1.31, and 1.24, , respectively) (p<0.05 for all). Conclusions: MH is associated with passive smoking in clinically prehypertensive non-smokers and adverse lifestyle attitudes may represent potential accelerators of this phenomenon. This finding underscores the need for the amelioration of smoking status assessment in combination with other demographic and lifestyle markers along with the routine clinical BP evaluation. P2284 Smoking is related to subclinical inflammation and impairment of thrombosis/fibrinolysis system in essential hypertensive subjects: an insight into the tobacco-related vascular disease K. Dimitriadis, C. Tsioufis, A. Kasiakogias, A. Miliou, E. Andrikou, A. Mazaraki, C. Thomopoulos, D. Tsiachris, D. Tousoulis, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Despite the fact that smoking has numerous effects that promote atherosclerosis, the data regarding its association with inflammatory processes and thrombosis/fibrinolysis system in the setting of untreated essential hypertension are rather scarce. In the present study we investigated the interrelationships between smoking, high-sensitivity C-reactive protein (hs-crp), fibrinogen and plasminogen-activator inhibitor type 1 (PAI-1) levels in essential hypertensive subjects. Methods: 295 newly diagnosed untreated non-diabetic patients with stage I to II essential hypertension [192 men, mean age=50 years, office blood pressure (BP)=148/95] were classified according to their smoking habits as current smokers ( 1 cigarette/day, n=127) and the remaining subjects as non-smokers (n=165). All subjects underwent ambulatory BP monitoring and venous blood sampling was performed for estimation of metabolic profile, hs-crp fibrinogen and PAI-1 concentrations. Results: Hypertensive current smokers compared to non-smokers had increased office diastolic BP (96±9 vs 94±7 mmhg, p<0.05) and 24-h diastolic BP (84.7±10 vs 80.8±9 mmhg, p=0.001), whereas did not differ regarding age, sex, body mass index (BMI), and left ventricular mass index (p=ns for all). Although groups exhibited no difference regarding metabolic profile (p=ns), smokers compared to non-smokers were characterized by higher levels of hs-crp (3.18±0.95 vs 2.29±0.48 mg/l, p<0.005), fibrinogen (316.2±62.6 vs 292.7±66.9 mg/dl, p=0.01) and PAI-1 (38.08±9.54 vs 25.5±23.9 ng/ml, p=0.002). In the entire population, hs-crp was associated with BMI (r=0.281, p<0.0001), pack-years index (r=0.184, p<0.005), 24-h systolic BP (r=0.144, p<0.05), and fibrinogen (r=0.138, p<0.05), whereas PAI-1 exhibited a positive correlation with pack-years index (r=0.248, p<0.005) and 24-h diastolic BP (r=0.220, p=0.006). Regarding fibrinogen, it was related to pack-years index (r=0.176, p<0.05) and daytime pulse pressure (r=0.185, p<0.005). Analysis of covariance revealed that hs-crp, fibrinogen and PAI-1 concentrations remained significantly different between the two groups after adjusting for confounding factors (p<0.05 for all). Conclusions: Smoking in essential hypertension is accompanied by increased inflammatory processes and impairment of thrombosis/fibrinolysis system, as reflected by hs-crp, fibrinogen and PAI-1 levels. These findings may partially elucidate the complex mechanisms linking smoking with increased cardiovascular risk, in this setting. P2285 Chewing tobacco produces coronary vasoconstriction S. Ramakrishnan, R. Thangjam, A. Roy, S. Singh, S. Seth, R. Narang, B. Bhargava. All India Institute of Medical Sciences (AIIMS), New Delhi, India Background: The acute hemodynamic and coronary vasomotor effects of chewing tobacco are not known. Methods: Ten patients who are habitual tobacco chewers (age yrs) undergoing elective coronary angiography and consenting to be part of the study were included. Patients with unstable angina or advanced coronary artery disease were excluded. The study was approved by the institutional ethics Committee. Following coronary angiography, a right heart study was performed through right femoral vein using 8F sheath. A 7F thermodilution Swan Ganz continuous cardiac output pulmonary artery catheter was used to measure the cardiac output continuously and right heart pressures were measured from the respective ports of the catheter. Having obtained the baseline hemodynamic data, 1g of tobacco was given orally to be chewed. Subsequently, the hemodynamic data were obtained periodically till a period of 60 minutes. A repeat left coronary injection was obtained 15 minutes after giving tobacco, in the RAO view for estimation of the diameter of left anterior descending artery by QCA. Results: Chewing tobacco leads to a significant acute increase in heart rate, systemic blood pressure and cardiac output (from 3.64±0.45 lit/min to 4.44±0.68 lit/min p 0.04) peaking at 15 min. There were no significant changes in the right atrial, pulmonary artery and wedge pressures and hence no change in the pulmonary vascular resistance. More importantly, chewing tobacco was associated with coronary vasoconstriction (proximal LAD diameter 3.42±0.52 mm to 2.71±0.48; p value 0.04). Conclusion: Chewing smokeless tobacco leads to coronary vasoconstriction and also produces significant hemodynamic alterations. P2286 Smoking is associated with subclinical inflammation, impairment of thrombosis/fibrinolysis system and increased osteoprotegerin levels in essential hypertensives K. Dimitriadis, C. Tsioufis, E. Andrikou, D. Syrseloudis, C. Thomopoulos, I. Andrikou, A. Mazaraki, V. Tzamou, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Despite the fact that smoking has numerous effects that promote atherosclerosis, the data regarding its association with biological markers of risk in the setting of untreated essential hypertension are rather scarce. In the present study we investigated the interrelationships between smoking, high-sensitivity C- reactive protein (hs-crp), osteoprotegerin (OPG), fibrinogen and plasminogenactivator inhibitor type 1 (PAI-1) levels in essential hypertensives.

77 Other topics / Population trends 377 Methods: 245 newly diagnosed untreated non-diabetics with stage I to II essential hypertension [172 men, mean age=51 years, office blood pressure (BP)=148/95] were classified according to their smoking habits as current smokers 1 cigarette/day, n=115) and the remaining subjects as non-smokers (n=130). All subjects underwent ambulatory BP monitoring and venous blood sampling was performed for estimation of metabolic profile, hs-crp, OPG, fibrinogen and PAI-1 concentrations. Results: Hypertensive current smokers compared to non-smokers had increased office diastolic BP (97±8 vs93±7 mmhg, p<0.05) and 24-h diastolic BP (85±10 vs 80±8 mmhg, p=0.001), whereas did not differ regarding age, sex, body mass index and left ventricular mass index (p=ns). Although groups exhibited no difference regarding metabolic profile (p=ns), smokers compared to non-smokers were characterized by higher levels of hs-crp (3.25±1.1 vs 2.33±0.84 mg/l, p<0.005), OPG (5.8±0.7 vs 4±0.5 pmol/l, p<0.005), fibrinogen (318.5±56.6 vs 289.3±67.3 mg/dl, p=0.02) and PAI-1 (40.02±7.56 vs 24.5±22.7 ng/ml, p=0.004), independently of confounding factors. In the entire population, hs-crp was associated with pack-years index (r=0.175, p<0.05) and 24-h systolic BP (r=0.188, p<0.05), whereas PAI-1 exhibited a correlation with pack-years index (r=0.248, p<0.005) and 24-h diastolic BP (r=0.220, p=0.006). Regarding OPG, it was associated with age (r=0.228, p<0.05), waist to hip ratio (r=0.345, p<0.05), 24-h systolic BP (r=0.286, p<0.0001) and pack-years index (r=0.348, p<0.05), while fibrinogen was related to pack-years index (r=0.176, p<0.05) and daytime pulse pressure (r=0.185, p<0.005). Conclusions: Smoking in essential hypertension is accompanied by increased inflammatory processes, atherosclerosis progression and impairment of thrombosis/fibrinolysis system, as reflected by hs-crp, OPG, fibrinogen and PAI-1 levels. These findings may partially elucidate the complex mechanisms linking smoking with increased cardiovascular risk, in this setting. P2287 Aspirin use does not affect lipid efficacy of niacin extended-release treatment R. Thakkar 1,H.A.Punzi 2,M.H.Davidson 3,S.Krause 1, P. Jiang 1, C. Lovell 1, R.J. Padley 1. 1 Abbott, Abbott Park, United States of America; 2 Texas Woman s University, Dallas, United States of America; 3 University of Chicago, Chicago, United States of America Niacin is the most effective agent available for increasing high-density lipoprotein cholesterol (HDL-C), and has been shown to decrease low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and improve cardiovascular outcomes. However, some patients have difficulty tolerating niacin because of flushing, the most common adverse event associated with niacin therapy. Aspirin (ASA) is commonly used to decrease flushing, but its impact on the lipidaltering effects of niacin is not well-defined. The effect of ASA on the lipid efficacy of niacin extended-release (NER, Niaspan, Abbott) was evaluated in patients from a double-blind, placebo-controlled trial. Dyslipidemic patients were randomized (1:1:1) to 1 of 3 treatment groups: NER and ASA (NER + ASA); NER and ASA placebo (NER + ASA PBO); NER placebo and ASA placebo. NER or NER placebo was titrated as follows: 500 mg week 1, 1000 mg week 2, and 2000 mg weeks 3-6. Patients took ASA or ASA placebo 325 mg 30 minutes prior to NER or NER placebo dosing. Lipid efficacy was similar for patients treated with or without ASA after 6 weeks (Table). % Change from baseline to final visit n NER +ASA n NER + ASA PBO p-value Total-C a (1.5) (1.5) HDL-C a (2.2) (2.2) Non-HDL-C a (2.0) (2.0) LDL-C a (2.3) (2.2) TG b [-51.7, -8.7] [-52.0, -4.0] Lp(a) b [-35.1, 0.0] [-36.3, 0.0] a ANCOVA analysis of percent change from baseline to final visit: LS Mean (SE). b Non-parametric analysis of percent change from baseline to final visit: Median [Q1, Q3]. Over the course of the study, mean maximum flushing intensity decreased more (59% during week 6; 33% overall; p<0.001) in the group receiving NER + ASA than the group receiving NER + ASA PBO. Overall the adverse event (AE) profile was not higher in the NER + ASA group vs the NER + ASA PBO group, particularly, gastrointestinal AEs were experienced by 8.8% vs 12.2% of patients, respectively. This study quantitatively demonstrates that aspirin, when taken to reduce the severity of niacin extended-release-induced flushing in patients with dyslipidemia, does not compromise the lipid efficacy of niacin extended-release. P2288 Prediction of cardiovascular events by MMP-9 in elderly men T.W. Weiss, E.B. Furenes, M. Troseid, S. Solheim, I. Seljeflot, H. Arnesen. Oslo University Hospital (Ulleval), Oslo, Norway Purpose: Matrix metalloproteinase-9 (MMP-9) is thought to play a crucial role in the progression of atherosclerosis. Experimental data suggests interactions between MMPs and lipid metabolism, triglyceride hydrolysation and adipocyte maturation. We investigated the importance of MMP-9, its inhibitor tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and MMP-9/TIMP-1- ratio on cardiovascular events in elderly men at high risk for cardiovascular disease with respect to lipid levels. Methods: We prospectively studied 563 elderly men at high risk for cardiovascular disease. The variables were measured at inclusion and cardiovascular events were recorded over 3 years. MMP-9 levels were grouped by quartiles and related to cardiovascular event rate. Results: Cardiovascular events were recorded in 68 individuals. Higher circulating levels of MMP-9 (p = 0.046) but not triglycerides, total cholesterol, HDL, LDL or oxidised LDL were associated with cardiovascular events. Univariate regression revealed a significant association between higher MMP-9 levels (>75th percentile; 543 ng/ml) and cardiovascular events (OR 1.93; CI ; p = 0.016). When calculated in a multivariate model, the significance was lost (adjusted OR 1.59; CI ; p = 0.108). Analysing MMP-9 together with plasma lipid levels, it appeared that elevated MMP-9 levels are stronger predictors of cardiovascular events (OR 3.69; CI ; p=0.001) in individuals with hypertriglyceridaemia (>1.7 mmol/l). In a multivariate regression model, the prediction of cardiovascular events by MMP-9 was still significant in patients with hypertriglyceridaemia (adjusted OR 3.17; CI ; p = 0.009). Conclusions: MMP-9 is associated with cardiovascular events in elderly men. In the presence of hypertriglyceridaemia, elevated MMP-9 levels (>543 ng/ml) are a strong predictor of cardiovascular events. Even though not suitable as an independent marker for atherosclerosis, taking into account hypertriglyceridaemia, MMP-9 could be a useful tool to identify elderly men at particular high risk for cardiovascular events. POPULATION TRENDS P2289 Economic status and cardiovascular risk factors in rapidly developing country: Comparison between 1998 and 2005 in South Korea S.J. Ahn 1, S.Y. Jang 2,J.I.Park 3,S.Y.Park 1,S.J.Park 1,J.H.Cho 1, J.O. Jeong 1,Y.K.Kim 1,S.Y.Kim 1,Y.J.Kim 1. 1 National Police Hospital, Seoul, Korea, Republic of; 2 Seoul National University, Seoul, Korea, Republic of; 3 Seoul Veterans Hospital, Seoul, Korea, Republic of Purpose: South Korea is rapidly developing country which Gross National Income (GNI) pre capita in 1998 and 2005 were each 7,355 and 16,413 US dollars. This study examines the association between economic status and risk factors of CV disease in rapidly developing country, South Korea, and their changes according to economic growth. Methods: We analyzed data from the 1998 and 2005 Korea National Health and Nutrition Examination Survey (KNHANES). Total 7,353 and 5,192 persons of each KNHANES, who were 25 years and over and took health examination, were included. Risk factors included hypertension (HT), diabetes mellitus (DM), obesity, total cholesterol (TC), smoking and regular exercise (RE). Economic status was divided into quartiles, as equivalent income which is household income divided by the number of family in the same house. We compared odds ratios of CV risk factors in both 1998 and 2005 according to economic status. Results: 1) Using 1998 KNHANES data, for men, compared with the highest income quartile, those in the bottom quartile had odds ratios of 1.06 ( ) for HT, 1.32 ( ) for DM, 1.42 ( ) for smoking, 1.14 ( ) for TC, 0.61 ( ) for RE, 0.58 ( ) for obesity. 2) Using 2005 data, for men, those in the bottom quartile had odds ratios of 1.38 ( ) for HT, 0.61 ( ) for DM, 1.55 ( ) for smoking, 0.90 ( ) for TC, 0.49 ( ) for RE, 0.87 ( ) for obesity. 3) Using 1998 data, for women, those in bottom quartile had odds ratios of 1.12 ( ) for HT, 0.82 ( ) for DM, 2.13 ( ) for smoking, 1.00 ( ) for TC, 0.45 ( ) for RE, 0.96 ( ) for obesity, as compared with highest income quartile. 4) Using 2005 data, for women, those in bottom quartile had odds ratios of 1.35 ( ) for HT, 1.06 ( ) for DM, 2.55 ( ) for smoking, 0.90 ( ) for TC, 0.42 ( ) for RE, 1.53 ( ) for obesity. Conclusions: According to the increase of GNI per capita, more than double, some of the CV risk factors were changed in their inequalities. For men, inequality of HT and DM became clear but that of obesity was blunted with economic growth. RE and smoking shows more vivid changes of odds ratios. There were no significant inequalities in TC even no changes with economic growth. For women, Inequality of obesity became clear and smoking showed slightly increase of odds ratios. Inequality of RE continued according to increase of GNI per capita. There were no significant inequalities in HT, DM and TC. Further studies of the change of CV risk factors as larger economic growth are needed. P2290 The time course of risk of death following acute myocardial infarction and diabetes M.L. Norgaard 1, S.S. Andersen 1,T.K.Schramm 2, G.H. Gislason 2, F. Folke 1, M.L. Hansen 1,D.M.Bretler 1, L. Koeber 2,C.Torp- Pedersen 1. 1 Gentofte Hospital, Hellerup, Denmark; 2 Rigshospitalet (The Heart Centre), Copenhagen, Denmark Purpose: To examine long-term trends in risk of death in individuals with incident diabetes or incident myocardial infarction (MI) in a nationwide cohort of the Danish population (3.2 million individuals).

78 378 Population trends Methods: All residents in Denmark 30 years of age were followed for up to 10 years (1997 to 2006) by individual-level linkage of nationwide administrative registers. Patients either hospitalized with first-time myocardial infarction (MI) or patients with incident diabetes claiming a first prescription of a glucose lowering medication (GLM) were identified. Multivariable Cox proportional hazards model adjusted for age and gender was employed to analyse the risk of death over time in patients with diabetes compared with patients with a MI using the background population as a reference. Results: The total population included 3.2 million individuals. In the ten year period, patients were diagnosed with incident MI and were identified with incident diabetes. Patients with a MI had a particular high risk of death in the initial period. However over time the risk in MI patients declined and was surpassed by a higher risk in patients with diabetes after 5 years (Figure 1). P2292 Trends in cardiovascular risk factors in switzerland, : data from the national health surveys P. Marques-Vidal 1, A. Chiolero 2, F. Paccaud 1. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 McGill University, Québec, Canada Objective: to assess the prevalence and trends of the main cardiovascular risk factors (CVRF) in the adult population of Switzerland. Methods: data from the national health interview surveys conducted in 1992, 1997, 2002 and 2007 (28,692 men and 35,090 women overall) were used. Selfreported data on height, weight, smoking, high blood pressure, high cholesterol, diabetes, antihypertensive and hypolipidaemic drug treatment were used. Results: smoking decreased whereas the prevalence of the other CVRF increased during the study period (table, all trends p<0.001). The amount of cigarettes smoked per day decreased from 18±12 (mean±sd) in 1992 to 14±11 in 2007 in men, and from 14±10 to 11±9 in women (p<0.001). In subjects with high cholesterol, hypolipidaemic treatment increased from 18% in 1997 to 40% in 2007 (p<0.001), while in hypertensive subjects antihypertensive treatment increased from 52% to 64% (p<0.001). -: not available. Trends in CVD risk factors Figure 1 Conclusions: Acute myocardial infarction being an acute illness has a high shorttime risk of death, whereas diabetes being a chronic disease has a high long-term risk, exceeding that of MI after 5 years. P2291 Control of dyslipidemia in western switzerland: a long way to go P. Marques-Vidal 1, M. Firmann 1,F.Paccaud 1, V. Mooser 2, N. Rodondi 3, G. Waeber 1, P. Vollenweider 1. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 GlaxoSmithKline, Philadelphia, United States of America; 3 Polyclinique Médicale Universitaire (PMU), Lausanne, Switzerland Objective: assess the prevalence, treatment and control levels of dyslipidaemia in Lausanne, Switzerland. Methods: population based study of 3,238 women and 2,846 men aged Dyslipidaemia prevalence, treatment and control were defined according to PROCAM guidelines adapted to Switzerland. Results: 35% of the sample had dyslipidaemia, of which 33% were treated, and 57% of those treated were adequately controlled (23% near control ), see table. Among 710 subjects with personal history of CVD or diabetes, 89% had dyslipidaemia, of which 44% and 21% were treated and adequately controlled, respectively (11% near control ). On multivariate analysis, treatment was positively related with age, body mass index (p for trend <0.001), alcohol consumption (p for trend <0.05), family history of MI (OR=1.47, ) and personal history of hypertension (OR=2.38, ), CVD or diabetes (OR=3.93, ), and negatively related with female gender (OR=0.70, ) and educational level (p for trend <0.05). Adequate control of lipid levels was negatively related with body mass index and alcohol drinking (p for trend <0.05). Dyslipidaemia Treated Control among treated Poor control Near control In control All subjects (n=6,084) 2,111 (34.7) 692 (32.8) 137 (19.8) 161 (23.3) 394 (56.9) Gender Men (n=2,846) 1,129 (39.7) 401 (35.5) 81 (20.2) 89 (22.2) 231 (57.6) Women (n=3,238) 982 (30.3) 291 (29.6) 56 (19.3) 72 (24.7) 163 (56.0) Test 58.35*** 8.25** 0.62 NS Risk category (adapted PROCAM) High (n=1,109) 1,029 (92.8) 322 (31.3) 110 (34.2) 78 (24.2) 134 (41.6) Intermediate (n=806) 680 (84.4) 122 (17.9) 20 (16.4) 50 (41.0) 52 (42.6) Low (n=699) 244 (19.4) 157 (64.3) 7 (4.5) 24 (15.3) 126 (80.2) Very low (n=3,470) 158 (5.4) 91 (57.6) 0 (0.0) 9 (9.9) 82 (90.1) Test 3920*** 51.41*** *** Results are expressed as number of subjects and (percentage). Statistical analysis by chi-square: NS, not significant; **p<0.01; ***p< Conclusion: circa one third of the population presents with dyslipidaemia, one third of dyslipidaemic subjects is treated and one half of treated subjects is adequately controlled. Implementation of guidelines is urgently needed Men 6,575 5,537 8,563 8,017 Current smoking (%) Hypertension (%) High cholesterol (%) Obesity (%) Diabetes (%) Women 7,946 6,937 10,343 9,862 Current smoking (%) Hypertension (%) High cholesterol (%) Obesity (%) Diabetes (%) Results are expressed in percentages. Conclusion: the decrease in smoking is encouraging; the increase in hypertension and high cholesterol might reflect more frequent screening and lower threshold for treatment. The increase of obesity and diabetes is of concern. P2293 Change in medical treatment of European patients included in the REACH registry: comparison between the disease territories C. Suarez 1,U.Zeymer 2, T. Limbourg 2, J. Rother 3, P.G. Steg 4, D.L. Bhatt 5 on behalf of REACH Registry investigators. 1 Hospital Universitario de la Princesa, Madrid, Spain; 2 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Johannes Wesling Klinikum Minden, Minden, Germany; 4 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 5 Brigham and Women s Hospital, Boston, United States of America Purpose: The REACH Registry is an international prospective registry of outpatients with multiple risk factors for atherothrombotic events or with symptomatic atherothrombosis, with 67,888 patients enrolled in 44 countries worldwide. Baseline REACH data showed a substantial gap between guideline recommendations and clinical practice. Methods: We compared medication (antithrombotic agents, lipid lowering agents [LLA], antihypertensive agents [AHA] and antidiabetic agents [ADA]) use at baseline and at 2-year follow-up in European REACH patients, using McNemar s test. Disease territory groups were compared using the chi-squared test. Results: Of patients enrolled in the REACH Registry in Europe, completed the 2-year follow-up suffered single arterial disease (CAD, 65.1%; CVD, 23.9% & PAD, 10.9%). The use of all medications increased, except for 1 AHA in hypertensives, ADAs in diabetics, other antiplatelet agents in CAD, and ACE-I/ARBs in CVD patients. At both baseline and at two years, there were differences between territories in the use of each medication (all P<0.0001, except 1 ADA [P<0.01]). Medication use in REACH Patients: Europe CAD alone (n, 9308) CVD alone (n, 3421) PAD alone (n, 1561) Baseline (%) 24m (%) Baseline (%) 24m (%) Baseline (%) 24m (%) ASA Other antiplatelet agents * Oral anticoagulants antithrombotic agents * Statins Other LLA * 1 LLA ACE/I ARBs (%) Hypertensive patients with 1 AHA (%) Hypertensive patients with 3 AHA (%) Diabetic patients with 1 ADA (%) * *P<0.05, P<0.01, P<0.001, P<0.0001; Baseline vs 24 months.

79 Population trends 379 Conclusions: The improvement in medical treatment of single arterial disease was greatest in PAD patients. However, secondary prevention therapy is still suboptimal, particularly for PAD. This improvement may be due to increasing adherence to guidelines, but an educational effect of REACH is also likely. Conclusions: The occurence of CAD in PHC users in Portugal is strongly associated with cardiovascular risk factors, namely with HT, DM and obesity. Moreover, even after correction for all variables under analysis, MS remained a significant risk factor for CAD. P2294 Ireland Improved survival of incident dialysis patients with coronary disease in the United States: A.N. Nealon 1, I. Yousif 1, C.A.M. Wall 2, A.G. Stack 1. 1 Regional Kidney Centre, Letterkenny General Hospital, Letterkenny, Ireland; 2 Meath and Adelaide Hospitals, Trinity College Dublin, Dublin, Purpose: Coronary Disease (CAD) is a major risk factor for death in dialysis patients. Whether improved end-stage kidney disease care (ESKD) has impacted on annual mortality rates from coronary disease in successive cohorts is unclear. Methods: We hypothesized that improved ESKD care has led to improved coronary management and reduced mortality for patients with known coronary disease at dialysis onset. Data on all new ESKD patients between were obtained from the US Renal Data System and linked with all-cause mortality. Patients (N=1,003,305) were followed until 4/10/2006. Annual Mortality was calculated for those with and without coronary disease by year of incidence from Cox regression was used to estimate 1-year and 2-year mortality hazard (RR) ratios for each calendar year (with 2000 as referent) in sequentially adjusted models. The final multivariable model was adjusted for demographic, socioeconomic, comorbid and laboratory markers (n=21). Analysis were conducted using SAS V Conclusions: Although coronary disease remains a common diagnosis at dialysis initiation, mortality rates in these patients have declined from Improved survival in successive cohorts suggests improved coronary disease management in this high-risk population. P2295 Prevalence and risk factors for coronary artery disease in the primary health care. Insights of the VALSIM study M.M. Fiuza 1,N.Cortez-Dias 1,S.Martins 1,A.Belo 2. 1 Hospital Santa Maria, Lisbon, Portugal; 2 Portuguese Society of Cardiology, Lisbon, Portugal Purpose: To determine the prevalence of coronary artery disease (CAD) and to identify its association with gender, age, body mass index (BMI), waist circumference (WC), metabolic syndrome (MS), hypertension (HT) and diabetes mellitus (DM) in Primary Health Care (PHC) users in Portugal. Methods: Cross-sectional study performed in PHC setting, involving 721 general practitioners (GP) representative of all regions of Portugal. The first two adult patients scheduled for an appointment on a given day were invited to participate, irrespective of the reason for consultation. The inclusion criterion was the existence of laboratory results for HDL cholesterol, triglycerides and fasting glucose performed up to one year prior to the consultation. A questionnaire on sociodemographic, clinical and laboratory data was completed by the GP. WC and BMI were measured and two blood pressure (BP) measurements were obtained after a 5-minute seated rest. CAD was defined by angina pectoris or previous myocardial infarction; DM by fast glycaemia 126mg/dL or antidiabetic agents; HT by previous diagnosis or BP 140/90mmHg; and MS by NCEP-ATP III criteria. Logistic regression multivariate analysis was used to assess the association of age, BMI, WC, MS, HT and DM with the occurrence of CAD. Results: The study included 16,856 individuals (58.1±15.1 years; 61.6% women). The prevalence of CAD adjusted for gender and age was 5.1%, higher in men (M: 5.8%; W: 4.6%) and increased with age. The variable with the strongest link to CAD was age, being 76 times more frequent in individuals aged 80 years than in those aged years. Although the prevalence of CAD was 71% higher in men (OR: 1.71; 95%CI ), male gender ceased to be an independent risk factor when WC, HT and DM were introduced into the model. After correction for these variables, CAD prevalence was higher in women (OR: 1.40; 95%CI ), 2.5 times higher in those with HT, 42% higher in those with DM. Risk for CAD increased with BMI, reaching statistical significance for severe obesity (OR: 2.5; 95%CI ). Even after correction for all variables under analysis, MS remained a significant factor (OR:1.16; 95%CI ), but not WC. Based on the variables analysed in the model predicting occurrence of CAD, the area under the ROC curve was 0.76 (95%CI ; p<0.001). P2296 Young adults positively changed their cardiovascular risk over 16 years - a prospective registry with good news P.J. Sousa 1, M. Miranda 2, B. Monteiro 1, J. Ferreira 3, M. Mendes 3, J.C. Monge 1, H. Nunes 1, J. Varandas 1. 1 Centro de Medicina Aeronautica - FAP, Lisbon, Portugal; 2 Hospital de Curry Cabral, Lisbon, Portugal; 3 Hospital de Santa Cruz - CHLO, Lisbon, Portugal Purpose: Cardiovascular (CV) disease is the leading cause of death worldwide. Abnormalities in blood pressure (BP), lipid profile, smoking habits and body mass index (BMI) can lead to atherosclerosis manifestations more than 30 years later. The purpose of this registry is to study the changes of CV risk in similar samples of healthy young adults over a period of 16 years. Methods: Prospective registry of applicants to military careers in 1991/2 (G1), 1996/7 (G2), 2001/2 (G3) and 2006/7 (G4). Temporal evolution of CV risk factors and CV risk at 65 years (calculated using the Heart Score and Framingham Score) were assessed. Results: The registry included 923 applicants, 94% male gender, with mean age of 19.2±2.3 years and BMI 22.4±2.5. G2 was slightly older (19.8±3.0;p=0.04,IC:0.95) and no differences were found on BMI and percentage of male gender. Excepting mean BP, which raised over the registry period (p<0.05,ic:0.05: G1 vs others), there was an improvement in CV risk: Lower total cholesterol (p<0.05,ic:0.05: G4 vs others) and LDL cholesterol with elevation of HDL cholesterol (p<0.05,ic:0.05: G1 vs G2 and G2 vs G4) Lower fasting glucose from G1 to G3 with a slight increase thereafter (p<0.05,ic:0.05: G1 vs others and consecutive groups) Lower ratio of smokers (p<0.05,ic:0.05: G4 vs others). Risk scores raised initially (p<0.05,ic:0.05: G1 vs G3 in Heart Score) and decreased afterwards (p<0.05,ic:0.05: G2 vs G3 and G3 vs G4 in Framingham Score). Temporal evolution of CV risk factors 1991/2 1996/7 2001/2 2006/07 All population (n=190) (n=133) (n=258) (n=342) (N=923) SBP (mmhg) 122.3± ± ± ± ±11.7 Total Cholesterol (mg/dl) 169.5± ± ± ± ±30.9 LDL (mg/dl) 116.1± ± ± ± ±29.2 HDL (mg/dl) 46.1± ± ± ± ±10.5 Fast Glucose (mg/dl) 87.2± ± ± ± ±7.8 Smokers (%) Heart Score 3.0± ± ± ± ±1.4 Framingham Score 12.9± ± ± ± ±5.1 Mean ± Standard Deviation. Conclusions: In these 16 years, there was an improvement in global CV risk and individual CV risk factors, except for BP levels, which suffered an increase and demands specific measures. Global CV risk remains important, justifying new control strategies. P2297 Cardiovascular profile of years old adolescents T.M.R. Rocha, E. Paixao, A.C. Alves, V. Francisco, A.M. Medeiros, T. Santos, S. Silva, M. Bourbon. Instituto Nacional de Saude Dr Ricardo Jorge, Lisbon, Portugal Health promotion and cardiovascular disease (CVD) prevention should start in childhood and not only in adult age. It is difficult to motivate young people to have healthy life styles and that depends partially on their risk perception. The aim of this study was to evaluate the cardiovascular risk profile of high school students More than 800 adolescents have been studied to determine the prevalence of cardiovascular risk factors in this population. Until now the results from 542 students, age 16,2±0.9 yrs (52% male), from 6 different schools in the Lisbon area have been analyzed. Decimal balance/metric scale, digital sphygmomanometer and auto-analyzers for fasting biochemical determination were used to Abstract P2294 Table 1. Mortality Trends by Calendar Year Year Coronary disease prevalence (%) Annual mortality (%) With coronary disease (%) Without coronary disease (%) Year Relative Risk Death Unadjusted 0.91** 0.95** (ref) ** 0.92** Adjusted all factors ** 1.04* (ref) *** 0.90*** 2-Year Relative Risk Death Unadjusted 0.95** (ref) *** 0.92*** Adjusted all factors ** 1.07** 1.05** 1.04* 1.00 (ref) *** 0.89*** ***P<0.0001, **P<0.001, *P<0.01. Ref = referent group year.

80 380 Population trends determine/measure: age, sex, smoking habits, diabetes, BMI, blood pressure, cholesterol, triglycerides, and blood glucose. Absolute risk and relative risk were calculated by the Score System. Statistic analysis tested differences using Pearson Chi-Square and Fisher s Exact Test. According to the European Cardiology Society and NCTP consensual cut-offs for the ages in question, the results obtained were as follows: 29,5% with hypercholesterolaemia (>75 percentile (170mg/dl), being 8,7% >95 percentile (190mg/dl)), 14,5% overweight/obese (BMI>25), 13% smokers, 12% with potential hypertension (>95 percentile but 30% had >90 percentile or >120/80), 12% with blood glucose above 100 mg/dl and 10% with hypertryceridaemia (>95 percentile (150 mg/dl)). Gender differences are significant (p<0.001) for triglycerides and cholesterol, higher in girls; BMI and blood pressure higher in boys. About 33% presented 1 risk factor, 10% had 2 and 3% presented 3 cardiovascular risk factors. Absolute risk did not exceed 1%. Projecting risk estimation for age 60, did not reach 5%, nevertheless levels of 2%, 3% and 4% were estimated, respectively in 34%, 5% and 1% of participants. Relative risk of 2, 3 and 4 was calculated on 25%, 3% and 0.2%. In boys, risk was significantly higher (p<0.001) in either assessment. The prevalence of characteristics associated to CVD risk in young students is high, predominantly in males: Since relative risk is higher it should be a better option in the attempt to motivate behavior changes. It is essential that health promotion namely cardiovascular prevention, start in childhood to prevent that our adolescents reach adult age already with an increased cardiovascular risk. The adoption of healthy life styles and the early detection of adolescents at risk should be the priority of heath policies. These measures will hopefully decrease the mortality rates in adult age. P2298 Trends in Q-wave myocardial infarction case-fatality from 1978 to 2006 C. Sala 1,M.Grau 2, J. Vila 2,R.Masia 3, J. Aboal 3, A. Sureda 3, J. Marrugat 2,J.Sala 3,R.Elosua 2 on behalf of REGICOR Study. 1 ABS Manresa IV, Manresa, Spain; 2 Institut Municipal d Investigació Mèdica, Barcelona, Spain; 3 Hospital Universitari Josep Trueta, Girona, Spain Purpose: To analyze the trends in first Q-wave myocardial infarction (MI) casefatality from 1978 to 2006 and determine the variables related to these changes. Methods: Population-based hospital registry including patients with first Q-wave MI aged 25 to 74 years admitted between 1978 and Sociodemographic and clinical characteristics (medical history, severity variables) along with treatments used during hospital stay were recorded. Thirty-day case-fatality was also collected. Seven 4-year periods were analyzed. We used logistic regression for the multivariate analysis. Results: The study included 3845 patients. In the 29-year period, 30-day casefatality was 9.8% and showed a decreasing trend over time (p for trend<0.001). Age, sex (women), diabetes, hypertension, anterior MI, and KillipIII-IVwere associated with higher case-fatality, whereas smoking, reperfusion, beta-blockers and aspirin use were associated with lower case-fatality. The adjusted associations between the defined periods and case-fatality are shown in the table. Table 1. Crude case-fatality and multivariate adjusted ORs of case-fatality for different periods Crude case-fatality Model 1 Model 2 Model 3 (%) OR (95% CI) OR (95% CI) OR (95% CI) ( ) 0.9 ( ) 0.9 ( ) ( ) 0.5 ( ) 0.7 ( ) ( ) 0.4 ( ) 1.1 ( ) ( ) 0.3 ( ) 1.1 ( ) ( ) 0.2 ( ) 0.8 ( ) ( ) 0.1 ( ) 0.7 ( ) Conclusion: A dramatic decrease in 30-day case-fatality occurred over this 29- year period, and was mainly related to the use of aspirin and beta-blockers. P2299 Increased risk of acute myocardial infarction in patients with epilepsy: a nationwide study J.B. Olesen 1, P.R. Hansen 1, G.H. Gislason 2, C. Torp-Pedersen 1, P. Weeke 1,D.M.Bretler 1, C.H. Jorgensen 1,S.Z.Abildstrom 3. 1 Department of Cardiology, University Hospital Gentofte, Copenhagen, Denmark; 2 Department of Cardiology, University Hospital Rigshospitalet, Copenhagen, Denmark; 3 Cardiovascular Research Unit, Department of Internal Medicine, University Hospital Glostrup, Copenhagen, Denmark Purpose: Patients with epilepsy have increased risk of acute myocardial infarction (AMI), but it is unclear whether this is related to a common pathophysiological substrate, i.e., atherothrombotic disease. We investigated this association in a nationwide study. Methods: A cohort consisting of the total Danish population 10 year on January 1, 1997 was examined by individual-level linkage of nationwide registries. Patients with epilepsy were identified by code at discharge. The risk of AMI associated with epilepsy was estimated by Cox proportional-hazard analysis, adjusted for sex, age, prior AMI or cerebrovascular disease, concomitant medication, socioeconomic status, and comorbidity. Results: We included 4,614,807 individuals in the cohort, of which 54,693 (1.2%) had epilepsy. Previous cerebrovascular disease was identified in 85,073 (1.8%) patients, from these 6091 (7.2%) had epilepsy. Their mean age was 44.2 years (standard deviation: 19.9) and 49.1% were men. During the 10 year follow-up period ( ), 175,984 (3.8%) subjects experienced an AMI. The Cox regression analyses were stratified for cerebrovascular disease because of a significant interaction with epilepsy. In patients with cerebrovascular disease, we observed no association between epilepsy and AMI (hazard ratio [HR] 0.98; 95% confidence interval [CI] ). In patients without cerebrovascular disease, epilepsy was associated with increased risk of AMI (HR 1.20; CI ). Conclusions: Epilepsy is associated with increased risk of AMI in patients without previous cerebrovascular disease. The results indicate an association between epilepsy and AMI independent of a shared atherothrombotic etiology. Further investigations of cardiac risk factors among patients with epilepsy are warranted. P2300 Trends in management and outcome of acute myocardial infarction in Portugal, Switzerland and the United States P. Marques-Vidal 1, N. Rodondi 2,C.MatiasDias 3,F.Paccaud 1. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 Polyclinique Médicale Universitaire (PMU), Lausanne, Switzerland; 3 National Institute of Health (INSA), Lisbon, Portugal Background: little information exists whether trends in thrombolysis, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are similar between countries. This study assessed trends in thrombolysis, CABG, PCI and outcome of acute myocardial infarction (AMI) in Portugal, Switzerland and the US. Methods: trends in coronary interventions and 7-day in-hospital mortality rates were assessed for each country by analysis of national hospital discharge data between 1998 and 2003 (67,489 patients in Portugal, 62,067 in Switzerland and 5,680,241 in the US). Results: the number of subjects admitted with AMI increased by 4% in the US, 40% in Portugal and 50% in Switzerland. In all countries, mean age at admission increased for both genders. Average length of stay decreased in Portugal and Switzerland, whereas no clinically significant decrease was found in the US. PCI increased in Portugal (9.5% to 21.7%), Switzerland (8.9% to 26.8%) and the US (20.5% to 24.7%). Thrombolysis increased in Portugal (1.5% to 10.3%) but less in Switzerland (0.5% to 3.9%) or the US (1.9% to 2.1%). CABG decreased significantly in the US (9.6% to 6.7%), with a nonsignificant decrease in Portugal (2.1% to 1.6%) or Switzerland (4.5% to 2.9%). Unadjusted seven-day in-hospital mortality rates decreased in Portugal (12.9% to 11.5%) and the US (11.1% to 10.3%), but increased in Switzerland (7.6% to 9.8%). Conclusions: the number of subjects with AMI increased considerably in Portugal and Switzerland. Management and outcome of patients with AMI also changed substantially between 1998 and P2301 Efficacy evaluation of the national program of arterial hypertension monitoring A.D. Deev, S.A. Shalnova, V.V. Konstantinov on behalf of study participants. State Research Center for Preventive Medicine, Moscow, Russian Federation Objectives: The National Program of Arterial Hypertension (AH) Monitoring in Russia was established in It is research-practical program based of stratified random sample of households on the territorial plot of existing health care system. The Program design consists in 3 cross-sectional independent screenings in participating Region (42 Regions of RF are participating) in 4-5 year interval with mortality follow up of subjects from the 1st screening. To the end of 2008 two Regions performed 2 screenings and additional 4 all 3 screenings which were recognized as representative. Efficacy variables for those 6 Regions are presented. Methods: Efficacy variables are: hypertension prevalence (HP), awareness of hypertension (AWH), treatment of AH (TH) and treatment efficacy (TE) together with usage of AH drug classes (ACE inhibitors, beta-blockers (BB), Ca-antagonists (CAA), diuretics (DIU), still rare used drugs (angiotensin receptor antagonists and alpha-blockers) and other antihypertensive drugs (OAHD)). All data are ageadjusted with direct standardization (euro-standard). Results: Data on subjects were analyzed ( on the 1st screening, on the 2nd, 6858 on the 3rd). HP did not changed in women to the 3rd screening (46.3±0.5 vs. 46.7±0.6) and slightly decreased in men (41.7±0.9 vs. 39,7±1.1, p<0.08). At the same time AWH was increased in both sexes: (71.9±1.6 vs. 86.1±1.6, p< in men and 73.7±1.5 vs. 88.2±1.6, p< in women). TH was also increased (58.1±1.5 vs. 71.2±2.2, p< in men and 71.1±1.5 vs. 80.5±1.9, p< in women) together with TE (18.7±1.9 vs. 27.0±2.8, p<0.01 in men and 26.1±1.9 vs. 35.2±2.5, p<0.01 in women). This probably occurs due to increased ACE inhibitors prescription (intake) on 26.0%, DIU on 19.4%, still rare used new drugs on 29.0% and BB - on 27.2% in men (no trend in women) while OAHD prescription decreased 30.1%. For TH women the number of prescribed drugs were decreased (1.90±.03 vs. 1.77±.05,p<0.01). Additionally among hypertensives systolic BP mean dropped

81 Population trends / Coronary surgery Valvular heart disease mm Hg(p<0.0001), diastolic BP 2.5 mm Hg (p<0.0001), total cholesterol level 0,6 mmol/l (p<0.0001), stroke prevalence 4,3 percent (p<0.0001), retinopathy 3,4 percent (p<0.0001), kidney diseases 5.5 percent (p<0.0001). At the same time CHD prevalence among hypertensives increased 3.0 percent (p<0.01), diabetes mellitus percent (p<0.01) while left ventricular hypertrophy and creatinemia prevalence did not changed significantly. Conclusion: the data demonstrated slow but steady improvement in situation with AH for Regions which are participating in the Program successfully. P2302 Russian multicentral epidemiological survey: morbidity, mortality, quality of diagnostics and management of acute CHD (RESONANCE) S.A. Boytsov 1, N.N. Nikulina 2, S.S. Yakushin 2,R.A.Liferov 3, G.I. Furmenko 4, S.A. Akinina 5 on behalf of RESONANCE study group. 1 Russian Cardiology Research-and-Production Complex, Moscow, Russian Federation; 2 Academician I.P.Pavlov Ryazan State Medical University, Ryazan, Russian Federation; 3 Ryazan Regional Clinical Cardiology Center, Ryazan, Russian Federation; 4 Voronezh State Medical Academy, Voronezh, Russian Federation; 5 Region Clinical Hospital, Khanty-Mansiysk, Russian Federation Purpose: Acute coronary heart disease (CHD) represents the most common cause of morbidity and mortality in the world. Relative epidemiologic data for Russia are sparse. The aim of the study was to determine the acute CHD incidence and mortality, especially out-of-hospital cases. Methods: The fatal and nonfatal cases of acute CHD were actively revealed among representational cohort ( population, 76.4% of them 18 years) of three Russian regions for 12 months by review of symptoms, medical out-patient cards, hospital medical histories, ambulance reports and in cases of death - also by using of civil status acts, autopsy reports. Then refined data has been compared with official diagnosis and causes of death in death certification. Results: According to official data mortality from acute CHD among studied population amounted per male and per female. The results of acute CHD-induced deaths detection demonstrated that true death-rate from acute CHD exceeded officially registered level at the least in 2.13 times for males ( per , p<0.001) and in 2.28 times for female ( per , p<0.001). All unregistered cases of fatal acute CHD were revealed among out-of-hospital deaths. Thus, out-of-hospital mortality from acute CHD increased from 70.67% to 87.98% (p<0.01) for male patients and from 39.58% to 78.68% (p<0.001) for female patients. The incidence of acute CHD increased by 26% for male population (from to per , p<0.01) and by 32% for female population (from to per , p<0.01). Conclusions: The study results revealed detestability of acute CHD as cause of deaths, especially in out-of-hospital death cases. As a consequence, a realistic acute CHD incidence is higher than officially registered value. CORONARY SURGERY VALVULAR HEART DISEASE P2303 Prosthesis patient mismatch after mitral valve replacement is associated with persistent pulmonary arterial hypertension A. Tugcu 1,O.Kose 1, O. Yildirimturk 1,Y.Tayyareci 1,V.Aytekin 2, I.C.C. Demiroglu 1,S.Aytekin 2. 1 Florence Nightingale Hospital, Istanbul, Turkey; 2 T.C. Istanbul Bilim University, Florence Nightingale Hospital, Istanbul, Turkey Purpose: We aimed to determine the impact of prosthesis patient mismatch (PPM) on postoperative pulmonary arterial (PA) pressure after mitral valve replacement (MVR). Methods: Hundred patients who underwent isolated MVR with a preserved left ventricular ejection fraction were enrolled. Mitral valve effective orifice area (EOA) was determined by continuity equation and indexed for body surface area. Because atrioventricular compliance (Cn) has been shown to influence PA pressure in patients with mitral stenosis, it was also determined by echo-doppler measurements. Results: Thirty-three patients (33%) had PPM defined as indexed EOA 1.2cm 2 /m 2. Postoperative systolic PA pressure was significantly higher in patients Figure 1 with PPM compared to patients with no PPM (Figure 1). Patients with an Cn 4 ml/mm Hg had a significantly higher (p < 0.001) postoperative systolic PA pressure (37.2±8.8 mmhg) compared to those with Cn > 4.0 ml/mm Hg (31.6±7.4 mm Hg). Postoperative systolic PA pressure levels correlated well with indexed EOA (r=-0.537, p<0.001), mean transprosthetic gradient (r=0.433, p<0.001) and Cn (r=-0.422, p<0.001). In multiple stepwise linear regression analysis, the independent determinants of postoperative PA hypertension were: indexed EOA (β=-0.430, p<0.001), age (β=0.249, p=0.01), Cn (β=-0.197, p=0.025) and atrial fibrillation (β=0.186, p=0.013). An indexed EOA 1.2cm 2 /m 2 had a sensitivity of 89% and a specificity of 84% to predict PA hypertension. Conclusion: PPM after MVR is not uncommon. It is associated with persistent postoperative PA hypertension. In order to minimize the risk of PPM, a systematic estimation of the indexed EOA and planning a specific surgical strategy targeted towards each patient should be accomplished before the operation. P2304 Speckle-tracking correlates better than traditional parameters with the long-term systolic function decrease after mitral valve replacement J.A. De Agustin Loeches, J. Zamorano, L. Perez De Isla, C. Almeria, J.L. Rodrigo, A. Aubele, D. Herrera, C. Fernandez-Golfin, P. Marcos-Alberca, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Background and aim: The long-term development of left ventricular (LV) dysfunction after mitral valve replacement is frequent in patients with chronic severe mitral regurgitation (MR). Strain and strain rate analysis have emerged, as quantitative variables to accurately estimate the myocardial contractility. Our aim was to compare preoperative strain and strain rate obtained by 2D-echo based speckletracking with the traditional parameters to predict postoperative LV dysfunction after mitral valve replacement. Methods: Thirty four consecutive patients with chronic severe MR scheduled for mitral valve replacement were prospectively enrolled. Preoperative longitudinal strain (S) and strain-rate (SR) at the level of the interventricular septum (IVS) was performed by speckle-tracking. LV dimensions and ejection fraction (LVEF) was assessed by 3D-echocardiography. Preoperative examinations were performed within 48 hours before surgery, and postoperative ones 6 months after surgery. Results: Mean age of patients was 59.9±11.3 years and ten patients (29.4%) were men. Longitudinal Strain rate at the level of the basal IVS showed the better correlation with the LVEF decrease (see table). LV dimensions and Dp/dt also correlated well. Nevertheless, preoperative LVEF had not correlation with the LVEF decrease. Table 1 r p EDV (3D) ESV (3D) LVEF (3D) Dp/Dt Long. S basal IVS Long. SR basal IVS Long. S mid IVS Long. SR mid IVS Strain and strain rate obtained by 2D-echo based speckle-tracking compared with the traditional parameters to predict postoperative LV dysfunction. Conclusions: Longitudinal speckle-tracking-derived strain and strain-rate of IVS allows us to accurately detect early abnormalities of LV contractile function. This new tool may assist the clinician in the optimal timing of surgery in patients with chronic severe MR. P2305 Clinical and echocardiographic long term follow up of patients undergoing Ross procedure according to the predominant aortic valve lesion M. Delgado Ortega, M. Ruiz Ortiz, M. Mesa Rubio, E. Romo Penas, F. Toledano Delgado, M.C. Leon Del Pino, M. Anguita Sanchez, J.C. Castillo Dominguez, J. Casares Mediavilla, J. Suarez De Lezo Cruz Conde. Hospital Universitario Reina Sofia, Cordoba, Spain Aim: To study the clinical and echocardiographic long-term follow up of patients (pts) undergoing Ross procedure according to the predominant aortic valve lesion. Patients and Methods: We analyzed 79 pts who underwent Ross procedure since November/97 until January/09. Two subgroups were distinguished: a) Aortic Stenosis (AS) (n = 25, 32%) b) Aortic Regurgitation (AR) (n = 54, 69%). All echocardiographic measures were standarized by body surface area. Results: No significant difference in age was found between groups (29±13 years in AS versus 30±11 in AR). In AR group males predominated (77% versus 40%, p <0.05). The etiology of the lesion was congenital in 92% of AS compared to 61% of AR group (p <0.05). Echocardiographic parameters of both groups and their evolution after surgery are detailed in Table 1. After 67±32 months of clinical follow-up there was no significant difference in the need of autograft surgery between both groups (5% reoperations in AS versus 6.5% in AR). At least moderate regurgitation of the autograft was detected in 10% of pts with AS versus 13% in the AR group (p=0.78). Five percent of pts suffered an autograft endo-

82 382 Coronary surgery Valvular heart disease Table 1 AS p value AR p value p value pre follow pre follow AR vs AR vs AS pre AS follow Diastolic diameter, mm/m Sistolic diameter, mm/m < Septum, mm/m < Posterior wall, mm/m Ejection fraction, % < Mean aortic gradient, mmhg < Aortic ring diameter, mm/m AS: Aortic stenosis. AR: Aortic regurgitation. carditis in AS group compared to 2% in AR group (p =0.51). Most patients remained asymptomatic during follow-up: 94% in AS group and 93% in AR group (p =0.83). Conclusions: 1)Patients with aortic regurgitation as predominant aortic lesion have a worse ejection fraction and larger left ventricular diameters, which normalized after surgery. 2)Most of the pts who underwent Ross procedure are asymptomatic in long-term follow up. 3) Regurgitation of the autograft may appear over time, although the need for reoperation is low, regardless the type of valvular lesion. P2306 Autograft failure in the follow-up of Ross operation: a descriptive study and predictive factors in a prospective series M. Ruiz Ortiz, M. Delgado Ortega, D. Mesa Rubio, E. Romo Penas, F. Toledano, C. Leon, A. Lopez Granados, J.M. Arizon Del Prado, P. Alados Arboledas, J. Suarez De Lezo. Hospital Universitario Reina Sofia, Cordoba, Spain Purpose: Failure of the autograft in aortic position is one of the complications that can appear in the follow-up of patients after Ross operation. Our aim is to analyze the incidence of this complication in our series and to study factors associated with it. Methods: Out of 102 patients consecutively operated of Ross intervention at our centre between November 1997 and January 2009, we selected 83 patients (age 32±11 years, range 6 to 54 years, 60 males -72%) who were discharged without significant autograft regurgitation and had at least one follow-up echocardiogram. Autograft failure was defined as the presence of at least moderate regurgitation by echocardiography, judged according to the guidelines of the American Society of Echocardiography. We studied the frequency of this complication and tried to find predictive factors. Results: After 56±36 months of follow-up, 8 patients (9.6%) developed autograft failure: four severe regurgitation (three of whom underwent valve replacement), one moderate-severe insufficiency and three moderate regurgitation. The probability of autograft failure-free survival was 99% at one year and 90% at 5 years. In univariate analysis, autograft failure was associated with operation in the first 6 months of the learning curve (42% versus 4%, p <0.001), aetiology other than congenital (19% versus 4% in congenital aetiology, p = 0.024), a lower ejection fraction (60±7% versus 68±10%, p = 0.018) and a larger pulmonary annulus size -normalized by body surface area- (15±1 mm/m 2 versus 13±2 mm/m 2,p= 0.015) as measured by the echocardiogram prior to surgery. Patients with autograft failure presented larger autograft annulus size normalized by body surface area- (17±1 mm/m 2 versus 14±4 mm/m 2 ) in the last follow-up echocardiogram, but this difference did not reach statistical significance (p=0.13). In multivariate analysis, only operation in the first period of the learning curve (HR 9.1, 95% CI , p = 0.021) and larger normalized pulmonary annulus size (HR 1.4, 95% CI , p = 0.04) were independent predictors of this complication. Conclusions: Late autograft failure presents a low incidence after Ross procedure. In our experience, intervention in the first period of the learning curve and a larger pulmonary annulus size were independent predictors of this complication. P2307 When repair, when rather replacement for chronic ischemic mitral regurgitation-medium term results of undersized ring annuloplasty with echocardiographic follow-up D. Puszczewicz, R. Przybylski, S.Z. Pawlak, T. Niklewski, J. Pacholewicz, T. Kukulski, A. Kowalczuk, M. Zembala. Silesian Center for Heart Disease, Zabrze, Poland Background: Mitral valve annuloplasty is the standard surgical technique for the management of chronic ischemic mitral regurgitation (IMR). However up to 1/3 of patients develop recurrent IMR after surgical annuloplasty. Material and Methods: In a series of consecutive 284 patients with CAD undergoing CABG with mitral valve repair, first 134 were evaluated: 90 male (67,2%), mean age 63,1, mean EuroSCORE 6,6±2,6 and 106 pts with history of acute MI. Transthoracic echocardiography (TTE) with quantitative Doppler measurements revelaled moderate MR in 62 pts (46,3%) and severe in 72 pts (53,7%). Undersized ring was implanted in all pts (Ring diameter ranged 24-30mm, but sizes 26, 27, 28 were used in 93,7% of pts). Patients were observed for 4-20 months (Median 7,2±3,0). TTE was performed in all pts. Results: Severe MR occured in 8 pts (5,9%). 2 pts of them required reoperation. Statistical analysis revealed that length of coaptation (LC) (p=0,0002), NYHA class (p=0,034), CCS class (p=0,027), Euroscore (p=0,021) are the predictors of postoperative MR. Cox regression showed independent predictors of recurrent MR are: age (OR 0,9 p=0,041), post-op IABP (OR 3,4 p=0,023), BSA (OR 0,084 p=0,041), EROA (OR 154,4 p=0,001), LVEDVI (OR 1,024 p=0,011), LVESVI (OR 1,020 p=0,044) and LC (OR 0,011 p=0,014). Results depend on: LC (cut off 6, 3mm, sensitivity 94,0%, specificity 85,0%, p<0,05) and left ventricular geometry and function LVEDVI (cut off 82,6 ml/m 2, 60,0%, 61,3%, p<0,05), LVESVI (cut off 54,2ml/m 2, 60,0%, 68,8%, p<0,05), LVEF (cut off 35%, 75,0%, 65,0%, p<0,05). Risk of IMR recurrence-cox multivariate analyzes - if four predictors are present: LC 6,0mm, IMR severe preop, LVEF 35% pre-op, BSA 1,9 pre-op - 84,33%, for three predictors - LC, IMR and LVEF - 50,13%, for three predictors - LC, IMR, BSA - 60,08% respectively. Conclusions: We identified clinical and echocardiographic parameters associated with repair failure, that suggests some patients with IMR might be better served by MV replacement than repair. P2308 Decellularization reduces inflammatory reaction, calcification and extracellular matrix degeneration in pulmonary heart valve allografts P. Akhyari 1,H.Kamiya 1, P. Mambou 2, R. Tschierschke 2,M.Barth 3, S. Schilp 4, I. Berger 5, W.W. Franke 3,M.Karck 2, A. Lichtenberg 1. 1 Universitaetsklinikum Jena, Jena, Germany; 2 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 3 Helmholtz Group for Cell Biology, German Cancer Research Center, Heidelberg, Germany; 4 Phys. Chemistry, University of Heidelberg, Heidelberg, Germany; 5 Dept. of Pathology, Klinikum Kassel, Kassel, Germany Purpose: Aortic or pulmonary allografts are used in adult and pediatric patients. However, functional graft deterioration may be reduced by decellularization through elimination of immunogenic cellular antigens and proinflammatory components. Methods: Fresh (fpv, n=5) or detergent-decellularized pulmonary allografts (dpv, n=5) were implanted for 4 months in juvenile sheep. Echocardiography, haemodynamic measurements, immunohistological analysis for endothelial, interstitial, and inflammatory cells, von Kossa and Movat staining, scanning and transmission electronmicroscopy, western blot analysis of ECM proteins, endothelial markers and Poly (ADP-ribose) polymerase (PARP), and DNA content were obtained upon explantation. Results: After 4 months in vivo no significant stenosis or insufficiency occurred, but a trend towards smaller valve area and increasing peak gradients were noted in fpv. Furthermore, significantly higher total DNA, elastin and slightly increased laminin content were observed in fpv, although electronmicroscopical evaluation proved signs of architectural matrix disintegration. Histologically, interstitial hyperplasia and leaflet thickening were accompanied by increased numbers of apoptotic cells, infiltration of (CD3+) inflammatory cells and disseminated micro foci of calcium deposition in fpv as compared to dpv. In the decellularized group partial re-endothelialization and beginning interstitial repopulation at the base of the cusps were present with negligible calcium deposition and inflammatory infiltration. Conclusions: Despite comparable haemodynamic performance at 4 months, on the ultra-structural level higher rate of graft degeneration are present in fpv at this early stage. In contrast, dpv retain functional capacity and exhibit minor adverse matrix remodelling, particularly reduced inflammatory response and calcification. These changes are most likely responsible for late degeneration and chronic graft failure and deserve particular attention when novel heart valve prosthesis are developed for clinical application. P2309 Surgical coronary artery revascularization versus medical management before high risk non-cardiac surgery: a meta-analysis P. Singh, S. Adigopula, U. Bedi, M. Singh, J. Molnar, R. Arora, S. Khosla. Rosalind Franklin University of Medicine and Science, North Chicago, United States of America Purpose: Previous studies comparing pre-operative coronary artery bypass grafting (CABG) with medical management in patients undergoing elective high risk non-cardiac surgery have shown conflicting results. Hence, a meta-analysis was performed to evaluate the incidence of all-cause mortality and myocardial infarction (MI). Methods: A systematic review of literature identified six retrospective studies involving 1345 patients. As the studies were homogenous for both outcomes, combined relative risks (RR) and the 95% confidence intervals (CI) were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error <0.05 was considered statistically significant. Results: There were no differences in baseline demographics of patients in both groups. Compared to control group, the risk of all-cause mortality (RR: 0.38, CI: ; p<0.001) and MI (RR: 0.26, CI: ; p<0.001) was significantly lower in patients who had previous CABG. Conclusions: Pre-operative CABG before elective high risk non-cardiac surgery

83 Coronary surgery Valvular heart disease 383 may be superior to medical management in reducing the incidence of all-cause mortality and MI. P2310 Association between C-reactive protein, systemic inflammatory response syndrome and adverse outcomes in cardiac surgery H. Cohen Arazi, S.V. Waldman, R. Poggio, L.R. Carrizo, R. Spampinato Torcivia, H. Grancelli, M. Carnevalini, W. Rodriguez, C.E. Pensa, C. Nojek. FLENI Institute, Buenos Aires, Argentina Purpose: It is not fully established whether baseline blood levels of inflammatory markers may identify patients at risk for Systemic Inflammatory Response Syndrome (SIRS) and adverse outcomes in cardiac surgery. Methods: One hundred sixty-nine consecutive patients (77.3% men, age 61.1 years ± 15.9, Euroscore median 4.3 (IC )) who underwent cardiac surgery between April 2007 and December 2008, were prospectively included. SIRS was defined as described by the American College of Chest Physicians/Society of Critical Care Medicine Consensus, plus a norepinephrine infusion >0.5μg/kg/min. Cutoff values for high intermediate - sensitivity CRP were established in >2.0mg/dL. A combined end point included SIRS associated with atrial fibrillation (AF), shock, renal failure (RF) or death. Logistic regression was used for multivariate analyses. Results: Eighty-seven patients (54%) developed SIRS after cardiac surgery, and 50 (31%) patients had the combined end point. Nine patients (5.6%) died during the in-hospital stay. Eighty-one patients had preoperative CRP >2.0 mg/dl (50.3%). A univariate analysis demonstrated that CRP >2.0 mg/dl was associated with SIRS (OR 3.17-IC95% , p<0.0001), and the combined end point (OR 3.58-IC95% , p<0.001). An association was found between CRP and: SIRS associated with RF (OR 6.36-IC95% , p<0.0001), SIRS and Shock (OR 7.49-IC95% , p<0.004), SIRS and AF (OR 4.13-IC95% , p<0.006). As well as independent association among CRP and RF (OR 2.96-IC95% , p<0.002) and shock (OR 3.97-IC95% , p<0.020). Adjusted by preoperative variables (gender, age, diabetes, hypertension, crossclamp time, left ventricular diastolic diameter, BUN, creatinine, history of RF, history of myocardial infarction), CRP >2.0 mg/dl independently predicted: SIRS (OR IC95% , p<0.000), combined end point (OR 2.95-IC95% , p<0.018), SIRS and RF (OR IC95% , p<0.010), SIRS and shock (OR 6.50-IC95% , p<0.005), SIRS and AF (OR 3.51-IC95% , p<0.028), RF (OR 2.91-IC95% , p<0.019) and shock (OR 4.13-IC95% , p<0.020). Conclusions: Intermediate - sensitivity CRP levels >2.0 mg/dl might be useful in the identification of patients at risk for SIRS and adverse outcomes. P2311 Redox state in arterial grafts predicts left ventricular functional restoration after coronary artery bypass grafting C. Antoniades 1, T. Van-Assche 1, A.S. Antonopoulos 2, D. Tousoulis 2, C. Stefanadis 2, D. Taggart 1, K.M. Channon 1, P. Leeson 1. 1 University of Oxford, Oxford, United Kingdom; 2 University of Athens, Athens, Greece Myocardial oxidative stress is a critical parameter in left ventricular functional restoration after coronary bypass graft (CABG) surgery. Aim: We examined the effect of vascular redox state in CABG grafts, on patients functional rehabilitation post-surgery. Methods: In this study 147 coronary artery disease (CAD) patients who underwent CABG were recruited. We determined NYHA class before surgery and 6 weeks post-cabg. Paired segments of left internal mammary arteries (LIMA) and saphenous veins (SV) were harvested during CABG. Superoxide (O 2 - )production in the LIMA arterial wall was estimated by lucigenin chemiluminescence. SV vasomotor responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were determined ex-vivo. Results: Patients NYHA-class pre-cabg was independent of total O2- production in LIMA grafts (Fig. A). However patients in NYHA II at 6 weeks post-cabg, had higher O 2 - in LIMA grafts at the rime of surgery, compared to those in NYHA class I (Fig. B). In multivariate analysis overall O2- in the LIMA was the sole independent predictive factor of NYHA-class at 6 weeks post surgery (β(se): (0.015), p=0.02). None of the other peri-operative factors (SV vasorelaxations to ACh, demographic characteristics etc) were correlated with NYHA-class at 6 weeks post-cabg. Conclusions: Graft redox state is not correlated with severity of heart failure before CABG, but constitutes an independent predictive factor of left ventricular functional restoration and clinical rehabilitation post-surgery. Arterial graft redox state may affect graft vasomotor function and myocardial perfusion post-cabg. P2312 Coronary surgery: does patient risk profile change over years? B. Mihajlovic, S. Nicin, N. Cemerlic Adjic, K. Pavlovic, S. Dodic, M. Fabri. Institute of cardiovascular diseases of Vojvodina, Sremska Kamenica, Serbia Background: In current era of widespread use of PCI, it is debatable if CABG patients are of higher risk. The aim of the study is to evaluate risk profile of CABG patients. Methods: By analyzing the EuroSCORE and its risk factors, we reviewed a consecutive group of 4675 isolated CABG patients operated during the last 8 years ( ) at our Clinic. The number of PCI patients was compared to the number of CABG patients. For statistical analyses the Pearson Chi-square and ANOVA tests were used. Results: The number of PCI increased from 159 to 1595 (p<0.001), and the number of CABG from 557 to 656 (p<0.001). The mean EuroSCORE increased from 2.74 to 2.92 (p=0.06). The frequency of the following risk factors did not change over years: female gender (p=0.614), previous cardiac surgery (p=0.175), serum creatinine >200μmol/l (p=0.256), preoperative ejection fraction 30% (p=0.065), systolic PA pressure > 60 mmhg (p=0.473) and postinfarct septal rupture (p=0.275). Chronic pulmonary disease, neurological dysfunction, critical preoperative care and unstable pectoral angina decreased significantly (p<0.001). The mean age increased from 56.8 to 60.7 (p=0.001) and extracardiac arteriopathy increased from 9.2% to 22.9% (p<0.001). Recent preoperative myocardial infarction increased from 11% to 15.1% (p=0.021), while emergency operations increased from 0.9% to 4.0% (p=0.001). Conclusion: The number of CABG increases despite the enlargement of PCI. The risk for isolated CABG given by EuroSCORE increases over years. The risk factors, significantly contributing to higher EuroSCORE are: older age, extracardiac arteriopathy, recent myocardial infarction and emergency operation. P2313 Proinflamatory cytokines and the risk of perioperative myocardial infarction in patients undergoing coronary artery bypass grafting M. Sniezek-Maciejewska 1, E.L. Stepien 2, A. Undas 1,K.Sztefko 3, B. Kapelak 1,J.Sadowski 1. 1 Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland; 2 Krakowski Szpital Specjalistyczny im. Jana Pawlall, Krakow, Poland; 3 Polish-American Institute of Pediatrics, Jagiellonian University School of Medicine, Krakow, Poland Perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass grafting (CABG) implies negative prognostic consequences. In search for risk markers of this complication, various clinical and biochemical factors, including proinflammatory cytokines, Interleukin 6 and Tumor Necrosis Factor (IL-6 and TNFalpha) have been evaluated. The aim of the study was to evaluate the usefulness of preoperative measurements of proinflammatory cytokines IL 6 and TNFalfa in patients undergoing CABG. Material and methods: 176 patients undergoing elective CABG were evaluated, aged (mean, 61) years, 139 men and 34 women. Using our own algorithm (haemodynamic state, ECG, CK, CK-MB, ctn I and echocardiography) and ESC criteria to diagnose PMI, the patients were divided into 3 groups: group I patients with uncomplicated course; group II patients with minimal myocardial damage (MMD); group III patients with PMI. TheIL 6 and TNFalfa levels were measured using ELISA assays. Results: Mean IL 6 values for groups I III were: 2.96±3.01; 2.34±1.42 and 3.44±3.56 pg/ml, respectively. Mean TNFalfa values for I III group were: 2.55±3.1; 2.38±2.12; 3.27±4.43 pg/ml. There were no statistic differences for mean values (test t). Using ROC curve for sensitivity and specificity analysis we found a statistically significant difference for group I and III (p<0.005) at the cut-off level for IL 6 of 2.37 pg/ml. There was no such difference for TNFalfa.

84 384 Coronary surgery Valvular heart disease Patients Mean no. of grafts Occluded grafts Per patients irresp. of no. of grafts Number (no./all, %) (no., %) Arterial Venous All patent All occluded Mixed a M, n= ±0.9 40/244 (16.4) 105/465 (22.6) 129 (52.5) 13 (5.3) 105 (42.5) F, n= ±0.9* 5/41 (12.2) 32/92 (34.8)** 26 (49.1) 5 (9.4) 22 (41.5) *p<0.05 F vs M (ANOVA), **p<0.05, chi-square. a Mixed means patent and stenosed or occluded. all grafts patent (52%). In the remaining patients at least 1 of 2-5 conduits was occluded. Differences between females and males are presented in table 1. Conclusions: A noninvasive visualization of by-pass grafts by means of a 64- MDCT appears an attractive alternative to invasive method. Use of this method confirmed a lower patency rate of venous grafts compared to arterial conduits. Occlusion rate of venous grafts was found to be gender-related, being higher in females. Conclusion: Mean value IL 6 and TNFalfa measured preoperatively are higher in patients with PMI; the IL 6 cut-off level of 2.37 pg/ml discriminates patients with risk of PMI with 68% sensitivity and 52% specificity. Measurements of proinflamatory cytokines mainly IL 6 before CABG surgery may be useful for predicting the risk of PMI. P2314 Risk-prediction models for major postoperative morbidity in coronary surgery P.E. Antunes, J.F. Oliveira, M.J. Antunes. University Hospital, Coimbra, Portugal Purpose: There are several risk-prediction models for perioperative mortality but models for morbidity are not used. A prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to identify the preoperative risk factors and to develop and validate risk prediction models for major causes of postoperative morbidity. Methods: Data on 4,567 patients who underwent isolated CABG surgery over a 10-year period were extracted from our prospectivelygenerated clinical database. Five major postoperative complications (cerebrovascular accident, mediastinitis, acute renal failure, cardiovascular failure and respiratory failure) were analysed. A composite morbidity outcome (presence of two or more major morbidities) was also entered in the analysis. A risk model was developed for each of these endpoints and validated by means of logistic regression and bootstrap analysis. Discrimination and calibration were assessed by using the under the receiver operating characteristic (ROC) curve area and the Hosmer-Lemeshow (H-L) test, respectively. Results: The hospital mortality was 0.96%. The specific morbidity rates were: cerebrovascular accident (2.5%), mediastinitis (1.2%), acute renal failure (5.6%), cardiovascular failure (5.6%) and respiratory failure (0.9%). The composite morbidity rate was 9.0% The risk models developed demonstrate an acceptable discriminatory power (ROC curve area for cerebrovascular accident, 0.715; mediastinitis, 0.696; acute renal failure, 0.778; cardiovascular failure, 0.710; respiratory failure, 0.787; and composite morbidity outcome, 0.701) (Figure). The results of the H-L test showed that models predict morbidity accurately, both on average and across the ranges of patient deciles of risk, thus can be used clinically. Conclusions: As a complement to a previously reported mortality risk-prediction model, we developed a set of risk-prediction models that can be used as an instrument to provide information to clinicians and patients about the risk of postoperative major morbidity in our patient population anticipating isolated CABG. P2315 Coronary artery graft patency on a 64-MDCT angiography: single centre experience in 300 patients M. Sosnowski 1,A.Gola 2,K.Chromik 2,A.Sobczak 2, R. Bachowski 1, A. Bochenek 1, P. Buszman 1,Z.Gasior 1, M. Trusz-Gluza 1, M. Tendera 1. 1 Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland; 2 Gornoslaski Osrodek Kardiologii, Katowice, Katowice, Poland A visualization of coronary by-pass grafts on multi-detector computed (MDCT) coronary angiography focuses increasing interests as an alternative to invasive by-pass angiography. This method is totally noninvasive, relatively simple, with ambulatory accessibility and less complications. We reviewed results of a 64-MDCT coronary angiography in 300 consecutive patients with a history of coronary artery by-pass graft surgery (3 months to 8 years after surgery, median 6 months). There were 53 females (mean age 65±8ys) and 247 males (mean age 61±9ys, p<0.05). Among females, 7 had 1 arterial graft, 12 had only venous grafts and the remaining 34 - mixed (both arterial and venous). Among males, 12 had 1 arterial graft, 30 - venous grafts, and mixed grafts. Number of grafted vessels was 1 in 23 patients (7F, 16M), 2 in 82 (16F, 66M), 3 in 144 (24F, 120M) and 4 or more in 51 patients (6F, 45M). The total number of arterial grafts was 285 in 258 patients and of the venous grafts was 557 in 281 patients. Results: Out of 285 arterial grafts 45 (15.8%) were occluded. Total occlusion was found in 137 out of 557 venous grafts (24.6%, p<0.01, Chi-square). On patients basis, in 18 out of 300 (6%), all grafts were occluded, while 155 patients had P2316 Long term (7-to-20-year) patency of the radial artery as a coronary bypass conduit assessed by computed tomographic angiography R. Boutekadjirt 1, D. Toledano 1, P. Achouh 2,K.OuldIsselmou 2, P. Goube 3, B. Lancelin 4, R. Fouquet 5,C.Acar 1. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 European Hospital George Pompidou (AP-HP), Paris, France; 3 Centre Hospitalier Sud-Francilien, Corbeil, France; 4 Clinique Alleray-Labrouste, Paris, France; 5 Centre Hospitalier de Versailles, Le Chesnay, France Purpose: The radial artery (RA) as a coronary bypass conduit offers excellent mid-term results but its durability remains unknown. The aim of this study was to assess the long term RA patency using CT angiography. Methods: Sixty-four-slice CT angiography was performed in 115 patients having undergone coronary bypass with the RA. Follow-up extended from 7 to 20 years (mean: ). Age ranged form 48 to 88 years (mean:69 + 8). Five patients were in atrial fibrillation. Twenty one patients had evidence of myocardial ischemia and 94 were asymptomatic. The conduits used were: RA (129), left IMA (108), right IMA (15) and veins (43). RAs were anastomosed to: marginal (56%), diagonal (16%) and right coronary (28%) whereas IMAs were mostly anastomosed to the LAD (85%). Medications included antithrombotics: aspirin (71%), clopidogrel (23%), oral anticoagulant (15%) and vasodilators: nitrates (10%), beta-blockers (71%), Ca 2+ blockers (41%) and ACE inhibitors (49%). PTCA was required in 15 patients at years involving: 5 RAs, 1 IMA and 13 coronary arteries. Results: CT scanner allowed a reliable evaluation of graft patency in all cases for a mean radiation exposure of mgray.cm. The 11-year patency of RAs was 82.9%. It was lower than IMAs (94.3% p<0.01) and similar to veins (79.0% p=0,45). All graft patency was lower in case of myocardial ischemia than in asymptomatics (77.1% vs 89.5% p<0.01) and in non-lad than in LAD grafts (84.2% vs 95.3% p<0.01). RA graft patency appeared to be improved by aspirin (87.9% vs 71.0% p=0.02) and beta-blockers (87.0% vs 72.2% p=0.04). No other medication seemed to affect either RA or all graft patency. All dilated (2) or stented (3) RA conduits were patent. Conclusion: In this study the RA-to-coronary bypass conduit provided an excellent long term patency. CT angiography allowed a non-invasive and reliable method for assessing graft function. P2317 Predictors of early outcome after coronary artery bypass grafting in the elderly S.M. Oliveira, A. Goncalves, R. Almeida, A. Azevedo, P. Dias, P. Pinho. Hospital S Joao, Porto, Portugal Introduction: Improved life expectancy led to an increasing number of elderly patients (pts) submitted to coronary artery bypass graft surgery (CABG). As comorbidities are more prevalent in geriatric patients, a critical evaluation of cardiac surgical outcome is needed. The aim of this study was to identify predictors of in-hospital mortality in elderly patients undergoing CABG. Methods: We retrospectively analyzed records of pts aged 75 years submitted to CABG from January 2002 to December 2006 at our center. Demographic data, cardiovascular risk factors, postoperative complications and additive EuroSCORE classification were analyzed. High risk was defined as EuroSCORE 6 points. Results: A total of 115 pts 75 years were included. Mean (standard deviation (SD)) age at time of surgery was 78 (2) years and 80 (69.6%) were men. Sixty-six (57.4%) pts had arterial hypertension, 64 (55.7%) had dyslipidemia, 40 (34.8%) were diabetic and 21 (18.3%) were obese. Pre-operative co-morbidities (defined in EuroSCORE), were common: 34 (29.6%) pts had extracardiac arteriopathy, 9 (7.8%) had cerebral vascular disease, 8 (7.0%) had chronic pulmonary obstructive disease and 3 (2.6%) presented with renal insufficiency. Fifty-six (48.7%) pts had records of recent myocardial infarction, 22 (19.1%) had moderate to severely depressed left ventricular (LV) function and 5 (4.3%) presented a critical preoperative state. Ten (8.7%) pts were submitted to a combined carotid artery surgery. Mean EuroSCORE was 7.16 (range 4 to 19) points, and 84 (73.0%) pts were classified in the high risk group. Mean (SD) hospital stay was 12.6 (12.3) days and overall in-hospital risk of death was 6.1% (7 pts). In univariate analysis, significant predictors of hospital mortality were moderate to severely depressed LV function (18.2% vs. 3.3%, p=0.034), combined carotid artery surgery (30% vs. 3.8%,

85 Coronary surgery Valvular heart disease 385 p=0.009), hemodialysis after CABG (71.4% vs. 0.9%, p<0.001), major bleeding (40% vs. 3.7%, p=0.012) and prolonged orotracheal intubation (30% vs. 2.9%, p=0.004). EuroSCORE was not predictor of in-hospital mortality. Conclusion: CABG procedure in the elderly was associated with an in-hospital mortality rate of 6.1%. EuroSCORE is a validated risk stratification system for the prediction of cardiac surgical outcome, however it was not predictor in our patients. In addition to postoperative complications, LV function and associated carotid artery surgery were the only pre-operative predictors of early mortality. P2318 Impact of diabetes in elective on-pump and off-pump coronary artery bypass surgery in patients with multivessel coronary artery disease and preserved ventricular function E.G. Lima 1,R.D.Vieira 1, N.H. Lopes 1,F.S.Paulitsch 1,R.Rahmi 1, A. Hueb 1, A.C. Pereira 1, J.A.F. Ramires 1, M. Farkouh 2,W.A.Hueb 1. 1 Heart Institute of University of Sao Paulo, Sao Paulo, Brazil; 2 Mount Sinai Hospital, New York, United States of America Background: Diabetes mellitus (DM) is recognized as an important cardiovascular risk factor in patients submitted to on-pump coronary artery bypass graft (CABG). The development of off-pump CABG has been contributed to minimize the non physiological effects of on-pump CABG. There are few randomized and prospective studies with diabetic subjects comparing on-pump and off-pump surgery. Methods: Patients with multivessel coronary artery disease, stable angina, preserved ventricular function and cardiovascular surgeon s agreement that revascularization could be attained by either strategies, were randomized to on-pump or off-pump CABG. The primary end-points were cardiovascular death, stroke or unstable angina requiring revascularization. DM was defined in according of American Diabetes Association criteria. Results: In MASS III study 308 subjects were randomized to intervention, 153 were submitted to on-pump and 155 to off-pump surgery. There were 54 and 56 diabetic patients in on-pump and off-pump surgery groups, respectively. DM patients showed higher triglycerides level more hypertension and lesser tabagism. Baseline characteristics were similar among diabetic patients randomized to both strategies. There were no differences in the incidence of mortality, stroke, and refractory angina in diabetics patients submitted to on-pump or off-pump CABG along five-year follow-up. Conclusion: In MASS III study, the surgery strategy did not confer differences in primary end-points in diabetics patients. P2319 Myocardial bridge: Surgical outcome and midterm follow up A. Sajjadieh Khajouei 1,R.Parvizi 2. 1 Shahid Chamran Heart Hoapital, Isfahan, Iran (Islamic Republic of); 2 Shahid Madani Heart Hospital, Tabriz, Iran (Islamic Republic of) Myocardial bridge consists of muscle fiber bundle lining on epicardial coronary artery for variable distance. Although myocardial bridge associates with benign prognosis, their presence has also been considered a cause of angina, myocardial infarction, malignant arrhythmia and sudden death. There is not a general consensus about therapeutic strategies in symptomatic patients whit myocardial bridge (medical therapy, coronary artery bypass surgery, coronary stenting, supra arterial myotomy).we report results of surgery and long-term follow up in 26 patients who had disabling symptoms due to myocardial bridge refractory to medical therapy. From among more than coronary angiography which was performed in our centre 290 (1.5%) cases had the angiographic diagnosis of myocardial bridge out of them 26 (9%) patients underwent surgical myotomy for treatment of myocardial bridge causing significant systolic arterial compression. The patients (19 male-7 female) had history of typical chest pain and positive exercise test. All of them were examined with radionucleotide study preceding angiography that was positive for ischemia in 20 cases (76%). Coronary angiography and left hear catheterization in all patients revealed impaired blood flow due to myocardial bridge in left anterior descending artery and there was additional atherosclerotic stenosis of coronary arteries in 6 and mitral valve disease in one patient. supra arterial myotomy was performed in all patients. There was no mortality or major intraoperative complication. Post operative scintigraphic and angiographic studies demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. Except in one patient who had recurrent anginal chest pain after operation and coronary angiography showed residual narrowing in LAD despite myotomy and underwent CABG of LIMA to distal LAD. During 7-81 month of follow-up (mean: 34.2±21) only two patients had symptoms of angina that was not shown significant residual compression and symptoms controlled by medical treatment. In conclusion surgy of myocardial ischemia due to myocardial bridge can be accomplished with very low operative risk and excellent prognosis. P2320 Effects of surgical technique options in the mid-term results of coronary revascularization in octogenarians M. Serrao 1,F.Graca 2, M. Marques 2, M. Abecasis 2, J. Calquinha 2, R. Rodrigues 2,J.Neves 2, A. Moradas 2, J. Queiros E Melo 2. 1 Hospital Central do Funchal, Funchal, Portugal; 2 Hospital de Santa Cruz, Lisboa, Portugal Introduction: As surgical revascularization is becoming more frequent in octogenarians, we reviewed our data to analyze if complete revascularization and off-pump technique had impact in early and mid-term results. Methods: Retrospective study of 85 consecutive patients, aged 80 years or older, submitted to coronary artery bypass in a single thoracic center, between January 2003 and December We analyzed if off-pump technique (OPT) 69% vs. cardio-pulmonary bypass (CPB) 31% and complete revascularization (CR) 57,1% vs. uncomplete revascularization (UR) 42,9% had impact prognosis early and up to 5 years after surgery. Results: Baseline characteristics were similar between groups and follow-up was 91% complete.the groups had no significant differences in their mean age (CPB=82,8±2,3 years vs. OPT=82,6±1,8; p=ns) and in Logistic Euroscore (CPB=8,7±5,9 vs. OPT=11,4±13,1; p=ns). However, CPB group had longer mean hospital stay (CPB=12,1±7,7 vs. OPT=8,9±5,2 days; p=0,03) and more complete revascularization (CPB=84,6% vs OPT=15,4%, p=0,001). When comparing the revascularization there was no significant differences in mean age (CR=82,5±1,9 years vs. UR=82,9±2, p=ns) and in Logistic Euroscore (CR=11,6±13,8 vs. UR=9,2±6,6, p=ns). At 5-year follow-up, off-pump surgery patients had the same late prognosis (total mortality: OPT=22.6% vs. CPB=21,7%, p=ns; cardiovascular mortality: OPT=15,5% vs. CPB=15,4%, p=ns) as well as complete revascularization (total mortality: CR=20% vs. UR=25,8%, p=ns; cardiovascular mortality: CR=14,6% vs. UR=16,7%, p=ns). Conclusion: In octogenarians, off-pump technique, even though may imply to perform a less complete revascularization, leads to a shorter hospital stay and has the same 5 year results as of those patients operated under cardiopulmonary bypass. We conclude that off-pump technique should be the approach of choice to perform coronary revascularyzation in octogenarians P2321 Long-term clinical outcomes after drug-eluting stent implantation versus surgical treatment in patients with a single vessel disease C. Patsa 1, K. Toutouzas 1,E.Tsiamis 1, C. Tsioufis 1, A. Spanos 1, I. Chlorogiannis 2,E.Pattakos 3, M. Panagiotou 4, D. Iliopoulos 4, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Euroclinic of Athens, Athens, Greece; 3 Hygeia Hospital, Athens, Greece; 4 Athens Medical Center, Athens, Greece Purpose: Patients with an isolated lesion in the proximal segment of left anterior descending artery (plad) present a challenging clinical problem for interventionists. The optimal revascularization strategy using either drug-eluting stent (DES) or left internal mammary artery (LIMA) remains controversial. We investigated the long-term clinical outcomes of DES versus LIMA in patients with isolated plad lesion and chronic stable angina. Methods: We enrolled 412 patients with plad lesion: 302 underwent DES implantation and 110 LIMA grafting. Patients undergoing DES implantation were scheduled to receive double antiplatelet therapy for 12 months. Primary end points were the occurrence of major adverse cardiac events (MACE). MACE was defined as: Death, myocardial infarction and target lesion revascularization (TLR). Results: There was no difference regarding the demographic and angiographic characteristics between the two cohorts. The incidence of MACE was similar between the two groups (p=0.57) during the 29.31±9.78 months follow-up period. The incidence of death was 1.65% in DES group versus 1.81% in LIMA group (p=0.99). The rate of myocardial infarction was 0.66% in DES versus 0.90% in LIMA group (p=0.99). TLR was 2.31% in DES and 0% in LIMA group (p=0.19). Five patients (1.65%) from DES group underwent percutaneous coronary intervention and 2 patients (0.66%) underwent coronary artery by pass grafting. The event-free survival curve was similar in both groups: 95.36% (DES) versus 97.27% (LIMA) (p = 0.42) (Figure). Conclusion: The overall survival rate was similar between the two groups of patients during the long-term follow-up period. Hence, it seems that both revas-

86 386 Coronary surgery Valvular heart disease / Heart transplantation and left-ventricular assist devices cularization modalities can be used effectively and safely to treat this particular group of patients. P2322 Tissue engineering: optimal coating of inflow cannulae from cardiac assist devices placed in the apex of the left ventricular cavity J. Mueller 1, B. Kapeller 2, K. Brandes 1,K.Macfelda 2. 1 Berlin Heart, Berlin, Germany; 2 Medical University of Vienna, Vienna, Austria Purpose: To find the optimal coating for implantable material is a callenge for. The movement of the inflow cannula in the apex of the left ventricle stimulates the proliferation of fibroblasts around the cannula inside the left ventricle in patients with cardiac assist devices (VADs) to variable degrees. Moreover, the cannula is responsible for unfavourable flow conditions in the left ventricle which may induce thrombus formation around the cannula. VADs generate a negative pressure in the left ventricular cavity in order to induce a flow into the pump. To avoid suction of thrombi or uncontrolled grown tissue into the pump, the surface of the cannula should see for a proper adhesion of cells and potential thrombi to the surface of the inflow cannula. We investigated the degree of adhesion of fibroblast to different titanium surfaces under in vitro and invivo conditions lateron with the optimal coated surface. Materials and Methods: Seven titanium discs (25 mm diameter, 5mm thickness) served as samples and were coated with seven different biomaterials: silicone, spongy silicone, polished titanium, sintered titanium (150 and 300 μm roughness), velour, silver coated velour, plasma injected titanium and Ti/HA. Polystyrole served as control. Human cardiofibroblasts were isolated by using published methods. Cells were cultured under standard conditions (5% CO2, 95% humidity) in DMEM-culture medium supplemented with foetal calf serum and antibiotics. Test series were carried out in 6 well Ultra Low Attachments plates by using 1x104 cells per well and per material sample. After 2 weeks specimens and on growing cells were fixed with glutaraldehyde and prepared for electron microscopical analysis. The cell layer grown on the discs was exposed to different degrees of shears stress in order to test to adhesion of the cells to the surface. Results: Only silver coated velour did not show any cell cover. The cellular overgrowth of the other materials was of varying intensity. The most densely cell layer was observed on polished titanium followed by sintered titanium. Under shear stress conditions the best cell growth and optimal adhesion of the cell to the surface was obtained on sintered titanium (300) followed by plasma injected titanium and Ti/HA compared to the control. Conclusion: According to the test series carried out with and without exposure to shear stress conditions sintered titanium (300) can be suggested as appropriate biomaterial for optimizing adhesion of cells and thrombi to the surface and ingrowth of cannulas into the ventricle, which has been clinical confirmed in more than 9 patients. Table 1 EC no CsA EC w 400 ng/ml CsA Glycosaminoglycans [μg/10 6 cells] 2.8± ±0.2 Prostacyclin [pg/10 6 cells] 78±3 75±7 TGF-β [pg/10 6 cells] 864± ±167 Conclusions: MEEC are powerful regulators of vascular injury in pigs. Allogeneic MEEC failed to induce a significant Th1-driven alloimmune response but induced differentiation of splenocytes into Th2-cytokine producing cells. This induction and the therapeutic efficacy of allogeneic MEEC were alleviated by a concomitant 12- day course of CsA. Adventitial MEEC transplants even of allogeneic sources and without immunosuppressive treatment- may be useful in decreasing luminal narrowing in a clinical setting. P2324 Custodiol-n, a novel organ preservation solution, reduces ischemia/reperfusion injury in a rat heart transplantation model S. Loganathan, T. Radovits, K. Hirschberg, A. Koch, S. Korkmaz, P. Neugebauer, M. Karck, G. Szabo. Universitaetsklinikum Heidelberg, Heidelberg, Germany Custodiol (HTK-solution) is a widely used cardioplegic solution. The newly developed Custodiol-N additionally consists of intra- and extracellular ironchelators that have been reported to reduce free radical species which play a central role in ischemia/reperfusion injury. In the present study we investigated the effects of Custodiol-N in a rat transplant model. Heterotopic transplantation was performed in Lewis rats. Ischemia was standardized to 1h. 4 groups were assigned: 2 Custodiol-N groups and 2 Custodiol control groups with a reperfusion time of 1h and 24h, respectively. Coronary blood flow (CBF), left ventricular pressure (LVP), its first derivative (dp/dt), endotheliumdependent vasodilatation to bradykinine and endothelium-independent vasodilatation to sodiumnitroprusside as well as ATP-content were measured. TUNEL staining was performed to detect apoptotic cardiomyocytes. After 1h, CBF (3.99±0.24 vs. 2.86±0.35ml/min/g;p<0.05), LVP (117±18 vs. 82±4mmHg;p<0.05) and dp/dt (3453±577 vs. 1740±116mmHg/s;p<0.05) were significantly higher in the Custodiol-N group in comparison to the corresponding control. Vasodilatatory response to sodiumnitroprusside did not show differences between the groups. Bradykinine resulted in a significantly higher increase in CBF in the Custodiol-N group (92±4 vs.60±5%;p<0.05) as well as myocardial ATP-content (9.84±0.68 vs. 1.86±0.41μmol/g;p<0.05). TUNEL staining showed a significantly reduced apoptosis (21.58±1.59 vs ±1.54%;p<0.05). After 24 hours, there was no difference between the groups in CBF, LVP, dp/dt, LVEDP. HEART TRANSPLANTATION AND LEFT-VENTRICULAR ASSIST DEVICES MINIMALLY INVASIVE AND ROBOTIC SURGERY P2323 Cyclosporine A modifies immune-mediating and therapeutic efficacy of allogeneic perivascular porcine endothelial cell implants H. Methe 1, M. Nanasato 2, A.-M. Spognardi 2, A. Groothuis 2, E.R. Edelman 2. 1 Klinikum der Universitaet Muenchen-Grosshadern, Munich, Germany; 2 Massachusetts Institute of Technology, Cambridge, United States of America Objectives: Non-syngeneic endothelial cells (EC) embedded within threedimensional matrices (MEEC) when placed in the vascular adventitia control lumenal inflammation, occlusive thrombosis and intimal hyperplasia. Host immunity directed against engrafted allogeneic tissue is a predominant T helper (Th)1- driven immune response and is a major impediment for short- and long-term success of grafts. We therefore aimed to identify if cyclosporine A (CsA) would enhance immune compatibility and therapeutic efficacy of perivascular allogeneic MEEC. Methods: Pigs (n=4/group) underwent balloon injury of both carotid arteries and received a 12 days course of CsA (group 1), perivascular implants of porcine MEEC (group 2), combination of CsA and MEEC (group 3) or were left untreated (group 4). Host immune reactivity (EC-specific Abs, activation of splenocytes) was analyzed after 28 and 90 days in 2 pigs/group respectively. Results: In vitro CsA was without effect on biosecretion by EC (table). No immune reactivity against allogeneic EC was observed in treatment groups 1 and 4. MEEC treatment alone (group 2) induced formation of IgG1 antibodies specific for the allogeneic EC and differentiation of host splenocytes into Th2 but not Th1 cytokine-producing cells. Concomitant CsA-therapy reduced the frequency of IgG1 antibodies and Th2-cytokine producing splenocytes upon MEEC treatment. Compared with groups 1 and 4 treatment with MEEC (group 2) significantly inhibited luminal occlusion 28 and 90 days after balloon injury. Concomitant CsAtreatment reduced the ability of MEEC to inhibit luminal occlusion. TUNEL staining after 1h and 24h Our current results demonstrate the benefits of custodiol-n especially during the critical early phase of reperfusion after heart transplantation. We believe custodiol-n is a novel promising approach in the developement of cardioplegic solutions. P2325 Pretransplantation cytomegalovirus mismatch serology (D+/R-) is a risk factor for four year mortality after heart transplantation E. Bollano, B. Rundqvist, B. Andersson, U. Nystrom, V. Sigurdardottir, F. Nilsson, N. Selimovic. Sahlgrenska University Hospital, Gothenburg, Sweden Purpose: The aim of this study was to evaluate association between cytomegalovirus (CMV) serology in donors and recipients regarding outcome after heart transplantation. Methods: Retrospective analysis of all heart transplanted adult patients at University Hospital from January 1988 through December Risk factors tested were recipient age, sex, blood group, pretransplant CMV serology, allograft ischemic time, diagnosis, donator age, sex and blood group and donor CMV serology. Primary outcome was mortality during the first 4 years after transplantation. Results: During this period 362 adults underwent heart transplantation with a mean age at transplantation of 46±12 (mean ± SD), 79% were males. The diagnoses were: cardiomyopathy (n=226), coronary artery disease (n=110), retransplantation because of cardiac allograft vasculopathy (n=7), valvular disease (n=8) and others (n=11). The study population was devided into 2 groups according to

87 Heart transplantation and left-ventricular assist devices Minimally invasive and robotic surgery 387 Survival stratified by CMV serology donor and recipient serology at the time of transplantation [(D+/R+; D-/R+; D-/R- = low risk group) and D+/R- = high risk group]. By univariate analysis allograft ischemic time and CMV serology were associated with increased mortality but not recipient age, donator age and diagnosis. In multivariate analysis independent predictor of mortality was only mismatch of pretranslant CMV serology (D+/R-) (HR 0.55; 95% CI ; p = 0.035). Conclusion: In adults, mismatch of pretransplant CMV serology is an independent predictor for early and midterm mortality after heart transplantation. P2328 Cyclosporine A decreases muscular mitochondrial energetics by the effects of its vehicle without significant long term toxicity in the heart and muscle of heart transplant patients B. Mettauer 1, B. N guessan 2,J.Zoll 3, E. Epailly 4, J.P. Mazzucotelli 4, E. Lampert 3, F. Piquard 3,X.Bigard 5,B.Geny 3, R. Ventura-Clapier 6. 1 Hôpitaux Civils de Colmar, Colmar, France; 2 Institut de Physiologie, Université D Abidjan, Abidjan, Côte d Ivoire; 3 Institut de Physiologie, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; 4 Hopital Civil de Strasbourg, Strasbourg, France; 5 Département des facteurs Humains CRSSA, Grenoble La Tronche, France; 6 INSERM U769, Châtenay Malabry, France Ciclosporine A (CSA), still the keystone of most immunosuppressive regimens, has been suspected to have muscular toxicity at the mitochondrial level, potentially impairing heart and skeletal muscle function after heart transplantation (HTR). We examined the maximal O2 consumption (Vmax, μmolo2/min/g dry weight) of skinned muscular fibers from right ventricular (RV) and vastus lateralis (VL) biopsy samples in an oxygraphic chamber, at the time of HTR and 10 months after HTR as effect of chronic CSA treatment, and after adjunction within the oxygraphic chamber of 1, 10 and 100 μm of respectively CSA in Vehicle (Sandimmune), vehicle alone (Cremophor EL), CSA in ethanol (EOH) and EOH alone as representing acute effect of CSA. Values represent the means ± SEM of 10 patients. Patients chronically under CSA did not exhibit a decrease of Vmax (RV:10.8±0.6,13.9±0.9; VL:3.0±0.5,4.9±02 before and after 10 months following HTR respectively, all p=ns). Acutely CSA in Vehicle decreased Vmax in both RV and VL in a dose dependant manner, mainly by the effects of Vehicle alone and not due to CSA per se (figure). Acute effects of CSA and its vehicle We conclude that CSA has no clinically significant chronic muscular mitochondrial toxicity but may decrease mitochondrial oxidative capacity during acute intravenous administration by the effects of its vehicle, potentially affecting acutely skeletal and cardiac muscular energetics. S. Lemoine, M. Angioi, S. Mattei, C. Sirbu, N. Benzaghou, H. Aloui, O. Marcon, J.P. Carteaux, E. Aliot, J.P. Villemot. CHU de Nancy - Hopital de Brabois, Vandoeuvre les Nancy, France Purpose: The development of cardiac allograft vasculopathy (CAV) is the main long term complication of cardiac transplantation and has a very deleterious effect on its prognosis. We therefore aimed to determine long-term predictors of the occurence of a CAV in heart transplant defined by the occurence of a significant coronary lesion (>50% in reduction of diameter stenosis) diagnosed on systematic follow-up angiogram. Methods: Monocenter retrospective study. All 1-year survivors among hearttransplanted patients between January 1991 and December 2005 extracted from our propective database were included in this study. In our institution, a policy of systematic serial coronary angiography is usually applied to detect CAV. Patients were considered to have a CAV if a coronary stenosis >50% by visual analysis was evidenced. Probabilities of CAV occurence was assessed by Kaplan-Meier (KM) analysis and univariate and multivariate Cox analysis were performed to determine univariate and independent predictors of CAV. Results: 174 patients (mean age 50±10 years, male gender 77%) were included and followed during a median period of 2961 days (interquartiles ). Before transplantation, 45% of the patients suffered from ischaemic cardiomyopathy. During follow-up (FU), a CAV was evidenced in 33 patients (19%) after a median delay of 1961 days ( ). KM probabilty of being free of CAV at FU was 64%. Univariate predictors of the occurence of CAV were: absence of smoking cessation (p<0.003), total serum cholesterol level (p<0.028) and the number of previous episodes of acute rejection (p<0.0001). By multivariate analysis, absence of smoking cessation (OR % CI ( ), p<0.005) and the number of previous episodes of acute rejection (OR %CI ( ), p<0.001) were found to be independently correlated to the occurence of a CAV. At the end of FU, KM probability of being free of CAV was 72% in smokers and 59% in non-smokers, 94% in patients with less than 2 previous acute rejection episodes and 54% in those with more than 2. Conclusion: In heart-transplanted patients, the occurence of CAV is strongly correlated to previous episodes of acute rejection and absence of smoking cessation. A special effort has to be done to obtain smoking cessation in these patients. P2330 Circulating anti-heart autoantibodies are non-invasive markers of high cellular rejection burden in heart transplantation A.L.P. Caforio 1,A.Angelini 2,S.Bottaro 3,F.Tona 1, G. Thiene 2, G. Gerosa 4,S.Iliceto 1. 1 Cardiology,Dept Cardiological Thoracic and Vascular Sciences, Padua University, Padova, Italy; 2 Cardiac Pathology, Padua University, Padova, Italy; 3 Clinical Pharmacology, Padua University, Padova, Italy; 4 Cardiac Surgery, Dept Cardiological Thoracic and Vascular Sciences, Padua University, Padova, Italy Purpose: Autoimmune response may occur after solid organ transplantation. In autoimmune disease autoantibodies provide non-invasive early markers for active phases of immune-mediated inflammation in the target organ. We aimed at assessing frequency and potential predictive role of serum antiheart-autoantibodies (AHA) for acute rejection (AR) after heart transplantation (HTx). Methods: We studied 44 stable HTx patients (32 male, aged 51±16 years at HTx, at 100±72 months post-htx). Serum at last follow-up was assessed for anti-heart autoantibodies (AHA) by indirect immunofluorescence on cryostat sections of normal O blood group human myocardium and skeletal muscle, blindly from clinical features. AHA of the organ-specific type reacted with myocardium, but were unreactive with skeletal muscle, AHA of the partially organ-specific type were weakly reactive with skeletal muscle. Control groups included sera from patients with non-inflammatory cardiac disease (n=160, 80 male, aged 37±17), with ischemic heart failure (n=141, 131 male, age 51±12) and normal blood donors (n=270, 123 male, aged 35±11). A rejection score was assigned based on a modification of the ISHLT grading on follow-up endomyocardial biopsy as follows:1a=1, 1B=2; 2=3; 3A=4; 3B=5; 4=6. The following scores were calculated for each patient: RS in the total follow-up (TRS); RS in the 1st year (RS 1yr); TRS including only severe grades (greater or = 3A) (sev TRS); 1styr RS including only severe grades (sev RS 1yr). All scores were normalised for the number of biopsies taken in each patient. Antibody status was related to clinical and diagnostic features by univariate analysis. Results: The frequency of AHA was higher in HTx than in non-inflammatory cardiac disease (34% vs 1% respectively, p=0.0001), ischemic heart failure (34% vs 1% respectively, p=0.0001) or normal subjects (34% vs 2.5% respectively, p=0.0001). Positive AHA status was not associated with age at HTx, gender, pre- HTx diagnosis, time from HTx, type of immunosuppressive therapy. AHA positive patients had higher sev TRS compared to those who were AHA negative (1.3±0.1 vs. 0.46±0.4, p=0.006). Conclusion: The finding of AHA provides a non-invasive predictor of high acute cellular rejection burden after heart transplantation. P2329 Absence of smoking cessation: a major predictive factor of chronic allograft vasculopathy in heart-transplanted patients P2332 Detection and prognostic impact of echocardiographically assessed diastolic dysfunction in heart transplant recipients P. Jung, K. Berlinger, J. Rieber, F. Kroetz, M. Leibig, A. Koenig, P. Schneider, H. Gross, H.Y. Sohn, V. Klauss. Klinikum der Universitaet Muenchen, Munich, Germany Diastolic dysfunction represents a prognostically important finding during echocardiography. In patients undergoing cardiac transplantation (HTX) the anastomosis of graft and host atria alters the echocardiographic parameters commonly used to characterize diastolic function. Aim of the present study is to identify an

88 388 Heart transplantation and left-ventricular assist devices Minimally invasive and robotic surgery echocardiographic method for the assessment of diastolic function in HTX patients and to calculate its prognostic value. Methods: In 28 HTX patients (60.5±10 years, 20 male) the enddiastolic filling pressure of the left ventricle (LVend) was measured during routine cardiac catheterization. A LVend<16mmHg was considered normal. Within 2 days, a complete echocardiographic examination was performed including measurement of left atrial (LA) and left ventricular (LV) size, ejection fraction (EF), early (Em) and late diastolic mitral inflow (Am), deceleration time of the mitral E wave (Dt), systolic and diastolic pulmonary vein flow (PVs and PVd) and isovolumic relaxation time (IVRT). In addition, the TVI based early (Ea) and late diastolic (Aa) movement of the mitral annulus was assessed. The ratio Em/Am and Em/Ea was calculated in each patient. In 281 HTX patients clinical events (cardiac and non cardiac death, coronary intervention, re-transplantation) were registered during a follow-up period of up to 2.5 years after the initial echocardiogram. Results: 9 of 28 patients had a LVend >16mmHg and revealed a significantly higher Em (1.2 vs. 0.8m/s, p=0.006), Em/Am ratio (2.9 vs. 1.9, p=0.008) and Em/Ea (9.0 vs. 6.1, p=0.038). No significant differences were present regarding all other echocardiographic parameters. Clinical events occurred in 38 (13.5%) of the 281 follow-up patients (0.4% cardiac death, 1.4% non-cardiac death, 11.7% coronary intervention). Of all echocardiographic parameters only Em/Ea was able to predict an elevated clinical event rate using a threshold value of 8 (20 vs. 9%, p=0.057). Conclusion: The echocardiographic estimation of the diastolic function is feasible in HTX patients and provides prognostic information. P2333 Cardiac allograft vasculopathy (CAV) is different in CMV high-risk patients after heart transplantation T.H. Oberndorfer 1,M.Frick 1, C.H. Mussner-Seeber 1, D. Hoefer 2, H. Antretter 2, G. Poelzl 1. 1 Department of Internal Medicine III - Cardiology, Innsbruck, Austria; 2 Department of Cardiothoracic Surgery, Innsbruck, Austria Purpose: Cardiac allograft vasculopathy (CAV) is the leading cause of late mortality after heart transplantation (HTX). High-risk cytomegalovirus (CMV) mismatch constellation (D+/R-) has been repeatedly associated with increased mortality and accelerated CAV. Recently, investigation of coronary plaque composition in vivo has become possible with the introduction of intravascular ultrasound virtual histology (IVUS-VH). In this study we compared the plaque composition of high and low-risk CMV-missmatch patients using IVUS-VH. Methods and Materials: 7 patients (median age 62 years, range 34-65; median time after HTX 4 years, range 1-8) with high-risk CMV-mismatch and 26 patients (median age 52 years, range 25-65; median time after HTX 5 years, range 1-9 years) with low-risk CMV-mismatch (D+/R+, D-/R-, D-/R+) were included into this study. In all patients at least one coronary artery was investigated using IVUS-VH. Data were obtained using a continuous pullback (0.5mm/s) and a commercially available mechanical sector scanner (Eagle Eye Gold, Volcano Therapeutics). A region of interest (10-15mm) was selected at the side with the highest amount of plaque and analyses were done offline with pcvh-review software (Volcano Therapeutics). Four histological plaque components (fibrous, fibrolipid, necrotic and calcified) were correlated with a specific spectrum of the radiofrequency signal, which was assigned to different colour codes (green, greenish-yellow, red and white). Results: Patient characteristics between groups with regard to diabetes, hyperlipidemia, and hypertension were comparable. Also, total plaque burden was not significantly different (high-risk: mm 3 vs. low-risk: mm 3 ;p=ns).on the contrary, IVUS-VH demonstrated significantly higher necrotic plaque mass in high risk patients (18% vs. 11%; p<0.05) whereas fibrous (66% vs. 68%; p=ns), fibrolipid (10% vs. 12%; p=ns), and calcified (5% vs. 5.5%; p=ns) plaque tissue was comparable. Conclusion: Although total plaque burden of CAV is comparable between groups IVUS-VH reveals a significant higher proportion of necrotic plaque mass in CMV-high-risk patients. Increased necrotic plaque mass may indicate augmented plaque vulnerability and thus may explain excess mortality in these patients. P2334 Resting and exercise haemodynamic and metabolic responses to acute reduction of continuous-flow left ventricular assist device support D. Jakovljevic 1, R.S. George 2,G.Donovan 1, D. Nunan 1, R.S. Bougard 2, M.H. Yacoub 3,E.J.Birks 2,D.A.Brodie 1. 1 Research Centre for Society and Health, Buckinghamshire New University, Buckinghamshire, United Kingdom; 2 Royal Brompton and Harefield NHS Trust, London, United Kingdom; 3 Magdi Yacoub Institute, Harefield Heart Science Centre, London, United Kingdom Purpose: The present study assessed the effect of acute reduction of continuousflow left ventricular assist device (LVAD) support on resting and peak exercise cardiac power output and other haemodynamic and metabolic measurements. Methods: Twelve male patients (age 37±10 yrs) implanted with continuous-flow LVADs, visited the exercise laboratory twice during the same day with at least four hours rest between the two visits. During the first visit, LVAD support was optimal with speeds ranging from 9,000 to 9,600 revolutions per minute. During the second visit the LVAD support was reduced at 6,000 revolutions per minute. Measurements at rest and at the peak exercise of the modified Bruce protocol were undertaken using non-invasive, inert gas, rebreathing haemodynamic and respiratory gas procedures. Cardiac power output, expressed in watts (W), was calculated from cardiac output and mean arterial blood pressure as previously suggested. Results: In response to reduced LVAD support, resting cardiac power output decreased by 21% (from 0.87 to 0.69 W, p=0.068) as was cardiac output by 13% (from 5.3 to 4.6 l min -1, p=0.141) and mean arterial pressure by 9% (from 74.1 to 67.3 mm Hg, p=0.123). Resting stroke volume decreased by 18% (from 71.4 to 58.2 ml.beat-1, p=0.072) while resting heart rate increased by 5% (from 74 to 79 beats min -1, p=0.126). At peak exercise most of the measured haemodynamic and metabolic variables decreased significantly in response to reduced device support. Cardiac power output decreased by 39% (from 2.31 to 1.40 W, p<0.001), cardiac output by 30% (from 12.2 to 8.6 l min -1,p<0.001), mean arterial pressure by 13% (from 85.4 to 74.3 mm Hg, p=0.006), stroke volume by 24% (from 88.4 to 67.5 ml beats -1, p=0.039) and heart rate by 9% (from 138 to 126 beats min -1, p=0.046). Peak oxygen consumption reduced by 23% (from 18.2 to 14.1 ml kg -1 min -1, p=0.004) whereas exercise time decreased by 18% (from 628 to 516 seconds, p=0.032). Conclusion: The present study suggests that cardiac power output is more sensitive to acute reduction of LVAD support than conventionally measured peak oxygen consumption, and therefore should probably be used in the management of LVAD patients. P2335 Subclinical Ebstein-Barr virus (EBV) infection is frequent in long-term cardiac transplant recipients C.H. Mussner-Seeber 1,M.Frick 1,H.Antretter 2, D. Hoefer 2, G. Weiss 3, G. Poelzl 1. 1 Department of Internal Medicine III - Cardiology, Innsbruck, Austria; 2 Department of Cardiothoracic Surgery, Innsbruck, Austria; 3 Department of Internal Medicine I, Innsbruck, Austria Introduction: Viral infections account for substantial morbidity and mortality in solid organ transplantation. In heart transplant recipients viral infections have been associated with acute rejection, cardiac allograft vasculopathy (CAV), posttransplant lymphoproliferative disease (PTLD), and graft loss. The frequency of subclinical viral infections in the long-term course after heart transplantation (HTX) is unclear. It was the goal of our study to investigate the prevalence of various types of viral infections in stable heart transplant recipients. Patients and methods: From June to December consecutive heart transplant recipients (21% female) were tested for viral infection. All patients were on stable doses of immunosuppression and free from acute infection or rejection for at least 3 months before entry into the study. Mean patient age was 61±11 years (range 23-81). Median time after HTX was 8 years (range 1-24). Patients were tested for cytomegalovirus (CMV), Ebstein-Barr virus (EBV), parvovirus B19 (PV B19), herpes simplex virus (HSV) 1/2, human herpes virus (HHV) 6/8, and hepatitis C using qualitative PCR in peripheral blood. In addition, serologic antibody screening was applied for all the above viruses including hepatitis A and B. Results: Reliable test results were available in 98 patients, of which 30 (30,9%) were tested positive (EBV 26,3%, HSV1/2 2,7%, HHV6 2,6%, HHV8 1,3%, HVC 1,2%). Co-infection with EBV and HSV1/2 was found in one patient. There was no difference between virus-positive and virus-negative patients with regard to age, gender, time after HTX, CMV- and gender-mismatch at time of transplantation, and type of immunosuppression. Of note, no differences were seen either in graft function and laboratory parameters such as ALT, AST, GGT, LDH, leucocytes, lymphocytes, monocytes and haemoglobin. Conclusion: Subclinical EBV infections are unlike other viruses - frequent in stable heart transplant recipients. EBV infections were not correlated with donor a/o recipient related parameters and did not impact on blood count and liver function tests. Since the long-term consequences of subclinical EBV infections are unknown, effectiveness of routine viral testing in heart transplant recipients remains unclear and has to be addressed in a follow-up study. P2336 Effects of left ventricular assist devices on heart rate and Vo2 recovery trends following peak exercise: optimal vs reduced unloading speed G.C. Donovan 1, R.S. George 2, D.J. Jakovljevic 1, D. Nunan 1, R.S. Bougard 2, M.H. Yacoub 3,E.J.Birks 2,D.A.Brodie 1. 1 Buckinghamshire New University, Chalfont St Giles, United Kingdom; 2 Royal Brompton and Harefield NHS Trust, London, United Kingdom; 3 Magdi Yacoub Institute, Heart Science Centre, London, United Kingdom Purpose: This study assessed heart rate and Vo2 recovery trends following peak exercise in patients recently implanted with a left ventricular assist device (LVAD). Methods: Fourteen non-paced patients (2 females) age 35±8 yrs implanted with continuous-flow LVADs (mean duration of support 45±8.5 days), undertook two modified Bruce continuous progressive exercise tests during the same day. The first test took place with the LVAD on optimal unloading speed, pump-on, and the second at a reduced speed where there was minimal contribution from the device into the circulation, pump-down. There were at least four hours rest between the two testing conditions. Heart rate and metabolic measurements were

89 Heart transplantation and left-ventricular assist devices Minimally invasive and robotic surgery 389 continuously recorded. Repeated measures ANOVA and paired t-tests were used to assess individual and group change scores at rest, peak exercise and throughout five minutes of a seated recovery. Delayed heart rate recovery, post peak exercise, was defined as < 18 by minute one, for this recovery position. Results: There was a significant reduction in total exercise time for the pumpdown test, 683±131 vs. 617±151 seconds (p = 0.03), although three patients exercised for longer during the pump-down test. Change scores in heart rate, Vo2, RER, and perceived exertion were similar between tests at rest, during peak exercise, and during the recovery period. Four patients (29%, males) demonstrated a reduced heart rate recovery during the first two minutes (mean 15±1.1 by minute one; 22±1.3 by minute two), in both pump-on and pump-down tests. A further two patients demonstrated a delayed recovery (< 15bmin -1 by minute one) in the pump-down test. A post-exercise rise in Vo2 (3.6±0.7 ml kg -1 min -1 ) during minute one in the pump-down test was observed in four patients (29%, one female). In two of these patients, a smaller increase was also observed in the pump-on test. Interestingly, three of the patients (21%, males) showed a trend towards delayed heart rate and Vo2 recovery in both tests. Conclusion: This study shows that trends in heart rate and Vo2 recovery appear to be similar, despite an acute reduction in LVAD speed. However, withinindividual data suggest that further investigation is warranted in order to assess whether continued LVAD support improves post-exercise heart rate and Vo2 responses in those patients demonstrating a delayed recovery pattern. Purpose: The purpose of the study was to detect predictors of all-cause mortality in heart transplant patients. The influence of basic recipient characteristics as well as different biomarkes and histopathological rejection grades after HTx were investigated. The usefulness of inflammatory or myocyte damage markers as noninvasive method to monitor cellular rejection was examined. Methods: The patients enrolled had mean age of 48,7±12,4 years, the median follow-up was 26 months, in which 397 biopsy specimens were obtained. Troponin T,NT-proBNP,CRP,creatinine,urea and lipid profile were serially determined in 42 de novo and chronic heart transplant recipients at the time of routine endomyocardial biopsy. General patient records prior to HTX were collected, including age, gender, BMI, etiology of heart disease, preexisting diabetes, pulmonary vascular resistance, pulmonary artery pressure, cardiac output, and variables for period after HTx were included, such as hypertension, renal failure, BMI, steroid diabetes, CMV infection, rejection index. Results: NT-proBNP values posttransplant and CRP values 3 months after HTx in comparison between stable and deceased patients (NT-proBNP: vs ,p=0.005; CRP: 37.4 vs. 2.9,p=0.004) correlated significantly with mortality. Renal failure raised the mortality hazard ratio five times. Other variables showed no correlation to mortality. No correlation was found between NT-proBNP, CRP and troponin T values and grade of rejection. Higher NT-proBNP levels, as well as CRP, were observed in early posttransplant period, with declining trend over time. Mortality rate 2 years posttransplant was 18%. Conclusions: NT-proBNP mean values in early and late postransplant period and CRP values in late posttransplant period proved to be significant predictors of allcause mortality. CRP in the first 3 months showed no significance as predictor of survival, probably due to great oscillations associated with frequent infection episodes. Preserving normal renal function correlated with a lower rate of complications and mortality, so the significance of preventing steroid diabetes and strict control of cyclosporin levels and toxicity proved to be of great importance. Our results also implicate that NT-proBNP, CRP and troponin T are not useful markers for monitoring slight or moderate rejection episodes. The levels of NT-proBNP and CRP are highest in the first months with progressively decreasing trend during the first year in stable patients, reaching almost reference values in patients with no complications. P2338 Percutaneous left ventricular assist devices versus intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials J.M. Cheng, C.A. Den Uil, S.E. Hoeks, M. Van Der Ent, L.S.D. Jewbali, R.T. Van Domburg, P.W. Serruys. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Aims: Studies have compared safety and efficacy of percutaneous left ventricular assist devices (LVADs) with intra-aortic balloon pump (IABP) counterpulsation in patients with cardiogenic shock. We performed a meta-analysis of randomized controlled trials to evaluate potential benefits of percutaneous LVAD on hemodynamics and 30-day survival. Methods: In two trials, the TandemHeart was evaluated and, recently, a study on the Impella device was published. Results: After device implantation, LVAD patients had a higher cardiac index (mean difference (MD) 0.35, 95%CI 0.14;0.55), higher mean arterial pressure (MD 13.1, 95%CI 6.3;17.9) and lower pulmonary capillary wedge pressure (MD -5.3, 95%CI -9.4;-1.2) compared to IABP patients. The pooled relative risk estimate revealed no significant difference in 30-day mortality using mechanical support by percutaneous LVAD compared to IABP (RR 1.06, 95% CI 0.68; 1.66). Leg ischemia (p<0.01) and bleeding (p<0.001) were observed more freqently in TandemHeart patients than in IABP patients. P2341 Perioperative asymptomatic troponin release after endovascular abdominal aneurysm repair is associated with poor long-term outcome O. Schouten 1,T.A.Winkel 1, S.E. Hoeks 1, J.P. Van Kuijk 1,W.J.Flu 1, Y.R.B.M. Van Gestel 1,J.J.Bax 2, D. Poldermans 3. 1 Erasmus MC, Rotterdam, Netherlands; 2 Leiden University Medical Center, Leiden, Netherlands; 3 Erasmus, Rotterdam, Netherlands Background: Endovascular abdominal aortic aneurysm (AAA) repair is considered as treatment of choice in high-risk cardiac patients. However, endovascular AAA repair is not associated with long-term survival benefit. The aim of the current study was to assess the impact of perioperative asymptomatic troponin release after endovascular AAA repair on long-term prognosis. Methods: In 228 patients undergoing elective endovascular AAA repair routine sampling of cardiac troponin T (ctnt) and ECG recording was performed on days 1, 3, 7, and at the day of discharge. Elevated ctnt was defined as serum concentrations 0.01 ng/ml. Asymptomatic cardiac damage was defined as ctnt release without chest pain complaints or ECG changes. The median follow-up was 2.9 years and survival status was obtained by contacting the civil service registry. Results: A total of 29/228 patients had ctnt release, median 0.08 ng/ml, of who 24 (83%) were asymptomatic. Patients with asymptomatic ctnt release had an increased mortality rate after 2.9 years as compared to patients without perioperative ctnt release (56% vs 18%, p<0.001, figure). Also after adjustment for clinical risk factors and medication use applying multivariate Cox regression analysis, asymptomatic cardiac damage was associated with a 3.6 fold increased risk for mortality (HR 3.6, 95% CI ) while statin use was associated with a reduced risk for long-term mortality (HR 0.58, 95% CI ). Conclusion: Although percutaneous LVAD provides superior hemodynamic support in patients with cardiogenic shock compared to IABP, the use of these more powerful devices did not improve early survival. Yet, these results do not support the use of percutaneous LVAD as the approach of first choice in the mechanical management of cardiogenic shock. P2340 Predictors of mortality and clinical usefulness of NT-proBNP, troponin T and C-reactive protein in follow-up after heart transplantation D. Milicic, J. Ljubas, B. Skoric, I. Gornik, D. Jelasic, J. Samardzic. University of Zagreb School of Medicine, Zagreb, Croatia Conclusion: Asymptomatic cardiac damage in patients undergoing endovascular AAA repair is associated with poor long-term outcome. Routine perioperative cardiac screening after endovascular AAA repair might be warranted. P2342 Quality of Life Threee Years after MIDCAB versus Isolated RIVA-Stenting M. Breuer, B. Georgii, M. Ferrari. Universitaetsklinikum Jena, Jena, Germany Purpose: Studies regarding long-term follow-up of patients after MIDCAB versus isolated RIVA-stenting, in particular focused on quality of life, are rare. We present the results of a retrospective long-term follow-up in 330 patients comparing health status and quality of life 1 to 7 years after surgical/interventional therapy. Methods: The study was performed in 172 patients (28.5% female) after MID- CAB compared to 158 patients where stent-grafting of the LAD (27.2% female)

90 390 Heart transplantation and left-ventricular assist devices / Non-coronary cardiac interventions was the therapy. After an initial interview by phone postoperative quality of life was examined by short-form 36 questionnaire (SF-36). Mean follow-up was 38 months. MIDCAB group contained n=137 single-vessel (79.7%), n=23 doublevessel (13.4%), n=12 triple-vessel (7.0%) diseases. In the stent-grafted group were n=125 (79.1%) single-vessel, n=23 (14.6%) double-vessel, n=10 (6.3%) triple-vessel diseases. Results: Six of eight subscales were rated remarcably better after MIDCAB. Significantly better estimated was general health perception (p<0.04). Stentgrafted patients showed favourable results in role emotional functionning and mental health. Regarding subgroups with up to 2, 3-4, 5-7 years of follow-up there were no significant differences. Stent grafted patients >80 years showed better results in all eight sub- and summscales, with significant differences in role function and role emotional functionning (p<0.05). MIDCAB-patients <80 had significantly better results in general health perception and standardized physical summscale (p<0.02). Conclusions: Refering long-term results for quality of life, MIDCAB-patients <80 years seem to profit more than stent-grafted patients, in particular for physical reasons. In patients >80 years however quality of life is higher after stent-grafting. P2343 The role of echocardiography parameters in monitoring of patients treated with Transcatheter Heart Valve Implantation procedures (THVI) T. Niklewski, R. Przybylski, K. Wilczek, M. Krason, P. Chodor, P. Nadziakiewicz, S.Z. Pawlak, J. Glowacki, M. Zembala. Slaskie Centrum Chorob Serca, Zabrze, Poland Purpose: Echocardiography is one of the most important tools used for qualification and monitoring of high risk patients (pts.) with severe aortic valve stenosis (AS) for transapical and transfemoral valve implantation procedures (THVI). Precise measurement of aortic valve annulus diameter, severity and symmetry of calcifications, transvalvular gradients, LVOT narrowing, ejection fraction (EF) and aortic valve valve area (AVA), degree of regurgitation (AR) after balloon predilatation, Effective Orifice Area (EOA) of implanted prostheses, cusps opening, gradient and degree of perivalvular leakage are detrimental values assessing correct preprocedural valve selection and optimal placement after implantation. Material and method: Using transoesophageal echocardiography (TEE) our first 9 THVI patients were analyzed (8 females and 1male) with mean age 78,16 years, BSA 1,72m 2, logistic Euro Score and STS Score were 20,56% and 18,7% The mean preoperative EF was 50,5%, aortic valve area (AVA): 0,68cm 2, mean transvalvular gradient 65,9mmHg and mean annulus diameter 22mm In 3 pts. with 20mm we used 23mm and in 4pts with annulus larger than 22mm Edwards SAPIEN 26mm balloons and valves. Two of patients received only percutaneous balloon valvuloplasty because of intraoperative technical contraindications. Results: The intraoperative TEE revealed mean post balloon AV area extension over +0,28 cm 2 to 0,96cm 2 (NS) with mild AR and without significant decrease of transvalvular gradients. After valve implantation mean prosthesis annulus relaxation using the 23 and 26mm prostheses were 20 and 23mm measured in long axis view. We observed only trivial perivalvular leakage in 2 pts. Mean gradient decreased to 12,5mmHg (p=0,0001), EOA increased to 1,47cm 2,(p<0,05) mean EOAindex of all our group was 0,836cm 2 /m 2 (0,73cm 2 /m 2 for 23mm and 1,08cm 2 /m 2 for 26mm prostheses respectively). Mean postprocedural EF was 48,5%. Conclusions: Our echocardiography data shown that despite of significant improvement of mean AVA and decreased transvalvular gradient, implanted valves expanded only to preoperatively measured annular diameter, what may result in moderate patient prosthesis mismatch (0,85-0,60cm 2 /m 2 ), which could influence on left ventricular function and mass reduction in the future. Transcatheter-based balloon dilatation of stenotic, severely concentric calcified aortic valve did not improve the sufficient aortic valve opening in our material. P2344 Endoscopic removal of dislocated atrial septal closure devices and ASD repair T. Schachner, N. Bonaros, D. Wiedemann, S. Mueller, T. Bartel, A. Daburger, O. Pachinger, G. Laufer, J. Bonatti. Innsbruck Medical University, Innsbruck, Austria Purpose: Percutaneous closure of a patent foramen ovale or atrial septum defect is nowadays applied in the majority of the cases with acceptable results. Device displacement or incomplete closure of the interatrial communication may lead to residual shunt, hemolysis and recurrent neurological events. We report on our experience with 5 patients who underwent totally endoscopic removal of an insufficient atrial septal closure device at our institution. Methods: Between March 2003 and January patients (aged 37 (16-60) years, 13 (33%) male) underwent totally endoscopic ASD closure. Out of theses 40 patients between May 2007 and January patients (3 males and 2 females, age: 40 (30-57) years) with a displaced atrial septal closure device (Amplatzer Septal Occluder, or PFO Star Occluder) were referred to our department of cardiac surgery. All patients were operated in a completely endoscopic fashion using the Da Vinci Telemanipulator (Intuitive Surgical, Sunnyvale CA), intraaortic balloon endoocclusion and remote access perfusion via the right femoral vessels. Device removal was performed by means of Endo Catch 15 mm retrieval device Covidien (Norwalk, CT). Results: All 5 procedures were succesfully completed in a totally endoscopic fashion. The Amplatzer Septal Occluder and the PFO Star Occluder were removed in 3 and 2 cases respectively. Median size of the removed devices was 24 (22-26) mm. The entire procedure was completed in 319 ( ) min. Cardiopulmonary bypass time was 167 ( ) min, cross clamp time was 108 (88-169) min. All but one defects were closed using a Dacron patch. There was no patient with a rest shunt in the intraoperative transesophageal echocardiography, no interatrial communication was detected at the echocardiography before discharge. All patients had an uneventful postoperative course and were discharged home on the 5th or 6th postoperative day. No residual shunt was detected in the follow up period of 9 (1-19) months. Conclusions: Removal of a dislocated atrial septal closure device can be successfully performed in a totally endoscopic approach using the robotic system and remote access perfusion with balloon endoocclusion. Operative times are acceptable and intermediate results are not compromized by the endoscopic technique. P2345 NON-CORONARY CARDIAC INTERVENTIONS Transcatheter therapy of tricuspid regurgitation by heterotopic valve implantation: experimental results A. Lauten, M. Ferrari, C. Willich, H. Schubert, S. Bischoff, H.-R. Figulla. Universitaetsklinikum Jena, Jena, Germany Objective: Tricuspid regurgitation (TR) reduces cardiac output (CO) and increases central venous pressure with secondary organ dysfunction, e.g. leading to liver cirrhosis and portal hypertension. To date, the surgical approach is the only option to treat TR. Here we report the first experience of interventional treatment by percutaneous implantation of valved stents into the inferior (IVC) and superior vena cava (SVC) to replace tricuspid valve function in acute insufficiency. Methods: In nine sheep (54-75kg) acute TR grade III-IV was created by papillary muscle and chordae avulsion using a 0.07-inch retrograde wire blade. Successful creation of TR was confirmed by angiography and by a prominent ventricular wave in central venous pressure recording. Two self-expanding nitinol stents containing a porcine pulmonary valve where then implanted in the IVC and SVC in a transcatheter approach. Implantation was performed through the right jugular vein by means of a 21F catheter and guided by fluoroscopy. Hemodynamics where recorded throughout the experiment, valve function was verified by angiography and epicardial echocardiography. Results: TR grade III-IV was successfully created in nine animals and resulted in a reduction of CO from 5.15±1.69/min to 2.9±1.16/min. Right atrial and central venous systolic pressure increased to 12.9±3.14mmHg and 16.2±2.82mmHg, respectively. After deployment of the IVC- and the SVC-valve, systolic venous pressure decreased and cardiac output significantly increased to 4.20±0.84l/min. At autopsy correct device positions where verified in all successfully implanted animals. No macroscopic damage, central venous perforation or thrombus formation was observed by venous stents in the acute model. Conclusion: In high-grade TR implantation of valved stents in central venous position reduces venous regurgitation and improves hemodynamics in the acute experiment. Implantation of one or two valves in central venous position is technically feasable and partially or fully replaces tricuspid valve function in the animal model. These techniques could expand the therapeutic options for patients with relevant TR but high risk for open heart surgery. P2346 Italian patent foramen ovale survey (I.P.O.S.): early results G. Butera 1, G. Sangiorgi 2, A. Aprile 3, G. Ussia 4, I. Spadoni 5, E. Onorato 6, L. Caputi 7,A.Benassi 8,G.Anzola 9, M. Carminati 1 on behalf of IPOS Investigators. 1 policlinico san donato irccs, San Donato Milanese, Italy; 2 department of cardiology- Modena University, Modena, Italy; 3 department of cardiology, Bergamo, Italy; 4 ospedale ferrarotto, Catania, Italy; 5 ospeale apuano, Massa, Italy; 6 department of cardiology, Brescia, Italy; 7 istituto besta, Milan, Italy; 8 hesperia hospital, Modena, Italy; 9 department of neurology, Brescia, Italy Purpose: Percutaneous defect closure is well established in patients with a symptomatic patent foramen ovale (PFO). However, real-word practice derived from large patient populations are lacking. IPOS is a web-based, prospectic, observational, multi-centric real-world registry designed to analyze the current standards of PFO closure in Italy. Aims of the study were: (a) to analyse clinical practice regarding PFO closure; (b) to study indications, devices used, results of percutaneous PFO closure; (c) to evaluate follow-up of large series of patients treated by percutaneous closure. Methods: The survey lasted 12 months. Follow-up evaluations will be recorded yearly up to 5 years after procedure. Between November 2007 and October 2008, 50 centres accepted to participate. One thousand and ninety patients were included in the registry (58% females; median age 45 years (range 5-75 years). The large part of subjects were treated due to a previous history of TIA/Stroke (85% of pts). Fifteen percent of subjects had an associated migraine with aura. Results: Procedures were monitored by using trans-esophageal echocardiography and fluoroscopy in 70% of subjects while 30% were monitored by using intracardiac echocardiography. Procedures were performed under general anesthesia

91 Non-coronary cardiac interventions 391 in 54% and under local anesthesia/conscious sedation in 46%. An aneurysm of the interatrial septum was associated in 41% of patients. Devices used for PFO clusore were PFO/Cribriform Amplatzer devices in 68%, Cardiastar devices in 8%, Starflex/Biostar in 7%, Premere in 11%, Helex in 2%, other in 4%. Early complications occurred in 27 subjects (2.5%): 7 experienced transient atrial fibrillation, 1 had pericardial effusion, 2 needed vascular surgery due to the occurrence of femoral artero-venous fistula, 1 developed blood effusion due to oro-tracheal intubation, in 2 subjects a device was removed due to device malposition, 1 patients needed surgery due to device malposition, other minor complications in 13 subjects. Conclusions: Early results of the IPOS study shows that percutaneous PFO closure is a safe procedure. Long-term Follow-up will be available at the time of the meeting. P2347 Patent foramen ovale closure limits recurrence of cryptogenic stroke: MRI-based long-term follow-up study P. Guerin 1, T. Manigold 1, B. Guillon 2, H. Desal 3, E. Auffray-Calvier 2, J.M. Langlard 4, B. Delasalle 1, R. Fressonnet 1, N. Piriou 1, D. Crochet 1. 1 INSERM, UMR915, l institut du thorax, Nantes, France; 2 CHU Nantes, Service de Neurologie, Nantes, France; 3 CHU Nantes, Service de Neuro-radiologie, Nantes, France; 4 Nantes. L Institut du Thorax, Nantes, France Background and purpose: Patients with cryptogenic stroke and patent foramen ovale (PFO), especially when associated with atrial septal aneurysm (ASA), are at risk of recurrent cerebrovascular events. This study seeks to assess long-term outcome in cryptogenic stroke patients, based on clinical and MRI evaluation, because transient ischemic attacks (TIA) or stroke may be asymptomatic. Method: 72 consecutive patients, under 55 years of age, with ischemic stroke and PFO and associated ASA or large PFO with spontaneous right-to-left shunts, closed percutaneously, were assessed at least one year after closure. Follow-up included cardiac and neurological assessment, contrast transthoracic echocardiography (TTE), contrast transcranial doppler (TCD) and cerebral MRI. Results: Data were available in 71 patients (40.5±9.0 years; sex ratio: 1.5). Percutaneous PFO closure was successful in all patients; ASA was observed in 90.1%. At a mean follow-up of 17.8±8 months, no stroke recurrence was noted, clinically or on MRI. Residual shunt was absent on contrast TTE in 83.8% of cases, and in 65.6% after Valsalva, dropping to 65.2% and 24.6% respectively using TCD, with a majority of small shunts. Final clinical follow-up, at 3.0±1.1 years, found no stroke recurrence. Conclusion: In selected patients, younger than 55 years, PFO closure associated with antithrombotics after a first cryptogenic stroke is safe and prevent symptomatic or silent recurrent cerebral ischemic events, although residual shunt remained. To the best of our knowledge, this is the first study to assess ischemic stroke recurrence from clinical signs and MRI follow-up. MRI was more sensitive in detecting symptomatic or silent stroke. No closure complications were detected over at least one year after the procedure, as described in most studies using these new devices P2348 Cardiac veins and coronary arteries: relevant data for percutaneous indirect annuloplasty R. Del Valle Fernandez, V. Jelnin, G. Panagopoulos, C.E. Ruiz. Lenox Hill Heart and Vascular Institute, New York, United States of America Background: In percutaneous indirect mitral annuloplasty techniques, a cinching device is deployed in the coronary sinus (CS)-great cardiac vein (GCV) in an attempt to indirectly cinch the mitral annulus (MA). Prior reports showed that the coronary arteries may lie between these structures and that coronary flow may therefore be compromised. The aim of this study is to describe the anatomy of the cardiac venous system and its relations to the coronary arteries. Methods: Retrospective analysis of 50 patients (30% males) studied with 64 slices computed tomography angiography for coronary artery evaluation, between January-May, Data was analyzed using SPSS Results: Age was 67±14 years and ejection fraction 60±12%. Left and balanced coronary artery dominance were present in 6% and 4% of the patients (p), respectively. Length of the CS-GCV was ±11.42mm. Maximum vein dimensions were found at the CS ostium, with a progressive decrease in size along the CS/GCV trajectory (p<0.001). There was one CS/GCV-arterial intersection in 14p, two in 23p and three or more intersections in 13p. Mean distances from the CS ostium to the first and second arterial intersections were 83.7±19.8mm and 106.2±17.0mm, respectively. The CS/GCV crossed above an artery at least once in 41 patients (82%) and twice in 19 patients (38%). The artery crossed above was: the left circumflex (LCX) in 39 intersections (proximal LCX in 33, mid in 5 and distal in 1), the 1st and 2nd marginal branches in 4 and 1 intersections, respectively, and the intermediate ramus in 7. In one patient the vein crossed above the proximal left anterior descending artery. Tributary veins: a marginal vein crossed over a coronary artery in 23p and the middle cardiac vein crossed over the posterior descending artery or the posterolateral artery in 31p. Vein anatomy at crux cordis was Von Ludhinghausen type I in 16% and tipe III in 6%. Mean number of posterior veins (PV) was 1.5 and of marginal veins (MV) was Mean distances from the CS ostium to the origin of the PV1, PV2, PV3, MV1, MV2 and MV3 were 18.8±13.0, 25.6±11.5, 45.1±11.2, 62.3±15.1, 74.3±21 and 96.5±24.7mm, respectively. Conclusions: In most patients the CS/GCV crosses over a coronary artery at least once before reaching the interventricular groove and therefore, assessment of the individual anatomy may be worth prior to indirect annuloplasty interventions. Prospective studies analyzing the clinical implications of these findings are essential. P2349 Migraine evolution after percutaneous closure of patent foramen ovale A. Wahl, F. Praz, T. Tai, M. Schwerzmann, S. Windecker, H.P. Mattle, B. Meier. Inselspital Bern, Berne, Switzerland Background: Patent foramen ovale (PFO) has been linked to migraine, and retrospective studies reported an improvement in migraine prevalence and frequency after PFO closure for other reasons. We sought to identify predictors of migraine improvement after PFO closure. Methods: Of 497 patients undergoing PFO closure using the Amplatzer PFO Occluder for secondary prevention of paradoxical embolism, 125 (25%; aged 51±11 years; 57% male) suffered from migraine (63% with aura) according to the criteria of the International Headache Society. Clinical outcome was retrospectively assessed for up to 9 years. We used scales to evaluate the frequency (<1 /month, 1 /month, 2 3 /month, 1 /week, 2 6 /week, 1/day, >1 /day), the duration (<4hr, 4 72 hr, >72 hr), and the intensity (from 0 to 10) of headache episodes. Patients also self-rated the overall improvement or worsening in quartiles. Results: All implantation procedures were successful. There were no device related complications. No patient was lost during 5±2 years of follow-up. At 6 months, complete PFO closure as assessed by contrast TEE was achieved in 91%, whereas a minimal, moderate, or large residual shunt persisted in 6%, 2%, and 1%, respectively. One patient (1%) experienced a recurrent transient ischemic attack 4 years after PFO closure. Following the intervention migraine headaches totally disappeared in 43 patients (34%), and improved by at least 50% in 57 additional patients (46%); 8 patients (6%) reported a decrease of 25%. While headache remained unchanged in 11 patients (9%); 6 patients (5%) experienced worsening headaches. Mean subjective improvement was 74±32%. Overall, mean headache frequency (from 2-3 /month to 1 /month; p<0.001), duration (from 4-72 hr to <4hr; p<0.001), and intensity (from 7±2 to 2±3; p<0.001) improved significantly. There was a significant decrease of any migraine headaches (from 100% to 60%; p<0.001), of migraine with aura (from 63% to 18%; p<0.001), and of the number of patients taking any migraine medication (from 89% to 51%; p<0.001). In the responder group ( 50% improvement) the initial prevalence of migraine with aura was higher (40% vs. 68%; p=0.01). The presence of aura (Odds ratio 5; CI ; p=0.03) and high pain intensity (Odds ratio 1.6; CI ; p=0.02) were both independent predictors of response to treatment. Conclusions: These results suggest that percutaneous PFO closure durably alters the spontaneous course of migraine. Presence of aura and higher pain intensity at baseline are independent predictors of response to closure. P2350 Catheter closure of large atrial septal defects associated with deficient aortic and posterior rims using the greek maneuver B.D.T. Thanopoulos 1, P.D. Dardas 2, N.E. Eleftherakis 1, E.K. Karanasios 1, N.V. Ninios 2. 1 Aghia Sophia Children s Hospital, Athens, Greece; 2 Agios Loukas Hospital, Thessaloniki, Greece Objectives: In patients with large atrial septal defects (ASDs) and deficient aortic and/or posterior rim successful deployment of the Amplatzer septal occluder (ASO) is challenging and several times impossible. In this report we describe a modification of the technique (Greek maneuver) of ASD closure using the ASO to circumvent this problem. Methods and Results: During the last 3 years 65 patients (median age 14.8 years, range 4 to 52 years)with large ASDs and deficient aortic and/or posterior rim underwent catheter closure with the ASO using the Greek maneuver. The Greek maneuver is applied when protrusion of the aortic edge of a deployed (using the standard of ASD closure technique) device in to the right atrium is detected by echo. To circumvent this problem the sheath is advanced into the left atrium where the left disk and 2/3 rds of the right disk are deployed. Then the whole delivery system is pushed inward and leftward gently against the left atrial wall. This trick changes the orientation of the left disk which becomes parallel to the septum preventing protrusion of the device into the right atrium. The ASO was successfully implanted and was associated with complete closure in 62/65 (95.3%) patients. There were no early or late complications related to the procedure. Conclusions: The Greek maneuver is a quite useful trick that works well in preventing the protrusion of the aortic edge of the ASO in patients with large ASDs and deficient aortic and/or posterior rim.

92 392 Non-coronary cardiac interventions P2351 Clinical results of large secundum atrial septal defect closure in adult using percutaneous cocoon atrial septal occluder K. Lairakdomrong, S. Srimahachota, P. Lertsapcharoen, J. Chaipromprasit, S. Boonyaratavej, P. Kaewsukkho. King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand Background: Atrial septal defect (ASD) is a common congenital heart disease in adult. Amplatzer septal occluder is one of the most common devices used for transcatheter closure due to its high success rate and ease to implant. Cocoon atrial septal occluder is a new nitinol-based device, its shape resembles Amplatzer septal occluder but coated with platinum to prevent nickel release. Little is known about clinical results of large ASD closure using Cocoon atrial septal occluder. Objective: To review our experience in closure of secundum ASD in adult by Cocoon septal occluder and to compare the clinical and results of the pts who had ASD closure with the device 30mm and <30 mm. Methods: Between November 2005 and October 2008, 63 consecutive pts underwent transesophageal echocardiography (TEE)-guided transcatheter closure of secundum ASD at our institution. The patients were divided into Group 1 and 2 according to device diameter 30 mm (n=31) and <30 mm (n=32), respectively. Clinical outcomes, complications and transthoracic echocardiography (TTE) before hospital discharge, 1-3 month and 1 year were analyzed. Results: Device implantations were successful in 27 pts (87.1%) in group1 and 32 pts (100%) in group 2 (P=0.053). The maximum size of secundum ASD in group 1 determined by TTE, TEE and balloon sizing diameter (BSD) were 22.6±5.0 mm (range 15-32), 28.1±4.8 mm (range 19-39) and 31±3.5 mm (range 23-38) respectively. The maximum size of secundum ASD in group 2 determined by TTE, TEE and BSD were 19.7±4.4 mm (range 12-31), 20.4±3.4 mm (range 13-26) and 23.1±2.9 mm (range 15-30) respectively. The mean device size in group 1 and 2 were 33.5±3.1 and 24.6±3.3 mm, respectively. Four pts (12.9%) in group 1 had unsuccessful implantation. All of them were in the first 15 cases of using large device ( 30 mm) and two of them had device embolization requiring surgical removal. The patients in both groups were gradually improved in clinical symptoms and decreased in RV systolic pressure and RV size with complete ASD closure at 1 year. Conclusion: Transcatheter closure of large secundum ASD by Cocoon septal occluder is feasible with hemodynamic benefit. However, complication rates are higher with large ASD closed with device size 30 mm especially during the early learning curve period. With experience, the complication rate declines and the success rate is not different from the group with smaller device size. P2352 Long-term outcome of percutaneous balloon mitral valvotomy using multi-track technique in Kenya G. Yonga 1, P. Bonhoeffer 2,C.Jowi 3. 1 Aga Khan University Hospital, Nairobi, Kenya; 2 Great Ormond Street Hospital for Children, London, United Kingdom; 3 University of Nairobi, Nairobi, Kenya Purpose: To determine the outcome of up to ten years of follow-up of patients done percutaneous balloon mitral valvotomy (PBMV) using multitrack technique in Kenya. Method: Prospective and retrospective follow up study of post PBMV utilizing clinic visits, hospital records and telephone calls at three main cardiac catheterization laboratories in Nairobi. 702 patients aged 9-67yrs who underwent PBMV between 1994 and Results: 702 patients have so far been reported to have undergone PBMV by multitrack technique in Kenya. Age range is 9-67yrs. Mean age is yrs. Weights range 18-78kg. Mean echo score Mode NYHA functional class III. Immediate outcome MVA changed from to There was success rate of 97% and mortality rate of 0.5%. A significant proportion of patients was lost to follow up, therefore only 422 (60%) are reported in this study. Restenosis was encountered in 34 (8.1%) patients mostly occurring within 5yrs of PBMV. Immediate MVA outcome <1.8cm 2 and Wilkins score > 10 were significantly associated with Restenosis (95%CI). Event free survival at 3, 5 and 10 years were 94%, 91%, and 80%. Echo score, age, and MVA >1.8cm 2 were predictors of event free survival. The total cost of procedure was average of 1,600/= euros per patient. Conclusions: PBMV by multi-track technique offers our patients with severe mitral stenosis a safe, effective and relatively inexpensive option for therapy. The long term results are good especially amongst those with good post PBMV valve area. Follow up has been a major problem in our set-up but is improving. P2353 Clinical and hemodynamic results in percutaneous mitral valvuloplasty with mitral stenosis and pulmonary hypertension L. Abid, I. Trabelsi, D. Abid, M. Hadrich, R. Hammami, S. Krichene, S. Mallek, F. Triki, M. Hentati, S. Kammoun. cardiology departement of Hedi Cheker Hospital, Sfax, Tunisia Purpose: Percutaneous mitral valvuloplasty (PMV) became the procedure of choice of mitral stenosis with favorable morphology. It is also useful in cases of elevate operative risk, at the aged people and patients with a NYHA class IV or at that with severe pulmonary hypertension. The development of pulmonary hypertension (PH) is a known after- affect at patients with mitral stenosis. However its impact on PMV results at such patients is little described. our objective is to determine the impact of pulmonary hypertension on immediate and long term results of the PMV. Patients and methods: a retrospective study that spreads on 6 years ( ) including all patients undergoing PVM for the first time. Clinical, radiologic, echocardiographic and hemodynamic data of patients have been collected. 72 patients among 289 had PH > 60 (H group), whereas 217 patients had PH < 60 (N group). We compare the immediate and belated results of PVM between the 2 groups. Results: compared to the group without pulmonary hypertension, patients of the H group were younger (28,1 years versus 34,15 years, p<0,05), were presented more often with an acute pulmonary edema (18,6% versus 5% p=0,002), and have more often an echocardiographic wilkin score > 8 (29% versus 19% p=0,05). The mitral area before PVM was 0,8cm 2 against 1,01 cm 2 in the N group (p<0,05). A bad result was noted in 13% of H group against 6% of the N group (p=0,04). Post procedural complications were similar in the 2 groups except for the severe mitral regurgitation which was more often in the H group. The mitral area after PVM was 1,9cm 2 in the N group whereas it was 1,8 cm 2 in the H group (p=0,03). After the PVM, the NYHA class was improved in the 2 groups. During a mean follow up of 92 months, the rate of the cumulative survival was 34% in H group versus 30% in the N group (p=0,03). The NYHA class I or II were met more often in the N group. Conclusion: the PMV is a sure and an efficient procedure even in presence of pulmonary hypertension in spite of the pejorative character that confers the last parameter on the immediate on the long term prognosis. P2354 Safety and efficacy of biostar bioadsorbable atrial septal device for percutaneous patent foramen ovale closure G. Gioffre, M. Iamele, A. Giardina, R. Licitra, S. Rossi, L. Befani, G. Stefanini, G. Pendenza, C. Iani, A. Gaspardone. Divisione di Cardiologia, Ospedale S. Eugenio, Rome, Italy Purpose: The present study was aimed at assessing the feasibility, safety and efficacy of a novel bioadsorbable atrial septal repair device for percutaneous patent foramen ovale (PFO) closure in a single center experience. Methods: Between september 2007-august 2008, 46 consecutive patients (pts) (30 women, mean age 47±11 yrs, range 18-74) underwent percutaneous PFO closure with a bioadsorbable atrial septal repair device. Indications for closure were the presence of significant basal or Valsalva-induced right-to-left atrial shunt at transthoracic echocardiography (TTE) (>grade 1 defined as >10 bubbles during the first 5 cardiac cycles of contrast entering the right atrium) associated with cryptogenic stroke (S, 25 pts), repeated transient ischemic attacks (TIA, 11 pts), severe migraine ( 4 attacks/montly resistant to triple pharmacologic therapy) associated with multiple cerebral ischemic lesions at magnetic resonance imaging (7 pts), decompression illness (2 pts) and platypnea-orthodeoxia syndrome (1 pt). In 6 pts a septal aneurysm (>10 mm excursion) was present. Aspirin 100 mg per day for 6 months and clopidogrel at the dose of 75 mg per day for the 3 months was the standard discharge treatment. Results: The device was successfuly delivered and implanted in all patients. Fluoroscopy time was 5.9±3.5 min. Devise size was 23 mm in 10 pts, 28 mm in 30 pts and 33 in 6 pts. Median hospital stay was 1.6 nights. Four pts had intermittent fever <38 C within 10 days after discharge requiring anti-inflammatory drugs; 5 pts had transient Holter-detected atrial arrhythmias in the first 3 months after discharge and 1 pt only required pharmacological treatment; 4 pts complained atypical transient chest pain within 30 days after discharge. At 9.4±3.8 month follow-up, TTE revealed significant (>grade 1) Valsalva-induced residual shunt in 3 pts (6.5%). No recurrent cerebro-vascular episodes occurred in stroke and TIA pts. Migraine was abolished/improved in 6 pts and unchanged in 1. Conclusions: PFO closure by bioadsorbable device is safe and effective resulting in a high rate of early and complete shunt closure PBMV by Multi-track technique

93 Non-coronary cardiac interventions 393 P2355 Midterm follow-up after percutaneous closure of patent foramen ovale in patients with cerebral ischemia - experience with the Amplatzer PFO Occluder system D. Fischer, A. Schaefer, M. Fuchs, G. Klein, B. Schieffer, G.P. Meyer. Medizinische Hochschule Hannover, Hannover, Germany Background: Prevalence of patent foramen ovale (PFO) with detectable rightto-left shunt is high in patients with TIA/cerebral infarction and is associated with increased risk for recurrent paradoxical thrombembolism. Percutaneous closure represents a promising therapeutic concept since it avoids surgical closure or life-long anticoagulation with coumadin. In our experience, the Starflex occluder system in comination with anticoagulation (coumadin and aspirin) may be associated with an increased prevalence of bleeding complications and thrombus formation on the occluder system. Therefore, this study analysed the midterm follow-up after implantation of Amplatzer occluder with an antithrombotic regimen with clopidogrel and aspirin. Methods and Results: In the present study 114 patients (60 men; age: 47±13 years) with 1 TIA/stroke documented by CCT or MRI were included. All had PFO with significant right to left shunt (Valsalva: >50% of left atrium filled with contrast during TEE) and/or PFO with atrial septum aneurysm, since it has recently been demonstrated that particularly these conditions are associated with increased risk of recurrent stroke. Other sources of embolism were excluded. Implantation of the Amplatzer occluder system was performed under fluoroscopic and TEE guidance PFO-closure was successfull in all patients. Patients were treated for 6 months with an antithrombotic regimen (clopidogrel 75 mg/d and aspirin 100 mg/d). Follow-up included contrast-enriched TEE with Valsalva manoeuvre after 6 and 12 months and a health questionnaire. After a mean TEE follow-up of 10.7 months, PFO was completely closed in 93% of the patients, in 7% a minimal residual shunt was detected. None of the patients showed local thrombus formation on the occluder system. The mean follow-up with the health questionnaire is 17.7±9 months (range 3 to 37), completed in 100% of patients and revealed recurrent neurological symptoms in 5 patients (in these patients, the PFO was completely closed): 1 re-stroke, 2 TIA s and 2 epileptic seizures. One patient suffered from a gastrointestinal bleeding. Conclusion: Percutaneous closure of patent foramen ovale with the Amplatzer occluder system represents a safe and effective therapy for appropriately selected patients to prevent recurrent cerebral ischemic events. Six months of aspirin and clopidogrel prevented the occurrence of thrombi on the occluder. P2356 Atrial septostomy in patients with end-stage pulmonary hypertension. Novel approach to trans-septal puncture R. Baglini. IsMeTT, University of Pittsburgh, Palermo, Italy Purpose: Atrial septostomy in patients with end-stage pulmonary hypertension (PI) is a clinically useful procedure with high intra and periprocedural mortality mainly due to cardiac perforation and tamponade. Aim of this study was to develop a new method of septal perforation in order to reduce the risk of cardiac perforation and mortality during AS. Patients and methods: Five patients (3 males, 2 females, mean age 42,3±12,4 years) with severe, drug resistant PI, NYHA class III/IV and right ventricular failure, were selected to undergo elective atrial septostomy. Pre-procedure echocardiography and cardiac catheterization data were coherent with the clinical assessment. Left atrial dimension was significantly reduced (8,3±2,4 scm) and the interatrial septum was displaced toward the left atrial lateral wall in all patients. After mild sedation, a 9F, 9MHz ICE catheter (Boston Scientific ) was positioned into the right atrium by the left femoral venous route. A 5 F pigtail catheter was inserted through the right femoral artery to the ascending aorta as a mark point. An 8 F Mullins sheath, preloaded with an inner dilator and a 0,018 with a tip equipped by a radiofrequency energy erogator (Bayliss Medical Company )was inserted from the right femoral vein to the right atrium and pointed to the fossa ovalis region on ICE guidance. The Bayliss generator delivers high-voltage continuous radio-frequency energy at a fixed frequency in a high impedance range to create the desired perforation, causing minimal collateral damage to surrounding tissue. Following these steps, after a weight-adjusted heparin iv bolus, a short train of radiofrequency energy at 5 W was erogated during three seconds, to allow the septal perforation. The entire system was then passed through the septum to the left atrium and a balloon septostomy was performed with 5.0 to 10 mm diameter balloons. Results: Procedural immediate success was 100%. No patient developed cardiac tamponade or pericardial effusion. Septal perforation was successful at the first attempt in all patients but one in whom four attempts were needed. Procedure related complications were: a ventricular sustained tachycardia after 30 minutes from the end of the procedure in the fifth patient and a transient cerebral ischemia in the third patient. Closure of the septostomy was shown in the first patient after 20 days and a new septostomy with larger balloons was successfully performed. Conclusion: Radiofrequency perforation of the interatrial septum under ICE guidance seems to be a safe and feasible method for trans-septal catheterization and atrial septostomy in these patients. P2357 Percutaneous closure of large patent ductus arteriosus in adult patients F. Hernandez, J. Garcia-Tejada, M.T. Velazquez, I. Gomez, T. Bastante, L. Unzue, A. Gonzalez, M. De Riva. Hospital 12 de Octubre, Madrid, Spain Percutaneous closure of patent ductus arteriosus (PDA) using occluders and coils is well established. However, closure of very large PDA by surgery or with devices is still a matter of controversy. We describe our experience with percutaneous closure of very large PDA in adult patients using Amplatzer devices. Methods: Ten patients (9 female), mean age 30,6±8 years, with a diagnosis of PDA and left-to-right shunt, underwent right and left cardiac catheterization prior to PDA closure. Anatomical evaluation of PDA was performed with a 90 lateral aortography. Minimal and maximal internal diameters were measured, and size and type of device was chosen according to the anatomy. Results: All 10 patients were successfully treated with Amplatzer devices (eight with the Amplatzer Duct Occluder, two with the Amplatzer Post-MI Ventricular Septal Defect Occluder). Mean diameter of the PDA was 10,4 mm (4-19 mm). Three patients had severe pulmonary hypertension (mean >40 mmhg), that decreased immediately during transient balloon occlusion of the PDA. Echocardiographic follow-up at 9 months showed complete closure in all patients. There were no significant complications related to the procedure, and all patients were discharged after 24 hours. Mean follow-up has been 30±9 months, with no relevant events. PDA patients characteristics n=10 Sex Age PDA size Pulmonary hypertension Device Follow-up Closure (mm) (months) 1 Female 19 8 NO PDA 10/8 55 YES 2 Female 35 9 YES PDA 12/10 51 YES 3 Female YES POST-MI VSD YES 4 Female NO PDA 14/12 45 YES 5 Female 49 8 NO PDA 10/8 32 YES 6 Male NO PDA 14/12 26 YES 7 Female 36 9 NO PDA 10/8 15 YES 8 Female 19 4 NO PDA 6/4 11 YES 9 Female 49 7 NO PDA 10/8 11 YES 10 Female YES POST- MI VSD 18 4 YES Conclusions: Percutaneous closure of very large PDA in adults can be successfully and safely performed with Amplatzer devices. In cases anatomically not amenable for the duct occluder, other devices such as the ventricular septal defect occluder are a good therapeutic alternative. P2358 Transvenous removal of pacing and defibrillating leads using mechanical dilatation: a single center long term experience M.G. Bongiorni, E. Soldati, G. Zucchelli, A. Di Cori, L. Segreti, R. De Lucia, G. Solarino, G. Coluccia. Azienda Ospedaliero - Universitaria Pisana, Pisa, Italy Purpose: Transvenous Pacing (PL) and Defibrillating Lead (DL) extraction is a highly effective technique. Device related complications are currently rising the need of Transvenous Lead Removal (TLR). Aim of this report is to analyse the longstanding experience performed in a single Italian center. Methods: since January 1997 to November 2008, 1365 consecutive patients (1023 men, mean age 65.5 years, range 3-95) with 2413 leads (mean pacing period 68.9 months, range 1-336) were managed. PL were 2101 (1146 ventricular, 843 atrial, 112 coronary sinus leads), DL were 312 (297 ventricular, 2 atrial, 13 superior vena cava leads). Indications to TLR were class I in 33% and class II in 67% of the leads. We performed mechanical dilatation using the Cook Vascular (Leechburg PA, USA) polypropylene sheaths and, if necessary, other intravascular tools (Catchers and Lassos, Osypka, Grentzig-Whylen, G); a Internal Trans- Jugular Approach (ITA) through the internal jugular vein was performed in case of free-floating leads or failure of standard approch. Results: Removal was attempted in 2409 leads because the technique was not applicable in 4 PL (0.2%); 2369 leads (2057 PL, all the 312 DL) were completely removed (98.2%), 20 (0.8%) partially removed, 20 (0.8%) not removed. Among 2329 exposed leads, 353 were removed by manual traction (15.1%), 1754 by mechanical dilatation using the venous entry site (75.3%), 14 by femoral approach (FA) (0.6%) and 168 by ITA (7.2%). All the 80 free-floating leads were completely removed, 23.7% by FA and 76.3% by ITA. Major complications occurred in 8 cases (0.58%): cardiac tamponade (7 cases, 2 deaths), hemotorax (1 death). Conclusions: our experience shows that TLR using mechanical dilation has a high success rate and a low incidence of serious complications in centers provided with wide experience. The use of the ITA allows a very high effectiveness and safety in case of free-floating or difficult exposed leads.

94 394 Non-coronary cardiac interventions / Imaging and intervention in congenital heart disease P2359 Biodegradable magnesium stents in emergency interventions in critically ill babies. First clinical experiences P.A. Zartner 1,M.Sigler 2, D. Schranz 3, M.B.E. Schneider 1. 1 Deutsches Kinderherzzentrum, Sankt Augustin, Germany; 2 Universitätsklinikum, Goettingen, Germany; 3 Universitaetsklinikum Giessen und Marburg GmbH, Giessen, Germany With good early results and superior to balloon dilation only, stents have found its place in interventions in children with a congenital heart disease, but solutions are needed to cover early infancy and the neonatal period. Under compassionate care regulations we implanted absorbable metals stents (AMS, Biotronik, Berlin, Germany) in three patients (bodyweight 1,7 kg, 7 kg, 2 kg) with severe pulmonary vessel obstructions and critical clinical conditions. The AMS was made of an alloy of over 90% of magnesium and some rare earth elements. Projected degradation time was 4 to 8 weeks after implantation; intravascular stability of the stent was 1 to 3 weeks. All stents and the implantation procedures were well tolerated and follow-up was not noticeably influenced by the stent degradation. All three children recovered and could be dismissed home from the hospital. After 4 weeks all stents had lost its stability and gave room to further procedures. One patient died 5 months after implantation due to pneumonia not related to the stent. Autopsy and histopathology revealed a patent vessel at the stented area, with the stent dissolved completely. Biodegradable metals stents offer new strategies in the therapy of congenital heart diseases especially for newborns and small infants. Depending on the implantation site stent diameters of 6 mm and larger are needed. A prolonged degradation time may help to avoid early reintervention. To evaluate the possible domain of biodegradable metal stents in patients with congenital heart diseases is an important challenge to come. P2360 Papillary muscle rupture after percutaneous extraction of pacemaker leads P. Rucinski 1,A.Tomaszewski 1, A. Kutarski 1,B.Malecka 2, A. Zabek 2. 1 Medical University of Lublin, Lublin, Poland; 2 Jagiellonian University, Krakow, Poland Percutaneous leads removal due to cardiac device related infective endocarditis (CDIE) is complex however seems to be safe and effective. Mechanical extraction systems are widely used. Variety of complications and tricuspid valve injury had been described, however no one reported papillary muscle rupture. We performed an analysis of complications of 215 lead extraction procedures looking for tricuspid apparatus injuries. Methods: We analyzed procedures in patients subjected for percutaneous removal of leads with at least one lead was older than 1 year. In 215 patients we extracted 383 leads, (1-6; mean 1,78 per patient). Mean patients age was 64,6 years (5-91), and 29 (69%) were male. The methods of extraction were: extorsion and traction, mechanical (locking stylets, telescopic sheaths) and other mechanical devices (femoral work station, basket, snare, lasso). Transthoracic (TTE) and transespophageal (TEE) echocardiography were performed before and after procedure. Results: Mild to moderate tricuspid regurgitation (TR) was diagnosed in all patients with ventricular lead before and after procedure. In three patients we found new severe TR after extraction. In the first patient round structure connected to chordae and moving between right atrium (in systole) and right ventricle (RV) (in diastole) was observed and was characterized as complete rupture of papillary muscle. In the second patient in place of distal papillary muscle (near free wall of RV) hazy, swollen structure with some chaotic movement in RV (only) was visible and TEE confirmed incomplete. Those two pts had no significant heart failure exacerbation both in short and long term observation what is differentiating form other causes of acute TR. Third patient experienced complete RV papillary muscle rupture but the symptoms were so severe that she was subjected for cardiosurgery. Conclusion: For the first time we described the papillary muscle ruptures as a consequence of lead extraction procedure. This severe complication in some cases may be clinically silent. P2361 Percutaneous leads extraction using mechanical system in 188 patients - single centre experience A. Kutarski 1, B. Malecka 2, P. Rucinski 1, A. Zabek 2. 1 Medical University of Lublin, Lublin, Poland; 2 Jagiellonian University, Krakow, Poland Introduction: The growing problem with pacing system infections and leads excess made the percutaneous lead removal technology widespread. The aim of the study was to analyze efficacy and complications of mechanical percutaneous extraction of pacing and ICD leads in a single reference centre. Methods: In 188 pts (119 male) aged 4-90 years (mean age 64.5), we extracted 342 leads that were at least 12 (PM) or 6 months (ICD) old. Most leads (262) were active and 80 abandoned, 68.9% bipolar, 74.5% passive fixation, 49% - atrial, 48% - RV, 3% LV. Mean age of lead 86±57 months. In 40% of pts. single lead was extracted, 45% - two, 15% - 3 or more (max. 6). The most common indication was local pocket infection (41%); endocarditis (23%) and the necessity to remove abandoned lead (36%). Strategy: mechanical extraction, cardiosurgery in case of failure or complications. Results: Mean procedure time 114 min. Superior approach 95%, femoral 3%, combined 2%. Simple extorsion and traction used in 19.5% cases, mechanical (locking stylets, telescopic sheaths) 76.3%, other mechanical devices (femoral work station, basket, snare, lasso) used in 4,2%. Extraction success rate 98.2%. No peri-operative deaths reported. Complications: 7 pts (cardiac tamponade 2, pulmonary embolism 2, severe tricuspid regurgitation 2, persistent endocarditis requiring cardiosurgery 1). In 3 cases of tearing of extracted lead remained distal part of broken lead was extracted via femoral approach and in 1 case broken distal free part of extracted lead was removed from pulmonary artery via femoral approach using lasso catheter. Conclusions: Percutaneous lead removal using mechanical techniques in experienced centre is safe and has a high success rate. Simple mechanical techniques and subclavian approach are sufficient in most cases and advanced techniques are necessary to complete the procedure in less than 10% of patients. IMAGING AND INTERVENTION IN CONGENITAL HEART DISEASE P2362 High intensity transient signals measured by transcranial Doppler during transcatheter closure of atrial septal defect K. Suda 1,Y.Kudo 1, Y. Tananari 2,S.Itoh 2,H.Ishii 1,H.Nishino 1, M. Iemura 1, Y. Maeno 1, H. Yasunaga 2,T.Matsuishi 2. 1 Kurume University School of Medicine, Kurume, 2 St. Mary s Hospital, Kurume, Japan Purpose: To determine the frequency and nature of high intensity transient signals (HITS) measured by transcranial Doppler (TCD) during transcatheter closure of atrial septal defect (ASD) using Amplatzer septal occluder (ASO). Methods: During closure of ASD in 17 patients, we measured HITS using TCD. Procedure time was divided into 5 periods; Period 1, right heart catheterization; Period 2, left heart catheterization; Periods 3, left heart angiocardiography; Period 4, sizing and long sheath placement; Period 5, device placement and release. We compared HITS among the 5 periods and identified factors that correlated with HITS. Results: Mean patient s age was 19±10 years old and mean size of ASO was 17±5 (10 to 28) mm in diameter. Total number of HITS was 34±28 (3-113). HITS in period 2, 4, and 5 were not significantly different one another but were significantly higher than those in period 1 and 3, (period 2, 11.7±11.2; period 4, 9.3±11.0; period 5, 10.4±12.5 vs. period 1.4±3.6, and period 3, 1.4±1.6 HITS, p<0.05, respectively). Importantly, the time for device manipulation strongly correlated with HITS in period 5 (r=0.83, p<0.0001) and total HITS (r=0.77, p<0.0005). Conclusions: Closure of ASD using ASO produces certain number of microemboli. To decrease the number of microemboli, we have to decrease the time for device manipulation. P2363 Left ventricular twist and untwisting in patients undergoing transcatheter closure of secundum atrial septal defect L.L. Dong, X.H. Shu, D.X. Zhou, L.H. Guan, H.Y. Chen, C.Z. Pan, H.Z. Chen. Zhongshan Hospital of Fudan University, Shanghai, China, People s Republic of Objective: Transcatheter closure of atrial septal defect (ASD) has become a routine procedure. However, no data are available on the impact of overload relief on left ventricular (LV) torsional deformation of ASD. This study sought to evaluate LV twist and untwisting before and early after device closure of ASD using the new speckle tracking imaging (STI) method. Methods: We acquired basal and apical LV short-axis images in 30 patients (29±9 years, 9 males) with normal pulmonary pressure before and 1-day after transcatheter ASD closure (defect diameter 23.7±6.8mm). All data were offline analyzed. LV twist was defined as the difference between LV apical and basal rotation. Results: LV end-diastolic volume (69.6±6.3 ml vs. 62.1±5.0 ml, P = 0.007) and LV ejection fraction (69.3±5.7% vs. 65.9±5.2%, P = 0.007) was increased significantly after successful transcatheter closure of ASD while end-systolic volume was unchanged (22.4±5.0 ml vs. 22.5±4.7 ml, P = NS). After transcatheter ASD closure, there was no significant difference in peak apical rotation and time to the peak (P > 0.05 for both). However, an significantly improved basal rotation was recorded in patients with ASD after the procedure, including significantly increased peak clockwise rotation (-7.1±3.2 vs. -5.4±2.9, P = 0.014), decreased initial counterclockwise rotation (2.0±1.8 vs. 5.1±3.2, P < 0.001) and shortened time to peak clockwise rotation (105.5±16.5% vs ±18.5% of systolic period, P = 0.001). LV twist was significantly improved in patients with ASD after the device closure (16.1±6.7 vs. 12.2±6.3, P = 0.001), whereas there was no significant difference in untwisting rate, time to peak untwisting rate and untwisting during IVRT (all P > 0.05). Conclusions: LV systolic twist could be significantly improved but diastolic untwisting remained unchanged after successful transcatheter closure in patients

95 Imaging and intervention in congenital heart disease 395 with ASD. This improvement was mainly attributed to the improved LV basal rotation rather than the unchanged apical rotation. P2364 Intracardiac ultrasound imaging during percutaneous atrial septal defect or patent foramen ovale closure. Comparison with transesophageal ultrasound findings before the procedure M. Vavouranakis 1, C. Kavouras 1,I.Vlasseros 1, S. Vaina 1, T. Papaioannou 1, E. Sanidas 1, K. Speggos 2,D.Flessas 1, I. Kalikazaros 1, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Areteio General Hospirtal, Athens, Greece Purpose: Transesophageal ultrasound (TEE) has been traditionally used for the diagnosis and guidance of percutaneous atrial septal defect (ASD) and patent foramen ovale (PFO) closure. Intracardiac echocardiography (ICE) has been proposed as an alternative technique to guide these procedures. Methods: In the study we enrolled patients with ASD or PFO. Before the procedure all patients underwent TEE interrogation to image the defect and to study the anatomical characteristics. During closure ICE was performed with an 8Fr ultrasound tipped catheter. After the procedure all patients received aspirin 100 mg for 6 months and clopidogrel 75mg for 3 months. Results: In the study we included in total 65 patients (26 males, mean age 35±4), 40 with ASD (mean Qp/QS ratio: 2.5) and 25 with PFO (20 patients with stroke and 5 with transient ischemic attack). Mean procedural time was 44±23 min. The mean sizes of secundum defects as measured by ICE were larger compared with the respective sizes as measured by TEE (20mm vs. 17.5mm). ICE revealed a chiari network with thrombus in one patient and additional septal defects in two other patients that were not seen by the TEE performed the day of the procedure. Additionally, in 2 patients after microbubbles infusion, ICE showed that there was no PFO present, as it was suggested by TEE imaging. In 63 patients (97%) immediate complete closure was achieved, whereas in two patients a small residual shunt remained. There were no complications observed during or after the procedure. Conclusion: ICE seems to provide superior images of the atrial communications to those obtained by TEE. ICE tends to replace TEE as an imaging tool for ASD and PFO closure, since it can be very useful and more effective imaging technique for detecting details and guiding closure procedures, simultaneously eliminating the need for general anesthesia. P2366 The effect of percutaneous atrial septal defect closure on echocardiographic parameters of the left and right heart O.J. Monfredi, M. Luckie, H. Buckley, B. Clarke, V.S. Mahadevan. Manchester Royal Infirmary, Manchester, United Kingdom Introduction: Percutaneous device closure is an established treatment for secundum atrial septal defects (ASDs), though little is known about its effects on complex echocardiographic parameters. Methods: 26 consecutive patients undergoing percutaneous ASD closure underwent prospective echocardiography at baseline, 24 hours post-, and 6-8 weeks post-closure. Echo parameters were analysed by a single blinded operator. Results: Mean age of the study population was 46 years (±17.8). 69% were female. Mean device size was 27mm (range 11-40mm). Right atrial (RA) area fell by 4.2cm 2 over 8 weeks (p<0.05), whilst mean right ventricular (RV) diameter fell by 0.9cm (p<0.05). RV diastolic and systolic areas also fell by statistically significant amounts. Fractional area change (FRAC) of the RV decreased by a mean of 6.6% on day 1 post-asd closure, and by a total of 11.7% at 8 weeks (p<0.05). Mean RV tricuspid annular plane systolic excursion (TAPSE) decreased by 0.24cm on day 1, and by 0.49cm at 8 weeks (p<0.05). Mean septal mitral annular E/E ratio increased from 12.4 to 16.4 on day 1, and to 20.3 at 8 weeks (p<0.05). Mean lateral mitral annular E/E ratio showed similar statistically significant increases. P2365 Efficacy of percutaneous closure of patent foramen ovale: comparison between three commonly used devices R. Thaman, G. Faganello, M. Nelson, G.V. Szantho, G.R. Gimeno, S. Curtis, R. Martin, M. Turner. Bristol Royal Infirmary, Bristol, United Kingdom Purpose: For patients with stroke due to paradoxical embolus, percutaneous closure of patent foramen ovale (PFO) has become standard therapy with many occluders available. Studies examining the efficacy of the various occluders are lacking. We evaluated short/medium term PFO closure rates of 3 occluders used in a single centre. Methods: One hundred and fifty six adults aged 47±12 (18-81 years) undergoing PFO closure using transoesophageal echocardiography at the Bristol Royal Infirmary, UK were evaluated with transthoracic bubble contrast study before and 6 monthly after PFO closure. The PFO was considered small if <15, moderate if and large if 30 bubbles were counted in the left heart after valsalva. Only large PFO s were included. Results: Indications for PFO closure were: one or more transient ischaemic events/stroke (n=144, 87%), peripheral embolism (n=2, 1%), decompression illness (n=18, 11%) and orthodeoxia (n=2, 1%). Mean balloon PFO size was 8±3.3 (3-17mm), 45 (27%) had septal aneurysm, 29 (17%) had a long tunnel PFO. Three different occluders were used depending on anatomy: Amplatzer (AGA Medical Corporation, Golden Valley, MN) (n=80, 48%), Gore Helex septal occluder (n=48, 29%) and Premere TM (St Jude Medical) septal occluder (n=38, 23%). Complications occurred in 4 (2.4%) patients: pseudo aneurysm (n=1), arteriovenous fistula (n=1) and transient supraventricular tachycardia (n=2). One (0.6%) transient neurological event was recorded during follow up. At 6 months residual right to left shunting ( moderate) was highest in the Helex group [58.3% ( large 45.8%, moderate 12.5%], and lower for Premere [39.5% ( large 23.7%, moderate 15.8%)] and Amplatzer [32.5% ( large 17.5%, moderate 15%)]. Similarly at final follow up residual shunting remained higher in the Helex group [33.3% ( large 25%, moderate 8.3%)], compared to Premere [18.5% ( large13.2%, moderate 5.3%)] and Amplatzer [11% ( large7.5%, moderate 3.5%)]. The Amplatzer was associated with a significantly lower residual shunt rate compared to the Helex (p<0.05 for 6 months and final follow up). The Premere had intermediate residual shunt rate but was not significant in our sample. Multivariate predictors for residual shunts showed included the type of device (p<0.05 for amplatzer vs Helex) and septal aneurysm (RR 0.04, 95% CI ). Conclusions: PFO closure is a safe and efficacious treatment. PFO closure is progressive however closure rates depend on the device and presence of septal aneurysm. Echo changes post-closure Conclusions: The study confirmed that RV remodeling occurs following ASD closure. It demonstrates for the first time that certain echocardiographic effects are evident as early as the first post-procedural day. These effects are presumably related to decreases in RV volume loading consequent on ASD closure, and continue to at least 8 weeks post-closure. Further studies are in progress to elucidate whether certain pre-closure parameters can accurately predict favourable RV remodeling following ASD device closure. P2367 Results of transcatheter closure of unroofed coronary sinus defect J.-K. Wang, M.H. Wu. National Taiwan University Hospital, Taipei, Taiwan Purpose: Unroofed coronary sinus (CS) allows communication between left atrium and CS through the fenestration, resulting in increased pulmonary blood flow. We present the results of transcatheter closure of unroofed CS with Amplatzer septal occluder. Methods: Between January 2004 and May 2008, 9 patients (5 males and 4 females) with ages ranging from 26 to 65 years (median 39 years) underwent attempted transcatheter closure of unroofed CS defect. The procedure was performed under general anesthesia and transesophageal echocardiographic monitoring. Balloon sizing was performed in 8. The device size selected was within 2 mm larger than balloon sizing diameter. In the remaining 1 without balloon sizing, the device diameter selected was 6 mm larger than maximal diameter of CS ostium measured with transesophageal echocardiography. Results: No one had a persistent left superior vena cava. The mean Qp/Qs ratio is 2.4±1 and mean systolic pulmonary artery pressure was 35±19 mmhg. An Amplatzer septal occluder was deployed in all 9 patients of whom a device was deployed in the defect in 1 and at the CS ostium in 8. Four patients required 1-2 size larger devices to achieve success because of repeated pull through of the initially selected device. The mean device size used was 21±3.6 (16 28) mm. One patient in whom the device was deployed in the defect developed herniation of the left disk resulting in mild-to-moderate residual shunt. All patients were available for 3-month follow-up. No one had a residual shunt on the 3-month follow-up echocardiography. One patient who had uremia, hypertension and a history of laryngeal cancer died of a stroke 4.5 months after the procedure. Following a mean follow-up period of 31±15 months, symptomatic improvement was documented in the remaining 8 patients.

96 396 Imaging and intervention in congenital heart disease Conclusion: Transcatheter closure of unroofed CS defect in patients without a persistent left superior vena cava with Amplatzer septal occluder is safe and feasible. P2368 The effect of interatrial septal defect closure on migraine burden, five year single centre experience K.N. Asrress, O. Ormerod, N. Wilson, A.R.J. Mitchell. John Radcliffe Hospital, Oxford, United Kingdom Purpose: In patients with interatrial septal defect, in the form of patent foramen ovale (PFO) and atrial septal defects (ASD), the prevalence of migraine with aura is higher than the general population. This has led to the postulation that the presence of a shunt has a causal relationship with migraine, though there is no conclusive evidence that closure has an effect on migraine burden. We set out to prospectively assess the impact of interatrial device closure on migraine burden, in patients with migraine with aura. Methods: Data on all patients undergoing percutaneous PFO or ASD closure where there was also a prior diagnosis of migraine with aura was collected prospectively between 2003 and All patients were followed up at three months where they underwent transthoracic echocardiography to check for residual interatrial shunts. At follow up they were asked if there had been an impact on their migraine headaches. Responses were recorded and analysed. Results: 210 consecutive patients with PFO or ASD underwent percutaneous interatrial defect closure over the study period, of which 25 (12%) had a prior diagnosis of migraine with aura. Amongst patients with migraine with aura 21 (84%) were female. Mean age 40.2±10.2 years. Primary indication for device closure was cryptogenic stroke (28%), transient ischaemic attack not thought to be migrainous in origin (16%), systemic embolism (13%), decompression illness (8%) and dyspnoea (4%). In 32% severe migraine with aura was the primary indication for device closure. At three months follow up 20% of patients reported complete resolution of their migraine headaches, 44% reported improvement but not resolution in symptoms, 16% had no change and 20% had worsening of their symptoms. Therefore 16 (64%) had improved symptoms and 9 (36%) had no change or worsening symptoms (p<0.005). All 25 patients had well positioned devices with no evidence of a residual shunt at three months follow-up. Conclusions: Percutaneous closure of interatrial septal defects resulted in significant improvement in migraine burden three months post procedure, even in patients where the primary indication for closure was not migraine. Many patients in both groups reported an increase in migraine burden immediately post procedure, but this had improved in the majority by three months. This rebound phenomenon has been previously reported, and may reflect the presence of the device itself. At three months the device would have largely endothelialised coinciding with the improvement in symptoms. Despite the limitations of this small series, the results support ongoing trials. P2369 Usefulness of 64-slice cardiac computed tomography in the assessment of atrial septal defects in patients undergoing percutaneous occlusion S. Ojeda 1,M.PanAlvarez-Osorio 1,M.Romero 1, J. Suarez De Lezo 1, S. Espejo 1,R.Isamat 1,D.Mesa 1,D.Garcia 1, L. Burgos 2, A. Medina 2. 1 Hospital Universitario Reina Sofia, Cordoba, Spain; 2 Hospital Universitario Dr Negrin, Las Palmas De Gran Canaria, Spain During percutaneous closure of atrial septal defects (ASD) implantation failure may occur. We assess the usefulness of 64-slice computed tomography (CT) in patients with ASD submitted for cardiac catheterization and percutaneous closure of the defect. Methods: From June-93 to January-09, 297 patients with ASD were treated percutaneously at our center. Since March-08, 24 consecutive adult patients with ASD were evaluated by echocardiogram and CT before catheterization; 7 of them were referred to surgery due to unsuitable anatomy. The remaining 17 underwent catheterization with transesophageal echocardiographic (TEE) monitoring for percutaneous closure of the defect. Multiplanar reformation of the CT images were done using the same views as in the TEE (retroaortic, 4-chamber and caves projections). In all 3 views we assessed the entire atrial septum obtaining images at 1.5 mm intervals ( septal views per patient). We selected the size of the device according to the maximum ASD diameter on any plane and the minimum dimension of the interatrial septum, as measured by CT. No Balloon sizing of the defect was performed. Additional angiography (pulmonary and coronary) was avoided with CT information. Table 1 TEE (mm) CT (mm) r p< Posterior rim 12.05± ± AV rim 12.8± ± Inferior Cave rim 19±8 21± Superior Cave rim 19±7 14± Retroaortic rim 7.29± ± Superior rim 12.1±7.2 14± ASD Caves 13±4 20± ASD Retroaortic 17.7± ± ASD 4C 18.3± ± AV: Atrioventricular. Results: Amplatzer ASD occluders were used in all patients. Size was decided before catheterization. Primary success was obtained in all 17 patients. Correlations between TEE and CT measurements are summarized in table. Conclusion: Multiplane evaluation of the interatrial septum allows an accurate selection of occluder diameter and avoids the use of balloon sizing techniques and additional angiograms, simplifying the procedure. P2370 The influence of atrial septal defect percutaneous device on left ventricular mechanics: a bidimensional strain study B. Castaldi, F. Fratta, G. Di Salvo, G. Santoro, G. Gaio, C. Iacono, L. Baldini, G. Pacileo, M.G. Russo, R. Calabro. Ospedale Vincenzo Monaldi, Naples, Italy Atrial septal defect is one of the most frequent congenital heart disease. Today the percutaneous closure is feasible in the large majority of cases. Previous studies suggest that the imposition of a device could alter the longitudinal function of the left ventricular septum. The purpose of this study was to evaluate the mid-term effect of atrial septal occluder device on left ventricular mechanics in pediatric patients using 2D strain imaging. 70 subjects (aged 6 to 16 years) were studied: 35 patients 11±10 months after percutaneous closure of atrial septal defect and 35 healthy volunteers (CTRL) matched for age (mean age 9.7±3.5 vs 9.3±3.3 years), and BSA. In all subjects standard echocardiography was performed. Residual interatrial shunt and other cardiac abnormalities were excluded. Standard projections were acquired and stored for 2D strain off-line analysis. The analysis was performed with a dedicated software (Echopac PC 08). Of the 35 studied patients 25 had an Amplatzer Septal Occluder, 8 a Solysafe device and 2 a Helex device. Standard echocardiography failed to show any significant difference in left chamber volume and function between patients and CTRL (interventricular septum in diastole: 6.9±1.0 mm vs 7±1.0 mm; left ventricular diastolic dimension: 42.34±4.8 mm vs 42.0±6.0 mm; EF: 65±4% vs 65±4%; left atrial width 31.6±3.2 mm vs 30.5±5.0 mm; E/A: 1.89±0.4 vs 1.80±0.3; DecT 155±30 ms vs 151±15 ms; E/E 5.8±1.0 vs 5.5±1.0, respectively; p= ns for all data). Speckle tracking analysis showed a significant reduction in the mean basal circumferential strain (S) (-18.3±3% vs -23.3±4% p< ), strain rate (SR) (1.6±0.3 1/s vs -2.0±0.3 1/s; p=0.0002) and left ventricular torsion (10.5±4.2 vs 14.5±4.5 ; p=0.005) in ASD-treated group compared to CTRL. Conversely, radial SR values were reduced only in basal septal and basal antero-septal segments (1.84±0.57 1/svs2.33±0.68 1/s p=0.01 and 1.63±0.54 vs 2.09±0.67 1/s; p=0.01, respectively) in treated group, as was the longitudinal S of the basal septum (-17.8% vs -20.2%; p=0.003). However, the global longitudinal S was similar to CTRL (- 20.7±1.4% vs -21.2±1.4%; p=0.4). Not significant difference in longitudinal, radial and circumferential S and SR as well as in left ventricular torsion was found in the treated group according to the used device. In conlcusion percutaneous closure with atrial septal device causes abnormalities of the left ventricular mechanics. These abnormalities seems not to be related with the type of the device but probably they could be related to the device size. We need more patients to evaluate it. P2371 The safty and efficacy of transcatheter closure of perimembranous ventricular septal defect B. Han, L. Zhao, J. Zhang, Y. Wang, Y. Jin, Y. Yi. Provincial Hospital affiliated to Shandong University, Jinan, China, People s Republic of Purpose: We sought to evaluate the safety, efficacy, and followup results of transcatheter closure of perimembranous ventricular septal defect (pmvsd). Methods: During January 2005-January 2009, 118 patients underwent transcatheter closure of pmvsd in our Hospital. The mean age at closure was 9 years (range 2 to 31 years). Echocardiography and Electrocardiography were conducted at 1, 3, 6, and 12 months, and every year after VSD closure. The median follow-up time was 26 months (range 1 to 48 months). Results: 111 cases underwent transcatheter closure successfully (94.9%). 19 cases used eccentric VSD device and 92 cases used concentric VSD device. A total of 18 cases early complications occured (16.2%). 9 cases suffered from heart block after closure including 2 cases with complete right bundle branch block (CRBBB), 1 case with incomplete right bundle branch block (ICRBBB) and 6 cases with accelerated junctional tachycardia (AJT) and all of them recovered after 1 week to 3 months. 2 of 4 cases with residual shunt had mechanical hemolysis and resolved 3 days later after conservative therapy. Mild aortic valve regurgitation occurred in 2 cases and mild tricuspid regurgitation occurred in 3 cases. Conclusions: Transcatheter closure of pmvsd is safe and efficacious in excellent successful rate. Severe complications is rare. Heart block are the main complications after occlusion of pmvsd and recovered completely. The key point is selecting patients under strict indications.

97 Imaging and intervention in congenital heart disease 397 P2372 Transcatheter closure of the patent ductus arteriosus using the amplatzer duct occluder in symptomatic infants with low weight F. Godart, C. Francart, I. Bouzguenda, A. Richard, C. Rey. Hopital Cardiologique CHRU de Lille, Lille, France Purpose: Transcatheter closure of patent ductus arteriosus (PDA) using the Amplatzer duct occluder (ADO) is an effective treatment and a true alternative to surgical closure. However, closure of PDA in children with low weight remains a real challenge for the interventionist. Methods: From April 1999 to February 2009, 203 patients underwent percutaneous PDA closure. We focus here on the 17 infants weighing 6kgandin whom duct was closed using the ADO. All patients were symptomatic and indications included failure to thrive and/or shortness of breath and/or frequent respiratory infections. There were 15 females and 2 males; the mean age was 5.1±4 months, and the mean weight was 4.6±0.9 (range 2.8 to 6 kg). The procedure was realized under local anaesthesia (n = 14) and general anaesthesia (n = 3). In 5 of the 17 pts, implantation was performed from a sole venous femoral access without arterial puncture, and device release was controlled by transthoracic echocardiography. Size of the duct was 3.6±1.3 mm (range 1.7 to 6 mm) and systolic pulmonary artery pressure was 54±19 mm Hg (range 26 to 96 mm Hg). Implantation succeeded in all but one without any complication. Closure was realized by six 5/4 mm ADO, five 6/4 mm ADO, five 8/6 mm ADO, and one 10/8 mm ADO. One patient with failed procedure underwent subsequently surgical closure of the duct. During follow-up (0 to 58 months), Doppler echocardiography showed decrease in ductal residual shunt: complete occlusion was noticed in 5 pts at day one, 10 pts at one month, 14 pts at 3 months, and 16 pts at one year after implantation. No patient but one had persistent pulmonary hypertension and only one had a moderate stenosis on the left pulmonary artery due to device protrusion. One patient died 15 months after implantation from non cardiac related cause. Conclusions: In experienced hands, percutaneous closure of large PDA in symptomatic infants weighing 6 kg is safe, effective, and solves clinical problems. It offers a real alternative to the classic surgical treatment. P2373 Transcatheter closure of patent ductus arteriosus using the new Amplatzer duct occluder (ADO II). 1-year experience B.D.T. Thanopoulos, N.G.E. Elefterakis, S.L. Loukopoulou. Aghia Sophia Children s Hospital, Athens, Greece Objectives: The aim of this study was to report 1-year experience with 51 patients who underwent attempted transcatheter closure of a patent ductus arteriosus (PDA) using the new Amplatzer duct occluder (ADO II). Methods: The mean age of the patients was 7.5±7.8 years (range 0.3 to 45 years). The device is a modified Amplatzer duct occluder made of fabric-free fine Nitinol wire net in to 2 very low profile disks with an articulated connecting waist. Both disks are 6 mm larger than the diameter of the connecting waist. Connecting waist diameters and device lengths range from 3-6 mm and 4-6 mm, respectively. The ADO II is appropriate for closure of very small to moderate- large (up to 5.5 mm) PDAs of any morphological type. Results: The mean PDA diameter was 3.5±1.6 mm (range, 0.5 to 5.5 mm). The mean device diameter (waist diameter) was 4.2±1.3 mm (range 3 to 6 mm). The device was permanently implanted in 49 patients. Complete angiographic closure was observed in 47/49 (96%) patients. At 24 hours color Doppler flow imaging revealed complete closure in 48/49 (98%) patients. Major complications included device embolization and significant hemodynamic obstruction of the descending aorta in one patient, respectively. No other complications were observed. Conclusions: The ADO II is a highly effective prosthesis that can be safely applied in most patients with small to moderate-large PDA of any anatomical type. Further studies are required to establish long-term results in a larger patient population. P2374 Ductal stenting for duct-dependent pulmonary circulation: a multi-center experience N. Sreeram 1,H.Hamza 2, H. Agha 2,V.Kohli 3,M.Emmel 1, G. Bennink 1. 1 University Hospital, Cologne, Germany; 2 University Children s Hospital, Cairo, Egypt; 3 Apollo Hospital, New Delhi, India Background and Aims: Ductal stenting in neonates with pulmonary atresiavariants can potentially avoid the need for a surgical shunt. We report a multicenter experience with this therapeutic approach. Patients and Methods: 31 consecutive infants (17 female) from 3 centers, who were catheterised on an intention-to-treat are presented. They ranged in age from 3 to 120 days and in weight from 2.2 to 4.0 kg. The ductal morphology was horizontal and straight (n=22), tortuous (n=5), and vertical (n=4). Stenting was performed as an adjunct to RF perforation of the pulmonary valve in 16 patients. Prostaglandin E therapy was discontinued 6 hours prior to the procedure in 23 infants. Results: In 6 patients a stent was not implanted for the following reasons: failure to enter the duct (n=4), tortuous duct with concomitant stenosis of a branch PA (n=2). in the remainder, stents ranging from 3.5 to 4.5mm in diameter of varying lengths were implanted (retrogradely in 14, anterogradely in 11; 2 stents in series in 2). The procedure was uncomplicated in all; 1 infant in whom the initial stent did not cover the entire duct required a second ductal stent 3 days later. Following stent implantation, the systemic oxygen saturation at rest ranged from 75% to 88%. The duration of hospital stay ranged from 1 to 66 days. Patients were discharged from hospital taking aspirin 5mg/kg/day. Conclusions: Despite a learning curve, ductal stenting is relatively straightforward and provides adequate medium-term palliation. It is of particular relevance in centers with limited surgical backup. P2375 Percutaneous Closure of Hypertensive Ductus Arteriosus C. Zabal, J.A. Garcia Montes, A. Buendia, J. Calderon Colmenero, E. Patino Bahena, A. Juanico, F. Attie. National Institute of Cardiology Ignacio Chavez, Mexico City, Mexico Background: The Amplatzer duct occluder (ADO) has been used with success to close large patent ductus arteriosus (PDA), but some problems exist specially with hypertensive PDAs, such as incomplete closure, hemolysis, left pulmonary artery stenosis, obstruction of the descending aorta, and progressive pulmonary vascular disease. Methods and results: We analyze a group of 168 patients with isolated PDA and pulmonary artery systolic pressure (PSAP) 50 mmhg. Mean age was 10.3±14.3 years, PDA diameter was 6.4±2.9 mm, PASP was 63.5±16.2 mmhg, and Qp/Qs was 2.7±1.2. We used ADOs in 145 (86.3%) cases, Amplatzer muscular ventricular septal defect occluders (AMVSDO) in 18 (10.7%), Amplatzer septal occluders (ASO) in 3 (1.8%), and the Gianturco-Grifka device in 2 (1.2%) cases. Device diameter was 106.3±51% higher than PDA diameter. PASP decreased after occlusion to 42.5±13.3 mmhg (p< ). Immediately after closure, no or trivial shunt was present in 123 (74.5%) cases. Immediate complications were device embolization in five (3%) cases, and descending aortic obstruction in one case. The overall success rate was 98.2%. Follow-up in 145 (86.3%) cases for 37.1±24 months showed further decrease of the PASP to 30.1±7.7 mmhg (p<0.0001). Angio images of a hypertensive PDA Conclusions: Percutaneous treatment of hypertensive PDA is safe and effective. ADO works well for most cases, but sometimes other devices (MVSDO or ASO) have to be used. When cases are selected adequately, pulmonary pressures decrease immediately, and continue to fall with time. P2376 Echocardiographic determinants of successful balloon dilation in pulmonary atresia with intact ventricular septum A. Drighil 1,M.AlJufan 2,A.Slimi 2, S. Yamani 2. 1 Ibn Rochd university hospital, Casablanca, Morocco; 2 King faisal specialist hospital and research center, Riyadh, Saudi Arabia Pulmonary atresia with intact ventricular septum (PA-IVS) is a complex congenital heart malformation with multitude therapeutic approaches. Recently, balloon valvotomy has been used as an alternative to primary surgery. This study aimed to identify echocardiographic markers of balloon dilation success in PA-IVS. The echocardiograms of 26 patients diagnosed with PA-IVS who underwent primary pulmonary balloon valvotomy were reviewed. Tricuspid annulus Z score, pulmonary annulus Z score, right ventricular (RV) to left ventricular (LV) length ratio, RV to LV transverse diameter ratio and tricuspid valve (TV) to mitral valve (MV) annulus diameter ratio were measured. The tricuspid Z score, pulmonary Z score, RV/LV lenght ratio, RV/LV diameter ratio, and the TV/MV ratio were significantly different in the group which had successful balloon dilatation compared to the that failed. Based on decision trees using the Weka classifier package, only RV/LV diameter ratio > 0.76 predicts a 92.3% success rate. In contrast an RV/LV diameter ratio 0.76 associated with RV/LV lenght ratio 0.70 predicts 100% failure. In conclusion, successful balloon dilation in membranous type PA-IVS can be predicted by a scoring system using RV/LV diameter ratio and RV/LV length ratio.

98 398 Imaging and intervention in congenital heart disease P2377 covered stents for moderate-severe native aortic coarctation S. Abadir 1,S.Noble 2, G. Sarquella-Brugada 1, R. Ibrahim 2, N. Dahdah 1,J.Miro 1. 1 Hospital Sainte Justine, Montreal, Canada; 2 Montreal Heart Institute, Montréal, Canada Background: Covered stents (CS) have been suggested as an alternative to bare stents to decrease aortic complications in moderate-severe native coarctation (CoA). Methods: We retrospectively reviewed our 18 patients (26.7±14.6 yo; 12 to 58) who underwent CS implantation since 2003 (Cheatham-Platinium stent, 8 zig, length 22 to 45mm) for moderate-severe native CoA. Results: Preimplantation systolic blood pressure was 147.9±17.5 mmhg, with mean pressure gradient of 63.3 mmhg (41 to 103). 11/16 hypertensive patients were under medication, 8/11 had at least 2 medications. Significant collaterals were present in 15/18 patients. All attempts were successful. Lesion diameter/aortic diameter at diaphragm increased from 20.7%±11.0% to 90.2%±15.8%. Invasive gradient (under general anesthesia) decreased from 33.4±11.1 to 1.4±2.8 mmhg. One major complication occurred (mild cerebrovascular ischemic event in a 46.9 yo). Sub-clavian artery was partially jailed in 4/18, with none losing radial pulse. 4 patients had almost atretic lesion (< 1 mm), one needing radiofrequency perforation for acquired interruption. During follow up (mean 15.8 mo, 1 to 49.5), 13 patients have already undergone non invasive imaging, with one demonstrating a small (6 mm) aneurysm. No stent fracture was observed. Three of our 8 teenager patients underwent further dilatation to accommodate aortic growth. Normal blood pressure was obtained in 8/16 previously hypertensive patients. Only one patient has blood pressure gradient >20 mmhg, due to aortic arch hypoplasia. Conclusion: CS implantation is safe in moderate-severe native CoA, and provides excellent transcoarctation gradient relief. These results compare favorably to our previously reported experience with balloon dilatation and bare stents implantation in native CoA. P2378 Stent implantation for the treatment of aortic coarctation in children: Initial and five-year results N.G.E. Elefterakis, S.L. Loukopoulou, E.S.K. Karanasios, B.D.T. Thanopoulos. Aghia Sophia Children s Hospital, Athens, Greece Objectives: Long follow-up data following stent implantation (SI) for the treatment of coarctation of the aorta (CoA) in children are limited. This study reports initial and 5-year results following SI in children with CoA. Methods and Results: Fifty-four patients with CoA underwent SI (median age 9.2 years, range 7 14 years); 26 patients were treated for isolated native CoA and 28 for recurrent CoA. 60 stents were implanted. Palmaz 4014 stents were placed in 26 patients and Palmaz 308 in 28 patients. Excluded from the study were patients with significant hypoplasia of the distal aortic arch or aortic isthmus proximal to the CoA as well as those with complex CoA. Elective re-dilation of a previously implanted stent was performed in 28 patients. Immediately after SI the peak systolic pressure gradient (mean (SD)) fell from 60 (±17) mm Hg to 8.5 (±4.8) mm Hg (p< 0.05). The diameter of the CoA increased from 5.6 (±2.6) mm to 16.4 (±2.8) mm (p< 0.05). The most important procedural complications were proximal stent migration and stent fracture (after redilation) in 1 and 3 patients, respectively. There were no deaths, no evidence of aneurysm formation or any other complications related to SI throughout the follow-up period. At the 5-year follow-up no cases of recoarctation were identified on angiography, multislice CT, or MRI. In 91% (49/54) of the patients antihypertensive medication was either decreased or discontinued. Conclusions: SI is an effective and safe alternative to conventional surgical management for the treatment of selected children with CoA. P2379 Aortic valvuloplasty in children: impact of rapid ventricular pacing G. Sarquella Brugada 1, S. Abadir 1, J. Rodes Cabau 2, C. Houde 2, A. Dancea 3, N. Dahdah 1,J.Miro 1. 1 Hospital Sainte Justine, Montreal, Canada; 2 CHUL, Quebec, Canada; 3 McGill University, Montreal, Canada Introduction: Ventricular pacing for balloon stabilization in aortic valvuloplasty is increasingly used. We sought to evaluate its safety and benefits in a children population. Methods: Retrospective review of ten year experience in three pediatric centers. Control group was obtained based on age of patients and catheterizer in a match proportion of 2 non-paced to 1 paced procedure. Results: Overall, 140 procedures were performed in 130 patients with mean follow-up time of 32,07±34,98 months. There was male predominance (68,3%) with mean age of 5,6±6,97 years, and mean weight of 24,24±26,68 kg at procedure. Ventricular pacing has been used in 23 aortic valvuloplasties (16,4%) since Paced patients and control group were similar for procedure duration, radiation time and final gradient relief measured by echocardiography and catheterization. Non-paced procedures were much more associated with multiple (>3) balloon inflations (41,3% vs. 4,34%, X2 10,174 p=0,001), significant increase of aortic regurgitation at 1 year (28,2% vs. 4,34%, X2 5,42 p=0,017) and at last follow-up (30,4% vs. 4,34%, X2 6,133 p=0,011). Non-paced procedures were associated with a higher risk of reintervention (23,9% vs. 4,34%, X2 4,086 p=0,039). There was no difference in arrhythmia inducibilityduetoventricularpacing (13,4% vs. 8,69%, X2 0,87 p=0,7). Conclusion: Rapid ventricular pacing for aortic valvuloplasty does not increase the risk of arrhythmias, simplifies the procedure and is associated with lower rates of reintervention possibly by diminishing the number of balloon inflations needed. P2380 Japan Three-dimensional diagnosis of pulmonary-ductus descending aorta trunk in hypoplastic left heart syndrome and interrupted aortic arch with multi-slice CT for stent implantation I. Shiraishi Isao. National Cardiovascular Center, Suita, Osaka, Backgrounds: Recently, a combination therapy with pulmonary artery banding and stent implantation for patent ductus descending aorta-trunk (PDDT) has been approved as an initial interventional strategy of hypoplastic left heart syndrome (HLHS). However, it is hard to understand the precise 3-dimensional structure of PDDT by using conventional two-dimensional images with echocardiography and angiography because PDDT is sometimes bulge and tortuous. In this study, we evaluated the structure of PDDT in HLHS and IAA patients by using 3-D images with multi-slice (MS) CT. Patients and Method: We evaluated the shape and angle of the ascending aorta, main pulmonary artery, PDDT, anddescending aorta of neonatal patients with HLHS (n=13) and IAA (n=13) by using 64 detector-row MSCT. Results: The shape of PDDT in HLHS patients is divided into two groups, i.e., bulge (+) (n=7, angle between PDDT and descending aorta>20 degree) and bulge (-) groups (n=6, angle <20 degree). PDDT tilted to the left side of the body in 32.1±14.7 and 2.50±4.18 degree in bulge (+) and ( ) groups, respectively (p<0.05). The average angle of PDDT in the HLHS patients was 16.2±20.9 degree. In IAA patients, PDDT was bulged in only one of the 13 patients. Consequently, PDDT titled to the left side of the body in 1.54±5.5 degree (p<0.05 compared with HLHS). We also measured the angle of the ascending aorta, which showed that the ascending aorta tilted to the right side of the body in 16.1±14.8 and 1.31±12.5 degree in HLHS and IAA patients, respectively (P<0.05). Conclusions: In HLHS patients, 54% of the patients had bulged and tortuous PDDT. Three-dimensional diagnosis and measurement of PDDT with MSCT is recommended when the stent implantation is considered for HLHS patients. P2381 Cardiac catheterisation-related thrombosis in children with congenital heart disease is associated with 4G/5G polymorphism of PAI-1 gene M. Del Fiandra 1, V. De Lucia 2,N.Botto 2, I. Spadoni 2,S.Giusti 2, L. Ait-Ali 2, M.G. Andreassi 1. 1 IFC CNR - Ospedale Pasquinucci, Massa, Italy; 2 G. Monasterio Foundation, Massa, Italy Background: Vascular thrombotic complications are common adverse events during pediatric cardiac catheterization. Identification of acquired and genetic risk factors is essential in order to improve individual risk stratification. Aim: To examine the acquired and inherited risk factors associated with catheterrelated thrombosis in children with CHD. Methods: Within a case-only design, we enrolled 64 consecutive CHD in-patients (31 males, age=63.7±64.3 months) admitted to our pediatric cardiac surgery center for cardiac cath procedures. Hospital records of all patients were reviewed. Multiplex allele-specific PCR assay was used to analyze Factor V Leiden, prothrombin G20210A, MTHFR C677T, plasminogen activator inibitor-1 (PAI-1) 4G/5G, platelet glycoprotein IIIa Pl (A1/A2), cystationine beta synthase (CBS) 844ins68 genetic polymorphisms. Results: Five patients (7.8%) had thrombotic complication after cardiac cath procedures: 4 children (80%) had an arterial system thrombosis and 1 case (20%) had a venous system thrombosis. Children with thrombosis were younger (9.7±11.1 vs 68.3±64.9 months; p=0.04) and at lower weight (6.5±3.2 vs 21.9±20.0 kg; p=ns) than children without vascular complications. The carrier frequency of PAI-1 4G/4G variant was significantly higher in infants with thrombosis

99 Imaging and intervention in congenital heart disease 399 when compared to patients without (chi square=4.6, p=0.03). No statistical differences were found for other polymorphisms. Multivariate analysis showed that age [OR: 0.9, p=0.006] and homozygosity for 4G/4G PAI-1 variant [OR: 8.8, p=0.04] were independent risk factors for thrombosis. Conclusions: Patient age and PAI-1 promoter 4G/5G polymorphism are associated to catheter-related thrombosis. Other thrombophilic gene mutations do not have influence on vascular thrombotic complications. P2382 Neutrophil Gelatinase-Associated Lipocalin (NGAL): Is it a good predictor of radiocontrast nephrotoxicity in children undergoing angiography? D. Oguz, R. Olgunturk, F.S. Tunaoglu, C. Sanli, A. Eren. Gazi University School of Medicine, Ankara, Turkey Radiocontrast nephrotoxicity (RCN) is a common and important cause of hospitalacquired renal insufficiency and a well-recognized complication of cardiac angiography. RCN is generally mild and reversible but can lead to prolonged hospitalization, increased health care costs, and substantial morbidity and mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of renal failure unlike serum creatinine levels. We prospectively enrolled 46 children (age 0 16 years, median: 3 yrs) with congenital heart disease (9 cyanotic, 37 acyanotic) undergoing elective cardiac catheterization and angiography with non-ionic contrast (IOPROMID 769mg/ml) administration in our study. Serial urine and plasma samples (baseline, 4 hr, 24 hr, and 48 hr after the procedure) were analyzed for NGAL and creatinine. The volume of contrast medium injected was 4.20±2.18cc/kg. (0,65-10,6cc/kg). RCN, defined as a 25% increase in serum creatinine from baseline, was found in 17 subjects (34%). However, in 36 patients (72%) serum NGAL levels were increased (in some up to 9 fold) after 4 hours of contrast administration. The volume of contrast medium injected between the patient group who had increased NGAL levels and who had not differed significantly (4,77±2,04 vs 3,00±2,01cc/kg, p<0,01). The dependency of creatinine to some factors like age, gender, muscle mass, muscle metabolism, medications, hydration status, and delayed response to renal function loss which make take several days are important disadvantages. Thus, plasma NGAL levels have emerged as sensitive, specific and highly predictive early biomarker of RCN in children. P2383 Anomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA): clinical and echocardiographic aspects in 13 consecutive cases O. Milanesi 1, M.C. Baratella 2,A.Cerutti 1,E.Reffo 1, N. Maschietto 1, R. Biffanti 1, G. Stellin 3. 1 Department of Pediatrics- University of Padova, Padova, Italy; 2 Department of Cardiology- Dolo Hospital, Dolo (Ve), Italy; 3 Department of Pediatric Cardiovascular Surgery- University of Padova, Padova, Italy ALCAPA is a rare heart malformation, accounting for 0,5% of all the CHD. Asymptomatic at birth and during the firs days of life, it causes in the majority of the cases a progressive ischemic LV cardiomyopathy, frequently misdiagnosed as primitive. Aim of our work is to underline the most relevant clinical and echocardiografic features of such a disease. We reviewed the clinical records of all the patients with ALCAPA, observed at our Department during the period Dec 2004-Dec 2008, with special attention to the referring diagnosis, clinical presentation, ECG and echocardiographic typical aspects. During the study period 13 patients (7F), admitted in our Hospital, met this diagnosis. Mean age was 22 months (1-144) median 4. Referring diagnosis was dilated cardiomiopathy in 9, heart murmur in 3; one patient was already followed in our center after surgical coarctation repair. Overt congestive heart failure (CHF) was present in 8 cases, CHF controlled with anti-congestive therapy in 2. Three patients, 13, 44 and 141 months old were asymptomatic. In 12/13 cases ECG showed pathologic Q waves and/or ischemic S-T T changes. Two-D echocardiography showed severely dilated LV, with depressed pump function in 7, severe mitral regurgitation in 1, moderate in 5, mild in 4, absent in 3. Diagnosis was in every case established by means of the direct visualization of the inverted flow in the main left coronary artery (CA), obtained with a careful investigation of the origin of the CA in a short axis cut, at the base of the heart, using low PRF colour flow mapping, and confirmed detecting a low velocity diastolic flow in the pulmonary artery, due to the reverse flow in the ALCAPA. However, the warning light of the malformation was in 12/13 cases the ischemic sclerosis of the papillary muscles of the mitral valve, which appeared thin and bright, and the presence of colour flow spots into the interventricular septum due to the enhanced collateral vessels between the high pressure right and the low pressure left CA, present in all and more pronounced in the 3 older asymptomatic patients. All the patients were operated on with 1 death, due to post operative low cardiac output. The LV function totally recovered in the survivors. In conclusion ALCAPA is a rare malformation, lethal in natural history, but with a good surgical prognosis. In our series, the diagnosis was never suspected from the referring physicians. We believe that it is important to underline the echocardiographic warning lights, which can lead to a correct diagnosis and a prompt treatment. P2384 Do maternal cardiac structural abnormalities predispose to high resistance uterine artery Doppler indices? K. Melchiorre, G.R. Sutherland, A.T. Baltabaeva, B. Thilaganathan. St George s Healthcare NHS Trust, London, United Kingdom Objective: To compare the prevalence of previously undiagnosed cardiac abnormalities in women with normal and high resistance indices at midtrimester uterine artery Doppler screening. Methods: Maternal transthoracic echocardiography was undertaken in pregnant women after uterine artery Doppler screening for pre-eclampsia at weeks gestation. Women with a mean uterine artery pulsatility index above 95th centile (1.25) for the local population (multi-ethnic, socially diverse and migrant) were considered to have a high resistance uteroplacental blood flow indices. The prevalence of cardiac structural defects in these women was recorded. Results: A total of 210 women consented to have maternal echocardiography: 86 with high resistance and 124 with normal resistance uterine artery blood flow indices. There were five previously undiagnosed, functionally significant cardiac defects in this cohort, all in the high-resistance uterine blood flow group (p<0.05). The newly diagnosed cardiac defects included: large atrio-septal defects with unidirectional shunt, right/left heart disproportion and pulmonary hypertension (n=2), mitral valve disease possibly secondary to rheumatic heart disease (n=2) and bicuspid aortic valve with aortic regurgitation (n=1). Conclusions: The prevalence of previously undiscovered maternal cardiac structural malformations appears significantly increased in women with high midtrimester uterine artery Doppler resistance indices. This observation should be confirmed in a larger series of patients because it has important consequences for medical practice and the long-term care provided to these patients. P2385 Quantitative assessment of dynamic change of tricuspid valve geometry in hypoplastic left heart syndrome using real-time 3D echocardiography K. Takigiku, S. Yasukochi, K. Takei, I. Kajimura, Y. Nakano, N. Inoue, S. Tazawa. Nagano Children s Hospital, Nagano, Japan Background: Significant tricuspid valve (TV) regurgitation (TR) in the patients withhypoplastic left heart syndrome (HLHS) adversely affects on the outcome, however, the detail pathogenesisof TR is still unclear. The aim of study is to assess thedynamic change of tricuspid valve geometry in the patients with hypoplasticleft heart syndrome using real-time 3D echocardiography (RT3DE). Methods: We performed RT3DE (IE33,Phillips) in 11 patients with HLHS and 13 normal subjects (NL; 13 mitral valvesand 6 tricuspid valves). The full volume images were obtained with the apicalview using X7-2 matrix array transducer. We used recentry developed soft ware (Real View) to reconstruct the 3D morphology of annulus and leaflets automatically.the annular area (AA), annular height (AH), tentingvolume (TEV), tenting leaflet area (TEA) were calculated in early diastolic, mid systolic and end systolic phase. All thedata were corrected with body surface area. Results: In HLHS, The AA, TEV and TEA of TV markedly increased comparedwith those of MV and TV in normal subjects (p<0.01).throughout systole,while AA significantly decreased only in HLHS (p<0.01), AH increased only inmv. TEV decreased progressively during systole in three groups (p<0.01), however, TEA decreased only in HLHS (p<0.01). Conclusions: The newly developed quantitative software allows the identificationof dynamic geometrical differences between HLHS and NL. In HLHS, marked TV leaflettenting was reduced during systole by decrease in annular area, which results invalvular coaptation.

100 400 Imaging and intervention in congenital heart disease / Mitral, tricuspid and rheumatic valve disease P2386 Total isovolumic time relates to exercise capacity in patients with transposition of the great arteries after atrial switch E. Tay, M. Josen, D.G. Gibson, R. Inuzuka, R. Alonsa Gonzalez, G. Giannakoulas, W. Li, M. Bartsota, K. Dimopoulos, M.A. Gatzoulis. Royal Brompton Hospital, London, United Kingdom Introduction: Systemic right ventricular (RV) systolic dysfunction is a common sequelae amongst adult patients after undergoing atrial switch (AS) procedure for transposition of great arteries (TGA). Total isovolumic time (t-ivt) relates to exercise capacity in acquired systolic heart failure and may be a better predictor of response to cardiac resynchronization therapy (CRT) compared to markers of segmental dyssynchrony. We hypothesized that t-ivt is prolonged in patients after AS and relates to exercise capacity. Methods: We studied 29 consecutive adults with TGA who underwent transthoracic echocardiography and cardiopulmonary exercise testing. Clinical and demographic data were collected. Right ventricular size and function were assessed and t-ivt was measured by Doppler and calculated as: 60- (total ejection time + total filling time). Percentage predicted peak VO2 and VE/VCO2 slope were measured during maximal treadmill exercise. Results: Mean age was 30.3±7.3 years, 31.8% males. Mid RV diameter was 4.8±0.7cm. Ten patients (35%) had moderate to severe systolic dysfunction of the systemic RV and 5 (17%) had moderate to severe tricuspid valve regurgitation. Mean t-ivt was prolonged at 12.15±3.97s/min. Mean percent predicted peak VO2 and VE/VCO2 slope was 64.4±19.1% and 35.5±11.4 respectively. Total- IVT negatively correlated with % predicted peak VO2, (r=-0.53, p=0.0048). This correlation became stronger when patients with exercise induced cyanosis (n=8) were excluded, (r=-0.68, p=0.0016). Conclusion: Total IVT is prolonged in adult TGA patients after AS procedures and relates inversely to exercise capacity. Biventricular pacing with a view to shortening t-ivt may be a potential therapeutic option for these patients, which may be explored in prospective studies. P2387 Egypt Evaluation of pulmonary arterial anatomy in children with pulmonary atresia using non ECG gated MDCT M. Ghazy 1,M.ElSayed 1,A.ElFiky 1, G. El Shahed 1,H.Abd El Moniem 2, A. Roshdy 1, M. Abd El Kader 1, O. El Farouk 1. 1 Ain Shams University, Cairo, Egypt; 2 El Galaa Military Hospital, Cairo, Purpose: To evaluate the efficacy and safety of MDCT in establishing the pulmonary arterial anatomy in children with pulmonary atresia. Methods: The study was done using a 64 slices scanner. Younger patients received light sedation using oral chloral hydrate ( ml/kg) minutes before the scan. No sedation was needed for older cooperative patients. All the scans were done non-ecg gated after the injection of a low osmolar non ionic contrast material. Each study was reviewed by three operators; two cardiologists and a radiologist to assess the presence of pulmonary confluence, the size of pulmonary arteries, presence of peripheral pulmonary stenosis, and presence of MAPCAs and/or PDA. A study was considered successful if all these anatomical data could be reached clearly. The safety of the examination was evaluated by recording contrast related adverse effects and the overall well being of the patients after the study, also the amount of radiation exposure was calculated. Results: The study included 29 patients; the youngest was 17 days old while the oldest was 14 years old. Fifteen patients were below 2 years of age. The total amount of radiation delivered during the scans ranged from 0.75 msv to 3.48 msv (1.45±0.7). Only three studies (10%) were considered non successful, two of them were due to inadequate contrast opacification and the other due to excessive motion artifacts. In the remaining 26 studies (90%), all the pulmonary arterial anatomical data were obtained. Eighteen patients had confluent pulmonary arteries. In the eight patients with non confluent pulmonary tree the exact origin of the pulmonary arteries could be identified. The sizes of the pulmonary arteries were clearly measured in all patients. Twelve patients (46%) had peripheral pulmonary stenoses, six of which had origin stenoses of the left pulmonary artery. MAPCAs were clearly visualized in 50% of the patients. The PDA was also adequately visualized in 21 patients. The procedure was safe in all patients with no peri-procedural complications apart from one patient who had extravasation of the contrast from the injection site. Conclusion: Non ECG gated MDCT is a safe and effective approach for evaluating the pulmonary arterial anatomy in children with congenital pulmonary atresia as young as 17 days old with accurate data acquisition and low total radiation exposure. P2388 CMR tagging for measurements of the long axis function of the systemic right ventricular free wall S. Chen 1, J. Keegan 1,A.W.Dowsey 2,R.Wage 1,D.N.Firmin 1, G.Z. Yang 2,P.J.Kilner 1. 1 Royal Brompton Hospital, London, United Kingdom; 2 Imperial College London, London, United Kingdom Aim: The systemic right ventricle (RV) in transposition of the great arteries generally starts to fail later in life. Ejection fraction (EF) is used as a cardiovascular magnetic resonance (CMR) measurement of systemic RV function, but is time consuming and not reliably reproducible. We used CMR tagging of the free wall of the RV to measure systemic RV long axis function, comparing findings with EF. Methods: We studied patients with Mustard operation (OTGA), or unoperated congenitally corrected transposition of the great arteries (CCTGA), and controls. A breath-hold 4 chamber steady state free precession cine dataset was acquired, then a breath-hold cine gradient-echo echo-planar tagged acquisition in the same plane. Tagging was performed by a COMB prepulse, applied immediately after the R wave, which simultaneously tagged 2 short axis planes, a basal RV slice and another 40mm towards the apex. RV free wall systolic deformation (%) was calculated by measuring the difference between the tag lines at end-diastole and at peak myocardial displacement, and dividing the difference by the distance (40mm). RV end-diastolic and end-systolic volumes were measured by CMRTools (Imperial College, London). Results: Nineteen patients (13 OTGA + 6 CCTGA, age 30±7, 35±12 years) were studied and compared to 10 controls (31±9 years). Basal RV myocardial displacements in both OTGA and CCTGA were lower than controls (12±5 + 21±4 vs 26±3mm, p 0.001, p=0.01 respectively). Basal myocardial displacement in OTGA was more impaired than CCTGA, p= RV free wall systolic deformation tended to be lower in OTGA and CCTGA compared to controls (14±8 and 13±6 vs 22±9%, p=0.05, p=0.06 respectively). Compared to controls, CCTGA had higher EF, 65±10 vs 55±4%, p=0.02 but no EF difference between OTGA and controls, 55±9 vs 55±4%, p=0.7. Conclusion: RV free wall tagging showed lower RV free wall motion, and a trend towards lower systolic deformation in patients. Lower displacements in OTGA than CCTGA maybe due to surgery. EF is increased in CCTGA. Like patients with hypertrophic cardiomyopathy, high EF in CCTGA maybe due to approximation of endocardial borders as hypertrophied myocardial layers thicken. Deformation analysis suggest that high EF of CCTGA patients is not due to enhanced myocyte shortening, but to systolic elimination of blood spaces between the hypertrophied muscle layers, an effect that masks potential impairment of myocardial function if only EF is used. Therefore, RV free wall tagging may provide not only a quicker and simpler method for comparisons RV myocardial function, but also a more representative measurement. MITRAL, TRICUSPID AND RHEUMATIC VALVE DISEASE P2389 Early Results of the RHEUMATIC (Rheumatic Heart Echo Utilization and Monitoring Actuarial Trends in Indian Children) study A. Saxena 1, S. Ramakrishnan 1,A.Roy 1,S.Seth 1, A. Krishnan 1, S.K. Reddy 2,P.Misra 1, B. Bhargava 1, P.A. Poole-Wilson 1 on behalf of United Kingdom-India Education and Research Initiative. 1 All India Institute of Medical Sciences, New Delhi, India; 2 Carenidhi, New Delhi, India Purpose: Rheumatic Heart Disease (RHD) is estimated to affect over 20 million people worldwide, the vast majority being children in developing countries. Early detection of milder cases in asymptomatic children may prevent progression to severe valvular lesions by instituting secondary prophylaxis. Conventionally, auscultation has been used for diagnosing RHD, but echo-doppler is likely to be more sensitive and specific. We carried out a cross sectional survey to diagnose RHD in asymptomatic children aged 5-15 years, living in rural areas and crowded urban areas, using portable echocardiography. Methods: Children, aged 5-15 years, from government schools and private schools, in a pre identified rural area and from a crowded urban area were studied. After a history and physical examination, echo-doppler was performed, using a bedside portable echocardiography machine. A diagnosis of RHD was made by echo-doppler if one or more of the following were present: a) Mitral stenosis; b) Mitral regurgitation (MR) and/or aortic regurgitation (AR) with regurgitant jet length of more than 2 cm in at least two echo planes, along with abnormal valve morphology (a bicuspid aortic valve to be excluded in cases with AR); c) MR and/or AR with regurgitant jet length of 1-2 cm, and abnormal valve morphology, in the presence of a history suggestive of rheumatic fever. Results: A total of 859 children were screened, 458 from government schools, 175 from private schools and 226 from the crowded urban area. 452 were males. The mean age was years. All children were asymptomatic. History suggestive of rheumatic fever was obtained in 34 cases. MR was diagnosed by

101 Mitral, tricuspid and rheumatic valve disease 401 clinical examination in one case only (clinical prevalence of RHD 0.1%). Echo- Doppler diagnosed RHD in 28 cases, giving a prevalence of 3.2%. Thickening of the valve was present in all 28 cases. Doppler revealed MR in 25 and AR in four. Thirteen of these 28 cases had a history suggestive of rheumatic fever. Other cardiac lesions identified by echo-doppler were moderate sized atrial septal defect (one), bicuspid aortic valve, without stenosis or regurgitation (two) and mild left ventricular dysfunction, possibly due to dilated cardiomyopathy (one). Conclusions: This preliminary work demonstrates feasibility of echo screening in children for diagnosing RHD. In this study, the prevalence of RHD was found to be high, when screening echo-doppler was used. A larger study is necessary and is underway. P2391 Right ventricular pacing increases tricuspid regurgitation grade regardless the mechanical effect of the electrode placement M. Vaturi, J. Kuzniec, Y. Shapira, M. Perlmutter-Weiser, B. Strasberg, A. Sagie. Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel Background: The effect of RV pacing on tricuspid regurgitation (TR) is still debatable and is related to interference in valve closure by the electrode. The study aimed to determine the pacing impact on TR grade. Methods: Patients with permanent pacemaker (PM) (electrode at the RV apex) were studied. Exclusion criteria: PM dependence, atrial fibrillation and LV dysfunction. Each patient had a baseline echocardiography study followed by PM programming: if in sinus rhythm, the PM was set on a pacing mode ( 5 heartbeats of baseline rate) and vice versa. Echo study was repeated immediately thereafter. The TR was graded by vena contracta (TRvc). RV and LV areas (enddiastolic and systolic in the apical view) and the RV base systolic diameter (septum to free wall) were measured (arrow in Figure). Results: Twenty-one patients (12 males, 79±12 years, 81% with DDD pacing) were included. RV pacing was associated with increase in TRvc (from 0.2±0.2 to 0.4±0.2 cm, p<0.0001) and in the average TR grade (from mild to mild-moderate, p<0.0001). RV and LV areas and RV systolic pressure were not changed by the acute change in the pacing mode. However, RV base systolic diameter increased with pacing (3.3±0.7 vs. 2.9±0.5 cm, p=0.001) and was accompanied by visually leftward deviation of the basal septum (Figure). Patient characteristics Variable TR ERO = 0 TR ERO = 1-39 TR ERO 40 P value ERO, mm ± ±0.37 < Regurgitant Volume, ml ± ±17.9 < Annulus systolic diameter, cm 2.7± ± ±0.6 < Tenting Height 0.37± ± ± Tenting area 0.5± ± ±0.6 < RV length 7.7± ± ± RV basal diameter 3.1± ± ±0.7 < Conclusions: Isolated functional TR is not caused by valvular tenting but is associated with annular enlargement, consistent with the RV remodeling characterized by increased width rather than height. These mechanistic data may provide important clues on functional TR surgical correction. P2393 Left ventricular regional predictors of outcome post mitral valve repair in patients with functional ischemic mitral regurgitation T. Kukulski 1, A. Leopold 2,W.Streb 1, T. Niklewski 2, M. Zembala 2, Z. Kalarus 1. 1 Dpt of Cardiology Congenital Heart Disease and Electrotherapy, Zabrze, Poland; 2 Dpt of Cardiosurgery and Transplantology, Katowice, Poland Background: Although early and mid term outcome post valve repair using undersized mitral restrictive annuloplasty (UMRA)is satisfactory, the long term results might be compromised by recurrence of mitral regurgitation and poor reversed left ventricular remodeling (RLVR). It has been shown that morphologic indexes of mitral valve deformation can predict the success of surgical repair, however the role of LV functional parameters has to be still determine. The study was aimed to evaluate long term results post UMRA and to define LV functional predictors of poor outcome (combined end point: cardiac death and heart transplantation and hospitalization). Methods: 52 pts (61±7y, EF 40±11%, EDV 150±51, ESV 94±40 ml) with moderate-severe functional ischemic mitral regurgitation (FIMR) (MR degree 3,4±0,6) who underwent simultaneous UMRA (ring size 26,8±1,3mm) and CABG were evaluated retrospectively 40±8 months post surgery. Location of infarct was inferior in 50%, anterior in 21%,lateral in 13% of pts. Global LV function indexes and regional velocity (VEL sys) and deformation (S max)parameters were analysed at baseline and follow up. Mid-segment strain and velocity data were representative for each LV wall. Logistic regression was used to determine an impact of baseline LV function indexes and clinical variables on outcome. Results: 18/52 (34%)patients showed RLVR defined as EF increase by >5%. Inferior wall strain/esv and lateral wall velocity were found to be independent predictors of combined end-point (see table). Pacing effect on TR grade Discussion: RV pacing is associated with a small (but significant) increase in TR grade, independently of the electrode s presence. It is suggested that pacing increases TR via induction of dyssynchrony in RV contraction. P2392 Mechanism of functional,isolated tricuspid regurgitation A quantitative clinical study T.Y. Topilsky, M.E.S. Enriquez-Sarano. Mayo Clinic, Rochester, United States of America Background: Mechanism of functional tricuspid regurgitation (TR) remains unclear while recent studies suggested that functional mitral regurgitation is due valve deformation (tenting) rather than annular enlargement. Methods: To study the mechanism of functional, isolated (no valve disease, pulmonary hypertension, left heart disease, pacemaker, or congenital disease) TR we performed a triple quantitative (tricuspid valve deformation, regurgitation, right ventricular and atrial quantitation) study. We enrolled 141 patients with isolated functional TR, and 50 age- (71 vs. 70 years, p=0.54) sex- and ejection fraction- (63 vs 61% p=0.07) matched controls. Results: Patients with functional TR vs. controls had larger right atrial area (23.5±8.2 vs 15±3.3 cm 2,p<0.001) right ventricular (RV) area (27.8±9.4 vs. 22.7±5.9 cm 2,p<0.001) and lower RV area contraction (37±10 vs 44±13%, p<0.001). Patients were classified according to TR effective regurgitant orifice (ERO) as severe (ERO 40 mm 2 ), moderate (ERO 1-39 mm 2 ) and no TR (ERO 0mm 2 ) in Table 1. With increasing severity oftr, more valve and ventricular alterations were noted, but tricuspid tenting height was unchanged showing that the increasing tricuspid tenting area was due to annular enlargement. In multivariate analysis, the only independent predictor of ERO and regurgitant volume was systolic annular diameter. Importantly with increasing severity of TR, RV length did not increase while RV transversal diameter increased in parallel to annular dimension. Parameter Vel sys lat S max inf/esv Age EF baseline Estimate -3,70-4,29-1,54 2,57 p level 0,007 0,013 0,24 0,13 95%CI -6,35-7,63-4,17-0,83 +95%CI -1,06-0,94 1,08 5,97 chi square 8,16 6,82 1,43 2,35 p level 0,004 0,008 0,23 0,12 Odds ratio 0,02 0,01 0,21 13,06 95% CI 0,0017 0,0004 0,01 0,43 +95% CI 0,34 0,38 2,95 393,47 Conclusions: Regional LV function indexes can predict unfavourable outcome post mitral surgery in pts with FIMR P2394 Late referral of women for valve surgery - implications for complications and survival K. Zareba, R.O. Bonow, N. Akhter, B.R. Lapin, P.M. Mccarthy, V.H. Rigolin. Northwestern University, Chicago, United States of America Objective: Established guidelines for valve surgery are similar for men and women and include symptoms and left ventricular function. We sought to compare clinical and operative characteristics as well as outcomes in men and women referred for mitral valve (MV) surgery. Methods: An analysis of 758 patients (mean age 63±14, 48% females) admitted for MV surgery (replacement or annuloplasty) was conducted between April 2004 and July Patients undergoing concomitant aortic valve (AV), tricuspid valve (TV) or atrial fibrillation (AF) correction operations, coronary artery bypass grafting (CABG) and re-do operations were included. Clinical and operative variables were used to predict operative mortality and complications. Results: Compared to men, women were older (64±14 vs. 62±13, p=0.03), had more pre-op congestive heart failure (46% vs. 38%, p=0.04) and greater NYHA class III and IV symptoms (50% vs. 37%, p<0.0001) despite a higher mean ejection fraction (54±13 vs. 52±13, p=0.02). Women had more prior valve surgery (21% vs. 13%, p=0.004), and presented with more mitral and aortic stenosis. Women had more TV (36% vs. 17%, p<0.0001) and AF correction operations (40% vs. 33%, p=0.03). Equal numbers of men and women had concomitant AV

102 402 Mitral, tricuspid and rheumatic valve disease surgery while more men had CABG. Women also underwent more MV replacement (43% vs. 19%, p<0.0001), were given more blood products and required longer post-op ventilation and ICU stays. Mortality at 30 days post surgery was higher in women (6.1% vs. 3.0%, p=0.025), however operative mortality was not statistically different between women and men (3.3% vs. 1.8%, p=0.174). Multivariate regression analysis revealed that age (HR 1.09, p=0.003), concomitant TV operation (HR 1.65, p<0.001), and operative urgency (HR 1.43, p=0.034) were independent predictors of operative mortality or complications. Conclusions: Women present for MV surgery with more symptomatic heart failure. Women also undergo more complex operations, and have greater requirement for blood transfusions and mechanical ventilation. Therefore, earlier detection of symptoms in women is necessary, leading to earlier referral for MV surgery in appropriate patients. P2395 Comprehensive annular and subvalvular repair of chronic ischemic MR provides best long-term results with least ventricular remodeling C. Szymanski 1,A.Bel 1, I. Cohen 1, M.D. Handschumacher 1, M. Desnos 1, A. Carpentier 1, P. Menasche 1, A.A. Hagege 1, R.A. Levine 2,E.Messas 1. 1 European Hospital George Pompidou (AP-HP), Paris, France; 2 Massachusetts General Hospital, Cardiac Ultrasound Laboratory, Harvard Medical School, Boston, United States of America Background: In ischemic mitral regurgitation (IMR), leaflet tethering is caused by post-mi LV and annular remodeling. Severing second-order mitral chordae significantly decreases tethering and MR. We tested whether undersized ring annuloplasty can improve chordal cutting efficacy by reducing annulus-related tethering. Methods: Posterolateral MI created chronic remodeling and MR in 28 sheep. At 3 months, sheep were randomized to sham surgery vs isolated annuloplasty undersized by 2 sizes vs isolated bileaflet chordal cutting vs at the combined therapy (n=7 each). At baseline, chronic MI (3 months) and sacrifice (6.6 months) we measured LV volumes and ejection fraction (EF), wall motion score index (WMSi), MR Regurgitation fraction (MRRF) and vena contracta (VC), Mitral annulus area (MAA) and posterior leaflet (PL) restriction angle (PL to MAA) by 2D and 3D echo. Results: All groups were comparable at baseline and chronic MI, with mild- moderate MR (MRVC 4.6±1.0mm, MRRF 24±2.6%) and MA dilatation (p<0.01). At sacrifice, LV end-systolic volume (ESV) increased by 108% in controls vs 28% with ring + chordal cutting, less than with each intervention alone (p<0.01). Also, MR progressed to moderate-severe in controls but decreased to trace with ring + chordal cutting vs mild-moderate with ring alone and trace-mild with chordal cutting alone (MRVC 5.9±1.1mm in controls, 2.0±0.7 with ring, 1.0±0.9 with chordal cutting, 0.5±0.08 with both, p<0.01). Ring alone did not improve PL mobility (PL restriction angle 79.4±6.0 ), but chordal cutting did alone or with ring (PL restriction angle 54.2±5.0 with chordal cutting vs. 45.0±2.3 with both, p=ns). In multivariate analysis, LVESV and MAA most strongly predicted MR (r 2 =0.82, p<0.01). Conclusions: Comprehensive annular and subvalvular repair provides the most effective long-term reduction of both chronic ischemic MR and LV remodeling. Results: There were significant differences in the amount of left atrial fibrosis between group I and II (p=0.049) and group III and IV (p=0.008) (Table 1). The only clinical factors which significantly correlated with amount of atrial fibrosis were: patients age (p=0.048), left atrium diameter (p=0.024) and the degree of tricuspid regurgitation (p=0.004). Conclusion: Atrial fibrosis can provide pathophysiological substrate for atrial fibrillation in patients with mitral valve disease before and after mitral surgery. Atrial fibrosis is associated with patients age, left atrium diameter and the degree of tricuspid regurgitation. P2397 Long-term contribution of functional mitral regurgitation after a first non-st segment elevation acute coronary syndrome to left ventricular enlargement I. Nunez-Gil, J. Zamorano, L. Perez De Isla, C. Almeria, J.L. Rodrigo, C. Fernandez-Golfin, P. Marcos-Alberca, D. Herrera, A. Aubele, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Functional mitral regurgitation (MR) is frequent after an acute myocardial infarction. However, data about the long term influence of functional MR after a non-st segment elevation acute myocardial syndrome (NSTSEACS) are scarce. Our aim was to assess the relationship between functional MR after a first NSTSEACS and the development of LV enlargement. Methods: We prospectively studied 248 patients consecutively discharged from hospital in NYHA functional class I and II (74% men; mean age 65.1±12.3 years) after a first NSTSEACS. Every patient underwent an echocardiographic study during the first week after the NSTSEACS and were clinically and echocardiographically followed up between months later. Patients who were lost or died before were excluded. Results: One hundred and fifty eight patients were enrolled. MR was detected in 59 cases (38.3%). Patients were followed a median time of 1108 days (interquartile range: ). Onset mean LVEF was 55.76± LV diastolic (grade I: 12.7±40.7; grade II: 26.8±12.4; grade III: 46.3±50.9 cc, p=0.01) and systolic (grade I: 10.4±37.3; grade II: 10.12±12.7; grade III: 36.8±46.0 cc, p=0.02) mean volumes were higher after follow up in patients with MR, and the severity of the enlargement were related to the severity of the initial MR degree (See figure). In spite of LV remodeling no differences in revascularization were found between groups. Adverse events, including death, heart failure, unstable angina and infarction were more frequent in the MR group. P2396 Determinants and consequences of left atrial fibrosis in patients with mitral valve disease T. Mularek-Kubzdela, W. Seniuk, S. Grajek, A. Marszalek, A. Olasinska-Wisniewska, M. Jemielity, W. Stachowiak, W. Sarnowski, P. Breborowicz, M. Prech. Poznan University of Medical Sciences, Poznan, Poland The purpose of this study was to determine whether the amount of left atrial fibrosis is associated with development or persistence of atrial fibrillation before and after mitral surgery and to investigate which clinical factors are associated with increased fibrosis in patients with mitral valve disease. 101 consecutive patients (male 25, female 76) aged 23 to 71 (mean 52) with mitral valve disease admitted for mitral surgery were enrolled in the study. In all patients electrocardiography, echocardiography and clinical examination were performed before the operation. 36 patients were in sinus rhythm - group I, 65 had chronic atrial fibrillation- group II. Biopsies of the posterior wall of the left atrium were obtained during open heart surgery. Tissue was analyzed for percent of fibrosis using an image analyzer. 12 months after operation cardiac rhythm was checked. 8 patients died before 12- month-follow-up, 3 patients were lost to follow-up. Remaining 90 patients were divided into two groups according to the rhythm: group III - sinus rhythm (SR, 50 patients), group IV - atrial fibrillation (AF, 40 patients). Table 1 Group I Group II P SR before surgery AF before surgery N=36 N=65 Mean percent of left atrium fibrosis 32.1± ±10.7 P=0.049 Group III Group IV P SR one year after surgery AF one year after surgery N=50 N=40 Mean percent of left atrium fibrosis 32.8± ±10.4 P=0.008 Main results Conclusions: There is an increase in LV diastolic and systolic volumes in patients after a first NSTSEACS. Furthermore, the risk of LV enlergement is closely related to MR severity on admission. Thus, the remodelling could explain in part the worst prognosis observed regarding MR after a NSTSEACS. P2398 Subclinical left ventricular dysfunction in rheumatic mitral stenosis: correlation with high sensitivity C-reactive protein levels E. Khalifa. Dar Al Fouad Hospital, Cairo, Egypt Background: In pure rheumatic mitral stenosis (MS), varying degrees of left ventricular (LV) dysfunction occur. There is a controversy regarding whether this deterioration is result of functional or mechanical factors. Doppler tissue velocities of the mitral annulus correlate well with LV systolic and diastolic functions. C-reactive protein (CRP) is increased in patients with acute rheumatic fever but it is not known whether plasma levels increase in patients with chronic rheumatic valve disease and their impact on LV function. Objectives: To investigate left ventricular function by using pulsed wave Doppler tissue imaging (PWDTI) in rheumatic mitral stenosis and correlate this with high sensitivity (hs)-crp levels. Patients and methods: The current study enrolled 80 patients with chronic rheumatic mitral stenosis & 36 age and gender matched healthy volunteers as control group. PWDTI data (from each of 4 mitral annular sites, septal, lateral, inferior, anterior) were obtained. Mean peak annular systolic velocity (Sm), mean annular early (Em) and late (Am) diastolic velocities were calculated by averaging of values measured at each site. Precontraction time (PCT), ejection time (ET) and isovolumic relaxation time (IVRT) was estimated for calculation of the myocardial performance index (MPI).

103 Mitral, tricuspid and rheumatic valve disease 403 hs-crp levels were measured by rapid immunoassay and blinded to cardiologist making assessment of LV function. Results: Myocardial velocities of LV (Sm, Em, Am) were found to be significantly lower in MS patients compared to controls (8.1±0.61 vs 9.4±1.8 cm/s, 7.3±1.4 vs 14.4±0.28 cm/s, 9.2±2.1 vs 11.4±1.1 cm/s respectively, p<0.001 for all). MPI was higher in MS patients than control group (0.63±0.2 vs 0.47±0.3, p<0.001). Patients with MS were shown to have significantly higher plasma levels of hs-crp compared to controls (6.5±0.9 vs 2.2±0.8mg/L, p<0.001). Significant negative correlation could be established between hs-crp and Sm (r = -0.67), Em (r = -0.82), Am (r =-0.738) whereas significant positive correlation was established between hs-crp and MPI (r = 0.66) with p<0.001 for all correlations. Conclusion: Rheumatic mitral stenosis significantly impaired left ventricular long axis function evaluated by PWDTI, and this impairment was strongly correlated with hs-crp level. These results may be an evidence of ongoing low grade systemic inflammation in chronic phase of rheumatic heart disease. P2399 Does degenerative mitral regurgitation severity change during exercise echocardiography? J. Magne 1, M. Moonen 1, K. O Connor 1, P. Pibarot 2,L.A.Pierard 1, P. Lancellotti 1. 1 CHU de Liege - Domaine du Sart Tilman, Liege, Belgium; 2 Quebec Heart institute, Quebec, Canada Introduction: Recent studies revealed that mitral regurgitation (MR) severity may change during exercise in patients with functional MR. Significant exerciseinduced increases in MR is associated with poor outcome. By contrast, changes in MR severity during exercise remain undetermined in patients with degenerative MR. Method and results: Resting and symptom-limited semi-supine bicycle exercise Doppler-echocardiography were performed in 66 consecutive patients (61±15 years and 55% of male) with moderate to severe degenerative MR (i.e. mitral prolapse or flail). MR severity was evaluated, both at rest and during exercise, using vena-contracta (VC) width and effective regurgitant orifice (ERO) area calculated with the proximal isovelocity surface area (EROP) and the quantitative Doppler (EROD) methods. Systolic pulmonary arterial pressure (PAP) was derived from the peak regurgitant transtricuspid pressure gradient obtained at rest and during exercise. At rest, EROD was greater than EROP (52±16mm 2 vs. 31±17mm 2,p<0.0001). VC width (mean =5.3±1.5mm) was correlated with both EROP and EROD (r=0.57, p= and r=0.47, p=0.004, respectively). In addition, EROP and EROD were also correlated (r=0.51, p=0.0036). During exercise, VC, EROP and EROD increase in 71%, 54% and 54% of patients, respectively and there were good correlations between exercise VC and exercise EROP and EROD (r=0.42, p=0.035, r=0.47, p=0.017 and r=0.73, p<0.0001). Systolic PAP also increased during exercise (from 29±9 to52±16mmhg, p<0.0001) and changes in PAP during test were correlated with changes in EROP and EROD (r=0.33, p=0.04 and r=0.44, p=0.004). Moreover, patients with exercise peak PAP>60mmHg had higher exercise VC (6.2±1 vs. 7.8±3mm, p=0.04), EROP (33±21mm 2 vs. 45±22mm 2, p=0.04) and EROD (49±20mm 2 vs. 69±27mm 2, p=0.0047) and higher exercise-induced change in VC (0.6±2 vs. 2±1.6mm, p=0.04) and in EROD (-2.7±17 vs. 12±18 mm 2, p=0.006). After adjustment for age, sex and resting PAP, exercise-induced changes in EROD remained associated with changes in PAP (β=0.22, p=0.033) Conclusion: As in functional MR, degenerative MR can be dynamic and increases during exercise in more than 50% of patients. Changes in MR severity are associated with exercise-induced changes in systolic PAP, suggesting a potential impact on outcome. Further studies are needed to determine whether exercise-induced increase in MR has prognostic importance. compared with controls (112.19±15.45% and ±15.93% vs ±6.62% and ±10.08%, p<0.001 for both). With exercise, peak systolic twist increased in normals (18.44±6.24, p=0.002 vs. rest) but not in MR (16.74±5.4, p=ns). Times to onset and peak of untwisting both became earlier in MR (101.57±9.87 and ±15.76, p<0.02 vs. rest), but remained delayed compared with controls (93.46±8.03 and ±14.85, p<0.002 vs. MR). In the MR group, peak systolic twist on exercise correlated inversely with resting measures of left atrial volume (r=-0.402, p=0.03), regurgitant volume, and regurgitant fraction (r= and respectively, p<0.05 for both). Time to onset of untwisting on exercise correlated with resting LV end-diastolic volume (r=0.585, p=0.002), end-systolic volume on exercise, and the change in ejection fraction on exercise (r=0.562 and respectively, p=0.005). The change in time to peak untwisting from rest to exercise correlated inversely with left atrial volume (r= , p=0.049). Conclusion: In patients with chronic mitral regurgitation, abnormalities in LV twist on exercise worsen progressively with increased resting preload and with measures of exercise-induced systolic impairment. This provides further evidence that LV twist may play a role in the development of functional limitation with progressive disease. P2401 Functional mitral regurgitation and Non ST-segment elevation myocardial infarction: very long-term prognosis I. Nunez-Gil, J. Zamorano, L. Perez De Isla, C. Almeria, J.L. Rodrigo, C. Fernandez-Golfin, P. Marcoz-Alberca, M. Quezada, V. Serra, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Functional mitral regurgitation (MR) after an acute myocardial infarction is a frequent complication related with worse outcome. Nevertheless, data on MR after a Non-ST-segment elevation acute myocardial infarction (NSTEMI) is scarce in our environment. Our objective was to investigate the incidence, clinical predictors, and prognostic implications of MR in the setting of NSTEMI after a long term follow-up. Methods: We prospectively studied 255 consecutive patients admitted to our coronary care unit for a first NSTEMI. Every patient underwent an echocardiographic study during the first week after admission and was clinically and echocardiographically followed up (median 1011 days). Results: Mean age was 66.19±13 years (73.8%, men). MR incidence was 40% (75 patients, grade I; 15, grade II; 6, grade III and 3 grade IV). Only the age, diabetes mellitus, multivessel disease and MR (HR=2.17; , p=0.003) were independently related with long term worse outcome. The MR presence (see figure) and amount was proportionally related with more events. P2400 Left ventricular twist on exercise deteriorates with increased volume overload in chronic mitral regurgitation R.A. Argyle 1, R.P. Beynon 1, R. Aghamohammadzadeh 1, K.A. Pearce 1,A.N.Borg 2,S.G.Ray 1. 1 University Hospital of South Manchester, Manchester, United Kingdom; 2 Blackpool Victoria Hospital, Blackpool, United Kingdom Purpose: Left ventricular (LV) twisting and untwisting are important for normal systolic and diastolic function, and enhance on exercise in normal subjects. In chronic severe mitral regurgitation (MR), volume overload can result in LV dysfunction, initially apparent only on exercise. We studied how changes in LV twisting parameters on exercise relate to conventional markers of volume overload and LV function. Methods: Subjects underwent echocardiography at rest and during submaximal exercise on a supine bicycle ergometer. We used 2-dimensional speckle-tracking echocardiography in parasternal short axis views to assess LV twist by subtracting basal rotation from apical rotation. Times to onset and peak of untwisting were expressed as a percentage of systolic duration. Correlations with standard echocardiographic measures were carried out using the Spearman correlation coefficient. Results: 28 patients aged 60±14 years with asymptomatic chronic moderate to severe primary MR and 28 age-matched controls were included. At rest, peak systolic twist (degrees) was similar in both MR and controls (14.84±4.49 vs ±5.03 respectively). Both onset and peak of untwisting were delayed in MR Main results Conclusions: In our environment, MR is frequent after an NSTEMI. Its presence together with other negative factors establish a worse very long-term prognosis. In addition, this point seems to be proportionally related with MR degree. Therefore, the existence of MR should be specifically assessed and followed-up in every patient after an NSTEMI. P2402 Prospective single center registry of patients with ischemic mitral regurgitation considered for revascularization (PRAGUE 9 study registry) with one year clinical follow up V. Kocka, P. Widimsky, M. Penicka, H. Linkova, T. Budesinsky, J. Dvorak, L. Lisa, P. Tousek on behalf of Grant MSM Cardiac Center, Teaching Hospital Královské Vinohrady and 3rd Medical School of Charles University, Prague, Czech Republic Purpose: We aimed to characterize group of patients indicated for coronary revascularization, who have simultaneously ischemic mitral regurgitation (IMR). This was studied in population where primary percutaneous coronary intervention (PCI) is routine therapy of acute ST elevation myocardial infarction for at least 10 years. Best therapeutic approach to similar patients is not well established. Methods: 2408 patients undergoing cardiac catheterization at our institution from

104 404 Mitral, tricuspid and rheumatic valve disease 1.1. till were screened. 63 patients who were considered for coronary revascularization (percutaneous and/or surgical) and had at least mild to moderate (2+) ischemic mitral regurgitation were included. IMR was defined by detailed echocardiography evaluation of mitral valve morphology, excluding rheumatic heart disease, m.barlow and severe calcification. All patients were followed for one year. Population of Czech Republic is approx. 10 million and there were cardiac catheterizations performed in year Results: Clinical characteristics are: average age 69 years, 68% being of male sex, NYHA class 2.5, diabetes mellitus 44%, hypertension 78% (mean blood pressure at inclusion was 133/77mmHg, 2.2 antihypertensive medication per patient), positive troponin at inclusion 32%, prior revascularization 25%. In agreement with literature physical examination is not too helpful - 38% of patients have no detectable murmur, only 36% of patients have clearly audible murmur grade 2/6. Echocardiography showed mean left ventricle (LV) diastolic dimension 59mm, LV ejection fraction 41%, left atrium size 45mm. IMR severity was graded by experienced echocardiographer and there was statistically significant difference in LV diastolic dimension between mild to moderate (2+/4) and severe (4/4) IMR (p=0.01). Mean logistic Euroscore was patients underwent coronary revascularization (26 by PCI, 22 surgically with mitral valve repair in 13 cases), 14 were treated medically and 1 patient was referred for cardiac transplantation. There was no significant difference in mortality between patients treated medically (7%) and revascularized patients (19%) due to small sample size and small number of events, overall mortality was 16%. Conclusion: Incidence of patients with ischemic mitral regurgitation who are considered for coronary revascularization is 147 patients per 1 million per year, even in the era of primary PCI. These patients have high estimated surgical risk. One year mortality is also high at 16%. Our data might be useful for meta-analysis and planning future research. P2403 Pulmonary vascular resistances evaluation during exercise in patients with mitral valve stenosis A.R. Almeida, C. Cotrim, H. Vinhas, R. Miranda, S. Almeida, L.R. Lopes, I. Joao, P. Fazendas, M. Carrageta. Hospital Garcia de Orta, Almada, Portugal Background: Treadmill exercise echocardiography with Doppler evaluation during effort has been used for several years in our department. Purpose: Evaluate patients (pts) with mitral valve stenosis and sinus rhythm using Doppler parameters, during treadmill exercise test (TE), with assessment of pulmonary vascular resistances (PVR). Methods: From a total of 72 pts we have completed the study in 68 pts. The mean age was 50±10 years (27 to 74 years) and 59 were females. We evaluated the mitral functional area using pressure half-time method (PHT), the mean transmitral pressure gradient ( Pm), the stroke volume (SV) and cardiac output (CO) through aortic valve, and systolic pulmonary pressure (SPP) using the pressure gradient between right ventricle and right atria ( P RV/AD) in pts with tricuspid regurgitation in addition to right atrial pressure (assuming 5 mmhg at left lateral decubitus (LLD) and 0 mmhg at orthostatic position (OP)). We assessed these parameters with echocardiography at LLD and then at OP, during exercise (using the modified Bruce protocol), at peak workload (PW) before treadmill testing termination, and at early recovery (R) (first 90 seconds). To calculate PVR we assumed that pulmonary capillary wedge pressure (PCWP) is equal to Pm plus left ventricular telediastolic pressure (assuming it as 4 mmhg). The mean pulmonary pressure (MPP) was calculated with Chemla formula (MPP= 0,6 X SPP + 2 mmhg). We calculated PVR, in Wood units (WU), using the formula: PVR = (MPP-PCWP)/CO. Results: The mitral functional area was 1,46±0,35 cm 2 (0,8 to 2,5). The Pm at LLD was - 8,6±4 mmhg, at OP-6,2±3,5 mmhg (p<0,001 vs LLD), at PW - 23,3±9 mmhg (p< 0,0001 vs OP) and at R-15,3±5,6 mmhg (p<0,0001 vs PW). The mean SPP was at LLD - 44±11 mmhg, at OP - 31±11 mmhg, at PW- 63±20mmHg and at R- 56±15 mmhg (p<0,0001 vs PW). The mean PVR was at LLD - 4,2±2,8 UW, at OP - 2,8 UW (p<0,001 vs LLD) and at PW - 1,77 UW (p<0,001 vs OP). According to guidelines, the difference between SPP in PW and R lead to different indication to treatment (medical treatment vs mitral valvuloplasty or substitution with mechanical prosthesis) in 12 pts (18%). Conclusions: 1. The PVR decreased at OP and even more during exercise in treadmill in pts with mitral stenosis; 2. The Pm and the SPP decreased at orthostatic position; 2. The Pm and SPP increased significantly during exercise in studied population and were significantly higher at PW when compared to recovery; 4. The difference between SPP at PW and at R had influenced the clinical decision. P2404 The effect of severity of mitral regurgitation on ejection fraction and end-diastolic volume D.H. Maciver. Musgrove Park Hospital, Taunton, United Kingdom Purpose: Left ventricular ejection fraction (EF) and end-diastolic volume (EDV) are influenced by a complex interplay between pre- & after-load as well as the contractile function. In mitral regurgitation (MR) important clinical decisions, such as need for valve surgery, are influenced by the EF and EDV. Experimental animal studies show an initial increase in strain followed by a normalisation and finally a reduction in strain in severe MR. Therefore, a greater understanding and quantification of the effect of increasing mitral regurgitation on EF & EDV is crucial. Methods: A entirely new 2 shell three-dimensional mathematical model was used to assess the individual effect of increasing mitral regurgitation volume (0, 30, 60, 90 ml) on ejection fraction & end-diastolic volume. Net stroke volumes, left ventricular muscle mass, longitudinal stain & midwall circumferential strain (shortening) were fixed. Results: Increasing mitral regurgitation caused an increase in EDV but, unexpectedly, a fall in ejection fraction when myocardial shortening (strain) was unchanged. Conclusions: Mathematical modelling of ventricular contraction gives important insight into the complex changes that occur with increasing mitral regurgitation. Assuming no change in myocardial strain increasing mitral regurgitation resulted in an increase in EDV but a reduction in left ventricular EF. P2405 Three dimensional dobutamine stress echocardiography predicts the outcome of patients with functional mitral regurgitation K. Obase, N. Watanabe, N. Wada, A. Hayashida, Y. Neishi, T. Kawamoto, H. Okura, K. Yoshida. Kawasaki Medical School, Kurashiki, Japan Background: Dobutamine infusion improves functional mitral regurgitation (FMR) by its vasodilatory and inotropic effects. The aim of the study was to investigate the changes in geometry of mitral valve complex during dobutamine stress echocardiography (DSE) using transthoracic 3D echocardiography and to clarify its impact on the long-term prognosis of patients with FMR Methods: Thirteen patients with FMR underwent transthoracic 3D DSE (up to 40μg/kg/min). Effective regurgitant orifice (ERO) area of FMR was measured. The area of triangle formed by the tips of both papillary muscles and anterior annulus (PM area) was measured from the 3D data. The rate of change in ERO and PM area during DSE were calculated as following formula. % ERO = (ERO at baseline ERO at peak dose/ero at baseline); % PM area = (PM area at baseline PM area at peak dose)/pm area at baseline. Patients were divided into 2 groups according to the % PM area (% PM are a<10% and % PM area 10%). The long-term cardiac events, including cardiac death, valve and/or CABG surgery, percutaneous coronary intervention and congestive heart failure (CHF) were evaluated in both groups. Result: FMR improved in all the study patients during DSE. There was moderate correlation between % ERO and % PM area ( r =0.56). Incidence of cardiac event was significantly higher in group % PM area <10% than group % PM area 10 (p=0.021). Conclusion: Dynamic change in PM position during dobutamine infusion resulted in the reduction in FMR and is a strong predictor of cardiac events in patients with FMR. P2406 The association of natriuretic peptides to symptoms, severity and left ventricular remodelling in patients with organic mitral regurgitation M. Potocki 1,J.Mair 2, M. Weber 3, N. Jander 4,T.Burkard 1, P. Buser 1,C.H.Mueller 1. 1 University Hospital Basel, Basel, Switzerland; 2 Innsbruck Medical University, Innsbruck, Austria; 3 Kerckhoff Klinik GmbH, Bad Nauheim, 4 Herzzentrum Bad Krozingen, Bad Krozingen, Germany Background: Natriuretic peptides reflect cardiac stress and may therefore be useful in the management of patients with valvular heart disease.

105 Mitral, tricuspid and rheumatic valve disease / Prosthetic heart valves 405 Methods: We enrolled 144 patients with chronic moderate-to-severe organic mitral regurgitation (MR) in an international multicenter study to analyze the determinants of N-terminal pro-b-type natriuretic peptide (NTproBNP). NTproBNP levels were measured in a blinded fashion and we quantified symptoms, MR degree, left ventricular (LV) and left atrial (LA) remodelling. Results: NTproBNP levels (median 373 pg/ml [IQR pg/mL]) were associated with age, gender, NYHA functional class, atrial fibrillation, LV end-systolic dimension and LV ejection fraction. Independent predictors of increased NTproBNP levels were NYHA functional class (p<0.001), atrial fibrillation (p=0.008) and LV end-systolic dimension (p=0.026). Importantly, MR severity and LA dimension were not independently associated with NT-proBNP levels. NT-proBNP levels increased significantly with symptom class (p<0.001) but not with MR severity (p=0.144). The NT-proBNP levels were significantly higher in symptomatic patients than in asymptomatic patients (582pg/ml [IQR ] vs. 157pg/ml [64-256]; p <0.0001). The area under the receiver-operator-characteristic curve (AUC) to predict symptoms for NT-proBNP was 0.80 [95% CI, 0.71 to 0.88], which was significantly higher than for all echocardiographic measures (p<0.001 for all). The AUC for NT-proBNP to predict elevated LV end-systolic dimension (> 40mm) was 0.71[ ]. Receiver operating characteristic curves Conclusion: In patients with chronic moderate-to-severe organic MR NT-proBNP levels are determined by age, NYHA functional class, atrial fibrillation and LV endsystolic dimension. Thus, NTproBNP may be helpful in the clinical evaluation and management of patients with MR. PROSTHETIC HEART VALVES P2407 Platelet reactivity in patients with a history of obstructive prosthetic valve thrombosis E. Lev, T. Bouganim, Y. Shapira, M. Vaturi, A. Battler, R. Kornowski, A. Sagie. Rabin Medical Center, Petah Tikva, Israel Background and Purpose: One of the most serious complications of mechanical valves is obstructive prosthetic valve thrombosis (OPVT stuck valve ). Some patients develop OPVT despite an international normalized ratio (INR) in the therapeutic recommended range. We hypothesized that patients who develop OPVT have hyper-reactive platelets. We, therefore, aimed to examine platelet reactivity in patients who developed OPVT, despite therapeutic or neartherapeutic INR, compared with a matched control group. Methods: We compared platelet reactivity between patients who had an OPVT episode, despite therapeutic or near-therapeutic INR, during the years (n=19), and a matched group of patients with mechanical valves who did not develop this complication (n=19). Platelet reactivity was evaluated by platelet aggregation in response to various agonists, platelet deposition under flow conditions in the Impact-R system and plasma levels of platelet activation markers (soluble CD40-L and P-Selectin). Results: In the OPVT group the average INR during the index episode was 3.1±1.5, and 42.9±39 months have elapsed from the index episode to the current study. Both groups were matched for gender (63% women), age±10 yrs (mean yrs), valve position and type, active smoking and diabetes (15.8%). Patients with OPVT history had higher aggregation in response to collagen (P=0.05), higher platelet deposition in the Impact-R system (P=0.001), and tended to have higher levels of sp-selection and scd40l (P= ), than their control counter-parts. Platelet reactivity in the two groups Test Study Group (n=19) Control Group (n=19) P value Aggregation Collagen 1 μg/ml 67.2± ± Aggregation ADP 10 μmol/l 68.5± ± Impact-R: surface coverage % 9.1± ± Impact-R: average size (μm 2 ) 43.8± ± scd40-l (pg/ml) 193.3± ± sp-selectin (ng/ml) 3.0± ± Concluions: Patients with a history of OPVT appear to have increased platelet reactivity, which may contribute to an increased risk of thrombotic complications. These patients would, therefore, likely benefit from the addition of anti-platelet therapy to standard anti-coagulant treatment. P2408 Comparison of dabigatran, unfractionated heparin and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves, results of an in vitro study L. Maegdefessel 1,T.Linde 2, F. Krapiec 1, U. Steinseifer 2,J.Van Ryn 3, B. Hauroeder 4, U. Raaz 1, M. Buerke 1, K. Werdan 1, A. Schlitt 1. 1 Martin-Luther-Universitaet Halle, Halle, Germany; 2 Helmholtz Institute - RWTH, Aachen, Germany; 3 Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany; 4 Central Institute of the German Federal Armed Forces, Koblenz, Germany Purpose: Lifelong oral anticoagulation (OAC) therapy is required for the prevention of thromboembolic events after implantation of an artificial heart valve. Nevertheless, thromboembolic events occur in approximately 2-4% and bleeding complications in 2-9% of patients per year after mechanical valve replacement despite OAC. Thromboembolism and anticoagulant-related bleedings account for 75% of all complications experienced by heart valve recipients. Dabigatran etexilate, a new and orally available direct thrombin inhibitor, is currently investigated in a phase III trial in comparison to OAC in patients with atrial fibrillation. Dabigatran etexilate might also be an alternative to OAC in patients after mechanical heart valve replacement. The present study investigated the efficacy of dabigatran, in comparison to unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH; Enoxaparin) in preventing thrombus formation on mechanical heart valves in vitro. Methods: Blood (230 ml) from healthy young male volunteers was anticoagulated either by dabigatran (1 μm), UFH (150 IU), or LMWH (100 IU). Aortic valve prostheses (27 mm) were placed in a newly developed in vitro thrombosis tester and exposed to the anticoagulated blood samples under continuous circulation at a rate of 75 beats per minute. The total exposure time was 60 minutes. To quantify the thrombi that developed, electron microscopy was performed. Using a data acquisition unit (DAQ) flow and pressure differences were recorded before and after the heart valve and compared between the three groups. Finally, each valve was weighed before and after the experiment. Results: In whole blood with no anticoagulant, the apparatus completely clotted in minutes. When blood was treated with dabigatran, the mean thrombus weight was 168±92 mg, in the UFH group 162±98 mg, and in the LMWH group 194±117 mg (p-value: for comparison between all three groups via ANOVA). Electron microscopy showed no significant difference in thrombus formation in any group. The DAQ showed a decrease in flow and pressure curves when thrombi occurred in all three groups. Conclusions: Dabigatran was as effective as UFH and LMWH in preventing thrombus formation on mechanical heart valves in our in vitro investigation. Thus, we hypothesize that dabigatran etexilate might potentially be a useful and competitive orally administered alternative to UFH and LMWH for recipients of alloplastic heart valve prostheses. P2409 Twenty-years clinical outcome and hemodynamic performance of the HancockII bioprosthesis C. Valfre, G. Minniti, L. Salvador, V. Salandin, E. Cavarretta, F. Cesari, P. Ius. Treviso Hospital, Treviso, Italy Purrpose: The Hancock II (HII) is a second-generation of porcine bioprosthesis introduced into clinical use in The aim of this study is to evaluate the late clinical and echocardiographic outcome of this bioprosthesis. Methods: Between June 1985 and November 1993, 378 consecutive patients (pts) (234 male, mean age years, range 20-90) underwent valve replacement surgery with HII, respectively 250 (66.1%) in aortic (AVR) and 128 (33.9%) in mitral (MVR) position. Twenty-three year follow-up was complete for all pts at a median of 16 years (range 0-23). Results: Valve replacement was required in 53 patients (14%) after a mean of years ( ). Freedom from reoperation for any cause at 20-years was 77.8% (pts at risk 25). Among 325 pts who didn t undergo valve replacement, 87 pts (26.8%) were still alive with a mean follow-up of years (15-23) and echo data were collected on 45 of them (51.7%). In the whole population Table 1. Echocardiographic parameters Aortic valven=38 Mitral valven=7 Ejection Fraction (%) 59±8 56±9 End Diastolic Diameter (mm) 54±5 51±7 End Systolic Diameter (mm) 36±7 32±3 Valve Regurgitation None 29 (76%) 1 (14%) Trivial 5 (13%) 4 (58%) Mild 3 (8%) 1 (14%) Moderate Severe 1 (3%) 1 (14%) Paravalvular leak 1 (3%) 1 (14%)

106 406 Prosthetic heart valves the left ventricle function resulted preserved and none or trivial valve regurgitation was observed in 89% of the aortic patients and in 72% of mitral patients (Table 1). Conclusions: Based on the unusual high number of patients still alive and free from reoperation at 20-years, the HII bioprosthesis confirms excellent hemodynamic performance at very long-term observation. P2410 Clinical and echocardiographic study in patients reoperated for the prosthetic valve dysfunction M. Maciejewski, K. Piestrzeniewicz, A. Bielecka, M. Piechowiak, M. Lelonek, R. Jaszewski, J. Drozdz. Medical University, Lodz, Poland Introduction: Reoperation in patients with implanted artificial valves are still a serious problem; it is so mainly because of the higher early mortality rate. The incidence of reoperation (R) increases along with the increased number of implanted prosthetic valves (PV). Purpose: To analyse the risk factors of early and late mortality in patients undergoing the first R for prosthetic valve dysfunction (PVD) at the period Methods: Prospective study was performed in 194 consecutive pts (M-75, F- 119; mean age 53.2±11 years) with mechanical prosthetic valve (MPV: n=103 cases; 53%) or bioprosthesis (B: 91; 47%). The period since valve replacement to R was 6 days to 19 years. 22 pts were reoperated up to 30 days since PV replacement. 42 pts underwent urgent reoperation. III-IV NYHA functional class was observed in 105 pts. The types of PVD were: structural PVD in 82 pts (6 pts with MPV and 76 pts with B), endocarditis (IE) in 58 pts, PV blockade in 30 pts, periprosthetic leak in 17 pts, and other reasons in 7 pts. Univariate and multivariate Cox statistical analysis was performed to determine risk factors of early and late mortality. Results: The overall early mortality was 18.6%; 31.4% in pts with symptoms of III-IV NYHA functional class and 3.4% in pts with NYHA I-IIo. Univariate analysis revealed the following predictors of early mortality: urgent R (p<0.01), NYHA III-IVo (p<0.001), IE (p<0.001), R of MPV (p<0.005), plasma creatinine > 1.5 mg/dl (p<0.05), AF (p<0.02), hydropericardium (p<0.05) and EF<55% (p<0.01). Multivariate analysis identified symptoms of NYHA III-IV and IE as independent predictors of early mortality. The overall late mortality (> 30 days) was - 8.2% (0.62% year/patient). The next prosthetic valve replacement (rer) was performed in eight patients; three of these pts (26.3%) died at early period post rer. Univariate analysis revealed the following predictors of late mortality: age (p<0.05), male sex (p<0.05), R for IE (p<0.001), R for MPV (p<0.005), raised concentration of plasma creatinine > 1.5 mg/dl (p<0.05), atrial fibrillation (p<0.05) and left atrial enlargement >5.0 cm (p<0.01). Multivariate analysis identified age at the time of R as a strong independent predictor of late mortality. Conclusions: R in pts with PV, performed urgently especially in pts with symptoms of III-IV NYHA functional class or in case of IE bear high mortality rate. Risk of planned R, mostly in pts with symptoms of I-II NYHA class does not differ from the risk of the first valve reimplantation. P2411 Management of prosthetic valve thrombosis with low dose, prolonged infusion of tissue type plasminogen activator under the guidance of serial transesophageal echocardiography during pregnancy A.E. Oguz, N.E. Duran, M. Yildiz, M. Biteker, S. Gunduz, H. Kaya, A.C. Aykan, M.A. Astarcioglu, E. Erturk, M. Ozkan. Kartal Kosuyolu Heart Education and Research Hospital, Istanbul, Turkey Purpose: Prosthetic valve thrombosis occurring during pregnancy is a lifethreatening complication. We sought to evaluate the use of low dose, prolonged infusion of tissue type plasminogen activator (t-pa) for the treatment of a thrombosed prosthetic mitral valve under the guidance of serial transesophageal echocardiography (TEE) in pregnant women. Methods: Nine patients (mean age 24.8 years) with 10 pregnancies between 6 to 35 weeks of gestation (mean 21±15 weeks) had thromboses of mitral mechanical heart prosthesis during pregnancy. Four of the patients had obstructive thrombus (OT), and the remaining had non-obstructive thrombus (NOT). One patient had NOT in her two pregnancies. Five patients were using low molecular weight heparin in the first trimester and other four patients have ineffective INR (International normalized ratio) values while second and third trimester. Low-dose (25 mg), slow infusion (6 hours) of t-pa without bolus administration is used as a principal agent. Successive infusions are used if the desired effect was not achieved. 1.5 millions IU streptokinase infusion was administered in only one patient after partially successful infusions of t-pa up to 100 mg. TEE was performed at baseline and repeated after each thrombolytic treatment session. Results: The hemodynamic and morfologic results were completely successful in all patients. Four patients carried till 36 weeks of gestation and delivered by cesarean section a live newborn with an uneventful postpartum course and other six patients are followed up during their pregnancy. Complete success was achieved with a mean dose of 75.5 mg t-pa. There were no major or minor complications in terms of morbidity or mortality in these patients. Conclusions: Thrombolytic therapy should be considered primarly in the management of pregnant patients with prosthetic valve thrombosis. In this series we describe safe and successful use of low dose, slow infusion of tpa under the guidance of serial TEE in pregnant women is to be first presented. P2412 Prognostic value of geriatric assessment prior to aortic valve replacement in the elderly - the Albertinen study of GEriatric Care and Cardiac Surgery (AGE-CCS) B. Frilling 1,F.C.Riess 2, W. Von Renteln-Kruse 1. 1 Albertinen-Haus; Geriatrics and Gerontology Centre at the Universtiy of Hamburg, Hamburg, Germany; 2 Albertinen-Krankenhaus; Dpt of Cardiac Surgery, Hamburg, Germany Objective: An increasing number of elderly patients develop aortic valve disease requiring surgery. With the rise of new non-surgical treatment options assessing operative risk has become one of the key aspects of clinical decision-making. AGE-CCS is a prospective cohort study evaluating the predictive value of a routine geriatric assessment prior to cardiac surgery. Methods: Interim analysis of a prospective cohort study. Out of 320 consecutive patients referred for elective or urgent cardiac surgery, 170 patients underwent aortic valve replacement with or without additional CABG. Geriatric assessment on the day before surgery included mobility (Timed up and go), muscle strength (Handgrip Vigorimeter), cognitive function (DemTect), depression (Geriatric Depression Scale) and activities of daily living (IADL and ADL). Results: Mean age was 77.3 years; 49.4% were women. Mean Euro-SCORE was 17.3%. 32.4% of the patients had aortic valve replacement with additional CABG. 27.1% of the operations were urgent. Hospital mortality was 5.3%. Determinants of in-hopsital mortality In-hospital death No in-hospital death OR (95% CI) Age > 80 years 44.4% 31.7% 2.4 ( ) Low handgrip strength 66.7% 19.9% 8.6 ( ) Impaired mobility 100% 26.8% n/a Impaired cognitive function 77.8% 49.8% 6.5 ( ) Impaired IADL 44.4% 13.9% 5.3 ( ) Impaired ADL 11.1% 2.9% 3.5 ( ) Depression 22.1% 7.1% 3.4 ( ) Conclusion: Low muscular strength, impaired mobilityand cocgnitive functionas well as dependence in IADL are significantly associated with postoperative death. Comprehensive geriatric assessment may add valuable information in assessing operative risk of elderly patients requiring aortic valve replacement. P2413 Stentless aortic valve bioprosthesis dehiscence. A possible infective endocarditis with atypical presentation but serious consequences L. Lepage, L. Krapf, G. Hekimian, X. Duval, P. Nataf, B. Iung, U. Hvass, A. Vahanian, D. Messika-Zeitoun. AP-HP, Bichat Hospital, Paris, France Background: Stentless aortic valve bioprosthesis exhibits an excellent hemodynamic profile and very good midterm results similar to second-generation stented bioprosthesis. We recently reported an atypical presentation of a prosthetic valve infective endocarditis (PVIE) occurring on a stentless Cryolife O Brien aortic bioprosthesis without inflammatory markers, negative blood cultures but anatomic damage suggestive of IE. Stentless aortic valve prosthesis are widely used at our institution and we decided to look for other cases with similar presentation and to compare the clinical, bacteriological and echocardiographic features of PVIE according to prosthetic type. Methods: We reviewed all cases of possible or definite aortic PVIE according to the modified Duke criteria hospitalized in our institution between January 2002 and March Results: Sixty patients (65±14 years, 71% male) with possible or definite aortic PVIE were admitted during this period (mechanical prosthesis: 26 patients (44%), stented bioprosthesis: 11 patients (18%) and stentless Cryo-Life O Brien bioprosthesis: 23 patients (38%)). Compared to mechanical or stented prosthesis, patients with stentless valve presented less frequently with fever (39% vs. 77% and 91%, p=0.003), tended to present more frequently in congestive heart failure (54% vs. 23% and 36%, p=0.10), less frequently with positive blood cultures (44% vs. 65% and 82%, p=0.08) and with lower CRP levels (69±70 mg/l vs. 144±106 mg/l and 145±123 mg/l, p=0.02). Patients with stentless valve also presented less frequently with vegetations (22% vs. 58% and 63%, p=0.01) but more frequently with valve dehiscence (68% vs. 23% and 22%, p=0.006) and severe aortic regurgitation (65% vs. 23% and 36%, p=0.01). Forty patients were operated on within 30 days, more frequently in the stentless group (83% vs. 61% and 45% respectively, p=0.07). Compared to the previously reported incidence of stentless PVIE at our institution (1.5%), we observed a striking increase incidence after 2004 (>7%), which corresponds to changes in the manufacturing process. Conclusion: We report a frequent and atypical clinical and microbiological presentation of possible PVIE occurring with stentless bioprosthesis with a striking increased incidence after 2004 which corresponds to changes in the manufacturing process. Whatever, the exact etiology (infectious, toxic,...), clinicians should be aware of this atypical clinical presentation with serious consequences. The

107 Prosthetic heart valves 407 stentless Cryo-Life O Brien bioprosthesis is not anymore implanted at our institution. P2414 One year experience with the 2nd generation 3F-Enable sutureless aortic valve prosthesis A. Kadner 1, F. Eckstein 2, L. Englberger 1,M.Stalder 1,T.Aymard 1, M. Grapow 2, N. Walpoth 1, C. Zobrist 1,T.Carrel 1. 1 Inselspital Bern, Berne, Switzerland; 2 University Hospital Basel, Basel, Switzerland Background: Currently, percutaneous aortic valve replacement (AVR) is strongly promoted as an alternative to traditional open heart valve surgery. Beside its reduced invasiveness, this new approach shows severe limitations, such as no removal of the diseased valve, difficulty of accurate positioning of the prosthesis, and limitations of available sizes of valve prostheses. As an alternative, the nitinolstented 3F-Enable equine pericardial valve prosthesis was developed to allow a sutureless prosthesis implantation. We report our early experience with this new implant. Material and methods: Between 08/2007 to 12/2008, 30 patients (age 76±6 years, 23 females) underwent AVR with the 2nd generation sutureless 3F valve prosthesis. All patients were operated for symptomatic aortic stenosis (mean mean gradient: 42±14 mmhg, mean aortic valve area:0.5±0.24mmhg, NYHA III, Euroscore: median 7, range: 4-10). Echocardiography was performed pre-, intra-, and postoperatively, as well as at 6 and 12 months follow-up. Results: Prosthesis sizes were 27mm (n=4), 25 mm (n=6), and 23mm (n=12), 21mm (n=5), 19mm (n=3). A reduced sternotomy (incision length 6-8cm) was performed in 5 patients. ECC time was 56±15 min, X-clamp time 37±8 min, deployment-time 9±6 min (re-deployment: n=4). Follow-up is complete with a mean of 6 months (range: 1-14 months). One patient died of cardiac tamponade on post-op day one. A second patient died of CHF at 7 months postoperatively. One transient neurologic event occurred. Five patient (17%) required the implantation of a permanent pacemaker. Mean pressure gradients were 10±4 mmhg, peak gradients 17±6 mmhg. Three patient showed a paravalvular leakage of grade one. Two non-valve-related explants were performed, intraoperatively and at 4 months post-op. Conclusions: The new generation of the 3F Enable sutureless aortic valve shows promising results. This valve has the potential to reduce X-clamp time and might be particularly interesting for combined procedures. The modified design of the 2nd generation of this prosthesis appears to reduce the earlier reported complications with paravalvular leakage, however a high rate of pacemaker implantations were observed. P2415 Thrombolysis as first line treatment in prosthetic mitral valve thrombosis A. Nagy, M. Denes, M. Lengyel. Hungarian Institute of Cardiology, Budapest, Hungary Purpose: Treatment strategies and guidelines in management of prosthetic valve thrombosis (PVT) are still controversial. In this retrospective study our aim was to assess the success and complication rate of thrombolytic therapy (TT) comparing thrombus size, severity of symptoms, type of the prosthetic valve and time since valve implantation. Methods: Between April 1993 and December 2006 TT was given in 62 thrombotic events in 55 patients with mitral PVT. Thrombus size was measured by planimetry and its location and mobility was assessed by the use of TEE. Continuous thrombolytic treatment in obstructive PVT (OPVT) was monitored using gradient measurement by TTE every 2-5 hours and visual assessment by TEE every 24 hours. Results: All patients with non-obstructive PVT (NOPVT) were in NYHA class I or II. Out of the 52 cases with OPVT 8 patients were in NYHA class I or II and 44 patients in NYHA class III-IV (p<0.0001). Thrombus area by TEE before thrombolysis was <0.8 cm 2 in 24 cases, 0.8 cm 2 in 21 cases and couldn t be measured in 17 cases. Thrombolysis was successful in 45 cases (73%) including all NOPVT. In 13 patients (21%) the transvalvular gradient decreased but did not normalise. In 4 patients (6%) thrombolysis failed. Complications of thrombolysis were present in 11 cases (18%) and 4 (6%) patients died. The success rate of thrombolysis in cases of severely ill patients, in functional class III or IV was 70%, compared to 76% success in hemodynamically more stable patients (P=0.63). The complication rate in more stable patients was 22% while in NYHA class III and IV patients it was 16% (P=0.4). Patients with large thrombi were successfully thrombolysed in 76% compared to 79% in cases of patients with small thrombi (p=0.81) and there was no significant difference in complication and death rate between the two groups. There was no significant difference in outcome of thrombolysis regarding the type (tilting disk or bileaflet) of the artificial valve: success rate 83 vs. 87%, complication rate 27 vs. 18% (p=0.4). In cases of successful thrombolysis time since surgery was significantly shorter (median 2.5 years), than in cases of partially successful or failed thrombolysis (median 8 and 10.5 years respectively, p=0.01). Conclusions: Based on previous data and our findings thrombolysis can be considered as first-line treatment in all patients with PVT independently of valve type, functional class and thrombus size. A shorter time period since the implantation of the artificial valve to the thrombotic episode favors successful outcome of thrombolysis. P2416 Bovine pericardial single suture line stentless aortic valve: observational clinical and echocardiographic prospective study A. Repossini 1, P. Piccoli 2, E. Chiari 3, A. Manzato 4, N. Berlinghieri 3, C. Muneretto 2. 1 Division of Cardiac Surgery, Spedali Civili di Brescia, Brescia, Italy; 2 University of Brescia, Brescia, Italy; 3 Division of Cardiology, Spedali Civili di Brescia, Brescia, Italy; 4 Cardiothoracic Intensive Care Unit, Spedali Civili di Brescia, Brescia, Italy Objectives: The aim of this study is to perform a clinical and echocardiographic evaluation of a new pericardial bovine supraannular stentless valve (Sorin Freedom Solo). The study analyses prospectively the clinical outcome and one-year follow-up. Methods: 101 patients with pre-operative echocardiographic assessment undergoing aortic valve replacement with a bovine pericardial stentless valve (Sorin Freedom Solo) implanted with a single suture line in supraannular position were enrolled in the study. There were 60 females (59.4%) and 41 males (40.6%) with a mean age of 73.3±8.6 years (22-85). Etiology was: 89 degenerative disease, 5 congenital disease, 4 endocarditis and 3 rheumatic disease. Procedures were performed electively in 87 cases (86.1%), and urgently in 14 (13.9%). Associated procedures were performed in 33 cases: 26 CABG, 5 mitral annuloplasties and 2 ascending aorta replacements. Mean cross clamping time without concomitant procedures was 61.6±16.1 minutes (34-112), 92.2±32.0 minutes (40-240) with concomitant procedures. Valve prostheses measures were as follows: 19 mm in 5 patients (4.9%), 21mm in 25 patients (24.8%), 23mm in 25 patients (24.8%), 25mm in 20 patients (19.8%) and 27mm in 26 patients (25.7%). Mean clinical follow-up was 297±191 days and cumulative was days. A subgroup of 21 patients underwent stress-echo evaluation at 12 months. Results: Post-operative mortality was 1.9% (2 pts, 1 heart failure and 1 intestinal infarction). No early valve-related complications were observed. 2 Late deaths were reported: 1 due to pneumonia 175 days PO (not valve-related) and 1 endocarditis sepsys 48 days PO (valve-related). At the end of the follow-up 2 valverelated late complications were observed (1 non structural valve dysfunction, 1 embolic event). Echocardiographic evaluation showed that 60% of the LV mass regression occurred within 3 months; the follow-up at 12 months reported a mean gradient of 5 mmhg and a peak gradient of 12 mmhg with an EOAi of 1.03 cm 2 /m 2. In the stress-echo subgroup peak and mean basal gradients were 12.3 mmhg and 4.6 mmhg, while at maximum tolerance the gradients were 17.5 mmhg and 7.2 mmhg. Conclusions: The new bovine pericardial stentless valve implanted with a single suture line in a supraannular position proved to be safe and effective with a shortterm follow-up without major complications. Haemodynamic features even in the exercise stress subgroup were very promising. However, a longer follow-up is required to prove that haemodynamic advantages may affect prosthesis durability. P2417 Clinical significance of prosthetic valve fibrin strands and associations with anticoagulant status M. Kiavar, A. Sadeghpour, H. Bassiri, P. Tayyebi, M. Parsaee, M. Esmaeilzadeh, M. Maleki. Rajaei Cardiovascular Medical and Research Center, Tehran, Iran (Islamic Republic of) Purpose: We aimed to determine the frequency of prosthetic valve strands, and to assess their significance in relation to clinical cerebral ischemic events (CIE) and anticoagulant status. Background: Filamentous fibrin strands (FSs) attached to the valve prostheses have been well described in patients undergoing transesophageal echocardiography (TEE), but the frequency and clinical significance of these strands remain poorly defined. Methods: 300 consecutive patients with 421 prosthetic heart valves, were evaluated for the presence of FSs (highly mobile, filamentous masses less than 1 mm thickness). Results: Fibrin strands (FSs) were found in 141 (47%) patients, 147 prosthesis (38%) with a significant association between FSs, CIE and anticoagulant status (p < 0.001). We found more FSs on mitral (118 out of 241) rather than aortic valve Figure 1. INR, FSs Relationship

108 408 Prosthetic heart valves / Atrial fibrillation. Special issues (29 out of 148) prostheses (p < 0.001), with no statistically significant association between the number of prosthetic valves and FSs. The results of multivariate analysis revealed that coagulation state of patients (for average INR), presence of FSs and left ventricular ejection fraction have significant positive associations with CIE. Lower value of INR (less than 2.5) had a positive association with the occurrence of CIE. Conclusions: There is a significant association between FSs, CIE and patient s anticoagulant status, therefore we suggest aggressive anticoagulation (narrower window with INR above 3) and close follow up for these patients. ATRIAL FIBRILLATION. SPECIAL ISSUES P2418 Amiodarone versus sotalol: Safer antiarrhythmic treatment by amiodarone in heart failure due to lack of effect on dispersion of repolarization and creation of a rectangular action potential morphology G. Frommeyer 1, P. Milberg 1, P. Witte 1, J. Stypmann 1, G. Moennig 1, M. Luecke 2, G. Breithardt 1, L. Eckardt 1. 1 Hospital of the Westfälische Wilhelms-University, Department of Cardiology and Angiology, Münster, Germany; 2 Medical Faculty of the Westfalian Wilhelms-University, Experimental Animal Research Centre, Münster, Germany Background: Sudden cardiac death due to life-threatening arrhythmias is a major problem in chronic heart failure (CHF). The aim of the present study was to investigate the mechanism underlying the lower proarrhythmic potential of amiodarone as compared with sotalol in a model of pacing-induced heart failure. Methods and results: In 35 female rabbits, heart failure was induced by 4 weeks of rapid pacing (400 beats/min). 35 rabbits were sham-operated and observed for the same time. In 17 of 35 CHF-rabbits and 20 of 35 sham -rabbits amiodarone ( mg/d) was fed over a period of 6 weeks. All pacemaker-treated rabbits developed clinical signs of congestive heart failure. The mean ejection fraction decreased from 64±14% to 17±5%. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation in all hearts after induction of heart failure (p<0.05) but no increase in dispersion of repolarization. Amiodarone led to a further mean QT interval prolongation of 33±13ms in control hearts but showed no significant effect on QT interval in heart failure hearts. Moreover, amiodarone had no effect on dispersion of repolarization. Infusion of the class-iii drug sotalol (50-100μM) in failing hearts lead to a further significant action potential prolongation as compared to non-failing hearts (mean increase: +68ms; p<0.05) and a significant increase in dispersion of repolarization (+45%; p<0.05). Sotalol led to a triangular action potential configuration (ratio APD90/APD50 sham: 1.29 at baseline, 1.44 at 100μM sotalol; CHF: 1.11 at baseline, 1.35 at 100μM sotalol) whereas amiodarone did not cause triangularization but caused a more marked phase-ii prolongation (APD90/APD50 sham: 1.29 at baseline, 1.30 after treatment with amiodarone; CHF: 1.11 at baseline, 1.15 after treatment with amiodarone). After lowering of potassium concentration, 16 of 18 failing-hearts showed torsade de pointes (TdP) during sotalol infusion in contrast to an absence of TdP in amiodarone treated failing hearts (n=17). Conclusions: Chronic administration of amiodarone had no effect on action potential duration in heart failure in contrast to a significant QT prolongation after acute treatment with sotalol. Moreover, amiodarone does not increase dispersion of repolarization and results in a rectangular action potential morphology. This could be the reason for the absence of proarrhythmia in amiodarone treated hearts in this animal model and might also explain the lower proarrhythmic potential of amiodarone as compared with sotalol in humans. P2419 Efficacy, safety and advantages of a brief post-cardioversion anticoagulation protocol in patients with persistent atrial fibrillation and no long term indication to anticoagulation A. Conversano, C. Gardini, G. Fragasso, A. Mailhac, A. Margonato. San Raffaele del Monte Tabor Foundation, Milan, Italy Background: In patients with atrial fibrillation (AF), eligible for electrical cardioversion (C), the guided approach with transoesophageal echocardiography allows to avoid 3 weeks of pre-c anticoagulation therapy (AT). However, if the procedure is successful, at least 4 more weeks of oral AT (OAT) with warfarin are indicated by international guidelines. We suggest that a shorter period of AT, although never tested, might be safe since thromboembolic complications are very rare: in fact 98% of complications occurs in the first week after C and are almost invariably due to inadequate levels of OAT. We therefore prospectively compared a shorter AT protocol (10 days after C) with low molecular weight heparin (LMWH) with the standard OAT regimen in patients undergoing C for AF. LMWH was chosen since it allows rapid and stable achievement of anticoagulation which is appealing especially if a short AT course is planned. Methods: Between 2002 and 2006, 170 patients with AF of unknown duration of non rheumatic aetiology, referred for C as outpatient, were randomized to 2 alternative AT protocols. Group A: 86 patients (mean age 64.4±9) received LMWH (nadroparin 100UI/kg twice a day for 20 days before and 10 days after C). At day 10, LMWH was substituted with antiplatelet agents if SR was maintained and transthoracic echocardiography showed restoration of atrial contraction. Group B: 84 patients (mean age 63.6±10) received OAT for 3 weeks before and 4 weeks after C. Results: No primary C related events (cerebro-vascular accident, embolisation, major bleeding, death) were observed at 10 and 30 days following C in both groups. Follow up at 6 and 12 months also showed no differences between the 2 groups. There were 2 minor bleedings in group A requiring no treatment. Absence from work was significantly greater in group B (12 days± 1.39) versus group A (3.32±1.27), p value< The number of successful C was greater in group A (92%) versus group B (80%), p value< Conclusions: A shorter AT course (10 days versus 4 weeks) following C for AF appears to be safe when LMWH is used. When a short period of AT is desirable, primarily in patients at high risk of bleeding, choosing LMWH may be particularly appealing, since prothrombin time monitoring and associated impracticalities are eluded; an important feature in the elderly. Additionally, LMWH allows better planning of the day of C, since its use avoids the risk of inadequate anticoagulation before C with warfarin. While larger studies are needed, our results support the safety and efficacy of stopping AT early post C in patients at high risk of bleeding. P2420 Impact of epicardial fat pads ablation on acute atrial electrical remodeling D. Chang, S. Zhang, L. Gao, D. Yang, Y. Lin, Z. Zhen, X. Yin, X. Xiao, P. Jiang, Y. Yang. Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China, People s Republic of Objective: To investigate the impact of epicardial fat pads (FPs) ablation on acute atrial electrical remodeling (AAER). Methods: 28 adult mongrel dogs under general anesthesia with sodium pentobarbital were involved. Bilateral cervical vagosympathetic trunks were decentralized. AAER was performed through rapid atrial pacing (RAP) at 600 bpm for 4hrs at distal coronary sinus (CSD). Before RAP, 14 dogs underwent epicardial FPs ablation (ablation group) and the other 14 dogs underwent a sham procedure (control group). Atrial effective refractory period (ERP) and vulnerability window (VW) of atrial fibrillation (AF) were measured at high right atrium (HRA), ostium of coronary sinus (CSO) and CSD with and without vagosympathetic nerve stimulation (VNS) before and after different time courses (1hr, 2hrs, 3hrs and 4hrs) of RAP. Results: (1) In control group, RAP shortened ERP at all sites significantly with and without VNS [without VNS (105±15.06)msec vs (123.71±12.62) msec at HRA, P<0.01; (94.29±14.53) msec vs (107.71±14.86) msec at CSO, P<0.01; (90.71±16.85) msec vs (107.71±14.86) msec at CSD, P<0.01); with VNS, (58.57±29.05) msec vs (80±33.51) msec at HRA, P<0.05; (53.57±20.98) msec vs (73.57±26.20) msec at CSO, P<0.05; (48.57±24.13) msec vs (69.29±24.64) msec at CSD, P<0.05)], thereby resulting in AAER. Impact of RAP on VW was slight. VNS shortened ERP and augmented VW significantly (P<0.05). (2) In ablation group, after epicardial FPs ablation, VNS did not shorten ERP or increase VW (P>0.05). Even after RAP, ERP and VW still maintained unchanged with and without VNS (P>0.05). Conclusion: RAP could result in AAER, which may be mediated and aggravated by vagosympathetic nerve activity. Epicardial FPs ablation could abolish AAER. P2421 Arrhythmia vulnerability of aged haploinsufficient Cx43 mice is determined by heterogeneous downregulation of Cx43 combined with increased fibrosis J.A. Jansen, T.A. Van Veen, R. Van Der Nagel, M.A. Vos, J.M. De Bakker, H.V.M. Van Rijen. Interuniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands Purpose: Reduced gap junction expression and increased collagen deposition are commonly found in ventricles of electrically remodeled diseased hearts. Their interactive contribution to slow conduction and increased arrhythmogeneity is, however, unclear. In this study, we investigated the effect of increased fibrosis with normal or reduced levels of the ventricular gap junction protein Cx43 on impulse propagation and arrhythmogeneity. Methods: 11 Cx43fl/fl and 15 Cx43Cre-ER(T)/fl mice (expressing only 50% of Cx43 protein compared to Cx43fl/fl) were aged to months. Epicardial activation mapping (208 electrode terminals) of right (RV) and left (LV) ventricle was performed on Langendorff perfused hearts. Effective refractory period (ERP) was determined by premature stimulation and arrhythmia inducibility was tested by 1-3 premature stimuli and burst pacing. Epicardial conduction velocity longitudinal (CVL) and transverse (CVT) to fiber orientation and inhomogeneity of conduction was determined during BCL pacing (150 ms). Cx43, N-cadherin expression, and tissue collagen content was determined by (immuno)histology and Western blotting. Results: Sustained ventricular arrhythmias were induced in 0/11 Cx43fl/fl and 10/15 Cx43Cre-ER(T)/fl mice (p<0.01). CVL and CVT were unchanged, except for CVT in RV, which was decreased from 42.7±1.0 to 36.5±1.3 cm/s (Cx43fl/fl and Cx43Cre-ER(T)/fl respectively, p<0.01), which was more pronounced in the Cx43Cre-ER(T)/fl mice with arrhythmias (+VT) compared to Cx43Cre-ER(T)/fl mice without arrhythmias ( VT). ERP was decreased from 82.7±5.9 to 64.7±5.5

109 Atrial fibrillation. Special issues 409 ms in LV (p<0.05) and from 77.3±5.6 to 53.3±2.9 ms in RV (p<0.01, Cx43fl/fl and Cx43Cre-ER(T)/fl respectively). In both RV and LV, inhomogeneity of conduction was significantly higher in Cx43Cre-ER(T)/fl mice +VT compared to both Cx43fl/fl and Cx43Cre-ER(T)/fl mice VT. Cx43 expression levels were comparable between Cx43Cre-ER(T)/fl mice VT and +VT, though strongly reduced compared to Cx43fl/fl. Cx43 distribution was very heterogeneous in Cx43Cre- ER(T)/fl mice with large areas devoid of Cx43 while N-cadherin was unaffected, indicating the presence of intact intercalated disks. Compared to Cx43fl/fl, interstitial fibrosis was increased in Cx43Cre-ER(T)/fl mice, but more pronounced in Cx43Cre-ER(T)/fl mice +VT when compared to Cx43Cre-ER(T)/fl mice VT. Conclusions: Combined heterogeneous reduction of Cx43 and increased fibrosis strongly enhance arrhythmogenic vulnerability in aged haploinsufficient Cx43 mice. P2422 The human cardiac K2P3.1 (TASK-1) potassium leak channel is a molecular target for the class III antiarrhythmic drug amiodarone D. Thomas, J. Gierten, A.K. Rahm, R. Bloehs, K. Schloemer, J. Kisselbach, I. Staudacher, S. Obers, P.A. Schweizer, H.A. Katus. Universitaetsklinikum Heidelberg, Heidelberg, Germany Two-pore-domain (K2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, IKP. Class III antiarrhythmic drugs target cardiac K + currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the class III antiarrhythmic drug amiodarone on human K2P3.1 channels. Amiodarone produced concentration-dependent inhibition of hk2p3.1 currents expressed in Xenopus oocytes (IC50 = 0.51 μm), with a maximum current reduction of 81.9%. Open rectification properties that are characteristic to hk2p3.1 currents were not altered by amiodarone. Channels were blocked in closed and open states. hk2p3.1 channel inhibition was frequency- and voltage-dependent with more pronounced current reduction at voltages -40 mv. Modulation of protein kinase C activity by amiodarone does not contribute to hk2p3.1 current reduction, as pre-treatment with the PKC inhibitor, staurosporine, did not affect amiodarone block. It is concluded that amiodarone is a potent inhibitor of cardiac hk2p3.1 background channels. Amiodarone blockade of hk2p3.1 is expected to cause prolongation of cardiac repolarization and action potential duration, possibly contributing to the antiarrhythmic efficacy of the class III drug. P2423 Left atrial pressure as significant predictor of long-term success after pulmonary vein ablation L. Mittmann-Braun, M. Linhardt, O. Balta, G. Nickenig, L. Lickfett. Universitaetsklinikum Bonn, Bonn, Germany Introduction: Recurrences are still common after pulmonary vein (PV) ablation for atrial fibrillation (AF). In many patients PV ablation only is sufficient to control AF. Other patients need more extensive left atrial ablation. The goal of our study was to examine the role of LA pressure to predict long-term clinical outcome and possibly guide the extent of LA ablation. Methods: All pts undergoing their first a pulmonary vein ablation procedure (PVA) between February 2007 and September 2008 at our institution were included. Only patients with a follow up of at least 2 months were included. PVAs performed with cryo balloon or mesh ablator catheter were excluded. 132 Pts were included. According to their mean LApr determined at the beginning of the PVA procedure they were divided into a group with a LApr <18 mmhg ( group A, GA ) and a group with a LApr 19 mmhg ( group B, GB ). Pts were instructed to perform daily recordings with a a trans-telefonic ECG recorder for the first 3 months after the procedure. They were contacted 1, 3, 6 and 12 months after the PVA. The antiarrhythmic medication was discontinued in all pts free from AF recurrence. Results: 97 (73%) were male. 71 (54%) pts fell into group A and 61 (46%) into group B. 56/71 (79%) pts in GA and 34/61 (56%) pts in GB had paroxysmal AF. Mean onset of AF was 2 [1-18] years ago. The mean follow-up duration was 9 [2-20] months. There only statistically significant differences in the baseline characteristics between both groups was the average of age: GA: 58 [26-83±12] vs. GB: 64 [44-81±8] years (p= 0.05). The LApr was 12±4 mmhg in group A and 26±8 mmhg in group B. 10 of 71 (14%) of pts in group A and 20 of 61 (33%) in group B had recurrence of AF during follow up (p = 0.01, negative PV: 86%, sensitivity: 67%, specificity: 60%, positive PV: 33%). Conclusion: An intraprocedural mean LA pressure of < 18mm Hg is a significant predictor for long term success after pulmonary vein isolation procedure. This may allow to intra-procedurally guide the extent of LA ablation necessary for AF control. P2424 are rate-control drugs and antithrombotic therapies appropriately prescribed in atrial fibrillation? a survey of clinical practice G. Matharu, D. Wilson, A. Gunarathne, G.Y.H. Lip. University Department of Medicine, City Hospital, Birmingham, United Kingdom Purpose: Recommendations suggest digoxin can be added for atrial fibrillation (AF) rate-control if this is not achieved with beta-blockers (BB) or rate-limiting calcium antagonists (CA). Digoxin monotherapy should only be used in predominantly sedentary patients. AF patients should also be on antithrombotic therapy (ATT) based on predictive stroke risk. We conducted a survey of clinical practice to see if rate-control and antithrombotic drugs were appropriately prescribed in AF. Methods: Patients (40% male; age range yr) admitted over six-months to two teaching hospitals on digoxin for AF rate-control were identified. We recorded data on BB, rate-limiting CA, warfarin, and aspirin use. Patients with hypertension, diabetes, heart failure or previous stroke/transient ischaemic attack (TIA) were identified. CHADS2 scores were calculated to predict stoke risk. Results: Of 284 patients, 23.9% were on digoxin+bb and 4.2% on digoxin+ca (Table 1(a)). Of patients without heart failure (n=111) 88 were on digoxin alone for rate-control (31.0% of total cohort). There were 85 (29.9%) patients on warfarin and 116 (40.8%) on aspirin. Warfarin was prescribed to 36.9% of low risk patients (CHADS2=0). In high-risk patients (CHADS>1) 67.1% were not on warfarin and 31.4% were not on any ATT (Table 1(b)). Additionally, 36.3% of intermediate risk subjects (CHADS2=1) were not prescribed any ATT. Co-morbidities and CHADS2 scores (n=284) Whole cohort Digoxin only Digoxin+BB Digoxin+CC (a) Study population Total (71.8%) 68 (23.9%) 12 (4.2%) Heart Failure 173 (60.9%) 116 (67.1%) 48 (27.7%) 9 (5.2%) Hypertension 84 (29.6%) 60 (71.4%) 22 (26.2%) 2 (2.4%) Diabetes 45 (15.8%) 29 (64.4%) 14 (31.1%) 2 (4.4%) Stroke/TIA 24 (8.5%) 15 (62.5%) 9 (37.5%) 0 No aspirin or warfarin Aspirin only Warfarin only Aspirin + warfarin (b) ATT in relation to CHADS2 score 0 (n=19; 6.7%) 5 (26.3%) 7 (36.8%) 6 (31.6%) 1 (5.3%) 1 (n=80; 28.2%) 29 (36.3%) 34 (42.5%) 16 (20.0%) 1 (1.3%) 2-6 (n=185; 65.1%) 58 (31.4%) 66 (35.7%) 53 (28.6%) 8 (4.3%) Conclusions: We identified nearly a third of patients were prescribed digoxin monotherapy for AF rate-control when a BB, CA, or one of these plus digoxin would be the preferred approach. ATT was also inappropriately prescribed, with poor adherence to risk stratification and guidelines. P2425 Comparison of pulmonary veins anatomy in patients with and without atrial fibrillation: analysis by multislice tomography I. Wozniak-Skowerska 1, M. Skowerski 2, A.M. Wnuk-Wojnar 1, A. Gola 3, M. Sosnowski 4, A. Hoffmann 1,M.Trusz-Gluza 1. 1 Medical University of Silesia, 1st Department of Cardiology, Katowice, Poland; 2 Medical University of Silesia, 2nd Department of Cardiology, Katowice, Poland; 3 Unit of Noninvasive Cardiovascular Diagnostics Silesian Heart Centre, Katowice, Poland; 4 Medical University of Silesia, 3rd Department of Cardiology, Katowice, Poland A possible role of anomalies in number and insertion of pulmonary veins (PV) in initiating atrial fibrillation (AF) has been suggested. It has been shown as well that changes in anatomy of PVs such as enlargement may have an effect on arrhythmogenesis. The aim of the study was to compare anatomy of the left atrium (LA) and PVs in patients with AF and control subjects. Methods: Eighty two patients were evaluated with 64-slice computed tomography (MSCT). Fifty one of them were referred to catheter ablation with history of highly symptomatic AF - AF(+) group. Thirty one control subjects had no history of AF and were referred to MSCT for noninvasive evaluation of different pathologies which finally were excluded - AF( ) group. Study groups did not differ in regard to age, sex, presence of hypertension and left ventricular systolic function. Diameters of PV ostia were measured in anterior-posterior (AP) and superior-inferior (SI) directions. Venous ostium index was calculated as a ratio between these measurements. Results: The diameter of LA was higher in AF(+) pts than in the AF( ) pts (39±6 mm vs mm, p<0.005). In 68,6% of AF(+) patients and in 83,9% of AF( ) patients the anatomical pattern was typical with two right and two left PVs. Additional PVs were detected in 6 patients, only in AF(+) group (p<0,05). Common ostia were more frequently found in AF(+) subjects (37,2% vs. 19,3, p=0.08), mainly left-sided. In AF(+) group mean SI diameters of both-sided superior PVs and left inferior veins were larger. All AP diameters except for right inferior PVs were also larger in AF(+) group than in control cases. Conclusions: Variations in the PVs anatomy are more common and diameters of ostial portions of the veins are larger in AF patients than in control subjects. These findings suggest that structural abnormalities of PVs may have a possible role in arrhythmogenesis.

110 410 Atrial fibrillation. Special issues P2426 Non-uniform anisotropy and enhanced arrhythmogenesis in patients with lone atrial fibrillation C.X. Wong, M.K. Stiles, B. John, A.G. Brooks, D.H. Lau, H. Dimitri, P. Kuklik, N. Namboodiri, G.D. Young, P. Sanders. Cardiovascular Research Centre, Royal Adelaide Hospital and the University of Adelaide, Adelaide, Australia Purpose: Experimental studies have shown abnormal atrial substrates exhibit marked anisotropic conduction. Whether non-uniform anisotropy is greater in patients with lone atrial fibrillation (AF) and predisposes to arrhythmogenesis is not known. Methods: 25 patients (20M 53±8 y) with lone AF and 25 controls were studied. Conduction time along linear catheters at the coronary sinus (CS), lateral right atrium (RA) and left atrial (LA) roof, and double potentials at the crista terminalis (CT) were assessed in sinus rhythm (SR) and CS pacing. Biatrial electroanatomic maps were created in SR and CS pacing to evaluate conduction velocities, voltage properties and electrogram characteristics. Results: AF patients exhibited longer distal proximal vs proximal distal conduction times along linear catheters (59±13 vs 42±12ms, p=0.003). AF patients also showed a greater increase in DP at the CT from SR to pacing compared to controls (3.9±0.7 to 4.7±1.5 vs 0.7±0.8 to 0.5±0.9, p<0.05). Electroanatomic mapping revealed that compared to SR abnormal conduction direction in AF patients caused changes in regional conduction velocities, bipolar voltage and fractionation, and demonstrated widespread lines of conduction block represented by DP which increased in number and length with abnormal conduction direction. These changes were not seen in controls. Non-Uniform Anisotropy in Lone AF Sinus Rhythm Coronary Sinus Pacing p Value Electroanatomic Mapping Regional conduction velocity (mm/ms) 1.2± ±0.1 <0.001 Bi-atrial activation time (ms) 134±16 158± Regional bipolar voltage (mv) 1.65± ±0.22 <0.005 Complex electrograms (%) & Double Potentials at the CT (n) 27±8, 3.9±0.7 40±13, 4.7±1.5 <0.001 Lines of conduction block (n, mm) 2.7±1.1, 35.8± ±1.1, 64.7±12.3 <0.001 Linear Catheters Coronary sinus conduction time (ms) 41±11 52± Lateral RA conduction time (ms) 46±8 61± LA roof conduction time (ms) 40±12 59± Conclusions: Direction dependent conduction analysis revealed greater nonuniform anisotropy in AF patients but not in controls. This suggests non-uniform anisotropy contributes to the promotion of reentrant circuits critical to arrhythmogenesis. P2427 Catheter ablation for persistent AF: assessing impact of ablation on autonomic tone J. Tuan 1,M.Jeilan 1, S. Kundu 1, P.J. Stafford 2,G.A.Ng 1. 1 University of Leicester, Leicester, United Kingdom; 2 Glenfield Hospital, Leicester, United Kingdom Introduction: The autonomic nervous system is implicated in the pathophysiology of atrial fibrillation (AF). The 5th percentile RR interval during AF is thought to approximate the functional refractory period of the AV node, and hence can be used as a measure of autonomic tone. We explore the effects of catheter ablation on AF cycle length (AFCL), RR intervals and 5th percentile of RR intervals while in AF. Methods: Analysis of electrograms was carried out on patients in sustained AF at the start of catheter ablation for AF. In all cases, the ablation strategy included pulmonary vein isolation, linear ablation, and complex fractionated electrogram ablation in a stepwise manner. No attempts were made to specifically target ganglionic plexi during ablation. Mean AFCL, mean RR interval, mean standard deviation (SD) of RR intervals and 5th percentile of RR intervals over 1 minute were obtained at the start of the procedure (baseline) and just before termination of AF (post-ablation) either by ablation or DC cardioversion at the end of the procedure. AF CL readings were taken from coronary sinus electrodes and RR intervals were measured from surface ECG in lead V6. Results: A consecutive series of 30 patients attending catheter ablation for persistent AF were included in the study. On comparing baseline and post-ablation measurements, mean AF CL increased from 170±5 to 181±4 ms (p=0.006), mean RR interval decreased from 665±32 to 582±27 ms (p<0.001), mean SD of RR intervals decreased from 149±11 to 115±7 ms(p<0.001) and mean 5th percentile of RR intervals decreased from 477±23 to 440±20 ms (p=0.002) respectively. There was no significant correlation between percentage change in AF CL and mean RR intervals. (r= -0.17, p=0.37) Conclusion: Catheter ablation not only increases AF CL but decreases mean RR interval and also 5th percentile of RR intervals while in persistent AF. Our study suggests that these changes are likely to be due to alteration in the autonomic tone caused by standard ablation techniques. P2428 NT-proBNP in the diagnosis of new-onset persistent and paroxysmal atrial fibrillation R. Wachter 1, F. Edelmann 1, T. Grueter 1, H.D. Duengen 2, F. Weidemann 3, M. Zabel 1, L. Binder 1, C. Herrmann-Lingen 1, G. Hasenfuss 1,B.Pieske 4 on behalf of German Heart Failure Network. 1 University of Göttingen, Göttingen, Germany; 2 Charite - Campus Virchow-Klinikum, Berlin, Germany; 3 Medizinische Universitaetsklinik Wuerzburg, Wurzburg, Germany; 4 Medical University of Graz, Graz, Austria Background: Natriuretic peptides (e. g. NT-proBNP) have been widely used for the diagnosis of heart failure. However, they are also elevated in patients with atrial fibrillation (afib). Thus, we aimed to analyse the diagnostic value of NTproBNP in a large-scale prospective clinical trial. Methods: 1712 patients with cardiovascular risk factors (e. g. hypertension, diabetes) or heart failure were included into the DIAST-CHF-trial of the German Heart Failure Network (KNHI). ECGs were recorded at baseline and at follow-up of 1 and 2 years. NT-proBNP values were measured at baseline. All values are given as median (25-75 percentile). Groups were compared by Mann-Whitney-U- Test. Results: At baseline, 1593 patients were in sinus rhythm (SR) and 72 patients were in afib. NT-proBNP was significantly higher in afib (1070 ( ) vs. 100 (51-198) pg/ml, p<0.001). Receiver operating curve analysis revealed an AUC of (95% confidence interval ). At a cut-off of 402 pg/ml, sensitivity was 91%, specificity was 89%, positive predictive value 27% and negative predictive value 99.5%. Follow-up data on 1034 patients were available. 36 patients (3.5%) had newonset atrial fibrillation. NT-proBNP was significantly higher in patients with newonset atrial fibrillation 189 (96-510) pg/ml as compared to 105 (55-226) pg/ml in patients, who stayed in sinus rhythm, p=0.006). In addition, seven day holter-monitoring was performed in 163 patients with sinus rhythm. 10 patients had paroxysmal atrial fibrillation/atrial flutter. NT-proBNP was significantly higher in patients with paroxysmal afib/aflutter 221 (59-747) pg/ml vs. 62 (35-186) pg/ml, p= Conclusion: Beside its value in heart failure, NT-proBNP is a good marker for the prediction of atrial fibrillation and the diagnosis of paroxysmal atrial fibrillation/atrial flutter. Patients with elevated NT-proBNP should be evaluated for paroxysmal atrial fibrillation. P2429 Magnetically obtained remote-controlled left atrial reconstruction is comparable to manually acquired LA anatomy B. Koektuerk, J. Chun, M. Konstantinidou, E. Wissner, B. Schmidt, A. Metzner, T. Zerm, F. Ouyang, K.H. Kuck. Universitaeres Herzzentrum Hamburg ggmbh, Hamburg, Germany Background: Successful pulmonary vein isolation (PVI) relies on precise 3- dimensional (3D) reconstruction of the left atrial (LA) anatomy. Recently, the magnetic navigation system (MNS) Niobe II (Stereotaxis) has been combined with the electroanatomic (EA) reconstruction system CARTO RMT (Biosense Webster) to allow remote controlled magnetic (RCM) 3D LA mapping. Methods: The MNS consists of two computer-controlled permanent magnets positioned on both sides of a fluoroscopy table (AXIOM Artis, Siemens, Germany). The soft magnetic mapping catheter (4 mm, Navistar RMT) aligns parallel to the externally controlled magnetic field. Using the integrated EA system CARTO RMT different vectors can be applied from the mapping system. Selective PV angiographies were used to identify PV ostia. Intra-individual comparisons of reconstructed LA anatomy was performed: In a first step RCM LA reconstruction and tagging of PV ostia was performed (Navistar RMT, Biosense Webster). In the next step a manual LA map and tagging of PV ostia was performed using a conventional 3.5 mm irrigated tip catheter (Navistar, Biosense Webster). Results: Ten pts (5 males; 7 paroxysmal, 3 persistent AF, age: 62±15 years, LA: 47.0±7.3 mm) underwent both RCM and conventional LA reconstruction before PVI. A mean of 109±14 [RMC] vs. 157±18 [conventional] CARTO points resulted in a median (range) of 114 (88-197) ml [RMC] vs. 117 (76-186) ml [conventional] LA volume. Mean required LA reconstruction time was 39±13 [RMC] vs. 15.1±3 min [conventional]. There was a short learning curve for RMC LA reconstruction (Pt#1: 60 min, Pt#5: 36 min, Pt#10: 18 min). No complication was observed. Successful PVI was achieved in all pts. Conclusion: RMC LA mapping appears to be safe, feasible and is associated with a short learning curve. Obtained LA anatomy is comparable to conventional LA mapping. P2430 Atrial myocardial deformation properties in patients with persistent and paroxysmal atrial fibrillation S. Eroglu, E. Sade, E. Polat, I. Atar, B. Ozin, H. Muderrisoglu. Baskent University Faculty of Medicine, Ankara, Turkey Purpose: Atrial fibrillation (AF) is the most common arrhythmia. AF leads to structural and functional changes in the atrial myocardium. In this study, we aimed to investigate atrial myocardial deformation properties in persistent and paroxysmal AF by using Velocity Vector imaging (VVI) technique. Methods: Twenty patients with paroxysmal, 15 patients with persistent AF were

111 Atrial fibrillation. Special issues 411 enrolled. All subjects were examined by echocardiography during the sinus rhythm. Left atrial (LA) volumes were measured. Quantitative measures of LA deformation were obtained from the apical 4- and 2-chamber views by offline analysis using the VVI technique. Peak systolic and peak early diastolic velocity (S, E), strain (Epsilon-S, Epsilon-E) and strain rate (SR-S, SR-E) were measured from the interatrial septum, lateral, anterior and inferior LA walls and averaged. Values were compared among patients with paroxysmal AF and persistent AF. Results: Left atrial volumes were increased in patients with persistent AF as compared with paroxysmal AF (Table). Although systolic and diastolic velocities were similar in patients with persistent and paroxysmal AF; epsilon S and E and SR-S were lower in patients with persistent AF than those with paroxysmal AF (Table). Comparison of echocardiographic parameters in the groups Paroxysmal AF (n=20) Persistent AF (n=15) P LA volume (ml) 40.6± ± S (cm/s) 2.7± ±0.9 NS Epsilon-S (%) 33.2± ± SR-S (s -1 ) 1.6± ± E(cm/s) -2.3± ±0.8 NS A(cm/s) -1.2± ±0.5 NS Epsilon-E (%) 11.8± ± SR-E (s -1 ) -1.9± ± Conclusion: Atrial myocardial deformation properties are damaged in patients with persistent AF than paroxysmal AF. Strain and strain rate measurements of LA using by VVI are more sensitive than velocity measurements to reveal these alterations. P2431 Dynamic-CT integration in CARTO mapping system for atrial fibrillation ablation: validation of the technique in humans P. Vergara, P. Mazzone, M. Saviano, S. Sacchi, S. Crisa, G. Maida, V. Santinelli, G. Vicedomini, C. Pappone. San Raffaele del Monte Tabor Foundation, Milan, Italy Introduction: Three-dimensional anatomic navigation is frequently used during mapping and ablation of atrial fibrillation (AF). Traditionally, patients have to perform a cardiac CT o MRI before the AF ablation. DynaCT offers the possibility of CT-like reconstruction of left atrial and pulmonary veins anatomy during the AF procedure. The aim of the study was to investigate the feasibility and accuracy of DynaCT image integration in CARTO XP mapping system. Methods: Thirty-two patients (59.8±9.6 years; 31M) underwent AF ablation using DynaCT image integration (22 paroxysmal, 6 persistent, 4 permanent). Contrast was administered in the pulmonary artery trunk and image was acquired during a single ungated C-arm rotation over 200 of the x-ray scanner. Axial images were imported into a 3D reconstruction software; after successful segmentation, left atrial + pulmonary ostium volume (D-Vol) was evaluated. Results: Left atrial 3D map was performed with CARTO system using 113±28.5 points and bare left atrial volume (C-Vol) was calculated. DynaCT image was merged in CARTO map by visual allignment and surface best-fit algorhythms; circumferential pulmonary ablation was performed as previously described, including right cavo-tricuspid isthmus ablation. Total procedure (DynaCT+ left and right atrial ablation) fluoroscopy time was 24.9±9.2 minutes; mean dose was 11.6±7.5Gy cm 2. Average distance between CARTO map points and acquired DynaCT surface was 1.9±0.4 mm; D-Vol was 7.9±14.5 ml larger than C-Vol. Conclusions: DynaCT map was successfully integrated in CARTO system in patients undergoing AF ablation. This technology allows a precise appreciation of the complex left atrial and pulmonary vein anatomy with a very high accuracy. P2432 Predictors for long-term sinus rhythm maintenance in patients treated with episodic versus continuous amiodarone treatment S. Ahmed, A.C.P. Wiesfeld, M. Rienstra, D.J. Van Veldhuisen, I.C. Van Gelder. University Medical Center Groningen, Groningen, Netherlands Purpose: Amiodarone can cause many (non-) cardiac adverse events. Limiting amiodarone exposure may lower adverse event rates and still achieve adequate rhythm control in a selected persistent atrial fibrillation (AF) population. Our aim was to find predictors for long-term sinus rhythm maintenance in patients randomly assigned to episodic versus continuous amiodarone therapy, and to identify patients for whom episodic amiodarone therapy may be a viable treatment option. Methods: Patients with a recurrence of persistent AF were randomly assigned to receive either episodic (n=106) or continuous amiodarone therapy (n=103) after electrical cardioversion following 4 weeks amiodarone loading with 600 mg daily. Maintenance dose was lowered to 200 mg. In the episodic group amiodarone was discontinued 4 weeks after achieving sinus rhythm. The continuous group continued amiodarone throughout. During follow-up patients were evaluated for AF recurrence. Results: Median follow-up was 2.1 ( ) years. More first AF recurrences occurred in the episodic compared to the continuous group (85 [80%] versus 56 [54%], p<0.001). After multivariate regression analysis, continuous amiodarone therapy (OR=4.2 [95% CI ], p< 0.001) and CHADS2 score 1 at baseline (OR=2.5 [95% CI ], p=0.008) were predictors for sinus rhythm maintenance throughout follow-up in the whole group. In the episodic group, univariate predictors were age 67 years (OR=2.6 [95% CI ], p=0.06) and CHADS2 score 1 at baseline (OR=3.3 [95% CI ], p=0.07). In the continuous group, the only univariate predictor was CHADS2 score 1 at baseline (OR=2.3 [95% CI ], p=0.06). Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, statin use at baseline or AF duration were not predictors for sinus rhythm maintenance. Conclusions: CHADS2 score 1 and continuous amiodarone treatment are predictive for long-term sinus rhythm maintenance. In younger patients with low CHADS2 score episodic amiodarone treatment may be a valid rhythm control therapy option. In this light, CHADS2 score may also be used as a risk score for rhythm control outcome. P2433 Male gender is independent predictor of increased risk of tachycardiomyopathy in patients with nonvalvular atrial fibrillation T. Potpara, M. Polovina, M. Grujic, B. Vujisic-Tesic, M. Ostojic. Institute for Cardiovascular Diseases, Clinical Center of Serbia, Belgrade, Serbia Purpose: tachycardiomyopathy (TCMP) is defined as reversible left ventricular dilatation and/or reduction of systolic function caused by any prolonged tachycardia. The aim of present study is to examine the relationships between various clinical characteristics and the development of TCMP in patients with nonvalvular atrial fibrillation (AF). Methods: longitudinal, observational study included patients with AF treated in our hospital during , in concordance with the latest International Guidelines on AF in given study period, if total follow-up lasted at least 5 years or until death. Patients with acute causes of AF, or advanced heart or any other disease were excluded. Results: study population consisted of 1100 pts with mean follow-up of 9.9±6.0yrs. Clinical characteristic of pts are shown in Table. Multivariate Cox proportional hazard regression analysis with independent variables from Table identified tachyaf during follow-up (HR 6.9, 95%CI: , p<0.0001) and male gender (HR 4.2, 95%CI: , p ) to have significant relationship with the development of TCMP even after adjustment for numerous covariates. Variable Total 1100 TCMP 32 (2.9) Non TCMP 1068 (97.1) P Age 52.7± ± ± Males 711 (64.6) 29 (90.6) 682 (63.9) Females 389 (35.1) 3 (9.4) 386 (36.1) Lone AF 442 (40.2) 14 (43.8) 428 (40.1) NS Hypertension 552 (50.2) 12 (37.5) 540 (50.6) NS Coronary disease 53 (4.8) 0 (0.0) 53 (5.0) NS Diabetes mellitus 76 (6.9) 1 (3.1) 75 (7.0) NS Paroxysmal AF 665 (60.5) 16 (50.0) 649 (60.8) NS Persistent AF 225 (20.5) 11 (34.4) 214 (20.0) NS Permanent AF 210 (19.1) 5 (15.6) 205 (19.1) NS Asymptomatic AF 130 (11.8) 2 (6.3) 128 (12.0) NS Transition to permanent AF 321/890 (36.1) 18 (66.7) 303 (35.1) TachyAF at presentation 930 (84.5) 32 (100.0) 898 (84.1) TachyAF during follow-up 657 (59.7) 25 (78.2) 632 (59.2) <0.001 Conclusions: frequency control in patients with AF is obligatory. Men with AF are at increased risk of TCMP as compared to women. P2434 Atrial resynchronisation therapy can be used to treat paroxysmal atrial fibrillation in the modern treatment era in patients with prolonged inter-atrial conduction R. Sankaranarayanan 1, M.A. James 2, H. Gonna 3, S. Burtchaell 2, R. Holloway 2. 1 Blackpool Victoria Hospital, Blackpool, United Kingdom; 2 Taunton Hospital, Taunton, United Kingdom; 3 Worthing Hospital, Worthing, United Kingdom Introduction: Prolonged inter-atrial conduction has been proposed to initiate and perpetuate paroxysmal atrial fibrillation (PAF).We conducted this study to compare the long term outcome of atrial resynchronization with bi-atrial pacemaker (BiP) implantation in patients with and without inter-atrial conduction delay in the modern ablation era. Methods: Patients who were refractory to atleast 3 anti-arrhythmic drugs and remained sufficiently symptomatic, were treated with a bi-atrial pacemaker to manage paroxysmal AF. 31 patients received a BiP between 1999 to 2006 (mean duration from AF diagnosis 59±14 months). P wave duration was assessed from the surface ECG. 14 patients had a P wave duration of <0.12 (Group 1) seconds and 17 patients had a P wave duration of 0.12 seconds (Group 2). During the evaluation period (mean of 3±2 years), we compared these 2 groups with respect to symptoms, AF duration, AF admissions and anti-arrhythmic drugs for an equal duration pre and post-procedure. Results: Symptomatic improvement was seen in 8/14 (57%) of Group 1 (P wave duration <0.12 seconds) compared to 16/17 (94%) of Group 2 (P wave

112 412 Atrial fibrillation. Special issues Tabulated results Group 1 Group 2 (P wave duration < 0.12sec) (P wave duration 0.12s) N=14 N=17 AF duration (days/month) Before BiP -19.5±5.4 (SD 8.75) Before -23.2±4.1 (SD 8.4) After BiP- 12.8±5.4 (SD 10.8) After 3.5±4.1 (SD 8.2) p=0.08 p<0.001 Mean number of admissions Before BiP- 3.36±1.84 (SD 4.46) Before-2.06±0.7 (SD 1.85) After BiP 1.43±1.84 (SD 1.55) After 0.53±0.7 (SD 0.71) p=0.14 p=0.003 Mean number of anti- Before BiP -3.64±0.76 (SD 1.64) Before -3.35±0.55 (SD 1.37) arrhythmic drugs After BiP 2.6±0.76 (SD 1.03) After 1.41±0.55 (SD 0.8) p=0.12 p<0.001 Mean number of cardio- Before BiP- 1.29±1.34 (SD 3.22) Before -0.94±0.44 (SD 1.2) versions After Bip 0.93±1.34 (SD 1.27) After 0.18±0.44 (SD 0.39) p=0.7 p=0.12 duration 0.12 seconds) (p=0.01). As shown in the table significant reduction was seen in Group 2 in AF duration, AF admissions and anti-arrhythmic drug usage post-bi-atrial pacemaker implant whereas in Group 1 while there were reductions in the same these were not significant. The mean number of cardioversions was significantly reduced in Group 2 post-bip, however this did not reach statistical significance. Conclusions: Our study has shown that atrial resynchronisation therapy is effective in treating paroxysmal atrial fibrillation in patients with prolonged inter-atrial conduction on surface ECG (P wave duration 0.12 seconds). This strategy can therefore be considered to treat these patients if they don t qualify for left atrial ablation strategy. P2435 Evaluation of prognostic echocardiographic predictors of success of pulmonary vein isolation for treatment of atrial fibrillation E. Wellnhofer, T. Kim, C.H. Kriatselis, J.-H. Gerds-Li, E. Fleck, M. Graefe. Deutsches Herzzentrum Berlin, Berlin, Germany Purpose: Pulmonary vein isolation (PVI)is a recent approach to treat chronic atrial fibrillation (AF). We evaluated the predictive value of echocardiographic parameters sampled before PVI. Methods: In 80 consecutive patients undergoing PVI for treatment of AF (30 f, mean age 59±9.8 (30-75) years) trans-thoracic echocardiograms (including tissue Doppler in 4- and in 2-chamber view) were acquired by a Philips IE33 machine immediately prior to PVI (N=80, baseline). Rhythm was monitored at 1 month (N=49, FU1), 3 months (N=45, FU2) and 6 months (N=22,FU3) after PVI. A t-test was between groups with (R) and without (O) recurrent AF was used to select parameters eligible for further analysis by principal component analysis, cluster analysis, linear discriminant modelling and binary logistic regression. Results: In 42/80 patients transient sinus rhythm was present at baseline. AF recurred in 29/61 patients (30%) with follow-up after PVI. There were no significant group differences concerning age or sex. Patients with transient sinus rhythm at baseline had a significantly better prognosis (χ 2 =20, p<0,001 Wilcoxontest). The subsequent echocardiographic parameters turned out to be significantly (p<0.05) different between groups: M-mode end-diastolic LA-diameter (O: 3.8±0,6 cm, R: 4.2±0,6 cm), E-wave (O: 81±19 cm/s, R: 97±19 cm/s), E- deceleration time (O: 204±59 ms, R: 165±48 ms), S-wave of tissue Doppler of septal wall (O: 7.2±1.5 cm/s, R: 6.0±1.1cm/s) and of lateral wall (O: 9.5±2.8 cm/s, R: 7.5±1.8 cm/s) (4-chamber). Principal component analysis with these parameters suggests that 78% of variance are explained by three factors (factor 1: left ventricular function, factor 2: residual left atrial function, factor 3: remodelling). In cluster analysis the best separators of centres were transient sinus rhythm during echocardiography, M-mode end-diastolic LA-diameter, E-deceleration time and S-wave of tissue Doppler of septal wall. Discriminant analysis with the 4 parameters providing maximal group separation in cluster analysis allowed a 74% correct prediction of recurrence of AF. Only transient sinus rhythm during echocardiography, M-mode end-diastolic LA-diameter, and S-wave of tissue Doppler of septal wall were parameters with significant Wald statistics in binary logistic regression providing a 78% correct classification. Conclusion: Left ventricular function, residual left atrial function, and preserved atrial geometry are predictors of successful PVI. Echocardiography immediately prior to PVI should include a tissue Doppler in the 4-chamber view. P2436 Endothelial dysfunction is a risk factor for thromboembolism in atrial fibrillation H.W. Park, J.S. Koh, N.S. Yoon, Y.J. Hong, J.H. Kim, Y.K. Ahn, M.H. Jeong, J.G. Cho, J.C. Park, J.C. Kang. Chonnam National University Hospital, Gwangju, Korea, Republic of Objectives: It is well known that old age, mitral stenosis, hypertension, diabetes, prosthetic valve, prior history of thromboembolism, left ventricular dysfunction are risk factors for thromboembolism in atrial fibrillation. Even though there are some reports about endothelial dysfunction is related thromboembolic risks, it is not clear whether markers of endothelial dysfunction are useful to predict future development of thromboembolism. This study was done to verify the role of markers of endothelial dysfunction to predict thromboembolism. Methods: This study recruited 193 atrial fibrillation patients who were observed for more than 6 months without history of thromboembolism at baseline state. We divided them into 2 groups, group I (M:F = 16:10, 61±11 years) in whom thromboembolism developed, group II (M:F=98:69, 62±11 years) in whom thromboembolism did not develop. Echocardiography was done before enroll and serum markers for endothelial function, inflammation, platelet activity were evaluated at fasting state in the morning at baseline state. Anthrombotic treatment was done according to ACC/AHA guideline in both groups. Results: Mean follow up period was 32±9 months. The prevalence of hypertension, diabetes, mitral valve disease, dilated cardiomyopathy except for coronary artery disease (30.8% vs. 14.4%, p=0.045) was not different between the 2 groups. Numbers of used antiarrhythmic agents, use of ACEI, ARB, aspirin or warfarin, NYHA class, duration of atrial fibrillation were not different. Left atrial and ventricular end-diastolic and -systolic dimension were larger in group I than in group II but ejection fraction was not different. Levels of markers for inflammation (quantitative and high sensitive CRP, ESR, IL-6), platelet activity (p-selectin), coagulation abnormality (fibrinogen, FDP, d-dimer) were not different but marker of endothelial function (von Willebrand factor) was significantly higher (126±37 vs 103±42%, p=0.011) in group I than in group II. Conclusions: Endothelial dysfunction is considered a new risk factor for thromboembolism in atrial fibrillation and improvement of endothelial function may be beneficial in reducing thromboembolic risk. P2437 Management of patients with implantable cardioverter defibrillators and atrial fibrillation by using medtronic carelink network - remote monitoring system K. Thudt 1,C.H.Wollmann 1, S. Rhabek 2,P.Vock 1,H.Mayr 1. 1 Landesklinikum St.Poelten, St. Poelten, Austria; 2 Medtronic, Vienna, Austria Purpose: Atrial fibrilation (AF) has been shown to be an independent risk factor of mortality in patients with heart failure. In patients with symptomatic heart failure and an implantable defibrillator (ICD), the new remote monitoring system Care- Link Network (Medtronic Inc., USA) seems to be a reliable tool for early detection and treament of AF. Methods: To assess new onset AF we analyzed all remote follow-ups (FU) performed between september 2007 and january 2009 of patients implanted with an ICD capable of wireless remote monitoring within the Medtronic CareLink Network. New onset of AF was recognized due automatic alerts send by the remote monitoring system. In patients with paroxysmal AF the concomitant antiarrhythmic medication has been changed, whereas patients with persistent AF were admitted for electrical cardioversion. Values are expressed as mean ± SD. Results: Ninety-six ICD patients (pts) had ICDs capable of remote monitoring. 42 (44%) pts suffered from CAD, 45 (47%) from dilated cardiomyopathy, 9 (9%) from other cardiac diseases. Mean age was 67±11 years, 79 (82%) pts were male. Concomitant antiarrhythmic drugs were class III agents in 18 (19%) pts, betablockers in 88 (92%) pts. 88 (92%) pts had ACE inhibitors and/or ARB in their medication. Fifty-three 53 (55%)pts had oral anticoagulation with warfarine. During the observation periode 14 pts (15%) had remote alerts due to detection of AF (5 pts. with AF duration > 6h, in 9 pts persistent). Nine pts with persistent AF were evaluated for electrical cardioversion. One pt suffered from inappropriate shock due to fast conducted AF, but the inappropriate shocks treated AF successfully. Six pts were treated with external electrical cardioversion, 5 of them successfully. One pt had contraindication for oral anticoagulation, in one pt oral anticoagulation has been started. In 12 pts the concomitant antiarrhythmic medication has been changed. Conclusion: Remote monitoring with CareLink seems to be a reliable tool for the management of patients with an ICD and new onset atrial fibrillation. Early recognition of AF may help reducing adverse cerebrovascular events or worsening of pre-existing heart failure in pts with an ICD. P2438 Is outpatient bleeding risk index useful in patients on vitamin K antagonists undergoing PCI - The AFCAS trial H. Lahtela 1, A. Schlitt 2,M.Niemela 3, A. Ylitalo 4, P. Kirchhof 5, S. Vikman 6, J. Valencia 7, M. Puurunen 8, A. Rubboli 9, K.E.J. Airaksinen 1 on behalf of AFCAS. 1 Turku University Hospital, Turku, Finland; 2 Martin-Luther-Universitaet Halle, Halle, Germany; 3 Oulu University Hospital, Oulu, Finland; 4 Satakunta Central Hospital, Pori, Finland; 5 Universitaet Muenster, Munster, Germany; 6 Tampere University Hospital, Tampere, Finland; 7 Hospital General Universitario de Alicante, Alicante, Spain; 8 Helsinki University Hospital, Helsinki, Finland; 9 Univ. di Bologna - Istituto di Cardiology, Bologna, Italy Purpose: The optimal management of patients on long-term vitamin K antagonist (VKA) therapy undergoing PCI is not known. Outpatient Bleeding Risk Index (BRI) is useful in evaluating bleeding risk during VKA, but its value to guide therapies and predict bleeding events during PCI is obscure. Methods: These issues were studied in a prospective multicenter European registry (AFCAS trial) gathering data on treatment and outcome of patients with atrial

113 Atrial fibrillation. Special issues 413 fibrillation undergoing coronary stenting. In this interim analysis, we calculated BRI in the first 362 patients. Results: High ( 3) BRI representing elevated bleeding risk in 112 (31%) patients with no difference in the admission medications between the groups (Table). High BRI did not limit the use of periprocedural antithrombotic medications, but gastric protection (PPI) was more common in patients with high BRI, while radial route tended to be less often used (12% vs 22%, p = 0.05). High BRI did not guide antithrombotic treatment at discharge and did not predict in-hospital bleeding events or major adverse cardiac and cerebral events (MACCE) (Table). Medications and events BRI 3 BRI <3 Periprocedural medication LMWH or fondaparinux 73 (68%)* 131 (56%) GP blockers 32 (29%) 54 (22%) Discharge medication VKA 56 (55%) 151 (66%) Clopidogrel 102 (97%) 231 (97%) Aspirin 89 (85%) 197 (84%) Triple therapy 36 (39%) 94 (45%) PPI 45 (42%)** 64 (26%) In-hospital events Major bleeding 3 (3%) 3 (1%) Non-major bleeding 9 (8%) 15 (6%) MACCE 5 (5%) 5 (2%) LMWH = low-molecular-weight heparin, GP = glycoprotein, *p<0.05, **p<0.01. Conclusions: BRI had minimal effect on management during PCI in this large European registry and did not predict in-hospital bleeding events. These observations suggest that peri-interventional bleeding may have other causes than bleeding events on long-term VKA. P2439 The efficacy and the safety of long-term vitamin K antagonists therapy: the genetic predictors of bleedings Y.A. Mikheeva 1, E.S. Kropacheva 1, D.A. Sychev 2, A.B. Dobrovolsky 1, E.P. Panchenko 1. 1 Cardiology Research Centre, Moscow, Russian Federation; 2 Moscow Medical Academy, Moscow, Russian Federation Purpose: To estimate the efficacy and safety of long-term Vitamin K antagonists (VKA) therapy in patients with non-valvular atrial fibrillation (NVAF), and to determine the influence of CYP2C9 and VKORC1 genetic polymorphisms on bleedings during warfarin (W) therapy. Methods: Patients with NVAF (n=122, aged 60,7±8,9 (SD), M/F-86/36, mean CHADS2 score 1,7±1,3 (SD) were recruited from inpatients attending Cardiology Research Centre from 1998 till 2002 years. Clinical examinations and INR control were undertaken monthly. The observation period was 5 years. The frequency of stroke, transient ischemic attack (TIA), systemic embolism, pulmonary embolism, death, bleeding was analysed. Allelic variants of CYP2C9, VKORC1 (G3673A) were identified by polymerase chain reaction. Results: During 5 year VKA therapy 83% of pts were in target INR (2,0-3,0). Annual rate of ischemic stroke (IS) was 2,6% (1.2% in patients without and 2% in patients with prior IS). Only 25% of IS occurred at the therapeutic INR level. According to brain imaging (CT/MRI) 77% of IS had cardioembolic nature. Risk factors associated with thrombotic end points (IS/TIA, cardiovascular death, acute coronary syndrome) according to multivariate analysis were: age, female, ejection fraction 45%, CHADS2 score 3, heart Failure II-III class (NYHA), baseline INR 1,07. The annual rate of hemorrhage was 12,6% (major- 1,6%). Almost half of all bleedings (49%) happened during the 1-st year of AVK therapy. 63% of major and 44% of minor bleedings occurred at therapeutic INR levels. Risk factors of bleedings were: female, coronary artery disease, average INR>2,5 during study period, VKORC1 AA and/or CYP2C9*3 carriage. All carriers of combined polymorphisms (VKORC1+CYP2C9) had overanticoagulation events (INR>3), and most of them (67%) had episodes of bleeding. Conclusions: The efficacy of VKA therapy in patients with NVAF depends on stability of INR level. The carriage of VKORC1 AA, CYP2C9*3 increases the bleeding risk during W therapy. P2440 A critical pathway for electrical cardioversion for atrial fibrillation as a vehicle to get to the guidelines E.G. Zwaan, V.A. Umans, G. Kimman. Medical Center Alkmaar, Alkmaar, Netherlands Background: The methodology of critical pathways is known for its ability to expedite patient care and to better comply with the guidelines. We developed a digital critical pathway with full integration of nursing and physician documents. Method: Both nurses and physicians were guided through the clinical process. Special attention is paid to the recommendation of the guidelines and to a variance analysis in case of a deviance from the pathway/guideline. The efficacy endpoints were: CHAD-score, adequate INR, patient satisfaction and walk-through time. The outcome was compared with the control group of 100 consecutive patients who were treated in the preceding 12 weeks. Results: From , all 550 consecutive patients who electively underwent a cardioversion for atrial fibrillation were managed according to this pathway. The Results Control Critical pathway p-value Quality % CHAD score % Medication advice % Cardioversion success % Letter to fam physician Variance % Inadequate INR % No bed Walk-through time (weeks) table summarizes the improvement in quality and variance indicators. Part of the pathway was the introduction of a nurse out-patient clinic which reduced the waiting time to scheduled visits with 3 weeks and allowed us to improve patient knowledge on their disease management. Overall patient satisfaction increased from 86% to 91% (p<0.01). Conclusion: critical pathways improve standard of care and facilitate medical teams to comply with the guidelines. Physicians and nurses prevent duplication and spent more time to disease management information. Such personalized care improves patient satisfaction. P2441 Dominant frequency of atrial fibrillation correlates poorly with atrial fibrillation cycle length A. Elvan 1, A.C. Linnenbank 2,M.W.VanBemmel 1, W.P. Beukema 1, P.P.H.M. Delnoy 1, A.R. Ramdat Misier 1, J.M.T. De Bakker 2. 1 Isala Klinieken, Zwolle, Netherlands; 2 Academic Medical Center, Amsterdam, Netherlands Purpose: Localized sites of high frequency during atrial fibrillation (AF) are used as target sites to eliminate AF. Spectral analysis is used experimentally to determine these sites. Purpose of this study was to compare dominant frequencies (DF) with AF cycle length (AFCL) of unipolar and bipolar recordings. Methods: Left (LA) and right atrial (RA) endocardial electrograms were recorded during AF in 40 patients with lone AF, using two 20 polar catheters. Mean age was 53±9.9 years. Unipolar and bipolar electrograms were recorded simultaneously during 16s at 2 RA and 4 LA sites. AFCLs and DFs were determined. QRS subtraction was performed in unipolar signals. DFs were compared with mean, median and mode of AFCLs. Results: 4800 unipolar and 2400 bipolar electrograms were analysed. Linear correlation was poor for all spectral analysis protocols. Best correlation was accomplished with DFs from unipolar electrograms compared to median AFCL. (R2 = 0.54). A gradient in median AFCL of >25% was detected in 24/40 patients. Shortest median AFCL was located in 20/24 patients at LA (posterior in 10 patients). The site with median AFCL and highest DF corresponded in 25% if unipolar, and in 31% if bipolar electrograms were analysed. Conclusions: DFs from unipolar and bipolar electrograms recorded during AF correlated poorly with mean, median and mode AFCL. If a frequency gradient > 25% existed, the site with highest DF corresponded to the site of shortest median AFCL in only 30% of patients. Since spectral analysis is being used to identify ablation sites, these data may have important clinical implications. P2442 Predictors of normal left atrial appendage flow velocity profile one week after cardioversion of non-valvular atrial fibrillation A. Palinkas 1, A. Pizzuti 2, E. Antonielli 3, E. Nagy 1, B. Doronzo 2, A. Varga 4, T. Forster 4,E.Picano 5. 1 Elisabeth University Hospital, Hódmezovásárhely, Hungary; 2 I. Umberto Hospital, Torino, Italy; 3 Ss. Annunziata Hospital, Savigliano, Italy; 4 University of Sciences, Szeged, Hungary; 5 CNR, Institue of Clinical Physiology, Pisa, Italy Background: Mechanical dysfunction of the left atrial appendage (LAA) after successful cardioversion (CV) of non-valvular atrial fibrillation (AF) is a well known phenomenon. However, determinants and factors influencing this process have not been fully elucidated. These data would be helpful to gain insights into the required duration and mode of anticoagulant therapy in the post-cv period. Purpose: to evaluate the clinical and echocardiographic predictors of presence of normal LAA flow velocity profile one week after successful restoration of sinus rhythm (SR) in patients with non-valvular AF. Patients and method: clinical, transthoracic and transesophageal echocardiographic (TEE) data were measured immediately before and 1 week after successful CV in 87 patients (mean age: 67.6±9.4 years, 50 males) with non-valvular AF. The post-cv LAA flow profile was considered normal if the telediastolic LAA peak emptying flow velocity (LAAPEV) assessed by TEE guided pulsed Doppler echocardiography exceeded 40 cm/sec. Results: LAAPEV was > 40 cm/sec one week after successful CV in 65 (75%) patients. On multivariate logistic regression analysis, only the pre-cv LAAPEV > 30 cm/sec predicted (p =0.0014, Chi-square: 10.2, OR = 23.2, CI 95%= ) the normal LAA flow velocity one week after CV, outperforming other univariate predictors such as AF duration 2 weeks, left atrial parasternal diameter < 45 mm, absence of left atrial spontaneous echo contrast before CV, male sex and age 65 years. The area under-the ROC curve for pre-cv LAAPEV predict-

114 414 Atrial fibrillation. Special issues ing normal post-cv LAA flow profile (0.84, CI 95%: ) was significantly higher than that for LA parasternal diameter (0.66, CI 95%: , p < 0.05), age (0.63, CI 95%: , p<0.01) and duration of atrial fibrillation (0.61, CI 95%: , p<0.001). The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of the pre-cv LAAPEV > 30 cm/s for assessing the normal LAA flow velocity profile one week after CV were 73.8% (CI 95% = 63.2 to 84.5%), 90.9% (CI 95% = 78.9 to 100%), 96% (CI 95% = 90.6 to 100%), 54.1% (CI 95% = 38 to 70.1%) and 78.2% (CI 95% = 69.5 to 86.8%), respectively. Conclusion: LAA flow velocity pattern determined by TEE before CV has an independent value in predicting normal LAA flow velocity profile 1 week after successful CV of non-valvular AF. P2443 Surface electrocardiogram predicts successful cardioversion of atrial fibrillation C.X. Wong, M.K. Stiles, P. Kuklik, A.G. Brooks, B. John, D.H. Lau, H. Dimitri, S.R. Willoughby, G.D. Young, P. Sanders. Cardiovascular Research Centre, Royal Adelaide Hospital and the University of Adelaide, Adelaide, Australia Purpose: Electrical cardioversion is a frequently used modality to achieve sinus rhythm from atrial fibrillation (AF). We have previously shown that slower AF activity is associated with cardioversion success. Whether successful cardioversion can be predicted noninvasively from the surface electrocardiogram immediately prior to cardioversion, however, is not known. Methods: One-hundred and twenty-five patients (55±11 years, 90 male) undergoing cardioversion were studied. Dominant fibrillatory frequencies were determined from lead VI using spatiotemporal QRST cancellation and time-frequency analysis. AF cycle length and dominant frequency were also determined from intracardiac catheters within the coronary sinus. Results: A total of 218 cardioversions were performed. Of these, 171 (78%) were successful and 47 (22%) were unsuccessful in terminating AF to sinus rhythm. Cases where AF terminated with cardioversion had a lower dominant frequency in V1 (4.21±0.96 versus 4.91±1.39 Hz, p=0.001) and in the coronary sinus (4.77±1.01 vs 5.21±0.91 Hz, p=0.009) compared to those that did not terminate. Dominant frequencies in lead V1 correlated with dominant frequency in the coronary sinus (r=0.348, P<0.001). By receiver operating characteristic curve analysis, successful cardioversion be predicted by V1 dominant frequency, coronary sinus dominant frequency and coronary sinus AF cycle length (see table). Lead V1 Coronary Sinus Lead Coronary Sinus AF Dominant Frequency Dominant Frequency Cycle Length Cut Off <4.2 Hz <4.9 Hz >200 ms Sensitivity 46% 44% 56% Specificity 34% 36% 68% Conclusions: Successful cardioversion of AF can be predicted by lower dominant frequencies in the surface electrocardiogram with comparable efficacy to intracardiac recordings. This may allow for the noninvasive identification of patients likely to have successful electrical cardioversion of AF. P2444 Differences in clinical and echocardiographical parameters between paroxysmal and persistent atrial flutter in the AURUM 8 study: identification of factors perpetuating the arrhythmia? L. Lickfett 1, E.L. Mittmann-Braun 1, J. Holzmann 2, W. Bauer 3, C. Weiss 4,C.Mewis 5, S. Spencker 6, W. Jung 7,W.Haverkamp 8,T.Lewalter 1 on behalf of AURUM 8. 1 Universitaetsklinikum Bonn, Bonn, Germany; 2 Biotronik, Berlin, Germany; 3 Medizinische Universitaetsklinik Wuerzburg, Wurzburg, Germany; 4 Klinikum der Universitaet Mainz, Mainz, Germany; 5 Universitaetsklinikum der Saarlandes, Homburg, Germany; 6 Charite - Campus Benjamin Franklin, Berlin, Germany; 7 Schwarzwald-Baar Klinikum Villingen GmbH, Villingen-Schwenningen, Germany; 8 Charite - Campus Virchow-Klinikum, Berlin, Germany Introduction: Cavotricuspid isthmus dependent atrial flutter (AFL) represents one of the most common arrhythmias in clinical practice. It is unclear why some patients (pt) exhibit a paroxysmal and others a persistent AFL pattern. Goal of the current study was to search for circumstances associated with persistence of the arrhythmia. Clinical, echocardiographical, procedural and outcome data of the AURUM 8 Study were used to compare patients with both temporal pattern. Methods: The AURUM 8 study is a randomized, multicenter trial comparing the efficacy and safety of gold tip versus platinum tip ablation of typical AFL. 462 pt were included in the trial. 20 pt experienced both paroxysmal and persistent AFL and were excluded from the analysis. 226 pt had paroxysmal and 216 persistent AFL. Data from the trial s database were used for comparison of both groups, using the appropriate statistical test (Kolmogorov-Smirnov-Test, T-Test, Mann-Whitney-Test, Chi-Quadrat-Test). Results: At baseline, pt with persistent AFL had higher NYHA class (1.42 vs 1.17, p<0.01), shorter AFL history (1.1 vs 1.7 year, p<0.05), lower prevalence of palpitation history (74 vs 81%, p<0.001) and higher prevalence of dyspnoea history (77 vs 63%, p<0.05), cardiac disease history (75 vs 66%, p<0.05) as well as previous coronary bypass surgery (17 vs 9%, p<0.05). On echocardiography at baseline, pt with persistent AFL had higher incidence of tricuspid (40 vs 30%, p<0.05) and mitral valve regurgitation (51 vs 45%, p<0.01) as well as measurable pulmonary artery hypertension (17 vs 9%, p<0.05). Ablation procedure parameters and follow-up results were not significantly different between both groups. Conclusion: Pt with persistent AFL exhibit important differences in respect to clinical and echocardiographical parameters compared to pt with paroxysmal AFL. These parameters indicate a more advanced morphological and functional substrate resulting in persistence rather than spontaneous termination of the arrhythmia. P2446 Changes of cytokine concentration after successfull thoracoscopic ablation of atrial fibrillation P. Osmancik, Z. Peroutka, D. Herman, P. Stros, P. Budera, Z. Straka. Cardiocenter, 3rd Medical faculty, Charles University Hospital, Prague, Czech Republic Background: Atrial fibrillation (AF) is accompanied by the elevation of proinflammatory markers, such as C-reactive protein (CRP), interleukin-6 (IL-6), anti-inflamamtory cytokines (interleukin-10, IL-10) or markers of platelet activity (CD40 ligand or soluble P-selectin). Epicardial thoracoscopic isolation of pulmonary veins presents new approach for the treatment of atrial fibrillation. The aim of present study was to establish, whether successful epicardial ablation of atrial fibrilation leads to decrease of inflammatory cytokines. Methods: Twenty-two patients with high symptomatic paroxysmal or peristant atrial fibrillation were prospectivelly studied. All of them underwent epicardial isolation of pulmonary veins. Out-patient control with 48h Holter monitoring and blood sampling were done before surgery and 1m, 3m and 6m after surgery. The success of the ablation was assesed clinically and by three 48hour Holter recordings. Serum concentration of interleukin-6, interleukin-10, CRP, CD40L and P-selectin were measured by ELISA. Results: AF was successfully ablated in 15 patients, in the remaining 7 pts. AF reoccured during follow-up. Both groups did not differ with respect from age, gender, ejection fraction of left ventricle and duration of AF and preoperative concentration of measured molecules. While CRP decreased in successfully ablated patients ( vs ), there was no change of CRP concentration in patients on AF during follow-up ( vs ). Similarly, we found no changes in concentrations of IL-6, IL-10, CD40 L or P-selectin before and 6m after surgery neither in successfully nor in unsuccessfully ablated patients. Conclusion: The ablation of AF by epicardial thoracoscopis approach is associated with decreese of CRP, but not other inflammatory molecules. The markers of platelet activity remain unchanged after the restoriation of sinus rhythm. P2447 Wide area circumferential ablation for pulmonary vein isolation in patients with atrial fibrillation and pulmonary vein stenosis G.M. Nair, L. Armaganijan, A. Venancio, M. Hussein, S. Divakaramenon, S.C. Ribas, J.S. Healey, S.J. Connolly, C.A. Morillo. McMaster University, Hamilton, Canada Introduction: Pulmonary vein stenosis (PVS) isa complication of pulmonary vein isolation (PVI)for atrial fibrillation (AF).The incidence varies from 5%-20% in published literature. PVS can be asymptomatic and may not be diagnosed unless the pulmonary veins are imaged post ablation. PVS results from ablations performed in and around pulmonary vein ostia. Refinements in mapping and ablation techniques for preventing PVS during PVI include- use of non-fluoroscopic mapping systems, CT and MRI image integration and wide area circumferential antral ablation (WACA). Methods: A retrospective analysis of WACA procedures at our institution over the past three years was performed. Patients had post procedure contrast enhanced CT scan (CECT) or MRI scans to rule out PVS. Imaging to detect PVS was performed between 3 and 6 months post procedure. PVS was diagnosed if greater than 25% luminal stenosis was documented. Significant PVS was defined as- greater than 80% luminal stenosis or any degree of stenosis associated with symptoms (dyspnea, hemoptysis) and pulmonary perfusion defects on imaging. Results: 205 WACA procedures were performed over the study period. 188 (91%) patients had post procedure imaging to rule out PVS and were included in the analysis. All WACA procedures were performed with the aid of nonfluoroscopic mapping systems and CT or MRI image integration was performed in 71 (38%) patients. Cardiac imaging was performed using standard institutional protocol. All images were made available for analysis and pulmonary vein ostial size was reported in two orthogonal planes. None of the patients had any symptoms suggestive of PVS. A total of 749 pulmonary veins were imaged (3 patients had common trunks- 2 left sided and 1 right sided). None of the patients had evidence of PVS. Pre and post PVI pulmonary vein dimensions were available for 158 patients. 17 patients (9%) did not have post procedure imaging. None of these patients had any symptoms suggestive of PVS. Conclusions: WACA procedure for PVI, assisted by non-fluoroscopic mapping and image integration, was not associated with PVS in our series of patients. This technique is possibly a safer alternative to pulmonary vein ostial ablation for preventing PVS.

115 Atrial fibrillation. Special issues 415 P2448 Management of pericardial effusion during and after ablation for atrial fibrillation in patients on Coumadin therapy L. Di Biase 1, J.D. Burkhardt 2,R.Horton 2, J. Sanchez 2, G. Gallinghouse 2, P. Mohanty 2, D. Patel 2,W.Lewis 3, S. Beheiry 4, A. Natale 4. 1 Texas Cardiac Arrhythmia Institute at St David Medical Center, Un. of Texas and University of Foggia, Austin, United States of America; 2 Texas Cardiac Arrhythmia Institute at St David Medical Center, Austin, United States of America; 3 Metro Health Hospital, Cleveland, United States of America; 4 Sutter Pacific Hospital, San Francisco, United States of America Introduction: Pericardial effusion is a well known complication during and after catheter ablation of atrial fibrillation. The percentage reported in the literature is around 1.2%. The aim of this study is to evaluate the management of pericardial effusion in patients undergoing ablation of AF while on therapeutic coumadin. Methods: 2118 pts undergoing catheter ablation of atrial fibrillation on Coumadin at four different centers have been enrolled in this study. Periprocedural pericardial effusions have been prospectively collected in a data base. Results: A total of 9 pericardial effusions (0.4%) were reported. 5 were documented during the procedure and 4 occurred 1 to 4 weeks after the procedure. None of the patients with periprocedural effusion required surgery. In 3 of the 5 periprocedural cases fresh frozen plasma was given (2-4 units). In one patient a post procedural pericardial effusion resolved by reducing the Coumadin dosage and target INR from 3.5 to 2.0. In two patients, percutaneous pericardial tap was performed while on Coumadin. One patient was treated with a pericardial window after Coumadin was withdrawn and experienced a stroke. Conclusions: Pericardial effusion, although a potentially dangerous complication of catheter ablation of atrialfibrillation, is rare and does not appear to be increased by the continuation of Coumadin therapy. Once it does occur even in patients on Coumadin, it can be treated with conservative therapy in most patients. P2449 Longterm outcome in patients after cardioversion for persisting atrial fibrillation: prognostic value of clinical - and laboratory parameters and drug therapy W. Rademacher, A. Lauten, J. Schumm, D. Prochnau, R. Surber, H.R. Figulla. Universitaetsklinikum Jena, Jena, Germany Background: Predicting longterm rhythm stability after elective cardioversion is difficult. There are few predictors as N-terminal-ProBNP and CRP with established validity only in subgroups of patients with atrial fibrillation (AF). The purpose of this prospective study was to evaluate the prognostic value of NT-pro-BNP and echocardiographic parameters and the impact of optimized drug therapy on recurrence of AF in the average, unselected patient population of a large community hospital. Methods: Fifty three patients (Median age 68 years, 22 female) with permanent AF were included in this study. Complete diagnostic work-up including all relevant clinical-, laboratory-, echo- and electrocardiographic parameters was performed upon hospital admission. Cardioversion was performed according to standard protocoll and drug therapy was optimized with regard to current guidelines. Follow-up (f/u) visits were scheduled on days 1, 7 and 31 with 24h-ECG-recording and evaluation of patients drug compliance. After discharge f/u was aquired by telefone interview and ambulantory ECG-recording. Follow-up was 100%complete with a mean f/u period of 6 month. Results: Cardioversion was primarily successful in 94% of all patients. Recurrence of AF was documented in 68% of patients (n=40) during the follow-up period. Relapse of atrial fibrillation occurred on the first day in 17% (n=10), during the first week in 18% (n=11), during the first month in 14% and in 12% thereafter. Patients older than 70 years, with valvular heart disease, LAD > 45 mm and >1 preceding cardioversion had significantly more often recurrence of AF. Betablockers and/or amiodarone significantly decreased the risk of AF relapse, however administration of ACE-inhibitors or diuretics where without influence. Neither routine laboratory parameters nor NT-pro-BNP or CRP had a predictive value in this study population. Conclusion: In this prospective study recurrence of AF occurred in the majority of patients after elective cardioversion. None of the laboratory parameters was able to predict AF in this study population. Patients on optimized drug therapy with β-blockers had a lower risk of AF recurrence, however no benefit of ACE- Inhibitors was observed. As the long-term effect of elective cardioversion is low, this treatment option should be considered only once and only in younger patients with normal LV-Function without structural heart disease. P2450 Long term efficacy of catheter ablation for atrial fibrillation R. Hunter, T.J. Berriman, G. Thomas, L. Richmond, V. Baker, M. Dhinoja, D. Abrams, M.J. Earley, S. Sporton, R.J. Schilling. Barts and The London NHS Trust & QMUL, London, United Kingdom Purpose: Published long term follow up data for catheter ablation of AF is scarce. We present long term follow up of patients undergoing an identical AF ablation procedure. Methods: We began performing wide area circumferential ablation (WACA) with confirmation of electrical isolation in July Procedural outcomes and follow up were collected prospectively. We also attempted to contact all patients undergoing ablation up until March 2008 for an updated follow up. Patients were contacted by telephone to review symptoms, confirm complications, medications, and arrange an ECG through local doctors. Results: 469 procedures occurred in 286 patients. Mean age was 57±11 years, 74% male, 25% had structural heart disease and 55% paroxysmal AF. 149 patients had 1 procedure, 102 had 2, 25 had 3, 9 had 4, and 1 had 5 (mean 1.6 per patient). First time procedures took 240±89 min (201±58 paroxysmal v 287±98 persistent, p< 0.001), with fluoroscopy time of 52±31 min (47±33 v 59±27, p<0.01). Complications were: TIA/CVA in 0.7%, pericardial effusion in 2.4% (1.3% required drainage, surgically in one case), re-attendance with bruising or haematoma 16% (0.3% required transfusion), and clinically insignificant pulmonary vein stenosis in 0.9%. Median follow up from first procedure was 550 days (range days). Of the original 286 patients 3 had died and 10 could not be traced. Of the remaining 273 patients 198 had ECGs. 66% remained free from symptoms attributable to AF, 9% had minimal palpitations defined as less than 1 minute per week, 25% still had regular palpitations although improved symptomatically, 2% said they were unchanged, and 0.4% felt worse (97% improved or AF free). 82% were in sinus rhythm (90% paroxysmal, 71% persistent). 69% were no longer taking any antiarrhythmic drugs. For those that remained symptom free at 2 years, there was no further recurrence of AF. Conclusion: These data add to the small body of literature examining long term efficacy of catheter ablation of AF. This study shows that AF ablation is effective in the long term and that complications are low. Freedom from AF at 2 years predicts long term cure. P2451 Magnetic resonance imaging for acute and long-term identification of myocardial injury in patients undergoing pulmonary vein antrum isolation A.M. Sinha 1, N. Burgon 2, C. Mahnkopf 1,G.Ritscher 1,T.Haslam 2, T.J. Badger 2, M.P. Kunzelmann 1,M.Schmidt 1, N.F. Marrouche 2, J. Brachmann 1. 1 Klinikum Coburg, Coburg, Germany; 2 University of Utah, Salt Lake City, United States of America Background: Pulmonary vein antrum isolation (PVAI) is regarded as an effective therapy in patients with atrial fibrillation (AF). Extension and location of ablation lesions often remain unclear during the procedure. We report a new approach on visualization of myocardial injury using cardiac magnet resonance imaging (CMR) during PVAI procedures, and compared the results with long-term data. Methods: Patients who underwent PVAI, received CMR before, at the terminal phase of PVAI, and 13±3 weeks after PVAI. Delayed enhancement (DE) sequences were applied, and maximum intensity projections (MIP) obtained. Myocardial injury size was then measured on manually segmented 3D images by a computer algorithm using dynamic thresholding. Results: 20 patients (13 male, age 62±9 years) received CMR (Siemens Espree 1.5T, Germany) before, during and after the PVAI procedure. Using DE-CMR, the average lesion to healthy myocardium ratio was 15.3±7.2% during, and 15.7±6.4% long-term after PVAI. The figure shows an example of MIP of a DE- CMR scan in 2D (A-C) and 3D segmentation (D-F) in an anterior view pre (A,D), during (B, E), and long-term after PVAI (C, F). Myocardial injury is identifiable as white tissue around PV single ostia (full arrows) and common trunk (dashed arrows). MIP of DE-CMR in 2D and 3D segmentation Conclusion: CMR is feasible during and after ablation procedures, and allows identification of acute and long-term myocardial injury. Extension of scar tissues seemed to be stable during long-term follow-up. Therefore, this new CMR approach might support current ablation techniques, and thus might improve longterm success of PVAI.

116 416 Atrial fibrillation. Special issues / Implementable cardioverter-defibrillator Related issues P2452 Validation of voltage mapping criteria for catheter ablation of ischemic ventricular tachycardia by myocardial viability assessment using FDG PET J. Schreieck 1, K. Kettering 2, A.C. Schwegler 1,M.Reimold 3, H.J. Weig 1, R. Laszlo 1,S.Weretka 1,M.Gawaz 1. 1 Department of Cardiology, Medical University Tuebingen, Tuebingen, Germany; 2 Klinikum der Universitaet Mainz, Mainz, Germany; 3 Department of Nuclear Medicine, University of Tuebingen, Tuebingen, Germany Purpose: Most substrate-based catheter ablation strategies for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy based on the detection of areas of scar and border zones opposite to normal myocardium. Since the mapping criteria for identifying these areas have not been sufficiently validated so far, we have performed a comparison between electroanatomical bipolar voltage mapping and FDG PET studies. Methods: Seven patients with ischemic cardiomyopathy and repetitive VTs requiring catheter ablation were enrolled in this study. A FDG PET was performed prior to the ablation procedure and thereafter, a electroanatomical voltage mapping (CARTO, Biosense Webster) of the left ventricle was performed, followed by a substrate-based VT ablation. Finally, the FDG PET images and the bipolar voltage maps were compared in all patients. Results: The ablation procedure could eliminate 1-5 monomorphic VTs in each patient. At 1-year follow-up, 5 out of 7 patients (71.4%) remained free form any arrhythmia recurrence. In all patients, there were extensive areas of scar and adjacent low-voltage areas could be identified in the CARTO bipolar voltage maps. In areas commonly defined as dense scar (bipolar voltage amplitude <0.5 mv), the mean FDG uptake was 43.1% ± 18.2%. In the so-called low-voltage border zone the mean FDG uptake ranged between 49.5% ± 15.8% (bipolar voltage amplitude mv) and 60.1% ± 14.8% (bipolar voltage amplitude mv). In areas with so-called normal electrogram amplitudes the mean FDG uptake remained at 59.9±14.7% (voltage mv) and 61.2±11.2% (voltage >4.5 mv). Conclusions: The results of our study demonstrate that there is a significant amount of viable myocardium in the low-voltage border zones of scars frequently targeted as ablation sites for VTs. Furthermore, bipolar voltage mapping with standard ablation catheters have only modest ability to detect myocardial viability, since it does not sufficiently discriminate between partially scarred and normal myocardial wall areas in patients with ischemic cardiomyopathy. Therefore, substrate-based catheter ablation should be restricted to the minimum assumed to be necessary for succesful catheter ablation in order to avoid a further deterioration of the left ventricular function. IMPLEMENTABLE CARDIOVERTER-DEFIBRILLATOR RELATED ISSUES P2453 Early failure of sprint fidelis high-voltage implantable cardioverter-defibrillator lead. Our experience S. Rocha Costa 1, S. Almeida 1, R. Candeias 1,R.Gomes 1, J. Silva 1, J. Silva 2,D.Cavaco 1, V. Sanfins 2, P. Adragao 1, A. Silva 1. 1 CHLO - Santa Cruz Hospital, Lisbon, Portugal; 2 Alto Ave Hospital Center, Guimaraes, Portugal Purpose: On October 14th, 2007 Medtronic issued a recall for the sprint fidelis high-voltage lead wire because of its tendency to fracture, which can induce device failure and cause a patient to receive repeated and unnecessary shocks. Reports have been published highlighting a 3.3% number of lead malfunction. The aim of this study was to assess the actuarial survival of all sprint fidelis lead implanted at our centers. Methods: Patients who received an implantable cardioverter-defibrillator (ICD) with a sprint fidelis lead and followed up at our centers were evaluated. Those submitted to lead extraction were reviewed. Impedance and sensing information were acquired at routine clinic follow-up and, at the time of lead failure, sensing integrity counter and electrogram features were analyzed. Results: Between March 2005 and February 2009, 7 (4.37%) of 160 sprint fidelis leads followed up at our centers failed between 9 and 42 months after implantation (mean 32.81±14.2 months). Six patients received inappropriate shock therapy. Increased lead impedance was not apparent in the last routine follow-up visit in those patients. Interestingly, in two of them, the device had been reviewed some hours before the inappropriate shocks. In one patient, inappropriate shocks ultimately induced ventricular fibrillation. ICD tried but was unable to effectively treat the ventricular fibrillation due to ineffective shocks and finally to therapy exhaustion. Fortunately the patient was hospitalized and successfully treated with external defibrillation. In other circumstances the event would have been fatal. Conclusions: The sprint fidelis leads are prone to early failure and, at our centers, it has been increasing with time. Lead malfunction occurred in an unpredictable manner. No programming modification or increased follow-up visits can predict lead failure. Patients implanted with a sprint fidelis lead are at risk of serious adverse clinical events, including death. P2454 Ventricular pro-arrhythmic effect of chronic atrial fibrillation in patients with left ventricular dysfunction and implantable cardioverter-defibrillator S. Almeida, R. Gomes, S. Rocha, J. Silva, D. Cavaco, K. Santos, F. Morgado, P. Adragao, A. Silva. Centro Hospital Lisboa Ocidental - Hospital Sta Cruz, Lisboa, Portugal Background: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice and has been associated with increased mobility and mortality. It is known that AF can be responsible for inappropriate shocks in patients (pts) treated with implantable cardioverter-defibrillator (ICD). Some authors consider that AF may have a ventricular pro-arrhythmic effect, particularly in the setting of heart failure. Aims: To evaluate the impact of permanent AF present at ICD implantation date on the incidence of ventricular arrhythmic events during the follow-up. Methods and Results: A retrospective study was conducted on 277 consecutive patients with ICD therapy and left ventricular dysfunction (ischemic and nonischemic dilated cardiomyopathy with LVEF < 40%). Mean age at ICD implantation was 62.8±11.7 years and the majority were man (87.7%). Ischemic heart disease was present in 74.4%. Eighteen pts (6,5%) presented permanent AF at ICD implantation date. Overall, 37,5% of pts experienced appropriate ICD therapies over a follow-up of 35.6±32 months with a significant difference between subgroups (with or without permanent AF). The occurrence of appropriate therapies in pts with permanent AF was 61.1% comparing with an incidence of 35.9% in pts without AF at ICD implantation date (p<0,05). Conclusions: In a population of ICD recipients with left ventricular systolic dysfunction, the presence of permanent atrial fibrillation predicted an increased risk of ventricular tachyarrhythmias detected and treated by the ICD. P2455 Indications and outcome of laser lead extraction: a single centre experience P. Vergara, P. Mazzone, N. Sora, A. Marzi, A. Cuko, G. Paglino, G. Vicedomini, V. Santinelli, C. Pappone. San Raffaele del Monte Tabor Foundation, Milan, Italy Cardiac lead extraction is a expanding procedure because of the actual high number of cardiac device implantations. Various methods have been traditionally used: manual traction, forceps-assisted manual traction, mechanical traction locking stylets assisted, open chest surgery. AIM OF THE STUDY was to evaluate indications, effectiveness and complications of eccimer laser assisted leads extraction in a single center, single operator series of patients. Methods and Results: From december 2005 to september 2008 a total of 131 leads were removed in 68 patients. All leads implanted less than 6 months before extraction were not considered for analysis. Sixty-five leads were extracted by mechanical traction using locking stylets, 58 leads by eccimer laser extraction, 8 Leads (5 pts) by open chest surgery (1 pt for laser extraction failure, 4pts for the presence of large vegetations on the leads). Indication for extraction was infection in 60.3% pts (pocket infection in 24 pts, endocarditis in 14 pts), non functional leads in 26 (41.3%) pts, lead interference 4 (6.3%) pts. Eccimer laser extraction was required in 43.9% atrial, 67.2% right ventricular (10 pacing leads, 29 defibrillation leads) and 1 coronary sinus lead. Complete leads removal was obtained in 67 patients. Pericardial tamponade occurred in 1 patient; there were no deaths. Conclusion: Laser extraction has a high success rate and a low complication rate. Local and systemic infections are the most common indication to leads extraction. Laser extraction is frequently required for right ventricular ICD leads, while manual traction is usually sufficient for coronary sinus pacing leads. P2456 Influence of native QRS complex duration on Antitachycardia Pacing effectiveness: a prospective study J. Jimenez-Candil, A. Martin, J. Morinigo, C. Ledesma, C. Martin- Luengo. Hospital Universitario de Salamanca, Salamanca, Spain Shocks (SH) increase mortality in ICD patients (ICD-P) with left ventricle dysfunction (LVD). ICD-P with longer QRS complexes and LVD have higher mortality rates (due to heart failure) but not more risk of suffering appropriate therapies. We speculated that the duration of native QRS complex (QRSd), as marker of left ventricle size, fibrosis and ischemia, could be associated with lower rates of antitachycardia pacing (ATP) effectiveness because it may be related to longer times of conduction of stimulus from pacing site to MVT origin. Our aim is to determine prospectively the relationship between the QRSd and: a) the ATP effectiveness, and, b) the likelihood of suffering SH due to MVT. Methods: We followed 216 ICD-P with LVD (LVEF: 31±11; pacing site: right ventricular apex) for 21±12 months. Detection and ATP therapies for MVT were programmed as follows: a) Fast-MVT: Cycle Length (CL): ms; 1 burst of 5 pulses at 84% of CL, and: b) Slow MVT: CL > 320 ms; 3 bursts of 15 pulses at 91%. Failed ATP therapies were followed by shocks. QRSd was determined on the surface ECG (50 mm/s) at the ICD implantation. Results: We analyzed 551 MVT (CL: 329±35 ms; fast MVT: 41%) which were recorded in 67 patients (range MVT per patient: 1-44). ATP was successful in 86%

117 Implementable cardioverter-defibrillator Related issues 417 MVT and 11% were terminated by SH. Of ICD-P with MVT, 36% had a QRSd 100 ms (n=239 MVT), in 30% the QRSd was (n=139 MVT), and 36% had a QRSd 120 ms (n=173 MVT). Mean ATP efficiency per patient was 83% (95% Confidence Interval: 74-91). ICD-P with lower values of QRSd had higher ATP efficiency (mean [95% Confidence Interval]): 98%[96-100] (QRSd 100 ms) vs. 82%[69-94] (QRSd: ms) vs. 69%[51-87] (QRSd 120); p=0.001 (ANOVA). The proportion of ICD-P suffering SH due to MVT was higher in those with longer QRSd: 1%[ ] (QRSd 100 ms) vs. 21%[6-36] (QRSd: ms) vs. 26%[9-40] (QRSd 120 ms); p=0.004 (ANOVA). By logistic regression analysis (which included LVEF, CL of MVT, aetiology, indication and betablocker therapy), QRSd (ms) remained as an independent predictor of effective ATP (95% CI: ; p<0.001) and SH due to MVT (95% CI: ; p=0.001). Conclusions: Since the QRSd is a negative and independent predictor of effective APT, ICD-P with longer QRSd need more frequently SH to terminate MVT. This finding could partially explain the prognostic impact of QRSd in this population P2457 Remote device monitoring for CRT-D leads to substantial reduction in the need for routine visits to a pacing clinic L. Trembath 1,C.Azucena 2,N.Stain 1,M.R.Cowie 3. 1 Royal Brompton Hospital, London, United Kingdom; 2 Medtronic, London, United Kingdom; 3 Imperial College London, London, United Kingdom Remote monitoring of pacing technologies in HF patients has the potential to transform workload for pacing departments. The Carelink network is a web-based remote monitoring system for implantable devices that provides information identical to that obtained at a pacing clinic visit. We evaluated the impact of the introduction of this system into routine practice. Methods and results: A retrospective audit of all HF patients with CRT-D established on Carelink follow-up in the 15 month period from September 2007 in one centre was performed by review of case notes and pacing clinic records. 97 patients were included (mean age 66 years), mean period on Carelink 10 months (range 2-15 months)). According to the standard pacing clinic follow-up protocol, expected pacing clinic visits over the audit period was estimated to be 292. Actual scheduled pacing clinic visits that occurred using the Carelink system in the audit period was only 87, a 70% reduction in the need for scheduled pacing clinic visits. There were 104 scheduled Carelink downloads during the audit period: this led to no action in 87 instances (84%). 17 downloads (16%) required some action: 1 was related to rising lead impedance, 1 ICD discharge not noticed by patient, and 10 were rhythm-related and required medical review, and 5 were related to increasing AF burden, or decreasing transthoracic impedance (Optivol) readings, with involvement of the HF team. There were 8 unscheduled Carelink downloads, all but one triggered by a patient (3 ICD discharges, 2 lead alerts from the device, and 2 related to decreasing transthoracic impedance). Of the 87 scheduled pacing clinic visits, only 9 (10%) led to any action - 7 were rhythmrelated which resulted in medicine review and/or reprogramming of device, and 2 related to trans-thoracic impedance reductions. There were 22 unscheduled office visits, organised by the pacing clinic as a result of Carelink downloads or patient telephone contact, which led to action in 20 cases (91%). These were due to syncopal episodes (2), lead alarms (2), ICD discharges (2), rhythm disturbances (8) and 6 due to changes in trans-thoracic impedance or other HF- related parameters. Conclusions: Remote monitoring of implantable devices in HF patients shows considerable promise in reducing the need for routine pacing clinic visits. In the vast majority of cases alerts from patients (or the device) require action. The widespread adoption of remote monitoring is likely to improve the use of healthcare professionals time, and will free up patients from the need for more frequent routine visits to the pacing centre. P2458 Estimation of SCD primary prophylaxis need in patients with high-risk myocardial infarction treated with primary PCI A. Filipecki, K. Wita, Z. Tabor, W. Orszulak, J. Myszor, W. Kwasniewski, M. Turski, D. Urbanczyk-Swic, M. Trusz-Gluza. Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland SCD primary prevention based on left ventricular ejection fraction and NYHA class should end with implantation of cardioverter-defibrillator (ICD). Current acute myocardial infarction (MI) treatment with primary PCI and guidelines driven pharmacotherapy result in LVEF preservation and improved outcome. To assess the need for ICD placement in the prospectively enrolled 112 consecutive patients (aged 58±11 years, 76% male) with the first, only anterior wall STEMI after successful primary PCI. During 2-year follow-up major adverse cardiac events (MACE) defined as death, MI, sustained VT or hospitalization for acute heart failure (HF) were registered. At 1 and 6 months echocardiography was repeated and analyzed against MADIT-2 and SCD-HeFT criteria. Twenty MACE s were registered: 7 deaths (D; 6.25%), 3 MI, 1 sustained VT, 9 HF events. At 1 month 27 patients (24.1%) fulfilled class I criteria (table). At 6 months still 22 patients (19,6%; 11 MADIT-2 like and 11 SCD-HeFT like) meet the class I indication. ICD indication and 2-year MACE s ICD indication Patients meeting 2-year MACE s in patients indication at 1 month meeting indication MADIT-2 like (LVEF < 30%) 16 (14,3%) 7 (36,8%): 1 D, 1 MI, 5 HF SCD-HeFT like (LVEF < 35% + NYHA II/III) 11 (9,8%) 5 (45,5%): 2 D, 1 MI, 2 HF The others 85 (75,9%) 7 (8,2%): 4 D, 1 MI, 2 HF, 1 VT D - death, MI - myocardial infarction, HF - hospitalization for acute heart failure, VT - sustained ventricular tachycardia. Conclusions: Despite primary PCI and modern pharmacotherapy the proportion of patients after acute anterior STEMI with class I SCD primary prophylaxis indication is substantial. Total mortality was low, however, hospitalization for acute heart failure was the most frequent event type. P2459 Dynamic impedance for arrhythmia discrimination K. Jarverud 1,M.Broome 2,K.Noren 1, T. Svensson 1, S. Hjelm 1, A. Bjorling 1. 1 St. Jude Medical, Järfälla, Sweden; 2 Karolinska sjukhuset, Solna, Sweden Introduction: Approximately 15%-20% of all ICD shocks are inappropriate. This decreases both patient quality of life and device longevity. Improving arrhythmia discrimination performance in ICDs is very important. Cardiogenic impedance is a continuous beat to beat measure of cardiac function. Methods: We retrospectively analyzed cardiogenic impedance (CI) data from 9 impedance configurations recorded in 23 anesthetized animals with induced arrhythmias. Two aspects of CI were investigated: the ability to distinguish between SVTs and VTs, and the ability to distinguish between hemodynamically stable and unstable arrhythmias, regardless of arrhythmia origin. The hemodynamic stability of the subject was assessed by an observer, blinded to the type of arrhythmia. An arterialpressurebelow50mmhgformorethan6 8seconds was considered hemodynamically unstable; however, the observer employed clinical judgment in borderline cases. Results: CI from the RV bipolar impedance configuration measured in 12 animals during 45 different arrhythmia episodes was morphologically different during stable and unstable arrhythmias. In these subjects, using the CI signal alone for arrhythmia discrimination would have generated an average sensitivity and specificity of 94%. Using an RV-can tripolar impedance configuration, recorded only in 3 animals during 3 arrhythmias, the average sensitivity and specificity would have been 100%. For SVT/VT discrimination, CI would have yielded an average sensitivity and specificity of 95%. Conclusions: CI has the potential to be a powerful parameter for device-based arrhythmia discrimination. It should enable significant reduction in unnecessary ICD shocks and concomitant morbidity and accompanying reductions in patients quality of life. Further research is needed to identify the overall best impedance configuration for arrhythmia discrimination. P2460 Survival in patients with implantable cardioverter defibrillators - does age matter? I. Chung, W. Nicholson, I. Loke, M. Jeilan, G.A. Ng, P.J. Stafford. University of Leicester, Leicester, United Kingdom Aim: Implantable cardioverter defibrillators (ICD) reduce mortality in a wide range of patients at risk of sudden cardiac death. However, life expectancy after ICD implantation in an unselected patient cohort has not been defined and the effect of age at implant on survival remains uncertain. Therefore we assessed survival after ICD implantation in all patients and in older and younger individuals. Methods and results: We performed a retrospective cohort study of 1216 consecutive patients who received ICDs from 1993 to 2008 at a single university hospital. Age 63±13 years, male 84%, ischaemic etiology 62%, primary prevention 42% in all age groups. Overall survival and survival in patients aged <65, 65-74, and 75 years at ICD implantation were assessed by Kaplan- Meier analysis. Mean follow-up was 4 years, median survival was 13 years in all age groups and there were 241 all causes of deaths. At 4 years, 88%, 80% and 60% patients survived in age groups <65, and 75 respectively. 84% and 70% patients survived with non-ischaemic and ischaemic etiology respectively (both log rank p<0.0001). There was no difference in median time to death in the 3 age Figure 1

118 418 Implementable cardioverter-defibrillator Related issues groups, age<65, and 75 years were 913 (interquartile range ), 921 ( ) and 916 ( ) days respectively, (p=0.86). Conclusion: Age at ICD implantation and ischaemic etiology are independently associated with mortality. P2461 Remote Follow-up for ICD-Therapy in Patients Meeting MADIT II Criteria - The REFORM trial U. Wetzel 1,J.C.Geller 2, J. Kautzner 3, H. Moertel 4, B. Schumacher 5, G. Hindricks 1 on behalf of REFORM study group. 1 Herzzentrum der Universitaet Leipzig, Leipzig, Germany; 2 Zentralklinik Bad Berka GmbH, Bad Berka, Germany; 3 IKEM, Prague, Czech Republic; 4 Biotronik GmbH & Co. KG, Erlangen, Germany; 5 Herz- und Gefäßklinik, Bad Neustadt, Germany Introduction: The probability of the first ICD therapy in primary prevention is about 34% within 3 years. With a conventional 3 months ICD follow-up (FU) scheme the majority of patients (pts) might be followed more closely than necessary. Remote FU by home monitoring can reduce FU burden. REFORM is a prospective, randomized multicenter study comparing a simplified 1-year FU scheme with a conventional 3-month FU regimen with respect to the difference in FU burden, the associated costs, a possible impact on all cause mortality, the number of hospitalizations, and QoL. Primary endpoint is the difference of additional FU visits between both groups. Methods: 155 heart failure pts meeting the MADIT II criteria (LVEF 30%, 1 month post MI) were enrolled between Jan 2004 and Feb 2006, mean age 62.8 years, mean LVEF 25.0%. All pts received a single- or dual-chamber ICD capable of sending automatic daily home monitoring messages. After 3 months, pts were randomized in a 1:1 ratio to a simplified 1-year FU scheme or the conventional 3- month scheme. For both groups additional FU were scheduled after prespecified home monitoring warning messages or due to physician s decision or patient s wish. QoL was measured by the SF-36 questionnaire at enrollment, at the 15- and the 27-month follow-up. Cost factors like duration of follow-up, travel costs, and duration of hospitalizations were measured at every FU. Results: Pts in the 1-year group had 0.55±0.07, pts in the conventional scheme 0.21±0.05 additional FU per patient per year. With a difference of 0.34 FU, the primary study hypothesis can be accepted. No difference can be seen in mortality (p=0.62), the number of hospitalizations (p=0.64) or time to first ICD therapy (p=0.72) between the study groups. QoL was not significantly different between both groups. Physical health showed no difference between both groups (p=0.42), while mental health showed a positive trend for pts in the 12M group (p=0.08). Conclusions: Total FU burden in MADIT II pts can be reduced by more than 2.5 FU per pt per year while maintaining therapy safety and pt comfort using a simplified 1-year FU scheme with remote monitoring. P2462 Contemporary results and health care utilisation after ICD therapy for primary prevention in coronary artery disease and dilated cardiomyopathy T. Smith, J.L. Bosch, R.T. Van Domburg, A. Muskens-Heemskerk, D.A. Theuns, L. Jordaens. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Introduction: The actual benefit of implantable defibrillators (ICD s) as primary prevention remains debated, in spite of existing guidelines, and became again of interest after recent recalls. We analysed the implications of prophylactic ICD implantation according to the ESC/AHA/ACC guidelines in a Dutch health care setting, as preparation for a cost-effectiveness study, and made a complete health care utilisation inventory. Methods: The study population consisted of all consecutive patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) who received an ICD for primary prevention, between January 2004 and July The ErasmusMC ICD registry was used for follow-up, and was completed for mortality by using the official vital records. Additional data on readmission and mortality were obtained by sending questionnaires to the general practitioners. Results: Of 478 patients, 67% had CAD, and 43% had an ICD with resynchronization therapy. Over a mean follow-up of 761±446 days, 40 patients died (8%). Heart transplantation was performed in 17 of 41 patients on the transplantation list. Appropriate ICD intervention occurred in 104 patients (22%), including 16 of the deceased patients, and 9 patients on the transplantation list. The median interval to first appropriate ICD therapy was 205 days. During follow-up, there were 47 readmissions for ICD/lead revision (8 lead repositions, 12 lead replacements including 3 recalls; 27 ICD replacements, including 15 replacements within 36 months, 3 pocket infections, and no recalls). Analysis of the questionnaires showed device related problems in 11% of the patients, admissions for other cardiac problems in 44%, and admissions for non-cardiac problems in 24%. Additional cardiological outpatient visits were observed in 28% of the patients. Discussion: It is evident that over a mean follow-up of two years, one fifth of the patients receive appropriate interventions from a prophylactic ICD, even when using a high proportion of resynchronization devices. Patients from the transplantation list had the same benefit. Overall mortality over this time amounts to 8%. The number of early replacements is not low (3,4%). In total, 10% becomes readmitted for ICD revision and at least another 10% for device related problems. Furthermore, admissions for cardiac disease and other pathology occurred in respectively 44% and 24%, indicating that we are dealing with a very ill population. P2463 Importance of implantable cardioverter defibrillators in idiopathic ventricular tachyarrhythmias J. Delgado Silva, R. Gomes, S. Almeida, S. Rocha, K. Reis Santos, D. Cavaco, F. Bello Morgado, P. Adragao, A. Silva. Centro Hospitalar de Lisboa Ocidental, H. de Santa Cruz, Lisboa, Portugal Introduction: Idiopathic ventricular tachycardia (VT) and fibrillation (VF) are rare conditions diagnosed after exclusion of structural heart disease and primary electrical disease (Brugada syndrome and long QT syndrome, among others). Purpose: To evaluate, in a population of patients (pts) with an implantable cardioverter defibrillator (ICD) (after VT/FV with no identifiable cause), arrhythmic events diagnosed and treated by the device and assess long-term outcome. Methods: From a population of 486 pts with ICDs, we identified and studied 25 pts with idiopathic VT/FV. We evaluated device detections, therapies and survival during a mean follow-up period of 5 years. Results: Mean age was 54.4±17.5 years, 8% were female. Idiopathic FV was identified in 36% of pts (resuscitated from sudden death) and VT in 64% (syncopal). All pts had a left ventricular ejection fraction > 50%. During a mean follow-up of 63.8±46 months, the recurrence of VF/VT treated with appropriate shocks was detected in 10 pts (40%) (101 shocks delivered, 92% were successful on the first attempt); 5 pts received inappropriate shocks, sometimes several at a time. The most frequent causes for inappropriate shocks were atrial fibrillation, sinus tachycardia and T wave oversensing. Appropriate antitachycardia pacing (ATP) was detected in 11 pts (88 ATP delivered, 73% were successful). No mortality was registered during the follow-up period. Conclusion: In patients with idiopathic VF or syncopal VT, ICD has proven to be an effective therapeutic strategy, successfully detecting and treating arrhythmic recurrences and thus avoiding fatal outcomes. P2464 A comparison of induction by direct current pulse versus 50-Hz pacing on ventricular fibrillation and defibrillation H.S. Lim, S. Flannigan, H. Marshall. Queen Elizabeth Hospital, Birmingham, United Kingdom Background: Ventricular fibrillation (VF) by different modes of induction may have different characteristics and defibrillation thresholds. This study compares the cycle lengths and defibrillation of VF induced by direct current (DC) pulses versus 50-Hz pacing. Method: We compared DC pulse and 50-Hz pacing induction in 259 consecutive patients with ICDs in Inadequate defibrillation safety margin (DSM) were defined as failed defibrillation at 25J. The effective current was calculated in each patient to allow adjustment for ICD output based on capacitance, tilt, voltage and chronaxie of 3.5ms. Results: Of the 259 patients, 132 underwent induction with DC pulses and 127 with 50Hz pacing (Age 64±13 vs 65±13 years, p=ns and Males 80% vs 83%, p=ns). DC pulses induced VF of shorter cycle lengths compared to 50-Hz pacing [TABLE]. There were 17 patients with inadequate DSM: 13 (9.8%) with DC pulse vs 4 (3.1%) with 50Hz pacing (p<0.001). The induced VF cycle lengths were shorter in patients with inadequate DSM (186±25 vs 221±41ms, p<0.001). There was no significant difference in effective current between induction modes, and between patients with successful or failed defibrillation. On multivariate analysis, only the induced VF cycle length (p=0.001) was independently associated with inadequate DSM. DC pulse (n=132) 50-Hz (n=127) p Ischaemia (%) Biventricular pacemaker (%) Ejection fraction (%) 31±14 33± Amiodarone (%) SVC coil (%) HV impedance ( ) 52±15 54± VF cycle length (ms) 207±36 231±44 <0.001 VF duration (s) 9.7± ±1.1 <0.001 Effective current (A) 9.5 ( ) 8.6 ( ) Conclusion: Induction by DC pulses are associated with greater proportion of patients with inadequate DSM as it induces VF of shorter cycle lengths compared to 50-Hz pacing. The mode of induction and the resultant VF cycle lengths may contribute to the probabilistic nature of defibrillation and should be considered in interpreting DSM. P2465 Implantable cardioverter defibrillators at the end of life: How much do patients want to know? C.E. Raphael, N. Stain, I. Wright, M. Koa-Wing, P. Kanagaratnam, D.P. Francis. Imperial College London, London, United Kingdom Background: The implantable cardioverter defibrillator (ICD) is an effective way to decrease sudden death in the cardiac population. However, these devices are often implanted into patients with severe heart failure and a poor prognosis, effectively denying them the option of a quick and natural death. It is still unclear when the end of life and device deactivation should be dis-

119 Implementable cardioverter-defibrillator Related issues 419 cussed with patients and how much patients want to know prior to ICD implantation. Methods: 54 patients with an active ICD in situ (38 with chronic heart failure, 16 with primary arrhythmias) were interviewed regarding their attitude towards the ICD, their recollection of the consent procedure and how they felt end of life should be discussed with ICD patients. Results: Most patients were not aware that the ICD could be deactivated. 82% of patients would consider deactivating the ICD if they were very unwell, 12% would probably deactivate if they got lots of shocks and 30% would consider deactivation if the shocks were very painful. The vast majority (94%) of patients wanted to be involved in the switch-off procedure; 40% felt this discussion should be pre-operatively but 21% felt the discussion should only be if the patient was very unwell (16%) or in the last few days of life (5%). Conclusion: Patients with ICDs in situ often have poor knowledge about their device and its implications at the end of life. Reasons to consider device deactivation varied considerably but most patients would consider device deactivation if they were very unwell. Discussion regarding the ICD at the end of life needs to be varied according to patient preference. P2467 Preliminary results of the sprint fidelis recall J.B. Van Rees, C.J.W. Borleffs, J.J. Bax, L. Van Erven, M.J. Schalij. Leiden University Medical Center, Leiden, Netherlands Purpose: The Sprint Fidelis (SF) ICD lead has a higher-thanexpected failure rate. Recently, Medtronic put out new safety advisories regarding the SF lead: (1) installation of a lead-integrity algorithm (LIA), an audible alert for early detection of lead failure and (2) remote monitoring by CareLink. We have conducted such a recall and evaluated the implementation of these advisories in daily practice. Methods: All patients with a SF lead implanted in our hospital were recalled to comply with these advisories. Success rate and compliance during follow-up were assessed. Results: Since October 2008, 306 patients were recalled of whom 297 patients attended. LIA was downloaded into all software compatible ICDs (n=293, 99%). Of the attendees, 18 patients already used CareLink and 279 patients (85%) were offered to use CareLink. Causes of patient refusal were inaccessibility to a fixed telephone network (n=20, 6%), fear of constant confrontation with the ICD (n=7, 1%) or living abroad (n=5, 2%). Of the 247 patients, 209 (84%) patients were able to self-interrogate their ICD. For optimal safety, all patients were asked to interrogate on weekly basis, except for patients with LIA incompatible ICDs or deafness, which were asked to interrogate daily. During 12 weeks follow-up, mean transmission rate was 80% in the weekly group 77% in the daily group (see fig). Moreover, LIA was triggered twice, detecting one lead failure in time. Conclusion: Implementation of SF-advisories resulted in: 1) LIA installation in all compatible ICDs; 2) 84% successful self-interrogations; 3) around 79% transmission compliance; 4) two SF-lead failure detection during 12 weeks follow-up. groups had similar proportion of men (72% vs 65%;p ns), symptoms (65% vs 53%;p ns), dyspnea (53% vs 42%;p ns), angina (23% vs 17%;p ns) syncope (10% vs 25%;p ns) and pharmacological treatment (68% vs 75%;p ns). Patients in Group 1 were older (Age 57,6±19,1 vs 39,3±19,2 years; p<0.05), had higher ventricular diameters (LVED 45,6±8,8 vs 40,4±10,9mm; p<0.05) and smaller maximal LV-wall thickness (20,6±7,2 vs 26,3±7,9 mm; p<0.05). There were no statistical difference in posterior wall thickness (12,6±3,5 vs 12,8±4,78 mm;p ns), left atrial dimension (44,7±11,4 vs 40,1±15,5 mm;p ns), left ventricular outflow tract obstruction (42,5% vs 33,3%;p ns), basal gradient (39,2±51,5 vs 28,9±37,8 mmhg;p ns) and Valsalva maneuver gradient (48,2±63,2 vs 32,6±40,8 mmhg;p ns). There were more ICD implants in Group 2 than in Group 1 (15% vs 72%, p<0.05). In Group 1 the ICD was implanted because of: NSVT (66%), IVS 30mm (13%) and family history of SD (13%). During follow-up (3,5±3,7 vs 3,6±3,3 years;p ns), there were more appropriated device interventions in Group 2 than in Group 1 (0% vs 11.1%, p<0.05). Indeed in Group 2 a 15% of the patients in which an ICD was implanted received an appropriated shock versus none of the patients in Group 1 (0% vs 15.4%;p ns). There were no cardiovascular deaths in both groups. Conclusion: HCM patients with only one MRF for SD neither received appropriated shocks nor presented cardiovascular death. We concluded that in our population (as shown in others registries) the presence of only one MRF may not be enough reason to implant an ICD in PP. P2469 Pacemaker and ICD device related infections - Diagnosis and treatment of a serious problem - A growing challenge V. Moller, M. Schoepp, M. Seifert, M. Schau, J. Meyhoefer, C. Butter. Ev.-Freikirchliches Krankenhaus und Herzzentrum Brandenburg in Bernau, Bernau bei Berlin, Germany Introduction: With the increasing number of device implantations in patients with high comorbidity the number of device-related infections has been growing in the last few years. The device related Infection is a serious and life threatening complication after pacemaker and ICD implantation. Both the diagnosis and optimal treatment of such infections are a big challenge for the clinical everyday life. Methods: We examined retrospectively 107 consecutive patients (ø)69.1 years, 22 f, 85 m) who were referred to us with a device-related infection treated between January 2004 and September The diagnosis was made either by pocket erythema, erosion, abscess, persistent bacteremia and/or positive blood cultures or endocarditis with or without vegetation on the lead. Result: Of 107 patients with proven device-related infection, 84 patients had a pacemaker, 22 patients an ICD (5 biventricular systems) and 1 patient had an OPTIMIZER. 65 of these patients (70%) underwent a prior replacement. The average delay after replacement was 12 months. The bacteriologic organism (blood culture, purulent material from the pocket) was identified in 67% of our patients. The organisms were Staphylococci aureus in 26 patients, coagulase negative Staphylococci (e.g. Staphylococci epidermidis) in 21 patients, 4 patients with MRSA, Enterococci (6 patients), Streptococci (4 patients), 1 patient with Serratia marcescens, and 1 patient with Pseudomonas. Valvular or lead vegetations were detected by echocardiography in 34 of these patients. An interventional explantation succeeded in 88 patients. Only 19 patients had to be explanted by cardiac surgeons mainly due to the need of an epicardial pacemaker. Summary Device replacement or upgrade surgeries are associated with a high infection rate. Staphlococci is the most common organism causing a device-related infection. The bacteriologic organism is only identified in two-thirds of device-related infections. A complex strategy has to be chosen including clinical status (pocket inspection), blood samples, and transesophageal echocardiography to differentiate between vegetations, thrombi or scar tissue to identify an infection in order to avoid a risky device and lead explantation. P2468 Is one major risk factor for sudden death enough to indicate an Implantable cardioverter-defibrillator in patients with hypertrophic cardiomyopathy? F. Landeta, A. Fernandez, J.L. Gonzalez, J.H. Casabe, E. Guevara, L. Medesani, N. Galizio. Favaloro Foundation University Hospital, Buenos Aires, Argentina Purpose: Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiovascular disease and its most threatening consequence is sudden cardiac death (SD). There is general consensus that implantable cardioverter-defibrillator (ICD) should be offered as secondary prevention (SP) but it is not clear if only one major risk factor (MRF) for SD is enough to indicate an ICD for primary prevention (PP). Our aim was to investigate clinical characteristics and appropriated device interventions of ICD in patients with HCM for PP in a cohort of patients according to the presence of one or more MRFs of SD. Methods: From 345 patients with HCM we studied 76 PP patients with one or more MRFs for SD (family history of SD occurring < 40 years of age, unexplained syncope, left ventricular wall thickness 30mm, NSVT on Holter monitoring and abnormal blood pressure response to exercise). We compared patients with one (Group1) vs patients with two or more MRFs for SD (Group2). Results: There were 40 patients in Group 1 and 36 patients in Group 2. Both P2470 Catheter ablation for monomorphic VT induced by programmed electriacl stimulation, reduced electrical storm in patients with ICD K. Tanno, T. Onuki, Y. Minoura, T. Asano, Y. Kobayashi. Showa University, Tokyo, Japan Effectiveness of ICD has been established in patients with lethal ventricular tachyarrhythmia. The role of programmed electrical stimulation (PES) and catheter ablation (CA) is controversial for such a patient. [Method] The subject is consecutive 114 patients (62±12 years, Male;92 patients) who were implanted ICD from 1997 to Patients underwent PES before ICD implantation. When monomorphic VT (MonoVT-group) was induced, CA was performed. The relation between the inducibility of VT and outcomes of patients was investigated.[results] PES was performed in 102 of 114 patients. Monomorphic VT or polymorphic VT was induced in 41 patients or 39 patients (PolyVT-group). VT was not induced in 22 patients (VT( )-group). During a mean follow-up period of 42±30 months, there was no significant difference of mortality among these groups. However, the number of appropriate ICD discharge was significantly higher in MonoVT-group than PolyVT-group or VT( )-group (24/41 vs. 13/39 or 4/22, p<0.05). Twenty-six of 41 patients with MonoVT underwent CA. There was no significant difference of mortality or ICD discharge between patients with CA and without CA. However, the

120 420 Implementable cardioverter-defibrillator Related issues / Pharmacological therapy of heart failure incidence of electrical storm, defined more than 3 times ICD discharge per day, was lower in patients with ablation (6/26 vs. 8/15, p<0.05). [conclusion] PES is useful to identify patients susceptible to VT and catheter ablation for MonoVT is effective to reduce the incidence of electrical storm. Conclusions: Among MVT occurred in ICD patients, little changes in the CL significantly increase the efficiency of the subsequent ATP therapy. MVTs with the smallest degree of R-R fluctuations, especially when the pattern is a progressive CL shortening, are infrequently terminated by the F-ATP. P2471 Upgrade of implantable cardioverter-defibrillator to cardiac resynchronization therapy: rate of progression and baseline predictors G.L. Sumner, R. Sheldon, P. Cassidy, A. Gillis, D. Exner, R. Quinn, G. Veenhuysen, H. Duff, K. Kavanagh, B. Mitchell. University of Calgary, Calgary, Canada Background: Cardiac resynchronization therapy (CRT) is indicated for patients with LVEF <0.35, New York Heart Association (NYHA) class III, and QRS width >120 milliseconds (ms). However some patients may first receive an implantable cardioverter-defibrillator (ICD), then evolve to needing a CRT system. Can these patients be identified at time of first device implantation? Objectives: To assess the rate of progression from ICD to LV lead upgrade and to determine which baseline characteristics best predict future LV lead implantation. Methods: We evaluated the likelihood of upgrade to LV lead from an ICD in 505 pts from April 2001 to August All had 1 or 2 of 3 CRT implant criteria. Baseline characteristics were analyzed to assess the best predictors of upgrade to LV lead during follow-up. Student s T-Test was used to compare continuous variables and the Gehan-Breslow-Wilcoxon test was used to compare actuarial lead-free survival to 2000 days. Results: Patients had mean age 64±11 y and were 87% male. Mean LVEF and QRS width were 24.2±6.7% and 129.8±34.2 ms,respectively. Mean NYHA class was 1.9±0.7. NYHA class distribution was: I, 159 pts; II, 276 pts; III, 70 pts. The likelihood ofupgrade by 2000 days was 22.7%. At baseline, age (p=0.55) and LVEF (p=0.66) did not predict progression to LV lead during follow-up. In contrast, NYHA class (2.20±0.60 vs. 1.83±0.70;p=0.001) and QRS width (154.0±38.5 vs ±33; p< )predicted progression to LV lead. Pts with baseline NYHA I were far less likely to progress to LV lead by 2000 days than NYHA II and III (5.3% vs 29.1% and 100%, p=0.014). QRS width predicted progression only in NYHA class II, whereas progression to LV lead by 2000 days was 18% for QRS<120ms vs 38% for QRS>120ms (p=0.0028). Conclusions: The rate of progression from ICD implantation to LV lead upgrade is significant, and predicted by NYHA class and QRS width. Patients with NYHA I heart failure have negligible progression regardless of QRS width and LVEF, but patients with NYHA class II and III progress more rapidly. P2472 Antitachycardia pacing effectiveness in monomorphic ventricular tachycardias spontaneously occurred in ICD patients: importance of the cycle length fluctuations J. Jimenez-Candil, A. Martin, J.L. Morinigo, M. Ruiz Olgado, C. Ledesma, C. Martin-Luengo. Hospital Universitario de Salamanca, Salamanca, Spain Antitachycardia pacing (ATP) is not successful in 5-25% of monomorphic ventricular tachycardias (MVT) spontaneously occurred in ICD patients. ATP-refractory MVTs need shocks to be terminated; furthermore, shocks increase mortality in ICD-patients with left ventricular dysfunction (LVD). We speculated that small fluctuations of MVT cycle length (CL) may be related to the efficiency of the subsequent ATP, across two possible mechanisms: 1) being a marker of MVT instability -degree of CL fluctuations (CL-F)-; and, 2) becoming longer the excitable gap whenever the CL progressively increases -pattern of CL-F-. Our aim is to determine prospectively the relationship between these parameters -measured in he 12 RR intervals previous to ATP- and the effectiveness of this latter. CL- F degree was defined as the percentage of variation (P-RR) which was calculated by dividing the mean difference between each R-R interval with the next one (Mn) by the CL (Mn/CL) 100, whereas the CL-F pattern was defined by the acceleration index (AI) which was calculated by dividing the CL of the 6 R- R intervals preceding ATP therapy by the CL of the 6 R-R intervals inmediately precedent. Methods: We analyzed 551 MVT (CL: 329±35 ms) occurred in 67 patients with LVD. RR intervals were measured from the marker channel (P-RR: 2.44±1.7%; 81% MVT had an AI<1). Detection and first ATP (F-ATP) therapies, including two zones for fast MVT (CL: ms) and slow MVT (CL>320 ms) were standardized. Results: F-APT efficiency was 81%. After the demonstration of a significant correlation between P-RR and AI with the probability of effective F-ATP: C=0.78 (P-RR) and 0.73 (AI) (p<0.001 for both), by logistic regression analysis -which included the LVEF, CL, aetiology, functional class, indication and beta-blocker therapy-, the P-RR, % (OR=2.2; p<0.001), and an AI<1(OR=4.2; p<0.001) were found as independent predictors of successful F-ATP. Both variables provided complementary information. In fact, the efficiency of F-ATP was higher in AI<1 (85 vs. 64%; p<0.001). Additionally, classifying the events according to the tertiles of P-RR ( 1.32%, 1.33%-2.99%, 3%), F-ATP was more effective in higher values of P-RR: a) MVT with AI<1: 99% (P-RR 3%) vs. 85% (P-RR: 1.33%- 2.99%) vs. 76% (P-RR 1.32%), p<0.001; b) MVT with AI 1: 94% vs. 68% vs. 42% (p<0.001). P2473 arrhythmia specialists predict progression to upgrade of implantable cardioverter-defibrillator to cardiac resynchronization therapy more accurately than do clinical factors G.L. Sumner, R. Sheldon, P. Cassidy, D. Exner, R. Quinn, K. Kavanagh, H. Duff, A. Gillis, G. Wyse, B. Mitchell. University of Calgary, Calgary, Canada Background: Cardiac resynchronization therapy (CRT) is indicated for patients with left ventricular (LV) ejection fraction <0.35, New York Heart Association (NYHA) class III, and QRS width >120 milliseconds (ms). Many patients who receive implantable cardioverter-defibrillator (ICD) therapy have either 1 or 2 of these 3 criteria. Does clinical acumen predict the rate of progression to LV lead upgrade? Objectives: To assess whether cardiac electrophysiologists predict the rate of progression to LV lead upgrade more accurately than baseline clinical factors. Methods: We retrospectively evaluated the likelihood of upgrade to LV lead from an ICD in 505 pts from April 2001 to August Baseline characteristics were analyzed to assess the best predictors of upgrade to LV lead during follow-up. Student s T-Test was used to compare continuous variables and the Gehan-Breslow- Wilcoxon test was used to compare actuarial lead-free survivals to 2000 days. We compared the hazard ratios (HR) of various predictors of progression to LV lead upgrade. Results: Patients had mean age of 64±11 y and were 87% male. Mean LVEF and QRS width were 24.2±6.7% and 129.8±34.2 ms,respectively. Mean NYHA class was 1.9±0.7. NYHA class distribution was: I, 159 pts; II, 276 pts; III, 70 pts. University-based cardiac electrophysiologists (EP) made all clinical decisions. All patients at baseline had 1 or 2 of 3 CRT implant criteria. Subjects received either a plain ICD (N=307) or a CRT-capable ICD with plugged LV lead port (N=198). The likelihood of upgrade by 2000 days was 22.7%. At baseline, age (p=0.55) and LVEF (p=0.66) did not predict progression to LV lead during follow-up but NYHA class (2.20±0.60 vs 1.83±0.70;p=0.001) and QRS width (154.0±38.5 vs.128.0±33; p< ) did. Arrhythmia specialists accurately predicted progression to LV lead upgrade. More patients selected fora CRTcapable ICD platform than plain ICD eventually received LV lead (73% vs 11%; HR=0.18, p=0.001). In patients with NYHA class I and II symptoms, progression to LV lead upgrade was higher in patients selected by arrhythmia specialists for CRT than plain ICD (74% vs 9%, HR=0.12,p<0.001). Pts with baseline QRS width <120 ms vs >120 ms had 12% vs 31% progression, (HR=0.37, p=0.005). QRS width >120 ms more modestly predicted progression in pts with NYHA II (HR=0.42, p=0.0028). Finally, baseline NYHA I vs NYHA II and III moderately predicted progression (HR=0.38, p=0.014). Conclusions: In ICD patients, arrhythmia specialists predict the rate of progression to LV lead upgrade more accurately than do baseline NYHA class, LVEF, and QRS width. PHARMACOLOGICAL THERAPY OF HEART FAILURE P2474 Ivabradine improves systolic function and enhances FKBP12 expression after myocardial infarction followed by 3 weeks of reperfusion N. Couvreur 1, R. Tissier 1,S.Pons 1, V. Chetboul 1, V. Gouni 1, J.L. Pouchelon 1, P. Bruneval 2, J.L. Dubois-Rande 1, B. Ghaleh 1, A. Berdeaux 1. 1 INSERM U 955 Equipe 03, Creteil, France; 2 INSERM U 872, Paris, France Purpose: Heart rate reduction by the If current inhibitor ivabradine (IVA) improves left ventricular (LV) function in animal models of permanent coronary artery ligation and congestive heart failure. However, it remains unknown whether ivabradine also improves LV function of the infarcted and reperfused myocardium. Accordingly, our goal was to investigate the effect of chronic infusion of IVA on global and regional LV function following myocardial infarction and long term reperfusion in rabbits. Methods: Myocardial systolic function was assessed before a 20 min coronary artery occlusion and during the subsequent 3 weeks of reperfusion by echocardiography and tissue tracking imaging. Throughout reperfusion, rabbits received either IVA (10 mg/kg/day, n=9) or vehicle (Control, n=8) using implanted osmotic pumps. At 3 weeks reperfusion, LV remodeling was investigated by histology and expression of several proteins (SERCA2a, RyR2-P, phospholamban, FKBP12) involved in calcium handling. Results: After 3 weeks, IVA induced a significant decrease in heart rate by 20% as compared to Control (214±9 vs 266±14 bpm, respectively). In Control rabbits, ejection fraction and regional systolic displacement were significantly decreased as compared to baseline values (43±4% vs 63±2% and 1.4±0.2 vs 2.8±0.2 mm, respectively) and were associated with a progressive LV enlargement and a huge interstitial fibrosis within the reperfused zone (risk zone: 30±2% of LV and infarct

121 Pharmacological therapy of heart failure 421 size: 8% of LV). Chronic administration of IVA prevented the reduction in ejection fraction (58±3% vs 66±3% in baseline) and the decrease in regional systolic displacement of the territory that was submitted to ischemia (1.9±0.3 vs 2.6±0.3 mm). This improvement was not related to a difference in risk zone or infarct size nor to a difference in the interstitial fibrosis in the peri-infarction border zone. Interestingly, this improvement in LV global and regional function by IVA was associated with a significant increase in FKBP12 expression in myocardial samples issued from the reperfused area without any changes in SERCA2a, RyR2-P and phospholamban. Conclusion: Chronic heart rate reduction with IVA significantly improves systolic global and regional contractile functions after 3 weeks of reperfusion. These beneficial effects of IVA might at least partially result from an adaptation of calcium handling as suggested by the increase in FKBP12 expression. P2475 L-4F reverts left ventricular dysfunction in db/db mice via increases in pampk, penos and HO-1 expression C. Vecoli 1,L.Vanella 2,D.Neglia 3, S. Peterson 2,D.Bedja 4, N. Paolocci 4, N.G. Abraham 2, A. L Abbate 1. 1 Scuola Superiore Sant Anna, Pisa, Italy; 2 Columbia University Medical Center, New York, United States of America; 3 CNR Istituto di Fisiologia Clinica, Pisa, Italy; 4 Johns Hopkins University, Baltimore, United States of America Background and goals: Diabetes is a major social disease associated with cardiovascular complications. Several mechanisms have been proposed to explain the genesis and the progression of diabetic cardiomyopathy to eventual heart failure. We investigated the effects of L-4F, an apoliprotein A1 mimetic, on myocardial function and microvascular coronary reactivity in type 2 diabetic mice. We hypothesized that L-4F improves cardiac function and reduces coronary constriction increasing NO bioavailability via increases in pampk, pakt and HO-1. Methods: db/db mice were treated for 6 weeks with L-4F (200 ug/100 gm BW) or vehicle. Trans-thoracic echocardiography was performed in conscious animals. Isolated hearts were subjected to ischemia/reperfusion protocol: 20 at 65 mmhg perfusion pressure (PP), 30 at 30 mmhg (low PP) and finally 30 of reperfusion (65 mmhg PP). Left ventricular (LV) function (intraventricular balloon) and coronary tone were monitored. pakt, pampk, penos, HO-1 protein expression and HO activity were measured. Results: L-4F improved LV pump function compared to vehicle-treated: fractional shortening was 57.6±3.8% vs 44.4±4.3%, ejection fraction was 80.9±3.5% vs 67.8±5.2% (both p<0.001), LVEDD and LVESD were both significantly reduced (p<0.05) as well as LV mass. Hearts isolated from L-4F-treated animals confirmed the improvement in LV function in terms of RPP, dp/dtmax and dp/dtmin (p<0.0 01) in both baseline conditions and during reperfusion. L-4F reduced coronary resistance to levels less than in control (p<0.05). In db/db mice decreased levels of pakt, pampk and penos were seen in cardiac tissue. L-4F treatment increased pakt, pampk and penos in db/db mice and increased NO bioavailability as manifest by an improved vasodilator effect. L-4F treatment increased HO-1 protein and HO activity in cardiac tissue. Conclusion: L-4F treatment reversed the cardiac morpho-functional abnormalities that characterize diabetic cardiomyopathy through a mechanism that involved the increased expression of HO-1, pampk and pakt. These findings suggest HO-1 as a potential therapeutic target for diabetes and its associated health risks. P2476 Activation of histone/protein deacetylase SIRT1 by resveratrol induces MnSOD up-regulation via FOXO3a and improves survival of heart failure animals A. Kuno 1, M. Tanno 1,T.Miura 1,Y.Horio 2,K.Shimamoto 1. 1 Second Dept. of Internal Medicine, Sapporo Medical University, Sapporo, Japan; 2 Dept. of Pharmacology, Sapporo Medical University, Sapporo, Japan Purpose: Deletion of manganese superoxide dismutase (MnSOD), a major superoxide scavenger in the mitochondria, results in dilated cardiomyopathy and neonatal death in mice. SIRT1, an NAD+-dependent histone/protein deacetylase, has been shown to inhibit oxidant stress-induced cell death. Here, we examined the mechanism of cytoprotection afforded by SIRT1 and the effects of resveratrol (RSV), a polyphenol activator of SIRT1, on progression of heart failure in a model of cardiomyopathy. Methods and Results: Antimycin A (AA, 50 μm), an oxidant stressor, significantly increased the level of reactive oxygen species (ROS) determined by 2,7 - dichlorofluorescein and induced apoptosis in both C2C12 myoblasts and neonatal rat cardiomyocytes. Transfection of wild-type SIRT1 or treatment with RSV (10 μm) resulted in up-regulation of MnSOD, decrease in ROS production and suppression of apoptosis. The effects of wild-type SIRT1 were not mimicked by a deacetylase-inactive SIRT1 mutant H355Y. The protective effects of SIRT1 and RSV were abolished by knockdown of SIRT1 or MnSOD, or by the SIRT1 inhibitor nitotinamide. Chromatin immunoprecipitation assay in C2C12 cells showed that binding of SIRT1 and FOXO3a to the promoter of MnSOD was significantly increased after AA treatment, though binding of FOXO1 or FOXO4 to the promoter was unchanged. The expression level of p53 was not increased by AA, arguing against a role of p53 in AA-induced apoptosis. Treatment of TO-2 cardiomyopathic hamsters (TO-2) with RSV (4 g/kg in chow) from the age of 6 weeks decreased the level of acetylated histone H3 in the myocardium. Echocardiography showed that the left ventricular ejection fraction at 25 weeks was significantly better preserved in RSV-treated TO-2 than in controls (34.3±2.2% vs. 27.9±1.6%, p=0.02). At 35 weeks, heart weight-to-body weight ratio and the myocardial BNP-mRNA level were significantly lower, interstitial fibrosis was attenuated, and myocardial expression of MnSOD was significantly higher in RSV-treated TO-2 than in untreated controls. Kaplan-Meier analysis revealed that RSV improved survival of TO-2 from 7% to 27% during a 51-week follow-up period (p=0.028, hazard ratio = 0.41). Conclusion: Activation of SIRT1 by RSV improves the prognosis of heart failure. Suppression of apoptosis by SIRT1-mediated up-regulation of MnSOD through FOXO3a transactivation is likely to contribute to the protection afforded by RSV. P2477 Beta-blockers improve survival in patients with heart failure regardless of renal function. An analysis of the Cardiac Insufficiency BIsoprolol Study II (CIBIS II) trial D. Castagno 1, P.S. Jhund 2, J.J.V. Mcmurray 2,E.Erdmann 3, F. Zannad 4, W.J. Remme 5, J.L. Lopez Sendon 6, P. Lechat 7, H.J. Dargie 8 on behalf of CIBIS-II Investigators. 1 San Giovanni Battista Hospital, University of Turin, Cardiology Unit, Turin, Italy; 2 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; 3 Klinik III fur Innere Medizin der Universitat zu Koln, Cologne, Germany; 4 University of Nancy, Nancy, France; 5 Sticares Cardiovascular Research Institute, Rhoon, Netherlands; 6 Department of Cardiology, University Hospital La Paz, Madrid, Spain; 7 AFSSAPS (Agence Francaise de Securite Sanitaire des Produits de Sante), Saint Denis, France; 8 Western Infirmary, Glasgow, United Kingdom Purpose: Renal impairment is common amongst patients with chronic heart failure (HF) and is consistently associated with an increased risk of adverse outcomes. Beta-blockers improve survival in HF but are underused in those with renal impairment. We examined the effect of bisoprolol according to renal function in patients with HF taking part in the Cardiac Insufficiency BIsoprolol Study (CIBIS) II. Methods: We divided patients into four groups based on estimated creatinine clearance (Ccr) calculated using the Cockcroft-Gault formula corrected for body surface area (BSA): Ccr < 45, 45 to <60, 60 to < 75 and 75 ml/min/1.73 m 2. Cox proportional hazard models were used to compare clinical outcomes (the primary endpoint of all-cause mortality and a post hoc composite outcome of death or HF hospitalization) according to treatment intervention across Ccr groups. The model adjusted for age (years), gender, presence of diabetes mellitus, HF aetiology (ischaemic, idiopathic, others), baseline systolic blood pressure and ejection fraction. To assess whether renal function modified the relation between bisoprolol and outcomes, an interaction term combining treatment allocation and Ccr was entered into the model. Analysis was based on intention-to-treat. Results: Data were available for 2626 patients (99.2% of the original study). Median creatinine clearance was 64.6 ml/min/1.73 m 2 (IQR ). The following were more common in those in the lowest Ccr category: older age, female sex, diabetes, ischaemic aetiology of HF. Ejection fraction did not differ. There was no interaction between beta-blocker therapy and renal function on the risk of either outcome (Table). Conclusions: The beneficial effects of bisoprolol were not modified by baseline renal function in CIBIS II. Patients with HF and renal impairment should not be denied beta-blockers. P2478 The anti-diabetic drug voglibose reduces myocardial infarct size and improves left ventricular function via stimulation of GLP-1 receptors and PI3 kinase-akt-enos pathway in rabbits M. Iwasa 1, H. Kobayashi 1, S. Yasuda 1,S.Sumi 1,H.Ushikoshi 1, K. Nishigaki 1, G. Takemura 1,T.Fujiwara 2, H. Fujiwara 3, S. Minatoguchi 1 on behalf of Department of Cardiology, Gifu University Graduate School of Medicine. 1 Department of Cardiology,Gifu University Graduate School of Medicine, Gifu, Japan; 2 Kyoto Women s University, Kyoto, Japan; 3 Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan Background: Glucagon-Like Peptide-1 (GLP-1) has been reported to prevent Abstract P2477 Table 1 Outcome Creatinine Clearance Category (ml/min/1.73 m 2 ) p Value for Interaction <45 45 to <60 60 to <75 75 (bisoprolol and renal function) N=450 N=669 N=640 N=867 All-cause mortality No of events 105 (23.3%) 98 (14.6%) 87 (13.6%) 89 (10.3%) 0.87 Bisoprolol/Placebo Hazard Ratio (95% CI) 0.71 (0.48 to 1.05) 0.69 (0.46 to 1.04) 0.53 (0.34 to 0.83) 0.64 (0.42 to 0.98) All cause death or HF hospitalization No of events 152 (33.8%) 158 (23.6%) 140 (21.9%) 146 (16.8%) 0.41 Bisoprolol/Placebo Hazard Ratio (95% CI) 0.75 (0.54 to 1.03) 0.67 (0.48 to 0.92) 0.53 (0.37 to 0.74) 0.52 (0.37 to 0.73)

122 422 Pharmacological therapy of heart failure postprandial hyperglycemia and to protect the heart. On the other hand, it has been reported that α-glucosidase inhibitor lead to an increase in plasma GLP-1. Furthermore, a recent large-scale clinical trial, the STOP-NIDDM trial (a study to prevent non-insulin-dependent diabetes mellitus), showed that another α- glucosidase inhibitor acarbose reduces the risk of myocardial infarction. Therefore, we hypothesized that an α-glucosidase inhibitor voglibose might reduce myocardial infarct size via production of GLP-1. Methods: Japanese white rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Rabbits were assigned randomly to 6 groups (n=7 in each): a control group, a voglibose group fed diets containing 3.5mg/kg/day voglibose for 7days, and a voglibose + exendin (9-39) group (fed the same diet as the voglibose group along with i.v. exendin (9-39), a GLP-1 receptor blocker, 3 nmol/l), an exendin only (9-39) group (3 nmol/l), a voglibose + wortmannin group (fed the same diet as the voglibose group along with i.v. wortmannin, a PI3K inhibitor 0.6mg/kg), a wortmannin only group (0.6mg/kg). Myocardial infarct size was measured as a percentage of the risk area. Cardiac function was evaluated by echocardiography. Plasma GLP-1 levels were measured before and 1, 2 and 3 hours after eating. Western blotting was performed to examine the expression of Akt and enos in the myocardium. Results: The infarct size was significantly smaller in the voglibose group (23.4±3.0%) than in the control group (43.8±3.4%) (p<0.001), and this effect was abolished by pretreatment with exendin(9-39) (38.2±2.9%) or wortmannin (46.8±1.8%). By itself, exendin(9-39) (40.6±4.7%) or wortmannin (41.8±3.2%) had no effect on infarct size. Ejection fraction in the voglibose group (65.4±1.6%) was significantly larger than that in the control group (54.9±2.5%) (p<0.001). This effect was completely abolished by exendin(9-39) (53.4±1.2%) or wortmannin (50.0±2.6%), though, by itself, exendin(9-39) (54.5±0.9%) and wortmannin (49.6±1.0%) had no effect on ejection fraction. Voglibose increased plasma GLP-1 levels. Phospho-Akt and phospho-enos were over-expressed in the myocardium of the voglibose group. Conclusion: The α-glucosidase inhibitor voglibose reduces myocardial infarct size and improves left ventricular function via stimulation of GLP-1 receptors and PI3-kinase, Akt and enos in rabbits. This finding may provide new insight into therapeutic strategies for diabetic patients with coronary artery disease. P2479 Determinants and clinical relevance of cardiac function recovery in anthracycline-induced cardiomyopathy D. Cardinale 1,G.DeGiacomi 1, A. Colombo 1, C. Pandini 1, M. Civelli 1, N. Colombo 1, G. Lamantia 1, C. Fiorentini 2, C.M. Cipolla 1. 1 Cardiology Unit - European Institute of Oncology, Milan, Italy; 2 Centro Cardiologico Monzino, Milan, Italy Purpose: The response to modern heart failure (HF) therapy in patients with anthracycline (AC)-induced cardiomyopathy (CMP) has never been evaluated in clinical trials. Hence, evidence-based recommendations for management of this form of CMP are still lacking. We evaluated the response to HF therapy and its clinical predictors in a large population of patients with AC-induced CMP. Methods: From March 1, 2000 to March 1, 2008 we evaluated all consecutive patients, with a left ventricular ejection fraction (LVEF) 45% due to AC-containing chemotherapy (CT). Pharmacological therapy, including enalapril (up-titrated to 20 mg/day) and, when possible, carvedilol (up-titrated to 50 mg/day), was initiated. LVEF was measured at enrollment, every month for the first 3 months, every 3 months during the first two following years, and every 6 months afterwards. The primary outcomes were LVEF recovery and major adverse cardiac events during a follow-up time >1 year. Patients were considered Responders, Partial Responders, or Non Responders according to complete (LVEF increase 10 absolute points associated with LVEF 50%), Partial (LVEF increase 10 absolute points with LVEF <50%, or LVEF increase <10 absolute points with LVEF 50%) or no recovery of LVEF (LVEF increase <10 absolute points with LVEF <50%). Results: Two-hundred-one patients were enrolled. The mean follow-up duration was 37±28 months. Sixty-seven patients (33%) significantly improved their LVEF and were considered as Responders to HF treatment; 44 patients (22%) were Partial Responders, and 90 patients (45%) were Non Responders. The percentage of Responders progressively decreased as the time from the end of CT to the start of HF treatment (time-to-treatment) increased. In no case complete LVEF recovery was observed after 6 months. Responders showed a lower rate of cumulative cardiac events than Partial and Non Responders (3%, 23%, and 29%, respectively; P<0.001). At multivariate analysis, time-to-treatment was an independent predictor of lack of LVEF recovery (OR 2.8, 95% CI 2.0, 3.9; P<0.001 for each doubling in time-to-treatment). Conclusions: In cancer patients with AC-induced CMP a complete LVEF recovery may be achieved when cardiac dysfunction is early detected and a treatment with enalapril is promptly initiated, if possible in association with carvedilol. Recovery of LVEF is associated with reduction of long-term clinical events. P2480 Discontinuation of high-dose rosuvastatin treatment deteriorates endothelial function in patients with chronic heart failure E.B. Beck 1,S.Erbs 1, V. Adams 1,A.Linke 1, N. Kraenkel 1, R. Hoellriegel 1, S. Moebius-Winkler 1, R. Hambrecht 2, G. Schuler 1. 1 Herzzentrum der Universitaet Leipzig, Leipzig, Germany; 2 Klinikum Links der Weser, Bremen, Germany In patients (pts) with chronic heart failure (CHF) endothelial dysfunction has been partially attributed to an impaired regenerative capacity of circulating endothelial progenitor cells (CPC) and an increased oxidant stress. Previously, we were able to show that high-dose rosuvastatin augments amount and functional capacity of CPC in pts with CHF and reduces oxidised LDL cholosterol (oxldl) which was associated with a correction of endothelial dysfunction. Aim of the present study was to elucidate, whether these beneficial effects of rosuvastatin treatment outlast the active treatment period. Methods: Forty-two pts with CHF (LVEF 30±1%, 12 with ischemic heart disease, 30 with dilated cardiomyopathy) were randomized to 12 weeks of 40 mg rosuvastatin daily or placebo therapy in a double-blind manner followed by a 4 weeks washout period. At begin, 12 and 16 weeks, acldl/lectin+ CPC were recovered from blood-derived mononuclear cells by cell culture and counted using FACS. Functional capacity of CPC was determined by matrigel assay. OxLDL was measured by ELISA. Flow-mediated dilatation (FMD) of the radial artery was assessed by high resolution ultrasound. Results: The rosuvastatin mediated decrease in LDL cholesterol levels by 56±2% (p<0.05 vs. placebo) completely disappeared after the washout period. Rosuvastatin increased CPC number by 224% (p=0.04 vs. placebo), four weeks after treatment cessation the number declined to initial values. The ability of CPC to integrate into endothelial networks rose from 1.5±0.5 to 2.9±0.6 cells per 100 coronary endothelial cells (p<0.05 vs. placebo for change) in response to rosuvastatin and dropped to 1.7±0.3 cells per 100 coronary endothelial cells after washout. OxLDL level was reduced from 40±7 to 30±5 μmol/l after rosuvastatin treatment and increased to 46±6 μmol/l after treatment discontinuation (p<0,05 vs. placebo for change). FMD increased in the rosuvastatin group from 6.7±1.0% at begin to 17.7±2.5% after 12 weeks (p<0.05 vs. placebo) and returned to 7.5±2.0% after cessation of treatment. All parameters remained unchanged in the placebo group. Conclusion: High-dose treatment with rosuvastatin augments the regenerative capacity of circulating endothelial progenitor cells and reduces oxidant stress, which might contribute to the correction of endothelial dysfunction in pts with CHF. However, 4 weeks after treatment cessation, these beneficial effects are completely gone, indicating the importance of high-dose and long-term rosuvastatin therapy to obtain a prognostic cardiovascular benefit. P2481 Percutaneous aortic valve implantation for severe aortic stenosis using self expanding prosthesis: initial spanish experience P. Avanzas Fernandez 1, A.J. Munoz Garcia 2, J. Segura Saint- Gerons 3, M.F. Jimenez Navarro 2, M. Pan Alvarez-Ossorio 3, I. Lozano 1,C.Moris 1, J. Suarez De Lezo 3, J.M. Hernandez Garcia 2. 1 Hospital Universitario Central de Asturias, Oviedo, Spain; 2 Hospital Carlos Haya, Malaga, Spain; 3 Hospital Universitario Reina Sofia, Cordoba, Spain Purpose: To describe the procedural performance, 30-day and 1 year outcomes following implantation using the 18 Fr CoreValve Revalving System in Spanish patients with severe aortic stenosis. Methods: Patents with symptomatic severe aortic stenosis were included in the study (n=73). Additional inclusion criteria included the following: (1) aortic valve area <1 cm 2 (<0.6 cm 2 /m 2 ); (2) aortic valve annulus diameter measuring >20 mm and <27 mm; (3) sinutubular junction measuring 40 (small valve) or 43 mm (large valve), determined by echocardiography; (4) diameter of the femoral vessel >6 mm, in case of femoral approach. Results: From December 2007 to February 2008, 73 patients with a mean age of 78,1±6,6 years, mean aortic valve area 0.65±0.2 cm 2 and median logistic EuroSCORE of 9 [15,4-6,9] were recruited. After valve implantation, the mean echocardiographic transaortic valve gradient decreased from 79,4±18 to Hemodynamic profile (example, 1 patient)

123 Pharmacological therapy of heart failure ,5±6,4 mmhg (figure). All patients had no or paravalvular aortic regurgitation < grade 2. The rate of procedural success was 98,6%. None of the patients died in the procedure. Acute complications of the procedure presented in 9 patients (12,3%): tamponade, failure of femoral percutaneous closure, aortic dissection, myocardial infarction, acute aortic regurgitation that required in valve new prosthesis. At 30 days, the all-cause mortality rate and combined rate of death, stroke and conversion to surgery were 5,5%. Annual Kaplan-Meier estimated survival rate (median follow up period, 4,5 months) was 80%. Conclusions: In severe aortic stenosis patients with contraindications to surgery, percutaneous valve replacement is a good alternative. P2482 Soluble guanylyl cyclase activation with HMR 1766 provides additional benefit to ACE inhibition on cardiac remodeling postinfarction J. Bauersachs 1, D. Fraccarollo 1, P. Galuppo 1, S. Motschenbacher 1, H. Ruetten 2, A. Berbner 1, S. Schraut 1, A. Schaefer 1,G.Ertl 1. 1 Medizinische Klinik und Poliklinik I, Julius-Maximilians-Universität Würzburg, Würzburg, Germany; 2 Aventis Pharma Deutschland GmbH, Frankfurt Am Main, Germany Background: Impairment of nitric oxide (NO) signaling contributes to progression of heart failure. Activation of soluble guanylate cyclase (sgc) by NO is the key event in NO/sGC/cyclicGMP signaling. We investigated the effects of the NO independent sgc activator HMR1766 (Sanofi-Aventis) alone and in combination with the angiotensin-converting enzyme (ACE) inhibitor ramipril, on hemodynamics and cardiac remodeling in rats after extensive myocardial infarction (MI). Methods and Results: Starting 7 days after MI, rats were treated with placebo, HMR1766 (10mg/kg, twice daily), ramipril (1 mg/kg/day), or a combination of both, administered by gavage for 9 weeks. Infarct size was similar among the experimental groups. HMR1766 monotherapy, like ACE inhibition, improved left ventricular (LV) function, attenuated the rise in LV filling pressure (LVEDP), and LV volume compared to placebo. Combination therapy with ramipril more effectively improved LV function and LV ejection fraction, and led to a substantial further leftward shift of the LV pressure volume curve and reduction in LVEDP and LV volume. In addition, LV pressure isovolumic decay, LV dp/dtmax divided by instantaneous pressure, pulmonary fluid accumulation and right ventricular hypertrophy were significantly improved by the sgc activator HMR1766 and further ameliorated by HMR1766/ramipril. Interstitial fibrosis and myocyte cross-sectional area were markedly increased in placebo rats, significantly decreased by HMR1766 and further reduced by HMR1766/ramipril. Moreover, the addition of HMR1766 to ACE inhibition enhanced the ratio of capillaries to cardiomyocytes and reduced the increased superoxide anion formation in the failing LV myocardium more effectively than either monotherapy. Conclusions: Long-term treatment with the NO independent sgc activator HMR1766 improved LV dysfunction and remodeling in rats postinfarction to a similar extent as ACE inhibition. Combination of HMR1766 with an ACE inhibitor was more effective than either monotherapy. Thus, sgc activation constitutes a promising therapeutic approach to prevention of postinfarction ventricular remodeling and heart failure. P2483 Myelosuppressives protect post-myocardial infarction heart by activating cell survival signal, SDF-1/CXCR4 axis and attenuating fibrosis and apoptosis H. Ushikoshi 1,Y.Misao 1,Y.Li 1,T.Ohno 2,N.C.Khai 1, G. Takemura 1, T. Fujiwara 3,H.Fujiwara 1, S. Ogura 1, S. Minatoguchi 1. 1 Gifu University, School of Medicine, Gifu, Japan; 2 Aichi Gakuin University, Nagoya, Japan; 3 Kyoto Women s University, Kyoto, Japan Purpose: Leukocytosis is a well-known phenomenon of myocardial infarction (MI) at acute phase. Recently we reported that myelosuppressives improve left ventricular (LV) function following reperfusion-induced acute MI. However, the role of myelosuppressives in permanently occluded large MI remains unclear. Here we aimed to elucidate the beneficial effects of myelosuppressives using 5-fluorouracil (5FU) and cyclophosphamide (Cy) in post-mi heart. Methods: (1) In vitro study: Primary cultured mouse ventricular cardiomyocytes and cardiac fibroblasts were incubated in the presence or absence of 5FU and Cy. Cell growth and cytoskeleton was evaluated. (2) In vivo study: An murine MI model was created by permanent coronary occlusion. On the next day after MI, 5FU (100 mg/kg), Cy (50mg/kg) or saline (control, C) were injected intraperitoneally. Cardiac function, histological changes, cell survival signaling and apoptosis were evaluated. FACS analysis was performed to detect circulating CD34 positive cells. Results: (1) 5FU and Cy inhibited cardiac fibroblast proliferation in a dosedependent manner without any remarkable damage on cardiomyocyte. (2) 5FU and Cy increased peripheral CD34 positive cells (5FU: 30.5±5.5/μl, Cy: 21.8±4.6/μl vs. C: 11.2±6.1/μl, p < 0.05). Myelosuppressives also reduced the area of MI (5FU: 27.9±4.3%, Cy: 30.4±5.3% vs. C: 39.6±8.6%, p < 0.05) at one week after MI and improved cardiac function (by LVEF; 5FU: 42.9±6.4%, Cy: 38.8±6.9% vs. C: 28.2±6.2%, p < 0.05). Heart weight also decreased four weeks after MI (p < 0.01). Histological findings showed an enhancement of angiogenesis at the border area (by capillary density, p < 0.01), a decreased fibrosis area (p < 0.05) in 5FU treated hearts, and decreased Ki-67 positive and TUNEL positive cells in the MI area of both groups (5FU: 1.8±1.0%, Cy: 0.9±0.8% vs. C: 4.4±1.1%, p < 0.01). Immunoblotting analysis showed upregulated SDF- 1/CXCR4 axis, VEGF, ANP, activated Akt, STAT-3 and Bcl-2, indicating enhanced angiogenesis and cell survival signaling, and reduced apoptosis in treated hearts. Conclusions: Upregulation of cell survival signaling and angiogenesis, reduction of fibrosis and apoptosis may play important roles in the beneficial effects caused by myelosuppressives in acute-mi. These findings suggest that myelosuppressives are good candidates for novel protective therapy of the post-mi heart. P2484 Effects of parasympatthetic preservation on noninvasive myocardial function in Wistar rats with myocardial infarction R.A. Sirvente, R.N. Fuente, L.E. Souza, I.C.M. Silva, G.O. Candido, C. Mostarda, S. Lacchini, M.C. Irigoyen, V.M.C. Salemi. Instituto de Cardiologia da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil Purpose: The preservation of the parasympathetic function by the blockade of the acetylcholine degradation causes cholinergic stimulation. It leads to tone down the ventricular dysfunction and decrease heart injury after myocardial infarction (MI). The aim of our study is to evaluate the repercussion of the chronic inhibition of the acetylcholinesterase activity using of pyridostigmine bromide (acetylcholinesterase inhibitors) on the ventricular function and invasive hemodynamics characteristics of rats with MI in different times after coronary artery obstruction. Methods: Male Wistar rats were divided in groups control (C), treated with pyridostigmine bromide (P), myocardial infarction group (I) and myocardial infarction treated with pyridostigmine bromide (IP). These groups were studies 7, 21 and 42 days after MI. The methodology employed included invasive cardiac hemodynamics parameters, as left ventricular (LV) end-diastolic pressure and noninvasive cardiac parameters by echocardiography such as LV ejection fraction and mass, and MI size. The MI size was measured in shorts-axis view at level of papillary muscle as the ratio of akinetic area/lv area 100. Results: Results are shown in the Table (* vs C, + vs I, *+ p 0.05). The enddiastolic pressure and the LVEF presented negative correlation in all groups and all times (r = -0.65; p 0.05). Echocardiographic parameters Variable Group C Group P Group I Group IP LVEF (7 days) 0.70± ± ±0.16* 0.67± LVEF (21 days) 0.75± ± ±0.01* 0.43± LVEF (42 days) 0.74± ± ±0.02* 0.67± LV mass (g/kg, 7 days) 4.10± ± ± ±0.10 LV mass (g/kg, 21 days) 4.10± ± ± ±0.13 LV mass (g/kg, 42 days) 4.10± ± ± ±0.07 MI size (%, 7 days) 38.70± ± MI size (%, 42 days) 20.00± ± LVEF, ejection fraction left ventricular; LV mass, left ventricular mass; MI size, myocardium infarction size. Conclusion: The treatment with pyridostigmine bromide reverts or reduces the myocardial dysfunction in rats 42 days after MI and decreases the end-diastolic pressure to values near to control animal. This drug could represent a new therapeutic to patients with MI. P2485 Beta-blocker CONtinuation Versus INterruption in patients with Congestive heart failure hospitalized for a decompensation episode G. Jondeau 1, P. Lechat 2 on behalf of B convinced investigators. 1 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 2 Pitie-Salpetriere Hospital (AP-HP), Paris, France Background: Beta-blocker benefit is established in chronic systolic heart failure, but not in acute heart failure because its acute negative inotropic effect may be deleterious. Whether beta-blocker therapy should be stopped during acute heart failure is unknown. Methods: In a randomised, open labelled, controlled trial, we compared betablockade continuation with beta-blockade discontinuation during acute heart failure in patients with LVEF below 40% previously receiving stable beta-blocker therapy. Patients were randomised by a concealed, computerised telephone randomisation system. The design was that of an non inferiority trial, with 80% power to detect a 12.5% lower rate of improvement of dyspnoea and general well being at 3 days evaluated by physician blinded for therapy. This study is registered with ClinicalTrials.gov, number NCT Results: 169 patients were included, among which 147 were evaluable. Mean age was 72±12 years, 65% males. Mean EF was 32±7%, 31% were in atrial fibrillation, initial BNP was 1314±1180 pg/ml. After 3 days 92.8% of patients pursuing beta-blockade improved vs. 92.3% discontinuating beta-blockade (upper limit for unilateral 95% CI: 6.6% < 12.5%), indicating non-inferiority. Similar findings were obtained at 8 days and when evaluation was made by the patient. Plasma BNP at day 3, length of hospital stay, rehospitalisation rate and death rate after 3 months were also similar. Beta-blocker therapy at 3 months was given to more patients in whom beta-blocker therapy was kept during acute heart failure. Conclusion: In conclusion, during acute heart failure, beta-blocker therapy

124 424 Pharmacological therapy of heart failure should remain unchanged because this attitude is not associated with delayed or lesser improvement, but with a higher rate of prescription of beta-blocker therapy at 3 months, which benefit is well established. P2486 Time to treatment and vasodilator efficacy in acute heart failure: Results from the Pre-RELAX-AHF study G.M. Felker 1, J.R. Teerlink 2,P.Ponikowski 3, A.A. Voors 4, G. Filippatos 5, B.H. Greenberg 6,S.L.Teichman 7, G. Cotter 8, B.D. Weatherley 8,M.Metra 9. 1 Duke Clinical Research Institute, Durham, United States of America; 2 University of California, San Francisco, San Francisco, United States of America; 3 Military Clnical Hospital, Wroclaw, Poland; 4 University Medical Center, Groningen, Netherlands; 5 University Hospital Attikon, Athens, Greece; 6 University of California, San Diego, United States of America; 7 Corthera, Inc, San Mateo, United States of America; 8 Momentum Research, Durham, United States of America; 9 University of Brescia, Brescia, Italy Purpose: Rapid initiation of therapy is a cornerstone of the management of myocardial infarction, but this paradigm has not been applied to acute heart failure (AHF). Using data from the PreRELAX-AHF study, a Phase II randomized trial of the novel vasodilator relaxin, we sought to evaluate the impact of time to treatment on AHF outcomes. Methods: PreRELAX-AHF enrolled 234 patients with AHF and systolic blood pressure > 125 mmhg within 16 hours of admission (median 7 hours) and randomized them to 4 doses of relaxin or placebo. The relationship between time to treatment (time from presentation to randomization) and treatment effect was modeled for the most efficacious dose of relaxin (30 mcg/kg/24h for 48h) compared to placebo. Five endpoints were assessed: dyspnea relief (Likert and VAS), worsening heart failure (WHF) by day 5, length of stay, and days alive and out of hospital at 60 days. Results: There was a relationship between the time to treatment and treatment effect across all five endpoints examined. In particular, earlier treatment was associated with trends towards greater dyspnea relief (p=0.13 for VAS AUC at 5 days and 0.15 for Likert at 24 hours, Figure) and a lower probability of WHF out to day 5 (p=0.16). Quantitatively, patients randomized within 1 hour of presentation had almost twice the predicted treatment effect on dyspnea as those randomized at 8 hours (1808 vs. 891 for VAS AUC). Conclusions: The effect of relaxin on dyspnea appeared to be related to time to treatment, with greater treatment effect with early initiation of therapy. These data are among the first to suggest a time to treatment effect in AHF, and support early initiation of vasodilator therapy in patients presenting with AHF and normal or elevated systolic blood pressure. P2487 A natural p300-specific histone acetyltransferase inhibitor, curcumin, can prevent the development of heart failure in addition to ACE inhibitor after myocardial infarction in rats T. Morimoto 1,M.Fujita 2, Y. Sunagawa 2,H.Wada 3,T.Takaya 3, S. Yanagi 2, A. Marui 2, T. Ikeda 2,A.Shimatsu 3, K. Hasegawa 3. 1 University of Shizuoka, Shizuoka, Japan; 2 Graduate School of Medicine Kyoto University, Kyoto, Japan; 3 Kyoto Medical Center, National Hospital Organization, Kyoto, Japan Purpose: Signals activated by hemodynamic overload to the heart finally reach the nuclei of cardiac myocytes, activate hypertrophy-responsive transcription factors such as a zinc finger protein GATA-4, and cause their maladaptive hypertrophy. Activation of these factors is mediated, in part, through acetylation controlled by histone deacetylases and an intrinsic histone acetyltransferase (HAT), p300. While nuclear acetylation is being recognized as a critical event during myocardial cell hypertrophy, pharmacological heart failure (HF) therapy that targets this pathway has yet to be established. Recently, we found that curcumin, a p300 histone acetyltransferase inhibitor, prevents the deterioration of systolic function in two independent heart failure models of heart failure in rats. To apply this novel therapy for the clinical setting, it should be clarified whether curcumin possesses additional effects on conventional therapy for heart failure by angiotensin converting enzyme inhibitors (ACEI). The purpose of this study was to examine the effect of ACEI/curcumin combination therapy on heart failure after myocardial infarction (MI). Methods: Rats were subjected to sham operation or MI. One week later, we performed LV functional studies by echocardiography in all surviving rats. The rats with moderate size of MI (fractional shortening (FS) < 40%) were then randomly assigned to 4 groups: I: solvents (control) (n=8), II: enalapril (ACEI, 10mg/kg/day) alone (n=8), III: curcumin (50mg/kg/day) alone (n=8), and IV: curcumin plus enalapril (n=8). Oral treatments of these agents were repeated everyday and continued for 6 weeks. Results: There were no differences among 4 groups in all left ventricular (LV) geometric and functional data examined before treatment. After treatment, LVFS was significantly (p<0.05) higher in the ACEI group (29.0%) and in the curcumin group (28.7%) than the vehicle group (21.6%). Notably, LVFS significantly (p<0.05) increased by ACEI/curcumin combination therapy (34.7%) compared with therapy by either ACEI or curcumin. LV wall thickness and cardiomyocyte diameter were significantly smaller in the ACEI/curcumin than the ACEI group. Moreover, perivascular fibrosis was significantly reduced in the ACEI group and the curcumin group compared with the vehicle group. This reduction was further augmented in the ACEI/curcumin group. Conclusions: A natural compound, curcumin in addition to ACEI, has beneficial effects on LV post-mi systolic function in rats. Thus, this non-toxic dietary compound may be applicable for heart failure therapy in the clinical setting. P2488 Chronic heart failure patients with high collagen type I degradation marker levels benefit more with ACE-inhibitor therapy D.N. Tziakas 1, S. Chatzikyriakou 1, G. Chalikias 1,D.Stakos 1, A. Thomaidi 1, S. Manousakis 1, H. Boudoulas 2. 1 Democritus University Thrace, Alexandroupolis, Greece; 2 Biomedical Research Foundation, Athens, Greece Purpose: Not all patients respond to ACE-I equally. It has been hypothesized that genetic or other phenotypic variations might be useful in predicting the therapeutic efficacy of these drugs. With the present study we assessed the prognostic impact of angiotensin converting enzyme -inhibitor (ACE-I) therapy in chronic heart failure (CHF) patients with different degree of collagen metabolism as assessed by serum levels of a collagen type-i degradation marker (CITP). Methods: 196 (126 male, of mean age 69±10 years) CHF patients were studied prospectively for 12 months. Serum concentrations of CITP were measured at study entry and its association with survival was analyzed by using as a cut-off its median value. CHF patients were divided into groups according to whether (n=114) or not (n=82) they received ACE-I therapy as well as to their CITP levels. The endpoint of the study was cardiac death. Results: Survival was significantly lower in ACE-I naïve patients with high CITP levels (Group D) compared to other subgroups (overall p<0.001). In specific these patients had lower survival rate (52.2%) compared to ACE-I naïve patients with low CITP levels (Group A, survival rate 83.3%, p=0.003), to ACE-I users with low CITP levels (Group B, survival rate 80%, p=0.006) and to ACE-I users with high CITP levels (Group C, survival rate 70.4%, p=0.015). Survival rates did not differ between Group A, Group B and Group C. Conclusions: ACE-I related improve in mortality was most predominant in CHF patients with high CITP levels and the increased cardiac risk associated with high CITP levels was ameliorated with ACE-I therapy. CITP levels possibly reflect an activated status of the renin-angiotensin-aldosterone system and may be of clinical relevance since they identify a subgroup of patients that benefit more with ACE-inhibitor therapy. P2489 Effects of the new vasodilator relaxin for the treatment of patients with acute heart failure and normal to elevated blood pressure: results of a phase 2b study (Pre-RELAX-AHF) M. Metra 1, J.R. Teerlink 2, A.A. Voors 3,G.M.Felker 4, P. Ponikowski 5, B.D. Weatherley 6, G.S. Filippatos 7, E. Unemori 8,S.Teichman 8,G.Cotter 6 on behalf of RELAX-AHF Investigators. 1 University of Brescia, University of Cardiology, Brescia, Italy; 2 Section of Cardiology, Veterans Affairs Medical Center, University of California San Francisco, Ca, United States of America; 3 Department of Cardiology, University Medical Center, Groningen, Netherlands; 4 Cardiology, Duke Clinical Research Institute, Durham, Nc, United States of America; 5 Department of Cardiology, Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland; 6 Momentum Research, Inc., Durham, Nc, United States of America; 7 2nd University Department of Cardiology, Atticon University Hospital, Athens, Greece; 8 Corthera Inc, San Mateo, CA, San Mateo, Ca, United States of America Purpose: This prospective, double blind, placebo controlled, dose ranging study evaluated the efficacy, dose-response and safety of relaxin, a natural human peptide that modulates biologic responses to pregnancy, including vasodilation and

125 Pharmacological therapy of heart failure 425 increased renal function, in patients with acute heart failure (AHF) and normal or elevated blood pressure (BP). Methods: Eligible patients were those hospitalized <16 h for AHF with dyspnea (Class III or IV), congestion on chest X-ray, elevated BNP or NTpro-BNP (>350 or >1400 pg/ml, respectively), decreased renal function (egfr ml/min) and systolic BP >125 mmhg. Patients were randomized to a 48h IV infusion of placebo (PBO) or relaxin at 10, 30, 100 or 250 mcg/kg/d. Endpoints included improvement in dyspnea to Day 14 (by serial 7-point Likert and Visual Analog Scales [VAS]), clinical signs, renal function and clinical outcomes up to Day 180. Results: A total of 234 patients from 8 countries were enrolled at 8.4±5.4 hours from admission and were followed 4.5 months on average. The 5 treatment groups were well-balanced at baseline. Dyspnea improvement was greater with relaxin compared to PBO, and most pronounced for relaxin 30 mcg/kg/d (RLX- 30). Substantial dyspnea relief was rapid and sustained: Likert Scale showed moderate or marked improvement in dyspnea at 6, 12 and 24h in 41% of RLX-30 vs 23% of PBO, p= VAS change from baseline AUC to Day 14 was greater for RLX-30 (8214±8712 mm-hr) vs PBO (4622±9003 mm-hr), p= Other active doses had smaller, but similar effects. RLX-30 favorably affected other HF measures including greater diuresis and weight loss, lower IV diuretic and IV nitroglycerin use and lower rate of in-hospital worsening HF. There were no safety or tolerability issues. In the active arms vs PBO, mean hospital stay was 1-2 days shorter and, at Day 60, the mean days alive and out-of-hospital were 3-4 days greater. At Day 60, cardiovascular (CV) death or HF rehospitalisation occurred in 17%, 10%, 3%, 8% and 6% in PBO, 10, 30, 100 and 250 dose groups, respectively (p=0.06, RLX-30 vs PBO). CV death at Day 180 was estimated at 14%, 2%, 0%, 3% and 6%, respectively (p=0.04 for RLX-30 vs PBO). Conclusions: This study is the first to assess the effect of relaxin in patients with AHF and normal to high BP. When given early, IV relaxin for 48 hours was safe and was associated to rapid and sustained improvement in dyspnea and other HF measures. These early effects on symptoms may translate into longterm benefits. A larger study to confirm these effects is currently being initiated and conducted (RELAX-AHF). P2490 Initial observations of intravenous CD-NP, chimeric natriuretic peptide, on renal function in chronic heart falure patients H.D. Lieu 1,S.R.Goldsmith 2, J.M. Neutel 3, B.M. Massie 4, D.L. Mann 5, M. Komajda 6, J.B. Young 7, J. Hodge 8,H.H.Chen 9, J.C. Burnett 9. 1 UCSF; Nile Therapeutics, San Francisco, United States of America; 2 University of Minnesota, Minneapolis, United States of America; 3 University California Irvine, Irvine, United States of America; 4 University of California, San Francisco, San Francisco, United States of America; 5 Saint Louis University School of Medicine, St Louis, United States of America; 6 UPMC, Universite Pierre et Marie Curie, Paris, France; 7 Cleveland Clinic, Cleveland, United States of America; 8 Nile Therapeutics, San Francisco, United States of America; 9 Mayo Clinic, Rochester, United States of America Background: CD-NP is a novel chimeric natriuretic peptide engineered with venodilatory and renal protective properties. Preclinical studies have demonstrated that CD-NP has renal enhancing and less hypotensive effects than nesiritide. The effects of CD-NP in patients (pts) with chronic heart failure (HF) are unknown. The objective of this study was to evaluate the effects of increasing doses of CD-NP on renal function and diuresis in HF pts. Methods: Chronic HF pts with systolic blood pressure 110 mmhg and EF <40% with signs and symptoms of HF (NYHA class 2/3) received escalating doses of CD-NP infusion for 24 hours in this open-label trial. Daily medications, including furosemide and vasoactive medications, were administered to pts on the day prior to and withheld on the day of CD-NP infusion. Results: Eighteen HF pts completed the CD-NP infusion (6 at 3 ng/kg/min, 6 at 10 ng/kg/min, and 6 at 20 ng/kg/min). The mean age was 56±13 years and 85% were men. CD-NP s effect on blood pressure was dose dependent. The maximum tolerated dose was 20 ng/kg/min. Renal function was significantly improved following treatment with CD-NP (table). Improvement of renal function and filtration markers was consistent across the doses up to 20 ng/kg/min of CD-NP. CD-NP s effect on diuresis was observed for all doses. While the comparison is limited by the non-randomized temporal sequence, the volume of diuresis induced by CD- NP was comparable to that induced by physician-selected doses of furosemide over a 24 hour period. Chronic HF patients (n=16) Baseline Combined CD-NP doses P value (furosemide day) (without furosemide) CrCl (ml/min, CockCroft-Gault) 119±46 129±48 P<0.01 Creatinine (mg/dl, plasma) 1.09± ±0.4 P<0.01 Cystatin-C (mg/dl, plasma) 1.10± ±0.35 P<0.01 Absolute Urine Volume (ml, 24-hour urine collection) 2217± ±1274 P=0.14 Conclusions: In chronic HF pts, 24-hour infusions of CD-NP statistically improved renal filtration markers, while achieving similar diuresis to furosemide. Initial observations are supportive of CD-NP induced renal enhancing properties. Additional trials are needed to confirm these findings. P2491 Is there a role to erythropoiesis-stimulating proteins in the treatment of anemic chronic heart failure patients: a meta-analysis of randomized controlled trials F. Canario-Almeida 1, L. Azevedo 1, F. Ferreira 2, O. Azevedo 2, J. Guardado 2,F.Sousa 2,J.Almeida 2, A. Costa-Pereira 1. 1 Faculdade Medicina do Porto, Porto, Portugal; 2 Centro Hospitalar Alto Ave, Guimarães, Portugal Purpose: The recognition of the high prevalence and the independent prognostic role of anaemia in heart failure (HF) have contributed to intensification of research for an effective treatment. A central role of erythropoietin in cardiorenal anaemia syndrome has been proposed. Several randomized controlled trials (RCT) have demonstrated the safety and efficacy of erythropoietin-stimulating proteins (ESP) in correcting anaemia in patients with HF. However, as some studies have failed to show benefit, the role of this novel therapy in the treatment of HF is not defined. The objectives of this meta-analysis were to quantify the effects of recombinant human erythropoietin treatment on clinical efficacy, mortality, hospitalizations and quality of life of chronic HF patients. Methods: Systematic review of RCT that compare ESP therapy with standard care published in Medline, IsiWeb of Knowledge, Scopus and Cochrane Library. Eight studies (696 patients, 377 in the intervention group) fulfilled all inclusion criteria. The mean time of follow-up was 38±13 weeks. Data concerning haemoglobin and/or haematocrit levels, New York Heart Association (NYHA) functional class, exercise tolerance, number of hospitalizations, mortality rate and health related quality-of life (QoL) were extracted and pooled across studies using a random effects meta-analysis. Results: The overall incidence of adverse events was similar in both groups. There were significant increases in haemoglobin in the pooled intervention group (1.78±0.96 g/dl vs 0.08±1.23 g/dl, P<0.001). There were non-significant improvements in ESP group regarding NYHA functional class, exercise duration and tolerance or quality of life score compared with placebo. A non-significant trend was observed towards a lower risk of hospitalization (HR 0.78; 95% CI 0.5,1.14; p=0.4) and all-cause mortality (HR 0.84; 95% CI 0.61, 1.09, p=0.1) in intervention group compared with placebo. Conclusion: Initial studies using ESP that have shown improvement in cardiac function, functional capacity, health-related quality of life and exercise tolerance had small sample size and were underpowered. Recent RCT with long follow-up periods raised the question of clinical benefit of ESP therapy in chronic HF patients. This meta-analysis suggests that correction of anaemia with ESP therapy is well tolerated, effectively raise and maintain haemoglobin levels without significant objective clinical benefits, apart from a trend to reduce hospitalizations rate and mortality. Further investigation with adequately powered RCT is mandatory to clarify the appropriate treatment strategy of anaemia in HF. P2492 The olive constituent oleuropein prevents the doxorubicin-induced heart failure in anesthetized rats I. Andreadou 1,F.Sigala 1,K.N.Naka 2, K. Ioannidis 1,N.Kavantzas 1, N. Aligiannis 1, A.L. Skaltsounis 1,E.Mikros 1, E.K. Iliodromitis 3, D.T. Kremastinos 3. 1 University of Athens, Athens, Greece; 2 Dept.of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece; 3 Athens University Hospital Attikon, Athens, Greece Introduction: Oleuropein (OLEU) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves conferring protection to the heart. Doxorubicin (DXR) is one of the most effective chemotherapeutic agents but with a dose-dependent induction of cardiomyopathy and heart failure. The aim of the present study was to evaluate the effect of OLEU in DXR-induced heart failure in vivo. Methods: Ninety rats were randomly divided into 6 groups and treated as follows: Control group with no treatment, OLEU-1 and OLEU-2 groups, treated with 70 and 140 mg/kg -1 of OLEU respectively, given intraperitoneally (i.p.), for 14 consecutive days, DXR group treated with i.p. injection of 18mg/kg -1 of DXR, divided into 6 equal doses and given over a period of 2 weeks, OLEU-1-DXR and OLEU-2-DXR groups, rats treated with OLEU and DXR for 14 days as previously described. At the end of the injection protocols the rats were anesthetized and subjected transthoracic echocardiographic examination (Vivid-i, GE Healthcare with a 12MHz probe). Then the rats were sacrificed and the hearts were rapidly excised for histological evaluation and for tissue assessment of malondialdehyde (MDA) as an index of oxidative stress. Results: Eighty two rats completed the study. The mortality in the DXR group was 18.7% by end of the injection protocol. Normal morphology of the cardiac tissue was seen in the Control group and in groups OLEU-1 and OLEU-2. Myocardium exhibited morphological changes in DXR group only including edema, chronic inflammation and degeneration of myocardial cells such as vacuolization. In the OLEU-1-DXR and OLEU-2-DXR groups mild hypertrophy without edema, inflammation and myocardial degeneration was observed. OLEU treatment reduced the DXR induced lipid peroxidation by decreasing tissue MDA. DXR induced a small decrease in wall thickness, a decrease in left ventricular (LV) mass, a decrease in fractional shortening (an index of systolic function), an increase in end-systolic LV diameter, and a trend towards adverse cardiac remodeling. Combined OLEU- DXR and OLEU alone groups did not cause any change and the animals did not differ from the normal Control.

126 426 Pharmacological therapy of heart failure Conclusion: The present data suggest that OLEU successfully prevents DXR induced heart failure and serves as a novel treatment that would eliminate cardiotoxity when it is combined with DXR. P2493 Nebivolol is effective and safe in elderly heart failure patients with impaired renal function D. Kotecha 1, A. Cohen-Solal 2, D.J. Van Veldhuisen 3,M.Bohm 4, A.J.S. Coats 5, M. Roughton 1, D. Babalis 1, P. Poole-Wilson 6, L. Tavazzi 7, M. Flather 1. 1 Royal Brompton Hospital, London, United Kingdom; 2 Lariboisiere Hospital (AP-HP), Paris, France; 3 University Medical Center, Groningen, Netherlands; 4 Universitaetsklinikum der Saarlandes, Homburg, Germany; 5 The University of Sydney, Sydney, Australia; 6 Imperial College London, London, United Kingdom; 7 GVM Hospitals of Care and Research, Cotignola, Italy Purpose: Beta-blocker therapy improves outcomes in heart failure (HF) patients, as confirmed by the SENIORS trial (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure), a unique and realistic cohort of HF patients. However the efficacy and safety of nebivolol therapy in those with impaired renal function is not currently known. Methods: SENIORS recruited 2128 patients 70 years or older who had symptomatic heart failure, irrespective of ejection fraction with creatinine <250μmol/L, randomising to nebivolol or placebo. Participants were divided by tertile of glomerular filtration rate (GFR) and patient characteristics analysed within and across tertiles and compared against the primary outcome (composite of all cause mortality or cardiovascular hospital admission) and secondary outcomes. Results: Mean age was 76, 37% were female and mean GFR 65 ml/min. GFR was strongly associated with outcomes (primary outcome rate of 40% with low GFR, 31% in middle tertile and 29% in highest tertile; p<0.001). No interaction was noted between renal function and the effect of nebivolol on outcomes (primary outcome, p=0.442; mortality p=0.521; hospitalisations, p=0.637), suggesting that nebivolol was as efficacious in participants with low GFR; see figure. Safety data imply that nebivolol use in patients with moderate renal impairment is not accompanied by an increase in adverse events, apart from slightly higher rates of drug-discontinuation due to bradycardia (2.3% vs. 0.8% on placebo; p=0.046). Nebivolol was well tolerated; dose achieved was 7.3 mg in patients with GFR <60 versus 8.0 mg in those with GFR>60. Forest plot for primary outcome by GFR Conclusion: Mild to moderate renal dysfunction, even in the elderly, should not present a limitation to nebivolol use in heart failure patients. had their perhexiline discontinued due to side effects such as nightmare and insomnia. The first drug level check was on average at 10±9 days with 44.8% at therapeutic range and 20.3% were at supra-therapeutic range. The time of third level check was on average at 16±6 weeks with 68.8% of patients within therapeutic range and 20.8% at supra-therapeutic range. The third drug level at the therapeutic range (odds ratio (OR) 3.70, 95% confidence interval (CI) , P=0.003) and the presence of refractory angina (OR 3.57, 95% CI , P=0.004) were independent predictors of response to perhexiline therapy. The long-term follow-up period for mortality data was 37±24 months. The all-cause five-year mortality was 27.7%. Five-year mortality was non-significantly different between patients with refractory angina, chronic heart failure or both, (20.5%, 31.0% and 38.4%, respectively (p=0.11 by Tarone-Ware)). Conclusions: Perhexiline therapy provides symptomatic relief in the majority of patients with minimal side effects or toxicity. Patients with refractory angina and those with a therapeutic third drug level were likely to be responders. P2495 Effect of n-3 PUFA in heart failure patients with different dietary habits: preliminary results of the GISSI-heart failure trial R. Marchioli 1, M.G. Franzosi 2,R.Latini 2, A.P. Maggioni 3, R.M. Marfisi 1, G.L. Nicolosi 4,E.Picchio 5,M.Porcu 6,D.Severini 7, L. Tavazzi 8 on behalf of GISSI-Heart Failure Investigators. 1 Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 2 The Mario Negri Institute for Pharmacological Research, Milan, Italy; 3 Associazione Nazionale Medici Cardiologi Ospedalieri Research Centre, Florence, Italy; 4 Azienda Ospedaliera S Maria Angeli, Pordenone, Italy; 5 Ospedale San Camillo, Rome, Italy; 6 Ospedale G. Brotzu, Cagliari, Italy; 7 Presidio Ospedaliero, Città Di Castello, Italy; 8 Villa Maria Cecilia Ospedale, Cotignola, Italy Aims: To evaluate transferability of the benefit of n-3 PUFA treatment of the GISSI-Heart Failure (HF) trial to patients with different dietary habits (DH) we analyzed the results of a simple food frequency questionnaire (FFQ) on Mediterranean DH. A dietary score (DS) was built to the correctness of Mediterranean DH. Methods: GISSI-HF was a double-blind, placebo controlled trial testing 1 g daily of PUFA in 6,975 HF patients with NYHA class II-IV. DH were assessed with a FFQ collecting information on selected food indicators of Mediterranean dietary habits. To build a DS, the intake of fresh and cooked vegetables, fruit, fish, and olive oil were taken as positive indicators of correct DH at baseline. The effect of n- 3 PUFA according to DS in quartiles (Q1-Q4) and fish intake was assessed for (1) fatal events [total (TM), CV (CVM), HF (HFM), and Arrhythmic (AM)]; (2) CV hospitalization [i.e., total CV (CVH), HF (HFH), and ventricular arrhythmia (VAH)]; and (3) their combination (TM+CVH, HFM+HFH, AM+VAH, MIM+MIH, CM+CH). Cox proportional hazards models adjusted for potential confounders (p<0.15) were fitted. Chi-square tests and tests for trends were used as appropriate to assess possible heterogeneity of benefit. Results: 1,969 deaths (28.2%) from any cause were recorded; AM and HFM accounted for 29.4% and 33.0% of all deaths and together were the two leading causes of CV death (84.8%). No heterogeneity and no trend was found in the benefit of n-3 PUFA on fatal events, hospitalizations, and their combination across the various categories of the DS indicating correctness of Mediterranean DH. The figure shows the effect of n-3 PUFA on total mortality and arrhythmias from patients with the worst (Q1) to the best (Q4) DH. P2494 Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope T. Phan 1,G.NallurShivu 1, A. Choudhury 2, K. Abozguia 1, C. Davies 1, M. Nassimizadeh 1, A. Nassimizadeh 1, I. Ahmed 1, Z. Yousef 2, M. Frenneaux 1. 1 University of Birmingham, Birmingham, United Kingdom; 2 University Hospital of Wales, Cardiff, United Kingdom Purpose: To date, there is very limited long-term clinical data on the use of a metabolic modulator, perhexiline in patients with CHF and/or refractory angina. The objectives of this study is to report on our five years collective experience on the use of perhexiline in the UK, in patients with CHF and/or refractory angina with respect to real-life five-year mortality outcome, predictors of responders, drug side effects and toxicity. Methods: Data was retrospectively collated from two centralized perhexiline database. A total of 151 patients were on perhexiline therapy at the two centres during the period Feb 2003 Dec Patients were initially loaded with 100mg of perhexiline twice daily after initial medical assessments for peripheral neuropathy and liver function testing. Serum perhexiline levels are assayed at approx. 1, 4 and 12 weeks after initiating perhexiline. Results: 151 patients were on perhexiline therapy at two UK tertiary referral centres. Their mean age were 67±12 years old with males making up 69.5%. The indications for perhexiline was refractory angina (54.3%), chronic heart failure (33.1%) or both (12.6%). 58.9% of patients reported to have felt better on the perhexiline (responders). The proportion of patients who developed abnormal AST, ALP and bilirubin were 4.6%, 4.0% and 3.3%, respectively. Four patients (2.6%) Conclusions: The benefit of n-3 PUFA in HF patients was independent of their DH. P2496 Beneficial effects of correction of growth hormone deficiency in chronic heart failure: a randomized, controlled, single-blind study A. Cittadini, G. Carlomagno, L. Saldamarco, A.M. Marra, M. Arcopinto, F. Calabrese, S. Fazio, C. Vigorito, B. Merola, L. Sacca. Azienda Ospedaliera Universitaria Federico II, Naples, Italy Aims: A reduced activity of the GH/IGF-1 axis in chronic heart failure (CHF) has been described by several independent groups, and is associated with poor clinical status and outcome. Aim of the current study was to investigate the prevalence of GH deficiency in a patient population with CHF and to evaluate the cardiovascular effects of GH replacement therapy. Methods and results: We studied 158 consecutive patients with CHF, NYHA class II to IV, who underwent a GH stimulation test. Sixty-three patients satisfied the criteria for GH deficiency and fifty six of them were subsequently en-

127 Pharmacological therapy of heart failure 427 rolled in a randomized, single-blinded, and controlled trial. The treated group (n=28) received GH, on top of background therapy, at a replacement dose of mg/kg every second day ( 2.5 IU). GH replacement therapy improved clinical status and exercise capacity, as shown by a significant reduction of the Minnesota score (from 46±5 to 38±4;p<0.00), increased peak VO2 (from 12.9±.9 to 14.5±1 ml/kg/min; p<0.01), and flow mediated vasodilation of the brachial artery (from 8.8±1.3 to 12.7±1.2%; p<0.01). GH increased slightly the left ventricular (LV) ejection fraction (from 34±2 to 36±2%; p<0.01) and reduced LV circumferential end-systolic stress (from 396±40 to 300±52 kdynes/cm 2 ;p<0.001). This was associated with reduction of circulating NT-proBNP levels (from 3201±900 to 2177±720 pg/ml; p=0.006). Conclusions: GH replacement therapy in patients with CHF and GH deficiency improvesclinical status, exercise capacity, vascular reactivity, and LV function. P2497 Effects of different beta-blockers on arterial wall properties and markers of inflammation in patients with systolic ischemic heart failure used alone or in combination with atorvastatin E.M. Ozova, G.K. Kiyakbaev, Z.H.D. Kobalava, V.S. Moiseev. RPFU, Moscow, Russian Federation Purpose: To compare effects of carvedilol (C) and metoprolol SR (M) on elastic arterial stiffness and markers of inflammation in patients with chronic heart failure (CHF) and low ejection fraction (EF) used alone or in combination with atorvastatin. Methods: 74 patients (17 women) with CHF of ischemic etiology (NYHA class II-IV) and EF 40% were included (mean age - 63,4±9,2). All patients received standard therapy of CHF (including metoprolol as a beta-blocker) and were divided in 2 groups (37 patients each): in first group C was administered (37,5±13,7 mg/day), in second - taking of M was continued (107,9±47,6 mg/day). Atorvastatin (10 mg/day) was randomly administered to 18 patients in group of C and to 17 patients in group of M. Brachial-ankle pulse wave velocity (PWVba), carotidfemoral PWV (PWVcf) and cardio-vascular index (CAVI) were measured using volume sphygmography. Serum markers of inflammation - interleukin-6 (IL-6), IL- 1β, tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) were evaluated. EF was evaluated by 2D-echocardiography. Results: Both beta-blockers improved EF (increasing by 5,2 (p<0,005) and 3,3% (p<0,05) in groups of C and M respectively) but differed in influence on arterial wall properties and markers of inflammation: in group of C significant decrease in PWVcf (from 8,2±2,4 to 7,4±2,2 m/s), CAVI (from 8,8±2,0 to 8,0±1,5), levels of CRP (from 1,0[0,5;1,5] to 0,72[0,44;1,15] mg/dl), IL-1β (from 51,3[31,7;135,3] to 25,7[7,7;48,3]) and TNF-α (from 34,0[19,2;100,0] to 17,9[10,2;40,8] pg/ml) was revealed (for all p<0,05). There were no significant changes of the parameters in group of M. Analysis of subgroups with/without atorvastatin showed that decrease of studied parameters in group of C without atorvastatin wasn t significant (3 and 8% for PWVcf and CAVI and 15, 11 and 14% for CRP, IL-1 β and TNF-α respectively), whereas combination therapy with C and atorvaststin resulted in decrease of PWVcf by 15,2% (p<0,01), CAVI by 8,4% (p<0,01) and reduction of levels of CRP by 25% (p<0,001), IL-1 β by 19% (p<0,003), TNF- α by 20% (p<0,01). Arterial wall and inflammation characteristics didn t significantly change in group of M with atorvastatin, but this treatment was associated with tendency to decrease in PWVcf by 4,9% (p=0,1) and IL1β by 21% (p=0,08). Conclusion: therapy with carvedilol has an additional positive effect on stiffness of elastic type arteries walls and markers of inflammation which is more expressed in combination with atorvastatin and, probably, indicates the potentiating effects of these drugs. P2498 Comparative efficacy of carvedilol and ivabradine in severe chronic heart failure of ischemic origin with baseline heart rate below and above 70 beat per minute L.R. Tumasyan, K.G. Adamyan. Institute of Cardiology, Yerevan, Armenia The aim of study was to assess the efficacy of long-term therapy with carvedilol (C, up to 50 mg) and ivabradine (I, up to 15 mg) on prognosis, plasma brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro- BNP) levels in patients (pts) with ischemic dilated cardiomyopathy in III-IV NYHA class chronic heart failure (CHF) in relation to mean baseline HR below and above 70 beats per minute (b.p.m.). Methods: 96 pts (age 60.1±0.5) with HR 70 b.p.m. and 104 pts (age 58.8±0.3) with HR<70 b.p.m. were randomly assigned to groups receiving C (36 pts and 38 pts), I (30 pts and 34 pts) and non-receiving both drugs (30 pts and 32 pts) in addition to ACE inhibitors and diuretics. The assessment of BNP and NT-pro-BNP levels by ELISA was performed at baseline and after 12 months of follow-up. Results: The 1-year mortality and hospitalization rate were, 36.5% and 68.8% and 23.1% and 44.2% respectively, in pts with HR above and below 70 b.p.m. (p<0.01). The event-free analysis showed lower probability of mortality (RR [relative risk] reduction at 25% and 37.2%) and hospitalization rate (RR reduction at 22% and 36.1%), respectively, in groups of pts with HR below and above 70 b.p.m., treated by C (p<0.05 and p<0.01). The treatment with I was associated with significant (p<0.05) reduction of mortality and hospitalization rate (RR reduction at 20.1% and 21.2%) only in pts with HR 70 b.p.m. Treatment with C (p<0.05 and p<0.01) has resulted to 50% decrease of BNP and NT-pro-BNP in 42% and 65% pts with baseline HR<70 b.p.m. and HR 70 b.p.m., respectively. I use was associated with 50% decrease of BNP and NT-pro-BNP in 22% and 42% (p=ns and p<0.05) in pts with baseline HR below and above 70 b.p.m., respectively. Reduction from baseline of BNP and NT-pro-BNP values 50% and HR 60% was associated with significant improvement of prognosis compared to decrease of BNP and NT-pro-BNP < 30% (RR 0.35 [95% CI ] and 0.36 [95% CI ], p<0.01) and HR < 40% (RR 0.32 [95% CI ] p<0.01), respectively. In conclusions: 1) Heart rate was a strong predictor of 1-year mortality and hospitalization. 2) Decrease of levels of BNP and NT-pro-BNP 50% and HR 60% identified pts with cardiac events reduction. 3) Efficacy of C was revealed in both group of pts, while I use was associated with significant improvement of prognosis only in pts with baseline HR 70 b.p.m. 4) The effects of the C were most marked in the pts with the highest baseline heart rate. P2499 Heart rate reduction by ivabradine reduces diastolic dysfunction and atrial fibrosis in hypercholesterolemic rabbits D. Busseuil 1,Y.Shi 1, M. Mecteau 1, E. Thorin 1, T.K. Leung 1, M. Bouly 2, E. Rheaume 1,J.-C.Tardif 1. 1 Montreal Heart Institute, Montreal, Canada; 2 Institut de recherches internationales Servier, Courbevoie, France Purpose: Heart rate is an independent predictor of cardiovascular mortality and hospitalisations for heart failure in patients with coronary heart disease. The aim of our experimental study was to determine if heart rate reduction with ivabradine, a selective and specific inhibitor of the pacemaker If current, prevents cardiac dysfunction associated with dyslipidemia. Methods: Thirty-two male New Zealand White rabbits received either a standard diet (control group, n=6), a 0.5% cholesterol-enriched diet only (CD group, n=13) or a 0.5% cholesterol-enriched diet with ivabradine (18 mg/kg/day; ivabradine group, n=13) for 12 weeks. Heart rate, left ventricular systolic, diastolic function (classified into normal, mild, moderate and severe diastolic dysfunction) and left ventricular regional myocardial performance index were studied using transthoracic echocardiography. After sacrifice, cardiac interstitial fibrosis was evaluated by Masson s Trichrome staining. Plasma levels of angiotensin II and aldosterone were quantified by immunoassays. Results: Ivabradine reduced heart rate by approximately 11%. At 12 weeks, the severity of left ventricular diastolic dysfunction (DD) was attenuated by ivabradine (92% mild and 8% moderate DD) compared to the CD group (54% mild and 46% moderate DD) (P=0.027). Ivabradine also improved the left ventricular regional myocardial performance index (73±13 vs 101±29% for ivabradine vs CD, P=0.0046), reduced left atrial interstitial fibrosis (16.5±1.1 vs 20.9±1.4% for ivabradine vs CD, P=0.039), and decreased plasma angiotensin II levels (5.5±1.2 vs 16.7±4.8 arbitrary units/ml for ivabradine vs CD, P=0.042). Both angiotensin II and aldosterone levels were correlated with on-treatment heart rate (r=0.37, P=0.038; r=0.46, P=0.008). Conclusions: Selective heart rate reduction with ivabradine reduces diastolic dysfunction and atrial fibrosis in hypercholesterolemic rabbits. Circulating aldosterone and angiotensin II levels were lowered by ivabradine and correlated with on-treatment heart rate. These beneficial effects of ivabradine support testing pure heart rate reduction in patients with diastolic heart failure. P2500 Potential effects of trimetazidine with exercise training in patients with dilated cardiomyopathy M. Gad 1, H. Soliman 1, S. Mehani 2, K. Leon 1,M.AbdElrhman 1. 1 National Heart Institute, Cairo, Egypt; 2 Cairo University, Cairo, Egypt Background and purpose of the study: The improvement in energy metabolism should translate into enhancement in mechanical efficiency. Trimetazidine (TMZ) is effective pharmacological agent in manipulate cardiac energy metabolism, through modifying substrate utilization by failing heart. So, the current study was conducted to investigate the effect of combining TMZ with aerobic exercise training (ET) on exercise capacity and left ventricle (LV) remodeling in dilated cardiomyopathy (DCM). Methods: - Sixty male patients with DCM, (age ranged from 50 to 65 years), NYHA classification class II and III, and LV ejection fraction (EF) 40%, were randomized assigned to four equal number groups. Group (E) participated in graduated exercise training (ET) program, day after day for seven months; group (E&TMZ) received TMZ at doses of 30 mg twice daily in addition to ET; group (TMZ) received TMZ at the same dose without ET; and group (C) received standard medication without ET or TMZ. All patients were on optimal standard medication; and underwent cardiopulmonary exercise test (CPET) and echocardiography examination at the entry of the study and at cession after seven months. Results: - Peak oxygen uptake (VO2max) was increased significantly in E (38.7±19.7%), E&TMZ (43.4±20.2%) and TMZ group (7.2±11.6%) (p<0.01; E&TMZ vs. E, TMZ and C group). Maximum rate pressure product was reduced significantly (p<0.001) in E (17.0±11.6%) and in E&TMZ group (22.0±5.2%) After 7 months, LV dimensions decreased significantly (p<0.001) in both E

128 428 Pharmacological therapy of heart failure and E&TMZ groups. The LVIDd decreased from 68.98±5.89 to 60.05±9.36 (12.4±9.8%) in E, while in E&TMZ from 68.57±3.35 to 54.44±6.57 (20.6±9.0%). The LVIDs from 57.39±5.11 to 45.64±9.6 (21.0±17.2%) in E, while in E&TMZ from 58.04±3.31 to 40.0±7.04 (31.6±10.7%). Both dimensions decreased non significantly (p>0.05) in TMZ patients. EF and FS% improved significantly (p<0.001) in E and E&TMZ groups but nonsignificantly in TMZ (p>0.05). Non significant changes in measured parameters were observed in C group. Conclusion: - It was concluded that TMZ augments the beneficial effects of exercise training on physical work capacity and LV remodeling in patients with DCM. This may be attributed to improvement in endothelial function and/or cardiac energy utilization. Additions TMZ to standard medication without training for DCM require further study. P2502 Aldosterone blocking agents usage in patients with heart failure M. Gheorghiade 1,J.Margolis 2,K.Pan 3, C. Roberts 4, P. Gordon 4, R.A. Gerber 4. 1 Northwestern University, Chicago, United States of America; 2 Thomson Reuters, Bala Cynwyd, United States of America; 3 Thomson Reuters, Cambridge, United States of America; 4 Pfizer Inc, New London, United States of America Background: The use of aldosterone blocking agents when added to standard therapy in pts with severe HF or post-mi with LVSD has been shown to reduce hospitalizations and mortality. Objective: To evaluate usage patterns of aldosterone blockers for pts with recent HF and compliance, CV events, and hospitalizations associated with eplerenone (EPL) and spironolactone (S) in a US population. Methods: A retrospective cohort study using integrated pharmacy/medical claims covering 44.5 mil lives. Study inclusion criteria: pts 50 y/o newly prescribed either S or EPL from 2002 to 2006, with HF diagnosis within 12 mo prior to the index Rx, followed 6 mo to assess clinical outcomes and utilization and 12 mo to assess adherence. (Medication Possession Ratio [MPR]: Rx days supply in first yr/365; and persistence: days from first to last Rx). Results: Of 388,523 pts with HF, 60,183 pts (15.5%) received an aldosterone blocker (n=2,024 EPL and n=58,159 S). Of these, a subset of newly treated pts meeting above inclusion criteria was identified for further study (Table). Postindex, adherence was significantly greater for EPL than for S (p<0.01); 60% and 45% of pts respectively had MPR 80%. Persistence was significantly higher for EPL than for S (p<0.01); 49.5% of EPL pts discontinued tx prior to 1 year compared with 73.7% of S pts. Results* EPL (n=568) S (n=1,982)** p-value Age (yr) 72.0± ±10.7 <0.01 Female (%) <0.01 Post-Index: Follow-up (months) 26.5± ± Adherence (MPR) 0.79± ±0.42 <0.01 Persistence (days) 284± ±158 <0.01 CV events, eg ischemic (%) Hospitalizations (#/yr) 0.86± ± Hospital Days 4.77± ± *mean ± SD, **without combination products. Conclusions: In the US it appears that the majority of patients do not receive an aldosterone blocking agent following the diagnosis of HF, despite the risk for CV events. This analysis raises the hypothesis that the use of eplerenone is associated with higher compliance and fewer hospitalizations compared to S. P2503 Comparison of nitroglycerine and nicorandil in acute congestive cardiac failure V. Singh 1,B.Shah 2. 1 Queen Elizabeth Hospital NHS Trust, King s Lynn, United Kingdom; 2 Seth V S General Hospital, Ahmedabad, India Background: Continuous exposure to organic nitrates is associated with substantial tachyphylaxis. This study compares the therapeutic effects and development of tolerance during continuous intravenous treatment with nitroglycerin versus nicorandil over a 48-hour period. Methods and Results: Twenty patients with congestive heart failure and pulmonary capillary wedge pressure (PCWP) 18 mm Hg were randomly assigned to nitroglycerin (group A) or nicorandil (Group B) intravenous infusions. Doses were titrated to obtain a reduction of PCWP of at least 30% at 6 hours and the doses were maintained for 48 hours, unless clinically indicated. There was no statistical difference between the subgroups in terms of age, sex, and NYHA grade. The pre-treatment PCWP for nitroglycerin was 25.7mm Hg (SD 2.45), decreasing to 18.4 mm Hg (SD 1.96) at 6 hours. The values for nicorandil were 25.4 mm Hg (SD 1.9) and 17.3 mm Hg (SD 1.42), respectively. There was no statistical difference between the two groups till this time (p=0.79 pre-treatment and 0.23 at 6 hours). The mean PCWP values for 24 hours were 19.7 (SD 2.11), and 17.4 (SD 1.35) respectively, which was statistically significant (p=0.036). Similarly the values for 48 hours was 20.6 (SD 2.5) and 17.9 (SD 2.08), which was significant (p=0.026). More tachyphylaxis was seen in Group A patients. PCWP values in Group A and Group B Variables Group A Group B No of patients Males 8 7 Females 2 3 Age 49.9±15.1 (SD-8.05) 51.4±20.6 (SD-11.42) Pre-treatment PCWP 25.7±4.3 (SD- 2.45) 25.4±3.4 (SD-1.90) 6 hours PCWP 18.4±3.6 (SD-1.96) 17.3±2.3 (SD-1.42) 24 hours PCWP 19.7±3.7 (SD-2.11) 17.4±2.4 (SD-1.35) 48 hours PCWP 20.6±4.6 (SD-2.50) 17.9±3.1 (SD-2.08) Group A - Nitroglycerine, Group B - Nicorandil. Conclusion: This study demonstrates that intravenous nicorandil administration gives similar reductions in the PCWP compared to nitroglycerine with significantly less haemodynamic tolerance over a 48-hour period compared with nitroglycerin. This finding may represent a clinical advantage for nicorandil in the short-term treatment of patients with congestive heart failure. P2504 Beneficial electrophysiological effects of trimetazidine in patients with post-ischemic chronic heart failure M. Cera, A. Salerno, G. Fragasso, C. Montanaro, C. Gardini, G. Marinosci, F. Arioli, R. Spoladore, A. Facchini, A. Margonato. San Raffaele del Monte Tabor Foundation, Milan, Italy Purpose: Trimetazidine (TMZ), is an anti-ischaemic drug that could be also effective in patients with chronic heart failure (CHF). Its mechanism of action is analogous to Ranolazine (RNZ), which has also been shown to yield antiarrhythmic properties. Aim of the present study is to assess whether TMZ, analogously to RNZ, could potentially exert electrophysiological effects, particularly on dispersion of atrial depolarization and ventricular repolarization. Methods: P-wave-dispersion (P-w-d), QT interval, QT dispersion (QTd), corrected QT interval (QTc), QTc dispersion (QTc-d), Tpeak Tend and Tpeak-Tend dispersion (Tpeak Tend-d) were measured in 30 consecutive patients with CHF before and 6 months after randomization to conventional therapy plus TMZ (17 patients) or conventional therapy alone (13 patients). Results: No differences between groups were found regarding age, gender, risk factors, NYHA class, LVEF and for all baseline ECG indexes. At 6 months followup, mean P-w-d, QT, QTd, QTc, QTc-d indexes were unchanged from baseline in both groups, whereas Tpeak Tend-d index significantly decreased (from 63.53±24.73 msec to 42.35±21.07 msec, p=0.006) in TMZ group. When divided according to CHF etiology, only ischemic patients treated with TMZ showed a significant Tpeak Tend-d reduction (65.00±27.14 vs ±11.55 msec, p=0.001 in ischemic patients; 60.00±20.00 vs ±33.86 msec, p=ns, in non-ischemic patients). Conclusions: TMZ induces a significant Tpeak Tend-d reduction in patients with post-ischemic CHF. This result suggests the hypothesis that TMZ may reduce susceptibility to ventricular arrhythmias, as assumed by the observed Tpeak- Tend-d reduction. An anti-ischemic effect is probably the main mechanism; however, a direct electrophysiological effect of TMZ cannot be excluded. P2505 The influence of atorvastatin on the parameters of inflammation and the function of left ventricle in patients with dilated cardiomyopathy A. Bielecka-Dabrowa 1,J.H.Goch 2, J. Rysz 3, M. Maciejewski 2, M. Michalska 1, M. Banach 1. 1 Medical University, Department of Molecular Cardionephrology and Hypertension, Lodz, Poland; 2 Clinic of Cardiology, Institute of Cardiology and Cardiac Surgery, Medical University, Lodz, Poland; 3 Clinic of Nefrology, Hypertension and Family Medicine, Medical University, Lodz, Poland The purpose was to assess the influence of atorvastatin on indicators of an inflammatory condition and the function of the left ventricle in patients with dilated cardiomyopathy. Methods: In prospective, randomized study 68 patients with dilated cardiomyopathy (ESC 2007) with EF 40% were divided into two groups: A and B. Group A consisted of 41 patients (93% male) in medium age 56±10 commenced on atorvastatin 40 mg daily for two months and next 10 mg for 4 months. Group B was composed of 27 (74% male) in medium age 59±14 who were treated without statin therapy. Initial and control tests included clinical examination, the assessment of exercise capacity in 6-minute walk test, measurement of TNF-α, IL-6, and IL-10 cytokines concentration in blood plasma, measurement of NT-proBNP concentration in blood serum, echocardiographic examination with assessment of chambers size, ejection fraction, TEI index, dpdt index. Results: In group A compared to group B, IL-6 concentration was considerably lower (9.18±9.50 vs 22±18.58, p=0.000) after two months of treatment with atorvastatin. In group A, the decrease in IL-6 concentration compared to initial values from 16.93±14.52 pg/ml to 9.18±9.5 pg/ml, p=0,002 and the decrease in TNFα levels from 20.76±24.98 to 11.14±14, p=0,008 were achieved. The significantly lower concentration of NT-proBNP in group A ( ± versus ± , p = ) was observed. In group A the decrease of NT-proBNP concentration from ± to 1201±1146, p= was

129 Pharmacological therapy of heart failure 429 observed, while in group B the significant increase of NT-proBNP concentration was found. No significant differences concerning echocardiographic parameters of left ventricle were observed between the examined groups. In group A the decrease in the number of patients qualified as III class NYHA from 47% to 22.5% was observed after 6 months and the distance in 6-minute walk test lengthened considerably from 390±96.97 m to ± as well, while in group B this distance shortened significantly. Conclusions: 1. Atorvastatin treatment decreases the concentration of IL-6 and TNF-α in patients with dilated cardiomyopathy as soon as after 8 months of treatment; however, significantly lower concentration in the statin group was observed only for IL Adding 40 mg of atorvastatin to the optimum therapy results in considerable reduction of NT-proBNP concentration. 3. The clinical improvement in patients with dilated cardiomyopathy was not connected with statistically significant improvement of echocardiographic parameters of the left ventricle. P2506 Elevated HDL cholesterol and male gender predict adequate response to intensified ASA treatment in heart failure patients with ischemic etiology M.T. Dominiak, T. Wcislo, J. Drodz, J.D. Kasprzak. II Chair and Department of Cardiology, Medical University of Lodz, Lodz, Poland Purpose: We sought to determine the rate of resistance to acetylsalicylic acid (ASA) in patients with heart failure of ischemic etiology and whether the rate of platelet activation is related to clinical factors. Furthermore we hypothesized that simple doubling the usual ASA dose may be effective in suppressing ASA resistance. Methods: This study group includes 122 patients with heart failure of ischemic etiology and NYHA class II to IV symptoms (male 66%; mean age 61±10years; mean BMI 27,2±3,9kg/m 2 ; mean ejection fraction 47±13%, mean ARU/aspirin reaction unit/478,7), who used 75 mg/daily ASA for no less than last 7 days. Resistance to ASA was defined as ARU value 550 obtained with point-of-care test Rapid Platelet-Function Assay (RPFA). Subjects resistant to 75 mg ASA were switched to 150 mg/daily for the next 4 weeks. According to the suppression of resistance or lack thereof in a repeated RPFA, 2 subsets of patients were defined: those who regained ASA sensitivity (SensASA150) and those who failed (ResASA150). Results: The prevalence of resistance to 75mg/daily ASA was 18% (n=22; male 68%; mean ARU 601). ASA-resistant patients had higher LDL cholesterol (127±30 vs. 107±40 mg/dl; p=0,013) and lower glucose level (90±14,7 vs. 104,1±30,7 mg/dl; p=0,035) compared with ASA sensitive (n=100; mean ARU 451,9). There was a strong trend toward elevation of total cholesterol in ASA resistant group compared with ASA sensitive (203±39 vs. 186±44 mg/dl; p=0,066; respectively). In repeated RPFA resistance was ascertained only in 9 of 22 patients (ResASA150; mean ARU 576,1) who were previously resistant to 75 mg ASA (success rate after doubling daily ASA dose in 59%(n=13/22); SensASA150; mean ARU456). Only two variables appeared helpful to predict resistance suppression: male gender (OR6.9; PPV/Positive predictive value/84,6%; NPV/Negative predictive value/55,6%; p=0,058; borderline trend) and HDLcholesterol concentration>48,9 mg/dl (OR3,2; PPV 72,7%; NPV 54,6%; p=0,2). ROC curve analysis revealed the value of HDL>48,9 mg/dl as a best predictive for successful ASA resistance suppression (with 62% sensitivity and 75% specificity; p=0,043). Thus, dose increase success can be predicted by male gender and HDL>48,9 mg/dl but not other clinical variables. Conclusions: We demonstrated the prevalence of ASA resistance in 18% of patients with heart failure of ischemic etiology. Pilot substudy on suppression of ASA resistance indicated male sex and higher HDL-cholesterol as possible predictors of success with drug dose escalation. These finding has potential therapeutic implications if confirmed in a larger-sized study. P2507 Preliminary data on a cardioprotective effect of telmisartan in cancer patients treated with epirubicin A. Piras 1, C. Cadeddu Dessalvi 1, M. Dessi 2, M. Deidda 1, G. Binaghi 1, C. Madeddu 2, E. Massa 2, G. Mantovani 2,G.Mercuro 1. 1 Dept. Cardiovascular and Neurological sciences-university of Cagliari, Monserrato, Italy; 2 Dept. of Medical Oncology-University of Cagliari, Monserrato, Italy Purpose: It was previously shown that 1. early cardiac abnormalities occur after epirubicin (EPI) low dose (200 mg/m 2 ), in association with increased levels of inflammatory and oxidative stress markers; 2. the renin-angiotensin-aldosterone system plays an important role in the pathogenesis of EPI-induced cardiotoxicity. Methods: A phase II placebo-controlled study was designed to investigate the possible role of Telmisartan (Tel), an AngII type-1 receptor antagonist, in preventing preclinical myocardial damage induced by EPI. Twenty eight patients (20 women, 8 men, mean±sd age 58±14 years) affected by a variety of solid cancers, previously untreated and candidates for an EPI-based regimen, were enrolled. Further inclusion criteria were: LVEF 55%, Eastern Cooperative Oncology Group performance status 0-2, no history of cardiac disease nor previous mediastinal irradiation. Eligible patients were randomized to receive Tel (40 mg/day) or placebo, starting 1 week before chemotherapy. Patients were studied by means of conventional echocardiography, tissue Doppler (TDI) and Strain (S) and S rate (SR) imaging. Plasma concentrations of reactive oxygen species (ROS) and of the antioxidative defense capacity, by detecting glutathione peroxidase activity (GPx), were also measured. TDI as well as inflammatory/oxidative stress markers were assessed at baseline and 7 days after every new 100 mg/m 2 EPI dose. Results: A significant impairment of SR peak (1.82±0.36 s -1 vs 1.46±0.41 s -1 ; p<0.05) was observed at the 200 mg/m 2 EPI dose in the placebo arm. Moreover, at that time a significant increase in ROS in comparison with respective basal values was found (406±91 FORT-U vs 525±56 FORT-U; p<0.05). Conversely, no significant SR (1.75±0.17 s -1 vs 1.57±0.43 s -1 ; p=n.s.) and ROS (455±64 FORT-U vs 463±83 FORT-U; p=n.s.) changes occurred in the Tel arm. In both arms, GPx showed a significant reduction at the 200 mg/m 2 EPI. Conclusions: We confirmed that EPI cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defences. On the other hand, these preliminary results show that Tel treatment can reverse the early EPI-induced myocardial impairment. This study continuation has to confirm the protective effect of this drug against EPI cardiotoxicity. P2508 Ethnic difference in the response to beta-adrenoreceptor blockade in the treatment of heart failure C.P. Edwards 1,J.Rawlins 1, N. Chandra 1,J.DeCourcey 1, C. Chitty 1, M. Papadakis 2, S. Sharma 1. 1 King s College Hospital, London, United Kingdom; 2 University Hospital Lewisham, London, United Kingdom Objectives: Heart failure is a major cause of morbidity and mortality. The beneficial effects of B-adrenoreceptor antagonists (B-Blockers) in the treatment of heart failure has been demonstrated by several large randomised controlled trials. Patients enrolled in these trials were predominantly Caucasian and included only small numbers of Afro-Caribbean (AC) patients. Sub-group analysis of patients involved in trials based on ethnicity have shown conflicting results as to whether ACs with HF gain similar prognostic and symptomatic benefit from B-blockers as Caucasian. The aim of this study is to assess the response to B-bloackers in an ethnically diverse population of patients managed in a specialized HF clinic. Methods: The case notes of 352 patients (192 AC vs 160 C) with heart failure were reviewed and record was made of the use of B-blockers (including dose). Record was made of mortality, NYHA functional class and heart rate in order to assess response to treatment. Mean follow up was 3.04 years. Results: A similar proportion of AC and C were treated with B-Blockers (AC 84% vs C 83% p=0.88). The number of patients on a maximum tolerated dose was similar (AC 57% vs C 49% p=0.22). Of patients treated with B-Blockers a significant reduction in HR between first clinic and most recent follow up was seen in both ethnic groups (AC 80bpm vs 74bpm p<0.01, C 83 vs 72 p<0.01). NYHA class in both groups were similar at first clinic (p=0.87). There was no significant improvement in NYHA class in Caucasian patient during follow up (p=0.31), though a significant reduction was observed in AC patients (P<0.01). Crude mortality rate did not differ between both groups (AC 56.1 vs 56.2 per 1000 patient years, RR 0.99 CI ). The use of angiotensin converting enzyme (p=0.12) inhibitors and aldosterone antagonists (0.07) were similar in both groups. Conclusions: A similar proportion of patient from both ethnic origins tolerated the use of B-Blockers. The reduction in HR achieved by B-Blockers was similar in both groups. No difference in mortality rate was seen indicating that AC patients gain a similar prognostic benefit as that observed in Caucasian patients. AC gained a symptomatic benefit in NYHA class not seen in Caucasians. This difference could be explained by an ethnic difference in adrenergic response to reduce cardiac output. This study confirms that Afro-Caribbeans with heart failure must be treated with B-Blockers to prevent excess morbidity and mortality. P2509 Symptomatic and asymptomatic heart failure in patients undergoing major vascular surgery: prevalence and pharmacological treatment W.J. Flu 1,J.P.VanKuijk 1, S.E. Hoeks 1,R.Kuijper 1, O. Schouten 1, Y. Van Gestel 1,T.Winkel 1,D.Goei 1,J.J.Bax 2, D. Poldermans 3. 1 Erasmus, Rotterdam, Netherlands; 2 Leiden University Medical Center, Leiden, Netherlands; 3 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Purpose: Congestive heart failure (HF) is considered a large health problem with major clinical impact. As the prevalence of patients with asymptomatic and symptomatic HF is assumed to be similar, this may lead to an underestimation of the extent of HF. This study evaluated the prevalence of symptomatic and asymptomatic HF in patients undergoing vascular surgery and perioperative pharmacological treatment was assessed. Methods: In 1005 patients, routine preoperative echocardiography was performed. Systolic HF was defined as a newly diagnosed left ventricular ejection fraction <40% or patients with previously diagnosed systolic HF. Heart failure symptoms were defined according to the New York Heart Association Classification. Medication use, as recommended in the ESC guidelines was recorded and should have included 1) ACE-inhibitors (ACEI) and/or angiotensine receptor blockers (ARB) and 2) β-blockers. A diuretic should be added in patients with HF symptoms. Results: Symptomatic HF was present in 86 (9%) patients, asymptomatic HF

130 430 Pharmacological therapy of heart failure Figure 1 in 149 (15%) patients and no HF in 770 (77%) patients. 63 (73%) symptomatic and 70 (47%) asymptomatic HF patients were treated with ACEI and/or ARB. Furthermore, 52 (65%) symptomatic and 53 (36%) asymptomatic HF patients were treated with an ACEI and/or ARB in combination with a β-blocker. On top of this, 31 (36%) symptomatic HF patients were treated with a diuretic as well. Conclusions: The current study demonstrated a high prevalence of asymptomatic HF in vascular surgery patients. An under-treatment of recommended medical therapy was observed in both symptomatic and asymptomatic HF patients. Our results have demonstrated that adequate HF diagnosis and treatment is warranted in vascular surgery patients. P2510 Short-term heart rate reduction induced by ivabradine administered to rats with well-established heart failure improves cardiac function, augments neo-angiogenesis and reduces myocardial hypoxia P. Mulder 1,Y.Fang 1, F. Bauer 1, E. Brakenhielm 1, F. Lallemand 1, P. Gluais 2, J. Roussel 2, C. Thuillez 1. 1 INSERM U644, Rouen, France; 2 IRIS, Courbevoie, France Long-term heart rate reduction (HRR) initiated in a pathophysiological situation of moderate left ventricular (LV) dysfunction prevents the deterioration of cardiac function. This is probably related to short-term effects of HRR, i.e. improved myocardial perfusion and reduced O2 consumption, and long-term HRR effects on LV structure, i.e. improved capillary density. However, it is currently unknown 1) whether the short-term effects of HRR are sufficient to improve LV function when HRR is initiated in a setting of well-established chronic heart failure (CHF) and/or 2) whether short-term HRR triggers/activates early mechanism(s) involved in the structural long-term effects of HRR. Thus, we assessed, in a rat model of CHF (coronary ligation), the effects of short-term HRR induced by the If current inhibitor ivabradine (Iva; 10 mg/kg/day as food admix for 4 days starting 93 days after ligation). The table shows heart rate (HR; beats/min), cardiac output (CO; ml/min), LV end-systolic pressure (LVESP; mmhg), LVESP-volume relation (LVESPVR; mmhg/relative Volume Unit), LV end-diastolic pressure (LVEDP; mmhg), Tau (msec), LVEDP-volume relation (LVEDPVR; mmhg/relative Volume Unit) as well as myocardial hypoxia-inducible factor protein levels (HIF-α;arbitrary unit), micro-vessel density (nb/mm 2 ) and endothelial cell proliferation (nb BrdU positive cells/mm 2 ). We found that short-term Iva preserves CO despite the HRR, improves LV filling, contraction, relaxation and compliance, while it reduces myocardial tissue hypoxia and triggers endothelial cell proliferation. In conclusion, in rats with well-established CHF, acute HRR induced by Iva improves systolic and diastolic cardiac function, probably due to the decrease in myocardial O2 consumption and to the increase in myocardial perfusion induced by HRR, causing a reduction in LV tissue hypoxia. Iva also induces endothelial cells proliferation, illustrating neo-angiogenesis by a HIF-α independent pathway. The increase in endothelial proliferation might explain, at least in part, the increase of capillary density observed after long-term HRR. P2511 Does the kind of beta-blocker therapy influence the effect of physical training in heart failure patients? E. Piotrowicz, M. Bilinska, M. Piotrowska, T. Zielinski, R. Baranowski, R. Piotrowicz. Institute of Cardiology, Warsaw, Poland Beta-blockers (BBs) and physical training (PT) are an accepted form of therapy in patients (pts) with heart failure (HF). We can use one of the following BBs: bisoprolol, carvedilol or metoprolol in HF pts. The optimal choice is still disputable. Purpose: The aim of the study was to answer the question: Does the kind of BBs influence the effect of PT in HF pts? Methods: The study group comprised 129 pts (mean 58.2±10.2 years) with HF (NYHAIIandIII; EF<40%) who underwent an 8-week PT. The programmed work- load level was 40% - 70% of peak oxygen consumption (pvo2). Fatigue was not to exceed 11 in Borg scale. All pts during at least 3 months before PT start took an optimal dose of the following BBs: bisoprolol 44pts (B-group), carvedilol 55pts (C-group), metoprolol 30pts (M-group). PT effectiveness was assessed by decrease in rest heart rate ( HR), improvement in peak oxygen consumption ( pvo2), and concentration of high sensitivity c-reactive protein ( hs-crp) Results: The groups were comparable in terms of demographic data, baseline clinical parameters, and pharmacotherapy (angiotensin converting enzyme inhibitors, angiotensin receptor blockers, diuretics, statins). PT significantly improved all parameters studied in all groups. PT effectiveness: In B-group HR was (±6.75) (bpm) p = , pvo2 was 1.95 (± 2.52) (ml/kg/min) p = , hs-crp was 0.23 (±4.54) (mg/dl) p = In C-group HR was (±7.95) (bpm) p = , pvo2 was 1.32 (± 2.65) (ml/kg/min) p = , hs-crp was 0.34 (±2.86) (mg/dl) p = In M-group HR was (±6.42) (bpm) p = , pvo2 was 1.32 (± 2.36) (ml/kg/min) p = , hs-crp was 0.28 (±2.67) (mg/dl) p = The differences between all groups were statistically insignificant. Conclusions: Regardless of the kind of BBs, physical training significantly decreased rest heart rate, improved exercise tolerance and positively affected levels of hs-crp in patients with heart failure. P2512 Echocardiographic detection of increases in ejection fraction in patients with heart failure receiving the selective cardiac myosin activator, CK J.H. Goldman 1,J.R.Teerlink 2,K.G.Saikali 3, F. Malik 3,A.A.Wolff 3. 1 ICON Medical Imaging, Warrington, United States of America; 2 University of California, San Francisco, San Francisco, United States of America; 3 Cytokinetics, Inc., South San Francisco, United States of America Purpose: Ejection fraction (EF) remains a standard measure of left ventricular function in heart failure. Stroke volume by Doppler interrogation of the left ventricular outflow tract (LVOT SV) is more accurately measured than EF by the standard 2D image-derived Method of Discs (MoD), but it is not as familiar as EF. CK (CK-452) increases LVOT SV in heart failure patients by prolonging systolic ejection time (SET). We compared EF changes calculated by hybrid methods (employing both Doppler and 2D data) to EF changes calculated by MoD for patients receiving CK-452. Methods: Using echos obtained before, during and after infusion of the selective cardiac myosin activator, CK-452, EF was assessed by MoD and by Doppler derived LVOT SV as a percentage of ventricular volumes assessed by MoD. Results: EF by MoD did not increase significantly; hybrid EFs increased significantly at [CK-452] >300 ng/ml. Correlation (r-square) of change from baseline in EF vs. change from baseline in SET was 0.73 (p=0.02) for EF by MoD, 0.77 (p<0.0001) for the hybrid EF based on left ventricular end-diastolic volume (LVEDV) and 0.83 (p<0.0001) for the hybrid EF based on left ventricular endsystolic volume (LVESV). Placebo Corrected Changes from Baseline [CK-452] (ng/ml) > > > > > P-value for (n per range) (69) (50) (32) (19) (30) (20) Correlation Baseline vs. [CK-452] SET (ms) 318 3±4 24±5 54±5 65±7 72±8 98±7 < LVOT SV (ml) 68 1±2 1±2 6±2* 12±3 14±3 14±3 < LVESV (ml) 174 0±5-1±5-3±6-12±7-16±8-8±7 <0.05 LVEDV (ml) 251 0±6 2±6 0±7-13±9-16±10-4±9 NS EF-A (%) 32 0±1 0±1 1±1 1±1 1±1 2±1 <0.05 EF-B (%) 30 1±1 1±1 1±2 7±2 8±2 5±2# < EF-C (%) 30 0±1 0±1 1±1 5±1 6±2 3±1# < p<0.05, *p p<0.001, p<0.0001, EF-A = ([LVEDV - LVESV]/LVEDV) 100 (MoD), EF- B = (LVOT SV/LVEDV) 100 (Doppler, MoD), EF-C = (LVOT SV/[LVESV + LVOT SV]) 100 (Doppler, MoD). Conclusions: Hybrid EF calculations relating Doppler-derived LVOT SV to a 2D image-derived ventricular volume may be more sensitive to increases in systolic function than assessments of EF based entirely on 2D imaging. Abstract P2510 Table 1. Effect of Iva on LV function Group Heart Rate CO LVESP LVESPVR LVEDP Tau LVEDPVR HIF-α Micro-vessel density Endothelial cell proloferation Sham 402±16 141±4 133±2 36±1 1.1± ± ± ± ±16 0.5±0.4 CHF 387±6 116±12* 102±5 9±1* 9.0±1.7* 11.7±2.1* 4.4±0.9* 3.3±0.2* 364±66* 1.1±0.4* CHF+Iva 320±12* 124±7* 115±10 19±1* 5.3±0.9* 8.3±1.4* 2.4±0.5* 1.7±0.1* 311±62* 5.9±1.0* *p<.05 vs. sham; p<.05 untreated CHF; n=8-11 per group.

131 Pharmacological therapy of heart failure / Pharmacological and non-pharmacological therapy of heart failure 431 P2513 The combination of low dose furosemide and low dose dopamine is effective and prevents worsening of renal function and hypokalemia during hospitalization for acute decompensated heart failure G. Giamouzis 1, D. Economou 2, G. Karayannis 2,D.Rovithis 2, I. Nastas 3, T. Kyrlidis 3, T. Tsaknakis 3, J. Skoularigis 2,J.Butler 1, F. Triposkiadis 2. 1 Emory University Hospital, Atlanta, United States of America; 2 Department of Cardiology, Larissa University Hospital, Larissa, Greece; 3 General Hospital Volos, Volos, Greece Background: Worsening renal function (WRF) and hypokalemia related to diuretic use for acute decompensated heart failure (ADHF) are common and portend poor prognosis. Some evidence suggests that dopamine may favorably affect renal hemodynamics and function. Aim: To compare the effects of high dose furosemide (HDF) vs. low dose furosemide combined with low dose dopamine (LDFD) on renal function in patients admitted for ADHF. Methods: 32 consecutive patients admitted for ADHF (age 75.8±11.4 years; 50% female; ejection fraction 36±12%) were prospectively randomized to receiving either HDF (IV furosemide 20 mg/h) or LDFD (IV furosemide 5 mg/h plus IV dopamine 5μg/kg/min) after an initial 40 mg IV furosemide bolus. Serum creatinine (scr) and electrolytes were recorded on admission and hourly during the first 24 hours of hospitalization. The first 24-hour urine volume was measured and average hourly urine volume excretion was calculated. Estimated glomerular filtration rate (egfr) was calculated with the simplified MDRD formula. WRF was defined as a rise in scr of 0.3 mg/dl from baseline anytime during hospitalization. The Borg scale was used for dyspnea assessment. Results: Neither the urine volume (362±210ml in HDF vs. 472±407ml in LDFD group, p=0.35) nor the dyspnea score (Borg index at 24 hours -4.9±1.9 inhdfvs. -4.5±1.6 in LDFD group; p=0.58) differ between the two groups. WRF developed in 4/16 (25%) in the HDF vs. none in the LDFD group (p=0.033). When defined as an increase in scr of 25% from baseline, WRF developed in 5/16 (31.3%) patients in the HDF group vs. none in the LDFD group (p=0.015); when defined as 10% decrease in egfr, incidence of WRF in the HDF group still remained significantly higher [8/16 (50%) vs. 2/16 (12.5%) patients, p=0.022]. Incidence of hypokalemia was lower in the LDFD group; there was a 12.8% reduction in serum potassium at 24 hours in the HDF group (3.9±0.4 vs. 4.5±0.4 meq/l from baseline, p<0.001), compared to only 5.6% (4.3±0.6 vs. 4.5±0.5 meq/l from baseline, p=0.09) in the LDFD group (p=0.045 for comparison between the two groups). Conclusion: The combination of low dose furosemide and dopamine is equally effective and safer than high dose furosemide as it reduces the risk for WRFand hypokalemia among hospitalized ADHF patients. Larger studies are required to replicate these results and to further elucidate the effect of dopamine on renal function in these patients. P2514 Imaging options for the selection of anatomically suitable patients for transcatheter aortic valve implantation A.W. Asgar, B. Rana, M. Rubens, N. Delahunty, S. Davies, M.J. Mullen, N. Moat, R. Mohiaddin. Royal Brompton Hospital, London, United Kingdom Purpose: Transcatheter aortic valve implantation (TAVI) is an emerging technology for the treatment of aortic stenosis in high risk surgical patients. Current technology is limited by few available valve sizes which emphasizes the importance of anatomic assessment and patient selection. We compared aortic annulus assessment, done by transthoracic echo (TTE), multi-slice CT and cardiac magnetic resonance imaging (CMR) and calculation of aortic valve area by echo with valve planimetry by CMR. Methods: Patients referred for consideration of TAVI underwent assessment with transthoracic echocardiography, multi-slice CT and cardiac MR. The diameter of the aortic annulus was measured from the transthoracic echocardiographic parasternal long-axis view immediately below the insertion point of the valve leaflets. Aortic valve area by TTE was calculated using the continuity equation.aortic annulus assessment on CT was performed by analysing images in a left ventricular outflow tract (LVOT) view obtained during 65% of the R-R interval. CMR measurement of aortic annulus and aortic valve was made from steady state free precession images of the LVOT. Results: A total of eighteen patients (mean age 74 years, n=6 females) with all three imaging modalities were reviewed for evaluation of aortic annulus size. Bland-Altman analysis was performed and limits of agreement were as follows: between TTE and CMR were (5.3,-11.5) mm, between CMR and CT (6.9,-7.1) mm, and between TTE and CT -3.2 (4.8, 11.3) mm. Aortic valve area as determined by echo using the continuity equation was compared to CMR assessment by planimetry with good agreement; (0.34, -0.45) cm 2. Conclusion: A number of imaging modalities are available for anatomical assessment prior to consideration for TAVI, each method its advantages and limitations. The level of agreement between CMR and multi-slice CT is significantly better than with TTE and these methods should be considered in the routine assessment of these patients prior to consideration for TAVI. PHARMACOLOGICAL AND NON-PHARMACOLOGICAL THERAPY OF HEART FAILURE P2515 The price of being BEAUTIFUL: Does the benefit of Ivabradine in heart failure justify the cost? G.J. Wynn, H. Seetha Rammohan, N. Jakka, N.M. Hawkins, M.I. Burgess. Aintree University Hospitals, Liverpool, United Kingdom Purpose: The recently published BEAUTIFUL study assessed the use of Ivabradine, a selective sinus node If channel inhibitor, in patients with coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD). Despite failing to meet the primary endpoint, the study showed that Ivabradine reduced revascularisation rates and admissions for myocardial infarction (MI) and unstable angina (UA) in a prespecified subgroup of patients with a heart rate of 70bpm or higher (HR 70). We wondered if the findings of BEAUTIFUL were applicable to a real life heart failure population and whether the modest risk reductions seen justified blanket use of Ivabradine in patients with LVSD and HR 70, as suggested on the official BEAUTIFUL study website. Methods: All referrals to the Heart Failure service of a large UK university teaching hospital in 2007 were included. Information was collected retrospectively from electronic patient records. The costs of revascularisation and of hospital admissions for MI and UA were based on up-to-date local tariffs. The cost of Ivabradine was taken from the British National Formulary. Results: Of 389 consecutive referrals with adequate data 321 had impaired LV function of whom 222 patients were adjudged to have coronary artery disease but 89 of these had atrial fibrillation (a contra-indication to Ivabradine). This left 133 patients for analysis of whom 87 had HR 70. Compared to patients with a lower heart rate, a significantly smaller proportion of those with HR 70 were treated with a beta-bloker (67 cf. 85 p=0.04). However, there was a non-significant trend towards a greater incidence of COPD (29% cf. 16%). The mean age, NYHA class, proportion of males and usage of drugs that act on the rennin-angiotension system did not differ significantly between the two groups. Based on the BEAUTIFUL results, treating our patients with CAD, LVSD and HR 70 with Ivabradine for 19 months (the average follow up time in BEAUTI- FUL) would prevent 1 revascularisation, 1.6 hospitalisations due to MI and 0.2 due to UA. This reduction in events would produce a cost saving of (e e 14402) depending on whether the calculation is based on percutaneous or surgical revascularisation. The cost of prescribing Ivabradine for the same patients over the same period would be (e 77647). Conclusions: Although likely to be of benefit in carefully selected patients, routine administration of Ivabradine to patients with CAD, LVSD and HR 70 is not cost effective. P2516 Is there room for further heart rate modulation therapy in a stable heart failure population H.M. Sulaiman, N.F. Murphy, C. O Loughlin, M. Ledwidge, D. McCaffrey, K. McDonald. Heart Failure Unit St.Vincent s University Hospital, Dublin, Ireland Background: Beta-blockers (BB) are an effective therapy in systolic heart failure (HF) with recommendations to titrate to maximal tolerated dose. In select HF trial populations approximately 65% of patients reach target BB doses. Currently, newer heart rate (HR) modulation therapies such as ivabradine are being tested in a chronic HF population. However it is not known how many HF patients would potentially benefit from additional HR modulation therapy. Aim: To assess the frequency of reaching maximum target dose of BB in a community HF population and to document the reasons preventing up-titration. Furthermore we investigated suitability of our population for other HR modulation therapies. Method: A chart review of BB dose 6 months post initiation of therapy in patients with systolic HF (LVEF 45%) attending a HF disease management programme was carried out. The target dose was defined as per current guidelines. Reasons for not achieving target dose were documented in the chart by the doctor during the titration period. Results: 534 systolic HF patients were initiated on BB. The mean age was 68±12years, 68% were men and 61% had ischaemic aetiology. 41% achieved maximum target dose of BB, 48% did not achieve target maximum dose and 11% were intolerant of BB at 6 months. Failure to achieve target dose was due to bradycardia (30%), hypotension (11%) and respiratory symptoms (10%). Less common causes included worsening HF (9%), dizziness not related to blood pressure (10%), fatigue (11%), and physician preference (10%). Mean HR at 6 months was 74±16bpm in the intolerant group, 70±12bpm in the maximum BB group and 68±15bpm in the group not on maximum BB. Of the total population with a LVEF 35% and in sinus rhythm at 6 months (n=347), 19% had a HR 70 bpm (intolerant 20%; maximum BB 32%; not on maximum BB 49%). Conclusion: Target doses of BB are less frequently achieved in community populations than in select trial patients mainly due to haemodynamic reasons. A significant proportion of systolic HF patients are not adequately betablocked highlighting the potential role of newer heart rate modulating agents in HF.

132 432 Pharmacological and non-pharmacological therapy of heart failure P2517 Eplerenone improves endothelium function in patients with chronic heart failure A. Tiritilli, C. Le Gac, J. Clerc, P. Viard, P. Aouate. Centre hospitalier Laennec, Creil, France In chronic heart failure (CHF), a limited bioavailability of NO in peripheral and coronary arteries increases peripheral vascular resistance and decreases myocardial perfusion, contributing to a reduction in myocardial function. The purpose of this study was to investigate the effects of adding eplerenone to patients with stable CHF receiving maximal treatment in order to assess endothelium function. Methods: Twenty five patients with stable NYHA class III-IV were analysed at baseline, 3 and 6 months. Each patient received 25 mg of eplerenone per day. Each patient constituted his own control. At inclusion, all patients underwent a complete clinical examination with ECG, echocardiography-doppler and an extensive biological assessment including BNP, noradrenaline and adrenaline. Endothelial function in the form flow-mediated dilation (FMD) was measured by ultrasound. Concerning endothelium-dependent vasodilation, the variation in brachial artery diameter was evaluated at maximum dilation (from 60 to 200 seconds) in response to reactive hyperaemia. Results were compared with baseline measurements. In terms of endothelium-independent vasodilation, the diameter after sub-lingual nitroglycerin (NTG) spray (0.4 mg) was assessed. The responses to hyperaemia and NTG were expressed as a percent change relative to the diameter immediately prior to cuff inflation and to the diameter immediately before drug administration, respectively. Results: At baseline, the study population presented an FMD of 4.5±1.2% and an NTG-mediated dilation of 15.2±2.3%. For endothelium-dependent function, after 3 months of treatment all patients showed an increased relaxation of 6.7±1.3% (p<001 vs baseline) which was confirmed at 6 months when we observed an even greater increase of 8.5±1.1% (p<0.001 vs baseline). However, the response to the endothelium-independent vasodilator NTG was not significantly different throughout the study 15.1±2.1% (p=ns). Furthermore, we observed an increase in left ventricular ejection fraction (LVEF) of 13.1±1% after 3 months and of 13.9±0.9% at 6 months (p<0.001 vs baseline, p=ns vs 3 and 6 months). A reductions in BNP was also observed 81.3±0.5% after 3 months and 86.5±0.6% at the end of the study (p<0.001 vs baseline, p=ns vs 3 and 6 months). No significant change was seen concerning noradrenaline and adrenaline. Conclusions: In patients with stable CHF, eplerenone added to optimal treatment improve both endothelium-dependent function and LVEF. Although noradenaline and adrenaline remained unchanged, one of the most salient results was that BNP decrease when eplerenone was administered. P2518 Time course analysis of the effect of n-3 PUFA on fatal and non fatal heart failure: secondary results of the GISSI-HF trial R. Marchioli 1,G.Cucchi 2,A.Gualco 3, M.G. Franzosi 4, G. Levantesi 1, A.P. Maggioni 5, R.M. Marfisi 1,G.L.Nicolosi 6, M. Porcu 7, L. Tavazzi 8 on behalf of GISSI-Heart Failure Investigators. 1 Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 2 Ospedale Civile, Sondrio, Italy; 3 IRCCS-Fondazione Salvatore Maugeri, Pavia, Italy; 4 The Mario Negri Institute for Pharmacological Research, Milan, Italy; 5 Centro Studi ANMCO, Firenze, Italy; 6 Azienda Ospedaliera S. Maria Degli Angeli, Pordenone, Italy; 7 Ospedale G. Brotzu, Cagliari, Italy; 8 GVM Hospitals of Care and Research, Cotignola, Italy Aims: GISSI-Heart Failure (HF) trial showed that n-3 polyunsaturated fatty acids (PUFA) decreased absolute mortality by 1.8% during a median 4-year of followup. The contribution of reduction of HF deaths (HFD), hospitalizations (HFH) and their combination (HFE) to the overall benefit of n-3 PUFA has been examined. Methods: GISSI-HF was a double-blind, placebo controlled trial testing 1 g daily of PUFA in 6,975 HF patients with NYHA class II-IV. Analyses were intentionto-treat. Cox proportional models adjusted for clinical variables unbalanced at baseline were fitted. To assess when the curves started to diverge, data were left-censored at times 0, 6, 12, and 24 months. To assess whether the amount of relative risk reduction (RRR) increased during FUP, data were right-censored every 6 months until study end. Results: total deaths, HFD, HFH, and HFE were recorded in 1969, 651, 1974, and 2044 patients, respectively. Absolute risk reduction of HFD was 0.4%, i.e., 22% of the total benefit of PUFA on mortality. PUFA decreased HFE by 6% (0.94, , P=0.144). Survival curves for HFD, HFH, and HFE started to diverge early and remained slightly separated thereafter. As to HFE, RRR were 9%, 6%, 7%, and 6% when we right-censored data at 6, 12, 24, and study end. Figures present the effect of n-3 PUFA on HFE during the course of the study as well as after left-censoring data at 6, 12, and 24 months, respectively and show the divergence of the curves by using multiple starting time points for the analysis. Conclusions: n-3 PUFA decreased non significantly total HF events in HF patients and this effect contributed only in part to their clinical benefit. P2519 Phase II safety study evaluating the novel cardiac myosin activator, CK , in patients with ischemic cardiomyopathy and angina B. Greenberg 1, W. Chou 2, R. Escandon 2, J. Lee 2,M.Chen 2, K. Saikali 2,F.Malik 2,A.Wolff 2, T. Shaburishvili 3. 1 University of California, San Diego, United States of America; 2 Cytokinetics, South San Francisco, United States of America; 3 Diagnostic Services Clinic, Tbilisi, Georgia, Republic of Purpose: CK (CK-452) increases systolic function by directly activating cardiac myosin. In healthy volunteers and stable heart failure (HF) patients, CK-452 infusions resulted in concentration-dependent increases in systolic ejection time (SET), stroke volume, fractional shortening, and left ventricular ejection fraction. The dose limiting effect of CK-452 is related to excessive prolongation of SET, which can limit diastolic coronary flow and ventricular filling. This study investigated whether symptom-limited exercise capacity in HF patients with ischemic cardiomyopathy and angina was deleteriously affected by CK-452 at pharmacodynamically active concentrations. Methods: This double-blind, randomized, placebo-controlled Phase II clinical trial evaluated two dose regimens of CK-452, each including both IV and oral formulations. Two sequential cohorts (randomized 2:1, CK-452:placebo) underwent exercise treadmill testing at baseline and during a 20-hour infusion of study drug. Target IV Cmax for Cohorts 1 and 2 (C1 and C2) was 295 and 550 ng/ml, respectively. Patients then received oral study drug for 7 days. The primary safety endpoint was the proportion of patients who stopped exercise due to angina at a stage earlier than baseline. The study was specifically designed to gain clinical safety experience with CK-452 and not to test statistical hypotheses. Results: A total of 94 patients were treated: 29 with placebo, 31 with CK-452 in C1, 34 with CK-452 in C2. The primary safety endpoint was observed in one patient on placebo and no patients on CK-452. A total of 19 patients (5 placebo, 2 CK-452 C1, 12 CK-452 C2) experienced 27 unique adverse events (21 reported as mild in severity, 4 as moderate, and 2 as severe). No clinically important changes in other safety assessments, including vital signs, ECGs, and cardiac biomarkers, were observed for patients randomized to CK-452 vs. placebo. Conclusions: Results from this study demonstrate that CK-452 did not adversely affect exercise capacity at concentrations that improve cardiac function. The absence of deleterious effect on a broad range of safety assessments in a high risk HF population supports further clinical assessment. P2520 Angiotensin converting enzyme inhibitors in heart failure, do Afro-Caribbean patients gain the beneficial effects observed in Caucasians? C.P. Edwards 1, N. Chandra 1,J.Rawlins 1, M. Papadakis 2,J.De Courcey 1, S. Sharma 1. 1 King s College Hospital, London, United Kingdom; 2 University Hospital Lewisham, London, United Kingdom Objectives: Heart failure (HF) is a leading cause of morbidity and carries a poor prognosis. Epidemiological studies and sub-group analysis from clinical trials indicate that Afro-Caribbeans (AC) with HF have a worse prognosis than Caucasians (C) without conclusive explanation. Clinical trials demonstrating the benefit of angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (AIIRB) included only small numbers of AC patients. The aim of this study was to investigate whether outcome varied with ethnicity in patients treated with ACEI or AIIRB managed in a specialized HF clinic. Methods: The hospital records of 351 consecutive patients (AC 189, C 162) with HF were reviewed and treatment (including doses) with an ACEI or AIIRB, NYHA class at first clinic, most recent clinic and mortality were recorded. The mean follow up was 2.91 years. Results: The use of ACEI or AIIRB therapy did not differ between the groups (AC 94% vs C 94% p=0.91); therapy with ACEI was less common in AC patients (73% vs 83% p 0.05) and the use of AIIRB was more common in AC patients (28% vs 17% p<0.05). More AC were on a maximum tolerated dose of either ACEi or AIIRB (AC 86% vs C 70% p<0.05). NYHA class of patients treated with either ACEI or AIIRB in both groups were similar at first clinic (p=0.90) and at follow up (p=0.48). NYHA class improved significantly during follow up in both groups (p<0.05).

133 Pharmacological and non-pharmacological therapy of heart failure 433 Afro-Caribbean Caucasian NYHA Class First Clinic Most recent First Clinic Most recent I 22.4% 36.3% 22.9% 36.7% II 49.4% 47.6% 47.2% 37.6% III 26.4% 15.3% 28.5% 24.8% IV 1.7% 0.8% 1.4% 0.0% There was no significant difference in crude mortality rate (AC 72.1 vs C 74.7 per 1000 patient years, RR 0.95, CI ). Treatment with B-blockers (86% vs 85% p=0.92) and aldosterone antagonists (48% vs 41% p=0.22) did not differ between ethic groups. Conclusions: Contrary to previous reports this study indicates that AC with HF gain similar symptomatic and prognostic benefit from treatment with ACEI or AI- IRB as C. Treatment of Afro-Caribbean patients with heart failure with ACEI or AIIRB is essential to prevent excess morbidity and mortality. P2521 Prescription of betablockers at hospital discharge and beyond in patients with heart failure. Results from the DEVENIR study A. Cohen-Solal 1, P. Assyag 2, M. Guenoun 3, I. Leurs 4, P. Poncelet 5, P.L. Prost 6, J.F. Thebaut 5,C.Contre 4. 1 Lariboisiere Hospital (AP-HP), Paris, France; 2 AP-HP - Hopital St Antoine, Paris, France; 3 Private Cardiologist, Plan De Cuques, France; 4 MENARINI, Rungis, France; 5 Private Cardiologist, Sarcelles, France; 6 Discovey Cascade, Paris, France Rationale: Beta blockers are a corner stone treatment of heart failure (HF) in patients with altered systolic function (LVEF<40%). Guidelines are less clear for HF patients with preserved systolic function (LVEF>50%) or for patients belonging to the grey zone (LVEF 40-50%). Objectives: to describe the prescription rate of beta-blockers in HF patients Methods: Cross sectional observational survey with retrospective collection of data at hospital discharge. Patients must have been diagnosed with HF and have been hospitalised for HF within the previous 18 months. Patients are classified according to the LVEF at hospital discharge. Results: 1452 patients were included by 412 French outhospital cardiologists with known LVEF at hospital discharge have had at least one visit by the cardiologist between hospital discharge and entry in the survey (mean delay 5.76±4.51 months). In a multivariate model, BB prescription was more frequent in HF from ischaemic origin (OR=1.39) or with dilated cardiomyopathy (OR=1.44) and less frequent in older patients (OR=0.97 per year),in case of asthma/copd (OR=0.31) and in case of LVEF >50% (OR=0.62). LVEF<40% LVEF 40-50% LVEF>50% Total N=661 N=283 N=194 N=1137 At hospital discharge/at entry in the survey BB 78%/83% 78%/85% 62%/70% 76%/82% Recommended BB 75%/77% 72%/74% 54%/62% 71%/74% Reaching the target dose 8%/16% 7%/16% 7%/13% 7%/15% Changes since discharge BB added* 28% 34% 25% 28% BB stopped** 1% 1% 2% 1% BB dose increased* 27% 27% 17% 25% BB dose decreased 4% 1% 3% 3% Metoprolol, nebivolol, bisoprolol, carvedilol; *percentage calculated in patients without BB at hospital discharge (N=278); **percentage calculated in patients with BB at hospital discharge (N=859). Conclusion: Rate of betablockers prescription is high at hospital discharge (76%), 93% of the prescribed BB being one of the 4 recommended for HF. Outhospital cardiologists not only pursue but also amplify the care strategies defined during hospitalisation increasing the proportion of patients receiving BB and the percentage of patients reaching the target dose. P2522 Tranilast in a pharmacological dose has no beneficial effect on the cardiac remodeling and mortality in chronic ischemic heart failure after large myocardial infarction in rats S. Betge, H.R. Figulla. Universitaetsklinikum Jena, Jena, Germany Purpose: Tranilast reduces the interstitial fibrosis and the negative cardiac remodeling in the animal models of hypertensive heart failure and diabetic cardiomyopathy. One of the main mechanisms is the inhibition of the transformiggrowth-factor-β1 that induces the collagen synthesis in cardiac fibroblasts. In this study the influence of tranilast on the cardiac remodeling in the animal model of the chronic ischemic heart failure has been examined. Methods: A large myocardial infarction (MI) was induced in female Lewis rats by ligation of the proximal left anterior descending coronary artery. Time was given for the scar in the infarcted area to develop, then treatment with tranilast (TRA, n=40; 150 mg/kg bd) or placebo (PLA, n=36) was started at day 28. Animals after sham-operation (SHA, n=17) were treated with placebo and served as addition controls. Pressure volume curves of isolated hearts were obtained and analysis of the collagen content in the non infarcted left ventricles (LV) via HPLC and morphometry performed 182 days after operation. Results: The induction of a large MI (TRA, PLA) led to a significant hypertrophy of both ventricles, an increase of collagen content in the non infarcted LV, a dilatation of the LV and a shift of the chamber stiffness variables in the pressure volume analysis of the isolated heart compared with SHA but without any significant difference between both groups. The scar thickness and lengths as well as the total circumferences of the hearts after MI were found at the same levels in both treatment groups in the morphometric analysis. The six months survival rates were: TRA: 62.5%; PLA 75% und SHA 100%. The tendency to a higher mortality rate in TRA was statistically not significant compared with PLA in the Kaplan-Meier analysis. Conclusions: Oral treatment with Tranilast started four weeks after large MI does not have a beneficial effect on the cardiac remodeling and six months mortality in the rat. P2523 Subclinical inflammation and oxidative stress following de novo cardiac transplantation: similar impact of tacrolimus vs. cyclosporine microemulsion M. White 1,B.Cantin 2, H. Haddad 3, J. Kobashigawa 4,H.Ross 5, M. Carrier 1, L. Whittom 6,I.Ali 7,D.Isaac 8, S.H. Wang 9. 1 Montreal Heart Institute and University of Montreal, Montreal, Canada; 2 Hopital Laval, Quebec, Canada; 3 Centre Hospitalier du Centre du Valais, Sion, Switzerland; 4 University of California at Los Angeles, Los Angeles, United States of America; 5 Toronto General Hospital, Toronto, Canada; 6 Montreal Heart Institute, Montreal, Canada; 7 QEII Health Sciences Centre, Halifax, Canada; 8 Foothills Medical Centre, Calgary, Canada; 9 University of Alberta Hospital, Edmonton, Canada Rationale: Tacrolimus (TAC) provides benefit on cardiac rejection, lipid profiles and blood pressure compared with cyclosporine microemulsion (CsA). The evaluation of various biomarkers related to neurohumoral activation, subclinical inflammation and oxidative stress and the impacts of TAC vs CsA immunoprophylaxis have not been investigated following CTX. Methods: One hundred adult de novo CTX subjects were randomized 1:1 TAC: CsA and followed for 1 year. Biomarkers were measured prior to transplantation and at 2, 4, 12, 26 and 52 weeks thereafter. The biomarkers included BNP, high sensitivity C-reactive protein (hs-crp), sicam, monocyte chemotactic protein- 1 (MCP1), interleukin-6, interleukin-18, E-selectin, TBARS, F2-isoprostanes, nitrotyrosin and troponin T. Clinical endpoints included survival, biopsy-confirmed acute rejection (BCAR), dyslipidemia, dysglycemia and renal function (egfr). Results: One hundred patients (52±13 years; 81% male) were randomized of which 98 received study treatment. At 1 year/last visit, 96% of the TAC and 83% of the CsA patients remained on their randomized CNI (p=0.03 and p= 0.04 for time to, and number of, crossovers, respectively, for treatment failure). Eighty-six patients completed the study: 3 TAC and 4 CsA patients died. BCAR grade 3A were observed in 3 TAC and 7 CYCA patients. Changes in lipid {LDL (-0.3±1.1 [TAC] vs +0.2±1.1 mmol/l [CsA]), ApoB (-0.07±0.30 [TAC] vs +0.05±0.31 g/l [CsA])} and egfr (+11 [TAC] vs -51 ml/min/1.73 m 2 [CsA]) were observed at 12 months. There was no significant impact of TAC vs CsA on hypertension and glucose regulation. Changes in selected biomarkers hs-crp sicam Osteopontin F2-isoprostanes TAC CsA TAC CsA TAC CsA TAC CsA Pre-transplant 32.9± ± ± ± ± ± ± ±78.5 At 2 weeks 20.4± ± ± ± ± ± ± ±163 At 4 weeks 13.1± ± ± ± ± ± ± ±153 At 52 weeks/last visit 3.42± ± ± ± ± ± ± ±65.7 Conclusion: De novo CTX recipients exhibit a significant increase in various biomarkers related to subclinical inflammation and oxidative stress. This increase is maximum at 2 and 4 weeks but some biomarkers remain elevated up to 1 year following transplantation. There were no significant differences between TAC vs CsA on these selected parameters. P2524 Negative pre-transplant serostatus for toxoplasma gondii is associated with impaired survival after heart transplantation A.O. Doesch, K. Ammon, S. Celik, M. Konstandin, A. Kristen, L. Frankenstein, F.-U. Sack, H.A. Katus, T.J. Dengler. Universitaetsklinikum Heidelberg, Heidelberg, Germany Background: Chronic Toxoplasma gondii (T. gondii) infection is known to trigger potentially adverse immunoregulatory changes, but limited data exist regarding long-term implications for heart transplant (HTX) recipients (R). We evaluated the risk of all cause mortality regarding T. gondii serostatus prior to HTX. Patients and Methods: Pre-HTX T. gondii serostatus was obtained in serum of 344 recipients (77 female [22.4% of total]) and 294 donors (D). Mean age was 52.1 years (SD 10.2 years) and mean follow-up time after HTX was 5.7 years (SD 5.5, median 3.5 years). All seronegative patients received prophylaxis with daraprim/sulfomethoxazole or cotrimoxazol for 6 months after transplantation. Multi-

134 434 Pharmacological and non-pharmacological therapy of heart failure / Haemodynamics, heart and hypertension variable survival analysis adjusted for diabetes, coronary artery disease (CAD), recipient/donor age and gender, type of primary immunosuppression (AZA/MMF), and pre-htx renal function was performed. Results: Overall, 190 recipients (55.2% of total) were seronegative and 154 (44.8% of total) were seropositive for T. gondii prior to HTX. In total, 152 recipients died during follow-up (44.2% of total). Negative recipient toxoplasma serostatus was associated with a significantly higher risk of all-cause mortality (p= 0.02). Conditional survival analysis (>30 days post HTX) revealed similar results (p= 0.02). Recipient T. gondii serostatus did not influence the number of cellular or humoral rejection episodes. Analyses regarding specific causes of death showed a trend towards a higher number of infection-related deaths in the seronegative subgroup (p= 0.13). No statistically significant effects of T. gondii donor/recipient seropairing, or seroconversion were observed. Conclusions: Pre-operative serostatus for T. gondii in HTX recipients appears to be an independent risk factor associated with increased all-cause mortality. The cause of impaired survival in toxoplasma seronegative recipients is currently unclear, possible explanations include an alteration of immune-reactivity/-regulation or adverse effects of prophylactic medication. P2525 Characteristics of the interleukin family biomarker ST2 after heart transplantation D.A. Pascual Figal 1, I.P. Garrido 1,R.M.Blanco 1, J. Sanchez-Mas 1, A. Minguela 1,R.Gracia 1, M.D. Martinez 1, J. Ordonez 2,A.Bayes- Genis 2, M. Valdes 1. 1 University Hospital Virgen De La Arrixaca, Murcia, Spain; 2 Hospital de Sant Pau, Barcelona, Spain Background: Soluble ST2, an IL-1 receptor family member, has recently emerged as a promising biomarker of myocardial stress in patients with heart failure and acute myocardial infarction. The value of ST2 in heart transplant patients is not known. Aims: We aimed to define the clinical determinants of ST2 concentrations after heart transplantation and to study the relationship between ST2 and acute rejection. Methods: Blood samples were obtained at time of 80 programmed biopsies performed in 26 heart transplant patients, during the first year after transplantation. Aliquots of serum were stored at 80 C until ST2 (ng/l) was measured (Medical & Biological Laboratories, Woburn, MA). ST2 was studied as an absolute concentration and as a ratio, calculated by ST2 at current biopsy/st at prior biopsy. Results: In the entire population, ST2 concentration had a skewed distribution with median 0.29 (interquartile range, IQR: 0.14 to 0.87) (minimum and maximum 7.69). ST2 concentrations were high during the first 30 days after the transplantation (1.7 [IQR: 0.54 to 2.6]) and showed a rapid decline until 90 days after (0.16 [IQR: 0.12 to 0.48]). The correlates of ST2 concentration were: time after transplantation (rs=-0.488, p<0.001); right atrial pressure (rs=0.302, p=0.006), C-reactive protein (rs=0.439, p<0.001) and B-type natriuretic peptide levels (rs=0.510, p<0.001) at time of biopsy. ST2 concentrations were significantly higher among biopsies with rejection (n=32) (0.39 [IQR: 0.19 to 1.7]) vs. those without rejection (n=48) (0.23 [IQR: 0.13 to 0.56] (p<0.02). The ST2 ratio was also higher in biopsies with rejection than those without (p=0.013). After adjustment for time from transplant, the ST2 ratio was predictor of rejection (p=0.038, OR 2.54, CI95% ), but the absolute ST2 concentration did not reach significance (p=0.098). ROC analysis identified 1.0 as the optimal cutoff value of ST2 ratio for prediction of rejection. Patients with ST2 ratio>1showed an incremental risk of rejection (p=0.003, OR 4.39, CI95% ). Conclusion: ST2 concentrations were high early after heart transplant and showed a rapid decline at 90 days. ST2 concentrations were higher in presence of acute rejection and an increase of ST2 from prior biopsy was predictive of higher risk of rejection. HAEMODYNAMICS, HEART AND HYPERTENSION P2526 Gender differences in hypertension; risk factor identifiers in favour of women? A.J. Hogarth, D.A.S.G. Mary, S.G. Ball, J.P. Greenwood. Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom Objectives: Essential hypertension (EHT) has been associated with increased risk of developing cardiovascular events, which are known to be less likely to occur in women than in men. It is also known that EHT is associated with increased sympathetic neural activity (SNA) and impairment of baroreceptor reflex sensitivity controlling the heart rate (BRS). Both increased SNA and impairment of BRS have been shown to be risk factors in the pathogenesis and ensuing cardiovascular complications of EHT. However, normal women have both a lower muscle sympathetic nerve activity (MSNA) and BRS than men. We therefore planned to determine whether there is a difference in the degree of increase of MSNA and impairment of BRS between hypertensive women (F-HT) and hypertensive men (M-HT). Methods: We measured MSNA by peroneal microneurography and BRS by the Valsalva manoeuvre in 4 groups of subjects comprising 18 F-HT and 18 M-HT patients in comparison to two normal control groups of 18 normotensive women (F-NC) and 18 normotensive men (M-NC). All subjects were matched for age and body mass index (BMI), while hypertensive and normotensive groups were each matched for arterial pressure. Results: Data in Table are as mean±sem. There were no significant differences (ANOVA post-tests) in age, BMI or HR. As expected the EHT groups had increased mean blood pressure (MBP) and MSNA bursts/100b (b/100) in comparison to the normal groups, and normal women had lower BRS and MSNA than normal men (at least P <0.05). In EHT groups MSNA was lower in women (P <0.001) while the values of BRS were similar in both women and men, indicating both a greater sympathetic activation and impairment of BRS in hypertensive men. Data of the 4 groups as mean ± SEM No. Age BMI MBP Heart rate MSNA BRS (years) (kg/m 2 ) (mmhg) (b/m) (b/100) (msec/mmhg) F-HT 18 51±2.4 29± ±2.0 70±2.1 48± ±0.46 M-HT 18 51±1.7 27± ±2.8 66±2.0 62± ±0.52 F-NC 18 50±2.5 27±1.1 99±0.9 67±2.5 37± ±0.42 M-NC 18 51±2.4 27±0.7 98±1.3 66±2.4 47± ±0.82 Conclusions: Hypertension in women was associated with a lesser degree of sympathetic activation and impairment of BRS than in men. It is suggested that this could be one explanation for the observed lower hypertension-related cardiovascular events in women than in men. P2527 Association between serum uric acid and large artery stiffness in essential hypertensives: focus on gender differences G. Vyssoulis 1, E. Karpanou 2,S.-M.Kyvelou 1,V.Tzamou 1, D. Adamopoulos 1, G. Antonakoudis 1, C. Vlachopoulos 1, D. Cokkinos 2, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Onassis Cardiac Surgery Center, Athens, Greece Purpose: An association of uric acid with hypertension, diabetes, kidney disease, and cardiovascular disease has been observed for a century. The aim of the study was to investigate the possible association of arterial stiffness and uric acid levels according to gender in a large number of hypertensive patients. Methods: We studied 1225 consecutive never treated patients (728 men and 497 women) with a mean age 53 years, with uncomplicated essential hypertension. Patients were evaluated with full clinical and laboratory examinations. The participants were divided according to gender and serum uric acid (UA) levels (mg/dl) in quartiles (1st: 3.79±0.91, 2nd: 4.84±0.87, 3rd: 5.49±0.93 and 4th: 7.01±1.31). Patients with anti-hyperuricemic treatment were excluded Aortic stiffness and arterial wave reflection were assessed using carotid femoral (PWVc-f) and carotid radial (PWVc-r) pulse wave velocity and aortic augmentation index corrected for heart rate (Aix75). Results: UA was positively related to PWVc-f (r=0.145, p<0.0001), negatively to AIx75 (r=-0.70, p=0.01) whereas was no relation to PWVc-r (r=0.039, p=ns) after adjustment for age, sex, smoking frequency, glucose levels, egfr and BMI. Furthermore, a statistical significance among UA quartiles showed only for PWV c-f (p<0.0001) and PWVc-r (p=0.022). After adjustment for age, smoking frequency, glucose levels, egfr and BMI, the association remained significant in women between UA and PWVc-f, PWVc-r and AIx75 [(r=0.177, p=0.0001), (r=0.097, p=0.03) and (r=-0.95, p=0.04) respectively], while in men the association remained significant only between UA and PWVc-f (r=0.166, p<0.002). In addition, a statistical significance among UA quartiles was detected only for PWVc-f (p<0.0001) in men, while in women it was true for both PWVc-f (p<0.0001) and PWVc-r (p=0.02). Conclusions: These results suggest that UA is associated with an increase of arterial stiffness in hypertensives, especially in females. P2528 Renal artery stenting impacts left ventricle structure and serum aldosterone concentration D. Rzeznik, T. Przewlocki, A. Kablak-Ziembicka, A. Roslawiecka, A. Kozanecki, J. Lach, M. Kostkiewicz, W. Tracz. John Paul II Hospital, Department of Cardiac and Vascular Diseases, Krakow, Poland Renal artery stenosis (RAS) leads to activation of the renin-angiotensinaldosterone (RAA) system and may result in hypertension and left ventricular hypertrophy, however there are conflicting data whether renal stenting (RS) may exert beneficial effect on normalization of these parameters. The study aimed to evaluate the interrelation between left ventricular mass (LVM), diastolic function, and aldosterone levels in patients undergoing RS for RAS. Material: Study enrolled 55 patients (29 M), aged 63.3±8.7 (47-81)y.o, who underwent successful RS for severe RAS, and were observed at least 1 year. Hypertension was found in all patients, diabetes in 18.8%, hiperlipidemia in 98%, coronary artery disease on angio in 60%. Angiotensin converting enzyme and/or aldosterone inhibitors were taken by 37 patients. The change in LVM, LVM index (LVMI) and diastolic function (E wave velocity, Isovolumetric Relaxation Time - IVRT) was determined by echocardiography and Tissue Doppler Imaging (TDI) prior to RS and after 12-months. 24-hour ambulatory blood pressure (BP) mon-

135 Haemodynamics, heart and hypertension 435 itoring was performed in all patients prior and on 12-months after RS. Serum aldosterone level was determined. Results: Prior to RS, a positive correlation was found between aldosterone level and RAS grade (p=0.035;r=0.335), mean systolic BP (p=0.046;r=0,314); diastolic BP (p=0.038; r=0.325); systolic BP load (p=0.07;r=0,280); diastolic BP load (p=0.02;r=0,362). No correlations between aldosterone and initial echocardiographic parameters were found. On 12 month F-U, mean aldosterone level decreased from 24.7±25.1 ng/ml to 18.2±13.8 ng/ml (p=0.076). The mean LVM decreased from 178.3±43.3g to 142.1±33.1g (p<0.001), LVMI in women from 97.5±17.7g/m 2 to 79±18.4g/m 2 (p<0.001) and men from 101.6±419.6g/m 2 to 77.2±16.6g/m 2 (p<0.001). No improvement in diastolic function was seen (E : from 5.49 to 5.79 cm/s; p=0.151; and IVRT: from 117ms to 116ms; p=0.614). Initial aldosterone levels were similar in patients taking RAA system inhibitors as compared to those taking other hypertensive drugs (23.3±28.7 vs. 27.5±18.1 ng/ml; p=0.621), but significantly lower on 12-month (respectively: 16.0±131 vs. 22.5±145 ng/ml; p=0.07). After 12 month, aldosterone level was positively correlated with systolic BP (p=0.06; r=0.304), SBP load (p=0.044; r=0.325), LVM (p=0.085; r=0.263) and negatively with E wave velocity (p=0.031; r=-0.325). Conclusions: In RAS patients aldosterone level correlates with RAS grade, and BP values. RS induces significant regression of LVM and LVMI as well as aldosterone level. RS seems to facilitate RRA system inhibitors action on aldosterone reduction. P2529 Endothelium under attack in hypertensives with obstructive sleep apnea: relation of disease severity with biological markers A. Kasiakogias, C. Tsioufis, C. Thomopoulos, A. Mazaraki, P. Tolis, E. Andrikou, E. Stefanadi, I. Kallikazaros, D. Tousoulis, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: An atherogenic milieu coupled with endothelial dysfunction may be an important mechanism that links obstructive sleep apnea (OSA) to cardiovascular disease. In a cross-sectional study, we investigated the effect of OSA on various markers of impaired vascular function in the setting of hypertension. Methods: 87 subjects with stage I-II untreated essential hypertension and OSA (apnea-hypopnea index-ahi >5) diagnosed with polysomnography (PSG)(69 males, aged 48±7 years, 41 smokers, office BP 151±8/97±8mmHg) and a control group of 95 hypertensive patients without OSA (negative PSG) matched for age, sex, BMI and smoking habits were studied. All patients underwent ambulatory blood pressure monitoring and routine laboratory investigation. High sensitivity C-reactive protein (CRP) and asymmetric dimethyl arginine (ADMA) blood levels, as well as the albumin excretion rate measured as the albumin to creatinine ratio (ACR) in two non-consecutive urine morning samples, were used as markers of vascular dysfunction after logarithmic transformation. Results: Hypertensive subjects with OSA compared to the control group exhibited higher 24hour systolic (141±9 vs. 138±6mmHg, p<0.05) and diastolic (88±7 vs.84±7mmhg, p<0.001) BP values. The metabolic profile and estimated glomerular filtration rate (GFR) were similar between the two groups. However, the group with OSA exhibited significantly higher values of logcrp (0.57±0.22 vs. 0.39±0.22mg/L, p<0.001), logadma (-0.25±0.09 vs ±0.08μmol/L, p<0.001), and logacr (1.08±0.31 vs. 0.66±0.38 mg/g, p<0.001). Furthermore, in the entire population, logcrp, logadma, and logacr were significantly correlated to both the logahi (r=0.32, 0.41, and 0.35 respectively, p<0.001 for all) and to minimum oxygen saturation (min SatO2) (r=-0.36, and respectively, p<0.001 for all). In a model of multiple regression analysis, the logahi was independently predicted by logadma (b=0.42, p<0.001) and logacr (b=0.19, p=0.01) levels. Conclusions: Severity of OSA as defined by polysomnographic parameters is associated with higher levels of vascular dysfunction markers, reflecting a doseresponse relationship of OSA to an atherogenic load on tissue level. P2530 Influence of salt intake on carotid structure and hemodynamics in hypertensive subjects M.C.S. Ferreira-Sae, J.A. Cipolli, M. Cornelio, J.R. Matos-Souza, R. Schreiber, K.G. Franchini, R.C. Rodrigues, M.C.J. Gallani, W. Nadruz Junior. State University of Campinas, Campinas, Brazil Purpose: Despite the relationship between salt intake and cardiovascular risk has been largely established, little is known about the influence of salt intake on carotid structure and hemodynamics in hypertensive subjects. Methods: We evaluated 121 patients (55% women; average age 58±1 years) by clinical history, physical examination, anthropometry, analysis of hemodynamic, inflammatory and metabolic parameters and carotid ultrasound examination. Average daily salt intake (DSI) was measured using previously validated methodology and consisted of collecting a 24 hour recall, a sodium food frequency questionnaire and estimated discretionary salt used in the household. Descriptive data are presented as the mean ± standard error. Results: The studied sample had an estimated salt intake of 13.8±0.7 g/day. Univariate analysis showed that DSI correlated with common carotid intima-media thickness (r=0.19, p<0.05), systolic and diastolic diameter (r=0.36 and r=0.34; both p<0.001), peak and mean circumferential tension (r=0.44 and r=39; both p<0.001) and stiffness assessed by Young s Elastic Modulus (r=0.40, p<0.001) as well as with internal carotid artery resistivity index (r=0.20; p<0.05). Conversely, DSI showed no significant correlation with common carotid Stiffness Index and Arterial Compliance, which evaluated alternative aspects of arterial elasticity. Multivariate analyses adjusted for age, sex, body mass index, systolic and diastolic blood pressure, smoking, cardiac output and urinary sodium showed that DSI was associated with common carotid systolic and diastolic diameter (both p<0.001), peak and mean circumferential tension (both p<0.01) and Young s Elastic Modulus (p<0.01), but was not independently related to common carotid intima-media thickness and internal carotid resistivity index. Conclusions: Salt intake is an independent predictor of reduced elasticity, increased luminal diameter and higher local hemodynamic load in carotid arteries of hypertensive subjects. P2531 Hyperleptinemia is accompanied by a state of increased arterial stiffness in a community population sample K. Baou, C. Vlachopoulos, I. Dima, N. Ioakeimidis, D. Terentes- Printzios, G. Antoniou, K. Aznaouridis, A. Bratsas, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: Leptin, a hormone produced by adipocytes, plays a regulatory role in body weight by controlling appetite and energy consumption. Elevated plasma leptin levels (hyperleptinemia) have been suggested to contribute to pathogenesis of diabetes, hypertension, atherosclerosis and coronary heart disease. Arterial stiffness is an independent predictor of cardiovascular risk. We investigated the differential effects of adiponectin, leptin and resistin levels on wave reflections, an index of arterial stiffness in a community population sample. Methods: The study population consisted of 97 subjects (mean age: 46.4±10.5 yrs, 57M/40F), 28 subjects were hypertensives, 22 subjects had dyslipidemia, 4 suffered from diabetes and 32 individuals were obese. Subjects were free of overt cardiovascular disease. Wave reflections were evaluatedwith augmentation index (AIx) of the aortic pressure waveform using commercially available system. Leptin, adiponectin and resistin levels were measured by ELISA kit. Results: Leptin was associated with AIx (r=0.409, P<0.001) and Tr (an index of pulse wave velocity, r=-0.385, P<0.001). Levels of resistin and adiponectin were not correlated with AIx and Tr. After adjustment for confounding factors (age, brachial systolic pressure, fasting glucose, total cholesterol, weight, height, heart rate and hscrp) leptin levels were independently associated with AIx (R 2 =0.605, coefficient st=0.268 p=0.001). Conclusion: In contrast to other adipocytokines, leptin levels were associated with arterial stiffness, independently of other confounding factors. Given the prognostic role of arterial stiffness for cardiovascular events, these findings are important to further characterize the increase of cardiovascular risk in subjects with elevated levels of leptin. P2532 The value of systemic endothelial dysfunction and increased arterial stiffness for identifying wall motion abnormalities during stress echocardiography in hypertensive men with erectile dysfunction N. Ioakeimidis, C. Vlachopoulos, C. Aggeli, K. Aznaouridis, G. Antoniou, D. Terentes-Printzios, G. Roussakis, K. Rokkas, C. Fassoulakis, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: Hypertension is the most common comorbidity in patients with erectile dysfunction (ED) and impaired arterial function appears to be a link between these conditions. We evaluated the arterial functional determinants of wall motion abnormalities during stress testing in hypertensive ED patients. Methods: 83 consecutive asymptomatic non diabetic men with essential hypertension and ED underwent:(1) dobutamine stress echocardiography (DSE) (2) endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery during reactive hyperaemia using high-resolution ultrasound and (3) evaluation of aortic stiffness with carotid-femoral pulse wave velocity (PWV) and wave reflections with augmentation index (AIx) using high-fidelity PW analysis. Criteria of positivity were regional dysfunction >2 segments demonstrated by DSE. A group of 30 hypertensive men with similar age, normal erectile function and negative DSE were also studied. Results: 18 hypertensive men (21%) exhibited regional wall motion abnormalities. Age-adjusted FMD values were comparable among ED patients and significantly lower as compared to control group (figure). PWV values were significantly DSE and arterial functional parametres

136 436 Haemodynamics, heart and hypertension higher in ED patients with positive DSE compared to men with normal stress testing (figure). AIx did not differ among the three groups. In ED patients, DSE positivity was predicted on multivariate analysis by higher PWV values (P<0.05; OR=3.6; 95%CI= ), but not by either reduced FMD (P=0.81; OR=0.87; 95% CI= ) or increased AIx (P=0.13; OR=0.47; 95% CI= ). Conclusions: Increased aortic stiffness affects wall motion during stress, however, echocardiographic positivity is unrelated to systemic endothelial dysfunction. An integration of DSE and functional markers is warranted in evaluation of men with hypertension and ED. P2533 The mean platelet volume in patients with non-dipper hypertension compared to dippers and normotensives M.G. Kaya, M. Yarlioglues, O. Gunebakmaz, T. Inanc, A. Dogan, E. Gunturk, A. Oguzhan, N.K. Eryol, R. Topsakal. Erciyes University School of Medicine, Department of Cardiology, Kayseri, Turkey Objectives: We aimed to determine whether mean platelet volume (MPV) levels are elevated in non-dipper patients compared to dippers. So it might be significant parameter for assessing the potential risk for high incidence of cardiovascular events in non-dipper patients. Methods: This prospective randomized study included 56 hypertensive patients and 27 age and sex matched control subjects. Following ambulatory blood pressure monitoring for all patients, hypertensive patients were divided into two groups; 28 dipper patients (10 male, mean age; 51±8) and 28 non-dipper patients (11 male, mean age; 53±10). Mean platelet volume was measured in a blood sample collected in EDTA tubes and also was used for whole blood counts in all patients. Results: In non-dipper patient, 24-hour SBP (141.5±10.21 vs ±7.7 p<0.001), 24-hour DBP (88.2±8.5 vs. 81.0±8.2, p<0.01) and 24-hour average BP (105.7±8.5 vs. 97.7±7.4, p<0.001) are significantly higher than dippers. Whereas daytime measurements were similar between dippers and non-dippers, there was a significant difference between each group during nighttime measurements (nighttime systolic 137.1±11.0 vs ±8.0, p<0.001, nighttime diastolic 85.3±8.0 vs. 72.8±7.9, p<0.001). Non-dipper patients demonstrated higher levels of MPV compared to dippers and normotensives (9.61±0.42 to 9.24±0.35 p< 0.001, 9.61±0.42 to 8.87±0.33 p<0.001, respectively). Conclusion: Increased cardiovascular events and target organ damage in nondipper compared to dippers and normotensives is related with more frequent thrombotic events depends on intensive platelet activation. This relationship has been shown by using MPV which can be used safely to assess platelet activation. P2534 The effect of acute inhibition of renin-angiotensin system on coronary flow reserve in hypertensives K. Stamatelopoulos, D. Bramos, E. Alexaki, C. Trika, E. Manios, N. Zakopoulos, S. Toumanidis. Regional General Hospital Alexandra of Athens, Athens, Greece Pupose: Inhibition of the renin-angiotensin system acutely improves endothelial function in the peripheral circulation. Coronary flow reserve (CFR) is reduced in hypertensive patients with or without left ventricular hypertrophy, through mechanisms of endothelial dysfunction. The aim of the study was to investigate the acute effect of renin-angiotensin system inhibition on CFR in patients with hypertension. Methods: Nineteen patients (Table 1) with newly diagnosed, never-treated arterial hypertension, without any cardiovascular or systemic disease, were screened at our outpatient clinic. Standard transthoracic echocardiography and CFR assessment by a Vivid 7 GE system were performed. Coronary diastolic velocity time integral (VTI) was measured at the distal portion of the LAD artery at baseline and after IV adenosine infusion. CFR was defined as the ratio of hyperaemic to basal diastolic VTI. Patients were randomly assigned to Quinapril 20 mg or Losartan 100mg. CFR was measured before and 2 hours after per os administration of renin-angiotensin system inhibitors. Results: CFR increased in 16 patients. Mean CFR was increased significantly from 2.6±0.7 (baseline) to 3.3±0.5 two hours after drug administration (p=0.015). Systolic pressure (SBP) and diastolic blood pressure (DBP) did not change significantly (SBP was 141 mmhg before and 136 mmhg after administration of renin-angiotensin system inhibitors, p<0.064 and DBP was 96 mmhg before and 94 mmhg after,p<0.077, respectively). Conclusions: Renin-angiotensin system inhibitors acutely improve coronary flow reserve in patients with recently diagnosed hypertension. This effect was independent of arterial blood pressure changes, implying an acute direct beneficial effect on the coronary vascular wall. P2535 Waist circumference as a determinant of left atrial size in newly diagnosed subjects with essential hypertension E. Taxiarchou, C. Tsioufis, D. Syrseloudis, D. Chatzis, D. Tsiachris, I. Skiadas, N. Trikalinos, I. Vlasseros, D. Tousoulis, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Left atrial (LA) enlargement represents an early and common finding in hypertensive heart disease, is associated with adverse clinical outcomes and has been identified as independent determinant of new onset atrial fibrillation. Measurement of abdominal obesity is strongly associated with increased cardiometabolic risk, cardiovascular events, and mortality. The possible interrelationship between LA size and waist circumference (WC) in hypertensive subjects was investigated in this study. Methods: 460 consecutive newly diagnosed subjects (aged 51.3±9.8 years, 304 males) with stage I-II untreated essential hypertension [office blood pressure (BP) = 151/97 mmhg] underwent a complete echocardiographic study and 24-hour ambulatory BP monitoring. All subjects were classified according to their WC in group A (WC>102 cm in men and >88 cm in women, n=238) and in group B (WC>102 cm in men and >88 cm in women, n=222). LA volume was measured according to an established method and was indexed for body surface area to estimate LA volume index (LAVI). Results: Group A compared to group B had significantly increased age (52.6±9.5 vs 50.0±10 years, p=0.005), 24-h pulse pressure (52.2±8.8 vs 50.4±8.3 mmhg, p<0.05), LA diameter (LAD) (3.92±0.42 vs. 3.76±0.47cm, p<0.001), LA volume (48.3±14.0 vs. 43.5±13.5ml, p<0.001) while they did not differ according to LAVI. In the entire study population, WC exhibited positive relationships with LAD (r=0.429, p<0.001), 24-h pulse pressure (r=0.135, p<0.005) and LAVI (r=0.113, p<0.05). Multiple regression analysis models between anthropometrics and clinical (BP) parameters revealed that waist (B=0.417, p<0.001), 24-h systolic blood pressure (B=0.161, p<0.001) and age (B=0.132, p<0.005) were independent predictors of LAD and 24-h pulse pressure (B=0.187, p<0.001) and age (B=0.152, p=0.001) were independent predictors of LAVI. Conclusions: Our results indicated that in patients with newly diagnosed uncomplicated essential hypertension abdominal obesity is accompanied by greater LAD but not with augmented LAVI, suggesting the significant role of indexing in assessing LA size. P2536 Pronounced nocturnal blood pressure levels lead to erectile dysfunction in male hypertensives A. Kakkavas, C. Tsioufis, D. Tsiachris, D. Syrseloudis, V. Tzamou, D. Tousoulis, H. Tatsis, A. Trikas, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Erectile dysfunction (ED) reflects diffuse vascular damage while ambulatory blood pressure (ABP) exhibit strong correlation with target organ damage in essential hypertension. Our aim was to investigate the association between ED and circadian blood pressure variation in hypertensive males. Methods: We studied 142 consecutive, newly diagnosed and untreated, male subjects with uncomplicated stage I-II hypertension (mean age=50.6 years, office blood pressure=151/98mmhg). All subjects were non-diabetics, without any clinical evidence of atherosclerotic disease and were classified into dippers (n=78) and non-dippers (n=64) according to the criterion of 10% nocturnal reduction of the systolic and diastolic blood pressure (BP) measurements. By means of a validated questionnaire, the International Index of Erectile Function score (IIEF-score) was assessed and subjects were divided into those with ED (IIEFscore<26, n=43, 30.3%) and those without ED (IIEF-score 26, n=99). Results: Hypertensive men with ED compared to those without ED were older (54±9 vs. 49±7 years, p<0.05), whereas there was no difference regarding smoking status, body mass index, serum glucose, lipidaemic profile and office BP levels (p=ns for all). According to ABP measurements, subjects with ED, compared to those without ED, had greater values of 24-h pulse-pressure (51±9 vs. 47.5±7 mmhg, p<0.05), and night pulse-pressure (50.5±12.1 vs. 45.5±7.5 mmhg, p<0.005). Non-dipping status was significantly more prevalent in hypertensives with ED compared to those without ED (72.5% vs. 47.5%, p<0.05). ED status was positively correlated with age (r=0.365, p<0.001), 24-h pulse pressure (r=0.191, p=0.029) and non-dipping status (r=0.235, p=0.007). Multiple logistics regression analysis revealed that non-dipping status was an independent predictor of the presence of ED (OR=3.633, p=0.008). Conclusions: In hypertensive males without clinically atherosclerotic disease, abnormalities in circadian blood pressure variation and erectile function are closely interrelated. Increased haemodynamic load associated with non-dipping Abstract P2534 Table 1 Demographic Characteristics Cardiovascular risk factors Echocardiographic parameters 24-hours Ambulatory Holter parameters Age (years): 58.0±11.6 Systolic Blood Pressure (mmhg): 134.0±39.0 Ejection fraction (%): 66±10 Mean Systolic Blood Pressure (mmhg): 137.4±9.5 Male gender, number (%): 16 (84%) Diastolic Blood Pressure (mmhg): 86.5±14,15 Posterior Wall Diameter (mm): 10.63±1.383 Mean Diastolic Blood Pressure (mmhg): 86.0±8.4 Hyperlipidemia, n (%): 9 (47%) Intraventricular Septum Diameter (mm): 11.05±1.322 Mean Heart Rate 24 (bpm): 74.5±10.2 Smoking current, n (%): 7 (77%) End Diastolic Diameter (mm): 48.16±4.413 Pulse Pressure 24 (mmhg): 51.3±6.6 Diabetes: 0 (0%) End Systolic Diameter (mm):29.89±3.446 BMI (kg/m 2 ): 25.4±4.1 Left Atrium (mm): 39.63±4.924 Quinapril/losartan: 10/9 Left ventricular hypertrophy: 6 (31%)

137 Haemodynamics, heart and hypertension 437 status seems to be an important factor in the interpretation of ED-related vascular risk. This interrelationship may further elucidate the prognostic role of the abnormal systolic BP elevation at peak exercise. P2537 B-Type Natriuretic Peptide identifies asymptomatic hypertensive patients with abnormal diurnal blood pressure variation and increased LA volume D. Phelan 1,E.Omar 1, B. Hennigan 2, M. Ledwidge 1, D. O Shea 2, K. Mcdonald 1. 1 Heart Failure Unit, St. Vincent s University Hospital, Dublin, Ireland; 2 St Columcille s Hospital, Dublin, Ireland Background: Abnormal circadian BP variation and elevated levels B-type Natruiretic Peptide (BNP) are both associated with adverse cardiovascular outcome. The relationship between an elevated BNP, abnormal 24 hour blood pressure variation and structural cardiac abnormalities has not previously been investigated. Purpose: To examine the relationship between BNP level and both diurnal variability of blood pressure and echocardiographic evidence of cardiac dysfunction. Methods: Twenty-four hour ambulatory blood pressure monitoring was performed on 92 asymptomatic hypertensive patients. Two-dimensional echocardiography imaging, targeted M-mode and Doppler ultrasound measurements were obtained in each patient using standard techniques. Almost half of these patients had type 2 diabetes mellitus (DM) (44 vs 48 non-diabetics). The patients were divided into 3 groups according to their circadian BP variation profiles: dippers (n=50), nondippers (n=31), extreme dippers (n=9). Based on the distribution pattern of BNP values, the values were analyzed after logarithmic transformation. Results: There are significant differences in plasma BNP levels among the 3 different groups of BP profiles according to an anova analysis (p=0.008). Nondippers and extreme dippers had significantly higher BNP levels (median [interquartile range]: 26.2 [8.3,54] pg/ml and 29.8 [12.4,62.8] pg/ml respectively) compared to normal dippers (11.5 [6.3,17.5]pg/ml). The mean 24 hour BP was similar between the groups. No significant differences were found on sub-group analysis comparing diabetic and non-diabetic patients. Left atrial volume and left ventricular mass index, both early indicators of diastolic dysfunction, correlated significantly with plasma BNP (p<0.001, r=0.48 and p=0.03, r=0.24 respectively). Conclusion: Plasma BNP level is clinically useful for the identification of hypertensive patients who have abnormal circadian BP variability and early signs of diastolic dysfunction, both of which increase the risk of cardiovascular events. These findings are consistent in patients with and without type 2 DM. These observations demonstrate for the first time that the elevated BNP associated with non-dippers is linked to increased LA volume and LVMI. P2538 Excessive inotropic response during exercise as a marker of regional and systemic arterial stiffness in newly diagnosed essential hypertension D. Tsiachris, C. Tsioufis, C. Thomopoulos, A. Kasiakogias, D. Syrseloudis, D. Soulis, T. Papaioannou, A. Mazaraki, D. Tousoulis, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Ambulatory arterial stiffness index (AASI), a measure based on the relative behavior of 24-hour systolic and diastolic blood pressure (BP), has been suggested as a marker of arterial stiffness and a predictor of cardiovascular mortality. Exaggerated blood pressure response during exercise (EBPR) is associated with high risk for worsening hypertension and adverse cardiovascular outcomes. The aim of this study was to investigate the relationship between these parameters in the early stages of essential hypertension (EH). Methods: 70 newly diagnosed untreated non-diabetics (40 males, mean age 50 years) with stage I II EH underwent treadmill exercise testing and were classified as hypertensives with EBPR (n=75) based on the systolic BP elevation at 210 mmhg or more for men and 190 mmhg or more for women, at peak exercise. The remaining patients were classified as normal inotropic responders (n=147). All subjects underwent ambulatory BP monitoring, echocardiography and carotid femoral PWV measurement by a computerized device (Complior SP). AASI was defined as 1 minus the regression slope of 24hour ambulatory diastolic and systolic BP, while daytime and nighttime AASI were estimated accordingly. Results: Hypertensives with EBPR compared to normal inotropic responders had increased 24hour PP (51.47 vs 46.4 mmhg, p=0.001), while there was no difference regarding age, sex, body mass index 24hour systolic and diastolic BP, as well as dipping status. Hypertensives with EBPR did not differ also compared to those without EBPR with respect to left ventricular mass index and transmitral flow Doppler parameters (p=ns for all). Moreover, hypertensives with EBPR compared to those without exhibited significantly greater values of 24hour AASI (0.43±0.10 vs 0.34±0.13 cm/s, p=0.027) and PWV (9.8±1.5 vs 8.2±1.2, p<0.001). Exercise capacity was also significantly deteriorated in hypertensives with EBPR based on the lower values of achieved METs (9.6±2.3 vs 11.3±2.3, p=0.009). Peak systolic BP at exercise was correlated with 24-hour systolic BP (r=0.467, p<0.001), 24hour PP (r=0.440, p<0.001) and PWV (r=0.152, p=0.046). Moreover, 24hour AASI was correlated with 24hour PP (r=0.380, p=0.001) and PWV (r=0.243, p=0.041). Conclusions: Excessive inotropic response during treadmill exercise testing is accompanied by impaired regional and systemic arterial stiffness, as reflected by increased aortic PWV and 24hour AASI in the setting of newly diagnosed EH. P2539 Masked, white-coat and sustained hypertension: Associations with subclinical inflammation, arterial stiffness and thrombosis/fibrinolysis system K. Dimitriadis, C. Tsioufis, D. Syrseloudis, A. Mazaraki, A. Gennadi, M. Selima, V. Tzamou, I. Darladimas, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: The relation of masked hypertension (MHT) and white-coat hypertension (WCHT) to vascular damage is under debate, while inflammatory processes, impaired thrombosis/fibrinolysis and arterial stiffening are associated to atherosclerosis progression. In the present study, we examined the interrelationships of MHT, WCHT and sustained hypertension (SHT) with high-sensitivity C- reactive protein (hs-crp), plasminogen-activator inhibitor type 1 (PAI-1), and arterial stiffness. Methods: 335 consecutive untreated non-diabetic subjects who referred to our outpatient clinic for 24-h ambulatory blood pressure (BP) monitoring, were classified as subjects with sustained normal BP (office BP<140/90 mmhg and daytime BP<135/85, n=44), MHT (office BP <140/90 mmhg and daytime BP 135/85 mmhg, n=32), WCHT (office BP 140/90 mmhg and daytime BP <135/85 mmhg, n=81) and SHT (office BP 140/90 mmhg and daytime BP 135/85 mmhg, n=178). Moreover, in all hypertensives arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV), by means of a computerized method (Complior SP) and venous blood samples were drawn for estimation of hs-crp and PAI-1 levels. Results: Patients with SHT compared to WCHT and MHT group had higher 24- h systolic BP (138±10 vs 119±7 vs 129±15 mmhg, respectively; p<0.0001), while did not differ regarding sex, body mass index and metabolic profile (p=ns). Patients with SHT as compared to those with WCHT and MHT had greater levels of hs-crp (2.8±0.7 vs 2.2±0.6 vs 1.9±0.4 mg/l, respectively; p<0.05), PAI- 1 (35.41±5.1 vs 23.4±2.3 vs 18.1±1.8 ng/ml, respectively; p<0.05) and PWV (8.2±1.4 vs 7.8±1.2 vs 7.3±0.9 m/sec, respectively; p<0.05). However, there was no difference between the MHT and WCHT group regarding hs-crp, PAI-1 and PWV levels (p=ns for all cases). In the total hypertensive population, hs- CRP was associated with body mass index (r=0.285, p<0.0001), 24-h systolic BP (r=0.145, p<0.05) and PWV (r=0.232, p<0.0001), while PAI-1 was related to 24-h diastolic BP (r=0.326, p<0.0001). Conclusions: Patients with SHT compared to those with MHT and WCHT are characterized by pronounced inflammatory involvement, impaired thrombosis/fibrinolysis and arterial stiffening, as reflected by hs-crp, PAI-1 and PWV. These findings suggest that masking and white-coat effect may identify a state of lower cardiovascular risk, in this setting. P2540 Arterial stiffness leads to impaired microcirculation of the brain represented as cognitive dysfunction in non-dippers with newly-diagnosed essential hypertension H. Triantafyllidi, C. Arvaniti, J. Lekakis, I. Ikonomidis, P. Trivilou, S. Tzortzis, K. Kontsas, D. Kremastinos. University of Athens, Athens, Greece Background: Essential hypertension may be involved in the development of cognitive dysfunction which may be due to microvascular disease of the brain. Increased arterial stiffness of the large arteries due to hypertension may lead to microvascular changes due to increased pulsatile flow to microcirculation. This study investigates the hypothesis that large artery stiffness is related to brain microcirculation changes represented as impaired cognitive function, especially in non-dippers with newly-diagnosed essential hypertension. Methods: We studied 120 non-diabetic patients aged years (mean age years, 63 men) with recently diagnosed stage I-II essential hypertension, dippers (group A, n= 56, mean age= years, 26 men) and nondippers (group B, n= 64, mean age= years, 37 men). We used Mini Mental State Examination (MMSE) as a screening test for global cognitive dysfunction. We performed 2-D echocardiography, pulse wave velocity (PWV), office (BP) and 24h ambulatory blood pressure (24h BP) and pulse pressure (24h PP) measurements in order to evaluate arterial stiffness as well as dipping status. Results: No significant differences were found between groups A and B regarding age, sex, body mass index, office BP and PP, 24h BP and 24h PP, PWV, MMSE and echocardiographic aortic stiffness. In group B, MMSE was negatively related withpwv (r=-0.41,p<0.001) and 24h PP (r=-0.27, p=0.03). By receiver-operating (ROC) analysis, a cutoff value of 24h PP > 51.5 mmhg predicted the impaired cognitive function (MMSE<27) in non-dippers (AUC: 0.82, p=0.03, CI: , sensitivity 75% and specificity 60%). No relationship was revealed in group A between MMSE and indices of arterial stiffness. Conclusions: In the early stages of essential hypertension, impaired cognitive function correlates with large artery stiffness in patients with increased 24h blood pressure burden. The latter supports the hypothesis that cognitive dysfunction due to impaired brain microcirculation is linked to hypertension process.

138 438 Haemodynamics, heart and hypertension P2541 White coat hypertension vs. masked hypertension: influence on the development of sustained hypertension in children and adolescents C. Esis, M. Bracho, A. Gonzalez, E. Silva, S. Briceno, S. Briceno, G. Bermudez, J. Villasmil. Instituto de Investigación de Enfermedades Cardiovasculares - Universidad del Zulia, Maracaibo, Venezuela Purpose: To determine the predictive value of white coat hypertension (WCH) and masked hypertension (MH) for the development of sustained hypertension (SH) in children and adolescents. Methods: A cross-sectional study was carried out in 184 patients (91 boys and 93 girls, aged years, mean 14.27±2.19 years). At baseline, office blood pressure (BP) and a first ambulatory BP monitoring (ABPM) were performed to all patients. Initially, we excluded patients with SH which was defined as office BP measurements 95th percentile for sex and age or >140/90 mmhg for those 18 years, and systolic or diastolic daytime values obtained by ABPM 95yh percentile for sex and height or > 135/85 mmhg for those 18 years. The patients were classified according to the baseline condition of PA in one of three groups: normal, MH or WCH according to office PA and ABPM criteria. All subjects, after follow-up (3.80±1.89 years), were undergoing a second ABPM to identify new SH. A logistic regression model was used to evaluate the influence of WCH an MH on the development of HS, this model included age, gender, body mass index and baseline condition of PA. Results: Al baseline, we identified 22 patients with WCH (12.0%) and 12 with MH (6.5%). After follow-up, 7.6% (n = 14) of the population developed HS, 40.9% of WCH and 8.3% of MH (P <0.001). Variables that correlated significantly with SH were body mass index (BMI), gender, and baseline condition of BP. Logistic regression analysis showed that male (OR = 15.11, 95% CI = , P = 0.019) and WCH (OR = 36.50, 95% CI = , P <0.001) were significantly associated with SH in the follow-up, but not MH (OR = 3.56, 95% CI = , P = 0.309). Conclusions: In this group of children and adolescents, WCH was the factor most strongly associated with SH future, regardless of age, BMI and gender of the patient. The WCH represent a cardiovascular condition prior to the development of sustained hypertension in children and adolescents. P2542 Relationship between urine albumin/creatinine ratio and left ventricular mass in patients with hypertension and left ventricular hypertrophy: aliskiren in left ventricular hypertrophy (allay) study A. Pouleur 1, A. Shah 1, A. Desai 1, E. Appelbaum 2, V. Lukashevich 3, B.A. Smith 3, B. Dahlof 4, S.D. Solomon 1. 1 Brigham and Women s Hospital, Boston, United States of America; 2 Beth Israel Deaconess Medical Center, Boston, United States of America; 3 Novartis Pharmaceuticals Corporation, East Hanover, United States of America; 4 Sahlgrenska University Hospital/Östra, Göteborg, Sweden Background: Increased urine albumin/creatinine ratio (UACR) is associated with systemic and microvascular damage and increased cardiovascular morbidity/mortality. However, the relationship between microalbuminuria and left ventricular (LV) hypertrophy, another marker of cardiac end-organ damage, is not fully understood. Methods: The Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial randomized 465 overweight subjects with hypertension, and LV hypertrophy (increased LV wall thickness at screening echocardiography) to aliskiren 300mg, losartan 100mg or the combination and followed patients for 9 months. All patients were treated to standard blood pressure targets. LV mass index (LVMI) was assessed by cardiac magnetic resonance. A subset of 142 patients with UACR and other biomarkers measured at baseline and study end was analyzed. Results: At baseline, UACR was undetected in 8 (6%), ranged from 1 to 30 mg/g in 109 (76%) and was >30mg/g in 25 (18%) patients; mean blood pressure was 145±14/89±9mmHg and mean LVMI was 76±16 g/m 2. Higher UACR, even within the normal range, was associated with higher LVMI (p<0.0001), and higher NT-proBNP (p=0.003) (figure), independently of the egfr and other baseline covariates including age, sex, diabetes, systolic blood pressure, body mass index and race. There was no significant change in UACR between baseline and end of the study 6.5 (5-8.6) mg/g versus 6.1 ( ) mg/g, p=0.54) and no difference between treatment groups. Conclusion: In hypertensive patients with increased LV wall thickness, increased UACR is associated with higher LV mass and NT-proBNP, suggesting parallel cardiac and microvascular damage in the setting of increased load. Both markers of early end-organ damage may thus represent modifiable targets for treatment in hypertensive patients. P2543 Whether income is associated with blood pressure levels in a population sample? S. Malyutina 1, M. Bobak 2, S. Soboleva 3, D. Malyutina 2, A. Peasey 2, E. Veryovkin 1 on behalf of The HAPIEE Group. 1 Institute of Internal Medicine SB RAMS, Novosibirsk, Russian Federation; 2 University College London, London, United Kingdom; 3 Institute of Economics & Industrial Engineering SB RAS, Novosibirsk, Russian Federation Purpose: To investigate the relationship between household and per capita income and blood pressure levels in an ageing population sample in Russia. Methods: In the second wave of the HAPIEE Project, a representative population sample of men and women aged was surveyed in (n=3575) in Novosibirsk (Russia). Blood pressure (BP) was measured two times, and the average of readings was used for the analysis. Structured interview was used to estimate economic indicators (economic activity, personal and household income including benefits, informal transfers and non-monetary income in the last 12 months, and indicators of wealth). For the present analysis, we calculated the values of monthly household income and income per capita among household members. Crude, age-adjusted and multivariate-adjusted linear regression was applied. Multivariate models included age, gender, body mass index, antihypertensive treatment and education as covariates. Results: The average BP in studied sample was (SE 0.57)/91.0 (SE 0.29) mmhg. 77.5% of respondents were pensioners, and pension was the main source of income for 49% of families. The average value of monthly household income comprised roubles (approximately e 480 at the period of survey) with average income per family member of roubles (approximately e 180). In unadjusted models both systolic and diastolic BP in respondents were inversely linearly related to the levels of per capita income in their family (p=0,001 and 0.066, correspondently), but not to household income. In multivariate models the controlling for covariates explained the association between per capita income and systolic BP (mostly due to age impact). However, the inverse association between diastolic BP and per capita income was significant (p=0.032) independently from age, gender, body mass index, antihypertensive treatment and education. Conclusion: The levels of blood pressure in the ageing Russian population are inversely related to the measures of per capita income in the family, but not associated with household income. We found that negative association between diastolic blood pressure and per capita income was independent from age, gender, body mass index, antihypertensive treatment and education. The age explained mostly the relationship between systolic blood pressure and per capita income. The study was funded by grants from the Wellcome Trust (064947/Z/01/Z), the NIA (1R01 AG ). The present analysis was supported by grant from RGSF ( ). P2544 Hypertension: determinants of blood pressure control in primary health care in Portugal. Insights of VALSIM study M.S. Robalo Martins 1, N. Cortez-Dias 1,A.Belo 2,M.Fiuza 1. 1 Hospital Santa Maria, Lisbon, Portugal; 2 Portuguese Society of Cardiology, Lisbon, Portugal Purpose: To estimate the influence of sex, age, body mass index (BMI), waist circumference (WC), metabolic syndrome (MS, NCEP criteria) and region of residence in the hypertension (HT) treatment strategies and control rate. Methods: Descriptive cross-sectional study performed in a primary care setting, involving 721 general practitioners (GP) representative of all regions of Portugal. Patients (pts) 18 years consulting their GP irrespective of the reason were asked to participate. The participant GP enrolled the first 2 pts of each day. Two blood pressure (BP) measurements were obtained after a 5-minute seated rest. HT was defined as systolic BP 140 mmhg, diastolic BP 90 mmhg or use of antihypertensive medication (aht). Uncontrolled (UC) HT was defined as a BP higher than threshold among persons taking aht. Multivariate regression analysis was used to identify determinants of the decision to start aht and risk factors for UC-HT. Results: A total of 16,457 pts were evaluated (mean age: years; 61% women). The age and sex-adjusted prevalence of HT was 43.37% (M: 43.5%; W: 43.25%). Among those 9,568 hypertensive pts, 81.6% were on aht medication but only 43% had their BP controlled. The probability of being treated was higher in women (M: 77.2%; W: 79.8%; p<0.01), lower in mid-age pts and showed regional variance. Among pts submitted to aht (N=8,530), 52.2% had UC-HT (M: 53.8% vs W: 50.9%) and 4.65% had BP 180/110mmHg. The risk of UC-HT has 28% higher in men [odds ratio (OR) 1.28; 95% confidence interval (CI) ; p=0.001], in years old subjects (OR: 1.44; 95%CI ; p=0.020), in those with MS (OR: 1.92; 95%CI ; p<0.001] and in North and Center regions. Otherwise, residence in Lisbon and Tagus Valley and in Alentejo were independent protective factors. HT control rate decreased

139 Haemodynamics, heart and hypertension / Lifestyle modification: is it wothwhile? 439 with BMI and WC. In UC-HT pts, the mean BMI (29.54±4.78kg/m 2 ) and the mean WC (102.05±10.91cm) were significantly higher than those in controlled pts (29.07±4.69kg/m 2 and ±11.53cm). Conclusions: There is a low HT control rate in Portugal, even in those pts regularly followed in primary care setting. This is partially due to problems in diagnosis, decision to treat and adjustment of therapy, particularly in mid-age men. Moreover, obesity is associated with worse BP control. These results demand vigorous lifestyle interventions, as well as comprehensive preventive public health efforts. P2545 Severe uncontrolled hypertension treated with microvascular decompression of the brainstem V. Kapil, G. Rull, J. Wadley, M. Lobo. Bart s and The London NHS Trust, London, United Kingdom Background: A 74 year old man was referred to our clinic with hypertension of 8 years duration. BP control had deteriorated such that he was taking 6 antihypertensives at top doses without achieving BP control. Home BP charts demonstrated striking hypertension averaging around / mm Hg most of the time. These extraordinarily high readings were accompanied by symptoms of visual blurring and pronounced sweating. However his BP would suddenly drop to 140/70 occasionally, resulting in tremendous lethargy and incapacity. His symptoms resulted in poor quality of life. ABPM showed daytime means of 178/114 mm Hg with no nocturnal dipping. Repeat investigations failed to disclose a secondary cause for hypertension and CT brainstem imaging did not exclude microvascular compression of the brainstem. MRI was not performed due to presence of a pacemaker. Medication compliance was confirmed by observed tablet taking in our department. Methods and Results: The patient was referred for endoscopic exploration of the brainstem in November During surgery an aberrant arterial loop was found to be indenting the rostral ventrolateral medulla and dissection of this vessel from the brainstem with subsequent insertion of a teflon pledgelet to prevent pulsatile compression resulted in an immediate intraoperative drop in BP. There were no post-operative complications. After the operation he was documenting home BPs averaging <160/100 mmhg with no antihypertensive therapy and without significant lability and great improvement in his overall quality of life. During the summer of 2008 his BP control once again deteriorated drastically with home BPs reaching up to 250/140 mm Hg and the return of tremendous BP lability and episodic blacking out due to dramatic falls in BP as he had experienced previously. Catecholamine excess was once again excluded. He underwent repeat exploration of the brainstem in August 2008 and on this occasion further decompression of the microvascular loop was undertaken to include separating it from the root entry zones of the lower cranial nerves. 6 months postoperatively he remains well with no antihypertensive therapy and home BPs averaging 150/90 mm Hg. Conclusion: Neurogenic hypertension is thought to arise secondary to pulsatile compression of the rostral ventrolateral medulla by microvascular loops. The diagnosis of neurogenic hypertension should be considered in patients with resistant, severely labile hypertension in whom all known causes of secondary hypertension have been thoroughly excluded. Such patients may benefit from microvascular decompression of the brainstem. LIFESTYLE MODIFICATION: IS IT WOTHWHILE? 2640 Weight loss effect on hs-crp and fibrinogen levels in patients with metabolic syndrome E. Paschalidou, I. Efthimiadis, F. Dogramatzi, A. Efthimiadis. Hippocration general hospital of Thessaloniki, Thessaloniki, Greece Purpose: High-sensitivity C-reactive protein (hs-crp) and fibrinogen are well known inflammatory biomarkers predisposing to high cardiovascular risk. We sought to determine the effect of weight loss on hs-crp and fibrinogen levels in patients with metabolic syndrome. Methods: We followed 25 patients (13 men and 12 women) aged 48.18±15.44 years, with metabolic syndrome according to the IDF criteria (WC: ±5.66cm, HDL: 39.82±7.55mg/dl, TG: ±68.32mg/dl). At first visit, medical history and informed consent was obtained, clinical examination was done. All patients received hypocaloric diet (-500 Kcal/day, based on the Mediterranean concept) for six months. Before and after treatment, the lipid profile and fibrinogen levels of the individuals were examined by standard methods and serum levels of hs-crp was determined by the immunotholometric method. Anthropometric parameters (body weight, waist circumference and BMI) were also measured. Paired t-test was used to compare means at baseline and at the end of the study. Data are presented as mean±standard deviation. Results: After six months of hypocaloric diet, triglycerides decreased by 38.9% (from ±68.32mg/dl to ±27.69mg/dl, p<0.001), HDL increased by 26.8% (from 39.82±7.55 to 52.91±4.16mg/dl, p<0.001), body weight decreased by 20% (from 85.27±10.14kg to 70.00±8.75, p<0.001), waist circumference by 11.7% (102.27±5.66cm to 91.09±2.81cm, p<0.001), and BMI by 21.8% (from 32.09±4.25kg/m 2 to 26.27±3.04kg/m 2,p<0.001).Fibrinogen levels decreased by 20.13% (from ±140.46mg/dl to ±71.58mg/dl, p<0.005) and hs- CRP by 33.3% (3.29±1.82mg/dl to 1.81±1.05mg/dl, p<0.001). No significant changes were observed on levels of liver enzymes. Conclusions: Weight loss caused significant decrease on fibrinogen and hs-crp levels and improved lipid profile of the patients. Hypocaloric diet based on the Mediterranean concept seems to be the most effective therapy for the management of the metabolic syndrome. No adverse events were referred Improved exercise capacity has a beneficial effect in long term mortality risk of prediabetics A. Pittaras 1,J.Myers 2,E.S.Nylen 3,J.P.Kokkinos 3, M. Kallistratos 4, A. Giannakopoulos 4, H. Grassos 4, P. Narayan 3, A.J. Manolis 4, P.F. Kokkinos 3. 1 Mediton Medical Center, Athens, Greece; 2 VAMC, Palo Alto, United States of America; 3 VA & Georgetown University Medical Centers, Washington Dc, United States of America; 4 Asclepion Voulas Hospital, Athens, Greece Introduction: It is estimated that at least one fourth of U.S. adults have prediabetes (i.e., plasma glucose level of 100 to <126 mg/dl after an overnight fast and/or impaired glucose tolerance with plasma glucose level of 140 to <200 mg/dl post 2-hour oral glucose tolerance test). Prediabetics are known to have increased risk for developing type 2 diabetes, heart disease, and stroke. Importantly, lifestyle modifications can prevent or delay the development of diabetes and its complications. In our prior studies of type 2 diabetics, there was an inverse and graded association between fitness levels and mortality risk. In the current study, we sought to evaluate if the same relationship was present in prediabetics. Method: A total of 780 men with prediabetes at the Washington VAMC underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). Fitness categories were established based on peak METs achieved: Those who achieved <6 METs (lower 30%) established the Low-Fit category (n=242), those who achieved 11 METs (>75%) comprised the High- Fit category (n=99) and the remaining comprised the Moderate-Fit (n=439). Results: There were a total of 157 deaths. Survival analysis (Kaplan-Meier) revealed lower mortality rates among all fitness categories (Log-rank for linear trend=16.6; p<0.001).when adjusted for age and BMI, mortality rate was 55% lower (HR=0.45; CI: ) among the individuals in the High-Fit category compared to those in the Low-Fit. There were no significant differences in mortality between the low-and Moderate-Fit individuals. Conclusion: High exercise capacity is associated with lower rate of mortality in pre-diabetic individuals Impact of Poly Unsaturated Fatty Acids (PUFAs) on positive remodeling of coronary plaques, a study by 64 slice MDCT (MultiDetector Computed Tomography) T. Domei, S. Kuramitsu, K. Yamaji, Y. Soga, K. Ando, H. Yokoi, M. Iwabuchi, M. Nobuyoshi. Kokura Memorial Hospital, Kitakyusyu, Japan Objective: Many reports had revealed that balance of PUFAs is one of the key of coronary event. It is thought that the effect on coronary event is related with progress of coronary plaque, but it has not been fully evaluated. Therefore, we aimed to study the relation between serum PUFAs level and positive remodeling (PR) of coronary plaque by MDCT. Methods: A total of 49 patients with coronary artery disease, 62 diseased lesions with high quality CT image were enrolled in this study. In MDCT images, the Remodeling Index (RI) was calculated by dividing the vessel area of the lesion by the reference segment. We divided into two groups: group A (lesions of RI >1, n=21), group B (lesions of RI 1, n=41), and compared between two groups with the serum concentrations of 4 fraction of PUFAs (n3-pufas; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), n6-pufas; arachidonic acid (AA), dihomo-gamma-linolenic acid (DGLA)), andother coronary risk factors. Results: Group B had significant lower n3-pufas level, lower EPA/AA ratio than group A: EPA (87±57 μg/ml vs 57±27μg/ml; p=0.006), DHA (166±37μg/ml vs 137±39μg/ml; p=0.007), EPA/AA (0.57±0.34 vs 0.37±0.17; p=0.018), and other coronary risk factors had no difference between two groups. (Fig.1). N3 PUFAs and EPA/AA ratio had no significant relation with other risk factors. Figure 1. Remodeling index (RI) vs. serum n3 PUFAs, EPA/AA ratio

140 440 Lifestyle modification: is it wothwhile? / The obesity paradox: is it real? Conclusion: Our data indicated that low n3-pufas and low n3/n6 ratio make important role on coronary plaque formation Adherence to the Mediterranean diet and risk of atrial fibrillation A.V. Mattioli, A. Farinetti, C. Miloro, P. Pedrazzi, R. Melotti. University of Modena and R.E., Modena, Italy Background: Epidemiologic studies suggest a lower risk of coronary artery disease in subjects with high intake of fruit and vegetables. The Mediterranean diet has long been associated with lower incidence of cardiovascular disease and cancer. Little information is available on association between high antioxidant vitamins intake and arrhythmias. The present study evaluated the relationship between intake of antioxidant vitamins with diet and atrial fibrillation (AF). Methods: A group of 400 patients (pts), mean age 54±11 yrs; 205 men with a first detected episode of AF was investigated. A control group of 400 subjects, age and sex matched, was selected and compared. Nutritional parameters were assessed by a self-administered food frequency validated questionnaire with 116 items and completed by an interviewer-administered 24 h diet recall questionnaire. We evaluated adherence to a Mediterranean diet using a Score. Consumption of cereals, vegetables, legumes, fruit, fish, dairy products, number of cup of espresso coffee, chocolate snacks and soda drink, wine was investigated. Results: Adherence to the Mediterranean diet was higher in control pts. Total calories intake was similar in the 2 groups (2054±981 vs 1998±883 Kcal; p=ns), whereas the estimated intake of total antioxidants was lower in pts with AF (13.5±8.3 mmol/d vs 18.2±9.4 mmol/d in controls; p<0.001). The intake of coffee contributed for 64% (AF pts) and 54% (control pts) of the total antioxidant intake, followed by fruits (1.8 vs 1.6 mmol; p<0.001), wine (1.4 vs 1.8 mmol; p<0.001), cereals (0.8 vs 1.0 mmol; p<0.001), and vegetables (0.9 vs 1.3 mmol; p<0.001). Of the no coffee antioxidants, on average, beta-carotene, alfa-tocopherol, and vitamin C intake contributed 23.7% in AF vs 27% in control group (p<0.001). Conclusions: Patients with first detected atrial fibrillation had lower antioxidant intake compared to a normal population sex and age matched. They had higher intake of antioxidant from coffee than from fruit and vegetable while control patients had a higher intake of antioxidant from fruit and vegetables. Coffee contains several hundred different substances including caffeine that has effects on cardiovascular system. We found that patients with AF had high daily intake of coffee and caffeine. The association of low antioxidants intake and high caffeine intake can lead to AF Interrelationship of lifestyle characteristics with dietary habits and childhood obesity among Greek adolescents. Preliminary data from the 3L Study D. Tsiachris, C. Tsioufis, D. Syrseloudis, C. Thomopoulos, E. Andrikou, E. Stefanadi, A. Mazaraki, D. Chatzis, D. Tousoulis, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Sedentary lifestyle have been related to adverse cardiovascular outcomes while the Mediterranean diet (MD), one of the healthiest dietary models currently existing, has been postulated as having a protective role against cardiovascular diseases. Our aim was to evaluate the relationship between selected lifestyle characteristics, dietary habits and anthropometric patterns in Greek adolescents. Methods: During 2008, 365 schoolchildren (212 boys and 153 girls), aged years participated in the Lyceum Leontio ALbuminuria Study (3L study). Height, weight, waist and hip circumference were measured and the body mass index (BMI) was calculated. Cut-off points for BMI defining obesity and overweight for gender and age were calculated in accordance with international standards. For each child a questionnaire was completed that was developed in order to retrieve information on dietary habits (through a semi-quantitative Food Frequency Questionnaire), lifestyle and socio-economic characteristics. Adherence to the MD was assessed by the KIDMED score. The amount of the leisure time was calculated as the sum of hours of watching TV/electronic games and activities excluding sports. Based on the median value of hours of calculated leisure time, children were classified as those with increased and those with decreased leisure time. Results: Children with increased compared with those with decreased leisure time exhibited greater waist and hip circumference (by 2.1 cm, p=0.043 and 3 cm, p=0.001, respectively), BMI (by 2 kg/m 2, p=0.011) as well as prevalence of overweight/obesity status (40.2% vs. 29.2%, p=0.045). Moreover, children with increased leisure time reported greater adherence to MD compared with those with decreased leisure time according to the increased KIDMED score (4.4 vs. 3.7, p=0.003) while there was no difference in sex and smoking status. The amount of leisure time was positively correlated with BMI (r=0.119, p=0.023) and hip circumference (r=0.136, p=0.010) and negatively with the KIDMED score (r=-0.152, p=0.004). Conclusions: Greek adolescents with increased leisure time are characterized by a greater prevalence of overweight/obesity status and a poorer adherence to MD. Taking into account that childhood obesity and unhealthy eating habits have been related to adverse cardiovascular outcomes, school- or communitybased programmes should be conducted promoting healthy dietary and lifestyle behaviors Good cholesterol control in a large disease management initiative: lessons from the LIVE program K.T. Ho 1, R.S. Hameed 2, J.D. Molina 2, A. Razakjr 3,H.Y.Ong 4, B.H. Heng 2 on behalf of LIVE program investigators. 1 Tan Tock Seng Hospital, Singapore, Singapore; 2 National Healthcare Group, Singapore, Singapore; 3 National University Hospial, Singapore, Singapore; 4 Alexandra Hospital, Singapore, Singapore Purpose: A disease management program (LIVE program) was introduced in Singapore since 2005 to improve LDL-C control in coronary artery disease (CAD) patients. These are the results of the first 5000 consecutive patients. Methods: The ControL of Coronary RIsk Factors InitiatiVE (LIVE) Program aims to achieve goals of LDL-C levels <2.6mmol/L through a disease management process. All CAD patients admitted to the Cardiology Departments in 3 large public hospitals are automatically enrolled in the program and undergo patient education, dose titration of medications by case managers, and telephonic management. This is a multidisciplinary program that involve physicians, case managers & nurse-clinicians. Results: 5002 consecutive patients with documented CAD from 3 large public hospitals were prospectively enrolled from 1 Aug 2005 to 28 Feb patients (95%) remained in program. Mean period of followup was 18±6 months. Mean age was 60±13 years, 23% were women, 31% diabetic, 60% hypertensive, 30% both diabetic & hypertensive, 77% had elevated cholesterol, 60% both hypertensive & elevated cholesterol. At hospitalisation, mean Total Cholesterol was 6.5mmol/L, mean LDL-C 4.1mmol/L. At discharge 97% of patients with LDL > 2.6mmol/L were prescribed statins (90% simvastatin, 3% atorvastatin, 2% rosuvastatin), and 2350 (65%) were prescribed statins equipotent to simvastatin 40mg or more. Overall 4264 patients (90%) achieved LDL-C < 2.6mmol/L. Of those who achieved target, the mean simvastatin dose was 60mg; 1280 (35%) underwent dose titration. 232 (6%) patients did not achieve goal with simvastatin monotherapy but did so with simvastatin-ezetimibe dual therapy. To test for significant predictors of LDL-C goal attainment, the following factors were included in a logistic regression model: age, gender, ethnicity, history of diabetes, baseline total cholesterol levels, type of statin medication at presentation and duration of follow-up. Of these factors, male gender, lower baseline total cholesterol levels, shorter duration of follow-up and utilization of simvastatin as initial choice of statin were shown to be associated with achievement of LDL-C target. Conclusions: In CHD patients managed by 3 hospitals in Singapore s public health sector, 1) LDL-C goal attainment reached 90%, largely with generic statins using a disease management program, 2) males with lower baseline total cholesterol levels, who were prescribed simvastatin as initial choice of statin were shown to be associated with attainment of LDL-C goals. THE OBESITY PARADOX: IS IT REAL? 2647 Is there an obesity paradox after percutaneous coronary intervention (PCI) in the contemporary era? Findings from a large multicentre Australian coronary angioplasty registry T. Lancefield 1,D.Clark 1, N. Andrianopoulos 2, A. Brennan 2,C.Reid 2, J. Johns 1,K.Charter 1,S.Duffy 3,J.Proietto 1, O. Farouque 1. 1 Austin Hospital, Melbourne, Australia; 2 Monash Centre of Cardiovascular Research & Education in Therapeutics, Melbourne, Australia; 3 The Alfred Hospital, Melbourne, Australia Purpose: Overweight and obese patients may have better outcomes following PCI than patients with a normal or low body mass index (BMI), a finding known as the obesity paradox. We sought to determine if the obesity paradox exists in the contemporary era of PCI and whether obese patients are more likely to receive guideline-based medical therapy after PCI. Methods: We evaluated 3001 patients undergoing PCI between 1st April 2004 and 30 September 2006, enrolled in the Melbourne Intervention Group registry. Patients were classified as underweight, normal, overweight, mildly obese and very obese, BMI < 20, 20-25, , and > 35 kg/m 2, respectively. We compared in-hospital, 30 day and 12 month outcomes including major adverse cardiac events (MACE) and mortality. The use of guideline-based medical therapy at 30 days and 12 months was also reviewed. Results: Obese patients were younger but had a significantly higher prevalence of traditional cardiovascular risk factors including diabetes mellitus, hypertension, dyslipidaemia and cigarette smoking. The prevalence of high-risk coronary lesions, stent type and procedural success were similar. Compared with very obese patients, those with a normal BMI had higher in-hospital MACE (4.8 vs. 2.0%, P = 0.01), in-hospital mortality (1.1 vs. 0.4%, P = 0.046), 12 month MACE (13.3 vs. 10.0%, P = 0.032) and 12 month mortality (3.7 vs. 2.4%, P = 0.016). Very obese patients had higher 30 day renin-angiotensin system (RAS) blocker use (84.1% vs. 68.0%, P < 0.001) and 12 month beta-blocker and RAS-blocker use (59.3 vs. 52.8%, P = and 78.4 vs. 69.0%, P < 0.001, respectively). There was a trend to lower Clopidogrel use at 12-months in the normal BMI group (P = 0.061). Conclusions: Compared with normal-weight individuals, overweight and obese patients had lower in-hospital and 12 month mortality and MACE rates following PCI. Moreover, obese patients had a higher rate of guideline-based medical ther-

141 The obesity paradox: is it real? 441 apy use at 12 months, which may in part explain the obesity paradox seen after PCI. Background: Weight reduction is a recommended treatment goal in type 2 diabetes mellitus (DM) to improve metabolic balance and reduce cardiovascular risk. In contrast, the so-called obesity paradox suggests reduced mortality in overweight patients with pre-existing chronic cardiac disease. The impact of weight and weight change in a type 2 DM population with pre-existing cardiovascular disease on total mortality is analysed in the PROactive study population. Methods: PROactive was a double-blind, placebo controlled outcome study including 5,238 patients with type 2 DM and evidence of pre-existing cardiovascular disease. Patients were randomized to Pioglitazone (n= 2605) or placebo (n=2633) in addition to their concomitant glucose-lowering and cardiovascular medication. Mean Follow up was 34,5 months. Baseline weight and % weight change was analysed in univariable and multivariable models to predict all cause mortality. Results: Documented weight reduction during the study period was associated with increased mortality in the total study population (HR per 1%weight loss: 1.14; [95%CI ]) as well as in both treatment groups separately in univariable Cox Analysis (Pioglitazone: HR 1.13 [ ], Placebo: HR 1.14 [ ], all P<0.0001). In contrast, weight gain was not associated with increased mortality. In multivariable Cox proportional analysis including further cardiovascular risk factors (HR 1.13 [ ], P<0.0001) weight reduction but not weight gain remained as significant predictor of increased mortality risk. In Cox proportional analysis of body mass index (BMI) at baseline the lowest risk for all cause mortality was observed for patients with BMI 30-35kg/m 2.In comparison, patients with BMI <22 (HR 1.93 [ ; P=0.09) and BMI (HR 1.53 [ ]; P=0.03) had an increased risk of all-cause mortality. Conclusion: Weight reduction but not weight gain is associated with increased all-cause mortality in patients with type 2 DM and pre-existing cardiovascular disease. This suggests the presence of the obesity paradox in patients with type 2 DM who have a high risk of cardiovascular events Obesity, metabolic health and incidence of peripheral vascular disease during 9-years follow-up of the D.E.S.I.R. cohort M. Skilton 1, J. Chin-Dusting 1, C. Lange 2, J. Tichet 3,B.Balkau 2 on behalf of D.E.S.I.R. Study Group. 1 Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 2 INSERM U780, Villejuif, France; 3 IRSA, La Riche, France Purpose: While obesity is an established cardiovascular risk factor, much of this association is mediated via other risk factors such as hypertension and diabetes and potentiated by the increased prevalence of metabolic risk factors in obese subjects. There is some evidence that the metabolically healthy obese - those without the metabolic syndrome - may be at no greater risk of the complications of obesity than non-obese subjects. As such we sought to determine whether obesity per se is associated with an increased incidence of peripheral vascular disease, or whether an increased risk of incident peripheral vascular disease (PVD) is limited to the metabolically unhealthy obese. Furthermore, we studied whether the association of non-obesity metabolic syndrome components with incident PVD is the same in abdominally obese & non-obese subjects. Methods: The associations of obesity and the metabolic syndrome components with incident PVD (ankle brachial pressure index <0.90, or claudication) were determined in 3743 participants in the D.E.S.I.R. cohort over a 9-year follow-up period. Results given as odds ratio and 95% confidence interval for PVD relative to a low-risk ankle brachial pressure index of Results: Age (P=0.008), sex (P=0.001) and smoking status (P<0.0001) were all strongly associated with incident PVD, and as such all analyses were adjusted for these factors. Overweight (OR 1.42 [95%CI ]), and obesity (OR 1.50 [95%CI ]) at baseline were associated with non-significant increases in the 9-year incidence of PVD. In comparison to metabolically healthy healthy weight subjects, the metabolically unhealthy overweight subjects had the highest increase in PVD incidence (OR 2.16 [95%CI ]), which was markedly greater than amongst the metabolically healthy overweight (OR 1.10 [95%CI ]). Metabolic health had little impact in obese subjects (metabolically healthy: OR 1.48 [ ]; metabolically unhealthy: OR 1.69 [ ]). Furthermore, the associations between the non-obesity components of the metabolic syndrome and incident PVD did not differ between abdominally obese or nonobese subjects (Pheterogeneity>0.10 for all comparisons). Conclusions: Metabolically unhealthy overweight subjects are at a markedly higher risk of developing incident PVD than their metabolically healthy counterparts. In contrast, the metabolic health status of obese subjects had little influence on their risk of incident PVD. As such, metabolic health may be more important amongst overweight subjects than amongst obese subjects Obesity paradox in type 2 DM of the PROactive study population: Weight reduction but not weight gain is associated with increased mortality in patients with type 2 DM and high cardiovascular risk W. Doehner 1,E.Erdmann 2,R.Cairns 3, J.A. Dormandy 4, E. Ferrannini 5, S.D. Anker 1. 1 Charite - Campus Virchow-Klinikum, Berlin, Germany; 2 Universitaetsklinikum Koeln, Cologne, Germany; 3 Clinical Trials Center, Nottingham, United Kingdom; 4 St George s Healthcare NHS Trust, London, United Kingdom; 5 University of Pisa School of Medicine, Pisa, Italy 2650 Prevalence and trends of the metabolic syndrome in French adults: the MONA LISA study A. Wagner 1,B.Haas 1, V. Bongard 2, J. Dallongeville 3,D.Cottel 3, J. Ferrieres 2, D. Arveiler 1. 1 Laboratoire d epidemiologie Universite de Strasbourg, Strasbourg, France; 2 INSERM U558 Departement d epidemiologie Universite Paul Sabatier, Toulouse, France; 3 INSERM U744 Institut Pasteur de Lille Universite Lille, Lille, France Purpose: To assess ten-year change in the prevalence of the metabolic syndrome among French subjects using the National Cholesterol Education Program (NCEPATP III) criteria with the American Diabetes Association s updated definition of elevated fasting glucose (> 1g/l). Two definitions were assessed, one taking into account a treatment for hypertension and for elevated triglycerides or reduced high-density lipoprotein (HDL) cholesterol (Met2) and the other not (Met). Methods: Two cross-sectional representative surveys of the general population were carried out in 1996 and 2006 in three French areas: the Urban Community of Lille in the North, the districts of Bas-Rhin in the East and of Haute-Garonne in the South. Inhabitants aged years were randomly recruited from electoral rolls after stratification on gender, 10 year-age group and town size. Standardized sociodemographic, medical and anthropometric data were collected and a fasted blood sample was analysed centrally. Prevalences in the age group years were adjusted for the French population of year Results: A total of 3405 subjects in 1996 and 3554 subjects in 2006 were included in the analyses. In both years the metabolic syndrome was more common among men than among women and increased with age. The age-adjusted prevalences [95% confidence interval] of Met were 26.3% [ ] and 18.1% [ ] in 1996 and 23.1% [ ] and 15.1% [ ] in 2006, in men and women respectively. The equivalent results for Met2 were 30.5%, 21.5%, 24.8% and 16.4%. The age-adjusted prevalence of Met (Met2) decreased significantly by 12.1% (18.7%) in men and 16.6% (23.7%) in women. Of the five Met criteria, decreasing trends were observed in the prevalence of high blood pressure, elevated fasting glucose, low HDL cholesterol. By contrast, prevalence of abdominal obesity appeared unchanged whereas prevalence of hypertriglyceridemia increased significantly. Conclusions: In France, the prevalence of the metabolic syndrome tended to decline in the last decade in both genders, particularly in women Obesity is associated with better prognosis after implantation drug-eluting stents: the paradox of obesity M. Serrao, N. Santos, D. Pereira, J. Araujo. Hospital Central do Funchal, Funchal, Portugal Introduction: Obesity is a classical risk factorfor coronary heart disease. Some recent studies have shown that obesity appears to have a protective effect after percutaneous and surgical revascularization.objective: The authors evaluate the existence of the obesity paradox in patients revascularized with drug-eluting stents (DES). Methods: A retrospective study of 789 patients (pts) consecutive, submitted coronary intervention with implantation of DES, a non-tertiary hospital between January 2002 and June Body mass index (BMI in kg/m 2 ) was calculated from accordingto WHO recommendations. We divided them into 3 groups: obese (group O if BMI>30, n=210 pts, 26.6%), overweight (group OW if BMI>25 and <30,n=394 pts, 49.9%) and normal weight (group NW if BMI<25 n=185 pts; 23.4%). We analyzed demographic characteristics and clinical (coronary risk factors, previous AMI), left ventricular function, coronary angiography (n vessels, typeof lesion and segment involved), angioplasty data (stents - n, type, result), use of therapy adjuvant (inhibitors GPIIb/IIIa) and in-hospital complications.were determined by major adverse cardiac events (MACE) (nonfatal AMI,percutaneous or surgical revascularization, stroke and mortality) for 1-year follow-up. Results: The group O is consists of more women,(o=36.2%, OW=26.1%, NW=21.1%, p=0002), more diabetics (O=40.2%, OW=33.4%,NW=24.9%, p=0005) and hypertensive (O=57.7%, OW=53.1%, NW=44.9%, p=0.037).there were no differences in mean age, dyslipidemia, smoking and stroke. Incoronary angiography, the group O presented more multi-vessel disease (O=57.1%,OW=56.6%; NW=42.7%, p=0003), no differences were found in the presence of complexlesions and dysfunction left ventricular (EFLV<30%). In angioplasty, stents were implanted more (O=1.92±1.1, OW=1.82±1; NW=1.68±0.9, p=0.07 ns) and usedmore inhibitors GPIIb/IIIa (O=73.8%, OW=63.5%, NW=37.8%, p=0.004). No differences in complete revascularization and final success. In evaluating to 1year, there were no differences in the optimal medical therapy, MACE and mortality (O=5.8%, OW=4.5%, NW=5.6%; p=ns). Conclusion: In our sample, the obese patients presented a adverse clinical profile but this does not have unfavorable prognosis in the long period, validating the paradox of obesity in the era of DES.

142 442 The obesity paradox: is it real? / New aspects in cardiovascular drug therapy 2652 Obesity, waist circumference and metabolic syndrome in the Portuguese population. Insights of the VALSIM study M.M. Fiuza 1,N.Cortez-Dias 1, S. Martins 1,A.Belo 2. 1 Hospital Santa Maria, Lisbon, Portugal; 2 Portuguese Society of Cardiology, Lisbon, Portugal Purpose: To determine the prevalence of obesity (OB), abdominal obesity (AO) and metabolic syndrome (MS) in the portuguese population. Methods: Descriptive cross-sectional study performed in a primary care setting, involving 721 general practitioners (GP) representative of all regions of Portugal. Patients (pts) 18 years consulting their GP irrespective of the reason were asked to participate. The participant GP enrolled the first 2 pts of each day. After informed consent, a questionnaire was used to collect sociodemographic, clinical and laboratory data. OB was determined by body mass index (BMI): normal weight (NW: kg/m 2 ), overweight (OW: kg/m 2 ) and obese (OB: 30 kg/m 2 ). AO was considered when the waist circumference (WC) was greater than 102 cm in men and 88 cm in women. MS was defined by NCEP-ATP III criteria. Multivariate regression analysis was used to estimate the odds ratio (OR) of MS by age, gender, BMI and WC. Results: A total of 16,457 subjects were evaluated (58.1±15.1 years; 61.3% women). The sex and age-adjusted prevalence of MS was 29.47%. Risk of MS was higher in women [M:27.5%; W:31.4%; OR: % confidence interval (CI) ; p<0.001] and rose with age (from 11% in <35y to 46.7% in 65y). The sex and age-adjusted prevalence of OB was 26.7% (M:25.3%; F:28.4%); OW was 39.3% (M:45%; F:34.8%), and AO 46.4% (M:33.1%; W:58.4%). Both OB and AO were significantly more prevalent in women, increasing with age. OR for MS in OW and OB was three and nine times, respectively. The association between the risk of MS and AO was higher in women (OR:11.42; 95%CI ; p<0.001) than in men (OR:13.26; 95%CI ; p<0.001). There was a strong correlation between BMI and WC, but the association was not perfect, since 17.2% subjects with NW had AO. The overall relative frequency of high blood pressure, AO, hypertriglyceridemia, low HDL and fasting hyperglicemia was 57%, 46%, 31%, 26% and 20%, respectively. Pts with MS had also higher levels of serum total cholesterol (212±43 vs 205±38mg/dL, p<0.001) and LDL-cholesterol (131±35 vs 127±33mg/dL, p<0.001). Conclusions: MS, obesity and AO are highly prevalent and strongly associated. As a result of the anthropometric profile of the portuguese population, the correlation between BMI and WC is not perfect. So, both clinical parameters should be evaluated in order to correctly estimate the individual cardiovascular risk. NEW ASPECTS IN CARDIOVASCULAR DRUG THERAPY 2671 Survival benefit of combined secondary prevention therapy after acute myocardial infarction: Data from the UK Myocardial Infarction National Audit Project (MINAP) I.B. Squire 1, R. Chen 2, J.S. Birkhead 3, H. Hemingway 2, A. Timmis 2 on behalf of MINAP Academic Group. 1 University of Leicester, Leicester, United Kingdom; 2 University College London, London, United Kingdom; 3 Northampton General Hospital, Northampton, United Kingdom International guidelines recommend the prescription of anti-platelet (A), betablocker (B), ACE inhibitor (ACEI) and statin (S) after ACS.The impact of these treatments in practice can be assessed only through population-based data.the Myocardial Infarction National Audit Project (MINAP) collects data on ACS patients admitted to all 256 acute hospitals in England and Wales. Methods: We used the MINAP database to assess survival benefit associated with prescription, during index ACS admission,of A, B, ACEI and S. We used logistic regression analysis to assess survival benefit associated with (i) prescription of 1, 2, 3, or 4 drugs (ii) individual drug classes (iii) combinations of drugs. Results: Between Jan Dec patients were discharged alive after ACS. Of these, (80.6%) received four, 8597 (14.3%) three, 2431 (4%) two, and 699 (1.2%) one secondary prevention drug. Compared to those receiving 4 drugs, those receiving fewer were older, more often female or from deprived areas, and less often admitted under care of cardiology (p<0.001). 30-day and STEMI vs NSTEMI: 1yr mortality 1-year mortality showed a graded inverse relationship (p<0.0001) with number of secondary prevention drugs, for both STEMI and NSTEMI. Compared to 1 drug, adjusted HR for 1-year mortality was 0.73 for 2, 0.58 for 3 and 0.46 for 4 drugs, similar in men and women. For A (OR 0.85),B (0.68), ACEI (0.58) and S (0.67), prescription was less likely after NSTEMI.Compared to any prescription of A, prescription of B (OR 0.88), ACEI (0.55) improved 30-day survival, and each combination of A+B+S, A+ACEI+S or ACEI+B+S improved 30-day survival by >50%. Conclusions: In routine practice prescription of individual secondary prevention drugs show differing survival benefit after ACS. Drug combinations show incremental benefit Effects of tadalafil on health-related quality of life in patients with pulmonary arterial hypertension J. Pepke-Zaba 1, A. Beardsworth 2,M.Chan 3, M. Angalakuditi 2. 1 Papworth Hospital, Cambridge, United Kingdom; 2 Eli Lilly & Co, Indianapolis, United States of America; 3 Eli Lilly & Co, Toronto, Canada Purpose: Pulmonary arterial hypertension (PAH) is a serious condition for which there are approved treatments, but no cure. Current treatments for PAH target the prostacyclin, endothelin or nitric oxide pathways with the goal of improving exercise capacity, quality of life and ultimately survival. The effects of Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor currently indicated for treatment of erectile dysfunction, on exercise capacity and quality of life were assessed in patients with PAH. Methods: A double-blind clinical trial randomized 405 patients with PAH to placebo or oral Tadalafil at doses of 2.5, 10, 20, or 40 mg/d. At baseline and 16 weeks, exercise capacity was measured by the 6 minute walk test (6MWT), and quality of life was assessed using 2 generic instruments; the Short Form 36 (SF-36), which consists of 36 items in 8 health domains; and the EuroQol 5D (EQ-5D), which consists of 5 questions that together construct a utility index score, and a visual analog scale (VAS) for patient self-assessment of their own health. Change in 6MWT from baseline to end of study of each dose compare to placebo, the primary efficacy endpoint, was tested using a permutation test on rank, stratified by randomization factors. Change from baseline to week 16 in the SF-36 domains and EQ-5D measures of each dose compare to placebo were tested using ANCOVA controlling for baseline randomization factors. Results: Of the total 405 patients, 61% patients had idiopathic PAH and 65% had symptoms in WHO functional class III. Compared to baseline, at 16 weeks, the mean 6MWT distance was increased at all Tadalafil doses. However, the 40mg/d Tadalafil group showed statistically significant improvement (P<0.001) compared with placebo. All Tadalafil groups had significant improvement at 16 weeks compared to baseline in the Physical Functioning, Vitality, and Social Function domains of the SF-36, while the Tadalafil 40 mg/d group also had significant improvement in the Role-Physical, Bodily Pain, and General Health domains (all P<0.01 compared with placebo). For the EQ-5D, all Tadalafil groups had significantly greater utility index scores at 16 weeks, with the greatest improvement in the Tadalafil 40 mg/d group (P<0.0001) compared with placebo. Only the Tadalafil 40 mg/d group had an increase in VAS from baseline to 16 weeks compared with placebo (P<0.05). Conclusions: Tadalafil 40mg significantly improved exercise capacity and multiple aspects of quality of life, as measured using the SF-36 and EQ-5D, in patients with PAH Effects of insulin sensitivity and anti-inflammation after supplement with N-3 polyunsaturated fatty acid in metabolic syndrome J.Y. Kim 1, J. Yoon 1,Y.J.Youn 1, J.K. Seong 1, N.S. Lee 1, H.S. Wang 1, K.H. Lee 1, S.H. Lee 1, K.H. Choe 1,H.M.Choe 2. 1 Wonju College of Medicine, Yonsei University, Wonju, Korea, Republic of; 2 Inje University, Ilsan, Korea, Republic of Objective: Metabolic syndrome (MS) is characterized with insulin resistance and systemic inflammation. We investigated the effects of insulin sensitivity and antiinflammation after supplement with N-3 polyunsaturated fatty acid (N-3 PUFA) in patients with MS. Methods: Subjects with MS defined ATP-III were randomly enrolled in placebo and N-3 PUFA group. N-3 PUFA group was received 2 g of N-3 PUFA from baseline to 6 week and 4 g of N-3 PUFA from 6 to 12 week. Fasting serum lipid profiles, LDL subtraction, high sensitivity C-reactive protein (hs-crp), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fasting insulin and glucose level were measured at baseline, 6 and 12 week. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Results: Of the 60 subjects, 53 (26 of N-3 PUFA and 27 of placebo) completed the study. Baseline clinical and laboratory characteristics were similar in both groups. Mean percentage reduction in serum triglyceride (TG) level from baseline to 6 week (N-3 PUFA vs. placebo: 27.2% vs. 2.3%, p = 0.013) and 12 week (N-3 PUFA vs. placebo: 31.9% vs. -8.9%, p = 0.003) showed significant difference between two groups. Serum hs-crp level was significant lower in N-3 PUFA group than placebo group at 6 week (N-3 PUFA vs. placebo: 0.13±0.12 vs. 0.29±0.26 mg/l, p = 0.02) and 12 week (N-3 PUFA vs. placebo: 0.11±0.13 vs. 0.27±0.25

143 New aspects in cardiovascular drug therapy / Challenges for the clinician 443 mg/l, p = 0.01). Also serum IL-6 level at 12 week was significantly lower in N-3 PUFA group (N-3 PUFA vs. placebo: 1.14±0.56 vs. 1.60±0.88 pg/ml, p = 0.03) than placebo group. Mean value of HOMA-IR at 12 week (N-3 PUFA vs. placebo: 2.60±1.14 vs. 3.62±2.13, p = 0.04) was significantly lower in N-3 PUFA group than placebo group. Also mean percentage reduction in HOMA-IR value from baseline to 12 week (N-3 PUFA vs. placebo: 31.4% vs. -8.3%, p = 0.04) was significant in N-3 PUFA group. There was a significant negative correlation between HOMA-IR values and reduction of mean TG level at 6 week (r = -0.37, p = 0.000) and 12 week (r = -0.33, p = 0.000). Conclusion: Our study demonstrated that N-3 PUFA supplement improve systemic inflammation, and insulin resistance, which is associated with the lowering effects of TG in subjects with MS The use of beta-blockers in patients with moderate pulmonary obstruction A. Hummel 1,M.Doerr 1,K.Empen 1, A. Staudt 1, T. Reffelmann 1, M. Probst 1,J.Dahm 2, S.B. Felix 1. 1 Universitaetsklinikum Greifswald, Greifswald, Germany; 2 Internistisch-kardiologischen Gemeinschaftspraxis, Göttingen, Germany Background: The use of β-blockers has many undisputable indications, including coronary artery disease (CAD), hypertension and chronic heart failure. Chronic obstructive pulmonary disease (COPD) is a frequent co-morbidity in cardiovascular diseases. β-blockers have traditionally been considered contraindicated in patients with COPD and therefore remain underutilized despite their benefit in reducing mortality post myocardial infarction and chronic heart failure. Objective: To assess the safety and the efficacy of chronic treatment with a cardioselective, retarded β-blocker (metoprolol succinat) on respiratory function and cardiopulmonary exercise testing in patients with a moderate COPD (50% < FEV1 < 80% predicted) without evidence of largely reversible airflow limitation and with an indication for β-blockade. Methods: Twenty-seven patients (aged 64.7±9.1 years) orally received 95 mg metoprolol succinat (controlled release CR/XL) or placebo over a period of three months in a prospective, double-blind, placebo-controlled, randomized, intraindividual crossover study. After a washout period of 4 weeks the patients entered the second three month phase in the crossover group. The primary endpoint was the effect on static and dynamic pulmonary function parameters over a period of 3 months, as measured by body plethysmography. The secondary endpoint was change in cardiopulmonary exercise testing (upright cycle ergometer) or ventilatory efficiency. Results: There was no significant decrease in forced respiratory volume in 1 second (FEV1) in either period (basal vs. last FEV L ± 0.44 L vs L ± 0.41 L in the placebo period and 1.83 L ± 0.44 L vs L ± 0.41 L in the metoprolol period, p=0.47). No changes were detected in the forced vital capacity (basal vs last FVC 2.66 L ± 0.55 L vs L ± 0.59 L in the placebo period and 2.61 L ± 0.55 L vs L ± 0.48 L in the metoprolol period, p=0.78). In cardiopulmonary exercise testing there was no significant change in maximal work load or in ventilatory efficiency (defined as the slope of the linear relationship of VCO2 and ventilation VE), either in the placebo or treatment periods. Compared to placebo, metoprolol did not significantly affect FEV1, FVC, or cardiopulmonary testing. Conclusions: Cardioselective, retarded β-blockers given to patients with moderate COPD over a period of 3 months do not produce significant reduction in airway function or exercise capacity. Given their demonstrated benefit in conditions such as heart failure, CAD, and hypertension, cardioselective β-blockers should be considered for patients with COPD Heart rate control of beta-blockers is modulated by a common polymorphism in the G protein beta-3 subunit gene M. Dorr, C.O. Schmidt, K. Empen, H.K. Kroemer, H. Volzke, S.B. Felix, D. Rosskopf. Universitaetsklinikum Greifswald, Greifswald, Germany Background: Heart rate (HR) response to exercise is a predictor for beneficial effects of beta-blockers. We analyzed whether a common variant in the gene for the G protein beta3 subunit (GNB3) modulates the interindividual variation in beta-blocker responses. Methods and Results: 1614 subjects (828 women, 786 men; 347 current betablocker users) from the population-based Study of Health in Pomerania in Germany without pacemakers, atrial fibrillation and with normal left ventricular function were genotyped for the GNB3 C825T rs5443 and rs5442 polymorphism and analyzed regarding HR response and recovery during symptom-limited exercise testing. Multilevel linear regression models were adjusted for potential confounders. Among beta-blocker users the rs5443 polymorphism was associated with HR control. HR response during exercise and HR recovery were attenuated in T allele carriers (TC/TT) compared to non-carriers (CC). Adjusted HR was 2.2 (95%- confidence interval (CI) ; p=0.05) bpm lower during exercise, and 3.8 (CI ; p=0.02) bpm lower during recovery. The genotype-related HR reducing effect varied by up to 7 bpm (CC vs. TT), more than one fourth of the total betablocker effect of 24.7 bpm. GNB3 C825T was not associated with HR regulation among subjects without beta-blockers. There was no association between the rs5442 polymorphism and HR control in all subjects. Conclusions: The GNB3 825T allele significantly modulates chronotropic response and HR recovery under beta-blocker therapy. The results from this pharmacogenomic study may provide a useful biomarker for individual dose adjustment, thereby potentially reducing adverse effects of beta-blockers Inhibition of angiotensin-converting enzyme augments coronary tissue plasminogen activator release in hypertensive women T. Matsumoto, I. Nakae, T. Yamane, H. Takashima, M. Horie. Shiga University of Medical Science, Otsu, Japan Background: In the human forearm vasculature, it has been shown that angiotensin-converting enzyme inhibitors (ACEI) increase the release of tissue plasminogen activator (t-pa) through endogenous bradykinin. Thus, we tested the hypothesis that ACE inhibition and gender modulate coronary t-pa release. Methods: Forty-three hypertensive patients (mean age: 62±2 years) underwent diagnostic coronary angiography for chest pain or myocardial ischemia on ECG and had normal coronary angiograms. All patients were randomly assigned to two groups: 22 patients (12 men and 10 women) were treated with imidapril (5 mg/day) for 4-weeks (ACEI group) and 21 patients (12 men and 9 women) were treated with antihypertensive agents that did not include ACEI (nonacei group). All of the women were postmenopausal. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS) for measurement of t-pa and plasminogen activator inhibitor-1 (PAI-1) antigen. Coronary blood flow (CBF) in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Net coronary release of t-pa antigen was determined as a CS-Ao gradient CBF [(100 Hematocrit)/100]. Results: Age, arterial pressure, heart rate, lipid levels, coronary diameters and flows, and plasma levels of t-pa and PAI-1 antigen in the Ao and CS were comparable between the ACE-I and nonacei groups. The level of ACE was comparable between men and women in each group. In women, net coronary t-pa release in the ACEI group (12.1±6.4 ng/min) was significantly higher than that in the nona- CEI group (0.6±3.1 ng/min, p<0.05). These effects of ACEI were not seen in men (the ACEI group: -0.3±2.2 ng/min; the nonacei group: 2.2±1.6 ng/min). Adjustment of smoking status gave similar results. There was a significant negative correlation between serum ACE activities and coronary t-pa release in women (r=-0.37,p<0.05), but not in men. Serum ACE activities did not affect net PAI- 1production or extraction across the coronary circulation. Conclusions: ACEI enhance coronary release of t-pa in women, but not in men. The enhancement of coronary t-pa release may contribute to the cardioprotective effects of ACEI in hypertensive women. CHALLENGES FOR THE CLINICIAN 2677 Optimizing warfarin doses in chronically anticoagulated patients: the answer is in their genes E. Azenha Balhau Jorge, J. Pego, R. Baptista, M. Lourenco, I. Marques, A. Correia, P. Monteiro, L.A. Providencia, F. Antunes. Hospital and Medical School, Coimbra, Portugal Background: Warfarin presents a narrow therapeutic range and a wide interindividual variability. About 35% of the variation observed in the response to warfarin can be explained by genes affecting the pharmacokinetic and pharmacodynamic of warfarin. The most important are CYP2C9 and VKORC1. Objectives: We investigated the influence of variants of VKORC1 and CYP2C9 loci on the mean weekly warfarin dose in a population of cardiovascular patients on chronic anticoagulation. Methods: A total of 91 consecutive patients were genotyped using polymerase chain reaction and reverse hybridization. Results: The most frequent indications for warfarin were atrial fibrillation (56.8%), heart prosthetic valves (12.3%) and pulmonary embolism (12.3%). Prior history of heart failure, hypertension, renal failure and stroke were present in 74%, 49%, 14% and 9%, respectively. Table 1 summarizes the prevalence of the different genotypes influencing the response to oral anticoagulants and the respective dose of warfarin required to maintain patients on their desired anticoagulation target. Such doses were significantly different among carriers of the different CYP2C9 and VKORC1 genotypes. Table 1 Genotype % Warfarin daily dose/weight (mg/kg) CYP2C9 1/1 63,7 0,08 1/2 22,0 0,05 2/2 3,3 0,03 1/3 8,8 0,06 3/3 1,1 0,01 p-value 0,04 VKORC1 GG 33,0 0,10 GA 49,5 0,07 AA 17,5 0,04 p-value 0,0001 Conclusions: Our results confirm recently published data regarding the role of

144 444 Challenges for the clinician these two genes in modifying warfarin metabolism and maintenance dosage, by showing a significant correlation between genotype and warfarin dose required for optimal anticoagulation First in patient experience with a new, direct acting, reversible p2y12 inhibitor, elinogrel (prt060128): evaluation in patients with high platelet reactivity during clopidogrel therapy P.A. Gurbel 1, K.P. Bliden 1, M.J. Antonino 1, P. Andre 2, G. Sephens 2, D.D. Gretler 2, M.M. Jurek 2, A. Hutchaleelaha 2, P.B. Conley 2, U.S. Tantry 1. 1 Sinai Center for Thrombosis Research, Baltimore, United States of America; 2 Portola pharmaceuticals, San Francisco, United States of America Background: High platelet reactivity (HPR) is a risk factor for ischemic events in patients treated with clopidogrel. The effect of treatment with a new direct acting reversible P2Y12 inhibitor, elinogrel (PRT060128) in these patients is unknown. Methods: Previously stented stable coronary artery disease patients (n=50) treated with daily 81 mg aspirin and 75 mg clopidogrel were screened for HPR (>43% 5uM ADP-induced maximal platelet aggregation). Twenty patients with HPR were identified and treated hours after their last dose of clopidogrel with a single 60 mg oral dose of elinogrel. Platelet function was serially assessed by light transmittance aggregation (LTA), thrombelastography (TEG), VerifyNow P2Y12 assay, vasodilator stimulated phosphoprotein (VASP) phosphorylation, and Real Time Thrombosis Profiler (RTTP). Results: Elinogrel was well tolerated in all patients. Platelet reactivity fell within 4 hours of dosing, the earliest time point evaluated: maximum 5 μm and 10 μmadp LTA (p<0.001 for both vs. pre-dosing); maximum 20 um ADP LTA (p <0.05), VerifyNow (p<0.001); TEG (p<0.05); VASP phosphorylation (p=0.009); and RTTP (p<0.05); and was reversible within 24 hours (p=ns vs. pre-dosing for all assays). There was a good correlation between maximal inhibition of all pharmacodynamic markers and maximal plasma concentrations of elinogrel. Conclusions: HPR accompanying standard maintenance dose clopidogrel therapy can be rapidly and reversibly overcome by a single 60 mg oral dose of elinogrel. Based on these desirable pharmacokinetic and pharmacodynamic properties, elinogrel has promise as an important future antiplatelet agent and is undergoing further evaluation in a phase II clinical trial Proton pump inhibitors in patients treated with aspirin and clopidogrel A. Gaspar, S. Ribeiro, S. Nabais, S. Rocha, P. Azevedo, M. Pereira, A. Brandao, A. Correia. Sao Marcos Hospital, Braga, Portugal Purpose: Clopidogrel is an antiplatelet agent converted to its active metabolite by P-450 isoenzymes. Numerous drugs are known to inhibit P-450 isoenzymes, such as proton pump inhibitors (PPI) which are often associated to aspirin and clopidogrel to prevent adverse gastrointestinal effects. In vitro studies showed that PPI reduced the antiplatelet effect of clopidogrel. However, little information is known about the clinical relevance of PPI clopidogrel interaction. The aim of this study was to evaluate if the prescription of a PPI conferred worst prognosis to patients discharged with aspirin and clopidogrel. Methods: A total of 922 patients admitted with ACS and discharged with aspirin and clopidogrel, from January 2004 to April 2008, were reviewed. Patients were classified in 2 groups according to the association or not of a PPI to aspirin and clopidogrel. The PPI considered were omeprazol, rabeprazol and lansoprazol. Primary endpoint was the composite endpoint of death, nonfatal myocardial infarction or rehospitalization for anginal symptoms at 6 months. Results: Of the 922 patients discharged with aspirin and clopidogrel, 243 were also medicated with a PPI (omeprazol, rabeprazol or lansoprazol). Patients medicated with a PPI were older (65.4±13.6 vs 61.6±13.9; p <0.001), and more often had hypertension (69.1% vs 61.9%; p=0.04), renal insufficiency (29.7% vs 18.1%; p <0.001) and previous stroke (8.6% vs 4.9%; p=0.04). They also more often presented with Killip class > 1(p <0.001) and had lower haemoglobin concentration (13.6±1.8 vs 14.1±2.1; p <0.001) on admission. By multivariate analysis, independent predictors of PPI prescription were older age and Killip class > 1on admission. There were no significant differences between the 2 groups when considering invasive procedures. Patients with PPI didn t have a higher prevalence of the composite endpoint (8.8% vs 8.4%). By multivariate analysis including potential confounding variables (age, Killip class on admission, haemoglobin concentration on admission, hypertension and renal insufficiency), the prescription of a PPI with aspirin and clopidogrel remained not associated with a worse prognosis. Conclusions: In the present study, PPI prescription in addition to aspirin and clopidogrel was not associated with a worse prognosis in patients with ACS. However, randomized trials are necessary to obtain definite conclusions about the clinical relevance of PPI clopidogrel interaction Interaction of proton pump inhibitors (PPIs) with the antiplatelet effect of clopidogrel in patients undergoing coronary stenting C.S. Zuern 1, T. Geisler 1,N.Lutilsky 1,A.E.May 1, C. Herdeg 1, S. Winter 2,M.Schwab 2,M.Gawaz 1. 1 Medizinische Universitaetsklinik Tuebingen, Tubingen, Germany; 2 Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany Background: Nowadays, drug drug interactions negatively influencing the clopidogrel efficacy, especially statins, have been controversially discussed. Recently, the negative influence of proton pump inhibitors (PPIs) on the clopidogrel effect was suggested in the OCLA trial. A competitive metabolic effect at CYP 2C19 level is proposed to underlie clopidogrel s reduced effectiveness in patients receiving PPIs. However, conflicting data exist about this interaction. We conducted a single center study to assess effect of peri-procedural PPI co-administration on the metabolization of a loading dose of 600 mg clopidogrel followed by 75 mg maintenance dose on ex vivo platelet aggregation in patients undergoing coronary stent implantation. Patients and methods: 424 patients (29.8%) received a peri-procedural PPI treatment and 1001 (70.2%) were not treated with PPIs. 36 patients received omeprazole (mean dose (MD) 24.9±11.2mg), 108 esomeprazole (MD 24.3±9.2 mg) and 280 pantoprazole (MD 35.7±16.6mg), based on physician preference. Treatment differences of covariates were tested with Fisher s exact test or Wilcoxon-Mann-Whitney-tests. Results: In univariate analysis, there were significant differences between the two groups regarding age, gender, rate of acute coronary syndrome and comedication with statins. Residual platelet activity (RPA) assessed by final adenosine diphosphate (20 μmol/l)-induced platelet aggregation was significantly higher in PPI-treated patients (34.1±21.3%) than patients without concomitant PPI therapy (29.8±20.2%, p<0.001). In multivariable linear regression analysis using platelet aggregation as a dependent variable, PPI treatment showed a significant influence on RPA after adjustment for possible confounders [beta-coefficient (0.089), 95% confidence interval (CI): (0.015 to 6.67);(P =0.005)]. Discussion: In conclusion, we demonstrated that peri-procedural coadministration of PPIs significantly decreased the effect of clopidogrel on RPA. To our knowledge, this is the largest study investigating the influence of PPIs on ex vivo platelet aggregation in an unselected, consecutive cohort of patients with symptomatic CAD undergoing coronary stenting treated with dual antiplatelet therapy. Our data contribute to evidence that is pointing towards a potentially significant interaction between PPI and clopidogrel. A resulting higher susceptibility for thromboischemic events merits further investigation Is there a rebound effect after clopidogrel cessation in patients undergoing percutaneous coronary intervention and drug- eluting stent implantation? G. Lemesle, R. Torguson, L. Bonello, A. De Labriolle, G. Maluenda, A. Margulies, Z. Xue, J. Lindsay, A. Pichard, R. Waksman. Washington Hospital Center, Washington, United States of America Background: Clopidogrel cessation after percutaneous coronary intervention (PCI) with drug eluting stent (DES) implantation has been reported to be predictor of early events. However, it is currently debated if this increased short-term risk of adverse events after clopidogrel cessation is related to a rebound effect. This study aimed to determine the link between clopidogrel cessation and cardiovasculareventsafterpci. Methods: From 2003 to 2007, 1951 patients underwent PCI with DES implantation and were eligible for this study. We compared patients who stopped their clopidogrel within the first month (group 1, n=97), between 1 and 6 months (group 2, n=346), between 6 and 12 months (group 3, n=514) and after 12 months after the PCI (group 4, n=994). We indexed the primary composite endpoint death - myocardial infarction - stent thrombosis at 30 days after the clopidogrel cessation. Figure 1. Rates of primary composite endpoint death - myocardial infarction - stent thrombosis in the 4 groups at 30 days after the clodidogrel discontinuation

145 Challenges for the clinician / Biomarkers, genes and metrics in heart failure 445 Results: Baseline characteristics were similar among groups. The rate of the composite endpoint at 30 days after clopidogrel cessation was much higher in the group 1 vs the groups 2, 3 and 4: 5.2% vs 1.4%, 0.9% and 0.6%, respectively (p=0.004) (Figure). Conclusion: This study suggests that cardiac events seen immediately after clopidogrel cessation are not related to a rebound phenomenon, and more likely influenced by the lack of healing at the time of cessation which decreases over the time Which platelet function test is the most sensitive for the in vivo effects of clopidogrel? A pharmacokinetic analysis H.J. Bouman 1, J.W. Van Werkum 1, N. Breet 1, C.M. Hackeng 1, J.M. Ten Berg 1, D. Taubert 2. 1 St Antonius Hospital, Nieuwegein, Netherlands; 2 Universitaetsklinikum Koeln, Cologne, Germany Introduction: Multiple platelet function tests claim to be P2Y12-pathway specific and capable to capture the specific biological activity of clopidogrel. However, due to the instable nature of the active metabolite of clopidogrel (AMC), pharmacokinetic data of clopidogrel in relation to the performance of platelet function tests are scarce. The aim of the present study was to determine which platelet function test [ if any ] is the most sensitive to the in vivo biological activity of clopidogrel. Methods: Clopidogrel naïve patients scheduled for elective PCI visited the outpatient clinic and received a 600 mg loading dose of clopidogrel and 100 mg of aspirin. For pharmacokinetic analysis, blood was drawn at 0, 20, 40, 60, 90, 120, 180, 240 and 360 minutes after clopidogrel loading. Immediately after blood withdrawal, samples were centrifugated and pipetted into tubes containing a stabilizing agent [Pat. No. DE ]. Samples were stored at -80 C until AMC analysis with LC-MS/MS. At baseline and 360 minutes after clopidogrel loading, the following platelet function tests were performed: classical 5 and 20 μmol/l ADP-induced light transmittance aggregometry (LTA), the Verifynow P2Y12 assay, the flowcytometric VASP-assay, ADP-induced whole blood impedance aggregometry (WBA) and the IMPACT-R after pre-stimulation with ADP. Results: The flowcytometric VASP assay showed the strongest correlation with the peak plasma concentration (cmax) of the AMC [r=0.77, p<0.001], followed by the Verifynow P2Y12 assay [r=0.69, p<0.001] and 20 μmol/l ADP-induced LTA [r=0.68, p=0.001]. In contrast, LTA induced by a lower concentration ADP (5 μmol/l) did not show a significant correlation with cmax of the AMC [r=0.43, p=0.06], nor did WBA [r=0.25, p=0.31] and the IMPACT-R [r=-0.16, p=0.50]. Conclusion: The flowcytometric VASP assay, the Verifynow P2Y12 assay and 20 μmol/l ADP induced LTA are most sensitive to the in vivo biological effects of clopidogrel therapy. Further evaluation of these tests should be based on the relationship with clinical events in addition to the biological activity, the labour intensiveness and costs. BIOMARKERS, GENES AND METRICS IN HEART FAILURE 2761 Myocardial gene expression in peripheral blood of patients with idiopathic dilated cardiomyopathy is associated with myocardial function J.E. Kontaraki, A.P. Patrianakos, F.I. Parthenakis, E.G. Nyktari, P.E. Vardas. Cardiology Dept. Heraklion University Hospital, Heraklion, Greece Purpose: Heart failure is characterized by adverse left ventricular remodeling and reduced contractile function associated with altered gene expression profile. We evaluated gene expression levels of genes related to contractile function in peripheral blood of patients with idiopathic dilated cardiomyopathy (IDCM) in relation to echocardiography findings. We examined transcript levels of sarcoplasmic reticulum calcium ATPase 2 (SERCA) and phospholamban (PLB) as well alpha and beta myosin heavy chain (alpha-mhc, beta-mhc) in peripheral blood of IDCM patients. Methods: Echocardiography, tissue Doppler imaging and blood sampling were obtained in 73 consecutive IDCM patients. Gene transcript levels were determined by quantitative real time reverse transcription PCR. Results: SERCA2 transcript levels were significantly higher in IDCM patients with atrial fibrillation as compared to patients in sinus rhythm (6.76±0.94 versus 4.68±0.46, p=0.032). Significant negative correlations were observed between SERCA2 expression and LVEF (r=-0.339, p=0.011) as well as PLB and left atrial diameter (LA) (r=-0.363, p=0.006). In addition SERCA2/PLB ratio was negatively correlated with the septal peak systolic tissue velocity (Ss) (r=-0.395, p=0.002). alphamhc expression was negatively correlated with the mitral peak velocity of the early filling Em (r=-0.300, p=0.031) and positively correlated with the mean peak systolic tissue velocity S (r=0.323, p=0.019). betamhc expression was negatively correlated with left ventricular end systolic volume (LVESV) (r=0.279, p=0.043). In addition beta/alphamhc ratio was positively correlated with the mean early diastolic tissue velocity E (r=0.399, p=0.003). Conclusions: Our study provides data for the first time that demonstrate a correlation between SERCA transcript levels in peripheral blood and the presence of atrial fibrillation in IDCM patients. In addition, myocardial gene transcript levels in peripheral blood of IDCM patients are associated with left ventricular systolic and diastolic function as accessed by tissue Doppler echocardiography Early changes in intrathoracic impedance and right ventricular pressures in patients predict minor and major heart failure decompensation F. Braunschweig 1, M. Vanderheyden 2,S.Verstreken 2, M. Stahlberg 1, P. Reiters 3, R. Kessels 3, R. Houben 3. 1 Karolinska University Hospital, Stockholm, Sweden; 2 Department of Cardiology, Onze Lieve Vrouwe Ziekenhuis Aalst, Aalst, Belgium; 3 Medtronic Bakken Research Center, Maastricht, Netherlands Hospitalization for volume overload decompensation is a common complication in the course of chronic heart failure (HF) and predicts poor outcome. To better understand the hemodynamic characteristics of decompensated heart failure, we analysed information derived from intrathoracic impedance monitoring and continuous right ventricular (RV) pressure measurements. Methods: Sixteen HF patients (63±14 yr; LVEF 23±11%, NYHA 2.5) with a previous HF decompensation event received an ICD (InSync Sentry) providing a daily average of intrathoracic impedance and physical activity, and an Implantable Hemodynamic Monitor (Chronicle IHM, model 9520, both Medtronic Inc). The IHM consists of a memory unit and a transvenous RV lead containing a sensor (Model 4328) continuously recording various RV pressure parameters and an estimate of the pulmonary artery diastolic pressure (epad). After a stabilization phase of 3 months, patients were followed for 22±8 months. Hemodynamic baseline values were determined as the average over a 4-week period with the patient in stable clinical condition. Major HF events were defined as a HF decompensation requiring hospitalization, iv diuretics or leading to death while minor events required adjustments of oral diuretic medication in the outpatient setting Results: There were 16 major and 20 minor HF events in 10 and 8 patients, respectively. The day before a major HF event compared with stable baseline, filling pressures (epad) had increased by 6.8±6.5 mmhg (p<0.05) while the increase was 4.8±5.7 mmhg (p<0.05) for minor HF events. Correspondingly, impedance had decreased by -5.5±7.0 Ohm (p<0.05) before major but only -2.1±3.1 Ohm (p<0.05) before minor events. Importantly, significant increases in filling pressures were already observed 14 days before major (4.6±4.5 mmhg) and minor (2.7±4.0 mmhg) HF events. At this time, impedance had decreased by -4.3±7.8 Ohm (major) and -1.5±3.2 Ohm (minor, both ns). The clinical deterioration at the time of decompensation was also confirmed by significant decreases in physical activity by -44±60 au (major) and -40±39 au (minor). Conclusion: HF decompensation develops gradually on the basis of significant hemodynamic deviations from stable baseline conditions that are detectable already 14 days prior to the clinical event. Major HF events are characterized by larger derangements in filling pressures and pulmonary fluid retention than minor events. These findings emphasize the importance of maintaining low filling pressures in heart failure patients to prevent HF decompensation Patient-reported dyspnea in acute heart failure trials. Use of the Likert and the visual analog scales in the pre-relax AHF study S. Teichman 1, E. Unemori 1,M.Metra 2,J.R.Teerlink 3, A.A. Voors 4, G.M. Felker 5,P.Ponikowski 6, B. Weatherley 7, G. Filippatos 8, G. Cotter 7 on behalf of RELAX-AHF Investigators. 1 Corthera, Inc., San Mateo, California, United States of America; 2 Section of Cardiovascular Diseases, Dept of Experimental And Applied Medicine, University of Brescia, Brescia, Italy; 3 Veterans Affairs Medical Center, University of California, San Francisco, California, United States of America; 4 University Medical Center, Groningen, Netherlands; 5 Cardiology Dept., Duke Clinical Research Institute, Durham, North Carolina, United States of America; 6 Department of Cardiology, Centre for Heart Disease, Clinical Military Hospital, Wroclaw, Poland; 7 Momentum Resarch, Inc., Durham, North Carolina, United States of America; 8 University Hospital Attikon, Athens, Greece Patient-reported measures of dyspnea severity and relief are often used in trials of acute heart failure (AHF). Frequently, they are the primary endpoint for evaluation and regulation of new therapies. Despite its importance, there has been little research on the utilityof or the appropriate timing for the two standard instruments that are used for assessing dyspnea in AHF trials. Methods: In the present analysis, we compared the ability of two instruments to measure patient-reported improvements in dyspnea: (1) the 7-point Likert scale, which grades dyspnea change relative to baseline as categories from +3 to - 3 (markedly, moderately or minimally better, unchanged, minimally, moderately, or markedly worse) and (2) the visual analog scale (VAS), which rates absolute current severity of dyspnea on a 100-mm line (100 being the best possible and zero the worst score). These measurements were collected in Pre-RELAX-AHF, a 234 patient phase II placebo-controlled study evaluating the effect of IV relaxin in patients with AHF randomized within 16 hours from presentation. The Likert scale and VAS were used in parallel to measure dyspnea improvement at baseline (VAS only), 6, 12 and 24 hours, then daily through day 7 and at day 14. Results: In all groups at all timepoints, dyspnea improvement was measurable by both VAS and Likert scale and there was moderately good overall correla-

146 446 Biomarkers, genes and metrics in heart failure tion (r=0.69). The pattern of mean response over time differed for the two scales. Mean VAS change from baseline increased from +8.6±13.6 mm at 6 hours to +20.4±30.2 mm at day 14 while the same improvement was measured by the mean Likert scale as +1.1±1.0 at 6 hours and +1.4±2.3 at Day 14. At 6 hours, improvement by each Likert grade translated into a 7.5 mm increase in VAS while at 14 days, improvement by each Likert grade was associated with a 12.4 mm VAS increase. The report by Likert of moderate or marked improvement of dyspnea was associated with a VAS improvement of 14.1 mm at 6 hours and of 50.9 mm increase at day 14. Conclusions: In this study, the Likert scale appeared to be more sensitive to early relief of dyspnea than VAS. Improvements at later time points measured as small incremental changes by the Likert were quantified as larger changes using the VAS, suggesting that VAS is more sensitive for measuring continued dyspnea improvements at later time points Cystatin C as a marker of acute kidney injury in acute heart failure: definitions and impact on outcomes of the cardiorenal syndrome J.P.E. Lassus 1,M.S.Nieminen 1, K. Peuhkurinen 2,K.Pulkki 3, K. Siirila-Waris 1, R. Sund 4,V.-P.Harjola 5 on behalf of FINN-AKVA study group. 1 Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; 2 Department of Cardiology, Kuopio University Hospital, Kuopio, Finland; 3 Department of Clinical Chemistry, Kuopio University, Kuopio, Finland; 4 National Institute for Health and Welfare, Helsinki, Finland; 5 Division of Emergency Care, Department of Medicine, Helsinki, Finland Purpose: Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is part of the cardiorenal syndrome and has been associated with increased morbidity and mortality. Cystatin C (CysC) is a prospective new marker of AKI, but its use in clinical populations has not been well evaluated. The objective of this study was to investigate the use of CysC as a marker of early AKI in AHF. Methods: Patients (n=292) hospitalized for AHF from the multicentre FINN-AKVA study had meas-urements of CysC on admission and at 48 hours. Changes in CysC levels between the two measurements were assessed, and a rise in CysC was regarded a decline in renal function. The incidence of AKI and effect on length of hospital stay was evaluated. Odds ratios (OR) for mortality up to 12 months were calculated by logistic regression. Results: The population was on average 75 years old and 49% were female. On admission, me-dian CysC was 1.25 mg/l (interquartile range mg/l). Increments in CysC within 48 hours after hospitalisation were frequently observed, with the incidence ranging from 44% of patients having an increase of 0.1 mg/l or more to 8% with a rise in CysC>0.5mg/L. AKI was associated with adverse outcomes and the odds of death increased with severity of AKI (Figure). An increase in CysC >0.3 mg/l by 48 hours resulted in 5 days longer hospital stay (p=0.02) and was associated with significantly higher in-hospital mortality, OR 4.0 (95%CI ). In addition, a rise in CysC >0.3mg/L was an independent predictor of 90-day mortality, adjusted OR 2.8 (95%CI ). patients with chronic heart failure (CHF). We hypothesize that short telomere length, a marker of cellular ageing, contributes to the susceptibility to develop anaemia in patients with CHF. Therefore, we assessed the relationship between telomere length and anaemia in CHF patients. Methods: Telomere length was measured in circulating white blood cells with real-time quantitative polymerase chain reaction in 875 CHF patients. Results: The median age of the patients was 73 years [interquartile range 64-79], 61% was male, left ventricular ejection fraction (LVEF) was 30 [23-44]%, estimated glomerular filtration rate (egfr) 53 [40-68] ml/min/1.73m 2, and Hb levels 8.4 [ ]. 254 patients (29%) fulfilled the WHO criteria of anaemia. Anaemia was predicted by shorter telomere length (Odds ratio [OR] 1.31 per SD lower telomere length; 95% confidence interval [CI] ; p=0.001) in univariate logistic regression analysis. This effect persisted after adjustment for age, gender and all baseline differences, which were egfr, LVEF, a history of stroke and diabetes, age of onset of CHF, diastolic blood pressure, and Brain Natriuretic Peptide (BNP) levels (OR 1.35 per SD lower telomere length; 95% CI ; p=0.008). This effect was stronger than a 10 ml/min decrease of egfr (Odds ratio 1.13, 95% CI ; p=0.020). Finally, telomere length was inversely associated with continuous Hb levels (correlation coefficient 0.119, p<0.001). Conclusions: We found that shorter telomere length is an independent risk factor of anaemia in CHF patients. The effect of shorter telomere length is even larger than that of a decrease of renal function an established risk factor of anaemia of 10mL/min/1.73m 2 decrease of egfr Hand-held echocardiography in primary care patients with heart failure and heart failure risk factors M. Lipczynska, P. Szymanski, A. Klisiewicz, P. Hoffman. Institute of Cardiology, Warsaw, Poland Background: The real-world surveys have demonstrated limited availability of echocardiographic examinations. The aim of the study was to assess whether simplified hand-held echocardiograms, performed by the noncardiologists, would provide clinically important prognostic information. Methods: The physician without previous experience underwent a basic level training in echocardiography. Medical records of 5,521 inhabitants of a town were screened for the inclusion criteria: age 55 years and HF or HF risk factors: ischaemic heart disease and/or hypertension and/or diabetes mellitus. Hand held echocardiograms were performed and NT-pro-BNP levels were measured in patients fulfilling the inclusion criteria. Patients were prospectively followed for the occurrence of the combined end point of death or rehospitalization for cardiovascular causes. Results: 175 out of 218 patients fulfilling the inclusion criteria consented to participate in the study. Hand-held echocardiogram was abnormal in 94 (57%) patients. During 48±7 months of follow-up, combined end point occurred in 44 patients (25%). On multivariate analysis abnormal echocardiogram (OR 6.32, 95% CI ; p=0.0001), cerebrovascular disease (OR 3.93, 95% CI ; p=0.01), atrial fibrillation/flutter (OR 2.70, 95% CI ; p=0.001), Figure OR for death with rise in CysC. Conclusion: CysC can be used for detection of early AKI. A decline in renal function during the first 48 hours after hospitalization occurs frequently in patients hospitalized for AHF and has a detrimental impact on prognosis Telomere length is an independent risk factor for anaemia in patients with chronic heart failure L.S.M. Wong 1, J. Huzen 1,P.VanDerHarst 1, R.A. De Boer 1, G.F.J.D. Benus 1, A.A. Voors 1, W.H. Van Gilst 1, N.J. Samani 2, T. Jaarsma 1, D.J. Van Veldhuisen 1. 1 University Medical Center Groningen, Groningen, Netherlands; 2 University of Leicester, Glenfield hospital, Leicester, United Kingdom Purpose: Anaemia is highly prevalent and associated with poorer prognosis in Kaplan Meyer event-free survival curves

147 Biomarkers, genes and metrics in heart failure / Defining risk in heart failure subsets 447 and NT-pro-BNP 206 pg/ml (OR 2.68, 95% CI ; p=0.007) remained the independent predictors of the combined end point. Kaplan-Meyer event free survival curves for subgroups of patients with normal vs abnormal echocardiogram and normal vs abnormal NT-pro-BNP levels are presented below. Conclusions: Simplified hand-held echocardiographic examinations performed by non-cardiologists provide important prognostic information in patients with heart failure or heart failure risk factors. DEFINING RISK IN HEART FAILURE SUBSETS 2767 Predictors of plasma renin activity, a main prognostic determinant in systolic heart failure G. Vergaro, A.L. Iervasi, A. Valleggi, M. Fontana, A. Giannoni, R. Poletti, C. Passino, L.E. Pastormerlo, M. Emdin. Fondazione Toscana Gabriele Monasterio, Pisa, Italy Background: Even optimal pharmacological antagonism of adrenergic and reninangiotensin-aldosterone (RAAS) systems may be incomplete and prognostically ineffective in heart failure (HF) patients. We aimed to assess the prognostic value and determinants of plasma renin activity (PRA) as a marker of persistent RAAS activation in treated systolic HF patients. Methods: We selected 1029 patients with systolic heart failure (left ventricular ejection fraction, EF 50%) on optimal treatment (75% male, 25% female; age 65±13 years; EF, 33±10%; NYHA class I-II 63%, III-IV 37%; estimated creatinine clearance 71±34 ml/min; BB 80%; ACE-Is/ARBs 82%; spironolactone 57%) who underwent a complete clinical and neurohormonal characterization. All patients were then followed-up (median 33 months; range 1-130) for a composite endpoint of cardiac death and appropriate shock in patients carrying an implantable cardioverter defibrillator (ICD). Results: We reported an overall number of 122 events (108 cardiac deaths and 14 ICD shocks). At multivariate analysis EF, NT-proBNP and PRA were the only predictors of cardiac end-point (all p=0.000). Prognostic PRA cut-off level was established at 1.70 ng/l/h (ROC AUC 0,688; p=0.000; sensibility 67%; specificity 57%). Among several factors detected at univariate analysis, only EF (p=0.000), NT-proBNP (p=0.004), norepinephrine (p=0.001), aldosterone (p=0.000), insulin (p=0.014), gamma-glutamyl transferase (p=0.023), C-reactive protein (p=0.019) and spironolactone treatment (p=0.003) resulted independent predictors of PRA at multivariate analysis. These results suggest that PRA level is significantly affected by a wide spectrum of neuro-hormonal variables, and thus reflects the overall hemodynamic and endocrine equilibrium of patients. Conclusion: In systolic HF, PRA is a hallmark of poor outcome, depicting a subset of patients needing enhanced RAAS antagonism. Inflammation, cardiac and systemic damage, adrenergic activation and aldosterone feedback influence PRA level, indicating complementary therapeutical targets in this high risk subset The obesity paradox in stable chronic heart failure does not persist after matching for indicators of disease severity and confounders L. Frankenstein, B. Remppis, M. Nelles, D. Schellberg, H. Hees, A. Schmidt, H. Katus, C. Zugck. Medizinische Fakultaet Heidelberg, Heidelberg, Germany Purpose: It is unclear whether body-mass-index (BMI) conveys a prognostic benefit per se or acts as a confounder causing the obesity paradox in CHF. We sought to verify whether controlling for indicators of disease severity and other confounders might represent a solution to the obesity paradox in chronic heart failure (CHF). Methods: From 1790 patients we formed 230 nested matched triplets (=690 patients) by individually matching patients with stable systolic CHF and BMI>30 kg/m*m (group 3) with respect to NT-proBNP, age, sex, and NYHA to individual patients with BMI k/m*m (group 1) and with BMI kg/m*m (group 2), (triplet = 1 matched patient from each group). Results: In the pre-match cohort, increasing BMI-group was a significant indicator of favourable prognosis (HR: 0.83, 95%CI: , Chi 2 : 6.72). In multivariable analysis with group-propensities as co-variates, it did not retain significance (HR: 0.91, 95%CI: , Chi 2 : 1.67). In the matched cohort, 1-year Survival according to BMI-status mortality was 10%,8%,9% and 3-year mortality 20%,18%,13% for group 1,2,3, respectively (p=n.s., each). Regarding prognostication, BMI failed statistical significance both as a continuous or categorical variable, whether crude or adjusted. NT-proBNP, however, remained statistically significant (log(nt-probnp): HR: 1.59, 95%CI: , Chi 2 : 8.75) after adjustment for age, renal function, aetiology of CHF and mean blood pressure. Conclusion: The obesity paradox appears not to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP, however, remains an independent prognostic indicator of adverse outcome irrespective of obesity status Delayed mortality in peripartum cardiomyopathy indicates need for long-term follow up K. Sliwa 1, O. Forster 1, K. Tibazarwa 2, E. Libhaber 1, A. Becker 1, A. Yip 1, D. Hilfiker-Kleiner 3. 1 University of the Witwatersrand, Johannesburg, South Africa; 2 The University of Cape Town, Cape Town, South Africa; 3 Medizinische Hochschule Hannover, Hannover, Germany Background: Peripartum cardiomyopathy (PPCM) is a rare form of cardiomyopathy with heterogeneous presentation around the world occurring in women between 1 month antepartum and 5 months postpartum. It carries a substantial risk of mortality within the first 6 months after diagnosis but few studies have outlined the long-term outcome. The aim of this study was to assess long-term clinical outcome including mortality over a 2-year period in an African cohort. Methods: A prospective, single centre study of 80 consecutive women with PPCM enrolled at diagnosis was conducted over a period of 2 years. Patients were started on standard heart failure therapy (ACE-inhibitors, beta-blockers, diuretics) and detailed assessments, including echocardiography, were made in surviving patients at 6-month intervals for 24 months. Outcome at each 6-month interval was measured by NYHA functional class, left ventricular (LV) function and mortality. Additional clinical parameters (Heamoglobin, serum CRP, IL-6, TNFalpha, Fas/Apo-1, and T-cell count) were also measured. Results: At baseline, the mean age of this cohort was 30±7 years; 38% were in their first pregnancy and 34% of patients were co-infected with HIV. Overall, 89% of patients presented in NYHA functional class III-IV at baseline and mean left ventricular ejection fraction (LVEF) was 30±9%. During the 2-year study period, 4 patients were lost to follow-up, 9 moved to remote areas, and 7 were excluded for having had a subsequent pregnancy, which predisposes them to additional myocardial risk. Within the entire 2 year period, 22 women (28%%) died. The mortality rate at 6 months was 10% (8 of 80). Of the 69 patients still enrolled at 6 months, an additional 14 (20%) came to die over the remaining 18-month period; despite demonstrating clinical recovery of left ventricular function. Among those surviving to 6 months and beyond, mean LVEF was: 44±11% at 6 months, 46±13% at 12 months and 50±14% at 24 months follow up, respectively. No difference in cardiac function and mortality was observed between the two groups of PPCM patients with or without HIV co-infection. Conclusion: Overall the prognosis in this African cohort was poor; confirming the high mortality rate of PPCM. A novel and somehow unexpected finding of this study is the high mortality rate in PPCM occurring beyond 6 months despite optimal heart failure therapy, which seems independent from HIV infection. This finding strongly suggests the need for long-term clinical follow-up including risk assessment of arrhythmic death Predictive value of n-terminal pro-b-type natriuretic peptide and echocardiographic paramaters in patients with peripartum cardiomyopathy M. Biteker, N. Duran, H. Kaya, M. Yildiz, T. Gokdeniz, S. Gunduz, I.H. Tanboga, G. Kahveci, T. Akgun, M. Ozkan. Kartal Kosuyolu Heart Education and Research Hospital, Istanbul, Turkey Purpose: We sought to evaluate the value of plasma N-terminal pro B type natriuretic peptide (NT pro BNP) levels and echocardiographic parameters in predicting prognosis of peripartum cardiomyopathy (PPCM) patients. Background: Predictive value of plasma NT pro BNP concentration measured at presentatiton in patients with PPCM is unknown. Methods: We prospectively evaluated 24 consecutive women with PPCM. All patients were treated with optimal conventional heart failure therapy. Clinical evaluation, echocardiograms, NT pro BNP determinations were performed at baseline, and patients attended the cardiac clinic every 3 months. Mean follow-up period was 22.1±9 months. All women in the study presented with New York Heart Association functional class III to IV heart failure and a left ventricular ejection fraction (LVEF) of <0.40. Results: Eleven (45.8%) patients recovered completely, 6 (25%) died, and 7 (29.1%) were left with persistent left ventricular dysfunction (PLVD). Patients who died had lower LVEF, larger left ventricular dimensions and higher NT pro BNP levels at diagnosis (Fig) compared with those who survived (p < 0.05). Significant differences in the baseline data between deceased patients and survivors were seen in values for left ventricular end-diastolic diameter (LVEDD) (7.1±0.6 cm vs 6.4±0.5 cm, p = 0.031), left ventricular end-systolic diameter (LVESD) (6.4±0.8 cm vs 5.5±0.6 cm, p = 0.027), LVEF (19.7% vs 27.4%, p = 0.025), left atrial diameter (4.9±0.3 cm vs 4.3±0.4 cm, p = 0.011) and mean plasma NT pro BNP levels ( ±5245 pg/ml vs ±4532 pg/ml, p < 0.001).

148 448 Defining risk in heart failure subsets / Non-invasive risk assessment for sudden cardiac death: are there new opportunities? Conclusions: Baseline NT pro BNP levels, LVEF, LVESD and, left atrial diameter seem a reliable parameter to identify those at risk for clinical deterioration at mid-term follow-up Mid-region pro-atrial natriuretic peptide and the diagnosis of heart failure in the setting of atrial fibrillation: an exploratory analysis of the biomarkers in acute heart failure (BACH) trial K. Singh 1,N.Parekh 1, I. Anand 2, L. Daniels 1, S. Di Somma 3, G. Filippatos 4, C. Mueller 5,R.Nowak 6, S. Anker 7,A.Maisel 1. 1 University of California, San Diego, San Diego, United States of America; 2 Minneapolis VA Medical Center, Minneapolis, United States of America; 3 La Sapienza Universita, Rome, Italy; 4 Athens University Hospital Attikon, Athens, Greece; 5 University Hospital Basel, Basel, Switzerland; 6 Henry Ford Health System, Detroit, United States of America; 7 Charite - Campus Virchow-Klinikum, Berlin, Germany Purpose: B-type natriuretic peptide and amino-terminal pro-bnp are useful in diagnosing heart failure in acute dyspnea. They retain diagnostic utility in atrial fibrillation (AF). Atrial natriuretic peptide (ANP) is a novel peptide released by the overloaded atria. We asked whether the prohormone fragment mid-region proanp (MRproANP) would be less specific in diagnosing heart failure in the setting of AF. Methods: Acutely dyspneic patients in the emergency room were evaluated by ECG and natriuretic peptide levels at presentation. Primary diagnosis of HF was determined by independent review by two cardiologists blinded to study biomarker results. Results: Of 1641 patients, 242 had an admission ECG demonstrating AF, 1203 had an ECG without AF, and 196 patients did not have ECG data. Of patients with AF, 153 had a primary diagnosis of heart failure, while there were 404 diagnoses of heart failure in the non-af group. Receiver-Operator Characteristic (ROC) curve analysis demonstrated that among patients with AF, MRproANP had an area under the curve (AUC) of while amongst patients without AF, the AUC was (p < 0.001). These results were comparable to other natriuretic peptides (see Figure 1). In AF, the differences between ROC curves of the natriuretic peptides was not statistically significant. Methods: The association between preoperative characteristics and outcome was analyzed in 70 consecutive patients with heart failure (HF) that underwent isolated MVR. Median age was 68 years, 70% were men, preoperative NYHA class was 2.8±0.5, LVEF was 31±5%, RVSP was 50mmHg and 31% had ischemic cardiomyopathy. All patients had undersized flexible annuloplasty rings inserted; mean ring size was 28±1.7mm. Results: 30-day mortality was 7.1% by a mean Euroscore of 7.5. Median followup was 2.4 years. 25 patients (35.7%) reached the study end point of overall mortality or transplantation (one transplantation). One and three years survival rates were 88% and 72%. Predictors of outcome by Cox analysis were ischemic cardiomyopathy (p=0.001), right ventricular dilatation (p=0.0002) and age (p=0.008), next variables in order of significance were RVSP 50mmHg (p=0.05), preoperative NYHA (p=0.1), gender (p=0.2), previous hospitalization for HF decompensation (p=0.2). Based on the survival analysis, a score system was build. Two points were assigned for variables with the most statistical weight (ischemic cardiomyopathy, right ventricular dilatation and age) and one point for NYHA 3, previous HF decompensation, RVSP 50mmHg and male gender. Receiving-operating characteristics (ROC) analysis was used to assess the prognostic value of the developed model. The score allowed for accurate risk stratification: area under the curve 0.82 (CI ), p= (fig.1). Conclusion: A prognostic model developed on the basis of routine parameters can adequately stratify heart failure patients with severe mitral regurgitation for their postoperative outcome. NON-INVASIVE RISK ASSESSMENT FOR SUDDEN CARDIAC DEATH: ARE THERE NEW OPPORTUNITIES? 2773 Holter-based risk stratification in elderly patients with congestive heart failure I. Cygankiewicz 1, W. Zareba 2, R. Vaquez 3, A. Bayes-Genis 4, A. Bardaji 5, J. Almendral 6, J.R. Gonzalez Juanatey 7,V.Nieto 8, J. Cinca 4, A. Bayes De Luna 1 on behalf of the MUSIC investigators. 1 Catalan Institute for Cardiovascular Science, Barcelona, Spain; 2 University of Rochester Medical Center, Rochester Ny, United States of America; 3 Valme University Hospital, Sevilla, Spain; 4 Hospital de Sant Pau, Barcelona, Spain; 5 Hospital Joan XXIII, Tarragona, Spain; 6 Hospital General Universitario Gregorio Maranon, Madrid, Spain; 7 University Hospital of Santiago de Compostela, Santiago De Compostela, Spain; 8 Hospital Universitario De Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain Purpose: Ageing of population contributes to growing number of patients diagnosed with congestive heart failure (CHF). There is limited data on ECG risk stratification in elderly patients. We aimed to evaluate the prognostic significance of clinical and ECG-based parameters for predicting total mortality (TM) in a cohort of mild to moderate CHF patients aged >70 years. Methods: A study included 293 CHF patients at age >70 (av.76 years; 192 Fig. 1. ROCs of NPs in HF & A.fib Conclusions: MRproANP is as efficacious as other natriuretic peptides in the diagnosis of acute heart failure. It retains diagnostic capacity equivalent to that of other natriuretic peptides in the setting of AF A score system to predict outcome after mitral valve repair in patients with heart failure A. Chrustowicz 1, K. Matschke 2,A.Gackowski 1, R.H. Strasser 2, G. Simonis 2. 1 Krakowski Szpital Specjalistyczny im. Jana Pawlall, Krakow, Poland; 2 Herzzentrum Dresden Universitaetsklinik, Dresden, Germany Aims: To develop a prognostic model to predict outcome of the isolated mitral valve repair (MVR) in patients with impaired left ventricular (LV) function. Figure1

149 Non-invasive risk assessment for sudden cardiac death: are there new opportunities? 449 males) with ischemic or nonischemic etiology of CHF and NYHA II/III class. Surface ECG and Holter monitoring were performed at enrollment to assess traditional ECG markers (VT, VPBs>10/h, HR>80bpm, QRS>120ms) as well as heart rate variability (HRV), heart rate turbulence (HRT), deceleration capacity (DC) and repolarization dynamics (QT/RR). Patients were followed for median of 43 months with primary endpoint defined as TM. Results: There were 96 (33%) deaths among 293 patients. Atrial fibrillation (AFib) was present in 93 (33%) patients. Among traditional ECG markers only AFib was associated with an increased TM after adjustment for clinical covariates (HR 1.59, p=0.028). In patients with sinus rhythm (SR) only abnormal HRT was independently associated with TM (HR=2.18, p=0.05 for HRT1 and HR=3.27, p=0.008 for HRT2). Figure 1 displays Kaplan Meier curves representing TM in patients with SR and different categories of HRT as compared to patients with AFib. Patients with HRT2 have similar 3 year mortality rate (36%) as patients with AFib (40%) Conclusions: Increased risk of mortality could be predicted in CHF patients aged >70 yrs by combination of clinical variables and dynamic ECG parameters. Presence of AFib or abnormal HRT (in SR patients) are powerful predictors of mortality in elderly patients with CHF 2774 Non-invasive Wedensky Modulation of T- & RT-wave accurately predicts arrhythmic events P.A. Brady 1,P.Erne 2, J. Val-Mejias 3,J.Schwab 4,R.Schimpf 5, M. Orlov 6, T. Mattioni 7, M. Malik 8,J.Amlie 9. 1 Mayo Clinic, Rochester, United States of America; 2 Kantonsspital, Luzern, Switzerland; 3 Galichia Medical Group, Wichita, United States of America; 4 University of Bonn, Bonn, Germany; 5 Universitaetklinikum Mannheim, Mannheim, Germany; 6 Caritas St Elizabeth s, Boston, United States of America; 7 Arizona Arrhythmia Consultants, Scottsdale, United States of America; 8 St George s Healthcare NHS Trust, London, United Kingdom; 9 Rikshospital, Oslo, Norway Background & Objectives: Wedensky Modulation (WM) is based on subthreshold transthoracic electrical stimulation. The WM Index (WMIR) measured within R-waves accurately predicts arrhythmic events. We hypothesized WM Index measured within T-waves (WMIT) would accurately predict arrhyth-mic events. Methods: WMIT index was prospectively evaluated post-hoc using patient ECG data. 268 post-myocardial infarction (post-mi) patients with ICD implantation had at least one 6 month follow-up com-pleted. Patients were placed into the WMIT-L group (WMIT 0.5, n=203) or the WMIT-H group (WMIT>0.5, n=65). Cumulative ICD-treated arrhythmia event rates for the two WMIT groups were com-pared using Kaplan-Meier estimates. Results: 36 first-year events (18%) for the WMIT-L group compared to 22 firstyear events (34%) for the WMIT-H group yielded log-rank p=0.01. Comparing WMIT-L to WMIT-H, the hazard ratio for event rates was =1.9 at one year (95% CI of 1.1 to 3.3, Cox p<0.02). WMIT was significantly different from WMIR regarding future cardiac-related events prediction (p<0.0001). When combined with WMI study results to form an R-wave/T-wave index (WMIRT) the event rate prediction significantly improves, raising the sensitivity from 64% (WMIR) and 38% (WMIT) to 81%. The event rate for the WMIRT-L group (WMIRT 0.5, n=106) was 10% compared to the event rate of 29% for the WMIRT-H group (WMIR>0.5, n=162). Conclusion: Post-MI patients with a high WMIT may have significantly increased risk of life-threatening arrhythmia when compared to patients with a low index Distribution of microvolt T wave alternans in a general population of patients undergoing a clinically indicated exercise ECG C. Cohen 1,M.Tafflet 2, P. Jourdain 3,P.Bareiss 1, M. Chauvin 1, G. Roul 1. 1 Hopital Civil de Strasbourg, Strasbourg, France; 2 INSERM Unit 909, Villejuif, France; 3 Centre Hospitalier Rene Dubos, Pontoise, France Objectives: To assess the distribution of the microvolt T-wave alternans in a general population of patients undergoing a clinically indicated exercise stress test. Background: T-wave alternans (TWA) has been proposed as a promising risk marker of life-threatening cardiac arrhythmias. Its analysis may become a routine non-invasive tool in the risk stratification for primary prevention of sudden cardiac death (SCD). This raises the question of its distribution in a broad population of unselected patients. Methods: We analyzed the TWA measurements in 547 consecutive patients who had undergone an exercise stress test regardless of the clinical indication. TWA was measured using the modified moving average method. The distribution of the TWA values was tested for normality using the D Agostino-Pearson omnibus test. Results: The study population consisted of 85% men. Mean age was 58±14 yrs. The distribution of TWA measurements is a non-gaussian one. Its rightskewed shape shows most of the population have a very low microvolt TWA value. Median value in men and women respectively was 25μV and 27μV with a 30.9±22.7μV average value. We found slight correlations to the age (Spearman s rho = 0.12; p= ), to the maximum heart rate reached (Spearman s rho = 0.20; p<0.0001) and to the body mass index (Spearman s rho = 0.2; p= ). No specific correlation to the medical therapy, the type of cardiopathy and any other baseline characteristics or exercise parameters was found. A value of TWA above the reported cut-off of 65 μv was found in more than 6% of the population. Conclusion: In a general population, the distribution of TWA is a non normal one. It is slightly correlated some characteristics of the population. This reported independent risk marker is elevated in a small part of the population Heart rate variability predicts arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy P. Santangeli, A. Macchione, F. Marzo, A. Dello Russo, M. Casella, G. Pelargonio, F. Bellocci, M. Pieroni, G.A. Lanza, F. Crea. Catholic University of the Sacred Heart, Rome, Italy Background: Indication to prophylactic implantable cardioverter-defibrillator (ICD) therapy is a challenging issue in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods: We prospectively studied 30 patients who fulfilled the criteria for ARVC of the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology. All patients underwent signal-averaged ECG, 24- hour Holter ECG monitoring (to assess ventricular arrhythmias and heart rate variability [HRV]), electrophysiologic (EP) study (with right ventricular electroanatomic voltage mapping and programmed ventricular stimulation), and endomyocardial biopsy (EMB). Fifteen patients received an ICD for primary prevention of sudden cardiac death according to judgement of the attending physician who, however, was unaware of the results of non-invasive investigations. The primary end-point was the occurrence of major arrhythmic events (AEs) (i.e., sudden death, resuscitated ventricular tachycardia/fibrillation [VT/VF]). Results: During 19±7 months of follow-up (range 4-33) no death occurred. Five patients (16%) experienced AEs; all these patients belonged to the ICD group and received appropriate ICD therapy for VT/VF. Univariate predictors of AEs were history of unexplained syncope (hazard ratio (HR) = 12.1, P=0.02) and inducibility of sustained VT/VF at EP study (HR = 5.9, P=0.05). Reduced HRV parameters were all significantly associated with AEs, with the strongest association being found for standard deviation of RR intervals in the time-domain (SDNN, HR = 0.91, P=0.02) and for low-frequency amplitude in the frequency-domain (LF, HR = 0.84, P=0.01). All patients with AEs had evidence of fibrofatty replacement at EMB, but EMB results did not significantly predict AEs (P=0.2). At multivariate Cox regression analysis LF amplitude remained an independent predictor of AEs (HR = 0.88, 95% CI 0.78 to 0.95; P=0.04). The only other variable independently associated with AEs was history of unexplained syncope (HR = 16.1, P=0.03). Conclusions: Our data suggest that HRV analysis can be helpful for arrhythmia risk stratification in patients with ARVC Value for paced QRS duration to detect left ventricular dysfunction Y.G. Su, W.Z. Pan, X. Gong, X.H. Shu, J.B. Ge. Department of Cardiology,Zhongshan Hospital, Shanghai, China, People s Republic of Purpose: To investigate the value for paced QRS duration (pqrsd) to detect left ventricular (LV) dysfunction (LVSD) and to observe the association between pqrsd and left cardiac structures and functions parameters in a large right ventricular apical (RVA) paced patient cohort. Methods: A total of 272 RVA paced patients including 99 with LV systolic dysfunction (LVSD, defined as LV ejection fraction (LVEF) < 0.55) and 173 without LVSD (LVEF 0.55) were enrolled in this study. The pqrsd, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and some echocardiographic variables, including left atrial diameter (LAD), LV end-systolic diameter (LVDS), LV end-diastolic diameter (LVDD), interventricular septum thickness (IVST), LV posterior wall thickness (LVPWT) and LVEF were measured. Relationships between pqrsd and such echocardiographic variables, NT-proBNP levels as well as New York Heart Association (NYHA) class were analyzed. Results: The pqrsd was positively correlated with LVDD (r = 0.572, P < 0.001), LVDS (r = 0.625, P < 0.001), LAD (r = 0.278, P < 0.001), IVST (r = 0.216, P < 0.001) and LVPWT (r = 0.208, P < 0.001;). pqrsd in patients with NYHA class I, II, III and IV was ±17.88, ±23.48, ±22.40 and ±23.04 ms, respectively. There was a step-wise increase in pqrsd corresponding to increase in NYHA class (all P < 0.05). pqrsd was negatively correlated with LVEF (r = , P < 0.001). Multi-variables linear regression demonstrated that LVEF, NYHA class, LVDD, IVST were independently associated with pqrsd (all P < 0.01). In addition, pqrsd was positively correlated with log (NT-proBNP) (r = 0.342, P <0.001), even after adjusting for pacing mode, atrial fibrillation and age (P <0.001). To evaluate the value for pqrsd to detect LVSD, receiver operating characteristic (ROC)curve was drawn and the area under curve (AUC) was calculated as 0.849±0.024 (P < 0.001). The pqrsd cut-off derived from the Youden index, giving equal weighting to sensitivity and specificity, was 200 ms. It had sensitivity of 71.72% and specificity of 86.71% to detect LVSD. pqrsd 240ms gave a positive predictive value 100% while <180 ms excluded > 97.3% of patients with LVSD. Conclusion: In RVA paced patients, pqrsd is correlated with left cardiac structures and function and a cut-off value for pqrsd of 200 ms provides a satisfactory balance of sensitivity and specificity for detecting LVSD.

150 450 Non-invasive risk assessment for sudden cardiac death / Drugs for atrial fibrillation: a continuing effort 2778 Prognostic value of short-term ECG monitoring in patients with congestive heart failure I. Cygankiewicz 1, W. Zareba 2, R. Vazquez 3, A. Bayes-Genis 4, M. Fiol 5, M. Valdes 6,J.Cinca 4, A. Bayes De Luna 1 on behalf of the MUSIC investigators. 1 Catalan Institute for Cardiovascular Science, Barcelona, Spain; 2 University of Rochester Medical Center, Rochester Ny, United States of America; 3 Hospital Valme, Sevilla, Spain; 4 Hospital de Sant Pau, Barcelona, Spain; 5 Hospital Universitario Son Dureta, Palma de Mallorca, Spain; 6 University Hospital Virgen De La Arrixaca, Murcia, Spain Purpose: Assessment of autonomic nervous system and the presence of arrhythmia by Holter monitoring are considered as complimentary methods to LVEF evaluation in risk stratification of patients with congestive heart failure (CHF). However, the use of long term ambulatory Holter recordings for this purpose is frequently neglected, being considered as too costly and not well tolerated by patients. Short-term ECG recordings performed during a routine clinical visit may be an interesting alternative for traditional Holter monitoring. The aim of this study was to assess the prognostic value of 20 minutes ECG recordings in predicting total mortality and sudden death in CHF. Methods: In 584 patients (418 men, mean age 63) with mild to moderate CHF and sinus rhythm, 20 minutes ECG recordings were performed at the enrollment to evaluate mean heart rate, arrhythmia (# of VPBs, VT), heart variability (HRV), heart rate turbulence (HRT) and deceleration capacity (DC). Patients were followed for a median 44 months with a primary endpoint defined as total mortality (TM) and secondary as sudden death (SCD). Results: There were 125 deaths, including 50 sudden deaths during a follow up. Univariate analysis identified #VPB 3/20min, all spectral indices of HRV and abnormal DC ( 4.5ms) as risk predictors of total mortality. Frequent VPBs (HR=1.71, p=0.001), VLFln<5.6 (HR=1.56, p=0.025) and impaired DC (HR=1.74, p=0.006) remained significant after adjustment for clinical covariates. No parameter was independently associated with SCD risk. Due to methodological requirements (at least 1VPB during a recording) HRT could be calculated only in 47% of patients, however among these patients abnormal turbulence slope was found to be significantly associated with an increased risk of total mortality and sudden death (in multivariate analysis HR=2.61, p<0.001, and HR=2.44, p=0.018 for TM and SCD respectively). Conclusions: Arrhythmia and heart rate variability parameters assessed from 20 minutes ECG recordings are useful in evaluation of total mortality risk in patients with CHF. In patients with at least 1 VBP abnormal HRT indicates high risk of total and arrhythmic death. DRUGS FOR ATRIAL FIBRILLATION: A CONTINUING EFFORT 2779 Effects of dronedarone on clinical outcomes in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA study H.J.G.M. Crijns 1, S.J. Connolly 2, C. Gaudin 3,M.VanEickels 4, R.L. Page 5, C. Torp-Pedersen 6, S.H. Hohnloser 7 on behalf of ATHENA Investigators. 1 University Hospital Maastricht, Maastricht, Netherlands; 2 McMaster University, Hamilton, Canada; 3 sanofi-aventis R&D, Paris, France; 4 sanofi-aventis R&D, Frankfurt Am Main, Germany; 5 University of Washington, Seattle, United States of America; 6 Gentofte Hospital, Hellerup, Denmark; 7 Klinikum der J.W. Goethe Universitaet, Frankfurt am Main, Germany Background: Coronary heart disease (CHD) is a risk factor for atrial fibrillation (AF) and a strong predictor for cardiovascular morbidity and mortality. Many antiarrhythmic drugs are disallowed for use in CHD. Methods: Athena is a large randomized trial in patients with paroxysmal or persistent AF and additional cardiovascular risk factors. Patients were randomized to receive dronedarone (400 mg bid), a new multichannel blocking drug with vasodilating properties, or double-blind matching placebo and were followed for a minimum of one year. The present post-hoc analysis examines the subpopulation of patients with a history of CHD. Results: A total of 2732 patients (60% of the total population) with a history of CHD were enrolled in ATHENA. Compared to the overall population, CHD patients were older and had a higher incidence of heart failure and impaired left ventricular function. Baseline risk factors and medications for CHD were well balanced between the two treatment groups. Dronedarone reduced the primary study endpoint of the incidence of hospitalization or death by 27% (95%CI= , p-value<0.001). Cardiovascular hospitalizations, a prespecified secondary outcome of the trial, were reduced by 26% (95%CI= , p-value<0.001). This was mainly driven by a reduction in AF-related hospitalizations and hospitalizations for ischemic events. All-cause mortality, another secondary study endpoint, was reduced by 36% (95% CI= , p-value=0.027). This was mainly driven by a reduction in cardiovascular death, specifically sudden death and death due to stroke. Conclusion: This post-hoc analysis of the ATHENA trial provides evidence that dronedarone reduces the risk of cardiovascular hospitalization or death as well as all cause mortality in the subpopulation of patients with coronary heart disease when added to standard therapy Oral vernakalant for the prevention of atrial fibrillation recurrence post-cardioversion C. Torp-Pedersen 1, Y. Karpenko 2,D.Raev 3,J.Kaik 4,G.Dickinson 5, B. Mangal 5,G.N.Beatch 5. 1 Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; 2 City Clinical Hospital #9, Odessa, Ukraine; 3 MI Central Clinical Base, Sofia, Bulgaria; 4 Viimsi Hospital, Haabneeme, Estonia; 5 Cardiome Pharma, Vancouver, Canada Aims: Vernakalant, a novel antiarrhythmic drug with atrial selective properties, is effective at converting atrial fibrillation (AF) to sinus rhythm when administered as an intravenous infusion. This study was designed to determine the most appropriate oral dose of vernakalant for prevention of AF recurrence after cardioversion. Methods and Results: Patients with AF (3 days 6 months in duration) were double-blind and centrally randomized to receive daily doses of 150, 300, or 500 mg BID vernakalant or placebo, for up to 90 days, across 154 study sites. The efficacy analysis was conducted on 605/735 patients who entered the maintenance phase on day 3 following successful cardioversion. Within the 3-month follow-up period, the time to AF recurrence was significantly longer in the vernakalant 500 mg BID group, with a median of >90 days vs. 29 days in the placebo group (Hazard Ratio 0.735, P=0.0275). No significant effect was seen at the lower doses. The percent of subjects in sinus rhythm at day 90 was 44.8%, 43.3% and 51.5% in the 150 (N=147), 300 (N=148), 500 (N=150) mg BID vernakalant groups, respectively, compared to 37.9% in the placebo (N=160) group. Rates of adverse events and serious adverse events were similar between all active treatment groups and placebo. There were no cases of torsades de pointes reported in the study. There were few related Serious Adverse Events (SAEs) in the study, consisting of single events of angina and conduction disorder in the 150 mg BID group, an event of atrial flutter in the 300 mg BID group, an episode of sinus pause associated with attempted cardioversion in the 500 mg BID group and a case of ventricular tachycardia in the placebo group. Conclusion: Vernakalant 500 mg BID appears to be effective and safe for the prevention of AF recurrence after cardioversion Impact of dronedarone on hospitalization for atrial fibrillation: insights from ATHENA R.L. Page 1, H.J.G.M. Crijns 2, S.J. Connolly 3, C. Gaudin 4,M.Van Eickels 4, C. Torp-Petersen 5, S.J. Hohnloser 6. 1 University of Washington, Seattle, United States of America; 2 University Hospital Maastricht, Maastricht, Netherlands; 3 McMaster University, Hamilton, Canada; 4 sanofi-aventis, Frankfurt Am Main, Germany; 5 Gentofte Hospital, Hellerup, Denmark; 6 Klinikum der J.W. Goethe Universitaet, Frankfurt am Main, Germany Purpose: Dronedarone is a new multichannel blocking antiarrhythmic agent that was shown in ATHENA to significantly reduce the combined endpoint of cardiovascular (CV) hospitalization and all-cause mortality when administered in combination with standard therapy. This combined endpoint was primarily driven by reduction of CV hospitalization for atrial fibrillation or flutter (AFF). Methods: Patients with AFF or recent history of AFF (n=4628) were randomized to dronedarone (400 mg po bid) or placebo in a double-blind fashion and were followed months. This post-hoc analysis examined the frequency and characteristics of AFF-related hospitalizations. Results: As reported previously, more patients receiving placebo had at least one AFF-related hospitalization (510 vs 335, HR 0.63, P<0.001). In the current analysis we find that, in addition to a reduction in first hospitalization for AFF, the total number of hospitalizations was reduced in the patients receiving dronedarone as compared with patients receiving placebo (514 vs 829, HR 0.63, P<0.001). Furthermore, the total AFF-related hospitalization burden was lower in patients receiving dronedarone (3132 days) vs placebo (4637 days, P<0.001). The likelihood of electrical cardioversion being performed during hospitalization was identical between the two groups (27%), and when cardioversion was performed the mean duration of hospitalization was shorter (5 days with cardioversion versus 10 days with no cardioversion, in both treatment groups). Conclusions: In ATHENA dronedarone was associated with a reduction of the total number of AFF-related hospitalizations and the total burden of days in the hospital related to AFF. Only a quarter of the hospitalizations (in both treatment groups) included electrical cardioversion, suggesting that the reduction in AFFrelated hospitalizations in ATHENA was not simply the result of reduced admission for cardioversion but rather was related to other clinical factors Effect of statins on atrial fibrillation: a collaborative meta-analysis of randomised controlled trials K. Rahimi 1, J. Emberson 1, P. Mcgale 1, W. Majoni 1, A. Merhi 1, F. Asselberg 2, P.W. Macfarlane 3, C. Wanner 4, J. Armitage 1, C. Baigent 1. 1 Clinical Trial Service Unit, Oxford, United Kingdom; 2 University Medical Center, Groningen, Netherlands; 3 Royal Infirmary; Devision of Cardiovascular and Medical Sciences, Glasgow, United Kingdom; 4 Medizinische Universitaetsklinik Wuerzburg, Wurzburg, Germany Background: Two published meta-analyses, which included data from a selected sample of statin trials, have collectively suggested that statins may reduce the risk of atrial fibrillation. Objectives: We have sought to test this hypothesis independently in a much

151 Drugs for atrial fibrillation: a continuing effort / Novel treatments for stable angina: from old drugs to stem cells 451 larger set of trials which have collected, but not published, data on atrial fibrillation. Search strategy: MEDLINE (January 1966 to December 2008), EMBASE (January 1988 to December 2008) and the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008) were searched, as were reference lists of individual articles and reviews. Selection criteria: Randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with more than 100 participants and a follow-up duration of more than 6 months were considered for inclusion. Data collection: Two authors independently assessed trial quality and extracted data. Investigators of all trials fulfilling these eligibility criteria were contacted for unpublished data. Main results: In the 7 trials included in the hypothesis-generating meta-analyses (3609 randomised patients, 411 events), statin therapy appeared to reduce atrial fibrillation by 30% (risk ratio [RR] = 0.70, 95% confidence interval [CI] 0.56 to 0.88; p=0.002). There was, however, striking heterogeneity between the trials (p<0.001), with the largest trial indicating no significant benefit. In contrast, among 15 hypothesis-testing trials of statin versus control that provided data on atrial fibrillation ( randomised patients and 1514 events), statin therapy did not reduce the risk of atrial fibrillation significantly (RR=0.96 [95% CI 0.87 to 1.07; p=0.49]; p-value for test of difference between hypothesis-generating and hypothesis testing trials = 0.01). Inclusion of a further 7 trials that compared one statin with another yielded similar results (RR=0.99 [95% CI 0.92 to 1.06; p=0.73] based on the 22 trials comprising randomised patients and 3229 events). Conclusions: The proposed benefit of statin therapy on atrial fibrillation suggested by previous meta-analyses that examined just part of the randomised evidence is not supported by a more complete review of statin trials. These findings cast doubt over whether statins have any direct effects on atrial fibrillation Beneficial effect of atorvastatin in patients with recurrent atrial fibrillation and ischemic heart failure with preserved systolic function Y.M. Lopatin, E.E. Kozlova, E.E. Galaktionova, F.A. Nemchuk. Volgograd State Medical University, Volgograd, Russian Federation Aim: to investigate the effects of atorvastatin on recurrent atrial fibrillation (AF) in patients (pts) with ischemic heart failure (HF) with preserved systolic function. Materials and methods: It was a 24-week randomized placebo-controlled trial. 60 pts with ischemic HF (NYHA I-II), recurrent AF and ejection fraction 0.50 were included in the study. Pts were randomized into two groups the group of active therapy (basic therapy and atorvastatin) and the group of control (basic therapy and placebo). Basic therapy includes amiodarone or sotalol, ACE inhibitor, β-blocker or calcium blocker, aspirin and diuretic. The dose of atorvastatin was 10 mg/d over three months and then was increased in 15 patients to 20 mg/d until everybody reached the target level of LDL cholesterol < 2,5 mmol/l (<97mg/dL). Development of AF, parameters of the heart rate variability and echocardiography were recorded and compared at baseline, after three months, after six months in every group and between groups. Results: After three months atorvastatin significantly reduced the risk of developing AF versus control group by 28% (p < 0,05), length of incidence of AF by 12% (p < 0,05), also increased frequency- domain indices of HRV, including TP by 28% (p<0,03) and HF by 53% (p < 0,01). After six months atorvastatin significantly reduced the risk of developing AF by 41% (p < 0,05), length of incidence of AF by 20% (p < 0,05) and diminished left atrium volume by 8,7% (p<0,05), LVESV by 8,3% (p<0,05) and LVEDV by 9,4% (p<0,05), also it increased in time- and frequency- domain indices of HRV, including SDNN by 18% (p<0,05), RMSSD by 33% (p<0,02), TP by 42% (p<0,03), HF by 65% (p < 0,01) and decreased LF/HF by 37% (p < 0,01). Conclusion: Atorvastatin therapy was associated with reduced risk of developing AF and improved sympatho-vagal balance in patients with ischemic HF and preserved systolic function and recurrent AF. Large randomized clinical trials are needed How safe is flecainide treatment in clinical practice? Long-term incidence of sudden death and proarrhythmic events in an unselected group of patients with lone AF H. Almroth, T. Andersson, P. Linde, E. Fengsrud, A. Englund. Departement of Cardiology, Örebro, Sweden Purpose: To evaluate the long-term safety of flecainide treatment in clinical practice. Methods: All patients with lone AF treated with oral flecainide during 1998 and 2008 in our institution were identified. No patient had a history of ischemic heart disease and all patients underwent an exercise test and an echocardiogram to exclude structural heart disease prior to initiation of flecainide treatment. All patients were followed up at least once per year in our out patient clinic. In case of death this was classified as sudden or non-sudden according to standard definitions. Results: One-hundred and twelve patients with paroxysmal (49%, n=55) or persistent (51%, n=57) AF with a median age of 61 years (range 28-79) were started on flecainide treatment during the period. The median daily flecainide dose was 200 mg (range 100 to 400 mg) and the median treatment period was 1182 days (range 9 to 4173 days). Flecanide was usually combined with a betablocker or a calcium antagonist (79.5%). In 67 patients (60%) flecainide treatment was stopped. The main reasons for discontinuing treatment was lack of efficacy (44.8%), cardiac side effects and/or events (34.3%) and non-cardiac side effects in 9 patients (8%). Five patients discontinued treatment after successful ablation. In total 8 deaths were reported in which four were non-sudden whereas four were classified as sudden. Proarrhythmic events were seen in 6 patients (5.4%) (1:1 conducted atrial flutter n=3, ventricular tachycardia n=2 and one patient with syncope proceeded by palpitations). Conclusion: In this unselected group of patients with lone AF, treated with flecainide, the risk of sudden death and/or proarrhythmia was 8.9% during a median follow-up of 39 months. This corresponds to an annual incidence of almost 3%. NOVEL TREATMENTS FOR STABLE ANGINA: FROM OLD DRUGS TO STEM CELLS 2815 High dose allopurinol prolongs total exercise time and time to exercise induced ischaemia in chronic stable angina A. Noman, D. Ang, C.C. Lang, A.D. Struthers. University of Dundee, Dundee, United Kingdom Background: Experimental work has shown that allopurinol, a Xanthine Oxidase Inhibitor (XOI), improves mechano-energetic uncoupling of the myocardium in heart failure. This means that allopurinol reduces myocardial oxygen demand for a given stroke volume. Such an effect might be of value in angina pectoris. In addition, allopurinol has been shown to improve endothelial function and reduce oxidative stress in patients with coronary artery disease. This study was designed to investigate whether allopurinol had any anti-ischaemic effects in patients with chronic stable angina. Method: In a double-blind, placebo-controlled, crossover trial, 60 eligible patients with chronic stable angina and angiographically proven coronary artery disease were randomised to receive either placebo or allopurinol (600mg/day) for 6 weeks and were then crossed over to the alternative therapy for further 6 weeks. The main outcome measurements were changes in total exercise time (TET), time to onset of angina symptoms (Tsym) and time to ST depression (TST) on the exercise treadmill test using the Bruce protocol. These measures were assessed at baseline and after each treatment period. Results: The median baseline TET was 301 seconds (interquartile range, 251 to 446), Tsym was seconds (interquartile range, 188 to 381) and TST was 232 seconds (interquartile range, 182 to 379). Allopurinol increased TET by 53.7 seconds vs for placebo (p<0.001), Tsym by 49.5 seconds vs. 9.5 for placebo (p=0.01) and TST by 48.5 seconds vs seconds for placebo (p<0.001). Conclusion: In patients with chronic stable angina, high dose allopurinol improves total exercise time and time to angina and to ischaemia during exercise. These results support the use of allopurinol as a novel anti-ischaemic agent in patients with angina pectoris. They also point towards a potential role for the enzyme Xanthine Oxidoreductase in the pathophysiology of chest pain in angina pectoris Autologous mesenchymal stromal cell-derived endothelial progenitors therapy to improve vascularization and symptoms in patients with chronic coronary artery disease J. Kastrup 1, T. Friis 1, M. Haack-Soerensen 1,R.S.Ripa 1, U.S. Kristoffersen 2, A.B. Mathiasen 1,B.Hesse 2,A.Kjaer 2, E. Dickmeiss 3, E. Joergensen 1. 1 Rigshospitalet (The Heart Centre), Copenhagen, Denmark; 2 Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen, Denmark; 3 Department of Clinical Immunology, Copenhagen, Denmark Background: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) have been used, in the animal model, to create neovascularization in ischemic hearts. We aimed to evaluate the feasibility, safety and efficacy of ex-vivo expanded bone marrow derived mesenchymal-derived endothelial progenitor cells for autologous cell transplantation to the heart, to improve vascularization in patients with severe myocardial ischemia. Methods: A total of 30 patients with stable chronic coronary artery disease (Age: 66+7 years [mean±sd], 25 men and 5 females) were included in this first in man open investigators-initiated clinical trial. The patients had angina CCS 2-3 and reversible myocardial ischemia in an adenosine stress single photon emission computerized tomography (SPECT) and no further revascularization options. Bone marrow was aspirated by needle from the iliac crest. Mesenchymal stem cells were isolated and expanded in culture for 6-8 weeks. The last week cells were stimulated by rhvegf-a165 to promote differentiation into endothelial progenitor cells. A total of x106 cells were injected directly into a myocardial area of reversible ischemia using the NOGA-XP system. As a control group we used 16 patients previously treated with NOGA-XP -guided intramyocardial injection of placebo plasmid (Age: 6e+9 years, 14 men and 2 females). Primary endpoint is feasibilityand safety of the treatment. Secondary endpoint is effect on angina and myocardial perfusion.

152 452 Novel treatments for stable angina: from old drugs to stem cells Results: The study inclusion is finalised and the 6 months follow-up data will be available may The treatment has until now been safe without major adverse events during treatment and in the follow-up period. There is an ongoing followup of safety and efficacy data including exercise test, SPECT, MRI, PET Seattle angina questionnaire scores, angina frequency and nitroglycerine consumption compared to the control group. Conclusion: The study demonstrates the feasibility and short-term safety of autologous transplantation of ex-vivo expanded mesenchymal derived VEGFstimulated endothelial progenitor cells, in order to induce vasculogenesis in patients with severe chronic occlusive coronary artery disease. The 6 months safety and efficacy data will be available for presentation at ESC congress the control group CFIp and FFR did not change after 7 weeks. The ECP-group showed a significant reduction of the CCS (p=0.004) and NYHA (p<0.001) classification, whereas the control-group remained clinically unchanged Effect of atorvastatin on microrna 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease Y. Minami, M. Satoh, T. Tabuchi, Y. Takahashi, T. Itoh, M. Nakamura. Iwate Medical University, Morioka, Japan Background: Endothelial progenitor cells (EPCs) play an important role in the maintenance of vascular integrity. Lipid lowering therapy (LLT) with statins may contribute to biologically relevant activities including the proliferation of endothelial cells. The physiological role of microrna (mir)-221/222, a newly discovered class of small RNA, is closely linked to the proliferation of endothelial cells. We therefore investigated whether LLT with statins might affect mir-221/222 expression in EPCs obtained from patients with coronary artery disease (CAD). Materials and methods: This study included 44 patients with stable CAD and 22 subjects without CAD (non-cad). Patients with CAD were randomized to 12 months of LLT with atorvastatin or pravastatin. EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Levels of mir-221/222 in EPCs were measured by real-time RT-PCR. Results: The number of EPCs was lower in the CAD group than in the non- CAD group (P<0.01). Levels of mir-221/222 were significantly higher in the CAD group than in the non-cad group (mir-221: 0.64±0.27 vs. 0.16±0.09; mir-222: 0.99±0.06 vs. 0.28±0.15; CAD group vs. non-cad group, all P<0.01). Levels of mir-221/222 were weakly negatively correlated with EPC number in the CAD group (mir-221 levels vs. EPC numbers: r=-0.74, P<0.01; mir-222 levels vs. EPC numbers: r=-0.59, P<0.01). After 12 months of therapy, changes in lipid profiles were greater in the atorvastatin group than in the pravastatin group (all P<0.01). LLT with atorvastatin markedly increased EPC numbers (all P<0.05) and decreased mir-221/222 levels (mir-221: 0.66±0.29 vs. 0.48±0.23; mir-222: 0.97±0.50 vs. 0.58±0.29; baseline vs. 12 months, P<0.05), whereas LLT with pravastatin did not change EPC numbers or mir-221/222 levels. Fold changes in LDL-cholesterol levels were positively correlated with changes in mir- 221/222 levels in the atorvastatin group (mir-221 vs. LDL-cholesterol: r=0.52, P<0.05; mir-222 vs. LDL-cholesterol: r=0.61, P<0.05). On the other hand, changes in LDL-cholesterol levels were not significantly correlated with changes in mir-221/222 levels in the pravastatin group. Conclusions: This study provides novel evidence that mir-221/222 levels in EPCs are higher in CAD patients than in non-cad patients. Additionally, this study demonstrates that mir-221/222 levels decrease and EPC numbers increase after LLT with atorvastatin, but not after LLT with pravastatin, possibly contributing to the beneficial effects of lipid-lowering therapy with atorvastatin in this disorder Direct evidence for therapeutic induction of arteriogenesis in patients with stable angina pectoris via external counterpulsation: a prospective controlled proof of concept trial E. Buschmann 1, N. Pagonas 2,W.Utz 3, J. Schulz-Menger 3, A. Busjahn 4, L. Thierfelder 1,R.Dietz 5, V. Klauss 6,M.Gross 1, I. Buschmann 2 on behalf of Arteriogenesis Network. 1 Franz-Volhard-Klinik, Department of Cardiology, Helios-Klinikum Buch, Berlin, Germany; 2 Center for Cardiovascular Research, Charité Universitaetsmedizin, Berlin, Germany; 3 Cardiac Magnetic Imaging, Helios-Klinikum Buch, Berlin, Germany; 4 Health Twist GmbH, Berlin, Germany; 5 Charite - Campus Virchow-Klinikum, Berlin, Germany; 6 Department of Cardiology, Campus Innenstadt, Universitaet of Munich, Munich, Germany Purpose: Arteriogenesis (collateral artery growth) is nature s most efficient rescue mechanism to overcome the fatal consequences of arterial occlusion or stenosis. Here we present a first proof-of-concept trial providing direct evidence for a therapeutic effect of external counterpulsation (ECP) on collateral artery growth in the heart. Methods: 20 patients (age 62±2.5) with stable coronary artery disease (CAD) and at least one hemodynamic significant stenosis eligible for percutaneous coronary intervention were recruited. One group of patients underwent 35 1-hour sessions of ECP in 7 weeks. In the other group (control) the natural course of collateral circulation over 7 weeks was evaluated. All patients underwent a cardiac catheterization at baseline and after 7 weeks. The effect on collateral artery growth was assessed by invasive measurements of the pressure derived collateral flow index (CFIp, primary endpoint) and pressure derived fractional flow reserve (FFR). Results: In patients treated with ECP CFIp improved significantly from 0.08±0.01 to 0.15±0.02 (p<0.001) and FFR from 0.68±0.03 to 0.79±0.03 (p=0.001). In Change of CFIp from baseline to week 8 Conclusions: We here provide direct functional evidence for the stimulation of coronary arteriogenesis via ECP in patients with stable CAD. These data might open a novel non-invasive and preventive treatment avenue for patients with nonacute vascular stenotic disease Intramyocardial injection of bone marrow-derived mononuclear cells for chronic myocardial ischemia: a randomized, double-blind, placebo-controlled trial J. Van Ramshorst, J.J. Bax, S.L.M.A. Beeres, P. Dibbets-Schneider, S.D. Roes, M.P.M. Stokkel, W.E. Fibbe, E. Boersma, M.J. Schalij, D.E. Atsma. Leiden University Medical Center, Leiden, Netherlands Background: Previous studies have suggested improvement in myocardial perfusion and left ventricular (LV) function after bone marrow cell injection for chronic myocardial ischemia. This randomised, double-blind, placebo-controlled trial was designed to investigate the effect of intramyocardial bone marrow cell injection on myocardial perfusion and LV function in patients with chronic myocardial ischemia. Methods: Fifty patients (64±8 years, 43 male) were randomly assigned to injection of bone marrow cells or placebo solution. Using the NOGA system, injection of 98±6x106 bone marrow derived mononuclear cells or placebo solution was performed. Myocardial perfusion and LV function were assessed by SPECT and MRI at baseline and at 3 months follow-up. Canadian Cardiovascular Society (CCS) angina score and quality-of-life were evaluated at baseline and at 3 and 6 months. Results: After 3 months follow-up, summed stress score improved from 23.5±4.7 to 20.1±4.6 (P<0.01) in the bone marrow cell group, compared to a modest decrease from 24.8±5.5 to 23.7±5.4 (P<0.01) in the placebo group. The absolute decrease was significantly larger in the bone marrow cell-treated patients (-3.4±2.3 and -1.1±1.7, P<0.01). LV ejection fraction increased with 3±5% (P=0.02) in the bone marrow cell group, whereas no improvement (-1±3%, P=NS) was observed in the placebo group (P=0.03). The improvements in CCS angina score and quality-of-life were significantly greater in bone marrow cell-treated patients than in placebo-treated patients (P=0.03 and P=0.04 respectively). Conclusion: In patients with chronic myocardial ischemia, intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial perfusion, LV function, and anginal symptoms Long-term effects of spinal cord stimulation in refractory angina pectoris - 3-year results from the European Angina Registry Link (EARL) P. Andrell 1,W.Yu 2,L.Gillberg 3, K. Pehrsson 4, A. Stahle 5, P. Gersbach 6, I. Hardy 7, C. Andersen 8, C. Mannheimer 1 on behalf of EARL investigators. 1 Multidisciplinary Pain Center, Institute of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden; 2 Department of Medicine, Capio St Göran s Hospital, Stockholm, Sweden; 3 Department of Anesthesiology, Central Hospital, Kristianstad, Sweden; 4 Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden; 5 Deptartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; 6 Department of Cardiovascular Surgery, Centre Universitaire Hospitalier Vaudois, Lausanne, Switzerland; 7 Department of Anaesthesiology, Papworth Hospital NHS Trust, Cambridge, United Kingdom; 8 Department of Cardiothoracic Anaesthesia, Odense University Hospital, Odense, Denmark Purpose: The aim of the study was to assess the long-term effect of spinal cord stimulation (SCS) on angina symptoms and quality of life in patients with refractory angina pectoris, defined as severe angina due to coronary artery disease resistant to optimal pharmacological therapy and/or revascularization. Methods: The European Angina Registry Link (EARL) is a prospective, longterm follow-up registry study for refractory angina pectoris. During , all patients with refractory angina referred for SCS treatment at 10 European centers were consecutively included. The patients were followed-up up to three years after implantation regarding angina symptoms and quality of life. The quality of life was assessed using generic (Short Form 36, SF-36) and disease specific (Seattle Angina Questionnaire, SAQ) quality of life questionnaires.

153 Novel treatments for stable angina / Adjunctive therapy for coronary artery disease What is hot, what is not 453 Results: Initially, 235 patients were included in the study. After screening, in order to determine suitability for SCS implantation, 122 patients were implanted and followed-up. The implanted patients reported improved CCS class from 3.3 to 2.7 (p<0.0001), fewer angina attacks (p<0.0001) and reduced short-acting nitrate consumption (p<0.0001). Before implantation the quality of life was severely impaired both with regard to SAQ and SF-36. However, three years after implantation the quality of life was significantly improved in all dimensions of the SAQ and in all dimensions of the SF-36 except for the dimension general health. During the three-year follow-up period 26 patients died (21.3%). Conclusions: Patients with refractory angina pectoris have a high mortality rate and the patients suffer from severe angina pectoris which limits daily life and impairs quality of life. SCS treatment improves anginal symptoms and increases quality of life in patients with refractory angina pectoris. The effects of SCS seem to be persistent after three-year of follow-up. SCS might be a suitable alternative for pain relief in this patient population with severe coronary artery disease ADJUNCTIVE THERAPY FOR CORONARY ARTERY DISEASE WHAT IS HOT, WHAT IS NOT 2821 Ten years positive experience of long-term home self-treatment with thoracic epidural analgesia in patients with refractory angina pectoris: effects on angina, quality of life and exercise test A.J. Richter 1, I. Cederholm 1,M.Fredrikson 2, P. Wodlin 1,M.Gjerde 1, C. Mucchiano 3, B. Janerot Sjoberg 1. 1 Heart Center, University Hospital, Linkoping, Sweden; 2 Occupational and Enviromental Medicine, Faculty of Health Sciences, Linkoping, Sweden; 3 Dept. of Anesthesiology, Hogland Hospital, Eksjo, Sweden Patients with refractory angina do not respond to adequate medication and are on the basis of a recent coronary angiogram unsuitable for revascularization. They have a poor quality of life. Effective and safe adjuvant treatment is needed. We evaluated the effects of long-term home self-treatment with high thoracic epidural analgesia (TEDA) on angina, quality of life and exercise test. Methods: Between 1999 and 2008 we treated 153 consecutive patients (108 men, 45 women, aged years, mean 74) with TEDA. After insertion of a subcutaneously tunnelled epidural catheter the patients were trained to handle injections of 2 ml bupivacaine (Marcain ) 2.5 mg/ml. The daily dose was 1-5 injections (median 2). All patients were followed after 2 weeks and then every third month with analysis of Canadian Cardiovascular Society angina scale (CCS 1-4), frequency of anginal attacks, consumption of short-acting nitrates per week and overall self-related quality of life assessed by EuroQol 5D visual analogue scale (VAS 0-100). Standardized exercise bicycle test with a 12-lead ECG was performed in 21 patients before and after 3 months with TEDA. Results: During the 10 years follow-up all but two of the patients improved symptomatically. After 2 weeks the CCS angina class decreased from 3.5±0,5 to 1.4±0,7, frequency of anginal attacks decreased from 37,0±20,3 to 4,1±5,9 a week, nitroglycerine intake decreased from 26,2±17 to 2,9±4,9 a week, and the VAS quality of life increased from 27,9±20,0 to 72,7±13,9 (all p<0.001). The improvement was maintained throughout the period of treatment. The mean duration of TEDA-treatment per patient was 2,3 years (34 days - 9,1 years) and 28 patients have had the treatment for more than 4 years. No serious complications occurred during the long-term TEDA at home. Comparison of exercise test before and after three months with TEDA showed an increase in maximal workload (90,1±24,2 vs. 98,0±20,0 W, p=0.01) and less STsegment depressions on comparable workloads (1,03±0,74 vs. 0,57±0,46 mm, p=0.002) with TEDA. Conclusion: Long-term self-administered home treatment with TEDA is a safe widely available adjuvant treatment for patients with severe refractory angina. It produces symptomatic relief of angina, improves quality of life and increases working capacity with less signs of myocardial ischemia on exercise test. The exercise test results suggest that beside the analgetic effect, TEDA also seems to have an antiischemic effect. We have an ongoing placebo controlled study which vill produce further information about the antiischemic effect of TEDA. has been avoided with subsequent excellent prognosis. The purpose of this study was the assessment of aborted MI in IC abciximab bolus application as compared with a standard IV bolus in patients with STEMI undergoing primary PCI. Methods: To investigate the extent of aborted MI patients undergoing primary PCI were randomized to either IC (n=77) or IV (n=77) bolus abciximab administration with subsequent 12-hour intravenous infusion. Aborted MI was defined as maximal creatine kinase 2 upper limit of normal coupled with typical evolutionary electrocardiographic changes (ST-segment resolution > 50% within 2 h). For assessment of infarct size and extent of microvascular obstruction all patients underwent delayed enhancement magnetic resonance. Results: The baseline characteristics and medication were similar between groups. The incidence of aborted MI was significantly higher in the IC group (12 (16%) vs. 4 (5%); p=0.035). Patients with an aborted MI had a significant lower infarct size, shorter pain-to-balloon time and a significant better left ventricular ejection fraction as compared with patients with true MI. The median infarct size (15% vs. 23%; p=0.01) and extent of microvascular obstruction (p=0.01) were significantly smaller in IC compared with IV abciximab patients. Conclusions: Intracoronary bolus application of abciximab in primary PCI results in a higher incidence of aborted MI and is superior to standard IV treatment with respect to infarct size, extent of microvascular obstruction, and perfusion. Larger randomized multicenter trials using rigorous clinical end points such as death and MI are required to further substantiate the clinical benefits of this mode of drug delivery Routine use of Fondaparinux in acute coronary syndromes. A two year, multicentre experience and a comparison with Enoxaparin F. Schiele, N. Meneveau, M.F. Seronde, V. Descotes-Genon, J. Dutheil, R. Chopard, J.P. Bassand. University hospital, Besancon, France Background: Fondaparinux, a synthetic factor Xa inhibitor has been recently approved and recommended by guidelines in patients with acute coronary syndromes. The study aimed to describe, over a two year period, (1) the modality of use of this new drug in routine practice and (2) the impact on clinical outcome at 30 days, compared with patients treated with Enoxaparin. Methods and results: Between January 2006 and December 2007, 2776 patients were included in the registry. The rate of use of unfractionated heparin (UFH) remained stable, from 18% to 16% while that of Fondaparinux increased from 4% to 48% as a result of a switch from Enoxaparin, whose use decreased from 78% to 36%. The increase in use of Fondaparinux was higher in community centres without catheterisation (from 5% to 79%) than in the university centre (from 4% to 67%) and less marked in community centres with catheterisation laboratory (from 0% to 17%). Patients treated with UFH were older, had more comorbidities, received fewer guidelines-recommended treatments and had more often severe bleeding and higher 30 day mortality as compared with Enoxaparin and Fondaparinux groups. The propensity score adjusted comparison between Fondaparinux and Enowaparin showed no difference in 30 day mortality, but a higher rate of severe bleedingin the Enoxaparin group (2.3% versus 1.2%, p<0.01) Aborted myocardial infarction in i.c. compared with i.v. bolus abciximab application in patients with STEMI undergoing primary PCI I. Eitel, G. Fuernau, M. Sareban, M. Gutberlet, G. Schuler, H. Thiele. Herzzentrum der Universitaet Leipzig, Leipzig, Germany Purpose: Abciximab reduces major adverse cardiac events in patients with STelevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary (IC) abciximab bolus application results in high local drug concentrations and consequently might be more effective than a standard intravenous (IV) bolus. In a recent randomized, controlled trial, IC abciximab bolus application with subsequent 12-hour continuous intravenous infusion showed reduced no reflow and infarct size as assessed by contrast-enhanced magnetic resonance imaging. Aborted myocardial infarction (MI) is a new therapeutic target of effective and early treatment in STEMI. These patients are presumed that myocardial necrosis Trends in use of anticoagulants Conclusions: The increasing use of Fondaparinux was the result of a switch from Enoxaparin, whereas UFH use was stable, often in higher risk patients. No difference in 30 day mortality was observed between patients treated by Enoxaparin or Fondaparinux, but the rate of severe bleedings was lower in the Fondaparinux group Ivabradine reduces angina pectoris in patients after PCI: a subgroup analysis from the REDUCTION-study R. Koester, J. Kaehler, T. Meinertz on behalf of the REDUCTION Study Investigators. Universitaeres Herzzentrum Hamburg ggmbh, Hamburg, Germany Purpose: The antianginal and antiischemic efficacy through exclusive heart rate

154 454 Adjunctive therapy for coronary artery disease What is hot, what is not / Echocardiographic assesment of mechanics in valve disease reduction of ivabradine has been studied in controlled clinical trials. The objective of the REDUCTION multicentre study was to evaluate the efficacy and safety of ivabradine in stable angina in every day clinical practice. We performed a subgroup analysis to evaluate the efficacy of ivabradine in patients with stable angina pectoris who already underwent PCI. Methods: 1712 patients (pts) were followed for a mean of 4 months. Patients were treated with ivabradine twice daily (bid) in flexible doses (2.5, 5 or 7.5 mg bid). After baseline evaluation two consecutive visits were conducted after 1 and 4 months. Heart rate (HR) at rest, the number of angina attacks, nitrate consumption, overall efficacy and tolerance according to the physicians judgement were evaluated. Baseline and last observation values were compared. Results: All 1712 patients had undergone a PCI, in 67% more than one year ago. 43% of patients had a history of myocardial infarction. According to the initial use of ivabradine, mainly patients were included who did not tolerate betablockers. Almost all patients received concomitant standard medication (e.g. ACEI 60%, long acting nitrates 21%).Ivabradine reduced mean HR by 11.5 bpm in a mean dose of 10.8 mg per day. 77% of the patients had at least one angina attack per week. The number of angina attacks and nitrate consumption was significantly reduced (s. Table 1). 13 pts reported suspected adverse drug reactions (ADR). No severe adverse drug reaction was reported. For 98% of patients physicians considered the efficacy of ivabradine as very good/good. For 99% of patients the tolerance was rated as very good/good. Table 1 Baseline With ivabradineafter 4 months P-value Heart rate (bpm) 80.8± ±8.5 < Angina attacks (per week) 2.2± ±2.0 < Nitrate consumption (per week) 3.0± ±1.2 < Conclusions: Ivabradine significantly reduced heart rate, angina pectoris symptoms and nitrate consumption in a group of patients with coronary artery disease post PCI. Thus, in every day practice, ivabradine provides additional clinical benefit and reduction of cardiovascular risk in the complex patient group which suffers from ongoing angina symptoms despite successful PCI Effects of nicorandil on cardiovascular events in patients with coronary artery disease from the Japanese Coronary Artery Disease (JCAD) study S. Horinaka 1,A.Yabe 1, H. Yagi 1,H.Hara 1, H. Natsuoka 1, T. Yamazaki 2,S.Suzuki 2, T. Kohro 2, R. Nagai 2 on behalf of JCAD study investigators. 1 Dokkyo Medical University, Mibu, Japan; 2 University of Tokyo, Tokyo, Japan Objectives: Nicorandil has cardioprotective effects in the ischemic myocardium, mimicking ischemic preconditioning, which is expected to improve the prognosis of ischemic heart disease. The JCAD Study was a multicenter collaborative prospective observational study of a large cohort of coronary artery disease patients performed to investigate risk factors and current status of medication use and determine differences in outcome. As a part of this study, we examined whether nicorandil improved outcome. Methods: Propensity score analysis was preformed (n=2558 for each group). The mean follow-up interval was 2.7 years. Results: The primary endpoint of deaths from all causes was significantly lower by 35% in the nicorandil group compared with the control group. There were also significant reductions in secondary endpoints, including cardiac death (56%), fatal myocardial infarction (56%), cerebral or vascular death (71%) and congestive heart failure (33%). Number of all events tended to be reduced, by 12%, with non-significantly fewer cardiac events and no excess of deaths from other noncardiovascular causes as shown in Table. Primary and secondary endopoints Variables Nicorandil (n=2558) Control (n=2558) HR (95% CI) p value Rate per 1000 patient-years Primary endpoint Deaths, all causes ( ) Secondary endpoints Cardiac deaths ( ) Fatal MI ( ) Nonfatal MI ( ) Cerebralo or vascular deaths ( ) Other causes (Non-CVD deaths) ( ) All events ( ) Cardiac events ( ) CHF ( ) HR: hazard ratio, CI: confidential interval Does intracoronary infusion of metabolic cytoprotectors immediately after blood flow restoration in the infarct-related artery influence the limitation of myocaridal injury in AMI? D. Iosseliani, A. Koledinsky, D. Gromov, I. Topchian, O. Sukhorukov. Moscow City Center of Interventional Cardioangiology, Moscow, Russian Federation Purpose: Study of cardioprotective effect of metabolic cytoprotectors Neoton (phosphocreatin) and Mexicor (methyl-ethyl-piridimol succinate), infused intracoronary into the infarct-related coronary artery (IRA) immediately after its mechanical recanalization and before angioplasty within the first hours after the onset of Q-wave AMI. Clinical data and methods: The study comprised 263 patients (mean age 55,8±8,3 years) with acute IRA occlusion, in whom successful recanalization/ptca of the IRA was performed within the first 6 hours after the onset of AMI. All patients were randomized into 3 groups. Group 1 patients received intracoronary Neoton bolus infusion 2 g (n=62). Group 2 patients received Mexicor 0,2 g intracoronary (n=114). Group 3 (control) patients with AMI with successfully recanalized IRA did not receive intracoronary cytoprotectors (n=87). Baseline clinical, historical and angiographic data were not significantly different in all the three groups. Blood sampling for Troponin I and myoglobin was performed during IRA recanalization, 12 and 24 hours after the procedure. Coronary angiography and left ventriculography were repeated on day 10 of the disease. Results: The patients from Groups 1 and 2 had more favorable in-hospital clinical course as compared with Group 3. During in-hospital stay no deaths were observed in Group1, mortality rate in Group 2 was 1,8%, and in Group 3-5,3% (p1-3=0,058; p2-3=0,064). Mean values of Troponin I concentration at 12 hours after the procedure in Groups 1 and 2 were 335±49 and 458±37 ng/ml, respectively, vs. 841±52 mg/ml in the control group (p1-3=0,002; p2-3=0,004). ST segment depression after the procedure in Groups 1 and 2 was significantly lower as compared with the control group (3,2±2,4 mm, 4,1±2,6 mm, respectively, vs. 7,1±2,9 mm, p<0,05). LVEF at day 10 after the AMI in Groups 1 and 2 was 47,8±5,4% and 52,7±5,6%, respectively, vs. 36,8±7,2% in the control group (p<0,05). Conclusion: Intracoronary infusion of metabolic cytoprotectors Neoton and Mexicor immediately after IRA recanalization in acute myocardial infarction significantly improves clinical course of the disease as well as left ventricular function during in-hospital stay in comparison with similar patients who did not receive such treatment. This can be considered as an indirect proof of better preservation of ischemic myocardium s viability in patients treated by cytoprotectors. Significantly lower serum concentration of cardiospecific enzymes in the groups of study in comparison with the control group can serve as another proof of the same. ECHOCARDIOGRAPHIC ASSESMENT OF MECHANICS IN VALVE DISEASE 2860 Impact of net atrioventricular compliance on left atrial systolic function after mitral valve replacement A. Tugcu 1,Y.Tayyareci 1, O. Yildirimturk 1,V.Aytekin 2, I.C.C. Demiroglu 1,S.Aytekin 2. 1 Florence Nightingale Hospital, Istanbul, Turkey; 2 T.C. Istanbul Bilim University, Florence Nightingale Hospital, Istanbul, Turkey Purpose: In patients with native mitral valve stenosis net atrioventricular compliance (Cn) is an important physiological modulator of left atrial (LA) and pulmonary arterial pressures. In the context of mitral valve replacement (MVR), Cn is influenced by prosthesis patient mismatch defined as an indexed effective orifice area (EOA) 1.2 cm 2 /m 2. The aim of this study was to examine the effect of Cn on LA deformation and volumes in patients that underwent MVR using velocity vector imaging (VVI). Methods: Ninety-two patients who underwent isolated MVR with a preserved left ventricular function were enrolled. Mitral valve EOA was determined by continuity equation and indexed for body surface area. Cn was determined by comprehensive echo-doppler measurements. Patients were divided into four groups according to their indexed EOA and Cn values (group 1: indexed EOA 1.2 cm 2 /m 2,Cn Conculsions: The reductions in cardiovascular deaths with nicorandil were large, given the short follow-up period in patients with ischemic heart disease. These findings have implications for future ischemic heart disease treatment. Figure 1

155 Echocardiographic assesment of mechanics in valve disease 455 4mL/mmHg; group 2: indexed EOA > 1.2 cm 2 /m 2,Cn 4mL/mmHg;group 3: indexed EOA 1.2 cm 2 /m 2,Cn> 4mL/mmHg and group 4: indexed EOA > 1.2 cm 2 /m 2,Cn> 4mL/mmHg). LA peak systolic strain rate (LasSR) and LA strain (LAε) from septal and lateral walls, and LA volumes were analyzed using velocity VVI. Results: LA active emptying ejection fraction was significantly reduced in group 1 (p=0.003). Mean LasSR and LAε were reduced in group 1, group 2 and group 3 compared to group 4 (Figure 1). Cn was significantly correlated with septal, lateral and mean LasSR and LAε (p<0.001 for all). In multiple stepwise linear regression analysis, Cn was the independent determinant of mean LasSR and LAε (β=0.287, p=0.006 and β=0.228, p=0.03 respectively) and indexed EOA of LAε (β=0.214, p=0.047). Conclusion: the combination of reduced Cn and prosthesis patient mismatch is associated with reduced systolic LA function The impact of myocardial fibrosis on regional myocardial function and clinical outcome in patients with low gradient aortic valve stenosis S.H. Herrmann 1, J.S. Strotmann 2, M.N. Niemann 1, V.L. Lange 3, M.B. Beer 4, S.G. Gattenloehner 5, W.V. Voelker 1,G.E.Ertl 1, F.W. Weidemann 1. 1 Universitätsklinik Wuerzburg/Medizinische Klinik I, Wuerzburg, Germany; 2 Städtisches Krankenhaus Kiel, Kiel, Germany; 3 Herz-Thorax-Chirugie Universität Würzburg, Wuerzburg, Germany; 4 Radiologie Universität Würzburg, Wuerzburg, Germany; 5 Pathologisches Institut Universität Würzburg, Wuerzburg, Germany In this clinical study the interrelationship between myocardial fibrosis, regional myocardial function, mean valve gradient and long-term outcome after aortic valve replacement (AVR) was investigated in patients with severe isolated symptomatic aortic valve stenosis (AS). Methods: 70 Patients were examined before and 9 months after AVR by conventional echocardiography including septal and lateral ring displacement (for longitudinal wall function) as well as strain rate imaging measuring longitudinal peak systolic strain rate (for regional longitudinal deformation). Cardiac magnetic resonance imaging was performed to specify the amount of replacement fibrosis measured by late enhancement method (LE). During AVR biopsies were taken from the basal septum to evaluate interstitial fibrosis. All patients were determined into NYHA-Class 9 months after AVR. Results: The patients were divided according to their mean gradient and ejection fraction (EF) into 3 groups (group 1=gradient 40mmHg and EF 50%, n=49; group 2=gradient<40mmHg and EF 50%, n=10; group 3=gradient<40mmHg und EF<50%, n=11). At baseline before AVR both low gradient groups showed lower mitral ring displacement (group 1=10.4±1.9mm; group 2=5.8±1.4mm group 3=4.8±1.2mm; p<0.001 vs. group1) and lower longitudinal strain rate values (group 1=-1.1±0.3 s -1, group 2=-0.6±0.2 s -1, group 3=-0.5±0.1 s -1 ;p<0.001 vs. group 1). A significant higher degree of interstitial fibrosis in biopsies was seen in the low gradient groups. (Fibrosis score group 1: 67% no fibrosis, 33% mild; group 2: 5% no fibrosis, 15% mild, 55% moderate, 25% severe; group 3: 12% mild fibrosis, 45% moderate, 48% severe) In addition, 88% of the patients in group 3 had two or more positive LE segments. For follow-up, the patients of group 1 had a better clinical outcome and myocardial function 9 months after AVR. (NYHA class: group1=1.5±0.8, group 2=2.9±0.5, group 3=3.2±0.7; p<0.001 vs. group 1)/(Strain rate 9 months after AVR: group 1=-1.7±0.2 s -1, group 2=-0.7±0.3 s -1, group 3=-0.6±0.1 s -1 ;p<0.001 vs. group 1). Summary: These data suggest that in patients with severe aortic valve stenosis a low mean gradient is associated with a higher degree of myocardial fibrosis. Therefore myocardial fibrosis might be responsible for reduced longitudinal myocardial function and subsequently for the poor long term outcome even in patients with preserved EF at baseline Left ventricular torsion in patients with aortic stenosis, normal ejection fraction and diastolic dysfunction A. Calin 1, C.C. Beladan 1, B.A. Popescu 1,M.Rosca 1, D. Muraru 2, D. Deleanu 2, F. Antonini-Canterin 3, G.L. Nicolosi 3, C. Ginghina 1. 1 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 2 Institute of Cardiovascular Diseases, Bucharest, Romania; 3 Cardiology, ARC, Santa Maria degli Angeli Hospital, Pordenone, Italy Background: In patients (pts) with severe aortic stenosis (AS) and normal left ventricular ejection fraction (LVEF) diastolic dysfunction is frequently found. The role of LV torsion and subsequent untwisting to early diastolic filling was previously demonstrated. However, the relationship between LV torsion (LVtor) and degree of diastolic dysfunction (DD) has not been yet investigated in this setting. Purpose: To assess LVtor and untwisting in pts with severe AS, preserved LVEF and different degrees of DD. Methods: We studied 49 consecutive pts (65±8 years, 37 men), with severe AS (indexed aortic valve area, AVAi<0.6 cm 2 /m 2 ), preserved LVEF (62±6%), without significant coronary artery disease, and 36 normal subjects (46±12 years, 10 men). A comprehensive echocardiogram was performed in all, including PW Doppler of mitral inflow and pulmonary venous flow, mitral annulus velocity E by TDI at both septal and lateral sites, and flow propagation velocity (Vp). LV diastolic function was graded according to the recent ASE/EAE recommendations (J Am Soc Echocardiogr 2009;22:107). Pts with AS were divided according to DD severity in: mild DD group (DDm, 34 pts) including pts with grade 1 DD, and advanced DD group (DDadv, 15 pts) including pts with grade 2 and 3 DD. The parasternal basal and apical short-axis planes were recorded to quantify basal and apical LV rotation, LVtor and untwisting by speckle tracking echocardiography (STE) using dedicated software (2D strain, EchoPac). Peak LVtor has been corrected to the long axis diastolic diameter of the LV. Results: Normal subjects were younger than AS pts (p<0.001). Age, gender, NYHA class, LVEF, AVAi were similar in the 2 DD groups. Peak LVtor was significantly higher in DDm group (3.5±1.0 /cm) compared to DDadv group (2.7±1.1 /cm, p=0.03) and controls (2.6±0.8 /cm, p=0.001). We found no significant difference in peak LVtor between DDadv group and controls (p = 0.7). Peak apical rotation, peak apical rotation rate and peak apical untwisting rate were also significantly increased in DDm group compared to DDadv and control groups (p<0.05 for all). Conclusion: LV systolic torsion and parameters of apical rotation/untwisting are significantly increased in pts with severe AS, preserved LVEF and mild DD. With progression of DD, in pts with advanced DD these torsional parameters are normalyzed or reduced. These findings suggest that LVtor increases with reducing myocardial relaxation in the early stage of DD and then decreases and becomes pseudonormal with increasing filling pressures in pts with advanced DD Myocardial contractile reserve detected by dobutamine stress tissue Doppler imaging as a preoperative determinant of outcome after valve replacement in chronic mitral regurgitation H. Badran, S. Shalaby, A. Serag, H. Hassan, A. Barbary. Menoufiya University, Shebin, Egypt Background: The optimal timing for operation in severe rheumatic mitral regurgitation (RMR) is controversial. Accurate preoperative assessment of left ventricular function (LV) is difficult, and the ability to predict postoperative function is limited. OBJECTIVES: We evaluated thevalue of preoperative assessment of LV contractile reserve (CR) determined by dobutamine stress Doppler tissue imaging (DTI) in predicting ventricular function after valve replacement for RMR. Methods: Dobutamine stress DTI was performed in 48 patients with RMR (age 35±17 years, 21 (35.6%) were male. Resting, and low dose dobutamine (15-20 μ/kg/min), 2D echocardiographic parameters, and TDI data were obtained. Smean was defined as the average of peak systolic velocities of four mitral annulus corners by TDI. Myocardial CR was calculated from two methods conventional EF% and Smean by [stress rest/rest] 100. According to post operative EF% after 3 months follow up patients were classified into 2 groups: group I (n=28) with EF% reduction 10% and group (n=20) II with EF% reduction >10%. Results: At rest no significant difference between group I & II regarding the age, BSA,hemodynamics, prevalence of sinus rhythm, functional class, left atrial diameter, LV wall thickness, end diastolic diameter or volume, EF% or pulmonary pressure. End systolic diameter, volume and volume index were significantly higher in group II compared with group I (P<0.01). Smean at rest and stress were significantly lower in group II compared with group I (7.83±0.58 vs 10±0.88, 7.94±0.76 vs 12.6±1.42 cm/s). As Smean did increase from rest to stress in group II the CRS was significantly lower in group II (1.3±3.6) in comparison to group I (25.6±6.2) (P<0.001). Using Multivariate regression analysis CRS, CR EF%, resting Smean were the key independent predictors of post operative LV function in patients with chronic RMR (P<0.04, 0.001, 0.03 respectively). Conclusion: In patients with rheumatic severe MR, impaired contractile reserve assessed by dobutamine stress TDI velocity data may be an independent determinant of post operative LV function following mitral valve replacement Resting left ventricular longitudinal function predicts exercise pulmonary hypertension in organic mitral regurgitation J. Magne, M. Moonen, K. O Connor, L.A. Pierard, P. Lancellotti. CHU de Liege - Domaine du Sart Tilman, Liege, Belgium Introduction: Exercise pulmonary hypertension (PHT) can develop in patients with organic mitral regurgitation (MR), even when resting pulmonary arterial pressure is normal. Exercise PHT ( 60mmHg) is a criterion for surgical decisionmaking in patients with severe organic MR. However, systolic pulmonary arterial pressure (PAP) is not always available during stress echocardiography. The purpose of this study was to identify resting echocardiographic predictors of exercise PHT in patients with organic MR. Method and results: Resting and exercise transthoracic echocardiography including Doppler and tissue Doppler imaging (TDI) quantification were performed in 66 consecutive patients (61±15 years, 55% of male) with moderate to severe organic MR (mean effective regurgitant orifice area =41±14mm 2, regurgitant volume =72±22ml). Left ventricular (LV) longitudinal and filling functions were quantified by peak and time-to-peak velocities (TP) using TDI for Ea-, Aa- and Sa-wave in septal, lateral, inferior and anterior position and then averaged. Systolic PAP was derived from the transtricuspid pressure gradient and was available during exercise in 52 patients (79%). Systolic PAP significantly increased during exercise (from 31±10 to 54±17mmHg, p<0.0001) and exercise PHT (exercise PAP 60mmHg) was observed in 24 patients (46%). Patients with exercise PHT

156 456 Echocardiographic assesment of mechanics in valve disease / Echo: a reliable tool to assess coronary flow reserve?! were significantly older (69±11 vs. 59±15 years, p=0.004) and had higher resting PAP (36±9 vs. 27±7mmHg, p=0.0004), higher E/Ea ratio (16±6 vs. 13±4, p=0.03), slower TP-Sa (127±27 vs. 153±30ms, p=0.002) and TP-Ea (456±48 vs. 483±50ms, p=0.03) and lower septal Ea velocity (6.4±2 vs. 7.4±3cm/s, p=0.01). Exercise PAP was correlated with age (r=0.39, p=0.004), resting TP-Sa (r=0.42, p=0.002) and E/Ea ratio (r=0.28, p=0.04). Of note, no significant correlation was found between resting MR severity and exercise PAP. On multivariate analysis, after adjustment for age, sex and E/Ea ratio, the independent predictors of exercise PHT were resting systolic PAP (Odds-ratio (OR) =1.25, 95%CI: , p=0.003) and TP Sa (OR=1.04, 95%CI: , p=0.03). Moreover, when exercise PAP was examined as continuous variable, independent predictors were age (β=0.29, p=0.04), male gender (p=0.009), resting PAP (β=0.8, p<0.0001) and resting TP-Sa (β=0.13, p=0.04). Conclusion: This study shows that resting impaired LV longitudinal function is associated with exercise PHT in patients with organic MR. The presence of resting subclinical LV dysfunction could play an important role in PHT Left ventricular untwisting on exercise is impaired in advanced chronic mitral regurgitation - a possible mechanism for exercise intolerance R.A. Argyle 1, R.P. Beynon 1, R. Aghamohammadzadeh 1, K.A. Pearce 1,A.N.Borg 2,S.G.Ray 1. 1 University Hospital of South Manchester, Manchester, United Kingdom; 2 Blackpool Victoria Hospital, Blackpool, United Kingdom Purpose: Exercise limitation in chronic mitral regurgitation (MR) may relate to latent left ventricular (LV) impairment. Systolic impairment can manifest as absence of contractile reserve (CR) failure to increase ejection fraction (EF) on exercise. Twisting and untwisting of the LV are essential for efficient function and normally enhance on exercise. We investigated the change in LV untwisting on exercise in patients with chronic mitral regurgitation. Methods: 28 patients aged 60±14 years with Grade 3-4 primary MR and 28 agematched controls were recruited. Subjects underwent echocardiography at rest and during submaximal exercise on a supine bicycle ergometer. In the MR group, 12 patients had an increase in EF during exercise of 4% (CR+) and 16 patients were CR-. LV rotation/rotation rate were assessed using 2D speckle-tracking echocardiography in short axis basal and apical views. Basal rotation/rotation rate was subtracted from apical rotation/rotation rate to obtain overall LV twist/twist rate. Times to onset and peak of untwisting velocity were expressed as a percentage of systolic duration. Results: Resting and peak exercise heart rates (bpm) and resting EF (%) were similar in all groups (controls 69±12,109±5 and 65±6.5; CR+ 70±8, 109±6 and 63±6.6; CR- 75±14, 111±8 and 66±6.5; p=ns). EF on exercise was 73±4.4 in controls, 73±5.3 in CR+ and 63±6.9 in CR- (p<0.001 for CR- vs. other groups). At rest, early diastolic untwisting was delayed in onset and peaked later in the MR groups compared to controls (controls 96.0±5.9 and 120.9±10.0%, CR ±18.2 and 139.0±19.0%, CR ±13.7 and 139.2±13.8% respectively; p<0.05 for controls vs. CR+ and for controls vs. CR-). On exercise, untwisting showed a trend towards starting earlier in both CR+ (96.8±5.6%, p=0.07 vs. rest) and CR- (104.2±8.7%, p=0.03 vs. rest), but in CRwas still delayed compared to controls and CR+ (controls 93.8±7.2%; p=0.002 controls vs. CR-, p=0.04 CR+ vs. CR-, p=ns controls vs. CR+). Time to peak untwisting velocity shortened significantly in CR+ (122.1±8.8%, p=0.02 vs. rest), but not in CR- (135.0±13.1%, p=0.23 vs. rest) or controls (119.7±11.0%, p=ns vs. rest), such that it normalised in CR+ but remained significantly prolonged compared to controls in CR- (p<0.05 for CR- vs. controls and for CR- vs. CR+, p=ns for CR+ vs. controls). Conclusion: In chronic MR, the absence of contractile reserve is associated with delayed LV untwisting on exercise. Impaired untwisting compromises early LV diastolic filling and is likely to result in a rise in left atrial pressures on exercise and hence exercise intolerance. peak diastolic flow velocities. The CFR measurements by ultrasonography were compared with the results of gated-spect. All patients underwent coronary angiography as control. Results: Complete Doppler ultrasound data were acquired for 148 of 160 study patients. Of these 148 patients, SPECT confirmed reversible perfusion defects in the LAD territories in 94 patients (group A). Fifty-four patients had normal perfusion in the LAD territories (group B). Peak CFR (mean value ± SD) were 1.56±0.5 in group A and 2.43±0.7, respectively (p < 0.001). CFR < 2.0 predicted reversible perfusion defects, with a sensitivity and specificity of 84% and 78%, respectively. Conclusions: Noninvasive measurement of CFR by transthoracic Doppler ultrasonography provides a functional estimation of LAD stenosis severity comparable to gated-spect Multiparametric prognostic score for patients undergoing dipyridamole stress echocardiography with combined assessment of coronary flow reserve on left anterior descending artery L. Cortigiani 1, D. Gregori 2,F.Rigo 3, S. Gherardi 4, M. Galderisi 5, F. Bovenzi 1, E. Picano 6,R.Sicari 6. 1 Ospedale Civile, Lucca, Italy; 2 University of Torino, Torino, Italy; 3 Ospedale Civile Umberto I, Mestre, Italy; 4 Cesena Hospital, Cesena, Italy; 5 Universita di Milano, Milan, Italy; 6 Fondazione G Monasterio, Pisa, Italy Background: A multiparametric score for prediction of mortality was previously obtained in patients undergoing dipyridamole stress echo. Dual imaging of wall motion and coronary flow reserve (CFR) on left anterior descending (LAD) artery is now the state-of-the art technique for vasodilator stress echo. Aim: To find out a prognostic score in a large, unselected cohort of patients undergoing dipyridamole stress echo with combined assessment of CFR on LAD. Methods: 3,055 patients (age 65±11 yy; 1,790 men) with known (n=1,146; 38%) or suspected (1,909; 62%) coronary artery disease underwent dipyridamole (up to 0.84 mg/kg over 6 ) stress echo with combined evaluation of CFR on LAD by Doppler. All-cause mortality was the only accepted end-point. Results: Stress echo was positive for ischemia for wall motion criteria in 597 (20%) subjects. Mean CFR was 2.38±0.67. During a median follow-up of 16 months, 75 patients died. At Cox analysis, independent prognostic indicators were age (HR=3.72; 95% CI= ), male sex (HR=2.67; 95% CI= ), diabetes (HR=1.59; 95% CI= ), left bundle branch block (HR=3.07; 95% CI= ), peak wall motion score index (HR=1.34; 95% CI= ), ischemia at stress echo (HR=2.07; 95% CI= ), and CFR on LAD, whose prognostic effect was different in the ischemic (HR=0.27; 95% CI= ) and nonischemic (HR=0.32; 95% CI= ) subset. Thus, these variables were incorporated in a prognostic score allowing to estimate 1-year, 2-year, 3-year and 4-year survival in the single patient (Figure). ECHO: A RELIABLE TOOL TO ASSESS CORONARY FLOW RESERVE?! 2866 Coronary flow reserve in the functional assessment of coronary artery stenosis: a head-to-head comparison between high resolution echocardiography and gated single photon emission computed tomography L. Ferrara, M. Damiano, C. De Simone, A. D Errico, P. Gallo, M. Sidiropulos, C. Mita, A. Cacace, V. Tedeschi, P. Guarini. Cardiology and ICU Villa dei Fiori Hospital, Naples, Italy Aim: to evaluate coronary flow reserve (CFR), as measured by transthoracic Doppler echocardiography for functional assessment of left anterior descending (LAD) stenosis severity in comparison with exercise gated-single photon emission computed tomography (SPECT). Methods: We studied 160 patients (96 men, mean age 66±6 yrs) suspected of having coronary artery disease. The flow rate in the distal LAD was measured by echocardiography both at rest and during intravenous infusion of dipyridamole (0.84 mg/kg in 6 min). CFR was calculated as the ratio of hyperemic to basal Conclusions: From the analysis of a large and unselected cohort of patients investigated by dipyridamole stress echo the combined assessment of wall motion and CFR on LAD provides a powerful tool for risk assessment of death Effect of coronary calcification on coronary flow velocity reserve in mild - moderate coronary artery disease D. Tsiapras, I. Mastorakou, V. Vartela, O. Karapanagiotou, S. Kyrzopoulos, S. Katsilouli, V. Voudris. Onassis Cardiac Surgery Center, Athens, Greece Purpose: An estimate of total atherosclerotic burden in asymptomatic individuals, may improve coronary risk stratification and coronary calcium score (CCS) above 300 identify high risk patients (pts). The aim of this study was to evaluate the coronary velocity flow reserve in asymptomatic pts with mild coronary artery disease and wide range of calcification as there is inconsistency in SPECT myocardial perfusion studies and CCS.

157 Echo: a reliable tool to assess coronary flow reserve?! 457 Methods: We studied 48 asymptomatic pts who had underwent a cardiac scan with a dual source 64 slice computer tomography and left anterior descending (LAD) diameter stenosis less than 60% (range 20-60%) was detected. The CCS was calculated for all vessels (total CCS) and LAD territory separately (LAD CCS). A Vivid7 GE echocardiographic apparatus was used for distal LAD flow interrogation, from a modified 2 chamber apical view. LAD flow was recorded at baseline and after dypiridamole (0.56 mg/kg in 4 min) infusion and flow velocity (maximum and mean) was measured. Coronary flow reserve (CFR) was calculated as the ratio of peak to baseline maximum (CFRmax) and mean (CFRmean) velocities. Pts were divided in 2 groups, with low (Group L: 21 pts, CCS<300) and advanced (Group H: 27 pts, CCS>300) total CCS. Results: Despite the different LAD CCS (L: 30±33 vs H: 348±198, p<0.001), no significant difference was detected in LAD stenosis among groups (L: 36±14 vs H:42±17%, p:0.13). Left ventricular ejection fraction was similar in both groups (L: 63±7 vs H: 62±6%, p:ns) while no resting regional wall motion abnormalities were detected. In Group L, a significant increase in both CFRmax (L:2.70±0.53 vs H:1.93±0.28, p<0.001) and CFRmean (L:2.71±0.52 vs H:1.91±0.32, p<0.001) was detected. Using linear regression analysis correlation was detected between total CCS and CFRmax or CFRmean (r:0.58, p<0.05 for both) and LAD CCS and CFRmean (r:-0.63, p<0.05). LAD stenosis (in this range of values) did not show any significant correlation with CFR (max or mean). Conclusion: Coronary calcification seems to be more important in coronary velocity flow reserve than the absolute reduction of lumen diameter stenosis, in asymptomatic pts with mild coronary artery disease. Methods: Nineteen non-diabetic volunteers aged 31.8±8.6 years (mean±sd) participated. Hyperinsulinemic clamps were used to maintain sequential hyperinsulinemic euglycamia (HE, 4.83±0.21 mmol/l) and hyperinsulinemic hypoglycaemia (HH, 2.86±0.08 mmol/l) for 60 minutes each. Low power real-time myocardial contrast echocardiography (MCE) with flash impulse imaging was used to assess the myocardial blood flow (MBF). MBF was calculated as the product of myocardial blood volume (A) and myocardial blood velocity (β) and was measured before and after the administration of dipyridamole at baseline, HE and HH. MBFR was calculated as the ratio of MBF at peak stress to rest. Results: Baseline MBFR (2.46±0.24) was increased by 24% with insulin during HE (3.04±0.36, p < 0.001). This was secondary to a rise in the MBF at peak stress from 42.25±11.71 db to 53.72±9.50 db (p < 0.001). The MBFR decreased during HH (2.29±0.19) compared to baseline (7% reduction p < 0.01) and HE (25% reduction p < 0.001) This was due to an elevated resting MBF (22.10±4.33 db p < 0.001) and a reduced MBF at peak stress (48.89±8.40 db p < 0.01) during HH. ET-1 levels at baseline were 0.49±0.57 pg/ml which did not change following HE (0.52±0.50 pg/ml). At the end of HH there was a significant increase in the ET-1 levels (0.77±0.65 pg/ml, p<0.001 versus baseline levels) Determinants of non invasive coronary flow reserve early after successful primary angioplasty for acute anterior myocardial infarction and their relationship to left ventricular function at follow-up P. Meimoun 1, D. Malaquin 1, T. Benali 1,S.Sayah 1,H.Zemir 1, J. Boulanger 1, A. Luycx-Bore 1, L. Doutrelan 1, C. Tribouilloy 2. 1 CH Compiegne, Compiegne, France; 2 CHU Amiens Sud, Amiens, France The impairment of the coronary microcirculation is of prognostic value in STelevation myocardial infarction (STEMI). Objective: to assess the predictors of coronary flow reserve (CFR), an index of microcirculatory function, at the acute phase of STEMI and their relationship with left ventricular (LV) function at followup (fu). Methods: 50 consecutive patients (pts) (mean age 58±13 years, 18 women) with a first anterior STEMI successfully treated by primary angioplasty (PA), underwent 24 h later a transthoracic evaluation of CFR using intravenous adenosine infusion, in the distal part of the left anterior descending artery (LAD), and a transthoracic Doppler echocardiography. CFR was defined as hyperemic peak flow velocity (FV) divided by baseline FV. LV ejection fraction (LVEF) using the biplane Simpson s rule, wall motion score (WMS) using the 16 segments model, and infarct zone WMS (IZWMS) using the 9 segments assigned to the LAD territory were measured at the acute phase and at 3 months fu. Clinical, biochemical, angiographic parameters, and the TIMI and GRACE risk scores were also assessed. Results: The CFR (mean 1.77±0.5) was not significantly different in pts with and without traditional cardiovascular risk factors as in pts with and without glycoprotein IIb/IIIa inhibitors use (64%), and thrombus aspirating device use (TAD) (42%). A significant correlation was found between CFR and leucocytes count at admission (LC)(r = -0.36), troponin peak (TP)(r = -0.6), GRACE score (r =- 0.37), TIMI risk score (r = -0.34), and ECG ST-segment resolution (all p 0.01), but not between CFR and high sensitive C-reactive protein (CRP), LV mass, E/e (early diastolic transmitral flow velocity / early diastolic mitral tissue Doppler annulus velocity), and NT-pro-BNP. In multivariate analysis, the independent predictors of CFR were TIMI risk score (or GRACE risk score according to the model used), TP, baseline LAD FV, and LC (all, p < 0.05). Baseline LAD FV was independently predicted by baseline rate- pressure product, diabetes, pre- STEMI angina, and deceleration time of E (all, p < 0.05). At fu, LVEF improved from 47±6% to 56±11% and IZWMS from 21.3±3 to 16.4±5 (all, p < 0.01). In multivariate analysis, the independent predictors -of LVEF at fu, were CFR, TP, acute WMS, and TAD (all, p < 0.05), and -of IZWMS were CFR, TP, and CRP (all, p < 0.05). Conclusion: Early after successful PA for anterior STEMI, the main determinants of CFR are TP, LC, and clinical factors. Furthermore, CFR, infarct size, and inflammatory burden are independently related to the global and regional LV function at fu The effect of hypoglycaemia on myocardial blood flow reserve and endothelin-1 levels in healthy non-diabetic subjects using myocardial contrast echocardiography O.A. Rana 1, S. Zouwail 1,J.Begley 1,D.Kerr 2, D.V. Coppini 1, R. Senior 3,K.Greaves 1. 1 Poole Hospital NHS Foundation Trust, Poole, United Kingdom; 2 Royal Bournemouth Hospital, Bournemouth, United Kingdom; 3 Northwick Park Hospital, Harrow, United Kingdom Aims: We investigated the effects of hypoglycaemia on myocardial blood flow reserve (MBFR) and endothelin-1 (ET-1) levels using myocardial contrast echocardiography. Conclusion: In non-diabetic subjects hypoglycaemia is associated with a significant reduction in MBFR and a rise in ET-1 levels. This has important clinical implications in diabetic patients with acute coronary syndromes and on intensive insulin regimens Coronary flow reserve at the right coronary artery stenosis using transthoracic Doppler echocardiography A. Boshchenko, A. Vrublevsky, R. Karpov. Cardiology Research Institute, Tomsk, Russian Federation The aim of our study was a Doppler assessment of coronary flow reserve (CFR) in the right coronary artery (RCA) in CAD patients with single-vessel RCA stenosis and patients without single-vessel RCA stenosis using transthoracic echocardiography. Methods: The CFR study was performed in 63 consecutive patients (mean age 48±13 years; 51 men and 12 women) with sinus rhythm, ejection fraction of the left and the right ventricles >50% using ultrasound diagnostic system Vivid 7 GE Healthcare with a M3S narrow-band sector transducer within 1 week after quantitative coronary angiography (QCA). Patients with single-vessel RCA stenosis area at QCA >50% consisted group 1, patients without RCA stenosis area >50% - group 2. The distal segment (d) of the RCA was examined from the apical long-axis position of the left ventricle in the modified two or three chamber view. Doppler velocity patterns were obtained without contrast enhancement in the drca at baseline and after intravenous dipyridamole infusion (0.56 mg/kg). CFR was calculated as the ratio of hyperemic to basal peak diastolic velocity in the drca. Results: Doppler CFR was obtained in the drca at 51 (81%) of 63 patients: at 15 of 20 patients with single-vessel RCA disease (group 1) and at 38 of 43 patients without RCA stenosis (group 2). The basal peak diastolic velocity of blood flow in the drca was higher in the group 1 than in the group 2 (41±19 cm/s, and 25±7 cm/s, respectively; p<0.001). The dipyridamole-induced increase of peak diastolic velocity of coronary blood flow in the RCA was revealed in both groups (50±21 cm/s, and 67±16 cm/s, group 1, and group 2, respectively; p<0.01). However, an increase of the value was more pronounced in group 2. So, in CAD patients with RCA stenosis >50% CFR was significantly reduced, compared to patients without RCA stenosis and made 1.47±0.81 and 2.76±0.86 for groups 1 and 2 (p<0.001), respectively. We revealed a reverse correlation between the RCA stenosis area at QCA and CFR in this artery (r=-0.66, p<0.001). By individual analysis CFR <2.0 in the RCA was registered in 13 of 15 patients of group 1 and in only 6 of 38 patients of group 2. Thus, CFR in RCA<2.0 had 87% sensitivity and 84% specificity for the identification of RCA stenosis >50%. Conclusion: Stenosis of the RCA>50% is a cause of reduced CFR distal to the stenosis. The decrease of the CFR depends on RCA stenosis area. The CFR <2.0 in the distal RCA is a predictor of RCA stenosis >50% with 87% sensitivity and 84% specificity.

158 458 Cell recrutement in cardiovascular repair CELL RECRUTEMENT IN CARDIOVASCULAR REPAIR 2911 NFkappa B p50 subunit depletion in circulating cells enhances perfusion restoration after femoral artery ligation in mice D. De Groot, R.T. Haverslag, J.L.A. Embrechts, D.P.V. De Kleijn, G. Pasterkamp, I.E. Hoefer. University Medical Center Utrecht, Utrecht, Netherlands Rationale: Arteriogenesis (adaptive collateral artery growth) is an inflammatory process, depending on the recruitment of circulating leukocytes and expression of Nuclear Factor kappa B (NFkappa B) dependent cytokines. Previously it was shown, that the lack of the NFkappa B p50 subunit modulates inflammatory processes in cardiovascular disease, such as a reduced ventricular remodeling and more outward arterial remodeling. We hypothesized that after arterial occlusion, the absence of the NFkappa B p50 subunit enhances the inflammatory response and thereby will lead to an increased perfusion restoration. Methods and results: NFkappa B p50-/- (n=40) and corresponding wild type mice (B6/129PF2, n=40) were subjected to unilateral femoral artery ligation and contralateral sham operation. At day 7, maximum hind limb perfusion under vasodilatation was assessed using fluorescent microspheres. Perfusion restoration was significantly enhanced in the p50-/- animals compared to wild type mice (42.9±3.9 vs. 32.0±2.6% of sham hindlimb perfusion respectively, p<0.05). Transplantation of p50 -/- bone marrow into wild type mice and vice versa (n=15/group) showed that the effect of the subunit depletion can be solely attributed to the circulating cells (p50-/- bm in WT mice 42.1±1.5, WT bm in p50-/- mice 35.4±1.5% of sham hindlimb perfusion respectively). Macrophage accumulation around the developing collateral arteries was assessed by histological sections and showed to be faster and more elaborate in p50-/- animals. CD68 mrna expression analysis confirmed these findings, showing a significant up regulation in the p50-/- mice on day 3 (p50-/-: 5.9±1.8 fold; WT: 1.5±0.6 fold, p<0.05). Conclusion: Depletion of the NFkappa B p50 subunit enhances collateral artery growth. Its absence in the circulating cells improves perfusion restoration after femoral artery ligation by accelerating the inflammatory responses and increasing macrophage influx into the growing collateral vessels G-CSF treatment in postmyocarditic cardiomyopathy enhances homing of bone marrow-derived progenitor cells and increases the number of resident cardiac progenitor cells S. Brunner 1,H.D.Theiss 1, M. Leiss 1,R.Fischer 1, M. Vallaster 1, B.C. Huber 1, A. Keithahn 2, M. Sauter 3, K. Klingel 3, W.M. Franz 1. 1 Klinikum der Universitaet Muenchen-Grosshadern, Munich, Germany; 2 Technische Universitaet Muenchen, Munich, Germany; 3 University of Tübingen, Tübingen, Germany Objective: Recently, it was shown that the physiologic repair mechanism of mobilization and homing of bone marrow-derived stem cells (BMCs) is impaired in dilated cardiomyopathy. In our study we aimed to analyze resident cardiac progenitors (CSCs) and homing of BMC populations in a murine model of dilated cardiomyopathy due to coxsackie virus B3 (CVB3) induced myocarditis and the influence of G-CSF treatment on the number of CSCs, BMC homing and cardiac function. Methods and Results: First, SWR/J (H-2q)-mice were infected by intraperitoneal injection of 105 pfu CVB3. Healthy, age-matched SWR/J (H-2q)-mice served as controls. 12 weeks after infection, DCM was verified by MRI/Millar-tip-catheter and histology. In DCM mice, BMC populations (CD34+CD31+, CD34+Sca-1+, CD34+c-kit+ and CD34+CXCR-4+) measured by flow cytometry were significantly increased in peripheral blood, decreased in bone marrow and increased in the hearts in comparison to controls. Different from ischemic heart diseases, myocardial homing factors (SDF-1, SCF, HIF-1a, and ICAM) assessed by realtime PCR were not upregulated in the CVB3-DCM group. The number of CSCs (Sca-1+ and c-kit+) was increased in the diseased hearts. Finally, 18 DCM-CVB3 mice were analyzed by MRI 8 weeks after CVB3 infection and randomized into G-CSF-or saline-treatment (100 μg/20μl s.c. daily for 2x 5 days). 12 weeks after infection, cardiac function was assessed using MRI: Change of ejection fraction was significantly better in the G-CSF-group compared to the controls (4.1±1.8 vs. -2.5±2.2%; p=0.03). The improvement of cardiac function was associated with enhanced homing of BMC subpopulations and with an increase in the number of CSCs. Conclusions: We have shown that postmyocarditic cardiomyopathy is associated with an increased number of CSCs and migrated BMC populations in cardiomyopathic hearts. G-CSF-administration results in a moderately improved cardiac function, associated with a further increase in the number of CSCs and BMCs in the diseased hearts. Therefore, our data provides a promising non-invasive approach to ameliorate heart failure Impaired in vivo repair capacity of endothelial progenitor cells in patients with chronic heart failure: role of differential microrna regulation and paracrine factors C. Doerries, S. Briand, C. Besler, P. Mocharla, M. Mueller, C. Manes, F.T. Ruschitzka, G. Noll, T.F. Luescher, U. Landmesser. Cardiovascular Center, University Hospital Zurich and Cardiovascular Research, University Zurich, Zurich, Switzerland Background: Endothelial progenitor cells (EPCs) promote endothelial repair and ischemia-induced neovascularisation. Cell therapy is currently intensely explored as a potential novel therapeutic approach in patients with chronic heart failure (CHF). However, the effectiveness of cell therapy may critically depend on the in vivo repair capacity of patient-derived progenitor cells. We therefore characterized in vivo repair capacity of EPCs derived from patients with CHF (ICM and DCM) as compared to healthy subjects (HS) and analysed potential novel targets to improve their repair capacity. Methods: Endothelial progenitor cells were isolated from patients with chronic heart failure due to ICM or DCM and healthy subjects. In vivo endothelial repair capacity of EPCs was examined after transplantation into nude mice with vascular injury. NO and superoxide production of EPCs were determined by electron spin resonance spectroscopy. The microrna expression profile of EPCs was characterized using a microrna array (Exiqon; Denmark) and quantitative real-time RT-PCR analysis. Functional role of differentially regulated pro- and antiangiogenic micrornas is characterized using antimirs and mir-mimics. Furthermore, the secretom of EPCs is characterized by using a protein array. Results: In vivo endothelial repair capacity of EPCs derived from patients with chronic heart failure due to ICM and DCM was markedly reduced as compared to EPCs from healthy subjects (EPC-dependent re-endothelialization: 4.0±1.1 vs. 3.9±1.7 vs. 12.7±2.1%; P<0.05). EPCs from patients with heart failure due to ICM and DCM had an impaired NO production compared to healthy subjects (1892±110.9 vs. 1922±144.2 vs. 2502±185.7 nmol NO/h/ EPCs; P<0.05), that may, at least in part, account for an impaired endothelial repair capacity. Moreover, microrna profiling of EPCs indicated a differential microrna expression in EPCs derived from patients with CHF as compared to healthy subjects, with a reduced expression of pro-angiogenic and increased expression of anti-angiogenic micrornas in patients with CHF. Conclusions: In vivo repair capacity of EPCs is markedly reduced in patients with chronic heart failure due to both, ICM and DCM, as compared to healthy subjects that may limit effectiveness of cell-based therapeutic approaches in these patients. Reduced NO bioavailability of EPCs from these patients likely contributes to a reduced repair capacity. Moreover, differentially expressed micrornas regulating angiogenic growth factor signalling represent potential attractive targets to improve repair capacity of patient-derived EPCs in CHF Time course analysis of bone marrow derived progenitor cell transdifferentiation during neointima formation J.M. Daniel, H.H. Tillmanns, D.G. Sedding. Med. Clinic I, Molecular Cardiology, Justus Liebig University, Giessen, Germany Background: Recent studies claim that circulating bone marrow derived progenitor cells (BMPC) considerably contribute to vascular remodelling processes by differentiating into smooth muscle cells (SMC). In this study we examine the timepoints of accumulation, differentiation and the long term contribution of BMPC compared to media derived SMC in the process of neointima formation. Methods and results: Wild type mice were irradiated with 9.5 Gy and then reconstituted with bone marrow cells from enhanced green fluorescent protein (egfp) transgenic mice. FACS analysis of chimeric mice revealed that 95% of circulating mononuclear cells expressed egfp 12 weeks after transplantation. Wire induced dilatation of the mouse femoral artery was performed, and vessels were harvested after 3 days, 1, 2, 3, 4, 6 and 16 weeks (n=8 animals per timepoint). Neointima/media ratio and number of bone marrow derived (egfp+) cells in the vessel wall were quantified. To further analyse the egfp+ cells for the expression of α-smooth muscle actin (αsma) we used immuno fluorescence imaging and deconvolution analysis of high resolution z-axis image stacks. Three days after dilatation only a few resident SMC were detected in the medial layer, and the denuded/injured luminal surface was lined with thrombocytes. At one to two weeks an increase in both resident SMC in the media and accumulating egfp+ leucocytes to the injury sites was observed. After three weeks a peak in the recruitment of mononuclear cells was detected, and at the same time αsma expressing cells started to accumulate in the neointima with a high proliferative index, as determined by PCNA expression. Interestingly, following careful analysis throughout the complete lesion range, the expression of αsma in GFP+ cells occurred to be a very rare event. Moreover, some cells positive for egfp and αsma were also observed to express monocytic lineage markers like MoMa or CD11b, suggesting that egfp/αsma expressing cells may in part originate from a monocytic subpopulation. Furthermore, the number of egfp+ cells in the neointima constantly declined at later timepoints, so that hardly any egfp+ cells and no egfp/αsma expressing cells could be detected in the neointima 16 weeks after dilatation. Conclusions: These data provide evidence that transdifferentiation of bone marrow derived progenitor cells into SMC lineages seems to be a relatively rare event.

159 Cell recrutement in cardiovascular repair / Cardiac size: signs and signals 459 Moreover, the contribution of bone marrow derived cells to the cellular compartment of the neointimal lesion is limited to a temporary time period of the inflammatory response to the vascular injury G-CSF application combined with CD26-inhibition as a new therapeutic concept enhances stem cell homing and cardiac function after myocardial infarction in mice H.D. Theiss, M.M. Zaruba, M. Vallaster, S. Brunner, R. David, L. Krieg, E. Frank, P. Nathan, G. Steinbeck, W.M. Franz. Ludwig Maximilians Universitaet, Munich, Germany Background: The key issue of therapeutic stem cell approaches emerges to be the process of cardiac homing of stem cells via the SDF-1-CXCR4 axis. Myocardial SDF-1, which is crucial for incorporation of progenitors, is degradeted by the extracellular protease CD26. We hypothesized that pharmacological inhibition of CD26 leads to an increase of myocardial SDF-1 thus improving the homing of G-CSF-mobilized stem cells after myocardial infarction in a mouse model. Methods: We induced acute myocardial infarction (MI) in weeks old C57BL/6 mice using surgical occlusion of the left descending artery (LAD). Mice were then treated either with G-CSF (100 μg/kg/d s.c.) in combination with Diprotin A (140/kg/d μg p.i., G-CSF+DipA ), G-CSF or Diprotin A alone or saline ( control ). Findings: We show that pharmacological DPP-IV inhibition leads to decreased DPP-IV activity in the heart. Myocardial SDF-1 was enhanced after myocardial infarction as demonstrated by ELISA. An increased amount of circulating CD45+/CD34+c-kit+, CD45+/CD34+Sca-1+, CD45+/CD34+CXCR-4+, CD45+/CD34+Flk-1+ as well as lin-c-kit+sca-1+ cells was attracted to the ischemic heart of G-CSF+DipA mice. This effect was reversible by adding the CXCR-4 antagonist AMD 3100 (1.25 mg/kg/day). Probably by parakrine means, these progenitor cells stimulated resident cardiac stem cells (CD45-CD34-c-kit+ and CD45-CD34-Sca-1+ cells) as we show by cardiac FACS. In our experiments, enhanced myocardial homing of stem cells and expansion of resident cardiac progenitor cells finally lead to enhanced neovascularization (increased number of CD31+ cells in the border zone) 6 days after MI. In parallel, CD26 inhibition combined with G-CSF application reduced the cardiac remodeling (decreased infarct size and increased left ventricular wall thickness 30 days after MI). These effects also translated into significantly improved left ventricular function (G-CSF+Dip: 36±1%; wt control: 16±1%; p<0.01) and decreased end-diastolic volume 30 days after MI (as measured by conductance catheter). Finally, survival significantly improved 30 days after MI by CD26 inhibition combined with G-CSF application (G-CSF+Dip: 70%; G-CSF: 40%; DipA: 35%; control: 30%; n=20 in each group). Interpretation: This is the first study showing that combined application of G- CSF and a CD26-inhibitor improves cardiac function and survival after myocardial infarction by an enhanced cardiac homing of stem cells due to inhibition of SDF-1 degradation In situ activation of endogenous cardiac stem cells by intra-coronary administration of IGF-1 and HGF induces myocardial survival and regeneration in the infarcted pig myocardium G.M. Ellison 1, D. Torella 2, C. Perez-Martinez 3, A. Perez 3, S. Purushothaman 1, C. Vicinanza 2, V. Galuppo 2,V.Agosti 2, F. Fernandez 3, B. Nadal-Ginard 4. 1 Liverpool John Moores University, Liverpool, United Kingdom; 2 Magna Graecia Universita Degli Studi di Catanzaro, Catanzaro, Italy; 3 Escuela Veterinaria y Hospital de León, Leon, Spain; 4 Coretherapix, Madrid, Spain Purpose: In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as intramyocardial injection of specific growth factors results in regeneration and improved function post-myocardial infarction (MI). Extrapolation of these results to the human is doubtful because the human requires larger regenerated mass. Using a clinically relevant experimental infarct animal model, we investigated the effects of intracoronary injections of IGF-1 and HGF at varying doses on myocardial remodeling and regeneration after MI in pigs. Methods: In 31 closed-chest Yorkshire pigs, MI was induced by a 75 min PTCA LAD occlusion. IGF-1 and HGF were administered in 3 groups at incremental doses (2-16μg IGF-1; 0.5-4μg HGF) to 23 pigs (GF-treated), 30 minutes after coronary reperfusion. Saline was injected to 8 control pigs after MI (CTRL). To track myocardial regeneration, BrdU was administered via osmotic pumps. Cardiac function was measured by Echo and MRI. Pigs were sacrificed at 14, 21, 28 and 56 days and hearts processed for immunohistochemical and confocal microscopy analysis. Results: IGF-1/HGF injection significantly (p<0.05) preserved cardiomyocyte number and myocardial wall structure, reduced fibrosis, cardiomyocyte death and reactive hypertrophy. GF-treated infarcted pig hearts showed a significant increase (p<0.05) in the number of c-kitpos CSCs, c-kitpos/nkx2.5pos, c- kitpos/ets-1pos cardiac progenitors in the border and infarct region, compared to CTRL. A majority of the c-kitpos CSCs were BrdU positive, documenting their regenerative nature, and their actual proliferation was confirmed by Ki-67 staining. GF-treated hearts, both in the infarct and border regions (P<0.05), harbored a large population of very small, newly formed BrdUpos myocytes. These data were confirmed by the expression of Ki67. Newly formed BrdUpos capillaries and arterioles were also evident in the border and infarcted regions, with increased (p<0.05) number of capillaries in GF-treated pigs, compared to CTRL. Cardiac function was significantly preserved/improved by GF-treatment. There was a direct correlation between the GF dose and the number of c-kitpos CSCs, vascular (c-kitpos/ets-1pos or Gata6pos) and cardiomyocyte (c-kitpos/nkx2.5pos) progenitor cells, newly formed myocytes, new capillaries, preservation of myocardial structure and cardiac function. Conclusions: Intracoronary injection of IGF-1 and HGF after MI in pigs has a protective effect on myocardial tissue organization and structure and produces significant regeneration, which is correlated with GF dose, in hearts the size of human s. CARDIAC SIZE: SIGNS AND SIGNALS 2917 GRK2 and GRK5 regulate cardiac hypertrophy: in vitro andinvivostudies D. Sorriento 1,G.Santulli 1, P. Campiglia 2, A. Campanile 1,A.Fusco 1, B. Trimarco 1,G.Iaccarino 1. 1 Azienda Ospedaliera Universitaria Federico II, Naples, Italy; 2 Università degli Studi di Salerno, Salerno, Italy G Protein Coupled Receptors kinases (GRKs) belong to a family of kinases involved in desensitization of GPCRs. Heart failure is associated with increased levels of GRK2 and GRK5 shows a nuclear localization in cardiomyocites from spontaneous hyperthensive rats (SHR), suggesting a role for this kinase in the regulation of gene transcription. We evaluated the role of GRK2 and GRK5 on the ANF promoter activity, a marker of cardiac hypertrophy, by luciferase assay. In HEK293 cells, the hypertrophic stimulus Angiotensin II (ANG) increased ANF activity (ANG +300±6.5 vs control). GRK2 overexpression induced an increase of ANF activity (+332±15% vs control) and enhanced ANG response (+118±12% vs ANG). On the contrary, overexpression of GRK5 inhibited ANF activity both in basal conditions and after stimulation with ANG (- 54±5.1% vs ANG), suggesting a reciprocal role for GRK2 and GRK5. We then investigated whether GRK2 kinase activity is relevant to the expression of ANF. Two peptidic inhibitors of GRK2, Ant- 124 and Ant-107, designed on the HJ loop domain of GRK2, were both able to inhibit basal (Ant-124: -57±1.1%; Ant-107: -51±2.3%), ANG (-60±0.9%; - 58±1.5% respectively) and GRK2 (-43±0.8%; -43±1.0% respectively)-induced ANF promoter activity. Similarly, overexpression of a dead kinase GRK2 mutant inhibited basal (-76±1.8%) and ANG-induced ANF activity (-67±4.5%). It has been showed that activation of NFkB has a key role in hypertrophy. We have recently demonstrated that GRK5 inhibits NFkB activity (Sorriento et al., PNAS 2008). Thus, we evaluated the role of NFkB in GRK2-induced ANF expression. Overexpression of IkBα, the main inhibitor of NFkB, and GRK5 both inhibit GRK2- induced ANF promoter activity (IkBα -93±3.7%; GRK5-98±5% vs GRK2). These data suggest that GRK5 and GRK2 differently regulate ANF promoter activity by means of the regulation of NFkB activity. To confirm such in vitro data, we performed in vivo experiments in 3 different animal model of hypertrophy: Isoproterenol, Phenylephrine induced hypertrophy in normotensive WKY rats and hypertrophic SHR. Hypertrophy was confirmed by means of echocardiographic parameters. In all hypertrophic rats heart, GRK2 levels were increased as compared to WKY hearts. Also, by means of Elettrophoretic Mobility Shift Assay in nuclear extracts from rats hearts, NFkB activity was increased in all models of hypertrophy. Our results show that GRK2 participates in the setting of hypertrophic phenotype, by regulating nuclear transcription through NFkB. In conclusion, our results suggest a novel role for GRKs in the regulation of hypertrophy both in vitro and in vivo Mutations in the ANKRD1 gene encoding CARP are responsible for human dilated cardiomyopathy L. Duboscq-Bidot 1, P. Charron 2, V. Ruppert 3, L. Fauchier 4, A. Richter 3, T. Wichter 5,B.Maish 3, M. Komajda 2,R.Isnard 2, E. Villard 1 on behalf of EUROGENE HEART FAILURE. 1 INSERM UMR 956, Paris, France; 2 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 3 Universitaetsklinikum Giessen und Marburg, Marburg, Germany; 4 Centre Hospitalier Universitaire Trousseau, Tours, France; 5 Universitaet Muenster, Munster, Germany Dilated Cardiomyopathy (DCM) is familial in about 30% of cases, and to date, 15 responsible genes have been identified in isolated forms and up to 25 associated with additional phenotypes including myopathy, arrythmias or more complex syndromes. No major gene for the disease has been identified, demonstrating the genetic heterogeneity of DCM. However, in a majority of families the responsible genes are still to be discovered. The ANKRD1 gene is overexpressed in heart failure in human or animal models. The encoded protein CARP is interacting with partners such as Myopalladin or Titin, previously involved in DCM. We hypothesised that mutations in ANKRD1 could be responsible for DCM. We have screened a DCM affected population consisting on 231 caucasian independent familial (158) and sporadic (73) cases by direct sequencing of PCR-amplified coding exons. We identified 5 missense mutations: 3 sporadic

160 460 Cardiac size: signs and signals (mutations p.glu57gln, p.arg66gln and p.leu199arg) and 2 familial (mutations p.thr116met and p.ala276val) absent from 400 controls and affecting highly conserved residues. Expression of the mutant CARP proteins in rat neonate cardiomyocytes indicated that at least 3 of the mutations identified (p.glu57gln, p.leu199arg, p.ala276val) led both to significant less repressor activity and to greater phenylephrin induced hypertrophy suggesting altered function of CARP mutant proteins. Based on genetic and functional analysis of CARP mutations, we have identified ANKRD1 as a new gene associated with DCM, accounting for about 4% of cases Coupling of ErbB4 but not ErbB1/2 to intracellular activation of Akt-1 in the adult ventricle: implications for anti-erbb cancer therapy K. Doggen, K. Lemmens, G.W. De Keulenaer. University of Antwerp, Antwerp, Belgium Introduction: Neuregulin-1 is a cardio-protective growth factor through activation of ErbB receptor signalling. Adult cardiomyocytes express 3 members of the ErbB receptor family: ErbB1, ErbB4 and ErbB2, the latter being a ligand-less hetero-dimerization partner for ErbB1 and ErbB4. Recent proteomic screens in tumour cells have differentiated these ErbB receptor tyrosine kinases with regard to the phospho-tyrosine-dependent activation of downstream signalling pathways. We analysed the relevance of these findings for ErbB signalling in cardiac tissue. Methods: We studied cardiac ErbB receptor activity and downstream signalling in vitro (in neonatal cardiac myocytes) and in vivo. For in vivo experiments, mice were treated with epidermal growth factor (EGF, an ErbB1 ligand) and neuregulin-1 (NRG-1, an ErbB4 ligand) in the presence or absence of lapatinib, an ErbB1/ErbB2 tyrosine kinase inhibitor. ErbB receptors and downstream signalling were analysed by immuno-precipation and Western blotting. Results: Treatment of mice with EGF (40 μg/kg, 10 min, i.p.) induced phosphorylation of ventricular ErbB1, ErbB2 and ERK1/2, but not of ErbB4 and Akt-1. By contrast, treatment with NRG-1 (10 μg/kg) induced phosporylation of ErbB4, ErbB2, ERK1/2 and Akt-1, and variably, of ErbB1. Moreover, in neonatal cardiac myocytes, anti-erbb4 antibodies inhibited NRG-1-induced phosphorylation of ErbB4 and Akt-1, leaving ErbB2 unaffected. These results suggest specific coupling of ErbB4 to Akt-1 in cardiac tissue, which distinguishes it from ErbB1. Implications of these observations for anti-erbb treatment were shown as follows. First, as expected, lapatinib completely blunted EGF-induced phosphorylation of ErbB1, ErbB2 and ERK1/2. In addition, lapatinib completely blocked NRG-1- induced phosphorylation of ErbB2 and ERK1/2, but, importantly, failed to reduce NRG-1-induced phosphorylation of ErbB4 and of Akt-1. Conclusion: This study reveals the existence of a NRG-1/ErbB4/Akt-1 axis in cardiac tissue, which is resistant to pharmacological anti-erbb1/2 treatment by lapatinib. We speculate that NRG-1 activates the Akt-1 signalling pathway through formation of ErbB4/ErbB4 homodimers, this means independently of ErbB1/2. These data may have important implications for the mechanisms and treatment of anti-erbb-induced cardiotoxicity by receptor tyrosine kinase inhibitors Targeted deletion of BMP and Activin Bound Inhibitor (BAMBI) increases and accelerates left ventricular remodeling under pressure overload M. Llano 1, A.V. Villar 2, M. Cobo 1, M. Tramullas 2,R.Merino 3, D. Merino 2,R.Martin-Duran 1, J.F. Nistal 1,M.A.Hurle 2. 1 Hospital Universitario Marques de Valdecilla, Santander, Spain; 2 University of Cantabria, Santander, Spain; 3 Instituto de Biomedicina y Biotecnologia de Cantabria, Santander, Spain Purpose: LV remodeling under pressure overload (PO) features hypertrophy of cardiomyocytes, proliferation of fibroblasts and increased extracellular matrix (ECM). In this process, the Transforming Growth Factor-β (TGF-β) family of cytokines are crucial players. TGF-βs signal through serine/threonine kinase transmembrane receptor complexes, in which type II receptors phosphorylate type I receptors, leading to activation of Smad proteins and MAP kinases. At the cell membrane, TGF-β signaling is regulated by the glycoprotein BAMBI, structurally related to TGF-β type I receptors, but lacking the intracellular kinase domain. BAMBI is a pseudoreceptor that blunts TGF-βs signaling by preventing the formation of active receptor complexes. We aimed to assess whether the absence of BAMBI in KO mice affects myocardial remodeling under PO. Methods: PO was produced by transverse aortic arch constriction (TAC). BAMBI- WT and -KO mice were subjected to TAC for 1 to 4 weeks. Echocardiography was performed with Agilent Sonos-5500 (Philips) and VisualSonics Vevo-770 systems. LV expression levels of remodelling-related genes and proteins were determined by qpcr and Western Blot. Histology of LV sections was studied with Masson s trichrome. Results: KO mice presented higher basal heart mass index (KO: 5.0±0.1 mg/g; WT: 4.4±0.1 mg/g; p<0.05), and overexpression of β-myosin Heavy Chain (KO: 7741±1512 vs WT: 3046±804; p<0.05) and Collagen III (KO: 6.9±1.1 vs WT: 3.6±0.8; p<0.05). Over the 4 weeks after TAC, LV hypertrophy (echo and weight at sacrifice) and dilation developed faster and reached higher values in KO vs WT mice (KO: 7.5±0.2 mg/g; WT: 6.2±0.1 mg/g; p<0.001). LV ejection fraction was consistently lower in KO mice after TAC. KO mice showed higher values in expression levels of genes encoding ECM components: Collagen I (KO: 464±119 vs WT: 73.7±18.5; p<0.05), Fibronectin (KO: vs WT: 8.9±1.2; p<0.05) and Tissue Inhibitors of Metalloproteinase 1 (KO: 1.9±0.2 vs WT: 1.0±0.2; p<0.05) and 2 (KO: 10.0±1.4 vs WT: 6.4±0.8; p<0.05); as well as sarcomeric elements: β-myosin Heavy Chain (KO: 8.2±1.3 vs WT: 4.2±0.9; p<0.05). Western blot and histology confirmed these findings. Conclusions: The absence of BAMBI generates a cardiac phenotype characterized by myocardial hypertrophy and fibrosis under basal conditions and an accelerated remodeling response against pressure overload. Our results support a putative capability of BAMBI to prevent profibrogenic and hypertrophic effects mediated by TGF-β signaling, and emphasize its importance as a potential new target in the prevention of tissue fibrosis Liver X receptors attenuate cardiomyocyte hypertrophy I. Kuipers 1,J.Li 2, H.H.W. Sillje 1, L. Van Genne 1, S. Oberdorf-Maass 1, A.H. Maass 1, D.J. Van Veldhuisen 1, W.H. Van Gilst 1,R.A.De Boer 1. 1 University Medical Center, Groningen, Netherlands; 2 Second Xiangya Hospital of Central South University, Changsha, China, People s Republic of Purpose: Liver X receptors (LXRs) are transcription factors with established effects on cholesterol metabolism. Antiproliferative effects in tumor cells have also been reported, indicating that LXRs have additional functions. LXRs are expressed by the heart and in cultured cardiomyocytes (HL-1 cells, cell line derived from adult mouse atria, and primary neonatal rat ventricular myocytes [NRVM]). Here we have investigated a potential role of LXRs in the regulation of cardiomyocyte hypertrophy. Methods: We induced cardiomyocyte hypertrophy by treating HL-1 cells and NRVM with angiotensin II (AngII) and endothelin-1 (ET-1), with or without coincubation with the LXR agonist T (T09). Cells were stained with phalloidin to determine cell surface area (CSA) by morphometry. Expression of atrial natriuretic peptide (ANP) mrna was determined by quantitative RT-PCR. To assess whether the observed antiproliferative effects of T09 were mediated by LXRs, we employed sirna mediated knockdown of LXRs. Results: AngII and ET-1 caused a significant increase in CSA in HL-1 cells (99% increase and 64% increase, p<0.05 vs control, C). This was attenuated by cotreatment with T09 (p<0.05 vs AngII or ET-1 alone). ANP mrna expression was also increased upon AngII and ET-1 treatment (58% increase and 99% increase, p<0.05 vs C) and co-treatment with T09 normalized ANP mrna expression to control levels (p<0.05 vs AngII and ET-1 alone). After sirna mediated knockdown of LXR (both LXR-alpha and -beta), T09 no longer conferred its antihypertrophic effects, confirming that this T09 effect was LXR specific. These observations were subsequently confirmed with NRVM to rule out HL-1-specific effects. In NRVM, ET-1 treatment again increased CSA (75% increase, p<0.05 vs C) and ANP mrna expression (520% increase, p<0.05 vs C). Like in HL-1 cells, co-treatment with T09 attenuated the increase in CSA area and ANP mrna expression in NRVM (CSA: 25% increase, p<0.05 vs ET-1 alone; ANP mrna expression: 320% increase, p<0.05 vs ET-1 alone). Conclusions: Activation of LXRs attenuates AngII and ET-1 induced cardiomyocyte hypertrophy. These findings suggest a potential role of LXRs in reducing cardiac hypertrophy, and therefore constitute a potential target in the treatment of cardiac disorders Neuregulin/ErbB signaling in pregnancy-induced hypertrophy K. Lemmens, K. Doggen, G.W. De Keulenaer. University of Antwerp, Antwerp, Belgium Introduction: The neuregulin-1 (NRG-1)/ErbB system is a cardioprotective system that becomes activated during cardiac stress. Genetic deletion or pharmacological inhibition of ErbB signaling leads to ventricular failure. In this study, we analyzed ventricular ErbB signaling in pregnancy-induced left ventricular (LV) hypertrophy. Methods: LV expression of NRG-1, ErbB receptor phosphorylation and downstream activation of Akt-1 and ERK1/2 was studied by Western blot analysis in rat and mice at different stages of gestation. Mice were treated with lapatinib, an ErbB1/ErbB2 tyrosine kinase inhibitor (80 mg/kg/d by oral gavage) throughout pregnancy. Ventricular function was evaluated by echocardiography. Results: Pregnancy induced eccentric LV hypertrophy without reduction of LV fractional shortening, both in rat and mice (heart weight + 19%, LV end-diastolic diameter + 10% versus non-pregnant controls, p < 0.01, n=6). Ventricular expression of NRG-1 increased by 60% versus non pregnant controls (p=0.02, n=6). Levels of phosphorylated ErbB2 an ErbB4 increased by 93% and 61% respectively while total receptor levels remained unchanged (p= 0.02, n=6). Also, downstream Akt-1 and ERK1/2 were activated. The increase of NRG-1 expression was observed at early stages of pregnancy while receptor activation followed later in pregnancy. Treatment of pregnant mice with lapatinib inhibited phosphorylation of ErbB2 and ERK1/2 leaving ErbB4 and Akt-1 phosphorylation unaltered. At late pregnancy lapatinib treated mice developed a more pronounced eccentric cardiac phenotype as compared to vehicle treated pregnant controls (LV end-diastolic diameter + 12%, p < 0.01, n = 7) with a slight and borderline significant decrease in fractional shortening by 6% (p = 0.05, n=7).

161 Cardiac size: signs and signals / Recent randomized trials and registries in coronary revascularization 461 Conclusion: Our data demonstrate that the left ventricular NRG-1/ErbB pathway becomes activated in pregnancy-induced cardiac hypertrophy. ErbB2 and ERK1/2 activation seem to be important to counterbalance the eccentric phenotype and to preserve systolic function. This is the first study to show the importance of ErbB signaling in physiological hypertrophy. and safe. However, the rate of 6-month MACEs was significantly higher when compared to CrCo stents (mainly due to higher TLR). Furthermore, the finding of 6% of late-stent thrombosis in the EPC stent group is worrisome. Large randomized trials are needed to definitely address this issue, however, until that, the EPC stents should be avoided in patients with STEMI. RECENT RANDOMIZED TRIALS AND REGISTRIES IN CORONARY REVASCULARIZATION 2923 Six-month follow-up of RES-ELUTION NEVO-I, a randomized multi-center comparison of the nevo reservoir-based sirolimus-eluting stent with the TAXUS liberte paclitaxel-eluting stent J. Fajadet 1,A.Abizaid 2,J.Ormiston 3, J. Schofer 4, L. Thuesen 5, L. Mauri 6,J.Popma 7, P. Fitzgerald 8, H.P. Stoll 9, C. Spaulding Clinique Pasteur de Toulouse, Toulouse, France; 2 Instituto Dante Pazzanese, Sao Paolo, Brazil; 3 Auckland City Hospital, Auckland, New Zealand; 4 Herzkatheterlabor und Praxisklinik, Hamburg, Germany; 5 Aarhus University Hospital, Skejby, Aarhus, Denmark; 6 Harvard Clinical Research Institute, Boston, United States of America; 7 Brigham and Women s Hospital, Boston, United States of America; 8 Stanford University, Palo Alto, United States of America; 9 Cordis Clinical Research, Waterloo, Belgium; 10 Universite Paris-Descartes, Paris, France Background: Traditional drug eluting stents deliver an anti-proliferative drug to the vessel wall from a durable polymer which homogeneously covers the outer surface of the stent. More recently, the NEVO sirolimus releasing stent has been developed and combines a biodegradable PLGA (poly DL-lactide-co-glycolide) polymer with a novel reservoir technology on a chromium-cobalt stent platform that allows uni-directional delivery of sirolimus to the vessel wall. The dosage, delivery kinetics and resulting tissue concentrations of sirolimus are similar to those of the Cypher stent. The Nevo sirolimus-eluting coronary stent is being evaluated in a multi-center randomized trial (RES-Elution) which seeks to establish the efficacy and the safety of the NEVO compared to the TAXUS stent. Methods: This study is designed to demonstrate the non-inferiority of 6-month instent late lumen loss (primary endpoint) of the Nevo sirolimus-eluting coronary stent system compared to the TAXUS Liberté stent control arm in the treatment of single de-novo lesions up to 28 mm in length in native coronary arteries 2.5 mm to 3.5mm in diameter. Secondary end-points include target vessel failure, target lesion failure, MACE, stent thrombosis, and percent volume obstruction of the stent at 6 months in the IVUS cohort. Major exclusion criteria were acute myocardial infarction, ostial and unprotected left main stem lesions, and heavily calcified and tortuous lesions. Patients were randomized 1 to 1 after the guidewire crossed the lesion. IVUS was performed in a subgroup of 100 patients. Follow-up was planned at one, six, twelve months and annually up to five years and includes a control angiogram at six months. Dual antiplatelet therapy was administered for a minimum of six months in both groups. This non-inferiority study was designed with 90% power, an alpha of 0.05, and a non inferiority margin of 0.2 mm. The required minimal sample size was calculated at 388. If non-inferiority is demonstrated, testing for superiority will be undertaken. Results: A total of 394 patients were enrolled at 40 study sites in 9 countries from March to October Baseline, 30 day, 6-month angiographic primary endpoint data as well as the results from the IVUS substudy will be available in May A randomized comparison of genous stent versus chromium-cobalt stent for treatment of ST-elevation myocardial infarction. A 6-month clinical, angiographic and IVUS follow-up. GENIUS-STEMI trial P. Cervinka, P.C. Cervinka, M.B. Bystron, R.S. Spacek, M.K. Kvasnak. Department of Cardiology, Masaryk hospital, Usti nad Labem, Czech Republic Purpose: The objective of this trial was to assess the feasibility and safety of the use of endothelial progenitor cells (EPC) capture stent for treatment of STelevation myocardial infarction (STEMI) and randomized comparison of 6-month clinical, angiographic and IVUS outcome with chromium-cobalt stents (CrCo). Methods: Between January and December 2007, 100 consecutive patients with STEMI were randomly assigned to receive either EPC capture stent (N=50) (Genous stent) or CrCo stent (N=50). The stents were implanted at low pressure (<10 atmospheres) with high-pressure postdilatation with a short, bigger balloon in both groups. Dual antiplatelet treatment was administered for 30 days in both groups. A 6-month clinical, angiographic and IVUS follow-up was assessed in both groups. Results: Baseline demographic, angiographic and procedural characteristics were well balanced in both groups. All procedures have been performed without complication in both groups. The rate of MACEs at 30-day was comparable in both groups. However, there was statistically significant higher rate of MACEs in the EPC stent group when compared with CrCo stent (24% vs.10%; p=0.03) at 6- month follow-up. Furthermore, there was statistically significant difference regarding target-lesion revascularization between both groups (14% vs. 4%; p=0.04). Notwithstanding, there were 3 cases (6%) of late stent thrombosis in the EPC stent group and none in the CrCo stent group. Conclusion: The use of EPC capture stent in the setting of STEMI is feasible 2925 A randomized comparison of sirolimus- versus paclitaxel-eluting stent for treatment of bifurcation lesions by single stent and kissing ballooning: results of SINGLE KISS trial K. Nasu 1,Y.Oikawa 2,E.Tsuchikane 1,T.Aizawa 2, T. Suzuki 1 on behalf of SINGLE KISS trial group. 1 Toyohashi Heart Center, Toyohashi, Japan; 2 The Cardiovascular Institute Hospital, Tokyo, Japan Background: There was few randomized comparison has been carried out comparing different drug-eluting stents for treatment of coronary bifurcation lesions by single stent strategy. The purpose of SINGLE KISS trial was to assess the efficacy of single stent strategy with kissing ballooning after stent implantation using by sirolimus- and paclitaxel-eluting stents in patients with bifurcation lesions. Methods: Inclusion criteria were lesions >75% diameter stenosis within 5mm of a bifurcation in vessels mm in diameter in the main branch and >2.25mm in the side branch. Single drug-eluting stent was implanted and kissing ballooning was performed after stenting. Follow-up angiography was scheduled at 9 month and patients were follow-up prospectively for one year. Results: A total of 839 patients were enrolled at 22 clinical sites. Up to date, 428 patients completed one year follow-up. The Major Adverse Cardiac Events rates between both groups were similar (Table). There has been no reported stent thrombosis to date. One year Clinical results SES (n = 246) PES (n =182) p Death 0 2 (1.1%) Myocardial Infarction 2 (0.8%) 1 (0.5%) TLR 18 (7%) 16 (9%) TLR for main branch 18 (7%) 9 (5%) 0.59 TLR for side branch 0 3 (1.6%) TLR for both branches 0 4 (2%) TVR 19 (7%) 16 (9%) 0.72 Any MACE 21 (9%) 19 (10%) 0.51 Conclusions: The results of SINGLE KISS trial demonstrated that single stent strategy with kissing ballooning using by sirolimus- and paclitaxel-eluting stent systems were similar and effective in patients with bifurcation lesions. Complete angiographic and clinical results will be available at the time of presentation Thrombosis in real practice with second generation drug-eluting stents. Results from the ESTROFA-2 spanish registry J.M. De La Torre Hernandez 1,F.Gimeno 2,J.A.Diarte 3, R. Lopez Palop 4, A. Perez De Prado 5,F.Rivero 6, J. Sanchis 7, M. Larman 8, J. Elizaga 9, F. Hernandez 10 on behalf of ESTROFA study group.. 1 H. Marques de Valdecilla, Santander, Spain; 2 H. Clinico, Valladolid, Spain; 3 H. Miguel Servet, Zaragoza, Spain; 4 H. San Juan, Alicante, Spain; 5 Hospital de Leon, Leon, Spain; 6 H. de la Princesa, Madrid, Spain; 7 H. Clinico, Valencia, Spain; 8 P. Guipuzcoa, San Sebastian, Spain; 9 H. G. Marañon, Madrid, Spain; 10 H. 12 de Octubre, Madrid, Spain Background: First generation drug-eluting stents (DES) reduce restenosis significantly but are associated systematically to a variable incidence of late thrombosis, specially in off-label settings. There is no data regarding incidence and predictors for thrombosis with the second DES generation, zotarolimus-eluting stent (ZES) and everolimus-eluting stents (EES), in real practice with a frequent off-label indications. Methods: We have designed a large-scale, nonindustry-linked multicentered prospective registry in order to evaluate second generation DES-thrombosis in clinical practice. Complete clinical-procedural data and systematic follow up of all patients treated with these stents is reported in a web-based registry supported by the Spanish Working Group on Interventional Cardiology. Results: Up to now 4119 pts have been included in 32 centers, 2470 treated with ZES and 1649 with EES. After a median follow up of 355 days ( ) 60 (definite + probable + possible) thrombosis have been reported. The cumulative incidence of overall thrombosis for ZES was 0.9% at 30 days, 1.8% at 12 months and 2% at 18 months and for EES was 0.7% at 30 days and 1.6% at 12 months. Univariant predictors for thrombosis were: age, diabetes, bifurcations, ejection fraction, renal failure and acute coronary syndrome. A propensity score adjusted multivariant analysis yielded as independent predictors for thrombosis: ejection fraction (HR 0.96; 95% CI : p=0.01), HBP (HR 7; 95% CI : p=0.009) and stent diameter (HR0.36; 95% CI : p=0.04). The stent model was not predictor (for ZES HR 1.6; 95% CI 0.6-3: p=0.27). Conclusions: In a real practice setting with frequent off-label indications the incidence of thrombosis at months year with both models of second DES generation was low and not different. However, a longer follow up should be performed to assess the incidence of very late thrombosis.

162 462 Recent randomized trials and registries in coronary revascularization / Drug eluting stent restenosis: an emerging challenge 2927 Simple versus complex stenting strategy for coronary artery bifurcation lesions in the drug-eluting stent era: a meta-analysis of randomized trials F. Zhang, L. Dong, J. Ge. Zhongshan hospital, Fudan university, Shanghai, China, People s Republic of Purpose: To compare two strategies for treatment of coronary bifurcation lesions in the drug-eluting stent era: a simple (stenting only the main vessel [MV] and provisional stenting of the side branch [SB] only when bailout of the SB is necessary) vs a complex stenting approach (routinely stenting both MV and SB). Methods and results: Data sources included PubMed and conference proceedings. Prespecified criteria were met by 5 randomized studies comparing simple stenting strategy versus complex stenting strategy in 1,553 patients with coronary bifurcation lesions. Studies reported the clinical and angiographic outcomes of efficacy and safety during a minimum of 6 months. The risk of follow up myocardial infarction (MI) (relative ratio [RR] 0.54, 95% CI 0.37 to 0.78, P=0.001), especially that of early (in hospital or 30 day) MI (RR 0.52, 95% CI 0.35 to 0.78, P=0.002) was markedly lower in patients treated with the simple strategy compared to the complex strategy. There were no differences between two strategies with respect to the rates of cardiac death (RR 0.68, 95% CI 0.21 to 2.25, P=0.53), target lesion revascularization (RR 0.93, 95% CI 0.62 to 1.41, P=0.74) or definite stent thrombosis (RR 0.50, 95% CI 0.19 to 1.32, P=0.16). And the restenosis risk of MV and SB did not differ between two different strategy (RR 1.05, 95% CI 0.61 to 1.82, P=0.85 and RR 1.12, 95% CI 0.80 to 1.57, P=0.50, respectively). pts of the PCI cohort died. No further MI appeared within one year. In 12 pts after PCI we found restenosis and in 17 pts bypass occlusion, 11 of PCI pts (12.6%) and 5 CABG pts (5%) required reintervention. Cumulative MACE rate after 12 months was 17.2% for PCI group and 13.7% for the CABG group. The higher MACE rate in PCI group was driven solely by the rate of Reintervention. Conclusions: In pts with unprotected left main stenosis both CABG and PCI using drug eluting stents can be performed with few periprocedural complications and low mortality. At 12 month MACE rate is higher for PCI group. DRUG ELUTING STENT RESTENOSIS: AN EMERGING CHALLENGE 2929 Angiographic measures of restenosis following drug-eluting stent implantation have a bimodal pattern of distribution R. Byrne 1, S. Eberle 1,A.Kastrati 1,A.Dibra 1, G. Ndrepepa 1, R. Iijima 1, J. Mehilli 1, A. Schoemig 2. 1 Deutsches Herzzentrum Muenchen, Munich, Germany; 2 1. Medizinische Klinik rechts der Isar, Munich, Germany Background: Prior research has demonstrated that markers of restenosis post balloon angioplasty and bare metal stent implantation follow a bimodal distribution. While drug-eluting stent (DES) therapy has negated the impact of certain factors on restenosis, its effect on the distribution of indices of restenosis is not known. We performed detailed analysis of restenosis indices following DES implantation. Methods: Patients undergoing DES implantation (Cypher or Taxus) at 2 German centres underwent repeat angiography at 6-8 months. Primary endpoints of this analysis were in-stent late luminal loss (LLL) and in-segment percentage diameter stenosis (%DS) by quantitative coronary angiography. Results: Data were available for 2057 patients. Overall mean LLL was 0.31±0.50 mm; mean %DS was 30.3±15.7. Distribution of both LLL and %DS differed significantly from normal (Kolmogorov-Smirnov test; p<0.001 for each; figure). For both parameters a bimodal distribution better described the data (likelihood ratio test with 3df; p<0.001 for each; figure). This consisted of 2 normally-distributed subpopulations with means of 0.10±0.25 mm and 0.69±0.60 mm for LLL, and means of 22.2±8.6 and 40.1±16.6 for %DS. No effect on distribution patterns was evident when data was analyzed according to stent type or off-label implantation. Early MI With Simple Vs Complex Strategy Conclusions: Compared to the complex strategy for DES treatment of coronary bifurcation lesions, the simple strategy was associated with a lower risk of early MI and a similar rate of angiographic restenosis. Since the complex strategy could not improve the clinical or angiographic outcome, the simple strategy can be recommended as a preferred bifurcation stenting technique in DES era Unprotected left main stenosis: multicenter randomized trial between CABG and PCI with sirolimus eluting stent E. Boudriot 1, G.S. Schuler 1, H.T. Thiele 1, T.W. Walther 1, C.L. Liebetrau 2, P.B. Boeckstegers 3, B.R. Reichart 3,H.M.Mudra 4, F.-J.N. Neumann 5, F.-W.M. Mohr 1. 1 Herzzentrum der Universitaet Leipzig, Leipzig, Germany; 2 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 3 Klinikum der Universitaet Muenchen-Grosshadern, Munich, Germany; 4 Staedtisches Klinikum Muenchen, Bogenhausen, Munich, Germany; 5 Herzzentrum Bad Krozingen, Bad Krozingen, Germany Background: Unprotected left main stenosis is still considered an indication for bypass surgery. We conducted a randomized, multicenter study to compare PCI with Sirolimus eluting stents to bypass revascularisation for patients with significant left main stenosis. Methods and Demographics: From 8/2003 to 2/ patients with significant left main stenosis were recruited for the study. Additonal lesions in the remaining coronary arteries have been treated as well. They were randomized to undergo CABG or PCI using drug eluting stents (Sirolimus). Angiographic control was performed at 12 month. Primary endpoints were death, acute myocardial infarction and reintervention at 12 month. Out of the 174 pts 87 were randomized for CABG and 87 for PCI. Mean age was 67,4 years. Left ventricular function was well preserved. There were no significant differences between both groups with respect to other baseline variables. The left main lesion was located at the ostium in 22%, midshaft in 7% and at the bifurcation in 71%. An average of 2.6±1.1 stents were implanted, and 2.5±0.8 bypass grafts were performed. Half of operated pts received complete arterial revascularization. Results: Intrahospital. Early success was 96% in PCI and 100% in CABG. 3 pts assigned to PCI had to be converted to CABG, without complications. One of the operated pt. unterwent graft revision. Periprocedural infarction was noted in 3 pts after CABG, and in 2 pts in the PCI-group. Early mortality rate in surgery was 1.1%, no patient died after PCI. 1-year-Follow Up: Over the course of one year 4 pts from the surgical group and 2 Hanging histogram: (A) normal, (B) bimodal Conclusions: This is the first study to show that LLL and %DS at follow-up angiography post DES implantation have a complex mixed distribution pattern, accurately represented by a bimodal distribution model. The introduction of DES therapy has not resulted in elimination of variable propensity to restenosis among subpopulations of stented lesions. These findings are further evidence of nonuniform response to DES therapy and also have implications for the analysis of inter-des efficacy studies Optical coherence tomography patterns of stent restenosis N. Gonzalo Lopez, P.W. Serruys, T. Okamura, H.M. Van Beusekom, H.M. Garcia-Garcia, G. Van Soest, W.J. Van Der Giessen, E. Regar. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Purpose: Stent restenosis is an infrequent, but poorly understood clinical problem in the drug-eluting stent era. The aim of the study was to evaluate the morphological characteristics of stent restenosis by optical coherence tomography (OCT). Methods: Patients (n=24, 25 vessels) presenting with angiographically documented stent restenosis were included. Quantitative OCT analysis consisted of lumen and stent area measurement and calculation of restenotic tissue area and burden. Qualitative restenotic tissue analysis included assessment of tissue structure, backscattering and symmetry, visible microvessels, lumen shape and presence of intraluminal material. Results: By angiography, restenosis was classified as diffuse, focal and at the margins in 9, 11 and 5 vessels respectively. By OCT, restenotic tissue structure was layered in 52%, homogeneous in 28% and heterogeneous in 20%. The predominant backscatter was high in 72%. Microvessels were visible in 12%. The lumen shape was irregular in 28% and there was intraluminal material in 20% of

163 Drug eluting stent restenosis: an emerging challenge / Populations at risk after myocardial infarction: gender, age and lifestyle 463 the cases. The mean restenotic tissue symmetry ratio was 0.58±0.19. Heterogeneous and low scattering restenotic tissue was more frequent in focal (45.5 and 54.5% respectively) than in diffuse (0 and 11.1%) and margin restenosis (0 and 0%) (p=0.005 for heterogeneous, p=0.03 for low scattering). Restenosis patients with unstable angina symptoms presented more frequently irregular lumen shape (60 vs 6.7% p=0.007). Vessels with <12 months follow-up had more frequently layered appearance (84.6% vs 16.7% p=0.003). Conclusions: we demonstrate the ability of OCT to identify differential patterns of restenotic tissue after stenting. This information could help in understanding the mechanism of stent restenosis Recurrent restenosis after drug-eluting-stents implantation in a cohort of 5595 lesions J. Mehilli, A. Kastrati, S. Schulz, R.A. Byrne, O. Bruskina, K. Tiroch, A. Birkmeier, J. Pache, J. Dirschinger, A. Schomig. Deutsches Herzzentrum, Munich, Germany The widespread adoption of drug-eluting stent (DES) therapy across complex lesion and patient subsets has led to significant numbers of patients presenting with DES treatment failure. The incidence of recurrent restenosis after DES is not known and its management remains a challenge. Methods: Between August 2002 and December 2006, a total of 5595 lesions were treated with either sirolimus-eluting stent (Cypher) or paclitaxel-eluting stents (Taxus) in two German centres. The primary endpoint of this analysis was the incidence of recurrent clinical restenosis [repeat target lesion revascularization (TLR)]. Secondary endpoint was the incidence of repeat TLR according to the strategy of in-des-restenosis treatment. Results: Of 399 lesions requiring initial TLR, 156 underwent PTCA and 243 were treated with repeat DES implantation. Seventy-four of these lesions required a second TLR (35 treated with PTCA; 39 with DES). A third TLR was needed in 29 lesions (15 treated with PTCA; 14 with DES), Figure. Ultimately, 12 lesions were identified which were treated with a strategy of 2 sequential PTCA interventions 7 (58%) lesions required an additional intervention. Against this, 22 lesions had been treated with 2 sequential repeat DES implantations (with a total of 3 DES layers) of these 8 (36%) required an additional intervention. Conclusions: Rates of recurrent restenosis after repeat intervention for DES treatment failure remain significant. In lesions requiring at least 2 re-interventions, although plain PCTA remains a valid option, there is no reason to avoid use of DES in this setting Nonuniform stent strut distribution is not associated with angiographic restenosis or long-term clinical outcomes either in TAXUS or in bare metal stents. Integrated TAXUS IV, V and VI analysis R. Pracon 1, M.P. Opolski 1,G.S.Mintz 2, N.J. Weissman 1, L. Mandinov 3, J. Pregowski 4,M.Kruk 4, H. Wang 3,K.D.Dawkins 2,G.W.Stone 2 on behalf of TAXUS IV, V and VI Investigators. 1 Washington Hospital Center/Medstar Research Institute, Washington, United States of America; 2 Cardiovascular Research Foundation, New York, United States of America; 3 Boston Scientific Corporation, Natick, United States of America; 4 Institute of Cardiology, Warsaw, Poland Objectives: Nonuniform strut distribution (NUSD) has been reported to lead to increased neointimal hyperplasia (NIH) in sirolimus-eluting stents; however, there has been no large-scale, detailed intravascular ultrasound (IVUS) analysis to examine this potential relationship in TAXUS and bare metal stents (BMS). Methods: In 445 patients with volumetric IVUS from TAXUS IV, V and VI trials, the largest interstrut angles were measured every 1mm throughout the stented area at 9 months after implantation. Standard IVUS measurements of stent, lumen, and NIH were performed. Results: At follow-up TAXUS Express stents (n=225) compared to conventional bare metal Express stents (n=220) had larger mean interstrut angle (51.4±9.7 vs. 47.4±9.0, p<0.0001), larger per stent maximal interstrut angle (91.4±23.9 vs. 84.3±22.9, p=0.0015) and larger lumen area (6.6±2.4mm 2 vs. 5.4±2.2mm 2, p<0.0001). Receiver-operating characteristic (ROC) analyses showed that IVUS restenosis - defined as NIH >50% - was predicted by the per stent maximal interstrut angle in TAXUS (c=0.75), but not in BMS (c=0.51). Because the maximal interstrut angle of 81 best predicted IVUS restenosis in TAXUS stents, this cutoff value was used to define NUSD. In the overall stent population the risk of NUSD was increased in patients with longer lesions (p<0.0001), TAXUS stents (p=0.0014) and angulated vessels (p=0.0299). In the TAXUS subgroup NUSD was increased in longer lesions (p=0.0315), angulated vessels (p=0.0224), larger vessels (p=0.0331) and patients with prior PCI (p=0.0076), whereas lesion length (p<0.0001) was the only independent predictor of NUSD in the BMS subgroup. However, NUSD did not lead to increased rates of angiographic restenosis, target lesion revascularization or multiple adverse cardiac events during 3 to 5 years follow-up in either TAXUS or BMS group. Conclusions: NUSD predicts increased in-stent NIH in TAXUS, but not in BMS. Nevertheless, it does not translate into increased angiographic restenosis or longterm clinical outcomes either in TAXUS or BMS Quantitative coronary angiography (QCA) matched comparison between randomized multicentre cutting balloon angioplasty (CBA) with BMS (REDUCE III) and rapamycin-eluting stent evaluation Rotterdam study Y. Ozaki 1, P.A. Lemos 2, T. Yamaguchi 3, T. Suzuki 4, M. Nakamura 5, T.F. Ismail 6,M.Kitayama 7,H.Nishikawa 8,O.Kato 4,P.W.Serruys 9. 1 Fujita Health University Hospital, Toyoake, Japan; 2 Heart Institute, University of Sao Paulo Medical School, Sao Paulo, Brazil; 3 Toranonon Hospital, Tokyo, Japan; 4 Toyohashi Heart Center, Toyohashi, Japan; 5 Toho University Medical Center Ohashi Hospital, Tokyo, Japan; 6 Northwick Park Hospital, London, United Kingdom; 7 Kanazawa Medical University Hospital, Kanazawa, Japan; 8 Mie Heart Center, Meiwa, Japan; 9 Thoraxcenter, Erasmus Medical Center, Rotterdam, Netherlands Background: While bare metal stents (BMS) have been used safely for over two decades, there remains significant concern about the long-term safety of drugeluting stents (DES) including late and very late stent thrombosis. There is therefore a pressing need to explore alternative strategies for reducing restenosis with BMS. Methods: In the randomized REstenosis reduction by Cutting balloon angioplasty Evaluation (REDUCE III) study, 521 patients were divided into 4 groups based on device and IVUS use before BMS (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At followup the IVUS-CBA-BMS group had a significantly lower restenosis rate (6.6%) than the other groups (p=0.016). We performed a quantitative coronary angiography (QCA)-based matched comparison between an IVUS-guided CBA-BMS strategy (REDUCEIII) and a DES strategy (Rapamycin-Eluting-Stent Evaluation At Rotterdam Cardiology Hospital; RESEARCH). We matched the presence of diabetes, lesion location, vessel size, and lesion severity by QCA. Results: QCA-matched comparison resulted in 120-paired lesions from IVUS guided BMS following CBA (REDUCE III) and DES (RESEARCH). QCA matched procedures produced similar baseline reference vessel diameter (RD pre; IVUS guided BMS & CBA: 2.82±0.45mm vs. DES: 2.81±0.47mm, p=ns) and identical minimal lumen diameter (MLD pre; IVUS guided BMS & CBA: 1.06±0.31mm vs. DES: 1.06±0.33mm, p=ns) between the two. While acute gain was significantly greater in IVUS-CBA-BMS than DES ( mm vs mm, p=0.001), late loss was significantly less with DES than with IVUS-CBA-BMS ( mm vs mm, p=0.001). However, no difference was found in binary restenosis rate (IVUS-CBA-BMS; 6.7% vs. DES: 5.0%, p=0.582) and target lesion revascularization (TLR) rates (6.7% vs. 6.7% respectively, p=1.000). Conclusions: While IVUS-guided CBA-BMS strategy yielded restenosis rates similar to those achieved by DES, this strategy provided an effective alternative to the use of DES. POSTER SESSION 4 MODERATED POSTERS 1 POPULATIONS AT RISK AFTER MYOCARDIAL INFARCTION: GENDER, AGE AND LIFESTYLE P2935 Risk profile, quality of care and mortality and in women with acute myocardial infarction F. Schiele, R. Chopard, J. Dutheil, V. Descotes-Genon, N. Meneveau, M.F. Seronde, J.P. Bassand. University hospital, Besancon, France Rationale: In acute myocardial infarction (STEMI and NSTEMI), women are at higher risk for death. The reasons for this disparity remain unclear.

164 464 Populations at risk after myocardial infarction: gender, age and lifestyle We compared the risk profile and quality of care between men and women and they respective impact on 30 day mortality. Methods: Multicentre prospective registry including all consecutive patients admitted in the Franche Comte area (10 centres, 1.2 million inhabitants). Quality Indicators (QI) been defined for STEMI and NSTEMI: Unless indicated contra indication, in hospital use of aspirin, Clopidogrel, betablockers, ACEI (if LVEF<0.4), reperfusion by PCI or thrombolysis, discharge with aspirin, Clopidogrel betablocker, ACEI and statins. The risk profile, rate of use of QI and motality have been compared. Multivariate analysis was used to assess the independent impact of gender on mortality. Results: Among 2874 patients included in the study (1282 STEMI and 1592 NSTEMI), 1948 (68%) were males and 926 (32%) females. Women were at higher risk: older age, more diabetes, renal dysfunction, unstable hemodynamic at admission. The rate of use of most of QI was significantly lower in women. At 30 day, mortality rate was 12.6% in women and 7.0% in men (p<0.001). Multivariate analysis showed that the effect of gender was suppressed when age and comorbidities were included and similarly, the effect of gender was offset by adjustment on QI. The independent predictors of mortality were age, heart rate, systolic blood pressure, serum creatinin, previous infarction, use of ACEI, of beta-blockers and coronary angiography during index hospitalisation. When adjusted on risk level at admission and quality of care, gender was not an independent predictor of mortality. Conclusions: In acute MI, a 80% higher 30 day mortality was observed in women, explained by older age, higher com morbidity rate and worse hemodynamic conditions, but also by lower rate of QI. Whether higher use of QI in women is possible, safe and beneficial remain to be demonstrated. P2936 Female gender in STEMI: influence on mortality and reperfusion, results from the belgian STEMI registry S. Gevaert 1,A.DeMeester 2, M. Renard 3,P.Evrard 4, C. Beauloye 5, P. Coussement 6, P.H. Dubois 7, H. De Raedt 8,M.Claeys 9 on behalf of BIWAC. 1 Ghent University Hospital, Gent, Belgium; 2 Hopital de Jolimont, Jolimont, Belgium; 3 Hopital Erasme, Bruxelles, Belgium; 4 Université catholique de Louvain, Mont Godinne, Belgium; 5 Université catholique de Louvain, Bruxelles, Belgium; 6 AZ Sint Jan, Brugge, Belgium; 7 CHU de Charleroi, Charleroi, Belgium; 8 Cardiovascular Center OLV Hospital, Aalst, Belgium; 9 UZ Antwerpen, Antwerpen, Belgium Introduction: Prior studies have demonstrated higher mortality rates among women with ST-elevation myocardial infarction (STEMI). Potential confounding comprised age, hypertension (HT) and diabetes mellitus (DM). Purpose: Our aim was to determine whether female gender 1. is an independent predictor of in-hospital mortality in a prospective cohort of Belgian STEMI patients 2. influences the choice of reperfusion strategy 3. influences the outcome of thrombolysis (TL) versus (vs) primary PCI (PPCI). Methods: The Belgian STEMI registry is a prospective registry ( ) from unselected STEMI patients in 82 hospitals Results: 3872 (25.5% female and 74.5% male) patients were included. Women were older (69y vs 61y, p<0.001) had more DM (20% vs 15%, p<0.001), HT (57% vs 41%, p<0.001) and more frequently a body weight < 67 kg (44% vs 10%, p<0.001). They had less previous coronary artery disease (CAD) (17% vs 21%, p=0.02). They had a higher Killip Class (KC) (Killip>I: 30.6% vs 22.3%, p<0,001) and TIMI risk score at admission (5.6 vs 3.8, p<0.001). Women had a higher in-hospital mortality compared to men (11% vs 5%, p<0.001). In a logistic regression model including age, HT, DM, previous CAD, KC, weight<67, ischemic time>4h, CPR, infarct site, BP<100mmHg, HR>100/min and reperfusion (Y/N) there is a trend towards higher mortality for women (p=0.08). There was also a trend towards less use of reperfusion therapy in women (p=0.086). In a subgroup analysis according to reperfusion strategy women received less PPCI even after adjustment for appropriate covariates (p=0.016). The use of TL in women and men was the same. The Odds Ratio (OR) for mortality in women is larger in the TL (13 vs 5%, OR=2.6) as compared to the PPCI group (9 vs 4.5%, OR=2). Conclusions: Women with STEMI are older, more severely ill and have higher in-hospital mortality rates. After adjustment for appropriate covariates there is still a trend towards higher mortality and less use of reperfusion therapy in women. Primary PCI is significantly less used in women, despite the mortality benefit this technique may offer in this high risk population. P2937 Worldwide gender bias in angiographic obstructive acute coronary syndromes? O. Manfrini 1, J.L. Navarro Estrada 2,K.Nikus 3,A.S.Hall 4, R. Bugiardini 1. 1 University of Bologna, Bologna, Italy; 2 Italian Hospital of Buenos Aires, Buenos Aires, Argentina; 3 Pirkanmaa Hospital District, Tampere, Finland; 4 University of Leeds, Leeds, United Kingdom Background: Evaluating the number of medical or interventional treatments of a registry cohort allows the inclusion of women without obstructive CAD, potentially confounding the results toward an apparent sex bias against women. The aim of this study was to ascertain whether effective evidence based treatments for acute coronary syndromes (ACS) are underutilized among women with documented coronary disease in various geographic areas compared with men. Methods: We collected data from 3 registries: the Finnish TACOS (Tampere Acute COronary Syndrome), the British EMMACE 2 (Evaluation of Methods and Management of Acute Coronary Events), and the Argentine PACS-ITALSIA (Prognosis in Acute Coronary Syndromes and the ITALian hospital Sindrome Isquemico Agudo). The gold standard test to which effective discharge treatments were compared was required to be angiographic evidence of obstructive coronary disease (more than 50% lumen diameter stenosis). Results: The Finnish TACOS, the British EMMACE 2, and the Argentine PACS- ITALSIA enrolled 419, 1252, and 945 patients with ACS and at least 1 obstructive coronary lesion, respectively. We found substantial geographic variations. In Finland, there were no significant differences between men and women regarding discharge medications. Conversely, in the United Kingdom (UK) and Argentina men received more evidence-based therapy than did women. Women were remarkably less likely to receive aspirin (UK OR 0.50; CI 0.41 to 0.60; p<0.01 Argentina OR 0.50; CI 0.41 to 0.60; p<0.01), beta-blockers (UK OR 0.39; CI 0.33 to 0.47; p<0.01 Argentina OR 0.39; CI 0.33 to 0.47; p<0.01) and statins (UK OR 0.65; CI 0.54 to 0.77; p<0.01 Argentina OR 0.39; CI 0.33 to 0.47; p<0.01) at discharge. In UK, coronary revascularization tended to be done less frequently in women (OR 0.39; CI 0.33 to 0.47; p<0.01). Conclusions: Our study indicates the existence of large gender differences in ACS treatment even in patients with documented significant coronary disease. Substantial geographic variation exists. There is an urgent need to analyze disparities across population subgroups and between different countries. P2938 Primary percutaneous coronary intervention for ST elevation myocardial infarction in octogenarians; trends and outcomes from a nine-year single center experience B.E.P.M. Claessen, A.E. Engstrom, W.J. Kikkert, M.M. Vis, J. Baan, M.M. Meuwissen, R.J. De Winter, J.G.P. Tijssen, J.J. Piek, J.P.S. Henriques. Academic Medical Center, Amsterdam, Netherlands Purpose: The general population is gradually aging in the Western world. As a result, the number of octogenarians undergoing primary Percutaneous Coronary Intervention (PCI) for ST-Elevation Myocardial Infarction (STEMI) is increasing. Currently, little is known about the clinical characteristics and clinical outcome of octogenarians after primary PCI for STEMI. Methods: Between 1997 and 2005, we treated 3277 STEMI patients with primary PCI. Patients aged >80 years were indentified. We analyzed trends in baseline characteristics (sex, smoking, history of previous myocardial infarction, diabetes mellitus, cardiogenic shock), 30-days and one-year mortality. Annual trends were analyzed using the Chi Square statistic. Results: A total of 259 octogenarians (7.9% of the total population) were treated with primary PCI between 1997 and Of these patients 46% were males, 12% were smokers, 23% had a history of previous myocardial infarction, 17% were diabetic and 15% presented in cardiogenic shock. Over time, the proportion of octogenarians gradually increased from 4/113 (3.5%) in 1997 to 71/638 (11%) in 2005 (p for trend <0.01). There were no changes in aforementioned baseline characteristics in this population during our nine-year STEMI experience. In the total cohort of 259 patients, 30-day mortality was 21% (54 patients), one-year mortality was 27% (69 patients). Mortality rates were consistent during our nineyear STEMI experience. Nine-year trend in the proportion of octogenarians in the STEMI popukation Conclusion: Octogenarians constitute an increasingly important subgroup of STEMI patients. Mortality among these high-risk patients was high and did not improve during our nine-year STEMI experience. Further studies are needed to define the optimal STEMI management strategy for the elderly. P2939 Predictors of mortality in octogenarian patients with acute myocardial infarction A.T. Timoteo, R. Ramos, A. Toste, A. Lousinha, J.A. Oliveira, M.L. Ferreira, R.C. Ferreira. Hospital Santa Marta, Lisbon, Portugal Introduction: The octogenarian population admitted for an acute myocardial infarction is increasing in the last years, with significant mortality. Objectives: To evaluate the peculiarities of this population and the determinants of short- and medium-term mortality.

165 Populations at risk after myocardial infarction: gender, age and lifestyle / New challenges in exercise training 465 Methods: We included all patients admitted in our Intensive Care Unit for an acute myocardial infarction with an age 80 years, from January 2005 to December Data was collected from an internal registry of acute coronary syndromes, as well as data for in-hospital, 30-day and one-year mortality. We evaluated the predictors of mortality. Results: We included 143 patients, 42% males, with a mean age of 83±3 years. In this population, 83% had hypertension, 3% smokers, 39% with known hyperlipidemia, 31% diabetics, 12% with a previous stroke, 23% with previous myocardial infarction, 3% with previous coronary angioplasty and 6% with previous coronary artery bypass grafting. On admission, 54% had ST-segment elevation and 25% had signs of heart failure, with a mean GRACE score of 189±32. Coronary angioplasty was performed in 52% of the patients, and 87% received ACEI, 69% beta-blocker and 87% statins. In 15%, there was severe left ventricular dysfunction (ejection fraction <35%). In-hospital mortality was 20%, at 30-days 26% and 31% at the first year. In multivariate analysis, the only independent predictor for inhospital mortality is creatinine clearance (OR 0.94, 95% CI , p=0.01). Independent predictors of 30-day death were creatinine clearance (OR 0.94, 95% CI , p=0.003) and left ventricular dysfunction (OR 4.26, 95% CI , p=0.015). Independent predictors of one-year mortality were creatinine clearance (OR 0.96, 95% CI , p=0.02), left ventricular dysfunction (OR 3.11, 95% CI , p=0.05) and the use of statins (OR 0.20, 95% CI , p=0.01). Conclusions: The present population of octogenarian patients is a population with worst previous cardiovascular history, with more severe presentation forms. However, treatment is in accordance with international recommendations, which might have influenced the fact that the main determinants of prognosis in shortand medium-term are mainly related with renal function and left ventricular systolic function. P2941 Impact of obesity in the results after primary angioplasty in patients with ST-segment elevation acute myocardial infarction A.T. Timoteo, R. Ramos, A. Toste, J.A. Oliveira, L. Patricio, L. Patricio, R.C. Ferreira. Hospital Santa Marta, Lisbon, Portugal Introduction: Obesity is an important risk factor for the development of diabetes, hypertension, coronary disease, left ventricular dysfunction, stroke and cardiac arrhythmias. Paradoxically, previous studies in patients submitted to elective coronary angioplasty showed a reduction in hospital and long-term mortality in obese patients. In the context of primary angioplasty, the relation with Body Mass Index (BMI) is less well certain. Objectives: To evaluate the impact of obesity in the results of ST-segment elevation acute myocardial infarction treatment by primary angioplasty Methods: Study of 464 consecutive patients with ST-segment elevation acute myocardial infarction submitted to primary angioplasty, 78% males, and mean age of 61±13 years. We evaluated the occurrence of in-hospital, 30-day and one-year mortality according to BMI. Patients were characterized in 3 groups according to BMI: Normal, kg/m 2 (n=171); Overweight, kg/m 2 (n=204) and Obese, > 30 kg/m 2 (n=89). Results: Obese patients were younger (ANOVA, p<0.001) and more frequently males (p=0.014), with more hypertension (p=0.001) and hyperlipidemia (p=0.006). There were no differences in terms of the prevalence of diabetes, previous cardiac history, heart failure on admission, anterior location, multivessel disease, peak values of total CK or medication provided, except for the fact that obese patients received more beta-blockers (p=0.049).in-hospital mortality was 9.9% for patients with normal BMI, 3.4% for overweight patients and 6.7% for obese patients (p=0.038). Mortality at 30 days was 11.7%, 4.4% and 7.8% (p=0.032) and at first year 12.9%, 4.9% and 9% (p=0.023), respectively. In multivariate logistic regression analysis, adjusted for confounding variables, overweight is the only BMI class with a trend for better in-hospital prognosis (OR 0.25, 95% CI , p=0.059) and at first year (OR 0.33, 95% CI , p=0.06). Conclusions: Overweight patients are the only BMI class with better prognosis after primary angioplasty for ST-segment elevation acute myocardial infarction. Normal BMI and obese patients had worst prognosis. P2942 Lower rate of invasive revascularisation after coronary angiography, following acute coronary syndrome, the longer distance you live from an invasive centres A. Hvelplund 1, S. Galatius 2, M. Madsen 3, J.N. Rasmussen 1, S. Rasmussen 1, J.K. Madsen 2,S.Z.Abildstrom 4 on behalf of The DANAMICS group. 1 National Institute of Public Health, Copenhagen, Denmark; 2 Gentofte Hospital, Hellerup, Denmark; 3 University of Copenhagen - Institute of Public Health, Copenhagen, Denmark; 4 Glostrup University Hospital, Glostrup, Denmark Purpose: We studied the population of all acute coronary syndrome (ACS) patients examined with coronary angiography (CAG) in order to evaluate differences in invasive revascularisation rate. Denmark (population 5.5 million) has a universal health insurance coverage system and uniform national guidelines for the treatment of ACS. There are 5 tertiary invasive centres performing CAG, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), 8 hospitals with diagnostic units performing CAG only, and a further 36 hospitals without these facilities receiving patients with ACS. We investigated if there was a difference in revascularisation after CAG following admission with ACS, depending on distance between place of residence and invasive centre. Methods: All patients hospitalised with a first ACS from January 2005 to December 2007 were identified in the National Patient Register. We included those examined with CAG in the analysis. Information on distance from the patient s home to nearest invasive centre was obtained from Statistics Denmark along with information on education, personal income, previous medicine use and vital status. Patients were grouped in tertiles according to distance to centre. From the Danish Heart Registry procedures (CAG, PCI and CABG) were identified along with information on the result of CAG. A Cox proportional-hazard models with revascularisation as outcome was used to estimate the difference related to distance within 60 days of the admission. Result: Of patients with first ACS, 33% lived less than 21 km from one of the 5 invasive centres, 33% lived between km and 33% >64 km away. Revascularisation was performed in (73%) of the patients examined with a CAG. Among those examined with a CAG, the cumulative incidence of revascularisation was 79% for the third living closest to a centre vs. 74% for those living farthest away. When adjusting for variables like gender, age, vessel disease and the others mentioned above, there was a hazard ratio (HR) of 0.80 (95% CI , p < ) of receiving revascularisation for the patients living farthest away compared to those living closest. CAG was performed at a tertiary centre in 68% among those living farthest away vs. 90% among those living closest to a centre. Conclusion: Despite uniform national guidelines, patients who receive CAG following ACS are treated with a less aggressive invasive approach the farther away they live from an invasive centre. This difference could be due to differences in the treatment strategy between invasive centres and hospitals with only diagnostic units. MODERATED POSTERS 2 NEW CHALLENGES IN EXERCISE TRAINING P2944 diastolic dysfunction in chronic systolic heart failure and aging - effects of endurance training M. Sandri, S. Gielen, N. Mangner, R. Hoellriegel, S. Erbs, A. Linke, S. Moebius-Winkler, V. Adams, R. Hambrecht, G. Schuler. Herzzentrum der Universitaet Leipzig, Leipzig, Germany Background: Diastolic left ventricular dysfunction may occur in both physiologic aging and chronic systolic heart failure (CHF). It has, however, never been assessed, whether the degree of diastolic impairment in CHF patients is influenced by their age and if the previously observed beneficial effects of endurance exercise on left ventricular filling are diminished in old age. Methods: In this study we randomised 59 pts. with stable CHF (age 60.5±2.7 years, EF 27.6±1.4%, VO2max 14.9±4.6ml/kg*min) and 57 healthy subjects (HS) (age 60.3±2.8 years, EF 62±0.5%, VO2max 20.5±3.3 ml/kg*min) to a training (T) or a control group (C). To detect possible aging effects we included subjects below 55 (young) and above 65 years (old). Subjects in the T-group exercised 4 times daily at 60 to 70% of VO2max for 4 weeks under supervision. At baseline and after the intervention E/A ratio and lateral E/E ratio were determined by echocardiography with tissue Doppler. Results: As compared to young HS, old HS showed at baseline a reduced E/A ratio and an increased E/È ratio (young: E/A 1.1±0.2; E/È 7.5±0.1 old: E/A 0.7±0.1; E/È 13.4±0.3; p<0.05). In CHF patients, diastolic function was impaired (young E/A 0.7±0.2; E/È 12.9±0.5 old: E/A 0.6±0.1; E/È 13.8±0.4). No difference of these baseline parameters between the age groups was observed (p=0.79). As a result of ET, E/A ratio improved from 0.7±0.1 to 1.3±0.2 and E/È ratio improved from 13.5±0.3 to 9.2±0.4 inoldhs(p<0.05), while it remained unchanged in young training HS and C respectively. In young and old patients with CHF four weeks of ET resulted in a significant change in E/A ratio (young: from 0.8±0.1 to 1.1±0.1; p<0.05; old: from 0.7±0.1 to1.0±0.2 p<0.05) and E/È ratio (young: from 13.2±0.3 to 10.4±0.2; p<0,05; old: from 14.1±0.3 to 11.3±0.2; p<0.05). In C no effect was detectable. Conclusions: The present trial provides new insight into the chronobiology of cardiovascular training effects: Among HS aging is associated with the development of significant left ventricular diastolic dysfunction. In CHF both young and old patients exhibit a similar degree of LV-dysfunction. Four weeks of ET are effective in improving diastolic function in old HS and in all age groups of CHF patients. The lusitropic training effects were not significantly diminished among older patients underlining the potentials of rehabilitation interventions in this patient group.

166 466 New challenges in exercise training P2945 Aerobic interval training versus strength training as a treatment for the metabolic syndrome D. Stensvold, E.A. Skaug, U. Wisloeff, S.A. Sloerdahl. Norwegian University of Science and Technology, Trondheim, Norway Background: Physical inactivity and overweight is strongly associated with an increased risk for developing metabolic syndrome. The syndrome is characterized by a cluster of risk factors for cardiovascular disease and mortality such as increased blood pressure, impaired glycemic control, excess of abdominal fat and dyslipidemia. Regular physical activity and increased fitness can improve several metabolic factors and reduce the risk of developing cardiovascular diseases, however the optimal training regime to treat metabolic syndrome and its associated cardiovascular abnormalities remain undefined. Methods: Forty subjects were randomized and stratified by gender and age to either aerobic interval training (AIT, n=11), strength training (ST, n=10), combination of aerobic interval training and strength training (COM, n=9), or a control group (n=10). Training was performed 3 times per week for 12 weeks, and risk factors comprising the metabolic syndrome were measured before and after the intervention in all four groups. Results: AIT significantly increase VO2peak (from 146.2±34.2 to 156.5±36.9 ml/lbm-075/min -1 ) whereas ST, COM and the control group increased maximal strength (45%, 46% and 12%, respectively). AIT significantly reduced triglyceride levels (from 2.27±0.97 to 1.83±0.76 mmol/l) systolic blood pressure (from 140± ±12 mmhg) and diastolic blood pressure (from 89±8.1 to 85±5.5 mmhg). Only ST reduced waist circumference significantly (from 111.5±10.8 to 110±11 cm). Endothelial function measured as flow mediated dilution (FMD) was significantly improved in all three training groups (24%, 26% and 36% for AIT, ST and COM group, respectively). There was no change in weight, fasting plasma glucose, high density lipo-protein or insulin C-peptid in either group. Conclusion: Although all three training regimes improved abnormalities associated with the metabolic syndrome, AIT for 12 weeks was superior to both strength training and a combination of interval and strength training for improving risk factors defining metabolic syndrome. Three out of the six risk factors identifying the metabolic syndrome were significantly improved after 12 weeks of aerobic interval training. P2946 Metabolically guided exercise training in patients with diabetes mellitus type 2 and coronary heart disease is able to control postprandial hyperglycemia B. Schwaab 1,F.Kafsack 2, E. Markmann 2,N.Zwick 2, M. Schuett 3. 1 Kardiologische Klinik Höhenried, Bernried, Germany; 2 Curschmann Klinik, Timmendorfer Strand, Germany; 3 Medizinische Klinik I, Lübeck, Germany Background: It is generally well accepted that exercise training of moderate intensity is favourable to reduce blood glucose in patients with diabetes mellitus type 2 (DMT2). From the patients view, however, this recommendation is imprecise and not concrete. We investigated, whether it is possible to identify the individual aerobic exercise intensity for optimal glucose control in patients with DMT2 and coronary heart disease (CHD) by cardiopulmonary exercise testing (CPX). Methods: Patients with CHD were included, if the oral glucose tolerance test exhibited a 2-h value 200 mg/dl (OGTT-1). Using an incremental ramp protocol, a symptom limited CPX was performed on a bicycle ergometer until a respiratory exchange ratio (RER) 1,20 (CPX-1). One day later, a steady-state CPX of 30 min duration was performed targeting a RER of just below the anaerobic threshold, representing an aerobic exercise training (CPX-2). Immediately after CPX-2, patients had OGTT-2 simulating a postprandial glucose challenge. Results: Out of 15 consecutive patients, 5 discontinued CPX-1 prematurely due to dyspnea, angina or muscular fatigue. 10 patients (mean age 61±12 years, range years; mean BMI 28,3±2,8 kg/m 2, range 24,5-32,2 kg/m 2 ; mean HbA1c 5,9±0,6%, range 5,0-6,7%; mean left ventricular ejection fraction 50±13%, range 35-65%) exercised until RER 1,20 reaching a maximum exercise intensity of 99±32 Watt (range Watt) and a peak VO2 of 15,9±3,0 ml/min/kg (range 10,6-19,6 ml/min/kg). In CPX-2, aerobic exercise intensity averaged at 29±10 Watt (range Watt) representing 29% (range 10-44%) of maximum intensity and 61% of peak VO2 (range 44-76%). Compared to OGTT- 1, the 2-h value was significantly reduced by the metabolically guided aerobic exercise training in OGTT-2 (227±40 vs. 169±42 mg/dl; p<0.05). Conclusions: Aerobic exercise intensity for effective postprandial glucose control is rather low in patients with DMT2 and CHD. A precise and concrete recommendation for exercise prescription can be given individually by CPX in this cohort of patients. The dose of training therapy should also be prescribed individually and specifically as it is yet the case with pharmacotherapy. P2947 Benefits of chronic exercise training on aerobic capacity and NT-proBNP plasma levels in patients with Ventricular Assist Devices I.D. Laoutaris, A. Dritsas, S. Adamopoulos, A. Manginas, A. Gouziouta, M. Koulopoulou, P. Sfirakis, V. Voudris, D.V. Cokkinos, P.A. Alivizatos. Onassis Cardiac Surgery Center, Athens, Greece Purpose: Patients supported with ventricular assist devices are increasing and tend to stay longer on mechanical support. Studies show a maximal benefit on aerobic capacity 12 weeks post-implantation. The effects of chronic physical training long-term post-implantation in this population are unknown. Methods: Twelve patients, age 33.6±14 yrs, implanted with Left Ventricular Assist Device (LVAD) or BiVentricular Assist Device (BiVAD) (BerlinHeart) as a bridge to heart transplantation were randomly assigned, at a ratio 2/1, in a training group (TG) (n=8/lvad=4, BiVAD=4) or a control group (CG) (n=4/lvad=2, BiVAD=2), 6.2±4.1 months post-implantation. Training involved 10- week home aerobic exercise using a stationary bike for 45 min, at an intensity of Borg scale, 3-5/week as well as advice for everyday walk for min. In parallel with aerobic training, patients underwent high-intensity inspiratory muscle training (IMT) using a computer-designed software (TRAINAIR) at 60% of sustained maximal inspiratory pressure (SPimax) to respiratory exhaustion, 2-3/week inhospital. In contrast, patients in the CG were only advised for everyday walk for minutes. Both groups were evaluated for exercise capacity using cardiopulmonary exercise testing and the 6-min walk test (6MWT). Pulmonary function was tested by spirometry while dyspnea was assessed using the Borg scale at the end of the 6MWT. Plasma NT-proBNP levels were also measured. Results: TG improved inspiratory muscle strength (Pimax, 144±21.6 vs ±21.6 cmh2o, p=0.01), endurance (SPimax, 530±384 vs. 384±190 cmh2o/s/1000) and inspiratory lung capacity (2.5±0.9 vs. 1.8±0.8 L, p=0.01). Peak oxygen consumption improved (20.3±4.6 vs. 17.9±3.2 ml/kg/min p=0.03) and the ventilatory equivalent VE/VCO2 dropped (35.1±5.4 vs. 39.3±6.4, p=0.02). The 6MWT distance increased (553.7±54 vs ±52 m, p=0.01) while the Borg level of dyspnea did not change significantly. Plasma NT-proBNP levels decreased significantly post-training (995.6±477 vs. 1293±477 pg/ml, p=0.03). No significant changes in pulmonary function, exercise capacity, dyspnea or NT-proBNP levels were noted in the CG. Conclusions: A combined chronic aerobic exercise/inspiratory muscle training program resulted in improvement in pulmonary function and aerobic capacity in patients with VADs while plasma NT-proBNP levels, an index of heart failure severity, were significantly reduced with training. Our findings indicate the benefits of exercise training even long-term after device implantation and may have additional importance in cases of destination therapy. P2948 Cardiopulmonary test as a mesure of rehabilitation in a patient supported by a Cardiowest total artificial heart (TAH) F. Bellotto 1, P. Agostoni 2, L. Compostella 3,G.Torregrossa 1, T. Setzu 3, A. Gambino 1, A. Maddalozzo 3,G.Feltrin 1, G. Gerosa 1. 1 Dept. of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy; 2 Centro Cardiologico Monzino, Milan, Italy; 3 Istituto Codivilla-Putti, Cortina D ampezzo (Bl), Italy Introduction: The Cardiowest-TAH is a biventricular orthotopic pneumatic pulsatile pump that totally replaces the native ventricles and valves and is actually approved as a bridge to heart transplantation in selected patients. This paper reports our experience of the effect of one-year exercise-based training in a patient with a Cardiowest-TAH, evaluated by cardiopulmonary exercise test (CPET). Methods: After recovery from an emergency TAH implantation in November 2007, a 54 y.o. male was transferred to an intensive Cardiac Rehabilitation Unit and submitted to 4 weeks of exercise-based training and physiotherapy. At the end of the intensive rehabilitation period, a CPET (increasing workload of 10 W/min) was performed and the following parameters were considered: exercise duration and peak workload, VO2 max and VCO2 max, peak exercise ventilation and VE/VCO2 slope, VO2/Work relationship, and peak exercise cardiac output (C.O.). The test was repeated after 11 months of home-based regular physical training. Results: From the 1st to the 2nd CPET, exercise duration and peak workload increased (respectively from 10 20" to 14 36", and from 43 to 67 Watt); VO2 max and VCO2 max remained unchanged (respectively vs l/min, and vs l/min). Peak exercise ventilation was 40 l/min at the 1st test and 34 l/min at the 2nd test. Substantially unchanged remained the VE/VCO2 slope (27.60 vs 26.51) and the VO2/Work relationship (13.5 vs 11.5). The TAH provided a peak C.O. of 7.8 l/min in the 1st test and 8.5 lmin in th 2nd test. Haemoglobin (Hb) levels were constant at 10.1 vs 10.9 mg/dl. Conclusions: The present case is the first report of CPETs achieved in a subject with an artificial biventricular heart, to test the efficacy of one year exercise-based training program. Peak exercise capacity was greatly increased in terms of workload achieved, in spite of the unique physiological condition, where both right and left heart C.O. are fixed at rest with a similar and limited capacity to increase during exercise (similar peak exercise C.O. and VO2). Consequently peak exercise artero-venous O2 difference is also the same, as similar is the Hb concentration. So we are dealing with a workload increase with unchanged VO2, unchanged VO2 determinants (C.O. and artero-venous O2 difference) and similar anaerobic energy production (unchanged peak VCO2). Two explanations are possible: 1- a reduced VO2 in organs not directly involved with workload, as - for example - a reduction in respiratory muscle work; 2- a change of muscle fibers with training, in favour of most efficient muscle fibers.

167 New challenges in exercise training / The kidney and coronary artery disease 467 P2949 Four recommendations to maintain physical fitness of patients with chronic heart failure after cardiac rehabilitation: a prospective randomized study P.J.M. Beckers, N.M. Possemiers, K. Wuyts, C.J. Vrints, V.M. Conraads. University Hospital of Antwerp (Edegem), Edegem, Belgium Purpose: Rehabilitation of patients with Chronic Heart Failure (CHF) is now accepted as a valid adjunct treatment modality. However, maintaining the achieved physical performance after rehabilitation is a major challenge. This study was designed to compare the effects of different advices given at the end of a cardiac rehabilitation programme on maximal and sub-maximal exercise capacity, prognostic markers and biometrics in patients with CHF. Methods: 69 patients with stable CHF were trained for 6 months in a combined endurance-resistance training programme. At the end of the programme patients were randomly assigned either to Usual Treatment (UT) or either to UT combined with a controlled Home Training Programme (HT), or with a Self-managed Training (ST) or with a dedicated supervised Training (T). Cardio Pulmonary Exercise Testing (CPET) on treadmill, biometricsand Linear Isokinetic (LIK) measurements was assessed at baseline, at the end of rehabilitation and during 3 years at 3 monthly intervals. Results: At baseline and at 6 months of rehabilitation the four groups (UT, HT, ST, T) were comparable with regard to medication, risk-factors, aetiology, biometrics, cardiopulmonary parameters, Ejection Fraction and NYHA classification. During follow up over 3 years time Peak Oxygen Uptake (V02peak)(p=0.0435), Maximal Workload (Wmax) (p<0.0001) and Maximal strength of Lower Limbs (p=0.0484) decreased equally in all groups. When standardized for age, percentages of predicted V02peak and predicted Wmax did not change. Waist circumference (p<0.0001), Time to 1 VO2peak (p=0.0242) and VE/VO2 slope (p=0.0119) 2 both standardized for Wmax increased significantly, no matter which advice had been given. For interaction, repeated measures revealed a significant difference (p=0.0137) in workload at pulmonary compensation for lactic acid accumulation (WattVT2) in favour of the ST group. Conclusion: Evolution of maximal exercise capacity seems not to depend on the advice given at the end of a cardiac rehabilitation programme. However, patients stimulated in a self-managed training programme are more able to maintain their ability to perform at higher workloads before getting short of breath, which makes them much more comfortable to perform in daily life at sub-maximal activities. Compliance with the advice given stays a major confounder in the follow up of patients with CHF. P2950 Exercise training increases adiponectin levels in patients with stable coronary artery disease S. Moebius-Winkler 1,V.Adams 1, C. Walther 1,S.Erbs 1,A.Linke 1, M. Von Roeder 1, R. Hambrecht 2, G. Schuler 2. 1 Herzzentrum der Universitaet Leipzig, Leipzig, Germany; 2 Klinikum Links der Weser, Bremen, Germany Purpose: Adiponectin, synthesized by adipose tissue reduces blood glucose, reverses insulin resistance and is thought to have protective effects on the endothelium. Decreased circulating adiponectin level is associated with progression of coronary artery disease in patients with stable coronary artery disease. Also regular physical exercise training is able to reduce cardiovascular events. A slowering of coronary artery disease progression was observed in patients that undergo regular exercise training. Aim of study was to evaluate the change in circulating adiponectin in patients with stable CAD underwent a regular physical exercise program compared to those underwent interventional therapy with stent implantation. Method: In a subgroup of our PET-PILOT study adiponectin levels were measured from 96 patients with stable CAD at begin and after 24 months of therapy. After an initial coronary angiography with at least one significant coronary lesion patients were randomised either to a stent group or to an exercise training group. Patients of both groups received optimal medical treatment including beta-blocker, statins and ACE Inhibitors. Results: 53 patients were randomized in the training group, 43 patients were treated in the stent group. After 2 years of follow up circulating adiponectin levels had increased by %± 26.6 vs. begin, p= 0.02 in the training group (change in concentration) whereas the adiponectin level of the stent group remain unchanged (+ 1.1% ±12.8 vs. begin). No changes in weight were seen in both groups after 2 years of therapy. Conclusion: In patients with stable coronary artery disease, long term exercise training on top of an optimized medical therapy was able to increase circulating adiponectin level independently to weight changes, thereby contributing to a better outcome in patients with CAD after the training intervention. P2951 Sustained benefit after one year of regular physical exercise training on hemodynamics and exercise capacity in patients with end-stage chronic heart failure (NHYA IIIb) R. Hoellriegel 1,S.Erbs 1,A.Linke 1,E.Beck 1, M. Sandri 1, N. Mangner 1, S. Moebius-Winkler 1,V.Adams 1, R. Hambrecht 2, G. Schuler 1. 1 University of Leipzig-Heart Center, Leipzig, Germany; 2 Klinikum Links der Weser, Bremen, Germany In patients with stable, moderate chronic heart failure (CHF), exercise training (ET) enhances exercise capacity in the absence of harmful side effects. In contrast, the therapeutic benefits of regular ET in patients with end-stage heart disease (NYHA IIIb) over a long-term period are not established yet. Therefore, it was aim of the present trial to elucidate, whether long-term physical ET for a period of 12 months improves central hemodynamics and exercise capacity in patients with end-stage CHF. Methods: 37 pts with CHF (LVEF 24±2%, NYHA class IIIb) were randomized to 12 months of ET (30 min bicycle ergometer training daily at 50-60% of maximal work load) or sedentary lifestyle (C). At begin, after 3, 6 and 12 months patients were undergoing a spiroergometry and an echocardiography. Results: Patients of the training group had a continuous increase in left ventricular ejection fraction ( after 3 months +9.4±1.5%; after 6 months +15.5±2.0%; after 12 months +14.3±2.1%; p<0.05 for versus C). The positive effects on left ventricular performance were associated with a decline in end-diastolic diameter after 3, 6 and 12 months ( after 3 months -6.6±1.2mm; after 6 months -7.6±1.1mm; after 12 months -9.7±1.9mm; p<0.05 for versus C). In patients of the training group, exercise capacity measured by VO2 max increased by +16% after 3 months (from 15.3±0.8 to 17.8±0.8 ml/min/kg), by +24% after 6 months (to 18.8±0.8 ml/min/kg) and by +27% after 12 months (to 19.4±0.9 ml/min/kg; p<0.05 for 3, 6 and 12 months versus begin and C). These changes were associated with an improvement in clinical symptoms evident by a decline in at least 1 NYHA-class in all patients of the training group after 3, 6 and 12 months. All the above-mentioned parameters remained unchanged in patients of the control group. Number of clinical events (cardiac decompensation, hospitalization, life-threatening arrhythmias, instable angina, revascularization, cardiovascular and all cause mortality) did not differ between the two groups. Conclusion: In this trial, we are showing for the first time a sustained improvement of hemodynamics and exercise capacity by long-term exercise training in patients with endstage chronic heart failure (NYHA IIIb). These beneficial effects occurred in the absence of life-threatening arrhythmias or an increased number of cardiac decompensations in the training group. THE KIDNEY AND CORONARY ARTERY DISEASE P2953 Prevention of cardiovascular complication after renal transplantation E. Rossi, M.P. Salerno, E. Zichici, E. Favi, G. Spagnoletti, F. Citterio. Catholic University, Roma, Italy Background: Renal transplantation is today recognized as the best treatment available for chronic renal failure, but long term success of renal transplantation is hampered by cardiovascular morbidities and mortality, indeed the major cause of death in long term transplant recipients. The aims of this study in 359 white adults with a renal transplant functioning for at least 1 year (KTX), were: 1) to evaluate the incidence of cardiovascular events; 2) to identify current main CV risk factors; 3) to assess the predictive role of existing CV risk scores. Methods: Major Acute Clinical Events (MACE: angina, AMI, ictus cerebri, cardiac death), routine biochemistry and prescribed drugs at month 1, month 6, and then yearly after transplantation were prospectively analyzed in 369 adult renal transplant recipient who received a renal transplant between January 1997 and December 2007 (median follow up time 70 months), in a single center. All renal transplant candidates with positive cardiac history or age over 50 years were pretransplant evaluated with pharmacological stress echocardiography and positive patients underwent then coronary angiography and PTCA or CABG, as indicated. Results: The incidence of MACE increased over post-transplant time: MACE affected 0.27%, 2.41% and 8.94% of KTX within the first 6 months, 5 years, 10 years post-transplantation respectively. At univariate analysis risk factors associated with MACE were male gender (P=0.0051), age > 55 y (P=0.033), BMI > 27 (p=0.046), positive CAD history (p=0.0001), total pre-transplant cholesterol >204 mg/dl (p=0.003), posttransplant systolic blood pressure > 142 mmhg (p=0.002), presence of left ventricular hypertrophy before transplantation (P=0.0003), post-transplant diabetes mellitus on therapy (P=0.0002), post-transplant systolic blood pressure > 142 mmhg (p=0.002), serum creatinine levels after transplantation > 1.7 mg/dl (P=0.05). Evaluating the Framingham and the Indana CV risk score indexes, only Indana could significantly (p<0.05) predict the MACE observed in our population, as this index include also the renal function. Conclusions: The occurrence of MACE after successful renal transplantation relates to traditional pre and post-transplant CV risk factors. The very low incidence of MACE observed in the early post-transplant period reflect the benefit of our aggressive pre-transplant cardiac evaluation, the significative increase of MACE

168 468 The kidney and coronary artery disease between 5 and 10 years after transplantation indicate the need for an aggressive cardiac re-evaluation five years after transplantation. Indana index may help to select the population at high CV risk. P2954 Decreased renal function associated with incident adverse cardiovascular outcomes in patients with acute coronary syndromes D. Pereg 1, M. Benderly 2, S. Behar 2, M. Mossrei 1. 1 Meir Medical Center, Kfar Saba, Israel; 2 Neufeld Cardiac Research Institute, Tel Hashomer, Israel Background: While renal dysfunction is associated with increased cardiovascular mortality following acute coronary syndromes (ACS) it is not clear whether this association exists with other major cardiovascular events and whether it is linear. Methods: Included were 1744 patients with ACS enrolled in the 2008 ACS Israeli Survey (ACSIS). Estimated glomerular filtration rate (egfr) was calculated using the modified diet in renal disease equation. Patients were divided into 5 groups according to the guidelines of the national kidney foundation (<45, 45-59, 60-74, and >90 ml/minute/1.73m 2 ). Thirty-day composite of death, reinfarction and recurrent angina was compared between groups. Results: The average egfr in all patients was 73.4±27.1 ( ) ml/minute/1.73m 2. The prevalence of co-existing risk factors, prior cardiovascular disease and Killip class>1 was higher among patients with reduced egfr. These patients however were less treated with ACE-inhibitors, angiotensinreceptor blockers, IIb-IIIa antagonists and coronary revascularization. After ageadjustment, there was a progressive increase in 30-day composite of death, reinfarction and recurrent angina with declining egfr (OR=3.59, 95% CI , for comparison between the highest and lowest egfr groups). This association persisted after further adjustments for gender, diabetes mellitus, hypertension, smoking, dyslipidemia, prior cardiovascular disease, killip>1 and STEMI (OR=3.24, 95% CI ). When egfr was used as a continuous variable, the risk for 30-day composite of death, reinfarction and recurrent angina increased by 2% for any 1 ml/min/1.73m 2 decrease in egfr, (OR 1.02, 95% CI ) Conclusions: Renal dysfunction in ACS patients is associated with an increased risk for combined death, re-infarction and recurrent angina. This risk increases linearly with declining egfr. P2955 Effectiveness and safety of drug eluting stents in patients with chronic renal failure K. Toutouzas, C.H. Patsa, E. Tsiamis, C. Tsioufis, M. Vavuranakis, A. Synetos, D. Tousoulis, A. Spanos, E. Stefanadi, C.H. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: Patients undergoing percutaneous coronary interventions with chronic renal failure (CRF) have increased morbidity and mortality. The effectiveness and safety of drug-eluting stents (DES) have not been extensively investigated in patients with CRF, as these patients are consistently excluded from randomised studies. In this prospective, single centred study, we investigated the effectiveness and safety of DES in patients with CRF and an isolated de novo lesion in the proximal segment of the left anterior descending artery (plad). Methods: We enrolled 379 consecutive patients with an isolated de novo plad lesion. There were 101 patients with CRF (creatinine clearance 65 ml/min) and 278 without CRF (creatinine clearance >65 ml/min). Patients with acute coronary syndrome and contraindications for long-term double antiplatelet therapy were excluded. All patients were scheduled to receive double antiplatelet therapy for at least 12 months. Major adverse cardiac events (MACE) were defined as: Death, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR). All patients underwent either clinical or telephone follow-up. Stent thrombosis was also evaluated and classified according to the Academic Research Consortium (ARC) definition. Results: The baseline characteristics revealed an older population and a significantly higher rate of hypertension among patients with CRF, whereas there was a higher rate of smoking among the control group. The angiographic characteristics were similar between the 2 groups. There were no significant differences regarding the MACE between the two groups of patients (p=0.43) during the 14.80±5.70 months follow-up period. However, there was a significantly higher incidence of mortality in patients with CRF (n= 5) as compared with non-crf (n=1) (4.95% versus 0.35%, p=0.006, respectively). Two patients who died from CRF group had discontinued dual antiplatelet therapy at one year. The cardiac deaths in the remaining patients from both groups underwent under dual antiplatelet therapy. The rate of non-fatal MI was similar between the two cohorts (p=0.61), as well as the TLR rate (p=0.12). Notably, the rate of thrombosis was low for both groups (1.98%, CRF versus 1.07%, non-crf, p=0.61). Conclusions: This prospective study shows that DES implantation in patients with CRF and a plad lesion is effective and safe, with a similar reduction in the TLR and thrombosis rate, as compared with non-crf. However, the higher incidence of mortality in patients with CRF needs to be further explored. P2956 Impact of high-dose N-ACC versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in patients with ST-elevation myocardial infarction undergoing primary PCI H. Thiele, I. Eitel, L. Hildebrand, C. Schirdewahn, V. Adams, G. Fuernau, M. Gutberlet, G. Schuler on behalf of LIPSIA Study Group. Herzzentrum der Universitaet Leipzig, Leipzig, Germany Background: ST-elevation myocardial infarction patients undergoing primary angioplasty are at high risk for contrast-induced nephropathy (CIN). High-dose N- Acetylcysteine reduced the incidence of CIN in patients with high contrast volumes and might reduce reperfusion injury. Aim of this randomized, single-blind, controlled trial was to assess N-Acetylcysteine effects on CIN and reperfusion injury in moderate contrast volumes. Methods: Patients undergoing primary angioplasty were randomized to either high-dose N-Acetylcysteine (2x1200 mg/d for 48 hours; n=126) or placebo plus optimal hydratation (n=125). The two primary endpoints were: 1) Occurrence of more than >25% increase in serum creatinine level <72 hours after randomization; 2) reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging. Results: The median volume of an iso-osmolar contrast agent during angiography was 180 ml (interquartile range 140;230 ml) in the N-acetylcysteine and 160 (interquartile range 120; 220 ml) in the placebo group (P=0.20). The primary endpoint CIN occurred in 14% in the N-acetylcysteine and in 20% in the placebo group (P=0.28). Myocardial salvage index was also not different between both treatment groups (43.5; interquartile range 25.4;71.9 versus 51.5; interquartile range 29.5;75.3; P=0.36). Activated oxygen protein products and oxidized low-density lipoprotein as marker for oxidative stress were reduced by up to 20% in the N-acetylcysteine group (P<0.05), whereas no change was evident in placebo. Conclusions: High-dose N-acetylcysteine reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in non-selected patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration. P2957 The impact of kidney transplantation on the incidence of cardiovascular events is affected by the presence of cardiovascular disease L.H.W. Gowdak 1, F.J. De Paula 2, R.L. Arantes 1,A.L.V.DeOliveira 1, L.A.M. Cesar 1, L.E. Ianhez 2, E.M. Krieger 1, J.J.G. De Lima 1. 1 Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; 2 Renal Transplant Unit, Division of Urology, University of São Paulo Medical School, São Paulo, Brazil Background: Patients (pt) with end-stage renal disease (ESRD) are at risk of cardiovacular disease (CVD) and cardiovascular events (MACE). We determined the impact of kidney transplantation (KT) relative to chronic hemodialysis (HD) on the risk of MACE in pt with and without CVD. Methods: 1,060 pt with ESRD (61% men, 53±11 years-old) were referred for cardiovascular assessment and placed on a single waiting list for KT. Pt were divided in two groups depending on the presence of previous or current CVD, defined as coronary artery disease, heart failure, stroke, or peripheral artery disease. KT was performed on 204 (19.2%) pt. During a median follow-up of 20 (1-107) months, the primary endpoint (the composite incidence of fatal/non-fatal MACE) was determined for pt undergoing KT as well as for those on HD. The risk (RR) of MACE for pt undergoing KT relative to HD was calculated for the first 5 years of follow-up. Results: 34 (3.2%) pt were lost to follow-up. The incidence of the primary endpoint was 20.1% in the overall population. Pt kept on HD were older (54 vs. 51 years; P<0.001) with a higher prevalence of diabetes (36% vs. 27%; P=0.02) and CVD (39% vs. 26%; P=0.001). Left panel shows the RR of MACE in pt without CVD undergoing KT. Note that at 30 month-follow-up the RR = 1 and continue to decrease afterwards. In pt with CVD the RR of MACE for the KT group = 1 at about 18 months of follow-up, keeps lower than 1 between 18 and 45 months, and rises over 1 again at 45 months.

169 The kidney and coronary artery disease 469 Conclusions: In pt without CVD, there s a higher incidence of MACE early on after KT compared to pt on HD. Later on, pt who underwent KT had a lower incidence of MACE. On the other hand, in pt with CVD, the decrease in the incidence of MACE provided by KT occurs earlier but in the long-term this benefit seems to be lost. Background: Renal dysfunction is increasingly recognized as a major prognostic factor in acute myocardial infarction (AMI). The aim of our study was to determine the impact of Quercetin (Q) on clinical outcomes in pts with ST-elevation myocardial infarction (STEMI), and assess whether predictors differed between those with preserved GFR and those with reduced GFR. Methods: 184 pts (age 53.2±0.7 yrs) with STEMI within 12 hours of symptom onset (3.7±0.2 hrs) were prospectively followed up for 5 years. 89 pts (gr. 1) received study drug Q i.v. during 5 days in addition to standard therapy starting about 30 min before primary PCI or TLT. GFR was estimated using MDRD equation and analysis performed separately in pts with GFR < 90 ml/min (n=104) and GFR 90 ml/min (n=80). The protocol mandated a baseline creatinine and excluded pts with a creatinine > 180 μmol/l. We used multivariable Cox proportional modeling to compare the relation between egfr and composite CV outcome (CV death, recurrent MI). Results: Mean egfr was 89.2±22.2 for gr. 1 and 91.5±22.9 ml/min/1.73 m 2 for gr.2.gfr < 90 ml/min at baseline were associated with significantly more CV events, event-free survival rate 66.3% vs. 77,5%; p<0.05 by log rank analysis. Risk for CV events based on egfr < 90 ml/min was associated with a hazard ratio of 2.09 (95% confidence interval [CI], ). Q treatment significantly improves renal function in pts with egfr < 90 ml/min compared to the gr. 2 (p<0.05). P2958 Synergistic effects of asymmetric dimethylarginine accumulation and endothelial progenitor cells deficiency on renal function decline during a 2-year follow-up in stable angina A. Surdacki, E. Marewicz, E. Wieczorek-Surdacka, G. Szastak, T. Rakowski, E. Wieteska, J. Pryjma, D. Dudek, J.S. Dubiel. Jagiellonian University, Cracow, Poland Purpose: Renal insufficiency predisposes to coronary artery disease (CAD), but also CAD and traditional risk factors accelerate renal function loss. Blood endothelial progenitor cells (EPC) deficiency and elevated asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) formation, predict adverse CAD outcome. Our aim was to estimate changes in glomerular filtration rate ( GFR) in relation to EPC counts and ADMA in stable angina. Methods: We followed up 75 non-diabetic stable angina men (age 53±11 years, GFR 68±11 ml/min per 1.73 m 2 ) for 2 years after elective coronary angioplasty on a uniform standard medication. Exclusion criteria included a history of myocardial infarction, heart failure, ejection fraction (EF) <55%, GFR<30 ml/min/1.73 m 2 and coexistent diseases. Those with adverse cardiovascular events, EF depression or altered drug therapy during the follow-up were also excluded. Baseline blood count of CD34+/kinase-insert domain receptor (KDR)+ cells, a leukocytes subpopulation enriched for EPC, was quantified by flow cytometry (% of lymphocytes). Plasma ADMA was measured by ELISA. GFR was computed by the simplified MDRD formula. Results: GFR correlated to baseline GFR (r=0.27, p=0.02), ADMA (r= 0.25, p=0.03) and CD34+/KDR+ cells counts (r=0.23, p=0.05). Multivariate analysis revealed a synergistic interaction of high ADMA (>0.45 μmol/l, median) and low CD34+/KDR+ cells counts (<0.035%, median) as the sole independent predictor of GFR (Figure). GFR vs. ADMA and CD34+/KDR+ cells count Conclusions: Elevated ADMA and EPC deficiency may synergistically contribute to accelerated renal function loss in stable angina. This could result from the impairment of EPC-dependent endothelial renewal in the kidney, possibly due to decreased both EPC mobilization and differentiation, NO-dependent processes. P2959 Renal effects of intravenous lipoxygenase inhibitor Quercetin in patients with acute myocardial infarction: prospective randomized study S. Kozhukhov, A. Parkhomenko. NSC Institute of Cardiology, Kiev, Ukraine Conclusions: Impaired renal function is associated with greater rates of risk for CV events based on egfr and is an independent predictor of new MI and cardiac death during 5-years follow-up after MI. Q with lypoxigenase inhibiting activity can improve renal function in STEMI pts and may influenced on long-term prognosis. P2960 Contrast-induced nephropathy after an acute coronary syndrome A. Gaspar, S. Nabais, S. Ribeiro, S. Rocha, P. Azevedo, M. Pereira, A. Brandao, A. Correia. Sao Marcos Hospital, Braga, Portugal Purpose: Contrast-induced nephropathy (CIN) is a form of hospitalacquired acute renal failure that sometimes develops after giving iodinated radiocontrast agents. The growing number of patients who undergo coronary angiography and percutaneous revascularization after acute coronary syndrome (ACS) brought more relevance to this entity. It s actually one of the most frequent forms of hospital-acquired acute renal failure. The purpose of this study was to define the predictors and prognostic value of CIN in a population of patients admitted with ACS. Methods: A total of 558 patients consecutively admitted with ACS and submitted to cardiac catheterization procedure, from January 2004 to April 2006, were reviewed. CIN was defined as impairment of renal function occurring within 48 hours after administration of contrast media and manifested by an absolute increase in the serum creatinine level of at least 0.5 mg/dl or by a relative increase of at least 25% over the baseline value (in the absence of another cause). The patients were classified in 2 groups according to the occurrence of CIN. The primary endpoint was in-hospital mortality. Results: Of the 558 patients reviewed, 5% (n=28) developed CIN. Patients with CIN were older (69.6±10.5 vs 61.5±11.7; p <0.001) and more often had diabetes mellitus (42.9% vs 24%; p=0.02) and renal insufficiency (48% vs 14.7%; p <0.001). There were no differences regarding ACS presentation (with or without elevation in the ST segment) and in-hospital medical treatment. Patients with CIN had higher in-hospital mortality (10.7% vs 0.6%; p <0.001). After adjustment for confounding variables by multivariate analysis (age, renal insufficiency, heart rate on admission, systolic blood pressure on admission and Killip class on admission), CIN remained an independent predictor of in-hospital mortality. Conclusions: CIN occurred in 5% of our patients admitted with ACS. Risk factors associated with CIN were advanced age, diabetes and pre-existing renal insufficiency. CIN was an independent predictor of in-hospital mortality. P2961 Evaluation of Cockcroft-Gault and modification of diet in renal disease equations in post-acs patients M. Lafitte 1, L. Barandon 1, Y. Pucheu 1, M. Riedel 1, T. Couffinhal 2. 1 Hopital Haut Leveque - Groupe Hospitalier Sud, Pessac, France; 2 Hopital Haut Leveque and Bordeaux Victor Segalen University, Pessac, France Background: Chronic kidney disease (CKD) is a powerful predictor of adverse events after acute coronary syndrome (ACS). Evaluation of CKD by blood creatinine is not efficient, and creatinine clearance must be preferred. Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) equations are widely

170 470 The kidney and coronary artery disease available but neither formula was developed or validated in patients with cardiac disease. Objective: To compare formulae and to determine which one best predicted CV risk and events in post ACS patients. Method: Estimated GFR was assessed by C-G and MDRD formulae in 1431 post-acs patients included in CEPTA program (Centre d Exploration de Prevention et de Traitement de l Athérosclérose). CKD was defined as a GFR<60 ml/min. Dialysis patients were excluded. We recorded risk factors and CV events (2 years follow-up). Results: The median (interquartile range) GFR was 91.4 ml/min ( ml/min) by C-G and 81.6 ml/min ( ml/min) by MDRD. 12,6% of patients were classified as CKD by MDRD, 14,7% by C-G (p=ns). Formula agreement was found in only 52.8% of CKD patients. Patients with CKD by MDRD were younger (68,9±10 vs 72,2±9, p<0.001), had higher BMI (28.4±5.3 vs 25.4±4.6, p<0.001) and systolic blood pressure (127.2±19 vs 123.1±18mmHg, p<0.05) compared to those with CKD by C-G. No other significant difference was found for other CV risk factors. CKD patients defined by both formulae did not carry a higher risk profile compared to CKD diagnosed by a single formula. Atherosclerosis burden was similar in the two groups. A subgroup of 882 patients was followed for cardiovascular events (mean followup 2 years). Total CV events occurred in 17.5% of CKD patients defined by CG, 19.8% as defined by MDRD (P=NS), and 9.9% of patients without CKD (p< compared to CKD). Conclusion: Important CKD disagreements occur in post-acs patients in evaluating GFR by different formulae. CV events after ACS are higher in CKD patients than in those without CKD. Neither CG nor MDRD formula could better identify high risk subjects, nor predict occurrence of CV events in CKD patients after ACS. Chronic kidney disease (CKD) is one of the most important risk factor for cardiovascular complications. The prevalence and prognostic role of CKD among patients (pts) with acute myocardial infarction (AMI) and impaired glucose tolerance (IGT) is little known. Purpose: to evaluate the impact of CKD on long-term outcome in AMI pts with IGT treated invasively. Methods: Single-centre prospective study encompassed 2733 consecutive AMI pts treated invasively. In all in-hospital survivors without prior diabetes mellitus oral glucose tolerance test was performed and 560 pts with IGT were selected. CKD was defined as an estimated glomerular filtration rate (GFR) <60mL/min/1.73m 2 at baseline. All IGT pts were divided with respect to renal status into: those with CKD (IGT-CKD; n=80) and without (IGT-nCKD; n=480). Cumulative survival was compared using log-rank test. Independent predictors of death were selected with multivariate Cox-regression model. Results: IGT-CKD was associated with excessive total mortality (21.3%) when compared to IGT-nCKD (7.3%, p<0.001). More unfavorable clinical characteristic was observed in IGT-CKD group (more advanced age, higher prevalence of cardiogenic shock, hypertension, decreased ejection fraction EF), but angiographic results were similar in both groups. Multivariate analysis identified GFR<60 as a one of the strongest independent predictors of death in the population of AMI pts with IGT (HR 2.36; 95%CI , p<0.05). Other independent death predictors were: symptoms duration, advanced age, multivessel coronary disease, and decreased EF<35%. P2962 Intermittent claudication, history of cerebrovascular accident and renal failure each has prognostic value similar to the history of coronary artery disease in patients with acute coronary syndromes M. Zairis, P. Smilakos, C. Ritsatos, G. Tsiaousis, P. Margetis, Z. Katidis, I. Sarris, D. Beldekos, S. Handanis, S.G. Foussas. Tzanio Hospital, Piraeus, Greece Background: To compare the prognostics value of several atherosclerotic manifestations derived from distinct vascular beds with the prognostics value of the previously known coronary artery disease (CAD) in a large cohort of patients with acute coronary syndromes. Methods: From January 1998 through December 2006 a total of 7,743 patients (76.3% males; mean age 68.4±10.2 yrs) were hospitalized due to either ST elevation myocardial infarction or non-st elevation acute coronary syndromes in our department. Information concerning to the history of intermittent claudication (IC), cerebrovascular accident (CVA), renal failure (RF) (GFR<60 ml/min) and known CAD were prospectively collected following patient presentation. Cardiovascular mortality during the first year of follow up was the primary study end point. Results: There were 288 (3.7%) patients with a history of IC only (no manifestation from another vascular bed), 259 (3.3%) patients with a history of CVA only, 1214 (15.7%) patients with RF (a GFR<60 ml/min upon presentation) only and 1138 (14.7%) patients with a history of previously known CAD only. There were no significant differences among the aforementioned 4 groups of patients with a history of manifestations of 1 vascular bed only. The incidence of cardiovascular mortality at the end of the follow up was similar among the 4 groups (25.8%, 26.1%, 26.4% and 25.4%; p for trend=0.8) (Figure). Conclusions: The results of the present study have shown that history of intermittent claudication, cerebrovascular accident, renal failure have similar prognostic value to the previously known CAD in patients with an acute coronary syndrome. P2963 The impact of renal function on long-term prognosis in patients with impaired glucose tolerance and acute myocardial infarction J. Kowalczyk 1, A. Sedkowska 1, A. Swiatkowski 1, T. Zielinska 1, O. Kowalski 1, J. Stabryla-Deska 1, B. Sredniawa 1, K. Strojek 2, L. Polonski 3, Z. Kalarus 1. 1 Medical University of Silesia, Silesian Centre for Heart Diseases, Zabrze, Poland; 2 Department of Internal Diseases, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland; 3 3rd Department of Cardiology, Medical University of Silesia, Silesian Centre for Heart Diseases, Zabrze, Poland Kaplan-Meier survival curves in AMI pts Conclusions: IGT pts with CKD had significantly reduced long-term survival after AMI treated invasively when compared to pts without renal failure. GFR<60 was one of the most important risk factors for death in AMI pts with IGT. P2964 Prognostic significance of acute kidney injury after reperfused ST-elevation myocardial infarction: synergistic acceleration of renal dysfunction and left ventricular remodeling A. Anzai, T. Anzai, K. Naito, H. Kaneko, Y. Jo, Y. Nagatomo, Y. Maekawa, A. Kawamura, T. Yoshikawa, S. Ogawa. Keio University School of Medicine, Tokyo, Japan Purpose: Acute kidney injury (AKI) after myocardial infarction (MI) is associated with poor clinical outcome. However, mechanisms of the adverse effect of AKI on clinical outcome after MI are unclear. We sought to clarify the prognostic significance of AKI after reperfused ST-elevation MI (STEMI) in relation to left ventricular (LV) remodeling. Methods : We examined 141 consecutive patients with reperfused first anterior STEMI who received primary stenting. Patients were divided into 2 groups according to presence or absence of AKI, defined as an increase in serum creatinine of 0.3 mg/dl within 48 hours after admission (AKI group; n=31, non-aki group; n=110). Peripheral white blood cell (WBC) count, serum creatine kinase (CK) and C-reactive protein (CRP) levels were serially measured. Left ventriculography and measurements of plasma interleukin-6 (IL-6), malondialdehyde-modified low density lipoprotein (MDA-LDL) and neurohormones were performed on admission and 2 weeks after MI. Results: AKI group was older and had lower estimated glomerular filtration rate (egfr) on admission than non-aki group. Other variables, including coronary risk factors, medications, coronary angiographic findings and dose of contrast medium used for primary stenting, were similar between the 2 groups. AKI group had higher incidence of in-hospital cardiac death (P=0.0004) and major adverse cardiac events (MACE, P=0.020) during follow-up (39±40 months) compared with non-aki group. AKI was associated with greater LV end-diastolic (P=0.006) and end-systolic volumes (P=0.007) and lower ejection fraction (P=0.012) 2 weeks after MI, although these parameters on admission were similar between the 2 groups. WBC count on admission (P=0.004) and peak CRP (P=0.0009) were higher in AKI group than non-aki group, despite no significant difference in peak CK. Plasma norepinephrine (P=0.004) on admission, IL-6 (P=0.046), brain natriuretic peptide (P=0.0004) and MDA-LDL (P=0.012) 2 weeks after MI were higher in AKI group than in non-aki group. Multiple logistic regression analysis showed

171 The kidney and coronary artery disease / The wide world of coronary artery disease 471 significant determinants of AKI on admission were WBC count 13,000/mm 3 (P=0.002), age 70 years (P=0.003) and egfr<60ml/min/1.73m 2 (P=0.031). Cox proportional hazard model analysis revealed AKI was an independent predictor of MACE (HR=2.38, P=0.019). Conclusions: AKI after reperfused STEMI was a strong predictor of short- and long-term clinical outcomes in association with exaggerated LV remodeling. Enhanced inflammation, oxidative stress and neurohormonal activation may synergistically accelerate renal dysfunction and LV remodeling after STEMI. and ASA class 3 (HR 2.1, 95% CI ). In addition, patients who experienced asymptomatic troponin T-release had an independent 2-fold increased risk for mortality (HR 1.9, 95% CI , p=0.005, figure). THE WIDE WORLD OF CORONARY ARTERY DISEASE P2965 Cardiac troponin I at 24 or 48 Hours predicts infarct size in patients with STEMI as determined by cardiac magnetic resonance imaging. A FIRE-substudy J. Hallen 1, J. Schwitter 2,P.Buser 3, P. Petzelbauer 4, B. Geudelin 5, D. Atar 1. 1 Oslo University Hospital, Aker, Division of Cardiology, Oslo, Norway; 2 University Hospital Zurich, Zurich, Switzerland; 3 University Hospital Basel, Basel, Switzerland; 4 Medical University of Vienna, Vienna, Austria; 5 Fibrex Medical Research and Development GmbH, Vienna, Austria Purpose: i) To determine the correlation of single-point cardiac troponin I (ctni) and infarct size as measured by cardiac magnetic resonance (CMR) imaging at 5 days and 4 months; ii) To define predictors of infarct size above or below median at 4 months in a binary logistic regression analysis including early CMR estimated infarct size. Methods: A post-hoc analysis of the F.I.R.E. (FX06 in Ischemia-REperfusion injury) trial. 234 patients were randomised presenting with acute ST elevation myocardial infarction (STEMI) and receiving primary percutaneous coronary intervention within 6 hours from onset of symptoms. ctni sampling at 24 (ctni24) and 48 (ctni48) hours. Infarct size was measured by contrast enhanced CMR examination at 5-7 days and 4 months. Association between two variables was calculated by Spearman rank correlation. Binary logistic regression analysis for determining independent predictors (adjusting for BMI, age, and gender). Results: Median infarct size as % of left ventricle (IQR): 5 days: 17.2% (8.4;28.2); 4 months: 13.4%(6;24). Median ctni (IQR): 24 hours: 45.7 ng/ml (15.9;77.4); 48 hours: 17.7 ng/ml (9.2;35.5). Spearman s rho for infarct size at 5 days: (ctni24) and (ctni48). Spearman s rho for infarct size at 4 months: (ctni24) and (ctni48). Results of binary regression analysis presented in table. Table 1. Binary logistic regression analysis of independent predictors of infarct size above or below median at 4 months β-coefficient OR (95% CI) P-value Non-anterior location ( ) ctni ( ) < Early infarct size ( ) < Conclusion: We here report a strong correlation between early, single-point ctni measurements and infarct size as determined by state-of-the art CMR imaging. There was considerable shrinkage of IS during the follow-up period, which could explain why correlations with ctni were generally better at 4 months than at 5 days. Moreover, our results suggest that single-point ctni is an independent predictor of infarct size above or below median at 4 months in a model including early CMR estimated infarct size. P2966 Asymptomatic troponin T release after non-cardiovascular surgery is associated with poor long-term outcome O. Schouten 1, M. Dunkelgrun 1,T.A.Winkel 1,M.Voute 1,R.T.Van Domburg 1, H.J.M. Verhagen 1,J.J.Bax 2, S.E. Hoeks 1,W.J.Flu 1, D. Poldermans 1. 1 Erasmus, Rotterdam, Netherlands; 2 Leiden University Medical Center, Leiden, Netherlands Background: Cardiac troponin T (ctnt) is a sensitive marker for myocardial damage. The incidence of asymptomatic ctnt release after general noncardiovascular surgery might be as high as 10%. However, the impact of asymptomatic ctnt release on long-term outcome is unknown. Therefore, the aim of the current study was to evaluate the prognosis of patients with asymptomatic ctnt release after general noncardiovascular surgery. Methods: For this study data of 862 patients included in the randomized DE- CREASE IV study were analyzed. The majority of patients underwent general (39%), urologic (19%) or orthopedic (16%) surgery. ctnt was measured on days 1, 3, and 7 after surgery. Asymptomatic ctnt release was defined as ctnt > 0.03 ug/l without ischemic symptoms or ECG changes. Study endpoint was allcause mortality, assessed by contacting the civil service registry. Multivariate Coxregression analysis was applied to assess the association between asymptomatic ctnt release and long-term survival. Results: A total of 57 (7%) patient experienced asymptomatic perioperative troponin release. During a median follow-up of 2.4±1.2 years 229 (27%) patients died. Factors associated with poor long-term outcome included intermediate-high risk surgery (HR 3.6, 95% CI ), ASA class 2 (HR 1.7, 95% CI ) Conclusion: Patients with asymptomatic troponin release after general noncardiovascular surgery are at increased risk for long-term mortality. Routine ctnt sampling after noncardiovascular surgery might be considered. P2967 Differences in clinical presentation and 6-month outcomes in different age classes of elderly patients (75-80, 81-85, and >85 years). Data from prospective, nationwide, French PAPI registry J. Lipiecki 1, P. Dupouy 2, O. Wittenberg 3, E. Teiger 4, M. Hanssen 5, M. Slama 6. 1 G. Montpied University Hospital, Clermont Ferrand-Ferrand, France; 2 PCVI Hôpital Privé d Antony, Antony, France; 3 Centre Hospitalier Privé Beauregard, Marseille, France; 4 AP-HP - Hopital Henri Mondor, Creteil, France; 5 Centre Hospitalier Général, Haguenau, France; 6 AP-HP - Hopital Antoine-Beclere, Clamart, France Background: Percutaneous coronary interventions (PCI) are proposed with increasing frequency to elderly and very elderly patients (pts) owing to the high prevalence of coronary disease in this age group. There are limited data about differences between aged and very aged pts in respect to risk factors, co morbidities and outcomes after PCI. Objectives: We sought to define the differences in clinical presentation and outcomes in different age classes in elderly pts treated by PCI with stent implantation. Methods: 1955 pts aged >75 years (62% men, mean age 80.3±3.8 years) treated by 2072 PCI with 3352 stents implantations were prospectively included in this study. Results: There were 936 pts (47.8%) aged years, 707 pts (36.2%) between 81 and 85 years and 312 pts (16.0%) aged >85 years. Elderly and very elderly pts had less cardiovascular risk factors (hypercholesterolemia: 58% vs 54% vs 45%, p=0.01, diabetes: 36% vs 35% vs 32%, p=0.02, familial history of ischemic heart disease: 17% vs 12% vs 9.3%, p=0.002) but more often renal failure at admission (48% vs 65% vs 72% p<0.001). Unstable coronary syndromes as n indications for stenting increased with age (37% vs 44% vs 51%) p<0.001) as well as lesions concerning left main coronary disease or bypass grafts (p=0.04). 6-month cardiac mortality rate increased with age (1.6% vs 2.8% vs 5.2%, p=0.008) as well as cerebral vascular events (0.1% vs 0.8% vs 1.2%, p=0.03) while the rate of non fatal myocardial infarction remained similar (1.4% vs 2.0% vs 2.4%, p=ns). Conclusion: there are several difference in clinical presentation and 6-month outcomes in different age classes in elderly pts with ischemic heart disease treated by PCI with stent implantation with worse results in very elderly (>85%) pts. P2968 Outcome of acute coronary syndrome octogenarian patients in Israel M. Shechter 1,A.Roth 2,S.Atar 3,V.Boyko 4, S. Behar 4, S. Matetzky 1 on behalf of ACSIS Chaim Sheba Medical Center, Tel Hashomer, Israel; 2 Sorasky Medical Center, Tel Aviv, Israel; 3 Western Galilee Hospital, Nahariya, Israel; 4 Neufeld Resaerch Institute, Tel Hashomer, Israel Background: Few data are available regarding the outcome of acute coronary syndrome (ACS) octogenarians. Methods: We evaluated the clinical oucome of 1,766 patients [241 (14%) and 1,525 (86%) < 80 years] from the Acute Coronary Syndrome Israel Survey (AC- SIS), by analyzing data from ACS patients hospitalized in all coronary care units in Israel during a 2-month period in Results: Patients 80 (mean: 85±4) had higher incidence of risk factors, prior cardiovascular events, renal failure and cardiac medication use compared to <0 (mean: 60±11). Admission Killip was higher, while left ventricular ejection fraction was lower in ACS compared to <80. ST-elevation MI (STEMI) was more common in < than 80 (45% vs 32%). Throughout hospitalization ACS 80 received significantly less single/dual antiplatelet therapy, angiotensin-converting enzyme inhibitors, b-blockers and statins, but more calcium blockers, nitrates and diuretics, compared to those <80. In-hospital and 30-day mortality rates (Table) were significantly lower in ACS 80 who underwent any PCI during hospitalization compared with those who did not (4.8% vs 13% and 7.2% vs 22.8%, p<0.01) and the use of IIb/IIIa antagonist did not increase major bleeding and/or mortality. Seventy-seven patients 80 had

172 472 The wide world of coronary artery disease STEMI: 37 (48%) underwent primary PCI (14 with and 23 without IIb/IIIa), while 36 (47%) patients did not. No significant major bleeding was observed between the groups. In-hospital and 30-day mortality rates were significantly lower in patients 80 who underwent, compared with those who did not undergo primary PCI. Age < 80 (n=1525) Age 80 (n=241) P value Any PCI during hospitalization 1096 (72%) 124 (51%) <0.01 IIb/IIIa antagonist use during PCI 511 (47%) 36 (29%) <0.01 In-hospital mortality 23 (1.5%) 21 (8.8%) <0.01 In-hospital major bleeding 22 (1.4%) 6 (2.5%) NS 30-day MACE 179 (12%) 66 (27%) < day mortality 37 (2.5%) 35 (14.8%) <0.01 Conclusion: Octogenarians ACS patients have significantly worse in-hospital and 30-day outcome compared to those < 80 years. However, the low incidence of procedural complications, together with good in-hospital and 30-day survival, suggest that PCI in ACS octogenarians is safe and effective. P2969 The value of calprotectin as a prognostic marker of cardiovascular risk in acute chest pain T. Brugger-Andersen 1,V.Ponitz 1,F.Kontny 2,H.Staines 3, H. Grundt 4, D.W.T. Nilsen 1. 1 Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; 2 Department of Cardiology, Volvat Medical Center, Oslo, Norway; 3 Sigma Statistical Services, Balmullo, United Kingdom; 4 Department of Medicine, Stavanger University Hospital, Stavanger, Norway Background: Calprotectin is a heterodimeric calcium-binding protein abundantly present in the cytoplasm of neutrophils, and it is released upon cell activation. Elevated levels of Calprotectin, as well as high-sensitive C-reactive protein (hscrp) and B-type natriuretic peptide (BNP) are found in patients with acute coronary syndrome (ACS). The aim of this study was to assess the value of Calprotectin as compared to BNP and hscrp as a prognostic marker of cardiovascular risk within 24 months following hospitalization for acute chest pain. Methods: Calprotectin was measured in EDTA plasma using the Calprest ELISA kit. The blood samples were taken on admission in 785 patients. For statistical analysis, the study cohort was divided into quartiles according to Calprotectin levels. A Cox regression model was fitted which included standard risk measures. Results: At 24 months follow-up, 121 of the 785 patients included in the multivariable model had died and 93 patients had suffered a recurrent non-fatal Troponin T positive event. The hazard ratio (HR) for patients with Calprotectin, BNP or hscrp concentrations in the highest quartile (Q4) as compared to those with concentrations in the lowest quartile (Q1) for all-cause death were 0.31, 4.00 and 0.87 (p=0.752, p=0.005 and 0.666), respectively. Concerning recurrent non-fatal Troponin T positive events the HR were 1.07, 1.81 and 2.57 (p=0.830, p=0.124 and p=0.007), respectively. Conclusion: Calprotectin was not found to be a predictor of clinical outcome in patients with acute chest pain. However, BNP was significantly associated with fatal outcome only, whereas hscrp only predicted non-fatal cardiac events. P2970 Effects of subclinical hypothyroidism on cardiac and vascular morphological and functional changes D. Nikolic 1, D.K. Kalimanovska 2,V.M.Mitov 1, A.A. Aleksic 1. 1 General hospital-cardiologic unit, Zajecar, Serbia, Zajecar, Serbia; 2 Institute for Cardiovascular Disease,Clinical Center of Serbia, Belgrade, Serbia, Belgrade, Serbia The cardiovascular system is one of the major targets of thyroid hormone action and is a sensitive marker to detect the effects of subclinical hypothyroidism (SH) at tissue level. SH is defined as high thyrotropin levels and normal serum thyroid hormone concentrations. Recent data indicate that SH is associated with enhanced risk for atherosclerosis and functional cardiovascular changes. The aims of the study are evaluation of SH as a risk factor for: (a) accelerated atherosclerosis and coronary artery disease (CAD), and (b) left ventricular dysfunction. This study included 60 patients with SH and 62 euthyroid healthy persons as controls. Data on thyroid status, obesity measurement, biochemical analysis, echocardiography parameters of left ventricular morfology and function, carotid artery intima-media thickness (IMT) were obtained. Rest-stress myocardial per- Subclinical hypothyroidism Euthyroid (N=60) (N=62) Total cholesterol 6.49± ±1.02 p<0.01 Diastolic hypertension 94.67± ±8.05 p<0.01 Abdominal obesity - waist circumference 98.43± ±11.57 p<0.01 E/Em 11.04± ±1.36 p<0.01 CM mode 31.78± ±12.21 p<0.01 MPI 0.60± ±0.08 p<0.01 IMT 0.81± ±0.18 p<0.01 CAD 13 (21%) 0 p<0.05 Legend: E/Em - ratio of early mitral flow velocity and early diastolic myocardial tissue velocity, CM mode - color Doppler M mode recordings of left ventricular inflow propagation velocity, MPI - myocardial performance index. fusion imaging was performed for those who didn t have documented coronary artery disease while elevated troponins were obtained for hospitalized patients with acute coronary syndrome. SH was associated with a greater prevalence of: higher total and LDL cholesterol, abdominal obesity (p<0,01), diastolic hypertension (p<0,01), IMT (p<0,01) and coronary artery disease (p<0,05). There were statistically significant differences (p<0,01) between SH and age-matched controls for the E/Em, CM mode and MPI. SH is associated with dyslipideamia, hypertension, obesity, greater IMT and with diastolic dysfunction also. Despite greater prevalence of CAD, SH is not an independent risk factor for CAD. P2971 Morbidity profile and treatment status of patients nonadherent to a Disease Management Programme (DMP): Results from the DMP Coronary Artery Disease (CAD) northrhine I. Schwang 1, R. Griebenow 1, B. Hagen 2, L. Altenhofen 2. 1 Krankenhaus Koeln Merheim, Cologne, Germany; 2 Centr. Res. Inst. for amulatory health care, Koeln, Germany Introduction: In randomized clinical trials there may be selection bias due to the definition of inclusion and exclusion criteria. The DMP CAD is open for all patients with proven CAD but participation is voluntary and can be stopped at any time by the patient or the physician. The DMP consists of a set of consented treatment targets (leaving the treatment decision to the physician) and a structured documentation with feedback every 6 months. Currently (12/07) 4438 physicians have included more than 140,000 patients. Since this represents a significant part of the treatment reality in ambulatory health care it was the aim of this study to analyze those patients permanently stopping participation in order to exclude adherence bias in the interpretation of data. Methods: Descriptive analysis of data from a large population cohort. Results: Of the 11,926 patients documented for the last time in ,381 died and 10,545 stopped participation (A), leaving 146,613 (B) being treated in the DMP in Patient characteristics (A/B): age: 70/69 years, male: 62/64%, duration of CAD: 7/6 years, hypertension: 76/78%, diabetes: 31/31%, lipid disorder: 60/64%, current smoker: 15/14%, prior MI: 35/34%, heart failure: 21/17%, PTCA: 33/36%, CABG: 22/22%. Treatment status in 2006 (B/A+B): Aspirin: 84/84%, beta-blocker: 77/76%, statin (after MI): 78/77%, ACE-inhibitor (in heart failure): 72/72%, blood pressure normal (in hypertension): 62/62%. Conclusion: Patients nonadherent to the DMP more often have heart failure but their morbidity profile is otherwise comparable to group B patients suggesting that other medical or nonmedical events have led to nonadherence.the loss of 8% of all patients only marginally affects the results of treatment evaluation. Mi: myocardial infarction, PTCA: percutaneous coronary intervention, CABG: coronary bypass operation, ACE: angiotensin converting enzyme P2972 Timing and energy of the extracorporeal cardiac shock wave treatment have profound influence on the outcome of therapy in ischemic heart disease F. Di Meglio 1, D. Nurzynska 1,C.Castaldo 1, R. Miraglia 1, V. Romano 1, C. Bancone 2, E. Marlinghaus 3,S.Russo 1,C.Vosa 1, S. Montagnani 1. 1 Universita degli Studi di Napoli Federico II, Naples, Italy; 2 Seconda Universita di Napoli, Naples, Italy; 3 Storz Medical, Kreuzlingen, Switzerland The notion of the presence of stem and progenitor cells in the adult human heart imposes that all currently used treatments, as well as those in the experimental phase of the study, should be revisited with regards to effects on these cardiac cell population. In fact, novel therapies offer the possibility of inhibition or even reversal of heart failure progression by the mobilization and activation of cardiac stem and progenitor cells, as can be the case with extracorporeal cardiac shock wave (SW) therapy, suggested for patients with myocardial ischemia. The scope of the present study was to evaluate the effects of low and high energy SW treatment on cardiac primitive cells in vitro. CD117(+) cells have been isolated from age-matched adult human normal (n=4, males, mean age 51±5.6 years) and pathological hearts with end-stage ischemic cardiomyopathy (n=4, males, mean age 55±3.2 years). Cells have been treated with 800 shots of SW at the energy flux density of 0.05mJ/mm 2 and 0.1mJ/mm 2. After one week of culture, cardiac cell lineages were characterized by immunofluorescence and immunoblotting, and their total mrna was examined by stem cell-specific PCRbased microarray. Above all, the effects of high energy treatment differed profoundly from those observed at low energy, with none the same gene up- or downregulated in any of the groups studied. Moreover, cells isolated from pathological hearts were positively influenced in the more evident manner. In fact, low energy treatment of pathological cells induced the activation of a pool of transient amplifying progenitors of cardiomyocytes (expressing α-sarcomeric actin), endothelial (von Willebrand factor) and smooth muscle cells (smooth muscle actin). In these cell population, we observed the upregulation of mrna of 14 genes involved in the cytoskeleton biogenesis/organization, mitotic spindle formation and cell motility. In contrast, high energy SW application resulted in upregulation of 5 genes, mostly involved in the extracellular matrix- and cell-cell adhesion, and downregulation of 15 genes

173 The wide world of coronary artery disease 473 regulating protein kinase activity, signal transduction and cell-cell signalling. As regards cells from normal heart, remarkably only high energy treatment induced activation of endothelial cell precursors. On the basis of the above data it is possible to predict that timing (between onset and end-stage of disease) and energy of the SW treatment can have profound influence on the therapy outcome in ischemic heart disease. Further pre-clinical studies of these variables are warranted before broad introduction of the method into clinical practice. P2973 Predicting prognosis post acute coronary syndromes: can platelets do it? F. Saraiva, R. Baptista, E. Jorge, R. Teixeira, P. Mendes, S. Monteiro, F. Goncalves, P. Monteiro, M. Freitas, L.A. Providencia. Coimbra Hospital and Medical School, Coimbra, Portugal Background and purpose: Platelets have a recognized importance in the pathophysiology of acute coronary syndromes (ACS), because they are directly involved in its initiation and propagation, due to coronary thrombus formation. Our aim was to evaluate the impact of the platelet count variation in the prognosis of patients admitted with ACS. Methods: A total of 1454 consecutive ACS patients were distributed in three groups according to the tertiles of platelet count variation (admission-nadir): group 1 (91% to 21% drop), 2 (21% to 10% drop) and 3 (less than 10% decrease). All groups were studied according to epidemiological, clinical, laboratorial and therapeutic parameters. ANOVA was used to compare more than two parametric variables and Kaplan-Meyer survival analysis to determine one year mortality. Results: Mean age, gender distribution and history of prior cardiovascular risks were not statistically different between groups. Group 1 patients were less previously medicated with statins (28.2 vs vs. 34.8%; p= 0.028), but received more ezetemibe (11.7 vs vs. 5.9%; p= 0.014). They were admitted more often with STEMI (41.3 vs. 29 vs. 28.7%; p<0.001) and had a bigger hospitalization duration (5.63 vs vs days; p<0.001). Killip class at admission was not statistically different. Group 1 had also higher peak cardiac biomarkers (p<0.001) and total cholesterol (192 vs. 191 vs. 185 mg/dl; p=0.03), as well as creatinine (1.38 vs vs mg/dl; p=0.038), glycaemia (161 vs. 150 vs. 148 mg/dl; p=0.048) at admission, but lower nadir values of haemoglobin (11.4 vs vs g/dl; p<0.001). Ejection fraction was also significantly lower in this group (58 vs. 61 vs. 62%; p=0.017). In-hospital morbidity and mortality rates were similar among groups; however, mortality rate at one year follow-up was higher for group 1 (11.9 vs. 7.4 vs. 7%; p= 0.018). Conclusions: In ACS patients, a greater platelet drop during hospital stay is associated with significantly worse post-discharge prognosis. This fact should be taken into account in the risk stratification of ACS patients, along with classical outcome predictors. P2974 Diastolic function: another way to predict outcome in acute coronary syndromes R. Teixeira, C. Lourenco, E. Jorge, R. Baptista, F. Saraiva, P. Mendes, F. Goncalves, P. Monteiro, M. Freitas, L. Providencia. Hospitais da Universidade de Coimbra, Coimbra, Portugal Background: Left ventricular (LV) diastolic function has an important role during the acute phase of an acute coronary syndrome (ACS). Nevertheless, there is still debate regarding its prognostic value. Purpose: To assess ACS patients prognosis stratified by LV diastolic function. Population: Prospective, longitudinal, continuous study of 786 consecutive admissions in a single center for ACS and submitted to an invasive strategy. LV diastolic function was determined by LV end systolic pressure (LVESP) at the beginning of the coronary angiogram. Four groups were created based on LVESP value: A (normal diastolic function) LVESP 20 mmhg n=288; B (mild diastolic dysfunction) LVESP >20 and 25 n=139; C (moderate diastolic dysfunction) LVESP > 25 and 30 n = 117; and D (severe diastolic dysfunction) LVESP > 30 n= 131. A clinical follow up was performed, targeting all-cause mortality at the end of the first year. Results: There were no differences between the groups with respect to age (63.5±11.5 vs 62.3±12.5 vs 64.9±13.5 vs 63.2±13.3, years p=0.61), diabetes, hypertension, dyslipidemia, smoking habits and previous history of myocardial infarction. There was an association between ST elevation ACS and higher LVESP (31.2 vs 48.9 vs 51.3 vs 56.3% p<0.001). Groups were similar regarding coronary anatomy and revascularization. A worse LV diastolic function was also associated with a lower left ventricular ejection fraction and higher peak cardiac biomarkers. In-hospital mortality was lower for group A patients (1.0 vs 5.8 vs 4.3 vs 4.6%, p=0.039), and the one year survival was significantly lower for group D patients (96.2% vs 97.6% vs 95.3% vs 89.2%, log rank p < 0.01). On a multivariate Cox regression model that included age and left ventricular ejection fraction as continuous variables, a LVESP higher than 26.5mmHg remained an independent predictor of one year mortality (HR 2.38, 95% CI: ). Conclusion: In our population, diastolic dysfunction was associated with a worse in-hospital outcome, and the severity of the dysfunction related to one year mortality. These results reinforce the importance of assessing diastolic function to improve ACS management and outcome. P2975 Genetic variant rs A>G is associated with both angiographically determined coronary atherosclerosis and reduced bone mineral density C.H. Saely 1, S. Beer 1, A. Muendlein 1, A. Vonbank 2,P.Rein 1, J. Breuss 1, B. Gaensbacher 1,H.Drexel 1. 1 VIVIT Institute, Feldkirch, Austria; 2 Private University in the Principality of Liechtenstein, Triesen, Liechtenstein Objectives: A recent genome-wide association study found evidence for an association between bone mineral density (BMD) and variant rs on chromosome 8, near to the osteoprotegerin gene. Associations between bone mineral density (BMD) and atherosclerotic disease have been suggested. Potential links between variant rs and coronary artery disease (CAD) are not known. Methods: We performed genotyping of variant rs in a large cohort of 1593 consecutive Caucasian patients undergoing coronary angiography for the evaluation of established or suspected stable CAD; significant CAD was diagnosed in the presence of significant coronary stenoses with lumen narrowing 50%. BMD of lumbar spin and femur was by assessed by Dual Energy X-ray Absorptiometry (DXA) in a subset of 823 subjects. Results: The prevalence of significant CAD increased significantly from the AA over the AG to the GG genotype (55.0%, 57.6%, and 64.2%, respectively; ptrend=0.011). The odds ratio for homozygous carriers of the G allele vs. carriers of the A allele was 1.37 [95% CI ] after adjustment for age and gender. Further, BMD scores increased significantly from the AA over the AG to the GG genotype (1.10±0.20, 1.13±0.20, and 1.16±0.19, ptrend<0.001 and 0.96±0.18, 1.00±0.15, and 1.02±0.15 ptrend<0.001, respectively). Conclusions: Genetic Variant rs A>G is associated with both angiographically determined coronary atherosclerosis and reduced bone mineral density. P2976 Aortic root calcifiacation (ARC) can predict coronary artery disease (CAD) in albanian population N. Xhabija 1,F.Sula 1,S.Meco 1,E.Petrela 2,B.Horjeti 1. 1 American Hospital, Balkan Alliance Group, Tirana, Albania; 2 Medecine Faculty, Dept. of Public Health, Biostatistics, Tirana, Albania Background: Aortic sclerosis is considered not a mere benign finding. Aortic root calcification (ARC) is common with aging, and its association with CAD has been established from previous studies. Especially when early lesions of ARC are found, this association can be suspected. Using transthoracic echocardiography (TEE), we evaluated the presence of ARC in an relatively young Albanian population undergoing coronary angiography. Methods: In a prospective, cohort study, we examined 293 patients who all underwent coronary angiography. ARC was considered present when the anterior and/or posterior wall demonstrated increased echo reflectance and thickness of >2.4mm. All known cardiac risk factors for atherosclerosis were investigated. The mean age of the study population was 60.07±6.03 years. These patients were divided into two groups: 186 (63%) in the ARC group and 107 (37%) in the non-arc group. Results: The patients with ARC had a significant prevalence of CAD (81.1% vs 53.3%, with p=0.001) and a higher incidence rate of 3-vessel disease than the non-arc group. There was also a significant higher rate of disease in the left anterior descending artery in the ARC group (r=0.258, p=0.001). When the cohort was divided by presence of CAD, we found that 206 patients had obstructive CAD and 87 did not. In the CAD group 167 (72.3%) had ARC compared with 39 (41.1%) in the non-cad group (p=0.001). Mitral annular calcification, carotid artery disease, diabetes, smoke and dyslipidemia were found significantly more prevalent in CAD group. After adjusting for coronary risk factors, logistic regression analysis showed that aortic root calcification (ARC) was strongly and significantly associated with obstructive CAD in such clinical setting (OR 3.4, 95% confidence interval , p=0.001).others independent predictors were smoke (OR 4.88, CI 95% ,p=0.001) and diabetes (OR 3.79,95%CI ,p=0.003). In our study, the presence of ARC, diabetes and smoke were the best predictors of obstructive CAD. The sensitivity, specificity, positive and negative predictive values for ARC in diagnosing CAD were 72.2%, 60%, 81% and 50%, respectively. Conclusions: Our data further demonstrates that aortic root calcifications and obstructive artery disease are significantly associated with each other, even in our young population. The presence of early ARC detected by TTE, a simple, noninvasive imaging method, may help in predicting severity of CAD and may be added to conventional risk factors. Using ARC as a marker, we can define a subgroup of patients with a high prevalence of significant CAD.

174 474 The wide world of coronary artery disease P2977 Prognosis at one-year of acute coronary syndrome in HIV-infected patients F. Boccara 1, M. Mary-Krause 2, E. Teiger 3, S. Lang 1,P.Lim 3, K. Whabi 4, F. Beygui 5,G.Steg 6, D. Costagliola 2, A. Cohen 1. 1 AP-HP - Hopital St Antoine, Paris, France; 2 UPMC, Universite Pierre et Marie Curie, Paris, France; 3 AP-HP - Hopital Henri Mondor, Creteil, France; 4 Universite Paris-Descartes, Paris, France; 5 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 6 Bichat-Claude Bernard Hospital (AP-HP), Paris, France Purpose: The PACS-HIV study is designed to evaluate the 3-year prognosis of acute coronary syndrome (ACS) in HIV-infected patients (HIV+) as compared to HIV-uninfected patients (HIV-) in a prospective observational study. We aim to present the intermediate results at one-year follow-up. Methods: We enrolled prospectively and consecutively 103 HIV+ and 197 controls (HIV-) [mean age of the cohort 49.0±9.4 years and 93.0% men] admitted for a first episode of ACS matched for age (± 5 years), gender and type of ACS. We report the clinical outcome at 12-months, defined as MACCE [Major Adverse Cardiac and Cerebral Events: death from cardiac cause, recurrent acute coronary syndrome, recurrent coronary revascularization and stroke]. Results: At baseline, the 2 groups had similar coronary risk factors with high prevalence of smoking (> 70% for the entire cohort) as well as the severity of coronary lesions during coronary angiogram. MACCE at one-year are depicted in Table. Only 2 cardiovascular deaths occurred in the entire cohort after one year follow-up. The rate of occurrence of first MACCE at 12-months was similar in both groups (unadjusted hazard ratio = 1.15, 95% confidence interval, ; P=0.72). However, recurrent ACS was more frequent in HIV+ group as compared with HIV- group (unadjusted hazard ratio = 2.89, 95% confidence interval, ; P=0.043) along with urgent PCI (7 HIV+ vs 3 HIV-). The rate of recurrent coronary revascularization (PCI and/or CABG) was similar in both group (9 patients vs 15 patients, p=ns). This was related to the higher rate of PCI guided by silent ischemia detected in HIV- (11 vs 1, p= NS). Number of subjects with a first event HIV+ (n=103) HIV (n=197) HR P value MACCE CV death 0 2 Recurrent ACS 9 5 Recurrent coronary resvacularization 8 14 Clinical TLR 7 11 Conclusions: In this large cohort of HIV+ with a first episode of ACS, we observed that HIV+ had a higher rate of recurrent ACS and urgent PCI as compared to HIV- after one year follow up. Whether this observation at the planned 3-years follow-up as well as the occurrence of MACCE is confirmed will be related on time. P2978 Efficacy of two long-term intervention strategies to promote long-term adherence to lifestyle changes and to reduce cardiovascular events in patients with coronary artery disease M. Vona 1,M.Vona 1, L. Chapuis 1, T. Iannino 1,E.Ferrari 2,L.K.Von Segesser 2. 1 Cardiac Rehabilitation, Glion Sur Montreux, Switzerland; 2 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland Background: It is known that an incomplete adherence to life style changes and to medical treatment is responsible of an increase number of cardiovascular events (CE) in the follow-up (FU). Aim: We assessed the hypothesis that an economic and simple long term support can help coronary pts to improve adherence and to reduce CE, testing two different low-cost long- term strategy (12 months). Methods: 611 pts (57±9 y), after an acute coronary event, were randomised into 3 groups: usual care (G1,214 pts); phone FU group (G2,193 pts), intensive longterm intervention group (G3,204 pts). The G2 pts were called every month by a nurse to reinforce adherence to medical treatment and physical activity recommended and to check progress regarding lifestyle and other risk factors changes; the G3 pts underwent, every 3 months, 2 hours of a risk factors- educationcounselling session managed by nurse. After 1 year all pts were evaluated for risk factors and CE. The CE were re-evaluated again 1 year later. Results: at 1 year-fu the LDL cholesterol was 125±19 mg% in G1, 106±16 mg% ing2 (p<0.01 vs G1) and 101±22 mg% in G3(p<0.01 vs G1 and G2); among the 364 pts smoking before the coronary event, the % of smokers at FU was: 38% in G1, 40% in G2, and 10% in G3 (p<0.01 vs G1 and G2). The complete adherence to medical treatment was 47% in G1, 66% in G2 (p <0.01 vs G1), and 91% in G3 (p<0.01 vs G1 and G2), while the adherence to physical activity was 15% in G1, 49% in G2 (p <0.01 vs G1) and 83% in G3 (p<0.01 vs G1 and G2). Blood pressure in hypertensive pts was uncontrolled in 50% of G1, 17% in G2 and only 10% of G3 pts (p<0.001 vs G1) After 1 year no differences were observed in total and cardiovascular mortality and myocardial infarction in the different groups, but the number of the new hospitalisations for non-fatal CE (chest pain, angina, heart failure) was higher in G1 (28%) and G2 (21%) than in G3 (14,2%)(p<0.01 vs G1 and G2). After 2 years FU, a significant (p=0.003) reduction in the incidence of non fatal myocardial infarction was observed only in G3 pts. Conclusion: Both long-term low-cost strategies were effective in increasing adherence to lifestyle changes and to medical treatment: a more direct and intensive strategy had better efficacy and impact on non-fatal cardiovascular events and rehospitalisations. P2979 Superior long-term outcome after primary PCI compared to early thrombolysis in acute ST-segment elevation myocardial infarction M. Aasa 1,M.Dellborg 2, J. Herlitz 2,L.Svensson 1,L.Grip 2. 1 Södersjukhuset, Karolinska Institute, Stockholm, Sweden; 2 Sahlgrenska University Hospital, Gothenburg, Sweden Purpose: No single randomised study has convincingly shown superiority of primary PCI to thrombolysis in ST-segment elevation myocardial infarction (STEMI) at short term follow-up. Data on long-term outcome are scarce. We report the long-term outcome of the Swedish Early Decision (SWEDES) reperfusion trial that compared early thrombolysis to primary PCI. Methods: Patients with STEMI were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104) between November 2001 and May In 42% of the patients treatment was initiated in the prehospital phase. Data on survival status and hospital admissions for reinfaction for all patients were obtained from merging data from the swedish national quality registry for coronary care units (RIKS-HIA), the National Patient Registry and the National Cause of Death Registry. Mean follow-up time was 6±0.43 years. Results: Rates of death and death or MI were 10,9% and 24,8% in the primary PCI group vs. 20,2% and 39,4% in the thrombolysis group (p=0.07 and p=0.025 respectively). A Kaplan Meyer survival analysis showed a trend for better outcome for death and a significantly better outcome for the combined end point death or MI (log rank p=0.06 and p=0.029 respectively. In a Cox proportional hazard regression analyses primary PCI was significantly correlated to lower incidence of death (HR 0.26;CI ) and death or MI (HR 0.58;CI ). There was no significant impact of degree of resolution of ST-segment elevation or TIMI myocardial perfusion grade at 5-7 days post randomization. Conclusions: In the SWEDES trial primary PCI was associated with a better long term outcome compared to thrombolysis. This difference could not be explained by differences in parameters of myocardial reperfusion at the time of treatment. P2980 Outcome of primary angioplasty during off-hours is not worst than during routine office hours : experience at a high-volume interventional center E. Barge-Caballero, J.M. Vazquez-Rodriguez, R. Estevez-Loureiro, A. Rodriguez-Vilela, J. Salgado-Fernandez, G. Aldama-Lopez, R. Calvino-Santos, P. Pinon-Esteban, N. Vazquez-Gonzalez, A. Castro-Beiras. Hospital Universitario A Coruña, A Coruña, Spain Purpose: To compare clinical profile, medical care and outcome of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) during off-hours (OH) and during routine office hours (ROH) at a high-volume interventional center (>1500 PCI and >300 primary PCI procedures per year) with highly experienced operators (>300 PCI and >50 primary PCI procedures per year). Methods: Prospective registry including 1494 consecutive STEMI patients treated with primary PCI at our tertiary-level cardiovascular center from January, 2003 to August, PCI procedures performed on weekdays from 15:01 to 7:59 hours, weekends and holidays were considered as performed during off-hours. Three patients were excluded because of the lack of reliable information about this issue. Results: Of 1491 studied patients (mean age 63.2±12.7 years, 18% women), 1084 (72.6%) underwent primary PCI during off-hours. Patients treated during off-hours were more frequently referred from non-interventional hospitals (37.5% vs 31.0%, p=0.18) and were more frequently administered IIb-IIIa glycoprotein inhibitors before PCI than those treated during routine office hours (56.8% vs 44.2%, p 0.001). Median first contact-to-balloon delay (ROH: 99 vs OH: 113 min; p<0.001), interventional team activation-to-balloon delay (ROH: 56 vs OH: 79 min; p<0.001) and symtpoms-to-balloon delay (ROH: 214 vs OH: 242 min; p=0.002) were all longer during off-hours ; however, no significant differences were observed with regard to door-to-first contact delay (ROH: 106 vs OH: 116 min; p=0.45) or first contact-to-interventional team activation delay (ROH: 25 vs OH: 24 min; p=0.55). Rates of PCI failure were low both during off-hours (5.9%) and during routine hours (6.1%, p=0.86). Thirty-day mortality was 5.1% for patients undergoing PCI during off-hours and 5.4% for patients undergoing PCI during routine office hours (p=0.80). After multivariate adjustment for potential confounders, no significant increase in 30-day mortality was observed in the off-hours group (OR 0.99; p= ; p=0.96). Conclusion: Patients undergoing primary PCI during off hours are exposed to longer delays to reperfusion than those treated during routine office hours. However, our data support that the circadian variations in short-term outcome of STEMI patients may be significantly limited when primary PCI is performed at a high-volume center by highly experienced operators with high rates of procedural success.

175 The wide world of coronary artery disease 475 P2981 The R in V1 in non-anterior wall infarction indicates lateral rather than posterior involvement. Results from ECG/MRI correlations K. Van Der Weg, S.C.A.M. Bekkers, B. Winkens, M.E. Lemmert, S.M. Schalla, G. Snoep, H.J.G.M. Crijns, J. Waltenberger, A.P.M. Gorgels on behalf of MAST. University Hospital Maastricht, Maastricht, Netherlands Introduction: Tall R waves in V1, observed in the chronic phase of non-anterior wall myocardial infarction (MI) have been associated with posterior wall involvement of the left ventricle. This insight has been challenged by correlation studies linking contrast enhanced cardiovascular magnetic resonance imaging (CE-CMR) anatomy to the ECG. This study describes quantitative relationships between QRS characteristics in relevant precordial leads and MRI assessed involvement of CE-CMR determined segments. Methods: A total of 55 patients (pts) admitted with an acute non-anterior MI and treated with PCI were studied. All patients underwent CMR within a mean of 5 (SD 2) days after admission. Segments involved (according to AHA 17 segment model) and segmental transmurality were related to height and width of R in V1, V2, V5 and V6, R/S ratio in V1 and depth and width of Q in V6. Measurements were done manually after magnifying the ECG within a software environment. Multivariable linear regression analyses (B=increase of infarction size in % with every added mm and R2=R-square) and Kendall s (rτ) and Spearman s correlations (rs) were applied. Results: A total of 45 pts (82%) had an occlusion of the right coronary artery (RCA) and 10 pts (18%) of the circumflex branch (CX). The extent of transmurality of the basal inferior (previously known as true posterior) segment showed no significant correlation with the characteristics of R in V1 and V2 (rτ= , p= ). The width of R in V1 was however significantly (B=15.5, p=0.02) related to the extent of transmurality in the lateral segments, also after correcting for potential confounders (R2=0.45). The same applied to the other characteristics in V1, V2 and the height of R in V6 (R2= ) with a significant or marginally significant relation (B= , p= ). The width and depth of Q in V6 had a significant (B=7.3, p=0.02 and B=19.3, p=0.01) relation with the inferolateral segments when corrected for potential confounders (R2=0.19 and 0.20). Very strong correlations between the characteristics of V1 and V2 and the apical inferior segment (rs= , p 0.001) and apical lateral segment (rs= , p= ) were found for patients with an occlusion of the CX. Conclusion: In the chronic phase of non-anterior wall MI tall R waves and other characteristics of R in V1 and V2 are not related to the basal inferior segment, as previously thought, but to the extent of transmurality in the lateral segments. The depth and width of Q in V6 indicates the extent of transmurality in the inferolateral segments. P2982 Relation of N-terminal pro-b-type natriuretic peptide levels and their prognostic impact in acute STEMI patients treated with PCI to obesity status S.N. Hong 1, M.H. Jeong 1,Y.K.Ahn 1, S.C. Chae 2,Y.J.Kim 3, M.C. Cho 4, I.W. Seong 5,C.J.Kim 6, K.B. Seung 7,S.J.Park 8 on behalf of Korea Acute Myocardial Infarction Registry. 1 Chonnam National University Hospital, Gwangju, Korea, Republic of; 2 Kyungpook National University Hospital, Daegu, Korea, Republic of; 3 Yeungnam University Hospital, Daegu, Korea, Republic of; 4 Chungbuk National University Hospital, Cheongju, Korea, Republic of; 5 Chungnam National University Hospital, Daejon, Korea, Republic of; 6 Kyunghee University Hospital, Seoul, Korea, Republic of; 7 Catholic University Hospital, Seoul, Korea, Republic of; 8 Asan Medical Center, Seoul, Korea, Republic of Background: Obesity, as indexed by elevated body mass index (BMI), affects N- terminal pro-b-type natriuretic peptide (NT-proBNP) levels, with lower circulating levels in those with a higher BMI. To investigate the relationship between BMI and NT-proBNP level and resultant prognostic capacity in patients with acute STsegment elevation myocardial infarction (STEMI) to obesity status. Methods: A total of 2826 consecutive patients (62.5±12.4 years, male 74.8%) with STEMI who were registered in Korea Acute Myocardial Infarction Registry from Nov to Dec were enrolled. All of the patients underwent percutaneous coronary intervention (PCI). The patients were divided into three groups according to BMI [group I: BMI < 25 kg/m 2, n=1811; group II: BMI 25 kg/m 2, (group IIa: BMI kg/m 2, n=907; group IIb: BMI 30 kg/m 2, n=108)]. Primary study outcomes include in-hospital death (IHD), major adverse cardiac events (MACE: cardiac death, non cardiac death, MI, repeat PCI, and coronary artery bypass surgery) at 6 and 12 months after PCI. Results: Age, sex, glomerular filtration rate (GFR), and left ventricular ejection fraction (LVEF) were similar among three groups. NT-proBNP level was the lowest in group IIb (2157.2± pg/ml in group I, ± pg/ml in group IIa, 862.9± pg/ml in group IIb, p <0.001). The level of NT-proBNP was negatively correlated with BMI, GFR, and LVEF (r=-0.205, p<0.001; r=-0.242, p<0.001; r=-0.412, p<0.001, respectively) and positively correlated with age (r=0.401, p<0.001). NT-proBNP remained an independent predictor of MACE after correction for age, BMI, GFR, and LVEF. The level of NT-proBNP was an independent predictor of IHD (OR, 11.22, 95% CI , p=0.001), and 6 months (OR, 1.48, 95% CI , p=0.037) and 12 months MACE (OR, 1.52, 95% CI , p=0.016) in group I. Also, the level of NT-proBNP was an independent predictor of IHD (OR, 5.57, 95% CI , p=0.001) and 6 months (OR, 1.77, 95% CI , p=0.010), and 12 months MACE (OR, 1.88, 95% CI , p=0.003), in group II. Conclusion: Age, renal function, BMI, and LVEF affect significantly NT-proBNP levels in patient with acute STEMI. NT-proBNP retained an independent prognostic factor in patients with acute STEMI treated PCI to obesity status. P2983 Endothelin-1: a useful prognostic marker after acute myocardial infarction X. Freixa, A. Doltra, J.T. Ortiz, S. Argiro, E. Guasch, M. Heras, M. Jimenez, A. Betriu, M. Masotti. Cardiology Department.Thorax Institute. Hospital Clinic. University of Barcelona, Barcelona, Spain Introduction: High Endothelin-1 (E-1) levels have been linked to poor clinical outcomes after myocardial infarction (MI). Vasoconstriction of the coronary microcirculation seems to be the underlying mechanism. However, the relationship between E-1 levels and microvascular integrity in the setting of MI has not been analyzed. Objectives: To assess the effect of E-1 on microvascular integrity, necrosis volume, left ventricular ejection fraction (LVEF) and myocardial savage (M-sav) in evolving MI. Methods: We measured E-1 levels acutely (6-24 hours) in a consecutive series of 127 patients (pts) presenting with a first MI. MRI was performed within 1 week following presentation and microvascular obstruction (MO), necrosis volume and LVEF was assessed. M-sav was defined as the % of angiographic area at risk by the BARI score that spared necrosis on the MRI. Results: Mean age was 60.9±11,8 years and 94 (80%) were males. MI location was anterior in 47.2%. As shown in table, high E-1 levels were associated to admission Killip 2, higher prepci TIMI 0, worse postpci MBG and higher mortality at 30 days. MO was documented in 48%. High E-1 values were also associated with MO and worse M-sav while no significant correlation was obtained with necrosis volume and LVEF. Compared to Troponin I and CKMB peak values, E-1 levels showed better correlation with MO, M-sav, Killip on admission, MBG postpci and mortality at 30 days. Endothelin-1 CK-MB peak Troponin-I (pg/ml) (ng/ml) (ng/ml) Killip on admission p=0.011 p=0.017 p=ns I 6.6± ± ± >II 9.01± ± ± MBG postpci p=0.004 p=ns p=ns ± ± ± ± ± ± Mortality at 30 days p=0.003 p=0.026 p=ns Yes 10.83± ± ± No 7.60± ± ± Microvascular occlusion p<0.001 p=ns p=ns Yes 8.34± ± ±316 No 5.33± ± ±137 Myocardial savage p=0.03 p=0.04 p=ns <10% 6.51± ± ±146.1 >10% 8.31± ± ±39.9 Conclusions: In humans, high E-1 levels after MI are closely associated with the presence of MO and worse M-sav. E-1 assessment renders prognostic information, independent from that provided by LVEF and necrosis volume. P2984 Increased rho kinases (ROCKs) activity in patients with acute coronary syndrome C.M. Yu 1,M.Dong 1,R.J.Li 1, M. Zhang 1, Q.H. Zhang 1,J.K.Liao 2. 1 The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China, People s Republic of; 2 Vascular Medicine Research Unit, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America Background: Rho-kinases (ROCKs) are the first and the best-characterized effectors of the small G-protein RhoA, and have been demonstrated to be involved in hypercontraction of vascular smooth muscle and may play a pathophysiological role in acute myocardial ischaemia. This study examined if ROCKs activity is increased in patients with acute coronary syndrome (ACS). Methods: 165 patients admitted for ACS and 35 matched controls were studied. Patients were divided into 3 groups: ST elevation myocardial infarction (STEMI) (n=70), non-st elevation myocardial infarction (NSTEMI) (n=70) and unstable angina (UA) (n=25). ROCKs activity was determined by phosphorylation of myosin binding subunit in leukocytes from peripheral blood. Results: ROCKs activity was increased in STEMI (3.33±0.94), NSTEMI (3.37±1.05) and UA groups (2.52±0.59) when compared with controls (1.54±0.45, all p<0.001). Furthermore, ROCKs activity was higher in STEMI and NSTEMI than the UA group (both p<0.001). Univariate analysis showed that ROCKs activity correlated positively with Troponin T, creatinine, ejection fraction on admission, WBC, LDL- and total cholesterol, smoking status, presence of heart failure features on admission and severity of coronary artery disease. Multiple linear regression confirmed that LDL-cholesterol (β=0.310, p=0.008), creatinine (β=0.294, p=0.014), severity of coronary artery disease (β=0.325, p=0.007)

176 476 The wide world of coronary artery disease and smoking status (β=0.321, p=0.03) were independent predictors of elevated ROCKslevels(R 2 =0.421). Conclusion: ROCKs activity was increased in patients with ACS, in particular in those with myocardial infarction. The pathophysiological role of ROCKs activity in ACS warrants further investigation. P2985 Low hs-crp and von Willebrand factor levels and high brachial artery flow-mediated dilation corrrelates with the spontaneous reperfusion in STEMI patients I. Urazovskaya, D. Skrypnik, E. Vasilieva, A. Shpektor. Moscow University of Medicine and Dentistry, Moscow, Russian Federation Purpose: Endothelial dysfunction is one of the important risk factors of coronary artery disease. However it role remains unclear in the development of acute coronary syndrome. In this study we investigated endothelial function in patients with ST-elevation acute myocardial infarction. (STEMI). Methods: We included 72 patients hospitalized with STEMI. Endothelial function was assessed using the brachial artery flow mediated dilation (FMD) test. We also determined the plasma levels of tissue-plasminogen activator (t-pa) and it s inhibitor (PAI-1), von Willebrand factor (vwf), soluble vascular adhesive molecule (svcam), using the ELISA method, endothelin and NO concentrations using colorimetric detection with Griess Reaction and high sensitivity C-reactive protein (hs-crp) using the nephelometric method. Blood collection, FMD test and angiography were performed upon admission. Results: According to the results of angiography, all patients were divided into two groups. Group I (n=29) included patients with spontaneous reperfusion, GroupII (n=43) consisted of patients with total occlusion of the infarction-related artery. We found that the percentage of brachial artery dilation registered in the FMD test was significantly higher in GroupI than in GroupII (12.9±7.82 vs. 6.37±4.60, respectively; p= ). The levels of vwf and hs-crp in Group I patients were lower than those in Group II (0,98±0,42 vs. 1,23±0,29, respectively; p=0.027)and (6,27±4,3 vs. 42,1±61,1 respectively; p=0,046). In contrast, there were no significant differences between the groups in the plasma levels of PAI-1, t-pa, svcam-1, P-selectin, NO and endothelin. Conclusion: Spontaneous reperfusion in STEMI patients is associated with low plasma levels of hs-crp and von Willebrand factor and high flow mediated dilation of brachial artery. P2986 High sensitivity C-reactive protein kinetic and prognosis in patients with ST-elevation acute myocardial infarction S.S. Makrygiannis, M. Zairis, G. Tsiaousis, C. Vogiatzidis, P. Smilakos, Z. Katidis, C. Garefalakis, P. Batika, E. Adamopoulou, S.G. Foussas. Tzanio Hospital, Piraeus, Greece Purpose: It has been reported that increased levels of hs C-reactive protein (hs- CRP) are related with adverse long-term prognosis in the setting of ST-elevation acute myocardial infarction (STEMI). In previous studies the timing of CRP levels determination varies widely. In the present study, serial hs-crp measurements were performed in order to investigate if any of the measurements is superior, regarding long-term clinical outcome. Methods: 847 pts who receive intravenous thrombolysis in the first 6 hours from the index pain were studied. Hs-CRP levels were determined at presentation, at 24h, 48h, and 72h. Median follow-up time was 3.5 years. New non-fatal myocardial infarction (MI) and cardiac death (CD) were the study end-points. Results: By the end of follow-up, CD was observed in 22.4% and MI in 16.1% of pts. Hs-CRP levels were found to be increasing during the first 72h. In particular the median hs-crp value was 4.28, 9.21, 21.8 and 25.2 mg/l upon presentation, 24h, 48h and 72h thereafter respectively. By multivariate Cox regression analysis it was shown that CRP levels at presentation are an independent predictor for both end points (RR=2.8; p=0.002 and RR=2.1; p=0.03 for nnfmi and CD, respectively) while CRP levels at 24h did not yield statistically significant results (nnfmi: RR=1.4; p=0.4 and CD: RR=1.1; p=0.8). The relative values were at 48h nnfmi: RR=1.2; p=0.5, CD: RR=3.2; p=0.007 and at 72h: nnfmi: RR=1.6; p=0.3, CD: RR=3.9; p<0.01. Conclusions: Hs-CRP levels at presentation represent an independent predictor for both fatal and non-fatal events during long-term follow-up. Hs-CRP levels at 48h and 72h, which are close to peak CRP, independently predict only cardiac death. P2987 Matrix metalloproteinase-2 and oxidative stress in patients with STEMI treated by primary PCI J. Parenica 1, M. Goldbergova-Pavkova 2,P.Kala 1, M. Poloczek 1, J. Manousek 1, Z. Cermakova 1, O. Toman 1, J. Tomandl 3, D. Tomcikova 4, J. Spinar 1. 1 Faculty Hospital, Brno, Czech Republic; 2 Institute of pathophysiology, Medical Faculty MU, Brno, Czech Republic; 3 Institute of biochemistry, Medical Faculty MU, Brno, Czech Republic; 4 Institute of Biostatistics and Analysis, Masaryk University, Brno, Czech Republic Introduction: Reparative processes following myocardial infarction include inflammatory cell infiltration, activation of matrix metalloproteinases (MMPs), extracellular matrix remodelling and scar formation. The goal of the study was evaluation of MMP-2 serum activity early after MI and its association with signs of acute heart failure (AHF), left ventricle systolic dysfunction, in-hospital mortality and oxidative stress. Methods: 311 patients (75% male, mean age 62,7 years) with acute MI with ST elevations treated by primary PCI (without AHF 220 pts, with AHF 91 pts) were included (PROSPECT-STEMI substudy). Echocardiography was done 3-5 days after MI, left ventricular systolic dysfunction was assessed according to ejection fraction (EF) and end-diastolic volume corrected for BSA (EDV/BSA). MMP-2 (value B), Troponin I, BNP, NT-proBNP, malondialdehyd (MDA), TNF-alfa, vitamine A and E, uric acid were eveluated 24 hours after onset of chest pain. MMP-2 (value A) was also evaluated on admission before primary PCI, we counted difference of MMP-2 (value A-B). Left ventriculography was done before PCI and dp/dt/p and LVEDP were measured. Results: Median of levels of MMP-2 on admission was 1512 ng/ml (range ), median after 24 hours was 1179 (range ) (p<0.001). We did not find significant correlations between levels of MMP-2 (value A, B, A-B) and some biochemical and clinical parameters (BNP, NT-proBNP, troponin I, creatinine, uric acid, dp/dt/p, LVEDP, EDV/BSA, EF). No differences of levels of MMP-2 (value A, B, A-B) were found, if the patients were divided a) into two groups according to median of BNP, NT-proBNP, Troponin I, EDV/BSA, EF, b) into 3 groups according to EF ( 35%, 35%50%), c). into 2 groups according to chronic therapy by ACEI, betablockers, presence of AHF, one-month mortality. We found no significant differences in values of MDA, TNF-alfa, vitamine A and E and uric acid, BNP, NTproBNP, creatinine, Troponin I, LVEDP, EDV/BSA, presence of heart failure and one-month mortality in patients with either increase (26,4% of pts) or decrease (73,6% of pts) of MMP-2 values A and B. Conclusion: We determined levels of MMP-2 on admission and 24 hours after onset of chest pain in large homogenous group of patients with STEMI treated by primary PCI. We have not found any significant differences in levels MMP-2 dividing patients according to several biochemical and clinical parameters. We have not found any practical use of routine evaluation of MMP-2 levels in patients after STEMI. Further evaluation of possible determination of role of MMP-2 in LV remodelling processes is needed. P2988 Early statin treatment normalizes MMP-9 and MMP-2 activity and is associated with fewer thrombotic complications and left ventricular remodeling in acute Q-wave myocardial infarction patients O. Koval, A. Ivanov, G. Dzyak, P. Kaplan, A. Skoromnaya, O. Mararenko. State medical academy, Dnipropetrovsk, Ukraine It was previously proved by our investigations that frequency of thrombotic complications of Q-wave myocardial infarction (Q-MI) and level of left ventricle postinfarction remodeling (LVPR) was reliably defined by not only gelatinases absolute activity but their ratio. The aim was to investigate whether the early statin therapy in Q-MI pts changes the prognostically unfavorable indices of gelatinase activity ratio. Methods: In 64 Q MI (male -79.7%, 57.5±1.4 y.o.) patients (pts) admitted in 0 6 hours after symptom onset 67.2% pts started statin (st) therapy immediately at admission. Groups st (+) and st ( ) were comparable by age, sex and other known risk factors. Metalloproteinase (MMP)- 2, 9 activity evaluated by gelatin zymography with fibronectin (FN) degradation character like substrate of their activity detected simultaneously by Western blot analysis at 1st day, at 8th day and at 21st day. Results: MMP-9 activity (% of normal values) in st (+) group: 71.87± ± ±8.78; st ( ) group: 89.57± ± ± MMP-2 st (+) group: ± ±12.84 (p< 0.05 with the 1st day) ±27.34; st ( ) group: ± ±39.89 (p<0.05 with st (+) group) ±58. Favorable MMP-2 activity dynamics had been associated with reliably faster FN spectra normalization and native subunit content by the 21st day and reliable prothrombogenic FN spectra appearance decrease. MMP-9/MMP-2 activity ratio dynamics Study term Statin(+) Statin( ) 1st day 0.83± ±0.21 8th day 0.39±0.08 # 0.33±0.07** /## 21st day 0.82±0.25 ### 1.04±0.34*** /##### #p1= (for MMP-9/MMP-2st+ 1st and 8th day), **p2>0.5 (for MMP-9/MMP-2st+ and MMP- 9/MMP-2st- 8th day), ## p3>0.5 (for MMP-9/MMP-2st- 1st and 8th day), ***p4< (for MMP-9/MMP-2 st+ and MMP-9/MMP-2 st- 21st day), ### p5>0.5 (for MMP-9/MMP-2 st- 21st day), #### p5< (for MMP-9/MMP-2 st+ 21st day). Conclusion: Early statin assignment (1st day) in Q-MI pts characterized by reliable decrease of proteolysis activity, MMP-2 activity, MMP-9/MMP-2 activity ratio and FN degradation positive dynamics and associated with further favorable postinfarction course due to thrombotic complications frequency and pathological eccentric LVPR reduction.

177 The wide world of coronary artery disease 477 P2989 Cavotricuspid isthmus dependent flutter is associated with increased incidence of occult coronary artery disease J.P. De Bono, V.M. Stoll, A. Joshi, K. Rajappan, Y. Bashir, T.R. Betts. John Radcliffe Hospital, Oxford, United Kingdom Introduction: The aetiology of atrial flutter and fibrillation is complex. Although they share many clinical risk factors and potential mechanisms with atherosclerosis, an association between stable coronary artery disease and atrial arrhythmias has not been documented. To investigate this hypothesis we measured the incidence of asymptomatic occult coronary atheroma at in patients undergoing radiofrequency ablation. Methods: We carried out a retrospective analysis of coronary angiograms performed on patients presenting for elective ablation of arrhythmias with no history or symptoms of coronary artery disease. They were divided into three groups: Typical right atrial flutter (AFl), atrial fibrillation (AFib) and a matched control group undergoing ablation for either supraventricular tachycardia (SVT) or right ventricular outflow tract tachycardia (RVOT). Results: 138 patients were included (AFl 37, AFib 61, SVT/RVOT 40). Groups were evenly matched for age and risk factors for coronary disease. The incidence of asymptomatic, occult coronary atheroma was significantly greater in patients with AFl compared to either AFib or SVT/RVOT (AFl 54%, AFib 26%, SVT/RVOT 21%, p=0.005). In contrast there was no higher incidence of occult atheroma in patients with Afib. The majority of the atherosclerosis observed was mild nonobstructive plaque disease. Conclusion: There was a significantly greater incidence of coronary atheroma in patients undergoing ablation for atrial flutter. Patients undergoing ablation for AFib did not have a higher incidence of coronary atheroma than patients presenting for ablation of SVT/RVOT. This suggests that mechanism underlying the development of arterial atherosclerosis may be important in creating the substrate that allows right atrial flutter to develop. P2990 Is there an influence of advanced age on the results of percutaneous coronary interventions (PCI) in patients with ST-elevation myocardial infarction (STEMI)? Results from the ALKK PCI registry S. Tielke 1, H. Mudra 2, M. Hochadel 3,U.Zeymer 1,H.Darius 4, S. Kerber 5, K.E. Hauptmann 6, J. Senges 3, R. Zahn 1 on behalf of ALKK study group. 1 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Klinikum Neuperlach, München, Germany; 3 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 4 Vivantes Klinikum Am Urban, Berlin, Germany; 5 Rhön Klinikum, Bad Neustadt, Germany; 6 Krankenhaus der Barmherzigen Brüder, Trier, Germany Background: Advanced age is an important independent predictor of higher complication rates in most invasive procedures. However, there are little data on the age distribution and its influence on outcomes in patients presenting with non ST-elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary interventions (PCI). Methods: We analysed data from the prospective ALKK PCI Registry. Results: In PCIs in 7579 patients presenting with NSTE-ACS were performed at 42 hospitals. Mean age of the patients was 67.2 years, with a range of years. 43.8% of patients were >70 years old, 13.6% > 80 years and 0.4% > 90 years. Patient characteristics depending on age as well as clinical events in these patients are shown in the table. All >70y >80y >90y P for trend Women 27.2% 40.8% 54.5% 65.4% <0.001 Prior PCI 13.1% 15.1% 14.4% 3.8% Prior CABG 3.7% 5.5% 5.6% 0 <0.001 Cardiogenic shock 5.6% 6.7% 8.2% 11.5% Renal failure 11.9% 21.7% 29.4% 25.0% <0.001 Diabetes mellitus 18.2% 23.3% 22.0% 9.1% <0.001 Hospital events All cause death 6.1% 10.6% 14.0% 11.5% <0.001 Stroke/TIA 0.2% 0.4% 0.8% Re-myocardial infarction 1.0% 1.3% 1.0% Conclusions: In current clinical practice one third of patients suffering a STEMI and treated with ppci are older than 70 years. With increasing age the proportion of women, renal failure and cardiogenic shock is also increasing. In-hospital mortality and stroke rate is increasing with increasing age. P2991 Comparison of prognostic value of epicardial blood flow and early ST-segment resolution after primary angioplasty in acute myocardial infarction K. Ben Hamda, M. Hassine, W. Jomaa, S. Hamdi, M.A. Majdoub, F. Moatamri, H. Thawaba, K. Mzoughi, F. Betbout, F. Maatouk. Cardiology department, University Hospital, Monastir, Tunisia Background: TIMI scale is commonly used for angiographic assessment of reperfusion effectiveness and early risk stratification in patients treated with primary angioplasty for ST-elevation myocardial infarction (STEMI). Since STresolution analysis allows a noninvasive insight into the reperfusion status at the myocardial tissue level, it may be a better predictor of outcome after primary angioplasty. Aim: To compare the prognostic value of reperfusion effectiveness evaluation based on either epicardial blood flow assessment according to the TIMI scale, or ST-segment resolution analysis. Methods: 270 consecutive patients treated within 12 hours from onset of chest pain were studied. Based on the analysis of maximal ST-segment elevation/depression identified in a single ECG lead recorded after the procedure (max STE), patients were classified into groups of high versus medium/low risk. Independently, distinguished were groups with restored normal (TIMI 3) and abnormal (TIMI 0-2) final blood flow in infarct related artery. Results: The 30-day and one-year mortality rates were higher in high-risk max STE group (25% of all patients) than in the other patients (14.8% vs 2.5%, p<0.001 and 18.5% vs 5.4%, p<0.001 respectively). In subjects with restored TIMI grade 3 blood flow (82%), mortality at one-month and one-year was lower than in the group with abnormal final blood flow (3.1% vs. 15.6%, p=0.001 and 6.2% vs. 18.8%, p=0.005). Comparison in multivariate analysis revealed that max STE stratification but not final TIMI grade assessment remained an independent predictor of both, 30-day and one-year mortality (high vs. medium/low-risk category; OR 5.3, 95% CI , p=0.005, and OR 3.3, 95% CI , p=0.007, respectively). Furthermore, max STE proved to stratify the risk of death even in subgroup of patients with restored normal blood flow (OR 6.2, 95% CI , p=0.016, and OR 3.0, 95% CI , p=0.039, respectively). Conclusions: Analysis of extent of maximal ST-segment elevation or depression allows better prognosis of subsequent 30-day and one-year mortality than the assessment of final epicardial blood flow, stratifying risk of death even in a subgroup of patients with restored normal blood flow. P2992 A novel hospital discharge risk score system for the assessment of clinical outcomes in patients with acute myocardial infarction H.K. Kim 1, M.H. Jeong 1,Y.K.Ahn 1,Y.J.Kim 2,S.C.Chae 3, C.J. Kim 4, T.J. Hong 5,S.W.Rha 6,J.H.Bae 7, I.W. Seong 8. 1 Chonnam National University Hospital, Gwangju, Korea, Republic of; 2 Yeungnam University Hospital, Daegu, Korea, Republic of; 3 Kyungpook National University Hospital, Daegu, Korea, Republic of; 4 Kyunghee University Hospital, Seoul, Korea, Republic of; 5 Pusan Natoinal University Hospital, Busan, Korea, Republic of; 6 Korea University Hospial, Seoul, Korea, Republic of; 7 Konyang University Hospital, Daejon, Korea, Republic of; 8 Chungnam National University Hospital, Daejon, Korea, Republic of Background: The assessment of risk at the time of discharge could be a useful tool for guiding post-discharge management. The aim of this study was to develop a novel and simple assessment tool for the better hospital discharge risk stratification. Methods: Between Nov 2005 and Aug 2007, 4,635 hospital discharge patients with acute myocardial infarction (62.6±12.5 years, 71.0% males) were enrolled in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR). We added several risk factors for variables such as stroke or peripheral artery disease history, admission hyperglycemia and left ventricular systolic dysfunction. 4,353 (94%) patients were performed echocardiogram at the time of presentation or periprocedure, and left ventricular ejection fraction (LVEF) was checked in all patients. New risk score was constructed using the 6 independent variables related to the primary end point by utilizing a multivariable Cox regression analysis: Age (65-74: 1 point, >75: 2 points), Killip class (II: 1 point, III, IV: 2 points), serum creatinine ( 1.5 mg/dl: 1 point), no in-hospital percutaneous coronary intervention (1 point), LVEF <40% (1 point) and admission glucose ( 180 mg/dl: 1 point) based on the multivariate adjusted risk relationship. New risk score system was compared with the Global Registry of Acute Coronary Events (GRACE) postdischarge risk model for during 12-month clinical follow-up. Results: During one year follow up, all cause of death occurred in 247 patients (5.3%). The accuracy for one year mortality by GRACE and new risk score system was 0.77 area under the curve (AUC) (CI: ) and 0.83 (CI: ) respectively. A significant difference is existed (0.77 vs. 0.83, p<0.0001). New risk score (AUC: 0.79; CI: ) demonstrated a significant differences in predictive accuracy when compared with GRACE (0.79 vs. 0.73, p = ) for ST-segment elevation myocardial infarction (STEMI), And also for Non-ST segment elevation myocardial infarction (NSTMI) (0.86 vs 0.81, p = ). Conclusion: The new risk score system for AMI patients is a simple and better risk scoring system than GRACE hospital discharge risk model in the prediction of one-year mortality.

178 478 The wide world of coronary artery disease / Diabetes, obesity and hyperlipidaemi P2993 Utility of biomaker scoring system using multimaker approach as risk stratification modality in patient with Non-ST Elevation Myocardial Infarction (NSTEMI) J.S. Ko, M.H. Jeong, Y.G. Ahn, J.G. Cho, J.C. Park, J.C. Kang on behalf of Korea Acute Myocardial Infarction Registry Investigators. The heart center of chonnam national university hospital, Gwangju, Korea, Republic of Introduction: Various risk stratification system for non-st elevation acute myocardial infarction (NSTEMI) was proposed to date. Among them, TIMI risk scoring system had proven efficacy as bed side risk assessment modality. And then Biomarkers have emerged as interesting predictors of risk. The aim of this study was to identify the usefulness of the multiple biomarker approach including troponin I (TnI), C-reactive protein (CRP), NT probrain natriuretic peptide (NT pro- BNP) as predictor of adverse event. Methods: We included 1621 patients with NSTEMI in Korea acute myocardial infarction registry (KAMIR). Baseline measurement for TnI, CRP and NT-proBNP were performed. A positive biomarker test was considered upper than the 75th percentile of our population. The risk for major advance cardiac events (MACE) at 6 months follow-up was analysed. Results: 88 patients (9.5%) had MACE at 6 month follow up. In multivariate analysis, NT pro-bnp were predictors of adverse events [hazards ratio (HR): 2.85 ( ), P<0.001] but elevated CRP and TnI was not independent predictor of MACE. After adjusting for baseline characteristics, biomarker scoring that indicate the number of positive biomarker, from one to three point was associated with adverse events at 6 months [HR 4.09 (95%CI ), P<0.001]. When we divided patients by risk groups [Thrombolysis in Myocardial Infarction (TIMI) risk score], patients with two or three elevated biomarkers had higher event rates [P=0.004]. Conclusion: Biomaker scoring using multimarker approach based on TnI, CRP and NT-proBNP was independent predictor of MACE in patient with NSTEMI and can provide additional clinical information to TIMI risk score system. P2994 Cardiac Outcomes through Digital Evaluation (CODE) STEMI project R.A. Ducas, D.S. Jassal, R.K. Philipp, S.A. Hodge, E.R. Weldon, C.M.J. Schmidt, R.A. Grierson, J.W. Tam. University of Manitoba, Winnipeg, Canada Background: Guidelines for reperfusion strategies in acute ST elevation MI (STEMI) have recently been modified by the ESC in part to recognize the realities of delayed access to primary percutaneous coronary intervention (PPCI). We have developed a blended model of pre-hospital thrombolytic (PHL) therapy or transportation and activation of PPCI and report data from the first 6 months of initiation. Methods: In our urban centre of 658,700 people, emergency medical personnel were trained to perform and screen ECG s in acute chest pain to recognize suspected STEMI. ECG s were acquired in the field and transmitted digitally to hand-held devices carried by a cardiologist. The cardiologist coordinated care with the option of either PHL or direct transport for PPCI. Patients presenting during weekday hours ( ) as well as those with contraindication for PHL were sent preferentially for PPCI. Results: From July 21, 2008 to January 21, 2009, 118 calls were placed to the CODE STEMI project. Calls were excluded for failed transmission (5), absence of STEMI by ECG (51), absence of CP (2) and other (3). The remaining 57 patients (age 62±13; 68.% men) received PPCI (n=43), angiography without PPCI (n=3; 2 with normal coronaries, 1 with spontaneous reperfusion) or PHL (n=11). Peak CK was 1423±1185 Units, post infarction LVEF was 49.5±10.7%. Cardiogenic shock or cardiac arrest occurred in 14 patients. All but 1 of the 53 patients survived to hospital discharge. In PPCI, median time from first medical contact to reperfusion was 74 min (IQR 66-88). Thirty six of 43 (84%) of patients had PPCI within 90 min, while 40 (93%) had PPCI within 120 min. Fifteen of 18 patients received offhours PPCI in < 90 minutes from first medical contact. In those receiving PHL, median time from first contact to needle was 36 min (IQR 31-40). One patient had intracranial hemorrhage following PHL but survived with no neurologic deficit. Achievement of target time with PPCI (36/43 < 90 min, including 15/18 patients done afterhours) was more likely than achievement of target time with PHL (2/11 <30 min), Yates chi squared =15.0, p<0.0001). Conclusions: Through our blended therapy of digital transmission, direct communication with cardiologist and rapid coordinated service, we demonstrate that first medical contact time to reperfusion therapy in STEMI can be promptly achieved even in the early phases of the project. The creation and adoption of similar strategies in other urban centres would allow for achievement of ESC guideline times, particularly for PPCI, and regardless of time of day. DIABETES, OBESITY AND HYPERLIPIDAEMI P2995 Impact of diabetes mellitus on disease progression in non-stented coronary segments R. Byrne 1, R. Iijima 1, J. Mehilli 1,S.Schulz 1, A. Schoemig 2, A. Kastrati 1. 1 Deutsches Herzzentrum Muenchen, Munich, Germany; 2 1. Medizinische Klinik rechts der Isar, Munich, Germany Purpose: Patients with diabetes remain at higher risk of myocardial infarction and death in comparison with non-diabetic patients. Differential patterns of atherosclerotic disease progression may play a contributory role. We investigated this issue by performing serial quantitative coronary angiography (QCA) of the entire coronary tree. Methods: Patients underwent coronary stent implantation at 2 German centres between January 2003 and July Baseline and 2-year follow-up angiographic data were assessed off-line in a QCA core laboratory. Included segments were non-stented with reference vessel diameter 1.5 mm and mild atherosclerotic disease (stenosis 25-50%). Results: A total of 605 patients had paired baseline and 2-year angiographic data; 168 (27.8%) had diabetes. Secondary prevention medication uptake was high. Of 5486 non-stented segments, 1790 met criteria for inclusion. Overall late luminal loss was in non-diabetic patients versus 0.11 mm in patients with diabetes (p<0.001). In multivariate analysis presence of diabetes mellitus (OR 8.84; 95% CI ) and serum creatinine >0.9 mg/dl (OR 1.87; 95% CI ) were the only predictors of disease progression in non-stented segments. Conclusion: Significant differences in overall disease progression persist between non-diabetic and diabetic patients in spite of modern secondary prevention regimens. This may be contributory to the residual higher rates of myocardial infarction and death in diabetic patients. P2996 In-hospital metabolic changes and their consequences on short and long term outcome in patients with acute myocardial infarction R. Dragu, M. Kapeliovich, H. Hammerman. Rambam Health Care Center, Haifa, Israel Purpose: It has been demonstrated that albumin is a negative phase reactant and the development of hypoalbuminemia is in close relation to the inflammation status. In this light, the aim of the present study was to assess the prevalence and prognostic significance of changes in serum albumin levels along hospitalization in patients with acute myocardial infarction (AMI). Methods: We prospectively studied 1418 consecutive patients admitted with AMI and normal synthetic liver function. Serum albumin concentration was tested daily during hospitalization. The mean follow-up period was 24 months. Multivariate Cox models were used to assess the relationship between nadir albumin level and survival. Results: During hospitalization 54.5% of study population developed hypoalbuminemia. The mean nadir albumin was 3.38±0.58 g/dl (median 3.5, IQR ), 0.31 g/dl lower then admission levels (p<0.0001). In-hospital mortality according to nadir albumin quartiles (from lowest to highest) was: 21.9%, 4.8%, 2.3% and 2.3% respectively (p<0.0001). Long term mortality was: 30.2%, 10.1%, 5.5% and 3.9% respectively (p<0.0001). After adjusting for age, gender, diabetes mellitus, hypertension, ST-elevation AMI, anterior wall involvement, left ventricular systolic function and creatinine clearance, the nadir albumin in lowest quartile (<3.1 g/dl) remained a strong predictor for mortality (HR 3.23, 95% CI [ ], p<0.016). Conclusion: The development of hypoalbuminemia is frequent during hospitalization of patients with AMI and is strongly related to a worse short and long term outcome.

179 Diabetes, obesity and hyperlipidaemi 479 P2997 Prevalence of newly detected abnormal glucose regulation in routine catheterisation laboratory patients with known or suspected coronary artery disease R. Doerr 1, S.G. Spitzer 1,J.Stumpf 1, W. Otter 2, D. Tschoepe 3, L. Heinemann 4, W. Hunger-Dathe 5,B.Kulzer 6, T. Lohmann 7, O. Schnell 8. 1 Praxisklinik Herz und Gefaesse, Dresden, Germany; 2 ZIM Center for Internal Medicine, Unterschleissheim, Germany; 3 University Heart- and Diabetes-Center, Bad Oeynhausen, Germany; 4 Profil Institute, Neuss, Germany; 5 University Clinic, Jena, Germany; 6 Diabetes Center, Bad Mergentheim, Germany; 7 Dresden-Neustadt Hospital, Dresden, Germany; 8 Diabetes Research Institute, Munich, Germany Aims and Methods: The aim of the study was to analyse abnormal glucose regulation in routine cath lab pts. 764 pts (524 male, 240 female, mean age 68±9 yrs), who were referred for coronary angiography (CA), were assessed with an oral glucose tolerance test (OGTT). Pts with a history of diabetes mellitus (DM) or abnormal glucose regulation were excluded from the study. 654 pts underwent elective CA and 110 pts CA in acute coronary syndrome (ACS). Definition of coronary anatomy: no CAD; CAD lesions < 50%; 1-VD, 2-VD, 3-VD = 1-, 2- or 3- vessel disease. Definition of glucometabolic state: Normal; IFG = impaired fasting glycaemia; IGT = impaired glucose tolerance; DM = diabetes mellitus. Results: In pts with elective CA, the prevalence of normal glucose tolerance decreased with the progression of CAD (p<0.001), whereas the prevalence of IGT (p=0.02) and DM (p=0.03) increased respectively. A high prevalence of abnormal glucose regulation was also detected in pts with an ACS (n = 110). The following table presents results of pts with elective CA (n=654). CAD progression and glucometabolic state Elective group Normal (n = 330) IFG (n = 8) IGT (n = 236) DM (n = 80) No CAD (n = 35) 71.4% 2.9% 22.9% 2.9% CAD < 50% (n = 121) 62.8% 3.3% 28.1% 5.8% 1-VD (n = 147) 52.4% 0.7% 32.0% 15.0% 2-VD (n = 152) 43.4% 1.3% 42.8% 12.5% 3-VD (n = 199) 43.2% 0.0% 41.2% 15.6% p-value (for trend) p < n.s. p = 0.02 p = 0.03 Conclusions: In routine cath lab pts without a history of DM, the prevalence of abnormal glucose regulation was approximately 50% for both elective and acute pts. 12% of the elective and 17% of the acute group presented with DM. In the group with elective CA, the prevalence of normal glucose tolerance decreased with the progression of CAD, whereas the prevalence of IGT and DM increased respectively. The high prevalence of IGT (app. 40% in elective and acute pts) with advanced 2-VD and 3-VD indicates that not only DM but also IGT may be regarded as a CAD equivalent. The results emphasize the need to perform an OGTT in pts without known DM, who undergo an elective coronary angiography or a coronary angiography in the acute setting. P2998 Low HDL cholesterol. An independent risk factor of long term mortality in patients with acute coronary syndromes: results of the MITRAplus registry F. Towae, C. Juenger, U. Zeymer, R. Zahn, J. Senges, A.K. Gitt. Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany Background: Sub-group analyses of randomized trials have shown an impact of HDL cholesterol levels on long-term mortality in patients with acute coronary syndromes. However little is known about the impact of HDL cholesterol levels on long-term outcome of patients with acute coronary syndromes in clinical practice. Methods: Between 1998 and 2005, consecutive patients with acute coronary syndromes were enrolled in the MITRAplus registry (Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry). We analysed the influence of HDL cholesterol levels on hospital and 1-year mortality of patients with acute coronary syndromes. We compared patients with high HDL cholesterol levels (>45 mg/dl for female and >40 mg/dl for male) and patients with low HDL cholesterol levels (<45 mg/dl for female and <40 mg/dl for male). Results: Patients with low HDL cholesterol more often had concomitant diseases as well as a history of cardiovascular diseases. After correction for differences in Table 1. Results Parameter Low HDL High HDL p-value (n=5855) (n=9829) Age [years], median < Female gender [%] n-s. Prior MI [%] < 0.01 Prior PCI/CABG [%] < 0.01 Diabetes [%] < Hypertension [%] < LDL Cholesterol [mg/dl] < HDL Cholesterol [mg/dl] <0.001 STEMI [%] n.s. Hospital Mortality [%] < year Mortality [%] in patients discharged alive < patients characteristics and treatment using logistic regression analysis, patients with HDL >40/45 mg/dl have shown a 33% (OR 1.33, 95% CI ) lower long-term mortality compared to patients with lower HDL. Conclusion: Independent of LDL cholesterol levels and other cardiovascular risk factors, low HDL cholesterol is an independent risk factor for increased long-term mortality in patients with acute coronary syndromes in clinical practice. P2999 Among patients with acute myocardial infarction, does time from symptom onset influence the impact of hyperglycemia as a risk factor? J.C. Nicolau, R.R. Giraldez, C.V. Serrano, F.F. Lima, M. Franken, F. Ganem, R.C. Moraes, K.D. Rosa, C.C.F. Fernandes, L.M. Baracioli. Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil Purpose: The window between pain beginning and hospital arrival in pts with acute myocardial infarctio (AMI) varies widely, being unknown whether that variability could influence the role of glucose level as a risk factor in this population. The aim of this study was to verify the prognostic role of admission glucose level according to time interval between symptom onset and hospital arrival. Methods: AMI pts (n=1537), included prospectively in a databank, were divided according to the time between symptom onset: up to 24 hours (Group I, n=675 pts), >24-48 hours (Group II, n=438), >48-72 hours (Group III, n=180), >72 hours (Group IV, n=244). Univariable and multivariable analyses were applied as indicated, and ROC curves were developed in order to analyze the accuracy of glucose level as a risk factor for mortality in each group. Results: The mean (±SD) values for glycemia (mg/dl) were 153±81, 132±59, 130±65 and 132±63 respectively for Groups I, II, III and IV (P<0.001 for the trend; P<0.001, P=0.001 and P=0.001 respectively for the comparisons between Group I and Groups II, III and IV). There were no significant differences among the groups regarding age, gender, dislypidemia, relatives with coronary artery disease, diabetes, smoking and arterial hypertension; significant differences between the groups were detected for previous AMI (P=0.049) and history of heart failure (P=0.029). By logistical regression analyses, glucose level correlations with mortality were as follows: for Group I Odds-Ratio (OR) = 1.005, P<0.001; for Group II, OR = 1.006, P=0.007; for Group III, OR = 1.003, P = 0.451; for Group IV, OR = 1.003, P = Models adjusted for previous AMI and history of heart failure showed similar results. The areas under the ROC curves for each group are depicted in the table. Areas under the curves (AUC) AUC ± SE Group I 0.640±0.037 Group II 0.683±0.041 Group III 0.663±0.059 Group IV 0.607±0.055 P-Value SE = standard error. Conclusions: The accuracy of glucose level to predict in-hospital deaths is independent of the time between the pain beginning and blood sample collection. P3000 Admission glycaemia in non-diabetic acute coronary syndrome patients: a marker of acute stress or of chronic glucose metabolism impairment? P.F. Monteiro, S. Monteiro, E. Jorge, R. Baptista, P. Mendes, R. Teixeira, N. Antonio, F. Goncalves, M. Freitas, L.A. Providencia. University Hospital, Coimbra, Portugal Introduction: Admission glycaemia (AG) is an important outcome predictor in acute coronary syndrome (ACS) patients. However, a question remains: is AG a marker of acute stress or is it mainly an acute signal of a more chronic glucose metabolism imbalance? Aim: To evaluate, in patients not known to be diabetic, admitted for ACS and submitted to an oral glucose tolerance test (OGTT) during hospital stay, if there is a relationship between AG and chronic glucose metabolism, as assessed by OGTT. Population and methods: Retrospective analysis of 259 patients not known to be diabetic, admitted for ACS and submitted to OGTT during their hospital stay. Results: After OGTT performance, 79 patients (30.5%) had a normal glucose metabolism, while 92 (35.5%) showed impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and 88 (34.0%) where diagnosed as diabetics. When this population was stratified by AG quartile, there was a significant decrease of patients with normal glucose metabolism from the lower to the higher AG quartile, the opposite occurring with the number of diabetics (as determined by the OGTT) Table I. Only 7.6% of patients in the highest AG quartile ( 136 mg/dl) had a normal chronic glucose metabolism, clearly showing that AG is seldom a marker of acute stress and mainly an acute indicator of glucose dysmetabolism, although with a negative predictive value higher than the positive one, as most of the diabetics identified by the OGTT (53.6%) were not in the highest AG quartile. However, AG failed to accurately predict which patients had an OGTT result compatible with IFG or IGT.

180 480 Diabetes, obesity and hyperlipidaemi Table I. Results Admission glycaemia quartiles (mg/dl) Normal IFG/IGT Diabetes <101 (33/79) 41.8% (21/92) 22.8% (9/88) 10.2% [101; 115[ (23/79) 29.1% (26/92) 28.3% (15/88) 17.0% [115; 136[ (17/79) 21.5% (26/92) 28.3% (23/88) 26.1% 136 (6/79) 7.6% (19/92) 20.7% (41/88) 46.6% p<0.001 (Chi-square). Conclusions: In ACS patients without a previous history of diabetes, AG is not a marker of acute stress, but mainly an acute indicator of chronic glucose metabolism impairment. This result, never before described in an ACS population, may contribute to a better understanding of the role of metabolism in acute ischemia and thus to a better future clinical management of these patients. P3001 Multidisciplinary approach for diabetic patients with ischemic heart disease S. Nodari, A. Manerba, G. Milesi, C. Maiandi, A. Vaccari, M. Triggiani, G. Caretta, S. Frattini, M. Metra, L. Dei Cas. University of Brescia, Brescia, Italy Background: In the world, nearly 1/3 of the patients (pts) admitted for acute coronary syndrome (ACS) has diabetes. These pts still have a poor outcome despite improvements in coronary care. Aim of the Study: We assumed that employing more resources into the management and education of pts with diabetes would have translated into long term benefits after discharge. Therefore we prompted the proposal for the Day-Hospital Ischemia and Diabetes (DID) Pilot Study, a randomized, controlled study to examine the effectiveness of case-managed diabetes care using a multidisciplinary team approach in pts with diabetes admitted to manage concomitant acute coronary syndrome. Methods: We enrolled 445 consecutive diabetic pts (165 F, 280 M; 66.33±8.9 y) admitted to Intensive Coronary Care for ACS from January1st to June 30th Pts were randomized to multidisciplinary -cardiology/endocrinology- care (DH group) or usual care -cardiology- care (control group) at the time of their discharge from the ward. DH pts were scheduled for outpatient visit every six months or more frequently as required by pts clinical conditions. Targets of therapy in DH pts were: blood pressure was 130/80mmHg, LDL-C level was <100 mg/dl, and HbA1c <7%. Minimum goal of 30 minutes of moderate-intensity aerobic activity 4 times/week was also required. The primary endpoint of the analysis was all cause mortality. Secondary endpoints were: Cardiovascular (CV) mortality, myocardial infarction (MI), percutaneous coronary intervention (PCI) and bypass surgery (CABG). All pts were followed-up for 84±7 months. Results: Pts in the control group received less evidence based medications compared with the DH group (at the end of follow-up: aspirin and/or clopidogrel 73,9% vs 56,3% p=0.0114; statins 69,6% vs 40,7% p=0.0259; beta-blockers 78,3% vs 40,7% p=0.0317; and angiotensin enzyme inhibitors 66,7% vs 38,8% p=0.0168). Compared to controls, DH pts showed lower HbA1c (-9,18%; p=0.05), systolic blood pressure (-11,14%; p=0.0034), diastolic blood pressure (-1,77%; p=0.001), and heart rate (-6.9%; p=0.0217). The all cause mortality rates were 30,05% and 17,39%, in controls and DH pts, respectively (p=0,0315). The CV mortality, MI, PCI and CABG rates were 22,34% vs 11% (p<0,02); 21,28% vs 2,9% (p=0,0216); 7,71% vs 4,35% (p=0,32); and 0,27% vs 5,8% (p<0,0001), respectively. The risk-adjusted odds ratios for all cause mortality (control group: referent) was 1.20 (95% CI, ; p=0.02). Conclusion: Comprehensive education and therapy using a multidisciplinary approach should be utilized in diabetic patients with ischemic heart disease. P3002 Abdominal obesity and outcomes after acute coronary syndromes S. Nabais, S. Rocha, A. Gaspar, S. Ribeiro, J. Costa, P. Azevedo, M. Alvares Pereira, A. Correia. Sao Marcos Hospital, Braga, Portugal Background: A multitude of studies have described an inverse association between body mass index (BMI) and mortality in patients (pts) with acute coronary syndromes (ACS). However, waist circumference (WC) may be a better marker of cardiovascular risk than BMI, and there is a paucity of data on its impact on prognosis after an ACS. The aim of this study was to analyze the impact of WC on outcomes after an ACS. Methods: We prospectively evaluated 554 consecutive pts with ACS admitted to a Coronary Care Unit. We compared clinical and laboratory characteristics, management, and outcomes of pts classified as increased waistline (WC >88/102 cm for women/men; n=231, 41.7%) or normal (n=323, 58.3%). Clinical end points were death or myocardial infarction (MI) through 6 months. Results: Patients with increased WC were older (66.4±12.9 vs 60.3±14.2 years, p<0.001); had higher BMI (29.8±4.0 vs 25.8±2.9 kg/m 2,p<0.001); more often had hypertension (79.2% vs 57.9%, p<0.001), diabetes (38.1% vs 21.4%, p<0.001), dyslipidemia (62.8% vs 48.3%, p=0.001), and anaemia (28.1% vs 16.1%; p=0.001); were less frequently smokers (17.3% vs 34.4%; p<0.001); and presented less often with ST-segment elevation (38.5% vs 48.3%, p=0.024). Outcomes at 6 months were similar in the increased WC and normal WC groups: mortality, 5.3% vs 5.4% (p=1.0); death/mi, 13.7% vs 10.1% (p=0.22); there was BMI <25 kg/m 2 BMI kg/m 2 BMI 30 kg/m 2 p for trend WC 88/102 cm 7.9% (10/126) 11.7% (19/162) 4.5% (1/22) 0.39 WC >88/102 cm 27.6% (8/29) 8.8% (7/80) 12.6% (14/111) Stratification of 6-month death/mi rates (%, number of patients) according to BMI and WC. a non-significant trend to increased ocurrence of MI at 6 months (9.7% vs 5.7%, p=0.095) among pts with increased WC. Stratification of outcomes according to both BMI and WC (Table) showed that a high WC was associated with increased 6-month death/mi rates in pts with BMI <25 kg/m 2, which identified a subgroup of high-risk pts, compared with pts with both high WC and BMI values. Conclusions: Increased WC is a frequent finding and is associated with metabolic risk factors in pts with ACS, but is not an independent predictor of adverse events in this population. Patients with high WC but normal BMI, which probably reflects the presence of visceral obesity with low muscle mass, are at increased risk of adverse events after an ACS. P3003 Copeptin predicts and explains the association between IGFBP-1 and cardiovascular events in patients with type 2 diabetes and myocardial infarction L.G. Mellbin 1,K.Brismar 2, L. Ryden 1, N.G. Morgenthaler 3, J. Ohrvik 1, I.B. Botusan 2, S.B. Catrina 2. 1 Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 2 Department of Molecular Medicine and Surgery, Stockholm, Sweden; 3 Research Department, BRAHMS AG Biotechnology Centre, Berlin, Germany Bakground: High levels of the IGF Binding Protein-1 (IGFBP-1) are associated with impaired prognosis in patients with type 2 diabetes (DM) and acute myocardial infarction (MI). Copeptin, a surrogate marker for vasopressin, is a novel cardiovascular prognostic predictor. Infusion of vasopressin increases IGFBP-1 in humans. The present study analyzed the relation between copeptin and IGFBP-1 and their impact on the prognosis in patients with DM and MI. Methods: Copeptin and IGFBP-1 was analysed at the time for hospitalisation in 393 patients with type 2 DM and MI (a subgroup from the DIGAMI 2 trial). No patient was lost to follow and all endpoints were independently adjudicated. Multiple Cox proportional hazard regression was used to study the relation between copeptin, IGFBP-1 and cardiovascular (CV) events (cardiovascular death, reinfarction and stroke) and to adjust for a number of possible confounders of which only age was of significant importance. Results: There was a positive correlation between the levels of copeptin and IGFBP-1 (Spearman s rank correlation r = 0.53; p<0.001). During a median follow-up of 2.1 years 95 (24%) patients died, 77 of cardiovascular causes. Fiftynine (15%) patients had a nonfatal reinfarction and 25 (6%) a nonfatal stroke. The age adjusted Hazard Ratio (HR) for CV mortality was 1.32 (95% CI ; p = 0.05) for log IGFBP-1 and 1.33 (95% CI ; p = 0.008) for log copeptin. The age adjusted HR for CV events was 1.06 (95% CI ; p = 0.55) for log IGFBP-1 and 1.36 (95% CI ; p < 0.001) for log copeptin. Conclusions: This study shows that copeptin, a surrogate marker for vasopressin may, at least partially, explain the prognostic impact of IGFBP-1 in patients with type 2 DM and MI. Since copeptin is an independent predictor for fatal and non-fatal cardiovascular events it becomes of interest to study agents decreasing the action of vasopressin as a possibility to improve the serious prognosis in this category of patients. P3004 Familial combined hyperlipidemia in very young myocardial infarction survivors (below or equal 40 years of age) G. Goliasch 1, H. Blessberger 1,D.Azar 1, O. Wagner 1, K. Huber 2, K. Widhalm 1, G. Sodeck 1, G. Maurer 1, M. Schillinger 1, F. Wiesbauer 1. 1 Medical University of Vienna, Vienna, Austria; 2 Wilhelminen Hospital, Vienna, Austria Purpose: Myocardial infarction (MI) in very young individuals is a rare disease associated with an unfavourable prognosis. Familial combined hyperlipidemia (FCHL) increases the risk for MI in individuals below 60 years, however, its role in very young MI patients 40 years is not as well established. We investigated the prevalence and impact of FCHL in these very young MI patients. Methods and Results: We prospectively enrolled 102 consecutive MI survivors ( 40 years) from two high volume cardiac catheterization centres. Patients were frequency-matched for age, gender, and centre to 200 hospital controls free from coronary heart disease. MI patients were invited to send family members for FCHL screening. Overall, 37 families were screened. FCHL was diagnosed using a nomogram, which takes into account total cholesterol, triglycerides, and Apo B100 levels. Thirty-eight MI patients (38%) and five controls (2.5%) displayed the FCHL phenotype, 21 of these MI patients sent family members for screening, and FCHL was confirmed in 16 families (76%). The FCHL phenotype was associated with a 24-fold increased adjusted risk for MI (95% CI , p<0.001). Of all lipid parameters, VLDL-cholesterol and non-hdl-cholesterol were most strongly associated with MI. Conclusions: The present study suggests that the FCHL phenotype seems to be a major risk factor for the occurrence of MI at a very young age. It remains to

181 Diabetes, obesity and hyperlipidaemi 481 be determined whether this excessively increased risk can be favourably modified by therapeutic interventions. P3005 Is the impact of hyperglycemia as a risk factor homogeneous across different presentations of acute coronary syndromes? J.C. Nicolau, M. Franken, F.G. Lima, L.M. Baracioli, C.V. Serrano Jr, R.R. Giraldez, F. Ganem, R.T. Ladeira, M.D. Andrade, R.C. Moraes. Heart Institute (InCor) - University of São Paulo Medical School, São Paulo, Brazil Purpose: Hyperglycemia is an important risk factor for in-hospital mortality in patients with acute coronary syndromes (ACS). However, it is not clear if it is equally important across the different presentation forms of ACS, aim of this study. Methods: We analyzed 2032 patients with ACS included prospectively in a databank. From this population, 291 had unstable angina (UA - mortality rate of 1.37%), 807 non-st-elevation myocardial infarction (NSTEMI - mortality rate of 8.9%), and the remaining 934 ST-elevation myocardial infarction (STEMI - mortality rate 11.6%). The role of glucose level as a risk factor for in-hospital death was analyzed in each one of the groups, and a formal interaction analysis for glucose level and type of acute coronary syndrome regarding mortality was also developed. The statistical analyses utilized Logistic Regression, Mann-Whitney, ANOVA and Bonferroni test as indicated. Results: The mean glucose level was 130.5±76.2 mg/dl for the UA group, 133.4±65.9 mg/dl for the NSTEMI and 146.5±74.2 mg/dl for the STEMI (P<0.001 for the comparison between the groups; P<0.05 for the comparisons between STEMI-UA and STEMI-NSEMI; P=NS for the comparison between NSTEMI and UA). The mean glucose levels for patients that died or survived the in-hospital phase are depicted in the table. There was a clear interaction between glucose level as a risk factor for mortality and the type of ACS (P<0.001). Hyperglycemia as a risk factor in ACS Mean glucose ± SD (deceased) Mean glucose ± SD (survivors) P-value UA 91.2± ± NSTEMI 157± ± STEMI 179.8± ±70.7 <0.001 ACS = acute coronary syndromes, UA = untable angina, NSTEMI = non-st-elevation myocardial infarction, STEMI = ST-elevation myocardial infarction. Conclusions: The impact of glucose level as a risk factor for in-hospital mortality is not uniform across the different forms of ACS. P3006 Hyperglycemia treatment in the setting of acute coronary syndromes: the outcome of the Dutch nationwide questionnaire V.A. Umans, M. De Mulder, J.H. Cornel. Medical Center Alkmaar, Alkmaar, Netherlands Background: Hyperglycemia is common among patients admitted with Acute Coronary Syndromes (ACS) and is associated with inferior clinical outcomes. Clear guidelines on treatment of hyperglycemia in myocardial infarction have not been developed yet, partly due to lack of sufficient evidence. The purpose of this study is to describe current glucose management in ACS patients in The Netherlands. Methods: We designed a multiple-choice questionnaire that was ed to all 94 independent cardiology departments of every one of the 114 hospitals within The Netherlands. We interviewed cardiologists about their specific hospital setting, the presence, content and actual use of a dedicated hyperglycemia protocol in the setting of ACS. Results: 94 questionnaires were returned (response rate 100%). Only 32% of the respondents reported to have a routinely applied, dedicated hyperglycemia protocol in the setting of ACS. An admission glucose of 13.0 mmol/l is considered a stress value by 60% of respondents. Treatment of hyperglycemia is postponed until after the acute phase (i.e. after > 6 hours) in 41% of the cardiology departments and in 76% HbA1c is not routinely measured before discharge. In conclusion: Only a minority of Dutch cardiology departments have a routinely applied, dedicated hyperglycemia protocol for patients admitted with ACS. Different views exist on the interpretation of admission hyperglycemia in patients without previously diagnosed diabetes. Dedicated protocols with well established treatment goals that allow early treatment are mandatory in order to improve metabolic regulation. P3007 Serum Apolipoprotein J profile after myocardial infarction J. Cubedo 1, T. Padro 1, X. Garcia-Moll 2,L.Badimon 1. 1 Barcelona Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2 Hospital de Sant Pau, Barcelona, Spain Purpose: Apoprotein J/clusterin (ApoJ) is an HDL associated glycoprotein that has been related to anti-inflammatory, cytoprotective, and anti-apoptotic properties, including cardiomyocyte protection against ischemia-induced cell death. Clinical and experimental evidence suggest that HDL might lose proteins with antiflamatory and cytoprotective properties during acute phase response processes. In this study we have characterized by a proteomic approach and quantitative analyzed ApoJ in patients with an acute new onset myocardial infarction (AMI). Methods: Serum ApoJ levels in AMI patients (n=39) and in a control population (n=51) were determined by ELISA. Characterization of serum Apo J and serum glycosilated Apo J fraction was performed by Western blot analysis and 2Delectrophoresis (2DE) followed by mass-spectrometry (Maldi-ToF). Patient myocardial damage was determined by plamna T-Troponin levels and percentage of ventricular necrosis (NMR). Results: Serum ApoJ levels were significantly lower in AMI patients immediately after the event than in controls (Mean ± SEM; AMI: 36.3±3.2 μg/ml; Controls: 45.9±1.3 μg/ml; p=0.003). In a 60% of the patients, the lowest ApoJ level was detected within the 6 hours after the onset. Levels of ApoJ in AMI patients did not correlate with cardiovascular risk factors as diabetes, hypertension and hyperlipemia. Between hours after admission, Apo J values in AMI-patients had reached the control levels (47.5±5.8 μg/ml). Characterization of serum Apo J by 2DE depicted a cluster of 13 spots (pi= , MW:35-45kDa) with a significant different pattern in the relative volume distribution of the spots between AMI patients and controls. Western blot analysis for total serum Apo J depicted two major bands of 40-45kDa and 65-70kDa. The latest band represented more than the 90% of serum Apo J in controls and a 75% in AMI when only the serum glycosylated forms were analyzed. A 25% decrease (p=0.05) of Apo J glycosylated forms in serum from AMI patients was confirmed by 2DE. In conclusion, our results demonstrate a decrease in serum Apo J and alterations in its proteomic profile in AMI patients up to 72 hours after the onset of the event, window in which ischemia may induce death apoptotic cell and inflammation in the myocardium. P3008 Prognostic utility of lipoprotein(a) in patients with stable coronary artery disease M. O Donoghue 1, D. Morrow 1, E. Braunwald 1, S. Sloan 1, M. Domanski 2, M. Sabatine 1. 1 Brigham and Women s Hospital, Boston, United States of America; 2 NIH/NHLBI, Bethesda, United States of America Background: Some studies suggest that lipoprotein [Lp] (a) is a useful prognostic marker. The prognostic utility of Lp(a) in stable coronary artery disease (CAD) has not been well established. Methods: Lp(a) (Denka Seiken) was measured in 3395 subjects in PEACE, a randomized trial of trandolapril vs placebo in patients with stable CAD. The primary endpoint (EP) was CV death, myocardial infarction or coronary revascularization (median 4.8y follow up). Cox proportional hazards model were used to examine the association between Lp(a) and the risk of CV events. Results: Modeled as a continuous variable, increasing levels of Lp(a) were not significantly associated with the risk of the primary endpoint (HR per SD 1.02, 95% CI ), or any of its individual components (Figure, left). Patients with Lp(a) in the highest quartile (>39.1 mg/dl) did not have a significant increase in risk of CV events (HR Q4:Q1 1.04, 95% CI ). Based on prior studies with Lp(a), we further explored thresholds of risk (Figure, right). Only for patients with Lp(a) levels >95th percentile (>71.9 mg/dl) was there a trend towards increased risk (adj HR 1.32, 95% CI , P=0.09). There were no significant interactions observed between baseline Lp(a) concentration, and sex, baseline lipid profile, randomized treatment arm, hs-c-reactive protein and lipoprotein-associated phospholipase A2 activity or mass. In ROC analyses, Lp(a) did not significantly improve the C-statistic over traditional CV risk factors. Conclusion: In a large population of patients with stable CAD, Lp(a) level was not an independent predictor of the risk of CV death, myocardial infarction, or coronary revascularization. These results do not support the routine measurement of Lp(a) in patients with stable CAD.

182 482 Cardiac computed tomography: coronaries CARDIAC COMPUTED TOMOGRAPHY: CORONARIES P3009 Small coronary calcifications are not detectable by 64-slice computed tomography A.G. Van Der Giessen 1, F.J.H. Gijsen 1, J.J. Wentzel 1,T.Walsum 2, W.J. Niessen 2, F.N. Van De Vosse 3, P.J. De Feyter 1, A.F.W. Van Der Steen 1. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Erasmus MC- Biomedical Imaging Group, Rotterdam, Netherlands; 3 Eindhoven University of Technology, Eindhoven, Netherlands Purpose: Multi-slice computed tomography (MSCT) is a promising non-invasive tool for the assessment of coronary calcifications. Since smaller calcifications might be missed on MSCT due to its limited resolution we studied in which extent calcifications can be detected with MSCT as compared to the gold standard intra-vascular ultrasound (IVUS). Methods: The coronary arteries of patients with coronary disease were imaged by 64-slice MSCT angiography and IVUS. IVUS and MSCT cross-sectional images were co-registered resulting in a MSCT cross-sectional image for every IVUS image. Cross-sections were assessed on the presence of calcifications on both modalities independently. Additionally we measured the length and the maximum circumferential angle of each calcification on IVUS. Results: In 31 arteries of 23 patients, we found 99 calcifications on IVUS, of which only 47 (47%) were also detected on MSCT. The calcifications missed on MSCT (n=52) were significantly smaller in angle (27 ±16 vs. 59 ±31 ) and length (1.4±0.8 vs. 3.7±2.2 mm) than those detected on MSCT (see figure). Calcifications could only be detected reliably (sensitivity 80%) on MSCT if they were larger than 2.1 mm in length or 36 in angle. Conclusions: While CTA can be safely replaced from CAG in 30% of the patients with NSTEMI, CAG could be more suitable than CTA in the remaining 70% of the patients. No difference was found in overall MACE rate between CTA and CAG groups. CTA could be useful for the risk stratification of NSTEMI and subsequent decision making for PCI in the selected group of patients with NSTEMI. P3011 Multi-slice computed tomography coronary angiography assessment of plaque burden and plaque composition for risk stratification in coronary artery disease J.M. Van Werkhoven 1, J.D. Schuijf 1, O. Gaemperli 2, J.W. Jukema 1, E. Boersma 3, G. Pundziute 1, A.J. Scholte 1,E.E.VanDerWall 1, P.A. Kaufmann 2,J.J.Bax 1. 1 Leiden University Medical Center, Leiden, Netherlands; 2 University Hospital Zurich, Zurich, Switzerland; 3 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Purpose: The purpose of this study was to assess the prognostic value of plaque burden and plaque composition as determined on multi-slice computed tomography coronary angiography (MSCT). Methods: 64-slice MSCT was performed in 474 patients (47% male, age 58±12 years) with suspected coronary artery disease (CAD) referred for cardiac evaluation. MSCT was scored using a 17 segment model for the presence and severity of atherosclerosis and for plaque composition (non-calcified, calcified and mixed plaque). The following events were recorded: all cause death, non-fatal infarction, and unstable angina requiring revascularization. Results: MSCT was normal in 155 patients (33%), in the 319 with atherosclerosis non-significant CAD was observed in 203 (43%) and significant CAD ( 50% stenosis) in 116 (25%). An event was observed in 23 patients (4.9%), 3 (1.9%) events were observed in the normal MSCT reference group. Using univariate analysis, optimal segment cutoff values were obtained for plaque burden and plaque composition. After correction for baseline clinical variables plaque burden and plaque composition remained independent predictors of events.(figure) Example of missed and seen calcium Conclusion: We showed that more than half of the calcifications identified on IVUS were not visible on MSCT. The missed calcifications were smaller in length and angle. Since the missed calcifications are small, the direct impact on the total volume of calcium in the coronary arteries, which is a risk-predictor for cardiac events, will be limited. However, as small calcifications are associated with unstable plaque, restricted local calcium detection by MSCT may have significant implications for rupture risk assessment of individual plaques. P3010 Can coronary Computed Tomography Angiography (CTA) contribute to the risk stratification and subsequent decision making in patients with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)? H. Harigaya 1, S. Motoyama 2,M.Sarai 1,T.Hara 1, K. Hattori 1, M. Ishikawa 1,M.Okumura 1,S.C.Kan 1, H. Naruse 1,Y.Ozaki 1. 1 Fujita Health University Hospital, Toyoake, Japan; 2 University of California, Irvine, United States of America Background: Current ESC/ACC/AHA guidelines recommend an early invasive strategy for patients with non-st-segment elevation myocardial infarction (NSTEMI). However, randomized trials have not yet shown an overall reduction in mortality. We evaluated whether coronary computed tomography angiography (CTA) can be safe and useful for diagnosis and risk stratification of NSTEMI compared with conventional invasive coronary angiography (CAG). Methods: Patients with NSTEMI underwent CTA or CAG within 2 days after the onset. In the CTA group, elective coronary intervention (PCI) was scheduled in 2 weeks in patients with single or double vessel disease. In patients suspected triple vessel disease or left main trunk lesion, additional CAG was performed. In patients who underwent CAG, strategy was determined by operator discretion. Major adverse cardiac events (MACE; cardiac death, MI, revascularization, hospital admission due to ACS) were evaluated within 12 months. Results: Of the 108 patients enrolled in this study 7 patients subsequently disagreed with either CTA or CAG. Of the remaining 101 patients, CTA was performed in 31 (30%) patients and CAG was done in 70 (70%) patients. In CTA group, 5 patients (16%) underwent additional CAG but no patients required urgent PCI. Twenty-two patients had elective PCI with no major complications. One patient who refused PCI had re-mi in 7 months and one was hospitalized due to restenosis of PCI in CTA group (overall MACE rate in CTA; 6.5%). In CAG group, one patient required urgent PCI due to recurrence of ACS, 45 had successful PCI without major complications but 2 had distal embolism and side branch occlusion during PCI. At follow-up 4 patients were hospitalized due to recurrent angina in CAG group (overall MACE rate in CAG; 5.7%). Conclusion: Plaque burden and plaque composition assessed with MSCT may have important prognostic implications. In the future these variables may provide valuable prognostic information when integrated into risk models assessing individual patient risk. P3012 Gender differences in atherosclerosis burden determined by cardiac 64 slice CT in a patient cohort of patients with chest pain M. Winkens, E.M. Laufer, I. Joosen, M. Versteylen, T. Leiner, J. Wildberger, J. Narula, L. Hofstra. University Hospital Maastricht, Maastricht, Netherlands Purpose: Cardiovascular disease is underestimated as a health problem for women (ESC policy statement 2006). Cardiovascular risk profiling, such as the Procam-score (10 year risk of developing myocardial infarction) is considered to be a powerful tool to determine the expected event rate and to classify patients into risk groups. International guidelines recommend aggressive risk modification, including the use of statins in patients beyond a 10% 10 year risk. From several studies it has become evident that cardiovascular pathophysiology between men and women may differ. Since coronary atherosclerosis is the main determinant of acute coronary events, we sought to relate the atherosclerotic plaque burden detected by 64-slice multi-detector (MD) cardiovascular computed tomography (CCT) to the Procam risk score in men and women with stable chest pain syndromes. Methods: From February 2008 to February 2009 we determined the Procam risk score in patients referred from the outpatient clinic for CCT. This patient population consisted mainly of patients with chest pain and absence of detected cardiac ischemia. CCT was performed using a 64-slice MDCT scanner by either prospective gated imaging or retrospective gated Helical imaging. Atherosclerotic burden was classified as minor (one or more lesions less than 50% stenosis), moderate (50-70%) or severe (>70%). Results: We assessed the plaque burden and Procam risk score of 255 patients, 127 men and 128 women. The average age was 56,1 years and 59,5 years for men and women, respectively. The average Procam risk score for men was 12,2% and for women 4,4% (p<0,00001). Assessment of atherosclerotic burden in men revealed 73% minor lesions, 17% moderate lesions and 10% severe lesions. In

183 Cardiac computed tomography: coronaries 483 women 81% minor lesions, 11% moderate lesions and 8% severe lesions were found. Conclusion: Our data show that women despite a threefold lower cardiovascular risk profile showed an almost similar atherosclerosis burden compared to men with a much higher cardiovascular risk. Provided that coronary atherosclerosis is the main cause for acute coronary events, the data may suggest that current clinical risk profiling may markedly underestimate actual risk in women compared to men. Prospective studies that combine clinical risk profiling and CCT are required to verify these suggestions. Our findings may have considerable implications for the diagnostic work up of women with a given cardiovascular risk. p=0.03) (Panel D). Distance from os was more important in LCx and RCA compared to LAD (3σ: 33mm, 30 mm, >100mm, respectively). P3013 Plaque thickness determines whether non-calcified plaques are detected by dual-source computed tomography angiography A.G. Van Der Giessen 1, M.H. Toepker 2,P.M.Donelly 2, F. Bamberg 2, T. Irlbeck 2,C.Schlett 2,C.Raffel 2, F.J.H. Gijsen 1,J.J.Wentzel 1, U. Hoffmann 2. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 MGH - Harvard Medical School - Cardiac MRI PET CT Program - Department of Radiology, Boston, United States of America Purpose: While computed tomography angiography (CTA) permits noninvasive detection and characterization of coronary atherosclerotic plaque, size thresholds for the reliable detection of atherosclerotic, specifically non-calcified plaque have not been established. Thus, we studied the ability of CTA to detect atherosclerotic plaque as compared to intravascular ultrasound (IVUS) in an ex-vivo setting. Methods: Ten ex-vivo human atherosclerotic coronary arteries were imaged in a moving phantom by Dual Source CTA (Siemens Medical Solutions) and IVUS (Boston Scientific) and reconstructed at coregistered cross-sections every 0.4 mm. Cross-sections were assessed for the presence and composition of atherosclerotic plaque (non-calcified, mixed and calcified) on CT and IVUS. In addition, we measured lumen and plaque area, plaque eccentricity and plaque thickness on IVUS images. Results: In total, 1002 cross-sections were assessed containing non-calcified, mixed, and calcified plaque in 585 (58%), 162 (16%), 32 (3%) cross-sections by IVUS. The sensitivity of CTA to detect non-calcified plaques was significantly lower than for the mixed and calcified plaques (424/585; 69% vs 156/162; 96% and 32/32; 100%, p<0.05). In binary logistic regression analysis wall area, plaque area, eccentricity and plaque thickness were all predictors (p<0.05) for the detection of non-calcified plaque, however plaque thickness remained the only independent predictor (OR 6.2). Sensitivity analysis demonstrated that plaque can be detected with 80% sensitivity at a plaque thickness of > 1mm (Table 1). Table 1 Non-calcified plaque thickness (mm) Sensitivity Number of cross-section 0.5 <1.0 44% <1.5 83% <2.0 83% % 44 Conclusion: We establish plaque thickness as an independent predictor of the ability of CTA to detect non-calcified plaque as compared to IVUS in an ex-vivo setting with a plaque thickness of 1mm required for reasonable sensitivity (80%). Given knowledge from IVUS studies about the prevalence of such plaques in various patient populations, these results may provide a perspective for the ability of CTA to assist risk prediction and to assess plaque progression. P3014 Distance-weighted evaluation of coronary artery calcifications is more predictive of cardiovascular events compared to the agatston score and volume score I. Marvasty, Q. Zhen, G. Vasquez, S. Rinehart, S. Voros. Piedmont Heart Institute, Atlanta, United States of America Background: Coronary calcium (CAC) predicts events but CAC scans contain more information beyond Agatston score (AS). Most culprit lesions are in the proximal 3 cm of coronaries. We hypothesized that distance-weighted, lesion-specific Agatston and volume scores (DWLSAS and DWLSVS) are more predictive of events than AS. Methods: AS and volume score (VS) were determined in 30 pts (10 with events)(panel A, B). We measured VS and AS for each separate lesion and distance of each plaque from coronary ostium. We developed a model to predict risk of each lesion based on its lesion-specific AS/VS (LSAS, LSVS) and distance from the ostium, assuming Gaussian relationship between risk and LSAS/LSVS and distance (Panel C). We compared Framingham Risk Score (FRS), AS, VS, maximum LSAS/LSVS in each vessel and DWLSAS and DWLSVS between pts with/without events using unpaired t-test and ROC analysis. Results: FRS, AS, VS, maximum LSAS and LSVS were similar in pts with/without events (6.44±4.61 vs 6.30±4.89; AUC=0.50 and 826.5±819.2 vs 539.8±687.1; AUC=0.64 and 683.8±642.3 vs 480.0±628.0; AUC=0.66 and 433.3±471.9 vs 301.8±415.9; AUC=0.64 and 333.1±354.8 vs 226.5±316.8; AUC=0.64, respectively) (Panel D). However, DWLSAS and DWLSVS were significantly different (0.1078±0.055 vs ±0.043; p=0.03 and ±0.055 vs ±0.044; Conclusions: More proximal calcified lesions have higher risk of cardiac events; therefore, distance-weighted lesion-specific evaluation of standard CAC scans significantly improves predictive value. Such evaluation is easily implemented in clinical practice. P3015 Clinical significance of the coronary plaque with increased intraplaque ct density and its histopathological characteristics T. Yonetsu, T. Kakuta, T. Lee, K. Takayama, T. Iwamoto, N. Kawaguchi, H. Fujiwara. Tsuchiura Kyodo Hospital, Tsuchiura, Japan Backgrounds and Purpose: Atherosclerotic coronary plaque with heterogenic intraplaque enhancement (IPE) is sometimes observed in multislice computed tomography (MSCT). However, the clinical significance of IPE has not been clarified. We sought to determine the impact of IPE on coronary flow after coronary intervention (PCI), and to evaluate the histological features of IPE. Methods: We studied 178 coronary lesions in 152 consecutive patients with coronary artery disease who underwent MSCT before PCI (55 culprit lesions of ACS and 89 stable lesions). Sixteen-slice MSCT was performed within 14 days before PCI. In cross-sectional image of MSCT, mean CT density of plaque and presence or absence of IPE, positive remodeling, eccentricity, and calcification were evaluated. Thrombolysis In Myocardial Infarction (TIMI) flow grade was determined during and after the procedure. Corrected TIMI frame count (CTFC) and myocardial blush grade (MBG) were also assessed in final coronary angiogram at PCI. Slow or no reflow phenomenon (NF) was defined as TIMI 0-2 grade flow in the present study. Relation between coronary flow at PCI and MSCT findings was compared between the lesions with and without IPE. We further histopathologically evaluated 24 samples obtained from 13 lesions with IPE and 11 lesions without IPE by directional coronary atherectomy from randomly selected 24 patients who gave written consent. Results: IPE was observed in 70 lesions (39.3%), and significantly more frequent in culprit lesions of ACS than in stable lesions (56.4% vs 30.3%, p<0.01). NF was more frequently observed in lesions with IPE than in those without IPE (Transient NF during PCI: 18.6% vs. 3.7%, p<0.01; NF at the final angiogram: 11.4% vs. 1.9%, p=0.017; final CTFC: 19.0±11.0 vs 17.3±7.4, p=0.25). MBG 0-1 was more frequently observed in lesions with IPE than in those without IPE (21.4% vs. 8.3%, p<0.05). In MSCT, lesions with IPE frequently showed positive remodeling, soft plaque, and eccentric plaque distribution compared with the lesions without IPE. Histopathological assessment revealed that lesions with IPE showed similar characteristics to vulnerable plaque as documented by the presence of lipid rich plaque and cholesterol cleft. Conclusions: CT characteristics of plaques with IPE suggested the presence of fragile and unstable plaque, potentially resulting worse coronary flow after PCI. P3016 Evaluation of coronary atherosclerosis by 64-slice CT in patients with acute myocardial infarction without significant coronary stenosis A. Aldrovandi 1, D. Arduini 1,F.Ugo 1,A.Menozzi 1, F. Cademartiri 2, D. Ardissino 1. 1 Cardiology Department, Azienda Ospedalierouniversitaria di Parma, Parma, Italy; 2 Radiology Department, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy Purpose: It is known that 5-10% of patients with acute myocardial infarction (AMI) have normal coronary arteries or non significant coronary disease at angiography (CA). Multislice computed tomography (CTCA) can non invasively identify the presence of coronary plaques and evaluate their composition. We studied the role of CTCA for the detection of atherosclerotic plaques in pts with AMI without significant stenosis at CA. Methods: We studied 90 consecutive patients (31 men, mean age 63±14) with AMI defined as typical chest pain, ECG changes and increased cardiac enzymes, without any coronary lesion >50% at CA. All the pts underwent a contrast enhanced 64-slice CT. The localization of AMI was based on wall motion abnormalities detected by left ventriculography and echocardiography. All coronary seg-

184 484 Cardiac computed tomography: coronaries ments were analysed for presence of any coronary plaque. Plaque area, plaque density (Hounsfield Units), degree of stenosis and remodeling index were calculated. Coronary plaques were classified as non calcified if HU<130, calcified if HU >130 or mixed. Results: Globally, 101 segments out of 1350 (7,4%) were non evaluable because of artifacts or small vessel diameter. CTCA detected 125 plaques (35 non calcified, 41 mixed, 49 calcified) of which only 31 were detected also by CA. Positive remodeling was present in 85 lesions (68%). In 28/90 (31%) pts CTCA showed the complete absence of coronary plaques. CTCA identified 64 plaques in infarctrelated arteries (IRA) in 50 pts (46 LAD, 13 RCA, 5 LCX) and 39 plaques in non IRA. Coronary plaques located in IRA were mainly non calcified or mixed (see table). IRA plaques Non IRA plaques P-Value Non calcified (%) 25 6 Mixed (%) Calcified (%) Mean % stenosis 35±12 31± Remodelling index 1.21±0.2 1,17± Purpose: This study aimed to demonstrate the feasibility of a novel dedicated approach for automatic quantification of coronary artery disease (CAD) on 64- multi-slice computed tomography (MSCT) in comparison to quantitative coronary angiography (QCA). Methods: Patients underwent 64-MSCT angiography and conventional coronary angiography sequentially, within two months. The most severe lesion was quantified using QCA in each coronary artery. The particular lesions were also quantified using dedicated quantitative computed tomography (QAngio CT) software. Quantification process involved different processing steps (Figure 1). At first, segment definition (A) and automatic contour detection were performed in longitudinal (B) and transversal (C and D) planes. Next, stenosis severity was quantified using the interrelation of reference line (red line) and lumen diameter (yellow line) (E). QAngio CT was performed by an independent blinded observer. Results: In total, 100 patients (53 men, 59.9±8.1 yrs) were enrolled and 284 vessels (95%) could be analyzed. Good correlations were found for diameter stenosis on vessel-based (r = 0.82, p < 0.01) and patient-based (r = 0.83, p < 0.01) analyses. Mean differences ± standard deviations between QCA and QAngio CT were 3.3±12.9% and 5.2±14.5%, respectively. Similar results were found for calcium containing lesions alone; vessel-based (r = 0.79, p <0.01) and patient-based (r = 0.80, p < 0.01). Mean differences ± standard deviations between QCA and QAngio CT were 2.8±15.1% and 5.7±15.9%, respectively. Conclusions: Multislice CT can detect coronary atherosclerotic plaques in segments of non-stenotic coronary arteries that are underestimated by CA. Plaque composition is significantly different between IRA and non IRA plaques. CTCA may have an incremental diagnostic value for the diagnosis of AMI in patients without significant coronary stenosis at CA. P3017 Coronary artery calcification and Framingham risk score to predict coronary events in subjects under primary prevention care J. Shemesh, Y. Buber, N. Koren-Morag, A. Tenenbaum, S. Segev, E. Konen, E. Schwammenthal, M. Motro. Sheba Medical Center and Tel Aviv University, Tel-Aviv, Israel Objective: To study the contribution of coronary artery calcium score (CACS) and Framingham risk score (FRS) for risk stratification in subjects under primary prevention care. Methods: 652 consecutive participants of our annual check-up program (mean age 55±7 range yrs, 83% male), men above 40 and women above 50 years, without coronary artery disease or diabetes mellitus were included. All underwent 16-slice computerized tomography for CACS measurement and were followed for 7 years. Subjects and their physician were advised to treat risk factors according to the current guidelines. Coronary events, defined as acute MI, cardiac death, and unstable angina resulted in PCI or CABG, were recorded during the annual check-up and while a final phone call 7 years after the CT. Results: 6 subjects experienced acute MI and 12 unstable AP, 4 had CVA and 6 died of malignancy. Higher CACS category was associated with higher rate of coronary events while no significant difference was observed between FRS groups as shown in the Table: The mean area under the curve for the receiver operating characteristic curves for prediction of coronary events was 0.85 for FRS plus CACS, significantly greater than that of the FRS alone, 0.62 (p<0.001). CACS reclassified subjects with intermediate FRS: those with CACS=1-300 (199/227, 88%) were reclassified to the lowest FRS category (event rate 0.3%/y) while the remaining 27 (12%) with CACS 300 were reclassified to the highest category (event rate of 3%/y). Coronary events by CAS and FRS category CACS category Events FRS category Events 0 0/327 (0) 0-9 9/397 (2) /266 (2) /232 (3) >300 12/59 (20) >20 1/23 (4) P<0.001 P=0.601 Numbers are coronary events/subjects (percent). Conclusion: CACS contributes to risk stratification of subjects under primary prevention care. In those with intermediate FRS, the resulted reclassification may change treatment decision. P3018 Novel dedicated approach for automatic quantification of the degree of coronary artery stenosis on 64-slice multi-slice computed tomography: a comparison with quantitative coronary angiography M.M. Boogers, J.D. Schuijf, J.M. Van Werkhoven, P.H. Kitslaar, M. Frenay, J. Dijkstra, A. De Roos, J.W. Jukema, J.H.C. Reiber, J.J. Bax. Leiden University Medical Center, Leiden, Netherlands Automatic quantification process Conclusions: Good correlations were found for quantification of stenosis severity between QCA and the novel automated QAngio CT approach. P3019 Preinterventional coronary computed tomography significantly enhances success rate in PCI of complex chronic total occlusions A. Rolf 1, G.S. Werner 2,J.Rixe 1,M.Werle 1, H. Moellmann 1, H. Nef 1, C. Gundermann 1, K.H. Tischer 2,C.Hamm 1, T. Dill 1. 1 Kerckhoff-Heart-Center, Bad Nauheim, Germany; 2 Darmstadt General Hospital, Darmstadt, Germany Background: Successful revascularization of Chronic Total Occlusions (CTO) depends on the possibiltiy to cross the complete length of the occlusion with the guidewire. This is often hampered by the inability to detect the true intraluminal passage and the course of the vessel. 3D volume rendering technique (3DVRT) in coronary computed tomography angiography (CTA) enables the complete visualization of the vessel in patent and occluded segments. The tortuosity of the vessel and the degree of calcification can be determined accurately. It was the aim of this study to examine if coronary CTA can significantly enhance procedural success in a subgroup of patients with complex CTOs. Mehthods: 40 consecutive patients with complex lesion morphology were enrolled in the study and underwent preinterventional CTA. All patients then underwent PCI by one highly experienced interventionalist (GSW). Procedural success was defined as the ability to reach the distal vessel with the guidewire. A severity index was derived from the complexity criteria proposed by the EuroCTO club. Patients were then retrospectively compared to a control group of similar severity. In the study group all lesions were measured with respect to the complexity criteria on CTA and coronary angiography (XA) and tested for statistically relevant difference in complexity. Each criterion was graded from 0 to 2, a maximum score of 22 was possible. Non parametric Wilcoxon test was used to detect significant differences. Continuous variables are presented as mean ± SD. Results: 40 patients underwent PCI for CTO (22 RCA lesions, 8 LAD lesions, 10 CX lesions). The mean severity score was 19.1±2.9 in the study group and 18.8±2.9 among controls, p = Success rate was significantly higher in the study group (90%) as compared to controls (73%), p = The true course of the occluded vessel segment was visualized by 3DVRT in all of the 40 patients and by XA in only 11 cases, p = The lesion length was underestimated by XA alone (29.5±20.5 mm VRT vs. 21.9±18.1 mm XA, p = 0.001). The degree of calcification of the proximal cap was misjudged by XA alone (mean score 1.0±0.7 VRT vs. 0.41±0.6 XA p = 0.001). A side branch within the occluded segment was detected by VRT in 16 cases and only 8 cases by XA alone, p = 0.034). Conclusion: In this group of complex CTO, coronary CTA significantly contributed to a higher procedural success rate. This effect is due to better vessel visualization by VRT.

185 Cardiac computed tomography: coronaries 485 P3020 The use of 64-row multidetector CT in the investigation of patients with suspected coronary artery disease, initial 2 1/2 year single centre experience K.N. Asrress, G. Baldock-Apps, A. Bajpai, J. Pitts, K. Dickinson, J.A. Giles, D.M. Walker, E.T. Mcwilliams. Conquest Hospital, Hastings, United Kingdom Purpose: There are limited data comparing direct coronary angiography (DCA), stress myocardial perfusion imaging (MPI) and 64-slice multidetector cardiac CT (MDCT) in the investigation of patients with suspected coronary artery disease (CAD). We set out to analyse the impact of introducing MDCT in the workup of patients presenting to a rapid access chest pain clinic (RACPC), to gain insight into the most appropriate way of utilising it in our diagnostic algorithm. Methods: Clinical details of patients seen in RACPC between January 2006 and June 2008 were retrospectively reviewed. Patients were assessed by a cardiologist before undergoing non-invasive testing with ECG, echocardiography, exercise treadmill testing and biomarkers as necessary. This formed the basis for stratifying patients into low, intermediate or high risk of significant CAD, and subsequent referral to DCA, MPI or MDCT. Their progress through the diagnostic algorithm was analysed. Results: 1318 consecutive patients were assessed in the RACPC. 39% were felt to be very low risk of having CAD and discharged, 61% required further investigation (mean age 63.4±11.3 years, males 47%). Of these 32% were at high risk of CAD, 43% intermediate and a further 25% low risk but requiring further investigation. High risk patients were referred for DCA and of 232 subsequently studied 74% had CAD, defined as >50% stenosis in a significant vessel. Patients at low/intermediate risk underwent either MPI, MDCT or DCA. 217 had MPI, of which 72% were negative; 15% positive and 13% equivocal both these groups underwent subsequent angiography with 48% of those with a positive and 26% with an equivocal MPI having CAD. MDCT was performed in 107 patients with 86% being negative. Of the patients with a positive MDCT that underwent angiography 64% had significant CAD, with the other 36% having non-obstructive coronary disease. Conclusions: The results show a high number of patients undergoing invasive testing who do not have CAD, most marked in the intermediate/low risk group. There is an acceptable yield of DCA in patients at high risk but in intermediate/low risk patients almost half were found to have no significant CAD. A positive stress MPI performed similarly with an over 50% false positive rate. 86% of intermediate/low risk patients undergoing MDCT had no or minimal evidence of coronary calcification and therefore did not require invasive testing. Our series suggests that the majority of patients deemed at intermediate or low risk of CAD could initially be triaged with MDCT to avoid unnecessary invasive testing with the associated risks and resource implications. P3021 Diagnostic accuracy of multidetector computer tomography to detect in-stent restenosis as defined by invasive angiography in devices smaller than 3 millimetre diameter E.P. Gurfinkel, M. Cerda, G. Ganum, F. Landeta, G. Caponi, E. Duronto. Favaloro Foundation University Hospital, Buenos Aires, Argentina Purpose: Asymptomatic in-stent restenosis occurs to a significant proportion of patients. This phenomenon is observed among individuals with bare metal stents (BMS) and also in patients with drug eluting stents (DES). The aim of the present study is to determine the effectiveness of multislice computer tomography (MSCT) 64 rows as a non-invasive method to detect coronary in-stent restenosis and patency. Methods: From a total of 205 consecutive patients who underwent a coronary angiographic study by MSCT 64 rows, followed by an invasive angiography between September 2006 and December 2008, we selected those previously treated with stents in vascular segments to establish the sensitivity and specificity of the noninvasive method to detect - or not - a coronary restenosis and patency. Results: A total of 369 coronary segments were examined; 90 with coronary stents: 33 were bare metal stents (BMS), 51 drug eluting stents (DES) and 6 segments with both BMS and DES. The medium diameter of stents evaluated was 2.64mm ± 0.59mm. Of the 33 coronary segments with BMS, 90.9% were patent by MSCT 64 and 93.9% according to the invasive angiography (Sensitivity: 96.7% y specificity: 100%). In the same stents with a diameter lower than 2.5 mm we found 94.4% sensitivity to MSCT in detection of stent permeability. Regarding the DES, the medium diameter was 2.72 mm ± 0.59 mm. In the present study, 93% were patent at the time of performing the MSCT and the same percentage was found when conducting the invasive angiography (sensitivity: 100%, specificity: 100%). In the same DES with a diameter lower than 2.5 mm we found a 93.3% sensitivity and specificity of 100% using MSCT in detection of stent permeability. Finally, a 13.3% of stents had variable degrees of tissue proliferation by MSCT, confirmed thereafter by conventional angiography (sensitivity 100%, specificity 100%). Conclusions: In these consecutive patients evaluated, we found a high sensitivity to MSCT 64 rows in detection of stent permeability and proliferation as compared to invasive angiography even in stents of small lumen diameter. P3022 The accuracy of CT coronary angiography has been systematically underestimated by standard trial methodology J. Otton 1,A.Hayen 2, M. Feneley 1. 1 St. Vincent s Hospital, Sydney, Australia; 2 The University of Sydney, Sydney, Australia Purpose: To evaluate the effect of measurement variability of quantitative invasive coronary angiography on the assessed accuracy of computed tomography coronary angiography (CTCA) in recent trials. Background: The assessed accuracy of any diagnostic test is limited by the precision of the reference standard to which it is compared. Studies of the accuracy of computed tomography coronary angiography have hitherto contained the tacit assumption that invasive angiography is perfectly precise. It is known, however, that some day-to-day variation exists in the measurement of stenosis by invasive angiography. Failure to account for this factor leads to an underestimation of the accuracy of any comparator test. The assessed accuracy of CTCA in recent studies has varied greatly. Estimates of the per-vessel sensitivity and specificity in recent large 64-slice CT trials have been as low as 75% and 90% respectively. Methods: We performed a simulation of invasive angiography on one day compared to the next using standard trial methodology. The expected standard error of measurement of degree stenosis of invasive angiography was assumed to be 13% in concordance with recent empirical data. Results: Taking the imprecision of the reference standard into account, the maximum expected per-vessel sensitivity and specificity of CTCA in a population with uniform disease severity is 90% with a ROC area under the curve of The assessed accuracy is dependent of the distribution of disease in the population. The maximum achievable accuracy figures would be lower still if there is a greater prevalence of disease around the 50% stenosis threshold. Higher accuracy is possible if the overall population disease prevalence is low. Conclusion: A re-assessment of recent CTCA accuracy trials with more appropriate statistical methodology indicates that the accuracy of CTCA has been systematically underestimated. The effects of reference standard imprecision become more important as the accuracy of the comparator test increases. Future evaluations of CTCA should compare CTCA and invasive angiography to a third reference standard such IVUS or, at a minimum, account for the effects of variabilityof quantitative invasive angiography. The ideal gold standard is clinical outcome. P3023 Incremental value of 64-slice computed tomography in patients with known or suspected CAD after inconclusive stress test N. Carrabba 1, F. Cademartiri 2, M. Acquafresca 3, R. Valenti 1, M. Moroni 3,S.Pradella 3, L. Nicolaci 1, G. Parodi 1,G.F.Gensini 1, D. Antoniucci 1. 1 Department of Cardiology, Careggi Hospital, Florence, Italy; 2 Department of Radiology, Academic Hospital, Parma, Italy; 3 Department of Radiology, Careggi Hospital, Florence, Italy Aims: It is expected that multislice computed tomography (MSCT) will be used increasingly as an alternative imaging modality in the diagnosis of patients with suspected coronary artery disease (CAD). However, data on the incremental value of non invasive anatomical imaging are currently missing. This study sought to determine the incremental value of MSCT in patients with known or suspected CAD. Methods and results: A total of 113 patients (79 men, age 63±12 years; 53 (47%) with unknown CAD) who were referred for further cardiac evaluation, due to inconclusive stress test, underwent additional 64-MSCT coronary angiography to evaluate the presence and severity of CAD. Patients with normal coronary arteries or no restenosis of previous percutaneous coronary intervention (PCI) on MSCT (n=51, 45%) did not undergo invasive coronary angiography (ICA). Non obstructive (<50%) and obstructive ( 50%) CAD was detected in 24 (21%) and 38 (34%) patients, respectively. Of these patients 97% (60/62) underwent ICA (2 patients with obstructive CAD on MSCT refused ICA). Among 36 patients with obstructive CAD on MSCT, 33 patients were confirmed by ICA (TP) and 3 did not (FP). Among 24 patients with non obstructive CAD, 23 patients were confirmed by ICA (TN) and 1 did not (FN). On a patient-based model, the sensitivity, specificity, positive and negative predictive values, and accuracy to detect significant (both non obstructive and obstructive CAD) were 0.97 (95% CI ), 0.88 (95% CI ), 0.92 (95% CI ), 0.96 ( ), and 0.93 (95% CI ), respectively. Six (18%) patients with obstructive CAD underwent PCI at time of ICA. During 12 month follow-up the PCI rate was 0% in patients with normal coronary arteries on MSCT vs 8.3% in patients with non obstructive CAD on MSCT. Conclusions: In patients presenting with known or suspected CAD and showing inconclusive stress test, MSCT allowed us to avoid 45% of ICA when normal MSCT was found with an excellent 1-year prognosis. This results may be of value to improve our understanding of the potential role of MSCT in this patient population.

186 486 Cardiac computed tomography: coronaries / Novel techniques: computed tomography and cardiovascular magnetic resonance P3024 Epicardial adipose tissue relation to coronary artery calcification is independent from abdominal visceral fat: prospective multislice computed tomography study N. Bettencourt De Sousa, D. Leite, J. Rocha, M. Carvalho, F. Sampaio, M. Teixeira, L. Simoes, V. Gama. Hospital ES Silva, Villa Nova de Gaia, Portugal Introduction: Recent studies have suggested that epicardial adipose tissue (EAT) may play an active role in the development of coronary heart disease (CAD). Its close relation to the epicardial vessels and ability to produce proinflammatory cytokines led some authors to suggest an direct local paracrine effect over the coronary circulation. Purpose: To study the correlation between EAT volume evaluated by multislice computed tomography (MSCT) and coronary atherosclerotic burden evaluated by Agatston calcium score (CAC). Population and Methods: 214 patients without known CAD referred to MSCT for coronary angiography during a 6 month period were included in our study after informed consent. All patients were subjected to:1) short anamnesis including past medical history, vascular risk factors (RF), symptoms and cause of referral; 2) collection of anthropometric measurements (weight, height and abdominal circumference); 3) blood pressure and heart rate assessment; 4) blood tests and 5) MSCT (including quantification of visceral and subcutaneous abdominal fat, CAC and TAE, as well as coronary angiography). Results: 214 patients, mean age 58±11 years (26-84), 61% males, with mean body mass index (BMI) of 28±4 kg/m 2 (20-49) and abdominal circumference of 97±11 cm were included. 32% met the ATP III criteria for the diagnosis of metabolic syndrome. Dyslipidemia (58%) and hypertension (57%), were the most prevalent RF in this population of low-to-moderate cardiovascular risk (mean Framing risk score = 11±7). 67% of the patients had no significant CAD (defined as any stenosis >50% detected on MSCT angiography). 64% of the patients had some degree of coronary calcification (CAC>0) and mean CAC was 186±433. EAT volume, as assessed by MSCT, correlated positively with male sex, age, BMI, abdominal circumference, visceral fat (p<0.01 for all) and with the diagnosis of metabolic syndrome, risk factors, Hgb A1c and unfavourable lipid profile (p<0.05 for all). EAT volume correlated positively with CAC, justifying 6% of its variation (R=0.235,p <0.01). This correlation remained significant after adjustments for age and sex as well as for the visceral abdominal fat (p <0.05). Applying a linear regression model, an increase of 1 ml in EAT volume was associated with an increase of 13 units in CAC (p <0.01). Conclusion: In this population EAT volume was positively related to the degree of coronary calcification; this correlation was shown to be independent of visceral abdominal fat. P3025 A platform for quantitative and dynamic calcium signal study in small rodent heart in vivo using Manganese Enhanced MR (MnEMR) T1mapping without breath control Y.-X. Ye 1,X.Helluy 1, T. Basse-Luesebrink 1,V.Kocoski 2, A. Schlipp 3, P.M. Jakob 1, K.-H. Hiller 1, W.R. Bauer 4. 1 Experimentelle Physik 5,Universitaet Wuerzburg,Am Hubland, Wuerzburg, Germany; 2 Institut fuer Virologie und Immunbiologie, Universitaet Wuerzburg, Wuerzburg, Germany; 3 Institute of Pharmacology and Toxicology,Universitaet Wuerzburg, Wuerzburg, Germany; 4 Med.Klinik und Poliklinik 1,Universitaet Wuerzburg, Wuerzburg, Germany Introduction: Calcium dependent signaling is of great importance in the heart, while most of its research is based on ex vivo experiments. We report a dynamic and quantitative set up for detecting calcium influx in small rodent hearts in vivo and free of breath control by using fast Manganese enhanced MR T1mapping. Methods: 0.86nmol/min/g and 3.3nmol/min/g MnCl2 i.v. infused for 60min and 35 min in group 1 (N=3) and group 2 (N=3), respectively. Group 3: 3.3nmol/min/g MnCl2 infused for 15min at rest followed by 20 min with 20ng/min/g Dobutamin. At 7T, heart T1 maps were dynamicly acquired by a 2x segmented inversion recovery snapshot FLASH MR sequence with ECG-triggering only the first excitation pulse [1]. TR/TE/FA=[2.5ms/2ms/3 ], FOV= 3x3cm, matrix=64 64, slice thickness=2mm. Median R1 of LV anterior wall was plotted. The calcium influx variation index Qi=(S1-S0)/S0, where S0=slope at rest and S1=slope at stress in R1 plot. R1 Plot (1 animal from each group) Results: Each T1 map measurement lasted about 30 seconds. The preenhancement mean T1 (1.44±0.11 Sec.) well agrees with that from an established method with breath control (1.45±0.009 Sec) [1]. In group 1 and 2, R1 linearly increased shortly after the MnCl2 infusion started till its end. The 3.8 times higher dose MnCl2 infusion showed around 6 times steeper slope than the lower dose. The significant increase of the slope at stress was found in group 3 (p=0.018), of which mean calcium influx variation index Qi increased 72% with stress. Conclusion: This MnEMR T1mapping enables quantitative and dynamic observation of calcium influx in small rodent heart in vivo without breath control; the linear elevation of R1 at rest provides an internal reference, which increases the sensitivity of detecting calcium influx alteration. NOVEL TECHNIQUES: COMPUTED TOMOGRAPHY AND CARDIOVASCULAR MAGNETIC RESONANCE P3026 MRI-related heating at commercial cardiac pacemaker leads in vivo P. Nordbeck 1,O.Ritter 1,M.Warmuth 2,H.H.Quick 3, M.E. Ladd 3, K.H. Hiller 4, P.M. Jakob 2, W.R. Bauer 2. 1 Internal Medicine I, University of Würzburg, Würzburg, Germany; 2 Experimental Physics V, University of Würzburg, Würzburg, Germany; 3 Diagnostic and Interventional Radiology, University of Duisburg-Essen, Essen, Germany; 4 Research Center Magnetic-Resonance-Bavaria, Würzburg, Germany Introduction: Extensive in vitro investigations in the past have shown that there is a high potential for RF-related heating to appear at cardiac pacemaker leads during MRI. On the other hand, recent clinical studies found little evidence for adverse events due to pacemaker lead heating in MRI, therefore suggesting that the actual patient risk might be relatively small using modern pacemakers. Until then, there is a lack of sufficient systematic in vivo investigations which would support either of these suggestions. Therefore, the current study aimed at developing a measurement setup for reproducible and precise investigations on the temperature evolution at the tip of cardiac pacemaker leads in vivo. Methods and Results: An MRI-compatible temperature measurement system with modified fluoroptic probes incorporated inside slightly modified commercial pacemaker leads was used to prevent interferences of the measurement system with the electromagnetic fields inherent to MRI technology. After in vitro confirmation of feasibility of the measurement method to determine temperature evolution at the lead tip, the leads were implanted through the jugular vein in the RA/RV in 3 mini pigs (45-55 kg). Temperature recordings were then performed in various scenarios in a 1.5T MR scanner. The measurement system revealed to be able to precisely measure the temperature evolution at the lead tip in MRI both in vitro and in vivo. A passive pacemaker lead implanted in the RA of a pig from the left jugular vein showed remarkable heating at the lead tip during MRI, with an increase of 14.3K after 30s (SAR 2.1W/kg). Adding a second, RV lead only slightly affected the amount of heating, while connecting a pacemaker device in this scenario greatly decreased heating. In another pig, heating of pacemaker leads with the device implanted in either the left and right pectoral region was compared, showing significant heating in both configurations. After euthanizing the pigs, heating increased for further 15%, suggesting that blood flow hampers but insufficiently prevents unintended heating at cardiac pacemaker leads. Conclusion: In this study, a new technology for in vivo measurements of unintended heating at pacemaker lead tips in MRI was developed. The preliminary investigations in 3 pigs prove that significant lead tip heating in vivo can be in the same range as shown for in vitro experiments before. Ongoing investigations focus on the various aspects affecting implant heating in vivo to better specify the risk of relevant heating and, therefore, adverse events in cardiac pacemaker patients undergoing MRI. P3027 Direct comparison of 32-element magnetic resonance imaging at 3.0 T and 64-slice computed tomography for detection of coronary artery stenosis A. Hamdan 1,P.Asbach 2, H. Kilian 1, R. Gebker 1, I. Paetsch 1, C. Jahnke 1, A. Huppertz 2,E.Fleck 1. 1 Deutsches Herzzentrum Berlin, Berlin, Germany; 2 Charite - Campus Mitte, Humboldt-Universitaet, Berlin, Germany Background: Magnetic resonance imaging (MRI) and multislice computed tomography (CT) have emerged as potential noninvasive coronary imaging techniques; however, CT, unlike MRI, exposes patients to radiation and iodinated contrast agent. The objective of the present study was to clarify the accuracy of both modalities in the detection of significant coronary artery lesions compared to conventional coronary angiography as the gold standard. Methods: Forty-two consecutive patients (29 men, 68±7.9 years) with suspected or known coronary artery disease (CAD) prospectively underwent coronary MRI and CT before elective x-ray angiography. Coronary MRI was acquired with a 3.0-T MRI scanner equipped with 32-element cardiac coils. Free-breathing whole heart coronary MRI was obtained using a 3-dimensinonal, gradient echo sequence with T2 preparation and fat suppression. Typical spatial resolution of MRI images was mm 3 (reconstructed to mm 3 ). Coronary CT was

187 Novel techniques: computed tomography and cardiovascular magnetic resonance 487 performed on a 64-slice CT with a typical spatial resolution of mm 3. If no contraindications were present, each patient received a beta-blocker and sublingual isosorbide dinitrate. The sensitivity and specificity of both methods for detecting of clinically significant coronary artery stenosis ( 50% luminal diameter stenoses) in segments >1.5 mm size was compared using invasive coronary angiography as the reference standard. Results: Coronary MRI and CT were successfully completed in all 42 patients. According to the invasive coronary angiography, 64 of 394 coronary segments >1.5 mm diameter had 50% diameter stenosis. The number of excluded coronary artery segments on MRI and CT images was 39 and 20, respectively. In the per-segment analysis coronary MRI and CT had similar sensitivity (75% vs. 70%, respectively; P = 0.3), specificity (95% vs. 94%, respectively; P = 0.7), and diagnostic accuracy (92% vs. 90%, respectively P = 0.9). The vessel-based accuracy of MRI and CT was similar with a sensitivity of 83% vs. 77%, respectively; P = 0.9, specificity of 90% vs. 90%, respectively; P = 0.5, and diagnostic accuracy of 88% vs. 87%, respectively P = 0.5. Two patients had allergic reaction to contrast agent after CT angiography. Conclusion: This ongoing study demonstrates the ability of MRI and CT to identify significant coronary artery stenosis with a similar diagnostic accuracy in patients with suspected or known CAD scheduled for elective coronary angiography. P3028 Multislice multiecho T2* cardiac magnetic resonance can detect heterogeneous myocardial iron distribution in thalassemia patients A. Pepe 1, V. Positano 1, M.F. Santarelli 1, A. Meloni 1, B. Favilli 1, D. De Marchi 1, P. Keilberg 1,V.Caruso 2, L. Landini 1, M. Lombardi 1. 1 MRI Lab, Institute of Clinical Physiology, G Monasterio Foundation, Pisa, Italy; 2 Unità Operativa Dipartimentale Talassemia P.O. S. Luigi-Currò - ARNAS Garibaldi, Catania, Italy Purpose: Previous histological and T2* cardiovascular magnetic resonance (CMR) studies have demonstrated an uneven myocardial iron overload (MIO) and found a correlation between the pattern of MIO and proved indicators of prognosis in thalassemia. Aims of our study were 1) to determine whether T2* heterogeneity is related to inhomogeneous MIO or it could be generated by geometric/susceptibility artefacts; 2) to evaluate the MIO in a large thalassemia major (TM) population and its relationship with iron overload in the mid ventricular septum (MVS) where T2* evaluations have been traditionally performed in CMR. Methods: CMR was performed in 230 TM patients. Basal, medium and apical views of the left ventricle (LV) were obtained and analyzed using a custom-written software. The myocardium was automatically segmented into a 16-segments standardized LV model and the T2* value was calculated for each segment as well as for the whole myocardium (multislice, multiecho T2* approach). The level of heterogeneity of the T2* segmental distribution of each patient was evaluated by computing the coefficient of variation. Such measured heterogeneity was compared with that of a surrogate data set, obtained with the hypothesis that the variations in T2* are associated only with the effect of susceptibility artefacts. The Montecarlo simulation was performed on 10,000 surrogate data sets. Results: T2* values were all below the lower limit (20 ms) of normal (homogeneous MIO) in 20% of TM patients. T2* values were heterogeneous with respect to the normal threshold in 45% of patients. Of these patients, 77 patients (33%) showed a normal T2* global value. Eighty-one patients (35%) showed all normal segments. T2* heterogeneity for patients without MIO was compatible with the hypothesis that the heterogeneity was generated only by additive susceptibility artefacts. Below the normal limit of global T2* the heterogeneity abruptly increased of about 10%. Starting from this level, the heterogeneity decreased linearly. A mismatch between normal T2* values in the MVS and normal global heart T2* values was found only the 4% of the cases, however the 66% of the patients with normal T2* values in the MVS showed an heterogeneous MIO as well as no MIO and the 30% of the patients with abnormal T2* values in the MVS showed an heterogeneous MIO as well as homogenous MIO. Conclusions: In TM patients a true heterogeneity in MIO was present and the MVS could not exactly detach the MIO pattern distribution. Heterogeneity seemingly appears in the borderline MIO and stabilizes for moderate to severe MIO. placed in the right ventricular apex under MR-guidance before the valvuloplasty. After positioning of the balloon (Tyshak, NuMED, New York, USA) into the left ventricular outflow tract, aortic valve valvuloplasty was performed under rapid right ventricular pacing at a heart rate of 180 bpm to minimize cardiac output. For improved visualization the balloon was filled with Resovist (Bayer, Leverkusen, Germany). Results: Positioning of the pacemaker lead under MR-guidance was easily feasibleinallswine (Sensing 6±1 mv, threshold 1±0.5 V) The lead could be visualized with SSFP imaging without inducing any artifacts. Rapid right ventricular pacing was feasible in all cases at a heart rate of 180 bpm. Balloon stability at the time of inflation was achieved in all cases with no balloon movement during the inflation and deflation periods. Valvuloplasty was successfully accomplished in all experiments. At gross pathologic examination no signs of heating related myocardial damage were detectable documenting safety of pacing with MR-compatible leads. No complications such as pericardial effusion related to the pacemaker lead were observed. Conclusion: MR-guided aortic valvuloplasty under rapid right ventricular pacing with a MR-compatible pacemaker lead is feasible and safe. The balloon remained in stable position during the critical phase of the procedure. This study demonstrates that MR-guided aortic valve balloon valvuloplasty may soon become reality in humans. P3030 New simplified method for quantification of left and right atrial volumes by multimodality tissue tracking (MTT) MRI T. Helle-Valle, A. Redheuil, W.-C. Yu, J.A.C. Lima. Johns Hopkins University, Baltimore, United States of America Background: Atrial volumes provide important information regarding clinical outcome and are closely related diastolic function of the ventricles. However, assessment of atrial size is challenging by current methods. We have recently introduced multimodality tissue tracking (MTT) as a simple pixel based pattern matching technique for quantification of cardiac and vascular deformation. We hypothesized that left and right atrial volumes (LAV and RAV) could be measure in a simplified and quick fashion by MTT from conventional 4-chamber MR images. Methods: In healthy volunteers (n=8) cardiac short- and long-axis cine-stacks were obtained by MRI. Atrial volumes were calculated by MTT from a conventional 4-chamber recording after tracing the endocardial borders at onset of systole (modified Simpson s rule; Figure 1, Panel A). Atrial volumes from bi-plane cine-stacks were assessed by current reference method (QMass ). Results: Mean LAV by MTT and by the reference method were 29±7 and 29±8 at onset of filling (Figure 1, Panel B, A), 62±8 and 63±8 at maximum filling (B) and 47±9 and 42±10 ml at onset of the conduit phase (C), respectively. For maximum atrial filling the mean difference (mean±sd) between the two methods was 1±5 for LAV and 3±10 ml for RAV. For pooled data the correlation was r=0.94 (P<0.0001; Panel C) for LAV and 0.81 (P<0.0001) for RAV. Figure 1 Conclusion: We have introduced a new and simplified method for accurate quantification of atrial volumes from MRI, which is highly relevant in the evaluation of patients with cardiovascular disease. P3029 Magnetic resonance-guided aortic balloon valvuloplasty under rapid right ventricular pacing with MR compatible pacemaker lead in swine M. Neizel 1, N. Kraemer 2, F. Boenner 1,M.Kelm 1, R.W. Guenther 2, G.A. Krombach 2, H.P. Kuehl 1. 1 Department of Cardiology, Aachen, Germany; 2 Department of Radiology, Aachen, Germany Objectives: To assess the feasibility of magnetic resonance imaging (MRI)- guided aortic valvuloplasty under rapid right ventricular pacing with MRcompatible pacemaker lead. Background: The feasibility of MRI-guided aortic valvuloplasty in animal models has been demonstrated. However, to translate this MR-guided procedure into humans rapid pacing has to be performed to provide balloon stability. Methods: 6 pigs (weight 48±3 kg) were investigated. All experiments were performed using an interventional 1.5 Tesla MRI system. Interventions were monitored using a steady-state free precession real-time imaging sequence. An MRcompatible pacemaker lead (Capsurefix MRI, Medtronic, Mineapolis, USA) was P3031 A cardiac magnetic resonance study: the effect of correction for through-plane motion in patients with tetralogy of fallot D.H.F. Gommans 1,J.W.OpDenAkker 2, M.J. Van Der Vlugt 2. 1 Radboud University Medical Centre, Nijmegen, Netherlands; 2 Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands Purpose: Cardiac MRI is the gold standard for ventricular volumes. However, difficulties remain like correction for through-plane motion (TPM). The purpose of this study was to assess the effect of correction for TPM on volumetric results. Methods: 29 patients with Tetralogy of Fallot were included. Cardiac MRI was performed with a Siemens Avanto 1.5 Tesla. Data-analysis was performed twice with QMASS 7.1 (Medis, Leiden, The Netherlands) to measure end-diastolic (EDV) and end-systolic (ESV) volumes for the right and left ventricle. The first method did not correct for TPM and excluded all slices in which the left atrium appeared in end-systolic phase and the blood pool was surrounded by less than 50% (< 180 ) of myocardium. The second method corrected for TPM and ex-

188 488 Novel techniques: computed tomography and cardiovascular magnetic resonance cluded slices separately for the end-systolic and end-diastolic phase for each ventricle separately. The four-chamber view was used to assess the exact border between atrium and ventricle. Volumes derived with and without correction for TPM were compared with paired-samples t-tests. Results: All volumes and EF increase with correction (Table). The effect seemed to be more for RV volumes at first sight, but when transferred to a percentage of the original value the relative mean differences were similar, but RV EF increases more than LV EF. Results TPM TPM Paired samples correction correction + t-test Mean SD Mean SD Mean Relative mean P Difference difference (%) RV EDV (ml) <0.001 RV ESV (ml) <0.001 RV EF (%) <0.001 RV SV (ml) <0.001 LV EDV (ml) <0.001 LV ESV (ml) <0.001 LV EF (%) <0.001 LV SV (ml) <0.001 Conclusion: Correction for TPM has a significant effect on volumetric results. Although the work-load increases, it should not be neglected, because it could have clinical consequences. For comparison of different studies in the literature the method of TPM correction should be described clearly in future studies. P3032 Non-invasive quantification of myocardial fibrosis using in-vivo high-resolution MRI in diabetic mice and correlation with arrhythmias S.S. Bun 1, F. Kober 2, A. Jacquier 2, J. Kalifa 2,L.Espinosa 3, F. Kopp 3, M.F. Bonzi 3, J.C. Deharo 1, P.J. Cozzone 2, M. Bernard 2. 1 AP-HM - Hopital de la Timone, Marseille, France; 2 CRMBM, Marseille, France; 3 Department of Histology, Marseille, France Background: There is an established role for MRI in the assessment of myocardial fibrosis, in ischaemic and non-ischaemic cardiomyopathies. T2 transversal relaxation time directly depends on physico-chemical properties of each tissue. Thus, myocardial T2 time determination can help in quantifying fibrosis. Diabetic cardiomyopathy is characterized by myocardial structural modifications including interstitial fibrosis, hypertrophy and microcirculation impairment. Diabetes also increases sudden cardiac deaths depending on several mechanisms but the exact pathophysiology remains unclear. Purpose: To describe a non-invasive method using high-resolution myocardial T2 time measurement to assess myocardial fibrosis in diabetic mice in vivo and to correlate this fibrosis with ventricular arrhythmias. Methods: Cine-FLASH sequences for morphology and function were followed by two multi-slice spin-echo sequences for T2 time assessment, respectively at 20 and 9 ms echo time (resolution 85x85 μm 2, slice thickness 1.0 mm, imaging time 15 minutes), in ten 16-week old C57Bl/6J after 8 weeks of streptozotocininduced diabetes, and ten control mice, under isoflurane anesthesia using a Bruker Avance 500 WB system at 11.75T. Programmed atrial and ventricular stimulation was then realized to assess atrial and ventricular inducibility in both groups. MRI measurements were compared with histological quantification of collagen deposits using picrosirius red staining. Results: T2 time was significantly lower in diabetic mice (13.8±2.8 ms versus 18.9±2.3 ms in the control group; p<0.05). This was associated with a significant increase incollagen deposits, as evaluated by picrosirius red staining, in diabetic mice. Morphologic and functional analysis showed no difference in terms of ejection fraction (60.70±5% versus 60.35±4%) between the two groups, but end-systolic (1.28±0.26 μl/g versus 1.04±0.24 μl/g) and end-diastolic volumes (3.22±0.60 μl/g versus 2.67±0.65μL/g) were significantly increased in the diabetic group. During the electrophysiological study, 3 non sustained ventricular tachycardias were induced in diabetic mice (versus none in the control group; p<0.05) and 4 supra-ventricular arrhythmias: 3 atrial tachycardias and 1 atrial fibrillation (versus none in the control group; p<0.05). Conclusion: In diabetic cardiomyopathy, T2 assessment can detect the presence of fibrosis at an early stage, before the apparition of a more obvious systolic dysfunction. Myocardial fibrosis may be a potential substrate for the genesis of (supra)-ventricular arrhythmias in diabetes mellitus. P3033 CT coronary angiography with prospective ECG-triggering: body physique and heart rate variability determine the occurrence of stair-step artefacts L. Husmann, B.A. Herzog, R. Buechel, N. Burkhard, I. Valenta, O. Gaemperli, C.A. Wyss, U. Landmesser, P.A. Kaufmann. University Hospital Zurich, Zurich, Switzerland Objectives: To describe and characterize the frequency and extend of stair-step artifacts in computed tomography coronary angiography (CTCA) with prospective electrocardiogram (ECG)-triggering and to analyze their determinants. Methods: One-hundred-forty-three consecutive patients (55 women, 88 men, mean age 57±13 years) with suspected (n=122) or known coronary artery disease (n=21) were scheduled for 64-slice CTCA using prospective ECG-triggering. The occurrence of stair-step artifacts in the thoracic wall and in the coronary arteries was determined by two readers in consensus and the maximum offset was measured. In all cases with stair-step artifacts both in the thoracic wall and in the coronary arteries, a difference between thoracic wall and coronary artery offset 0.6mm was attributed to additional motion of the heart. Results: Mean heart rate was 57.6±6.1bpm (range 44-75bpm), mean heart rate variability 1.5±1.0bpm (range bpm), mean body mass index (BMI) 25.6±3.7kg/m 2 (range kg/m 2 ), mean weight 74.9±14.2kg (range kg), and mean effective radiation dose 2.1±0.7mSv (range mSv). Stair-step artifacts were found in the coronary arteries of 89 patients (62%); in 77 patients (54%) these were associated with stair-step artifacts of the thoracic wall. The mean stair-step offset was significantly larger (P<0.001) in the coronary arteries (1.7±1.1mm) vs. the thoracic wall (1.0±0.3mm). Stair-step artifacts in the thoracic wall were associated with BMI (P<0.01) and weight (P<0.01), while artifacts in the coronary arteries were associated with heart rate variability (P<0.05). Conclusion: Stair-step artifacts in CTCA with prospective ECG-triggering are determined by a) motion of the entire patient during table travel, particularly in large patients and b) by motion of the heart, particularly when heart rates are variable. P3034 Comparison between visual score and 3d quantitative analysis of coronary angiography MDCT. How to overcome subjectivity D. Tavella 1, R. Malago 2,F.Beltrame 1, R. Pozzi Mucelli 2, P. Benussi 1. 1 Cardiology Unit Ospedale Policlinico, Verona, Italy; 2 Radiology Departiment University of Verona, Verona, Italy Background: MSCT-CA allows the quantification of coronary artery stenosis with a high level of accuracy; however the inherent imprecision of visual score still remains. Computed quantitative vessel analysis systems (QCTA) are intended to remedy, considering quantitative coronary angiography (QCA) the reference standard. The aim of the study is to evaluate the accuracy of QCTA in comparison to QCA and visual score. Methods and materials: Two operators, unaware of the results of coronary angiography, visually scored 50 consecutive patients referred for MSCT-CA in order to assess stenotic segments according to a modified 17 segments AHA classification model. Coronary angiography was performed within one week. Stenosis level is classified as 0%, <20% (wall irregularities) <50% (without significant disease), >50% (significantly diseased). Each segment is then analysed using electronic callipers of the QCTA system part of Comprehensive Cardiac (Philips, The Netherlands). Data are compared to QCA results. Each segment is finally classified as non calcified, calcified and heavily calcified. Comparison between QCTA results, visual score and QCA are performed by means of Spearman rank correlation. Interobserver variability is calculated using κ-statistics. Results: 876 segments were analysed. Interobserver agreement between the two operators resulted very high (k=0.97). Good correlation was found between Visual score and QCA (rho = 0.932; p<0.0001) and between Visual score and QCTA (rho = 0.845; p<0.0001). Moderate correlation was found between QCA and QCTA (rho = 0.810; p<0.0001). Conclusion: Accuracy of QCTA is comparable to QCA and visual score especially in non calcified vessels. P3035 Feasibility of a single-heart beat scan protocol in dual-source cardiac CT angiography B. Bischoff, F. Hein, T. Meyer, M. Hadamitzky, S. Martinoff, J. Hausleiter. Deutsches Herzzentrum Muenchen, Munich, Germany Background: With the introduction of 64-slice CT and thus improved image quality cardiac CT angiography (CCTA) is increasingly being used. Nonetheless, there remains concern regarding radiation exposure and its potential hazards. Due to the unique configuration of dual-source CT systems (DSCT) with a second X-ray acquisition system, DSCT might allow for cardiac CT data acquisition with very fast table movement (table pitch > 3) during a single-heart beat and thus with the potential for significant radiation dose reduction. Objective: To assess the feasibility of single-heart beat CCTA with DSCT. Methods: Single-heart beat CCTA was performed in 14 patients who were examined for visualization of the gross cardiac anatomy (left atrium with the pulmonary veins and/or the ascending aorta). Diagnostic image quality of the gross cardiac anatomy and of all coronary segments 1.5 mm was rated as either diagnostic or non-diagnostic. Radiation dose was estimated from the dose-length-product (DLP). Results: Mean heart rate during examination was 52.6±5.5 bpm. CCTA acquisition was started in the end-systoly and lasted approximately 600 ms into the midto-late diastoly. Image quality for the assessment of the gross cardiac anatomy was rated diagnostic in all patients. Furthermore, 83% of coronary segments were rated as diagnostic. Motion artifacts were the main reason for non-diagnostic coronary image qualtiy. These motion artifacts occurred predominantly during the early diastoly. The mean DLP was 145±47 mgy cm resulting in an estimated

189 Novel techniques: computed tomography and cardiovascular magnetic resonance 489 radiation dose of 2.0±0.7 msv. Single-heart beat CCTA with the use of 100 kv tube voltage even reduced the radiation dose to < 1mSv. Conclusions: Single-heart beat dual-source CCTA is feasible and allows for diagnostic image quality of the cardiac structures with a concomitant reduction in radiation exposure. However, improvements in this technology with a further reduction of the acquisition time to approximately 300 ms are needed to avoid the early diastoly for data acquisition, which will reduce the frequency of motion artifacts for the assessment of coronary arteries. In summary, single-heart beat dual-source CCTA could be an effective means for high-quality CCTA at very low radiation exposures in the future. P3036 Coronary artery spatial distribution of vulnerable plaques in non-culprit segments by computed tomography angiography in patients with acute myocardial infarction A. Sato, D. Akiyama, H. Watabe, Y. Seo, T. Ishizu, N. Murakoshi, S. Watanabe, K. Aonuma. Cardiovascular Division, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan Previous studies reported that acute coronary occlusions leading to ST-segment elevation myocardial infarction (STEMI) tend to cluster within the proximal third of coronary arteries. We assessed morphology and spatial distribution of vulnerable plaques in non-culprit lesions in patients with STEMI by 64-slice computed tomography angiography (CTA). Methods and results: Sixty-four patients with STEMI underwent 64-slice CTA within 1 week after admission. Among the 64 patients, coronary plaques (5.7±2.7 plaques/patient) of 60 patients (95%) were observed in the non-culprit coronary arteries, while 42 patients (66%) had vulnerable plaques (2.7±2.2 plaques/patient), which were defined as low CT density (<35 Hounsfield Unites) and positive remodeling or hypo-dense spots (lipid pools). In the left anterior descending (LAD) and left circumflex (LCX) coronary arteries, non-calcified (p=0.003, p=0.019, respectively), calcified (p=0.007, p=0.0005, respectively) and mixed plaques (p=0.0005, p=0.010, respectively) were more frequently distributed in the proximal segments, whereas there were no differences in distribution of non-calcified (p=0.434), calcified (p=0.152), and mixed plaques (p=0.283) in the right coronary artery (RCA). Vulnerable plaques were more frequently distributed in the proximal segments of the LAD (p<0.0001), whereas there were no differences in distribution of vulnerable plaques in the RCA (p=0.687) and LCX (p=0.062). (Figure). with regard to coronary artery segments contrast was assessed by two blinded readers independently in consensus by using transverse sections and maximum intensity projections. For evaluation of subjective image quality, a five-point scale (score of 5, excellent; 4, good; 3, moderate; 2, still diagnostic; 1, nondiagnostic) was applied. Effective dose was calculated on the basis of dose length product and volume CT dose index. Results of both protocols were compared by using the Student t test. Results: CT examinations in the SSP mode were successful in 29/30 patients (97%). In one patient the CT examination had to be repeated because of nondiagnostic quality because of increased in hear rate. The average (SD) heart rate was 56 (6) bpm (range 42 65) There was no significant difference in subjective image quality between protocols. Mean effective dose for the SSP technique was significantly lower than that for the conventional technique (5.43±0.39 msv vs 16.44±0.97 msv; 77% reduction; P 0.005). Conclusion: The use of an SSP technique resulted in significant reduction of effective radiation dose by 77% dose at CT coronary angiography, without significant loss of subjective image quality. P3038 Progressive decline in the dual source cardiac CT radiation dose with time: a two years single center experience P.J. Sousa, P. De Araujo Goncalves, H. Marques, R. Dourado, A. Gaspar, F. Pereira Machado, J. Roquete. Hospital da Luz, Lisbon, Portugal Purpose: Computed Tomography coronary angiography radiation dose has been pointed as a limitation for this technique, but it can be effectively reduced with protocol optimizations. The purpose of this study was to evaluate the temporal evolution of the radiation dose in Dual Source Cardiac CT (DSCT). Methods: Single-center prospective registry including 643 consecutive patients who performed a DSCT (Somaton Definition ) during 2007 and Results: Population mean age was 58±11 years and 60% were male. Mean acquisition time was 8.6±4.9 sec, 87±29 ml of isoosmolar contrast (Iodixanol, 320 mgi/ml) was administered and mean radiation dose was 8.5±4.7 msv. Mean heart rate was 68±15 bmp (no additional heart rate reduction for the scan). Population was divided in quartiles, according to the chronological order of the exams. There was a progressive reduction in mean radiation dose in the analyzed quartiles (Q1: 10.7±6.1mSv, Q2: 8.3±4.2mSv, Q3: 7.8±3.9mSv, Q4: 7.4±3.6mSv; p<0.05;ic:0.95 for Q1 Vs others). There was also a progressive more frequent use of a tube voltage of 100kV (Q1: 54%, Q2: 79%, Q3: 87%, Q4: 93%; p<0.001). A subgroup (31%) of patients (with history of surgical revascularization, exam acquisition in atrial fibrillation, impossibility to use 100 kv or when triple rule out protocol was applied) was also compared with the remaining population, and there was a marked difference in mean radiation dose (13.4±5.1 Vs 6.3±2.1 msv; p<0.001, IC:0.95). Distribution of vulnerable plaques Conclusion: Sixty-four-slice CTA may identify spatial distribution of vulnerable plaques in non-culprit segments throughout the coronary arteries. Identification of these high risk zones for future events will lead to more aggressive follow-up and medical intervention, and potentially locally directed preventive strategies. P3037 Low-dose CT coronary angiography matchs regular-dose in image quality A.P. Bayol, J.A. Vallejos, R.E. Peloso, M.A. Aguero, R. Obregon, A.C. Zarza, M.A. Collante Bohle, D.H. Sandoval, P.A. Pozzer, J.I. Parras. Cardiology Institute J.F.Cabral, Corrientes, Argentina Purpose: To prospectively compare 64-slices computed Tomography (CT) coronary angiography with SnapShot Pulse (SSP) technique and conventional technique for image quality and radiation dose. Materials and Methods: Prospective, singlecentre study conducted in a referral centre enrolling 60 patients, 55 men, mean Standard Desviation (SD) age 55 (9) years, mean (SD) body mass index 26.2 (3.2 kg/m 2 ) Median Agatston score: 238. The study had institutional review board approval; written informed consent was obtained. All studied patients were referred for evaluation of suspected coronary artery disease with CT coronary angiography. Patients were randomly assigned to a SSP technique (n: 30; 27 men, 3 women; mean age, 54±17 [SD] years; range, years) or conventional technique (n: 30; 25 men, 5 women; mean age, 55±15 years; range, years) protocol. Other scanning parameters were kept constant. Contrast medium was injected using the bolus timing method. Patients were excluded if a target heart rate (60 bpm could not be achieved by b blockers or when the patients were in nonsinus rhythm. Subjective image quality Conclusions: In this population there was a progressive reduction in the radiation dose with time. After the exclusion of some higher radiation dose predictors, it was possible to identify an important subgroup (2/3 of the population) with a mean radiation dose of 6.3 msv. P3039 Oral Ivabradine: an alternative to endovenous beta-blockade in the context of CT coronary angiography (CTCA). Heart rate reduction, image quality and motion artifacts L. Perez De Isla, J. Zamorano, G. Pizarro, P. Marcos-Alberca, C. Fernandez-Golfin, C. Almeria, J.L. Rodrigo, D. Herrera, A. Aubele, C. Macaya. Hospital Clinico San Carlos, Madrid, Spain Backgroud: heart rate (HR) control is an essential issue for a propper CTCA exam. The lower the HR, the better the image quality and the less radiation dose. Aim: the objective of our study is to assess whether oral Ivabradine (a new If current inhibitor) is a valid alternative to routinely used Betablockers in terms of heart rate reduction, image quality and presence of artifacts. Methods: 67 patients (42 male/25 female; mean age, 63.0±12.8; BMI, 27,24±3,45) referred for coronary 64-Slice MDCTA were studied. A BB group (26p), with a basal heart rate (BHR) >65 bpm received endovenous propranolol (1-5 mg) in order to reach <65 bpm; an I group (20p), with a BHR>65 bpm received two dosis of oral ivabradine (2,5-7,5 mg). Randomization was made by

190 490 Novel techniques: computed tomography and cardiovascular magnetic resonance / Monitoring and analysis clusters. A control group (21p) with a BHR<65 bpm did not need any drug. Sublingual nytroglicerine was administered in 64 p (95%). We studied heart rate reduction (%), image quality (1-3 bad, 4-5 good) and presence of step artifacts in each group. Results: Heart rate reduction was 10,4±1,7% in BB group, 15,2±3% in I group and 1,4±1,7% in control group (p<0,05). No significant difference was found between groups in image quality or presence of artifacts (p>0,5). MDCT visualization for IVR of PDA Main results Conclusion: Ivabradine is a valid alternative (not inferior) to Betablockers in terms of heart rate reduction, image quality and presence of image motion artifacts. P3040 Coronary-CT is not indicated in patients with agatston calcium score above 400 A. Diederichsen, H. Petersen, L.O. Jensen, P. Thayssen, O. Gerne, N.C.F. Sandgaard, P.F. Hoilund-Carlsen, H. Mickley. Odense University Hospital, Odense, Denmark Purpose: Coronary computed tomography angiography (CCTA) has proven clinically useful for non-invasive assessment of coronary anatomy and pathology. However, coronary calcium can reduce the diagnostic value of CCTA. The major topic of this study was to define a calcium score above which CCTA appears less reliable. Methods: We prospectively investigated 109 patients referred for elective coronary angiography. With a 64-slice CT-scanner, coronary calcium was determined and expressed in Agatston unit (U). A significant coronary stenosis was defined as 50% luminal diameter reduction. Following blinded interpretation, diagnostic values of CCTA at different levels of Agatston U were calculated using quantitative coronary angiography as reference. Results: The mean age of the patients was 63 (±11), and 47% were women. In 88 patients (81%) angina was the reason for referral. The diagnostic accuracy decreased in patients with stent and deteriorated with increasing severity of coronary calcium. Table 1. Influence of coronary stents and coronary calcium on diagnostic performance of 64-slice CT coronary angiography for the detection of 50% stenosis in patient-based analysis N Sensitivity, % Specificity, % PPV, % NPV, % All patients Patients with stent Patients without stent Calcium score (in pts without stent): 400 Agatston U > 400 Agatston U Conclusions: The diagnostic accuracy of CCTA in patients with no or little coronary calcium is excellent. However, in patients with an Agatston score > 400 U specificity declines and therefore, these patients should not go on to CCTA, but preferably be referred to conventional coronary angiography. P3041 ECG-gated MDCT of the patent ductus arteriosus in adult cases. Imaging findings and impact on management K. Takase, S. Matsumoto, S. Yoshida, Y. Morita, H. Saito, S. Takahashi. Tohoku University, School of Medicine, Sendai, Japan Purpose: The purpose of this presentation is to describe the usefulness of ECG gated MDCT in the management of patent ductus arteriosus (PDA) in adult cases. Materials: Seven adult cases with PDA (five women, age y.o.). Methods: ECG gated MDCT with 0.5 mm collimation was performed. In all cases, cardiac catheterization and descending aortography in left posterior oblique position was obtained. Five cases were successfully treated by IVR: three by coil embolization using detachable and PDA coils and two with Porstmann method. Two cases were treated by surgery, one of which simultaneously performed patch closure of co-existing atrial septal defect (ASD). Results: ECG gated MDCT successfully visualized the shape of PDA including neck and infundibulum in all cases. Length and diameter of PDA could be precisely measured by MDCT. In 2 cases, MDCT visualized narrow neck less than 3.5mm diameter and infundibular shape which are suitable for coil embolization. In two cases, MDCT accurately revealed the shape of PDA with 6.2mm and 7.0mm in diameter which were difficult to evaluate by aortography. Adequate plugs were made based on the CT findings. In one case, short and straight shape of the PDA was thought to be inadequate for IVR and treated by surgery. In one case, ASD that was overlooked by US was found by CT. Conclusion: ECG gated MDCT is useful in diagnosis, treatment planning, and pre-interventional imaging of adult case PDA. MONITORING AND ANALYSIS P3042 A textile monitoring system for polysomnography at high altitude M. Di Rienzo 1, C. Lombardi 2, P. Meriggi 1, P. Mazzoleni 1,F.Rizzo 1, G. Parati 3. 1 Biomedical Technology Department, Fond. Don Carlo Gnocchi Onlus, Milan, Italy; 2 Univ. Milano Bicocca; Istituto Auxologico Italiano IRCCS, Milan, Italy; 3 Universita di Milano-Bicocca, Milan, Italy Aims: Recently, we developed a new textile-based system for ECG, respiratory rate and motion monitoring in unrestrained subjects. For its simplicity of use, we employed this system to investigate sleep-related cardiorespiratory changes in a group of healthy subjects at high and very high altitude on Mount Everest as part of the Highcare Research Programme. In this paper we provide the methodological details of this application. Methods: The new system is composed of a vest and a small electronic module. At the thorax level the vest includes two woven ECG electrodes, a textile plethysmograph and electric wiring all made of textile conductive fibers. The electronic module includes a 3D accelerometer for movement assessment and is connected to the vest through a connector. It receives data from the textile sensors and stores them on a memory card or transmits them to a remote computer via bluetooth. For this expedition the electronic board was modified to record also data coming from a pulsoxymeter. The performance of the system was compared with that of a commercially available device for cardiorespiratory polysomnography. Thirty healthy subjects participating in the Highcare expedition were recruited for the study. Five recordings were performed throughout the expedition time: two at sea level before and after high altitude exposure, one at 3500 m, one during the first nights (acute conditions) and one in the last night (chronic conditions) at Everest base camp (BC) at 5400m. Moreover additional recordings were successfully performed by 7 professional climbers at about 6800m. Results: Despite the challenging environmental conditions carrying considerable discomfort to Highcare team members (hypoxia, cold weather, hard living conditions, small room available), most of the planned recordings were performed on scheduled time and the signals quality was good and comparable with that of the portable polisomnographic devices. Only few recordings could not be performed because of the unavailability of subjects suffering from manifest mountain sickness symptoms at BC. The simplicity of the system setup allowed us to instrument all subjects in a very short time. Hence, despite the availability of very few operators, we were able to monitor during the same night up to thirty subjects. Use of textile-based system did not influence sleep quality. Conclusions: These findings show that the performance of the new system was more than adequate for the purpose of the Highcare project, and encourage its use in a wide spectrum of applications, ranging from telemedicine and telemetry in clinical practice and research. P3043 Detection of stable atrial fibrillation sources from standard 12-lead ECG C. Duchene, M. Lemay, J.M. Vesin. Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Introduction: The evaluation of the presence of stable atrial fibrillation (AF) sources (or triggers ) remains one of the major challenges in AF management. In this simulation study, we investigated the feasibility of detecting such sources from the standard 12-lead ECG. Methods: A 3D biophysical model of the atria was developed, which simulates the propagation of the electrical impulse based on the Courtemanche membrane kinetics. Twenty-one episodes of AF were generated. These differed in the ar-

191 Monitoring and analysis 491 rhythmogenic substrates that were used in order to make the model vulnerable to AF, by introducing either heterogeneities in action potential duration or a focal source (at a fixed firing rate). The presence of stable AF triggers was established by observing the electrical propagation on the epicardium, identifying group A: without a stable source, and group B: with one or more stable sources. This classification constituted our gold standard. The corresponding twenty-one 12-lead ECGs were computed by using an inhomogeneous compartmental torso model. An advanced frequency tracking algorithm was applied to the simulated ECGs to detect the presence of any stable frequency components. These were identified by using the averaged power ratio, rp, of each frequency component and its respective 12-lead ECG signals as the discrimination feature. Results: The epicardial signals identified 9 cases characterized by complex dynamics: group A. The remaining twelve cases comprised eleven AF episodes characterized by a unique stable AF source (3 showing focal activity and 8 exhibiting mother-rotors) and one having two stable sources (a mother-rotor around the lower right pulmonary vein and a mother-rotor in the leftappendage): group B. Analysis of the ECG data revealed rp values that were lower in group A (mean ± SD: 0.05±0.04) than in group B (0.28±0.17). Based on a discrimination threshold of rp = 0.14, all 9 cases of group A were correctly classified as having complex dynamics; in group B there were 2 cases (incorrectly) classified as such, corresponding to 90% correct classifications, 100% sensitivity and 83% specificity (p < 1.54x10-4). Conclusion: The results of our study strongly suggest that, by applying the proposed feature, the standard 12-lead ECG signals can be used for discriminating between stable and unstable types of AF. This information may lead to a more accurate identification of patients suitable for specific AF ablation procedures. from the correlation integral. The study population consists of 168 patients (age: 64.8±7.4 male/female: 84/84) with paroxysmal atrial fibrillation (PAF) and sinus rhythm recurrence within 24 hours. The internet-holter registration was started within 6 hours after the onset of PAF and lasted continuously for 14 days. At the end of the observation the patients were divided into two groups: (A-group (21 pts): recurrent PAF, B-group (147 pts): without it). Using the multivariate discriminant analysis three variables (the amplitude values of the 2D plots of the Cm (r) at r value of -1.0 (x1), and -0.5 (x2), of the CGCD at r value of -0.4 (x3)) were determined for the model. The separation of the two groups revealed excellent (Wilks lambda p< 0.001), the equation of the discriminant score: D = 0.43 x x2 2.6 x In the second study, a cascade-like ECG telemedicine scenario was performed. 47 patients with high risk of AF recurrence, but without any documented AF events, were selected for an 8-day repeated wireless ECG monitoring. The maximum (MPD) and total p-wave duration (TPD), the isoelectric interval (TPD-MPD), the PR interval, the P terminal force, P-wave variance were measured after the special signal-preprocessing (filtering, PQRST template matching, QRST elimination). Detecting any change of any above mentioned (> 20%) parameters, the frequency of telemedicine monitoring increased to every forth day, in the case of additional parameter changing to every second day, and to every day (cascade scheme). During the 8 months follow up, in 30 patients the parameters did not change. The overall statistics for the patients: specificity (SP): 0.76, negative predictivity (NP) (p<0.01); for the all 182 cascade registrations: SP: 0.77, sensitivity: 0.46, positive predictivity: 0.73, NP: 0.52 Our study showed a powerful method for the predicting of PAF recurrence and it would be help in the managing strategy. P3044 Nonlinear dynamic analysis of short-term R-R interval time series in patients with Sarcoidosis T.G. Papaioannou 1,E.Gialafos 1,A.Rapti 2, C. Aggeli 1, D. Soulis 1, M. Vavuranakis 1,G.Siasos 1, C. Kostopoulos 3, D. Tousoulis 1, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Sotiria Regional Chest Diseases Hospital, Athens, Greece; 3 Regional General Hospital Alexandra of Athens, Athens, Greece Impaired autonomic nervous system and ventricular arrhythmias are common in patients with Sarcoidosis (Sar). Analysis of heart rate variability (HRV) is often used to assess the autonomic nervous system. Nonlinear dynamic ( Chaotic ) features of HRV may reveal valuable diagnostic and prognostic information independently from the traditional time or frequency domain indices. Although an impairment of HRV has been reported in Sar pts, there are no data regarding the nonlinear features of HRV. The aim of this study was to examine the short-term nonlinear characteristics of HRV in Sar pts. Methods: 57 consecutive Sar pts and 18 controls were studied. Sar pts underwent chest radiography to determine disease stage using standard radiographic staging for Sar. Pulmonary function tests were also performed: forced expiratory volume at 1 sec (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusing capacity (DLCO). 20min RR-intervals were recorded and analyzed by means of approximate entropy (ApEn) and detrended fluctuation analysis. The nonlinear a1 and a2 scaling-exponents were calculated, indicating randomness of HRV pattern. Results: At first, 18 untreated Sar normotensive pts were compared to 18 age matched healthy individuals. A significantly increased a2 was observed in Sar pts compared to controls (0.90±0.09 vs 0.82±0.07, p=0.008), indicating an increased randomness in HRV in Sar pts. No difference was observed in ApEn between Sar pts and controls. In the total Sar population, the scaling-exponent a2 was independently related with body mass index (b=0.384, p=0.003) and TLC (b= , p=0.009). Logistic regression analysis showed that a2 was a significant predictor of increased disease stage (III and IV) (p=0.033), even after adjustment for age and cortisone use. Conclusions: It was shown that untreated normotensive Sar pts present significantly higher randomness in short-term HRV compared to controls which implies that the pattern of RR-interval variability becomes more chaotic with a potential negative effect in their cardiovascular risk. Furthermore, it was revealed that decreased total lung capacity was independently associated with the increased randomness of HRV. The short-term analysis of nonlinear dynamics of RR-intervals may be a useful tool for the assessment of autonomic nervous system with potential clinical relevance. P3045 Prediction of atrial fibrillation recurrence: non-linear and time domain analysis of the f- and P-waves K. Fugedi 1, S. Khoor 1, N. Balogh 2, M. Khoor 2,B.Kail 2,I.Kovacs 1. 1 Szent Istvan Hospital, Budapest, Hungary; 2 Artintell TM, Budapest, Hungary The extended length (14 days) internet Holter registrations were performed with our mobile ECG system with GPRS transmission. The modified Frank orthogonal leads were implemented with higher resolution than the conventional Holter equipments, and the morphology analysis of the p-, and f-waves could be performed. The internet server collected continuously the data for further analysis. In the first study, the dynamics of the atrial fibrillation waves were investigated by estimating the coarse-grained correlation dimension (CGCD) and entropy (CGCE) P3046 Electrocardiographic patterns of early repolarization attributable to increased transient outward current in the subepicardial region. A simulation study A.D. Corlan 1,B.Amuzescu 2, I. Milicin 3, L. De Ambroggi 4. 1 University Emergency Hospital, Bucharest, Romania; 2 University of Bucharest, Bucharest, Romania; 3 Scalacalc Laboratory, Quattro Electronic Design, Bucharest, Romania; 4 IRCCS Policlinico San Donato, University of Milan, San Donato Milanese, Italy Background: An association between the presence of ECG patterns of early repolarization (prominent J wave and/or QRS slurring) and occurrence of malignant ventricular arrhythmias has been reported. Purpose: We aimed to characterize the effect on body surface ECG potentials of one of the proposed causes of early repolarization: the increased maximal conductance for the transient outward current in the subepicardial region. Methods: We simulated single cardiac cycle electrocardiograms using 3D finite element models of the ventricular myocardium, with six strata in each ventricle. Action potentials were simulated with modified Luo-Rudy dynamic models, with parameters adjusted for the human myocytes. 370 surface electrograms were computed on a human thorax-shaped volume conductor. Pairs of simulations were run with the same maximal conductivities for the fast and slow K, the ATPdependent K, plateau K, T and L-type Ca and Na/Ca exchanger currents. In one member of the pair the maximal conductance of the transient outward current was 0, while in the other it had a randomly assigned value between and ns/pf in the subepicardial stratum. In each of 1000 pairs of simulations random values in a range of ±60% from literature reference values were used for the channels other than transient outward. The body surface effect of the Ito (ItoECG) was computed in each pair by substracting the ECG of the non-ito case from that of the Ito case. Results: The maximal amplitude of the root mean square (RMS) of the ItoECG was 28±4% of the maximal amplitude of the RMS of the non-ito QRS. The ItoECG reached this maximum 28 ms before the J point It was correlated (R=0.97) and linearly related with the Ito maximal conductance but not with any other maximal conductances, except slightly with that of the plateau K current (R=-0.11, p<0.001). At the end of ventricular activation (the J point) the ItoECG contribution to the RMS of the J point was 5.5±2.9% of the QRS RMS amplitude, then ItoECG continued to decrease for 21±2.4 ms. ItoECG was constant during the rest of the ST and then increased again in amplitude during the T wave. Conclusions: Parameters of the simulated effect of physiological levels of Ito on the body surface potentials are consistent with ECG observations of the early repolarization phenomenon. Most of the Ito effect was superimposed on the last part of the depolarization. P3047 The detection of new-onset atrial fibrillation in vascular surgery patients with an implantable continuous electrocardiography monitoring device T.A. Winkel 1, D.R. Hampton 2,W.-J.Flu 1,A.Pietersma 3, O. Schouten 1, J.P.C.M. Oomen 1, H.J.M. Verhagen 1, D. Poldermans 1. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Medtronic BRC, Maastricht, Netherlands; 3 Qserve Consultancy B.V., Purmerend, Netherlands Background: Vascular surgery procedures may be accompanied by cardiovascular complications, including myocardial infarction and cardiac arrhythmias, which can lead to increased postoperative morbidity and mortality. Paroxysmal

192 492 Monitoring and analysis atrial fibrillation (AF) is the most common form of postoperative cardiac arrhythmias, but it is often short-lived and asymptomatic, making detection difficult and causing the true incidence to be understated. Developing postoperative AF, however, has important patient consequences, suggesting therapeutic interventions to prevent subsequent complications. In this current ongoing study we measured, for the first time, the incidence of AF beyond the perioperative vascular surgery period using continuous cardiac monitoring. Methods: Seven patients scheduled for an abdominal aortic aneurysm repair (4 open procedures and 3 endovascular) were enrolled, each with baseline sinus rhythm and no preexisting AF. One month prior to surgery a cardiac loop recorder (ILR Reveal XT ) was implanted subcutaneously; it continuously monitored for AF until it was explanted one month post-surgery. Patients were also monitored perioperatively with a conventional 72-hour Holter ECG, starting 1 day before surgery until 2 days afterward; standard 12-lead ECGs were collected 3 and 7 days after surgery. New-onset AF was detected by automatic interpretation and confirmed by skilled over read. Results: New-onset AF occurred in 2/7 (29%) patients; one was also detected by 72-hour Holter ECG, but none by standard 12-lead ECG. The continuous monitor detected an average of 155 AF episodes, all of which were asymptomatic. One patient developed AF preoperatively, while the other developed AF 26 days after surgery. Conclusion: There is a higher than suspected incidence of paroxysmal AF in the perioperative period after vascular surgery procedures. Vascular surgery patients may develop paroxysmal AF outside the recording window of the 72-hour Holter ECG and in the majority of cases being asymptomatic. Continuous implanted cardiac monitors can detect these paroxysmal episodes during and after hospital discharge. There is 100% agreement with 72-hour Holter monitoring for in-hospital detection of AF. P3048 Measures of heart rate variability from the Polar S810 and HRV analysis software 1.1: a validity and reliability study in chronic heart failure David Nunan 1, D. Jakovljevic 1, G. Donovan 1, G. Sandercock 2, R. Grocott-Mason 3, S. Mcdonagh 3, D. Brodie 1. 1 Buckinghamshire New University, Chalfont St Giles, United Kingdom; 2 University of Essex, Colchester, United Kingdom; 3 Hillingdon Hospital NHS Trust, London, United Kingdom Purpose: The Polar S810 and HRV analysis systems were assessed in terms of their reliability and validity to determine heart rate variability (HRV) in chronic heart failure (CHF) patients, using appropriate statistical procedures. Methods: Five min R wave interval (R-R) data for 16 male and four female mildto-moderate CHF patients during 10 min of quiet rest on two separate occasions at one week intervals were obtained using the Polar S810. Separate measures of HRV were obtained from the same R-R data using Polar specific software and two different settings (with or without detrend) in a seperate software package (HRV Analysis Software 1.1., Kuopio, Finland). Measures of the validity of HRV analysis software 1.1 (HRV 1.1) without detrend were estimated by regression analysis. Measures of reliability of the Polar S810 and HRV 1.1 with detrend were estimated by analysis of change scores (standard error of estimate (SEE) and intraclass correlation coefficients (ICC). Linear measures of the SD of normal-to-normal intervals (SDNN), the root mean square of successive differences (rmssd), and the low-frequency (LF), the high-frequency (HF) spectral power and nonlinear Poincare plot measures (SD1 and SD2) were analysed after log transformation, whereas mean RR, LF and HF in normalised units (nu) and their ratio (LF:HF) were analysed without transformation. Results: Measures of HRV from the Polar S810 demonstrated similar reliability compared with estimates previously observed in healthy participants. There were marginal differences between the Polar and the HRV 1.1 (without detrend) for all time-domain and nonlinear measures of HRV. Uncertainty in the differences was small and high correlations (>0.98) indicated near-perfect validity for these measures from the HRV 1.1 Normalised and log LF and HF power were underestimated by the HRV analysis software, but uncertainty in differences was large (R = 0.66 and 0.38) and small (R > 0.98) for the former and later measures respectively. For LFnu and HFnu, the HRV 1.1 with a detrend applied did not add any substantial technical error to the within-subject variability in repeated Polar S180 measures of HRV. Large inter- and intra-individual variation in HRV was observed, but was similar to that observed in healthy individuals. Conclusion: The Polar S810 is no less reliable in patients with CHF. The HRV 1.1 adds no appreciable bias to most Polar S810 measures, indicating its valid use in CHF. Applying a detrend to the R-R data does not alter its reliability. The Polar S810 and HRV 1.1 may be used as valid and reliable tools in the assessment of autonomic function in CHF. Purpose: To evaluate the accuracy of remote assessment of digitally stored cardiac sounds and resulting referrals, against the final echocardiographic diagnosis, in a random sample of asymptomatic school aged children. Methods: A random subset of Cretan Pediatric Cardiology Survey study population, underwent both a detailed echocardiographic study and a digital phonocardiogram recording. An experienced pediatric cardiologist, blind to the diagnosis, performed an off-line analysis of the digitally stored sounds. The accuracy of his referrals for echocardiography, based on the presence and type of murmurs and of additional findings (click, 2nd heart tone abnormalities) was tested against the echocardiographic diagnosis. Results: Two hundred eighteen children (average age 8.5yrs) were included in the study. Echocardiography often revealed trivial or mild heart defects, without any clinical significance in most cases. Based on remote assessment of heart murmurs only (approach A), a referral indication was stated in 22 (10,1%) of cases. If referrals were based on the presence of abnormal murmur and/or additional auscultatory findings (approach B) a total of 70 children (32,2%) would have been referred. Approach A could detect 10% of subtle echocardiographic anomalies while approach B had a diagnostic yield of 38% (Table 1) Table 1. Digital phonocardiography referrals vs echocardiographic diagnosis Variable Referal Echo Echo + MI/MVP AoS/BAoV PS PFO ASD LVH/D PERIC Murmur no yes correct (%) Murmur + ad. sounds no yes correct (%) Conclusions: The performance of digital phonocardiography to detect minor forms of heart disease among school aged children is suboptimal when based solely on murmur analysis. The interpretation of additional auscultatory findings increases the diagnostic yield, at the cost though of increased overall referrals. The appropriate selection of auscultatory variables, the severity level of heart disease we wish to detect and the available resources have a great influence on the performance of a screening program based on remote cardiac auscultation. P3050 Implementation of simulator based training for paediatric echocardiography M. Weidenbach 1, V. Razek 1, R. Wagner 1, F. Wild 1, T. Berlage 2, J. Janousek 1. 1 Herzzentrum der Universitaet Leipzig, Leipzig, Germany; 2 Fraunhofer Institute for Applied Information Technologies, St. Augustin, Germany Objectives: Testing the feasibility of implementing simulator training into courses for pediatric echocardiography. Methods: We used EchoCom, a simulator for echocardiography that we have developed at our institution, as an additional tool during a board certified echocardiography course at the Heart Center Leipzig. EchoCom consists of a manikin, a electromagnetic tracking system and a computer application (see figure). The application visualizes two-dimensional echocardiographic images derived from stored 3D data sets according to the tracker position and represents them sideby-side with a virtual 3D scene of the heart and ultrasound probe. It is linked with a data base of 3D data sets covering most congenital heart diseases. The course is divided into a theoretical and a practical part. Within the practical part children (with/without cardiac disease) volunteer as training models. Participants were divided into groups of 5 and had two training sessions with children and one simulator session. After completion they filled out a standardized questionnaire regarding the usefulness of the simulator. Results: A total of 30 physicians participated in the study. All regarded the implementation of the simulator as useful and said it has advantages compared to training on volunteers. 92% said the simulator could impart aspects they would have not acquired without the simulator. 53% voted to have more simulator training, while 47% said that the extent was adequate. No one wanted to have less simulator training. P3049 Digital phonocardiography as a screening tool in school aged children I. Germanakis 1, F. Parthenakis 2, R. Perakaki 2, P.E. Vardas 2, M. Kalmanti 1. 1 Dpt of Obstetrics and Gynecology, University Hospital Heraklion Crete, Heraklion, Greece; 2 Dpt of Cardiology, University Hospital Heraklion Crete, Heraklion, Greece Simulator Conclusion: Implementing simulator training in addition to traditional learning methods in echocardiography courses is useful and rated positively by course participants.

193 Monitoring and analysis 493 P3051 Expert system to predict in-hospital mortality after ST elevation myocardial infarction E. Garcia Moran, C. Tapia, C. Hernandez Luis, M. Sandin, I. Amat, E. Zatarain, F. Gimeno, R. Andion, I. Gonzalez, J.A. San Roman. ICICOR, Valladolid, Spain Guidelines on ST elevation myocardial infarction (STEMI) recommend risk assessment based on standard tools. OBJECTIVE: To develop an expert system (ExSys) from a local database to predict in-hospital mortality after STEMI for comparison with the TIMI risk score (TRS). Methods: Consecutive cases admitted for STEMI were included to develop an ExSys using the variables included in the TRS except delay to treatment. The ExSys was built using a box kernel density estimation (10-bin histograms) to compute the probability of death in the multidimensional space. Classification parameter was the difference of densities. The ExSys was written in Java 5.0. Generalization was assessed by a leave-one-out (LOO) validation method. Results: Patients n= 688, age (64.9±13.3), male 62%; Killip III-IV: 16%. Death during hospital stay occurred in 96 patients (13.95%). Our ExSys was able to perform a powerful discrimination between alive and dead patients at discharge as shown by the ROC curve (figure). The area under the curve for the ExSys was 0.89, significantly higher (p<0.05) than that of the TRS (0.54). The maximal value of accuracy (c-index)of the ExSys at the training stage was 0.89 and at the LOO validation 0.87, in contrast with that of the TRS (score 5); c-index: Sensitivity, especificity, positive and negative predictive values of ExSys were: 0.50; 0.96; 0.69; 0.92; TRS corresponding values: 0.38; 0.87; 0.35; Results: The sensitivity analysis shows that the mean value of the maximum stress is about MPa (sd MPa). For Dmax less that 50 mm the peak stress is primarily affected by ecc with a correlation coefficient (C.C.) equal to 0.88, while for Dmax in the range of mm the C.C. is for ecc and for the Dmax. Conclusions: The maximum diameter can not be considered as a unique criterion to estimate the aneurysm rupture risk. This study points out the capability of our method to offer a new and efficient procedure of generating patient-specific computational models that can be applied to clinical work-out in preoperative estimation of aneurysm rupture risk. P3053 Electronic pathways in cardiology V.A. Umans, E.G. Zwaan, G. Kimman, A. Wals. Medical Center Alkmaar, Alkmaar, Netherlands Computers can assist in providing guidelines, protocols and optimizing patient outcome. With a bedside electronic medical record, there is the possibility of linking patient data with these aids. Such techniques may prevent variations in a care protocol that are dependent on who is using the protocol. Clinician compliance may be further improved when protocols are customised into a critical pathway. We describe the implementation of a digitized critical pathway for cardioversion therapy for atrial fibrillation. Methods: an IT solution was created for integrating the medical and nursing charts into the existing hospital IT architecture. The SDE module was used to design a digital version of the clinical pathway. All of the requested clinical and paramedical items from the patient history and physical examination were included in separate tabs. Results: Since its launch in 2008, 600 consecutive patients have been treated using this new pathway. We acquired a fully digital integration of the medical and nursing chart and it was used for every one of these patients, without exception. The variance analysis showed: no drop-out due to errors in the appointment module, while cardioversion was not performed in 4% of patients due to inadequate anticoagulation, or insufficient sedation in 4%. All outpatient appointments at the nurse specialist clinic were kept. The walk-through time was significantly reduced compared to a control group: Modelo Expert System ROC curve Conclusion: A locally derived expert system is able to provide adequate prediction of in-hospital mortality after STEMI. Our ExSys outperforms external risk assessment tools like the TRS proving usefulness of machine learning techniques on small samples. P3052 Investigation on additional parameters for thoracic arc aneurysm rupture risk estimation by probabilistic finite element approach S. Celi 1,S.Berti 2, M. Mariani 2,F.DiPuccio 3,P.Forte 3. 1 IFC CNR - Ospedale Pasquinucci, Massa, Italy; 2 Fondazione Gabriele Monasterio, Massa, Italy; 3 Dip. Ing. Mecc. Nuc. Prod., Università di Pisa, Pisa, Italy Aim: In clinical practice, the maximum diameter is used as criterion to estimate the aneurysm rupture risk. This criterion, however, is only a general rule and not a reliable indicator since also small aneurysm can rupture. From a biomechanical perspective, the rupture event include both material properties and morphology aspects and occurs when the mechanical wall stress exceeds the tensile strength of the tissue. The aim of this study is to identify of geometric parameters that can be a reliable predictor of rupture. A new method based on an patient-specific model is presented. Methods: CT images have been analysed and the main geometrical features of TA arch diseases have been identified. Several 3D TA models were developed and sensitivity analyses were performed by using a probabilistic approach implemented in a FE code. As random parameters were assumed the maximum diameter (Dmax) and the eccentricity (ecc). Material was considered as hyperelastic, homogeneous, isotropic with data taken from literature. The stress state at the peak systolic pressure has been analysed. Up to 200 virtual models have been investigated. Von Mises maximum stress. Walk through time Conclusion: this digitized critical pathway achieved a full integration of medical and nursing charts and improve clinical care by structured clinical care along the pathway protocols. It only allows objective protocol deviations which are continuously monitored in the on-going variance analysis. This ICT solution resulted in a significant reduction in walk-through times. P3054 Efficacy of self optimizing neural network (SONN) for predicting long-term outcomes in patients with STEMI treated with primary percutaneous coronary intervention J. Forys 1, A. Popa 2, P. Fulmanski 2, A.M. Nowakowski 2, J.D. Kasprzak 1. 1 Medical University of Lodz, Lodz, Poland; 2 University of Lodz, Lodz, Poland Background: Self Optimizing Neural Network (SONN) may be used for creation of expert systems in cardiology. We aimed to create and test the ability of SONN for the prediction of individual risk in patients after acute myocardial infarction treated with primary percutaneus coronary intervention. Methods: We based our study on the database of 805 patients with coronary disease with known follow-up of 24 months duration. We chose 17 clinical categories (including standard risk factors). Every patient was represented with one input vector, containing demographic and biochemistry data, cardiovascular risk factors, numerous angiographical and echocardiographic data and was assigned to 1 of 5 distinct output classes reflecting clinical course. The coefficient of discrimination and weight of neurons were computed only once allowing the computation of appropriate network topology. The described learning process works only on discrete input data. In order to use this network for continuous data, the data were transformed to discrete classes. Such a transform was necessary to change each data from continuous to discrete value. Intervals for each medical data were made by medical expert. This type of neural network works only with three learning data: 1 (feature exist), -1 (feature not exist) and 0 (we don t have any information about that feature). which explains the need to convert each medical feature into classes. Results: From the group of 805 patients, data of 666 were used to teach neural network. Remaining 139 patients were used for network testing. The result of

194 494 Monitoring and analysis / Stem cells in situ classification are: univocally classified: 116 patterns (83,45%), equivocally classified: 3 patterns (2,16%), not classified: 20 (14,39%). Thus, our neural network can correctly assign patient into one of five prognostic output classes with 83% probability. Next step will be the selection of features with best discrimination value and optimization of neural network topology. Conclusion: SONNs are potential means for creation of advanced tools for prognosing the survival and cardiovascular adverse events in individual patients with AMI treated interventionally in long-term aspect. Standard SONN algorithms may not be optimal for clinical expert systems, however, with a proper combination of network structure and learning algorithms, it is possible to obtain >90% correct prediction of future clinical course. Results: The target vessel was reached in 14 cases. NYHA-class and EF improved significantly with a low rate of non responders of 15% (EF) and 20% (NYHA). Image registration was possible in all patients. Post-process 3D-analysis revealed no correlation between the distance FIS-RLC and functional or echocardiographic improvements. There was a trend towards a shorter distance FIS-RLC in patients classified as responders (EF). NYHA-class improved significantly better in patients with target vessel implantation. Conclusions: Registration of CT/MRI-images is possible supporting efforts to reach the RLC by preoperative identification of corresponding veins. Larger randomized trials must define the definite therapeutic benefit. P3055 Are there objective methods for choosing the best compression algorithm for coronary angiograms? K. Kronberg, R. Kussebi, A. Franz, R. Motz, A. Elsaesser. Klinikum Oldenburg, Oldenburg, Germany Background: The amount of cardiac catheterization procudures increases every year and many hospitals take advantage of an electronic patient record. For long term storage and network transmission of heart catheterisation films a data compression is desirable. Methods: We used 10 different sequences of catheterization films for compression. All films were compressed with 6 different compression rates and standards: DICOM (Digital Imaging and Communications in Medicine) conform as JPEG (Joint Photographic Experts Group), as MPEG-2, MPEG-4 (Moving Picture Experts Group with DivX und XviD) and with the new MPEG-4/AVC H.264 Standard for High Definition Television (HDTV with Advanced Video Coding and x264 und x264high). The signal to noise ratio (SNR) was evaluated with the free software AviSynth and the blocking artefacts with the MSU Video Quality Measurement Tool. As a simulation of coronary arteries a moving pythagoras fractal was choosen. The results were matched with subjective assessment from 10 experienced cardiologists. Results: The analysis of the signal to noise ratio (SNR) for an entire picture were around 40 db and showed no significant differences between the compression methods. The SNR and the blocking artefacts for each pixel in a picture are valuable tools for evaluating the compression algorithm (see picture). The simulation with the pythagoras fractal gives a quick estimate about the considered range of artefact free reproduction. STEM CELLS IN SITU P3057 Association of genetic variants with myocardial infarction in Japanese individuals with chronic kidney disease T. Fujimaki 1,K.Kato 1, S. Tanaka 1,T.Kawamiya 1, K. Yajima 1, T. Hibino 1,K.Yokoi 1, T. Murohara 2,G.Kimura 3, Y. Yamada 4. 1 Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan; 2 Nagoya University Graduate School of Medicine, Nagoya, Japan; 3 Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medi, Nagoya, Japan; 4 Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan Purpose: Chronic kidney disease (CKD) is a serious clinical condition that is associated with a high incidence of cardiovascular disease and end-stage renal disease. Although CKD has been recognized as a risk factor for myocardial infarction (MI), genetic factors for predisposition to MI in individuals with CKD have remained largely unknown.the purpose of the present study was to identify genetic variants that confer susceptibility to MI in Japanese individuals with CKD. Methods: The study subjects comprised 1339 Japanese individuals with CKD, including 496 subjects with MI and 843 controls. The genotypes for 248 polymorphisms of 181 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results: An initial screen of allele frequencies by the chi-square test revealed that the 11496G A (Arg353Gln) polymorphism of F7 (rs6046) was significantly (false discovery rate < 0.05) associated with the prevalence of MI in individuals with CKD. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure also revealed that this polymorphism was significantly (P < 0.005) associated with MI, with the variant A (Gln) allele protecting against this condition. Conclusions: Determination of genotype for the 11496G A (Arg353Gln) polymorphism of F7 may prove informative for assessment of the genetic risk for MI in individuals with CKD. Visualisation of compression artefacts Conclusion: Modern image analysis programs offer a valuable computer simulation tool for the choice of the best compression algorithm. Finally a subjective evaluation of skilled cardiologist is essential. In our study the HDTV standard H.264 was the best currently available compression algorithm for coronary angiogramms. P3056 A technical approach for registration of coronary venous anatomy to the site of latest mechanical contraction using cardiac CT and MRI C. Knackstedt 1, G. Muehlenbruch 2,K.Mischke 1, G. Schummers 3, A. Mahnken 2, R. Guenther 2,M.Kelm 1, P. Schauerte 1. 1 RWTH Aachen University, Department of Cardiology, Pulmonology and Vascular Medicine, Aachen, Germany; 2 RWTH Aachen University, Department of Diagnostic Radiology, Aachen, Germany; 3 Tomtec imaging system, Unterschleissheim, Germany Purpose: Cardiac resynchronizing therapy (CRT) provides a therapeutic option for patients with congestive heart failure (CHF). There is evidence that the optimal pacing site (OIS) is vicinal to the region of latest contraction (RLC). However, the RLC is not identified routinely to guide lead implantation to the coronary venous system (CVS). The aim of this study was to develop a software overimposing CVS-anatomy on parametric images of left ventricular dyssynchrony in a 3D-format obtained from CT and cardiac MRI and apply this 3D-software for a post-process analysis whether the distance between final implantation site (FIS) and RLC correlates with functional/clinical improvement. Methods: In 20 CHF-patients (11 male, 65.6±6.8 years, ejection fraction (EF): 27.5±6.1%) CRT-leads implanted; follow-up included echocardiographic and exercise evaluation. The OIS and the FIS was noted on 3D-registrations and the distances OIS-RLC and FIS-RLC measured. P3058 Sporadic arrhythmogenic right ventricular cardiomyopathy due to a de novo mutation E. Gandjbakhch 1,V.Fressart 1, G. Bertaux 2,L.Faivre 2,R.Frank 1, G. Fontaine 1, E. Villard 1, C. Coirault 1, B. Hainque 1,P.Charron 1. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 Centre Hospitalier Universitaire de Dijon, Dijon, France We report the case of a 41-year-old man with a diagnosis of sporadic arrhythmogenic right ventricular cardiomyopathy (ARVC). The electrocardiogram displayed extensive T waves inversion in précordial leads. The 24-hour ECG monitoring documented more than 500 polymorphic ventricular ectopies. Signal-averaged ECG with 40Hz filter showed late potentials. The echocardiogram showed right ventricular (RV) abnormalities with global mild RV dilatation, wall motion abnormalities localised in the inferior wall and the apex, and excessive trabeculations, while left ventricle appeared normal. RV abnormalities were confirmed by cardiac noncontrast cine-mri. The electrophysiological study easily induced reproducible fast ventricular tachycardia with two different left-bundle-branch block morphologies. The genetic screening of the four desmosomal genes plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2 (that have been shown to be involved in ARVC) identified the heterozygous missense mutation R49H in the desmoglein-2 gene. This mutation is located in the highly conserved cleavage motif RXK/RR that is recognised by pro-protein convertases and is thus predicted to prevent efficient pro-desmoglein-2 maturation. The mutation was absent in both parents, and we demonstrated that it was a de novo mutation. To the best of our knowledge, this is the first description of a de novo mutation in ARVC. Appearance of a de novo mutation in the desmoglein-2 gene (that is an essential component of desmosome that mediates cell-to-cell adhesion) provides compelling genetic evidence for the involvement of this gene in ARVC. The recognition of de novo mutations has important implications, including for clinical practice, since individuals with sporadic ARVC caused by a de novo mutation can transmit the disease gene to 50% of their offspring. This suggests that the benefit of molecular genetics can be extended to sporadic ARVC, and may improve genetic counselling.

195 Stem cells in situ 495 P3059 Stem cell therapy in pulmonary hypertension-induced right heart failure reduces right ventricular hypertrophy, dysfunction and remodeling by inhibiting pulmonary arteriolar medial hypertrophy S. Umar, P. Steendijk, G. Wagenaar, C. Schutte, W. Bax, D. Pijnappels, D. Atsma, M. Schalij, E. Van Der Wall, A. Van Der Laarse. Leiden University Medical Center, Leiden, Netherlands Background: Pulmonary arterial hypertension (PAH) is a chronic lung disease which leads to right ventricular (RV) hypertrophy, RV failure and extracellularmatrix (ECM) remodeling. Current therapies are inadequate for treating PAH. Autologous mesenchymal stem cell (MSC) therapy is a novel option for treating PAH. Purpose of the study: Whether bone marrow-derived MSCs from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH, mimicking autologous cell therapy, results in reversal of (i) PAH, (ii) RV hypertrophy, (iii) RV dysfunction (iv) pulmonary medial hypertrophy and (v) RV and lung remodeling. Methods: At day 1, rats received s.c. saline (group 1, n=10) or 60 mg/kg s.c. MCT (groups 2-3, each n=10) to induce PAH. At day 14, group 1 (Control) and group 2 (untreated PAH) received i.v. saline, group 3 (MSC-treated PAH) received i.v MSCs obtained from donor rats which received MCT 28 days before bonemarrow harvesting. MSCs were labelled with a lipophilic DiI dye before injection. At day 28 recipient rats were instrumented to assess RV function by combined pressure-conductance catheter and were subsequently sacrificed. RV hypertrophy was quantified by the weight ratio of RV/{LV+interventricular septum (IVS)}. Lungs and hearts were excised, weighed, fixed and examined by histology. Expression of ECM components (tenascin-c, collagen-i, collagen-iii) was quantified by RT-PCR. Results: Comparing group 2 vs. 1 indicated that MCT had induced PAH (42±17 vs. 27±5 mmhg, p<0.05), RV hypertrophy (RV/(IVS+LV) of 0.47±0.12 vs. 0.25±0.04, p<0.001) and depressed RV ejection fraction (RVEF) (43±6% vs. 56±11%, p<0.01). Lung weight was increased (1.7±0.3 vs. 0.9±0.1 g, p<0.01) and lung tissue demonstrated arteriolar medial hypertrophy (3.4 times increased vs. group1; p<0.001). DiI labelled MSCs were retrieved in the lung sections by microscopy and were located in the perivascular regions. MSC therapy (group3) reversed PAH (31±4 mmhg; p=n.s. vs. group 1), and RV hypertrophy (0.32±0.07; p<0.01 vs. group2), normalized RVEF (52±5%; p=0.05 vs. group2), expression of tenascin-c (n.s. vs. group1), collagen-i and collagen-iii (both p<0.01 vs. group2), reduced lung weight (1.16±0.24g; p<0.05 vs. group2) and inhibited pulmonary arteriolar medial hypertrophy (p<0.001 vs. group2). Conclusion: Intravenous stem cell therapy for rats with PAH by MSCs obtained from rats with the same illness, reverses PAH and RV hypertrophy, improves RV function and reverses RV remodeling, suggesting that patients with PAH may be treated successfully using autologous MSC therapy. P3060 Use of heterologous non-matched Cardiac Stem Cells (CSCs) without immunosuppression as an effective regenerating agent in a porcine model of acute myocardial infarction G.M. Ellison 1, D. Torella 2, C. Trigueros 3, A. Gonzalez 3,C.Waring 1, C. Perez-Martinez 4,A.Perez 4, C. Indolfi 2, F. Fernandez 4, B. Nadal-Ginard 5. 1 Liverpool John Moores University, Liverpool, United Kingdom; 2 Magna Graecia Universita Degli Studi di Catanzaro, Catanzaro, Italy; 3 InBiomed, San Sebastian, Spain; 4 Escuela Veterinaria y Hospital de León, Leon, Spain; 5 Coretherapix, Madrid, Spain Purpose: In humans, transplantation of a variety of cell types post myocardial infarction (MI) has produced modest results. It is postulated that a paracrine mechanism supports cell survival and neo-angiogenesis. The regenerative properties of c-kit positive (c-kit+) cardiac stem cells (CSCs) potentially renders them as the best cell type for future effective therapy. However, the time needed for their isolation and ex vivo expansion makes them unavailable for regeneration protocols in acute MI management. We investigated the effects of intracoronary injections of cloned c-kit+ heterologous HLA not-matched porcine CSCs on myocardial remodeling and regeneration after MI in pigs. Methods: MI was induced by a 75 min PTCA LAD occlusion in 24 female Yorkshire pigs. Cloned male egfp-transduced porcine CSCs, were administered at differential doses (5x10e6, 5x10e7 and 1x10e8) in 3 groups of pigs, 30 minutes after coronary reperfusion. Pig serum was injected to 6 control pigs after MI (CTRL). BrdU was administered via osmotic pumps to track myocardial regeneration. Left ventricular function was measured by Echocardiography and cardiac MRI. Pigs were sacrificed at 30 min, 1 and 21 days. Heart samples were processed for immunohistochemistry and confocal microscopy. Results: Heterologous CSC administration was well tolerated and without adverse effects. CSCs nested into the damaged myocardium with an efficiency of >95%, at 30 minutes through to 1 day after MI. Minimal spill over of CSCs was detected in the coronary sinus, spleen, lung or liver. Despite the immunomodulatory activity of CSCs in vitro, all injected cells had disappeared from the myocardium at 21 days. CSC-treated infarcted pig hearts showed a significant increase in the number of autologous c-kit+ (GFPneg) CSCs in the border and infarct regions, compared to CTRL. Many of these c-kit+ CSCs expressed BrdU and the transcription factors for the cardiomyocyte (Nkx2.5) and endothelial (Ets-1) lineages. CSC injection significantly preserved myocardial wall structure and reduced fibrosis. CSC-treated hearts exhibited an increase in the number of small, newly formed BrdU+ myocytes and capillaries. Cardiac function was significantly preserved/improved by heterologous CSC-treatment. Conclusions: Intracoronary injection of heterologous CSCs after MI in pigs, which is a clinically relevant MI model, activates the endogenous CSCs through a paracrine mechanism resulting in improved myocardial cell survival and physiologically meaningful regeneration. P3061 Epicardium-derived cells and CD117-positive cells in the adult human heart: common origin through epithelial-mesenchymal transition F. Di Meglio 1, D. Nurzynska 1,C.Castaldo 1, V. Romano 1, R. Miraglia 1,N.Amatruda 1, C. Bancone 2, V. Russolillo 1, G. Langella 1, S. Montagnani 1. 1 Universita degli Studi di Napoli Federico II, Naples, Italy; 2 Seconda Universita di Napoli, Naples, Italy Growing number of studies indicate epicardium-derived cells (EPDCs) as cardiac stem cells. While it is beyond doubt that these cells contribute to the normal development of the heart during organogenesis, it remains an open question whether mesothelial epicardial cells can undergo epithelial mesenchymal transition, giving origin to cardiac primitive cells, in the adult human heart. We examined epicardium and subepicardium of the atria of human adult normal (n=11, mean age 41±12 years, 7 males, 4 females) and pathological hearts with chronic heart failure due to ischemic cardiomyopathy (n=22, mean age 55±5.5 years, 14 males, 8 females, mean ejection fraction 25±1%). Strikingly, only the normal adult human hearts were layered with epicardial cells. On the contrary, cell nuclei were absent from the surface lining of the diseased hearts. While normal epicardium resulted positive for cytokeratin 5/6, E-cadherin and Bves, in the pathological hearts the cells with epithelial markers were distributed among loose connective tissue of the subepicardium. Remarkably, these cells were CD117- positive and, when compared with subepicardium of normal heart, their number was 8.7-fold (p 0.005) higher in the subepicardium of hearts with ischemic cardiomyopathy. In the PCR-based array of CD117-positive cells isolated from normal and pathological hearts, TGFβ and HGF receptor signaling pathways (both known inducers of EMT) resulted activated in the latter. Considering the hypothesis that EPDCs contribute to the cardiac CD117-positive cells population in the adult heart, fragments of epicardium of adult human cardiac atria were cultured on the extracellular matrix produced by cardiac fibroblasts, to obtain the outgrowth of the mesothelial cells forming epithelial sheets. When stimulated with TGFβ and HGF, intercellular contacts were lost and cells acquired mesenchymal characteristics and CD117 expression. Altogether, these results indicate that EPDCs enrich the pool of cardiac primitive cells that contribute to the regenerative properties of the adult human heart. It could be reasonably argued that CD117-positive and EPDCs represent the same primitive cell population. P3062 GLP-1 CellBeads enhance myocardial angiogenesis and improve LV function K. Farrell 1, M. Hawthorne 1, C. Wallrapp 2, P. Geigle 2,A.L.Lewis 3, P.W. Stratford 3, N. Malik 1,C.M.Holt 1. 1 The University of Manchester, Manchester, United Kingdom; 2 CellMed AG, Alzenau, Germany; 3 Biocompatibles UK Ltd, Surrey, United Kingdom Stem cell therapies are currently being investigated as possible treatments for myocardial infarction (MI) and ensuing heart failure. GLP-1 CellBeads have been engineered as a hybrid approach to treat ischaemic myocardium. GLP-1 Cell- Beads consist of an alginate matrix containing genetically modified human mesenchymal stromal cells that constitutively secrete a GLP-1 fusion protein. We hypothesised that delivery of GLP-1 CellBeads in vivo would attenuate ischaemic damage due to MI through neovascularisation of the myocardium and improve LV function. Methods: GLP-1 CellBeads were selectively delivered to branches of left anterior descending coronary artery in Yorkshire White pigs (n=6), with the control group receiving cell-free alginate beads (n=6). Transthoracic echocardiography (TTE) was used to assess LV function (EF = Ejection Fraction). Four weeks after intervention, hearts were explanted for morphometric quantification of infarcted area, with MI area represented as % of LV area. Angiogenesis was assessed by quantification of immunohistochemical von Willebrand Factor positivity (mean vessel count and diameter/field of view). Results: TTE confirmed onset of mild LV dysfunction in both groups at time of delivery of the beads (EF = 44.0±1.2 vs 43.4±1.1; p=ns). Four weeks after intervention, repeat TTE demonstrated normal LV function in the GLP-1 CellBead group but not the control group (EF = 49.7±1 vs 41.2±2.2; p<0.01). Morphometry showed significantly decreased infarction area in the GLP-1 CellBead group, compared to control group at four weeks (4.7±2.1% vs 21.8±4.8%; p<0.018). Hearts with GLP-1 CellBead delivery also contained significantly more vessels, compared to control (54.8±4.1 vs 23.8±5.1; p=0.0001). This pattern was seen within regions of the LV (apex-lv: 39.25±7.5 vs 6.8±2.2; p=0.002 and mid-lv: 34.5±3.8 vs 14.6±6.2; p=0.04). In relation to vessel size, vessels measuring 4-10μm in diameter were most abundant, in both control and GLP-1 CellBead groups.

196 496 Stem cells in situ Conclusion: Treatment with GLP-1 CellBeads at the time of MI reduces infarct size and LV dysfunction. This is associated with increased angiogenesis. Further studies are aimed at determining the mechanism underlying this neovascularisation. P3063 Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model A. Schuh, A. Sasse, E.A. Liehn, M. Kelm, C. Weber, M.W. Merx. Universitaetsklinikum Aachen, Medizinische Fakultaet der RWTH, Aachen, Germany Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1α (SDF-1α) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. In a rat ischemia/reperfusion model and utilising endothelial progenitor cells (EPCs) aim of the presented study was to investigate the role of exogenously applied and endogenous mobilised cells in a regenerative strategy for myocardial infarction therapy. Cells were injected intramyocardial and intracoronary using a new rodent catheter system. EPCs were lentivirally transfected with SDF-1α to further improve migration of endogenous progenitor cells towards infarcted myocardial areas. After 90 minutes of ligation and reperfusion of the LAD SDF-1α transfected BrdU labelled EPCs (106, n=8) were injected into the myocardium or intracoronarily respectively (n=8). In additional animal goups we injected EPCs without a lentiviral transfection (intramyocardial (n=8) and intracoronary (n=8)) and medium as control group (n=10 per group). 8 weeks after transplantation echocardiography and isolated heart studies according to Langendorff revealed a significant improvement of left ventricular function after intramyocardial application of lentiviral with SDF-1 transfected EPCs (Fractional shortening (FS): Control 34.7±8%, EPCs + SDF-1α 42.2±4.3% (p<0.05). LV developed pressure (LVDP): Control 103.4±19.2 mmhg, EPCs + SDF-1α 144.1±16.2 mmhg (p<0.05). Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells (TUNEL staining) and augmented proliferation by Ki-67 positive cells after transplantation of EPCs and EPCs + SDF-1α in infarcted myocardium. Additionally, a significant increased density of CD31+ vessel structures, a lower collagen content and higher numbers of inflammatory cells (monocytes) in infarcted areas after transplantation of transfected cells were detectable. In conclusion, intramyocardial application of lentiviral transfected EPCs is associated with a significant improvement of myocardial function after infarction as shown by echocardiographic and Langendorff results, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation. P3064 The influence of intracoronary autologous mononuclear bone marrow cell transplantation E. Trzos, M. Krzeminska-Pakula, T. Rechcinski, M. Bugala, J.D. Kasprzak, M. Plewka, J.Z. Peruga, M. Kurpesa. Second Chair&Department of Cardiology, Lodz;, Poland The results of treating by intracoronary transfer of autologous bone marrow cells (BMC)after acute myocardial infarction (AMI) are not definite. It is especially important to assess the potential proarrhythmic effect, because these therapy concerns patients with post-infarction left ventricular dysfunction a group with significantly higher risk of dangerous arrhythmias The aim of this study was to evaluate the pro-arrhythmic safety of patients with STEMI who received intracoronary transfer of BMC into the infarct-related artery. Methods: 62 pts with STEMI who had been treated by means of primary coronary angioplasty (PTCA) were randomly assigned to two groups: Group 1 36 pts, qualified for intracoronary transfer of BMC and group 2 26 pts, constituting the control group. BMC were taken from the iliac bone on average on the seventh day after STEMI. In all the pts the infarct-related artery was the LAD, and the leftventricular EF < 40%. Both groups had an initial Holter session (MH1) on average 5 days. The Holter monitoring was repeated one month after the randomly applied procedure of stem cells implantation (MH2), and after 12 months (MH3). The results of MH1, MH2 and MH3 were compared. From these recordings the mean number of premature ventricular complexes, the frequency of occurrence of non-sustained VT (nsvt) episodes and the parameters of heart rate variability (HRV) were calculated. Also HM provided the QT interval analysis, and signal averaged ECG analysis. For all the pts a 2-year follow-up period has been planned. The study endpoint was: death, hospitalization due to cardiovascular causes or revascularization. Results: Both groups were comparable in regard to demographical data, the presence of risk factors and coexisting diseases. An increased number of nsvt episodes was recorded in Group 1 in MH2 (25% vs 12,5%), but insignificantly. In MH2 in the control group the HRV parameters increased significantly. In the BMC group the QTc lengthened by 13,6 msek. No significantly differences was observed after 12 months. During the follow-up 3 pts died (2 from gr 1 and 1 from gr 2).The hospitalization due to cardiovascular causes or revascularization was observed in 11 pts (8-group1 and 3 group 2). The differences was not significantly. Conclusions: During the first month after the intracoronary transfer of BMSC an increase in the frequency of nsvt was observed. However, during the follow-up no dangerous arrhythmic episodes were recorded in the active treatment group, which suggest that intracoronary implantation of mononuclear bone marrow stem cells is safe P3065 Doxorubicin causes depletion of cardiac primitive cell pool that may add to the mechanisms of doxorubicin-mediated delayed cardiotoxicity D. Nurzynska 1,F.DiMeglio 1,C.Castaldo 1, V. Romano 1, R. Miraglia 1,L.Marina 2, E. Piegari 2, A. De Angelis 2, C. Bancone 2, S. Montagnani 1. 1 Universita degli Studi di Napoli Federico II, Naples, Italy; 2 Seconda Universita di Napoli, Naples, Italy Doxorubicin is one of the most active anti-cancer drugs, widely used for the treatment of several malignancies, however its clinical implementation is limited by high incidence of cardiovascular events, most serious of them being the cardiomyopathy followed by congestive heart failure. Known studies of the mechanisms of doxorubicin toxicity focused on cardiomyocyte damage. But then cardiac primitive cells are considered to provide the adult heart with a substantial growth reserve determining the function of the heart throughout life. The role of this cell population in the myocardial response to different pathologic stimuli has been documented in animals and humans, suggesting cardiac primitive cells as possible pathophysiologic target in cardiac diseases. We advance the hypothesis that cardiotoxicity of doxorubicin may be due to its effects on cardiac primitive cells. Hence, we examined doxorubicin toxicity on this cell population. CD117-positive cells isolated from adult human normal atria were incubated with increasing concentrations of doxorubicin hydrochloride (0.1, 0.5 and 1μM), followed by the evaluation of proliferation and apoptosis after 12, 24, 48 and 60 hours. Proliferation was evaluated by BrdU incorporation and its rate dropped from 12.84±1.83% (control, n=4) to 2.41±0.27% (24 hours, 1μM, n=4, p<0,05). Immunoblotting of proteins from cardiac primitive cells lysate indicated the upregulation of cyclin B1 paired with reduced expression of phospho-cdk1 and increased expression of p27, corresponding to the presence of cell cycle block at G2/M transition. The expression of phospho-p53 (Ser15) the ratio phosphop53/total p53 increased 2.1-fold and 1.2-fold (p<0,05), respectively. Apoptosis was evidentiated by the detection of early mitochondrial potential disruption, followed by 2,4-fold increase in caspase-3 activity (4.8x10e-3 μmol p- nitroaniline/min/ml in control vs 11.5x10e-3 at 48 hours). With respect to control, apoptotic cells were 6.2-fold and 10.4-fold (p<0,05) more numerous after 12 hours and 48 hours of incubation with 1μM of doxorubicin, respectively. Taking into consideration the known mechanism of doxorubicin cardiotoxicity, namely oxidative stress, we observed reduced expression of catalase and manganese superoxide dismutase in cardiac primitive cells after 36 hours of incubation with 1μM doxorubicin. In conclusion, doxorubicin has profound effects on cardiac primitive cell proliferation and survival. The depletion of CD117-positive cardiac primitive cell pool may add to the mechanisms of doxorubicin-mediated delayed cardiotoxicity. P3066 Time-course of the electrophysiological maturation and integration of transplanted cardiomyocytes M. Halbach, B. Krausgrill, T. Hannes, F. Pillekamp, M. Reppel, J. Hescheler, J. Muller-Ehmsen. Universitaetsklinikum Koeln, Cologne, Germany Electrophysiological maturation and integration of transplanted immature cardiomyocytes are essential to enhance the benefit of cardiomyoplasty. Yet, little is known about the time course of maturation and integration. Methods: Fetal cardiomyocytes expressing enhanced green fluorescent protein were transplanted into cryoinjured non-transgenic adult mouse hearts. At 6, 9 and 12 days after transplantation, viable tissue slices of recipient hearts were prepared and intracellular action potentials of transplanted and host cardiomyocytes within the slices were recorded by sharp glass electrodes. Slices were stimulated by a unipolar electrode placed in healthy host tissue. Results: In transplanted cells embedded in healthy host myocardium, (i) action potential duration at 50% repolarization (APD50) decreased from 32.2±3.3 ms at day 6 to 27.9±2.6 ms at day 9 and 19.6±1.6 ms at day 12. The latter value was equal to the APD50 of host cells (20.5±3.2 ms, P=0.78). (ii) At day 12, 53% of cells showed no conduction blocks up to a stimulation frequency of 8 Hz, the delay of electrical activation of these cells compared to optimally coupled host cells was low. (iii) APD50 was inversely proportional to the quality of electrical integration. (iv) In transplanted cells embedded into the cryoinjury, which showed no electrical integration, APD50 was 49.2±4.3 ms at day 12. This value was significantly shorter compared to day 6, pointing to a very slow maturation. Conclusions: Electrophysiological maturation and integration of transplanted cardiomyocytes are time-dependent processes. Maturation depends on the quality of electrical integration.

197 Stem cells in situ 497 P3067 Phenotypic analysis of adult human cardiac progenitor cells characterized by high aldehyde dehydrogenase activity and cardiosphere-forming ability A. Spicher 1, M.-E. Roehrich 1,P.Vogt 1, G. Pedrazzini 2,T.Moccetti 2, G. Vassalli 2. 1 CHUV, Lausanne, Switzerland; 2 Fondazione Cardiocentro Ticino, Lugano, Switzerland Introduction: Recent evidence suggests the human heart contains resident stem cells that have regenerative potential. In previous studies, cardiac progenitor cells (PC) have been isolated based on surface marker expression. However, no individual marker allows to definitively establish cardiac cell stemness. We have characterized adult human cardiac PC isolated based on high aldehyde dehydrogenase (ALDH) activity, a common property shared by PC in different tissues, and ability to form cardiospheres in vitro. Methods: Human atrial myocardial samples collected at surgery were digested or processed as primary explant cultures. ALDH activity was assessed by flow cytometry using a fluorescent substrate. Surface markers were determined by FACS. Magnetic antibody-coupled cell sorting (MACS) was used to purify cells expressing CD146 (melanoma cell adhesion molecule), an endothelial PC and mesenchymal stem cell (MSC) marker. Results: Atrial samples contained a variable number of ALDH-bright cells (median: 25%; range: 2-49% of all non-myocytic cells; n=22), which tended to increase with age, but was not correlated with ischemic or valvular heart disease, diabetes, or hypertension. ALDH-bright cells were CD45-negative but positive for CD34, CD105 and CD29 (endothelial PC and MSC markers). Expression of CD271, one of the most specific markers of BM-derived MSC, was restricted to ALDH-bright cells. These cells were grown for more than 20 passages but progressively lost ALDH activity. Cells derived from primary explant cultures were enriched for ALDH-bright cells (61±11%; n=24) compared with freshly isolated cells. CD146-sorted cells were positive for CD105, CD54 and, in part, CD31 and the stem cell marker c-kit (40%). CD146-positive cells were able to form clones and cardiospheres, the latter more efficiently when cultured in cardiac differentiation medium. Cardiosphere-derived cells were expanded by serial passages from P1 to P5 and maintained their ability to form spheres. They were positive for CD13, CD44, CD105, CD29 and CD49b and contained significant subsets positive for CD31, CD38, CD49a, CD49d, CD71, CD90 or CD106. This profile is consistent with MSC, with a subset of endothelial PC. Conclusions: We have characterized a heterogeneous population of adult human cardiac PC enriched for ALDH-bright cells, MSC, and endothelial PC, which are able to form cardiospheres. Cardiosphere-forming cells can be enriched for by CD146-positive cell sorting. After several passages in culture, cardiosphereforming cells show a homogeneous phenotype characteristic of MSC. P3068 Circulating Oct-4+SSEA-4+ very small embryonic-like cells and improvement of LVEF in patients with acute myocardial infarction W. Wojakowski 1,J.Ciosek 1,M.Kucia 2, E. Paczkowska 3, M. Kazmierski 1,P.Buszman 1,A.Ochala 1,B.Machalinski 3, M.Z. Ratajczak 2, M. Tendera 1. 1 Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland; 2 Stem Cell Institute, Louisville, United States of America; 3 Pomeranian Medical University, Szczecin, Poland Acute myocardial infarction (MI) is associated with rapid mobilization of bone marrow stem cells including rare population of very small embryonic-like stem cells (VSEL), expressing markers of embryonic pluripotent stem cells (PSC), early cardiac markers and displaying following imunophenotype: lin-cd133+cd34+cd45- CXCR4+. We recently showed that mobilization of VSELs is compromised in patients with acute MI and reduced LVEF. AIM of the study was to evaluate the association between mobilization of VSEL and improvement of LVEF in patients with acute MI in 6 months follow-up Methods: 30pts with acute MI and 30 healthy subjects (CTRL) were enrolled. Blood (20 ml) was sampled 24 hours after primary PCI and after 6 months. Isolation of VSELs: erythrocytes were lysed and CD34+CXCR4+lin-CD133+CD45- cells were isolated using live cell sorting system (FACSAria). LVEF was measured using echocardiography. Results: In healthy subjects number of circulating VSEL is very low (1,1±0,2 cells/μl). In acute MI the number of VSELs increased significantly (4,95±1,1; p<0,001). Circulating VSELs were enriched in mrna of PSC markers (Oct-4; Nanog) and cardiac lineage (GATA-4, Nkx2.5/Csx, MEF2C) markers. Number of circulating VSELS in acute MI was significantly correlated with absolute increase of LVEF in 6 month follow-up (r=0.53, p<0.01). Conclusion: Mobilization of very small embryonic-like stem cells expressing pluripotent markers is significantly correlated with improvement of LVEF in 6 months follow-up. P3069 Stem cell combination therapy for the treatment of severe limb ischaemia G. Lasala, J. Silva, J. Minguell. TCA Cellular Therapy, Covington, United States of America Purpose: In the last few years, endothelial progenitor cells (EPCs) have been used to increase blood flow in patients with severe limb ischemia (SLI). Results have demonstrated that the infusion of this single cell type is safe and may stimulate angiogenesis; however the long-term clinical benefits have not been established. Vasculogenesis involves the interaction of EPCs with many other cell types, including mesenchymal stem cells (MSCs)-derived pericytes. Following this rationale, we used a combination of autologous bone marrow-derived EPCs and MSC to treat SLI patients. Methods: Ten SLI (Fontaine, stage 2b-4) patients were enrolled in a Phase I, randomized, open label, safety/efficacy clinical trial. MSC and EPCs, obtained by bone marrow aspiration, mixed and infused in the most hypoperfused area of the Gastrocnemius muscle of the worst leg. Follow-up included evaluation of pain-free walking test (WT), ankle brachial pressure index (ABI), transcutaneous oxygen pressure (TcO2), digital subtraction angiography (DSA), 99mTc-TF perfusion scintigraphy (SPECT) and a Quality of Life Survey (QOL). Results: No adverse events occurred after infusion. Efficacy assessed periodically after infusion demonstrated a time-dependent improvement in all clinical parameters. As compared to baseline values, 6 months after cell infusion its was observed that ABI improved from 0.34±0.19 to 0.69±18 (p 0.001), QOL increased from 1.09±0.40 to 2.39±0.65 (p 0.001) and WT improved fold. Conclusions: Improvement in all variables as well as a concomitant increase in collateral vessels suggests that the combination cell therapy is safe and effective. The outcome of this study could be due to either a cell-dependent stimulation of pre-existing collateral vessels or the development of new mature and stable capillaries (vasculogenesis). The later is strongly supported by the persistence of clinical effects after 12 months of cell infusion and by an increase in radionuclide uptake in the ischemic areas. P3070 Characterisation of a post-natal cardiac progenitor cell population that spontaneously forms beating cardiospheres with no need for differentiation media nor for co-culture with cardiomyocytes M.-E. Roehrich 1, A. Spicher 1,P.Vogt 1, G. Pedrazzini 2,T.Moccetti 2, G. Vassalli 2. 1 CHUV, Lausanne, Switzerland; 2 Fondazione Cardiocentro Ticino, Lugano, Switzerland Introduction: Post-natal cardiac progenitor cells (CPC) described in previous studies do not give rise to spontaneously beating cardiomyocytes in vitro, or do so only rarely when exposed to cytokine-rich differentiation cocktails or co-cultured with mature cardiomyocytes. Using a novel protocol, we have isolated a homogeneous population of post-natal mouse CPC that show unique phenotypic, growth and differentiation characteristics. Methods: Cells were isolated from neonatal or adult mouse hearts, and analyzed by flow cytometry and immunochemistry. Aldehyde dehydrogenase (ALDH) activity, a metabolic property shared by stem cells in different tissues, was assessed by using a specific fluorescent substrate. Cells were also seeded on extracellular matrix (ECM) scaffolds derived from mouse hearts. Results: Neonatal cells adhering to plastic dishes were cultured for more than 6 months in serum-containing proliferation medium. At 4-8 weeks, cells acquired a distinctive morphology, expressed the side population (SP) marker ABCG2, and were markedly enriched for ALDH-bright cells. Cells also expressed the hematopoietic marker CD45, the stem cell marker c-kit, CD44, and the monocytic markers CD11b and CD14, but not stem cell antigen-1 (Sca-1), T and B lymphocyte markers, and dendritic cell markers. A significant proportion of cells expressed the pericyte/mesoangioblast marker NG2. Cells formed cardiospheres that, in many cases, showed spontaneous rhythmic beating, lasting for up to 1 month, in the absence of any change in the composition of the proliferation medium. Cardiosphere formation was enhanced by TNF-alpha, while beating activity was further enhanced by switching the cells to a low-serum medium. Cardiospheres were responsive to beta-adrenergic stimuli that increased beating rates and contractile activity, a typical feature of mature cardiomyocytes. Upon seeding on a cardiac ECM scaffold, cells proliferated, colonized the scaffold, and expressed the cardiac marker alpha-sarcomeric actinin. Adult CPC showed similar growth characteristics and marker expression as neonatal CPC, while also expressing Sca-1. Adult cardiospheres did not beat spontaneously. Conclusions: This post-natal CPC population shows a unique morphology and immunophenotype that is characterized by stem cell, SP, hematopoietic/monocytic, and pericyte markers. While expressing monocytic markers, these cells share several features with cardiac mesoangioblasts, especially the ability to spontaneously form beating cardiospheres with no need for a particular differentiation medium nor for co-culturing with mature cardiomyocytes.

198 498 Stem cells in situ P3071 Characterisation, isolation and expansion of human Islet-1 stem cells and their progeny- from progenitor stage to spontaneously beating cardiomyocytes K.H. Grinnemo, R. Genead, C. Danielsson, M. Simonsson, E. Wardell, M. Corbascio, M. Westgren, E. Sundstrom, C. Sylven. Karolinska Institute, Stockholm, Sweden Background: The human heart has limited regenerative capacity. Among the different cardiac stem cells identified in rodents, the Isl1+ cells represent true cardiomyocyte progenitor cells. These cells have been identified in humans in the early postnatal period after which they disappear. Methods and Results: We have succeeded in identifying the Isl1+ progenitor cells in the human embryonic heart from abortion material, where the distribution differs with time. At 5 weeks the Isl1+ cells are mainly clustered in the outflow tract, while at later periods they are also observed in the atria and right ventricle. Furthermore, using a special isolation technique we have been able to enrich human Isl1+ cells (fig). Following isolation and culturing of cardioblasts from the atria and outflow tracts, they differentiate and form spontaneously beating cardiospheres and monolayer cells. These cells were Nkx2.5+, c-kit- and they form gap junctions. Part of the cardiospheres and a majority of the monolayer cells were Troponin T+ while a few Isl1+ cells were found in the cardiospheres. In a multielectrode array system the beating cardiospheres exhibit rate responsive action potentials. hearts but leads to similarly poor mid-term persistence and survival of transplanted cells. Strategies to improve engraftment, persistence and survival of transplanted cells must be identified in order to optimize the effectiveness of cardiac cell replacement therapy. P3073 America Left atrium of adult porcine heart as a source of progenitor cells L. Ye 1,L.P.Su 2,K.K.Poh 1, K.H.H. Haider 3. 1 National University Hospital, Singapore, Singapore; 2 National Heart Centre, Singapore, Singapore; 3 University of Cincinnati, Cincinnati, United States of Background: The study aims to identify, isolate and characterize cardiac progenitor cells from left atrium of adult porcine heart. Methods: Pigs weighting from kg were used. 0.5 gram of tissue samples were obtained from left atrium. The harvested samples were cut into 1 to2mm 3 pieces and enzyme digested. The tissue fragments were cultured in basal medium for 2-3 weeks to obtain migrating cells. The migrating cells were harvested and cultured in poly-d-lysine coated wells or flasks to obtain cardiospheres using cardiosphere forming medium. The cardiospheres were screened for SSEA-1, CD31, CD34, and c-kit expression. Results: Young animal (<50kg) has a higher successful rate than old ones (>80kg) in obtaining cardiospheres. Migrating cells could be obtained from left atrial sample from freshly euthanized pig. Migrating cells appeared at 1-2 weeks and peaked at 3 weeks after tissue fragment culture. Migrating cells harvested at 3 weeks most efficiently formed cardiospheres. The cardiosphere contained mixed cell population: SSEA-1+ (2-5%), CD31+ (2-5%), CD34+ (1-3%), and c-kit+ (10-25%). c-kit+ CPCs were purified by magnetic activated cell sorting (MACS) and got up to 90% purity. They were self-renewing and clonogenic. Conclusion: Cardiac progenitor cells could be isolated from left atrium of adult pig heart. They may have great potential for regeneration of cardiac tissue. Enriched human Islet-1+ cells Conclusion: We believe that the Isl1+ cells and their progeny already can be used for pharmacological studies and might be a future tool for cardiomyoplasty. P3072 Mid-term cell loss of mouse embryonic stem cell derived cardiomyocytes after intramyocardial injection into cryo-injured hearts is similarly high, but occurs earlier than in sham-operated mouse hearts B. Krausgrill, M. Halbach, S.P. Soemantri, T.G. Plenge, K. Schenk, N. Lange, J. Hescheler, T. Saric, J. Mueller-Ehmsen. University Hospital of Cologne, Cologne, Germany Purpose: Cardiac cell replacement therapy is a promising strategy to restore impaired cardiac function. Embryonic stem cell derived cardiomyocytes (ES-CM) integrate into host myocardium and improve cardiac function after transplantation into injured hearts. Here, we quantified engraftment, persistence and survival of transplanted ES-CM as these are crucial factors for this therapy s effectiveness. Methods: Male murine ES-CM were generated from a transgenic clone of D3 embryonic stem cells (αpig44) and were highly purified (>99%) using an antibiotic selection strategy and a genetic resistance under cardiac specific promoters. In female adult mice (129/S2; syngeneic to ES-CM), ES-CM were transplanted with 2 direct intramyocardial injections (10μl each) into healthy regions at the border of previous cryo-injury (CRYO) or into sham-operated (SHAM) hearts. In control samples (to assess the 100% signal), the cell suspension was added to explanted hearts ex vivo. After surgery and randomization, hearts were explanted immediately (0h) or after 6h, 24h, 48h, 5 days or 3 weeks, and genomic DNA was isolated. The number of transplanted cells in each sample was determined by quantitative real-time PCR with Y-chromosome specific primers. Results: Engraftment efficiency was similar in both groups with detection of 15.1±6.7% (SHAM) and 16.6±5.8% (CRYO) of the transplanted ES-CM at 0h, which was significantly less than in controls (both P<0.001). At 6h, numbers remained unchanged in SHAM (11.4±3.6%) but tended to decrease in CRYO (2.8±0.9%, P<0.08 vs 0h, P=0.1 vs SHAM). At 24h, numbers declined significantly in SHAM (0.9±0.3%, P<0.05 vs 6h) to similar levels as observed in CRYO (1.6±1.4%). At later time points, numbers remained without changes in both groups with 1.9±0.9% (SHAM) and 3.4±3.3% (CRYO) at 48h, 0.9±0.3% (SHAM) and 5.7±5.6% (CRYO) at 5 days and 1.1±0.6% (SHAM) and 2.3±1.9% (CRYO) at 3 weeks. Conclusions: Direct intramyocardial injection of ES-CM into mouse hearts leads to low mid-term persistence and survival of only 1-2% of the transplanted cells. Cell loss occurs in 2 phases: immediately during/after injection (>80% of transplanted cells lost) and within 24h after cell injection (>90% of successfully engrafted cells lost). The second phase occurs earlier in injured than in healthy P3074 Activin A or inhibition of BMP-2/4 by a specific inhibitor combined with Wnt-3a enhances the differentiation into cardiac myocytes in mouse embryonic stem cells S. Ueno. Jichi Medical University School of Medicine, Tochigi, Japan Purpose: Cardiac myocytes derived from embryonic stem (ES) cells are promising cell source for cardiac repair, but only a small percentage of ES cells spontaneously differentiate into cardiac myocytes. Previously we showed that Wnt-3a induced cardiac mesoderm cells resulted in remarkable enhancement of cardiogenesis. However, the efficacy of cardiogenesis by Wnt-3a is still not enough for clinical application. Based on the developmental studies in chick and Xenopus, we hypothesized that Activin A or bone morphogenic proteins (BMPs) signaling combined with Wnt-3a could improve cardiogenesis in ES cells. Methods and Results: Mouse ES cells were differentiated in suspension for 7 days to form embryoid bodies (EBs) and grown under adherent conditions for another 7 days. EBs received 100 ng/ml of mouse recombinant Wnt-3a from day 2 to 5 to induce cardiac mesoderm cells. EBs were additionally stimulated with 10 or 100 ng/ml of human recombinant BMP-2, BMP-4 or human recombinant Activin A at various time points (day 0-1, 2-5 or 6-8). At day 14, addition of Activin A from day 2 to 5 significantly increased % beating EBs (10 ng/ml of Activin A + Wnt-3a: 79.4±5.1%, Wnt-3a only: 63.6±4.8%, p < 0.01, n = 3, 100 ng/ml of Activin A + Wnt-3a: 81.6±1.5%, Wnt-3a only: 53.6±3.1%, p < 0.01, n = 3). Neither BMP-2 nor BMP-4, however, had additional effect on the beating activity and addition of BMP-2 or BMP-4 from day 2 to 5 drastically diminished % beating EBs at day 14 (BMP-2 + Wnt-3a: 6.1±3.3%, Wnt-3a only: 40.5±7.0%, p < 0.01, n = 3, BMP-4 + Wnt-3a: 7.6±2.4%, Wnt-3a only: 46.8±7.8%, p < 0.01, n = 3). To evaluate inhibition by BMPs, EBs were treated with Wnt-3a, BMP-2 and a specific inhibitor, anti-human BMP-2/4 antibody from day 2 to 5. Unexpectedly, the complete inhibition of BMPs signaling significantly enhanced % beating EBs (Inhibitor of BMPs + BMP-2 + Wnt-3a: 74.9±9.0%, Wnt-3a only: 54.2±6.1%, p < 0.01, n = 3). The quantification of alpha-myosin heavy chain expression in the every culture is currently being examined to confirm the enhancement of cardiogenesis. Conclusions: Activin A additionally improves cardiogenesis induced by Wnt-3a. The transient inhibition of BMPs signaling is more critical for the differentiation into cardiac myocytes by Wnt-3a than the activation of BMPs signaling. P3075 Beta-catenin regulates cardiac resident precursor cells M.P. Zafiriou 1,C.Noack 1, A. Renger 1,R.Dietz 2, L. Zelaryan 1, M.W. Bergmann 3. 1 Max-Delbrueck-Centrum fuer Molekulare Medizin, Berlin, Germany; 2 Charite - Campus Virchow-Klinikum, Berlin, Germany; 3 Asklepios Klinik. St. Georg, Hamburg, Germany We recently described that conditional αmhc-driven β-catenin depletion in the adult heart attenuates post infarct left ventricular (LV)remodeling via increased differentiation of αmhcpos/tbx5pos/sca-1pos/troptneg resident cardiac progenitor cells (CPC s).(2) Here, we tested the hypothesis that adult heart CPC s resembles first heart field (FHF) progenitors present in the embryonic heart.

199 Stem cells in situ 499 We analyzed both mrna and protein expression of several cardiac developmental markers by quantitative real time PCR and co-immunofluorescence. Cells were isolated from adult mice ventricles and depleted by size filtrationof adult cardiomyocytes. Analysis of resident cardiac progenitor cells (CPCs) revealed the expression of other early cardiac markers as Nkx2.5 and ehand as well as co-expression of the Sca-1 epitope. CPCs also expressed Tbx5 and αmhc confirming the cell population to be very similar to the first heart field progenitors but different to the isl-1pos second heart field progenitors. CPCs proliferate, as demonstrated by the expression of the Ki67 antigen; and they differentiate towards Troponin T expressing cells in a co-culture assay system with adult cardiac fibroblasts. CPC s isolated from Wild type (WT) animals demonstrated a significantly higher proliferation rate compared to CPCs isolated from mice with αmhc-driven β-catenin depletion. Next, CPCs were treated with BIO (Calbiochem), which inhibits glycogen synthase kinase 3b (GSK3b) and thereby stabilizes β-catenin. As expected, BIO enhanced the proliferationrate of both β-catenin depleted cells as well as WT cells incomparison to sham isolated cells. Furthermore, even WT CPCs increased theirproliferation rate when treated with BIO. β-catenin dependent signaling controls embryonic heart formation. Cell proliferation is initially enhanced by β-catenin activation while later on (is blocking cardiac cell differentiation. These observations suggest the existence of a αmhcpos/ctntneg cardiac committed FHF stem cell population in the adult heart and that they are governed by the same signalling pathways controling embryonic cardiac differentiation. P3076 Regenerative potential of adult human cardiac primitive cells is influenced by chronic pathological conditions: a phenotypic and genetic study F. Di Meglio 1,C.Castaldo 1, D. Nurzynska 1, R. Miraglia 1, V. Romano 1, C. Bancone 2, G. Langella 1,C.Vosa 1, S. Montagnani 1. 1 Universita degli Studi di Napoli Federico II, Naples, Italy; 2 Seconda Universita di Napoli, Naples, Italy According to recent hypothesis, pathological processes may deplete the heart of stem cells and uncertainty still prevails as to whether functionally competent primitive cells can be obtained also from failing hearts. The scope of the present study was to assess proliferation, apoptosis, differentiation and commitment of cardiac primitive cells resident in normal (n=8) adult human hearts and in hearts with ischemic cardiomyopathy (n=8). Immunofluorescence and immunoblotting of CD117(+) cells isolated from normal and pathological hearts revealed higher expression of cardiac-specific nuclear and cytoplasmic markers in the latter. Proliferation of CD117(+) cells isolated from hearts with ischemic cardiomyopathy was 3.2±0.7-fold higher (p 0.005), while the apoptosis induced by oxidative stress was 1.8±0.2-fold higher (p 0.005) when compared with cells from normal hearts. Gene expression was examined by stem cells specific PCR-based microarray. We confined our analysis to genes with at least a 1.7 fold differential expression and identified 38 downregulated and 39 upregulated genes in CD117(+) cells from failing hearts. The downregulated genes included snail1 homolog, jagged-1 and ephrin b1 that are involved in the early stages of the developmental process; mdm2, p15 and p16 belonging to the cell cycle control functional group, as well as genes from the neurogenesis, skeletal development, bone remodeling and cartilage development functional classes. Upregulated genes, among which OTF2, endothelin receptor, CD105 and MRG1, were involved in developmental maturation, mesenchymal cell differentiation, heart development and circulatory system processes. One major finding emerging from the analysis is the acquired capability of cells from pathological heart of responding to wounding, as well as the upregulation of the response to external stimuli and stress. In comparison with normal cells, those from pathological heart become readily committed to cardiac cell lineages, at the expense of stemness and multipotentiality. Moreover, the epithelial-mesenchymal transition (EMT), which has been proposed as the mechanism behind cardiac stem cells origin, resulted activated, as well as known inducers of EMT, TGFβ and HGF signaling pathways. Cardiac stem cells in the normal and in the pathological heart differ in several respects and the differences reflect the activation of cardiac stem cells pool in the chronic pathological conditions. Given the apparent failure of intrinsic heart regeneration, further studies are warranted to optimize the strategies for cardiac stem cells application in regenerative medicine. P3077 Endothelin1-induced postnatal rat cardiac stem cells with transfected padcgi-hcn2 and co-expressed beta-kcne2 for functional assembly of self-organizing pulsatile myocardial tubes A.N. Kharlamov 1, J.L. Gabinsky 2. 1 Ural State Medical Academy, Yekaterinburg, Russian Federation; 2 Ural Institute of Cardiology, Yekaterinburg, Russian Federation Background: We hypothesized that cardiomyocyte sheets harvested from temperature-responsive culture dishes with endothelin-1-induced pacemaker-like stem cells and transfected cardiac ion channels can help us in the progression of tissue assembly and creation of pulsatile myocardial tubes with native biophysical regulation. Methods: Neonatal rat cardiomyocyte sheets were sequentially wrapped around a resected adult rat thoracic aorta and transplanted in place of the abdominal aorta of athymic rats (n=21, endothelin-1+hcn2+beta-kcne2; n=19, control). Results: Four weeks after transplantation, the myocardial tubes demonstrated spontaneous and synchronous pulsations independent of the host heartbeat. The progression of tissue assembly (21.4±2.2 days as compared with 29.5±3.1 days in control, p<0,05) were revealed. Independent graft pressures with a magnitude of 5.1±2.1 mmhg due to their independent pulsations were also observed. Endothelin-1 increased a number of pacemaker-like cells (from 18.3±1.7% to 30.3±2.1%, p<0,001), and assisted in the (re)vascularization of the pump (11.2±2.3% in control vs 21.4±3.5%, p<0,01), and raised a tissue concentration of connexin-40, 45 (25.1±2.5% as compared with 16.1±1.4% at control rats, p<0,001). The thickness of the tubes was 80±30 μm in control vs 175±26 μm (p<0,01) after four week. Transfection of beta-kcne2 increased HCN2/I(f) whole-cell currents ( ±12 vs ±7.6 in control, p<0,001), activated most single-channel gating parameters (74.47±12% in control vs 99.25±0.7%, p<0,001), stimulated the activation kinetics (from 179.8±94.8 to 652.6±14.7, p<0,01), and activated spontaneous action potential activity (from -1.9±0.3 to -2.62±0.2, p<0,05). Conclusions: Functional myocardial tubes that have the potential for circulatory support can be created with cell sheet engineering, and using of endothelin-1- induced pacemaker-like stem cells and transfected cardiac ion channels (HCN2, beta-kcne2). P3078 Kruppel-like factor 15 (KLF15) represses beta-catenin-dependent gene transcription in cardiomyocytes C. Noack 1, A. Renger 1, M.P. Zafiriou 1,R.Dietz 2, L. Zelarayan 1, M.W. Bergmann 3. 1 Max-Delbrueck-Centrum fuer Molekulare Medizin, Berlin, Germany; 2 Charite - Campus Virchow-Klinikum, Berlin, Germany; 3 Asklepios Klinik. St. Georg, Hamburg, Germany Although several studies addressed the signaling pathways playing a role incardiac hypertrophy, no specific mechanism is known to enhance adaptivehypertrophy. Our recent studies suggest that downregulation of b-catenin is required for adaptive hypertrophy preserving left ventricular (LV) function in the adult heart.(2) We therefore aimed to identify a potentialeffector repressing the transcriptional activity of b-catenin specifically in the heart. Here, we tested the transcriptionalregulator Kruppel-like factor15 (KLF15) concerning his interaction with b-catenin and functional effects in cardiachypertrophy. Employing HEK293 cells as well as neonatal rat cardiomyocytes KLF15 wasfound to repress b-catenin-lef/tcf-mediated gene transcription in adose-dependent manner. Both, the C-terminus containing the DNA binding domainand the nuclear localization signal, and an N-terminal repression domaininvolving at least the amino acids 46 to 152 of KLF15 were identified to berequired for inhibition. Protein-protein interaction studies revealed that thesame N-terminal region is necessary for binding of KLF15 to Nemo-like kinase, aknown inhibitor of Wnt/bcatenin signaling. The firstn-terminal 45 amino acids of KLF15 were found to be required for interactingwith b-catenin suggesting a complex formation leading tothe inhibition of b-catenin-lef/tcf-dependent genetranscription. Similar to our previous findings in conditional mice with enhanced cardiacspecificb-catenin activity, theglobal deletion of Klf15 inknockout adult mice resulted in a decline of systolic function. Baseline measurementsrevealed decreased fractional shortening and ejection fraction. Although nochanges in wall size were observed, histologic analysis of the mice showed lesscardiac LV tissue compactness. Beside the observed cardiac phenotype, thesystemic Klf15 knockout micewere viable and fertile without signs of impairment of other organs, turningthe transcription factor KLF15 into a potential candidate for cardiacspecificgene regulation as therapeutic target to improve cardiac remodeling afterinjury. P3079 Enhanced in vivo endothelialisation of allogenic decellularized heart valves by surface coating using autologous fibrin P. Akhyari 1,H.Kamiya 1, P. Mambou 2,M.Barth 3, H. Ziegler 2, S. Schilp 4, I. Berger 5, W.W. Franke 3,M.Karck 2, A. Lichtenberg 1. 1 Universitaetsklinikum Jena, Jena, Germany; 2 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 3 Helmholtz Group for Cell Biology, German Cancer Research Center, Heidelberg, Germany; 4 Phys. Chemistry, University of Heidelberg, Heidelberg, Germany; 5 Dept. of Pathology, Klinikum Kassel, Kassel, Germany Purpose: Tissue engineered and decellularized heart valves represent promising alternatives to currently available prosthesis. In this context, integrative capacity, growth potential and anti-thrombogenic characteristics have been attributed to an endothelial surface lining. We propose rapid in vivo re-endothelialisation of decellularized heart valves by coating with bioactive substances to decrease thrombogenicity and provide for improved graft integration in vivo. Methods: Using a clinically approved system (Vivostat ) 0.5ml of freshly isolated autologous fibrin solution was used for coating of detergent-decellularized ovine pulmonary valves (cpv) prior to implantation in juvenile sheep (n=5), controls were non-coated (npv, n=5). Efficiency of decellularization and fibrin coating was confirmed by histology (H&E/Pearse staining), and electron microscopy

200 500 Stem cells in situ / Stem cells in trans (EM). Explanted PV after 4 months were analyzed by echocardiography, histology, immunohistology (IH), western blot (WB), and EM. Results: Functional differences or thrombosis were absent. An endothelial monolayer covered almost completely the cpv, confirmed by IH for vwf+/cd31+cells, WB of endothelial markers (enos/vwf), and EM. In contrast, reendothelialization of npv cusps was only present in the proximal part, lacking at free margins, accompanied by neointimal hyperplasia. Interstitial repopulation was similar in both groups, as confirmed by H&E, vimentin+-cells, and total DNA content. ECM proteins (WB of laminin/collagen-iv/elastin/gags) and inflammatory reaction (CD3+-cells) were likewise similar. Conclusions: Fibrin coated decellularized heart valves show good endothelialisation with low neointimal hyperplasia accompanied with excellent functional valve characteristics after 4 months in vivo. Considering the pivotal role of an intact endothelial lining for functional capacity and structural integrity of heart valves, coating strategies, e.g. with autologous fibrin, may represent an alternative to demanding in vitro re-endothelialization techniques with clinical perspectives. P3080 Human cardiac stem cells are present in a severely damaged, ischemic myocardium M.O. Zembala 1,P.Wilczek 2,T.Cichon 3, R. Smolarczyk 3, R. Przybylski 1, K. Filipiak 1,A.Sokal 1,S.Szala 3, M. Zembala 1. 1 Slaskie Centrum Chorob Serca, Zabrze, Poland; 2 Foundation For Cardiovascular Research, Zabrze, Poland; 3 National Institue of Oncology, Gliwice, Poland Objectives: Functional restoration of the damaged heart presents a formidable challenge and developing strategies for treatment and prevention of ischemic heart failure remain of utmost priority. Cells capable of self-renewal and bearing the potential of plasticity have recently been proven to reside in the myocardium. These specific Cardiac Stem/Progenitor Cells (CSCs/CPCs) are multipotent and clonogenic, giving rise to cardiomyocytes, smooth muscle cells and endothelial cells in both in vivo and in vitro. The aim of this study was to assess pool of CSC/CPCs present in severely damaged, ischemic human heart excised from patients undergoing cardiac transplantation. Methods: Myocardial tissue samples were taken from the explanted hearts (right atrium, left atrium, left ventricular apex) under sterile conditions, immediately the heart had been removed from the recipient. Tissue samples were then minced and cultured in IMDM medium (standard conditions 5% CO2 at 37?C). Culture medium was changed every 2-3 days. After the cells had grown to confluence they were detached by gentle enzymatic digestion and reseeded for expansions on fibronectin coated dishes. After the expansion cardiosphere forming cells were cultured on the PoliD-lisyne coated dishes, in cardiosphere-specific medium. Flow cytometry and fluorescent microscopic techniques were used to verify presence/absence of specific markers (c-kit, CD105, CD 166, CD31 and CD166) Results: After days of culture a monolayer of fibroblast like cells was generated from the adherent explants, over which small phase-bright cells migrated. After expansion of the primary culture, cells were reseeded on the polid-lisyne coated dishes, on which cells formed cardiospheres. The size of the cardiospheres altered from 20um at the beginning to 180 um after 1-2 weeks. Both in the in the primary and secondary culture cells were positive for c-kit, CD105 and CD166, which were found to be specific for cardiac stem/progenitor cells. Moreover cells were negative for hematopoietic, endothelial (CD 31) myocardial and smooth muscle cell markers. Conclusions: Severely damaged, ischemic human heart still contains pool of undifferentiated cells able to mature into cardiac tissue. However, quantity of these cells may be insufficient for successful auto-repair to occur. P3081 Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy R. Panovsky 1, A. Vasku 2,J.Meluzin 1, S. Janousek 3,J.Mayer 4, M. Kaminek 5,V.Kincl 1,L.Groch 1,M.Navratil st Dept. of Internal Medicine/Cardioangiology, St. Anna Hospital, Masaryk University, Czech Republi, Brno, Czech Republic; 2 Departments of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republi, Brno, Czech Republic; 3 Dept of Internal Medicine/Cardiology, Brno University Hospital, Brno, Masaryk University, Czech Repu, Brno, Czech Republic; 4 Dept. of Internal Medicine/Hematooncology, Brno University Hospital, Masaryk University, Brno, Czech, Brno, Czech Republic; 5 Dept. of Nuclear Medicine, University Hospital, Olomouc, Czech Republic, Olomouc, Czech Republic Aim: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes (MMP-2, ACE) with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. Methods: The randomized, double centre study included 73 patients with a first acute myocardial infarction treated with primary coronary angioplasty and stent implantation. The cell therapy was performed in 48 patients, while the patients of control group (n=25) were not treated with cells. According to the changes of perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dsami) after cell therapy the patients were retrospectively divided into group A (responders), group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. Results: Out of 48 patients who received MBMC transplantation, 17 responded to the therapy (at least 5% improvement in left ventricle ejection fraction and at least 10% improvement in other followed parameters). There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGC- CTT between responders/non-responders groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (P=0.933). As compared to patients with ACE genotype ID or DD, the patients with II genotype significantly improved regional systolic LV function of the infarcted wall after implantations of MBMC (dsami - 0,4 versus 1,4cm/s, p=0.037). Conclusion: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene is not associated with clinical response to cell therapy. STEM CELLS IN TRANS P3082 Loss of CD26 function promotes stabilization of SDF-1 protein yielding enhanced stem cell homing and attenuation of ischemic cardiomyopathy after treatment with G-CSF M.-M. Zaruba 1, H.D. Theiss 1, U. Mehl 1,M.Vallaster 1,R.David 1, S. Brunner 1, B. Huber 1,G.Assmann 2,J.Mueller-Hoecker 2, W.M. Franz 1. 1 Ludwig-Maximilians Universität, Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, München, Germany; 2 Ludwig-Maximilians Universität, Institut für Pathologie, München, Germany Ischemic cardiomyopathy is one of the main causes of death, which may be prevented by stem cell based therapies. SDF-1 is the major chemokine attracting stem cells to the heart. Therefore, inhibition of the protease CD26/dipeptidylpeptidase-IV (DPP-IV), which is responsible for cleavage and inactivation of SDF-1, may prevent cardiac SDF-1 disruption and improve homing of circulating stem cells. This prompted us to investigate in a genetic CD26-/- mouse model the expression of SDF-1 and to analyze stem cell homing after myocardial infarction. Methods: MI was induced by ligation of the LAD in CD26-/- or C57Bl/6 (wt) mice (n=20), either treated with G-CSF (100 μg/kg/d) or saline for up to 6 days. Functional and immunohistochemical analyses were performed at day 6 and 30 after MI. SDF-1 protein in the heart was analyzed by ELISA and mass spectrometry. Results: Compared to wt, G-CSF treatment of CD26-/- animals improved survival, myocardial function, ameliorated LV wall thinning, associated with an increased neovascularization. In contrast to wt, CD26-/- mice lacked DPP-IV activity in the heart. Consistent with the lack of proteolytic activity, heart lysates of k.o. mice revealed stabilization of active SDF-1 protein (7.98 kda) whereas wt animals showed high abundance of a DPP-IV related SDF-1 cleavage product (7.74 kda). Combined treatment of G-CSF and inhibition of CD26 resulted in an enhanced recruitment of CXCR4+ progenitors to the heart. In conclusion, the strategy of DPP-IV inhibition and G-CSF based stem cell mobilization may represent a novel tool to improve stem cell therapies. P3083 Regulation of cardiac angiogenesis in pressure overload by endothelial progentior cells from the bone marrow P. Mueller, P. Jagoda, A. Kazakov, A. Semenov, M. Boehm, U. Laufs. Universitaetsklinikum der Saarlandes, Homburg, Germany Purpose: Cardiac pressure overload leads to systemic vascular effects whose signal transduction is still unknown. The endothelial nitric oxide synthase (enos) regulates the mobilisation of endothelial progenitor cells (EPC) and their function in the peripheral vessels. We characterised therefore the role of enos in myocardial repair processes in cardiac pressure overload. Methods and Results: After lethal irradiation, C57Bl/6 mice were transplanted with enos-/- (BM-) bone marrow and enos-/- mice with wildtype bone marrow (BM+). 4 weeks after transplantation, pressure overload was induced by transaortic constriction (TAC, 360 μm for 35 days, respectively SHAM surgery (S)) (n=10-15 per group). Elevated left ventricular pressure by TAC was diminished in mice receiving enos-/- bone marrow ([mm Hg]; S-BM- 76±4, TAC-BM-102±7, S-BM+ 116±13, TAC-BM+ 137±8; TAC vs S p<0.01, BM+ vs BM- p<0.0001). Transplantation of enos-/- bone marrow enhanced cardiac hypertrophy [ratio of heart weight to tibia length in mg/mm]: S-BM- 9±0.7, TAC-BM- 13±0.8, S-BM+ 7±0.4, TAC-BM+ 9±0.6; TAC vs S p<0.0001, BM+ vs BM- p< While TAC did not change cardiac capillary density (Ratio of CD31+ cells per cardiomyocytes) animals with enos-/- bone marrow showed significantly reduced capillarization (S-BM- 0.9±0.1, TAC-BM- 1±0.1, S-BM+ 1.3±0.1, TAC-BM+ 1.3±0.1; TAC vs S

201 Stem cells in trans 501 n.s., BM+ vs BM- p<0.01). BM- mice had - independent of TAC - less EPC in the peripheral blood ([EPC per cells] S-BM- 204±19, TAC-BM- 205±21, S-BM+309±25, TAC-BM+312±16; TAC vs S n.s., BM+ vs BM- p<0.001). The reduced migratory capacity of DiLDL+/Lectin+ EPC in the Boyden chamber after TAC was further downregulated in mice with enos-/- bone marrow ([cells per 0.3 cm 2 ] S-BM- 127±7, TAC-BM- 107±7, S-BM+ 202±22, TAC-BM+ 128±9; TAC vs Sp<0.001, BM+ vs BM- p<0.001). Following transplantation of green fluorescent protein positive (GFP+) bone marrow in wildtype (WT-GFP) and in enos-/- mice (enos-/- GFP), TAC increased the number of bone marrow derived endothelial cells in the myocardium compared to the respective SHAM groups although there was no difference between WT and enos-/- mice ([%] S-WT-GFP 2.4±0.4, S- enos-/- GFP 1.7±0.6, TAC-WT-GFP 7.7±1.4, TAC-eNOS-/- GFP 4.4±0.9; TAC vs S p<0.01, WT vs enos-/- n.s.). Therefore enos outside of the bone marrow seems to play a minor role for the myocardial function of bone marrow derived EPC. Conclusion: Cardiac pressure overload in mice leads to an increase of bone marrow derived cardiac endothelial cells. enos of the bone marrow but not of the extramedullar tissue plays a key role for amelioration of cardiac capillarization. P3084 Intracoronary delivery of endothelial progenitor cells transfected with endothelial nitric oxide synthase in a porcine model of myocardial infarction J. Graham 1,M.R.Ward 1, K.A. Connelly 1, R. Vijayaraghavan 2, G.A. Wright 2,D.J.Stewart 3,A.J.Dick 2. 1 St. Michael s Hospital, University of Toronto, Toronto, Canada; 2 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; 3 Ottawa Health Research Institute, Ottawa, Canada Purpose: Patients with CAD have dysfunctional circulating endothelial progenitor cells (EPCs). Nitric oxide is a determinant of EPC function. Efficacy of autologous EPC administration in clinical trials of acute MI may be limited by inherently poor EPC function. Preliminary work has shown that EPC transfection with enos improves the cell s migratory and angiogenic capacities. We assessed the hypothesis that intracoronary delivery of bone-marrow-derived EPCs transfected to over-express enos would augment LV functional recovery post-mi through increased peri-infarct neovascularization. Methods: 15 female Yorkshire pigs underwent bone marrow aspiration and creation of MI by percutaneous 90-minute balloon inflation in the distal LAD. EPCs were cultured on fibronectin-coated flasks in growth factor-supplemented endothelial basal medium. Subjects were randomized to receive either EPCs transfected with pvax1-enos plasmid via electroporation (enos-epc, n=7), nontransfected EPCs (nt-epc, n=4) or PBS control (n=4). Baseline cardiac MRI followed by percutaneous intracoronary delivery of assigned therapy via injection through an over-the-wire balloon in the distal LAD took place 7-10 days postinfarct. Final MRI to assess LV function, wall motion, volumes and perfusion as well as infarct size was performed at 6 weeks post-mi followed by immediate sacrifice and tissue harvest for histology. Results: Transfection resulted in a 1000 fold increase in enos expression. Absolute LVEF increased significantly in the nt-epc group (29.05±2.70 to 36.90±3.27%, p=0.013) whereas the enos-epc group increased nonsignificantly (28.86±1.38 to 33.50±2.02%, p=0.153). The LVEF worsened in the PBS control group (35.53±2.21 to 28.65±2.74%, p=0.034). When the mean absolute improvement in LVEF was compared to PBS control, both cell groups showed significant improvement (nt-epc: 7.85±1.46 vs ±1.94, p=0.029); enos-epc: 4.64±2.83 vs ±1.94, p=0.042) as well as the combined cell therapy group (enos- and nt-epcs groups merged, 5.81±.88 vs ±1.94, p=0.016), with no significant difference between enos and non-transfected cell groups (p=0.573). Histological examination of the infarct border regions revealed a decrease in fibrosis in both cell treated groups compared to controls with no difference between cell treated groups. Conclusions: enos transfection of EPCs results in overexpression of enos. Cell therapy post-mi is safe and results in improvement in infarct size and LV function. The lack of additive effect with enos transfection likely reflects normal function of the nt-epcs in these low cardiovascular risk animals. P3085 STRO-1 immunoselection enhances the biological properties and cardiovascular paracrine effects of bone marrow mesenchymal stromal cells P.J. Psaltis 1,F.See 2, S. Paton 3, T.P. Martens 2, S. Itescu 2, S.G. Worthley 1, S. Gronthos 3, A.C.W. Zannettino 3. 1 Cardiovascular Research Centre, Royal Adelaide Hospital; Dept of Medicine, University of Adelaide, Adelaide, Australia; 2 Columbia University Medical Center, New York, United States of America; 3 Institute of Medical and Veterinary Science and Hanson Institute; University of Adelaide, Adelaide, Australia Purpose: In contrast to traditional plastic adherence isolation, immunoselection has been advocated as a strategy to enrich the purity of mesenchymal stromal cells (MSC) from bone marrow (BM) preparations. This study set out to determine whether immunoselection using the STRO-1 monoclonal antibody confers biological differences to BM MSC compared to conventional plastic adherence isolation. It also investigated whether the paracrine effects of MSC on cardiac and endothelial cells are enhanced by higher levels of STRO-1 expression. Methods: Plastic adherent (PlAd) and STRO-1 positive (SP) MSC were isolated from healthy human BM. Assays were performed to study the clonogenicity, replicative potential and plasticity of the two populations. Conditioned media (CM) from 4th passage cells was used to compare for differences in paracrine effects on human umbilical vein endothelial cells and rat cardiac muscle cells (CMC). Paracrine assays were also repeated using CM from fractionated MSC populations with highly discrepant STRO-1 expression (STRO-1Bright (SB) and STRO- 1Dim (SD)). Finally, SB and SD MSC were assessed for their in vivo capacity to induce mitogenic and angiogenic effects in a rat model of myocardial infarction. Results: Cells isolated by STRO-1 immunoselection yielded more colony forming units-fibroblastic and more population doublings than those prepared by plastic adherence. During ex vivo culture, SP MSC maintained higher levels of (1) STRO-1 surface expression; (2) gene expression for early stem cell markers (TWIST-1, DERMO-1); and (3) gene and protein expression of various cytokines (SDF-1/CXCL12, HGF, IGF-1 and VEGF). SP CM augmented the proliferation and migration of CMC and endothelial tube formation to a greater extent than PlAd CM. Paracrine responses were most enhanced by the presence of SB CM, while SD CM had the converse effect. These observations were supported in vivo, as injection of SB MSC into rat myocardium was associated with higher numbers of proliferating (Ki67-positive) cardiomyocytes and greater vascular density than SD MSC. Conclusions: STRO-1-based immunoselection gives rise to a population of mesenchymal cells with favourable biological characteristics, compared to plastic adherence isolation. In addition, higher STRO-1 expression is associated with enhanced cardiovascular-relevant paracrine effects. Immunoselection may be a useful strategy for optimising the cardiac reparative properties of MSC. P3086 A randomised trial of Autologous Bone marrow Cells in Dilated cardiomyopathy (ABCD) S. Seth, B. Bhargava, R. Narang, S. Mohanty, R. Ray, G. Gulati, B. Airan, P. Venugopal on behalf of AIIMS Stem Cell Study group. All India Institute of Medical Sciences, New Delhi, India Purpose: Some studies have suggested that stem cell therapy has benefit in patients with ischemic cardiomyopathy and heart failure. There is limited data on dilated non ischemic cardiomyopathy (DCM). We have previously reported the promising results of our pilot study in DCM (JACC 2006,48: ). We now report the completed study with the three year follow up results. Methodology: Eighty five patients of DCM were enrolled. The first twenty patients chose their therapy and subsequently sixty five were formally randomized into the stem cell and control arms. Bone marrow was taken from the Iliac crest and mononuclear cells separated. The cells were injected over 3 minutes into the coronary arteries keeping the coronary sinus blocked by a Swan Ganz balloon. The mean number of cells injected in each patient was estimated to be million (89% mononuclear cells and a CD34 count 1.6 million per ml). Control patients were not catheterized. End points were improvement in ejection fraction, functional class and quality of life (using the Kansas City Cardiomyopathy questionnaire, normalizing each score to a maximum of 100). An endomyocardial biopsy was done at 3 months. Results: In the stem cell arm, two patients were lost to follow up, 2 required biventricular pacing and 41 patients completed follow up (mean follow up 2.8 years). Improvement by one NYHA functional class occurred in 22 patients and 10 patients died. In the control arm, 4 improved by one NYHA class and 12 died. The ejection fraction in the stem cell arm increased from 22.5±8.3% to 28.4±11.8% (p<0.05). This was associated with a significant improvement in the parameters of quality of life (Clinical summary score increased from 51.19±19.9 to 67.02±21.8, p<0.05). Endomyocardial biopsy revealed no evidence of persisting stem cells, no evidence of any new immature myocytes, and also no evidence of any inflammation, infarction, or neovascularization. There was also no change in the number of capillary endothelial cells. The ratio of capillaries to myocytes showed an increase, but it was not significant. Conclusion: This trial shows benefit from stem cell therapy in patients with dilated cardiomyopathy. The benefit is sustained for 3 years. Absence of regeneration on histopathology suggests that the benefit could be due to a paracrine effect. P3087 Expression and subcellular localization of f-channels in early human development using hesc-derived cardiomyocytes A.G. Bosman 1, L. Sartiani 2, V. Spinelli 2, M. Del Lungo 2, E. Cerbai 2, M.E. Jaconi 1. 1 University of Geneva, Geneva, Switzerland; 2 University of Florence, Florence, Italy Purpose: Hyperpolarization-activated cyclic nucleotide-gated (HCN) genes coding for f-channels are typically expressed in autorhythmic cardiomyocytes (CMs). HCN4 is the predominant isoform in the sinoatrial node and, in the rabbit, appears tobe associated withcaveolin-3 (cav3). HCN4is abundant in undifferentiated human embryonic stem cells (hesc) and immature hesc-derived CMs. Maturation of hesc-cms toward ventricular phenotype is accompanied by changes in functional and molecular expression of f-channels. To date, no information exists on (i) subcellular localization of HCN4 in human ventricular CMs and (ii) changes in cav-3 and HCN4 and their associative relationship upon maturation.

202 502 Stem cells in trans Methods: hesc (H1 line) were differentiated into spontaneously beating CMs and characterized at different stages of maturation using patch-clamp to measure f-current and qrt-pcr to evaluate mrna expression. CMs were pooled in two groups: early CMs (15-40 days of differentiation) and late CMs ( days). Adult human CMs were isolated from ventricular biopsies excised during corrective cardiosurgery. Immunocytochemistry was performed by using mouse monoclonal antibodies (Oct-4, alpha-actinin, cav3) and rabbit anti-hcn-4 and visualized by laser scanning confocal microscope. Results: Confocal analysis showed that HCN4 and cav3 colocalize in adult human ventricular CMs. In the same cells, f-current was consistently recorded upon hyperpolarization (70% cells), with a voltage of half maximal activation (Vh) of -94 mv. Protein and mrna for Cav3 were not detected in undifferentiated hesc, but expression increased during maturation of hesc-cms. Oppositely, HCN4 was highly expressed in hesc and early hesc-cms, but a 5-fold decrease in mrna levels occurred in late hesc-cms; in these cells, HCN4 appeared to be associated with cav3. Activation properties of f-current recorded in late hesc-cms resembled those measured in adults ventricular CMs (Vh=-93 mv). Current activation was faster and occurred at more negative potentials in hesc and early CMs. Finally, beta-adrenergic modulation of f-current was detected in late hesc- CMs, but not in early hesc-cms. Conclusions: Our data shows for the first time a HCN4/cav3 association in human ventricular myocytes. Expression of cav3 and its association with ionic channels likely represents a crucial step of cardiac maturation, which may result in changes of cellular electrophysiological properties and modulation by endogenous signals. P3088 Comparation of cardiac regenerative capacity of human mesenchymal stem cells from different sources N. Ma 1, R. Gaebel 1, D. Furlani 1,W.Li 1, K. Bieback 2, K. Luetzow 3, A. Lendlein 3,R.K.Li 4, G. Steinhoff 1 on behalf of Department of cardiac surgery. 1 Klinikum der Universitaet Rostock, Rostock, Germany; 2 Universität Heidelberg, Mannheim, Germany; 3 Institute of Polymer Research, GKSS-Forschungszentrum, Teltow, Germany; 4 Division of Cardiovascular Surgery, Department of Surgery, Toronto General Hospital, University of T, Toronto, Canada Background: The therapeutic efficacy of human mesenchymal stem cells (hm- SCs) from umbilical cord blood (CB), adipose tissue (AT) and bone marrow (BM) for the treatment of acute myocardial infarction has not been compared. This study is designed to evaluate the cardiac therapeutic efficacy of 3 different hm- SCs in a scid mice model of acute myocardial infarction. Methods: hmscs isolated from different sources were characterized by flow cytometry, immunostaining and their multipotency was evaluated by differentiation assay. Apoptotic rate and extracellular acidification under hypoxic condition was measured by Tunnel assay and Bionas silion chips. Male scid mice underwent LAD ligation and intramyocardially received one cell type ( ) or PBS. Cell survival was measured by quantitative PCR for human GAPDH and by immunostaining. Left ventricle function was assessed by cardiac catheterization. Results: Under hypoxia condition, remarkable increased extracellular acidification and apoptosis has been detected from CB hmscs than BM/AT. Real time PCR (P<0.05) revealed the significantly higher cell presence of BM/AT hmscs and less apoptotic cell, as confirmed by histology. Cardiac catheterization showed significant preservation of ejection fraction and systolic volume in BM/AT group compared to controls (P<0.05) 6 weeks after cell transplantation. BM/AT hmscs limited infarction size and enhanced the capillary density significantly compared to nontreated infarction group (MIC). Conclusions: This is the first study to show that compared to CB hmscs, BM hmscs and AT hmscs exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function. Methods: In patients from actively treated group 120 ml of BM was aspirated median 7 (3 12) days after the primary PCI. CD34+CXCR4+ cells were isolated using two-step immunomagnetic selection with monoclonal antibodies coupled with magnetic beads (Miltenyi Biotec GmbH). The median number of infused cells CD34+CXCR4+ cells was 1.90 mln. Cells were infused using the stop-flow technique into the infarct-related artery on the same day. Carotid artery intima-media complex and brachial artery FMD were measured as previously described prior to the BMC infusion and after 6 months. Circulating CXCR4+ cells were enumerated by FACS (FACSCalibur,Beckton Dickinson). Results: There were no differences between the groups in relation to demographic characteristics. In all patients from the actively treated group the intracoronary infusion of BMC was carried out without complications. Baseline FMD was not statistically different in both croups (0.025±0.009 mm vs ±0.008 mm, p=0.9) but after 6 months (6M-FMD) it was higher in a study group compared to controls (0.036±0.019 mm vs ±0.014). There was no significant correlation between baseline FMD and 6M-FMD (r=0.2, p=0.6). Absolute increase of FMD between baseline and follow-up values was statistically significant ( =+0.01, p=0.01) in patients treated with BMC but not in the control group ( =+0.002, p=0.4). Number of circulating CD34+CXCR4+ cells was significantly correlated with absolute increase of FMD (r=0.5, p<0.05). Conclusions: Patients receiving BM-derived CD34+CXCR4+ cells after acute MI have better improvement of endothelium-dependent regulation of vascular tone. P3090 Circulating CD34 + /VEGFR2 cells derived from endothelial colony-forming cells are associated with infarct size reduction N. Meneveau, F. Deschaseaux, V. Descotes Genon, F. Schiele, P. Tiberghien, J.P. Bassand, S. Davani. CHU de Besancon - Hopital Jean Minjoz, Besancon, France Background: Endothelial colony-forming cells (ECFCs) have proliferative and vasculogenic capacities and can be detected in patients with myocardial infarction (MI). Although high levels of ECFCs have been reported to lead to positive left ventricular (LV) remodelling after acute MI, the potential mechanism by which these cells improve LV function has never been assessed. The aim of this study was to evaluate the relationship between ECFCs levels and and the relative change in infarct size as assessed by magnetic resonance imaging (MRI) in patients (pts) with acute coronary syndrome (ACS including ST and non ST elevation MI). Methods and results: One hundred and nine patients <75 years old, admitted with a first ACS within 12 hours of onset of symptoms were enrolled. Peripheral blood samples were drawn to assess ECFCs colonies and progenitor cells expressing CD34, CD144, VEGF-R2, CD31, CD117, CD133. Measurements of MRI infarct size were performed at day 5 and at 6 months followup. ECFCs colonies were detected in 51 patients (47.2% of pts) at admission (ECFCspos patients) and significantly correlated with the relative change in infarct size (r 2 =0.33, p<0.0001). Phenotypic study showed that only level of circulating CD34+/VEGF-R2+ cells was correlated with the relative change in infarct size (r2=0.23, p<0.0001) and with ECFCs colonies (r2=0.12, p<0.017), while level of circulating CD34+/144+ cells significantly correlated with ECFCs colonies (r2=0.10, p<0.03) but not with change in infarct size. P3089 Improvement of flow-mediated dilatation in patients with acute myocardial infarction treated with intracoronary infusion of CD34 + CXCR4 + cells M. Kazmierski, W. Wojakowski, A. Michalewska-Wludarczyk, J. Ciosek, W. Rychlik, E. Hrycek, M. Tendera. Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland Background: Intracoronary infusion of bone marrow-derived mononuclear cells (BMC) in patients with acute myocardial infarction (MI) successfully treated with primary PCI restores microvascular function of the infarct-related artery. No data on the effects of administration if BMC on endothelial function measured by flowmediated dilatation of the brachial artery were reported. Aim: evaluation of brachial artery flow-mediated dilatation (FMD) in patients with acute MI treated with intracoronary infusion of bone marrow-derived CD34+CXCR4+ cells in 6-months follow-up. Patients: 20 patients randomized to receive intracoronary infusion of selected CD34+CXCR4+ cells (active group) and 16 patients without BMC infusion (control group) were analyzed. Inclusion criteria: 1) AMI treated successfully with primary PCI < 12 hours; 2) reduced LVEF 40%. Exclusion criteria: 1) significant coronary stenoses in other than infarct-related coronary arteries qualifying for PCI Correlation ECFCs/change in infarct size Conclusion: The presence of ECFCs colonies is associated with the mobilization of CD34+/VEGF-R2+ cells and can be considered as a marker of regenerative capacity in pts with acute coronary syndromes. P3091 Which type of stem cells to choose for endocardial injections in ischemic heart failure patients: bone marrow or peripheral blood? E. Pokushalov, A. Romanov, S. Artemenko, P. Larionov, O. Poveshenko, I. Terehov, E. Kliver, A. Cherniavskiy. State Research Institute of Circulation Pathology, Novosibirsk, Russian Federation Purpose: To compare the results of endocardial injections of the mononuclear

203 Stem cells in trans 503 stem cells derived from bone marrow (BMMC) or peripheral blood (PBMC) in patients with severe ischemic heart failure. Methods: In this study we included 52 ischemic heart failure patients (age 54±7) with left ventricle ejection fraction (LVEF) 35% and III-IV NYHA and CCS functional classes without possibility for conventional revascularization. The patients of the first group (n=25) received endocardial injections of the BMMC using Noga system and the patients of the second group (n=27) received PBMC injections. The injections of both BMMC and PBMC were performed into the infarction border zone. There were no differences of baseline data between two groups. Also the percentage of the CD 34+ cells was 2.4± 0.5% in both groups. We analyzed all clinical data at 6 month of the follow-up period. Results: None of the periprocedural complications following BMMC and PBMC injections were observed. In the BMMC group we revealed improvement of CCS class (2.1±0.6 vs 3.5±0.5; p<0.05 vs. baseline) and NYHA functional class (2.3±0.2 vs 3.4±0.1; p<0.05 vs. baseline) at the moment of 6 month follow up. The same characteristics were observed in patients of the PBMC group. CCS and NYHA functional classes decreased from 3.3±0.4to2.0±0.4 and from 3.2±0.4 to 2.2±0.3 respectively (p<0.05 vs. baseline; NS between groups). LVEF increased in group BMMC (39±2% vs 30±3%; p<0.05 vs. baseline) as well as in the PBMC group (40±2% vs. 32±2%; p<0.05 vs. baseline; NS between groups). Summed rest and stress score improved in the BMMC group after 6 months (14.7±5.8 vs. 22.5±5.2 and 16.4±4.2 vs. 25.2±4.7 respectively; p<0.05 vs. baseline). Also there were the same data of the summed rest and stress score in the patients of the PBMC group (14.1±5.2 vs. 20.9±4.8 and 15.9±3.9 vs. 24.8±4.1 respectively; p<0.05 vs. baseline; NS between groups) Moreover, there was significant improvement in quality of life in the patients of both groups based on SF-36 data (p<0.05 vs. baseline; NS between groups). Conclusion: There was no difference between BMMC and PBMC injections on clinical data. Endocardial injections of autologous mononuclear cells derived from bone marrow and peripheral blood in ischemic heart failure patients improves clinical symptoms and has beneficial effect on LV function. P3092 Canada Human c/kit+ amniotic fluid derived stem cells: first step in vitro and in vivo before cardiomyoplasty G. Walther 1, J. Gekas 2,D.Skuk 2, E. Larose 1, O. Costerousse 1, E. Bujold 2, O. Bertrand 1. 1 Heart and Lung Research Center, Quebec, Canada; 2 University of Laval Hospital Center, Quebec, Purpose: Cellular cardiomyoplasty is undergoing intensive investigation as a new form of therapy for severely damaged hearts. Recently, amniotic fluid has been investigated as a novel source of stem cells (SC) obtained without destroying human embryos, thus preventing most of the ethical and social controversy. Amniotic fluid (AF) mesenchymal stem cells (SC) have properties intermediate between embryonic and adult mesenchymal SC, which make them particularly attractive for cardiac cellular regeneration. As a first step before the use of an animal model of myocardial infarction, we investigated whether these human cells could be efficiently differentiate into myogenic lineage in vitro and integrate skeletal muscle in immuno-defficient SCID mice. Methods: C/kit immunomagnetic-sorted AF cells (AF c/kit+ SC) were characterized by immunocytochemistry and Western blotting for myogenic and early cardiac markers (desmin, MyoD). Flow cytometric analysis was also performed for HLA-ABC and HLA-DR antigens. In vitro, AF c/kit+ SC phenotypic conversion was assayed by myogenic-specific induction media (5-Aza). 1 x 106 AF c/kit+ SC without ex vivo manipulation were injected in the tibialis anterior muscle of immuno-defficient SCID mice. Results: Acquisition of a myogenic-like phenotype (desmin, MyoD) in AF c/kit+ SC was observed after culture in myogenic-specific induction media. As to HLA antigens, AF c/kit+ SC were positive for HLA-ABC and negative HLA-DR. In vivo, transplanted AF c/kit+ SC showed an engraftment in the skeletal muscle of SCID mice but with an unexpected differentiation in tubular gland tissue. No cellular rejection, inflammatory response or tumorogeneicity of these cells was shown in vivo. Conclusion: This study showed the ability of these cells to proliferate extensively and transdifferentiate in vitro into the myogenic lineage. Indeed, we showed that these AF c/kit+ SC possess a high myogenic potential with the expression of cytoskeletal markers MyoD and desmin well known to play an important role in cardiac and skeletal muscle function. Moreover, immunological profile in this study suggests that AF c/kit+ SC are able to survive after allogenic cell transplantation. Nevertheless, despite no immuno-rejection, our results also suggested that ex-vivo engagement in a specific pathway may be needed to induce the differentiation of AF c/kit+ SC into a desired cell lineage before cell transplantation therapy. Overall, our data suggest that AF c/kit+ SC represents a new and very promising source for cell therapy and their potential use in cellular cardiomyoplasty. P3093 Impaired Function of Bone Marrow Derived Mesenchymal Stem Cells from Type II Diabetic Rat Y.S. Kim, Y. Ahn, J.S. Kwon, M.H. Jeong, J.G. Cho, J.C. Park, J.C. Kang. Chonnam National University Hospital, Gwangju, Korea, Republic of Background: We assessed the hypothesis that diabetic pathological environments would impair the function of diabetes mellitus (DM)-mesenchymal stem cells (MSCs). Methods: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an outbred strain of Long-Evans Tokushima Otsuka (LETO) rat, develops obesity and type 2 DM. MSCs were isolated and cultured from bone marrow of OLETF (DM-MSC) and LETO (non-dm-msc) rats. MSCs were stimulated with tumor necrosis factor (TNF)-α (10 ng/ml), H2O2 (0.2 mm), and glucose (25 mm). After 30 min, 2h, and 24h of stimulation, protein expression levels of plasminogen activator inhibitor (PAI)-1, signal transducers and activators of transcription (STAT)-3, Akt, Toll-like receptor (TLR)-2, and hepatocyte growth factor (HGF) were determined by Western blot. To evaluate the therapeutic potential of MSCs, myocardial IRI was induced by ligation of LAD for 30 min followed by release in Sprague-Dawley rats. Prior to release of LAD, MSCs ( cells/0.1 ml of PBS) were injected onto infarct myocardium. After 1 week and 2 weeks, cardiac fibrosis and histologic changes were analyzed by Masson s trichrome staining and immunohistochemistry. Results: PAI-1 and TLR2 were highly expressed in DM-MSCs in compared with non-dm-mscs. Cellular responses to TNF-α, H2O2, and glucose were different between the two types of MSCs.Phosphorylation of Akt and STAT-3 were induced by TNF-α, H2O2, and glucose in non-dm-mscs, while no changes were detected in DM-MSCs. The cardiac fibrosis was reduced in non-dm-msc injected rats, while it was not changed in DM-MSC injected rats. In non-dm-msc injected rats, the expression of von Willebrand factor (vwf) in peri-infarct myocardium was increased, while vascular cell adhesion molecule (VCAM)-1 expression was reduced. On the other hand, the expressions of vwf and VCAM-1 of DM-MSCs injected myocardium were similar to those of IRI control myocardium. Conclusion: Diabetic environments would impair of BM-MSCs in regard to stem cell function in vivo and in vitro. P3094 From SWISS-AMI to CARDIASTIM - translation of a clinical, progenitor-cell based protocol into GMP D. Surder 1,T.Moccetti 1,G.Astori 1, G. Soldati 1,J.Schwitter 2, P. Erne 3, A. Moschovitis 4, S. Windecker 4, T.F. Luescher 2,R.Corti 2. 1 Fondazione Cardiocentro Ticino, Lugano, Switzerland; 2 University Hospital Zurich, Zurich, Switzerland; 3 Kantonsspital, Lucerne, Switzerland; 4 Inselspital Bern, Berne, Switzerland Under International regulations, cell based medicinal products (CBMP) are requested to be produced following Good Manufacturing Practices (GMP). Moreover, any procedure used to manipulate the cell population of interest should be validated and performed in a controlled environment (clean room). Finally, the CBMP release testing should ensure cell identity, potency, sterility, absence of adventitious agents and low endotoxin levels. Translating an experimental protocol to GMP conditions implies a re-analysis of the process step by step. Here we report on our experience with the ongoing SWISS-AMI trial, that aims to define the optimal time point of cell administration, which has never been adressed prospectively in clinical trials. Methods: Randomisation in a 2:1 pattern of 150 patients with AMI treated within 24 h by PCI of the infarct-related coronary artery (IRA) in 1 control and 2 BMC treatment groups. Intracoronary (i.c.) administration of BMC either 5-7 days or 3-4 weeks after AMI, respectively, in the treatment groups. Cardiac magnetic resonace imaging (CMR) at baseline, after 4 and 12 months in a blind core-lab. Aspiration of 50ml bone marrow from the iliac crest. Isolation of BMC by density gradient centrifugation, washing and resuspension in 10ml injectable medium in a centralized laboratory, reinfusion of the BMC in the IRA via an over-the-wire balloon. Primary Endpoint: Change in global LVEF by CMR at 4 months vs. baseline. Results: In the past 18 months, cell processing has been revised and optimized according to GMP criteria. Quality controls have been introduced in-process as for sterility, identity and potency of the cells. In autumn of 2008, Swiss regulatory authorities SWISSMEDIC certified CARDIASTIM as the first CBMP according to GMP criteria in Switzerland. So far 4 active centers have included 92 of the planned 150 patients. A mean of 170±110 Mio BMC per patient (n=53) have been infused. The fraction of CD34+/CD45+ cells was 2.7±2.9 Mio. Cell viability was 95.4±3.5%. As a functional test an invasion assay has been built up that showed an invasion capacity of 47.49±22.13% (n=15). In-vivo quality tests in an animal model are ongoing. Conclusions: With the present study we were able to get the GMP certification for CARDIASTIM, the first CBMP of Switzerland. With the ongoing clinical trial we hope furthermore to confirm therapeutical benefit of i.c. administration of BMC after AMI and to learn more about the optimal time point for cell therapy and patient characteristics that predict clinical benefit.

204 504 Stem cells in trans P3095 Early passage mesenchymal stem cells could display abnormalous genotype, karyotype and metabolism D. Furlani 1,W.Li 1, L. Wang 1,R.Li 2, A. Lendlein 3, G. Steinhoff 1, N. Ma 1. 1 Klinikum der Universitaet Rostock, Rostock, Germany; 2 Division of Cardiovascular Surgery, Department of Surgery, Toronto General Hospital, University of T, Toronto, Canada; 3 Institute of Polymer Research, GKSS-Forschungszentrum, Teltow, Germany Introduction: Accumulating clinical and preclinical evidence indicate mesenchymal stem cells (MSCs) are a promising cell source for regenerative medical therapies. However, unpredicted immortalization, spontaneous transformation and tumorigenic potential from long term cultured MSCs have been reported in human and mouse. As we have previously described, rat MSCs isolated from young donors could undergo transformation in early passage culture. We aimed to investigate growth, senescence and tumorigenesis potential of abnormal MSCs (AMSCs). In addition, we characterized their metabolism, karyotype and level of proliferative and cancer related mrna. Materials and Methods: MSCs were isolated from bone marrow of Lewis rats and cultured under standard conditions. Cell growth and senescence were evaluated among normal MSCs and AMSCs by sequential counting and senescence β-galactosidase staining, respectively. For tumorigenesis assay or cells were injected intravenously or subcutaneously into BALB/c athymic (nude) male mice. After one and four months, organs were analyzed. Karyotype and genotype of growing cells was assessed by Giemsa staining and Quantitative Real Time PCR, respectively. Representative parameters for cell metabolism were measured by cell culture on chip and the innovative Bionas 2500 analyzing system. Results: AMSCs revealed aberrant cell proliferation and show low β- galactosidase activity. They exhibited a very wide range of chromosome numbers, from 49 up to 221 with an average of 90. The mrna level of c-myc, p53, cyclin D1, cdk1 and cdk4 was significantly increased. AMSCs showed distinctly higher metabolic activities. Their respiration and acidification rates were particularly elevated. Moreover, AMSCs showed a low impedance signal, a parameter that indicates cell adhesion or cell density. Within four months after cell injection to immunodeficient mouse there was no indication of tissue abnormalities or tumor formation. Conclusion: Extensive investigations are needed to ensure the safe usage of MSCs in regenerative therapies. In our study, rat AMSCs showed aberrant karyotype and metabolism, up-regulation of oncogene c-myc and lost of cell cycle control. Although AMSCs did not induce sarcoma in nude mouse after four months the cells could hide undesirable effects after transplantation. Systematic characterization, standardized, rigorously tested protocols and quality control will be highly recommendable before MSCs in clinical application. P3096 Junctional adhesion molecule-a is expressed on human CD34 + cells and promotes adhesion to immobilized platelets and differentiation to endothelial progenitor cells K. Stellos, H. Langer, S. Gnerlich, V. Panagiota, E. Ninci, I. Mueller, B. Bigalke, A. Bueltmann, S. Lindemann, M. Gawaz. Eberhard-Karls Universitaet Tuebingen, Tubingen, Germany Background: Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. It has been recently reported that platelets recruit circulating progenitor cells and that they express the junctional adhesion molecule-a (JAM-A), which is a cell adhesion molecule involved in inflammation. The aim of the present study was to investigate the role of JAM- A on platelet-mediated adhesion and differentiation of human CD34+ cells into endothelial progenitor cells. Methods and Results: CD34+ cells adhere over platelets adherent on collagen under static and flow conditions. The role of JAM-A in platelet-induced adhesion was investigated by using a neutralizing soluble protein (sjam-a-fc) and a blocking mab (anti-jam-a). Treatment with sjam-a-fc resulted in a significantly decreased adhesion of human CD34+ cells to platelets. Human CD34+ cells express at a high level JAM-A, as defined by flow cytometry and immunoblot. Adhesion of CD34+ cells to immobilized JAM-A was inhibited by a neutralizing antibody to JAM-A or to LFA-1 (alβ2 integrin). Colony forming unit assays revealed that treatment with sjam-a-fc, but not with sjam-c-fc or control-fc, significantly reduced the platelet-mediated differentiation of CD34+ cells to endothelial progenitor cells. Moreover, immobilized JAM-A-Fc promoted the differentiation of CD34+ cells into endothelial progenitor cells in a similar manner like immobi- lized fibronectin. Verification of differentiation to endothelial progenitor cells was conducted through a multimarker approach by flow cytometry and RT-PCR. Blockage of JAM-A resulted in decreased CD34+ cell-induced re-endothelialisation, as shown by endothelial injury assays in vitro. Conclusions: Together these results indicate that the expression of JAM-A on CD34+ cells mediates adhesion to immobilized platelets and differentiation into endothelial progenitor cells, a mechanism potentially involved in vascular regeneration. P3097 Efficiency of intramyocardial injections of autologous bone marrow mononuclear stem cells in patients with ischemic heart failure: long-term results A. Romanov, E. Pokushalov, S. Artemenko, P. Larionov, I. Terehov, E. Kliver, O. Efanova, A. Cherniavskiy. State Research Institute of Circulation Pathology, Novosibirsk, Russian Federation Purpose: Intramyocardial injection of autologous bone marrow mononuclear cells (BMMC) is believed to be a promising method for the treatment of patients with chronic ischemic heart disease. The aim of this study was to evaluate long-term results of intramyocardial bone marrow cell injection in patients with severe ischemic heart failure. Methods: Ninety nine ischemic heart failure patients (age 58±5) with left ventricle ejection fraction (LVEF) 35% and III-IV NYHA and CCS functional classes without possibility for conventional revascularization were randomized into two groups: 1 group (n=49) - received intramyocardial BMMC injection and patients of the second group (n=50) were treated with standard medical therapy for HF. The NOGA system was used to administer 4.9 x107 BMMC into the infarction border zone. We analyzed all clinical data at 6 and 12 month of the follow-up period. Patients from group 1 underwent repeated left ventricle mapping using NOGA system at the same follow-up period. Results: None of the patients developed periprocedural complications following BMMC injections. In the first group, the injections led to improvement of CCS class (3.5±0.5 vs 2.1±0.6 after 6 months and 1.9±0.6 after 12 months (p<0.05 vs. baseline) and NYHA functional class (3.4±0.1 vs 2.3±0.2 after 6 months and 2.0±0.2 after 12 months; p<0.05). The same characteristics in patients of the 2 group therapy remained unaltered (p=ns). LVEF increased in group 1 (34±2% vs 40±3%; p<0.05) while it tended to decrease in the control group (34±2% vs 31±3%; p=ns). Summed rest score improved in the first group after 6 months (14.7±5.4 vs 11.7±4.9; p<0.05). The improvement of stress score was more noticeable (19.4±5.4 vs 9.7±4.9; p<0.05). Neither stress nor rest score changed in patients of the second group. At the moment after12 month follow up period 5 patients (10.2%) from group 1 died compared with 16 patients (32%) from group 2 (p<0.05). Conclusions: Intramyocardial injection of autologous bone marrow mononuclear cells in ischemic heart failure patients is a safe procedure that improves clinical symptoms and has beneficial effect on LV function. P3098 Intracoronary infusion of mononuclear cells from the bone marrow or peripheral blood on the recovery of microvascular function in acute myocardial infarction patients: HEBE Doppler substudy A. Hirsch 1, J.D.E. Haeck 1, R. Nijveldt 2, A.M. Van Der Laan 1, J.G.P. Tijssen 1, K.M.J. Marques 2, F. Zijlstra 3, A.C. Van Rossum 2,J.J.Piek 1 on behalf of HEBE Investigators. 1 Academic Medical Center, Amsterdam, Netherlands; 2 VU University Medical Center, Amsterdam, Netherlands; 3 University Medical Center, Groningen, Netherlands Background: Neovascularisation has been suggested as a mechanism by which cell therapy may enhance functional cardiac recovery. The HEBE trial investigated the effect of intracoronary infusion of mononuclear bone marrow cells (BMC) or mononuclear peripheral blood cells (PBC) in acute myocardial infarction patients treated by primary percutaneous coronary intervention (PCI). In this substudy we assessed the effect of cell therapy using intracoronary Doppler flow measurements. Methods: Doppler flow measurements were available for 23 BMC patients, 18 PBC patients, and 19 control patients. Coronary blood flow velocity was measured in the infarct vessel and reference vessel at 3 to 8 days after primary PCI (in the BMC and PBC group before cell infusion) and at 4 months follow-up. Coronary flow velocity reserve (CFVR) (cm/s) and hyperaemic microvascular resistance index (HMRI)(mm Hg s/cm) were calculated. Results: Data are summarized in Table 1. CFVR at baseline was reduced in the Abstract P3098 Table 1. Coronary flow velocity data Variable BMC (N=23) PBC (N=18) Control (N=19) p-value* p-value* Baseline Follow-up Change Baseline Follow-up Change Baseline Follow-up Change BMC vs. Control PBC vs. Control Baseline APV (cm/s) 23±10 17±7-6±10 22±11 18±13-5±7 24±10 17±8-7± Hyperaemic APV (cm/s) 42±13 51±19 8±22 46±19 52±26 6±20 45±16 53±14 8± HMRI (mmhg s/cm) 2.0± ± ± ± ± ± ± ± ± CFVR 2.0± ± ± ± ± ± ± ± ± CFVR (RV) 2.6± ± ± ± ± ± ± ± ± *Changes from baseline to follow-up were compared between groups by analysis of covariance. Infarct-related artery. APV = average peak flow velocity; BMC = bone marrow cell group; CFVR = coronary flow velocity reserve; HMRI = hyperaemic microvascular resistance index; PBC = peripheral blood cell group RV = reference vessel.

205 Stem cells in trans 505 infarct vessel and improved over time in all three groups equally (BMC: 2.0±0.5 to 3.1±0.7; PBC: 2.2±0.6 to 3.2±0.8; control: 2.0±0.5 to 3.4±0.9). The change in HMRI in the infarct vessel from baseline to follow-up was also not different between groups (BMC: 2.0±0.5 to 1.8±0.6; PBC: 1.9±0.8 to 1.8±0.6; control: 1.9±0.5to1.7±0.5). Conclusions: Intracoronary infusion of BMC or PBC in patients with reperfused acute myocardial infarction did not result in a reduction of microvascular resistance to support the hypothesis of induced neovascularisation following this mode of cell therapy. P3099 Hypoxia accelerates and enhances cardiomyogenesis in mesenchymal stem cells: an environmental cue for a cardiac challenge A.A. Ramkisoensing, D.A. Pijnappels, J. Swildens, C.I. Schutte, A. Van Der Laarse, A.A.F. De Vries, M.J. Schalij, D.E. Atsma. Leiden University Medical Center, Leiden, Netherlands Purpose: In cardiac cell therapy, stem cells are transplanted in the border zone of the infarcted myocardium, which is an environment with low oxygen tension. Little is known about the influence of this hypoxic environment on the cardiomyogenic differentiation potential of mesenchymal stem cells (MSCs). Therefore we assessed, in an in vitro model, the capacity of neonatal rat MSCs to differentiate into cardiomyocytes under hypoxic and normoxic conditions. Methods: Bone marrow-derived MSCs of 2-day old neonatal rats (nr) were cultured under normoxic (21% O2) or hypoxic (5% O2) conditions and studied for their surface-marker profile by flow cytometry. Real-time polymerase chain reaction (PCR) was used to detect expression of cardiomyocyte genes in nrmscs cultured under both conditions. To induce cardiomyogenic differentiation egfplabeled nrmscs were co-cultured with nr ventricular cardiomyocytes under normoxia and hypoxia up to 10 days. Cardiomyogenic differentiation of the egfplabeled cells was assessed both at day 3 and 10 of co-culture by immunostaining for cardiac marker proteins and functional analysis. Results: Flow cytometric analysis of nrmscs cultured under hypoxic and normoxic conditions, showed expression of traditional MSC surface-markers with only minor differences in expression levels. Real-time PCR showed no difference in mrna levels of Islet-1, GATA-4 and VEGF. However, connexin 43 expression was significantly increased in nrmscs cultured in a hypoxic environment as compared to nrmscs cultured under normoxic conditions (1.4±0.07 fold change, P<0.001). At day 3 of co-culture, the cardiac protein α-actinin was expressed in egfp-labeled nrmscs co-cultured under both conditions. However, the typical cardiac-specific cross-striated pattern of the sarcomeric protein was only present in nrmscs incubated in a hypoxic environment (2.1±0.35%), but not in nrmscs maintained in a normoxic environment. At day 10 of co-culture, positive staining in the typical cardiac cross-striated pattern was also observed in nrmscs cultured in normoxia (1.2±0.75%), while it was significantly increased in nrmscs kept in hypoxia (3.3±0.91%, P<0.05). Conclusion: Cardiomyogenic differentiation is accelerated and enhanced in neonatal rat (nr) mesenchymal stem cells (MSCs) co-cultured with nr cardiomyocytes in a hypoxic environment. In cardiac cell therapy, circumstances at the site of engraftment might therefore have a critical influence on the regenerative potential of MSCs. Purpose: Sildenafil and bone marrow-derived endothelial progenitor cells (BMDEPCs) have been shown to ameliorate monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in the rat. We test whether sildenafil offers additional benefits on BMDEPC treatment against MCT-induced PAH in rats. Methods and Results: Male Sprague-Dawley rats were randomized to receive saline injection only (group 1), MCT (70 mg/kg) only (group 2), MCT plus autologous BMDEPC (2.0x106 cells) transplantation (group 3), MCT with combined BMDEPCs-sildenafil (10 mg/kg/day) (group 4), and MCT with combined BMDEPCs-sildenafil (30 mg/kg/day) (group 5). Intravenous BMDEPC and oral sildenafil were given on day 3 after MCT administration. By day 35 following MCT treatment, Western blot showed reduced connexin43 and protein kinase C-ε expression in right ventricle (RV) in group 2 than in other groups (all p<0.009). Additionally, mrna expressions of matrix metalloproteinase 9, tissue necrotic factor-α, and caspase 3 were higher, whereas Bcl-2 and endothelial nitric oxide synthase were lower in lung and RV in group 2 than in other groups (all p<0.05). The number of alveolar sacs and lung arterioles were also lower in group 2 than in other groups (all p<0.05). The RV systolic pressure (RVSP) and weight were significantly increased in group 2 than in other groups (all p<0.0001). Moreover, RVSP and RV-to-final body weight ratio were higher in group 3 than in groups 1, 4, and 5(p<0.0001) that showed no significant difference among themselves. Conclusions: Combined therapy with autologous BMDEPC and sildenafil is superior to BMDPEC only for preventing MCT-induced PAH. P3101 Intracoronary infusion of mononuclear cells potentially prevents post-infarct ventricular remodeling in patients with an initial dilated left ventricle: a HEBE substudy A.M. Van Der Laan 1, P.A. Van Der Vleuten 2, A. Hirsch 1,R.Nijveldt 3, W.J. Van Der Giessen 4, B.J. Biemond 1, J.G.P. Tijssen 1, A.C. Van Rossum 3, F. Zijlstra 2,J.J.Piek 1 on behalf of the HEBE investigators. 1 Academic Medical Center, Amsterdam, Netherlands; 2 University Medical Center, Groningen, Netherlands; 3 VU University Medical Center, Amsterdam, Netherlands; 4 Erasmus University Medical Center, Rotterdam, Netherlands Purpose: The HEBE trial did not show a beneficial effect of intracoronary delivery of bone marrow mononuclear cells (BMMC) or peripheral blood mononuclear cells (PBMC) on regional and global systolic myocardial function in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention. However, results from other clinical trials have suggested that the beneficial effects of BMMC therapy may be confined to patients with large AMI. In this study we evaluated the effects of cell therapy in patients with an initial dilated left ventricle (LV). Methods: In the HEBE trial, 200 patients were randomly assigned to either intracoronary infusion of BMMCs (n=69), infusion of PBMCs (n=66), or standard therapy (without placebo infusion)(n=65). Paired MRI images (baseline and 4 months follow-up) were available in 189 patients. The patient population was dichotomized according to the median value of baseline LV end-diastolic volume (EDV)(96 ml/m 2 ). Analysis of covariance was used for comparison of changes in MRI variables between treatment groups. Results: In patients with a baseline LV EDV 96 ml/m 2 the change in LV EDV and ejection fraction did not differ significantly between the three groups. However, in patients with a baseline LV EDV >96 ml/m 2 the increase in LV EDV over 4 months was significantly augmented in the control group compared with the two treatment groups (see figure). This was not accompanied by a significant improvement of LV ejection fraction in the cell therapy groups. P3100 Sildenafil enhances endothelial progenitor cell protection against pulmonary hypertension in rats H.K. Yip 1,C.K.Sun 2,C.M.Yuen 3,S.Chua 1, L.T. Chang 4, F.Y. Lee 5, M. Fu 1. 1 Cardiology, Chang Gung Memorial Hospital,KMC,Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan; 2 General Surgery,Chang Gung Memorial Hospital-KMC,Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan; 3 Neurosurgery, Chang Gung Memorial Hospital-KMC,Chang Gung University College of Medicine, Kaoshsiung Hsien, Taiwan; 4 Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung, Taiwan; 5 Cardiovascular Surgery, Chang Gung Memorial Hospital,KMC,Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan Conclusion: Intracoronary infusion of either BMMCs or PBMCs potentially prevents post-infarct LV remodeling in patients with an initially dilated left ventricle. P3102 Subpopulations of endothelial progenitor cells-isolation, culture, adhesion and migration K. Walenta, C. Rischar, M. Boehm, E.B. Friedrich. Universitaetsklinikum der Saarlandes, Homburg, Germany Endothelial Progenitor Cells (EPCs) have been implicated in myocardial repair after infarc-tion, in the propagation of angiogenesis following ischemia, and in vascular repair after in-jury. Uncertainty remains about the exact nature of EPCs and it is a matter of debate whether these cells represent a uniform subpopulation of cells. Identification of a CD34-/CD133+ EPC- subpopulation gave rise to the hypothesis that subpopulations may play each a distinct role in endothelial regeneration. CD133+/CD34- cells are to be precusors of more mature CD34+/CD133+/VEGFR-2+ EPCs. It has been assumed that this cell popula-tion has functionally more potential with respect to homing and vascular repair. Up to now, all approaches are further hampered by the fact that only a minimal amount of cells can be isolated from blood or bone marrow. Therefore, extensive analysis or even treatment op-tions remain elusive. The aim of this study was to establish a method enabling isolation, expansion and beyond this characterization of peripheral circulating EPCs and their sub-populations. Cell populations (CD133+/CD34+, CD34-/CD133+) were isolated by a new method of hu-man depletion procedure. This allowed isolation of the EPC- subpopulations without loss of cells. Purity and amount of cells was, in contrast to other isolation techniques, more pure and effective. Afterwards, expansion and further analysis of the subpopulations were per-formed. Several surface markers were analysed via Fluorescent Activated Cell Sorter (FACS). Specific endothelial markers such as CD31 (PECAM) and VEGFR-2 were detect-able on CD34-

206 506 Stem cells in trans / Mechanisms of vascular disease /CD133+ and CD34+/CD133+ cells but had a significant higher expression on CD34+/CD133+ cells (p<0.001). Next to this, CD34-/CD133+ cells showed a significant higher rate of proliferation (p<0.005) analysed with Ki67. Annexin- V, a marker indicating necrosis, could be measured in a significantly higher amount (p=0.005) on CD34+/CD133+ cells than on CD34-/CD133+ cells. Adhesion assays revealed a higher adhesive feature of CD34-/CD133+ cells. Likewise, CD34- /CD133+ cells had a significant higher migratory ca-pacity after stimulation with SDF-1 (p<0.001). Our data prove that circulating EPCs comprise of heterogeneous subpopulations. Differ-ences apply to distinct qualitative and quantitative surface marker expression and prolifera-tion in culture. EPC- subpopulations differ in their adhesive and migratory capacities. Fur-ther investigations have to be performed analysing the capacity of differentiation, the power in regard to vascular repair and the molecular mechanisms liable for homing of these EPC-subpopulations. P3103 MECHANISMS OF VASCULAR DISEASE Systematic evaluation of CAD in hemodialysis patients: from screening to evaluation of the artery structure A.M. Varela 1, E. Taniguchi 1, J.R. Faria Neto 2, R. Pecoits-Filho 1. 1 Pontificia Universidade Catolica do Parana, Curitiba, Pr, Brazil; 2 Hospital Cardiologico Costantini, Curitiba, Pr, Brazil Dialysis patients present a high cardiovascular (CV) mortality, but careful screening and systematic investigation of patients for CAD, as well as a comparative description of the characteristics of the lesions of dialysis patients (using IVUS) has not been reported. We aimed to identify patients at high risk for CAD in all hemodialysis patients treated in a large university based clinic, to estimate the prevalence of CAD and its morphology through IVUS in comparison with their counterparts with normal renal function. One hundred and thirty nine patients (53±13 years old, 62% male) were investigated through medical interview and chart review for symptoms and the presence of risk factors of CAD. Those at high risk were referred to a cardiology clinic where patients presenting indication were sent to coronary angiography and IVUS. IVUS results were compared to a group of patients with CAD who presented normal renal function matched for all Framingham risk factors. Half of the patients did not report chest pain (58%) and among those who did, 22% presented pain during stress, 24% during dialysis sessions and only 3% reported pain at rest. Ninety-five (68%) patients were considered as high risk and were evaluated for CAD. From those, 13% presented criteria to be submitted to coronary angiography, which confirmed CAD in 12 patients. The IVUS revealed a greater proximal reference diameter in ESRD patients when compared to control group ( vs ; p<0.007) and a smaller cross sectional area ( vs ; p< 0.02). Extensive coronary calcification by IVUS was identified in 81% of the lesions in the study group, 31% of those with more than 180 of coronary arch and the calcification was located in a deeper arterial layer in 69% vs. 30% in the control group (p<0.004). In conclusion, the current methods of screening CAD in the general population did not identify many ESRD patients at high risk for CAD, and only a small proportion was referred to an angiographic evaluation, as expected in a high CV mortality population. The lesions of ESRD patients differ from the controls since they presented a larger proximal diameter and intense calcification in the deeper layer of the vessel suggesting a greater positive remodeling effect in response to a more aggressive atherosclerotic process in the medial part of the artery. In concert, these data show that evaluation; diagnosis and therapeutic approaches for CAD should be reevaluated in ESRD patients, who present clinical and structural peculiarities. P3104 Heterogeneity in abdominal aortic aneurysm wall composition R. Hurks 1,A.Vink 1, I.E. Hoefer 1, J.P.P.M. De Vries 2, C.A. Seldenrijk 2,F.L.Moll 1,G.Pasterkamp 1. 1 University Medical Center Utrecht, Utrecht, Netherlands; 2 St Antonius Hospital, Nieuwegein, Netherlands Purpose: Media degeneration is a known feature in Abdominal Aortic Aneurysm (AAA) formation, but its pathophysiological mechanism is largely unknown. Since it is unknown at which diameter which AAA ruptures, different types of AAA are likely to exist. We examined AAA wall composition in a large patient cohort compared to normal aortic wall, and studied among AAA the media in relation to inflammation of the aortic wall. Methods: Patients undergoing open AAA repair were included (n=175). During surgery a specimen of the ventral AAA-wall was collected and used for histology to assess elastin, collagen and inflammatory infiltrate. Postmortem obtained normal aortic wall specimens (n=27) served as control. Results: Compared to normal aortic walls, AAA walls show a larger lipid core (p<0.001), more calcium (p<0.001), less elastin (p<0.001), less collagen (p=0.002), less SMC (p<0.001), more vasa vasorum (p<0.001), more T- lymphocytes (p<0.001), more B-lymphocytes (p<0.001) and more plasma cells (p<0.001). Remarkably, AAA walls contain less macrophages (p=0.016). Severe media degeneration (nearly absence of elastin fibers and SMCs) was observed in 94/175 (54%) AAAs, whereas in 81/175 (46%) AAAs the media revealed only moderate changes. An abundant adventitial infiltrate of T- and B- lymphocytes was more often observed in AAAs with media absence compared to AAAs with media presence (p=0.003 and p=0.024, respectively). No association was observed between the amount of elastin and SMCs in the media versus AAA diameter. The amount of T-lymphocytes was positively associated with AAA diameter (R=0.226 p=0.004). Conclusions: Our results clearly show arterial degradation in AAA compared to normal aortas. Even though all AAA show some degeneration of the media, a group with only moderate degenerative changes of the media and low numbers of adventitial lymphocytes can be distinguished from AAA with an absent media and many T- and B-lymphocytes in the adventitia. Media degeneration is not associated with diameter, suggesting different pathophysiological mechanisms between these two types of AAAs. P3105 Predicting cardiovascular events and mortality following abdominal aortic aneurysm surgery R. Hurks 1, I.E. Hoefer 1, J.P.P.M. De Vries 2, S.M.W. Van De Weg 1,M.Kerver 1, D.P.V. De Kleijn 1,F.L.Moll 1,G.Pasterkamp 1. 1 University Medical Center Utrecht, Utrecht, Netherlands; 2 St Antonius Hospital, Nieuwegein, Netherlands Background and purpose: Experimental studies support a role for osteopontin (OPN) in Abdominal Aortic Aneurysm (AAA) development. It has been shown that OPN-/- mice do not develop aortic aneurysms. Moreover OPN is a predictor of e.g. future angina in cardiovascular disease, indicating that local biomarkers predict future cardiovascular outcome. We therefore hypothesized that OPN levels in AAA tissue have a predictive value for future adverse events following AAA surgery. Methods: In this study, 179 patients undergoing elective open AAA surgery were included. Of all patients, ventral infrarenal arterial wall specimens (used for protein extraction and histology), clinical and follow-up data were collected. Infrarenal aortic walls of 28 patients without arterial aneurysm were collected post-mortem and served as control. Clinical endpoints were defined as cardiovascular death, MI, stroke or limb amputation. Results: Mean follow-up time was 2.3 years. Compared to normal aortic vessel walls, OPN levels were significantly higher in AAA (p<0.001), supporting its role in AAA pathogenesis. Local OPN levels in the aneurysm wall of patients with clinical events during follow-up were significantly increased compared to patients free of events (p=0.045). Kaplan-Meier analysis showed that high OPN values predict cardiovascular events (p=0.051) and mortality (p=0.008). Furthermore, it became evident that most cardiovascular events occurred during the early postoperative phase. Hence, high OPN levels are associated with a prolonged hospital stay (p=0.010). Use of Atorvastatin (p=0.026) and Clopidogrel (p=0.017) were associated with lower OPN values, thus representing a possible therapeutic option. Conclusions: High OPN in the AAA-wall is predictive for future events and mortality. This leads to identification of a possible subgroup of patients with an increased risk of postoperative morbidity and mortality. Therefore, OPN might be used to identify high risk patients requiring intensified treatment, possibly with Atorvastatin or Clopidogrel. P3106 Association of increased carotid intima-media thickness and arterial stiffness with enhanced monocyte expression of adiponectin receptors in patients with coronary artery disease I. Ikonomidis 1, A. Kollias 2, J. Lekakis 1,I.Palios 1,P.Tsiotra 2, E. Maratou 2, K. Fountoulaki 1,G.Dimitriadis 2, S.A. Raptis 2,D.T.Kremastinos nd Cardiology Department, Attikon Hospital, University of Athens Athens, Greece; 2 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Attikon Hospital, Athens, Greece Purpose: Adiponectin is reduced in patients with CAD. Adiponectin receptors 1 (ADR1) and 2 (ADR2) are expressed on cells within atheromatic lesions and on monocytes transformed to macrophages and are activated by PPAR-receptor agonists. Carotid intima-media thickness and arterial stiffness are markers of subclinical atherosclerosis with prognostic significance. We investigated whether ADR1 and 2 are associated with carotid intima-media thickness and arterial stiffness in patients with angiographically documented chronic CAD. Methods: We studied 68 patients with suspected CAD who underwent coronary angiography (mean age: 59±7 years). We measured a) expression of ADR1 and 2 on blood monocytes [mean fluorescence intensity arbitary units MFI-AU] by flow-cytometry b) carotid to femoral artery pulse wave velocity (PWV), as an estimate of arterial stiffness using the Complior apparatus c)mean intima-media thickness (IMT) in common carotids and carotid bulbs using ultrasound imaging. Results: ADR1 and 2 expression was lower in patients with coronary stenosis >50% in at least one vessel (n=48) than in those with no significant stenosis (63±25 vs. 84±27 and 82±37 vs.111±46 MFI-AU respectively, p<0.05). Both groups had similar atherosclerotic risk factors. Within patients with significant CAD, increased expression of ADR2 was related to increased PWV (rs=0.65, p=0.01), carotid bulb IMT (rs=0.44, p=0.03) and presence of carotid plaques (IMT>1.5mm) (rs=0.40, p=0.03). Increased expression of ADR1 was also related to increased PWV (rs=0.47, p=0.03). These associations were not observed in patients without significant CAD.

207 Mechanisms of vascular disease 507 Conclusions: Expression of adiponectin receptors is reduced in patients with significant CAD. Increased expression of ADR2 receptors on monocytes is related to peripheral vascular atherosclerosis in vivo. This increased expression of ADR in patients with more extensive atherosclerosis may reflect a compensatory mechanism for the low circulating adiponectin levels and may offer a potential therapeutic target for the use of PPAR-receptor agonists to activate the anti-inflammatory and anti-atherogenic action of these receptors. P3107 Hemodynamic influences on abdominal aortic aneurysm wall composition R. Hurks 1, I.E. Hoefer 1, J.A. Van Herwaarden 1,A.Vink 1, J.P.P.M. De Vries 2, G. Pasterkamp 1,F.L.Moll 1. 1 University Medical Center Utrecht, Utrecht, Netherlands; 2 St Antonius Hospital, Nieuwegein, Netherlands Purpose: Current Abdominal Aortic Aneurysm (AAA) research focuses on either wall composition or hemodynamics. Human data on combining both topics is lacking. Endovascular (EVAR) treatment separates the aneurysm from the modulating hemodynamic forces and thus allows studying their effects on aneurysm wall composition. Therefore, we compared aneurysm wall composition of EVAR treated patients after redo open surgery and of primarily open repaired AAA. Methods: Patients undergoing elective open AAA repair, either primary (n=60) or endovascular (EVAR)-redo due to type 2 endoleaks (n=6), were included and matched for diameter. Pre-operatively, patients filled in an extensive questionnaire and during surgery a specimen of the ventral AAA-wall was collected and freshly frozen to study cytokine levels. Part of the wall was used for histology to assess elastin, collagen and inflammatory infiltrate. Results: Baseline characteristics showed no differences in gender, age, other risk factors of AAA development and medical history. Aneurysm wall of the EVARredo patients contained more smooth muscle cells (p=0.013), more collagen in the intima and media (p=0.010), both consistent with a more robust type of AAA-wall being less prone to rupture. No differences in elastin content were found. Histological analysis of inflammatory infiltrates revealed that EVAR-redo AAA contained more lymphocytes in the intima and media (p=0.001) and more macrophages in the media (p=0.004) compared to primary open repair AAA. However, these inflammatory cells are by far outnumbered by the number of inflammatory cells in the adventitia, which did not differ between groups suggesting that absolute numbers do not differ significantly. This is supported by the lack of difference in levels of il1beta, il2, il4, il5, il6, il8, il10, il12p70, TNFalpha, TNFbeta and IFNgamma. Conclusions: Our results indicate that the isolation of the aneurysm from the molding hemodynamic forces by EVAR treatment stabilizes AAA walls. These findings raise the question of shifting the 5mm diameter increase in 6 months cut-off point as sole indication for conversion of EVAR-treated AAA with type 2 endoleaks and await evolution. Further research is needed to confirm these findings. P3108 Bone marrow-derived dendritic cell-like cells accumulate low-shear stress region in mice M. Tsuzuki. Nagoya University Hospital, Nagoya, Japan Background: It has been shown that vascular dendritic cells (DCs) accumulate in atherosclerosis-prone lesions, neointimal lesions, and in-stent lesions in the aorta and arteries. Although it is speculated that the DCs accumulate in low-shear stress lesions, the accumulation of the DCs have not shown in induced low-shear stress models of artery. Methods and Results: Because it has not reported precise systems to evaluate wall shear stress in mice, two types of bandage model of common carotid artery (CCA) and two types of partial ligation models of brunched arteries of CCA were evaluated as induced low-shear stress arterial models of mice. In the bandage models, 0.1-mm or 0.2-mm fine needle and the left CCA were tied with 11-0 nylon suture, subsequently the needle was removed. In the partial ligation models, the left internal carotid artery instead of the occipital artery with or without the left external carotid artery (ECA) were ligated with 6-0 silk braid. (As the former model of each procedure made less blood flow through the operated CCA than the latter model, the wall shear stress of the former model was thought to be less than the latter model, respectively.) Bone marrow (BM)-derived DC-like cells were visualized using a BM transplantation model, in which male wild-type C57BL/6 mice irradiated 10 Gys of X-ray were transplanted the BM cells derived from age-mached green fluorescent protein (GFP)-transgenic C57BL/6 mice. The BM transplanted mice were operated at at least 4 weeks after BM transplantation, and sacrificed at 7 days after operation. In terms of the bandage models, the CCAs were occluded and made thrombi in the mice with 0.1-mm-bandage otherwise the CCAs banded with 0.2-mm fine needle were patent. GFP positive BM-derived DC-like cells were accumulated between the aortic bifurcation and the clot in the 0.1-mm-bandage model however DC-like cells were seen only in just proximal site of the bandage in the 0.2-mm-bandage model. In terms of partial ligation model, there was no accumulation of DC-like cells in the CCAs without ECA ligation while DC-like cells accumulated in the ECA ligation model. In right CCA, control side of these experiments, there was no DC-like cell accumulation in main trunk, otherwise DC-like cells usually accumulated in the aortic bifurcation and the subclavian bifurcation, where it is thought that the blood stream should separate from the vessel wall and that the wall shear stress must be low. Conclusions: The regulation system of the accumulation of BM-derived DCs may involve the wall shear stress of blood stream. P3109 Central aortic pulse wave analysis among offspring of patients with high cardiovascular risk and symptomatic coronary artery disease A. Rapaee 1, M.A. Nor Hanim 2,T.K.Ong 2,C.K.Ang 2,H.B.Liew 2, S.A.R.S. Alwi 1, S.K. Chua 2,K.L.Yew 2, B.C. Chang 2,K.H.Sim 2. 1 Unimas, Kuching, Malaysia; 2 Sarawak General Hospital, Kuching, Malaysia Introduction: Arterial stiffness determined by central aortic pressure indices such as augmentation pressure, augmentation index and central pulse pressure has been shown to be associated with the risk and severity of atherosclerosis in patients with coronary artery disease (CAD). However, arterial stiffness among the offspring of high risk and symptomatic CAD patients has not been previously evaluated. Objective: The objective of this study was to determine arterial stiffness using a non-invasive assessment of central aortic pulse wave among the offspring of patients with high risk and symptomatic CAD. Methodology and Results: We studied a total of 203 individuals. Central aortic wave analysis was quantified non-invasively using a commercially available applanation tonometry. Their mean age was 21.1±1.2 years. 49.5% were male. 20.6% of their parents were known to have CAD, 41.1% had diabetes mellitus, 37.9% had high LDL cholesterol, 48.1% were hypertensive and 20.6% had more than 3 risk factors. However, none of the study subjects had any of these risk factors. The mean augmentation pressure (AP) for those with and without family history of CAD was 10.9±4.6 mmhg and 4.5±3.8 mmhg respectively, p< The mean augmentation indices (AIx) were 22.3±4.8 mmhg and 6.1±3.6 mmhg respectively, p< After normalization of heart rate at 75 bpm (AIx@75) the difference remains significant (p<0.0001). There were no significant differences in central aortic pressure indices between individuals with and without family histories of hypertension and diabetes. However, one way Anova testing showed p=0.001, p=0.002 and p=0.04 for AP, AIx and AIx@75 respectively if their parents had more than 3 cardiovascular risk factors. Conclusions: The offspring of patients with coronary artery disease and high cardiovascular risk factors were found to have early abnormalities in arterial stiffness determined non-invasively using measurements of central aortic pulse pressure indices. Hence, non-invasive assessment of arterial stiffness might be useful to detect early atherosclerosis and to risk stratify these individuals. P3110 Influencing the anticontractile properties of adipose tissue: the effects of aldosterone, its antagonists and hypoxia C. Agabiti-Rosei, S.B. Withers, A. Greenstein, R. Aslam, K. Khavandi, R.A. Malik, A.M. Heagerty. The University of Manchester, Manchester, United Kingdom Background: Obesity induced changes in the inflammatory and hypoxic environment of perivascular adipose tissue has been linked to abnormalities in the adiponectin-mediated anticontractile characteristics of adipocytes. The Renin- Angiotensin-Aldosterone-System has been implicated in BOTH obesity and hypoxia, the aim of these studies was to investigate the effect of Aldosterone, hypoxia and two aldosterone antagonists; Eplerenone (non-genomic) and Spironolactone (Genomic), on the anticontractile property of adipose tissue. Methods: Mesenteric arterial segments ( 250μM) from healthy male wistar rats were studied using wire myography. The effects of Aldosterone, and its antagonists were assessed following short and long incubation (10min & 3hrs), and after 2.5hours of experimental hypoxia (95%N2/5% CO2). Contractile responses to noradrenaline were calculated as a percentage of KCl contraction and expressed as mean±sem Results: Healthy adipose tissue had an anticontractile effect on arteries (no adipocytes: 155±7% vs adipocytes: 88±4%, n=25) which, following 10min incubation with Aldosterone (5nM) was lost (165±4%, n=25). Under normoxic conditions, short incubation with Eplerenone, but not Spironolactone, restored contractility to levels similar to arteries with adipose tissue alone (Eplerenone: 88±3%, n=8, Spironolactone: 171±9%, n=6). Incubation with Aldosterone for three hours was associated with a loss of contractility similar to short incubation (172±12%, n=5), although neither Spironolactone, or Eplerenone was able to fully able to restore this effect (Eplerenone: 137±18%, n=4, Spironolactone: 111±4%, n=4). Experimental hypoxia in the absence of any additional Aldosterone attenuated the anticontractile effect of the adipose tissue, this was fully restored by incubation with Eplerenone, but not Spironolactone, which had a marginal effect (adipocytes+hypoxia: 134±9%, n=10, adipocytes+hypoxia+eplerenone: 95±14%, adipocytes+hypoxia+spironolactone: 118±11%, n=5, P<0.05). Contractility of arteries without adipose tissue was not significantly affected by any intervention Conclusions: Hypoxia and Aldosterone share a common pathway in effecting the anticontractile property of adipose tissue, as the Aldosterone antagonists are able to inhibit the response to hypoxia in the absence of Aldosterone. As Eplerenone has greater capacity to restore the anticontractile property of the adipose tissue

208 508 Mechanisms of vascular disease / Effects of primary and secondary prevention following hypoxia when compared to Spironolactone, we believe this is due to the differences in specificity of the antagonists for the mineralocorticoid receptor, which is currently under investigation. P3111 Human circulating monocyte subpopulations significantly differ in their functional properties F.S. Czepluch, S. Olieslagers, R. Van Hulten, S.A. Voo, J. Waltenberger. Maastricht University Medical Center, Maastricht, Netherlands Monocyte recruitment into the vessel wall is a crucial initial step for cardiovascular repair as well as atherosclerosis. Human monocytes show an immunophenotypical heterogeneity. They can be classified according to their CD14/16 surface expression [CD14++CD16- monocytes (CD16-mo) vs. CD14+CD16+ monocytes (CD16+mo)]. The proinflammatory CD16+mo are elevated in the blood of CAD patients. However, the functional consequences of this increased cell count are unclear. We investigated different functional properties of the two monocyte subsets. CD16-mo/CD16+mo were isolated from human buffy coats by immunological magnetic bead isolation. Monocyte chemokinesis (random migration) and chemotaxis (directed migration) were assessed in a microchemotaxis chamber. Cell adhesion was investigated on different surfaces (plastic, collagen, fibronectin). qpcr, Western blot and FACS analyses were performed to quantify receptor expression. Chemokinesis of CD16+mo was clearly decreased compared to CD16-mo (p<0.01; n=16). Likewise, adhesion capacity of CD16+mo was weaker (p<0.05). The decreased CD16+mo chemokinesis might be explained by reduced adhesion, as adhesion is a crucial component of cell migration. Median monocyte chemotaxis towards the potent peptide N-formyl-methionine-leucinephenylalanine (fmlp) was significantly different, as it measured 426% in CD16- mo and 280% in CD16+mo (p<0.01). In contrast to CD16-mo, CD16+mo chemotaxis was also significantly reduced towards the angiogenic ligand Vascular Endothelial Growth Factor-A (VEGF-A) (p<0.05). The same was observed for Placenta Growth Factor-1 (PlGF-1). Flt-1 is the receptor for VEGF-A and PlGF-1 on monocytes. Flt-1 mrna and protein expression were lower in CD16+mo than in CD16-mo (p<0.05). The impaired VEGF-A- and PlGF-1-induced CD16+mo chemotaxis might therefore be attributed to the reduced Flt-1 expression. CD16-mo and CD16+mo significantly differ in their functional properties, as chemokinesis, adhesion and chemotaxis are strongly reduced in CD16+mo. This functional heterogeneity of human monocyte subsets is a novel, potentially important parameter for future functional ex vivo monocyte analyses. Our data suggest that a differential monocyte subset recruitment to areas of vessel formation - characterized by secretion of angiogenic cytokines such as VEGF-A - takes place. Presumably, the two monocyte subsets play different roles in atherosclerosis and vessel formation. Future clinical studies will elucidate the functional significance of monocyte subpopulations in CAD patients. decrease vs day-1). Cardiac Tn-I and CKMB/total CK peak at day 1 post-r and returns to basal values at day 6 post-r. Conclusions: Akt/mTOR/P70S6k and TGF-β1 signalling pathways play a key role in left ventricle remodelling. Understanding the mechanisms involved in tissue repair is warranted to timely determine and better define novel cardioprotective therapeutical strategies. EFFECTS OF PRIMARY AND SECONDARY PREVENTION P3113 Cycling and sports are inversely associated with non-fatal and fatal cardiovascular diseases M.P. Hoevenaar-Blom 1, G.C.W. Wendel-Vos 1, A.M.W. Spijkerman 1, D. Kromhout 2, W.M.M. Verschuren 1. 1 National Institute of Public Health and the Environment, Bilthoven, Netherlands; 2 Wageningen University, Wageningen, Netherlands Purpose: Although the inverse association between physical activity and cardiovascular events is well-known, it remains unclear which moderate to vigorous activities mainly contribute to these beneficial effects. Therefore, the present study investigates the relation of cycling and sports with non-fatal and fatal cardiovascular diseases (CVD). Methods: The Monitoring Project on Risk Factors for Chronic Diseases (MOR- GEN Study) was carried out in the Netherlands in 6959 men and 8211 women aged at baseline. Between 1994 and 1997, information on physical activity was collected with a modified version of the EPIC Physical Activity Questionnaire. During an average follow-up time of 9.8 years, data on non-fatal and fatal cardiovascular diseases were obtained through record linkage. Cox Proportional Hazards models were used, and adjustments were made for demographic factors, lifestyle factors, and biological risk factors. Results: As is shown in figure 1, we found inverse associations between cycling and both non-fatal (HR: 0.83; 95%CI: ) and fatal CVD (HR: 0.64; 95%CI: ). Also, for sports we observed inverse relations with non-fatal (HR: 0.73; 95%CI: ) and fatal CVD (HR: 0.63; 95%CI: ). The combination of cycling and sports was strongly associated with non-fatal (HR: 0.64; 95%CI: ) and fatal CVD (HR: 0.41; 95%CI: ). P3112 Role of Akt/mTOR/P70S6k and TGF-beta1 pathways on left ventricle remodelling after myocardial infarction G. Vilahur 1, B. Onate 1, B. Ibanez 2, J.J. Badimon 2, L. Badimon 1. 1 Barcelona Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2 Mount Sinai School Medicine, New York, United States of America Purpose: Because of the importance of cardiac remodelling on survival after myocardial infarction (MI) we sought to evaluate the molecular and cellular mechanisms involved in myocardial remodelling after acute MI. Methods: Pigs (N=36) were subjected to AMI by closed-chest 90 min mid-lad balloon inflation (modelling a complete thrombotic vessel occlusion) followed by 2.5h, 1, 3, 6 and 21 days post-reperfusion (R). At sacrifice, tissue from ischemic (IM) and remote (non-ischemic; RM) myocardium was obtained for the molecular analysis of: 1) activation of p-akt/p-mtor and its downstream effector p-p70s6k, targets involved in protein translation and autophagy regulation; 2) the fibrogenic cytokine TGF-β1 and its downstream effectors Collagen type-i and III and MMP-2 and -9; and 3) histopathological assessment of collagen content. LVEF (echocardiography), markers of cardiac damage (Tn-I and CKMB/CK) and infarct size (TTC) were evaluated in all animals. Results: Akt/mTOR and its downstream target P70S6K are activated 2.5h post- R and remain elevated up to day 3 in RM and 6 IM. TGF-β1 mrna expression peaks 90 min post-mi, remains elevated until day 1 (p<0.005), and thereafter returns to basal values. TGF-β1 signalling induces a gradual rise in collagen-type I and III from day 3 to 21 post-r (p<0.001) in both regions although IM showed a 2-fold higher expression than RM (p<0.05). In agreement, total collagen content increases moderately from day-3 leading to a 25- and 10-fold increase at 21- days post-r in the IM and RM, respectively (p<0.05 vs basal, 1, 3, and 6 days). MMP-2 active-form (66kDa) is observed as early as 90min post-ami and persists until day-1 post-r in both cardiac regions whereas no changes are detected in active-mmp-9 (84kDa). LVEF is similarly deteriorated in all animals after 90-min occlusion ( 30% reduction; p<0.05 vs. basal) but gradually improves at 21 days (6-8% absolute improvement; p<0.05 vs post-ami). Infarct size is greatest 1-day post-r (34% LV) but is significantly smaller 3 to 21 days post-r (6% absolute Figure 1. Cycling and sports (yes vs. no) in relation to non-fatal and fatal CVD Conclusions: In an adult Dutch population, cycling and sports, especially the combination of cycling and sports, were strongly inversely associated with both fatal and non-fatal cardiovascular diseases. P3114 Reported lifestyle habits and lifestyle changes in high risk patients from 12 European regions: The EUROASPIRE III survey in general practice C.S. Jennings 1,K.Kotseva 1, P. Amouyel 2,G.Debacker 3, D. Debacquer 3,U.Keil 4, Z. Reiner 5,D.Wood 1 on behalf of EUROASPIRE III Study Group. 1 Imperial College London, London, United Kingdom; 2 Institut Pasteur de Lille, Lille, France; 3 University of Ghent, Ghent, Belgium; 4 Universitaet Muenster, Munster, Germany; 5 University of Zagreb School of Medicine, Zagreb, Croatia Purpose: The EUROASPIRE III survey in general practice investigated lifestyle management in high risk patients being treated with drugs to lower BP, lipids and manage diabetes. Methods: EUROASPIRE III was undertaken in selected geographical areas and general practices in 12 countries. Consecutive patients <80 years of age, without a history of atherosclerotic disease, either started on antihypertensive and/or lipid lowering and/or anti-diabetes treatments, were identified retrospectively. Data collection was based on a review of patients medical notes and a prospective interview and examination at least six months after the start of drug treatment. Results: 4366 (78% of all eligible) patients (mean age 60 years, 58% female) were interviewed. They reported lifestyle habits and changes made since starting treatment. Prevalence of smoking at interview was 17% overall. 73% of smokers had been advised to quit, but in only 11% was NRT advised. Only 3% accessed a specialist smoking cessation service. Self reported dietary changes were: reducing fat 82%; changing from saturated to unsaturated fat 76%; increasing fruit and vegetables 79%; eating more oily fish 40%. 51% of all patients reported incorporating more everyday physical activity in their lives, and in 11%

209 Effects of primary and secondary prevention 509 with specific advice from a professional. 83% of patients were overweight (BMI 25kg/m 2 ), 44% obese (BMI 30kg/m 2 ) and 53% centrally obese (waist circumference 102cm men, 88cm women). Amongst overweight (obese) patients, 69% (83%) had been told they were overweight, 45% (43%) had followed dietary recommendations and 36% (32%) had tried regular physical activity to lose weight. Conclusions: Only a small proportion of smokers had received professional medical support to stop smoking. Sedentary habits were reported by a majority, although nearly one half reported trying to incorporate more everyday physical activity into their lives. Overweight and obesity are very prevalent with less than a half of all patients attempting to lose weight. High risk patients require professional help to make healthy lifestyle changes and reduce their risk of developing CVD. P3115 Screening for asymptomatic peripheral artery disease: first results of the Evaluation of ankle/brachial index in hungarian hypertensives (ERV) screening program K. Farkas 1,Z.Jarai 2, E. Kolossvary 1, A. Ludanyi 3,I.Kiss 1 on behalf of ERV study group. 1 St. Imre Teaching Hospital, Budapest, Hungary; 2 Semmelweis University, Budapest, Hungary; 3 EGIS Pharmaceuticals PLC, Budapest, Hungary Background and Objective: Epidemiological data have shown that clinical, but also preclinical stages of peripheral artery disease (PAD) are characterised by a high risk of cardiovascular mortality. PAD can be diagnosed already in the early, asymptomatic stage, with a simple, noninvasive test, the ankle/brachial index (ABI). A low ABI is an indicator of high cardiovascular risk in asymptomatic patients. The objective of the present study was to evaluate the prevalence of clinical and preclinical PAD in hypertensive patients. Patients and Method: Hypertensive patients (age years) who were attended at 53 hypertension outpatient clinics from Hungary, during a 17 month period, were included in the prospective study. All patients had a clinical history, a physical examination, a blood analysis, and a measurement of the ankle/brachial index. Results: A total of patients (9162 males; mean age: years), were included in the study. 58% of the subjects were at low (0-1%) or moderate (2-4%) risk according to the calculated SCORE risk. The prevalence of a low ABI ( 0.9) was 14.0%. In the low, moderate and high SCORE risk groups, the prevalence of low ABI was 6.5%, 9,7% and 17.5% in males; 8.7%, 11.9% and 17.4% in females, respectively. In a multivariate analysis, factors associated with a low ABI were age, smoking, diabetes, hypercholesterolemia, elevated serum uric acid level, a reduced glomerular filtration rate, blood pressure >140/90 mmhg, microalbuminuria, the presence of myocardial infarction in the patient history and the presence of PAD in the family history. Conclusions: Prevalence of a low ABI is elevated in hypertensive patients. The use of ABI screening may improve cardiovascular risk prediction and the treatment can be modified according to the guidelines for high risk patients. Cardiovascular morbidity and mortality data will be evaluated after the 5 years long prospective phase of the ERV program. P3116 Risk factor control and treatment for patients with known CHD coronary heart disease D. Vulic 1, S. Loncar 2,M.Krneta 3,R.Skrbic 4, A. Lazarevic 5, B. Lee 6, N.D. Wong 6. 1 Center for medical research, Banja Luka, Bosnia and Herzegovina; 2 Clinical center, Banja Luka, Bosnia and Herzegovina; 3 Intermedik, Banja Luka, Bosnia and Herzegovina; 4 School of Medicine, Banja Luka, Bosnia and Herzegovina; 5 Cardio, Banja Luka, Bosnia and Herzegovina; 6 Heart Disease Prevention Program,University of California, Irvine, United States of America Background: European treatment guidelines in persons with known coronary heart disease (CHD) focus on compliance to antiplatelet therapy, beta-blockers, ACE/ARBs, and lipid-lowering agents, with goals for blood pressure (BP) of <140/90 mmhg and LDL-cholesterol of <115 mg/dl.data on compliance to these measures are limited among Eastern European nations. Methods: The Republic of Srpska Coronary Prevention Study (ROSCOPS III) was conducted at 10 primary health care centers in selected areas.601 patients (36% female,mean age 55 years) with CHD including acute myocardial infarction (MI),urgent revascularization following MI,angina pectoris following revascularization or angioplasty were studied with interviews and examinations at least 6 months after the events.we compared treatments patterns and control of BP Proportion on Treatment or at Goal ROSCOPS III 2005/2006 ROSCOPS II 2002/2003 (n=601) (n=363) Antiplatelet Therapy 74% 70% Beta-Blockers 61% 59% ACE/ARBs 79% 53% Lipid-Lowering Therapy 62% 28% All four recommended 30% 8% BP < 140/90mmHg 59% 57% LDL-C < 115 mg/dl 39% 42% and LDL-C with ROSCOPS II,a study of similar methodology conducted in 363 patients (21% female,mean age 56) among 7 centers. Results: The table below shows the % of adults on treatment as well as at goal. While two-thirds to three-fourths of patients are on recommended therapies,with recent increases in statin and ACE/ARB use,approximately 40% for BP and 60% for LDL-C remain inadequately controlled.the proportion of patients on all four recommended treatments was 30% in compared to 8% in Conclusions: Our data show a substantial proportion of our patients with known CHD are at target for BP and/or LDL-C. Improved educational efforts targeted both at physicians and patients to address these issues are needed P3117 Predictors of risk factors management in patients after percutaneous coronary intervention-single center experience M. Licina, V. Giga, B. Beleslin, A. Djordjevic-Dikic, J. Stepanovic, I. Grozdic, I. Stankovic, M. Ostojic. Institute for Cardiovascular Diseases, Belgrade, Serbia Objective: Cardiovascular disease (CVD) are leading cause of death and the third cause of disability in Europe. Prevention programmes should include interventions aimed at a reduction of conventional risk factors as well as behavioral risk factors (sedentary lifestyle, smoking, high fat intake and low fruit and vegetable intake). Aim: The aim of a study was to find independent predictors of good/poor regulation of risk factors in patients after percutaneous coronary intervention (PCI). Methods: The study included 500 consecutive patients (mean age 57±9 years; 322male) scheduled for exercise stress test (standard Bruce protocol) after PCI. All patients underwent laboratory examination (lipid status, fasting blood glucose) and evaluation of blood pressure, waist circumference, body-mass index (BMI) and smoking status according to ESC guidelines. Patients answered a questionnaire about their physical activity, socio-economic status, education and nutrition habits. Risk factors control was considered optimal if five risk factors were wellregulated (blood pressure, cholesterol, smoking, BMI and waist circumference). Result: Mean systolic BP was 137±14mmHg, diastolic blood pressure was 86±9mmHg. Slightly increased values of total and LDL cholesterol were observed (4,97±1.2mmol/L and 2.8±1.2mmol/L, respectively). Mean value of HDL cholesterol was 1.2±0.4mmol/L, whereas mean triglyceride value was 1.89±1.4mmol/L. There was high prevalence of obesity (73%) with mean BMI of 27±3.6kg/m 2 and waist circumference of 101±10cm in male and 91±13cm in female. DM type II was present in 16%. There was only 13% of population with five well-regulated risk factors. In the univariate analysis physical activity and education were predictors of good regulation whereas DM and heritage were predictors of poor regulation of risk factors. The multivariate regression analysis shows that DM and physical activity were independent predictors of regulation of CV risk factors. Conclusion: Presence of diabetes mellitus and physical inactivity were the independent predictors of poor regulation of cardiovascular risk factors in patients after PCI. P3118 Prevention of ischaemic events in patients with peripheral arterial disease according to the European guidelines on cardiovascular disease prevention in clinical practice A. Blinc 1, M. Kozak 1,M.Sabovic 1,M.Bozic 1, M. Stegnar 1, P. Poredos 1,A.Kravos 2, B. Barbic Zagar 3, M. Pohar Perme 4,J.Stare 4 on behalf of PID-PAB investigators. 1 University of Ljubljana Medical Centre, Department of Vascular Diseases, Ljubljana, Slovenia; 2 Department of Family Medicine, University of Maribor School of Medicine, Maribor, Slovenia; 3 Krka, d.d., Novo Mesto, Slovenia; 4 Institute of Biophysical Informatics, University of Ljubljana School of Medicine, Ljubljana, Slovenia Aim: To test the efficacy of the European guidelines on cardiovascular disease prevention in patients with stable peripheral arterial disease (PAD). We report on the initial findings of a study comparing survival, incidence of major atherothrombotic events and revascularization procedures in patients with stable PAD compared to subjects without PAD, both groups treated according to their respective cardiovascular risk. Patients and methods: 822 patients with PAD and 782 control subjects of comparable age and sex distribution have been recruited from primary care settings. All subjects have been treated according to the European guidelines on cardiovascular disease prevention, and followed yearly for occurrence of death, nonfatal acute coronary syndrome, stroke and revascularization procedures. Adherence to treatement standards has been assured by introductory seminars and yearly progress-report meetings. Results: The average age of the subjects at baseline was 65 (standard deviation 9) years, with a male/female ratio of about 6/4 in both groups. The ankle-brachial pressure index of the more affected leg was 0.72 (0.18) in the PAD group and normal in controls. At baseline, risk factors such as diabetes, hypercholesterolaemia, hypertension, active smoking and former smoking were significantly more prevalent in the PAD group. However, protective cardiovascular medication was prescribed to patients with PAD more frequently than to control subjects: antiplatelet drugs 87.4% vs. 32.4% (p<0.001), statins 80.8% vs. 43.7% (p<0.001), angiotensin converting enzyme inhibitors or angiotensin receptor blockers 74.1% vs.

210 510 Effects of primary and secondary prevention 51.3% (p<0.001). During up to 2 years of follow-up, 20 deaths were documented in the PAD group and 7 deaths in the control group, resulting in a Kaplan-Meier 2-year survival estimate of 97.5% (95%, CI %) in patients with PAD vs. 99.1% (95% CI %) in control subjects, p= A total of 108 revascularization procedures, predominantly on the lower extremities, were performed per 950 patient years at risk in the PAD group vs. 3 revascularization procedures on the coronary or carotid arteries per 878 patient years at risk in the control group, p< Conclusions: The diagnosis of PAD still implied a more than doubled risk of death and increased risk of non-fatal cardiovascular events compared to ageand sex-matched subjects without PAD. However, treatment according to the European guidelines on cardiovascular disease prevention resulted in low absolute mortality and morbidity. P3119 Use of national intervention coronary registry data as evaluation tools for cardiovascular prevention strategies and treatment in developing countries G. Saade, A. Sarkis, G. Ghanem, J. Haddad, S. Dada, C. Abdallah, G. Kiwan, M. Tabbal, W. Chalak, F. Farhat on behalf of LICOR group. Lebanese Society of Cardiology, Beirut, Lebanon Purpose: Since 2004, the interventional working group of the lebanese society of cardiology has established the Lebanese Intervention Coronary angiography Registry (LICOR) to collect and analyze data from centers that undertake catheterization procedures. The level of information obtained provides, on the one hand, knowledge of the situation in Lebanon and, on the other, how it relates to international guidelines. However, data assessing long-term outcomes and followup are lacking. Methods: Software has been developed specially adapted to the needs of the proposed registry, and installed in 40 centers around the country. Defects and confusing items were recorded through continued communication between LICOR technicians and their correspondents in reporting centers. Data were collected monthly electronically by or by soft copy. Results: In 2004 a total of angiography procedures and 5653 angioplasties were performed with the ratio of 3.65/1. In 2007 a total of angiography procedures and 6869 angioplasties were performed. From these data, the estimated incidence in 2007 was 6612 angiographies and 1832 angioplasties per million inhabitants. Stents were used in 95.5% of coronary interventions. However, only 30% of these stents were drug-eluting (DES). Glycoprotein IIB/IIIA inhibitors were used in only 5% of angioplasty procedures. These findings indicate that Lebanon has one of the highest reported per capita rates of coronary invasive procedures in the world with approximately a 17% increase of angiographies and angioplasties from 2004 to During similar period, data from the United States Hospitals Discharge Survey has reported approximately 16% decrease of cardiac catheterization. This high increase of interventions reported from 2004 to 2007 in Lebanon may be attributed to three factors: a surplus of catheterization facilities, the wide case-based reimbursement of coronary angiography, and more probably the increase of the incidence of ischemic heart disease in developing countries. Data from LICOR showed huge under use of DES and GPIIB-IIIA inhibitors as compared to clinical guidelines and registries from developed countries. Conclusions: Data from national intervention coronary registry could be used as evaluation tools for cardiovascular prevention strategies and treatment especially in developing countries. However, long term outcomes follow-up after percutaneous coronary intervention is indispensable to evaluate the cost-effectiveness of medical practice in comparison to international guidelines, and stimulate research in order to develop national guidelines. P3120 Classical risk factors in secondary prevention results from the atherogene study C.R. Sinning 1, S. Blankenberg 1, R. Schnabel 1, E. Lubos 1, P.S. Wild 1,T.Keller 1, T. Zeller 1, K.J. Lackner 1, T. Muenzel 1, C. Bickel 2 on behalf of AtheroGene. 1 Johannes Gutenberg Universitaet, Mainz, Germany; 2 Federal Armed Forces Central Hospital, Koblenz, Germany Introduction: Classical risk factors like arterial hypertension, smoking status, diabetes mellitus, LDL/HDL ratio and positive family history for ischemic heart disease are used in cardiovascular medicine for risk stratification of patients in the primary prevention setting. Still a matter of ongoing cliniclal trials is the question to what extent these classical risk factors influence the risk for a secondary event in patients with established coronary vessel disease or with an acute coronary syndrome (ACS). Methods: In the current analysis, 3275 patients from the AtheroGene-Study were included. The primary endpoint (PE) was death from cardiovascular causes, the secondary end point (SE) death from cardiovascular causes or an non-fatal myocardial infarction (PE=255; SE=438). The mean follow up time was 4.4±2.0 years for the PE and 4.1±2.0 for the SE. Results: In univariate analysis by Kaplan-Meier curves analysed with the logrank test, patients with either diabetes mellitus, current smoking or an increased LDL/HDL ratio >4 showed a higher event rate (P value in all three <0.01; log-rank test). Multivariate Analysis with a Cox proportional hazard regression revealed in the fully adjusted model that diabetes mellitus had a hazard ratio (HR) of 1.87 (95% CI: 1,42 2,46), P value <0.01, current smoking HR:1,64 (95% CI: 1,26 2,13), P value <0.01 and LDL/HDL-ratio HR:1,38 (1,01 1,90), P=0.04. These results were augmented by binary logistic regression analysis adjusted for the same confounders regarding PE and SE after 3 and 5 years of follow-up, showing the same significant results for all three factors. For the incidence of the PE and SE, the area under the ROC curve was calculated; here also diabetes had the largest AUC as single factor (PE=0.579, P value < and SE=0.555, P value <0.0005). The combined AUC of all five classical risk factor showed the best prediction of PE (AUC=0.636, P value <0.0005) or SE (AUC=0.612, P value <0.0005). After ROC curve analysis, diabetes mellitus was inferior to the combined approach after 3 years in a ROC curve comparison, but after five years, the combined classical risk factor score was not superior to diabetes mellitus alone. Conclusion: Classical risk factors sustain a major role in prediction of secondary events after treatment for stable angina or even acute coronary syndrome. The most predictive factor was diabetes mellitus followed by current smoking. Further efforts have to be undertaken to reduce the risk by a reduction of classical risk factors in combination with standard medical therapy. P3121 Case method assisted implementation of guidelines decreases mortality, a ten-year follow up of a randomized controlled study A. Kiessling, P. Henriksson. Danderyd Hospital - Karolinska Institute, Stockholm, Sweden Aim: The aim was to determine the size of any patient survival benefit from the interactive pedagogic method case method learning (CML) to facilitate implementation of guidelines in primary care. Material and methods: Prospective randomized controlled trial in clinical practice in the Stockholm area, Sweden. New guidelines for secondary prevention in coronary artery disease (CAD) were mailed to all general practitioners (GPs) in the area and presented at a common lecture in The GPs were clustered according to their Primary Health Care Center (PHC) into two well-matched pairs and randomly allocated to active intervention with CML or usual care. GPs in the intervention group participated in recurrent CML dialogues at their PHCs during a two-year period. A locally well-known cardiologist served as facilitator. Consecutive patients (n=255) with CAD were included. Ten-year mortality rates were obtained from the Cause of Death register and were assessed as all cause and cardiovascular mortality. Results: The two PHC groups of patients respectively physicians were well matched and did not differ at baseline. Attendance rate at the seminars was >82%. 19 (44%) of the included patient in the control group had deceased after ten years as compared to 10 (22%) in the intervention group (p=0.0174; log rank test). The inclusion of the covariates age, sex, hypertension, smoking and diabetes did not change its significance. Patients treated by a specialist deceased at a rate comparable to the intervention group (23%). Cardiovascular mortality was 32% in the control group and 16% in the intervention group (p=0.007). Conclusions: CML for general practitioners improved survival in patients with CAD. The hazard ratio (HR) between intervention and usual care is 0.45 (95% CI ) if case method learning is used to assist implementation of evidence based care. P3122 The benefits of statin therapy in patients without cardiovascular disease: meta-analysis of randomized controlled trials J.J. Brugts 1, T. Yetgin 1, S.E. Hoeks 1,A.M.Gotto 2, J. Shepherd 3, R.H. Knopp 4, H. Nakamura 5,P.Ridker 6, R. Van Domburg 1, J.W. Deckers 1. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Weill Medical College of Cornell University, New York, United States of America; 3 University of Glasgow, Glasgow, United Kingdom; 4 Department of Medicine & Northwest Lipid Research Clinic, Washington, United States of America; 5 Mitsukoshi Health and Welfare Foundation, Tokyo, Japan; 6 Brigham and Women s Hospital, Boston, United States of America Purpose: The benefits of statin treatment in patients with established cardiovascular disease (CVD), i.e. secondary prevention, have been clearly demonstrated. Whether these benefits can be extrapolated to a primary prevention setting is still unclear. Our aim was to clarify the role of statins in subjects without established CVD, and to study whether the effects are similar in men and women, in young and elderly (>65 years), and in subjects with diabetes mellitus. Methods: We performed a meta-analysis of randomized trials with statins according to the QUOROM-guidelines and searched databases to identify relevant studies. We included randomized clinical trials investigating the clinical effects of statin use versus placebo/control group with a follow-up of at least one year, with at least 80% or more participants without established CVD, with outcome data on mortality and major CVD events. We identified ten trials that together enrolled 70,388 patients, of whom 23,681 (34%) were women and 16,078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Summary odds ratios were calculated using random effects models. Results: Statin therapy significantly reduced all-cause mortality (OR 0.88; 95% CI, ), major coronary events (OR 0.70; 95% CI, ), and ma-

211 Effects of primary and secondary prevention 511 jor cerebrovascular events (OR 0.81; 95% CI ). No evidence of an increased risk of cancer was observed. There was no heterogeneity of the treatment effect in clinical subgroups. OR plots all-cause mortality Conclusion: In patients without established CVD but with risk factors, statin use is associated with significantly improved survival and large reductions in the risk major cardiovascular events. P3123 Individualized stepped care prevention based on voluntary risk profiling; a promising approach to battle the chronic disease burden B.E. Colkesen 1,B.S.Ferket 1, M.R. Hoppener 1, J.J. Mathijssen 1, R.J.G. Peters 2,C.K.VanKalken 1, R.A. Kraaijenhagen 1 on behalf of NDDO Institute for Early Diagnostics and Prevention (NIPED), Amsterdam, the Netherlands. 1 NDDO Institute for Early Diagnostics and Prevention (NIPED), Amsterdam, the Netherlands., Amsterdam, Netherlands; 2 Academic Medical Center, Amsterdam, Netherlands Current risk profiling in primary care is mainly restricted to high risk case finding triggered by obvious risk factors, i.e. age above 50, obesity, heavy smoking or positive family history. Although at individual level this approach seems logical it incorporates the risk that in seemingly healthy individuals relevant risk factors will be missed. A voluntary risk profiling approach could reduce this problem and can diminish the prevention paradox, a major drawback of the high risk approach, if integrated risk profiling has a stimulating effect on health improvement. In recent years, NIPED developed an evidence-based health management approach according to the WHO chronic care model. The central theme in this approach is a periodic integrated risk profiling for major chronic disorders (including cardiovascular (CV) diseases, diabetes, kidney disease and common mental disorders) with use of a patented knowledge- and decision support system, the PreventionCompass (PC). Based on the participants risk and personality profile, the PC defines an individually tailored stepped care health maintenance program. The program is designed to optimize empowerment, self management and shared decision making. From the program was piloted in large corporations and a pension fund in the Netherlands. In this period 4821 participants (59% man, mean age 48) underwent integrated health risk assessment including a web-based questionnaire (medical & family history, lifestyle, motivation, personality), biometrics (blood pressure, BMI, waist) and lab. testing (blood, urine). Regarding CV risk it was shown that blood pressure (2 measurements) was increased in 38% of participants (>140/90 mmhg) and 20% exhibited increased cholesterol levels (TC >6.5 mmol/l). Kidney function showed abnormal lab. results in 6% (4% MDRD <60 ml/min, 3% albuminuria). (Pre)diabetes de novo was shown in 1.2% (HbA1c >6.1%). According to the ESC guidelines preventive treatment was indicated in 12% months after participation more than 60% had undertaken actions to improve their health. Of the participants receiving lifestyle advice according to the guidelines, more than 70% improved diet, 53% increased physical activity, 40% took action to reduce stress, 25% decreased alcohol consumption and 9% stopped smoking. Results from this pilot study indicate that with a voluntary risk profiling strategy a significant number of high risk individuals are detected which would have been missed in a high risk case finding strategy and with use of the PreventionCompass a large percentage of participants is motivated to change their lifestyle. P3124 Cardiovascular screening of potentially sinister cardiac disorders in young apparently healthy individuals: the Northern Ireland experience N. Chandra, C. Edwards, M. Papadakis, J. Rawlins, S. Sharma. King s College Hospital, London, United Kingdom Objectives: The Italian pre-participation cardiovascular screening (PPS) programme has been shown to reduce the incidence of sudden cardiac death (SCD) from hereditary cardiomyopathy and primary electrical disorders in young competitive athletes. There is a paucity of data regarding the potential outcome of screening all young apparently healthy individuals outside the context of organised competitive sport. The aim of this study was to analyse the outcomes of PPS in order to assess the impact on health care services of general population screening. Method: 1039 subjects (mean age 18.1 years; range years; male:female ratio 5:1) were screened with a health questionnaire (HQ) and 12-lead electrocardiography (ECG). The questionnaire related to symptoms suggestive of cardiovascular disease and a family history of premature cardiovascular disease and/or SCD. ECGs were analysed for specific abnormalities as described in the ESC sports cardiology consensus. Individuals suspected to harbour a structural cardiac abnormality based on the findings of the HQ and 12-lead ECG underwent trans-thoracic echocardiography (TTE). Individuals suspected to have a primary electrical disorder were referred for additional Holter monitoring and an exercise stress test. Results: Of the 1039 individuals, 348 (33.5%) expressed one or more symptoms that could be consistent with cardiac disease, 75 (7.2%) had a family history of hereditary cardiomyopathy or SCD and 124 (11.9%) had a 12-lead ECG abnormality warranting further investigation. Following preliminary investigation echocardiography, Holter monitoring and exercise stress testing was necessary in 129 (12.4%), 51 (4.9%) and 49 (4.7%) respectively. A cardiac diagnosis was made in 1.5% of individuals (Wolff-Parkinson-White: n=4, atrial septal defect: n=3, long QT: n=4; minor valvular heart disease: n=7 and atrial fibrillation; n=1). Conclusions: The beneficial effects of the Italian PPS programme in protecting an athlete from SCD should not be undervalued. Extrapolation of this programme to a general young population is associated with a significant number of individuals (5.3%) requiring additional investigations that are associated with a relatively low yield for conditions capable of causing SCD. P3125 Beta-blocker doses in coronary heart disease patients treated in UK primary care E. Setakis 1, G. Kassianos 2,S.Cockle 3, T.P. Van Staa 1,C.Morley 4. 1 GPRD Division, MHRA, London, United Kingdom; 2 Birch Hall Medical Centre, Bracknell, United Kingdom; 3 Servier Laboratories Limited, Slough, United Kingdom; 4 Bradford Royal Infirmary, Bradford, United Kingdom Purpose: To investigate beta-blocker doses: (i) at 12 months after initiation (proportion of target dose), (ii) average daily dose; (iii) proportion of patients being titrated. Methods: Retrospective cohort study (UK General Practice Research Database (GPRD)). Patients were included if they had a 1st ever diagnosis of CHD (angina, heart failure, previous MI) after 1st April 2004 and a 1st ever prescription for a beta-blocker on or after this CHD diagnosis. Patients with hypertrophic (obstructive) cardiomyopathy were excluded. ESC Guidelines or British National Formulary target doses were used. Results: 12,493 patients (68.0% male; mean age 58.0 yrs (s.d yrs)) were included. The proportion of patients receiving target dose at 12 months is shown (Table). In the overall CHD population, the average initiation dose was approximately 33% of the target dose. There was little evidence of up-titration, with the maximum daily dose rising to around 40% of target over time. Differences were observed between the 3 cohorts. For angina patients, 71.5% received no titration, 10.6% were up-titrated, 8.5% were up-titrated but then subsequently down-titrated and 9.5% required down-titration from their starting dose. A similar pattern was observed for previous MI patients (72.2% stable dose, 9.2% up-titration, 9.5% uptitration then subsequent down-titration, 9.1% down-titration from initiation dose). In contrast, heart failure patients started on a lower dose (approximately 20% of target), but there was greater up-titration (22.7% plus 15.0% being up-titrated but requiring a subsequent down-titration. However, more than half (55.6%) received no titration. Dose category versus target at 12 months Dose vs Target Overall CHD Angina Heart Failure Previous MI Low (<50%) 58.8% 57.2% 57.2% 60.7% Intermediate (50-99%) 35.0% 38.2% 26.0% 34.0% High ( 100%) 6.2% 4.6% 16.8% 5.3% Conclusions: The majority of CHD patients treated in UK primary care receive sub-optimal doses of beta-blockers. This may be due to practical or tolerability issues. Heart failure patients are more likely to be up-titrated than angina or previous MI patients, probably due to the associated protocols and existence of specialist heart failure nurses in the UK. Heart rate data is currently being assessed, but is not generally well recorded in primary care. P3126 Determinants of physical inactivity among men and women from Greece; a 5-year follow-up of the ATTICA Study C. Chrysohoou 1, D. Panagiotakos 2,C.Pitsavos 2, J. Skoumas 1, J. Lentzas 1, A. Zeibekis 1, L. Papadimitriou 1, C. Masoura 1, I. Papaioannou 1, C. Stefanadis 1. 1 University of Athens, Athens, Greece; 2 Harokopio University, Athens, Greece Objective: Physical inactivity has been recognised as a risk factor for cardiovas-

212 512 Effects of primary and secondary prevention cular disease. The aim of this study was to evaluate factors that are associated with physical activity changes among adults within a 5-year period. Methods: From May 2001 to December 2002 we randomly enrolled 1514 men and 1528 women, without any evidence of cardiovascular or any other chronic disease. The sampling was stratified by the age gender distribution of the greater area of Athens. Weekly energy expenditure assessed by considering frequency, duration and intensity of sports-related physical activity. During 2006, the 5-year follow-up was performed in 1955 participants, which included, among others, current physical activity status. Results: 587 (61%) men and 673 (68%) women were classified as physically inactive at baseline, whereas 661 (69%) men and 728 (73%) women were classified as physically inactive at follow-up; thus, a 13% increase in physical inactivity rate was observed in men and a 7% in women during the follow-up period (p<0.01). Multivariate analysis revealed that male sex, non-smoking, healthy eating, better self-reported quality-of-life and lower prevalence of hypercholesterolemia and incidence of cardiovascular disease were the characteristics of people that remained physically active; advanced age, anxiety and depression, increased body mass, and low quality-of-life, were the baseline predictors of physical inactivity among initially active participants, which also had the higher incidence of cardiovascular disease. Conclusions: Gender, aging, psychological disorders, body mass, smoking, dietary habits, perceived health status and quality-of-life were the most important discriminating factors of physical activity changes. Results: Overall 658 pts (477men, mean age 59.9±10.3years) with confirmed CAD were enrolled. 325pts received active vaccine, and 333 pts placebo. Median follow-up was 298 (IQR ) days. The CIE estimated 12-month cumulative event rate was 6.02% in vaccinated, versus 9.97% in placebo pts, log rank p<0.05). Results of the subgroup analysis are presented in the figure. P3127 Long term results of optimal medical therapy with or without cardiac rehabilitation after an acute coronary syndrome M. Lafitte 1, X. Pillois 2, T. Couffinhal 1. 1 Hopital Haut Leveque and Bordeaux Victor Segalen University, Pessac, France; 2 INSERM U828, Pessac, France Background: In patients after acute coronary syndrome (ACS), it remains unclear whether cardiac rehabilitation (CR) associated with optimal medical therapy OMT (intensive pharmacologic therapy and lifestyle intervention) is superior to optimal medical therapy alone in reducing cardiovascular (CV) risks and events. Aim: To compare long term risk profile and prognosis of post ACS patients receiving OMT plus CR to OMT alone Methods: An observational survey was carried out in , in 902 consecutive patients admitted for ACS and alive at discharge. Patients were offered an initiation to secondary protection measures before hospital discharge and a 2 days hospital program 3 months after the ACS with or without CR. The program focused on global management of coronary patients through complete evaluation of risk factors, atherosclerosis burden, diet and therapeutic education combined with improved drug prescription. Primary endpoints were CV risk factors control and CV events at 2 years. Results: Of the 902 patients included in the study, 239 (26.4%) underwent cardiac rehabilitation (CR). At 3 month evaluation after ACS, the only differences in patient characteristics between the CR and non-cr groups were, respectively, gender (82% male vs 68%; P <0.001), age (54±12 vs 60±12; P <0.001), HbA1c (5,8±0,8 vs 6,1±1,0; P <0.01), systolic blood pressure (115±14 vs 120±17; P <0.001) and moderate to vigorous physical activity (54% vs 34%; P <0.001). ACS parameters, treatment, ejection fraction, atherosclerosis burden, dyslipidemia, inflammatory markers, BMI and smoking habit were similar in the two groups. At 2 years follow-up assessment, CR patients had a lower rate of HbA1c (5,7±0,6 vs 6,1±1,1; P <0.05), systolic blood pressure (127±13 vs 130±11; P <0.05), and better moderate to vigorous physical activity (71% vs 58%; P <0.02). Other risk factors were similar. There was no difference in term of CV events between the 2 groups at 2 years follow-up (Total CV events in 11.6% of OMT group and 11.7% in OMT+CR group; P=0.96). Conclusions: OMT including therapeutic education is as effective as OMT plus CR on secondary prevention goals achievement except for long term physical activity. In patients with optimized secondary prevention, CR does not improve clinical outcomes at 2 years after an ACS. P3128 Influenza vaccination as a secondary prevention for coronary artery disease. A subgroup analysis of the FLUCAD study A. Ciszewski 1, Z.T. Bilinska 1,M.Kruk 1,C.Kepka 1, L.B. Brydak 2, M. Romanowska 2, E. Ksiezycka 1, W. Piotrowski 1,A.Witkowski 1, W. Ruzyllo 1. 1 Institute of Cardiology, Warsaw, Poland; 2 National Influenza Center, Warsaw, Poland Purpose: FLUCAD study showed that influenza vaccination reduces Coronary Ischemic Events (CIE) in patients (pts) with coronary artery disease (CAD). The aim of this analysis was to evaluate the effect of influenza vaccination on CIE in subgroups of pts enrolled into the FLUCAD study. Methods: Single center, randomized 1:1, double-blind, placebo controlled study. A composite study end-point Coronary Ischemic Event comprised: cardiovascular death, myocardial infarction, coronary revascularization or hospitalization for coronary ischemia. We used a Cox proportional-hazards regression model with covariates of interest, and their interactions with the study intervention. Conclusion: Influenza vaccination reduced the incidence of Coronary Ischemic Events among the patients with CAD who were: younger, non-diabetic, after primary PCI, had good left ventricular and renal function. For other subgroups the effect was insignificant, and for none of the analyzed subgroups influenza vaccination was harmful. P3129 A multidisciplinary prevention program improves the outcome in non-diabetic patients undergoing percutaneous coronary intervention J.M. Vegas Valle 1,J.M.DeLaHera 2,J.M.Garcia-Ruiz 2, E. Henandez-Martin 2,J.Bayon 2, F. Torres 2, E. Delgado 2, P. Avanzas 2, I. Lozano 2. 1 Hospital Clinico Universitario de Valladolid, Valladolid, Spain; 2 Hospital Universitario Central de Asturias, Oviedo, Spain Background: Diabetes Mellitus (DM) is associated with a worse outcome after percutaneous coronary intervention (PCI). A sizeable number of patients undergoing PCI have abnormal glucose regulation (AGR) i.e. occult DM and impaired glucose tolerance (IGT). A more rational therapy may improve the outcome in these patients without known DM. Objective: To asses the impact of a multidisciplinary intervention program (cardiology, endocrinology and education for health) in the outcome of non-dm patients undergoing PCI. Methods: In a prospective study, an oral 75-gr glucose tolerance test was performed 15 days after hospital discharge in 330 consecutive patients without diagnosed DM and undergoing PCI. Patients were randomized: 103 (treatment/intervention) were enrolled in a specific secondary prevention program and 227 (control) underwent his/her cardiologist habitual therapy. An end-point of mayor adverse cardiac event (MACE) including death, myocardial infarction, need for new revascularization and in-hospital admission due to an ACS were established. We analyzed clinical, analytical, angiographyc and treatment variables. A multivariate Cox-regression model and Kaplan-Meier test were carried out for end-point survival analysis. Results: A total of 314 patients (95%) completed the follow-up, median 14 months. Age 66 years, men 80%. 77 patients (23%) were diagnosed with newly detected DM and 140 (42%) had IGT. There were no differences in baseline characteristics between groups. Intervention patients had better risk and treatment profile after 15-months follow up: blood systolic pressure 127 mmhg (IR 24) vs 135 (RI 30) p<0,001, LDL cholesterol 78,5 mg/dl (IR 31) vs 88 (IR 42) p=0,05, statins therapy 98,2% vs 82%, p=0,003, ACE inhibitors 78,6% vs 37,8% p<0,001. Treatment group shown better metabolic control (glycosylated hemoglobin A1c 4,9 vs 4,7, p=0,024) and inflammation status (high-sensitivity C-reactive protein 0,42 vs 0,17 p=0,029). Mace: 8,7% (treatment) vs 18,1% (control), multivariate Cox-regression OR 0,36 (CI 95% 0,15-0,86, p=0,02. Log-rank test p=0,038. Absolute risk reduction (ARR) 10%, relative risk reduction (RRR) 52%, number needed to treat (NNT) 11 patients. Conclusions: Approximately 65% of patients undergoing PCI have abnormal glucose regulation. Patients undergoing a specific program in secondary prevention presented better treatment, risk and metabolic profile and a less rate of mayor adverse cardiac events in a mid-term follow up.

213 Effects of primary and secondary prevention / Regional / Ethnic differences 513 P3130 Antibiotic use and risk of death in patients with myocardial infarction- a nationwide study S. Skott Andersen, M.L. Hansen, M.L. Norgaard, F. Folke, E.L. Fosbol, P. Weeke, G.H. Gislason, L. Kober, C. Torp Pedersen. Gentofte University Hospital, Copenhagen, Denmark Purpose: To examine whether treatment with antibiotics in the setting of gastrointestinal ulceration is associated with increased risk of death in patients with myocardial infarction (MI). Methods: Employing nationwide Danish registries all patients with incident MI from who subsequently claimed prescriptions for dual antibiotic treatment for gastrointestinal ulceration were identified. The antibiotic regimens selected for study were combinations of clarithromycin, amoxicillin and metronidazol. Follow-up was initiated at the time of the MI diagnosis and adjusted for time of onset of antibiotic treatment. The primary endpoint was all cause mortality. Results: individuals were identified with incident MI, 1322 of these claimed prescriptions for the selected antibiotic regimens. Multivariate Cox proportional hazards models adjusted for age, gender and charlson s index of comorbidity, and using the remaining MI population as reference, no increase in the risk of all cause mortality was demonstrated (Table 1). To strengthen the analyses incidence rate ratios were also calculated for each year following diagnosis (Table 1). Table 1. Risk of all-cause mortality in MI patients treated with antibiotics and incidence rate ratios between the groups Time HR [95% CI] P-value IR >30 days 0.71[ ] < year 0.73 [ ] < years 0.77[ ] years 0.75 [ ] years 0.79 [ ] years 0.78 [ ] years 0.67 [ ] Conclusions: In a large unselected cohort of MI patients no increased of risk of death was associated with antibiotic treatment in the setting of gastrointestinal ulceration. Furthermore the absence of risk persisted over time in a follow-up period of six years. more likely to worsen their diet if at baseline they were male, young, smoker, hypertensive, had a low education level, and did not perform physical exercise regularly. Conclusions: Modification of DH is feasible in general practice. Patints characteristics are differently associted with the likelihood of modyign DH. P3132 Racial disparities in survival in patients with pulmonary hypertension S.A. Hart 1,A.Wang 2,J.K.Harrison 2, T. Bashore 2, R.A. Krasuski 1. 1 Cleveland Clinic, Cleveland, United States of America; 2 Duke University Medical Center, Durham, United States of America Background: The U.S. C.D.C. has reported racial differences in pulmonary hypertension (PH) mortality and the gap is widening. The reason for this is unclear. Methods: Demographics, echo data and hemodynamic measurements were collected from 169 consecutive patients with PH referred for vasodilator testing in two large U.S. academic medical centers. The cohort included 134 whites (79%) and 30 blacks (18%). Survival was assessed using the SSDI. Results: No demographic differences were seen between whites and blacks including age (56±15 vs. 51±13 years, p=0.05), sex (72 vs. 83% female, p=0.19) and function class (27/54/19 vs. 41/41/19%, class II/III/IV, p=0.33). Black patients had higher right atrial pressure (13±8 vs. 10±6 mmhg, p=0.02) but similar pulmonary artery (PA) pressure (50±14 vs. 46±15 mmhg, p=0.17), cardiac index (2.5±1.1 vs. 2.7±1.0, p=0.34) and pulmonary vascular resistance (10±8 vs. 9±7 Wood units, p=0.26). PA pressure drop with nitric oxide was also similar (14±11 vs. 15±13%, p=0.78). By echo blacks had larger (p=0.01) and less contractile right ventricles (p=0.02) and more tricuspid regurgitation (p=0.03), though similar right ventricular pressure. Median follow-up time was 2 years and 42 patients died (25%). No differences in drug utilization were noted. Proportional-hazards analysis using known predictors of mortality demonstrated that blacks had significantly worse survival (HR 2.7; 95% CI [ ]). However, when echo measurements were included in the model, the discrepancy disappeared (HR 1.5; 95% CI [ ]). P3131 Predictors of change of dietary habits in cohort of 12,513 patients at high risk of cardiovascular risk followed by 860 Italian general Practitioners: preliminary analysis of the risk & prevention trial M.G. Silletta 1, R. Marchioli 1, F. Avanzini 2, P. Longoni 3, I. Marzona 2, R. Pioggiarella 1, M.C. Roncaglioni 2, M. Scarano 1, G. Tognoni 1, M. Tombesi 4 on behalf of R&P and RIACE Investigators. 1 Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 2 The Mario Negri Institute for Pharmacological Research, Milan, Italy; 3 CoS Consorzio Sanità, Milan, Italy; 4 CSeRMEG Centro Studi e Ricerca in Medicina Generale, Monza, Italy Aims: To assess the modification of dietary habits (DH) after 1-year of intervention by caring GPs, we analyzed the DB of Risk&Prevention (ReP), an ongoing trial aimed at testing the effect of 1 g daily of n-3 PUFA on top of optimization of CV risk management and lifestyle modification in 12,513 outpatients at high CV risk, but without prior MI. Methods: 860 GPs participated in the study. We included in the analysis 10,214 patients with complete information at baseline and at 12 months. DH were assessed with a simple, self-administered frequency questionnaire collecting information on selected food indicators. To build a dietary score (DS), intake of vegetables, fruit, fish, olive oil from one side and of butter and salami on the other side were taken as positive and negative indicators of correct Mediterranean DH at baseline and 12 months. Cox proportional models adjusted for potential confounders were fitted to assess predictors of the likelihood of change of DS by dividing patients into 3 groups according to DS at baseline (DSL: low <7, DSI: intermediate 8-9, DSH: high 10). Results: DS at baseline significantly improved at 1 year (median from 8.9 to 10). Among 5,642 patients with incorrect DH at baseline, those who were dyslipidemic, diabetic, and with positive familiar history for CHD at young age, high education level, and performing physical exercise regularly were more likely to improve their dieat after 1 year. Conversely, the 4,572 patients with correct DS (DSH) were Kaplan-Meier Survival Curves Conclusions: In a cohort of PH patients, blacks, though similar demographically and hemodynamically, had worse survival than whites. This may be explained by worse right heart function suggesting more rapid disease progression or delayed diagnosis in these patients. REGIONAL / ETHNIC DIFFERENCES P3133 Cuba singularity: different environmental and coronary heart disease mortality but similar life expectancy at birth than Spain A. Morales 1, R. Duenas 1, B. Martinez 2, A. Rodriguez 3, G.A. Perez 3, M. Grau 4,R.Elosua 4, J. Marrugat 4, R. Ramos 1,M.Reyes 3. 1 Cardiocenter Ernesto Che Guevara, Santa Clara, Cuba; 2 Hospital Celestino Hernandez Robau, Santa Clara, Cuba; 3 Departament of Epidemiology, Villa Clara, Santa Clara, Cuba; 4 Institut Municipal D investigacio Medica - Imim, Barcelona, Spain Purpose: to compare life expectancy at birth and coronary heart disease (CHD) mortality rates, related burden of disease, risk factors and health systems resources between Cuba and Spain. Methods: We examined the databases of World Health Organization and United Nations. Difference ( 1.2 or 0.8) in Cuba/Spain ratio were considered significant. Results (see table, p. 514): Healthy life expectancy, life expectancy at birth and at age 60 were also very much alike. Population under age 5 and between 15 to 60 years had higher mortality in Cuba. CHD mortality and the cardiovascular/non cardiovascular mortality rates ratio were higher in Cuba. Spanish population had higher prevalence of diabetes, alcohol consumption and obesity. Cuban women were more often sedentary Conclusions: The similarities in life expectancy could be related with the higher number density of doctors in Cuba. Cuban women had higher CHD mortality, which does not parallel their cardiovascular risk factors prevalence.

214 514 Regional / Ethnic differences Abstract P3133 Table 1 Cuba Spain Cuba/ Cuba Spain Cuba/ (M) (M) Spain (W) (W) Spain Coronary heart disease mortality rate , Life expectancy at birth Healthy life expectancy (HALE) at birth Adult mortality rate (15-60 years) Expectancy at 60 years * Tobacco (%) 43 36, ,3 30,9 0.9 Obesity (%) Systolic blood pressure mean (mmhg) Total cholesterol mean (mmol/l) 5 5, ,1 5,1 1.0 Physical Inactivity (%) ,8 33,1 1.2 Cuba (M&W) Spain (M&W) Cuba/Spain Diabetes (%) 4,7 7,7 0.6 Alcohol consumption (litres per person year) ,26 11, Under age 5 mortality Mortality ratio: Cardio-vascular/Non communicable 0,49 0, Mortality ratio: Cardio-vascular/cancer 1,67 1, Physicians: Density (per 10,000 population) Per capita government expenditure on health M, Men; W, Women. P3134 Heavy alcohol intake coincides with impaired arterial elasticity in hypertensive immigrants of Eastern European countries V. Katsi, I. Skiadas, E. Androulakis, G. Moustakas, G. Souretis, P. Theodoropoulos, C. Stefanadis, I. Kallikazaros. Hippokration General Hospital of Athens, Athens, Greece Purpose: The association between excessive alcohol consumption and increased cardiovascular (CV) risk is robust. Arterial stiffness provides a summary measure of atherosclerotic arterial damage and CV risk. We examined if there is any difference regarding alcohol consumption and arterial stiffness between first generation Eastern European immigrants and native Greeks. Methods: We studied 67 immigrants with newly diagnosed untreated stage I-II essential hypertension (EH), (aged=51.5±15 years, 35 male, office blood pressure (BP)=158/92 mm Hg) coming from Eastern Europe to Greece within the previous two years and 61 EH native inhabitants matched for age, gender, office BP and smoking status. Aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV) by means of a computerized method (Complior SP). Current alcohol intake was assessed by responding to a question on how many alcohol units they consumed during the day (0, < 1, 1-2, 3-5 and >5 units/day). Results: Hypertensive immigrants compared to natives exhibited significantly higher values of c-f PWV (8.4±0.3 vs 7.1±0.5 m/sec, p=0.003). As shown in the following table, a significant greater proportion of immigrants reported excessive alcohol intake compared to natives (18% vs 5%, p= 0.02). In the immigrants group, c-f PWV was positively associated with alcohol intake (r= 0.28, p=0.004). Drinking Habits Between 2 Ethnic Groups Conclusion: Hypertensive immigrants in the setting of similar hemodynamic load are characterized by higher alcohol consumption and increased arterial stiffness compared to autochthonous population. If this unfavourable BP profile contributes to the rather disproportionate CV risk of this frail population, remains to be tested in future larger studies. P3135 A comparison of all coronary angiographies performed in 2008 in two European countries T. Gudnason 1, B. Lagerqvist 2, K. Eyjolfsson 1, T. Nilsson 2, T.F. Jonasson 1, R. Danielsen 1, G.S. Gudnadottir 1, G. Thorgeirsson 1, K. Andersen 1, S. James 2. 1 Landspitali University Hospital, Reykjavik, Iceland; 2 Uppsala Clinical Research Center, Uppsala, Sweden Purpose: To compare all coronary angiographies (CA) performed in 2008 in two European countries, Iceland and Sweden. Methods: In 2008 every CA in both countries was registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) where predefined parameters were registered prospectively and analysed. Results: Registration was 99% complete. The median age was 64 years in Iceland and 66 in Sweden. In Iceland more CA were performed per inhabitants, 574 vs. 411 in Sweden (p<0.001). Differences were found in the following; women were 29% vs. 33%, hypertension 63% vs. 53%, diabetes 14% vs. 19%, smoking 22% vs. 16%, and lipid lowering treatment 64% vs. 53% in Iceland and Sweden, respectively (p< 0.05 for all). The indications for CA differed between the countries and were; stable angina in 34% vs. 23% of cases, unstable angina or non-st elevation myocardial infarction in 30% vs. 38%, and ST elevation myocardial infarction in 9% vs. 16% in Iceland and Sweden, respectively (p<0.001 for all). Normal CA or non significant atherosclerotic lesions were found more often in Iceland 33% vs. 30% (p<0.05) as was left main disease 10% vs. 7% (p<0.001). Triple vessel disease vas more commonly found in Sweden 14% vs. 17% (p<0.01). The proportions in both countries were similar for single vessel (around 27%) and two vessel disease (around 17%). An inconclusive CA result was rare less than 0.3% in both countries. Stenosed CABG grafts were found in 6% of CA in both countries and restenosis after PCI was also found equally often in 6-7% of cases. The femoral approach was used in 99% of CA in Iceland vs. 62% in Sweden (p<0.001). Median radiation time was similar 2:48 and 2:45 min, but more contrast was used in Iceland 90 ml vs. 67 ml. Complications were rare, around 0.5% in the cathlab and around 4% during hospital stay in both countries. The most usual complications were pseudo aneurysms, minor bleedings and allergic reactions. One patient died due to CA in Iceland and 2 in Sweden during Conclusion: This study gives an unselected picture of CA in two countries and as a whole the results are strikingly similar. A number of differences are though observed i.e. in CA rate, indications, and risk factors, while success rate and safety are comparable. Restenosis in these real world, nationwide, all-comers registries seem to be rare 6-7%. Participation in the SCAAR registry is feasible to quality control CA and may shed light on differences between countries or regions. Participation of more European countries in the SCAAR registry might be feasible in the future. P3136 Prevalence of lipid disorders in statin treated patients from Sweden, Norway and Denmark: Results from the Dyslipidemia International Study (DYSIS) K. Korsgaard Thomsen 1, P. Lundman 2, S. Salling 3, G. Journath 4, T. Pedersen 5. 1 Department of Cardiology, Sydvestjysk Sygehus, Esbjerg, Denmark; 2 Danderyd Hospital - Karolinska Institute, Stockholm, Sweden; 3 Merck Sharp & Dohme, Glostrup, Denmark; 4 Merck Sharp & Dohme AB, Sollentuna, Sweden; 5 Preventive Medicine Clinic, Ulleval University Hospital, Oslo, Norway Background: Treatment of lipid abnormalities is a focus in Scandinavia, particularly on low density lipoprotein cholesterol (LDL-C), but also on high density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Sweden, Norway and Denmark use the same guidelines for treating lipid abnormalities and have the same lipid modifying drugs. Objective: To study the prevalence of dyslipidemia in statin-treated patients in Scandinavia. Methods: This cross-sectional survey in Scandinavia was part of a 2008 pan- European and Canadian study. Included were 958, 956 and 933, respectively, statin-treated patients 45 year or older seen consecutively in clinic. Patients had used statins for at least 3 months. ESC-Guidelines classified patient risk and defined lipid treatment goals/normal levels. Results: In Sweden 59% were male, the average age was 66 - males and 69 - females. In Norway 57% were male, the average age was 65 - males and 68 - females. In Denmark 56% were male, the average age was 66 - males and 68 - females. Table 1. Dyslipidemia rates by ESC risk categories Patients with CHD or Diabetes Patients or SCORE risk 5% with SCORE risk <5% Men Women Men Women LDL-C not at goal [%] [ 2.5/2.0 mmol/l (high risk); 3.0 mmol/l (low risk)] Sweden (n=804) 35.3/ / Norway (n=847) 40.4/ / Denmark (n=889) 36.0/ / TC not at goal [%] [ 4.5/4.0 mmol/l (high risk); 5 (low risk)] Sweden (n=950) 38.5/ / Norway (n=954) 38.3/ / Denmark (n=911) 37.0/ / Low HDL-C [%] [<1.0 mmol/l (male); <1.2 mmol/l (female)] Sweden (n=818) Norway (n=919) Denmark (n=895) Elevated TG [%] [>1.7 mmol/l] Sweden (n=802) Norway (n=786) Denmark (n=866) Conclusion: A large gap between recommendations and practice in patients at high risk of cardiovascular disease remains. More intensive management of dys-

215 Regional / Ethnic differences 515 lipidemia is warranted. Further investigation into the reasons for the variation in reaching treatment goals between Sweden, Norway and Denmark is necessary to explain the numbers presented in this abstract. P3137 Arterial compliance and angiotensin converting enzyme gene I/D polymorphism with acute high altitude reaction N.L. Sun, L.Y. Wang, Y. Xi. Peking University People s Hospital, Beijing, China, People s Republic of Purpose: Angiotensin-converting-enzyme (ACE) gene and Renin-angiotensinaldosterone system (RAAS) affect arterial-functions (AF) and oxygen-saturation (SaO2). This study aimed to understand correlations of ACE I/D gene polymorphysm, AF and SaO2 of healthy-plain-men traveling to high-altitude, and to evaluate clinical values for managing acute high altitude illness. Methods: We studied 230 healthy men (age 42.82±7.68 year-old), who lived in plain, traveled to 4,500 meters above-sea-level. We measured BP, SaO2, arterial compliance and resistance, and collected blood samples for determining ACEgene types. Statistical analyses of ACE-genes vs. acute high altitude reaction development were performed. Routine BP and hemodynamic values were obtained using DynaPulse 200M-monitor and Pulse-Wave-Analysis (Pulse-Metric-USA). Results: 1) Among the 230 men, 88 have type-ii-gene, 118 have ID-gene and 24 have DD-gene, (38.2%:51.3%:10.4%), which matched Hardy-Weinberg balance. 2) Within 24-hour traveling to high-altitude, men with ID+DD gene had significant (P<0.05) lower systemic-vascular-resistance (SVR) and less SaO2 variation when compared to those with II genes, and men with type-ii gene are less vulnerable to acute high altitude reaction. 3) Logistic analysis showed that SVR is a key factor in development of acute high altitude reaction (F=16.04, P=0.000). Conclusions: In this study, we found SVR, ACE genes and SaO2 were essential factors associated to acute high altitude reaction. Routine BP and hemodynamic monitoring for people traveling to high-altitude would be valuable in early warning of acute high altitude reaction. P3138 Why better risk factors profile but more cardiovascular mortality in Romania compared with Poland? M. Doborobantu 1, P. Bandosz 2,E.Badila 1,T.Zdrojewski 2, S. Ghiorghe 1. 1 Emergency Hospital of Bucharest/Spitalul Clinic de Urgenta Bucuresti (Floreasca), Bucharest, Romania; 2 Medical University of Gdansk, Gdansk, Poland Cardiovascular diseases are the main cause of death in Europe, accounting for 49% of all deaths and 30% of all premature deaths before the age 65. One in 8 of all men (12%) and one in 20 of all women (5%) die from CVD before the age of 65. Purpose of our study was to compare the risk factors profile between two adult WHO standard populations from two European high-risk countries and to try to explain the existent differences in the incidence of CV fatal events. Methods: In 2005, a survey of CV risk factors SEPHAR - was performed in Romania, conducted after the same protocol as the NATPOL III PLUS study in Poland (2002), in order to compare the CV risk from the two countries Romanian subjects and 2334 Polish subjects were included. The data of this present study are referred to WHO standard population (age yrs); the statistical analysis was performed on 1286 Romanian and 1936 Polish adults, representative numbers for both populations. Results: see table. Risk factors in the yrs age group Parameter Romania Poland p BMI% 26±6.2% 25.6±4.8% ns Total cholesterol mg/dl 188± ± Fasting glucose mg/dl 91.1± ± Mean SBP mmhg 131.3± ±20.6 ns Prevalence of HTN% 13.9% 23.3% 0.01 Newly diagnosed HTN% 69.7% 29.2% 0.01 Controlled HTN% 3.6% 13.3% 0.01 Metabolic syndrome% (ATPIII) 21% 16.4% 0.01 Mean values of SCORE 2.8± ±4.9 ns SCORE risk 5% 10.9% 14.7% 0.01 BMI - body mass index; SBP - systolic blood pressure; HTN - hypertension. Conclusions: Despite of better risk factor profile, the mortality from CVD is higher in Romania than in Poland (208 deaths per 100,000 from CHD and stroke in Romania and 118 deaths per 100,000 in Poland, European CV disease statistics). These differences may be explained by a higher prevalence of newly diagnosed hypertension in Romania, a very poor control of this major CV risk factor and maybe a higher value of fasting glucose. However, the most likely explanation seems to be the difference in health care costs and the amount spent on health care for people with CVD in the two countries. P3139 Abdominal obesity, hypertension and cardiovascular disease in Poland compared to North-West Europe Region: insights from IDEA study M. Chrostowska 1, A. Szyndler 1, R. Szczech 1,J.Wolf 1,P.Paczwa 2, K. Narkiewicz 1. 1 Medical University of Gdansk, Gdansk, Poland; 2 Sanofi Aventis, Warszawa, Poland The aims of this study were: to (1) compare the prevalence of abdominal obesity (AO), hypertension (HT) and cardiovascular disease (CVD) in Poland and in North-West Europe Region (Austria, Belgium, Denmark, Finland, France, Germany, Ireland, The Netherlands, Norway, Sweden, Switzerland); (2) to assess the relationship of AO, HT and gender with CVD in Polish primary care patients. Methods: The IDEA (International Day for Evaluation of Abdominal Obesity) study was an international cross sectional study including patients in 62 countries. In Poland, 200 randomly selected general practitioners included 5371 consecutive patients, aged 18 to 80 years, 2024 men and 3347 women. Waist circumference (WC) was measured and the presence of known HT, and CVD (defined as coronary heart disease, stroke, or revascularization) were recorded in all patients. AO was diagnosed according to the NCEP criteria (WC >102 for men and >88 cm for women). Results: The mean age of participants was similar in Poland and NW Europe (51.7 years for both locations). The prevalence of AO was higher in Poland than in NW Europe. This difference was more striking for women (54% in Poland vs. 45% in NW Europe; P<0.001) than for men (36 vs. 33% respectively; P<0.01). CVD was more prevalent (28 vs. 11% for females and 33 vs. 19% for males; P<0.001 for both) in Polish patients than in their counterparts from NW Europe. Similarly, the prevalence of HT in Poland was higher than in NW Europe (45 vs. 30% for females and 47 vs. 36% for males respectively; P<0.001 for both). Abdominal obesity, HT and gender were independent predictors for CVD in primary care patients in Poland. CVD was recorded more frequently in men than in women (OR=1.61, 95% C.I ; P<0.001). In multiple logistic model for CVD, AO was significantly associated with CVD (OR=1.50, 95% C.I ; P<0.001). HT was associated with over 3-times higher odds of CVD (OR=3.19, 95% C.I ; P<0.001). The impact of AO and HT on CVD were independent of gender (P>0.1 for interaction). Conclusions: Abdominal obesity, hypertension and CVD in primary care patients are found more frequently in Poland than in NW Europe. High prevalence of abdominal obesity and hypertension in primary care patients might contribute to increased burden of CVD in Poland, and require novel preventive strategies focusing on these risk factors. P3140 Quality of care and outcomes of acute coronary syndromes in aboriginal Australians: data from the CASPA study A. Brown 1,S.Stewart 1,W.Beever 1, T. Weeramanthri 2,B.Currie 3. 1 Baker IDI Heart and Diabetes Institute, Melbourne, Australia; 2 Menzies School of Health Research, Darwin, Australia; 3 Department of Health and Community Services, Darwin, Australia Purpose: Aboriginal Australians remain some of the most disadvantaged individuals in the developed world in respect to premature mortality. The CASPA Study is the first assessment of acute coronary syndrome (ACS)events in Aboriginal people, recording the pattern, quality and outcomes of care across metropolitan and rural/remote settings in the Northern Territory [NT] of Australia. Methods: Performance indicators across the continuum of care for ACS specifically designed for rural, remote and Aboriginal patients recorded the provision of care and outcomes in 235 Aboriginal and 287 non-aboriginal patients admitted to the two major hospitals in the NT in Results: Aboriginal patients were younger (mean age 50±12 vs. 60±12 years: p=0.001), and more likely to have pre-existing diabetes, hypertension, end stage renal failure and chronic kidney disease than non-aboriginal ACS patients. They had significantly longer delay times from onset of symptoms until arrival at emergency service (270 vs. 180 mins, p=0.002). Aboriginal patients were more likely to present with a high-risk ACS (69 vs. 53%, p<0.001 but equally as likely to be treated with evidence based therapies as non-aboriginals: with the exception of Statin therapy (45 vs. 58%, p=0.006). Alternatively, Aboriginal patients were less likely to undergo cardiac procedures (combined angiography/pci or CABG [38 vs. 49%, p=0.017]) or angiography (36 vs. 48%, p=0.012). The greatest difference in procedure rates were in Aboriginal patients suffering high-risk ACS (38% vs. 49%, p=0.023). Aboriginal patients were significantly more likely to have died during follow-up, with the difference becoming apparent by 6 months postdischarge. Aboriginal males were almost 4 times more likely to die (age adjusted HR 3.76; p<0.001), and twice more likely to experience a major coronary event (age-adjusted HR 2.06; p<0.001). Smaller but similar differentials were noted in females. Among those surviving to 30 days after onset of ACS, ethnicity remained an independent predictor of mortality at 3 years (OR 4.8, ; p=0.001) after controlling for demographic, past medical history, clinical features and treatment patterns. Conclusions: Aboriginal patients with ACS surviving to hospital are at elevated risk of death in the ensuing years - despite their younger age. This survival disadvantage appears by 6 months and widens thereafter. Despite some differences in gold-standard procedures, the principle contributors to adverse outcomes are

216 516 Regional / Ethnic differences most likely the elevated burden of chronic disease co-morbidity among Aboriginal patients. P3141 Cardiovascular risk profiles and outcomes of Chinese living in mainland China, Hong Kong/Singapore/Taiwan, Western Europe, and North America: the REACH OCEAN substudy J.F. Chiu 1,A.B.Bell 2,R.H.Herman 3, M.D. Hill 4,J.A.Stewart 5, E.A. Cohen 6,C.S.Liau 7,S.C.Smith 8, P.G. Steg 9,D.L.Bhatt 10 on behalf of The REACH Registry Investigators. 1 University of Alberta, Edmonton, Canada; 2 Humber River Regional Hospital, Toronto, Canada; 3 University of Calgary, Calgary, Canada; 4 University of Calgary Foothills Hospital, Calgary, Canada; 5 sanofi-aventis, Laval, Canada; 6 Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Canada; 7 Buddhist Tzu Chi General Hospital, Taipei, Taiwan; 8 The University of North Carolina at Chapel Hill, Chapel Hill, United States of America; 9 AP-HP Universite Paris 7, Paris, France; 10 VA Boston Healthcare System and Brigham and Women s Hospital, Boston, United States of America Purpose: Assess whether cardiovascular risk differs among Chinese patients living inside and outside mainland China. Methods: 3482 East Asian patients were enrolled in the REACH Registry in mainland China (n=694), Hong Kong/Singapore/Taiwan (n=1943), Western Europe (n=201) and North America (n=644). Baseline demographics, medication use, risk factor control and 30-month cardiovascular outcomes of the 2938 patients with coronary artery, cerebrovascular, or peripheral arterial disease were compared. All values were adjusted for age and sex. Statistical significance was considered as a two-tailed probability of <0.05. Logistic and Cox regression were used to examine differences among regions for baseline and outcome characteristics, respectively. Results: Rates of hypertension, hypercholesterolemia, diabetes mellitus, abdominal obesity and body mass index 25 kg/m 2 were lowest in mainland China, increased in Hong Kong/Singapore/Taiwan, and were highest in Western Europe and North America. Diabetes mellitus prevalence was 23% in mainland China, 2-fold lower than the other regions. Antihypertensive, antidiabetic and antiplatelet agent use was similar in all regions (approximately 99%, 92% and 86%, respectively); lipid-lowering agent use was more common outside Asia (approximately 84% vs 64%). Risk factor control (ie, the percentage of patients at target levels for fasting glucose, blood pressure and total cholesterol) was significantly lower in Western Europe and, except for glucose control, was significantly better in North America. 30-month nonfatal stroke rates were highest in mainland China (5.2%) and fell in a step-wise manner in more westernized societies, with the lowest rate in North America (2.5%; P=0.0003). Conversely, rates of nonfatal myocardial infarction were higher in more westernized societies (3.6% in North America, 2.9% in Western Europe, 2.3% in mainland China and 1.9% in Hong Kong/Singapore/Taiwan). Conclusions: Obesity and other risk factors progressively worsen as patients move from mainland China to Hong Kong/Singapore/Taiwan and Western Europe and North America. Despite similar medication use, risk factor control and cardiovascular outcomes were significantly different. The magnitude of these changes is larger than formerly estimated, suggesting that population differences in cardiovascular risk and disease prevalence likely result more from lifestyle and cultural habits than differences in genetic make-up. P3142 Despite the high incidence of IHD in Asians mortality post PCI for NSTEMI is the same as Caucasians D. Jones, K.S. Rathod, E. Wicks, N. Qureshi, A. Kapur, P.G. Mills, C. Knight, M.T. Rothman, A.D. Timmis, A. Wragg. Barts and The London NHS Trust, London, United Kingdom Background: Asian patients have a high incidence of coronary artery disease (CAD). However the outcome of asian patients after ACS has not been well studied. We assessed the mortality of asians and caucasian patients treated by PCI after NSTEMI. Method: 3525 patients were treated with percutaneous coronary intervention following NSTEMI at a single, London centre between October 2003 and Dec Clinical information was prospectively collected onto a database at the time of the procedure and outcome assessed by all-cause mortality provided by the Office of National Statistics. Results: There were 635 asian and 2890 caucasian patients. 78% of the asians and 71% of caucasians were male. The asians with acute coronary syndromes were younger than caucasians at presentation (59.9±11.2 vs. 64.5±11.3 years, p<0.0001). Asians had significantly increased prevalence of diabetes (48% vs 15%, p<0.0001), dyslipidaemia (p=0.008), hypertension (p=0.003), and history of CAD (p=0.0003) compared to Caucasians. There was no difference in the smoking rates between the two groups. Three vessel CAD was more common in asians than caucasians (12% vs. 7%, p <0.0001). Mortality was the same between the two groups with no significant difference noted from 30 day to 5 year follow-up figure 1 (despite correcting for age using multivariate analysis). Conclusion: Asians with ACS present earlier, have greater risk factor profiles and more extensive angiographic CAD than caucasians. Despite this over a five year follow-up period, the mortality for the two groups was the same. These results Figure 1 suggest that treatment of CAD in asian patients can reduce their risk to that of caucasian patients. This work would suggest that improving the detection of CAD in asian patients could improve mortality further. P years of experience in invasive treatment of acute myocardial infarction with 24-hours on-site cathlab service M. Gasior, Z. Kalarus, M. Gierlotka, A. Lekston, T. Was, P. Chodor, R. Wojnar, M. Swierad, M. Zembala, L. Polonski. Slaskie Centrum Chorob Serca, Zabrze, Poland Current guidelines recommend invasive treatment of ST-segment as well as non- ST-segment myocardial infarction. 20 years ago the main reperfusion treatment was thrombolysis. In our center in hours on-site cath-lab servise for invasive treatment of acute myocardial infarction was opened. We present the data from 20-years experience in the field of invasive treatment of acute myocardial infarction. Results: See table. During 20 years the mean age of patients admitted with acute myocardial infarction raised from 51 to 60 years. In the beginning the rescue PCI was a main king of invasive recanalization of infarct related artery (almost all patients in 80 ties). Nowadays thrombolysis in our region is almost not used. Hospitalization time was shortened from almost 30 days to 6 days in In-hospital mortality lowered of about 50% during the last 20 years from 14% to 8% together with the increase in the rate of PCI procedures in STEMI Mean age, years Thrombolysis before PCI, % <1 % of PCI in STEMI No of PCI in STEMI Stenting rate, % Hospitalization time, days Mortality (Allpts), % Mortality (PCI), % Conclusions: More widespread use of invasive treatment leads to lower mortality in acute myocardial infarction during 20 years of observation. P3144 A comparison of all percutaneous coronary interventions, performed in 2008 in two European countries T. Gudnason 1,S.James 2, K. Eyjolfsson 1,S.Scheving 1, T. Gudjonsson 1,G.Karlsson 1, A.F. Sigurdsson 1, K. Andersen 1, G. Thorgeirsson 1, B. Lagerqvist 2. 1 Landspitali University Hospital, Reykjavik, Iceland; 2 Uppsala Clinical Research Center, Uppsala, Sweden Purpose: To compare all percutaneous coronary interventions (PCI) performed in 2008 in Iceland and Sweden. Methods: Predefined parameters, for all PCI s performed in 2008 in both counties were prospectively registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and then analysed. Results: Registration was complete in more than 99% of cases. The PCI rate per inhabitants was 238 in Iceland and 206 in Sweden (p<0.001). There were younger patients (median 63 years) and proportionally fewer women (22%) in Iceland compared to Sweden (67 years and 28% women). The indications for PCI were stable angina in 34% vs. 25% (p<0.001), unstable angina in 39 vs. 44% (p<0.05), and ST elevation myocardial infarction or cardiac arrest in 22% vs. 27% (p<0.01) in Iceland and Sweden, respectively. The coronary distribution of treated lesions was identical. Hypertensive s were 59% vs. 57% (p=ns), diabetics 14% vs. 20% (p<0.001), smokers 27% vs. 19% (p<0.001), and 67% vs. 54% (p<0.001) were on lipid lowering treatment in Iceland and Sweden, respectively. For PCI s including coronary angiography the median radiation time was 10:40 vs. 10:24 minutes, and median contrast volume 185 vs. 150 ml in Iceland and Sweden, respectively. In both countries the general success rate was 94% and a mean of 1.5 stents were used per procedure. Complete revascularisation was achieved in 59% vs. 60% of cases, stent use was 88% and 90% and drug eluting stent use was 29% vs. 28% in Iceland and Sweden, respectively (p=ns for all). There were no differences in the use of aorta balloon pumps, pacemakers and distal pro-

217 Regional / Ethnic differences 517 tection device. Thrombectomy (3.7% vs. 7.2%), IVUS (1.8% vs. 3.6%) and FFR measurements (0.0% vs. 9.6%) were less frequently used in Iceland compared to Sweden. There were no complications in 96.6% vs. 97.1% of patients in the lab and 88.6% vs. 90.8% in the ward in Iceland and Sweden, respectively (p=ns for both). Mortality due to PCI in the lab was 0% (n=0) vs. 0.1%, and in the ward 0.3% vs. 0.1% in Iceland and Sweden, respectively (p=ns for both). Conclusion: This study compares all PCI s performed in two countries during a year. Success and complication rates and a number of other key parameters are similar in the countries. However, some parameters regarding technique, indications, and risk factors differ between the countries. Participation in the SCAAR registry is feasible to compare and quality control the PCI practice in different countries and an excellent tool to illuminate national or regional variation. Participation of more European countries in the SCAAR registry might be considered. P3145 The Maori population of New Zealand carry a high burden of coronary heart disease S. Mann 1, M. Tobias 2,L.-C.Yeh 2,C.Wright 2, W.C. Chan 3, T. Riddell 3,R.Jackson 3. 1 University of Otago, Wellington, Wellington, New Zealand; 2 Public Health Intelligence, Ministry of Health, Wellington, New Zealand; 3 School of Population Health, University of Auckland, Auckland, New Zealand Aim: We wished to estimate coronary heart disease (CHD) incidence, prevalence, survival, case fatality and mortality specifically for Maori within the context of the New Zealand population. Methods: Incidence included all first CHD hospital admissions and all outof-hospital deaths attributed to CHD where no previous admission had been recorded in the preceding five years. Prevalence, survival and other parameters were derived using multi-state lifetables. We obtained data for the years from the New Zealand Health Information Service and record linkage was carried out using a unique patient identifier, the national health index. Results: Maori had both a higher CHD incidence and higher case fatality than the non-maori population. Maori developed CHD at a younger age (medians 56.5 years for males and 58.8 years for females) than non-maori (medians 67.5 and 77.5 respectively), reflecting both higher age specific risks and a younger population age structure. The lifetime risk of CHD for Maori (36% for males and 34% for females), was only slightly higher than that for the non-maori population (35% and 28% respectively) despite higher Maori CHD incidence. This appears to reflect increased age-specific mortality for non-chd illnesses as well as CHD. Duration of survival with CHD in Maori (9.2 years) was similar to that of the non-maori population for males (9.5 years) but longer for females (11.2 v. 6.2 years), which is most likely related to the earlier age of onset in the Maori population. Conclusions: We have developed internally consistent estimates of CHD incidence, prevalence, survival, case fatality and mortality for Maori in which show higher impact of disease than in the wider population at younger ages. This reflects similar findings for ethnic minority and indigenous populations elsewhere. The inequality identifies areas requiring prioritisation, particularly in primary prevention but also in access for Maori to secondary care services. P3146 Correlates of microalbuminuria in Greek adolescents: Preliminary insights from the Lyceum Leontio Albuminuria (3L) study K. Dimitriadis, C. Tsioufis, D. Syrseloudis, C. Thomopoulos, D. Chatzis, A. Gennadi, E. Taxiarchou, D. Tsiachris, I. Kallikazaros, C. Stefanadis. First Cardiology Clinic, University of Athens,Hippokration Hospital, Athens, Greece Purpose: Microalbuminuria (MA) is a potent marker of cardiovascular risk in adult populations while its role in adolescents remains largely undetermined. The aim of the study was to determine the prevalence of MA in a cohort of Greek adolescents and to investigate the relationships of urinary albumin excretion, expressed as the albumin to creatinine ratio (ACR), with demographic, clinical, dietary and lifestyle characteristics. Methods: A total of 365 adolescents years of age [212 males, aged 13.9 years, office blood pressure (BP)=115/67 mmhg] that were included in the Lyceum Leontio Albuminuria (3L) study were considered for analysis. According to ACR values determined in a morning spot urine, subjects were divided into those with MA (ACR= mg/g in males and ACR= mg/g in females) and those without MA (ACR<22 mg/g in males and ACR<30 in females). For each adolescent a questionnaire was completed that was developed in order to retrieve information on dietary habits (through a semi-quantitative Food Frequency Questionnaire), lifestyle and socio-economic characteristics. Furthermore, adherence to the Mediterranean diet was assessed by the established Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. Results: 49 subjects (13.4%) had MA and when compared to those without MA (n=316) exhibited higher heart rate (88 vs 85 bpm, p=0.039), whereas did not differ regarding age, sex, body mass index, waist circumference, systolic and diastolic BP levels (p=ns for all). Moreover, microalbuminurics compared to normoalbuminurics exhibited no differences in smoking status, hours of studying per day or watching television or engaging in sport activities (p=ns for all). Moreover, the presence of MA was accompanied by a trend towards lower KIDMED score (3.94 vs 4.15, p=0.059). In the total population, ACR was associated with age (r=-0.11, p=0.044), male sex (r=0.160, p=0.003), body mass index (r=-0.131, p=0.016), waist circumference (r=-0.161, p=0.003), systolic BP (r=-0.144, p=0.008), heart rate (r=0.141, p=0.011) and KIDMED score (r=-0.111, p=0.041). By multiple regression analysis it was revealed that only male sex, waist circumference and heart rate were independent predictors of ACR (p<0.05 for all). Conclusions: Among Greek adolescents that participated in the 3L study, MA is not associated with higher BP levels, unfavorable anthropometric, dietary and lifestyle characteristics except for increased heart rate. These findings suggest a role of early sympathetic activation in the pathogenesis of albuminuria and question the prognostic role of MA in this setting. P3147 Increased burden of high blood pressure and related risk factors among participants of World Heart Day in Cameroon D. Lemogoum 1, N. Hamadou 2,J.J.Pik 3, J. Dieuboue 4, W. Ngatchou 1, A. Nana 1, M. Leeman 1, J.P. Degaute 1,P.H.Van De Borne 1 on behalf of none. 1 ULB-ERASME HOSPITAL, Brussels, Belgium; 2 polyclinique du Diamaré, Maroua, Cameroon, Maroua, Cameroon; 3 CENTRE HOSPITALIER CLERMONT D OISE, Clemont Oise, France; 4 AES SONEL, Douala, Cameroon Purpose: Sub-Saharan Africa (SSA) is facing an increase epidemic of cardiovascular diseases (CVD), however, epidemiological data on cardiovascular (CV) risk factors are scarce. To face the challenge, population opportunistic screening of blood pressure (BP) and other CVD risk factors is highly recommended by World Heart Federation (WHF). In that perspective, the Cameroon heart Foundation (CAMEHF) organized a free CV risk factors screening at the occasion of the WHD 2008 and of the Cameroon Heart Awareness Week (CHAW) 2008 in Cameroon. Methods: A total of 560 subjects (mean age: 54 years old) participed between, 22 and 30 september 2008 a community-based, cross sectional study, conducted to determine the burden of hypertension and cardiovascular risk factors among participants of WHD and of the CHAW in Maroua city, Far North Cameroon. A standard questionnaire accessed self reported behavior/life style risk factors, personal history of diabetes and hypertension, familial history of premature CVD, stress, and socio-demographic parameters. BP was measured in duplicate (OM- RON M6). Weight and height, waist circumference, heart rate were measured using standardized methods. Results: Age-adjusted adjusted prevalence of hypertension (HT) (BP>140/90 mmhg, or under antihypertensive treatment) was 25% among all participants and was greater in men than in women (28.5% vs 18.2%, p= 0.02). 54% and 74% of participants reported consuming regularly fruits and vegetables respectively, while 52% were physically active and 12% were heavy alcohol drinkers. The prevalence of obesity, diabetes, smoking, and socio-economic stress was: 14%, 7.1%, 6.4%, and 58%, respectively. The prevalence of HT was 37.14% among obese subjects, 17% in smokers, 83.5% among diabetic patients, 31% among socio-economic stressed participants, 27% in physical inactive subjects. In univariated analysis, the prevalence of HT increases with aging, familial history of premature CVD, divorced/single status, socio-economic stress, and diabetes (all p<0.001). In multiple logistic regression analysis, HT risk increased with socio-economic stress (odds ratio (OR): 6.5 ( ), p<0.001); diabetes status (OR=10.4 ( ), p<0.0001); family history of premature CVD (OR=4.1 ( ), p=0.001), and was lower in female gender (OR=0.4 ( ), p=0.015). Conclusion: This survey reveals an increase burden of HT and associated CV risk factors among participants of the WHD and CHAW 2008 in Cameroon and, underlines the relevance of vulgarisation and implementation of opportunistic BP and CV risk factors screening in SSA settings. P3148 Can one drug fit all? - urban Chinese population has high prevalence of CAD and stroke with unique pattern of risk factors - a study of CCMR D.Y. Hu 1,J.M.Yu 2,Y.H.Sun 1,F.Jian 1,H.Liu 2, J.H. Wang 1, F. Wang 2,H.L.Wang 1, D.Y. Zhang 2 on behalf of CCMR. 1 People s Hospital, Beijing, China, People s Republic of; 2 Fudan University, Shanghai, China, People s Republic of Introduction: Rapid economic development and adverse changes of lifestyle in China have resulted in increasingly high incidence of cardiovascular mortality and morbidity. China Cardiometabolic Registries (CCMR), which includes both community based population surveys and prospectively designed cohort studies in patients with cardiovascular or metabolic diseases, was designed to establish longitudinal database that can provide valid information on disease progression and scientific basis for allocation of health care resources. Objectives: As part of CCMR program, the Capital Community Cholesterol Education and Intervention Program (CCEIP), was conducted to assess the prevalence of cardiovascular diseases, general awareness of risk factors, and outcomes of disease education. Method: The survey was conducted in a 15 million people community in Beijing. Multistage sampling was taken based on geographic region. Participation in the survey was voluntary. The baseline data collection was performed from May 2007 to August Follow up visit is planned in 2 years. Multivariate analysis was performed.

218 518 Regional / Ethnic differences / Psycho-social factors Results: A total of 10,002 individuals participated in the survey, with a mean age of 53 years old (range from 16 to 96). Among them, 36.6% were male, 30.4% were smokers of 10 years or longer, 33.7% had hypertension, 35.8% had dyslipidemia (20% high TC, Tg, or LDL, 15.8% low HDL), 10.1% were overweight (>80kg), 6.8% were diagnosed with type II diabetes, 9.5% had history of coronary artery diseases, and 4.2% had history of ischemic stroke or TIA The prevalence of CAD and stroke were higher in those with metabolic syndrome, almost doubled if also diabetic as shown in the table below. Men were in much higher risk of CAD and stroke than women (17.9% men vs.4.6% women for CAD, p<0.001, 7.0% men vs. 3.6% women for stroke, p < Impact of metabolic syndrome Metabolic Syndrome Metabolic Syndrome with Diabetes p Value (N=2325) (N=357) Ischemic Stroke n, (%) 159 (6.8) 42 (11.8) CAD n, (%) 351 (15.1) 94 (26.3) < CAD - Corornary artery disease. Conclusion: The survey showed that Chinese adult population is no less vulnerable to CAD and ischemic stroke than westerners. The unique pattern of risk factors warrants testing of western developed therapy in Chinese patients and may require modification of regimens in order to achieve the optimal therapeutic outcomes P3149 Population-based study of pediatric sudden death in Taiwan M.H. Wu 1, H.C. Chen 2, J.K. Wang 1, S.C. Huang 3, S.K. Huang 3. 1 National Taiwan University Hospital, Taipei, Taiwan; 2 The Genomics Research Center, Academia Sinica, Taipei, Taiwan; 3 Taiwan Bureau of National Health Insurance, Taipei, Taiwan Objectives: Epidemiological data on pediatric sudden death are scarce and have not been described for Asians. This study sought to estimate the sudden death rate in the population aged 0-18 years in Taiwan, an Asian country. Patients and Methods: Patients who met the criteria listed for sudden death (ICD-9-CM, 798.0, and 798.2) were identified from National Health Insurance databases that contained health care data from >98% population. Results: In this pediatric population of 5.44 million, the neonatal, infant, postneonatal infant and under-5 mortality were 3, 6, 2.81 and 8 per 1000 live births, and the 1-18 years annual mortality was 33/100,000 persons, respectively. There were 1528 SDs (59% male). In the population 1-18 years, annual incidence of SD was 2.7 (95% CI: ), ranging from 0.7 (11-12 years) to 6.1 (1-2 years) per 100,000. Male predominance was noted (3.2 versus 2.2 per 100,000, p=0.0002), particularly significant in groups aged 16, 17 and 18 years. In infants, the incidence was 0.36/1,000 live births (male/female rate ratio, 1.06). The proportionate mortality ratio by SD ranged % (median 8.8%, 8.7±2.2%) and was lowest in group aged 12 years. The proportionate mortality ratio by SD was 1.0% and 11.7% in the neonates or postneonatal infants. Conclusions: The incidence of pediatric SD in Taiwan revealed male prdominace and was within the reported range of Western reports. Age-specific SD incidence indicated a nadir around years. The proportion of mortality accounted by SD was however relatively low, even in the infants. P3150 Prevalence and risk factors for stroke in the primary health care. Insights of the VALSIM study N. Cortez-Dias 1, S. Martins 1,A.Belo 2,M.Fiuza 1. 1 Hospital Santa Maria, Lisbon, Portugal; 2 Portuguese Society of Cardiology, Lisbon, Portugal Background: The incidence and mortality of stroke in Portugal are among the highest in the world, remain unknown causes that justify it. Purpose: To determine the prevalence of stroke and to identify its association with gender, age, body mass index (BMI), waist circumference (WC), metabolic syndrome (MS), hypertension (HT) and diabetes mellitus (DM) in Primary Health Care users. Methods: Cross-sectional study performed in a PHC setting, involving 721 general practitioners (GP) representative of all regions of Portugal. The first two adult patients scheduled for an appointment on a given day were invited to participate, irrespective of the reason for consultation. A questionnaire on sociodemographic, clinical and laboratory data was completed by the GP, WC and BMI were measured and two blood pressure (BP) measurements were obtained after a 5-minute seated rest. DM was defined by fast glycaemia 126mg/dL or antidiabetic agents; HT by previous diagnosis or BP 140/90mmHg; and MS by NCEP-ATP III criteria. Logistic regression multivariate analysis was used to assess the association of age, BMI, WC, MS, HT and DM with the previous occurrence of stroke. Results: The study included 16,856 individuals (58.1±15.1 years; 61.6% women). The prevalence of stroke was 2.1%, higher in men (M: 2.3%; W: 1.9%) and increased with age. The variable most strongly associated with stroke occurrence was age, being 16 times more frequent in individuals aged 80 years than in those aged years. Although the prevalence of stroke was 69% higher in men (OR: 1.69; 95%CI ), male gender ceased to be an independent risk factor when HT, DM and WC were introduced into the model. After correction for these variables, stroke prevalence was higher in women (OR: 1.36; 95%CI ), twice as high in patients with HT, and 83% higher in those with DM. Although occurrence of stroke increased with BMI, WC and MS, these variables were not independent risk factors in the final model. Taking all the relevant variables into account in the model predicting occurrence of stroke, the area under the ROC curve was 0.75 (95%CI ; p<0.001). Conclusions: The prevalence of stroke in PHC users is extremely high. HT is the most potent treatable risk factor associated with stroke, but DM is also relevant in this population. These results highlight the need to implement preventive strategies to improve the management of HT and DM, in order to reduce the high incidence and mortality due to stroke in the Portuguese population. PSYCHO-SOCIAL FACTORS P3151 The influence of stress at work on the risk of developing of cardiovascular diseases in general population years old in Russia (program WHO MONICA-psychosocial) V. Gafarov, E. Gromova, I. Gagulin, Y. Kabanov, A. Gafarova on behalf of Collaborative laboratory of Epidemiology Cardiovascular Diseases SB RAMS. Collaborative laboratory of Epidemiology Cardiovascular Diseases SB RAMS, Novosibirsk, Russian Federation Aim of study: To study the influence of stress at work on the risk of developing arterial hypertension (AH), myocardial infarction (MI), stroke in 10- years. Materials and methods: Within the framework of WHO program MONICA - psychosocial in 1994 random representative sample of men at the age years, residents one of the Novosibirsk (Russia) districts were investigated. A total sample was 657 persons. Stress at work was measured at baseline with the use of the MONICA. During the period all first cases of AH, MI, stroke were investigated in the cohort. Statistical analysis were used software package of SPPS Cox- proportional regression model was used for an estimation of relative risk (RR). Results: The men had higher figures AH with testing stress on the workplace. On average the SAP from mm Hg at the men who are not testing stress at work, rose up to mm Hg at men with the expressed stress at the workplace. On average DAP also it was increased about 86 mm Hg (stress at the workplace is absent) up to 87.3 mm Hg at the expressed stress at work (p < 0.05). Within 5 years the tendency of increase in 2 times (95%CI , p>0.05) RR of development AH, and in 2.8 times (95%CI ,p < 0.05) MI, in 2.6 times (95%CI , p < 0.05) stroke among the men testing stress at work was observed, in comparison with men of not testing stressful situations at the workplace. During 10-years period RR AH in 6.8 times was higher (95% CI , p < 0.01), MI in 2.7 times is higher (95% CI , p < 0.05) and stroke in 4.5 times is higher (95%CI , p < 0.001) among the men testing stressful situations at work, in comparison with at whom stress at the workplace was not observed. Frequency CVD was higher in groups of workers heavy and average physical work, divorced men with stress at work. Conclusion: The received results show that in population of men years old risk CVD was connected to stress at work. Abstract P3149 Table 1. International comparison Taiwan (2000-6) China Japan Korea US UK China HK Infants Mortality* (2006) 2.3 (2003) 3 (2006) 5 (2006) 6.79 (2004) 5 (2006) Sudden death* (1987) 0.26 (2000-1) PNM* (2004) 1.70 Under-5 mortality* (2006) 4 (2006) 5 (2006) 8 (2006) 6 (2006) Newborn mortality* (2006) 2 (2000) 3 (2000) 4.52 (2004) 4 (2000) Population 1-18 yrs Mortality (2004) (1-19 yrs) (40) (2000-6) Sudden death ( ) (1-21 yrs) 3.3 ( ) 1.3 ( ) (1-22 yrs)

219 Psycho-social factors 519 P years influence of stress in the family on the risk of developing of cardiovascular diseases in general population men years old in Russia (program WHO MONICA-psychosocial) V. Gafarov, E. Gromova, I. Gagulin, Y. Kabanov, A. Gafarova on behalf of Collaborative laboratory of Epidemiology Cardiovascular Diseases Siberian Branch of RAMS. Collaborative laboratory of Epidemiology Cardiovascular Diseases SB RAMS, Novosibirsk, Russian Federation Aim of study: To study the influence of stress in the family on the risk of developing arterial hypertension (AH), myocardial infarction (MI), stroke in 10- years. Materials and methods: Within the framework of WHO program MONICA - psychosocial in 1994 random representative sample of men years old, residents one of the Novosibirsk (Russia) districts were investigated. A total sample was 657 persons. Stress in the family was measured at baseline with the use of the MONICA. During the period all first cases of AH, MI, stroke were investigated in the cohort. Statistical analysis were used software package of SPPS Cox- proportional regression model was used for an estimation of relative risk (RR) Results: Men with stress in the family SAP mmhg (p<0.05) it was increased from at moderately expressed stress in family up to 136 mmhg (p<0.05) at the expressed stress. The tendency to increase DAP 87.3 mm Hg up to at moderate stress in family, with the expressed stress DAP up to 86 mm Hg was observed. Within the first 5 years the tendency of increase RR of development AH was higher in 1.61 times (95%CI , p>0.05), by MI in 5.8 times (95%CI , p < 0.001), stroke in 2.5 times (95%CI , p < 0.05) at the men testing high stress in family in comparison with men, marking moderate stress in family was observed. During the 10-years period of supervision of the men testing stress in family, RR AH was higher in 5 times (95%CI , p < 0.05), MI in 4.5 times is higher (95%CI , p < 0.01), stroke in 2.4 times (95%CI , p < 0.05) in comparison with men who were not testing stressful situations in family. Frequency of development CVD was higher among pensioners, working of heavy physical work with high level of stress in family in comparison with men head, engineer technical worker not testing stressful situations in family. Frequency development CVD was higher by divorced men. Conclusion: The received results show that in population of men of years old risk CVD was connected to stress in family. P3153 Relationship between circulating endothelial progenitor cells, vascular dysfunction and depression status in diabetes mellitus subjects H. Chen 1,J.Qiuwaxi 2, C.Y. Wong 2,S.W.Li 3,H.T.Chan 2,S.Tam 4, C.P. Lau 2,H.F.Tse 2. 1 Anzhen Hospital of The Capital Medical University, Beijing, China, People s Republic of; 2 The University of Hong Kong, Hong Kong, China, People s Republic of; 3 Tung Wah Hospital, Hong Kong, China, People s Republic of; 4 Queen Mary Hospital, Hong Kong, China, People s Republic of Purpose: Although the mechanisms remain unclear, depression is associated with endothelial dysfunction and the development of diabetes mellitus (DM). Recent studies suggest that circulating endothelial progenitor cells (EPC) play an important role in endothelial repair and correlate with endothelial function. However, there is no data on the relationship between the level of circulating mature and immature EPCs, vascular function and depression status in patients with DM. Methods: We studied 71 patients with DM (61±10 yrs, 39 men) without prior cardiovascular disease (CVD). All subjects had coronary artery calcium score <10 as assessed by cardiac computed tomography. The numbers of circulating CD34/KDR+EPCs and CD133/KDR+EPCs were determined by flow cytometry, and the depression status was estimated by Depression Anxiety Stress Scales. Carotid mean of the maximum intima-media thickness (mmimt) was measured by high-resolution vascular ultrasound imaging. Results: The median depression score (DS) of the study population was 6 (range 0 to 34). After dividing into different tertile of DS, there were no significant differences in baseline clinical characteristics in subjects in different tertiles of DS (all P>0.05). However, DM patients in the 3rd tertile of DS had a significantly higher percentage of circulating CD133/KDR+EPC (0.52±0.60%) than those DM patients in the 1st tertile (0.19±0.13%, P=0.015) or the 2nd tertile of DS (0.21±0.22%, P=0.044). There was also a significant linear trend of percentage of circulating CD133/KDR+EPC in subjects in different tertiles of DS (P=0.009). Furthermore, there was a significant positive correlation between the percentage of circulating CD133/KDR+EPC with mmimt (r=0.271, P=0.033). Multivariate regression analysis also demonstrated that only old age (OR 1.11, 95%CI: , P=0.005) and a high systolic blood pressure (OR 1.03, 95%CI: , P=0.041) were independent predictors for increased mmimt. However, DS and the percentages of circulating CD34/KDR+EPC and CD133/KDR+EPC did not predict increased mmimt in DM patients (P>0.05). Conclusions: The results of this study demonstrated that in DM patients without significant CVD, a relatively high DS was associated with increased percentage of circulating immature EPC and percentage of circulating immature EPC positively correlated with mmimt. However, the presence of depression status was not associated with mmimt and percentage of mature circulating EPC. P3154 Depressive symptoms and outcomes in patients with heart failure: data from the COACH I. Lesman-Leegte 1, D.J. Van Veldhuisen 1,H.Hillege 1, D. Moser 2, R. Sanderman 1, T. Jaarsma 1. 1 University Medical Center, Groningen, Netherlands; 2 College of Nursing, University of Kentucky, Lexington, United States of America Purpose: Depression is common in heart failure (HF) and has been associated with worse outcomes. It remains unknown whether poorer outcomes are secondary to HF, or to the depression itself. Methods: Patients with mild to advanced HF were enrolled after a hospitalisation for HF. Depressive symptoms were scored at baseline using the Centre for Epidemiological Studies-Depression Scale (CES-D), and patients with a CES-D 16 were considered to have depressive symptoms. Results: We studied 958 patients; 37% female; mean age 71±11 years; New York Heart Association class II (51%) or III/IV (49%). Mean left ventricular ejection fraction (LVEF) was 33±14%, and median B-type natriuretic peptide level (BNP) level was 454 pg/ml (75% CI, pg/ml). The mean CES-D score was 15±10; 377 patients (39%) had depressive symptoms, and 200 (21%) severe depressive symptoms (score 24). During 18 month follow-up, 386 (40%) patients reached the primary endpoint of death or readmission for HF. Increased CES-D score was independently associated with reduced survival or HF readmission (p=0.02). Multivariable Cox regression analyses, adjusted for age, sex, and BNP, showed a 33% higher risk of reaching the primary endpoint for patients with severe depressive symptoms (p=0.05), but not for those with moderate symptoms. Patients with severe depressive symptoms had a higher risk for either HF readmission (HR 1.47, p=0.03), or death (HR 1.43, p=0.04). Conclusions: In patients with HF, severe depression is common and independently associated with poor outcomes. These findings highlight the need for continued exploration of whether improvements in depression lead to better cardiovascular outcomes. P3155 Association of depressive and anxiety symptoms with heart rate variability and C-reactive protein in clinically non-depressed patients with acute coronary syndrome J.A. Hanash 1, B.H. Hanasen 1,M.Birket-Smith 1,O.W.Nielsen 1, A. Rasmussen 2, A. Sajadieh 1, J.F. Hansen 1 on behalf of the DEpression in patients with Coronary ARtery Disease trial. 1 Copenhagen University Hospital, Bispebjerg, Copenhagen, Denmark; 2 Psychiatric Center Rigshospitalet, Copenhagen, Denmark Background: Clinical depression is associated with an increased risk for morbidity and mortality after acute coronary syndrome (ACS). Much less is known about subclinical symptoms of depression and anxiety which are more common than full-blown symptoms. The purpose of this study was to examine the associations between subclinical depressive and anxiety symptoms with markers of the autonomic nervous system and inflammation in non-depressed post-acs patients. Methods: Two hundred forty patients with a recent ACS and no depression were enrolled in the DEpression in patients with Coronary ARtery Disease (DECARD) study. At baseline, these patients were assessed with Hamilton Rating Scale for Depression (Ham-D) and Hamilton Anxiety Rating Scale (Ham-A). Ham-D and Ham-A were dichotomised as high- and low-score groups at cutoff point of 7 and 5, respectively. At the same time 24-h time-domain parameters of heart rate variability (HRV) and high sensitivity C-reactive protein (CRP) were measured. Results: Fortyone patients (17.1%) had scores of >7 on the Ham-D and 54 patients (22.5%) had scores of >5 on the Ham-A. On univariate analysis, Ham-D was associated with younger age, smoking, and lower levels of physical activity. Ham-A was associated with female gender, less alcohol consumption, and higher NYHA and CCS classes. Both Ham-D and Ham-A were associated with lower meannn (mean value of Normal-to-Normal [NN] intervals) and SDANN (standard deviation of the averages of NN intervals in all 5-min segments of the entire recording), and higher CRP. On multivariate logistic regression analyses adjusting for covariates of sociodemography, life style, cardiovascular profile, medication, and comorbidity, Ham-D was significantly associated with reduced physical activity and lower age, while Ham-A was significantly associated with female gender and higher CCS classes. Ham-D was associated to meannn (odds ratios [95% CI] 2.46 [ ], p 0.034), while Ham-A was associated with SDANN (3.58 [ ], p<0.001). Conclusion: We found a significant association of HRV and CRP with depressive and anxiety symptoms among clinically non-depressed survivors of a recent ACS. These results emphasize importance of detecting and managing even minor dysphoric mood changes after ACS.

220 520 Psycho-social factors P3156 Sertraline ameliorates endothelial dysfunction and inflammation in coronary heart disease patients with depression C. Pizzi 1,S.Mancini 2, L. Angeloni 3, F. Fontana 1,G.M.Costa 4. 1 University of Bologna, Bologna, Italy; 2 Universita di Modena e Reggio Emilia, Modena, Italy; 3 Ospedale Maggiore Carlo Alberto Pizzardi, Bologna, Italy; 4 Mario Negri Institute for Pharmacological Research, Bergamo, Italy Purpose: Patients with CHD and depressive symptoms have a worse cardiac outcome compared to patients with CHD only. Impairment of endothelial function and increased inflammation represent the major phato-physiologic mechanisms involved in this association. The effect of antidrepressive therapy on endothelial function and inflammatory status is still ill defined.this study investigated the effect of Sertraline on inflammation and endothelial function in patients with coronary heart disease (CHD) and depression symptoms. Methods: One hundred patients with CHD and depression were randomized to receive, in a double-blind fashion, Sertraline or a placebo 50 mg daily for the first 6 weeks of treatment; the amounts of the Sertraline and Placebo were gradually increased to a maximum dosage (200 mg/daily) between 7 and 12 weeks. We determined depressive symptoms (Beck Depression Inventory, BDI), inflammation markers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and flow endotheliummediated dilation (FMD) before and at 20 weeks after treatment. Results: Sertraline treatment significantly reduced BDI score (12.87±7.43) as compared with baseline (20.85±7.54) and placebo (20.68±10.34). CRP levels decreased as well after 20 weeks of Sertraline treatment, whereas did not significantly change in the placebo group. Accordingly, Patients on Sertraline had a significant improvement in FMD, which remained unchanged in the placebo arm. After therapy, change in BDI was negatively correlated with changes in FMD (r=0.67; p<0.001), and positively with changes in CRP (r= -0.56; p<0.001) and IL- 6 (r=0.54; p<0.001). After 20-week of therapy, a reduction in CRP, and IL-6 were found to correlate with the improvement of FMD (r= -0.56, and 0.6, respectively; all p<0.001). Conclusions: Twenty weeks of therapy with Sertraline improves endothelial function and reduces inflammation markers in patients with CHD and depression symptoms. P3157 Plasma B-type natriuretic peptide and anti-inflammatory cytokine interleukin-10 predict adverse clinical outcome in chronic heart failure patients with depressive symptoms: A one-year follow-up study M. Nikolaou, J.T. Parissis, D. Farmakis, D. Birmpa, V. Bistola, T. Katsoulas, G. Filippatos, D. Kremastinos. Athens University Hospital Attikon, Athens, Greece Objective: To assess the prognostic value of a wide spectrum of neurohormonal and inflammatory markers along with functional status and exercise capacity in chronic heart failure (CHF) patients with depressive symptoms. Methods: A total of 300 consecutive hospitalized CHF patients were screened for depressive symptomatology by the Zung self-rated depression scale (SDS). Patients with depression underwent a clinical, echocardiographic and biochemical evaluation, including New York Heart Association (NYHA) class, 6-min walking test (6MWT), left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP) and plasma inflammatory/anti-inflammatory cytokines and adhesion molecules (IL-6, IL-10, TNF-α, soluble ICAM-1 and VCAM-1). Patients were subsequently followed for up to 1 year for major cardiovascular events (MACE), including death or hospitalization due to cardiovascular causes. Results: From a total of 300 patients, 113 (38%) had a Zung SDS 40 and were considered as having depressive symptoms. One-year event-free survival of patients with depressive symptoms was 19% (mean±se, 150±12 days). In multivariate analysis (including NYHA class, 6MWT, LVEF, BNP, soluble VCAM- 1, IL-6, IL-10, IL-6/IL-10 and TNF-α), only BNP (OR=1.001, p=0.015) and IL-10 (OR=0.864, p=0.015) remained as independent predictors of MACE. Using ROC analysis-derived cut-offs, a BNP value of 290 pg/ml predicted MACE with 86% sensitivity and 69% specificity, while an IL-10 value of 5 pg/ml predicted MACE with 61% sensitivity and 78% specificity. Event-free survival differed significantly between patient with BNP<290 and IL-10>5 pg/ml (261±44 days) and those with BNP>290 and IL-10<5 pg/ml (79±11 days, p=0.0001). Conclusion: High Plasma BNP (as a marker of neurohormonal activation) and low IL-10 (as a marker of defective anti-inflammatory properties) are independently associated with increased adverse clinical outcomes in CHF patients with depressive symptoms. This is a clinically relevant finding that also provides important pathophysiological insights concerning the relationship between heart failure and depression. P3158 Five-year follow-up of quality of life in randomized patients to receive coronary bypass surgery, percutaneous coronary intervention or medical treatment: the medicine angioplasty or surgery study M.E. Takiuti, P. Girardi, C.R.S.R. Nogueira, T. Nakano, E.G. Lima, R.D. Vieira, C.L. Garzillo, N. Lopes, W.A. Hueb, J.A.F. Ramires. Heart Institute of University of Sao Paulo, Sao Paulo, Brazil Background: Although coronary bypass surgery (CABG), percutaneous coronary intervention (PCI) are used for the relief of symptoms and for a better tolerance to exercises, there is no conclusive evidence showing that these methods offer more benefits than the medical treatment (MT) to the quality of life (QoL) in patients with symptomatic coronary artery disease (CAD). This study sought to compare the QoL scores during 5-year in patients with stable multivessel CAD, who underwent one of the 3 therapeutic approaches. Methods: From May 2000 and May 2005 a total of 611 patients were randomly assigned to a CABG (n=203), PCI (n=205) or MT (n=203). Of these patients, 546 (89%) were followed for assessments of QoL and demographic profile questionnaire for a 5-year period. 187 (34%) underwent CABG, 181 (33%) PCI and 178 (33%) underwent MT. The Short Form Health-Related QoL Questionnaire (SF-36) was used to assess the patients, before randomization, six months, and 12months and annually until the end of study. The SF-36 comprises 36 items that can be combined into the following eight multi-item summary scores: physical functioning, vitality, bodily pain, mental heath, social functioning, and role limitation due to physical health, emotional problems and general health perceptions. Results: At baseline, we found no difference relating to overall mortality between three groups. The eight domains of QoL showed improvement in all groups at 6-month follow-up visit compared with the baseline evaluation (p<0.001). Surgical therapy, PCI and MT showed improvements over baseline in most domains of quality of life (p<0.001). The improvements was observed mainly in surgical group and especially in physical role functioning. On the other hand medical therapy group showed fewer changed in their rating of general health. PCI group showed significant superiority over medical group in terms of physical functioning, vitality and general health after randomization. Conclusion: All patients had improvement in QoL detected at 6 months persisting until 60 months. Moreover, CABG patients had better improvement of QoL compared with other groups. Furthermore, the QoL of PCI patients was better than MT patients at the end of follow-up. P3159 Improvement in walking performance affects long-term quality of life in non-vascular peripheral artery patients I.I. De Liefde 1, S.E. Hoeks 2, K.G. Smolderen 3,J.Klein 1, J.J. Bax 4, H.J.M. Verhagen 5,R.T.VanDomburg 2, D. Poldermans 5. 1 Anesthesiology, Erasmus MC, Rotterdam, Netherlands; 2 Cardiology, Erasmus MC, Rotterdam, Netherlands; 3 Medical Psychology, Tilburg University, Tilburg, Netherlands; 4 Cardiology, LUMC, Leiden, Netherlands; 5 Vascular Surgery, Erasmus MC, Rotterdam, Netherlands Purpose: We performed an observational study to assess the effects of walking performance, resting or exercise ankle brachial index (ABI) improvement on quality of life on the long-term in non-surgical and surgical peripheral arterial disease (PAD) patients. Methods: 261 non-surgical and 324 vascular surgical (elective abdominal aortic or lower limb arterial revascularisation) patients performed 2 times a single-stage treadmill walking test to evaluate their PAD. During follow-up 33% died. To all survivors the Dutch version of 36-item Short-Form Health Survey (SF-36) was sent, consisted of 8 sub-domains; physical functioning (PF), role limitation due to physical health (RP), social functioning (SF), role limitations for emotional problems (RE), mental health (MH), vitality (VT), bodily pain (BP), general health (GH), 2 component scores; physical health (PCS) and metal health (MCS). Delta walking distance, resting and exercise ABI consisted of the difference between the first and the second test. All three variables were categorised into 2 groups: stable/improvement or decline. Results: Responders (220) and non-responders were comparable for baseline characteristics. In the non-surgical group walking distance improvement was related with significant higher long-term quality of life on all sub-domains and component scores, except for SF, BP and borderline significance for PF (figure). Improvement in resting or exercise ABI was not associated with long-term quality SF-36 and walking distance improvement

221 Psycho-social factors 521 of life. In the surgical group no significant associations were observed between improvement in walking distance, resting or exercise ABI and long-term quality of life. Conclusion: Improvement in walking distance at single-stage exercise tests is strongly related with quality of life on the long term in non-surgical PAD patients. P3160 Strong association between subclinical atherosclerosis and type of occupation in 3711 high risk European individuals F. Veglia 1,C.C.Tedesco 1, K. Nyyssonen 2,D.Baldassarre 3, M. Amato 1,E.Tremoli 3 on behalf of IMPROVE Study Group. 1 Centro Cardiologico Monzino IRCCS, Milan, Italy; 2 University of Kuopio, Kuopio, Finland; 3 University of Milan, Milan, Italy Purpose: The relation between socio-economical status (SES) and cardiovascular disease has been extensively addressed. We evaluated the association between the main lifelong occupation reported by the participants of the IMPROVE study and their carotid intima-media thickness (c-imt) measurement. Methods: The IMPROVE study recruited 1935 men and 1776 women with 3 or more vascular risk factors from 5 European countries. c-imt was measured by B-mode ultrasound and data about the occupational history were collected by a structured questionnaire. Jobs were ranked into 5 categories in a scale of SES (labourers, housewives, service workers, white collars, professionals). Results: The job scale was highly correlated with education level (r=0.46, P<0.0001) and the categories were associated with different grades of physical activity (P<0.0001). Mean c-imt was strongly associated with job type, exhibiting an inverse relation with SES (Figure 1). This association was highly significant after adjustment for relevant confounders, with a difference of -8.3% from the lowest to the highest job category (P for trend <0.0001). The negative trend was observed in both genders and was independent from education level, diet, alcohol intake and latitude, in addition to conventional risk factors. Of interest, employment in manual jobs, although characterized by a high level of physical activity, was associated with the highest IMT measures. vs 6%, p=0.0003; women: 7% vs 5%, p=0.0012), rarely made regular physical activity (men: 39% of physically inactive persons vs 26%, p<0.0001; women: 44% vs 31%, p<0.0001) and rarely measured their BP (men: 22% of men did not measure BP during last year vs 15%, p<0.0001; women: 15% vs 10%, p=0.0017). The same situation concerned persons with DS. Both men and women with DS more often than those without DS smoked cigarettes (men: 42% vs 37%, p<0.001; women: 26% vs 23%), rarely made regular physical activity (37% of physically inactive men vs 30%, p<0.001; in women: 43% vs 35%, p<0.001), more often drank alcohol more than 3 times a week (men: 4% vs 2%, p<0.05; women: 0.3% vs 0.1%, p=0.003) and more often did not take the prescribed medication, although they bought them (men: 18% vs 12%, p<0.001; women: 22% vs 14%, p<0.0001). Conclusions: Persons with negative psychosocial risk factors had more unhealthy behaviour than those without, so because of still growing population of such persons, it could be the significant limitation of CVD prevention. P3162 Brief depression screening with the PHQ-2 predicts poor prognosis following percutaneous coronary intervention with drug-eluting stenting S. Schmidt Pedersen 1, J. Denollet 1, P. De Jonge 2,C.Simsek 3, P. Serruys 3, R. Van Domburg 3. 1 Tilburg University, Tilburg, Netherlands; 2 University Medical Center, Groningen, Netherlands; 3 Erasmus Medical Center, Rotterdam, Netherlands Depressive symptoms are associated with adverse clinical events in cardiac patients, warranting the availability of brief and valid instruments to identify depressed patients in clinical practice. We examined the prognostic value of the Patient Health Questionnaire (PHQ-2) in percutaneous coronary intervention (PCI) patients at 1-year follow-up. Consecutive PCI patients (N =796; 72.1% men; mean age=62.5±11.5) completed the PHQ-2 at baseline and were followed up for 1- year adverse clinical events (i.e., death and non-fatal myocardial infarction (MI)). At follow-up, 47 patients had experienced an event. In unadjusted analysis, depressive symptoms, using the continuous score of the PHQ-2 and the recommended cut-off 3, were not associated with death/mi (ps>.05). However, the incidence of events was significantly higher in depressed patients using a cut-off 2 (8.8% versus 4.7%; OR: 1.96; 95% CI: ) and remained significant (OR: 1.98; 95% CI: ) in adjusted analysis. In secondary analysis, entering the main effects for depressive symptoms (cut-off 2) and gender, and depressive symptoms by gender, the interaction effect was near significant (OR: 3.77; 95% CI: ). Depressive symptoms were associated with an increased risk of death/mi in men (OR: 2.85; 95% CI: ) but not in women (OR: 0.76; 95% CI: ). These results remained in adjusted analysis. Depression screening with a 2-item scale independently predicted 1-year clinical events. The PHQ-2 is a brief and valid measure that can easily be used post-pci to identify patients at risk for adverse health outcomes. Figure 1 Conclusions: In analogy to what observed for other important pathologies, our results show that the type of job is a strong determinant of subclinical atherosclerosis. This relation is not completely explained neither by differences in conventional risk factors nor by the major life-style or cultural variables (education, smoke, diet and physical activity). P3161 Do negative psychosocial risk factors influence the person s behaviour to more unhealthy? The results of National multicenter health survey (WOBASZ) J. Piwonski 1,A.Piwonska 1, W. Drygas 2, T. Zdrojewski 3, J. Gluszek 4,A.Pajak 5, K. Kozakiewicz 6 on behalf of Wobasz investigators. 1 National Institute of Cardiology, Warsaw, Poland; 2 Medical University, Lodz, Poland; 3 Medical University, Gdansk, Poland; 4 Poznan University of Medical Sciences, Poznan, Poland; 5 Jagiellonian University, Cracow, Poland; 6 Medical University of Silesia, Katowice, Poland Purpose: Negative psychosocial risk factors such as a lack of social support or depression can reflect the behaviour to more unhealthy. We try to assess the unhealthy behaviour of persons with low social support level (SSL) comparing to persons with high SSL and persons with and without depressive symptoms (DS). Methods: The Polish population sample of 6076 men and 6846 women, aged 20-74, was studied in SSL was assessed using Berkman and Syme questionnaire and DS using Beck Depression Scale. Results: Persons with low SSL, both men and women, were in general characterized by more unhealthy behaviour than those with high SSL. Out of 6 analyzed components of unhealthy behaviour, 3 or more were observed in 17% of men with low SSL and 6% of men with high SSL (in women respectively in 16% vs 10%). Persons with low SSL more often smoked cigarettes than those with high SSL (men: 42% vs 35%, p< ; women: 26% vs 22%, p=0.0013), more often drank alcohol more than 3 times a week (men: 3% vs 1%, p<0.0001; women: NS), rarely try to quit smoking (9% of low SSL men had never try to quit smoking P3163 The impact of elevated serum levels of glucose and inflammatory biomarkers on the long term mortality in non-diabetics with acute coronary syndromes S.S. Makrygiannis, M. Zairis, C. Vogiatzidis, C. Ritsatos, S. Karvounaris, A. Benopoulos, C. Garefalakis, N. Patsourakos, C. Katsaros, S.G. Foussas. Tzanio Hospital, Piraeus, Greece Purpose: Serum levels of glucose and inflammatory biomarkers upon presentation seem to confer incremental predictive value for no-diabetics (and diabetics) with acute coronary syndromes. We sought to investigate the possible interrelation of serum levels of glucose and inflammatory biomarkers upon presentation as well as the interaction of all these biomarkers in the prediction of 1-year death in this setting. Methods: 848 STEMI and 666 NSTE-ACS consecutive pts, without history of diabetes, who presented in the first 12 and 24 h of index pain respectively, were studied. Serum glucose levels upon presentation and during hospitalization was 11 mmol/l in all pts. Each cohort was divided into 3 groups according to the serum glucose levels upon presentation: Group A with <6.1 mmol/l, Group B with mmol/l and Group C with 7-11 mmol/l. Serum levels of inflammatory biomarkers including hs-crp, interleukin-6 (IL-6) and fibrinogen (FIB), were measured upon presentation. Results: There was a significant gradual increase of serum levels of all inflammatory biomarkers from Group A to Group C in pts with STEMI and NSTE-ACS. Particularly, serum levels of hs-crp (p<0.001 and p<0.001), IL-6 (p<0.001 and p<0.001) and FIB (p=0.02 και p=0.01) were gradually and significantly increased from Group A to Group C in pts with STEMI and NSTE-ACS. The incidence of 1- year mortality in A, B, and C Groups was 11.2%, 16.2%, 20.4% and 8%, 12.6%, 19.1% for STEMI (p=0.02) and NSTE-ACS (p=0.002) pts respectively. Inflammatory biomarkers were significantly related to the incidence of 1-year mortality in pts with STEMI and NSTE-ACS. Particularly, hs-crp (p<0.001 and p<0.001), IL- 6 (p=0.004 and p=0.008) and FIB (p=0.03 και p=0.02) were significantly related to 1-year death in STEMI and NSTE-ACS pts respectively. By multivariate Cox analysis (in which inflammatory biomarkers were not included), glucose levels upon presentation was an independent predictor of 1-year death (p=0.007 and p<0.001, for STEMI and NSTE-ACS pts respectively). However, by multivariate Cox analysis (in which inflammatory biomarkers were included), glucose levels

222 522 Psycho-social factors upon presentation was not an independent predictor of 1-year death (p=0.5 and p=0.6, for STEMI and NSTE-ACS pts respectively). Conclusions: According to the present results serum glucose levels upon presentation are strongly associated with the degree of inflammatory response in non-diabetics with acute coronary syndromes. This may at least partially explain the association of serum glucose levels upon presentation and adverse outcome in non-diabetics with acute coronary syndromes. P3164 Type D personality and reduced benefit following exercise therapy in peripheral arterial disease K.G.E. Smolderen 1, L.M. Kruidenier 2,J.Denollet 1,S.P.Nicolai 2, P.W. Vriens 3, J.A.W. Teijink 2. 1 Tilburg University, Tilburg, Netherlands; 2 Atrium Medical Center, Heerlen, Netherlands; 3 St. Elisabeth Hospital, Tilburg, Netherlands Background: Supervised exercise therapy in peripheral arterial disease (PAD) improves functional capacity, lower-leg functioning, and possibly prognosis. To identify barriers that compromise the outcome of supervised exercise therapy, we examined the effect of having a Type D personality (tendency to experience psychological distress) on walking ability, benefit finding, and invasive treatment during follow-up. Methods: A total of 218 patients (mean age 65 years ± 10 years) who participated in supervised exercise therapy in an observational registry completed the Type D personality scale (DS14). Medical chart review was completed at baseline and at 52 weeks follow-up. Walking ability (Functional and Absolute Claudication Distance) was assessed at baseline, 4, 12, 26, and 52 weeks follow-up. Results: Adjusting for sex, age, cardiac history, diabetes, and Ankle-Brachial Index, Type D personality was correlated with a shorter Functional Claudication Distance (p<0.01), and a trend was observed for the Absolute Claudication Distance (p=0.071). The time by Type D interaction was not significant, showing that Type D personality exerted a stable adverse effect on walking distance across time. Patients with a Type D personality were more likely to rate exercise therapy as less beneficial (32% vs. 15%, p<0.01) and eventually received more invasive treatment within follow-up (28% vs. 12%, p<0.01) as compared to non-type D patients. Conclusions: The recovery of PAD patients with a Type D personality was less optimal as compared with non-type D patients following supervised exercise therapy. Since Type D personality has been associated with poor prognosis in PAD, this group may need extra support in order to fully benefit from intervention programs. P3165 America Type D personality predicts clinical events after myocardial infarction, above and beyond disease severity and depression E.J. Martens 1,F.Mols 1,M.Burg 2, J. Denollet 1. 1 Tilburg University, Tilburg, Netherlands; 2 Yale University, New Haven, United States of Objective: To investigate the effect of Type D personality (high negative affectivity and social inhibition) on cardiac death and/or recurrent myocardial infarction (MI) in acute MI patients, after adjustment for disease severity and depression. To explore the differential effect of Type D on early ( 6 months) vs. late (>6 months) events, separately. Methods: Patients (n=473) were assessed on demographic and clinical variables and completed the Type D Personality Scale (DS14) within the first week of hospital admission for acute MI; depression severity was assessed with the 17-item Hamilton Depression Scale (HAM-D). The average follow-up period was 1.8 years. Findings: There were 44 events attributable to cardiac death (n=16) or recurrent MI (n=28), with 26 early and 18 late events. Type D patients were at cumulative increased risk of death/recurrent MI compared with non-type D patients (16.3% versus 7.8%;p=0.012). Cardiac history, left ventricular ejection fraction and use of statins were predictors of total and late death/recurrent MI, with statins showing a substantial protective effect. In addition, cardiac history and use of statins were significantly associated with early death/recurrent MI. Type D patients had a 2-fold increased risk of total death/recurrent MI after adjustment for disease severity and depression (HR:2.23;95%CI: ;p=0.019), and a more than 3-fold increased risk of late death/recurrent MI (HR:3.57;95%CI: ;p=0.019). Conclusions: Type D was a strong predictor of adverse cardiac outcome after acute MI, above and beyond disease severity and depression severity, and the associated risk was similar to that of traditional cardiovascular risk factors. Type D may be an important psychosocial factor to assess in post-mi patients for risk stratification purposes. P3166 Psycho-social factors and outcome of very young adults following acute myocardial infarction, a single center experience M. Hammoud, D. Sharif, U. Rosenschein. Bnai Zion Medical Center, Haifa, Israel Background: Acute myocardial infarction is very rare in young adults especially in people under age 35. The psycho-social outcome of very young patients is not well understood and underestimated. Objective: To determine psychosocial factors and social outcome in young patients under age 35 presented with first acute myocardial infarction, (AMI) compared with adults years old age. Methods: Single center registry-based study of 2450 patients admitted with myocardial infarction during a period of 7 years, ( ), 40 patients (1.6%) were younger than 35 years old, all were male, we identified the psychosocial factors and outcome, rehabilitation program, depression and sexual dysfunction following the acute event and return to work rate, data were gathered through a questioners that were completed through personal interview. Data were compared with control group of 110 male patients after acute MI years old age. Results: 40 patients with mean age years, (range 26-35), 21 patients (55%) found working in the high-tech industries. Another 110 male adults with mean age 47±4 years, (range 36-55) formed the control group. Signs of depression were found in 42.5% compared 20% in the control group, (p=0.01). Sexual dysfunction was observed in 42.5% v.s 18% in the control group, (p=0.007).time to return to work after the acute event was (34.9± 16 vs. 59.5±33 days, p=0.0005). The rate of short or long-term involvement in rehabilitation program was 12.5% vs. 40%, p=0.007). Permanent failure to return to work was observed in (37.5% vs. 15.5%, p= 0.01). 12.7% of the patients in the control group had CABG compared with no patients in the young group and the rate of return to work was comparably long, (140± 30 days). Depression was negatively associated with the likelihood of returning to work and with sexual dysfunction rate, (p= ) for both groups. Conclusion: AMI is rare in very young patients. We observed a high rate of depression and sexual dysfunction with a low rate of employment in rehabilitation programs and return to work among very young patients following AMI. Early recognition and treatment of depression and sexual dysfunction among very young patients is an important indicator of positive psycho-social recovery. P3167 Quality of life and depressive symptoms in an outpatient population with heart failure B. Gonzalez, L. Cano, R. Cabanes, F. Pons, C. Diez, A. Urrutia, S. Altimir, R. Coll, T. Pascual, J. Lupon. Hospital Universitario Germans Trias I Pujol, Badalona, Spain Background: The presence of depressive symptoms (DS) is quite frequent in patients (P) with heart failure (HF) and can influence their level of quality of life (QOL). An important objective of HF Units should be the improvement in QOL of P and also to try to reduce their emotional disorders. Objective: to assess whether QOL scores improved during follow-up (one year), whether the presence of DS was reduced during this period of time and wheter changes in QOL were influenced by the changes in the presence of such DS in an outpatient population followed in a HF multidisciplinary Unit. Methods: We used an abbreviate Geriatric Depression Scale (GDS) of 4 items to assess the presence of DS and the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) to assess the level of QOL. Both assessments were performed during the first visit to the Unit and again at one-year of follow-up. Patients: we studied 515 P (72% men, median age 67 years, range years), who where in NYHA functional class I (6.6%), II (55.3%), III (36.1%) and IV (1.6%). Baseline LVEF was 30% (median, range 5-76%). Etiology of HF was mainly ischemic heart disease (58.1%), followed by hypertensive (10.9%) cardiomyopathy. Median time since HF onset of symptoms was 13 months, range months. Results: DS were present in 128 P (24.9%) at first visit. This percentage falls moderately although statistically significantly to 20% (103 P) at one-year of followup (McNemar test p=0.03). Higher scores in the MLWHFQ (worse QOL) were statistically associated with the presence of DS both at first visit (P with DS: median 39.5, range 8-85; P without DS: median 21, range 0-88; Mann-Whitney U p<0.001) and at one-year of follow-up (P with DS: median 28.5, range 0-94; P without DS: median 14, range 0-65; p=0.001). We observed a statistically significant improvement in QOL at one-year in the global population (Wilcoxon test for paired data p<0.001). However, when we divided the P in 4 groups according to the presence of DS in the two visits (DS present-absent, DS present-present, DS absent-absent and DS absent-present), QOL scores improved in all groups (p<0.001) except in those P without DS at the first visit that developed them during follow-up (p=0.15). Conclusions: the presence of DS assessed by an abbreviated GDS was associated with a statistically significant worse QOL assessed by the MLWHFQ both at the first visit and after one-year of follow-up. Management of P in the HF Unit improved their QOL after one year except in those P with new DS developed during follow-up. P3168 It is just a game: lack of association between watching football matches and risk of acute cardiovascular events F. Barone Adesi, L. Vizzini, F. Merletti, L. Richiardi. University of Turin, Turin, Italy Purpose: The role of trigger factors in acute cardiovascular events has been much studied in the last years. A recent study found a 2.7-folds increase in incidence of cardiac emergencies during the 12 hours before and after matches

223 Psycho-social factors 523 involving the German team. A risk of such a magnitude, if confirmed, would be alarming. Methods: We studied daily hospital admissions for acute coronary events (ICD- 9: ) in Piedmont region (Northern Italy) during three international football competitions: World Cup 2002, European Championship 2004 and World Cup Poisson regression was used to estimate the relative risk of hospital admission for acute coronary events during the days when football matches involving the Italian team were disputed, compared with the other days of the three competitions. Furthermore, we conducted a systematic review of the available published studies on the association between football matches and risk of cardiovascular events. Results: We did not find an increase in rates of admission for acute coronary events neither in the three competitions combined (relative risk [RR] 0.95, 95% confidence interval ), nor in the single competitions. Such a figure is consistent with results of most of the published studies on the same topic. With the exception of the German study (Wilbert-Lampen et al), all the other studies reported RRs between 0.7 and 1.3. Conclusions: Cardiovascular effects of watching a football match are likely to be, if anything, very small. This is reassuring in terms of public health. Figure 1. Funnel plot of results (with 95% confidence intervals) of studies on football matches and risk of acute vascular events. P3169 Poor patient-rated health status predicts 1-year prognosis in patients treated with percutaneous coronary intervention with drug-eluting stenting S. Schmidt Pedersen 1, H. Versteeg 1, J. Denollet 1,P.Serruys 2, R. Van Domburg 2. 1 Tilburg University, Tilburg, Netherlands; 2 Erasmus Medical Center, Rotterdam, Netherlands Patient-rated health status is becoming an increasingly important outcome measure in cardiovascular research. Health status may also have clinical utility and aid in clinical decision-making and risk stratification, and the optimization of quality of care, in particular since physicians tend to underestimate the disabilities of patients. In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts 1-year clinical events. Consecutive patients (N=870; 72.2% men; mean age = 62.6±11.5) treated with PCI with the paclitaxel-eluting stent completed the EuroQol-5D at baseline and were followed up for adverse clinical events, defined as a combination of death or non-fatal myocardial infarction (MI) at 1-year. The EuroQol-5D health status dimensions mobility (HR: 2.08; 95% CI: ), self-care (HR: 2.75; 95% CI: ), and self-reported health status as measured by the EuroQol-5D visual analogue scale (HR: 2.54; 95% CI: ) were independent predictors of 1- year death/mi, adjusting for gender, age, multi-vessel disease, cardiac history, hypertension, hypercholesterolemia, diabetes, and smoking. The health status dimensions usual daily activities, pain/discomfort, and anxiety/depression were not associated with adverse clinical outcome in adjusted analysis. Several health status dimensions of the EuroQoL-5D predicted death or non-fatal MI at 1-year follow-up in PCI patients treated with drug-eluting stenting, with the risk being more than 2-fold. The impact of health status on prognosis was independent of disease severity and other demographic and clinical characteristics, indicating that health status as reported by the patient has unique prognostic value that cannot be derived from the patient s clinical profile. Given the brevity of the EuroQoL-5D, it could be used in clinical practice as a means of risk stratification. P3170 Comprehensive cardiac rehabilitation improves self-estimated health and patient satisfaction - important factors in future risk factor and life style management A.M.B. Soja 1, A.D.O. Zwisler 1,N.Nissen 2, S. Rasmussen 2, T.M. Melchior 3, E. Hommel 4, J. Fischer Hansen 5, M. Madsen 2 on behalf of The DANREHAB Study Group. 1 The Heart Centre, Rigshospitalet, Department of cardiology, Copenhagen University Hospital, Copenhagen, Denmark; 2 National Institute of Public Health, Copenhagen, Denmark; 3 Department of cardiology, Roskilde, Denmark; 4 Steno Diabetes Centre, Gentofte, Denmark; 5 Bispebjerg University Hospital, Department of cardiology, Copenhagen, Denmark Background: Besides promoting secondary prevention, the explicit goal of comprehensive cardiac rehabilitation (CR) is to improve quality of life. Patients with glucose intolerance (GI) eligible for CR have to cope with both the cardiovascular disease and GI, and this might be the reason for increased level of depression and lack of adherence to treatment among these patients. Therefore CR should consider these patients situation and their special needs. We aimed to investigate the patients satisfaction with CR with integrated diabetes care compared to usual care (UC) in a randomized clinical trial using standardised methods. Methods: In the DANSUK study, we used a centrally randomized clinical trial comparing CR with UC. Of 201 patients eligible for CR, 104 were diagnosed with GI having either type 2 diabetes (N=68) or impaired glucose tolerance (N=36). Patients were randomized after being discharged from a cardiac care unit to CR (N=51) and usual care (N=53). Mean age was 64 years; 34% were women; 7% had congestive heart failure, 67% had ischemic heart disease, and 26% had high risk for ischemic heart disease. Patients randomized to CR received 12 weeks of an individually tailored, multidisciplinary programme with an integrated diabetes module and clinical control after 3, 6 and 12 months. Patient satisfaction was measured as a secondary outcome after 12 month using a standardised interviewquestionnaire with closed answers to questions covering overall satisfaction and level of information. A total of 95 patients (91%) answered the questionnaire about satisfaction. Results: Among cardiac patients with GI receiving CR, 92% reported a high level of overall satisfaction with follow up treatment compared with 30% among patients receiving usual care (p< ). The CR group reported a higher level of satisfaction according to information about their disease (CR: 94%, UC: 42%; p<0.0001), information on diagnose and treatment (CR: 91%, UC: 47%; p< ), self-management of life-style changes (CR: 84%, UC: 43%; p=0.01), and self-management of medicine (CR: 36%, UC: 17%; p<0.05). Subgroup analysis showed no differences in degree of satisfaction according to gender, age or ethnic group. Conclusion: We found that CR with an integrated diabetes module significantly improves overall satisfaction with follow-up treatment together with level of information and self-management among glucose intolerant patients receiving CR compared with patients receiving UC. Programmes of CR should offer special courses for patients with glucose intolerance optimizing the environment to life style change. P3171 Divergent effects of laughter and mental stress on peripheral/central blood pressures and blood markers P. Xaplanteris, C. Vlachopoulos, C. Vassiliadou, D. Kardara, I. Dima, K. Baou, C. Stefanadis. Hippokration General Hospital of Athens, Athens, Greece Purpose: Peripheral and central (aortic) pressures predict cardiovascular risk. Psychological stress is an independent risk factor for cardiovascular events and deteriorates vascular function. We investigated the effect of laughter and mental stress on peripheral/central pressures; markers/mediators of hormonal status, endothelial function and inflammation were also assessed. Methods: 18 healthy individuals were studied on 3 occasions in a randomized, single-blind, crossover, sham procedure-controlled fashion. A 30 min segment of 2 films inducing laughter or stress was pjojected. Peripheral pressures were measured by a sphygmomanometer; central pressures were calculated by applanation tonometry. Measurements were made immediately (0 min), 15 and 30 min after the end of projections. Cortisol, sp-selectin, von Willebrand factor (vwf), total oxidative status (TOS), interleukin-6 (IL-6), scd-40 ligand (scd40l) and fibrinogen were measured from blood samples drawn before and 15 min after the projection. Changes in pressures were assessed by 2-way repeated-measures ANOVA; in blood markers by the Wilcoxon matched-pairs sign-ranks test. Results: Comedy did not alter mean/peripheral/central pressures when compared to sham procedure. Viewing of the comic film decreased cortisol (by 1.67 μg/dl, P=0.02) and sp-selectin (by 26 ng/ml, P=0.02). vwf showed a trend towards decrease following comedy (by 2.4%, P=0.07) and TOS was increased (by 61 μmol/l, P<0.001). IL-6, scd40l and fibrinogen levels were not altered. Stress resulted in an increase in mean pressure (P=0.04; max increase by 4.7 mmhg at 15 min) and trend of increasing peripheral systolic pressure (P=0.08; max increase by 4.3 mmhg at 15 min) and peripheral diastolic pressure (P=0.08; max increase by 4.6 mmhg at 15 min). Central pressures increased (P=0.03 for systolic aortic pressure; trend of increase for diastolic aortic pressure: P=0.06) and remained elevated throughout the 30 min following stress (systolic aortic pressure maximum increase by 4.9 mmhg at 15 min; diastolic aortic pressure

224 524 Psycho-social factors / Procedural complications of percutaneous cardiac interventions Part I max increase by 4.6 mmhg at 15 min). IL-6 was decreased (by 0.11 pg/ml, P=0.04) and TOS increased (by 44 μmol/l,p=0.007), while no changes in the other measured markers were observed. Conclusions: Positive (laughter) and negative (stress) behavioral interventions have divergent acute effects on blood pressure and markers/mediators of hormonal status, endothelial function and inflammation. These findings have important clinical implications extending the spectrum of lifestyle modifications that can ameliorate arterial function. P3172 Different psychological features of Takotsubo cardiomyopathy and acute myocardial infarction A.C. Compare 1, P. Silva 2, D. Gregori 3,R.Proietti 3, E. Grossi 1, R. Bigi 4. 1 Centro Diagnostico Italiano, Milan, Italy; 2 Ospedale Niguarda Ca Granda, Milan, Italy; 3 University of Padua, Padua, Italy; 4 Centro Cardiologico Monzino, Milan, Italy Purpose: Takotsubo cardiomyopathy (TTC) is a syndrome typically triggered by emotional or physical stress. The exact mechanism linking emotional stress to TTC is still unknown. The possible mediator role of stable traits of personality in hyperarousal reactions to stressors has not been specifically addressed. We aim at verifying whether a different pattern of personality traits can be identified in TTC compared to acute myocardial infarction (AMI). Methods: 37 patients with TCC, diagnosed according to the Mayo Clinic criteria, and 37 sex and age-matched controls with AMI underwent personality assessment: Type-D (DS-14; Negative Affectivity (NA) and Social Inhibition (SI)), Cynicism Hostility (sub-scale of Cook Medley Questionnaire), Anger (Trait Anger Scale). The male to female ratio was 1:9; mean age was 68 (59-75) years. According to rules of standardization for every psychological scales It has been calculated the clinical relevance. Results: The effect of psychological variables in separating TTC from AMI (Table 1). SI provided a complete separation of TTS from AMI on continuous scale. However, at multivariable analysis, by a conditional logistic regression model, the more complex Type D personality, including SI, has mostly been the remarkable variable in the distinction between TTC and IMA groups. Takotzubo AMI OR (95% CI) P-value Negative Affectivity 15 (12-17) 10 (9-11) 1.62 ( ) <0.001 Social Inhibition 21 (19-23) 9 (6-11) N.E. <0.001 Anger 14 (11-19) 15 (11-19) 1.02 ( ) Clinical Relevance Scales Social Inhibition: Clinical Relevance 37 (100%) 12 (32%) N.E. <0.001 Type D: Clinical Relevance 36 (97%) 10 (27%) ( ) <0.001 Negative Affectivity: Clinical Relevance 36 (97%) 27 (73%) ( ) Anger: Clinical Relevance 5 (14%) 5 (14%) 1 ( ) Conclusions: Our findings suggest stable inhibition of expressing emotions in social interaction as psychological marker of TTC patients. This may provide a possible mechanism underlying the excessive sympathetic reactivity triggering TTC syndrome after acute strain. PROCEDURAL COMPLICATIONS OF PERCUTANEOUS CARDIAC INTERVENTIONS PART I P3173 Relationship between myocardial blush grades and microvascular damage assessed by cardiac magnetic resonance after primary angioplasty M. Perazzolo Marra 1, F. Corbetti 2,L.Cacciavillani 1, A.B. Ramondo 1, G. Tarantini 1, M. Napodano 1,C.Basso 3,A.Marzari 1, F. Maddalena 1,S.Iliceto 1. 1 Department of Cardio, Thoracic and Vascular Sciences, Univerisity of Padua, Padua, Italy; 2 Service of Radiology, University of Padua Medical School, Padua, Italy; 3 Department of Medic-Diagnostic Sciences and Special Therapies, University of Padua Medical School, Padua, Italy Background: Although angiographic perfusion assessment has been traditionally evaluated by myocardial blush grade (MBG), pathophysiologic features underlying different blush grades, especially concerning the persistent blush (traditionally named staining ), have been poorly explained. Aim: We evaluated the correlation between angiographic perfusion patterns and morphologic aspects on CMR, in general and in particular the relationship between staining phenomenon and severe microvascular damage (SMD) identified by CMR. Methods: In a series of consecutive AMI patients treated by primary PCI, who underwent CMR, the angiographic perfusion pattern including definition of staining were evaluated. In each patient the ventriculography was also performed. Results: 294 pts enrolled were classified into two groups according to the angiographic perfusion pattern: 115 pts (39,1%) had MBG 0/1 and if compared to patients with MBG 2-3 exhibited a larger enzimatic infarct size (p<0,001), a greater transmural infarct size (p<0,001) and SMD (33,9%, p 0,001) at CMR. In the MBG 0/1 pts it was also possible to identify a subgroup of 51 pts with staining phenomenon (MBG-0-staining), who showed a worst CMR profile as SMD (p<0,001). Multivariate analysis confirmed the strong association between MBG 0/1 and mean number of transmural segments (OR 1,62, 95% CI 1,17-2,24, p = 0,003), and the worst CMR perfusion pattern as SMD index (OR 3,13, 95% CI 1,185-8,286, p = 0,021). Conclusions: Angiographic parameters of impaired reperfusion correlates in a large population study with SMD detected by CMR. Inside MBG 0 the presence of staining phenomenon reflects a subgroup of patients with more SMD on CMR. P3174 Distal embolisation in complex percutaneous coronary interventions:: A CMR and inflammatory biomarkers study D. Locca 1, C.H. Bucchiarelli-Ducci 2, G. Ferrante 2, A. La Manna 2, N. Keenan 2, A. Grasso 2, P. Barlis 2, J.C. Kaski 3, D.J. Pennell 2,C.Di Mario 2. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 Royal Brompton Hospital, London, United Kingdom; 3 St George s Healthcare NHS Trust, London, United Kingdom Background: Cardiac Magnetic Resonance Imaging (CMR) can identify myocardial damage due to embolization after percutaneous coronary interventions (PCI). Late Gadolinium Enhancement (LGE) can non-invasively detect myocardial fibrosis however the association of High sensitive C-reactive protein (HS-CRP) or Neopterin levels with myocardial damage in PCI is currently unknown. Methods: Patients admitted with potential PCI were enrolled. LGE CMR scan was performed 24hours pre- and 24 hours post-pci. Fourty five patients were enrolled, 61±12 yrs old, 33 (73%) male. CMR performed pre PCI failed to show LGE in the area of the target vessel. TnI were not elevated at baseline. New LGE areas in the 2nd CMR scan were classified in distal (> 10 mm downstream from the stent) or adjacent (close to the stent). Troponin I was assessed at baseline and at 12 and 24 hours after PCI. Results: In 35 out of 45 pts, baseline levels of HS-CRP and neopterin were measured.troponin I elevation occurred in 26 (58%) patients, 0.56 ng/ml ( ). New areas of LGE were detected in 15/45 (33%) patients, 0.83 grams ( ), all with troponin rise after PCI. In 7 out of 15 (47%) patients new LGE areas were distal to the stent, in 8 (53%) patients adjacent. Grams of myocardial damage correlated with troponin levels after PCI, r = 0.64, p<0.001, in the overall population, although there was no linear relationship. Patients with new distal LGE showed a trend toward higher levels of baseline CRP compared to the remaining patients [7.4 mg/l ( ) vs 2.5 mg/l ( ), p=0.08]. HS-CRP was a weak predictor of new distal LGE (odds ratio 1.03, 95% confidence interval ( , p=0.07)). There was no significant difference in the neopterin levels between patients with or without new distal LGE [7.1 nmol/l ( ) vs 6.1 nmol/l ( ), p=0.39]. Conclusions: Patients who develop myocardial damage due to distal embolization show a trend toward higher baseline CRP levels. This suggests that increased systemic inflammation may be a marker of higher friability of coronary plaques and/or of enhanced inflammatory response of myocardium to embolizing particles, responsible for subsequent myocardial damage. Larger studies are needed to confirm these preliminary hypothesis generating data. P3175 High dose atorvastatin reload pre PCI increases circulating levels of endothelial progenitor cells. The ARMYDA EPC study R. De Caterina 1, R. Madonna 1,L.Gatto 2, E. Ricottini 2, A. Tatasciore 1,G.Patti 2, G. Di Sciascio 2. 1 Institute of Cardiology, G. d Annunzio University, Chieti, Italy; 2 Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy Purpose: Endothelial progenitor cells (EPCs) contribute to vascular repair. Statins promote EPCs mobilization. In the randomized ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) trials, pretreatment with atorvastatin (A) reduced periprocedural myocardial infarction in patients with both stable or unstable angina during percutaneous coronary intervention (PCI). Mechanisms underlying this effect are not fully characterized. Goal of the study was to investigate whether protection from myocardial injury during PCI by A is concomitant to a parallel increase in EPCs availability, possibly affording cardioprotection. Methods: In a planned subanalysis of the ARMYDA-RECAPTURE trial, a subgroup of 64 patients (n = 36 with stable angina, n=27 with acute coronary syndromes), on chronic low dose statin therapy, underwent a blinded measurement of EPCs in peripheral blood; 33 patients were randomized to A (80 mg at randomization 12 h before PCI, with a further 40 mg preprocedural dose) and 31 to placebo. EPCs were evaluated 12 h before intervention, immediately before PCI, and after 8 and 24 h. Circulating EPCs (CD45dim/CD34+/CD133+/KDR+ cells) number was determined by flow cytometry with the ISHAGE protocol. Results: Incidence of peri-procedural myocardial infarction (post-intervention increase of cardiac biomarkers >3 times UNL) was 0% in the A and 10% in the placebo arm (primary end-point). At 24 h, the proportion of patients with elevated creatine kinase-mb (CK-MB) and Troponin-I (TnI) above UNL was significantly lower in the A arm (CK-MB 6% vs. 26%, p<0.01; TnI 39% vs. 61%, p<0.05) (secondary end-point). Post-PCI average percent increase of C-reactive protein from baseline was significantly lower in the treatment arm (16±65% vs. 40±60%, p = 0.01). EPCs were not significantly different at randomization in the two arms (0.32±0.25% of total events in the A vs. 0.24±0.27% of total events in the placebo group, p=ns). At the time of procedure, EPCs became significantly higher in the A arm (0.75±1.04% vs. 0.21±0.28% of total events; p = 0.004). Elevation of EPCs in the statin group

225 Procedural complications of percutaneous cardiac interventions Part I 525 was observed at 8 h (0.88±1.37 vs. 0.20±0.19% of total events; p = 0.005) and 24 h (0.80±1.01 vs. 0.24±0.26% of total events; p = 0.002). Conclusions: The ARMYDA-EPC substudy, in parallel with a reduction of periprocedural myocardial damage after administration of only two doses of A even in the background of chronic statin therapy, demonstrates the prompt elevation of EPCs in the A reload group, providing insights into the mechanisms of cardioprotection afforded by such therapy. P3176 IVUS insights into coronary rupture during PCI A.S.P. Sharp, R.T. Gerber, A. Latib, M. Bande, C. Godino, M. Ferraro, A. Colombo. San Raffaele Hospital, Milan, Italy Background: As vessel rupture is such an infrequent event during PCI, limited data are available on the causative factors. We examined all cases where IVUS imaging was performed prior to a balloon or stent-induced Type IV vessel rupture, in order to better understand these events. Methods: We examined data from all PCIs performed between October 1997 and October 2008 at a single centre in Milan, Italy. Subjects who underwent IVUS examination during a case involving a type IV rupture were analyzed. Using QCA, we were able to accurately identify the point of rupture on IVUS allowing vessel size, character and degree of calcification to be established. Results: Among vessels treated, there were 28 type IV ruptures, of whom 6 had adequate IVUS examinations. There were two factors amongst the rupture cases evident from IVUS data that were not apparent from the coronary angiograms. Firstly, five of the six had an arc of calcification extending from 70 degrees round to 270 (mean arc of calcification for these 5 cases was 120 degrees) but none of the patients had evidence of circumferential calcification of the vessel at the rupture site, despite this phenomenon being present at other points in the treated segment. Secondly, four of the six patients had evidence of fibrotic or calcific negative remodeling at the site of the rupture (Figure 1 shows two examples). Conclusion: Eccentric calcification and fibro-calcific negative remodeling identified on IVUS at the site of vessel rupture may be significant contributors to type IV coronary ruptures. P3177 Impact of isolated troponin elevations after PCI on two-year mortality P. Sbarzaglia 1,S.Savonitto 2, R. Violini 3,G.Arraiz 4,Z.Olivari 5, S. Notaristefano 1,S.DeServi 6, G. Steffenino 7,D.Ardissino 8, C. Cavallini 1 on behalf of Italian Atherosclerosis, Thrombosis and Vascular Biology and Society for Invasive Cardiology-GISE Investigators. 1 Azienda Ospedaliera Di Perugia, Perugia, Italy; 2 Ospedale Niguarda Ca Granda, Milan, Italy; 3 Azienda Ospedaliera San Camillo Forlanini, Rome, Italy; 4 Universita di Milano, Milan, Italy; 5 Ospedale Ca Foncello, Treviso, Italy; 6 Ospedale Civile, Legnano, Italy; 7 Azienda Ospedaliera Santa Croce E Carle, Cuneo, Italy; 8 Azienda Ospedaliero Universitaria di Parma, Parma, Italy Purpose: Slight elevations in the cardiac Troponin levels are frequently detected after percutaneous coronary intervention (PCI), but their clinical significance, when not associated with concurrent elevations in CK-MB, is still uncertain. In a multicentre prospective cohort study we evaluated the influence of isolated elevations of cardiac Troponin I (ctni) on two-year all-cause mortality. Methods: The CK-MB and PCI study included 3,494 consecutive patients undergoing PCI at 16 Italian tertiary centers. Pre- and post-pci CK-MB and ctni levels were centrally analyzed and the patients were followed for two years. For the purpose of the present analysis we selected 2362 patients showing normal values of both CK-MB and ctni at baseline and no-ck-mb elevation after PCI. Results: ctni elevation above the Upper Reference Limits (>URL) was detected in 932 patients (39.4%); in 467 of them the elevation was higher than 3 times the URL (>3xURL), fulfilling the criteria of the Universal Definition of Myocardial Infarction. ctni elevation was associated with a non-significant trend for higher two-year mortality (3.8% vs. 2.6%, RR 1.5; 95% CI 0.9 to 2.4; p=0.08), which was more elevated in those with ctni >3xURL (4.5% vs. 2.7%; RR1.6; 95% CI 0.9 to 2.7; p=0.052). Patients with postprocedural ctni elevations had a worse risk profile at baseline (advanced age, unstable angina, chronic renal insufficiency, multivessel disease, complex coronary anatomy, long coronary lesions and coronary thrombosis) in comparison with patients without elevation. In a multivariate regression logistic model, ctni elevation >3xURL was not independently associated with mortality (O.R. 1.5, 95% CI 0.8 to 2.6, p=0.13). Conclusions: Minor, isolated post-pci elevations of Troponin I, even when consistent with the Universal Definition of Myocardial Infarction, do not adversely affect mortality at 2-year. P3178 Background. Cardiac Magnetic Resonance Imaging (CMR) can identify myocardial damage due to embolization after percutaneous coronary interventions (PCI). Late Gadolinium Enhancement (LGE) can non-invas D. Locca 1, G. Ferrante 2, C.H. Bucchiarelli-Ducci 2, A. La Manna 2, F. Delfuria 2,A.Grasso 2,P.Barlis 2,S.K.Prasad 2, D.J. Pennell 2,C.DiMario 2. 1 Centre Hopitalier Universitaire Vaudois, Lausanne, Switzerland; 2 Royal Brompton Hospital, London, United Kingdom Purpose: Little is known about balloon predilatation before stent implantation in term of myocardial damage. Cardiovascular Magnetic Resonance (CMR) can non-invasively detect less than 1 gr of myocardial fibrosis. Aim of this study was to assess if predilatation in PCI with stent implantation might be associated with new areas of late gadolinium enhancement (LGE) measured by CMR and postprocedural troponin elevation. Methods: Patients admitted to the hospital with stable/unstable angina or silent ischemias and with potential PCI were enrolled. LGE CMR scan was performed 24hours pre- and 24 hours post- PCI. The amount of enhancement was quantified by planimetry based on signal intensity (> 2SD) of surrounding nulled myocardium. Troponin I was measured at baseline, 12 and 24 hours after PCI. Results: In a total recruitement of 69 patients, 51 underwent a PCI with pre and post LGE CMR scan. 45 patients had a successful PCI and good quality pre and post CMR scan, mean age 61.6±12.1 (mean ± SD) years old, 73% male, 84% were affected by stable angina. TIMI flow grade, TIMI perfusion myocardial grade (TMPG) (score 0,1,2,3) were assessed before/after balloon dilatation, after stenting and at the end of the PCI. No patient with baseline TnI elevation or baseline LGE evidence in the territory of the vessel treated was included. Increased postprocedural TnI above the upper normal limit (0.04 ng/ml) occurred in 26 patients (57.7%) 0.51 ng/ml ( ) (min-max). New LGE was detected in 15 patients (33.3%). All of them were in the group with TnI elevation. Patients with predilatation showed a more frequent elevation of TnI (65.7% vs 14.3%, p=0.03), but no significant difference in the occurrence of LGE (36.8% vs 14.3%, p=0.39). Predilatation was an independent predictor of TnI elevation, after adjusting for the presence of more than one lesion treated per patient and the occurence of a reduction of TMPG score from baseline during PCI (OR 11.4, 95% CI ( ), p=0.036), area under ROC curve 0.76 (95% CI ), although it was not associated with new area of LGE (OR 3.45, 95% CI ( ), p=0.28). Conclusions: In patients undergoing PCI with stent implantation, the use of balloon predilatation is associated with a significantly greater risk of postprocedural troponin elevation. This study demonstrated the accuracy of TnI in identifying potential consequences of periprocedural myocardial necrosis after PCI with balloon predilatation. Even if CMR is a useful tool but larger studies are needed to assess if predilatation might be associated with LGE postprocedural myocardial damage. P3179 Altered fibrin clot structure and function are associated with in-stent thrombosis J. Zalewski 1, A. Undas 1,M.Krochin 1, Z. Siudak 2,M.Sadowski 3, J. Pregowski 4, M. Janion 3, A. Witkowski 4, D. Dudek 2, K. Zmudka 1. 1 Jagiellonian University, John Paul II Hospital, Cracow, Poland; 2 Jagiellonian University, Cracow, Poland; 3 Swietokrzyskie Center of Cardiology, Kielce, Poland; 4 Insitute of Cardiology, Warsaw, Poland Purpose: Incomplete reendotelialization and persistent fibrin deposition are considered a primary substrate underlying in-stent thrombosis (IST). We sought to investigate whether patients with IST display altered fibrin clot properties. Methods: We studied 47 definite IST patients, including 15 with acute, 26 subacute and 6 late IST, and 48 controls matched for demographics, cardiovascular risk factors, and angiographic/stent parameters. The median of time from first PCI to IST was 6 (interquartile range 1-11) days. All patients with procedure-related IST were excluded. Plasma clot permeability (Ks, μm 2 ) and compaction (%) which indicate fibrin clot pore size, turbidity (lag phase (s), indicating start of fibrin polymerization, Absmax (405 nm), maximum absorbance of fibrin gel, reflecting the fiber thickness), lysis time (t50%, min), maximum rate of D-dimer release from clots (D-Drate, mg/l/min) and maximum concentration of D-dimer released from clots (D-Dmax, mg/l) were determined ex vivo 2-73 (median 14.7) months after IST. Results: IST patients had 21% lower Ks, 12% lower compaction, 14% higher Absmax, 24% lower D-Dmax, 11% lower D-Drate, 30% longer t50% (all p<0.0001) and 5% shorter lag phase compared to controls (p=0.042). There were no correlations of clot variables and the time of IST or that from IST to blood sampling. Multiple regression analysis showed that Ks (OR=0.36 per 0.1 μm 2, 95%CI

226 526 Procedural complications of percutaneous cardiac interventions Part I , p<0.001), D-Drate (0.16 per 0.01 mg/l/min, , p<0.001) and stent length (1.1 per 1 mm, , p=0.043) were independent predictors of IST (R 2 =0.58, p<0.001). Conclusions: Survivors of IST tend to form fibrin clots that begin polymerization more quickly, have thicker fibers, are less permeable, more compact and more resistant to lysis compared to controls. Unfavorably altered fibrin clot structure and function might help identify patients at high risk of IST. P3180 The impact of age on the results of percutanous coronary intervention (PCI) in patients with stable angina. Results from the ALKK PCI registry S. Kim 1, M. Hochadel 2,U.Zeymer 1,H.Darius 3, S. Kerber 4, K.E. Hauptmann 5, J. Senges 2, U. Sechtem 6, H. Mudra 7,R.Zahn 1. 1 Klinikum der Stadt Herzzentrum Ludwigshafen, Ludwigshafen am Rhein, Germany; 2 Institut fuer Herzinfarktforschung Ludwigshafen, Ludwigshafen am Rhein, Germany; 3 Vivantes Klinikum Berlin-Neukölln, Berlin, Germany; 4 Herzund Gefäß-Klinik GmbH, Bad Neustadt/Saale, Germany; 5 Krankenhaus der Barmherzigen Brüder, Trier, Germany; 6 Robert-Bosch Krankenhaus, Stuttgart, Germany; 7 Klinikum Neuperlach, München, Germany Background: In many invasive procedures advanced age is an independent predictor of more complications. The aim of this study was to evaluate the age distribution of patients with stable angina pectoris undergoing a percutanous coronary intervention (PCI), and to analyse the clinical outcome for elderly persons. Methods: Data from the prospective ALKK PCI registry in 2006 were analysed. The ALKK PCI registry is a German multicenter registry of consecutive PCI procedures. Results: patients with stable angina pectoris underwent PCIs in 42 German hospitals in The mean age was 67 years, with a range of years. 42% of the patients were over 70 years old, 8.6% > 80 years, and 0.1% > 90 years. Patient characteristics and the event rates in relation to the age are shown in the following table. Patient characteristics and event rates in relation to the age <70y >70y >80y >90y p for trend Female 21.9% 33.7% 46.1% 50.0% <0.001 Prior PCI 49.0% 46.0% 43.8% 26.1% <0.001 Prior CABG 12.5% 17.6% 16.0% 4.2% <0.001 Renal failure 8.1% 16.7% 24.4% 33.3% <0.001 Diabetes mellitus 21.9% 26.8% 22.9% 25.0% <0.001 In-hospital events Death 0.2% 0.4% 1.1% 0 <0.001 Stroke/TIA 0.02% 0.3% 0.2% 0 <0.001 Myocardial infarction 0.4% 0.7% 0.3% Conclusion: In current clinical practice more than 40% of patients with stable coronary artery disease undergoing a PCI are over 70 years old. Advanced age is associated with a higher rate of hospital death. P3182 Early stent thrombosis in patients undergoing primary coronary stenting for acute myocardial infarction M. Ergelen 1,H.Uyarel 2, D. Osmonov 1,E.Ayhan 1, E. Akkaya 1, O. Ozer 3,M.Bozbay 1, A. Turer 1,C.Turkkan 1, E. Yildirim 1. 1 Siyami Ersek Cardiovascular and Thoracic Surgery Center, Cardiology, Istanbul, Turkey; 2 Balikesir University Medical Faculty, Cardiology, Balikesir, Turkey; 3 Gaziantep University Medical faculty, Cardiology, Gaziantep, Turkey Purpose: One of the major remaining concerns in the treatment with stenting of acute myocardial infarction (AMI) patients is the occurrence of stent thrombosis (ST). The aim of the present study was to investigate incidence, predictors, and long-term outcomes of early ST after primary coronary stenting for AMI in a large population. Methods: We reviewed 1960 consecutive patients (mean age 56±11.6 years, 1658 male) treated primary coronary stenting for AMI between 2003 to All clinical, angiographic and follow-up data were retrospectively collected. Early ST was defined as thorombosis occurred in the first 30 days after primary coronary stenting. Results: Early ST was observed in 89 (4.5%) patients. Five variables, selected from the multivariate analysis, were weighted proportionally to their respective odds ratio for early ST (premature clopidogrel therapy discontinuation [10 points], stent diameter 3 mm [5 points], current smoker [4 points], diabetes mellitus [3 points], age>65 years [2 points]). Three strata of risk were defined (low risk, score 0 to 4; intermediate risk, score 5 to 12; and high risk, score 13 to 24) and had a strong association with early ST and long-term cardiovascular mortality. Longterm cardiovascular mortality was fivefold more in patients with early ST than without ST (24,1% vs 4,7%, respectively, p<0.001). Conclusions: Early ST after primary coronary stenting in AMI is strongly related with increased long- term cardiovsacular mortality. Premature clopidogrel therapy discontinuation is the most powerful predictor of early ST. P3183 Impact of preoperative multidetector computed tomography in percutaneous coronary intervention of chronic total occlusion K. Ueno, A. Kawamura, Y. Jo, K. Hayashida, S. Yuasa, Y. Maekawa, T. Anzai, M. Jinzaki, S. Kuribayashi, S. Ogawa. Keio University School of Medicine, Tokyo, Japan Objectives: Multidetector computed tomography (MDCT) provides precise information about the composition of stenotic lesions including a track of vessel, vessel diameter, lesion length, the presence and distribution of atherosclerotic plaques and calcification. The impact of preoperative MDCT in percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) has not been fully examined. Methods: The study population was 100 consecutive patients who underwent PCI of CTO from January 2005 to December 2007 in our institution. CTO was defined as a lesion with total occlusion (100% angiographic diameter narrowing) and Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 of native coronary vessels with the duration of at least 3 months. Patients with acute occlusions and those with chronic total occlusions of bypass grafts were not included. They were divided into 2 groups according to the absence (non-ct group, n = 60) or presence (CT group, n = 40) of preoperative 64-MDCT. The impact of preoperative MDCT was assessed in the outcomes, complications, irradiation time and the dose of contrast agents. Results: Procedural success rates were similar in both groups (non-ct group; 80% vs. CT group; 78%, p = n.s.). Irradiation time and the dose of contrast agents were also similar between 2 groups. However, the occurrence of complications was significantly lower in CT group than non-ct group (8% vs. 23%, p = 0.04). Especially coronary perforations occurred solely in non-ct group (10.0% vs. 0.0%, p = 0.04). Multiple logistic regression analysis revealed that the use of rotablator (RR = 4.40, p = 0.003) and the absence of preoperative MDCT (RR = 4.26, p = 0.04) were the independent determinants of complications during PCI of CTO. Conclusion: Preoperative MDCT might be useful to prevent the complications during PCI of CTO. P3184 Furosemide-induced diuresis with matched hydration compared to standard hydration for contrast-induced nephropathy prevention: preliminary results of the MYTHOS trial G. Marenzi, C. Ferrari, E. Assanelli, I. Marana, G. Lauri, J. Campodonico, G. Teruzzi, D. Trabattoni, A.L. Bartorelli. Centro Cardiologico Monzino, Milan, Italy Purpose: Contrast-induced nephropathy (CIN) is a frequent cause of hospitalacquired acute kidney injury and is associated with prolongation of hospital stay and increased short and long-term mortality. We investigated the effect of a new CIN preventive strategy based on a dedicated device (RenalGuard; PLC Medical System Inc., USA). The system is capable of delivering i.v. saline solution to a patient in an amount matched to the volume of urine produced after an i.v. bolus of furosemide. The aim of the study was to evaluate if furosemide-induced highvolume diuresis with concurrent maintenance of intravascular volume may prevent CIN. Methods: To date, 43 chronic kidney disease (CKD) patients (egfr<60 ml/min/1.73 m 2 ) undergoing elective or urgent percutaneous coronary interventions (PCI) were enrolled in the MYTHOS trial. They were randomized to matched hydration (RenalGuard group, n=20) or to i.v. isotonic saline hydration (control group; n=23) at a rate of 1 ml/kg/hour for 12 hours before and after PCI. Matched fluid replacement was started approximately 90 minutes pre-pci, maintained during catheterization, and for up to 4 hours afterwards. Patients were given an initial i.v. bolus of 250 ml of normal saline over 30 minutes and then an i.v. bolus of furosemide (0.5 mg/kg). The RenalGuard measures the patient s urine volume and then automatically adjusts the infusion pump rate to precisely replace the measured urine output in real time. When a significant (>300 ml/hour) urine output rate was obtained, patients underwent PCI. CIN was defined as a >0.5 mg/dl or >25% rise in serum creatinine over baseline. Iomeron was used in all patients. Results: Overall, the mean egfr was 40±10 ml/min/1.73 m 2. The mean contrast volume was 206±104 ml in RenalGuard group and 206±125 ml in controls (P=ns). In RenalGuard group, urine output ranged from 319 to 1788 ml/hr (mean 844±379 ml/hr). There were no serious device- or therapy-related complications, including clinically significant electrolyte changes (asymptomatic ipokalemia was corrected in 1 case). CIN occurred in no patient (0%) of the RenalGuard group and in 4 (17%) controls (P=0.05). Two controls (8.7%) required temporary renal replacement therapy. Conclusions: These preliminary results indicate that furosemide-induced high urine output with maintenance of intravascular volume through matched hydration can be safely obtained with the RenalGuard system and may reduce the risk of CIN in CKD patients undergoing PCI.

227 Procedural complications of percutaneous cardiac interventions Part I 527 P3185 Is rescue PCI related to worse outcome? C. Hernandez, C. Tapia, R. Andion, J.M. Vegas, F. Gimeno, I. Gonzalez, I. Amat, H. Gutierrez, M. Sandin, J.A. San Roman. ICICOR, Valladolid, Spain Background and purpose: Patients undergoing rescue percutaneous coronary intervention (rescue-pci) after thrombolytic therapy have poor outcome. ESC guidelines for management of ST-myocardial infarction (MI) suggest the benefit of 24-hour-post-lytic angiography if primary PCI is not feasible. The aim of our study is to establish the clinical profile and outcome of patients undergoing rescue and elective 24-hours-coronariography, and to compare both invasive strategies. Methods: We included 518 consecutive patients under thrombolytic therapy admitted in our coronary care unit due to an acute MI from 2006 to Clinical, laboratory, angiography variables and in-hospital mayor cardiac adverse events (death, re-infarction) were analyzed. Results: A total of 131 patients (25%) underwent urgent rescue PCI and 283 (75%) were referred to angiography after successfully lytics within 24 hours. Diabetes (27% vs 15%, p= 0,006) and worse functional class at admission (Killip III- IV 15% vs 6%, p=0,003) were more frequent among rescue-pci patients. There were no-differences in sex, age and other classical risk factors. Pain-to-needle time was similar between groups (120 vs 127 minutes, p=0,9). Rescue-PCI patients presented more frequently anterior MI (42% vs 34%, p= 0,01), more extensive infarction related area (Maximum-CK peak: 3102 vs 1570, p=0,001) and worse angiographic results (TIMI flow 2-3: 85% v 97%, p=0,05). Complete revascularization: (66% vs 70%, p=0.05). Need for intra-aortic balloon pump counterpulsation (13% vs 6%, p=0,013), mechanical ventilation/assisted breathing (14% vs 5%, p=0,02) and post-intervention renal failure (13% vs 6%, p=0,012) were more common in rescue-pci patients. More re-infarction (8% vs 2%, p=0,016) and in-hospital mortality (14% vs 3%, p=0,001) determine more unfavourable outcome in these patients. Conclusion: Rescue-PCI has worse clinical and angiographyc profile, and higher rate of adverse events and poorer outcome compared with 24-hours routine postlytics intervention. P3186 Radial anomalies in the transradial access in percutaneous coronary intervention: characteristics and results of 7 years experience A. Rodriguez Vilela, J. Salgado Fernandez, G. Aldama Lopez, R. Estevez Loureiro, E. Barge Caballero, J.M. Vazquez Rodriguez, R. Calvino Santos, N. Vazquez Gonzalez, A. Castro Beiras. Complejo Hospitalario Universitario de A Coruña, La Coruña, Spain Background: Previous studies have demonstrated the feasibility and safety using radial artery as an access path for coronary angiography (CA). In fact, some centres use this via as a routine access as both diagnostic and interventional coronary procedures. Anatomic variations of the radial have been related to failure of transradial approach in the setting of percutaneous coronary intervention (ICP). Purpose: The purpose was to assess the rate and features of radial anatomic variations and its influence on the outcome of ICP. Methods: Cohort-based study including consecutive patients submitted to CA in our hospital from 2001 to Results: The mean patient age was 64,5±11,5, 25% women; 7,4% had a STelevation myocardial infarction (STEMI) and 39% underwent ICP. 267 (2,2%) abnormalities were identified, including 77 (0,6%) loops, 18 (0,1%) high radial origin, 32 (0,3%) retroesophageal right subclavian artery (lusoria), and 147 (1,2%) that showed a significant tortuous configuration at radial level. The presence of radial artery anomalies was related to more frequent change of via (32% vs 4,4%, p<0,001), a greater duration of procedure (33±24 vs 48±31 minutes, p<0,001), higher fluoroscopic times and a higher contrast volume (204±146 vs 245±175ml, p<0,001). However, in those cases underwent ICP, radial anomalies were not associated to a lower rate of ICP success (97,1% vs 96,9%, p NS). Conclusion: The rate of radial anomalies found in our cohort of patients who underwent CA was low and was associated to change of vascular access, greater procedure and fluoroscopic times, and the use of a higher contrast volume. Interestingly, the rate of ICP success was no penalized by radial anomalies. P3187 Factors predicting neurological complications following percutaneous coronary angiography and interventions in a large series of transfemoral and transradial approach H. Tizon Marcos, G.R. Barbeau, C.M. Nguyen, B. Noel, R.H. Bagur, J.R. Rodes-Cabau, E. Larose, S. Rinfret, R.H. Delarochelliere. Institute de Cardiologie et Pneumologie de Québec, Québec, Canada Introduction: Neurologic complications (NC) following coronary angiography or coronary interventions have been described in literature as a rare complication with still high mortality rate. Predictors of per-procedural neurological complications following transfemoral approach are described in literature but there is no data concerning a large transradial and transfemoral cohort. Objectives: Determine univariate and multivariate factors predisposing a NC in our large series of transradial and transfemoral approach. Methods: Analysis of all patients with coronary angiography or interventions from April 1990 to October 2007 (83409 patients) and per-procedural NC (63 patients) in our center with a matched control group of patients (254). Results: Patients with NC, compared with the control group, are older (68±12 vs 60±12, p<0.0001), more frequently female (43% vs 24%, p = 0.035), with more hypertension (68% vs 44%, p= ), peripheral vascular disease (35% vs 9%, p <0.0001), more severe coronary disease (3 vessel disease 56% vs 24%, p < ), higher creatinine level (112±34 vs 93±27, p <0.001), lower clearance of creatinine (61±25 vs 85±33, p<0.0001) and lower left ventricle ejection fraction (p=0.004). Also, patients with NC are equally radial approached (48% vs 63%, p=0.14), more prone to have by-pass angiography (29% vs 6%, p<0.0001), more dye used (203±106 vs 168±96, p=0.012) and more per-procedural complications (13% vs 0.8%, p < ). Independent predictors of CVA are clearance of creatinine (OR 0.97, CI 95% , p=0.0018), peripheral vascular disease (OR 6, CI 95% , p=0.0003), by-pass angiography (OR 6.2, CI 95% , p=0.002) and per-procedural complications (OR 13.5, CI 95% 2-87, p=0.0062). Conclusions: Factors predisposing a NC following coronary angiography or interventions in our series of transradial and transfermoral approach are a lower clearance of creatinine, peripheral vascular disease, by-pass angiography and per-procedural complications. The approach in coronary angiography or interventions appears not to be a predictor of per-procedural NC. P3188 Impact of preinterventional plaque composition and eccentricity on the late acquired stent apposition after sirolimus-eluting stent implantation: an intravascular ultrasound radiofrequency analysis T. Sato, T. Kameyama, T. Noto, H. Inoue. University of Toyama, Toyama, Japan Purpose: Incomplete stent apposition has been reported to be highly prevalent in patients with very late stent thrombosis after drug-eluting stent implantation. The present study investigated differences of the coronary plaque components between patients with and without late acquired incomplete stent apposition (LISA) with the use of Virtual Histology intravascular ultrasound (VH-IVUS). Methods: The study consisted of 31 patients who underwent elective coronary stenting. VH-IVUS was performed at index and 12-month follow-up. LISA was defined as a separation of stent struts from the intimal surface of the arterial wall that was not presented at stent implantation. Plaque eccentricity index was calculated by dividing (luminal diameter + maximal plaque thickness minimal plaque thickness) by (luminal diameter - maximal plaque thickness + minimal plaque thickness). The plaque was defined as eccentric if the index was >2 and as concentric if 2. Preinterventional plaque morphology and interventional procedure were compared between patients with or without LISA. Results: At 12-month follow-up, LISA occured in 11 patients (LISA group). Compared to non-lisa group (n=20), LISA group had longer stents (LISA: 19.1±2.1 vs non-lisa: 16.3±3.3mm, p<0.03), larger plaque area (LISA: 9.5±2.9 vs non- LISA: 7.3±1.9mm 3, p<0.03) and higher eccentricity index (LISA: 2.8±1.3 vs non-lisa: 1.7±0.3, p<0.01). Plaque morphology, however, were not different between LISA and non-lisa groups. LISA subgroup with concentric plaque (LISA- CON: n=5) had smaller composition of fibrous (54.2±14.7%) compared to LISA subgroup with eccentric plaque (LISA-EC: 70.3±9.4%, n=6, p<0.01) and non- LISA group (69.3±10.0%, p<0.05). LISA-CON subgroup had larger composition of dense calcium (16.4±4.9%), compared to LISA-EC subgroup (7.5±5.2%, p<0.02) and non-lisa group (7.5±4.7%, p<0.01). LISA-CON subgroup also had larger composition of necrotic core (22.2±13.4%), compared to non-lisa group (12.1±8.0, p<0.05), and LISA-EC subgroup (11.6±4.5%, p=0.10). Conclusions: Late acquired incomplete stent apposition is related to large, eccentric plaque and concentric plaque with increased component of dense calcium and necrotic core. Preinterventional VH-IVUS is a useful tool to predict late acquired incomplete stent apposition after sirolimus-eluting stent implantation. P3189 Usefulness of urinary neutrophil gelatinase associated lipocalin to urinary creatinine ratio for monitoring of n-acetyl cysteine efficacy in contrast induced nephropathy C. Demponeras, N. Kafkas, K. Makris, A. Nikolaou, K. Triantafillou, G. Mertzanos, S. Potamitis, I. Drakopoulos, D. Babalis. General Hospital of Attika KAT, Athens, Greece Contrast induced nephropathy (CIN), usually defined by an increase in the serum creatinine >0.5mg/dL or >25% from baseline, is a common complication of contrast agent used during coronary angiography. This increase typically occurs 3-5days after contrast administration. Neutrophil gelatinase-associated lipocalin (NGAL) is highly accumulated in the human kidney cortical tubules, blood and urine after nephrotoxic and ischaemic injuries, has been proposed as an early, sensitive biomarker for CIN. N-acetyl cysteine and hydration are used for prevention of CIN. Purpose: The aim of our study was to evaluate the use of the urinary- NGAL/urinary-creatinine ratio in order to monitor the efficacy of hydration and

228 528 Procedural complications of PCIs Part I / Procedural complications of PCIs Part II NAC administration in patients who receive contrast during percutaneous coronary intervention. Methods: Thirty six patients with renal impairment (baseline cystatine-c>1.0 mg/l) undergoing either coronary angiography alone (n=14) or angioplasty with stenting (n=22) were included. Saline 0.9% (1mL/kg/hr for 12hrs pre/post) and n- acetylcysteine (NAC) administration (600mg per-os pre/post) were administered to all patients. Low-osmolar contrast agent (iodixanol) was used in all patients. Serum and urine samples obtained just before PCI (baseline), 6-hours after contrast administration and 24 and 48 hours thereafter. NGAL was measured with ELISA (Bioporto,Gentofte,Denmark). Urine and serum-creatinine were measured with Jaffe method, and cystatin-c with immunoturbidometric assay on Architect analyzer (Abbott Diagnostics, Abbott Park,Il). Results: CIN was documented in 4 patients (serum creatinine increase >25% from baseline within 48 hours after contrast administration). Urinary- NGAL/urinary-creatinine ratio was significantly increased in these patients 6 hours after coronary angiography compared to non-cin patients ( ng/mg vs ng/mg, p<0.001). ROC analysis showed that urinary- NGAL/urinary-creatinine ratio at 6 hours after contrast administration can predict NAC efficacy (AUC=0.983, 95%CI ). Using as cut-off ng/mg NAC efficacy can be predicted with sensitivity/specificity 91.4% and 88.3% respectively. Conclusion: We conclude that measurement of urinary NGAL/urinary creatinine ratio 6 hours after contrast administration can be used as an early marker to monitor the efficacy of NAC in CIN prevention P3190 Comparison influence oral versus intravenous hydratation on renal function in diabetic patients before and after coronary angiography and angioplasty W. Wrobel 1, W. Sinkiewicz 1, M. Gordon 1, M. Zielinski 2. 1 Oddzial Kardiologii z Zakladem Diagnostyki Kardiologicznej Szpital Uniwersytecki nr 2, Bydgoszcz, Poland; 2 Oddzial Kardiologii Szpital Specjalistyczny, Chojnice, Poland Purpose: Contrast induced nephropathy (CIN) is an important complication of angiographic procedures. Hydratation with sodium chloride solution is recommended for prevention of contrast induced nephropathy after coronary angiography. Patients with diabetes mellitus have an increased risk of CIN. The aim of this study was to determine the effects of oral hydratation with mineral water versus intravenous hydratation with isotonic solution (0,9% NaCl) on renal function in diabetic patients undergoing elective coronary angiography and angioplasty. Patients and methods: The study was prospective, randomized, single-center and it included consecutive 102 patients (age 67±7,8 years, 44f/58m). Eligible patients(group 1 52 pts) were hydrated intravenous (1ml/kg/h) 6 hours before and 12 hours after coronary angiography or intervention with isotonic solution (0,9% NaCl). 50 patients (group 2) were randomized to receive oral mineral water (1ml/kg/h) 6-12 hours before and 12 hours after coronary angiography or angioplasty. All patients during procedure received non-ionic, low-osmolar contrast medium ioversol. Results: Primary endpoint of the study was the evaluation of renal function defined as creatinine clearance (Cockroft-Gault formula) before (baseline) and 72h after contrast medium administration. Baseline creatinine clearance was in the group 1: 70,3±21,22ml/min and 78,69±19,92ml/min in the group 2 (p=ns). The mean volume of contrast medium was in the group 1: 101,1±36,7ml and 110,4±45,3ml in the group 2 (p=ns). 72 hour after procedure creatinine clearance was in the group 1: 65,3±23,39ml/min and 73,5±21,94ml/min in the group 2 (p=ns). Conclusion: Our study demonstrates that the oral hydratation with mineral water and intravenous hydratation with isotonic sodium chloride solution have similar influence on renal function in diabetic patients during coronary angiography and angioplasty. Oral hydratation protects renal function with no adverse effects and at a low cost. P3191 Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition L. Testa 1, P. Agostoni 2, G.G.L. Biondi Zoccai 3,R.A.Latini 1, M.L. Laudisa 1,S.Pizzocri 1, S. Lanotte 1, N. Brambilla 1, A.P. Banning 1, F. Bedogni 1. 1 S. Ambrogio Clinical Institute, Milan, Italy; 2 University Medical Center Utrecht, Utrecht, Netherlands; 3 University of Turin, Turin, Italy Aim: Elevation of Troponin after scheduled percutaneous coronary intervention (PCI) is a recognised consequence. We sought to evaluate the prognostic significance and impact of the newly published definition of PCI-related myocardial infarction (MI) according to which any troponin elevation > 3x the upper reference limit identify a peri-procedural MI. Methods: Search of BioMedCentral, CENTRAL, mrct, and PubMed (updated May 2008). Outcomes of interest were: MACE (the composite of all cause death, MI, repeat target vessel PCI (re-pci) and coronary artery bypass grafting (CABG)); single end points were also assessed. Results: Fifteen studies have been included totalling 7578 patients. Troponin elevation, occurred in 28.7% of the procedures. The incidence of PCI-related MI according to the new definition was 14.5%. During the hospitalisation, any level of raised troponin was associated with an increased risk of MACE [OR ( ), Number needed to harm (NNH) 5], death [OR 7.16 ( ), NNH=100], MI [OR ( ), NNH=4], re-pci [OR 4.13 ( ), NNH=50]. Patients with PCI-related MI had an increased risk of death [OR ( ), NNH=100] and re-pci [OR ( ), NNH=25]. At follow up of 18 months any troponin elevation was associated with an increased risk of MACE [OR 1.48 ( ), NNH=20], death [OR 2.19 ( ), NNH=50], MI [OR 3.29 ( ), NNH=33], and re-pci [OR 1.47 ( ), NNH=25]. In patients with PCI-related MI the risk of MACE was further increased: OR 2.25 ( ), NNH=3. An increase of the troponin level below the cut-off was not associated with MACE. Conclusion: A diagnosis of MI according to the new guidelines applies to 15% of patients undergoing PCI and these patients are at high risk of further adverse events both during the hospital stay and at 18 months. P3192 Safety of balloon occlusion in angiographically normal coronary arteries S. Gloekler 1, P. Meier 2, T. Traupe 1,S.F.DeMarchi 1,C.Seiler 1. 1 Inselspital Bern, Berne, Switzerland; 2 University of Michigan Medical School, Ann Arbor, United States of America Introduction: Temporary balloon occlusion of an angiographically normal coronary artery segment may be necessary for collateral function assessment and procedures such as optical coherence tomography and angioscopy. Theoretically, this can injure the vessel wall. So far, there are no data on the safety of normalvessel coronary balloon occlusion, and accordingly, the purpose of the present study was to assess the complication rate related to such a procedure. Methods: Normal-vessel coronary balloon occlusion for seconds at low inflation pressures of 1-3 atm for collateral function assessment was performed in 426 cases between 1996 and The term normal referes to normal angiography with absence or presence of stenoses in remote vessels. In all cases, procedural complications, findings at repeat coronary angiography and clinical adverse events were recorded. Results: In 1 of 426 cases (0.2%), acute thrombus formation during guidewire probing occurred. In 150 patients (35%), re-angiography was performed with a mean follow-up of 10 months. There were no de-novo stenoses at the site of previous occlusion (0%). During long-term follow-up of >1 year and up to years, 2 patients (1.3%) developed de-novo stenoses. Of the 276 patients without re-angiography (65%), 3 (in all 1 coronary artery diseased) died (2 cardiac, 1 noncardiac death), and 2 were lost to follow-up (mean duration of 45 months). Conclusion: Brief angioplasty balloon occlusion at low inflation pressure in a normal coronary artery is a safe procedure with long-term angiographic de-novo stenosis development of approximately 1 out of 100. Considering the almost 4- year follow-up duration, it cannot be deduced whether the stenotic lesions had occurred due to the normal-vessel occlusion or due to the natural course of atherosclerosis. PROCEDURAL COMPLICATIONS OF PERCUTANEOUS CARDIAC INTERVENTIONS PART II P3193 Prevention of contrast-induced nephropathy in patients undergoing coronary angiography: comparison of two strategies S. Rocha Costa 1, M. Torres 1,P.Azevedo 1,J.Costa 1, R. Rodrigues 2, S. Nabais 1, A. Gaspar 1, S. Ribeiro 1, A. Salgado 1, A. Correia 1. 1 Sao Marcos Hospital, Braga, Portugal; 2 S. Joao Hospital, Oporto, Portugal Purpose: Contrast-induced nephropathy (CIN) is a frequent complication of coronary angiography and is associated with prolonged hospitalization and increased morbidity and mortality. Some studies have suggested that sodium bicarbonate may be superior to sodium chloride in the prevention of CIN. The aim of this study was to compare two hydration strategies (sodium chloride versus sodium bicarbonate) for preventing CIN in a subgroup of high risk patients (Pts) undergoing coronary angiography. Methods: Prospective, randomized study, conducted from April 2006 to November 2008, enrolling 201 Pts with acute coronary syndrome who were undergoing non-emergent coronary angiography. Inclusion criteria were (at least one): diabetes mellitus, age older than 70 years, serum creatinine (Cr) >1.5 mg/dl or Creatitine Clearance (CrCl) <60 ml/min. CrCl was estimated using the Cockcroft- Gault formula. Pts were randomized to receive either sodium chloride (group A Pts) or sodium bicarbonate (group B Pts) administered at 3 ml/kg/h an hour before the procedure, reduced to 1 ml/kg/h during and up to six hours after the procedure. CIN was defined as a 25% or greater decrease in CrCl up to 48 hours after contrast exposure. Results: Pts median age was 71 (interquartile range, 67-78) years and 64.7% were male. Baseline characteristics were similar in both groups, including the rate of Pts submitted to coronary intervention. Of the included Pts, 57.2% were

229 Procedural complications of percutaneous cardiac interventions Part II 529 diabetic and 21.8% had Cr>1.5 mg/dl or CrCl <60 ml/min. CIN occurred in 24.0% of Pts in group A and 16.0% in group B. Those who underwent hydration with sodium bicarbonate had a lower risk of developing CIN (RR 0:47, 95% CI , p = 0.04). In a subgroup analysis it was found that sodium bicarbonate is particularly superior to sodium chloride in diabetic Pts (12.1% vs 31.6%, p = 0.01). Conclusion: In this population, hydration with sodium bicarbonate was superior to sodium chloride for the prevention of CIN in patients with acute coronary syndrome undergoing coronary angiography, particularly in the subgroup of diabetic patients. P3194 Management and outcomes of coronary artery perforation during percutaneous coronary intervention- eight years of institutional experience A. Shimony, D. Zahger, R. Ilia, H. Glilutz, A. Shalev, C. Cafri. Soroka University Medical Center, Beer Sheva, Israel Background: Coronary perforation (CP) is a rare, sometimes lethal complication of percutaneous coronary intervention (PCI). We sought to define the incidence and outcome of CP in the current era of interventional techniques and devices. Objectives: We analyzed a cohort of patients who had CP during PCI at our hospital over an 8-year period to examine incidence, management and outcomes. Methods: All patients who had a CP as a complication of PCI between 1/ /2008 were identified retrospectively from our computerized database. Demographic, clinical and procedural data and outcome variables were obtained. CPs were classified by an interventional cardiologist according to an accepted grading score. Type I perforations were defined as an extraluminal crater without extravasation, type II by a pericardial or myocardial blush without contrast jet extravasation and type III by extravasation through a frank (1 mm) perforation or cavity spilling into an anatomic cavity chamber. Results: 57 cases (Age 67.9±11.7 years) with CP (12.3%, 52.6% and 35.1% for grade I, II, III respectively) were identified among 9568 interventions performed during the study period (0.59%). The indications for PCI were STEMI, UA/NSTEMI or stable CAD (7%, 73.7%, 19.3% respectively). Perforated vessels were LAD (24.5%), LCX (26.3%), RCA (42.1%), and SVG s (7.1%). Vessels were perforated by wires (52.6%), balloons (26.3%) and stents (21.1%). Associated lesion characteristics were chronic total occlusion (50.8%), calcified lesions (40.3%), and bifurcation lesion (35%), small diameter ( 2.5mm) (35%) and instent restenosis (7%). Four patients (7%) died in hospital, 9 (15.8%) had tamponade, 9 patients (15.8%) required urgent pericardiocentesis and 4 (7%) required urgent surgery. 13 patients (22.8%) were managed percutaneously with covered stents or balloon inflation. Those followed conservatively were younger than those who needed any intervention (PCI, pericardiocentesis and/or surgery) (65.6±12.8 vs. 72.2±7.9 years, respectively; P=0.04). All severe complications occurred with grade III perforations (death 4/20 (20%); tamponade 9/20 (45%)) but 35% (7/20) of grade III cases did not require any intervention. Most cases with grade I and II were followed conservatively. Conclusions: Most patients with grade I and II perforations can be managed conservatively while patients with grade III perforations usually require a more aggressive approach. A sizeable minority of patients with grade III perforations can be managed without any intervention. P3195 Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction: Incidence, a simple risk score, and prognosis H. Uyarel 1, M. Ergelen 2,E.Ayhan 2,E.Akkaya 2,M.Gul 2, D. Demirci 2,T.Isik 2,G.Cicek 2,D.E.Demirci 2,R.Ozturk 2. 1 Balikesir University Medical Faculty, Cardiology, Balikesir, Turkey; 2 Siyami Ersek Cardiovascular and Thoracic Surgery Center, Cardiology, Istanbul, Turkey Purpose: Patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) may be at increased risk of contrast-induced nephropathy (CIN) because of inadequate prophylaxis. We investigated the incidence, predictive factors, and outcomes of CIN after primary percutaneous coronary intervention (PCI). Methods: 2521 consecutive STEMI patients (mean age 56.5±11.8, years, 2091 male, baseline creatinine 0.97±0.3 mg/dl) undergoing primary PCI were retrospectively enrolled into the present study. CIN was defined as an increse in serum creatinine level 0.5 mg/dl or 25% from baseline within 72 hours of radiocontrast administration. Results: 630 patients (25%) developed CIN. Patients with baseline creatinine >1.5 mg/dl developed CIN more often than those with creatinine 1.5 mg/dl (45.9% versus 24% respectively; p<0.001). The following factors were predictors of CIN; diabetes mellitus (odds ratio [OR] 1.34, 95% confidence interval [CI] ; p=0.03), time to reperfusion 6 h (OR 1.46, 95% CI ; p=0.02), use of intraaortic balloon pump (OR 2.46, 95% CI ; p=0.006), radiocontrast medium volume >250 ml (OR 1.34, 95% CI ; p=0.04), age 75 years (OR 2.07, 95% CI ; p=0.001), anterior infarction (OR 1.26, 95% CI ; p=0.05). Higher in-hospital mortality rate was observed in patients developing CIN (9.5% and %1.2; p<0.001). Cox regression analysis showed that CIN was predictor of long-term cardiovascular mortality (hazard ratio, [HR] 1.90, 95% CI ; p=0.01) and major cardiovascular event (HR 1.34, 95% CI ; p=0.025). Conclusions: CIN in patients with STEMI undergoing primary PCI is associated with a markedly increased risk of major cardiovascular events, in-hospital and long-term mortality. P3196 Combined treatment with ascorbic acid and N-acetylcysteine prevents contrast-induced nephropathy in patients with acute coronary syndome undergoing coronary intervention M. Grygier 1, M. Janus 1, A. Araszkiewicz 1,J.Kowal 2, T. Mularek- Kubzdela 1, M. Lesiak 1, M. Popiel 1, A. Olasinska 1, W. Seniuk 1,S.Grajek 1. 1 Poznan University of Medical Sciences, 1st Department of Cardiology, Poznan, Poland; 2 Poznan University of Medical Sciences, Department of Clinical Pharmacology, Poznan, Poland Background: Patients with acute myocardial infarction undergoing coronary intervention (PCI) are at high-risk of contrast-induced nephropathy. Conflicting evidence suggests that administration of the antioxidant acetylcysteine (NAC) prevents the renal impairment. The action of other antioxidant agents has not been investigated in that setting. The ascorbic acid has been shown to attenuate the renal damage in some studies, however there are no data on the usage of combination of NAC and ascorbic acid especially in patients with acute coronary syndrome. Objectives: The aim of our study was to examine the role of combined treatment with NAC, ascorbic acid and fluids in comparison to NAC with fluids, and fluids alone for the prevention of contrast induced nephropathy in high-risk patients undergoing emergency PCI. Material: A prospective, single-center, randomized trial in 139 consecutive patients with acute coronary syndrome and at least one risk factor of contrastinduced nephropathy, undergoing emergency PCI was conducted. Contrastmediated nephropathy was defined by an absolute increase of serum creatinine 0.5mg/dl or relative increase of 25% measured 2-5 days after the procedure. Methods and Results: Patients were randomized to 3 groups. Group A received hydratation (0.9% saline) started just before contrast injection and continued for 12h after PCI. Group B received hydratation and high-dose NAC (1200mg iv before PCI followed by 1200mg orally twice daily for the next 2 days after procedure). Group C received hydratation, high-dose NAC and ascorbic acid (3000 mg iv before PCI followed by 2000 mg orally in the night and morning after procedure). Contrast mediated nephropathy occurred in 9 of 52 patients (17.3%) Group A, 5 of 42 patients (11.9%) Group B and 2 of 45 patients (4.4%) Group C (p<0.05). The mean serum creatinine concentration increased significantly in Group A in comparison to Group B and Group C (p<0.05). Conclusions: Prophylactic administration of high-dose NAC and ascorbic offers better protection against contrast-mediated nephropathy in high-risk patients with acute coronary syndrome undergoing coronary intervention. Further studies are needed to confirm these observations. P3197 Fate of jailed side branch during stent deployment -comparison between paclitaxel- and sirolimus -eluting stent- M. Yamawaki, T. Muramatsu, R. Tsukahara, Y. Ito, T. Sakai, H. Ishimori, K. Sasao, M. Nakano, K. Hirano, M. Araki. Saiseikai Yokohama City Eastern Hospital, Yokohama, Japan Purpose: In drug eluting stent era, long stent deployment is preferred for diffuse lesions, and concern for jailed side branch is emerging. However, little is known regarding side branch occlusion or spontaneous racanalization after Paclitaxel eluting stent (PES) deployment. The purpose of the present study is to compare the fate of jailed side branch after PES deployment with that after Sirolimuseluting stent (SES) implantation. Method: Of 527 patients treated with DES from April to December in 2007, we analyzed de novo 107 side branches jailed by PES cross-over implantation (82 patients), comparing to 107 side branches jailed by SES deployment (85 patients) at acute phase and after 8 months. TIMI flow grade in the side branch was assessed before procedure, immediately after stenting and on the follow up angiogram. Spontaneous racanalization was defined as an increase in flow from TIMI grade 0 to 1 after 8 months. The side branch was considered to exhibit delayed occlusion if its TIMI grade was 1 after the procedure, but decreased to 0 at follow up. Aggravation of side branch was identified if TIMI flow in branch was aggravated after stenting or on follow-up angiogram, compared to pre-procedure TIMI grade. Result: There was no difference in patient or lesion background between two groups. No difference was also seen in clinical outcome in hospital or after 8 month regarding the rate of stent thrombosis, cardiac death, AMI, and CABG. In main vessel, late loss was larger in PES group, compared to SES groups (0.45±0.7mm vs. 0.17±0.6mm; p<0.05), whereas TLR was similar (13% vs. 7%; NS). Regarding jailed side branch immediately after procedure, either occlusion or aggravation rate of side branch was similar between two groups (occlusion: 5.6% vs. 4.7%; NS, aggravation: 13.1% vs. 12.1%; NS). Of these side branches, flows were identified to improve (71.4% vs. 92.3%; NS), and spontaneously recanalized (50% vs, 80%; NS) after 8 month. No delayed occlusion of jailed side branch was seen in both groups. Conclusion: In spite of higher late loss in PES group, the fate of jailed side branch

230 530 Procedural complications of percutaneous cardiac interventions Part II after PES is favorable and similar with SES, suggesting PES deployment did not adversely affect side branch flow at least in 8 month. P3198 Serial follow-up of coronary artery aneurysm after drug-eluting stent implantation at 6 months and 2 years W.-J. Kim, Y.-H. Kim, D.-W. Park, S.-W. Lee, S.-C. Yun, C.-W. Lee, M.-K. Hong, S.-W. Park, S.-J. Park. Asan Medical Center, Seoul, Korea, Republic of Background: There is limited data on the long-term incidence and clinical outcomes of coronary artery aneurysm (CAA) after drug-eluting stents (DES) implantation. Methods: We enrolled 774 lesions which were treated with either sirolimuseluting stents (79%) or paclitaxel-eluting stents (21%) and received 6-month and 2-year angiographies. CAA was defined as vessel distension of 50% or more in diameter compared with the reference vessel. Results: One lesion had CAA at baseline angiography. At serial angiography, new CAA was identified in 6 and 6 lesions treated with sirolimus-(11 lesions, 84.6%) or paclitaxel-eluting stents (2 lesions, 15.4%) at 6-month and 2-year follow-up, respectively. The figure denotes the serial angiographic changes of CAA. All patients with CAA did not have ischemic symptom and were not associated with any adverse cardiac event. Figure 1. Development of coronary aneurysm after drug-eluting stents implantation Conclusions: From the novel angiographic follow-up study, the incidence of new CAA after DES placement over 2 years was 1.7%. Although the clinical course of CAA was benign to 2 years, new CAA was still observed even at 2-year angiography. P3199 Impact of coronary plaque characteristics on distal embolization during elective PCI - tissue characterization using integrated backscatter intravascular ultrasound (IB-IVUS) Y. Muraoka, S. Sonoda, M. Okazaki, Y. Otsuji. University of Occupational and Environmental Health, Kitakyushu, Japan Background: High pressure stent deployment during elective PCI is considered a major cause of distal embolization. It is important to prevent distal embolization before stent implantation procedure, however, it is unclear which plaque characteristics lead to distal embolization. Methods: We investigated 45 consecutive patients who performed elective PCI after IB-IVUS assessment. Tissue characteristics in stented segments (each 0.5mm slice) were analyzed and plaque components of each slice were divided by four categories (calcification, dense fibroisis, fibrous, and lipid). Post-procedural myocardial damage (PMD) was evaluated by analysis of corrected TIMI Frame Count, Myocardial Blush Grade, CPK and CK-MB. Results: The PMD was observed in 4 patients (9%). CAG showed similar lesion characteristics between PMD and non-pmd. Quantitative IVUS analysis of culprit lesion showed no significant difference in plaque area and lumen area between groups. Culprit plaque compositions identified with IB-IVUS did not differ significantly in dense fibrosis, fibrosis, and calcification area, although lipid area was significantly larger in PMD (p <0.05). Furthermore, Lesion length with 50% of lipid area was longer in PMD (10.4±3.4mm vs. 4.8±4.9mm, p <0.05). Max lipid area 75% and above 8mm length with 50% of lipid area was the best cut-off value for prediction of PMD, with a sensitivity of 75% and a specificity of 90%. Conclusions: Coronary plaque characterization using IB-IVUS is useful method to predict distal embolization during elective coronary stent implantation. This study may lead to prevent critical myocardial damage using distal protection devices. P3200 Women undergoing coronary angiography have increased risk of bleeding compared to men S. Simek 1, P. Widimsky 2, Z. Motovska 2,P.Kala 3,R.Pudil 4, H. Skalicka 1,P.Kuchynka 1,R.Petr 2,F.Holm 4, M. Aschermann 1 on behalf of PRAGUE-8 trial investigators. 1 2nd Med. Dep. of Cardiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic; 2 Clinic of Cardiology, Charles University in Prague, Third Faculty of Medicine, Prague, Czech Republic; 3 Cardiology clinic, University Hospital Bohunice, Brno, Czech Republic; 4 Cardiocenter, University hospital, Hradec Kralove, Czech Republic Purpose: To determine gender differences in characteristics and outcomes of patients with stable angina undergoing elective coronary angiography. Methods: We compared the characteristics and in hospital outcomes of 377 women and 651 men with stable angina enrolled in the randomized multicenter PRAGUE-8 trial testing effect of routine clopidogrel pretreatment >8h before planned elective coronary angiography. Results: Women were significantly older than men (mean age 67 vs. 64 years, P<0.001). Hypertension was more prevalent in women (81% vs. 65%, P<0.001), but the diabetes and hyperlipoproteinaemia were similarly present in both genders. Prior cardiac surgery or PCI and previous myocardial infarction (MI) were less common among women (15% vs. 31%, P=0.001 and 17% vs. 34%, P<0.001, respectively). Coronary angiography revealed less severe coronary artery disease in women than in men, with 2-, or 3-vessel disease more often found in men (52% vs. 28%, P<0.001). PCI was performed in 25.5% of women and in 31% of men (P=0.058). Stents were placed in 83% of PCIs in both groups. Inhospital adverse outcomes including death, post-pci MI, emergency bypass surgery, abrupt closure, stroke, appeared in 5.1% of men and 2.4% of women (P=0.036). Non serious bleeding was observed in 4.5% of women and in 0.8% of men (P<0.001), serious bleeding was observed in 0.5% of women and in 0.15% of men (P=0.28). Conclusions: Women with stable coronary syndrome are older than men and have more comorbidity. The worse outcome with PCI in men in this group may be related to higher severity of CHD in men. Women had higher risk of bleeding with clopigogrel pretreatment >8h before elective CAG compared to men. The higher rate of bleeding complications with clopidogrel pretreatment observed in the PRAGUE-8 study was mainly caused by higher bleeding in women. Supported by the project MSM P3201 Multivessel PCI in stable angina, is there an avoidable cost to the myocardium? A.S.P. Sharp, R.T. Gerber, A. Ielasi, M. Ferraro, A. Colombo. San Raffaele Hospital, Milan, Italy Background: If a patient has stable angina and more than one target vessel for treatment, it remains unclear whether there is any potential downside to treating all these vessels in one procedure. We examined a cohort of patients who underwent two-vessel (TV) PCI for stable angina to see whether they were more likely to suffer a peri-procedural rise in CKMB than those undergoing single vessel (SV) PCI and if so, to establish whether such a rise was proportionate. Methods: We examined patients undergoing elective PCI for stable angina at a single centre in Milan, Italy. CKMB was measured the morning of the procedure (pre- sample) and the morning after the procedure (post-sample). Rise in CKMB was then adjusted for potentially confounding demographic and procedural factors using a multivariate linear regression model. Results: Of 198 patients assessed, 86.8% were male, mean age was 63.0 yrs and 16.7% were diabetic. A CTO procedure was performed in 14.9% of cases, whilst 20.0% underwent a bifurcation procedure. Mean length of stent used per patient was 27.9mm. TV procedures involved more stent (30.9mm vs 25.2; p=0.02) and TV procedures were more likely to involve bifurcations (27 vs 14%;p=0.04), but otherwise the groups were evenly balanced. On univariate analysis, TV PCI was associated with a significantly increased CKMB rise (Mean TV CKMB 12.5 ± SD22.0 vs. Mean SV CKMB 3.5 ± SD9.3; p<0.0001). After adjustment for age, sex, diabetes, CTO procedure, bifurcation procedure and length of stent used, multi-vessel PCI was associated with a 3.7 times increased risk of a rise in CKMB (p<0.0001). Conclusion: These data suggest that the degree and frequency of enzyme rise associated with multi-vessel PCI procedures is out of proportion to the number of vessels treated. A randomized trial examining the risk of peri-procedural MI from staged, versus non-staged multi-vessel PCI in stable angina should be considered. P3202 Factors influencing the use of femoral route by default radial operators in coronary angioplasty may contribute to increased access site bleeding complication I. Mahmood, M.M. Uddin, T.D. Kinnaird, R.A. Anderson. University Hospital of Wales, Cardiff, United Kingdom Background: Percutaneous Coronary Intervention (PCI) via the radial route causes less access site bleeding complication than the femoral route. However, not all PCI cases are suitable for radial approach. Many of the bleeding risk fac-

231 Procedural complications of percutaneous cardiac interventions Part II / Intervention: Pre-clinical studies 531 tors may be present in cases undertaken for clinical or technical reasons from the femoral route by default radial operators. In this study, we evaluated the profiles of patients by access route for radial operators. Methods: Data was obtained from the British Cardiovascular Interventional Society (BCIS) Central Cardiac Audit Database (CCAD). All cases performed by four experienced default radial operators in a tertiary cardiac centre from were included (n=1392). Data was analyzed using Statistical Package for Social Sciences (SPSS) software. Results: The femoral route was used in 25.2% of cases (n=351). Such cases were more likely to be female (41% vs 21.9%, p<0.001), older (65.1 vs 63.1 years, p=0.003) and weigh less (80.0 vs 84.2 kg, p<0.001) than radial cases. The PCI was more complex with larger sheath sizes (14.3% vs 0.5%, p<0.001), more left main stem (6.7% vs 4.0%, p<0.001), graft (9.9% vs 3.3%, p<0.001) and multi-vessel intervention (8.1% vs 4.9%, p=0.033), and a greater proportion of emergency cases (10.5% vs 9.8%, p=0.047) requiring circulatory support (2.3% vs 0.5%, p=0.002). Interestingly, despite cases complexity, glycoprotein inhibitors were used less frequently in femoral cases (26.5% vs 36.8%, p<0.001). See Figure 1. Figure 1. Odds Ratio (95% Confidence Interval) Conclusion: Many of the risk factors for access site bleeding are present in cases performed femorally by radial operators, and this may significantly influence the operator(s) overall bleeding complication. Access site bleeding is likely to remain a problem and require further strategies such as alternative pharmacotherapy. INTERVENTION: PRE-CLINICAL STUDIES P3203 Modification of contrast medium-induced renal tubular cell apoptosis via endoplasmic reticulum stress response C.K. Chiang 1,C.T.Wu 2, M.L. Sheu 2,S.H.Liu 2. 1 National Taiwan University Hospital, Taipei, Taiwan; 2 Institute of Toxicology, Nationa Taiwan University, Taipei, Taiwan Purpose: Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of contrast mediuminduced nephropathy (CMIN). Endoplasmic reticulum (ER) is primarily recognized as the site of synthesis and folding proteins. When the intracellular environment disrupted, ER stress and individual unfolded protein responses turned on. As the cells failed to restore their homeostasis, apoptosis would be committed. This study was undertaken to examine whether ER stress response participated in CM-induced renal tubular cells apoptosis. Methods: Normal rat kidney (NRK) 52E cell line was treated by CM at different time points and dosages to study the participants of ER stress-induced renal cell apoptosis in vitro. Unilateral ureteral obstruction (UUO) rat model was used to evaluate the role of ER stress response in CM exposure kidney. Results: We found CM could induce expression of endogenous ER stress markers, glucose-regulated protein 78 (GRP78), GRP94 and Caspase 12 cleavage in normal rat kidney (NRK 52E) cell line. Double-stranded RNA-dependent protein kinase (PKR)-like ER kinase (PERK) and eukaryotic translation initiation factor-2α (eif-2α) were phosphorelated and attenuated these signals by pretreatment with salubrinal promoted cells survival. Activating transcription factor-6 (ATF 6) and camp response element-binding transcription factor (C/EBP) homologous protein (CHOP) were also activated and then modulated the signals by 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF)suppressed cells apoptosis in early time. Moreover, although inositol-requiring 1-α (IRE-1α) and X-box-binding protein 1 (XBP- 1) expression were increased, treated c-jun N-terminal kinase (JNK) inhibitor SP failed to suppress cells apoptosis. Knock down GRP78 expression prompted cell apoptosis suggest that GRP78 could play a protection roles during unfolding protein response. Furthermore, we found CM intravenous injection would additively induce ER stress response in UUO model. Conclusions: This is the first time that we demonstrate the activation of ER stress response play a role in CM-induced kidney cytotoxicity. P3204 Assessment of a new biodegradable drug eluting stent for the inhibition of neovascularisation and neointimal hyperplasia: an experimental study with Optical Coherence Tomography K. Toutouzas 1, A. Synetos 1, A. Karanasos 1,E.Tsiamis 1, E. Stefanadi 1,N.Kipshidze 2, C. Stefanadis 1. 1 Hippokration General Hospital of Athens, Athens, Greece; 2 Cardiovascular Research Foundation, New York, United States of America Background: Neovascularization seems to play an important role in the development of the vulnerable plaque. Vascular endothelial growth factor (VEGF) appears to be the most important mediator of neovascularisation. We assumed that inhibition of VEGF, using local delivery of bevacizumab, a monoclonal antibody specific for VEGF, could affect neovascularization and intimal hyperplasia in hypercholesterolemic rabbits. Methods: We used 10 New Zealand white rabbits under atherogenic diet for 3 weeks. Eleven bevacizumab-eluting stents were implanted in the distal aorta. The stents were coated with a biodegradable polymer which was loaded with bevacizumab, after immersion into a solution of 4 ml of the drug. The control group consisted of 7 New Zealand white rabbits undergoing implantation of 7 stents with biodegradable polymer not loaded with bevacizumab. All animals were treated with aspirin and clopidogrel for 4 weeks. Follow-up angiography and Optical Coherence Tomography (OCT) study were performed at 4 weeks. OCT images of each stent taken at 1 mm intervals were analyzed and each strut was examined for apposition. A strut was defined as embedded when it was buried in the intima for more than half its thickness, protruding when apposed to the intima but not embedded, and malapposed when there was no intimal contact. Mean neointimal area for each arterial segment was measured. Results: Angiography in all stented arteries revealed no acute or subacute thrombosis or restenosis. OCT image acquisition was successful in all cases. OCT revealed no severe stenosis or thrombus. We acquired 121 cross-sectional images from 110 mm of 11 stents in 10 arteries in the bevacizumab-eluting stent treated group and 77 cross-sectional images from 70 mm of 7 stents in 7 arteries in the control group. From the total of 1103 struts analyzed in the bevacizumabeluting stent treated group, 1075 (97.5%) were embedded, while only 28 (2.5%) struts were protruding and none malapposed. In the control group, 710 struts were analyzed, of which 697 were embedded (98.1%), 13 protruding (1.9%), and none malapposed (p=ns). Mean neointimal area in the bevacizumab group was 0.15±0.09 mm 2 comprising 2.45% of the lumen area, versus 0.78±0.21 mm 2 and 14.3% respectively in the control group (p <0.001). Maximal intimal thickness was significantly lower in the bevacizumab group compared to the control (60±11 μm versus 135±7 μm, p<0.001). Conclusions: This study demonstrated the safety and effectiveness of a new biodegradable eluting stent in animal model. Further studies in humans are required for the evaluation of the safety and effectiveness. P3205 Early endothelialization in Paclitaxel eluting stents is similar to other drug-eluting and bare metal stents but shows transient endothelial dysfunction O. Sorop, M. Van Den Heuvel, Y. Onuma, A.H.J. Danser, D.J. Duncker, W.J. Van Der Giessen, H.M.M. Van Beusekom. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Purpose: Drug eluting stents (DES) have been proven superior to bare metal stents (BMS) in preventing restenosis. However, some DES have been associated with late stent thrombosis and endothelial dysfunction. Delayed vascular healing and re-endothelialization have been proposed as possible explanations. Methods: In swine coronary arteries, we compared three DES eluting Tacrolimus (TES), Sirolimus (SES) and Paclitaxel (PES) and BMS with respect to early reendothelialization of the stent struts and endothelial function both within and distal to the stent. The stents were implanted in non-injured coronary arteries with a stent/artery ratio of 1.1. Animals were followed for 5 (early) and 28 days. Reendothelialization was assessed at 5 days (15 BMS, 13 TES, 13 SES, 14 PES) by scanning electron microscopy (SEM). Endothelial function was assessed instent by enos and vwf expression at 28 days and distal by in vitro vasomotor tests at 5 and 28 days (4 BMS, 12 TES, 11 SES and 12 PES). Results: All stents showed extensive re-endothelialization at 5 days (SEM), with-

232 532 Intervention: Pre-clinical studies out significant differences between the different DES (TES 82.6±13.2%, SES 89.7±14.3%, PES 76.3±26.7%) and BMS (95.5±6.4%), (Fig. 1A). However, assessment of in-stent endothelial function showed a diminished enos expression in PES at 28 days. Microvascular vasomotor tests also showed a decreased contribution of NO to the endothelial-dependent dilation distal to PES at 5 days (*, # P<0.05 L-NAME vs Control at 5, 28 days, **P<0.05 effect of L-NAME at 5 days PES vs TES) which improved at 28 days (Fig. 1B). Conclusion: All DES show high re-endothelialization rates as early as 5 days post stenting similar to BMS. However, PES did affect endothelial function both within and distal to the stent as late as 28 days. P3206 Inhibition of coronary neointimal hyperplasia in swine using a novel zotarolimus-eluting balloon catheter B. Cremers 1, J. Toner 2,L.B.Schwartz 2, R. Von Oepen 2, U. Speck 3, N. Kaufels 3, D. Mahnkopf 4, M. Boehm 1,B.Scheller 1. 1 Universitaetsklinikum der Saarlandes, Homburg, Germany; 2 Abbott Laboratories, Illinois, United States of America; 3 Charite - Campus Mitte, Humboldt-Universitaet, Berlin, Germany; 4 IMTM GmbH, Immune Technologies & Medicine, Rottmersleben, Germany Background: Non-stent-based delivery of antiproliferative agents using drugcoated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic nature of the antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery since effective uptake into the vessel wall can be expected. The aim of the present study was to evaluate the safety and efficacy of a novel zotarolimus-eluting balloon catheter (ZEB) in comparison to a zotarolimus-eluting stent (ZES) on neointimal proliferation in the porcine coronary overstretch model. Methods: Eighty-four stents (diameters, 3.0 and 3.5 mm; length, 15 mm) were implanted in LAD and Cx of 42 domestic pigs: Control (polymer-coated stent without drug, implanted with uncoated PTCA catheter, n=56); ZES (stent coated with zotarolimus in polymer, implanted with uncoated PTCA catheter, n=14); ZEB (polymer-coated stent without drug, implanted with zotarolimus-coated PTCA catheter, n=14). After four weeks, quantitative angiography and histomorphometry of the stented arteries was performed. Results: After 28 days the zotarolimus-eluting stent (ZES) led to a reduction of neointimal area from 4.32±1.45 mm 2 to 3.32±1.11 mm 2 (p=0.019 vs. Control). The effect of neointimal inhibition was even more pronounced with the novel zotarolimus-eluting balloon (ZEB) (2.79±1.43 mm 2, p=0.001 vs. Control). Inflammation score was significantly reduced in vessels treated with the ZEB (to 0.75±0.86 from 1.45±0.94 (p=0.013 vs. Control) and 1.65±0.90 (p=0.012 vs. ZES)). There were no thrombotic complications and no other significant adverse events in the treatment groups during or after coronary interventions. Conclusion: Zotarolimus-coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary overstretch model. Inflammation scores were significantly reduced after treatment with the ZEB. Zotarolimus balloon coating might be a novel option in preveting and treating vascular restenosis. Table 1 IS BMS (mm) DES-ST (mm) P 1 0,420±0,031 0,298±0,013 0, ,655±0,036 0,438±0,017 0,0001 (11,07±0,37% vs. 5,51±1,8%). Inflammatory cell infiltrates were significantly reduced. Conclusions: The IRIST stent shows a therapeutic benefit in the prevention of in-stent coronary hyperplasia after one month of deployment in the porcine model of coronary restenosis. P3208 Serum hs-crp levels predict plaque rupture identified by optical coherence tomography, in acute coronary syndromes or stable angina K. Bouki, M. Katsafados, D. Chatzopoulos, S. Psychari, H. Gika, E. Kapsali, H. Sakali, K. Paravolidakis, G. Liakos, T. Apostolou. General Hospital of Nikea, Pireaus, Greece Purpose: The purpose of this study was to evaluate the relation between hs-crp levels and culprit lesion morphology identified by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS) or stable angina (SA). Methods: Thirty-one patients who underwent percutaneous coronary intervention (PCI) because of ACS (19 patients) or SA (12 patients) were enrolled in this study. OCT images were taken in all the patients before any intervention and were analyzed using validated criteria for plaque characteristics. Serum hs-crp was also measured prior to the procedure. Results: Analyzable OCT images were obtained in all the patients. Plaque rupture was detected more frequently in ACS patients (Figure 1) compared with SA patients, (68% vs. 0%, p<0.001). The fibrous cap of the culprit lesion was significantly thinner in ACS patients compared with the others (56.0±22.3μm vs ±18.8μm, p<0.001). Higher levels of hs-crp were found in patients with plaque rupture (median value: 30.6mg/L vs. 2.6mg/L, p<0.001). Moreover, an inverse correlation was observed between hs-crp and culprit lesion fibrous cap thickness (r=-0.52, p<0.01). Logistic regression analysis revealed that elevated hs-crp levels correlated with the presence of plaque rupture, (p<0.05; odds ratio 1.19; 95% CI, 1.02 to 1.37). Finally, concentration of hs-crp>6.4mg/l was used to predict ruptured plaque identified by OCT, with a sensitivity of 85% and a specificity of 78% (area under the receiver-operating characteristics curve=0.93, p<0.001). P3207 A new DES with antiinflammatory and antiproliferative activity reduces in-stent restenosis. Experimental studies in the pig coronary model L. Casani 1, O. Juan 1,A.Serra 2, L. Duocastella 3,M.Molina 3, J. Garcia-Rafanell 4, L. Badimon 1. 1 Barcelona Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2 Hospital del Mar, Barcelona, Spain; 3 Iberhospitex SA, Barcelona, Spain; 4 URIACH, SA, Barcelona, Spain Objectives: Despite the successful use of bare metal stents (BMS) for treating coronary artery stenotic lesions, restenosis remains the main cause of reintervention. The use of drug-eluting stents (DES) has proved a marked reduction in restenosis and reintervention. However inflammation, inhibition of reendothelisation and stent thrombosis are still generating clinical complications. The objective of the study was to evaluate the effect of a new DES (IRIST), based on a polymer with antiplatelet and antiinflamatory activities (triflusal) which elutes a dosedependently modulated concentration of simvastatin to preserve endothelial cell proliferation while inhibiting smooth muscle cell proliferation. Methods: Pigs were treated with AAS and Clopidogrel before the deployment of the stent and until completion of follow up. Monitorization of the anti-aggregation status was performed throughout the study by LTA. A BMS (Apolo, IHT, Barcelona, Spain) and the IRIST with the same platform were directly compared. The placement of the stents was randomly allocated to the left anterior descending (LAD), circumflex (CX) or right coronary artery (CR) and deployed with mild oversizing model (ratio artery/stent: 1:2). Twenty eight days after stent implantation restenosis was morphometrically evaluated. Heart and coronaries were fixed in situ with formalin, later excised, embedded in resin and cut in successive slices (6μm). Histological cuts were stained with modified H/E to calculate the % of stenosis and neointima thickness and evaluation was performed for each strut of the stent and at every injury score (IS) following the Schwartz score. Results: IRIST induced a significantly (P<0, 0001) reduced neointimal hyperplasia with respect to BMS for the same injury scores (see table) and a significantly (P<0,0001) reduced luminal encroachment in the pig coronary arteries Plaque rupture with flap and thrombus Conclusions: Serum hs-crp seems to be related to culprit lesion characteristics detected by OCT. Elevated hs-crp can predict the presence of plaque rupture. P3209 Endothelial progenitor cell (EPC) capture in stented porcine coronary arteries increases endothelialization but does not affect intimal thickening H.M.M. Van Beusekom 1,G.Ertas 2, O. Sorop 1, I. Peters- Krabbendam 1, W.J. Van Der Giessen 3. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Cardiology - Kocaeli University Medical Faculty, Kocaeli, Turkey; 3 Erasmus MC Thoraxcenter and ICIN-KNAW, Rotterdam, Utrecht, Netherlands The introduction of drug eluting stents (DES) has reduced the need for target lesion revascularization, but their effects on healing, inflammation and vascular dysfunction has emphasized the need to design strategies that improve current DES. One such strategy is to improve endothelialization (EC) by capturing CD34- positive endothelial progenitor cells (EPC) by the stent surface, an approach supposed to improve healing and reduce neointimal thickening (NIT). The first human clinical trial using coronary EPC capture stents showed stent safety, but (though underpowered) NIT was not reduced as compared to bare metal stents (BMS). In order to understand these responses we studied the coronary response to the EPC capture stent between 48 hours and 90 days. Methods & Results: The stent, coated with a murine anti-human monoclonal CD34 antibody, was assessed in normal coronary arteries of swine for a) % EC

233 Intervention: Pre-clinical studies 533 at 2, 5 and 7 days and b) NIT at 28 and 90 days in comparison to BMS (n=12 per stent). The main finding was that EPC capture-stents demonstrated a higher % EC at 2 days. This reached statistical significance at 5 days following stent placement with a difference of 10%. Morphometry of NIT at 28 and 90 days showed no significant differences for EPC (339±56 and 169±49μm) and BMS (210±18 and 185±31μm) when corrected for parameters of vascular injury (0.7±0.1 and 0.1±0.04). Efficacy of drug eluting stents (DES) to reduce neointimal thickness (NIT) varies between clinical reports. Alarmingly, some studies show a slow but steady increase of NIT in time. This is probably determined by positive drug effects versus irritant effects of permanent or coating degradation products. Thus, for each stent, these factors must be carefully balanced for efficient and stable long-term NIT reduction. We assessed in polylactide-polyglycolide (PLGA)-Tacrolimus (T) eluting stents how the balance between drug elution and coating degradation affects NIT in Yucatan swine coronary arteries up to 1 year after stenting. Methods & Results: We compared fast-degrading high dose T (F-TH, 2 μg/mm 2, N=21), slow degrading low dose T (S-TL, 1 μg/mm 2, N=21) and slow degrading PLGA-only coated stents (S-P, N=21) to BMS (N=14). Arteries were pre-injured with a balloon/artery ratio of 1.1 to 1.3. Then, stents were implanted at that site with a stent/artery ratio of 1.1 and a follow-up period of 90 to 365 days. Morphometry at 90 days indicated that NIT in both DES was reduced compared to BMS and S-P (Fig, P=0.05 ANOVA). PLGA degradation induced inflammation in S-P, but this was effectively suppressed in both DES. At 180 days, S-TL showed >50% catch-up of NIT, becoming similar to S-P. And while F-TH showed a stable and low NIT, BMS showed NIT regression (BMS vs S-P, P<0.015; F-TH vs S-P, P<0.03). At 1 year both DES and S-P were similar to BMS. High % EC on stent struts after 2 days. Conclusion: The EPC capture stent increases early EC, but this does not affect thickness and composition of the neointima as compared to BMS at 28 and 90 days. Clinical Relevance: Increasing early re-ec does not affect NIT in swine and this may explain the lack of effect on restenosis in clinical trials. We propose that only strategies that improve EC function may be more effective. Thus, EPC capture may increase safety but not efficacy. P3210 Only specific coronary drug-eluting stents interfere with distal microvascular function M. Van Den Heuvel, O. Sorop, W.W. Batenburg, S.C. Krabbendam, H.M.M. Van Beusekom, D.J. Duncker, A.H.J. Danser, W.J. Van Der Giessen. Erasmus MC, Rotterdam, Netherlands Purpose: Coronary endothelial dysfunction has been reported in patients six months after drug eluting stent (DES) implantation. However, the effects of DES on the microvasculature downstream of the stent have not been studied to date. Therefore, in this animal study, we assessed the acute effects of DES drugs and the chronic effects of sirolimus-eluting and paclitaxel-eluting stent versus bare metal stent (SES, PES vs. BMS) implantation on different components of microvascular function in both in vivo and in vitro settings. Methods: To study the acute effects of DES drugs on microvascular function, coronary microvessels were incubated for 30 minutes with two different concentrations of sirolimus and paclitaxel (0.5ng/ml and 5.0ng/ml) and function was measured in vitro as described below. To examine the chronic effects of DES on distal microvascular function, SES, PES and BMS were implanted in eight pigs. After five weeks, changes in distal vascular flow induced by different doses of intracoronary administered bradykinin (BK) and nitrates were measured. Afterwards, epicardial microvessels ( 300μm diameter) distal from the stent were isolated. In vitro, endothelium-dependent and -independent vasodilations to different doses of BK and nitrates were assessed, as well as vasoconstriction to endothelin-1 (ET- 1). In addition, after use of a NO-synthase blocker (L-NAME), contribution of NO to BK-induced vasodilation was examined. Results: Acutely, both concentrations of sirolimus and paclitaxel did not affect BK-induced vasodilation. Chronically, both DES types did not alter coronary flow velocities distal from the stent, indicating intact microvascular function. However, in detailed in vitro studies, PES showed a reduced BK-response after inhibition of NO-synthesis as compared to BMS and SES (P<0.01). BK-induced vasodilatation, ET-1-induced vasoconstriction and vascular smooth muscle cell function were unaffected by PES. SES implantation did not affect any component of distal microvascular function. Conclusions: Clinically relevant plasma concentrations of DES drugs did not affect microvascular function acutely. In addition, after chronic SES and PES implantation, the distal microvasculature did not show evidence of endothelial dysfunction. However, PES altered distal endothelial microvascular function under conditions of reduced NO-bioavailability. In clinical reports, DES affect coronary function in atherosclerotic patients. This study indicates that in particular PES might be potentially harmful with regard to local cardiac perfusion downstream of the stent in patients with endothelial dysfunction. P3211 The balance between polymer degradation and drug concentration determines the neointimal response to stents eluting Tacrolimus from a biodegradable polymer coating up to 1 year post stenting H.M.M. Van Beusekom 1, O. Sorop 1,J.Wentzel 1, D.J. Duncker 1, W.J. Van Der Giessen 2. 1 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 2 Erasmus MC Thoraxcenter and ICIN-KNAW, Rotterdam, Utrecht, Netherlands Conclusion: Tacrolimus can suppress the pro-inflammatory effects of PLGA degradation at a high enough concentration. When during elution and degradation the balance becomes unfavorable, such as in S-TL, irritant effects start to outweigh the drug effects resulting in late catch-up. At 1 year, when all coating has disappeared, all stents are similar to BMS. P3212 Beneficial gene profile after local rosiglitazone treatment of in-stent-restenosis in a porcine coronary model K. Pels, S.I. Utchil, D. Boesel, J. Klinowski, C. Loddenkemper, H.P. Schultheiss, C. Dang-Heine. Charite - Campus Benjamin Franklin, Berlin, Germany Purpose: Rosiglitazone activates the transcription factor PPAR-gamma, which is involved in the control of blood glucose, lipid metabolism, inflammation, apoptosis and cell proliferation. Systemic rosiglitazone treatment has shown to reduce coronary restenosis but may be associated with an increased risk for the development of heart failure. Herein, we investigated the expression of genes involved in migration, apoptosis and cell proliferation after local intracoronary rosiglitazone treatment using Rosiglitazone-coated drug eluting stents (RDES) in comparison to Bare Metal Stents (BMS). Methods: In 5 pigs, RDES and BMS were randomly implanted in coronary arteries with an overexpansion (ballon/stent to artery ratio :1) in order to induce inflammation and neointimal hyperplasia. The expression of genes regulating apoptosis (GADD45) and proliferation genes (p27kip1), MMP9 and its inhibitor TIMP1 were evaluated after 3 months by quantitative real time RT-PCR (qpcr) and Western blot. Results: In arteries with RDES, the pro-apoptotic gene GADD45 and antiproliferative gene p27kip1 were significantly up-regulated compared to arteries with BMS. The matrix-metalloproteinase-9 (MMP9) facilitating cell invasion, was downregulated and its inhibitor TIMP1 overexpressed by rosiglitazone, in contrast to in RDES. Expression of p27kip1 protein and MMP9 is enhanced by rosiglitazone RDES compared to BMS. Conclusion: The gene expression profile of local Rosglitazone-treatment suggests a reduction of intracoronary cell invasion and proliferation after arterial injury and this may explain in addition to the previously from our group described anti-inflammatory effect the observed reduced in-stent-restenosis following RDES implantation. The Rosiglitazone-DES could therefore improve the current treatment of coronary artery disease and restenosis, wich targets mainly only one pathomechanism.

234 534 Procedural complications of percutaneous cardiac interventions Part III. Complications PROCEDURAL COMPLICATIONS OF PERCUTANEOUS CARDIAC INTERVENTIONS PART III. COMPLICATIONS P3213 Impact of heparin dosage on bleeding in primary PCI for ST-elevation myocardial infarction R.S. Hermanides, J.P. Ottervanger, J.H.E. Dambrink, M.J. De Boer, J.C.A. Hoorntje, A.T.M. Gosselink, H. Suryapranata, A.W.J. Van T Hof. Isala Klinieken, Zwolle, Netherlands Purpose: There is limited information about the influence of dosage of unfractionated heparin (UFH) on bleeding and prognosis after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Methods: A large scale, prospective, observational study was performed between 1991 and 2004 of all consecutive STEMI patients who underwent primary PCI. High dose UFH was defined as IU, low dose as 5000 IU. Bleeding was classified according to the TIMI criteria. Patients who had cardiac surgery within 48 hours were excluded. Results: Data on bleeding <48 hours were available in 4717 patients (96%). A total of 49 patients (3%) in the high dose UFH group had major bleeding versus 31 patients (1%) in the low dose UFH group (p<0.001). Minor bleeding was observed in 214 patients (13%) in the high dose UFH group versus 134 patients (4.3%) in the low dose UFH group (p<0.001). After multivariable analyses patients in the high dose UFH group had an increased risk of both major bleeding (OR 2.66, 95% CI ) and minor bleeding (OR 3.22, 95% CI ). High dose UFH was associated with an increased risk of death at one year (HR 1.45, 95% CI ). Conclusion: In patients with primary PCI, high dose heparin is associated with increased risk of bleeding and a higher mortality. P3214 Determinants of bleeding in ST-elevation myocardial infarction patients treated with triple antiplatelet therapy - a subanalysis of the ONTIME II study R.S. Hermanides 1, J.P. Ottervanger 1, T. Dill 2, G. Van Houwelingen 3, J.M. Ten Berg 4,C.Hamm 2, A.W.J. Van T Hof 1. 1 Isala Klinieken, Zwolle, Netherlands; 2 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 3 Medisch Spectrum Twente, Enschede, Netherlands; 4 St Antonius Hospital, Nieuwegein, Netherlands Purpose: Bleeding is currently the most common non-cardiac complication in patients treated for ST-elevation myocardial infarction (STEMI). We investigated the determinants of bleeding in patients undergoing primary percutaneous coronary intervention (PCI) treated with triple antiplatelet therapy and whether bleeding is related to prognosis. Methods: We undertook a subanalysis of the double-blind, multicenter, randomised, placebo-controlled ONTIME II trial. All of the 1398 ONTIME patients, were enrolled in this substudy and 1339 patients (95.8%) had clinical follow up. Bleeding was defined according to the TIMI criteria. Results: Bleeding (minor and major) was observed in 111 patients (8.3%). Independent predictors of bleeding were age (OR 1.03, 95% CI ), killip class > 1 (OR 1.31, 95% CI ), IABP (OR 6.90, 95% CI ), smoking (OR % CI ) and three vessel disease (OR 2.58, 95% CI ). Independent predictors of non-cabg related bleeding were age (OR 1.05, 95% CI ), killip class >1 (OR 1.83, 95% CI ) and IABP (OR 4.08, 95% CI ). Bleeding showed a trend towards an increased risk of death at 30 days (HR 1.67, 95% CI ). Conclusion: Advanced age, acute heart failure and IABP are important predictors of overall bleeding and non-cabg related bleeding in STEMI patients. Antithrombotic and antiplatelet regiments should be given cautiously in these patients. P3215 Do not miss the presence of deep echo attenuation without calcification on intravascular ultrasound N. Mitsuba, H. Teragawa, K. Nishioka, S. Mikami, Y. Fujii, N. Fujimura, T. Okada, F. Tadehara, Y. Kihara. Hiroshima University, Hiroshima, Japan Background: Previous studies have reported a correlation between periprocedural myonecrosis after percutaneous coronary intervention (PCI) and in-hospital cardiovascular accidents. Therefore, it is important to predict the occurrence of periprocedural myonecrosis after PCI. However, it is not clear what factors are associated with periprocedural myonecrosis after PCI. Therefore, we investigated clinical as well as angiographic data and intravascular ultrasonographic (IVUS) findings for a possible association with periprocedural myonecrosis after PCI. Methods: Thirty-four consecutive patients (23 men, mean age 65 y) with coronary artery disease who underwent PCI with IVUS were enrolled. Patients with acute myocardial infarction having complex lesions such as chronic total occlusion, bifurcation lesion, and severely calcified lesion with suboptimal findings were excluded. Besides the routine IVUS measurements, we assessed the presence of deep echo attenuation (DEA) without calcification, which was defined as a lesion with DEA in spite of severe calcification within the stenotic lesion. Periprocedural myonecrosis was defined as troponin T elevation (>0.01 ng/ml) measured 24 h after PCI. Patients were divided into two groups based on the presence (Group I) or absence (Group II) of periprocedural myonecrosis. Results: Sixteen patients (47%) had periprocedural myonecrosis. Patient characteristics, including the frequencies of coronary risk factors, taking statins, and acute coronary syndrome, were similar in the two groups. Angiography showed that the distribution of the target vessel was different in the two groups (p < 0.05). IVUS showed that DEA was significantly more frequent in Group I than in Group II (85% vs. 25%, p < 0.01) and the presence of positive remodeling tended to be higher in Group I than in Group II (46% vs. 14%, p = 0.07). Logistic regression analysis demonstrated that the presence of DEA (kai2 = 6.83, p < 0.01) was the only predictor of periprocedural myonecrosis after PCI. Conclusions: Our data suggest that the presence of DEA was a significant factor in the development of periprocedural myonecrosis after PCI. Thus, attention needs to be paid to the presence of DEA on IVUS before PCI. P3216 Can we estimate safe doses of contrast media during PCI without risk of contrast media induced nephropathy H.J. Yoon, H.T. Kim, I.C. Kim, H.S. Park, Y.K. Cho, H. Kim, C.W. Nam, S.H. Hur, Y.N. Kim, K.B. Kim. Keimyung University DongSan Hospital, Daegu, Korea, Republic of Background: The systemic exposure of contrast agent is strongly associated with risk of contrast induced nephropathy (CIN) and it can be quantitatively expressed contrast media (CM) dose-to-estimated glomerular filtration rate (egfr). Purpose: The aim of this study is to evaluate clinical and laboratory risk factors of contrast media induced nephropathy (CIN) and to find relative safe dose of contrast media according to individual egfr level. Methods: In this single center prospective study, 226 consecutive patients who underwent elective percutaneous coronary intervention were enrolled from April 2008 to January Before and 24/48hr after PCI, serum creatinine level was checked. CIN was defined as a 25% elevation or an absolute increase of > 0.5mg/dL (>44umol/L) in the serum creatinine level compare to the baseline. We estimated systemic exposed contrast agent amount by contrast medium dose (grams iodine; g I) to egfr (ml/min) ratio (g-i/egfr). Results: Overall, CIN occurred in 16 patients (7.1%). On univariate analysis, diabetes and hypertension, dipstick urine protein positive finding, higher BUN, Cr, homocysteine level, uric acid, egfr and g-i/egfr level were significantly associated with CIN. Multivariate logistic regression analysis identified two significant parameters; patients who developed CIN demonstrated significantly higher g-i/egfr and homocysteine (see Table). Furthermore, additional analysis of patients grouped by quartiles based on g-i/egfr level: Group 1, g-i/egfr 0.75 (n=56); Group 2, 0.75< g-i/egfr 1.04 (n=56); Group 3, 1.04 < g-i/egfr 1.42 (n=57); Group 4, g-i/egfr > 1.42 (n=56), Group 1 (1.8%) and Group 2 (0%) showed very low incidence for CIN, but Group 3 (3.5%) and Group 4 (23.2%) showed gradual increased occurence of CIN (p < 0.001). Multivariate anaylsis for CIN Odd raio p value 95% CI for Exp g-i/egfr Homocysteine Conclusions: Higher systemic exposure of contrast media compared to egfr level and homocysteine level are valuable predictor of CIN. Contrast media dose to egfr (g-i/egfr) appear to be a useful pharmacotoxic model to assess CIN risk. Limiting the CM dose compared to pre-procedural egfr may be reduce the risk of CIN in elective PCI cases. P3217 Clinical outcomes and predictors of adverse events of patients presenting with documented stent thrombosis D. Zavalloni 1,L.Porcu 2,V.Torri 2,M.L.Rossi 1, G.L. Gasparini 1, M. Scatturin 1, D. Soregaroli 1, E. Corrada 1, V. Lisignoli 1, P. Presbitero 1. 1 Istituto Clinico Humanitas, Rozzano, Italy; 2 Istituto Mario Negri, Milano, Italy Objectives: to assess outcomes and predictors of adverse events of patients with documented stent thrombosis (ST) treated with percutaneous coronary intervention (PCI). Background: ST is a life-threatening complication following PCI mainly presenting with ST-elevation myocardial infarction (STEMI). Little is known about treatment and outcomes of patients living through ST. Methods: clinical outcomes and adverse events of a cohort of consecutive patients with STEMI due to documented ST were compared with those of a cohort of consecutive patients with STEMI due to de novo lesion thrombosis, both treated with primary PCI. Results: 47 patients with ST were compared with 279 with de novo lesion thrombosis. The HR for major adverse cardiovascular and cerebrovascular events (death, re-ami, stroke, new revascularizations) of patients with ST vs STEMI was 1.30 (95% IC [0.82;2.06], p=0.269). Independent predictors of MACCE were EF<45% (HR=2.11; 95%CI [1.43;3.10]; p<0.0001) and multivessel disease (HR=3.40; 95%CI [2.06;5.61]; p<0.0001). Predictors of all-cause mortal-

235 Procedural complications of percutaneous cardiac interventions Part III. Complications 535 ity were EF<45% (HR=7.74; 95%IC [3.17;18.88]; p<0.0001) and chronic renal failure (HR=2.70; 95%CI [1.21;6.02]; p<0.07). A separate univariate analysis focusing on in-hospital and post-hospitalization outcomes showed hyperlipidemia as predictor for mortality (HR=8.21; 95% CI [2.31;29.18]; p=0.001) in the longterm follow-up. The use of further stents to treat ST was not associated to worse outcomes. Conclusions: baseline clinical conditions are the most relevant predictors of adverse outcomes in patients with ST. Primary PCI in this particular setting provides acute and long-term clinical outcomes similar to those of an unselected population of patients with STEMI. The need of further stenting during PCI was not associated with adverse events P3218 Clinical experience of catalyst ii wire vascular access management device in diagnostic and interventional percutaneous procedures with the same day discharge (The BOOMERANG same day discharge trial) R.S. Kiesz 1, B.K. Wiernek 1, S.L. Wiernek 1,G.V.Nazarewicz 1, J.L. Martin 1, P.E. Buszman 2. 1 San Antonio Endovascular & Heart Institute, San Antonio, United States of America; 2 Uppersilesian Heart Center, Acute Coronary Care Unit, Katowice, Poland Background: The main disadvantage of existing vascular closure devices (VCD) are that parts of the device have to be left in the body potentially causing inflammation or scarring. Considering this fact, the recently available Cardiva Catalyst II Wire System Boomerang might be an attractive alternative to existing VCDs. The BOOMERANG Same Day Discharge Trial is a prospective, single-center trial for subjects who require diagnostic or interventional angiographic procedures. The objective is to achieve hemostasis of the arterial access site using the Catalyst II Wire System in combination with manual compression with same day discharge after coronary and peripheral procedures. Methods: To date, there are 185 patients who form the study population for this analysis. Follow up was at 16±6.8 days post diagnostic procedures and at 1.5±0.9 days as well as at 15.1±6.7 days post interventional procedures. The main endpoint is major and minor vascular complications. Results: The mean age was 59.3±10.7 (range 27-85), 102 (55.1%) patients were males, 151 (82.1%) had hypertension, 162 (82.9%) had hyperlipidemia, 76 (41.1%) had diabetes and 18 (9.7%) were on dialysis. A total of 200 procedures were performed. Forty one procedures (20.5%) were interventions and all were performed with Bivalirudin monotherapy. Device success was achieved in 199 (99.5%) procedures. For diagnostic procedures the mean arterial dwell time was 10.6±6.2 min, compression time was 7.9±3.7 min., bed rest was 104.8±16.9 min., time to discharge was 147.0±21.0 min. For interventions the mean arterial dwell time was 135.5±31.8 min., compression time was 12.9±4.7 min., bed rest time was 127.6±23.3 min., time to discharge was 299.4±45 minutes. No major vascular complications were noted at 2 weeks follow-up. Site ecchymosis was noted after 15 (9.4%) diagnostic and 16 (39%) intervention procedures. Haematoma (2-5 cm) was present after 3 (1.9%) diagnostic procedures. No haematomas (>2 cm) were observed after interventions. Conclusions: The Catalyst II Wire System is a safe and effective device in achieving hemostasis. In combination with Bivalirudin monotherapy efficiently allows patients to go home the same day. P3219 Effect of two-day atorvastatin pre-treatment on the incidence of peri-procedural myocardial infarction following elective percutaneous coronary intervention J. Veselka, D. Zemanek, P. Hajek, M. Maly, R. Adlova, L. Martinkovicova, D. Tesar. CardioVascular Center, University Hospital Motol, Prague, Czech Republic Purpose: Both randomized and observational studies have suggested that pretreatment with statins may reduce a peri-procedural myocardial infarction (PMI) in patients with stable angina during an elective percutaneous coronary intervention (PCI). The purpose of this randomized study was to investigate, the effect of a two-day atorvastatin therapy on the incidence of PMI in patients with stable angina pectoris undergoing elective PCI. Methods: Two hundred patients with stable angina pectoris not taking statins and referred for PCI were enrolled and randomized (ratio 1:1) to a 2-day pretreatment with atorvastatin of 80 mg daily and subsequent PCI, or immediate PCI. Serum concentration of creatine kinase (CK-MB mass) and troponin I (TnI) were measured prior to and 16 to 24 hours after PCI. The incidence of PMI was assessed using the established criteria. Results: Ten percent of patients in the Atorvastatin group and 12% of patients in the Control group had a post-procedural CK-MB mass elevation 3 times the ULN (p=0.65). The incidence of PMI based on post-interventional release of TnI ng/ml was 17% in the Atorvastatin group and 16% in the Control group (p=0.85). Median CK-MB mass peak after PCI was 1.46 (interquartile ranges ) ng/ml in the Atorvastatin group and 1.40 ( ) ng/ml in the Control group (p=0.70). Median peak of TnI after PCI was ( ) ng/ml in the Atorvastatin group and ( ) ng/ml in the Control group (p=0.54). By multivariate analysis, the only independent predictor of PMI was age of the patients (OR=1.09; 95% CI= ; p=0.006). Conclusions: In this study 2-days pre-pci therapy with atorvastatin did not reduce the occurrence of PMI in patients with stable angina pectoris undergoing elective PCI. P3220 Intravenous glutathione prevents contrast-induced nephropathy by reducing renal oxidative stress after coronary angiography: a new use of an old drug T. Saitoh, H. Satoh, M. Saotome, T. Urushida, H. Katoh, H. Hayashi. Hamamatsu University School of Medicine Department of Cardiology, Hamamatsu, Japan Purposes: The contrast-induced nephropathy (CIN) increases morbidity and mortality of the patients with coronary arterial disease. The renal oxidative stress is one of the critical causes for CIN. N-acetylcysteine (NAC) which is deacetylated in liver to yield glutathione (GSH) has been applied to prevent CIN. However, oral NAC has a limitation for the emergent coronary angiography (CAG) because it has to be taken up several hrs before CAG. Recently, it is shown that intravenous GSH can be efficiently transferred into renal proximal tubular epithelial cells. Therefore, the intravenous administration of GSH just before CAG is expected to prevent CIN by scavenging reactive oxygen species generated immediately after CAG. In this study, we compared the protective effects of oral NAC and intravenous GSH against CIN by evaluating renal function and oxidative stress serially after CAG. Methods: Twenty one patients with creatinine clearance < 60 ml/min who underwent CAG were randomly assigned to the three groups: the control group (n = 7); the NAC group (n = 7), oral NAC at a dose of 704 mg twice daily for two days; the GSH group (n = 7), GSH infusion at 100 mg/min for 30 min before CAG. All the patients received intravenous saline at 1 ml/kg/hr for 24 hrs from 12 hrs before CAG. Results: (1) Each one case (14%) developed CIN in the control group and in the NAC group, but no case did in the GSH group. (2) The serum creatinine level decreased significantly at 24 hrs after CAG in the GSH group (-6.3±0.8%, p < 0.01 vs. the baseline), whereas it did not change in the control group or in the NAC group (2.4±5.2% and -2.4±2.7%, respectively). (3) In the control group, the urinary lipid hydroperoxides (LOOHs), an intermediate which indicates renal damage by oxidative stress, increased to 299.5±94.4% of the baseline at 2 hrs after CAG (p < 0.05). The increase in LOOHs was completely abolished in the GSH group (5.4±8.8%) but did not in the NAC group (217.4±96.0%, p < 0.05). (4) In the control group, the serum GSH levels fell by -9.4±2.3% at 2 hrs after CAG (p < 0.01). The decrease was prevented in the GSH group (-1.8±8.5%) but did not in the NAC group (-10.0±3.3%, p < 0.05). Conclusions: The intravenous administration of GSH just before CAG can be a more effective strategy to protect the kidney from CIN than oral NAC because it strongly diminished renal oxidative stress, and can be applied for emergency cases. P3221 Prediction of contrast-induced nephropathy in diabetic patients undergoing elective cardiac catheterization or PCI S. Worasuwannarak, S. Pornratanarangsi. Siriraj Hospital, Bangkok, Thailand Objectives: To assess a role of volume-to-creatinine clearance ratio (V/CrCl) and iodine dose-to-creatinine clearance ratio (I-dose/CrCl) in predicting contrastinduced nephropathy (CIN) in diabetic patients undergoing elective cardiac catheterization or percutaneous coronary intervention (PCI). Background: In diabetic patients undergoing cardiac catheterization or PCI, the incidence of CIN is higher than nondiabetic patients. High doses of contrast media also increase the likelihood of renal dysfunction. The ratio of the volume of contrast media to creatinine clearance (V/CrCl) and iodine dose-to-creatinine clearance (I-dose/CrCl) has been shown to correlate with the area under the curve of contrast media concentration over time and was used to predict the occurrence of CIN in unselected patients. No study has been conducted specifically in diabetic patients undergoing cardiac catheterization or PCI before. Methods: We conducted a prospective, single center study. The V/CrCl and I-dose/CrCl were calculated in diabetic patients undergoing elective cardiac catheterization or PCI. An increase in serum creatinine of >0.5 mg/dl or >25% by 7 days from baseline was considered CIN. The incidence of CIN was determined. The predictive value of V/CrCl and I-dose/CrCl for CIN were assessed using multivariable logistic regression. Results: The total number of patients that had been enrolled in the study was 248; Male 50.8%. The overall incidence of CIN was 5.2%. The mean age for the entire population was 65±9 years; the mean body mass index was 25.6±4.0 kg/m 2 ; and the mean creatinine clearance was 60.6±27.4 ml/min. The mean values of V/CrCl for patients with and without CIN were 3.7±2.9 and 2.2±1.7 (p=0.041). The mean values of I-dose/CrCl for patients with and without CIN were 1.31±0.94 and 0.82±0.63 (p=0.042). The receiver-operator characteristic curve analysis indicated that a V/CrCl ratio of 2.60 and I-dose/CrCl of 0.98 were a fair predictors of CIN. After adjusting for other known predictors of CIN, a V/CrCl ratio 2.60 remained the only significant predictor of CIN (Odds ratio 5.5; 95% confidence interval , p=0.006). Conclusions: A V/CrCl ratio 2.60 was a significant predictor of CIN in diabetic patients undergoing elective cardiac catheterization or PCI.

236 536 Procedural complications of percutaneous cardiac interventions Part III. Complications P3222 Is contrast-induced nefropathy an independent predictor of long-term mortality in patients who undergo primary PCI? G. Crimi, V. Rancati, G.M. De Ferrari, A. Repetto, M. Lettino, B. Marinoni, F. Russo, A. Potenza, S. Pica, L. Oltrona Visconti. Policlinico San Matteo, Pavia, Italy Background: The use of contrast media (CM) in coronaryintervention can lead to a form of renal failure known as contrast-inducednefropathy (CIN). Haemodinamic instability in patients that undergo primary PCI (ppci) for ST-elevation myocardial infarction (STEMI) can transiently impair renal function and increase serum creatinine (SCr). CIN is associated to high-risk patients and poor prognosis, but whether this complication is an independent predictor of mortality is still unknown. Aim of the study: To evaluate if CIN is an independent predictorof long-term mortality in patients who undergo ppci for STEMI. Patients and Methods: We observed 618 consecutive patients who were hospitalized for STEMI in our Hospital and subjected to ppci in the period between January, 2005 and June, Data were available for 497 patients (80,4%), after exclusion of those not surviving 48 hours or with missing SCr levels at either baseline, 24 or 48 hours. CIN was defined as a SCr increase>25. Results: The incidence of CIN was 17.5% (87/497). Patients who develop CIN were significantly more likely to be older, female, diabetic and with positive history for previous infarction. They presented more likely with Killip class > 2, anterior MI and 3-vessel disease. They were more likely characterized by sub-optimal reperfusion flow (TIMI<3), use of intra-aortic balloon counterpulsation, higher CK peak, lower left ventricular ejection fraction (LVEF) at discharge and longer coronary care unit stay. There were no significant differences in history of previous myocardial revascularization, pain to balloon time, type (hypo-osmolarvs isoosmolar) and dose of CM. After an average follow up of 500 days overall mortality was 7,3%. At multivariable analysis, independent predictors of all-cause mortality were age (OR 95% CI 1,03 1,13, per 1 year) and LVEF atdischarge (OR 95% CI 0,89 0,99), CIN did not reach the statistical significance (OR 2,5, 95% CI 0,73 8,7). Conclusion: In a large single-center series of consecutive patients undergoing ppci for ST-elevation MI, contrast-induced nefropathy occurred in 17,5% of patients. It was more frequent among older, diabetic, female patients with haemodinamic instability and large MIs. Although CIN was associated with a worse prognosis, it was not an independent predictor of long-term mortality. P3223 Long term results after switch from abciximab to eptifibatide during percutaneous coronary interventions M. Koutouzis 1, B. Lagerqvist 2, P. Albertsson 1, G. Matejka 1,L.Grip 1. 1 Sahlgrenska University Hospital, Gothenburg, Sweden; 2 Uppsala University Hospital, Uppsala, Sweden Introduction: The usage of platelets glycoprotein (GP) IIb/IIIa receptor blockers improves outcomes during high risk percutaneous coronary interventions (PCI). The aim of this study is to evaluate the long term results after a planned switch from abciximab to eptifibatide. Methods: In order to reduce costs, a general switch from abciximad to eptifibatide was performed in two Swedish University hospitals. Patients treated six months before and six months after the switch were followed up long term in order to identify differences between these two antiplatelet regimens. Primary end point was a composite of death, myocardial infarction, stroke or target vessel revascularization and secondary endpoints were the individual components of the composite. Data were collected from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Results: One thousand and sixty eight patients underwent PCI and received a GP IIb/IIIa receptor blocker during the study period: 589 received abciximab and 479 received eptifibatide. All patients were followed for at least 30 months after the procedure. There were no differences in patients baseline clinical characteristics. There were no differences between the groups in the primary endpoint (Figure 1) or in any of the secondary end points. Conclusions: A switch from the general usage of abciximab to eptifibatide as GP IIb/IIIa receptor blocker in connection to PCI did not have any negative effects of long term clinical outcomes. P3224 The 5352 A allele of the pro-inflammatory Caspase-1 gene predicts late acquired stent malapposition in STEMI patients treated with sirolimus stents S.C. Bergheanu, D. Pons, B.L. Van Der Hoeven, S.S. Liem, B. Siegerink, M.J. Schalij, J.G. Van Der Bom, J.W. Jukema. Leiden University Medical Center, Leiden, Netherlands Purpose: Late acquired stent malapposition (LASM) is a common finding after sirolimus-eluting stent (SES) implantation and appears to be the cause for late stent thrombosis. Inflammation may play a pivotal role in LASM just as it plays in stent restenosis. We have investigated 7 polymorphisms involved in inflammatory processes, related in previous reports to restenosis, on the risk of LASM in SES patients. Methods: Patients with ST-elevation myocardial infarction who underwent SES implantation and had intravascular ultrasonography (IVUS) data available for both immediate post-intervention and 9-month follow-up were included in the present study. Results: In total, 104 patients from the MISSION! intervention study were genotyped for the caspase G/A, eotaxin 1382 A/G, CD A/G, colony stimulating factor C/T, IL C/T, IL C/T and the tumor necrosis factor alpha 1211 C/T polymorphisms. LASM occurred in 26/104 (25%) of patients. We found a significantly higher risk for LASM in patients carrying the caspase-1 (CASP1) 5352 A allele (RR= 2.32; 95% CI ). In addition, mean neointimal growth was significantly lower in patients carrying this LASM risk allele (1.6 vs 4.1%, p=0.014). The other 6 polymorphisms related to inflammation were not significantly related to the risk of LASM. Conclusions: Carriers of the 5352 A allele in the caspase-1 gene are at increased risk of developing LASM after SES implantation. Screening for this polymorphism in patients undergoing percutaneous coronary interventions could eventually help cardiologists to better select between commercially available stents. P3225 The impact of elevated body mass index versus metabolic abnormalities on mortality following percutaneous coronary intervention L. Razzouk, P. Muntner, A.S. Kini, M.C. Kim, P.M. Moreno, S.K. Sharma, M.E. Farkouh. Mount Sinai Hospital, New York, United States of America Purpose: To compare the relative impact of elevated body mass index (BMI) to metabolic abnormalities on long-term outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: Consecutive patients (n=12,198) undergoing elective PCI between July 1, 1999 and December 31, 2006 were followed through June 30, Patients were classified into normal weight, overweight, class I and class II obese groups based on their BMI ( , , and 35 kg/m 2 respectively) and by number of metabolic abnormalities present (impaired fasting glucose or diabetes, hypertension, serum triglycerides 150 mg/dl and HDL <40 mg/dl). All-cause mortality was assessed through linkage with the National Death Index. Results: The mean age of patients was 65.9 years (SD=11.9), 65.6% were men, and 77.1% white, 16.4% Hispanic, 10.2% African-American and 6.3% Asian. Overweight, class I and II obese patients had more metabolic abnormalities on average as compared to normal weight patients. After adjustment for age, raceethnicity, sex, smoking status, history of MI, statin use, chronic kidney disease, and left ventricular ejection fraction, patients who were normal weight had an increased risk of mortality when compared to patients with elevated BMI (Table). Within each BMI category, including normal weight, a direct and graded association was present between more metabolic abnormalities present and an increased risk of mortality. Hazard Ratios of Mortality Multivariable adjusted associated with BMI category Normal Weight Overweight Class I Obesity Class II Obesity Hazard Ratio 1.18 ( ) 1.00 (ref) 1.01 ( ) 1.04 ( ) Multivariable adjusted associated with metabolic abnormalities 0-1 metabolic abnormalities 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) 2 metabolic abnormalities 1.64 ( ) 1.39 ( ) 1.12 ( ) 1.78 ( ) 3 metabolic abnormalities 2.19 ( ) 2.02 ( ) 1.74 ( ) 2.12 ( ) 4 metabolic abnormalities 2.13 ( ) 3.39 ( ) 2.57 ( ) 3.28 ( ) Conclusions: Normal weight patients had the highest risk of mortality following PCI. However, metabolic abnormalities, which are more common among obese patients, maintained a graded mortality risk suggesting the need for efforts to aggressively treat metabolic abnormalities in patients following PCI. Composite endpoint curves

237 Procedural complications of percutaneous cardiac interventions Part III. Complications 537 P3226 Radiation doses to patients in interventional cardiology A. Benini, F. Pedersen, S. Helqvist, J. Kastrup, H. Kelbaek, K. Saunamaki, E. Jorgensen. Cardiac Cath Lab, Department of Cardiology, University Hospital Rigshospitalet, Copenhagen, Denmark Purpose: We analysed radiation doses in interventional cardiology, in order to increase the awareness of the known importance of deterministic and stochastic radiation effects on long term outcomes. Methods: Dose area product (DAP) and flouro time (FT) were recorded consecutively during 10 years. Data from diagnostic coronary angiographies, and percutaneous coronary interventions (PCI) were entered into a clinical database. Results: In diagnostic procedures, DAP values >100 Gy/cm 2, are infrequent (3.7%), and FT s > 30 min are 1.1%, only. In PCI, DAP and FT is highly significantly related to body mass index (BMI), number of treated lesions (PCI complexity), and to operator (p<0.000). Radiation doses are doubled, if BMI is >35, when compared to a normal BMI (20-25) (p<0.000). In patients with one lesion, only, doses were half, when compared to those with 3 lesions (p<0.000). The average DAP per procedure differed up to 40% between experienced operators in comparable procedures (p<0.000). Less than 1% of PCI patients had procedures needing DAP >300 Gy/cm 2, and skin lesions were not registered. Conclusions: When possible, a patient risk assessment, before one or a number of interventional procedures, should include the influence on radiation doses of BMI, PCI complexity, and operator. P3227 Positive influence in survival of operator defined strategies during percutaneous coronary intervention R. Teles, L. Raposo, M. Almeida, P. Goncalves, F. Pereira-Machado, P. Sousa, J. Brito, R. Cale, J. Abecasis, A. Silva. Hospital de Santa Cruz, Carnaxide, Portugal Risk assessment for percutaneous coronary interventions (PCI) is often surpassed by unavoidable ominous prognostic factors. The aim of this study is to determine which variables under operator influence determine survival in contemporary PCI patients (pts). Methods: We conducted a prospective single centre registry between 2003 and 2007, including 4351 pts submitted to 5129 consecutive PCI. Mean age was 64±11 years (24% females) and 27% were diabetics. PCI was performed for non ST myocardial infarction (MI) in 20% and an STEMI in14%. Drug-eluting stents (DES) were used in 69% of PCI. Demographic, clinical and procedural variables were considered for independent multivariate assessment of prognostic factors selected on the main endpoint, all cause mortality, at the follow-up (median 15 months, IQ: 11-28). Results: The overall survival probability (OSP) was 98.5% (95%CI: %) at one month and 95.7% (95%CI: %) at one-year. Among prognostic variables two operator dependent were identified has having a positive influence on survival: DES use (adjusted Odds Ratio (OR): 0.50, 95%CI: ) and the number of coronary segments treated (OR: 0.68; 95%CI ). The remaining independent factors were age, insulin-dependent diabetes, hypercholesterolemia, peripheral vascular disease, chronic renal failure, neoplasm and emergent procedures, as evidenced in the OR Graphic. Conclusions: In this large cohort the operator strategy has impact on survival. This is favorably influenced by an aggressive extension of revascularization and to drug-eluting stent use. P3228 Differential impact of bleeding complications on inhospital outcome at the time of PCI D. Faes, J. Jamart, P. Chenu, V. Dangoisse, A. Guedes, L. Gabriel, M. Gerard, B. Marchandise, P.H. Colles, E. Schroeder. Mont-Godinne University Hospital, Yvoir, Belgium Purpose: As bleeding complications are known to be associated with poor outcome in the setting of acute coronary syndromes (ACS), we aimed to assess the respective impact of access site versus non access site related bleedings on the inhospital mortality after PCI in patients with stable angina and ACS. Methods: a consecutive series of 7268 PCI procedures performed in our institution during a 12-year period ( ); bleeding complications were classified according to TIMI and GUSTO definitions; renal failure was defined by creatinin 2 mg% or dialysis. Results: among the 322 bleeding events (4.4%), 235 (3.2%) were related to the vascular access (pseudoaneurysms, local bleedings) and 87 (1.2%) were not access site related bleedings (intracerebral, tamponade, other bleedings). 97 (1.3%) events were classified as TIMI major/gusto severe events. By multivariate analysis, local bleedings were predicted by age (OR per year: 1.05) HTN (OR: 1.48) and acute myocardial infarction (OR: 1.62), whereas non access site related bleedings were predicted by acute MI (OR: 3.85), shock (OR: 3.55), renal failure (OR: 2.52), number of lesions treated (OR per lesion: 1.32) and age (OR per year: 1.05). Inhospital mortality was predicted by shock (OR: 84), non access site related bleeding (OR: 10.92), periprocedural myocardial infarction (OR: 6.74), renal failure (OR: 2.44), acute MI (OR: 2.44), cerebrovascular disease (OR: 2.08), age (OR per year: 1.04). No relationship was found between local bleeding and inhospital mortality. By selecting only the TIMI major/gusto severe classified bleedings (n = 97), the same results were observed. Conclusion: in these large consecutive series of PCIs - performed in a routine clinical practice a major negative impact of non access-site related bleeding complications on inhospital mortality was observed, in contrast to the local bleeding complications the latter without impact on early survival. Therefore, bleeding complications in the setting of interventional cardiology should be analyzed and reported according to the nature of bleeding events on the basis of a differential impact on inhospital outcome. P3229 Intra-procedural continuous venous venous hemofiltration in preventing contrast induced nephropathy in patients with very low creatinine clearance undergoing coronary intervention L. Politi, F. Sgura, R. Rossi, D. Monopoli, F. Rollini, S. Perrone, G.M. Sangiorgi, M.G. Modena. Ospedale Policlinico, Modena, Italy Background: Contrast-induced nephropathy (CIN) is a frequent complication of percutaneous coronary interventions (PCI) and it is associated with significant in-hospital and long-term morbidity and mortality. Despite wider use of hydration protocols, patients with pre-procedural renal failure remain at higher risk to develop CIN. Continuous venous-venous hemofiltration (CVVH) has been tested only before and after procedure, but there is evidence that contrast medium has an immediate toxic effect on kidneys. Thus, we sought to evaluate the feasibility, safety and efficacy of performing intraprocedural in addition to peri-procedural CVVH for prevention of CIN in patients with very low creatinin clearance undergoing PCI. Methods: 26 consecutive patients with severe renal failure (creatinine clearance 35ml/min by Cockroft Gault formula) received a treatment with CVVH (1000ml per hour of fluid replacement rate without weight loss) starting 30 minutes before the procedure until 6 hours after. In addition all patients received sodium bicarbonate (154mEq/L intravenously at 3mL/kg/h for 1h immediately before contrast injection and 1mL/kg/h during contrast exposure and for 6 h after the procedure) and N-Acetyl Cysteine orally at a dose of 1200 mg twice daily for 48h from the day of administration of contrast agent. Serial serum creatinine measurements were made 24 h and 1 h before the procedure and daily for 72 h after the procedure. CIN was defined as an absolute increase of serum creatinine 0.5 mg/dl or more than 25% from the baseline value within 72 h after procedure. Results: Mean age of our population was 74.8±8.9 years, 67.7% were men and 38.7% diabetics. Mean contrast agent used was 177.7±85.1 cc. All patients were successfully treated with CVVH for the entire procedure duration. CIN occurred in 3 (11.5%) patients, a lower incidence compared to patients not receiving CVVH. Mean duration of CVVH treatment was 6.9±0.6h. Thus, compared to the 24hrs pre and post procedural CVVH regimens, intra-procedural CVVH reduces the time of patient immobilization with similar efficacy. No patients required in-hospital dialysis and no major adverse events were observed during the hospital stay. Conclusions: Intra-procedural CVVH is feasible, safe and effective to prevent CIN after a coronary intervention in patients with very low creatinine clearance. Further randomized studies are needed to evaluate the advantage of intraprocedural CVVH compared to long-term pre and post procedural regimens. P3230 The role of renal function at discharge in patients with acute myocardial infarction and contrast-induced nephropathy after invasive treatment J. Kowalczyk 1, R. Lenarczyk 1,A.Sedkowska 1, M. Mazurek 1, P. Pruszkowska-Skrzep 1, A. Wozniak 1, T. Kukulski 1, J. Gumprecht 2, L. Polonski 3, Z. Kalarus 1. 1 Medical University of Silesia, Silesian Centre for Heart Diseases, Zabrze, Poland; 2 Department of Internal Diseases, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland; 3 3rd Department of Cardiology, Medical University of Silesia, Silesian Centre for Heart Diseases, Zabrze, Poland Background: Contrast-induced nephropathy (CIN) is associated with worse prognosis in patients (pts) with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI). The role of improved glomerular filtration

238 538 Procedural complications of percutaneous cardiac interventions Part III. Complications / Genetic aspects of cardiomyopathies rate (GFR) at discharge in AMI pts, who developed CIN after PCI is unknown and it was the aim of the study. Methods: Single-center study evaluated 3593 consecutive AMI pts treated with PCI. Among 3366 in-hospital survivors 2841 pts with GFR 60mL/min/1.73m 2 on admission were selected as the final study population. The occurrence of CIN after PCI in this study cohort was 18.5% (527 pts). All CIN pts were divided with respect to GFR at discharge into two study groups: pts with decreased GFR<60 (CIN-GFR<60; n=130) and those with GFR 60 (CIN-GFR 60; n=397). CIN was defined as a rise in serum creatinine of 44.2μmol/L (0.5mg/dL), or a 25% increase from the baseline value within 48 hours after PCI. Cumulative survival was compared using log-rank test. Multivariate Cox regression model was used to identify independent predictors of death. Results: Total mortality among AMI pts with GFR 60 on admission was significantly higher in CIN pts than in subjects without CIN (11.8% vs. 7.0%, p<0.001). 30-day, 1-year and remote mortality rates were similar in CIN pts irrespectively of renal function at discharge (Table). Pts with CIN and GFR<60 at discharge were older, less frequently smokers and males, more often hypertensive and diabetic. Other clinical parameters, especially angiographic, were similar in both study groups. Multivariate analysis identified diabetes mellitus (HR 1.70; 95%CI , p<0.05), advanced age (HR 1.89; 95%CI , p<0.05) and decreased ejection fraction <35% (HR 3.21; 95%CI , p<0.001) as independent predictors of death in AMI pts, who had GFR 60 on admission and developed CIN after PCI. CIN-GFR < 60 (n=130) CIN-GFR 60 (n=397) p value 30-day mortality 3 (2.3%) 4 (1.0%) year mortality 11 (8.5%) 30 (7.6%) 0.76 Remote mortality 17 (13.1%) 43 (10.8%) 0.49 Conclusions: CIN negatively influences outcome even in those pts, who had GFR 60 at discharge. AMI pts who had normal renal function on admission and developed CIN after PCI had worse prognosis irrespectively of renal function improvement at discharge. P3231 Ratio of Urinary Neutrophil Gelatinase Associated Lipocalin to urinary creatinine as predictor of contrast induced nephropathy after coronary angiography N. Kafkas, C. Demponeras, K. Makris, A. Nikolaou, K. Triantafillou, G. Mertzanos, S. Potamitis, I. Drakopoulos, D. Babalis. General Hospital of Attika KAT, Athens, Greece Contrast induced nephropathy (CIN), usually defined by an increase in the serum creatinine >0.5mg/dL or >25% from baseline, is a common complication of contrast agent used during coronary angiography. This increase typically occurs 3-5days after contrast administration. Neutrophil gelatinase-associated lipocalin (NGAL) highly accumulated in the human kidney cortical tubules, blood and urine after nephrotoxic and ischaemic injuries, has been proposed as an early, sensitive biomarker for CIN. Purpose: The aim of our study was to evaluate the use of the urinary- NGAL/urinary-creatinine ratio in order to detect CIN after coronary angiography. This ratio was used in order to normalize the urine NGAL concentrations due to the different levels of diuresis among our patients. Methods: Forty-two patients with normal renal function (cystatine-c<1.0 mg/l and creatinine <1.2 mg/dl) undergoing either coronary angiography alone (n=15) or angioplasty with stenting (n=27) were included. Low-osmolar contrast agent (iodixanol) was used in all patients. Serum and urine samples obtained just before angiography (baseline), 6-hours after contrast administration and 24 and 48 hours thereafter. NGAL was measured with ELISA (Bioporto,Gentofte,Denmark). Urine and serum-creatinine were measured with Jaffe method, and cystatin-c with immunoturbidometric assay on Architect analyzer (Abbott Diagnostics, Abbott Park,Il). Results: CIN was documented in 10 patients (serum creatinine increase >25% from baseline within 48 hours after contrast administration). Urinary- NGAL/urinary-creatinine ratio was significantly increased in CIN patients 6 hours after coronary angiography compared to non-cin patients ( ng/mg vs ng/mg, p<0.001) while serum creatinine did not differ ( mg/dl vs mg/dl, p=ns). ROC analysis showed that urinary-ngal/urinary-creatinine ratio at 6 hours after contrast administration can predict CIN (AUC=0.967, 95%CI ). Using as cut-off ng/mg CIN prediction is possible with sensitivity/specificity 90.0% and 92.4% respectively. Conclusion: We conclude that measurement of urinary NGAL/urinary creatinine ratio 6 hours after contrast administration can be used as an early marker to identify CIN in patients undergoing coronary angiography. P3232 Hypoglycemia predicts peri-procedural myocardial damage in patients undergoing elective percutaneous coronary rivascularization A. Nusca 1, G. Patti 1,F.Marino 1, A. Abbate 2,A.D Ambrosio 1, F. Mangiacapra 1, G. Di Sciascio 1. 1 Universita Campus Bio-Medico, Rome, Italy; 2 Virginia Commonwealth University, Richmond, USA Background: Hyperglycemia and hypoglycemia, with or without pre-existing diabetes mellitus, are associated with adverse outcomes in patients with acute coronary syndromes. However, few data are available with regard to the association between blood glucose levels and peri-procedural outcome in patients undergoing percutaneous coronary interventions (PCI). We aimed to investigate the relationship between glycaemic status and procedural myocardial damage in a large population of patients treated with coronary stenting. Methods: We retrospectively enrolled 573 patients who underwent PCI at our Institution. In all patients, blood glucose levels were measured before PCI and, according to these, pre-defined groups were considered: hypoglycemia < 80 mg/dl; euglycemia mg/dl; mild hyperglycemia mg/dl; hyperglycemia > 150 mg/dl. Troponin I levels were recorded before and 8 and 24 hours after the procedure. Periprocedural myocardial infarction (MI) was defined as a postprocedural increase in Troponin I > 3 times the upper normal limit (0.06 ng/ml). Results: An increase in troponin levels above the upper normal limit was significantly more frequent in patients with pre-procedural hypoglycemia compared to the other groups (69% vs 54% in euglycemia, 53% in mild hyperglycemia and 42% in hyperglycemia group; P for trend= 0.028). A trend toward a higher incidence of MI was observed in patients with glucose levels < 80 mg/dl before PCI (31% vs 22%, 23% and 18% in other groups; P for trend=0.31). The association between hypoglycemia and post-procedural myocardial damage detected by troponin levels was present irrespectively of the diabetic status. Multivariate analysis demonstrated that hypoglycemia was an independent predictor of post-pci troponin elevation. Conclusions: This study demonstrated that a hypoglycemic status at the time of PCI is associated with increased incidence of peri-procedural myocardial damage. Thus, optimal glycemic control is an important target to improve periprocedural results in the setting of percutaneous coronary revascularization. GENETIC ASPECTS OF CARDIOMYOPATHIES P3233 Mutations in Desmocollin-2: is A897KfsX3 pathogenic for arrhythmogenic right ventricular cardiomyopathy? M. De Bortoli 1, G. Beffagna 1, B. Bauce 2, A. Lorenzon 1, G. Smaniotto 1,C.Basso 3, G. Thiene 3, G.A. Danieli 1,A.Nava 2, A. Rampazzo 1. 1 Department of Biology, University of Padua, Padua, Italy; 2 Department of Cardio-thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy; 3 Department of Medico-Diagnostic Sciences and Special Therapies, University of Padua Medical School, Padua, Italy Purpose: Mutations in genes encoding desmosomal proteins have been reported to cause arrhythmogenic right ventricular cardiomyopathy (ARVC), an autosomal dominant disease characterized by progressive myocardial atrophy with fibro-fatty replacement. We screened 110 ARVC probands for mutations in desmocollin-2 (DSC2), the only desmocollin isoform expressed in cardiac tissue. In vitro functional studies were also performed to evaluate the pathogenic effect of detected mutations. Methods: Mutation screening was performed by denaturing high-performance liquid chromatography and direct sequencing. To evaluate the pathogenic potentials of the DSC2 mutations, DSC2a full-length wild-type and mutated cdnas were cloned in eukaryotic expression vectors to obtain a fusion protein with green fluorescence protein (GFP); constructs were transfected in murine cardiomyocytes (HL-1 cell line), immunostained for endogenous desmoglein and analyzed by confocal microscopy. We also examined the expression pattern of DSC2 splice forms (DSC2a and DSC2b, showing a different C-terminal domain) by PCR amplification of different human tissues cdnas. Results: Three different mutations (E102K, I345T, A897KfsX3) have been detected in 5 (4.5%) patients. The N-terminal missense mutations E102K and I345T, previously reported by our group, affect the normal localization of the mutant protein in cultured cardiomyocytes, thus suggesting a pathogenic effect. Three unrelated probands resulted to carry the A897KfsX3 variation, previously reported as E896fsX900 mutation. Two of them showed also other ARVC mutations. The A897KfsX3 variation affects the last five amino acids of the DSC2a isoform but not of DSC2b. In contrast with what we found in other tissues, in the heart DSC2a expression level was lower than DSC2b. In vitro functional studies demonstrated that, unlike wild-type DSC2a, the C-terminal mutated protein was localised in the cytoplasm. Unexpectedly, A897KfsX3 variation was also found in 6 (1.5%) out of 400 control chromosomes, occurring with a frequency of a polymorphism. The two probands carrying multiple mutations showed a severe form of ARVC with evident right ventricular dysfunction. Conclusions: DSC2 gene mutations are not frequently involved in ARVC. The previously reported A897KfsX3 mutation, altering only one of the two DSC2 isoforms, could be considered a probable polymorphism, which could affect the phenotypic expression of other ARVC mutations.

239 Genetic aspects of cardiomyopathies 539 P3234 Severe familial left ventricular noncompaction cardiomyopathy due to a novel troponin T (TNNT2) mutation P. Ehlermann 1, M. Luedde 2, D. Weichenhan 3, R. Will 1, A. Mueller 1,S.Rupp 4, H. Steen 1,B.Kern 1,H.A.Katus 1, N. Frey 2. 1 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 2 Universitaetsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany; 3 German Cancer Research Center, Heidelberg, Germany; 4 Universitaetsklinikum Giessen und Marburg GmbH, Giessen, Germany Background: Recently it could be shown that LVNC may be caused by mutations in multiple genes, including several that encode for sarcomeric proteins. Yet, it is still unclear whether the noncompaction phenotype is the primary determinant of cardiomyopathy or rather a secondary phenomenon with intrinsic cardiomyocyte dysfunction being the actual cause of the disease. We sought to identify the molecular cause of a severe form of familial left ventricular noncompaction cardiomyopathy (LVNC) and to assess the correlation between the LVNC-causing mutation and cardiac dysfunction in a transgenic animal model. Methods: LVNC was identified in an index patient and affected family members by echocardiography and MR imaging. Mutation screening in genes LDB3, LMNA, MYH7, MYBPC3 and TNNT2 of the index patient was performed by denaturing gradient gel electrophoresis (DGGE) and subsequent sequencing. Transgenic mice were generated expressing human wild-type human cardiac troponintn T (hctnt) or a human troponin T harbouring the pe96k mutation (mut TNT). Transgenic animals were characterized on a functional (echocardiography), morphological (histology) and molecular (gene expression) level. Results: A novel missense mutation (pe96k) in the cardiac Troponin T gene was identified in the index patient and all affected relatives, but not in healthy family members. Mutations in G4.5, LDB3, DTNA, LMNA, MYH7 and MYBPC3 were excluded. Moreover, the newly identified TNNT2 mutation was absent in 430 control individuals. The cosegregation of the mutation with the disease in the affected family and the exclusion of other candidate genes suggest that this new mutation causes LVNC in children and adults. Consistently, mutant transgenic mice carrying the pe96k troponin T mutation display cardiomyopathy with impaired left ventricular function in the absence of left-ventricular non-compaction. Moreover, marked induction of molecular markers such as ANF, BNP, β-mhc was observed. Conclusion: The DCM-like phenotype of mut TNT mice confirms the causal relationship of the pe96k mutation and cardiomyopathy in this family. Moreover, our data suggest that the non-compaction phenotype is not essential for cardiac dysfunction in LVNC but may rather be a secondary phenomenon. P3235 Systolic dysfunction in hypertrophic cardiomyopathy caused by Arg723Gly mutation in the beta-myosin gene F. Navarro-Lopez, A. Francino, J.C. Pare. Hospital Clinico Universidad de Barcelona, Barcelona, Spain Purpose: To assess the prevalence, natural history and clinical significance of systolic impairment (SI) of Hypertrophic Cardiomyopathy caused by Arg723Gly mutation in the β-myosin Gene (BCN mutation). Isolated soleous muscle fibers and myocyte experiments had shown this mutation to be associated with a severe contractil disfunction. Method: Thirty patients out of 73 genotyped members of three families carried the mutation and 24 were followed up with serial clinical, ECG and echocardiographic studies. SI was defined as a left ventricular ejection fraction (EF) 0.50 and dilatation as an end diastolic diameter (LVEDD) 55 mm. No myocardial heart disease was detected in members without the mutation. Results: Six patients had SI at the initial study (age of 39.1± 15) and 4 more were detected after a mean followup of 6.7±2 years (prevalence of 41.7%). Mean age of SI appearence was 46 ±.9 year (range 33-58). EF showed a strong negative correlation with age (r=-0.635, p=0.001) and a mean reduction of 7.56±13 points during the follow up. LVDD correlated with age (r=0.545, p=0.007) and inversely with septal thickness (r=-0.523, p=0.001). A significant Doppler out-flow tract gradient was present only in two cases. One had previous myomectomy at 11 years of age. Patients with SI had a rapid deterioration to functional Class III-IV, 6 were heart transplanted and 2 died of sudden death. The probability to reach age 50 without a cardiac event and with a NYHA functional class II or better was about 21%. Pathological studies revealed very extensive fibrosis of the myocardium and myocyte loss, predominantly in the interventricular septum. Conclusions: The dilated-hypokinetic evolution of HCM is highly prevalent in BCN mutation in the absence of previous myomectomy, and is associated with severe prognosis. P3236 Hereditary transthyretin-related amyloidosis with exclusive cardiac phenotype P. Ciliberti 1,C.C.Quarta 1,L.Riva 1, S. Longhi 1, G. Galati 1, C. Villani 1,F.Salvi 2, M. Lorenzini 1, A. Branzi 1, C. Rapezzi 1. 1 Azienda Ospedaliera S. Orsola Malpighi, Bologna, Italy; 2 Department of Neurology, Bellaria Hospital, Bologna, Italy Background: In hereditary transthyretin-related amyloidosis (ATTR), cardiac involvement usually occurs in patients with clinically predominant neurologic signs. On the contrary, African-American carryiers of the Val122Ile TTR mutation, exibit exclusively cardiac manifestations mimicking hypertrophic cardiomyopathy (HCM). Since little is known about the frequency of this exclusively cardiologic phenotype among Caucasians, we assessed its prevalence and clinical features in a nationwide Italian setting. Methods: Within a coordinated ATTR diagnosis/treatment network, we classified the phenotype at the time of diagnosis as follows: 1) exclusively cardiac involvement (echocardiographically defined amyloidotic cardiomyopathy in the absence of spontaneously reported neurologic symptoms); 2) exclusively neurologic involvement; 3) mixed cardiologic/neurologic involvement Results: Prevalence of the three phenotypes and patients characteristics are shown in Table 1. Median value of follow-up was 49 months. Table 1. Patients characteristics according to cardiologic/neurologic phenotype Phenotype Overall Cardiac Neurologic Mixed p (n=124) (n=14, 11%) (n=41, 33%) (n=69, 56%) Men, n (%) 80 (64%) 13 (93%) 21 (51%) 47 (68%) Age at diagnosis, years (mean ± SD) 51±14 63±9 47±17 51± Age at onset of symptoms, years (mean± SD) 48±14 59±8 44±17 48± Diastolic interventricular septum thickness, mm (mean ± SD) 15±4 18±3 10±2 16± * Restrictive filling pattern, n (%) 25 (20%) 5 (36%) 1 (2%) 19 (27%) 077* Left ventricular ejection fraction, % (mean ± SD) 59±13 47±10 68±10 59± * TTR mutation, n (%) Val30Met 35 (28%) 0 (0%) 18 (44%) 17 (25%) Ile68Leu 13 (11%) 10 (71%) 3 (7%) 0 (0%) <0.001 Other 76 (61%) 4 (19%) $ 20 (49%) 52 (75%) n.a. Orthotopic liver transplantation, n (%) 33 (26%) 0 (0%) 12 (29%) 21 (30%) 0.05 Heart and liver transplantation, n (%) 8 (6%) 3 (21%) 0 (0%) 5 (7%) Mortality rate (100 pts/year) ,24 *Comparisons restricted to cases with amyloidotic cardiomyopathy; $ Glu89Gln n=1, Ser23Asn n=1, Hys88Arg n=1, Val14Leu n=1. Conclusion: A clinically relevant subset of Caucasian, non-endemic ATTR patients presented with an exclusive cardiac phenotype hypertrophy mimicking HCM. The majority of these patients carried the Ile68Leu mutation and tended to be elderly men. So the possibility of ATTR must be consider in Caucasians with unexplained left ventricular hypertrophy, even in the absence of overt neurologic manifestations. P3237 Endothelial nitric oxide synthase polymorphisms interact with glucose homeostasis and inflammatory profile to cause coronary microvascular dysfunction in dilated cardiomyopathy M. Coceani 1, M.G. Colombo 2, T. Sampietro 1, D. Adlerstein 3, M.G. Andreassi 2, C. Carpeggiani 4, A. L Abbate 5, D. Neglia 1. 1 Fondazione Toscana Gabriele Monasterio, Pisa, Italy; 2 CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Massa, Italy; 3 DiaSorin S.p.A., Vercelli, Italy; 4 CNR Istituto di Fisiologia Clinica, Pisa, Italy; 5 Scuola Superiore Sant Anna, Pisa, Italy Purpose: Dysfunction of the coronary microcirculation constitutes a hallmark of dilated cardiomyopathy (DCM). Microvascular function is controlled by several factors including inflammatory mediators, glycometabolic status, and endothelium-derived factors, such as nitric oxide (NO) and endothelin-1. The aim of the study was to test the hypothesis that endothelial NO synthase (enos) genetic polymorphisms interact with the aforementioned factors in determining microvascular phenotype in DCM. Methods: Seventy seven patients (mean age 59.9±10.3 years, 73% males) with DCM underwent clinical evaluation, blood sampling for laboratory analyses, transthoracic echocardiography, and measurement of absolute myocardial blood flow and coronary resistance by N13-ammonia positron emission tomography, both at rest and during pharmacological stress with intravenous dipyridamole (0.56 mg/kg administered in 4 minutes). The Glu298Asp polymorphism of the enos gene and the T-786C polymorphism located in the promoter region of the same gene were examined. Results: Mean left ventricular ejection fraction and end-diastolic diameter were 35±8.1% and 64±5.9 mm, respectively; values did not vary significantly according to enos genetic polymorphisms. Patients with at least one Asp allele, compared to Glu/Glu homozygotes, had higher levels of endothelin-1 (5.7±8.9 vs. 1.4±1.3 pg/ml, P=0.007) and interleukin-6 (2.8±3.3 vs. 1.3±0.9 pg/ml, P= 0.03), as well as higher minimal coronary resistance during dipyridamole (116.9±62.8 vs. 82.7±38.1 mmhg*min*g/ml, P=0.03). C/C, compared to T/T, homozygotes had higher levels of insulin (17.4±10.8 vs. 8.3±2.5 μiu/ml, P=0.03) and were more insulin-resistant as determined through the homeostatic model assessment index (5.3±3.6 vs. 1.9±0.7, P=0.03). In addition, carriers of at least one C allele had higher coronary resistance at rest (155.0±63.1 vs ±34.9 mmhg*min*g/ml, P=0.05). Conclusions: Polymorphic variants of the enos gene are associated with the extent of endothelial and microvascular dysfunction in DCM, as assessed by levels of endothelin-1 and coronary resistance. The data of the present study point to the existence of a close interplay between variants of the enos gene, on one hand, with insulin-resistance and systemic inflammation, on the other, in determining microvascular phenotype. Because each of these latter manifestations

240 540 Genetic aspects of cardiomyopathies has already been linked to mortality in heart failure, future studies are needed to assess whether polymorphisms of the enos gene influence prognosis in DCM. P3238 Myocardial atrophy onset is a postnatal event initiated by cardiomyocyte necrosis in desmoglein-2 transgenic mice with arrhythmogenic cardiomyopathy K. Pilichou 1,C.Basso 1, C.A. Remme 2,S.Rizzo 1, M.E. Campian 2, B. Bauce 1, A.A.M. Wilde 2, A.F.M. Moorman 2, G. Thiene 1, C.R. Bezzina 2. 1 University of Padua, Padua, Italy; 2 University of Amsterdam, Amsterdam, Netherlands Background/Objectives: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by progressive fibrofatty replacement of ventricular myocardium. Recently, mutations in the desmoglein-2 (DSG2) gene in humans have been associated with ARVC and a transgenic mouse model with cardiac-restricted overexpression of the mouse homolog N271S dsg2 mutation (Tg-NS) and a high incidence (30%) of sudden death at young age (3.6 weeks) has been set up. This study aimed to investigate the sequence of pathologic events leading to ARVC. Methods: Evans Blue dye (EBD) was administered in vivo to assess the integrity of the cardiomyocytes plasma membranes. Hematoxylin-eosin, Heidenhain trichrome and Sirius Red were performed to examine the cardiomyocytes, inflammatory cells and fibrosis, Vonkossa stain for the detection of calcium, and Oil red O staining to assess the presence of neutral lipids. Cardiomyocyte features with special focus on intercalated discs were assessed by electron microscopy (EM). Confocal microscopy was applied in order to assess intercalated discs proteins and, to evaluate apoptosis. Mice were assessed at different age groups (2, 4 and >6 weeks). Results: Gross morphology and histology on <2 weeks-old TgNS mice demonstrated absence of pathological changes. 3-to-5 weeks old Tg-NS mice displayed whitish streaks in the epicardial layers and progressive thinning of both ventricles, at difference from age-matched control mice. Histologically, these features corresponded to extensive myocyte necrosis with acute inflammatory cells and massive calcification in both ventricles, followed by macrophage infiltrates, granulation tissue and early loose connective tissue deposition. Moreover, Tg-NS mice older >5 weeks showed dense fibrosis with collagen bundle formation, biventricular chamber dilatation and aneurysms. EM investigation in 2-3 week old mice, showed disruption of the sarcolemma, disgregation of myofilaments and other cytoplasmic contents, and mitochondria swelling. EBD administration in vivo showed increased cell membrane permeability and disrupted sarcolemma integrity in TgNS mice >3-weeks. Cleaved caspase 3 and TUNEL showed significant level of apoptosis in TgNS mice>4 weeks. Conclusions: In the dsg2-related ARVC mouse model, we provide evidence that the ARVC phenotype, although genetically determined, is acquired and progressive and is initiated by necrotic myocyte death, which subsequently triggers an inflammatory response and massive calcification, followed later by injury repair with fibrous tissue, wall thinning and aneurysm formation. P Tc-DPD scintigraphy can detect early myocardial amyloid deposition in transthyretin-related familial amyoloid polineuropathy L. Riva, C.C. Quarta, S. Longhi, P.L. Guidalotti, P. Ciliberti, G. Galati, E. Biagini, C. Pettinato, A. Branzi, C. Rapezzi. Azienda Ospedaliera S. Orsola Malpighi, Bologna, Italy Purpose: We previously reported, in a small series of patients, that 99Tc-DPD (DPD) scintigraphy tests positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) echocardiographically diagnosed cardiac amyloidosis (CA). We assessed the usefulness of DPD scintigraphy for detecting initial cardiac involvement in asymptomatic TTR mutation carriers with normal electrocardiographic and echocardiographic evaluations. Methods: We evaluated three groups of subjects: 1) 35 patients with TTR-related CA (23 mutant; 12 wild-type); 2) 28 patients with AL-related CA; 3) 11 asymptomatic carriers of TTR mutations (4 with Val30Met, 7 with non Val30Met) without any clinical/electrocardiographic/echocardiographic sign of cardiac amyloidosis. Myocardial uptake of DPD (740 MBq iv) was semiquantitatively/visually assessed by experts at 3 h (and also 5 min). Results: Semiquantitative measures of late (3 h) DPD uptake were 2-fold higher in TTR-related CA (table). Among the asymptomatic TTR mutation carriers, DPD Table 1 AL TTR-related CA TTR mutation P value (n=28) (n=35) carriers (n=11) Age, yr 62±9 61±14 40± Left Ventricular Mass index, g/m 2 169±56 230±85 95± Heart tracer retention: median (iqr) 3.5% ( %) 7.9% ( %) 2.3% (2 3%) Heart/body retention ratio: median (iqr) 5.2 ( ) 10.3 ( ) 4.7 ( ) Visual cardiac score: (no uptake) 20 (72%) 0 (0%) 8 (73%) 1 (mild uptake) 6 (21%) 0 (0%) 0 (0%) 2 (moderate uptake) 2 (7%) 12 (34%) 1 (9%) 3 (strong uptake) 0 (0%) 23 (66%) 2 (18%) myocardial scintigraphy tested positive in 3 cases (27%: Ala36Pro, Thr49Ala and Gly47Ala mutations, respectively). Conclusions: In a larger cohort of patients with CA, 99Tc-DPD scintigraphy was confirmed to be useful for differentiating TTR-related from AL-related etiology. Among asymptomatic carriers of non Val30Met TTR mutations, DPD scintigraphy can identify preclinical myocardial amyloidotic involvement, even before the appearance of abnormal electrocardiographic and/or echocardiographic signs. P3240 NEBL encoding the cardiac Z-disc protein nebulette as a novel disease gene for cardiomyopathies P. Tomasov 1,A.Perrot 2, D. Zemanek 1, S. Homolova 1, M. Sedlakova 1,J.Lossie 2,R.Dietz 2, M.G. Posch 2,C.Ozcelik 2, J. Veselka 1. 1 Univesity Hospital Motol, Cardiovascular Center, Cardiology Department, Prague, Czech Republic; 2 University Hospital Charité, Cardiology at Campus Buch and Max-Delbrück-Center for Molecular Medicin, Berlin, Germany Purpose: Recent discoveries suggest a common genetic basis for familial cardiomyopathies. The distinct forms of these diseases can be caused by mutations in the same genes. More than 10 such disease genes have been published to date. Recently, we have described a mutation in the NEBL gene encoding for the cardiac Z-disc protein nebulette in a patient with dilated cardiomyopathy (DCM). We have decided to extend our analysis of this gene and to study a cohort of patients with hypertrophic cardiomyopathy (HCM) as well. Methods: We analyzed further 30 German patients with familial DCM and 95 Czech patients with HCM. The 28 coding exons of the NEBL gene were amplified from the patients DNA samples and sequenced using ABI chemistry. Results: We detected two novel heterozygous missense mutations in two patients. The first mutation (Gln581Arg) was found in a DCM patient whereas the second mutation (His171Arg) was found in a HCM patient. The affected amino acids are highly conserved among different species. Neither of these variants were detectable in 676 control alleles. The patients showed typical phenotype for the respective form of cardiomyopathy. The analysis of the family members of the DCM index patient is ongoing. A sister of the HCM index patient carried the mutation but had no sign of the disease phenotype, showing typical reduced penetrance of HCM. Interestingly, the HCM mutation is located close to the initially found variant in NEBL (Ala175Thr). Exon 6 coding for the fourth nebulin-like repeat containing both of these mutations seems to be a mutational hot spot. Conclusion: In total, we identified three different NEBL mutations. These results constitute NEBL as a novel disease gene for hypertrophic and dilated cardiomyopathy. This underlines the notion that the cardiomyopathies are true allelic diseases. P3241 Diagnostic mutation analysis in hypertrophic cardiomyopathy by DNA resequencing array S. Fokstuen 1, A. Munoz 2, P. Melacini 3,A.Perrot 4, X. Jeanrenaud 5, M. Farr 6,U.Sigwart 7, R. Lerch 8, S.E. Antonarakis 1,J.L.Blouin 1. 1 Genetic Medicine University Hospitals of Geneva, Geneva, Switzerland; 2 Department of Genetic Medicine and Development University of Geneva School of Medicine, Geneva, Switzerland; 3 Department of Cardiac, Thoracic and Vascular Sciences University of Padua, Padua, Italy; 4 Cardiology at Campus Buch/Experimental & Clinical Research Center Charité-Universitätsmedizin Berlin, Berlin, Germany; 5 Cardiology University Hospitals of Lausanne, Lausanne, Switzerland; 6 Kardiologische Klinik, Herz-und Diabeteszentrum NRW, Bad-Oeynhausen, Germany; 7 University of Geneva School of Medicine, Geneva, Switzerland; 8 Cardiology University Hospitals of Geneva, Geneva, Switzerland Purpose: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (1/500) characterized by a remarkable clinical and genetic heterogeneity. More than 450 different pathogenic mutations in at least 20 genes have been identified so far. Genetic testing for HCM has a growing impact on the medical management of patients and their families, however routine diagnostic mutation analysis by classical methods remains very time-consuming and expensive. Methods: We have developed a 30 Kbp HCM-DNA-resequencing-array (Custom- Seq Affymetrix) for all exons (n=160), splice-sites and 5 -UTR of 12 HCM genes, which we currently use for mutation analysis in clinical practice. This HCM-array is very efficient to detect single nucleotide substitutions accounting for up to 86% of all HCM mutations. Actually it does not detect small indels. Results: We analysed 115 patients from 5 different centres. Overall, we identified 30 different single nucleotide substitutions in the coding regions or splice sites of MYH7, MYBPC3, TNNT2, TNNI3, TPM1 and MYL3 in 42 patients (37%). Twelve variants were reported as known mutations and 14 were novel changes not found in a control population study (>200 chromosomes). Furthermore, we identified 4 known SNPs/variants previously reported as mutations for HCM. Conclusions: Our DNA resequencing array appears to date as the most rapid and cost-effective technology for mutation screening in HCM. Further improvement of the software may detect small insertions/deletions in the future. The HCM-array provides a first attempt of high throughput sequencing methodology which will further develop and probably become the method of choice for routine molecular diagnosis of heterogeneous disorders such as HCM.

241 Genetic aspects of cardiomyopathies 541 P3242 Validation of revised task force criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy in families with dominant mutations A. Tsatsopoulou 1,A.Anastasakis 2, L. Antoniades 3, G. Chlouverakis 4,P.Syrris 5,A.Asimaki 5,C.Eutychiou 3, C. Stefanadis 2, W.J. McKenna 5, N. Protonotarios 1. 1 Yannis Protonotarios Medical Center of Naxos, Naxos, Greece; 2 University of Athens, Athens, Greece; 3 Nicosia General Hospital, Nicosia, Cyprus; 4 Biostatistics Laboratory, University of Crete Medical School, Heraklion, Greece; 5 University College London, London, United Kingdom Purpose: To compare the sensitivity and specificity of recently revised versus original Task Force Criteria (TFC) for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) in families with dominant desmosomal mutations. Methods: The study population included 68 carriers of a pathogenic mutation (32 men and 36 women, age 40±17 years) and 76 genotyped normal healthy relatives (38 men and 38 women, age 42±18 years). All 6 TFC: 1) Repolarization abnormalities (12-lead ECG), 2) depolarization abnormalities (12-lead ECG, signaled averaged ECG), 3) right ventricular structural/functional alterations (2-dimensional ECHO), 4) ventricular arrhythmias (ECG recording, 24-hour ECG monitoring), 5) tissue characterization (cardiac biopsy), and 6) family history/molecular genetic results were evaluated. The diagnosis of ARVC was based on 2 major or 1 major plus 2 minor or 4 minor TFC. Sensitivity and specificity between original and revised TFC were compared using the McNemar test, at the 5% level of significance. Results: In addition to 28 carriers fulfilling the original TFC, the revised criteria diagnosed ARVC in 12 more, increasing significantly the diagnostic sensitivity among carriers from 41% to 59% (p<0.001). Of 8 normal relatives fulfilling original TFC only one fulfilled the revised, increasing specificity from 89% to 99% (p=0,016). Excluding the criterion of family history/genetics, the original TFC diagnosed 25 carriers (sensitivity 37%) and no one among normal relatives (specificity 100%). The revised criteria diagnosed 2 more carriers but missed other 2, thus sensitivity remained the same (37%) while specificity was at 100% since no one of normals was considered as affected. Examining the ability of non-invasive TFC to detect carrier status, the revision increased the sensitivity of repolarization (p=0.004) and depolarization abnormalities (p<0.001) as well as ventricular arrhythmias (p=0.031) without significant reduction of specificity while, in revised TFC the sensitivity of right ventricular structural/functional alterations was significantly reduced (p<0.001) without significant improvement of specificity. Conclusion: Revision of TFC increased their diagnostic sensitivity as well as specificity in dominant ARVC families. When there is no family history or molecular genetic result, the revised criteria are not superior to the original ones in establishing ARVC diagnosis. P3243 Familial noncompaction cardiomyopathy: genetic and cardiologic features in adults and children Y.M. Hoedemaekers 1,K.Caliskan 2,M.Michels 2, I. Frohn-Mulder 3, J. Van Der Smagt 4, J.E. Phefferkorn 1, F.J. Ten Cate 2, D. Dooijes 1, D.F. Majoor-Krakauer 1. 1 Erasmus MC Dept. of Clinical Genetics, Rotterdam, Netherlands; 2 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands; 3 Erasmus MC Dept. of Paediatric Cardiology, Rotterdam, Netherlands; 4 University Medical Center Utrecht, Dept. of Clinical Genetics, Utrecht, Netherlands Background: Noncompaction cardiomyopathy (NCCM) features a thickened bilayered left ventricular wall with a thin, compact epicardial layer and a thick endocardial layer with prominent intertrabecular recesses. NCCM is genetically heterogeneous. Similarly to hypertrophic (HCM) and dilated cardiomyopathy (DCM), NCCM has been associated with mutations in sarcomere genes. In order to contribute to a genetic classification for NCCM a systematic cardiologic family study was performed in a cohort of 56 consecutively diagnosed and molecularly screened patients with isolated NCCM (47 adults and nine children). Methods and Results: Cardiologic screening with electrocardiography, echocardiography and physical examination of 169 relatives from 46 unrelated NCCM probands revealed familial cardiomyopathy in 34 families (74%), including NCCM, HCM and DCM. Seventy-four percent of the relatives newly diagnosed with cardiomyopathy were asymptomatic, explaining that 54% of familial disease remained undetected by ascertainment of family history prior to cardiologic screening. The molecular screening included analysis of 17 genes yielding 29 different mutations in 23 probands (41%); 16 adults (34%) and seven children (70%). Fifteen single mutations and one double mutation on the same allele were transmitted in an autosomal dominant mode. Six adults and two children were compound or double heterozygous for two different mutations. In 19/34 (56%) of familial NCCM the genetic defect remained unknown. Conclusion: NCCM is predominantly a genetic disorder, requiring genetic counseling, DNA diagnostics and, also in absence of a genetic cause, cardiologic family screening. P3244 Outcome of genetic screening of sarcomere protein genes in isolated left ventricular noncompaction S. Klaassen 1,S.Probst 1,E.Oechslin 2, B. Gerull 1, F. Berger 3, L. Thierfelder 1, R. Jenni 4. 1 Max-Delbrueck-Centrum fuer Molekulare Medizin, Berlin, Germany; 2 Toronto General Hospital, Toronto, Canada; 3 Charite - Campus Virchow-Klinikum, Berlin, Germany; 4 University Hospital Zurich, Zurich, Switzerland Introduction: Left ventricular noncompaction (LVNC) has recently been recognized as a primary cardiomyopathy. Recently, mutations in genes encoding sarcomere proteins β-myosin heavy chain (MYH7), α-cardiac actin (ACTC), and cardiac troponin T (TNNT2) were shown to be associated with LVNC. We report on the frequency of mutations in sarcomere protein genes in a cohort of adult patients with isolated LVNC. Methods and Results: Mutational analysis of 8 sarcomere protein genes was carried out in a cohort of 72 unrelated Caucasian adult probands (mean age, 40 years) with LVNC and absence of other congenital heart anomalies. Denaturing high performance liquid chromatography (DHPLC) analysis and direct DNA sequencing were performed. Heterozygous mutations were identified in 18 of 72 samples (25%). Two new disease-genes were identified: cardiac myosinbinding protein C (MYBPC3) and α-tropomyosin (TPM1). 5 mutations were found in MYBPC3, and 2 in TPM1. MYH7 was the most prevalent disease gene and accounts for 11% of cases followed by MYBPC3 as the second most frequent disease gene (7%). Conclusions: Mutations in sarcomere protein genes account for a significant proportion of cases of isolated LVNC in this cohort (25%). We describe the first mutations in MYBPC3 and TPM1 associated with LVNC in adult patients. These findings open new perspectives for genetic investigations and counseling. P3245 Myosin mutations in familial hypertrophic cardiomyopathy: primary functional defects and development of contractile dysfunction T. Kraft 1, S. Dunda 1, S. Tripathi 1, E. Becker 1, A. Perrot 2, C. Oezcelik 2, W.J. McKenna 3, F. Navarro-Lopez 4,A.Francino 4, B. Brenner 1. 1 Medical School, Hannover, Germany; 2 Max-Delbrueck-Centrum fuer Molekulare Medizin, Berlin, Germany; 3 The Heart Hospital, London, United Kingdom; 4 Hospital Clinic i Provincial, Barcelona, Spain Purpose: Familial hypertrophic cardiomyopathy (FHC) in about one third of families is caused by point mutations in the ventricular myosin heavy chain (β-mhc). Little, however, is known about basic functional effects of these mutations at the molecular level. We addressed this question in functional studies of muscle cells from FHC patients with β-mhc mutations R723G (Barcelona mutation), R719W and I736T, respectively. Since for some other mutations no or only minor functional changes were found, we also determined the ratio of mutant (MT) to wildtype (WT) β-mhc at the protein and mrna-level in muscle biopsies of the patients. Methods: Since in humans β-mhc is also expressed in slow skeletal muscle, M. soleus biopsies of FHC patients and of healthy controls were used. We measured force, kinetic parameters and calcium-sensitivity of single fibers. NanoLC/ESI-MS and a restriction digest method were used for relative quantification of the ratio of MT:WT myosin and β-mhc-mrna, respectively. Results: Mutations Arg723Gly and Arg719Trp both are associated with reduced calcium sensitivity, while for mutation Ile736Thr larger active forces were found, particularly at low calcium-concentrations. Most surprisingly, compared to fibers from controls, individual fibers from each FHC patient showed a much larger variability in calcium sensitivities ranging from almost normal to highly significant differences. Protein and mrna quantification showed a deviation from the generally assumed 1:1 ratio of MT:WT, ranging from <20% up to nearly 70% of MT myosin, and seemed to correlate with magnitude of functional changes and malignancy of disease. Patients with the same mutation had a very similar average fraction of MT myosin and/or β-mhc-mrna, even if they were siblings of different generations or from unrelated families. Conclusions: (1) The observed Ca 2+ -desensitizing effect of two mutations studied is in conflict with the idea that increased vs. decreased Ca 2+ -sensitivity of isometric force generation could be one critical parameter for development of FHC vs. DCM. (2) Despite heterozygozity of the mutations the ratio of MT vs. WT myosin mostly deviates from 1:1. The deviation seems characteristic for the respective mutation and is present already at relatively young age. (3) The observed deviation from 1:1 may result from a variable ratio of MT:WT myosin in individual muscle fibers. We hypothesize that variable fractions of mutated myosin in individual cardiomyocytes, resulting in imbalances of contractile function among neighboring cells, might trigger contractile dysfunction and development of myocyte disarray.

242 542 Genetic aspects of cardiomyopathies P3246 The growth hormone inducible transmembrane gene is a novel genetic modifier of left ventricular hypertrophy in families with hypertrophic cardiomyopathy M. Parker 1, C. Kinnear 2,B.Keavney 3, H. Watkins 4,B.M.Mayosi 1, J. Moolman-Smook 2. 1 University of Cape Town, Cape Town, South Africa; 2 University of Stellenbosch, Cape Town, South Africa; 3 Newcastle University, Newcastle-upon-Tyne, United Kingdom; 4 University of Oxford, Oxford, United Kingdom Purpose: To test positional candidate genes for association with quantitative variation in left ventricular hypertrophy. These positional candidate genes were identified by genome-wide mapping in a collection of families with hypertension from Oxford, United Kingdom in a previous study. In this study, South African families with hypertrophic cardiomyopathy were used as a model for studying genetic modifiers of left ventricular hypertrophy. The most promising candidate gene, from a region on chromosome 10 with a LOD score >2, was selected for investigation. This gene, GHITM, encoding a growth hormone inducible transmembrane protein, is highly expressed in the heart and is likely to be involved in growth hormone signalling and energy metabolism. Methods: We performed the quantitative genetic association analysis in a unique panel of South African families with hypertrophic cardiomyopathy due to known founder gene mutations. All 267 affected and non-affected members of these families were studied. SNaPshot was employed for single nucleotide polymorphism (SNP) genotyping of 8 haplotype tagging SNPs across the GHITM gene. Familybased tests of genetic association were implemented in the Quantitative Transmission Disequilibrium Test. Results: Despite a modest size of the cohort, our results show significant association between the rs SNP in GHITM and a range of measures of echocardiographic left ventricular hypertrophy, including the cumulative wall thickness score and interventricular septum (p<0.005). The rs SNP in GHITM was associated with ECG QRS duration (p=0.028) Conclusion: Our data suggest that the GHITM gene is a novel genetic modifier of echocardiographic and electrocardiographic LVH in families with hypertrophic cardiomyopathy. P3247 Complex sarcomeric genetic status is not an important modifier of disease severity in MYBPC3 associated hypertrophic cardiomyopathy M. Van Tienhoven 1, Y.M. Hoedemaekers 1,M.Michels 2,F.J.Ten Cate 2, D.F. Majoor-Krakauer 1, D.J.J. Halley 1, D. Dooijes 1. 1 Erasmus MC Dept. of Clinical Genetics, Rotterdam, Netherlands; 2 Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Background: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder with a high degree of inter- and intrafamilial variability in clinical expression. Mutations in more than 11 genes, mostly encoding sarcomeric proteins, are known to cause HCM. Variability in clinical expression is thought to be caused by the action of currently unknown modifying factors Current consensus partially explains the variability in disease severity by the effect of additional, secondary, mutations in sarcomeric genes. To analyse whether a complex HCM genotype is an important modifier of disease severity in HCM we completely analysed 11 HCM genes in a large cohort, homogeneous with respect to primary HCM causing mutation. Methods: We analysed the complete coding regions of MYH7, MYBPC3, MYL2, MYL3, TNNT2, TNNI3, TNNC1, ACTC1, TMP1, TCAP and CSRP3 in a large cohort of patients with a truncating MYBPC3 mutation as primary HCM defect. The patients from the cohort were clinically diagnosed as either having a mild (no cardiac complaints, IVS<20mm) or a severe phenotype (myectomy, HTX, (aborted) sudden cardiac death, necessary ICD implantation, cardiac related stroke, IVS>30mm). Results: no additional mutational burden was seen in the group with severe HCM compared to the group with milder HCM. Conclusion: Contrary to general consensus, the severity of phenotypic expression of HCM is not primarily dependent on the modifying effects of secondary sarcomeric mutations. Disease prognosis and severity in HCM is more likely to be modified by environmental factors as well as genetic factors, other than additional mutations in the analysed sarcomeric and Z-disk genes. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder. It is the most frequent cause of sudden cardiac-related death in young people and a major cause of cardiac failure and death in the elderly. However, HCM frequently goes undiagnosed until the appearance of overt signs and symptoms, thereby delaying prophylactic and therapeutic measures. We screened patients for sarcomeric genes associated with HCM to obtain information useful for an early diagnosis and so limit the severe consequences of silent HCM. We recruited 39 HCM families from Southern Italy and found mutations in 41% of families (12 with familial HCM and 4 with sporadic HCM). The remaining 23 families (59%) were negative for myofilament gene mutations. Of the 12 mutations identified, 8 were novel. Screening of the other family members available revealed that 27 had mutations; 11 of these subjects had no signs or symptoms suggestive of HCM. Childhood- and Elderly-onset HCM Mutation Childhood- Childhood- Elderly- Elderly- OnsetHCM a OnsetHCM b OnsetHCM c OnsetHCM d (n=39) (n=84) (n=203) (n=197) MYH7 23% 23.8% 17% 25.4% MYBPC3 10.2% 23.8% 34% 26.4% TNNT2 5.1% 4.7% 3.4% 4% TPM1 2.6% 2.4% 1% 0% TNNI3 0% 2.4% 0.5% 4% ACTC 0% 2.4% 0.5% 0% MYL2 0% 0% 3.4% 2.5% MYL3 0% 1.2% 0% < 1% Total detected 40.9% 60.7% 59.8% 62.9% Undetected 59.1% 39.3% a This study, b Morita et al. 2008, c Olivotto et al. 2008, d Richard et al This study, besides characterizing the spectrum of mutations in another childhood population (Table 1), and revealing an even greater genetic heterogeneity than formerly recognized, may increase genotype-phenotype correlations, and thus may help to identify asymptomatic candidates for early preventive or therapeutic measures. P3249 Fabry Mice (Knock-Out) have infiltrative cardiomyopathy with atrial arrhythmia and dilated ascending aorta B. Escoubet 1, D.G. Warnock 2, A. Nguyen Dinh Cat 3,V.Griol- Charhbili 3,M.Beck 4, C. Kampmann 4, F. Jaisser 3. 1 AP-HP, Hopital Bichat- Claude Bernard, Physiology, University Paris 7 Denis-Diderot, Inserm U872, Paris, France; 2 University of Alabama, Birmingham, United States of America; 3 Inserm U872, University Pierre et Marie Curie, Paris 6, Paris, France; 4 Johannes Gutenberg Universitaet, Mainz, Germany Purpose: Fabry disease is an X-linked deficiency of alpha-galactosidase A (AGAL), with kidney disease, strokes, and an infiltrativecardiomyopathy with arrhythmias, and myocardial fibrosis. A knock-out (KO) mouse model is available for, but the cardiac phenotype has not been studied. Male KO mice are hemizygous ( /0) and females are homozygous ( / ); in humans, males are ( /0), but females are heterozygous ( /+). Methods: Tail cuff blood pressure and heart rate, EKG and echocardiographic studies were done on mice ranging from 2 to 4 months of age, and compared to wild-type (C57BL/6J) mice. Results: KO mice had lower heart rate and systolic blood pressure than controls. Heart weight, relative to tibia length was increased in male Fabry KO mice. EKG studies showed lower heart rate at 2 to 4 months in males and females compared to controls. Male KO mice had 4-fold increase in occurrence of atrial premature contractions (APC) compared to controls and no ventricular arrhythmia. In the KO mice, ECHO studies showed increase in ascending aorta diastolic diameter and in Left Ventricular Mass Index without LV systolic alteration (ejection fraction) but increase in isovolumic relaxation time consistent with diastolic dysfunction. P3248 Analysis of sarcomeric gene proteins in a child choort enlarges the genetic spectrum of hypertrophic cardiomyopathy G. Frisso 1, G. Limongelli 2,G.Pacileo 2, A. Del Giudice 1, L. Forgione 1, P. Calabro 2,M.Iacomino 2,L.M.DiFonzo 1, R. Calabro 2,F.Salvatore 1. 1 CEINGE Biotecnologie Avanzate-Dipartimento di Biochimica e Biotecnologia Medica-Università Federico, Naples, Italy; 2 AO Monaldi-Second University of Naples, Naples, Italy APC in Fabry mice Conclusions: 1). KO mouse has a phenotype consistent with a mild infiltrative cardiomyopathy and large vessel alteration. 2) The phenotype has similar severity in the male and female mice, which are completely devoid of AGAL activity.

243 Genetic aspects of cardiomyopathies 543 P3250 Screening of the four genes most commonly involved in hypertrophic cardiomyopathy G. Smaniotto 1,P.Melacini 2,C.Calore 2,V.Pescatore 2, A. Lorenzon 1,S.Iliceto 2, G.A. Danieli 1. 1 Department of Biology University of Padua, Padua, Italy; 2 Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy Purpose: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease with a prevalence of 1:500 in the general population. The clinical presentation and natural history is heterogeneous, ranging from benign asymptomatic forms to more malignant expressions that may result in sudden or heart failure death. To date, over 455 mutations have been reported in 20 different genes encoding proteins of the cardiac sarcomere, proteins of the z-disc, protein of the intercalated discs. Pathogenic mutations in the β-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2) and troponin I (TNNI3) genes account for about 70% of the total. The aim of the present study was to perform a systematic screening of these genes in an Italian consecutive cohort of HCM patients. Methods: We analyzed a series of 82 patients (age: 33±17 years; 60 males, 43 index cases and 39 isolated cases) enrolled at a tertiary Center. The method involved PCR amplification of exons or exon segments of MYH7, MYBPC3, TNNT2, TNNI3 genes, denaturing high performance liquid chromatography of amplicons and direct sequencing. Results: In 24 (29%) of the 82 patients we identified 22 distinct mutations of which 16 were classified as novel (not found in a control series of 300 chromosomes). Nine (41%) mutations were identified in MYH7 gene, 7 (32%) in MYBPC3 gene, 4 (18%) TNNI3 gene and 2 (9%) in TNNT2 gene. Two patients carrying MYH7 (G407C) and MYPC3 (A364T) mutation suddenly died at young age; five patients with single mutation in MYH7 (I1207M), MYBPC3 (A364T e Q366X), TNNI3 (K207T) o TNNT2 (R94L) are transplanted at age 60, 12, 62, 28, and 59 yrs respectively. Moreover, we detected 3 patients carrying a double mutation: one young proband showing two mutations in the MYH7 gene suddenly died and one of two patients carrying one mutation in MYH7 and the other in MYBPC3 gene died of heart failure at young age. In 5 malignant families for SD and HFD with identification of causative mutation, genetic testing was performed in 17 first degree relatives. Of these, 4 affected familial members had the same mutations of index cases, 7 relatives were unaffected and not carriers and 6 affected familial didn t share the same mutation of proband. Conclusions: Mutation screening of the four genes most frequently involved in HCM is complex, expensive and pathogenic mutation was detected only in 30% of patients. Therefore, these results might have implications for genetic diagnosis strategy leading to improve genetic counselling and better clinical management in families with HCM. P3251 Cytokine gene polymorphisms are associated with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy S. Adamopoulos 1, F. Kolokathis 2, A.G. Gkouziouta 1, P. Georgiadou 1, A. Chaidaroglou 1,G.Karavolias 1, D. Degiannis 1, V. Voudris 1, D.T.H. Kremastinos 2. 1 Onassis Cardiac Surgery Center, Athens, Greece; 2 University of Athens, Attikon Hospital, Athens, Greece Aims: To identify potential genetic associations of 5 cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). Methods: 80 DCM patients (age=48.5±13.8 years, NYHA=1.6±0.7, LVEF=29.5±8.5%, VO2max=23.6±8.0 ml/kg/min) were included to the study. All participants were genotyped for transforming growth factor beta1 (TGF-β1) +869 T/C, TGF-β G/C, interleukin (IL)-6-174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ) +874T/A, IL A/G, IL T/C and IL A/C gene polymorphisms. Patients were followed up for 70±31.2 months considering as end points of the study: 1) cardiac death, 2) cardiac transplantation and 3) hospitalisations due to heart failure decompensation. Results: In homozygous TT for TGF-β T/C polymorphism VO2 max was significantly higher than in CC homozygous (25.6±6.7 ml/kg/min vs. 20.2±6.3 ml/kg/min, p=0.04). C carriers of TGF-β G/C polymorphism are 4.2 times more likely to be in worse NYHA stage (III-IV) than non C carriers (OR: 4.25, p=0.006). During follow up, 19 patients were hospitalised, 14 patients died and 1 underwent transplantation. Kaplan-Meier plots revealed that the T/T homozygosity of IFN-γ +874G/A polymorphism were associated with increased probability for cardiac death or transplantation (p=0.02 picture) and the combination of the TGF-β T/C and TGF-β G/C with increased probability for cardiac death, transplantation or hospitalization (p=0.014). Conclusion: Specific cytokine gene polymorphisms seem to be associated with disease severity and worse prognosis in DCM. These associations may identify genes in pathways important for DCM pathogenesis, clinical expression and therapy. P3252 Connexin expression patterns in the pathophysiology of arrhythmogenic right ventricular cardiomyopathy M. Paul, G. Weiss, P. Milberg, E. Schulze-Bahr, V. Arps, M. Kaestel, J. Wiekowski, C.G. Wollmann, G. Breithardt, T. Wichter. University Hospital of Muenster, Muenster, Germany Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable myocardial disease accounting for ventricular tachyarrhythmias (VT) and sudden death in a young population. It is characterised by fibro-fatty replacement of cardiac myocytes. Genetic analyses have identified disease causing mutations in desmosomal proteins. In some patients (pts) life-threatening VT occur in the absence of substantial myocardial replacement so that an additional disruption of gap junction integrity has been hypothesized. Therefore, we analysed the expression of specific gap junction proteins (connexins, Cx) in endomyocardial biopsies (EMB) from ARVC pts. Methods: Right ventricular EMB were sampled from 16 pts with definite ARVC (48±16 years) and analysed for Cx40, Cx43, and Cx45 mrna expression (relative to GAPDH mrna expression). Results were compared to those obtained from non-diseased donor hearts (n=6; 32±11 years). In addition, genetic analyses for mutations in the gene encoding for the cardiac plakophilin2 (PKP2) were performed. Results: ARVC pts showed a significant reduction in the mrna expression of Cx40 (0.28±0.18 vs. 0.67±0.11; P<0.0001) and Cx45 (0.08±0.07 vs. 0.51±0.12; P< ) when compared to controls. Expression levels of Cx43 were comparable between ARVC and control pts (0.42±0.08 vs. 0.49±0.09; P<NS). <br non-carriers. and carriers mutation between comparable were levels expression Cx but (50%) pts 14 7 in identified mutations PKP2. Conclusions: In pts with ARVC, a significant reduction in gap junction proteins independent of the presence of known desmosomal mutations was detected in vivo. This may provide a substrate for arrhythmogenesis and may explain an altered coordination of cellular formation eventually leading to fibrofatty replacement in pts with ARVC. Further studies are necessary to prove this concept. P3253 Phenotypic characterization of hypertrophic cardiomyopathy associated with K600fs mutation in cardiac myosin-binding protein C gene M.F. Ortiz 1, M. Hermida-Prieto 2, R. Barriales-Villa 3, X. Fernandez 4, M.I. Rodriguez-Garcia 2,L.Cazon 2, L. Nunez 2,E.Veira 3, A. Castro-Beiras 5, L. Monserrat 5. 1 Fundación Carolina/BBVA, A Coruna, Spain; 2 Instituto Universitario de Ciencias de la Salud, A Coruna, Spain; 3 Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruna, Spain; 4 Red de Investigación Cardiovascular - RECAVA, A Coruna, Spain; 5 Complexo Hospitalario Universitario A Coruna, A Coruna, Spain Purpose: Hypertrophic cardiomyopathy is usually associated with sarcomeric gene mutations. Myosin-binding protein C (MYBPC3) is one of the most frequently mutated genes. Genotype-phenotype correlations are often difficult due to limited number of cases reported in each mutation. Here we characterize K600fs mutation carriers in MYBPC3 gene, found in several Spanish families. Methods: Clinical study and phenotypic characterization of probands and family members of eight families in which K600fs mutation was detected. Results: We found 21 carriers in 8 families. All families were original from a small region of Galicia, North West of Spain. Mutation penetrance was 90% in older than 30 years and cosegregation with the disease was found in all families. Mean maximal wall thickness was 20 mm (two subjects had >30 mm). Morphology of hypertrophy (asymmetric septal reverse curvature) and late enhancement localization at cardiac magnetic resonance images (mid septal) was reproducible in several cases through different families. Most carriers were in NYHA class II and left ventricular outflow tract obstruction was present in 4 patients. Left atrium dilation (mean diameter 48 mm) and early atrial fibrillation (AF) were present in 9 (42%) and 6 (28%) carriers respectively. Most of those with AF have practiced competitive sports. Surgical miectomy was done in 1 carrier and automatic defibrillators were implanted in 2 (primary prevention at 26 and 37 yo). Two sudden deaths (18 and 42 yo) and one cardiac transplant (35 yo) were reported in young family members. Stroke related death was reported in two young carriers (41 and 55 yo) and 3 family members (rank: yo) without genetic study. This mutation was previously reported only in one French patient and is supposed to produce a truncated protein with lost of C4 to C10 domains. Conclusions: Correct familial and clinical evaluation in suitable number of mutation carriers allows genotype-phenotype correlations. K600fs mutation could have a common founder effect in North West of Spain. Mutation carriers develop se-

244 544 Genetic aspects of cardiomyopathies vere left ventricular hypertrophy at young age and main complications are early AF and strokes. Sport practice could act as an environmental modifier factor in carriers. P3254 The +49A/G polymorphism in exon 1 of the cytotoxic T lymphocyte-associated protein 4 (CTLA4) gene is associated with dilated cardiomyopathy V. Ruppert 1,T.Meyer 1,C.Struwe 1,A.Perrot 2, M.G. Posch 2, C. Oezcelik 2, A. Richter 1, B. Maisch 1, S. Pankuweit 1 on behalf of German Competence Network of Heart Failure. 1 Philipps Universitaet, Marburg, Germany; 2 Experimental and Clinical Research Center (ECRC), Max-Delbrück Center for Molecular Medicine, Berlin, Germany Introduction: Infections with cardiotropic viruses often lead to ongoing autoimmune reactions in the myocardium that may result in the transition from chronic myocarditis to dilated cardiomyopathy (DCM). Since cytotoxic T lymphocyteassociated protein 4 (CTLA4) is expressed as an inhibitory receptor on T cells, we examined whether mutations in the CTLA4 gene are associated with DCM. Methods: From 417 patients with clinically diagnosed DCM and 370 healthy controls the promoter as well as all four coding exons of the CTLA4 gene were amplified by different PCR reactions. The resulting PCR products were analysed for mutations using denaturing gradient gel electrophoresis (DGGE). In case of the promoter polymorphism ( 318C/T) a restriction fragment length polymorphism (RFLP) analysis was performed by digesting PCR products with the restriction endonuclease Mse1. Results: In the CTLA4 gene two polymorphisms at positions -318 and +49 were confirmed. For both polymorphisms no deviations from the Hardy Weinberg equilibrium were observed. In the whole sample no significant association of the 318C/T polymorphism with DCM was found. In contrast, for the A/G polymorphism in exon 1 we demonstrated a significant association with DCM. The G/G genotype was detected more frequently in patients with DCM than in controls (13.9% vs. 7.6%, p=0.01, see Table). Table 1. Allele frequency of CTLA4 polymorphisms at positions -318 and +49 in patients with DCM and controls Alleles -318C/T Alleles +49A/G DCM patients Controls DCM patients Controls (n=417) (n=374) (n=417) (n=374) CC 84.5% 81.6% GG 13.9%* 7.6% CT 15.0% 17.4% AG 45.9% 45.9% TT 0.5% 1.0% AA 40.2% 46.5% *p=0.01. Conclusions: In patients with DCM a significant association of the G/G genotype at position +49 of the CTLA4 gene was demonstrated. This polymorphism leads to a substitution of alanine for threonine at position 17 of the corresponding gene product. These genetic data point to a functional relevance of the CTLA4 gene in the immunopathogenesis of at least some subentities of dilated cardiomyopathies. P3255 Genetic screening in patients with cardiomyopathy in the west of Scotland I.N. Findlay 1,V.Murday 2 on behalf of National Service Division of the Scottish Government. 1 Western Infirmary, Glasgow, United Kingdom; 2 Duncan Guthrie Institute of Clinical Genetics, Glasgow, United Kingdom A regional service for patients with Inherited Cardiac Conditions was established in the West of Scotland (population 3 million) in Funding for molecular genetic analysis for abnormalities of the 4 common sarcomeric proteins is provided by the National Services Division of the Scottish Government. Analysis by the Oxford Regional Molecular Genetics Laboratory. We describe our experience with our first 121 genotyped families, 84 with hypertrophic cardiomyopathy (HCM) and 33 with definite familial dilated cardiomyopathy (DCM) and 4 with left ventricular non-compaction (LVNC). In families with HCM we have detected mutations in 59 (70%) being MYBPC3 in 58%, MYH7 in 27%, TNNT2 in 7% and double mutation MYH7/MYBPC3 in 1 family. In those with no family history (FH) the detection rate was 40%, in those with a FH detection rate was 84%, and in those with FH of sudden cardiac death detection rate 93% (table). In 33 with familial dilated cardiomyopathy, 30 families have had sarcomeric proteins assessed, seven of these have in addition had lamin A assessed and three families Lamin A only. Overall detection rate was much lower with 6 mutations detected (18%). Sarcomeric mutations were detected 4/30 (2 MYH7, 1 TNNT2, Pattern of genetic mutation in HCM No FH FH FH of Sudden Cardiac Death MYBPC3 (%) MYH7 (%) TNNT2 (%) MYH7/MYBPC3 (%) TNNI3). Lamin A mutations were found in 20% (2/10 + one variant of unknown significance). In the 4 families with LVNC we have detected 2 mutations (1 MYH7 and 1 MYBPC3) Conclusion: In patients with HCM, molecular genetic analysis of 4 common sarcomeric proteins detected a pathogenic mutation in 70% overall with a high detection of 93% in those with a family history of sudden cardiac death but a low pick up rate of only 40% in those with no antecent family history. The turn around time for results from the index case is now down to around 3 months making cascade screening efficient and realistic in patients with HCM. This is not the case yet in DCM and a reassessment of the genes to be screened is underway. P3256 Lamin A/C mutations in patients with dilated cardiomyopathy and conduction disease, ventricular dysrhythmia or family history of sudden death P. Ehlermann 1, K. Georgiev 2, B. Ivandic 1,R.Zeller 1,R.Pribe 1, C. Zugck 1, A. Remppis 1, E. Gruenig 3, D. Weichenhan 4, H.A. Katus 1. 1 Universitaetsklinikum Heidelberg, Heidelberg, Germany; 2 Herzzentrum Bad Krozingen, Bad Krozingen, Germany; 3 Thoraxklinic Heidelberg ggmbh, Heidelberg, Germany; 4 German Cancer Research Center, Heidelberg, Germany Background: Mutations in the lamin A/C gene (LMNA) are among the most frequent genetic causes of dilated cardiomyopathy (DCM). They are reported to result in a specific phenotype characterized by DCM in combination with early incidence of conduction disease and a high risk of sudden death. We sought to determine the frequency of LMNA mutations in a study cohort with was selected for conditions with a higher probability for this gene defect. Methods: We performed screening of LMNA in 65 patients with DCM and additional conduction disease, status after pacemaker implantation, history of ventricular fibrillation or sustained ventricular tachycardia, evidence for muscular disease, history of dilated cardiomyopathy or sudden unexplained death in first degree relatives before the age of 50 years. Results: Three new mutations were identified in one sporadic and two familial cases: A missense (Arg335Gln), a nonsense (Arg321ter) and a splice mutation. Compound mutations in MYH7, MYBPC3, and TNNT2 were excluded. The two families with nonsense and splice mutations respectively showed a striking history of sudden deaths and pacemaker implantations. The cosegregations of the mutation with the disease in these affected families suggest that they are causing DCM and sudden death. Conclusion: LMNA mutations can be found with a significant amount under DCM families with a high burden of pacemaker implantations and sudden death. Therefore, genetic screening including Lamin A/C should be considered in order to identify persons at risk. P3257 Striking ethnic differences in the prevalence of apical hypertrophic cardiomyopathy L.A. Mcgill, S.P. Page, F. Choudhry, J. Orpin, P.G. Mills, S.A. Mohiddin. The London Chest Hospital, London, United Kingdom Introduction: Hypertrophic cardiomyopathy (HCM) presents with different morphological patterns of left ventricular hypertrophy (LVH) including asymmetric septal LVH, and distal LVH (mid-cavity and apical). The prevalence of these HCM variants varies between different ethnic groups. Our local population includes a large number of South East Asians (SE-A) in whom apical HCM appeared to be the predominant morphologic variant of HCM. We therefore sought to describe the features of HCM in SE-A patients and to determine if they differed from other ethnic groups. Methods and Results: Of 75 HCM patients studied, 28 (37%) were of SE-A origin, of which the majority (20 or 71%) were Bengali. SE-A patients more commonly reported chest pain (75% vs. 47%; p<0.05) but were similar for a range of other symptoms including dyspnoea, palpitations and syncope. The distribution of morphologic variants of HCM were strikingly different, with distal LVH far more commonly seen in SE-A patients (61% vs. 23%; p=0.001). In non Asian HCM patients asymmetric septal LVH was the predominant variant (66% vs. 39%; p<0.05). When only Bengali patients are considered, distal LVH remains the most frequently observed morphologic variant (65% vs. 27%; p<0.005). Considering all patients, 57% had chest pain on presentation, this was more frequent in patients with distal LVH (71% vs. 47%; p<0.05), many of whom presented acutely with presumed coronary syndrome. Conclusions: The importance of an appreciation of ethnic differences in hereditary disease phenotype and natural history is emphasised by the significant ethnic diversity in many modern European communities. In our cohort, more than half the SE-A HCM patients have distal LVH, an HCM variant uncommon in Caucasians. Acute chest pain was a frequent feature of the initial presentation in this group.

245 Disease mechanism and outcome in cardiomypathies 545 P3258 DISEASE MECHANISM AND OUTCOME IN CARDIOMYPATHIES Incidence, clinical characteristics and outcome of patients with tako tsubo syndrome D. Primetshofer, A. Rusudan, H. Kratzer, J. Reisinger, P. Siostrzonek. Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria Introduction: Tako-Tsubo cardiomyopathy is characterized by an acute onset of transient akinesia of the left ventricular apex and mid ventricle, without underlying presence of significant obstructive coronary artery disease. The apical ballooning syndrome therefore shares typical features of acute myocardial infarction and is supposed to account for up to 2.0% of patients with ST-segment elevation infarctions. We prospectively collected all diagnosed cases duringa4yearperiod. Methods: Among 963 patients with suspected acute STEMI and Non STEMI 31 patients with Tako Tsubo cardiomyopathy were identified. Demographic and clinical parameters were evaluated. Comorbid diseases and the present medication were explored. Standard 12-lead electrocardiography, cardiac markers, twodimensional transthoracic echocardiography analysis and coronary angiography were performed on all patients. In-hospital complications and mortality were investigated. Results: Among 448 patients with suspected acute STEMI and 963 patients with Non-STEMI, 31 patients (2.2%) were diagnosed to have Tako-Tsubo cardiomyopathy. ECG findings in the acute period showed acute ST elevation and ST/T wave abnormalities. All patients had a distinct increase in cardiac enzyme. None of the patients had an epicardial stenosis of more than 50% in the cardiac catheterization. All patients had an abnormal left ventricular ejection fraction and exhibited the characteristic picture of apical ballooning with a large wall-motion abnormality. A control echocardiography showed a complete resolution of the wall motion abnormalities. In the acute phase, patients were treated according to the established guidelines of ST elevation myocardial infarction or acute coronary syndrome. There was a low rate of in hospital complications. All 31 patients survived the acute event. Patients were discharged in stable cardiac condition and were maintained on various cardiac and non cardiac medications. Conclusion: The present study reports the so far largest series of patients with Tako Tsubo cardiomyopathy in Austria. It demonstrates the presence of Tako Tsubo cardiomyopathy in 2.2% of patients, who are acutely referred to a cardiologic department for coronary angiography with suspected myocardial infarction. The prevalence of the disease is particularly high in elderly women, in whom immediate diagnosis by cardiac catheterization is required to rule out coronary disease and to avoid inadequate treatment for acute myocardial infarction. In hospital complications and long term outcome are usually benign, although rare occurrences of the syndrome may occur. P3259 Anthracyclin-induced cardiomyopathy: long-term follow-up of 106 patients C. Lestuzzi 1,E.Viel 1,L.Massa 2,L.Tartuferi 1,G.Sinagra 2, A. Lleshi 3, F. Martellotta 3, G.M. Miolo 3, D. Lombardi 3, N. Meneguzzo 1. 1 Cardiology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano (Pn), Italy; 2 Azienda Ospedaliero - Universitaria Ospedali Riuniti, Trieste, Italy; 3 Oncology, Centro di riferimento Oncologico, National Cancer Institute, Aviano (Pn), Italy Introduction: Anthracyclines (ANTHRA) as Adriamycin (ADM), and analogues as EpiADM, Mitoxantrone (MITO), Daunorubycin (DAUNO) are used for chemotherapy (CT) in various tumors, but may be cardiotoxic and lead to a cardiomyopathy (CM) with left ventricular (LV) dysfunction and congestive heart failure (CHF) commonly considered refractory to standard therapies and with poor prognosis. We report a long-term clinical and echocardiographic follow-up (FU) of 106 patients (pts) with ANTHRA-CM. Methods: ANTHRA-CM was diagnosed after CT in presence of: LV ejection fraction (EF) at echo <50% if it was normal before, or drop of >10% (absolute value) of EF with symptoms of CHF. Pts with acute coronary syndrome, myocarditis, or other possible causes of LV dysfunction and pts with FU <1 month were excluded. FU was made after 3, 6, 12 months and every year thereafter, and as clinically needed. Basic therapies were ACE-inhibitors and beta-blockers; digitalis, diuretics, antiarrhythmic or other drugs were added as needed. Results: We selected 106 pts (9 males, 97 females), aged 20 to 73 (mean 51). Tumors were breast carcinoma in 65, lymphoma in 33, sarcoma in 9, other in 2. Drugs employed were ADM (total dose mg, mean 680) in 55 pts, Epi- ADM (total dose mg, mean 1018) in 73, MITO or DAUNO in 21 (some pts received more than one drug). FU lasted months (mean29, median 20). During FU 74 pts died (one of stroke, the others of neoplastic progression), 32 are currently alive. The main echocardiographic and clinical findings are summarized in the table. Conclusions: In pts with ANTHRA-CM clinical conditions and LV function at echo usually improve at least in the first years with standard therapies. Death is usually due to the neoplastic disease rather than to CHF. Echocardiographic and clinical findings Base 3 months 6 months 12 months 24 months 36 months No. of pts on FU EF min-max 20%-52% 32%-65% 28%-65% 32%-65% 25%-63% 29%-61% pts with EF>55% 0 9 (13%) 18 (29%) 22 (40%) 16 (44%) 7 (21%) NYHA 1 (%) 24 (22.6) 20 (29.8) 32 (51.6) 31 (56.4) 21 (58.3) 19 (58) NYHA 2 (%) 46 (22.6) 44 (65.7) 26 (41.9) 23 (41.8) 15 (41.7) 10 (30) NYHA 3 (%) 31 (29.2) 2 (3) 4 (6.5) 1 (1.8) 0 4 (12) NYHA 4 (%) 5 (4.7) 1 (1.5) pts = patients; FU = Follow-up; EF = Ejection Fraction (echo). P3260 Morpho-functional correlates of the electroanatomic abnormalities in arrhythmogenic right ventricular cardiomyopathy P. Santangeli, M. Pieroni, F. Marzo, A. Dello Russo, G. Pelargonio, M. Casella, A. Camporeale, N. Vitulano, F. Bellocci, F. Crea. Catholic University of the Sacred Heart, Rome, Italy Background: The sensitivity and specificity of cardiac magnetic resonance (CMR) findings in the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) are still debated. Recently three-dimensional electroanatomic mapping (EAM) has been proposed as a reliable tool to identify right ventricular (RV) electrical and structural abnormalities in patients with ARVC. In this study we compared EAM and CMR findings to evaluate the diagnostic and pathophysiologic relevance ofdifferent CMR parameters considered in ARVC diagnosis. Methods: Twenty-two consecutive patients (age 47±16 years, 11 males) with a noninvasive diagnosis of ARVC according to current criteria, underwent CMR with delayed enhancement study and EAM. Right ventricular EAM was divided into 5 areas: outflow tract (OT), postero-inferior wall (PW),free wall (FW), apex (Ap), septal wall (SW). Low-voltage areas (LVA) at EAM were defined as mean electrogram voltage <1.5 mv in >1RV areas. Results: LVAs were present in 11 (50%) patients and were localized in the OT in 6 (27%), in the PW in 7 (32%), in the FW in 3 (14%) and in the Ap in 1 (5%). At CMR, RV global dysfunction was present in 6 (27%) patients. Regional RV wall-motion abnormalities were present in 14 (64%) cases and were localized in the OT in 5 (23%), in the PW in 9 (41%), in the FW in 6 (27%) and in the apex in 4 (18%) patients. Right ventricle fat infiltration was reported in 8 cases (36%) and RV delayed enhancement in 13 (59%) patients. The CMR finding more significantly associated with the presence of LVA was delayed enhancement (P = in the OT, P = in thepw, and P = in the FW). Moreover, with the exception of the apex, also wall-motion abnormalities detected in other regional RV segments correlated with the presence of LVA, with the most significant association being found with the OT (p < 0.001). Global RV dysfunction correlated with the extent of RV involvement at EAM, with patients showing >1 LVA having significantly lower RV ejection fraction compared to those without LVAs (50.5±4.5% vs 55.3±4%, respectively, P = 0.031). Right ventricle fat infiltration was correlated with LVA at EAM only if associated with regional wall-motion abnormalities. Conclusions: The presence and distribution of RV delayed enhancement and regional wall-motion abnormalities are the CMR morpho-functional abnormalities more strongly associated with electroanatomic abnormalities. Fat infiltration without a concomitant regional dysfunction is not associated with electroanatomic abnormalities, thus being confirmed as the less reliable CMR diagnostic criterion for ARVC. P3261 Comparison of electroanatomic voltage mapping and contrast-enhanced magnetic resonance imaging for delineation of fibrofatty scar in arrhythmogenic right ventricular cardiomyopathy/dysplasia M. Perazzolo Marra 1,B.Bauce 1, F. Corbetti 2, L. Cacciavillani 1, G. Buja 1, L. Leoni 1,A.Nava 1, C. Basso 3, S. Iliceto 1, D. Corrado 1. 1 Department of cardiac, thoracic and vascular sciences, University of Padua, Padua, Italy; 2 Service of Radiology, University of Padua Medical School, Padua, Padua, Italy; 3 Department of medical-diagnostic sciences, University of Padua, Padua, Italy Background: Three-dimensional electroanatomic voltage mapping (EVM) by CARTO system has been demonstrated to identify low voltage regions ( electroanatomic scar ) which in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) correspond to areas of myocardial depletion and correlate with fibrofatty myocardial replacement at endomyocardial biopsy. Delayed contrast enhancement (DCE) by cardiac magnetic resonance is an emerging non-invasive technique for demonstration of ventricular scar in different pathologic settings. This study was designed to compare EVM and DCE for detection of fibrofatty scar in ARVC/D. Methods: The study group comprised 21 patients (15 males and 6 females; mean age 38±12 yrs) with a clinical diagnosis of ARVC/D based on the ISFC/ESC criteria and validated by right ventricular (RV) EVM. RV electroanatomic scars (i.e. low amplitude areas with bipolar electrogram <0.5 mv) were identified by sampling multiregional RV bipolar electrograms. All patients underwent a magnetic resonance study including DCE. DCE images were analyzed in long-axis (2C, LAX, 4C), short axis and RV two-chamber views after intravenous injection of 0.02 mmol/kg of Gd-DTPA. Results: Right ventricular DCE was found in 9 of 21 (43%) patients with EVM evidence of RV electroanatomic scar. A total of 26 RV DCE scars were identi-

246 546 Disease mechanism and outcome in cardiomypathies fied in the 9 patients: 8 (31%) in the anterolateral region, 6 (23%) in the apical region, 4 (15%) in the infundibular region, 8 (31%) in the inferobasal region. Regional comparison of DCE zones and electroanatomic low-voltage areas showed a mismatch in 16 RV scar areas, with presence of 14 electroanatomic scars not confirmed on the magnetic resonance views (3 in anterolateral region, 1 in apical region, 4 in infundibular region and 6 in the inferobasal), and 2 DCE scars (both in the infundibular region) undetected by the EVM reconstruction. Left ventricular (LV) DCE was found in 14 of 21 patients (67%), either as isolated-lv involvement in 9 patients (42.8%) or in the form of biventricular involvement in 5 (23.8%). LV DCE predominantly involved the subepicardial and/or mid-wall layers of the anterolateral (10 patients), inferolateral (9 patients), anterior (2 patients), and posteroseptal (1 patient) regions. Overall, any ventricular DCE scars (RV, LV, or biventricular) were detected in 87% of ARVC/D patients. Conclusions: In patients with ARVC/D, DCE shows a significant lower sensitivity than EVM for identification of RV fibrofatty scars. LV DCE, either isolated or associated with RV involvement, is a more common finding and provides higher diagnostic sensitivity. P3262 Correlation between SCD risk factors and appropriate ICD shocks in HCM patients - 13-years-single centre experience P. Syska, M. Lewandowski, A. Przybylski, K. Gepner, A. Maciag, M. Pytkowski, I. Kowalik, R. Maczynska-Mazuruk, L. Chojnowska, H. Szwed. Institute of Cardiology, Warsaw, Poland Purpose: Patients with hypertrophic cardiomyopathy (HCM) should be referred to prophylactic ICD implantation, when they present one or more major risk factors of sudden cardiac death (SCD). The aim of the study was to assess the correlation between patients risk profile and the appropriate ICD shocks rate in the population of patients with HCM. Methods: We retrospectively analyzed SCD risk factors in 104 HCM patients, 47 male, who underwent ICD implantation between Identified risk factors were compared to the number of ventricular arrhythmic events and subsequent ICD interventions. Results: The age of study population was 6 to 75.3 years (mean 35.6). ICD was implanted for secondary prevention of SCD in 26 pts (25%) and for primary prevention in 78 patients (75%). SCD major risk factors were identified as follows: massive ( 30mm) left ventricular wall hypertrophy 28% of pts, family history of SCD 48% pts, non-sustained ventricular tachycardia in 24-hours ECG monitoring (nsvt) 64% pts, syncopies 54% pts and inadequate exertional blood pressure reaction 54% pts. Number of risk factors found in one patient varied: 0 (2pts/2%), 1 (11pts/11%), 2 (44pts/42%), 3 (30pts/29%), 4 (16pts/15%), 5 (1pt/1%). The average follow-up period was 4.6 years (range ). The appropriate ICD interventions occurred in 13/26 patients (50%) implanted for secondary prevention (SP) and in 13/78 patients (16.7%) from the group of primary prevention (PP). The annual rate of appropriate ICD shocks was 7.4%/yr in SP group and 4%/yr in PP group. Arrhythmias leading to appropriate ICD interventions were (group SP/PP): VF (44/12 discharges), VT (18/26 discharges) and VT/VF storm (2/0 episodes). In PP group the only risk factor which was associated with greater probability of appropriate ICD shock was nsvt (Kaplan-Meier curves; log rank: p=0.03). Positive correlation was observed between number of identified risk factors and probability of VF episode (r=0.30, p=0.0107). High rate of inappropriate discharges was observed in the study group: 13/26 patients (50%) from the SP and 22/78 patients (28%) implanted for PP. Four patients died during the follow-up: two from the SP group and two from the PP group. Conclusions: ICD is an effective tool in SCD prevention in HCM patients. NsVT appears to be the strongest predictor of appropriate ICD shocks, but importance of each risk factor, the exact risk stratification and minimazing the number of inappropriate discharges are still goals of challenge. P3263 Myocardial fibrosis and apoptosis, but not inflammation, are present in long-term type I diabetes O. Lorenzo 1, S. Ares-Carrasco 1, B. Picatoste 1, E. Camafeita 2, J.A. Lopez 2, J. Egido 1, J. Tunon Fernandez 1. 1 Fundacion Jimenez Diaz, Madrid, Spain; 2 CNIC, Madrid, Spain Purpose: To study the molecular mechanisms of myocardial damage secondary to long-term type I diabetes mellitus and/or hypertension. Methods: Normotensive and Spontaneously hypertensive rats received a single streptozotocin injection to develop type I diabetes. After 28 weeks, diabetic normotensive (DM1), hypertensive (SHR), diabetic-hypertensive (DM1/SHR) and control rats (6-8 per group) were sacrificed and the left ventricles studied by histology, Quantitative-Protein Chain Reaction, Western Blot, Electro-mobility Shift Assay and two-dimensional electrophoresis/matrix-assisted laser desorptionionization (2DE-DIGE/MALDI) mass spectrometry. Results: The expression of pro-fibrotic factors Transforming Growth Factor-β (TGFβ1), Connective tissue growth factor (CTGF) and matrix proteins was increased, and the TGFβ1-linked transcription factors p-smad3/4 and AP-1 were activated in DM1 rats. The expression of pro-apoptotic molecules Fas Ligand, Fas, Bax and cleaved caspase-3 was also augmented. Myocardial injury in SHR shared these features. The combination of DM1 and hypertension resulted in non-significant additive effects. In addition, hypertension was associated with activation of NF-kB transcription factor, increased inflammatory cell infiltrate and expression of interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), which were absent in DM1. The coexistence of DM1 blunted the inflammatory response to hypertension. Expression of the anti-inflammatory cytokine IL-10 was induced in DM1 and DM1/SHR hearts. In addition, by proteomic approaches we found new altered expression of redox, apoptosis and glucose and fatty acid metabolism-related proteins in DM1, SHR and DM1/SHR animals. Conclusions: Fibrosis and apoptosis are features of myocardial damage in longterm experimental DM1. Associated hypertension does not induce additional changes. Myocardial inflammation is present in hypertension but is not a key feature in late DM1. Furthermore, new factors identified by proteomic approaches may play a role in these processes. P3264 Apparent and persistent healing in spite of severe presentation in idiopathic dilated cardiomyopathy: long-term analysis of a subgroup of patients S. Pyxaras 1,M.Merlo 1, G. Barbati 1, G. Sabbadini 2, G. Lardieri 1, B. Pinamonti 1, A. Di Lenarda 1, G. Sinagra 1 on behalf of Heart Muscle Disease Study Group. 1 Cardiovascular Department, Ospedali Riuniti and University, Trieste, Italy; 2 Depatment of Internal Medicine-Geriatrics, Ospedali Riuniti and University, Trieste, Italy Purpose: A small proportion of patients affected by Idiopathic Dilated Cardiomyopathy (IDCM) presents an apparent healing under tailored treatment. Currently, there are no studies referred to this patient subgroup, that remains still largely unrecognized. In this study, we analyzed the clinical and instrumental characteristics and evolution of this selected IDCM patient population. Methods: In our Heart Muscle Disease Registry were enrolled 361 consecutive patients from 1988 to 1997 (males 73%; age 44±14 years; NYHA functional class III-IV 23%; Left Ventricular Ejection Fraction (LVEF) 30±10%, duration of heart failure at diagnosis 14±25 months). Thus, we statistically analyzed the course, during a follow-up of at least ten years, of the main clinical-instrumental parameters of patients presenting a LVEF at enrolment 35% and a normalization (LVEF 50%) after 24 months on tailored treatment. This subgroup of apparently healed IDC patients was also characterized by a survival-free from heart transplant and appropriate ICD shock during follow up. Results: The so-called healed patient subgroup counted 22 (6%) cases (mean age of 42±9 years, males 77%). At enrolment, they presented NYHA III-IV functional class in 27% of cases, mean LVEF and mean left ventricular end diastolic volume (LVEDV) were respectively 28±6% and 214±90 ml, moderate-severe mitral regurgitation (MR) was present in 46% of patients; they showed a short history of heart failure (6±8 months). At six, 24, 48 and 120 months of follow-up, none of the healed patients was in NYHA III-IV class (p<0.05 within the first six months), mean LVEF was 48, 55, 51 and 46% (p<0.05 between 0-6 and 6-24 months) respectively, a moderate-severe MR was present in 15, 0, 0 and 18% of all cases (p<0.05 between 0-6 months) respectively, while mean LVEDV values were respectively 154, 128, 128, and 136 ml (p<0.05 between 0-6 and 6-24 months). Conclusions: In our study population, the healed patients were a strict minority. They were characterized by a short heart failure history, despite the initial severity of LV remodelling and dysfunction at enrolment. The main clinical-instrumental parameters achieved and maintained long-term improvement and reverse remodelling. Late worsening was possible in same cases. Genetic background, associated predisposing factors, length and severity of disease history and tailored medical treatment are probably determinant in these benign IDC forms. P3265 High incidence of left ventricular involvement in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy determined by tissue deformation imaging A.J. Teske 1, W. Noordzij 1,M.G.Cox 1, B.W. De Boeck 1, M. Burgmans 2, B.K. Velthuis 2, P.A. Doevendans 1, R.N. Hauer 1,M.J.Cramer 1. 1 University Medical Center Utrecht, Department of Cardiology, Utrecht, Netherlands; 2 University Medical Center Utrecht, Department of Radiology, Utrecht, Netherlands Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by fibro-fatty replacement of myocardium, primarily in the right ventricle (RV). However, left ventricular (LV) involvement is associated with poor outcome but is often not recognized on conventional echocardiography. The aim is to detect LV involvement in patients with ARVD/C using conventional and tissue deformation echocardiography. Methods: 34 ARVD/C patients (ARVD/C-p) according to Task Force criteria (TFC) 4 points, 14 of their relatives (either 3 TFC-pt or <3 pt plus mutation, ARVD/Cr), and 34 helathy controls were enrolled consecutively. Conventional echocardiography and deformation imaging were performed. Doppler (TDI) derived as well as speckle tracking (ST) strain(-rate) were calculated in three segments in all six LV walls. Peak systolic strain >-12% was considered abnormal (based on results from the control group). In a subgroup (n=23) CMR was performed with late enhancement (LE) and related to the echocardiographic findings.

247 Disease mechanism and outcome in cardiomypathies 547 Results: In ARVD/C-p (58% men), mean age was 44.7±15.3 yrs and in ARVD/Cr (36% men) 42.2±14.8 yrs. PKP2-mutations were present in 23 patients and 8 relatives, DSG mutation was present in 1 patient. LVEF was reduced in 14 ARVD/C-p (<45%: n=3 and 45-55%: n=11) and 5 ARVD/C-r (<45%: n=2 and 45-55%: n=3) although mean values were comparable (58.6%± 10.6 vs. 55.7% ± 9.9, p=ns). Diastolic dysfunction was present in 9 ARVD/C-p and 2 ARVD/C-r (p=ns). In the ARVD/C-p group, abnormal deformation was found in 93 (17.6%) segments in 26 individuals (76.5%, mean 3.8±3.2 abnormal segments, range 1-12) for TDI and in 73 (13.7%) segments in 20 individuals (58.8%, mean 3.7±3.7, range 1-14) for ST. Predilection sites were the anteroseptal and posterolateral regions. In the ARVD/C-r group both TDI and ST showed 14 (6%) abnormal segments in 7 (50.0%, 2.3±1.8 abnormal segments, range 1-6) and 6 (42.9%, mean 2.3±2.0, range 1-6) individuals for TDI and ST, most often located in the lateral and anteroseptal walls. Feasibility was high for both TDI (88.7%) and ST (86.5%). CMR LE was present in 6 ARVD/C-p and correlated closely to deformation imaging in all but one, in whom we found a deformation of -13% at the site of LE. Visual assessment however, was inaccurate. Conclusion: Deformation imaging detected LV involvement in 76.5% and 50% of ARVD/C-p and ARVD/C-r, respectively, while conventional echocardiography showed abnormalities in only 40%. This novel technique, in particular TDI, shows additional value in detecting subtle LV involvement in patients with confirmed or probable ARVD/C. P3266 Endothelial dysfunction in hypertrophic cardiomyopathy is related to more severe disease F. Cambronero 1, F. Ruiz-Espejo 1,J.A.Vilchez 1, A. Garcia- Honrubia 2, V. Roldan 3, D. Hernandez-Romero 1, G. De La Morena 1, V. Climent 2, M. Valdes 1, F. Marin Ortuno 1. 1 Hospital Universitario Virgen de la Arrixaca, Murcia, Murcia, Spain; 2 Hospital General Universitario de Alicante, Alicante, Spain; 3 Hospital Morales Meseguer, Murcia, Spain Hypertrophic cardiomyopathy (HCM) is characterised by inappropriate hypertrophy, small-vessel coronary artery disease, myocyte disarray and increased interstitial fibrosis. Microvascular dysfuncion is a common finding in HCM and its extent has been proposed as an important prognostic markers. Plasma von Willebrand factor (vwf) is an established marker of endothelial damage or dysfunction, however it has scarcely been studied in HCM, and two small studies did not find any statistical differences compared with controls and no relationship with functional status. We hypothesised that vwf could be raised in patients with HCM and be related to different variables associated with severity of HCM. Methods: We included 124 HCM patients, 91 males, aged 48±15 years and 59 healthy control subjects with similar age and sex. All patients fulfilled conventional criteria for HCM. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, 24 hours ECG-Holter monitoring, and symptom limited treadmill exercise test performed Bruce protocol. MET values (metabolic equivalent units) were calculated. Risk factors for sudden death were evaluated. A blinded cardiac MRI was performed with late myocardial-enhanced study with Gadolinium. Plasma vwf levels were assayed by commercial ELISA. Results: Patients showed higher levels of vwf (140±65UI vs 105±51UI, p<0.001). vwf correlated with age (r:0.25; p:0.009). vwf was found raised in patients with severe functional class (168±66UI/mL vs 131±60UI/mL, p:0.016), atrial fibrillation (172±69UI/mL vs 133±59UI/mL, p:0.012) and significant obstruction (154±68 vs 128±57UI/mL). We did not find any significant association with non sustainded ventricular tachycardia, abnormal blood pressure response to effort test or late Gadolinum enhancement in MRI. Conclusions: We show, for the first time, patients with HCM patients present signficantly raised levels of vwf. The levels of vwf are associated with different conditions related to the severity of the disease. P3267 Blood pressure changes associated with enos gene polymorphism at engine-drivers with stress cardiomyopathy E. Kovaleva, M. Bogdanova, E. Zemtsovsky, V. Larionova. Pediatric Medical Academy, St.-Petersburg, Russian Federation Background: Possibilityof pathological changes in myocardium caused by acute stress is well recognized. At the same time chronic psychoemotional stress (PES) could be an independent reason of stress cardiomyopathy (SCMP) in a person from the high-risk professional group, who has some genetic markers of low stress resistance, associated with vascular reactions caused by PES. Objective: to investigate blood pressure (BP) level and endothelial NO-synthase gene (enos) polymorphism in persons exposed to chronic professional PES and also with noncoronarogenic heart damages. Study population and methods: The subjects of research were railway enginedrivers: 58 men with SKMP selected because of clinically significant arrhythmia and electrical conductivity disturbance at 24-h ECG monitoring and also nonischemic repolarization abnormalities on ECG and/or ECG stress test. Excluding criteria were coronary disease, arterial hypertension (above 140/90 mmhg), Primary/secondary cardiomyopathy of other genesis, including inflammatory and 78 men without a cardiovascular pathology. Patient age of basic (33,9+7,5 years) and control groups (31,8+6,9 years) significantly. All patients underwent clinical BP measurement and testing for 4a/4b enos gene polymorphism by PCR. Results: The systolic (SBP) and diastolic (DBP) blood pressure levels in 4a allele (genotypes 4a/4b and 4a/4a) SKMP patients were increased compared to 4b homozygous SCMP patients (123,07±8,3 vs 128,9±7,2 mm Hg, P<0,01; 78,8±5,7 vs 82,4±5,6 mm Hg, P<0,02). There was not any significant difference SBP and DBP levels in patient in control patient in control group with different genotypes. Conclusions: 4a allele enos gene was bound to be associated with increased SBP and DBP levels in engine-drivers with SCMP. This supports the genetic predisposition to a vascular reactions caused by emotional stress. P3268 Early detection of left ventricular diastolic abnormalities in asymptomatic well-chelated b-thalassaemia major patients with excellent systolic function D. Mytas, L. Kosma, I. Kyriazis, E. Athanasopoulou, P. Stougiannos, L. Pappas, I. Dendrinou, M. Bader, K. Farmaki, V. Pyrgakis. Corinth General Hospital, Corinth, Greece Purpose: Iron overload contributes to cardiac dysfunction due to cardiomyopathy in patients with b-thalassaemia major (bth). We evaluated the reliability of modern echocardiographic markers for the investigation of early left ventricular (LV) diastolic function abnormalities of patients with bth. Methods: We studied 40 well-chelated bth patients (19 male/21 female, aged 30.5±10.3 years), with excellent LV systolic function and absence or past history of heart failure. We accessed both myocardial and liver ironing, while we also calculate LV systolic function applying magnetic resonance imaging (MRI). Then, we registered conventional echocardiographic indices and performed Tissue Doppler Imaging (TDI) on the basal segment of lateral LV wall evaluating systolic and diastolic LV function. Finally, we compared them with 33 normal subjects (15 male/18 female, aged 30.4±13.5 years) that were used as controls. Results: According to all MRI indices, bth patients had normal myocardial (mean T2*Heart: 34.5±4.7msec) and liver (mean T2*Liver: 29.9±6msec) iron concentration measurements. Their systolic LV function was normal (LVEF>60% for all) as accessed by echocardiography (mean LVEF: 65.7±3.3% vs 65.3±1.7%, p=ns) and MRI (mean LVEF: 67.5±3.8%). Besides, their TDI systolic myocardial velocity (Sm) appeared to be in normal range compared to controls (9.08±1.81 vs 9.51±1.49cm/sec, p=0.143). When we evaluated LV diastolic function we observed only minor but no significant increases in E/A and Em/Am indices (both p=ns). Vice-versa, left atrial volume index (LAVI) and velocity propagation (Vp) of mitral valve inflow were found to be significantly affected in bth pts compared to controls: 33.2±8.74 vs 25.34±5.46 ml/m 2 BSA, p<0.001 and 63.57±8.65 vs 70.32±9.22 cm/sec, p= Besides, E/Em and E/Vp ratios that correlate well with LV filling pressure were also increased significantly (7.26±2 vs 6.44±1.82, p=0.05 and 1.54±0.32 vs 1.23±0.31, p<0.001). Finally, Myocardial Performance Index (MPI) were increased in bth group compared to control subjects (0.56±0.11 vs 0.36±0.07, p<0.001). Since LV systolic function was similar in the two study groups, the difference in MPI could be attributed to the impaired LV diastolic function of bth patients. Conclusions: Modern echocardiographic markers can reliably reveal early abnormalities of diastolic left ventricular function even in asymptomatic well-chelated bth patients with preserved systolic function. P3269 Marfan s cardiomyopathy: a novel entity from a well-known disease? F. Alpendurada 1, A. Kiotsekoglou 2, J. Wong 1,W.Banya 1, R. Mohiaddin 1. 1 Royal Brompton Hospital, London, United Kingdom; 2 St George s Healthcare NHS Trust, London, United Kingdom Introduction: Marfan syndrome (MFS) is the commonest inherited connective tissue disease. The cardiovascular system is frequently involved and constitutes the main cause of mortality. The heart can be affected as aortic root dilation and mitral valve prolapse are common causes of valvular regurgitation. However, there is still debate whether there is a primary cardiomyopathy (CM), with previous studies showing conflicting results. Purpose: To evaluate the existence of a primary CM in this population. Methods: From an original cohort of 154 Marfan patients (diagnosis based on Ghent criteria) consecutively referred to our centre for cardiovascular magnetic resonance (CMR), we assessed 72 adult patients with no history of surgery or significant valvular regurgitation on CMR or echocardiogram. Aortic dimensions were evaluated from the aortic annulus, sinuses of Valsalva, ascending aorta, arch and descending aorta. Left ventricular (LV) and right ventricular (RV) volumes, ejection fraction (EF) and mass were evaluated using semi-automated analysis software (CMRtools, London, UK). Volumes and mass values were then normalized to age, gender, and body surface area, and compared with published data in a normal population using the same methodology. Results: A significant proportion of patients (27.8%) showed a mild reduction in LVEF when compared to the patient group with normal EF (53.8%± 3.2% vs. 66.3±4.4%, p<0.01). LV end-diastolic and end-systolic indexed volumes were increased in the same population (27.8% and 25.0%, respectively). Similarly, RVEF

248 548 Disease mechanism and outcome in cardiomypathies was reduced (16.7%) and RV end-diastolic and end-systolic indexed volumes were increased (15.0 and 18.3%, respectively) in a subset of patients in this cohort. When performing multiple regression analysis of LVEF with age, gender, height, weight, aortic dimensions and presence of mitral valve prolapse, no significant predictor of reduced EF was found. Conclusions: This study supports the existence of a primary CM in MFS, which is usually associated with mild systolic impairment. Furthermore, this entity appears to be independent from other cardiovascular manifestations of MFS, warranting precise cardiac assessment in addition to the routine evaluation of other organs and systems. Further studies are needed to assess underlying causes, natural history and outcomes of this condition. Treatment may need to be tailored not only to prevent further aortic root expansion but also to support myocardial function in these patients. P3270 Myocardial fibrosis by late-enhancement magnetic resonance is related to ventricular arrhythmias in dilated cardiomyopathy A.M.G. Almeida, J.S. Marques, L.M. Sargento, C. David, N. Cortez-Dias, D. Brito, M.J. Correia, M.G. Lopes. Hospital Santa Maria, Lisbon, Portugal Objectives: In patients (pts)with dilated cardiomyopathy (DCM), late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) has been found in nearly two-thirds.however, the clinical significance of this finding is not well established. The objective of this study was to assess, in pts with DCM, the relationship of the presence and amount of LGE and the occurrence of complex ventricular arrhythmias. Methods: 40 consecutive pts with DCM were included. Exclusion criteria: ischemic heart disease (normal coronary angiography) and secondary cardiomyopathies (clinical and laboratory assessment). All were classified according to the NYHA functional class and plasmatic NT-pro-BNP was evaluated in all. All underwent CMR study, using the sequences: a) SSFP in short-axis, covering all left ventricle (LV) for volumes and ejection fraction (EF) evaluation; b) LGE (segmented inversion-recovery FGE), mn after 0,2mmol/kg of Gd-DTPA in 2, 3, 4-chambers and short-axis. LGE was classified as subendocardial and midwall and quantified using a LGE Index (LGE mass/lv mass). All pts underwent 24h-Holter, less than one month from the date of CMR, for detection of complex arrhythmias (pairs, triplets,ventricular tachycardia). Results: 23 pts were in NYHA class II and 17 in class III. Mean NT-pro-BNP was 533±143 pg/ml, LV end-diastolic volume was 173±44mL/m 2, EF was 31±8%. LGE was present in 27 pts (68%) and was midwall in all, involving a mean of 8 segments. Complex arrhythmias were found in 30 pts. In comparison with pts without LGE, pts with LGE had higher NT-pro-BNP (974 vs 422 pg/ml, p=0.001), larger LV end-diastolic volume (182 vs 137ml/m 2, p=0.001), lower EF (26% vs 35%, p=0.001) and higher number of complex arrhythmias episodes (p=0,0004). There was no correlation between the LGE Index and the number of arrhythmias. By multivariate analysis, the presence of LGE was an independent predictor of non-sustained ventricular tachycardia (p=0.002) among clinical, laboratory and LV functional variables. Conclusions: In pts with DCM, the presence of LGE was related to complex ventricular arrhythmias and was an independent predictor for non-sustained ventricular tachycardia. P3271 Low accessibility of human cardiomyocytes with advanced Fabry disease to enzyme replacement therapy A. Frustaci 1, E. Morgante 1, D. Antuzzi 2, R. Verardo 1, M.A. Russo 1, C. Chimenti 1. 1 La Sapienza Universita, Rome, Italy; 2 Catholic University of the Sacred Heart, Rome, Italy Purpose: Real impact of enzyme replacement therapy (ERT) on Fabry disease s cardiomyopathy (FDCM) is still unclear. The purpose of the study is to evaluate the ability of ERT to increase enzyme activity in the myocardium, to enter the cardiomyocytes and to remove the storage material, in FD patients with mild and severe left ventricular hypertrophy. Methods: Ten male patients (45.0±7.3 years) with advanced FDCM (echocardiographic maximal wall thickness (MWT) 19.3±2.1 mm), and two young men (25±1.4 years) with early FDCM (MWT 11.9±0.1 mm) underwent left ventricular endomyocardial biopsy before and 4 hours after beta-agalsidase infusion (1 mg/kg). Comparative studies between pre and post infusion samples included: a) assessment of myocardial alpha-galactosidase A activity, b) immunohistochemistry for alpha-galactosidase A and semiquantitative evaluation (from 0 to 3) of its cardiomyocyte content, c) histology and electronmicroscopy. Controls were surgical left ventricular biopsies from patients with mitral stenosis. Results: Myocardial alpha-galactosidase A activity increased in post infusion samples by overall 90% in the 10 patients with severe FDCM, and by more than 500%, up to control values, in the 2 patients with early FDCM. Alphagalactosidase A immunostaining was absent at baseline in all patients; it did not significantly improve in postinfusion samples in severe cases (from 0 to 0.5), while it increased in patients with mild FDCM (from 0 to 2). Ultrastructural evaluation showed in the former group no removal of storage material from lysosomes, while in the latter 2 patients vacuolar area occupied by myelin figures decreased by overall 35% in post-infusion samples. Conclusions: Our study shows an impact of ERT only for the early phase of FDCM. For the most severely affected subjects a higher ERT dosage should be considered. P3272 Deleterious impact of anemia on survival in patients with idiopathic dilated cardiomyopathy A. Aleksova 1,M.Merlo 1, G. Barbati 1,S.Brigido 1, G. Sabbadini 2, F. Silvestri 3, A. Di Lenarda 4,G.Sinagra 1 on behalf of Heart Muscle Disease Study Group. 1 Cardiovascular Department, Ospedali Riuniti and University, Trieste, Italy; 2 Depatment of Internal Medicine-Geriatrics, Ospedali Riuniti and University, Trieste, Italy; 3 Department of Morbid Anatomy, Ospedali Riuniti and University, Trieste, Italy; 4 Cardiovascular Center, Azienda per i Servizi Sanitari (A.S.S.) n 1, Trieste, Italy Purpose: Anemia occurs frequently in patients with heart failure. Dilated cardiomyopathy (DCM) is a common cause of heart failure. The impact of anemia on outcome was not previously evaluated in patients with DCM. We sought to determine the predictive role of anemia present at enrolment and developed during the follow-up for the subsequent outcome in large population of young patients affected by idiopathic DCM on optimal medical treatment with ACE inhibitors and Beta Blockers. Methods: For the purpose of the present study we analyzed the data of 557 patients with idiopathic DCM enlisted in the Trieste Heart Muscle Disease Registry after the year 1988 (mean age 45±14 years, males 75%, NYHA III-IV 27%, LVEF 30±10%, haemoglobin (Hb) 14.2±1.5 g/dl, creatinine 1.1±0.2 mg/dl, glomerular filtration rate 86±26 ml/min). Anaemia was defined, according to OMS, as Hb concentration <13g/dL for males and <12 g/dl for females. Results: Anaemia was present in 63 (11.3%) patients at baseline, while in 94 (17%) was diagnosed during follow-up. Patients with anemia at baseline were more likely to have a glomerular filtration rate 90 ml/min (70 vs. 54%, p=0.02), lower BMI (24±4 vs.26±4 kg/m 2,p<0.001) and more dilated left ventricle (LV) (indexed LV end-diastolic diameter 38±7 vs. 36±5, p=0.004, indexed LV endsystolic diameter 32±7 vs. 30±6, p=0.03) in comparison to non anaemic patients while no difference was found regarding LV systolic and diastolic function and medical treatment. During follow-up 23 (36%) out 63 anaemic patients and 147 (30%) of 494 patients non presenting anaemia died or underwent heart transplantation (p=0.09). At Cox proportional hazards model, the presence of anaemia at baseline was independent predictor of death or heart transplantation (HR=1.76, p=0.02). During a follow-up of 96±61 months the new-onset of anaemia emerged as an independent predictor of worse outcome (HR= 5.2, p=0.01) at multivariable Cox model and was associated to a worse survival (p<0.001). Conclusions: In this selected population of young patients with idiopathic DCM optimally treated with ACE inhibitors and Beta Blockers the presence and the development of anaemia was associated to a worse outcome. P3273 Electrophysiological and molecular remodeling in septal myocytes from fhcm patients R. Coppini, F. Stillitano, S. Suffredini, L. Sartiani, J. Olivotto, F. Cecchi, A. Mugelli, E. Cerbai. University of Florence, Florence, Italy Familiar Hypertrophic Cardiomyopathy (fhcm) is the most common cause of sudden death in the young.molecular and electrophysiological mechanisms underlying ventricular hypertrophy and remodeling in fhcm,likely predisposing to fatal arrhythmias,remain largely unknown. To get insight into the cellular arrhythmogenic mechanisms of fhcm, we investigated:the electrophysiological properties of freshly isolated septal myocytes,the role of serotonin 5HT2B receptors and the functional and molecular abnormalities of f-channel (HCN),taken as a marker of remodelling. Septal myocytes were enzymatically isolated from specimens obtained from patients undergoing myectomy;myocytes were patch-clamped to record action potentials (AP), transient outward current (Ito) and f-current (If).Control septal myocytes were isolated from patients undergoing aortic valve replacement.biopsies,obtained from fhcm patients,were used for relative quantification of HCN2/4 isoforms and 5-HT2B receptor gene by Real-Time PCR. Undiseased hearts not used for transplantation served as controls. Results: Duration at 90% of repolarization (APD90) is increased in the fhcm septal myocytes compared to control (762±169ms vs 243±111ms). fhcm action potential does not show the typical notch of phase 1 fast repolarization,clearly evident in control cells.specific density of Ito at +50mV is reduced in fhcm septal myocytes (0.81±0.60pA/pF) compared with control myocytes (4.91±0.45pA/pF). HCN2/HCN4 ratio was significantly increased in hypertrophied samples (6.82±4.6) relative to the controls (1.46±1.08, p<0.01). Consistently with a relative over-expression of HCN2 isoform, If activates at more negative potential in patch-clamped fhcm compared to control myocytes 5-HT2B mrna was significant increased in fhcm with respect to the controls (5.83±1.6 vs 1.27±0.17, p<0.05). Functional coupling of 5-HT2 was confirmed by measuring the effect of the 5-HT2 selective agonist α-metil-serotonin (1μM) on action potential in single fhcm myocytes:it increased action potential duration, an effect which was reverted by wash-out; no effect was detected in control cells.

249 Disease mechanism and outcome in cardiomypathies 549 Conclusions: fhcm is associated with typical molecular and electrophysiological alterations. These changes are consistent with those described in myocytes from other arrhythmogenic disorders,such as heart failure. 5-HT2B receptors overexpression could represent a novel mechanism responsible for induction and maintenance of an altered functional phenotype in the human heart. 5HT2B receptors and f-current could represent novel targets for effective pharmacological interventions aimed to prevent and treat fhcm. P3274 Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy R. Maczynska-Mazuruk, M. Klopowski, K. Kukula, B. Kusmierczyk, M. Polanska, M. Dabrowski, L.A. Malek, L. Kalinczuk, L.S. Chojnowska, W. Ruzyllo. Institute of Cardiology, Warsaw, Poland Purpose: Approximately 25% of patients with hypertrophic cardiomyopathy (HCM) have dynamic left ventricular outflow tract obstruction (LVOTO) at rest with a gradient 30 mmhg or more. Significance of resting LVOTO in predicting sudden cardiac death (SCD) is discussed. We analyzed prognostic implications of resting LVOTO in a large HCM population. Methods: Incidence of LVOTO and outcome were assessed in 736 consecutive HCM patients (54% male, age at diagnosis: 33,6±18,3 years). Patients were followed for 11,8±7,2 years (1 to 32 years). Factors predisposing to SCD were analyzed. Logistic regression was used to assess independent risk factors of SCD. Long-rank test was used to evaluate survival in LVOTO and non-lvoto group. ORs and 95% CIs were calculated using Cox proportional-hazard regression. Results: LVOTO with a gradient 30 mmhg occurred in 263 HCM patients. LVOTO with a gradient 50 mmhg occurred in 189 HCM patients. LVOTO with a gradient 70 mmhg occurred in 127 HCM patients. LVOTO with a gradient 30 mmhg was an independent risk factor for SCD (OR 3,2, 95%CI 1,6-6,3, p=0,0008). If LVOTO was accompanied by any other recognized risk factors, the risk of SCD was further increased (OR 2,9, 95%CI 1,01-8,5, p=0,0489). LVOTO with a gradient 50 mmhg was an independent risk factor for SCD (OR 3,5, 95%CI 1,8-6,9, p=0,0002) when compared with group with a gradient <50 mmhg. LVOTO with a gradient 50 mmhg was an independent risk factor for SCD (OR 4,8, 95%CI 2,3-10, p=0,0001) when compared with group with a gradient <30 mmhg. If LVOTO with a gradient 50 mmhg was accompanied by any other recognized risk factors, the risk of SCD was further increased (OR 4,44, 95%CI 1,02-19,25, p=0,046). Patients with HCM diagnosed 30 years and LVOTO with a gradient 50 mmhg had often SCD when compared with older HCM patients and LVOTO with a gradient 50 mmhg (log rank p=0,032). In a subgroup of patients with LVOTO gradient mmhg SCD occurred only with the coexistence of any other recognized risk factors for SCD. LVOTO with a gradient 50 mmhg without coexistence of any other recognized risk factors for SCD was an independent risk factor for SCD with low positive predictive value (PPV) of 8,3%. In a subgroup of patients with HCM and LVOTO with a gradient 70 mmhg without coexistence of any other recognized risk factors for SCD, PPV of SCD rose to 12% (log rank p=0,0414). Conclusions: Our study shows that LVOTO is associated with an increased risk of SCD that is related to the severity of obstruction and the presence of other recognized risk factors for SCD as well as age. P3275 Presence of myocardial scar is strongly associated with abnormal regional myocardial blood flow in hypertrophic cardiomyopathy H. Nakajima, K. Onishi, T. Kurita, M. Ishida, M. Nagata, K. Kitagawa, K. Dohi, M. Nakamura, H. Sakuma, M. Ito. Mie University Graduate School of Medicine, Tsu, Japan Background: Late gadolinium enhancement (LGE), which indicates myocardial scarring, is frequently found in hypertrophic cardiomyopathy (HCM). However, the relationship between LGE and myocardial perfusion abnormality has not been fully clarified. Purpose: The purpose of this study was to determine the relationship between LGE and myocardial perfusion abnormality in HCM patient using cardiovascular magnetic resonance (CMR). Method: Thirty nine HCM patients (64years ±11, male 64%) underwent first pass perfusion MRI at rest and during ATP-stress by using a 1.5-T MR system with 32- channel cardiac coils (TR 3.0ms; TE 1.2ms, TI=180ms, Gd-DTPA 0.05mmol/kg, 4ml/sec). After correcting blood signal saturation, absolute myocardial blood flow (MBF) was quantified in 16 left ventricular (LV) segments. Presence or absence of myocardial scar was determined on LGE images. Results: The averaged rest MBF, stress MBF and myocardial perfusion reserve was 1.07±0.75ml/min/g, 2.26±1.26ml/min/g and 2.43±1.21, respectively. Enddiastolic LV wall thickness >12mm was observed in 269 (45.4%) of 592 LV segments, and LGE was found in 169 (28.5%) of 592 segments. Rest MBF and stress MBF were significantly reduced in LGE (+) segments when compared with those in LGE( ) segments (rest MBF: 0.84±0.53 vs 1.08±0.74 ml/min/g, p<0.001, stress MBF: 1.83±1.09 vs 2.32±1.42 ml/min/g, p<0.001). End-diastolic LV wall thickness was 16.2±6.3mm in LGE(+) segments and 11.1±4.8mm in LGE( ) Segmental MBF, MPR and Wall thickeness segments (p<0.001). Binominal logistic regression analysis demonstrated that presence of LGE is more closely associated with altered rest MBF as compared with stress MBF and LV wall thickness. Conclusion: Resting MBF is the most important affecter of LGE in patients with HCM. P3276 High prevalence of cardiac involvement in type 2 myotonic dystrophy K. Wahbi 1, C. Meune 2, H.M. Becane 1, A. Lazarus 3, P. Laforet 1, G. Bassez 1, H. Radvanyi-Hoffman 4,B.Eymard 1, D. Duboc 2. 1 Pitie-Salpetriere Hospital (AP-HP), Paris, France; 2 AP-HP - Hopital Cochin, Paris, France; 3 InParys clinical research group, Paris, France; 4 APHP - Hopital Ambroise Pare, Boulogne, France Purpose: In contrast with Steinert s disease (DM1), type 2 muscular dystrophy (DM2) is not known to be associated with a high prevalence of cardiac involvement. Our objective was to compare the results of detailed cardiac investigations in populations of DM2 and DM1 patients, and in controls. Methods: 38 DM2 patients (17 males; age = 57.1±15.2 years) were investigated and their results compared with 76 DM1 patients and controls; all were matched for age, sex and atherosclerosis risk factors. All underwent physical examination, resting and 24-h ambulatory electrocardiogram and echocardiography; in addition, an electrophysiological study (EPS) was performed in DM1 and DM2 patients when major conduction disturbances were suspected. Results: Cardiac abnormalities were present in 15 DM2 patients, including conductive defects in 14, LV systolic dysfunction in 6, supraventricular arrhythmias in 6 and stroke in 5 patients. Compared to the control group, all cardiac abnormalities were significantly more frequent. When compared to DM1 patients, conductive defects were less frequent; supraventricular arrhythmias had similar prevalence and there was a trend towards more left ventricular dysfunction in DM2 patients. The DNA mutation size, the presence of adverse health events among close relatives, muscular or respiratory failure, and the existence of any cardiac disease manifestation were not significantly associated with overt cardiac involvement or adverse cardiac events. Conclusions: A high proportion of patient suffering from DM2 develop major cardiac abnormalities. Our study suggests that systematic cardiac investigations should be recommended in these patients. P3277 Circadian and seasonal variation in the onste of tako-tsubo cardiomyopathy - results of the German Tako-tsubo registry A. Athanasiadis 1, B. Schneider 2,J.Schwab 3,W.Pistner 4,W.Von Scheidt 5, S. Kerber 6, U. Gottwald 7, U. Sechtem 1. 1 Robert-Bosch Krankenhaus, Stuttgart, Germany; 2 Sana-Kliniken Luebeck GmbH, Luebeck, Germany; 3 Klinikum Nuernberg, Nuernberg, Germany; 4 Klinikum Aschaffenburg, Aschaffenburg, Germany; 5 Klinikum Augsburg, Augsburg, Germany; 6 Herz- und Gefaessklinik, Bad Neustadt, Germany; 7 Allgemeines Krankenhaus Celle, Celle, Germany Background: The German tako-tsubo cardiomyopathy (TTC) registry has been initiated to further evaluate this syndrome in a western population. We aimed to assess a circadian and seasonal variation in patients (pts) with TTC. Methods: Inclusion criteria were: 1) acute chest symptoms (angina, dyspnea) or syncope, 2) reversible ECG changes (ST-segment elevation ± T-wave inversion), 3) reversible left ventricular dysfunction with a wall motion abnormality not corresponding to a single coronary artery territory, 4) no significant coronary artery stenoses. The time of symptom onset was categorized into four 6-hour intervals (night: 00:00 06:00; morning: 06:00 12:00; afternoon: 12:00 18:00; evening: 18:00 24:00) for circadian analysis. For seasonal analysis the day of the index event was classified into four 3-month intervals. Results: Information on timing of the index event according to clinical history and records of the emergency physician was available in 221 of 297 pts included in the registry (74.5%). Mean age was 68±12 years; 90% were women and 10% men. An apical ballooning was observed in 141 pts (64%) and a mid-ventricular ballooning in 80 pts (36%). Most TTC events occurred during summer (33%) with the highest peak in July (14%). During night time onset of TTC was low (11%.). There was an equal distribution among the other daytime-intervals (morning: 30%, afternoon: 31%, evening: 28%). In men, TTC predominantly occurred in autumn (36%) and in the evening (45%). Women presented with TTC mainly in summer (33%) with an equal distribution in the morning, afternoon and evening (31%, 30% und

250 550 Disease mechanism and outcome in cardiomypathies 28%, respectively). Younger pts up to 40 years had a TTC onset mainly in autumn and in the morning or evening (33%, respectively), whereas older pts > 80 years presented with TTC in summer und mostly in the morning (40%). There were no differences in TTC onset regarding apical or mid-ventricular ballooning. Conclusion: A seasonal pattern of TTC onset with a peak in summer, especially in July, was found. This seasonal variation is opposite to the trend detected in acute myocardial infarction. The low manifestation of TTC during night time confirms the concept of sympathetic activation in the pathogenesis of TTC. P3278 Chagas cardiomyopathy patients with preserved ventricular function and sustained ventricular tachycardia present regional myocardial sympathetic denervation and increased sympathetic activity C.H. Miranda, E. Arfeli, A.B. Figueiredo, A.O. Pintya, B.C. Maciel, J.A. Marin-Neto, M.V. Simoes. Medical School of Ribeirão Preto - University of São Paulo, Brazil, Ribeirão Preto, Brazil Purpose: This study aimed at assessing the cardiac sympathetic activity in chronic Chagas cardiomyopathy (CC) patients with preserved global left ventricular (LV) function and sustained ventricular tachycardia (SVT) by using 123I- Metaiodobenzilguanidine (123I-MIBG) scintigraphy. Methods: We prospectively investigated 22 CC patients with LV ejection fraction (EF) 40% exhibiting arrhythmia complaints and distributed in 2 groups: group I (n=12, 61±7 y.o., 10 males), presenting spontaneuous SVT (75%) or SVT induced during programed ventricular stimulation (25%); and group II (n=10, 57±10 y.o., 7 males) with similar clinical presentation but no SVT. Patients were submitted to LVEF assessment by using Echocardiogram, and Single Photon Emission Tomography (SPET) scintigraphic studies using 123I-MIBG (images acquired 10 min. and 3 hours after rest injection of 5 mci) and 99mTc-Sestamibi (images acquired 1 hour after rest injection of 20 mci) for the assessment of regional myocardial sympathetic innervation and myocardial viability, respectively. The 123I- MIBG studies also included planar images of the anterior chest view. After SPET reconstruction, 2 experienced observers analysed visually the regional myocardial uptake for both tracers, using a visual semi-quantitative score (0=normal, 4 =absent) employing a 17-segments LV model. Segments presenting MIBG defect but normal Sestamibi uptake were deemed as mismatch (viable but denervated myocardium). The quantitative analysis of planar images included assessing the MIBG uptake in regions of interest around the mediastinum and the heart. The heart:mediastinum rate (H:M) at 3 hours and the MIBG washout rate (WOR) between 10 m and 3 hours were calculated. Results: The LVEF was similar in Group I (50±8%), and in Group II (55±10%), p>0.05. The mean value of segments with mismatch per patient was higher in Group I (6.3±2.4) than in Group II (2.9±3.6), p=0.0047; and predominated in inferior, posterior and apical LV walls. Group I patients presented reduced H:M rate at 3 hours (1,65±0,2) as compared to the group II (1.90±0.30), p=0.01. The WOR was significantly higher in Group I (6.8±4.7%) as compared to Group II (-2.2±6,4%), p= Conclusions: In patients with CC regional myocardial sympathetic denervation and increased cardiac sympathetic activity may participate in the mechanism of severe ventricular arrhythmia. The results indicate that evaluation of cardiac sympathetic function may pontentially identify patients in early stages of CC with higher risk of severe ventricular arrhythmia and sudden death. P3279 Survival and clinical outcome of 154 patients one year after diagnosis of dilated cardiomyopathy A. Richter, B. Schwalb, S. Pankuweit, R. Funck, A. Ramadanovic, B. Maisch. Universitaetsklinikum Giessen und Marburg, Marburg, Germany Purpose: The prognosis of patients with dilated cardiomyopathy (DCM) has improved significantly during the last decades due to heart failure medication. We prospectively evaluated 154 patients (pat.) with newly diagnosed DCM in a 1- year-follow-up. Methods: From we examined 118 men and 36 women, mean age 45,3 yrs, with an ejection fraction (EF) 45% and enddiastolic left ventricular diameter (LVEDD) 117% according to Henry. Date of diagnosis was 12 months ago, for 109 pat. 1 month. All patients underwent endomycardial biopsy. After a mean follow-up time of 14,4 months we performed a second echocardiography and recorded the actual NYHA class, cardiac decompensations in the meantime, ICD shocks and death. Results: EF significantly improved from 28,9±8,5% to 43,8±13,2%. LVEDD also significantly decreased from 67,7±7,7mm to 61,5±9,3mm. Additionally patients reported a better exercise tolerance (NYHA class 1,8±0,7 vs.2,4±0,7). 8 pat. were hospitalised for heart failure, 1 underwent heart transplantation. 5 pat. died (2 sudden cardiac deaths, 1 progressive heart failure, 2 non-cardiac deaths). 44 pat. had an ICD, 2 pat. received adequate shocks. We could identify a subgroup of 22 pat. whose EF increased up to 55%, and another 22 whose LVEDD came to normal range. Both parameters normalized for 12 pat. A significant improvement of these parameters could be documented in all etiological subgroups (DCM, inflammatory DCM, with and without viral persistence),but there were no significant differences between the subgroups. Atrial fibrillation (AF) was seen in 15,6% of pat. with and 11,7% without inflammation, left bundle brunch block (LBBB) in 15,6% resp. 25%. Both patients with AF and sinus rhythm improved significantly until follow-up, the same applied to pat. with and without LBBB. Clinical parameters at inclusion (in) and 1-year-follow-up (fu) EF (in,%) EF (fu) LVEDD (in, mm) LVEDD (fu) NYHA (in) NYHA (fu) DCM 28,9±8,7 44,8±13,4 67,7±7,3 60,1±7,4 2,4±0,7 1,9±0,7 DCMi 30,0±6,3 44,5±11,8 67,1±5,8 63,1±9,0 2,5±0,7 1,8±0,8 viral DCM 28,0±8,0 40,8±12,0 68,1±7,3 62,8±8,8 2,3±0,7 1,5±0,7 viral DCMi 28,1±11,3 43,5±15,8 69,2±10,8 64,1±16,5 2,2±0,8 1,7±0,6 Conclusion: 1-year survival was 96,7%, event-free survival in consideration of transplantation and ICD-shocks was 94,8%. These notable results will be followed by a detailed analysis of further predictors. P3280 Left ventricular outflow tract obstruction in patient with hypertrophic cardiomyopathy: increase in gradient after dynamic exercise A. Palinkas 1, R. Sepp 2,E.Nagy 1,L.Halmai 2, A. Rigopoulos 3, H. Seggewiss 4,V.Nagy 2, T. Forster 2, M. Csanady 2. 1 Elisabeth University Hospital, Hódmezovásárhely, Hungary; 2 University of Sciences, Szeged, Hungary; 3 University of Athens, Athens, Greece; 4 Leopoldina Hospital, Schweinfurt, Germany Background: Determination of the specific cause of a syncopal episode in patients with hypertrophic cardiomyopathy (HCM) is often challenging. Left ventricular outflow tract (LVOT) obstruction during or after cessation of physical activity is a well known mechanism of syncope in HCM patients. However the behaviour of LVOT obstruction during different phases of dynamic exercise has not yet been evaluated systematically. Aim: to define alterations in the magnitude of LVOT gradient during and short after semi-supine exercise Doppler echocardiography (SEDE) in patients with symptomatic HCM. Patients and method: 35 patients (18 males, mean age: 45±12 years) with HCM underwent a multistage symptom limited SEDE. The SEDE protocol started at 25 W with increments of 25 W every 3-minute stage. Peak LVOT gradient was measured by conventional Doppler echocardiography at baseline, at the peak of exercise and at 2 minutes into recovery. Hemodynamically significant LVOT obstruction was defined as presence of peak LVOT gradient 30 mmhg. Results: Significant LVOT obstruction developed during SEDE in 7 out of 18 patients (39%) without significant resting LVOT obstruction. Resting LVOT gradient increased significantly during peak exercise, and rose further significantly in the recovery phase (Figure). Resting LVOT gradient correlated significantly with both exercise induced and recovery phase LVOT gradient (r=0.782, p<0.001 and r= 0.762, p<0.001). Change of LVOT gradient during SEDE Conclusion: In HCM patients the LVOT gradient increases significantly in the recovery phase compared to the peak of dynamic exercise. Measurement of LVOT gradients by Doppler echocardiography short after exercise testing should be included in the evaluation protocol of patients with HCM. P3281 Magnetic resonance stress perfusion imaging in patients with left ventricular hypertrophy commonly detects perfusion defects and does not identify coronary disease S.P. Page, L.A. Mcgill, T.R. Burchell, C. Davies, A. Mathur, P.G. Mills, M.A. Westwood, S.A. Mohiddin. The London Chest Hospital, London, United Kingdom Introduction: Patients with left ventricular hypertrophy (LVH), including those with hypertrophic cardiomyopathy (HCM) and hypertensive LVH frequently present with chest pain on exertion in the absence of coronary artery disease (CAD). Imaging in such patients often detects stress-induced perfusion defects and in-

251 Disease mechanism and outcome in cardiomypathies 551 vasive coronary angiography may be indicated to exclude co-existing CAD. We sought to determine if the high spatial resolution of cardiac magnetic resonance (CMR) perfusion imaging distinguished between CAD and hypertrophic perfusion abnormalities in patients with LVH. Methods and Results: We studied a consecutive cohort of 54 patients with LVH (maximal wall thickness 13mm) and chest pain in whom CMR perfusion imaging and coronary angiography were performed. Adenosine stress perfusion imaging was performed according to standard protocols and abnormalities designated by experienced observers as CAD (sub-endocardial and territorial) or myopathic (mid-wall and/or non-territorial) defects. Perfusion defects were detected in 36 patients (67%), and were CAD pattern in 19 (53%), myopathic in 14 (39%) and both in 3 (8%). At angiography, 23 (72%) patients had CAD (stenosis >50% or prior intervention) in whom 27 (69%) had perfusion defects. Nine of 15 LVH patients without CAD (60%) also had perfusion defects (p=ns). In the 27 CAD patients with perfusion defects, 18 were CAD pattern (67%), 7 were myopathic (26%) and 2 had both (7%). Considering the 9 LVH patients without unobstructed coronary arteries in whom stress perfusion imaging was abnormal, 1 had a CAD pattern defect, 7 (78%) non-coronary pattern defects and 1 had both patterns. Thus, the CAD pattern of perfusion abnormality predicted coronary disease (χ 2 =6.4, p=0.01; specificity 87%, sensitivity 51%, NPV 41%, PPV 91%). Negative predictive values were low, and importantly, although a myopathic pattern was associated with unobstructed coronaries, its presence did not reliably exclude CAD (χ 2 =5.6, p<0.03; specificity 77%, sensitivity 53%, NPV 81%, PPV 47%). Conclusions: CMR stress perfusion imaging in LVH patients with chest pain is frequently abnormal. In patients with LVH, the nature of the perfusion defect does not reliably differentiate CAD from myopathic or microvascular causes. Finally, assessing revascularization indications in symptomatic LVH patients with CAD and perfusion defects may require the development and validation of coronary lesion-specific assessments. P3282 Implantable cardioverter defibrillator (ICD) treatment and cardiac death after percutaneous transluminal septal myocardial ablation (PTSMA) in hypertrophic obstructive cardiomyopathy (HOCM) M. Jensen 1, O. Havndrup 2, S. Helqvist 1, H. Kelbaek 1, E. Joergensen 1, C. Hassager 1, L. Koeber 1, H. Bundggaard 1. 1 Rigshospitalet (The Heart Centre), Copenhagen, Denmark; 2 Roskilde Hospital, Roskilde, Denmark Reports on long term risk of cardiac death after PTSMA are sparse. We assessed the long term prevalence of ICD indication and cardiac death in HOCM patients treated with PTSMA. Methods: Survival data and ICD recordings from a consecutive cohort of HOCM patients treated with PTSMA was obtained from in-hospital and national registries. All available patients were risk stratified according to current guidelines by Holter-monitoring, exercise test, clinical- and echocardiographic examination. Left ventricular wall thickness 30 mm (WT), unexplained syncope (US), nonsustained ventricular tachycardia (NSVT), family history of sudden death (<40 years of age) (FH) and abnormal blood pressure response (ABPR) (patients <50 years) were considered risk factors for sudden cardiac death (SCD). Presence of two risk factors or VT was considered indication for ICD treatment. Results: Seventy-two patients were treated with 2.6±0.9 (mean±sd) ml alcohol per PTSMA procedure. Four patients had ICD indication before the procedure. In the follow up period of 4.0±2.6 years three patients had an ICD implanted. Twelve patients died before follow up (7 cardiac deaths) and 8 refused participation in the risk stratification program. In 52 patients entering the program the distribution of risk factors were: FH 0%, WT 2%, ABPR - 43%, NSVT - 19%, US - 6% and VT 2%. ICD indication was found in four patients (8%), and only one out of five examined ICD patients had two risk factors at follow up. The five year cardiac mortality was 11%, while the five year survival free of ICD indication and cardiac death was 79% (Figure 1). Figure 1. Cardiac risk after PTSMA Conclusion: Severely affected HOCM patients treated with PTSMA remain at increased cardiac risk at long term. However, this risk is comparable to the risk of similar HOCM populations never treated with PTSMA. P3283 Sublingual isosorbide dinitrate for detection of obstruction in hypertrophic cardiomyopathy D. Zemanek 1, P. Tomasov 2, S. Homolova 2, K. Linhartova 1, J. Veselka 1. 1 University Hospital Motol and 1st Medical Faculty Charles University, Prague, Czech Republic; 2 University Hospital Motol, Prague, Czech Republic Objectives: Hypertrophic cardiomyopathy (HCM) is predominantly a disease of left ventricular (LV) outflow tract obstruction. However, the obstruction is present only in approximately 25% of patients at rest. The assesment of obstruction in LV outflow tract with provoked test should be a routine component of the evaluation of HCM. The exercise echocardiography is a gold standard for this testing, but it is space- and time-consuming. Method: We prospectively analyzed consecutive HCM patients in our center (hypertrophied and non-dilated left ventricle and maximum wall thickness 13 mm in the absence of other cardiac or systemic causes of left ventricle hypertrophy), measuring LV outflow gradient at rest, using sublingual application of isosorbide dinitrate (ISDN) 2.5 mg (measured after 2, 5 and 10 min), and with exercise echocardiography. The obstruction in LV outflow tract was defined as gradient 30mmHg. Results: We evaluated 57 patients (age 55.3±14.6 years, 75% male). LV outflow tract obstruction was present at rest in 12 patients (21%), after application of ISDN in 28 patients (49%), and during exercise testing in 36 patients (63%). ISDN test has sensitivity 75% and specificity 95% for obstruction in contrast to the rest measurement (sensitivity 31%, specificity 95%). The obstruction in LV outflow tract during ISDN test was present only in 21 patients (37%, gradient 27.9±2 4.3 mmhg) in two minutes after the application of ISDN, but in 28 patients (49%, gradient 41.3±39.4 mmhg) in 5 to 10 minutes after ISDN. The chronological difference in prevalence of obstruction during ISDN test was statistically significant (p<0.05). The results are summarized in table 1. Table 1 Rest 2 min 5-10 min Exercise measurement after ISDN min after ISDN echocardiography Gradient (mmhg) 17.7± ± ± ±24.2 Positive test (%) Conclusion: High prevalence of LV outflow tract obstruction in our HCM group (63%) was in accordance with latest results for tertiary cardiology centers. ISDN test is a reliable screening method for the detection of obstruction in LV outflow tract, but measurement should be postponed 5-10 min after application of ISDN. Patient with negative ISDN test should undergo exercise echocardiography. P3284 Incidence of adequate ICD interventions for primary prophylaxis of sudden cardiac death in patients with hypertrophic cardiomyopathies C. Prinz, J. Vogt, B.G. Muntean, J. Heintze, D. Hering, D. Horstkotte, L. Faber. Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany Purpose: In patients (pts.) with hypertrophic cardiomyopathy (HCM) risk assessment for sudden cardiac death (SCD) is currently based on presence or absence of risk markers (RM) like family history of SCD, recurrent syncopes, non-sustained ventricular tachycardias (nsvt) on Holter ECG, excessive left ventricular hypertrophy (LVH) >30 mm, and abnormal blood pressure response (abpr) during exercise. Recently, detection of myocardial fibrosis by gadolinium-enhanced magnetic resonance imaging (GE-MRI) has been considered as an additional RM. Patients and Methods: In a cohort of 1291 clinically characterized HCM-pts. 50 individuals (33 men, 17 women; mean age: 44±13 years, NYHA class: 2.0±0.9) were identified who had more than 1 (2-4) RM and GE-MRI prior to their ICD implantation. ICD implantation was performed for secondary SCD prophylaxis in 2, and for primary prophylaxis in 48 pts. Outflow obstruction was present in 25 pts., the other 25, including 1 pt. each after septal ablation and myectomy, were non-obstructive. With GE-MRI maximum wall thickness and LV mass were measured, and the presence of fibrosis was scored semiquantitatively (from 0=absent, 1=point-shaped, 2=limited to 1 LV segment, 3=involving 2 segments). During follow-up device-related problems were noted, and the ICD memories were analized for arrhythmic events and especially for adequate ICD interventions. Results: The number of RM per pt. was 1.7±0.8. Evidence of myocardial fibrosis 2 was present in 39 pts. with a mean score of 2.2±0.9. During follow up (1.9±1.7 [ ]) years, adequate ICD interventions (11 episodes) were documented in 5 pts., 13 pts. had at least 1 episode of atrial fibrillation. Inadequate ICD interventions were noted in 3 cases. Pts. with vs. without event had a longer follow-up (3.2±4.3 vs. 1.8±2.6 years, p<0.05), and were more frequently nonobstructive (all 5; p<0.05). Conclusions: The incidence of appropriate ICD discharges in our cohort of 50 pts. with HCM who received an ICD for SCD prevention was 4-5%/pt.-year, supporting the proposed risk stratification. However, no single RM nor additional GE- MRI was predictive for arrhythmic events.

252 552 Disease mechanism and outcome in cardiomypathies / Ventricular arrhytmias: diagnosis and treatment P3285 Impact of myocardial Iron loading on right ventricular function F. Alpendurada, M. Deac, J.P. Carpenter, P. Kirk, G.C. Smith, D.J. Pennell. Royal Brompton Hospital, London, United Kingdom Introduction: Iron-overload cardiomyopathy is a potential complication of transfusion-dependent chronic anemic patients, resulting in significant morbidity and mortality. β-thalassemia major is the commonest cause of iron-overload cardiomyopathy worldwide, representing a major health problem in endemic areas, where heart failure due to iron overload is the principal cause of death. Cardiovascular magnetic resonance (CMR) has emerged as a non-invasive technique to quantify the amount of iron in the heart. T2-star (T2*) levels correlate with left ventricular (LV) ejection fraction and can predict patients who will develop heart failure. However, correlation between myocardial T2* and right ventricular (RV) function has not yet been established. Purpose: To evaluate the relationship of myocardial T2* and RV ejection fraction (RVEF), as well as the relationship between RVEF and occurrence of heart failure within one year, in a population of patients with thalassemia major. Methods: We studied 326 consecutive patients (average age: 26.5 years, 45% males) with β-thalassemia major who were referred for their first scan for assessment of iron loading status by CMR. All patients were on deferoxamine therapy only at presentation. Those taking other forms of chelation therapy were excluded. RV volumes and RV ejection fraction (RVEF) were calculated and compared with myocardial T2* measured within the interventricular septum. Other variables included LV volumes, left ventricular ejection fraction (LVEF), and the occurrence of heart failure within 1 year of the scan. Results: There was a curvilinear relationship between heart T2* levels and RVEF. As T2* decreased to critical levels (indicating significant iron loading), there was a decline in RVEF (r=0.43, p<0.001) and an increase in RV end-systolic volume (RVESV). There was also a significant difference (p = 0.009) in RVEF between patients who developed heart failure (RVEF: 55.8±11.8%) when compared with those who did not (RVEF: 63.2±6.8%). Furthermore, we noted a direct linear relationship between the LVEF and the RVEF (r=0.69, p<0.001) in these patients. Conclusions: Myocardial iron deposition as assessed by CMR is associated with RV dysfunction, which is related with the development of heart failure. This mirrors the decrease in LV function seen with worsening cardiac iron loading (which has previously been described). Therefore, iron-overload cardiomyopathy not only affects the LV, but also involves the RV to a similar extent. These parameters can subsequently be used as a guide to the management of this condition. P3286 Dilated cardiomyopathy: prevalence of familial, inflammatory and viral forms S. Pankuweit, A. Richter, V. Ruppert, B. Maisch on behalf of German Heart Failure Network. Universitaetsklinikum Giessen und Marburg, Marburg, Germany Indroduction: The phenotype DCM is assumed to be the endstage of a multifactorial etiopathogenetic pathophysiology, which includes a yet not defined part of patients with inflammatory/familial cardiomyopathy. Precipitating factors include enhanced autoimmunity, predisposition for viral infections, environmental factors in addition to a specific genetic background of the individual patient. Methods: Within the German Heart Failure Network we finished our project Ikarius with the inclusion of patients with dilated cardiomyopathy (ejection fraction <45%, left ventricular enddiastolic diameter > 56mm) and in addition the inclusion of all relevant data regarding a possible familial, infectious or autoimmune etiology of the disease. A questionnaire was added to the CRF s, to ascertain data regarding a possible familial history for each patient, a pedigree of all patients is available. Derived from the data base, the biopsy and serum bank further aims of the project are the search for a genetic link or predispisition to autoimmune diseases in patients with familial/inflammatory DCM. Results: After screening of more than 1600 patients we have included 274 index patients (211 m/63 f) in total with an age of 51±13 years, an ejection fraction (EF) of 29%±8% and a left ventricular enddiastolic volume (LVEDD) of 68±8mm. Blood samples and endomyocardial biopsies from all patients, a pedigree including data for a familial history for heart diseases or autoimmune diseases are available in all cases. In total, we identified 57 families (21%) with a minimum of two affected family members. We were able to identify in 23,5% of the index patients an inflammatory DCM and in 24.5% of index patients a viral heart disease. In more than 50% of all patients families a history of autoimmune diseases was detected. Genetic analysis of the patients resulted so far in identification of a lamin A/C mutation in two patients, a new phopholamban mutation and a N-cadherin mutation in one patient each. An association of HLA-DR polymorphisms with a better prognosis was shown in a subgroup of patients with DCMi. After 1-yearfollow-up of all patients EF (39±13%) and a LVEDD (65mm±9mm) improved in all patients. 13 pts died and 3 pts underwent heart transplantation. Conclusion: Epidemiological data with a special focus regarding an familial, infectious and inflammatory etiology of the disease are now available for this large patient cohort. In addition, one-year and five year follow-up data will be available to identify new prognostic biomarker in patients with dilated cardiomyopathy. P3287 Interobserver variability in the detection of myocardial parvovirus B19 genomes U. Lotze 1, R. Egerer 2,R.Zell 2,O.Scheck 2, H. Sigusch 3, C. Ehrhardt 2,A.Heim 4, R. Kandolf 5,P.Wutzler 2, H.R. Figulla 2. 1 Saale-Unstrut-Klinikum, Klinik für Innere Medizin, Naumburg, Germany; 2 Universitaetsklinikum Jena, Jena, Germany; 3 Klinik für Innere Medizin, Zwickau, Germany; 4 Medizinische Hochschule Hannover, Hannover, Germany; 5 Institut für Pathologie, Abt. für Molekulare Pathologie, Universitätsklinik Tübingen, Tübingen, Germany Purpose: Parvovirus B19 (PVB19) genomes have recently been shown to be often associated with idiopathic dilated cardiomyopathy, and even in control hearts PVB19 has been found in a high percentage. We therefore investigated the interobserver variability in the detection of myocardial PVB19 genomes. Methods: In the present study, myocardial tissue samples from the right atrial appendage from ten control patients undergoing bypass surgery with normal LVEF (>55%) were investigated for PVB19 genomes as detected by quantitative real time polymerase chain reaction in three different virological laboratories. Results: see Table. Conclusions: The frequency of PVB19 genomes in the myocardium of control patients with a normal LVEF varies between 30, 50 and 60%, associated with a low number of gene copies. Obviously, there is a complete conformity of the results between the three virological laboratories in 60% and an interobserver variability in 40% of the cases in the detection of myocardial PVB 19 genomes. P3288 Early cardiac manifestations of Fabry Disease (FD) in male and female children C. Kampmann 1,C.Whybra 1,G.Kalkum 1, B. Escoubet 2,A.N.Dinh Cat 2, V. Griol-Charhbili 2, F. Jaisser 2, D. Warnock 3,M.Beck 1. 1 Klinikum der Universitaet Mainz, Mainz, Germany; 2 Bichat-Claude Bernard Hospital (AP-HP), Paris, France; 3 University of Alabama, Birmingham, United States of America Purpose: FD is an X-linked inherited disorder ofthe lysosomal alphagalactosidase A (AGALA) enzyme. The accumulation of the major substrate globotriaosylceramide (Gb3) results in kidney disease, strokes, and an infiltrative cardiomyopathy with arrhythmias, and myocardial fibrosis in advanced life. Little is known about early cardiac manifestation in affected children with FD. Methods: Echocardiographic and Holter ECG data of 51 FD children (26 males) below age 18 years (mean 11±5 years) at first presentation were compared to aged matched healthy children. Results: Pts did not differ in age, BSA, BMI, systolic or diastolic blood pressure from gender-appropriate controls, but showed slightly increased aortic diameter (NS) and significant increased LVmass indexed to body height 2.7 (male pts: 46.7±13g/m 2.7 versus30.3±8g/m 2.7 ; female pts: 44.4±10.6 vs. 27.6±8g/m 2.7 ; p<0.01) with significant increase in relative wall thickness (p<0.05), indicating that the increase in LV mass is related to an increase in wallthicknesses. 6 of 26 male and 6 of 25 female FD children had LV masses >8g/m 2.7. Holter EKG studies showed significantly more bradyarhrythmias (8-fold increase) and premature atrial contractions (4-fold increase) in male and female pediatric FD patients compared to controls. Conclusions: Male and female children with FD show early signs of cardiac involvement with increased LV mass and an early occurrence of atrial dysrhythmias compared to age- and gender- matched control subjects. VENTRICULAR ARRHYTMIAS: DIAGNOSIS AND TREATMENT P3289 Incidence and characteristics of spontaneous ventricular tachyarrhythmias in 778 patients with coronary artery disease and idiopathic dilated cardiomyopathy and implantable defibrillator J. Kuschyk, F. Streitner, N. Schoene, S. Ammar, C. Veltmann, R. Schimpf, C. Wolpert, C. Dietrich, E. Mahl, M. Borggrefe. 1st Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany Aim of the study: To assess the incidence and characteristics of spontaneous Abstract P3287 Table 1. Results Sample-No. 1/10 2/10 3/10 4/10 5/10 6/10 7/10 8/10 9/10 10/10 Jena Neg. 120 copies/μg DNA 100 copies/μg DNA Neg. Neg. 120 copies/μg DNA Neg. 100 copies/μg DNA 100 copies/μg DNA Neg. Tübingen Neg. Neg. 184 copies/μg DNA Neg. Neg. 122 copies/μg DNA Neg. Neg. 91 copies/μg DNA Neg. Hannover 80 copies/μg DNA Neg. 60 copies/μg DNA 40 copies/μg DNA Neg. 60 copies/μg DNA Neg. 130 copies/μg DNA 30 copies/μg DNA Neg.

253 Ventricular arrhytmias: diagnosis and treatment 553 ventricular tachyarrhythmias episodes in ischemic heart disease (IHD) compared to idiopathic dilated cardiomyopathy (IDC). Methods: 778 consecutive patients with either IHD (n=555) or IDC (n=223) were implanted with an Implantable Cardioverter Defibrillator (ICD) and followed for a mean period of 34 months. Results: The proportion of males was significantly higher in both groups (IHD 85% vs. IDC 75%, p<0.05). Patients with coronary artery disease were significantly older (70±10 years vs. 66±12 years, p<0.05). The mean ejection fraction was 33±11% in IHD and 28±10% in IDC patients (p<0.05). Indication for ICD implantation was primary prophylaxis in 445 (80%) patients with IHD and 201 (90%) patients with IDC. The mean time to the first spontaneous ventricular tachyarrhythmia (ventricular tachycardia or ventricular fibrillation, VT/VF) was 17 months in patients with IHD and 21 months in patients IDC (ns). Spontaneous VT/VF episodes occurred in 28% of patients with IHD and 30% of patients with IDC (p=ns), with a mean number of 21 vs. 22 episodes per patient, respectively. The episodes consisted in VT in 24% of IHD patients and 26% of IDC patients and VF in 12% vs. 13.5%, respectively (p=ns). 87% off all ventricular tachyarrhythmias were successfully terminated by antitachycardia pacing (ATP) with an empiric programming of VT/VF cut off rates of 360 ms and 280 ms, respectively. Conclusion: 1) In contrast to prior data, there were no significant differences in the characteristics of VT/VF events between patients with IHD and IDC 2) A probable explanation could be the increasing rate of primary prophylactic ICD implantation in this population with severely reduced ejection fraction. 3) The high incidence of spontaneous VT/VF events in IDC supports the primary prophylactic ICD-Implantation in this patient group. P3290 Relationship between abnormalities of ventricular repolarisation and occurrence of malignant arrhythmias in Takotsubo Cardiomyopathy D. Haghi 1, I. Wiitstein 2,K.Hamm 1, A. Baranchuck 3, Y. Akashi 4, H. Nef 5, P. Hilpert 5,L.Bonello 6, C. Wolpert 1, M. Borggrefe 1. 1 Universitaetklinikum Mannheim, Mannheim, Germany; 2 Johns Hopkins Hospital, Boltomore, United States of America; 3 Kingston General Hospital, Kingston, Canada; 4 St. Marianna University School of Medicine, Kawasaki, Japan; 5 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 6 AP-HM - Hopital Nord, Marseille, France Purpose: The purpose of this study was to assess the relationship between indices of ventricular repolarisation and the occurrence of syncope or malignant ventricular tachyarrhythmias in patients with Takotsubo Cardiomoyopathy (TC). Methods: Resting 12-lead ECGs from 27 patients with TC and syncope (n=2) or documented malignant ventricular arrhythmias (n=25) were compared to ECGs from 20 randomly selected patients with TC and no arrhythmic events. ECGs of days 1 and 3 were used to assess ventricular repolarisation by measuring QT interval, corrected QT interval, QT dispersion (QTD), interval from the peak to the end of the T wave (Tp-e), corrected Tp-e, and Tp-e dispersion (Tp-eD). QT intervals were measured in each of the 12 leads. Tpe intervals were measured in the precordial leads only. Results: Documented arrhythmic events consisted of sustained ventricular tachycardia (VT) in 3 patients, ventricular fibrillation (VF) in 4 patients, both VT and VF in 6 patients, non-sustained VT in 8 patients, and Torsades de Pointes in 4 patients. On day 1, patients who had arrhythmic events had longer Tp-e in lead V3 (116±63 ms vs. 84±17ms, p = 0.041). No differences were observed with regard to other repolarisation indices. On day 3, the difference among both groups was preserved with regard to Tp-e in lead V3 (130±50 ms vs. 105±21 ms, p = 0.048). Additionally, TpeD was significantly prolonged in patients who had experienced arrhythmic events (62±35 ms vs. 36±21 ms, p = 0.01). Conclusions: In TC, patients with arrhythmic events have prolongation of Tp-e and Tp-eD. These indices are believed to be a measure of spatial dispersion of ventricular repolarisation and could be prognostic of arrhythmic risk in TC. P3291 Endocardial electrograms in epicardially ablated ventricular tachycardias T. Boussy 1, A. Berruezo 1,J.Ortiz 2, E. Guasch 1,D.Perez 1, D. Andreu 1,E.Silva 2,T.DeCaralt 2,L.Mont 1, J. Brugada 1. 1 Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Arrythmia Section, Barcelona, Spain; 2 Hospital Clinic, University of Barcelona - Thorax Institute. Cardiology Dep., Echocardiographyc Lab., Barcelona, Spain Background: There are no reliable criteria derived from endocardial mapping to identify or predict an epicardial origin of ventricular activation. The vast majority of VT s in patients with structural heart disease (SHD) are scar-related re-entries. Scars can be identified by local electrogram (EG) abnormalities and by the presence of late enhancement on cardiac MRI. Objective: To analyze local endocardial EG s of the epicardial VTs and to correlate them with the extent of interposed undiseased tissue seen on cardiac MRI. Methods: an endocardial voltage map (CARTO system) was performed in 16 patients (14 male; 56±19y) with SHD (2 ARVD, 9 ICMP, 4 NICMP and 1 without SHD) who presented with a clinical monomorphic VT. The origin of the clinical VT was localized (and ablated) in the endocardium in 10 patients, while an additional epicardial approach (and RF application) was required in the remaining 6. Analysis of EG duration, voltage and fractionation was performed in all endocardial voltage maps, at the site of origin. All patients underwent a ce-mri prior to the procedure to identify the transmural extent of scarred tissue. Results: the duration of the local endocardial EG s in the endocardial-vt patients was significantly longer than in the epicardial-vt group (131,5±39,7 msec vs 61,80±21,8 msec; P < 0.001). Endocardial voltage maps were completely normal in 5 out of 6 epicardial VT patients. (6,9±3,6 mv versus 0,81±0.91 in the endocardial VT group; P < 0,001). In contrast to other endocardial maps, no fractionation was seen in these five patients. Ce-MRI identified scarred tissue in 12 (75%) patients. The mean distance between the scar lesion and the endocardial surface in epicardially ablated VT s was 4,6±2,1 mm, with a minimum of 1,5 mm in the patient with an abnormal endocardial voltage map. Conclusion: A normal endocardial voltage map likely indicates an epicardial origin of the VT that is consistent with the presence of interposed preserved tissue between the endocardial surface and the scar. However, voltage map alterations can be seen when the preserved endocardial rim is thinner than a minimum value. P3292 Usefulness of contrast enhanced-cardiac magnetic resonance to identify the epicardial origin of ventricular tachycardias A. Berruezo, J.T. Ortiz, E. Guasch, P. Perez, T. Boussy, T.M. De Caralt, A. Olaya, A. Cuesta, L. Mont, J. Brugada. Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Arrythmia Section, Barcelona, Spain Introduction: The epicardial origin of ventricular tachycardia (VT) can be inferred from detailed ECG analysis. However, despite its clinical usefulness, this is an imperfect method. Critical anatomic substrates sustaining VTs (scarred tissue) can be identified by contrast enhanced-cardiac Magnetic Resonance (ce-cmr). We hypothesized that the distribution pattern of the scarred tissue across the LV wall can be useful in differentiating between endocardial and epicardial VTs. Methods: A ce-cmr study was carried out before the indexed ablation procedure among 24 patients with structural heart disease (SHD) and a clinical documented sustained VT. Sequential short axis slices from base to apex were analyzed by an independent cardiologist (blinded to clinical and EP data) who assigned the presence on hyperenhancement (HE) according to the 17-segment model as absent, subendocardial, epicardial, transmural or mid-myocardial. Additionally, an electrophysiologist determined the LV segment and the true endocardial or epicardial origin of the VT according to the location and approach needed for VT ablation. Results: A total of 5 patients (21%) had ischemic heart disease, 13 (54%) had non-ischemic cardiomyopathy, 6 other SHD (59±19 y, 83% males, 43±12% LVEF). A total of 22 (92%) inducible VTs and 2 (8%) noninducible, were considered successfully ablated, 79% from the endocardium and 21% from the epicardium. Nineteen (79%) patients were found to have HE on ce-cmr. In all segments with successful ablation, HE was found to be absent in 25%, subendocardial in 37%, transmural in 17% and epicardial in 21%. The presence and distribution of the HE on the ce-cmr had a sensibility of 47% (9/24) and a specificity of 100% (9/9) to predict an endocardial origin of the VTs and a 100% sensibility and specificity in predicting an epicardial origin of the VTs. Conclusions: Ce-CMR might be helpful to target the VT ablation as well as to plan the approach needed, epicardial or endocardial, prior to the procedure. The presence of an epicardial scar on ce-cmr supports an epicardial origin of the VT and therefore, the need of an epicardial approach might be anticipated. P3293 Incidence and recurrence of electrical storm in patients with a cardioverter-defibrillator implanted for primary or secondary prevention F. Streitner, N. Schoene, E. Mahl, C. Dietrich, C. Veltmann, S. Ammar, C. Wolpert, M. Borggrefe, J. Kuschyk. 1st Department of Medicine, University Hospital Mannheim, Germany Purpose: Occurrence of an electrical storm (ES) is a serious clinical problem among patients with an implantable cardioverter-defibrillator (ICD). Except for the MADIT II substudy, there are no reports that specifically investigated ES in patients who underwent ICD implantation for primary prevention. This study sought to determine differences in the incidence of ventricular tachyarrhythmia (VT/VF-) or ES-episodes in ICD-recipients implanted for primary (PP) or secondary prevention (SP). Methods: Data of 955 ICD-patients were retrospectively analysed. All VT/VFevents were classified by detailed event data logs and device-stored electrograms. Electrical storm was defined as 3 separate VT/VF-episodes leading to appropriate ICD-therapy 24h. Results: In 274/955 patients (28.7%), 2406 episodes in the VT-detection (mean 8.8±20.8) and 465 episodes in the VF-detection zone (mean 1.7±5.6) occurred. 772/955 patients (80.8%) received an ICD for PP (19.2% for SP respectively). Out of 211/955 patients (22.1%) with single VT/VF-episodes during follow-up, 164 (77.7%) received an ICD for PP (22.3% for SP respectively). When analysing patients with single ES-episodes (31/955, 3.3%), 19 patients (61.3%) were implanted for PP and 12 (38.7%) for SP, but assessment of this distribution in patients with recurrent ES-episodes during follow-up (32/955, 3.4%) revealed a significantly increased percentage of ICD-patients implanted for PP (27/32 patients, 84.4%) compared to implantation for SP (5/32, 15.6%, p=0.015).

254 554 Ventricular arrhytmias: diagnosis and treatment Conclusions: 1) More than half of the ICD-patients with an electrical storm experience ES-recurrence. 2) After experiencing an ES, ICD-patients implanted for primary prevention are at high risk for ES-recurrence. P3294 Torsade de Pointes arrhythmias in the chronic AV-block block dog are not determined by changes in conduction nor dominated by reentrant mechanisms M. Boulaksil 1, J.G. Jungschleger 2, G. Antoons 3, R. Wilders 4, J.D. Beekman 1,J.G.Maessen 2, F.F. Van Der Hulst 2, H.V.M. Van Rijen 1,J.M.DeBakker 5,M.A.Vos 1. 1 Medical Physiology, Division Heart and Lungs, UMC Utrecht, Utrecht, Netherlands; 2 University Hospital Maastricht, Maastricht, Netherlands; 3 Catholic University of Leuven (KULeuven), Leuven, Belgium; 4 Academic Medical Center, Amsterdam, Netherlands; 5 Interuniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands Introduction: The remodeled heart of the chronic AV-block (CAVB) dog has a high susceptibility for drug induced Torsade depointes (TdP). Lability of repolarization has been documented. Re-entry has been suggested as arrhythmogenic mechanism, implying altered conduction parameters. Methods: 17 TdP sensitive CAVB and 10 sinus rhythm (SR) dogs were studied. In 6 animals, 66 needles were evenly distributed transmurally (27 septal, 27 in LV and 12 in RV) to record 240 unipolar local electrograms simultaneously. Activation times and recovery intervals (ARIs) were determined prior and during ibutilide induced TdP. In 12 CAVB and 9 SR dogs, LV and RV epicardial electrograms were recorded with a 208 point multi-terminal electrode allowing conduction velocity (CV) and refractory period (ERP) measurements. Biopsies were processed for Cx43 expression and collagen. Ventricular myocytes were isolated to determine sodium current density (INa + ) and Luo-Rudy modeling was used to verify obtained experimental data. Results: In CAVB, ERP and ARI were increased, while CV was unaltered in LV. Transversal but not longitudinal CV was increased in RV. INa + was reduced by 37% in LV but unaltered in RV. LV and RV cell size was increased, but levels of fibrosis and Cx43 expression were unchanged. Computer simulations showed increases in CV as a consequence of increased cell size at normal INa +. Ibutilide increased ARI, ERP, and maximal transmural dispersion (60±35 to 110±65 ms*). 28/47 episodes of self terminating TdP (43±72 beats) were analyzed. The majority (>90%) of beats were focal, although reentry was occasionally observed. Conclusions: Focal activity is the dominant mechanism involved in ibutilide induced TdP, which is compatible with unaltered conduction and documented repolarization lability. the incidence of VT 8 beats, CVD and SCD. These findings suggest that pts with NSTE-ACS undergoing PCI may derive additional antiarrhythmic benefit from treatment with RAN. P3296 Primary prevention ICD implantation in patients with ischemic heart disease: A narrow QRS-T angle predicts arrhythmia free survival R.W.C. Scherptong, C.J.W. Borleffs, S.C. Man, G.H. Van Welsenes, J.J. Bax, L. Van Erven, C.A. Swenne, M.J. Schalij. Leiden University Medical Center, Leiden, Netherlands Purpose: Widening of the QRS-T angle, caused by inhomogeneous depolarization and repolarization, was reported as a marker of increased incidence of ventricular arrhythmias. In primary prevention implantable cardioverter defibrillator (ICD) patients with ischemic heart disease (IHD), the incidence of ventricular arrhythmias, resulting in anti-tachy pacing or shock, is low, prompting for better risk stratification. We assessed the predictive value of the QRS-T angle for both the occurrence as well as the absence of appropriate ICD therapy in those patients. Methods: ICD recipients (n=412, 361 male, age 63±11 years) with IHD and primary prevention indication were included. The ECG pre-implantation was analysed and after device implantation, the occurrence of appropriate ICD therapy was noted. A survival analysis was performed comparing patients with a frontal plane QRS-T angle 90, pre implantation, to patients with a frontal angle > 90 ; and patients with a spatial QRS-T angle 100 were compared to those with a spatial angle >100. Results: For patients with a frontal plane QRS-T angle >90, the adjusted (age, sex, ejection fraction, QRS duration) hazard ratio for the occurrence of appropriate device therapy was 2.4 (95% CI ). A spatial QRS-T angle > 100 was associated with an adjusted hazard ratio of 7.3 (95% CI ). Furthermore, in the patients with a spatial QRS-T angle 100, an absulote risk of 2% for ventricular arrhythmias was observed, the first event occurring after two years of follow-up. See figure. P3295 Effect of ranolazine on ventricular tachycardia in patients with non-st elevation acute coronary syndrome undergoing percutaneous coronary intervention E. Karwatowska-Prokopczuk, W. Wang, E. Layug, L. Belardinelli. CV Therapeutics, Inc, Palo Alto, United States of America Introduction: The incidence of ventricular tachyarrhythmias after percutaneous coronary intervention (PCI) is low, but has been associated with worse clinical outcomes. We determined the effect of ranolazine (RAN) on the incidence of ventricular tachycardia (VT) 100 bpm lasting at least 8 beats but < 30 sec in patients hospitalized with non-st elevation acute coronary syndrome (NSTE-ACS) who underwent PCI within the first week of randomization. Methods: The MERLIN-TIMI 36 trial randomized 6560 pts to RAN or placebo (PLA) stratified according to whether an early invasive or conservative medical strategy was planned. The target RAN dose was 1000 mg bid and could be titrated downward at the investigator s discretion. Continuous Holter monitoring was performed for the first 7 days after randomization. Patients (RAN=737, PLA=754) with 2 hrs of evaluable Holter data from start of PCI or pts with 1 hour of evaluable Holter data if Holter was restarted within 1 hour from start of PCI were included in this post-hoc analysis. The incidence of outcomes was compared using Cochran-Mantel-Haenzel test for general association, stratified by intent for early invasive strategy. Results: Within 2 hours from start of PCI, significantly fewer pts had at least 1 episode of VT 8 beats with RAN compared to PLA (1.1% vs 2.7%, p=0.026). The incidence of cardiovascular death (CVD) and sudden cardiac death (SCD) during an average follow-up of 1 year was also lower in RAN- compared to PLA-treated pts (CVD: 0.9% vs 2.9%, p=0.006; SCD: 0.1% vs 1.2%, p=0.012). Similar trends were observed for the incidence of CVD and SCD within 30 days (CVD: RAN 0.5% vs. PLA 1.2%, p=0.18; SCD: RAN 0.1% vs. PLA 0.4%, p=0.33) Incidence of outcomes post PCI PLA (n=754) RAN (n=737) p-value VT 8 beats 20 (2.7%) 8 (1.1%) CVD - anytime 22 (2.9%) 7 (0.9%) CVD - 30 days 9 (1.2%) 4 (0.5%) 0.18 SCD - anytime 9 (1.2%) 1 (0.1%) SCD - 30 days 3 (0.4%) 1 (0.1%) 0.33 Conclusion: In pts with NSTE-ACS undergoing PCI, RAN significantly reduced Conclusions: A wide QRS-T angle is a strong predictor of appropriate device therapy in primary prevention ICD recipients with IHD. Furthermore, a spatial QRS-T angle 100 identifies patients at very low risk of appropriate device therapy during follow-up. P3297 The synergic effect of amiodarone and beta-blockers on antitachycardia pacing effectiveness reduces the need of shocks to terminate ventricular tachycardias J. Jimenez-Candil, J. Hernandez, M. Ruiz Olgado, J. Morinigo, A. Martin, C. Ledesma, C. Martin-Luengo. Hospital Universitario de Salamanca, Salamanca, Spain Background: Monomorphic ventricular tachycardias (MVT) are the most frequent cause of appropriate therapies in ICD patients (ICD-P) with left ventricular dysfunction (LVD). Despite the high efficacy of antitachycardia pacing (ATP), in 10-30%, depending on their cycle length (CL), ATP is not successful and, then, shocks (SH) are needed to terminate these arrhythmias. Although amiodarone is widely used to prevent ventricular tachyarrhythmias, its effect on ATP effectiveness (ATP-E) has not been well established. Objectives: To determine the relationship between the chronic treatment with amiodarone (CT-ADR) with: a) the ATP-E, and b) the occurrence of shocks (SH) due to MVT. Methods: We prospectively analyzed 551 MVT (CL: 329±35 ms) occurred in 67 ICD-P with LVD (LVEF: 31±11; pacing site: right ventricular apex). ATP programming was standardized including two zones for fast and slow MVTs. Failed ATP therapies were followed by SH. All medical treatments were determined at each MVT presentation. Results: Of 551 MVT, 147 (27%) had CT-ADR. ATP-E was 87% and 11% MVT required at least one SH to be terminated. MVT under CT-ADR had similar CL (331±30 vs. 327±29; p=0.4) and were less frequently under beta-blocker treatment (BB-T) (17 vs. 60%; p=0.01). In the univariate analysis, the ATP-E was similar regardless the CT-ADR (present vs. absent): 89% vs. 85%; p=0.5. However, we found a positive interaction between BB-T and CT-ADR: a) MVT without BB-T: CT-ADR did not improve the ATP-E: 79% vs. 75% (p=0.6); b) MVT under BB-T: CT-ADR was associated with an increase in the ATP-E: 98% vs. 87% (p=0.001). In a logistic regression analysis -which included the LVEF, CL, indication, aetiology- both BB-T (OR: 4.5; p<0.001) and CT-ADR (OR: 3; p=0.001)

255 Ventricular arrhytmias: diagnosis and treatment 555 remained as significant predictors of successful ATP. As a result, BB-T and CT- ADR were associated with an adjusted reduction of SH due to MVT of 78% and 74%, respectively (p<0.001 for both). The frequencies (%) of SH according to these treatments are shown in the table. No CT-ADR CT-ADR p No BB-T BB-T Conclusions: In MVT occurred in ICD-P with LVD, BB-TT and CT-ADR have a positive and synergic effect on ATP-E which reduces the need of SH to terminate these arrhythmias. P3299 Left bundle-branch block reentrant ventricular tachycardias. Elucidation of the mechanism based on activation time to the right ventricular apex R. Cozar, R. Peinado, J.L. Merino, S. Moreno, A. Perez, E. Diaz, D. Filgueira, L. Pena, J.L. Lopez Sendon, J.A. Sobrino. Hospital Universitario La Paz, Madrid, Spain Background: The diagnosis of bundle-branch reentry (BBR)ventricular tachycardia (VT) in patients (P) with leftbundle-branch block reentrant VT, by the standard approach, is challenging and has limitations. Thismay lead to misrecognition of this tachycardia mechanism easily amenable tocatheter ablation. This study was aimed at analysing the usefulness of theactivation time to the right ventricular apex (the exit zone of the classicalbbr-vt circuit) to elucidate the reentrant mechanism of these VT. Methods: We retrospectively evaluated 29consecutive P with left bundle-branch block reentrant VT in whom the reentrantmechanism (BBR versus myocardial reentry MR-), diagnosed by electrophysiogicalcriteria, was confirmed by successful catheter ablation. Sixteen P (12 male,mean age 58±19 years, mean VT cycle length 297±35 ms) had BBR-VT and 13 P (12male, 69±8 years, mean VT CL 392±71ms) had MR-VT. All P in MR-VT group had post-myocardialinfarction VT. In BBR-VT group 5 P had previous myocardial infarction, 4 hadmyotonic dystrophy, 3 dilated cardiomyopathy, 2 aortic valve disease, and 2non-specific cardiomyopathy. The timing of the right ventricular apicalelectrogram in relation to the onset of the QRS complex during VT (QRS-RVa),was measured by two independent observers (intraclass correlation coefficient0.88; p=0.007). QRS onset was determined from the surface lead that showed theearliest deflection. The difference in QRS-RVa according to the VT mechanismand the usefulness of this criterion to predict the VT mechanism wereanalysed. Results: The QRS-RVa was significantlyshorter in BBR-VT than in MR-VT (- 7.5 ms, interquartil range 13.5 to 8 versus38 ms, interquartil range 18 to 50; p<0.0001). The QRS-RVa predicted thetype of reentrant mechanism (area under the ROC curve = 0,94). A QRS-RVa 10ms had a sensitivity of 93,8%, a specificity of 84,6%, a positive predictivevalue of 88,2% and a negative predictive value of 91,6% to establish a BBR-VTmechanism. Conclusions: The QRS-RVa time is shorter inbbr-vt as compared to MR-VT. AQRS-RVa time 10 ms is highly suggestive of BBR-VT and makes MR-VT unlikely. (RV) function. Multidirectional LV strain (radial, circumferential and longitudinal) and RV free wall longitudinal strain were calculated by 2-D speckle tracking imaging (STI). Results: At baseline and at follow-up LVEF and volumes were normal (Table). 2-D STI demonstrated a reduction in LV and RV strain at baseline. At 12 months follow-up there were no changes in LVEF and RV systolic function. However, radial, circumferential and longitudinal strain significantly improved in patients after RFCA but remained unchanged in the control group. Conclusions: Frequent PVCs can induce subtle cardiac dysfunction detected by STI analysis in patients without apparent cardiomyopathy. RFCA can successfully eliminate PVC s and improve cardiac function. P3301 Impact of the shortness of the repetitive response intervals for the initiation of the polymorphic VT/VF in idiopathic outflow tract tachycardia M. Igarashi 1, H. Tada 1,D.Akiyama 1, K. Kurosaki 2, Y. Sekiguchi 1, T. Arimoto 1, H. Yamasaki 1, K. Kuga 1, A. Nogami 2, K. Aonuma 1. 1 University of Tsukuba, Tsukuba, Japan; 2 Yokohama Rosai Hospital, Yokohama, Japan Purpose: Idiopathic, monomorphic ventricular tachycardia (MVT) or premature ventricular contractions (PVCs) arising from the right ventricular outflow tract (RVOT) are considered benign. On the other hand, polymorphic ventricular tachycardia or ventricular fibrillation arising from the RVOT (PVT/VF) has been reported. Aim: The aim of this study was to clarify the detailed electrocardiography (ECG) and clinical characteristics of the PVT/VF. Methods: The ECG findings and clinical data were compared between 16 patients with idiopathic PVT/VF originating from RVOT-PVCs (PVT-group) and 20 with idiopathic MVT (MVT-group). All patients underwent radiofrequency catheter ablation (RFCA). Results: Syncopal episodes were more prevalent in PVT-group (50%) than in MVT-group (10%; p<0.05). History of cardiac resuscitation including DC/AED were only observed in PVT/VF group (18.8%). No difference was found in the echocardiographic findings between the 2 groups. In PVT-group, the QRS morphology of the first 3 consecutive beats were almost identical among the PVT/VF episodes. The coupling interval (CI) of the first beat of the VT (CI: 0-1) was comparable between the 2 groups (PVT-group=469 vs. MVT-group=494 [ms]). However, the premature index of the first beat of the VT (ratio of the CI to the R-R interval of the sinus cycle just before the VT) was smaller in PVT-group (0.62) than in MVT-group (0.73; p<0.01). Furthermore, the CI of the second beat of the VT (CI: 1-2) and that of the third beat of the VT (CI: 2-3) were also shorter in PVT-group than in MVT-group (CI:1-2; 319 vs. 385 ms; p<0.05, CI:2-3; 269 vs. 378 ms; p<0.01). In 14 (87.5%) PVT-group patients, RFCA targeting the first beat of the VT eliminated the PVT/VF. In the remaining 2, a repeat RFCA cured the recurrent PVCs. All patients have done well with no recurrence of any tachycardia during a follow-up period of 44.8±16.8 months. Conclusions: The CIs of the second and third VT beats as well as that of the first VT beat are important for determining the QRS morphology of the VT, and shorter CIs of the initial several beats of the VT may cause a polymorphic QRS morphology in PVT/VF. RFCA is effective for curing PVT/VT. P3300 Beneficial Effects of successful ablation on LV and RV function in patients with frequent PVC and preserved ejection fraction A.P. Wijnmaalen, V. Delgado, M.J. Schalij, E.R. Holman, J.J. Bax, K. Zeppenfeld. Leiden University Medical Center, Leiden, Netherlands Purpose: Successful radiofrequency catheter ablation (RFCA) of frequent monomorphic premature ventricular contractions (PVC) can result in dramatic improvement of left ventricular (LV) function in selected patients. Subtle and early forms of PVC induced LV impairment may not be detected by standard echo techniques. Methods: Forty-nine patients (30 male, 49±16yr) with frequent PVCs (burden 26.2±12.9%, history of palpitations 1.5±1.6yr) were studied. In 34 patients who underwent RFCA the PVC burden decreased to <1% after the procedure. Fifteen patients not scheduled for RFCA served as controls. Patients underwent 2-dimensional (2-D) echocardiography prior to ablation and at follow-up (median 12, range 3 16 months). LV volumes and ejection fraction (EF) were calculated by Simpson s rule. Fractional area change was calculated to assess right ventricular Echocardiographic findings PVC ablation (n=34) Baseline Follow-up p-value LV end-diastolic volume (ml) 127±39 120± LV end-systolic volume (ml) 56±22 49± LV ejection fraction (%) 57±8 59± RV fractional area change (%) 43±9 45± Radial strain (%) 31.1± ±16.2 <0.001 Circumferential strain (%) -16.2± ± Longitudinal strain (%) -17.8± ± RV-free wall Longitudinal strain (%) -24.2± ± P3302 Comparison of electroanatomical voltage map and contrast enhanced-cardiac magnetic resonance in determining the true endocardial scar area in post myocardial infarction ventricular tachycardia T. Boussy 1, A. Berruezo 1,J.Ortiz 2, D. Perez 1,E.Guasch 1, E. Silva 2, D. Andreu 1, P. Perea 2, L. Mont 1, J. Brugada 1. 1 Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Arrythmia Section, Barcelona, Spain; 2 Hospital Clinic, University of Barcelona - Thorax Institute. Cardiology Dep., Echocardiographyc Lab., Barcelona, Spain Background: substrate mapping of the left ventricle (LV) identifies scarred tissue as low voltage areas. Over or underestimation of these areas can result in misinterpretation of the electroanatomical maps. Combination of the endocardial scar surface defined by the voltage map and that derived from contrast enhanced cardiac magnetic resonance (ce-cmr) may better delineate the true arrhythmic substrate. Methods: twelve patients (11 men, age (61±9 y) who presented for ablation of scar-related VTs underwent both electro-anatomical voltage mapping (CARTO, Biosense Webster) of the LV and a ce-cmr. On the endocardial voltage map, dense scar was defined as having a local voltage amplitude < 0.5 mv (marked in red). The area of these red regions was acquired by an area measuring tool provided by the CARTO system. On ce-cmr, the endocardial scar surface was obtained by manual plannimetry on sequential short axis slices. Results: Ce-CMR identified a scar in the endocardium in 8 (66%) patients. The scars were located in the inferior (4), anterior (2), inferoposterior (1) or anterolateral (1) wall of the LV. The scar areas measured by ce-cmr were consistently larger than those obtained on the voltage maps (27,4±6,5 cm 2 ce-cmr versus 18,96±20,4 cm 2 CARTO) in all 8 patients. Four patients who had no endocardial scar on ce-cmr had a normal endocardial voltage map. Two of them had an epicardial scar and the other two had no scar at all.

256 556 Ventricular arrhytmias: diagnosis and treatment Conclusions: An important mismatch is seen between endocardial scar areas defined by voltage mapping set to 0,5 mv and those obtained by ce-cmr. Irrespective of the scar localization, the amount of affected tissue as shown by hyper enhancement on ce-cmr, is underestimated on the voltage maps. P3303 A vasodilating agent without cardioactive effect can inhibit the early afterdepolarization-related ventricular tachyarrhythmias in rabbits S. Yamagishi, K. Tsutsui, N. Yamagishi, N. Hayami, T. Kunishima, Y. Murakawa. Fourth Department of Internal Medicine, Teikyo University School of Medicine, Kawasaki, Japan Purpose: We tested whether a vasodilating agent without direct cardioactive effect can inhibit the occurrence of ventricular tachyarrhythmia (VT) caused by abnormal repolarization. Methods and Results: Fifty-six anesthetized rabbits were used. [Part 1] To estimate the minimum arrhythmogenic doses of methoxamine (α-stimulant) and nifekalant (Ikr blockade) to induce early afterdepolarization-related VT, methoxamine (ME) and nifekalant (NI) were intravenously administered at three different doses [n=5 (17.5 μg/kg/min and 0.2 mg/kg/min: High-ME/NI), n=5 (8.7 μg/kg/min and 0.1 mg/kg/min: medium-me/ni), n=20 (5.2 μg/kg/min and 0.06 mg/kg/min: low-me/ni)]. While high-me/ni and medium-me/ni invariably caused VT (5/5 and 5/5), VT failed to occur in 4 of 20 rabbits treated with low-me/ne (incidence of VT: 80%). [Part 2] Hydralazine, which is suggested to inhibit IP3-induced release of Ca 2+ from the sarcoplasmic reticulum in vascular smooth muscle cells and have little effect on myocardial ionic channels, was given at a rate of 2mg/kg/min together with low-me/ni in 14 rabbits. Rabbits with low-me/ne in Part 1 were used as control. Systolic arterial blood pressure was 107±32 mmhg (p<0.01 vs. control [168±18 mmhg]). VT occurred only in two of 14 rabbits treated with hydralazine (14%, p<0.01 vs. control). [Part 3] In the remaining 12 open-chest rabbits, the monophasic action potential (MAP) of the left ventricular epicardial surface was recorded. Early after depolarization (EAD)-like hump was detected in all eight rabbits without hydralazine. MAPs did not show marked hump in four of six rabbits with hydralazine. Conclusion: These results suggest that reduction of pressure load itself has antiarrhythmic effect on EAD-related VT. P3304 Electrical Storm in patients with an Implantable Cardioverter-Defibrillator G. Leibundgut, S. Osswald, C. Sticherling, M. Kuehne, B. Schaer. University Hospital Basel, Basel, Switzerland Background: Electrical storm (ES) is defined as the occurrence of 3 ICD interventions (ATP and/or shocks) within 24 hours and has been identified as a prognostic factor of subsequent death. However, ES might have its seeds in different reasons and the definition usually used is quite broad, as series of ATP cannot be compared to series of shocks. We therefore tried to determine outcome, triggers and measures taken in patients with coronary artery disease (CAD) and severe ES. Methods: In our prospective ICD registry we identified all patients with ES. We used a more constricted definition of ES: a series of ÿ3 episodes of ventricular tachyarrhythmia (VT) or fibrillation (VF) that required high energy shocks, usually leading to urgent hospitalisation. We restricted the study to CAD patients, as in these patients ischemia as a potential trigger is often excluded by non-/invasive testing in addition to routine lab tests and history taking. In all patients follow-up was defined as the 12 months following the first ES. Results: From our ICD registry database we retrieved 431 patients with CAD. 32 (7.4%) patients fulfilled our criteria of ES. 4 patients were excluded due to missing follow-up data. In the remaining 28 patients mean age was 68±11 years, 12 (43%) patients died, 1 (4%) in direct correlation with ES. To identify possible ischemia myocardial perfusion szintigraphy (MPS) was performed in 12 (43%) and coronary angiography in 15 (54%) patients. We identified as triggers: hypokalemia or physical activity in 1 (4%) patient respectively, infection in 3 (11%) and ischemia in 6 (21%) patients. Identification of a trigger was not possible in 15 (54%) patients and 2 (7%) patients had an inadequate ICD-therapy. Measures taken were: adjustment of anti-ischemic medication in 4 (14%) and percutaneous coronary intervention (PCI) in 6 (21%) patients, no adjustments were done in 18 (64%) patients. After the first ES, which occurred 33±34 months after implantation of the ICD, 10 (36%) patients sustained at least one other ES during follow-up. 1 (17%) of the patients who had a negative MPS and 3 (50%) of the patients with PCI to correct ischemia sustained another ES during follow-up. Conclusion: Most of the identified triggers for ES in patients with known CAD remain unknown and are different from ischemia. Patients with suspected or proven ischemia triggering an ES undergoing PCI have more frequent future events than patients without ischemia. P3305 Evaluation of ventricular radiofrequency ablation lesions with contrast enhanced-cardiac magnetic resonance T. Boussy 1, A. Berruezo 1,J.Ortiz 2, E. Guasch 1,D.Perez 1, E. Silva 2, D. Andreu 1,T.DeCaralt 2,L.Mont 1, J. Brugada 1. 1 Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Arrythmia Section, Barcelona, Spain; 2 Hospital Clinic, University of Barcelona - Thorax Institute. Cardiology Dep., Echocardiographyc Lab., Barcelona, Spain Introduction: It has been described that the lesions produced by radiofrequency (RF) application in the myocardium may be detected by ce-cmr in animal models, but so far, there is no evidence showing that RF-lesions can be observed in vivo in humans. We sought to characterize RF-lesions applied during VT ablation by means of contrast enhanced cardiac magnetic resonance (ce-cmr) Methods: Twenty one patients referred for VT-ablation underwent a ce-cmr within 3 months. Of them, 10 patients had coronary artery disease without (4) or with prior anterior (1), inferior (4) or lateral (1) infarction, 3 patients had ARVD, 5 NICMP and 3 patients presented with SMVT s in the absence of SHD. A Voltage (10) or activation (3) map was performed with the CARTO system in 13 patients to target 17 clinical VT s. Conventional mapping was used in the remaining 8 patients (11 VT s). RF lesions created were classified as focal (7) or linear (14). On ce-cmr, RF lesions were depicted in the right and left ventricles according to a 20 segment model. Location, depth, transmural extent (% of wall thickness) and continuity of the RF lesions were assessed. Results: Location: RF lesions were depicted in 83% of ce-cmr studies performed within two weeks as compared to 57% beyond this period. Ten (77%) of the 13 visible RF lesions were located in the left ventricle (LV), 11 (85%) at the endocardium and 2 (15%) at the epicardial layer of the right ventricle (RV) and LV respectively. Depth: RF lesions were deeper in the LV than in the RV (6,2±1,4 mm vs 3,6±1,7 mm;) The depth of lesions caused by endocardial applications was higher in the LV, but the transmural extent of RV lesions was significantly higher in the RV (52%) than in the LV (38%). No significant difference in depth or trasmurality could be demonstrated between endocardial (4,5±1,4 mm) or epicardial (5,2±2,3 mm) RF-lesions. Interestingly, RF energy applied in scarred tissue resulted in deeper lesions (5,6±1,3 mm, 48% transmurality) than when applied in healthy tissue (3,6±1,6 mm, 37% transmurality). Continuity: the continuity of 8 visible linear RF-lesions was confirmed on ce-cmr in all but one case (87,5%). Conclusion: RF lesions can be characterized by ce-cmr when performed soon after the ablation. RF lesions tend to be more transmural when applied in scarred tissue or in the RV wall. P3306 Left ventricular mechanical dispersion predicts ventricular arrhythmia in patients after myocardial infarction K.H. Haugaa, M.K. Smedsrud, E. Kongsgaard, O.A. Smiseth, J.P. Amlie, T. Edvardsen. Rikshospitalet University Hospital and University of Oslo, Oslo, Norway Purpose: Electrical dispersion in infarcted myocardium facilitates ventricular arrhythmia. Electrical dispersion leads to mechanical dispersion (heterogeneous contraction pattern) which can be assessed by myocardial strain echocardiography. We therefore hypothesized that mechanical dispersion by myocardial strain can predict risk for ventricular arrhythmias in patients after myocardial infarction (MI). Methods: We prospectively included 33 post MI patients with ICD implanted according to secondary prevention criteria. After 1.7±0.8 years follow up, 20 had no and 13 patients had one or more arrhythmic events requiring appropriate ICD therapy. Healthy individuals (n=21) served as a control group. Contraction duration was measured as the time from ECG Q/start R to maximum LV shortening by strain. Standard deviation (SD) of contraction duration in a 16 LV segment model was calculated as a parameter of mechanical dispersion. Results: EF did not discriminate ICD patients with arrhythmias from those without (38±8% vs. 38±13%, ns). ICD patients showed increased mechanical dispersion compared to healthy individuals (68±19ms vs. 22±10ms, P<0.001). Mechanical dispersion was significantly more pronounced in ICD patients with arrhythmia compared to those without (76±20ms vs. 61±15ms, P=0.03). Figure displays increased mechanical dispersion (right panel) in an ICD patient with recorded arrhythmic events. Arrows indicate difference between longest and shortest contraction duration. Conclusions: Cardiac mechanical dispersion assessed by strain echocardiography was present in post MI patients compared to healthy individuals. Increased

257 Ventricular arrhytmias: diagnosis and treatment 557 mechanical dispersion predicted further ventricular arrhythmias in post MI patients. P3307 Cheyne-Stokes respiration indicates an increased risk for the manifestation of malignant arrhythmias in patients with heart failure T. Bitter, C. Prinz, C. Langer, D. Horstkotte, O. Oldenburg. Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany Purpose: In heart failure patients prevalence of Cheyne-Stokes respiration (CSR) and obstructive sleep apnoea (OSA) is high. Recently, an association of OSA with cardiac arrhythmias and sudden cardiac death has been recognized. Evidence for an increased arrhythmogenic potential is lacking in patients with CSR. Aim of this study is to investigate whether CSR in heart failure patients is linked with an increased risk for arrhythmogenic events. Methods: A total number of 216 patients (pts, 52 female, 63±10 years) with systolic heart failure were screened for sleep disordered breathing by means of cardiorespratory polygraphy 6 month after guideline conform implantation of a cardiac resynchronisation therapy device/cardioverter-defibrillator (CRT-D). In case the apnoea-hypopnoea-index (AHI) was < 5/h, patients were considered to have no sleep apnoea (nosdb), in case of an AHI 5/h and the majority of events, patients were grouped as having CSR or OSA. During follow up (mean 43±7 months) appropriate monitored ventricular arrhythmias (non sustained ventricular tachycardia, sustained ventricular tachycardia and ventricular fibrillation) as well as appropriate cardioverter-defibrillator therapies were documented. Results: Out of 216 pts 78 (36%) presented with CSR, 80 (37%) with OSA and 58 (27%) with nosdb. OSA (65±9 years, p=0.005) and CSR (65±7 years, p=0.002) pts were older than nosdb pts (59±12 years). Left ventricular ejection fraction (LVEF) was lower in the CSR group (26±8%, p=0.002) compared to nosdb (31±8%; OSA 29±9%, p=n.s.). Other confounding factors showed no significant differences. Time period to first monitored ventricular arrhythmias was significantly shorter in the CSR (17±2 months) and OSA (24±3 months) group compared to pts with nosdb (68±7 months). Time period to first appropriate cardioverter-defibrillator therapy was significantly shorter in pts with CSR (39±5 months) and OSA (44±3 months) compared to pts with nosdb (80±7 months). On multivariate analysis CSR (hazard ratio (HR) 2.55, 95% confidence interval (CI) 1.55 to 4.22, p=0.002) and OSA (HR 2.09, CI 1.25 to 3.47, p=0.005) were independent predictors for occurrence of monitored appropriate ventricular arrhythmias as well as for appropriate cardioverter-defibrillator therapies (CSR: HR 3.16, CI 1.68 to 5.94, p=0.004; OSA: HR 1.96, CI 1.00 to 3.82, p=0.049). Conclusion: This study reveals, that in analogue to OSA, CSR indicates an increased risk for malignant arrhythmias in patients with heart failure. Whether adequate therapy of CSR is accompanied by a superior event-free survival needs to be determined. P3308 Utility of modified moving average analysis of T-wave alternans with exercise test to predict ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy J. Zou, X. Hou, S. Xue, D. Xu, K. Cao. Nanjing Medical University, Nanjing, China, People s Republic of Background: T wave alternans is useful for predicting the ventricular arrhythmia events and prognoses in the ischemic or non-ischemic cardiomyopathy with low left ventricular ejection fraction. However, the pridective value of T wave alternans for Arrhythmogenic right ventricular cardiomyopathy patients is unclear. Objective: To explore the character of T-wave alternans in patients with Arrhythmogenic right ventricular cardiomyopathy (ARVC) and the predictive value of ventricular arrhythmia events. Methods: T wave alternans (TWA) was assessed with modified moving average (MMA) analysis method by treadmill exercise testing in 35 ARVC patients and 60 healthy volunteers. Alternation voltage of T wave in the precordial leads V1- V6 was measured and the greatest alternation voltage of each individual in all precordial leads was defined as MaxAlt. All ARVC patients were followed up. The clinical ventricular arrhythmia events included sudden cardiac death, sustained symptomatic ventricular tachycardia/fibrillation or appropriate ICD discharge. Results: The 35 ARVC patients (28 males) have an mean age of 38. 6±11.0 y/o. Despite the morphologic changes of the right ventricular, the patients have preserved left ventricular function with an average LVEF of 65.0±5.5%. There was significant difference between ARVC patients and healthy people in alternation voltage of lead V1 V6 and MaxAlt. Receiver-operating characteristics (ROC) curves for MMA-TWA showed that the cut point of MaxAlt 11.5 μv was optimal (the sensitivity and specificity for predicting ARVC were 74.3% and 88.3%, respectively). 26 ARVC patients (74.3%) had positive test result when MaxAlt 11.5 μv was defined as TWA positive. During 13.3±1.7 months follow-up, 6 patients (17.1%) had clinical ventricular arrhythmia events. Among these 6 patients, five were TWA positive and one negative. The negative predictive value (NPV) and positive predictive value (PPV) of the TWA test for the prediction of clinical ventricular arrhythmia events were 88.9% and 19.2%, respectively. Neither the difference of events rate between TWA-negative and positive subjects nor the difference of alternation voltage value between patients with and without clinical events has been found. Kaplan-Meier survival curve showed that TWA positive had no relation with clinical ventricular arrhythmia events. Conclusions: ARVC patients have much higher level of T wave alternation voltage than healthy controls; TWA test had good negative predictive value of ventricular arrhythmia but was not able to predict the clinical rate in this group of ARVC patients with preserved LV function. P3309 Determinats of long term success of radiofrequency catheter ablation of postinfarction ventricular tachycardia L. Geller, S.Z. Szilagyi, A. Magyar, E. Vegh, M. Srej, E. Zima, L. Molnar, T. Tahin, B. Merkely. Semmelweis University, Cardiovascular Center, Budapest, Hungary Purpose: Ventricular tachycardia (VT) is an important cause of mortality and sudden cardiac death in patients with ischaemic heart disease. If the antiarrhythmic and/or ICD therapy is uneffective or impair quality of life, catheter ablation (RFA) may be considered. The aim of the study was to evaluate the acute and long term efficacy of RFA in treatment of ischaemic VT. Methods: 50 postinfarction VT ablations were evaluated. Clinical and electrophysiological data of the 43 (3 females) patients (age: 67±8 y) were studied. In 17 cases (34%) RFA was performed during incessant VT, in 3 cases (6%) epicardial ablation was also applied. Follow-ups were performed every 3 or 6 months. Results: Mean follow-up period was 23±12 months. 24 patients (56%) had dilatative cardiomyopathy, 23 patients (53%) had left ventricular aneurysm and 26 patients (60%) underwent percutaneous and/or surgical revascularisation. The prior myocardial infarction localization was anterior in 22 (51%), inferior in 14 (33%) and multiple in 7 (16%) patients. Acute ablation success in all patients with regard to noninducibility of the clinical VT was 96%. In 7 cases (14%) VF was induced. Chronic success was 67%, it was defined as freedom from any ventricular tachycardia during follow-up. Mean left ventricular ejection fraction (LVEF) was 35±8% (21-60). There was a lower LVEF in patients who had VF/VT recurrency (31±4% vs. 37±8%, p=0,036). Determinant of chronic success of the procedure was the LVEF >35% (p=0,012). Redo procedures were performed in 6 patients (14%) for two and 1 patient (2%) on three occasions, respectively. 5 patients (12%) died during the follow-up, four of them by progressive heart failure, one by cancer. Conclusions: RFA is an effective and successful treatment of postinfarction VT with a low complication rate. It is a recommended method to treat VT in highly specialized and experienced centers if the AADs and the ICD are not effective or reduce the quality of life, beside noninducibility ejection fraction seems to be the main determinant of the long term success. P3310 Influence of diabetes on time of onset of life-threatening cardiac arrhythmias in a population-based study A. Bardai, M.T. Blom, J. Berdowski, H.L. Tan. Academic Medical Center, Amsterdam, Netherlands Purpose: Severe cardiac events, e.g. acute myocardial ischemia and sudden cardiac death, display a diurnal pattern, occurring more often in the morning. Diabetes Mellitus (DM) is associated with heart failure, myocardial infarction and increased risk of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF). Small studies suggest that patients with DM have an increased risk of sudden death at night. Studies showing that nocturnal hypoglycaemia lead to prolongation of the QT-interval in DM patients suggest that these patients die of VT/VF. To study this hypothesis we compared the time of onset of VT/VF between DM patients and non-dm patients. Methods: Patients were enrolled from the AmsteRdam REsuscitation STudy (AR- REST), an ongoing population-based study in The Netherlands, in which all patients with Out of Hospital Cardiac Arrest (OHCA) are prospectively included. Patients with ECG documented VT/VF were included. Drug use histories of these patients were retrieved from the patient s pharmacist(s). Anti-diabetic drug use during one year prior to the OHCA was used to classify patients as DM or non- DM. For each DM patient, three age/gender matched non-dm patients were selected. Time of onset of VT/VF was derived from the ambulance ECG. Four time intervals were defined: 0:00-5:59, 6:00-11:59, 12:00-17:59 and 18:00-23:59 hours. ORs with 95% CI were calculated of the incidence of VT/VF in each time interval (DM vs. non-dm). Results: We identified 97 DM patients (22 females and 75 males) and 291 non- DM patients. Females had an OR of 3.87 (CI ) in the evening, while Table 1. Gender stratified DM patients with non-dm age matched controls and the Odds Ratios of occurrence of VT/VF during four time intervals (DM vs. non-dm) Time interval DM Non-DM OR (95% CI) DM Non-DM OR (95% CI) (female, (female, (male, (male, N=22) N=66) N=75) N=225) 00:00-05: ( ) ( ) 06:00-11: ( ) ( ) 12:00-17: ( ) ( ) 18:00-23: ( ) ( )

258 558 Ventricular arrhytmias: diagnosis and treatment males had an OR of 2.35 (CI ) at night. ORs were not different at other intervals. Conclusion: The highly significant ORs at two different time intervals for male and female patients suggest that DM affects time of onset of VT/VF. Elucidation of mechanisms governing this influence may be relevant in prevention of sudden cardiac death in DM patients. P3311 Baseline QTc duration predicts changes in QTc duration during Haloperidol use in an in-hospital population M.T. Blom, A. Bardai, M. Nieuwland, S.E.J.A. De Rooij, H.L. Tan. Academic Medical Center, Amsterdam, Netherlands Purpose: Haloperidol is a frequently prescribed antipsychotic drug. It is associated with HERG channel blockade, leading to QT interval prolongation and cardiac ventricular arrhythmias (Torsade de Pointes), and sudden death. Since the incidence of QT prolongation by Haloperidol use and its determinants are not fully resolved, we examined changes in QT duration after Haloperidol use and associations with clinical determinants. Methods: Patients receiving Haloperidol during hospital admission between 2005 and 2007 were studied. A random selection of 97 patients of whom an ECG was made before, during and after Haloperidol use was analyzed. We defined gender, age, dose of Haloperidol and medical history, using the hospital database. We analyzed use of other QT lengthening drugs 72 hours before each ECG, and electrolytes and inflammation parameters within 48 hours of each ECG. QT-intervals were measured blindly by hand and corrected for heart rate using Bazett s formula (QTc). Changes in mean QTc durations were calculated using a mixed model analysis in SPSS. Results: Overall, QTc duration increased slightly during Haloperidol use. However, when divided into subgroups based on baseline QTc duration, we found a significant increase in the Normal group (QTc <430 male, <450 female), but a significant decrease in the Borderline (QTc male, female) and Abnormal groups (QTc >450 male, >470 female). Subgroup division was not associated with any of the measured variables. K and leucocytes only correlated significantly with QTc duration in the Abnormal group. Table 1. Mean QTc before, during and after Haloperidol use, and pair wise differences QTc before dqtc1 (during-before) dqtc2 (after-during) before during after Total Normal (N=50) * Borderline (N=19) * -3.8 Abnormal (N=28) * -5.6 All values in ms. *Significant at 0.05 level. suppressed TdP (F 0/10* and V 0/7*) by returning STV to baseline values. F reduced APD, whereas V did not. Prevention of TdP was achieved by both drugs F: 0/8 and V 0/6. F but not V reduced baseline APD and STV (F: 1.5±0.6 to 1±0.5 ms*) and prevented D induced increases in APD and STV completely. EAD suppression was confirmed after F (not tested with V). Besides blocking ICaL, F also blocks late INa +, which was not seen with V. Peak INa + was not affected by either drug. Ca 2+ sparks were not suppressed by F, but reduced after V. Combining V with Lidocaine in vivo reduced baseline STV, similar to F. Conclusions: Complete anti-arrhythmic efficacy was seen with the ICaL blockers F and V. Their different electrophysiological actions may be related to differential additional effects of the two drugs. P3313 Purkinje fiber injury and electrical remodeling in non-ischemic cardiomyopathy: Implications for sudden cardiac death P.J. Psaltis 1, A. Carbone 1,D.Lau 1, T. Jantzen 2, K. Williams 1, P. Sanders 1, S. Gronthos 3, A.C.W. Zannettino 3, S.G. Worthley 1. 1 Cardiovascular Research Centre, Royal Adelaide Hospital; Dept of Medicine, University of Adelaide, Adelaide, Australia; 2 Biosense Webster Inc., Johnson & Johnson, Adelaide, Australia; 3 Institute of Medical and Veterinary Science and Hanson Institute; University of Adelaide, Adelaide, Australia Purpose: The Purkinje network is implicated in the initiation of ventricular fibrillation, the most common cause of sudden cardiac death (SCD). This study investigated Purkinje network injury and electrical remodeling in a preclinical model of cardiomyopathy. Methods: Sixteen sheep underwent fortnightly intracoronary doxorubicin infusions to induce moderate-severe systolic dysfunction. Left ventricular electromechanical mapping was then performed to determine segmental local activation times (LAT), unipolar voltage (UV) and bipolar voltage (BV) amplitudes. Results were compared to six, weight-matched, healthy sheep. Animals were euthanized and hearts prepared for histopathology. Results: 4/16 animals died during cardiomyopathy induction with sudden, nonprocedural causes. In the remaining 12, total doxorubicin dose administered was 3.7±0.5mg/kg and the resultant left ventricular ejection fraction was 32.6±6.0%. Doxorubicin recipients demonstrated the following compared to controls: prolongation of corrected QT interval (529.2±49.0ms v 451.0±47.0ms P<0.05); prolongation of the left ventricular total activation time (LAT interval 73.1±21ms v 21.2±4.2ms, P<0.01); delay and distortion in the electrical activation sequence between different LV segments (Figure 1); and segmental reductions in UV amplitude, most prominently in the anterior and septal walls and apex. Histopathology showed consistent damage to Purkinje cells with vacuolar degeneration and inflammatory infiltrates. Conclusion: Baseline QTc duration predicts QTc duration changes during Haloperidol use. Prolongation occurs mostly in patients with normal QTc intervals before use, while most patients with QTc prolongation at baseline show reduction in QTc duration. Future studies must resolve the pathophysiological basis of these findings. We recommend close monitoring of all patients receiving Haloperidol. P3312 Anti-arrhythmic efficacy of Verapamil and Flunarizine against dofetilide induced Torsade de Pointes arrhythmias is based upon a shared and a different mode of action A. Oros 1, M.J. Houtman 1,P.Neco 2,A.M.Gomez 2, S. Rajamani 3, N.J. Attevelt 1, L. Belardinelli 3, S. Richard 2, G. Antoons 1,M.A.Vos 1 on behalf of INSERM U-390, Physiopathologie Cardiovasculaire, Montpellier, France and Department of Pharmacological Sciences, CV Therapeutics, Palo Alto, CA, US. 1 Medical Physiology DH&L, UMC, Utrecht, Netherlands; 2 INSERM U-390, Physiopathologie Cardiovasculaire, Montpellier, France; 3 Department of Pharmacological Sciences, CV Therapeutics, Palo Alto, Ca, United States of America Objective: The high predisposition for drug-induced Torsade de Pointes (TdP) in anaesthetized dogs with chronic AV-block (CAVB) is well documented and associated with electrical remodeling and reduced repolarization reserve. The antiarrhythmic efficacy and mode of action of flunarizine (F) and verapamil (V) were evaluated. Methods: Anaesthetized CAVB dogs (n=17) were selected on the basis of a positive TdP inducibility test with the IKr blocker dofetilide (D: 25 μg/kg/5 min i.v.). Anti-arrhythmic effects of Ca 2+ channel antagonists (ICaL) F (2 mg/kg/2 min) and V (0,4 mg/kg/3 min) were assessed after TdP (suppression) and in different experiments to prevent D-TdP. ECG and ventricular action potentials (APs) were recorded. Electrical parameters and beat-to-beat variability of repolarization (STV = APDn- APDn1 /30*sqrt(2) were determined. In single isolated ventricular myocytes (VM), F (1 μm) and V (10 μm) were added to determine their effect on 1) dofetilide (1 μm) induced EADs in canine VM, 2) diastolic Ca 2+ sparks in VM of CPVT mice and 3) peak and late INa + in (ATX treated) SCN5A-HEK 293 cells. Results: In CAVB dogs, D increased STV (1.8±0.5 to4.5±1.5, p<0.01*) prior to TdP and in VM (10±3 to56±9 ms*) prior to EADs (8/8). Both drugs completely Figure 1 Segmental local activation time Conclusions: In this model of non-ischemic cardiomyopathy there is profound Purkinje fiber injury associated with substantial LV electrical remodeling. Such Purkinje injury may be responsible for SCD in patients with cardiomyopathy. P3314 Asssociation of paroxysmal supraventricular and ventricular tachycardia. Clinical significance B. Brembilla-Perrot, J.M. Sellal, P.Y. Zinzius, M. Valla, N. Benzhagou, Y. Lefrancois, D. Beurrier, A. Abdelaal, S. State, J. Cedano. CHU de Nancy - Hopital de Brabois, Vandoeuvre les Nancy, France The purpose of the study was to evaluate the significance of the association of paroxysmal supraventricular tachycardia (SVT) and ventricular tachycardia (VT) in the same patient. Fine-QRS complex tachycardia alternating with wide-qrs complex tachycardia can lead to the erroneous diagnosis of SVT with or without aberrancy. Population: 888 patients aged from 11 to 88 years were consecutively admitted for a sustained VT; 812 patients had associated heart disease (history of myocardial infarction 375, idiopathic dilated cardiomyopathy 68, arrhythmogenic right ventricular dysplasia 85, miscellaneous 284) and 76 had no apparent heart disease. Methods: Electrophysiological study including programmed atrial and ventricular stimulation, 2D cardiac echocardiography, coronary angiography in patients older than 40 years, right ventricular angiography and cardiac RMI since 2002 were performed in these patients. Results: Eleven patients presented (1%) with either SVT or VT. All SVT s were

259 Ventricular arrhytmias: diagnosis and treatment / Supraventricular arrhythmias: from mechanisms to treatment 559 related to an atrioventricular node reentrant tachycardia (AVNRT). The association of SVT and VT was significantly more frequent in patients without heart disease (6.5% vs 0.7%) (p<0.001): five patients had no heart disease and had a verapamil-sensitive VT. Two patients had arrhythmogenic right ventricular dysplasia and 4 patients had history of myocardial infarction. Among 689 patients with AVNRT, 35 had associated heart disease and only 5 have both tachycardias. Radiofrequency ablation of AVNRT performed in all patients did not change the recurrence of VT which required ablation in 3 patients, antiarrhythmic drugs in 4 and the implantation of a antitachycardia device with defibrillator in 3 patients. Conclusions: Fine QRS complex tachycardia alternating with wide QRS complex tachycardia leads generally to the erroneous diagnosis of SVT with or without aberrancy, because the association of SVT and VT was significantly more frequent in patients without heart disease. The association can be underestimated in these patients. In patients with heart disease, this association is exceptional. P3315 Cardiac resynchronization therapy-defibrillator utilization rates in 234 elderly patients at a single center T.A. Charlton 1, E.E. Johnson 1, M.A. Coppess 1,F.A.Mcgrew 1, B. Hamilton 1, S.B. Charlton 2,J.J.Sims 2. 1 Stern Cardiovascular Clinic, Memphis, United States of America; 2 Medtronic, Inc, Moundsview, United States of America Purpose: Few reports document the benefit of utilizing tachyarrhythmia therapies in elderly CRT patients (>75 years). The average age of large randomized clinical trials documenting the value of CRT-D has been approximately 66 years. We sought to document the time to first appropriate tachyarrhythmia therapy in our elderly patient cohort. Methods: A retrospective analysis of our CRT database was performed in June All patients with an FDA approved CRT-D device were evaluated for inclusion. The date of first CRT-D implant was documented along with all tachyarrhythmia therapies. All therapies were adjudicated by an electrophysiologist for appropriateness. We compared our data to the COMPANION trial for historical comparison. Results: 26.9% (63/234) of CRT-D patients had a tachyarrhythmia therapy (1142 episodes) with an average follow-up of 2.5 years. The average time to first appropriate therapy was 322±318 days. Figure 1 represents the time to first appropriate tachyarrhythmia therapy. 22.2% of patients (mean implant age 80±4.9) experience an appropriate therapy by the second implant year. This is similar to the COMPANION trial where time to first appropriate therapy was 19.3% at two years (average implant age 66). Time to first appropriate therapy A significant proportion of patients with typical cavotricuspid isthmus dependent atrial flutter (CTIDAF) presents with surface electrocardiogram (ECG) without typical features. Information is limited in the published literature to help identify this group of patients. Since ablation is safe and effective first line therapy for CTIDAF, it would be useful if any clinical and/or electrocardiographic criteria can be established to identify patients with CTIDAF presenting with atypical ECG features. A retrospective study was conducted to evaluate the patients with atrial flutter (AFl) undergoing radiofrequency ablation from May 2003 to December Out of 282 patients (age 65±12 years, male 83%), who underwent ablation for AFl, 261 (93%, male 75%) had typical right sided AFl (CTIDAF) confirmed by entrainment from cavo-tricuspid isthmus during ablation procedure while 21 (7%) had non-ctidaf. Among the patients of CTIDAF, 160 (61%) could be easily identified from the surface ECG but the remaining 101 (39%) patients did not demonstrate characteristic ECG patterns. Demographic, clinical, echocardiographic and, electrocardiographic parameters were studied to identify the patients with CTIDAF without typical features in the surface ECG. Two independent cardiologists interpreted the ECGs and any disagreement was resolved by a third interpreter. A combination of regression methods and discriminant analysis were performed. Stepwise Univariate ANOVA was used as statistical tool and Wilk s lambda test was used for computation of significance tables. We found the following 2 variables as the most important predictors for the prevalence of CTIDAF with atypical ECG patterns: 1) ECG finding of positive flutter waves in the first precordial lead (V1) and inferior leads (p=0.007); 2) Presence of hypertension (p=0.032). When Receiver Operating Characteristic Curves (ROCC) were computed for these predictors, the respective areas under the curves (AUROCC) were 0.57 and 0.54 signifying marginal usefulness of the test. Overall, the analysis could classify the patients with an accuracy of 66%. In our study a significant proportion (39%) of patients with CTIDAF presented with atypical ECG patterns. Hypertension and the ECG features of positive flutter waves in both inferior leads and V1 have the potential to predict the presence of CTIDAF even when the established ECG features fail. Identification of these patients will help offer ablation therapy early in the course rather than subjecting them to long-term anti arrhythmic drugs or cardioversions. P3317 SUPRAVENTRICULAR ARRHYTHMIAS: FROM MECHANISMS TO TREATMENT Magnetocardiography can identify abnormal atrial electrical activities during sinus rhythm in patients with paroxysmal atrial fibrillation H. Sato, H. Takaki, W. Shimizu, S. Kamakura, M. Sugimachi. National Cardiovascular Center, Suita, Osaka, Japan Background: Several alterations in atrial electrophysiological properties are important in the genesis of paroxysmal atrial fibrillation (PAF), however, no noninvasive technique for the estimation is currently available. MCG (magnetocardiography), possibly sensitive to minute electrical activities, may identify atrial electrical abnormalities during sinus rhythm in patients with PAF. Methods: We recorded a 64-channel MCG (MC-6400, Hitachi) and echocardiograms in 25 patients (19 males, 68.4±10.3 years) with documented PAF. Organic heart disease was present in 6 (HCM 4, others 2). Normal subjects (n=19) without a history of PAF paroxysmal atrial fibrillation and normal 12-lead ECGs served as controls to determine the normal atrial MCGs. We analyzed signal-averaged normal components (Figure) and transformed tangential components (2-D current mapping). Results: PAF patients frequently showed abnormal P-wave morphology (Figure); the ratio of max positive deflection to max negative deflection (P index) was greater in controls than in PAF (8.2±5.3 vs 4.7±4.7, p<0.001). P index <4.0 could diagnose PAF with a sensitivity of 68% (17/25) and a specificity of 95% (18/19). 2-D mapping revealed 2 different types of abnormal MCGs; (1) left atrial (LA) overload pattern with late (>80msec) currents observed in LA area (n=10), and (2) ectopic atrial rhythm pattern with initial currents occurring in non-sa node area (n=9). Echocardiographic LA enlargement (>40mm) was found in 14 of 25 (6/8 with normal and 8/17 with abnormal MCGs). All patients but one (24/25) had either abnormal MCG or LA enlargement, or both. Conclusions: Based on this single center retrospective analysis, it appears CRT- D patients greater than 75 years of age utilize CRT-D tachyarrhythmia therapies in a similar manner to younger patients observed in large randomized clinical trials. This study suggests patients greater than 75 years of age derive significant benefit from CRT-D and therefore defibrillaor therapy in conjunction with CRT should be considered, irrespective of age. P3316 Clinical and electrocardiographic identification of cavotricuspid isthmus dependent right sided atrial flutter presenting without typical patterns on surface electrocardiogram M. Ray, N. Hoang, A. Narula, R. Misra, S. Siddique. Lehigh Valley Hospital, Allentown, United States of America P-wave MCG (P index) Conclusions: MCG analysis often revealed abnormal atrial electrical activities during sinus rhythm in PAF patients. The tool may be useful for identify patients prone to PAF. P3318 Heart rate variability and occurrence of atypical atrial flutter after circumferential ablation for atrial fibrillation A. Ardashev, A. Shavarov, Y. Belenkov. Moscow State university clinic, Moscow, Russian Federation Purpose: To determine prognostic power of normal R-R interval fluctuation with

260 560 Supraventricular arrhythmias: from mechanisms to treatment occurrence of atypical atrial flutter (AFl) in patients (pts) after circumferential radiofrequency ablation (RFA) of atrial fibrillation (AFib) using traditional heart rate variability (HRV) and nonlinear dynamics techniques. Materials and methods: One hundred and forty consecutive pts (111 males and 29 females, mean age 54±11 years) who underwent RFA for symptomatic paroxysmal (61%) and persistent (39%) AFib were studied. Occurrence of atypical AFl was documented in 41 pts (AFl group). Ninety-nine (71%) were still free of arrhythmias during 12 months follow-up (sinus rhythm (SR) group). Time (ln SDNN, ln rmssd) and frequency (ln TP, ln LF, ln HF, LF/HF ratio) domain HRV measurements were analyzed. Nonlinear dynamics characteristics we used as follows: information, correlation and fractal dimensions, entropy and Lapunov s parameter. All parameters were determined based on consecutive 4000 R-R intervals recordings before RFA, 2, 6, 24 hrs, 2 months, 6 months and 12 months after RFA. Results: Six hrs after ablation HF was significantly higher in AFl group pts comparing with SR group pts (4.4±1.3 vs. 4.0±1.2, p=0.04). Twenty-four hrs after RFA SDNN and LF were significantly higher in AFl group pts comparing with SR group pts (3.4±0.6 vs. 3.2±0.5, p=0.04; 5.1±1.7 vs. 4.3±1.3, p=0.04, respectively). Twenty-four hrs after RFA Lapunov s parameter was significantly lower in AFl group pts comparing with SR group pts (4.23±0.73 vs. 4.75±0.50, p=0.0005). There were no significant differences among other HRV measurements. Conclusion: Traditional and nonlinear HRV measurements might be considered as an instrument in prognosis of occurrence of atypical AFl in post-ablation AFib pts. P3319 Evaluation of atrial refractoriness early after radiofrequency catheter ablation of accessory pathway in Wolff-Parkinson-White syndrome K. Cagli, S. Topaloglu, D. Aras, N. Sen, I. Akpinar, A. Durak, H. Kisacik. Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey Background: The intrinsic atrial vulnerability is proposed as one of the mechanisms of paroxysmal atrial fibrillation (PAF) in Wolff-Parkinson-White (WPW) syndrome. In this study we examined the early changes in atrial refractoriness after radiofrequency (RF) catheter ablation of accessory pathway (AP). Methods: Twenty-four consecutive WPW-patients without PAF (Study group, 14 M, mean age 39,0±9,5 y) were enrolled. Twenty-seven patients (21 F, mean age 51,4±10,1 y) with AV nodal reentrant tachycardia (AVNRT), who underwent the slow pathway ablation served as controls. In each patient, atrial effective refractory periods (AERPs), AERP dispersion, and intra- and inter-atrial conduction times were obtained before and 30 minutes after ablation. In study group, patients with and without inducible AF by incremental atrial pacing or atrial extrastimulation were compared. Results: In study group, AERPs in high right atrium (AERP-HRA) and right posterolateral (AERP-RPL) were increased, and AERP dispersion, intra-atrial (PAHIS) and inter-atrial (HRA-DCS) conduction times were decreased significantly after ablation; AERP in distal coronary sinus (AERP-DCS) was unchanged (Table 1). Inducibilityof AF was significantly reduced following ablation of AP (from 7 of 24 patients to 0 of 24, p=0.016). Comparison between patients with (n=7) and without (n=17) AF revealed that left atrium was larger, AERP-RPL before and after ablation, and ERP of AP were shorter in AF group (p<0,05). Table 1. Changes in atrial refractoriness parameters after successful catheter ablation Variable (msn) WPW-Patients (n=24) P value AVNRT Patients (n=27) P value Before After Before After PAHIS 44,8±14,5 34,8±5,9 0,001 35,5±9,2 34,2±8,7 0,097 HRA-DCS 67,5±15,7 58,9±14,8 0,001 63,2±9,9 61,8±10,6 0,244 AERP-HRA 233,3±33,4 246,6±28,8 0, ,5±20,8 260,3±19,3 0,394 AERP-RPL 242,5±25,9 251,6±27,4 0, ,6±17,9 269,2±21,3 0,183 AERP-DCS 268,75±31,9 265,8±35,2 0, ,2±20,3 273,3±20,0 0,327 AERPdisp 40,0±11,8 20,4±11,9 0,000 21,1±8,9 17,7±10,1 0,083 Conclusion: In WPW- patients, RF ablation of AP results in an immediate decrease in atrial vulnerability. Since inducibility of AF becomes more difficult in this less vulnerable atrium, the AP itself may play an important role in the development of AF. P3320 Asymptomatic ventricular preexcitation mimicking dilated cardiomyopathy: the location of the pathway is predictive of this association N. Sreeram, F. Udink Ten Cate, M. Kruessell, M. Emmel. University Hospital, Cologne, Germany Background: Ventricular preexcitation is common. Dilated cardiomyopathy (DCM) is usually the result of longstanding tachyarrhythmia (tachycardiomyopathy). We demonstrated a causal relationship between ventricular preexcitation and DCM in the absence or recorded tachyarrhythmias. The relationship appears to be accessory pathway (AP) location-specific. Patients and Methods: 10 consecutive children (age range 0.6 to 17 years) were studied. All had ventricular preexcitation on the ECG, with the vector of the AP suggesting a right sided septal pathway. None had documented tachyarrhythmias, or symptoms suggestive thereof. All however had evidence for DCM, with LVEDD >97th centile for weight and LV FS <25% on echocardiography. Diagnostic cardiac catheterization was performed in the first 4 children, in whom the LVEDP was normal. Biopsy findings were negative for myocarditis. Metabolic and viral screening were negative, as was the family history. Results: Eight of the 10 patients underwent invasive EPS. The AP was confirmed to be a right sided septal pathway in 7; one child had a fasciculo-ventricular AP. All APs were successfully ablated using either RF energy or by cryoablation. Two patients had spontaneous loss of ventricular preexcitation during clinical followup. Loss of preexcitation was associated with normalization of LV diameter and function in all patients, usually within 6 weeks. Conclusions: Right sided septal APs with overt preexcitation may result in marked ventricular dyssynchrony, which mimics DCM. A causal relationship between the AP and DCM is confirmed by normalisation of LV function following loss of preexcitation, either spontaneously or following ablation. P3321 Atrial flutter ablation after pulmonary veins isolation: the coronary sinus atrial activation pattern is useful for circuit localization P. Adragao 1,D.Cavaco 1,P.Carmo 2, K. Santos 1, F. Morgado 2, R. Bernardo 2, D. Cabrita 3, A. Silva 2. 1 Hospital de Santa Cruz; Hospital da Luz, Lisbon, Portugal; 2 Hospital de Santa Cruz, Carnaxide, Portugal; 3 Hospital da Luz, Lisbon, Portugal Background: Relapses after pulmonary veins isolation are sometimes not atrial fibrillation recurrences, but instead due to sustained tachycardias with circuits involving slow conduction peri-cicatricial areas. Such arrhythmias present electrocardiographically as regular tachycardias with atrial activity similar to that described for atrial flutter, and respond poorly to pharmacological treatment, thus frequently leading to a new ablation procedure. We evaluated whether the coronary sinus activation pattern is useful for localizing the reentry circuit. Methods: We studied 14 patients (pts) undergoing ablation of atrial tachycardia (16 procedures) after an initial AF ablation which included isolation of pulmonary veins and a cavo-tricuspid isthmus line. We used activation and entrainment mapping to localize the tachycardia circuit. Three catheters (coronary sinus, left atrium, and right atrium) were used in each electrophysiological study. A conventional mapping system was employed in 8 procedures, and a magnetic system in the remainder. The arrhythmia was suppressed in all pts during ablation. Results: The tachycardia circuit was localized in the left atrium in 14 cases and was related to the cavo-tricuspid isthmus in 2. Arrhythmias dependent on circuits in the left atrium were suppressed by ablation close to the pulmonary vein isolation lesions in 12 cases. In the other 2 procedures, we identified a flutter dependent on the mitral isthmus and the left atrial roof. The pattern of coronary sinus atrial activation was: septal to lateral in 10 procedures (2 right and 8 left flutters), simultaneous in 1 case, and lateral to septal in 5 cases. Conclusions: The lateral to septal and simultaneous patterns of coronary sinus atrial activation localized the arrhythmia in the left atrium. In 57% of left flutters, the activation was similar to activation from the right atrium (septal to lateral). Irrespective of the coronary sinus activation pattern, careful mapping of the left atrium is required in patients with post pulmonary vein isolation tachycardias. P3322 Mortality of patients with lone atrial fibrillation is similar to mortality in general population T. Potpara, M. Grujic, B. Vujisic-Tesic, M. Ostojic, M. Polovina. Institute for Cardiovascular Diseases, Clinical Center of Serbia, Belgrade, Serbia Purpose: to compare all-cause and cardiovascular mortality of patients with lone/idiopathic atrial fibrillation (AF) to correspondent mortality of general population of Serbia. Methods: longitudinal observational study included pts with nonvalvular AF as main indication for in-hospital and/or outpatient treatment in the Clinical Center, during , with total follow-up of at least 5 years (minimum 1 year prospectively), or until death. Principles of oral anticoagulation and rhythm or frequency control were concordant to the latest international guidelines for AF in given study period. Lone/idiopathic AF were defined as AF in pts without any underlying disease and 60yrs old (lone AF) or older (idiopathic AF). Cause of death was obtained from medical records (hospital discharge letter, death certificate). To compare mortality of study population with mortality of general population we used standardized mortality ratio (SMR) and chi-square test with P<0.05. Results: out of 1100 pts included in the study, 442 (40.2%) had lone/idiopathic

261 Supraventricular arrhythmias: from mechanisms to treatment 561 AF (mean age 47.0±12.6yrs). Majority of them had paroxysmal AF (67.0%) and normal left atrium (78.7%) at baseline. During mean follow-up of 11.5±7.2yrs development of cardiac disease was noted in 25.2% of pts, and transition to permanent AF occurred in 128/390 pts with previously intermittent AF (32.0%). Twelve patients (2.7%) died: 7 from non-cardiovascular causes and 5 (1.1%) from cardiovascular death. When compared to general population of Serbia, all-cause mortality (Figure) and cardiovascular mortality of pts with lone/idiopathic AF were not higher (p>0.05). Conclusions: all-cause and cardiovascular mortality of patients with lone/idiopathic AF are similar to all-cause and cardiovascular mortality in general population of Serbia. P3323 Increase in the prevalence of atrial fibrillation compared to aging in the general population: its kinetics and risk factors T. Tomizawa, M. Otaka, M. Kanashiki, H. Watanabe, I. Yamaguchi. Ibaraki Health Service Association Institute, Mito, Japan Aim: To clarify the prevalence, trend and risk factors of atrial fibrillation (AF) in the general population of Ibaraki Prefecture, located 60 miles to the northeast of Tokyo, Japan. Methods: AF was diagnosed from 1,874,182 electrocardiograms (ECG) recorded during the annual community health care program held for eight fiscal years from 2000 to 2007, and its prevalence was calculated. Kinetics of the prevalence was analyzed among examinees who had participated in the exam for two consecutive years. Moreover, relationships between AF and cardiovascular risk factors were analyzed. Results: AF was found in 17,891 ECG recordings. The mean age of subjects with AF (men, 70%) was 71.0±7.9 (men) and 72.5±7.9 (women) years. AF was significantly more frequent in men and the elderly, and its prevalence increased annually independent of aging (Fig). During the eight years, there was a 52% increase in subjects with AF and a 24% increase in the population older than 65 years. The annual AF incidence (/1000 persons/year) increased from 1.9 ( 01) to 2.3 ( 07), p<0.01, whereas the annual AF disappearance rate (/1000 persons with AF/year) decreased from 111 ( 01) to 70 ( 07), p< Regular drinking, history of cardiac disease, hypertension, and diabetes mellitus were related to AF, and body mass index (BMI) and blood glucose level (HbA1c) were significantly higher in subjects with AF than in those without AF. In contrast, smoking, history of dyslipidemia, and blood cholesterol level were not related to AF. in a significant reduction of both total radiation time and dose for the robotic navigation group with a mean duration of fluoroscopy in group A 24.7 minutes and standard deviation of 11.8 minutes compared to a mean of 6.3 minutes and standard deviation of 2.2 minutes in group B as well as mean radiation dose of μgy m 2 and standard deviation of μgy m 2 in group A, compared to mean radiation dose of μgy m 2 and standard deviation of μgy m 2 in group B Conclusions: Robotic catheter navigation ablation of atrial fibrillation significantly reduced total radiation exposure time and dose in comparison to manual ablation P3325 Effect of angiotensin-receptor- blockers on dynamics of left atrial size after pulmonary vein isolation in patients with atrial fibrillation and hypertension A. Berkowitsch, T. Neumann, M. Kuniss, S. Zaltsberg, S. Janin, M. Wojcik, C. Hamm, H.F. Pitschner. Kerckhoff Klinik GmbH, Bad Nauheim, Germany Effect of angiotensin receptor- blockers (ARB) on maintenance of sinus rhythm and dynamics of left atrial size (LAS) after pulmonary vein isolation (PVI) has not been fully investigated. It is supposed that the local angiotensin system in the heart plays an important role in protection against remodeling and may also promote reverse remodeling. Aim of this study was to analyze the dynamics of LAS one year after pulmonary vein isolation in patients with paroxysmal (PAF) and persistent (PersAF), and hypertension. A total of 117 consecutive patients (72 men, age 59 y, PAF= 73, CAD =17) were enrolled in the study. The antral PVI was performed by either radiofrequency (80 pts) or cryoballoon (37 pts). Left atrial short (parasternal measurement; SA) and long (apical measurement; LA) axis were assessed in the apical four-chamber projection at baseline and one year after PVI. LAS was calculated as SA x LA and expressed in cm 2.TheAF recurrence was defined as documented AF > 30 sec. First 3 months after PVI were considered as blanking period. The antihypertensive drugs were administered as follows: β-blockers (n=91), diuretics (n=33), Ca-antagonists (n=20), ACE (n=45) and ARB (n=42). The continuous data were analysed with Wilcoxon- Test and given as median and IQR. During follow up of 1 year 18 pts (25%) with PAF and 19 pts (40%) with PersAF had at least one recurrence. The LAS measured in patients with PAF was 19.8 ( ) and 19.2 ( ) cm 2, at baseline and one year after PVI, respectively (p<0.0.04). In pts with PersAF LAS was 22.8 ( ) cm 2 at baseline and 21.7 ( ) cm 2 one year after PVI (p>.3). The subgroup analysis provided follows results: PAF: (ARB (n=20): 18.6 ( ) vs ( ) cm 2 (p<0.05); NoARB: 19.9 ( ) vs ( ) cm 2 (p<0.02)); PersAF: (ARB (n=22): 23.0 ( ) vs ( ) cm 2 (p<0.001); NoARB: 21.5 ( ) vs ( ) cm 2 (p>.4)). ARBs were also found to be associated with maintenance of sinus rhythm in both groups: (PAF: 18 (90%) vs. 37 (70%); (p<0.001); PersAF: 14 (70%) vs. 11 (50%); (p<0.01)). Our results suggest that ARBs support maintenance of sinus rhythm and promotes reverse remodelling in patients with enlarged left atrium and persistent AF. Figure 1. Prevalence of AF by age group Conclusions: AF is more frequent in men and with aging, and its prevalence is increasing independent of aging as indicated by an increasing incidence and a decreasing disappearance rate. Drinking, hypertension, diabetes mellitus, HbA1c and BMI are related to AF, however, smoking and dyslipidemia are not. P3324 Impact of use of robotic catheter navigation on fluoroscopy exposure during atrial fibrillation ablation procedures A. Kamal, R. Cihak, P. Peichl, D. Wichterle, J. Kautzner. Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic Introduction: Catheter ablation of AF frequently requires a long fluoroscopy time and this may indeed begin to produce a measurable risk increase. Despite the use of very low frame rate pulsed fluoroscopy and use of 3D Electroanatomic mapping systems, further efforts can be made to minimize radiation exposure. Because of better catheter stability and easier navigation, total radiation exposure should be reduced with the use of robotic catheter navigation combined in a 3D visualization module. Methods: Forty patients with symptomatic, drug resistant paroxysmal AF who underwent AF ablation. The patients underwent the procedure under standardized protocol of preprocedural cardiac CT, double transseptal puncture under intracardiac echocardiography guidance and 3D LA electroanatomic map using the EnSite NavX system (St. Jude Medical, Minneapolis, MN). All pulmonary veins were targeted for ablation using PV antral isolation technique with no additional lines. All cases were designed for a uniform radiofrequency energy, ablation parameters and a 3.5 mm irrigated tip ablation catheter. Patients were divided into 2 groups, Group A: 20 patients who underwent manual ablation and Group B: 20 patients who underwent remote robotic catheter navigation ablation using ablation catheter mounted on the Artisan sheath of Sensei Robotic System CoHesion 3D visualization module (Hansen Medical, Inc.) Results: Comparison between data of the conventional manual group and the robotic navigation group resulted P3326 Predictive value of atrial electromechanical coupling time for paroxysmal atrial fibrillation H. Karapinar 1,Z.Kaya 2,S.Pala 2, Y. Karavelioglu 2,T.Dasli 2, D. Sirma 2,O.B.Esen 3, M. Akcakoyun 2,A.M.Esen 2,C.Kirma 2. 1 Van High Speciality Education and Research Hospital, Van, Turkey; 2 Kartal Kosuyolu Heart Education and Research Hospital, Istanbul, Turkey; 3 Istanbul Memorial Hospital, Istanbul, Turkey Background: Atrial fibrillation (AF) is the most common arrhythmia and may cause morbidities such as thromboemboli, cardiomyopathy and medication related complications. Thus prediction of AF is very important and helpful for the clinician. We sought the importance of total atrial electromechanical coupling time (EMCT) and interatrial and intraatrial EMCT difference (interatrial and intraatrial asynchrony) as a predictor of paroxysmal AF (PAF). Methods: Thirty-eight patients with PAF diagnosed by 24 hour Holter ECG monitoring (18 male, mean age 56±13 years) constituted the study group. The control group was composed of 54 age and sex matched control whose 24 hour Holter ECG monitoring was free from PAF. A full echocardiographic study including conventional and annular pulse wave tissue Doppler (TDI) assessment was performed under ECG monitoring. Late diastolic wave (A ) velocities from right atrial lateral (RA), interatrial (IAS), and left atrial lateral (LA) wall below the atrioventricular plan were acquired by TDI. The time difference from the onset of the P wave to the onset of the A wave at right atrium (PRA), IAS (PIAS), and left atrium (PLA) were measured. Maximal EMCT is defined as the time from the beginning of P wave to the beginning of the A wave obtained from LA (P-LA). The right atrial EMCT is defined as [PRA]-[PIAS], and left atrial EMCT is defined as [PLA]-[PIAS]. Finally, interatrial difference of EMCT is defined as [PLA]-[PRA]. Asynchrony was defined as the differences between P-IAS and P-RA (RA asynchrony), P-LA and P-IAS (LA asynchrony), and P-LA and P-RA (interatrial asynchrony). Results: In patients with PAF, right atrial EMCT and maximum EMCT, RA A wave velocity and the frequency of hypertension differed significantly from the control group. (16±13.1 ms vs. -8.7±18.6 ms p<0.001; 91.5±32.6 ms vs. 72±23.1 ms p=0,001; 14.3±3.8 cm/s vs. 12.5±3.4 cm/s p=0.022; 68% vs. 26% p<0.001 re-

262 562 Supraventricular arrhythmias: from mechanisms to treatment spectively). There was no difference between the left atrial EMCT, and IAS and LA A wave velocities, and LA diameter. Logistic regression analysis revealed only RA EMCT and maximum EMCT as significant variables (p<0.001 and p=0.025 respectively). We defined a cutoff point for the right atrial EMCT and chose -4 msn for categorization, which yielded 100% sensitivity and 64.3% specificity for the prediction of PAF (AUC:0.865 p<0.001). Conclusion: Maximum EMCT, and especially right atrial EMCT obtained by transthoracic tissue Doppler echocardiography could be a valuable method for identifying patients with risk of developing PAF. P3327 Risk factors for atrial fibrillation in elderly subjects without cardiovascular disease D. Zachariah 1,P.R.Kalra 1, P.R. Roberts 2,R.N.Foley 3. 1 Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom; 2 Southampton University Hospitals NHS Trust, Southampton, United Kingdom; 3 University of Minnesota, Minneapolis, United States of America Purpose: Atrial fibrillation (AF) is a common arrhythmia with increased prevalence at older ages. Inclusion of subjects with overt cardiovascular (CV) disease may be a confounding factor when evaluating epidemiological cohorts.moreover clinical variables associated with developing AF in older age groups have not yet been fully defined. We sought to identify these risk factors in a cohort of elderly subjects free of CVdisease at study inception. Method: We evaluated data from the Cardiovascular Health Study (CHS), a US population-based prospective cohort study of risk factors for coronary heart disease (CHD) and stroke/transient ischaemic attack (TIA) in adults 65 years. Subjects underwent extensive baseline evaluation to identify CV risk factors and clinically overt disease. Parameters assessed included blood pressure, heart rate, echocardiographic variables, lipid, creatinine and C-reactive protein (CRP)levels. Annual examinations and interim telephone contacts were used to collect data regarding medication, hospitalisation and CV events. 32%(1847) of the total study population (n=5795) found to have CV disease (AF, CHD or stroke) at baseline were excluded from data analysis. Baseline parameters associated with development of AF were identified and their independence tested in a multivariable model. Results: 4041 individuals (38.2% females) with mean age 72.9±5.4 years without baseline CV disease were followed up for 10.3 years. 16.7% of this population developed AF. This was independently associated with age,blood pressure, CRP level, smoking, diabetes and left ventricular mass - Table 1. Having excluded CV disease at the outset, incident AF was not related to exercise intensity, lipid levels or renal function. Risk factors for development of AF Variable (interval) Adjusted Hazard Ratio 95% CI p value Age (5.4 years) <0.001 Systolic blood pressure (21mm Hg) <0.001 Diastolic blood pressure (12 mm Hg) C-reactive protein (5.6mg/L) Pulse rate (12 bpm) Creatinine (0.29mg/dL) Conclusions: The development of AF is associated with older age, evidence of reduced arterial compliance (elevated systolic and lower diastolic blood pressure) and low grade inflammation. P3328 Effect of obesity on P wave duration and dispersion in a Chinese population T. Liu 1,Z.Fu 1, P. Korantzopoulos 2, X. Zhang 1, S. Wang 1,G.Li 1. 1 Second Hospital of Tianjin Medical University, Tianjin, China, People s Republic of; 2 University of Ioannina Medical School, Ioannina, Greece Objective: To study the effect of obesity on P wave duration and P wave dispersion (Pd) in order to evaluate the potential association between obesity and atrial fibrillation (AF) in Chinese subjects using the definitions applied for Asian populations. Methods: The study population consisted of 40 obese (BMI 25kg/m 2, according to the World Health Organization classification for the Asian population) and 20 age, sex-matched normal weight control subjects. Maximum P-wave duration (Pmax), minimum P wave duration (Pmin) and Pd were calculated on the 12-lead ECG. Baseline clinical and echocardiographic characteristics were also recorded. Results: There were no significant differences between the two groups on age (54±10 vs 50±9 yrs), sex (Male 80% vs 75%), history of hypertension or diabetes, and hyperlipidemia. Compared with controls, BMI (29.4±3.0 vs 21.5±2.0 kg/m 2,P<0.01) and left atrial diameter (37.6±7.3 vs 29.6±4.8mm, P<0.01) were increased, while Pmax (111.9±9.3 vs 101.1±6.0ms, P<0.01) and Pd (47.9±9.3 vs 31.8±6.9ms, P<0.01) were significantly prolonged in the obese group. Pmin was similar between the 2 groups (64.5±12.8 vs 69.3±5.6ms, P>0.05). Pearson s correlation analysis showed that there were positive correlations between Pd and BMI (r = 0.6, P < 0.001), Pd and left atrial diameter (r = 0.366, P < 0.05). Conclusion: Our data suggest that obesity is associated with increased Pmax and Pd, parameters that have been shown to predict the development of AF. The correlation of these ECG parameters with the LA diameter indicates the association of increased BMI with atrial remodeling in Asian subjects. P3329 Echocardiographic predictors of the transformation of primary paroxysmal atrial fibrillation into permanent form L.G. Tunyan, S.V. Grigoryan. Institute of Cardiology, Yerevan, Armenia The objective of this study was to assess the importance of echocardiographic examination in predicting of the maintenance of sinus rhythm in patients with primary diagnosis of paroxysmal (P) atrial fibrillation (AF) and to prove the hypothesis that patients who subsequently developed constant type of AF had pre-existent structural remodeling. Material and methods: This study included a sample of 80 patients (aged 42±21 years, 49 men) with primary diagnosis of PAF <48 h of onset and without structural heart disease. The patients passed transesophageal and transthoracic echocardiography on the 1-th day, on the 3-th day and on the 14-th day after restoration of the sinus rhythm. All patients were under our observation during 12 months. Results: During the study period PAF transformed into permanent AF in 15 patients (18.75%, Group A). On the other hand, 65 patients (81.25%, Group B) had sinus rhythm continued till the end of the study period. Retrospective analysis of echo examination showed that the patients of both groups had problems related to the functioning of left atrium (LA): in both groups, after restoration of the sinus rhythm, the phenomenon of stunning of LA was observed. However, while on the 3-th day a normalization of functioning of LA was observed for the patients of the B group (transmitral A wave on 1-th day 30±5.3 cm/sec, 14-th day 57±4.3cm/sec, p <0.005), among the patients of the A group a functional impairment of the LA remained until the 14th day (transmitral A wave on 1-th day was 30±4.3 cm/sec, 14-th day was 35±6.5cm/sec, p >0.5). Compared to group B, the patients in group A on the 1-th, 3-th and 14-th days had larger LA diameter (43.2±2.1 mm vs 39.3±1.6 mm, p <0.05), larger LA appendage (LAA) minimum (4.2±1.6 cm 2 vs 1.5±1.4 cm 2,p<0,005) and maximum (5.6±1.7 cm 2 vs 3.5±1.2 cm 2,p<005) areas, and decreased LAA flow velocity (42±13 cm/s vs 61±17 cm/s, p<0.05). On the 14-th day compared to group B in group A had a lower peak systolic (PS) and atrial reverse (AR) pulmonary venous flow (PVF) pattern (the PS PVF was 76.4±12.6 cm/s vs 62.6±10.5 cm/s, p<0.005 and AR PVF was 24.4±6.5 cm/s vs 32.6±5.2cm/s, p<0.005). Conclusion: The findings of the study show that stunning (delayed mechanical recovery) of the LA and the LAA function after AF paroxysm caused by mechanical remodeling and leads to formation of permanent type of AF. We conclude that larger sizes of LA, LAA and the reduction of PS PVF and AR PVF promote and contribute to this transformation and may be predictors of transformation of PAF into permanent form. P3330 Short-term kinetics of NT-proBNP in recent-onset atrial fibrillation S. Deftereos 1, G. Giannopoulos 1, A. Theodorakis 2,C.Toli 3, C. Kossyvakis 1,M.Driva 1, A. Kaoukis 1, I. Rentoukas 4, I. Mantas 3, E. Matsakas 1. 1 General Hospital of Athens G. Gennimatas, Athens, Greece; 2 General Hospital of Mesologgi, Mesologgi, Greece; 3 Halkida General Hospital, Halkida, Greece; 4 A. Fleming General Hospital, Athens, Greece Purpose: High levels of N-terminal pro-b-natriuretic peptide (NT-proBNP) have been identified in patients with atrial fibrillation (AFib), irrespective of the presence of heart failure. However, the short-term kinetics of NT-proBNP during the first hours after AFib onset have not been investigated. Methods: Blood samples were drawn, at presentation and at regular intervals during the first 48 hours after presentation, from patients with new-onset AFib (<6 hours before presentation). NT-proBNP was measured using a commercially available assay. NT-proBNP serum levels were plotted against time from AFib onset to determine its variation over the first 48 hours. Only patients who did not revert to sinus rhythm, despite standard pharmacologic conversion treatment, were included. Patients with heart failure or unable to pinpoint the time of arrhythmia onset were excluded. Results: 26 patients (12 male, 66.5±7.8 years) were included. Mean serum NT- Figure 1

263 Supraventricular arrhythmias: from mechanisms to treatment 563 probnp on presentation was 1649,8±1237,4 pg/ml (range 213,0-3628,0 pg/ml). All patients demonstrated a similar pattern of NT-proBNP variation over the first 48 hours after AFib onset (F value=4.99; p=0.0003), with an initial increase and a subsequent decrease (despite persistence of AFib) (see Figure). Peak levels were observed at hours after AFib onset, with a gradual decrease towards initial levels. Mean peak levels were 1873,7±1056,7 pg/ml and the mean NTproBNP level at 48 hours was 1099,3±877,3 pg/ml. Conclusion: NT-proBNP serum levels demonstrate a pattern of increase, peak and decrease during the first 48 hours after AFib onset. This observation, should it be confirmed in larger series of patients, apart from its purely theoretical value, might be used to confirm the recency of AFib onset on the basis of NTproBNP levels, in the clinical setting. P3331 Bleeding risk during oral anticoagulation in atrial fibrillation patients older than 80 years D. Poli 1, E. Antonucci 2, E. Grifoni 2, R. Marcucci 2, L. Mannini 1, R. Abbate 2, G.F. Gensini 2,D.Prisco 2. 1 Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliera Universitaria Careggi, Florence, Italy; 2 Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy Purpose and Methods: Stroke prevention in atrial fibrillation (AF) patients is an increasingly crucial public health target, particularly in patients aged 80 years and an appropriate assessment of risk-benefit ratio of oral anticoagulant treatment (OAT) is needed. We conducted a prospective observational study on 783 OAT AF patients to evaluate: the rate of bleeding in relation to age (<80 and 80 years), the quality of anticoagulation and factors associated with bleeding events. Results: The observational period was 1738 patient/years (pt/yrs) for patients <80 years and 829 pt/yrs for patients 80. During follow-up 94 patients had bleeding complications (rate 3.7x100 pt/yr), 37 major (rate 1.4x100 pt/yr) and 57 minor (rate 2.2x100 pt/yr). Different rates of major haemorrhage were observed between patients younger and older than 80 years (0.9 vs 1.9x100 pt/yr; p=0.004). Bleeding risk was higher also in patients with history of previous cerebral ischemic events (OR 2.5; 95% CI ; p=0.007). A multivariate analysis adjusted for age, history of previous ischemic event; and CHADS2 score confirmed age 80 years and history of previous ischemic events to be independently associated with bleeding risk (ORs 2.7 and 2.1 respectively). Regarding OAT quality, no difference was found between patients with bleeding complications and those without, both in patients younger and older than 80 years. Conclusion: These results indicate that the rate of major bleeding complication is higher in elderly, however it may be kept acceptably low provided a careful management of anticoagulation is obtained. P3332 Is it always possible to follow the guidelines for the treatment of atrial fibrillation? Different realities between Switzerland and Cameroon M. Zimmermann 1,M.N tep 2, A. Meiltz 1,L.Conti 1,N.Tran 1, S. Kingue 2 on behalf of Groupe des Cardiologues du Canton de Genève. 1 Hôpital de la Tour, Meyrin - Geneva, Switzerland; 2 Hôpital Central, Yaoundé, Cameroon Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and guidelines concerning treatment of AF have been recently published by experts from the ACC/AHA/ESC. However, only few studies have been devoted to application of these guidelines into clinical practice and no data are available concerning treatment of AF in Africa. The aim of this study was to evaluate AF treatment and guidelines application in Switzerland on one side and in Cameroon on the other side, with special attention paid to anticoagulant therapy. Methods: This prospective study was conducted by 23 cardiologists in Geneva (GVA) and by 10 cardiologists in Cameroon (CAM) between and Patients were included if they had > 18 years and if AF was documented by an ECG during the consultation. Data on clinical profile, mode of presentation and therapeutic strategy were collected and analyzed. Results: 622 pts (390 male, 232 female; mean age 69.8±12 yrs) were included in GVA and 172 pts (75 male, 97 female; mean age 65.8±13 yrs, p=0.003) were included in CAM. AF was permanent in 46% of cases in GVA and in 55.8% in CAM (p=0.02). Structural heart disease was present in 82.5% of cases in GVA (513/622) and in 90.7% of cases in CAM (156/172)(p=0.009), and CHADS2 score was1.44ingvavs1.93incam(p<0.0001). Rhythm control was the option in 47.1% of cases in GVA (293/622) and in only 16.3% of cases in CAM (28/172) (p<0.0001). The most common drugs used were betablockers in GVA (327/622 vs 20/172, p<0.0001) whereas digoxin (159/622 vs 108/172, p<0.0001) or amiodarone (128/622 vs 49/172, p=0.03) were preferred in CAM. Oral anticoagulant treatment (OAT) was prescribed in 80.2% of cases in GVA (499/622) and in 32.6% of cases in CAM (56/172) (p<0.0001); aspirin was prescribed in 31.5% of cases in GVA (196/622) vs in 61.6% of the cases in CAM (106/172) (p<0.0001). OAT was prescribed in 82% of pts >75 years in GVA (196/239) and in only 20% of pts > 75 years in CAM (10/50)(p<0.0001). According to the CHADS2 score, 88% (403/458) of pts eligible for an OAT in GVA and 33.5% (53/158) of pts eligible for an OAT in CAM received such a treatment (p<0.0001); among pts without risk factors (CHADS2 score = 0), 58.5% of cases in GVA (96/164) received OAT vs 21.4% of cases in CAM (3/14) (p=0.007). Conclusion: Rate of OAT prescription for AF is very high in GVA even in the elderly but an excess of OAT prescription is observed for low-risk patients. In CAM, despite the fact that the thromboembolic risk of AF is higher, OAT is prescribed in only on third of the cases, essentially because of economical and social reasons. P3333 Impact of atrial fibrillation on inflammatory and fibrinolytic variables in the elderly A. Tveit 1, S.R. Ulimoen 1, S. Enger 1, H. Arnesen 2, I. Seljeflot 2. 1 Asker & Baerum Hospital Trust, Rud, Norway; 2 University of Oslo, Oslo, Norway Purpose: Atrial fibrillation (AF) is associated with inflammation and a prothrombotic state, however it is still unclear whether this is independent of ageing and comorbidity. The objective of this study was to investigate the impact of AF on circulating levels of inflammatory and fibrinolytic markers in a 75-year-old general population. Methods: All 75-year-old citizens in Asker and Baerum counties in Norway were invited to participate in a prevalence study of AF. Blood samples were collected at rest from 63 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. C-reactive protein (CRP), tumour necrosis factor alpha (TNFa), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), P-selectin, CD40 Ligand, tissue plasminogen activator antigen (tpa ag) and plasminogen activator inhibitor-1 (PAI-1) activity were analysed using commercially available assays. Results: Subjects with AF had higher levels of IL-6 (median 3.07 pg/ml (interquartile range 2.11, 4.36) vs (1.70, 3.26); p=0.002) and PAI-1 activity (12.9 U/mL (6.6, 17.1) vs. 9.0 (4.6, 14.0); p=0.005). No difference was found for the other markers. The presence of AF was still significantly associated with higher levels of IL-6 and PAI-1 activity after adjusting for body mass index and the presence of heart failure, coronary heart disease and hypertension (p=0.028 and p=0.007, respectively). Conclusion: AF was independently associated with higher levels of IL-6 and PAI- 1 activity. Thus, there is evidence of a proinflammatory state and reduced fibrinolysis also in this stable, out-of-hospital group of 75-year-old AF patients. P3334 Preoperative atrial mechanical dysfunction may predict postoperative atrial fibrillation after coronary artery bypass graft operation: a tissue Doppler and velocity vector imaging study Y. Tayyareci 1, O. Yildirimturk 1, A. Tugcu 1,V.Aytekin 2, F. Behramoglu 2,K.Memic 2, I.C.C. Demiroglu 1,S.Aytekin 2. 1 Florence Nightingale Hospital, Istanbul, Turkey; 2 TC.Istanbul Bilim University, Istanbul, Turkey Objectives: In this study, we aimed to determine the hypothesis that patients who subsequently developed postoperative atrial fibrillation (POAF) had pre-existent, subclinical mechanical atrial dysfunction by using novel echocardiographic techniques, tissue Doppler imaging (TDI) and velocity vector imaging (VVI). Methods: Ninety-six consequative patients with sinus rhythm, undergoing isolated CABG were prospectively enrolled. Preoperative left atrial (LA) reservoir and conduit functions were measured by conventional echocardiography. Peak velocity of LA contraction (VA) was measured by TDI. LA systolic peak strain, strain rate (SRs), late diastolic strain rate (SRd) were measured from lateral, septum, anterior, posterior and superior segments. Results: POAF occured 25 of 96 patients (26%) in this study. Patients with POAF were older (p=0.04), had larger LA volume index (p=0.0001), lower atrial index (p=0.02), higher mitral valve VTI (0.003) and increased E/E ratio (p= 0.001). TDIderived peak VA was found to be similar in two groups. However, in VVI analysis, a significant LA systolic and diastolic deformation were observered in patients with POAF (p=0,0001) (Table 1). The optimal cutoff point for LA strain was 44.0% (88.7% sensitivity, 96% specificity), SRs was 1.7 s -1 (88% sensitivity, 86.2% specificity) and SRd was 1.95 s -1 (sensitivity 72%, 70.4% specificity) predicted POAF. In addition, in multivariate logistic regression analysis, age, LA volume index, LA peak systolic strain, SRs and SRd were significantly independent predictors of POAF. Table 1. Preoperative LA deformation properties of the study patients POAF (+), n=25 POAF ( ), n=71 p TDI-LA VA (m/sec) 0.12± ± VVI-LA strain % 39.9± ± VVI-LA SRs (1/s) 1.5± ± VVI-LA SRd (1/s) 1.87± ± Conclusions: VVI-derived strain imaging is a novel echocardiographic technique which may be used as a sensitive, accurate and non-invasive method for evaluating subclinical atrial mechanical dysfunction in patients undergoing CABG. This may help us to identify patients with high risk of POAF and take acuse for averting occurence of AF after CABG.

264 564 Supraventricular arrhythmias: from mechanisms to treatment P3335 Noninvasive mechanoanatomical mapping to detect atrial fibrillation substrates M. Amnueypol, O. See, T. Ngarmukos, S. Apiyasawat, P. Chandanamattha, S. Yamwong, T. Tangcharoen, C. Charoenpanichkit. Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Purpose: Complex Fractionated atrial electrogram (CFAE) were used in AF ablation. The combination of Tissue Doppler Imaging (TDI) and three dimension (3D) echocardiography can create virtual 3D mechano anatomical mapping (as figure). This could be novel non invasive tool to identify CFAE. This study aim to validate relationship between complex fractionated atrial mechanogram (CFAM) identified by mechano anatomical mapping created and CFAE by electro anatomical mapping. Methods: Adult paroxysmal or persistent AF patients were enrolled for catheter ablation while they were in spontaneous AF at our institution. TDI and 3D tranthoracic echocardiography were performed before ablation. The maps were separately analyzed by electrophysiologists and echocardiographers and blinded from each other finding. The CFAE and CFAM maps were spatial compared for agreement. Results: Five AF patients were enrolled from January to December Mean age 48±10.67 years and AF duration 6 (3 13) years. Total 45 sites from LA and RA were analyzed. Our study showed significant high agreement between both CFAE and CFAM maps, with Kappa (p value <0.001); sensitivity 94%; specificity 92%; PPV 97%, NPV 86%, positive LR and negative LR P3337 Efficacy of the circumferential pulmonary vein ablation of atrial fibrillation in endurance athletes N. Calvo 1,L.Mont 2, D. Tamborero 2, A. Berruezo 2, D. Andreu 2, B. Vidal 3,M.Sitges 3,G.Viola 2,E.Guasch 2, J. Brugada 2. 1 Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Arrythmia Section, Barcelona, Spain; 2 Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Arrhythmia Section, Barcelona, Spain; 3 Hospital Clinic, University of Barcelona - Thorax Institute; Cardiology Dep. - Echocardiographic Lab, Barcelona, Spain Introduction: Endurance sport practice has been increasingly recognized as a risk factor for lone atrial fibrillation (AF). However, data on the outcome of circumferential pulmonary vein ablation (CPVA) in this population are scarce. The aim of the study was to evaluate the efficacy of CPVA in AF secondary to endurance sport practice. Methods: Patients submitted to CPVA due to drug-refractory symptomatic AF answered a questionnaire about lifetime history of endurance sport practice. Endurance athletes were defined as those engaged in >3 hours per week of maximal effort physical activity for at least 10 years when AF was diagnosed. Results: A series of 182 consecutive patients was included (51±11 years, 65% with paroxysmal AF, 81% men, 42±6 mm mean left atrial diameter); 107 (59%) patients had lone AF and 42 of them (23% of the study population) were classified as athletes (>3 hours/week for >10 years of endurance sport practice). Mean duration of the ablation procedure was 122.3±33.1, with 26.0±9.3 minutes of fluoroscopy and 35.07±14.08 minutes of radiofrequency delivery. Freedom from arrhythmia after a first CPVA was similar in the lone AF sport group as compared to the remaining patients (p=0.446) (Figure). Left atrial size and long-standing AF were the only independent predictors for arrhythmia recurrence after ablation. Mechano-Anatomical mapping Conclusions: Complex fractionated electrograms (CFAEs) in patients with spontaneous atrial fibrillation can be identified with precision non-invasively, using combination of TDI and 3D echocardiography. P3336 Impact of catheter ablation of atrial fibrillation on quality of life: preliminary results from the EVABLAF study G. Moubarak 1,P.Jais 2, P. Mabo 3,E.Aliot 4, J.S. Hermida 5, D. Lacroix 6, E. Vicaut 7, F. Extramiana 1, A. Leenhardt 1. 1 Lariboisiere Hospital (AP-HP), Paris, France; 2 Hopital Haut Leveque - Groupe Hospitalier Sud, Pessac, France; 3 CHU de Rennes - Hopital de Pontchaillou, Rennes, France; 4 CHU de Nancy - Hopital de Brabois, Vandoeuvre les Nancy, France; 5 Hopital Sud - Centre Hospitalier Universitaire Amiens, Amiens, France; 6 Hopital Cardiologique CHRU de Lille, Lille, France; 7 AP-HP- Hopital Fernand Widal, Paris, France Purpose: Atrial fibrillation (AF) may cause disabling symptoms which alter patients quality of life (QoL). There are few data regarding the impact of catheter ablation AF on QoL. Methods: EVABLAF is a French prospective multicenter study evaluating catheter ablation in patients presenting with symptomatic paroxysmal or persistent AF refractory to at least one class 1 or 3 antiarrhythmic drug. Symptoms were evaluated by a score taking into account their frequency and severity (varying from 14 to 210, with higher scores indicating more severe symptoms). QoL was rated using the SF-36 questionnaire (higher scores indicating a better QoL). Results: We report data on the first 372 patients recruited in 16 centers, with a mean follow-up of 326±113 days. There were 285 (77%) men with a mean age of 55±11 years. Symptoms improved significantly by the end of the first year (score decreasing from 48.5±17.1 to 33.7±17.8, p< ), both in patients remaining free from AF relapse (p<0.0001) and in patients experiencing AF relapse (p<0.0001). This improvement was of a greater magnitude in the absence of AF recurrence (improvement of 17.5±19.7 points vs 11.7±19.8 points in case of AF recurrence; p=0.03). QoL improved from baseline to follow-up (from 69.7±8.8 to 73.0±8.9; p< ). This trend was observed for all SF-36 questionnaire items (p<0.05). Both patients without AF recurrence (p<0.0001) and with AF recurrence (p=0.02) had their QoL improved, but to a lesser extent in case of arrhythmia relapse (improvement of 2.5±10.3 vs 4.6±7.6; p=0.049). Conclusions: In EVABLAF study, preliminary results indicate that catheter ablation of AF decreases symptom severity and improves quality of life at 1 year, even in case of AF relapse. Conclusions: CPVA was as effective in AF secondary to endurance sport practice as in other etiologies of AF. P3338 Polyunsaturated fatty acids, inflammatory markers and the incidence of postoperative atrial fibrillation R. Heidarsdottir 1,D.O.Arnar 2, O.S. Indridason 2,B.Torfason 2, R. Palsson 2, V. Edvardsson 2, G. Gottskalksson 2, G.V. Skuladottir 1. 1 University of Iceland, Reykjavik, Iceland; 2 Landspitali University Hospital, Reykjavik, Iceland Introduction: Inflammatory response is believed to play a role in the pathophysiology of postoperative atrial fibrillation (POAF). Reports indicate that the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), have anti-inflammatory effects. The purpose of this study was to investigate the relationship between the incidence of POAF and the concentration of n-3 PUFA and C reactive protein (CRP). Methods: A total of 144 patients undergoing open-heart surgery have been enrolled in this ongoing study and full data are currently available for 108 patients. Immediately prior to surgery, plasma phospholipid (PL) fatty acids were analyzed using gas chromatography and CRP levels were measured postoperatively by ELISA. POAF of more than 5 minutes duration documented by continuous electrocardiographic monitoring was defined as the endpoint. Results: The median age was 67 years (range 45-82) and 88 were males. POAF occurred in 55.6% of the patients (males 81.6%). Their median age was higher compared to those without POAF, 69.5 (45-82) vs. 65 (45-79) years (P = 0.003). The patients with POAF had higher median plasma PL concentrations of EPA, 34 (9-104) vs. 26 (9-70) μg/ml (P = 0.03), DHA, 70 (33-129) vs. 56 (33-93) μg/ml (P = 0.001), and total n-3 PUFA 116 (47-256) vs. 96 (47-294) μg/ml (P=0.008) than those without POAF. No difference in peak postoperative levels of CRP, 213 (81-386) vs. 201 (55-370) mg/l (P=0.08) was observed in patients with and without POAF. Multivariate logistic regression revealed that POAF was significantly associated with age, OR 1.07 (95% CI ), and peak levels of CRP, OR ( ) but neither with n-3 PUFA concentration nor other variables, including type of operation, body mass index and gender. Conclusion: These preliminary results suggest that POAF is associated with advancing age and inflammatory markers, but no beneficial effect of n-3 PUFA was

265 Supraventricular arrhythmias: from mechanisms to treatment 565 noted. Indeed, PUFA concentration was higher among those with POAF but due to a significant correlation between age and PUFA concentration the association with POAF was not significant in multivariate models. P3339 Relationship of circulating endothelial progenitor cells to the recurrence of atrial fibrillation after successful conversion and maintenance of sinus rhythm C.W. Siu 1,T.Watson 2, W.H. Lai 1,Y.K.Lee 1, Y.H. Chan 1,K.M.Ng 1, C.P. Lau 1,G.Y.H.Lip 2,H.F.Tse 1. 1 The University of Hong Kong, Hong Kong, Hong Kong SAR, People s Republic of China; 2 City Hospital, Birmingham, Birmingham, United Kingdom Objectives: To determine whetherthe number of circulating endothelial progenitor cells (EPCs) in patients withpersistent atrial fibrillation (AF) predicts arrhythmia recurrence after directcurrent cardioversion (DCCV). Background: Number of circulatingepcs is inversely correlated to the presence and severity of variouscardiovascular diseases; however, the role of EPCs in AF remains unclear. Methods: Numbersof circulating CD34+/KDR+ EPCs were quantified using flowcytometry in 51 patients with persistent AF, who were compared with matched diseasecontrols (with coronary artery disease and stroke) and healthy controls. TheAF recurrence rate at one year was determined. Results: The EPC counts in patients with persistent AF, coronaryartery disease and ischemic stroke were significantly lower than that amongst matchedhealthy controls (437 cells/ml, IQR: cells/ml) (p<0.01).one year after DCCV, patients withhigh EPC count (>/=50th percentile) had a higher AFrecurrence rate than those with low EPC count (<50th percentile)(73% vs. 40%, p=0.02). A Coxregression analysis revealed a high EPCcount was the only independentpredictor for AF recurrence (HR:2.29, 95% CI: , p=0.047). Kaplan-Meier estimate of AF recurrence Conclusion: Thenumber of circulating EPCs is reduced in patients with persistent AF andpredicts AF recurrence after DCCV. P3340 France Radiofrequency ablation of coronary sinus dependent atrial flutters guided by mid-diastolic atrial potentials A. De Sisti 1, J. Tonet 2,W.Amara 2. 1 Cardiology Department, Poissy-St Germaine Hospital, Poissy, France; 2 Rhythmology Department, Cardiology Institute, Pitié-Salpêtrière Hospital, Paris, Introduction: Radiofrequency (RF) ablation of coronary sinus (CS) dependent atrial flutter (AFL) has episodically been described. Methods: Criteria for ablating into CS were the presence of a CS mid-diastolic fractionated atrial potential (AP) associated with entrainment showing a postpacing interval (PPI) within 20 ms. Acute success was defined as termination of AFL and subsequent noninducibility. Patients with previous ablation for atrial fibrillation (AF) in left atrium were excluded. Results: Fourteen consecutive patients (12 M, 70±9 years, 79±15 kg) were included. A cardiac disease was diagnosed in 9. Basical 12 leads surface ECG morphology suggested typical AFL in 10 patients and atypical in 2. Basical AFL cycle length was 281±68 ms. Lateral RA activation was counterclockwise (CCW) in all patients but 1. CS activation was CCW in all. CTI was the first target in 10 patients, while in 4 ablation was directly performed inside the CS with further CTI ablation. After CTI ablation, AFL persisted in 6 patients (with the same cycle length in 2, while in 4 patients AFL cycle length increased 37±15 ms without ECG and intracardiac atrial activation pattern modifications); in other 4 cases, CTI ablation interrupted AFL (bi-directional CTI block was subsequently confirmed), but an AFL was still inducible with the same morphology in 1 and different in 3. At the time of ablation into the CS, AFL ECG morphology was typical in 7 patients and atypical in the other 7. Lateral right atrial activation was CCW in all patients, but 1. CS activation was CCW in all. Overall, mean AFL cycle was 299±69 ms, and APs duration (located 1-4 cm from CS ostium) 119±30 ms spanning 42±14% of the AFL cycle. A cooled catheter was used in 4 patients and a 8- mm-tip RF catheter in 10 (maximal power and temperature 25 W-40 C and 45 W-55 C, respectively). Acute success was achieved in 10 patients (9 with previous CTI ablation and 1 directly ablated into the CS). Time to AFL termination, measured from the beginning of RF delivery to the AFL interruption, was 42±59 sec. At hospital discharge, 8 patients with associated AF were on amiodarone. Over a follow-up of 11±9 months, no patients with successful procedure had AFL recurrence. There were no complications. Conclusions: CS is a critical part of some AFL re-entrant circuits. In some cases, both CTI and CS seem involved in the circuit. These AFLs can be easily terminated in most patients targeting CS mid-diastolic fragmented APs. P3341 Direction-dependent conduction abnormalities: implications for the development of atrial arrhythmias in humans C.X. Wong, M.K. Stiles, B. John, A.G. Brooks, P. Kuklik, D.H. Lau, H. Dimitri, G. Sharma, G.D. Young, P. Sanders. Cardiovascular Research Centre, Royal Adelaide Hospital and the University of Adelaide, Adelaide, Australia Purpose: Direction-dependent conduction abnormalities may predispose to atrial arrhythmias by facilitating reentry arising from ectopy. Whether directiondependent conduction abnormalities exist in abnormal human atria is unknown. Methods: 20 patients (18M 59±10 y) with paroxysmal atrial flutter (AFL) and 20 age matched controls were studied. Conduction time along linear catheters at the coronary sinus (CS) and lateral right atrium (RA), and conduction characteristics at the crista terminalis (CT) were assessed in sinus rhythm (SR) and CS pacing. Electroanatomic maps were created in SR and CS pacing to evaluate direction dependent conduction velocities, voltage and electrograms. Results: AFL patients demonstrated longer distal proximal vs proximal distal conduction times along linear catheters (61±20 vs 45±9ms, p=0.04). AFL patients also exhibited a greater increase in CT double potentials (DP) from SR to pacing compared to controls (4.1±2.6 to5.8±2.8 vs 0.5±0.9 to 0.5±1.3, p=0.04). Electroanatomic mapping revealed abnormal conduction direction in AFL patients caused heterogeneous changes in regional conduction velocities, bipolar voltage and fractionation, and demonstrated widespread lines of conduction block represented by DP which increased in number and length on abnormal conduction direction. These changes were not seen in controls. Direction-dependent conduction in AFL Electroanatomic Mapping Sinus Rhythm Coronary Sinus Pacing p Value Regional Conduction Velocity (mm/ms) 1.17± ±.19 <0.001 Atrial Activation Time (ms) 102±13 127± Regional Bipolar Voltage (mv) 2.1± ±0.3 <0.005 Complex Electrograms (%) and Double Potentials at the Crista Terminalis (n) 16±4, 4.1±2.6 48±10, 5.8±2.8 <0.05 Lines of Conduction Block (n, mm) 1.2±0.4, 42±10 2.2±0.9, 70± Linear Catheters Coronary Sinus Conduction Time (ms) 40±6 53±19 <0.05 Lateral RA Conduction Time (ms) 53±19 73±28 <0.05 Conclusions: Analysis of conduction properties when activity originates from the CS compared to the sinus node revealed significant conduction abnormalities in AFL patients that were not present in controls. This suggests direction-dependent conduction contributes to the promotion of reentrant circuits critical to the genesis and perpetuation of atrial arrhythmias. P3342 Difference in ventriculoatrial intervals during entrainment and tachycardia: a simpler method for distinguishing supraventricular tachycardias with long ventriculoatrial intervals E. Gonzalez Torrecilla 1, J. Almendral 1, F.J. Garcia-Fernandez 2, A. Arenal 1, F. Atienza 1,L.F.Atea 1,D.Calvo 1,C.Hadid 1, M. Pachon 1, F. Fernandez-Aviles 1. 1 Hospital General Universitario Gregorio Maranon, Madrid, Spain; 2 Hospital General Yagüe, Burgos, Spain The usefulness of the difference between stimulus-right atrium (SA) interval after entrainment from right ventricle (RV) minus tachycardia ventriculoatrial (VA) interval in the differential diagnosis of paroxysmal supraventricular tachycardias has not been studied in a large, consecutive series of patients (P) with such tachycardias showing long ( 100 ms) VA intervals. Methods: We included 187 consecutive P (82 females; 39±19 yrs) with inducible sustained supraventricular tachycardias with long VA intervals ( 100 ms in high right atrium) undergoing an electrophysiologic (EP) study. Atrial tachycardias, P with >1 tachycardia mechanism or showing ventricular preexcitation in sinus rhythm were excluded. Tachycardia entrainment was attempted through trains of 5-15 RV apex pacing pulses. The SA (in last entrained atrial electrogram) - VA (in tachycardia) difference was calculated in every P. Results: EP study demonstrated atypical atrioventricular nodal reentrant tachycardia (AVNRT) in 53 P and orthodromic reentrant tachycardia (ORT) in 134 P using a concealed septal (61 P) or free-wall accessory pathway (AP) (73 P). A difference in SA-VA >110 ms identified atypical AVNRT patients with a sensitivity,

266 566 Supraventricular arrhythmias: from mechanisms to treatment / Heart failure: ventricular function Side-effects were noted in two patients (visual disturbances, extrasystolic beats originated from the right ventricular outflow tract). Based on our clinical experiences, IST can be treated with the sinoatrial node modulator drug ivabradine successfully and safely. Ivabradine was better tolerated on long term than beta-blockers. The chronic ivabradine treatment might be considered as an alternative to the invasive transcatheter radiofrequency modification/ablation of the sinoatrial node with the inherent risk of pacemaker implantation. HEART FAILURE: VENTRICULAR FUNCTION specificity, positive and negative predictive values of 100%, 98%, 95% and 100%, respectively. Similarly, these values were 90%, 88%, 84%, and 95%, respectively for SA-VA difference 55 ms in identifying ORT patients through a concealed septal AP (Figure). Conclusion: The difference SA-VA provides a simple, two-catheter based EP manoeuvre that reliably differenciates atypical AVNRT from ORT regardless of AP location. A SA-VA difference 55 ms strongly suggests ORT through a septal bypass. P3343 Cavotricuspid isthmus ablation using the maximum voltage guided technique: acute success and mid-term follow-up results C.L. Foldesi 1, A. Kardos 1, P. Abraham 1, A. Mihalcz 1,Z.Som 1, J. Borbola 1,J.Vanyi 1, T. Szili-Torok 2. 1 National Institute of Cardiology, Budapest, Hungary; 2 Erasmus Mc, Thoraxcentrum, Rotterdam, Netherlands Background: Atrial flutter (AFLU) is one of the most common supraventricular arrhythmias beside atrial fibrillation. Cavotricuspid isthmus (CTI) ablation is the standard therapy for CTI dependent atrial flutter. The endpoint of CTI ablation is to create a bidirectional isthmus block (BIB). The CTI is composed of distinct anatomically defined bundles as functionally different routes of conduction. Based on this observation the maximum voltage guided ablation technique (MVGT) has been developed.this technique, based on mapping of the CTI atrial electrogram amplitude, achieved bidirectional isthmus block (BIB) with considerably fewer RF applications and shorter procedural times and fluoroscopic exposure. Objective: To determine the acute success and the mid term follow-up results using the MVGT for CTI ablation. Methods: 196 patients (age: 61.9±9.6 year, 59% male) who underwent MVGT CTI ablation were enrolled into this prospective, single centre study. The ablation was guided by the highest amplitude bipolar atrial potentials in CTI assessed by sequential mapping. Ablation was performed during proxymal coronary sinus pacing (53%) or during ongoing atrial flutter (47%) using 8mm radiofrequency (164 pts, 84%), 8mm cryoablation (12 pts, 6%) and 3,5mm irrigated tip catheters (20 pts, 10%). The endpoints of the study were the number of ablations (AN) needed for BIB, the fluoroscopy time (FT), procedure time (PT) and the complication rate. During the follow-up of 6,4±3,8 months recurrent AFLU, redo CTI ablation procedures and the presence of atrial fibrillation (AF) were recorded. Results: BIB was achieved in all patients (100%) with 7.4±5.8 AN. PT was 58.4±20.6 min and the FT was 9.3±8.4 min. In one patient (0.5%) a procedurerelated AV block requiring definitive pacemaker implantation was observed. During the follow-up the incidence of recurrent AFLU was 8.4%, redo CTI ablation was performed in 6.2%. Post CTI atrial fibrillation developed in 34% of the patients. Conclusion: The MVGT for CTI ablation is an effective and safe technique for typical AFLU ablation with considerably short procedure and fluoroscopy times. P3344 Successful treatment of inappropriate sinus tachycardia with ivabradine J. Borbola. Gottsegen György Hungarian Institute of Cardiology, Budapest, Hungary Inappropriate sinus-node tachycardia (IST) is a rare disease defined as increased heart rate at rest and/or inadequate response to physical or emotional stress. In the last years 9 patients (7 women, 2 men; age:18-57 (32) years) were treated with IST due to palpitations. Patients had no structural heart disease, TSH values were within normal limits, but resting heart rates were repeatedly high (102±8/min). The results of Holter recordings (expressed as minimal-maximal and average heart rate/min) without any medication showed high heart rate values: 60±2-172±8-100±4/min. Beta blocker treatment decreased the high heart rates significantly: 52±5-138±6-81±6/min (p 0.01), but several side-effects (low blood pressure, faintness) appeared. The If channel inhibitor ivabradine decreased the heart rate significantly and dose-dependently compared to the control values: ivabradine 5 mg b.i.d.: 52±3-138±4-81±4 (p 0.01), ivabradine 7.5 mg b.i.d.:46±2-134±4-74±3 (p 0.01). The ivabradine tretment was well tolerated, there was no sinus bradycardiac episode leading to treatment discontinuation. P3345 Mechanotransduction-related signalling via focal adhesion kinase is preserved in pressure overload hypertrophy but absent in congestive cardiomyopathy L. Delrue 1, M. Vanderheyden 1, M. Goethals 1,F.Casselman 2, S. Verstreken 1, J. Bartunek 1. 1 Cardiovascular Center OLV Hospital, Aalst, Belgium; 2 Dpt of Cardiovascular Surger, OLV Hospital, Aalst, Belgium Background: β1-integrin-fak and melusin pathways mediate mechanotransduction-dependent hypertrophic signalling. Deletion of melusin is associated with heart failure in experimental pressure overload. Aim: To investigate whether β1-integrin, melusin and FAK are altered in human pressure-overload cardiac hypertrophy and failure. Methods: LV biopsies were obtained in 8 patients (pts) with normal LV function (C) undergoing cardiac bypass surgery, in 17 pts with aortic stenosis (AS) undergoing aortic valve replacement and in 15 pts with congestive cardiomyopathy (CCMP) at cardiac catheterization. LV message levels of adult β1 integrin isoform (ITGB1D), FAK and melusin were determined by real time quantitative TaqMan PCR (relative units). Protein levels were determined by Western Blotting including FAK phosphorylation analysis. Results: (Table) LV ejection fraction (EF) was lower in CCMP vs C and AS. LV mass index was increased in both AS and CMP pts. In contrast, relative wall thickness (RWT, 2x posterior wall thickness/lv diastolic diameter) was increased in AS pts vs C and was lower in CCMP pts vs AS pts. ITGB1D and melusin message levels were significantly increased in CCMP pts vs C. In AS pts, overall ITGB1D expression tended to be higher but melusin expression remained unchanged vs C. Transcriptional changes were corroborated by the Western blotting (not shown). Note, though FAK message levels and protein expression were similar in AS and CCMP pts vs C, phosphorylation of FAK at Tyr-397 was detected only in AS pts. C (n=8) AS (n=17) CCMP (n=15) LV EF (%) 71±4 59±6 22±2*+ RWT 0.27± ±0.06* 0.22±0.05+ LV mass (g/m 2 ) 56±7 124±13* 114±9* ITGB1D (rel units) 0.21± ± ±0.03* Melusin (rel units) 0.11± ± ±0.01* FAK (rel units) 0.55± ± ±0.06 +p<0.01 vs AS; *p<0.5 vs C. Conclusion: β1d-integrin and melusin are elevated in CCMP patients. Nevertheless, FAK phosphorylation was preserved only in pressure overload hypertrophy. Absence of FAK phosphorylation despite increased melusin and β1-integrin levels suggests intracellular disruption of the mechanotransduction-dependent hypertrophic signalling in the failing myocardium. P3346 Impaired left ventricular twist and untwist in heart failure and normal ejection fraction is associated with reduced ventricular suction Y.T. Tan 1, F. Wenzelburger 1,E.Lee 2, G. Heatlie 2,K.Patel 1, F. Leyva 1, M. Frenneaux 1, J.E. Sanderson 1. 1 University of Birmingham, Birmingham, United Kingdom; 2 University of North Staffordshire, Stoke-On-Trent, United Kingdom Background: Left ventricular (LV) untwist plays a vital role in the generation of intraventricular pressure gradient which is necessary for the left ventricular suction in early diastole. The ability of the LV to untwist in diastole is dependent on systolic twist. We hypothesise that patients with heart failure and normal ejection fraction (HFNEF) have reduced LV untwist to facilitate rapid early diastolic filling particularly during exercise thus symptoms of breathlessness on exertion. Methods: 34 patients with clinical diagnosis of HFNEF and proven cardiac limitation with metabolic exercise test (72±7years, 23 female, LVEF 60±7%, VO2max 17.9±3.0 ml/min/kg) and 23 age-matched healthy controls (70±8years, 15 female, LVEF 63±8%, VO2max 30.9±4.6 ml/min/kg) were recruited. Rest and submaximal supine exercise echocardiography were performed to comparable heart rate and blood pressure. 2D apical short axis images were used for the analysis of apical rotation and untwist by speckle tracking using custom software (Echopac).The mitral flow propagation velocity (Vp) was derived from colour M- mode Doppler obtained through the mitral valve and measured by the slope along the aliasing isovelocity line. Measurements were compared between patients and controls using unpaired Student s T Test.

267 Heart failure: ventricular function 567 Results: LV apical systolic rotation and early diastolic untwist are significantly less in patients compared to controls both at rest (apical rotation 10.7±4.1 vs 13.9±3.2 p=0.002; early diastolic untwist 24.3±9.4 vs 30.9±9.7, p=0.013) and on exercise (apical rotation 13.5±4.8 vs 17.6±4.0, p=0.006; early diastolic untwist 22.1±8.9 vs 29.5±7.8, p=0.008). Vp at rest is comparable between the two groups (40.2±10.8m/s vs 39.8±7.3m/s, p=0.875). On exercise, the increase in Vp is significantly less in patients hence Vp is significantly lower than controls (52.6±12.0m/s vs 62.4±13.8m/s, p=0.012). LV early untwist correlates significantly with the increase in Vp (r=0.43, p=0.005)and VO2max (r=0.526, p=0.007). Exercise Vp also correlates with VO2max (r=0.347, p=0.03). Conclusion: LV rotation and untwist mechanics are impaired in HFNEF. This is associated with reduced LV suction in early diastole and reduced exercise tolerance. The efficiency of LV rotation and untwist is crucial to aid rapid early diastolic filling particularly on exercise when heart rate is increased and diastole shortens. P3347 The induction of mild hypothermia preserves myocardial contractility after ventricular fibrillation/resuscitation in pigs H. Post 1,M.Schwarzl 1, S. Huber 1, H. Maechler 1, P. Steendijk 2, M. Truschnig-Wilders 1,B.Pieske 1. 1 Medical University of Graz, Graz, Austria; 2 Leiden University Medical Center, Leiden, Netherlands The induction of mild hypothermia (MH) in patients with depressed cardiac function is discussed controversially due to a concomitant reduction of cardiac output (CO). In 10 anaesthetized pigs (51-70 kg), ventricular fibrillation (VF,5 min)was induced electrically. After resuscitation and return of spontaneous circulation (ROSC), pigs were assigned to normothermia (NT, 38 C, n=5) or MH (33 C, n=5, intravascular cooling device). MH was reached after 112±18 min. Data are reported at 6h after ROSC vs control. Heart rate (HR, bpm) was unchanged in NT (85±4 vs87±4) but lower in MH (55±2 vs85±6, p<0.05). LV maximum pressure (mmhg) decreased in both groups (NT: 89±3 vs 109±5; MH: 86±4 vs 104±5, both p<0.05). CO (l/min) decreased in MH (3.4±0.3 vs 5.1±0.4, p<0.05), but not in NT (4.7±0.5 vs 5.3±0.2, p=ns). However, mixed venous oxygen saturation (%) decreased in NT (55±2 vs 65±4, p<0.05) but not in MH (65±1 vs 62±1), due to lowered whole body oxgen consumption (WB-VO2, ml/min) in MH (168±11 vs 282±20, p<0.05), but not in NT (272±25 vs 268±16). LV dp/dtmax (mmhg/sec) was decreased in NT (1122±143 vs 1553±161, p<0.05) but preserved in MH (1525±157 vs 1468±124). From end-systolic pressurevolume relationships (aortic balloon catheter inflation), the end-systolic volume corresponding to an end-systolic pressure of 100 mmhg (LVV-Pes100) was calculated and normalized to control values. LVV-Pes100 increased in NT (138±21%) but not in MH (91±8%, p<0.05 vs NT). At control HR (pacing) in MH, LVV-Pes100 remained unchanged (81±10%), but diastolic filling deteriorated. The induction of MH prevents the decrease of LV contractility after ventricular resuscitation, and a lowered CO is balanced by decreased WB-VO2. These data indicate that the induction of MH represents a positive inotropic intervention. P3348 Increased baseline diastolic volume and filling pressure blunt the response to cardiac resynchronization therapy E. Carluccio, P. Biagioli, G. Alunni, V. Leonelli, F. Ascani, A. Murrone, P. Pantano, G. Ambrosio. Division of Cardiology, University of Perugia, Perugia, Italy Background: Cardiac resynchronization therapy (CRT) is effective in heart failure patients with left ventricular (LV) dysfunction and wide QRS complex. However, it is unclear why many patients fail to respond. We investigated whether baseline factors other than severity of dyssynchrony could predict response to CRT. Methods: We studied 54 patients with heart failure (68±8 yrs, male= 78%) and evidence of both electrical (QRS width>120 ms) and mechanical intraventricular dyssynchrony (IVD). Patients underwent 2-D echo, transmitral Doppler, and Tissue Doppler (TDI) examination at baseline and 6 months after CRT. Diastolic function was assessed by measuring LV filling parameters, E velocity, and E/E ratio. IVD was defined either by TDI, as an electromechanical delay 65 ms measured among 6 LV basal segments, or as left lateral wall post-systolic displacement (LWPSD). Results: Six months after CRT, in the overall population end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) decreased, from 152±42 to 128±44 ml/m 2 and from 115±38 to 88±43 ml/m 2, respectively (P<0.001 for both). Ejection fraction (EF) increased, from 24±6% to 34±11% (P<0.0001). An increase in EF 5% was found in 31 (57%, Resp). NYHA class, prevalence of LWPSD, transmitral filling pattern, severity of mitral regurgitation, and etiology did not differ between Resp and non-resp. However, Resp differed from non- Resp as having at baseline smaller EDVI and ESVI (P<0.05 for both), larger QRS (P<0.05), greater IVD at TDI (P<0.001), higher E velocity (P<0.01), and lower E/E ratio (P<0.05). At multivariate regression analysis, baseline independent predictors of improvement in EF at follow-up were IVD at TDI (beta 0.36, P<0.01), EDVI (beta -0.27, P<0.05), and E/E ratio (beta 0.31, P<0.01). Conclusion: In heart failure patients with intraventricular electrical and mechanical dyssynchrony, increased LV volumes and severe diastolic dysfunction negatively impact on the likelihood to improve function after CRT. P3349 Advanced heart failure due to chronic volume overload in rats is characterized by profound downregulation of myocardial fatty acid metabolism J. Benes 1, P. Skaroupkova 1, L. Kazdova 1, D. Sedmera 2, J. Benes 2, F. Papousek 2, H. Strnad 2, M. Kolar 2, V. Melenovsky 1. 1 IKEM, Prague, Czech Republic; 2 Academy of Sciences, Prague, Czech Republic Purpose: Factors responsible for progression of compensated cardiac hypertrophy to heart failure are inadequately understood, but the alterations of cardiac energetics and metabolism seem be the primary culprit. Volume overload is frequent component of advanced heart failure. The purpose was to establish and characterize a model of decompensated heart failure in chronically volume-overloaded rats. Methods: Volume overload was induced in 300g Wistar male rats by aorto-caval fistula using needle technique (1.2 mm). Echocardiography (GE Vivid 5) was performed at 12th week. At 24th week, invasive hemodynamics (2F Millar, ADInstruments), and confocal immunoflorescence microscopy were performed together with gene expression profiling of ventricular myocardium (RatRef-12 BeadChip, probes, Illumina). Expression data were analyzed using gene set enrichment analysis (KEGG database). Results: At 12th week (compensated stage), AVF rats showed increase (1.7x) in heart mass/bw, biventricular end-diastolic dimensions (both 1.5x), 3x higher cardiac output (326±64 vs 110±16 ml/min) but no signs of heart failure. At 24th week, rats in AVF group showed clinical signs of congestion and electrical instability. AVF animals had 2.4x elevated heart mass/bw (5.1±0.5 vs 2.2±0.5 g/kg) and pulmonary congestion as evidenced by 1.7x increase of lung weight/bw. Invasive LV hemodynamics showed marked elevation of LVEDP (15±5 vs 4±2 mmhg, p<0.001), prolonged relaxation tau and depressed dp/dtmin. Histomorphometry showed that ventricular myocytes in AVF group had with similar cross-sectional area, but 19% increase in the length compared to sham (p=0.01). Ratio ventricular WGA-positive fibrosis to myocyte area was similar between AVF and sham animals gene probes (13.8%) indicated significant difference in expression (adjusted p<0.05). Gene set enrichment analysis showed extensive (FDR < 0.004) downregulation of fatty acid oxidation, oxidative phosphorylation, citrate cycle, proteasome and branched AA degradation pathways. Reduced expression of PGC1α and mitochondrial transcription factor A (Tfam) in AVF suggest impaired mitochondrial biogenesis. In contrary, TGF-β signaling pathway and genes involved in cell adhesion and communication were upregulated. Conclusion: Chronic volume overload in rats for 24 weeks induces eccentric left ventricular hypertrophy without excessive fibrosis, but with features of advanced decompensated heart failure including congestion and dysregulation of myocardial energy-proving pathways. P3350 Myocardial performance index determined by Doppler Tissue Imaging in patients with congestive heart failure identifies patients with poor prognosis M. Alam 1,J.Olson 2, B.A. Samad 1. 1 Danderyd Hospital - Karolinska Institute, Stockholm, Sweden; 2 South Hospital, Karolinska Institute, Stockholm, Sweden Aim: Myocardial performance index (MPI) is an echocardiographic parameter to express left ventricular (LV) function. A high value of MPI might be an expression of decreased LV function. The MPI determined by Doppler tissue imaging (DTI) especially at different sites of the LV and its long-time prognostic implication in congestive heart failure (CHF) is not evaluated. Methods: 112 patients with CHF due to dilated cardiomyopathy (DCM, n=32) or ischemic heart disease (IHD, n=80) were examined during acute hospitalization and followed up to 4 years. The longitudinal myocardial velocities at 4 different LV sites (corresponding to septal, lateral, anterior and inferior walls) near the mitral annulus from apical 4-chamber view were recorded using pulsed-wave Doppler tissue imaging. From myocardial velocity profiles, the MPI at each LV sites was calculated as follows: MPI = [(isovolumic contraction time + ejection time + isovolumic relaxation time) ejection time]/ejection time. The global MPI was also calculated from 4 LV sites.

268 568 Heart failure: ventricular function Results: The mean ejection fraction was 25%. The LV myocardial velocities were almost similar in both DCM and IHD groups (systolic velocity 4.6±0.9 vs. 5.1±1.1 cm/s, and early diastolic velocity 5.7±1.4 vs. 5.8±1.7 cm/s respectively). The DCM patients had a decreased global MPI compared to IHD (0.59±0.15 vs. 0.67±0.17, p<0.05). A total of 37 patients died of cardiac reason. The nonsurvivors had higher age and MPI compared to survivors (MPI 0.76±0.18 vs. 0.59±0.13, P<0.001). Most of the mortality occurred in patients with IHD (DCM 12%, and IHD 41%). Separate analysis of IHD shows similar significant increased MPI in non-survivors (0.74±0.18 vs. 0.61±0.14, P<0.001) but no age difference between non-survivors and survivors. A cutoff MPI value of 0.7 identified patients with cardiac mortality within 4 years with a sensitivity of 73% and a specificity of 84%. Conclusion: Using Doppler tissue imaging, the global MPI in patients with CHF shows a significant higher value in non-survivors compared to survivors. During the 4 years follow up time, MPI determined at the acute stage identified patients with poor prognosis with relatively high sensitivity and good specificity. respectively). LV systolic and diastolic synchrony were significantly impaired in LVH and was more prominent in DCM (systolic dyssynchrony: 70±17* msec in LVH, 94±36* msec in DCM, and 48±12 msec in Control, diastolic dyssynchrony: 55±16* msec in LVH, 79±35* msec in DCM, and 42±13 msec in Control,*p<0.05 vs. Control and p<0.05 vs. LVH, respectively). There were strong correlations between global PSS and PRR (r=0.87, p<0.05) and systolic and diastolic dyssynchrony (r=0.82, p<0.05) in all subjects. P3351 Importance of haemodilution in haemoglobin concentrations in outpatients with chronic heart failure. Results of IMPACT-RECO Program III M. Galinier 1,N.Demil 2, P. Assyag 3, P. De Groote 4,R.Isnard 5, A. Ducardonnet 6, G. Jondeau 7, J.F. Thebaut 8, M. Komajda 5. 1 CHU Rangueil, Fédération des services de Cardiologie, Toulouse, France; 2 AstraZeneca, Rueil Malmaison, France; 3 Hôpital Saint Antoine, Paris, France; 4 Pôle Cardiologie et Maladies Vasculaires, Hôpital Cardiologique, Lille, France; 5 Hopital Pitie-Salpetriere, Paris, France; 6 Institut Coeur Effort Sante, Paris, France; 7 Hôpital Bichat, Service de Cardiologie, Paris, France; 8 Centre Cardiologique Alfred Kastler, Sarcelles, France Background: The prevalence of anaemia in chronic heart failure (CHF) ranges widely from 4 to 70% due to a lack of an established consistent definition of anaemia in CHF. Furthermore haemodilution impacts haemoglobin concentrations and could be an important cause of anaemia in CHF. Aims: The IMPACT-RECO program III analysed the impact of NYHA class of CHF and of comorbidities on therapeutic management of French outpatients with stable CHF and left ventricular systolic dysfunction. Methods: This survey was carried out from March 2007 to December 2007 among randomly selected French private cardiologists patients with CHF and left ventricular ejection fraction (LVEF) < 40% were included. Results: Mean age was 71±11 years, 75% of the patients were men, 34% were in NYHA class III-IV, 54% had coronary artery diseases, 30% had atrial fibrillation and the mean LVEF was 34±7%. Haemoglobin concentration was recorded in 953 patients. Anemia was defined as a haemoglobin concentration < 12 g/l in women and < 13 g/l in men. The impact of NYHA class and congestive status in haemoglobin concentrations are summarized in the table. Haemoglobin (g/l) NYHA I NYHA II without NYHA II with NYHA III NYHA IV congestive signs congestive signs n Men 13.3± ± ± ± ±1.6 Women 12.7± ± ± ± ±2.1 AnaemiaN (%) 33 (30.8) 150 (33.5) 42 (67.7)** 149 (50.5)* 15 (40.5) *p<0.05: NYHA III vs NYHA I, II/**p<0.05: NYHA II with congestive signs vs NYHA I, II without congestive signs III, IV. Conclusions: Congestive status impacts haemoglobin concentrations more than the severity of CHF estimated by NYHA class. Haemodilution is an important aetiology of anaemia in CHF, thus haemoglobin concentration should be evaluated if possible in patients without congestive signs. P3352 Coupling of systolic and diastolic function and regional synchrony in normal, hypertrophic, and failing myocardium quantified by speckle-tracking echocardiography K. Dohi, K. Onishi, T. Takamura, E. Sugiura, H. Nakajima, K. Ichikawa, M. Tanabe, M. Miyahara, M. Nakamura, M. Ito. Mie University Graduate School of Medicine, Tsu, Japan Aim: To quantify left ventricular (LV) function, regional synchrony, and their systolic-diastolic coupling in normal, hypertrophic, and failing myocardium. Methods: 50 normal subjects (Control: EF 65±6%), 50 patients with hypertensive LV hypertrophy (LVH: EF 61±8%), and 50 patients with dilated cardiomyopathy (DCM: EF 31±10%) had echo-study. Global and regional longitudinal LV myocardial peak systolic strain (PSS) and peak relaxation rate (PRR) during early diastole were measured from apical 4-, 2-, and long axis views. LV dyssynchrony during systole and diastole were assessed by calculating standard deviation of the segmental time-to-pss and time-to-prr over longitudinal regions and were normalized by RR interval. Results: Global LV systolic and diastolic functions were significantly impaired in LVH and were more prominent in DCM (PSS: -16±3* % in LVH, -10±3* # % in DCM, and -19±2% in Control, PRR: 0.8±0.3* 1/s in LVH, 0.5±0.2* 1/s in DCM, and 1.2±0.3 1/s in Control, *p<0.05 vs. Control and p<0.05 vs. LVH, Conclusion: Speckle-tracking echocardiography quantified regional and global LV function, regional synchrony, and their strong systolic-diastolic coupling sequentially from normal to failing myocardium, regardless of their heterogeneous pathophysiology. P3353 Epirubicin late cardiotoxicity 5 years after chemotherapy for breast cancer: usefulness of 2D strain analysis H. Samet, A. Trinh, C. Cohen, S. Louboutin, P. Bareiss, G. Roul. Pôle d activités médico-chirurgicales cardiovasculaires. Nouvel Hôpita Civil, Strasbourg, France Aim: We sought to evaluate the 2D strain contribution in the detection of epirubicin (E) induced late cardiotoxicity in women previously treated for breast cancer. Method: Pts suffering from breast cancer underwent 5 years before our study the same treatment protocol including the anthracycline drug E and consisting in FEC 100 (neoadjuvant chemotherapy - 6 cycles) followed by surgery. They were examined in our cardiology department 5 years later. As part of their workup, a transthoracic echo was performed recording left ventricular (LV) systolic and diastolic function, LV dimensions, longitudinal strain over 17 segments and radial strain over 6 middle segments in all possible views. Normal subjects were also analyzed. Result: 57 patients and 39 controls (exclusively women; 57±9 vs 53±13 yrs - NS) were studied. Radiotherapy was associated in 74%, Docetaxel was used in 11% and hormonotherapy in 70% of cases. Trastuzumab was on board in 2% of the pts. Only one pt experienced congestive heart failure 67 months after completion of treatment. Mean dose of E was 577±78 mg/m 2 and average delay from chemotherapy was 62±18months. Compared to the control group, LV end diastolic diameter was slightly increased in the pts group (49±3.4 vs 45±4.8 mm, p<0.0001) and LV ejection fraction moderately reduced (62±7 vs 68±6%, p< ), though the values remained in the normal range. LV relaxation was also significantly prolonged in the E treated group. Radial and longitudinal strains were decreased (respectively: 45±2 vs 54±2.9%, p= and -18±2.6 vs -21±3%, p<0.0001). Moreover, changes in elementary strain were heterogeneous in all cases. Unlike mean radial strain, mean longitudinal strain was related to LV ejection fraction in controls and even more so in E treated pts (r = -0.37; p = 0.02 in controls and r = -0.52; p<0.001 in patients), suggesting that changes in mean longitudinal strain bring valuable piece of information in this setting. ROC curves showed that among all the parameters obtained at rest, LV end diastolic diameter and mean longitudinal strain were the most discriminating parameters between patients and controls further underlining the interest of the latter. Conclusion: E, though used at lower dose than permitted, is associated with a reduction in LV performances both in systole and diastole. These modifications are moderate but significant stressing the need for serial evaluation in such patients. Analyzing of the strain, specially the mean longitudinal strain, seems to add information and should be included in routine evaluation of these patients P3354 Longitudinal, but not global systolic dysfunction is a mechanism of acute hypertensive pulmonary edema A.D. Margulescu 1,R.C.Sisu 2,M.Florescu 1,M.Cinteza 1, D. Vinereanu 1. 1 University Emergency Hospital, Bucharest, Romania; 2 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Mechanisms of acute hypertensive pulmonary edema (AHPE) are poorly understood. Detailed echo assessment of left ventricular (LV) systolic and diastolic function, including deformation imaging, during AHPE has not been performed yet.

269 Heart failure: ventricular function 569 Methods: 20 consecutive patients (73±10 years, 17 women), admitted to an intensive cardiac care unit with the diagnosis of AHPE, were evaluated by conventional and tissue Doppler echo, during the acute episode, and again at 48 to 92 hours. Inclusion criteria were: acute respiratory distress within the preceding 8 hours with clinical and radiological pulmonary congestion, systolic BP 160 mmhg, and sinus rhythm. We excluded patients with acute myocardial infarction, and moderate and severe left-sided valvar diseases. Global systolic function was assessed by cardiac power (mean arterial pressure X cardiac output/451), dp/dt, indexed cardiac output (ico), isovolumic acceleration (IVA), LV outflow tract acceleration (Acc), and ejection fraction (LVEF). Longitudinal systolic function was assessed by tissue-velocity strain (ST) and strain rate (SR), as a mean from 6 basal LV segments. Diastolic function was assessed from the mitral flow profile (E, A, deceleration time), E/Ea ratio, E/Vp ratio, and diastolic filling time (DFT). Tissue-velocity derived dyssynchrony indexes, and the presence of dynamic mitral regurgitation (MR) were also assessed. Results: Systolic BP at admission was 195±31mmHg. However, because echocardiography was performed 76±49 minutes after the first dose of treatment, mean BP was similar between evaluations (95 vs. 102 mmhg, p=0.15). HR was increased during AHPE (93 vs. 73 bpm, p=0.001). Longitudinal mean systolic strain was lower during AHPE (10.7% vs. 14.4%, p = 0.04), which was independent of differences in BP and heart rate. However, global systolic function was similar during AHPE compared to follow-up (cardiac power 0.92 vs W; ico 2.4 vs 2.3 l/min/m 2 ; IVA 1.3 vs. 1.0 m/s 2 ; Acc 15.6 vs m/s 2 ; LVEF 36% vs. 41%; all p = NS); dp/dt was measurable in only 5 patients (854 vs 1021 mmhg/s, p = 0.18). DFT was reduced during AHPE (44% vs. 49%, p = 0.07), but high diastolic filling pressures persisted at follow-up (E/Ea 19 vs. 24, p=0.07; E/Vp = 2 vs 2). All other diastolic parameters, echocardiographic dyssynchrony indexes, and the severity of MR were similar between evaluations. Conclusion: AHPE is associated with LV longitudinal systolic dysfunction, which might lead to depressed LV global systolic reserve during increased HR. Acute LV global diastolic dysfunction, LV dyssynchrony, and dynamic MR are not mechanisms associated with AHPE. P3355 Echocardiographic parameters as a non-invasive means of volume response to asymptomatic, diuretic-induced volume changes in stable left ventricular systolic dysfunction M.J. Ng Kam Chuen, G.Y.H. Lip, R.J. Macfadyen. City Hospital, Birmingham, Birmingham, United Kingdom Introduction: A range of easily-measured echocardiographic parameters correlate with left ventricular filling pressures. These parameters may act as noninvasive means of volume assessment in left ventricular systolic dysfunction (LVSD). We tested their response to diuretic-induced volume changes in stable LVSD. Methods: 30 patients with stable LVSD (26 male; 69.8±7.4 years, range 55-82; LVEF24.9±7.7%, range 10-38%; 20 on furosemide 40 mg daily, 10 on furosemide 80 mg daily) were studied. Patients received their normal oral diuresis on Day 1, omitted their diuretic on Days 2-4, and received a bolus dose of intravenous furosemide (50 mg) following baseline measures on Day 4. Normal oral dosing was reinstated on Days 5-7. Echocardiographic parameters were obtained on Days 1, 2, 3, 4 and 7. Early peak mitral inflow velocity (MVE), the ratio of MVE to late peak mitral inflow velocity (MVE/A), the ratio of MVE to peak early diastolic mitral annulus velocity at the lateral (MVE/Eal) and septal (MVE/Eas) walls, and inferior vena cava diameters (IVC) in expiration (e), inspiration (i) and maximal inspiration (i) were measured. IVC was corrected for body surface area (IVCD). Results (Table 1): All patients remained asymptomatic throughout the diuretic manipulation protocol. All echocardiographic parameters, except for MVE/Ea indices, changed significantly. Table 1 Parameter Baseline Diuretic withdrawal Diuretic resumption p Day 1 Day 2 Day 3 Day 4 Day 7 MVE (m/s) (0.238) (0.238) (0.213) (0.224) (0.240) MVE/A ( ) ( ) ( ) ( ) ( ) IVCDe (cm/m 2 ) 1.13 (0.25) 1.09 (0.26) 1.11 (0.24) 1.17 (0.25) 1.09 (0.25) IVCDi (cm/m 2 ) 0.89 (0.23) 0.87 (0.23) 0.91 (0.23) 0.95 (0.27) 0.86 (0.22) IVCDmi (cm/m 2 ) 0.71 (0.21) 0.70 (0.22) 0.74 (0.23) 0.78 (0.24) 0.71 (0.22) MVE: early peak mitral inflow velocity; A: late peak mitral inflow velocity; IVCD: inferior vena cava diameter corrected for body surface area; e: expiration; i: inspiration; mi: maximal inspiration. Conclusion: Hand-held echocardiography is easily accessible in clinical practice. Targeted measurements of the above echocardiographic parameters could potentially be used for routine non-invasive assessment of asymptomatic volume changes in LVSD. Further studies to establish their sensitivity and specificity are indicated. P3356 Comparison of echocardiographic parameters between systolic and diastolic dysfunction in elderly patients with heart failure R. Handschin 1, K. Goetschalckx 2, B. Julius 3,P.Hilti 4,S.Kiencke 1, A. Bernheim 2, P. Buser 2, M. Pfisterer 2, H.P. Brunner-La Rocca 2, P. Rickenbacher 1 on behalf of TIME-CHF Investigators. 1 Kantonsspital Bruderholz, Bruderholz, Switzerland; 2 University Hospital Basel, Basel, Switzerland; 3 Praxisgemeinschaft, Bülach, Switzerland; 4 SRO Spital Langenthal, Langenthal, Switzerland Background: Doppler echocardiographic data in large heart failure (HF) populations are limited. We compared baseline echocardiographic data between patients with systolic (SHF) and diastolic (DHF) heart failure participating in the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure. Methods: SHF was defined as LVEF 45%. LVEF, left and right atrial (LA and RA) area and tricuspid annulus peak systolic excursion (TAPSE) were assessed. RV to RA pressure gradients (RVPG) were measured as an estimate of systolic pulmonary artery pressures. The ratio of early (E) and atrial (A) transmitral inflow velocities and the Tissue Doppler-derived septal mitral annular early velocity (e septal) were used to assess LV diastolic properties. LV filling pressures were estimated by E/e septal. Results (Table): Expectedly, patients with SHF had a lower LVEF. Lower TAPSE indicated a likewise worse systolic RV function in SHF, but RVPG as well as LA and RA area did not differ between groups. Patients with DHF exhibited a higher E, A and e septal. However, E/e septal was elevated to a similar extent in both groups. No differences in NYHA class were found between SHF and DHF (NYHA III: 74% vs 83%, p=0.11). Systolic versus Diastolic Heart Failure SHF (n=391) DHF (n=100) p-value LVEF, % (n=622) 30±8 56±7 < LA Area, cm 2 (n=466) 27±10 27± E, cm/s (n=491) 80±28 90± A, cm/s (n=314) 63±27 71±28 <0.05 E/A (n=314) 1.5± ± e sep, cm/s (n=325) 4.4±2 5.3± E/e sep (n=318) 20±11 22± TAPSE, mm (n=465) 15±5 17± RA area, cm 2 (n=463) 20.4± ± RVPG, mmhg (n=382) 34±11 35± Conclusion: Despite worse systolic function of both ventricles and worse relaxation of the left ventricle in SHF, no differences in atrial size, LV filling pressure and systolic pulmonary artery pressure were present between patients with SHF and DHF. This may explain the similar symptom severity of patients with SHF and DHF. P3357 Anthracycline-induced subclinical right ventricular dysfunction in adults M.A. Ustaoglu 1, D. Duman 1, M. Gucun 1,V.Konya 1, F. Dane 2, M. Gumus 3. 1 Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey; 2 Marmara University, Istanbul, Turkey; 3 Kartal Research and Training Hospital, Istanbul, Turkey Background: The aim of this study was to assess the effects of anthracyclines on rigth ventricular function and serum B-type natriuretic peptide (BNP) in adult patients. Methods: In this study, 32 adult patients who had no documented previous history of cardiovascular disease and scheduled to receive moderate anthracycline doses (270 to 540 mg/m 2 ) and 20 healthy subjects were prospectively studied. Right ventricular function was evaluated by echocardiography using the standard two-dimensional, M-Mode, and conventional Doppler as well as tissue Doppler imaging (TDI) and before and after the entire chemotherapy course. Serum BNP measurements were also performed. Results: Baseline TDI derived myocardial performance index (MPI) of the right ventricle, tricuspid annular plane systolic excursion (TAPSE) and peak systolic myocardial velocity at tricuspid lateral annulus were similar in both patients and control groups. BNP was not significantly changed after anthracycline therapy. TAPSE and peak systolic myocardial velocity at tricuspid lateral annulus (Svel) were significantly decreased after subsequent chemotherapy doses (from 21.8±3.4 mm to 19.01±3.2 mm, P = and from 12.9±2.5 cm/sn, 11.0±2.2 cm/s, P= 0.003). TDI derived MPI of the right ventricle after therapy was also significantly impaired compared to baseline MPI (from 0.35±0.17 to 0.44±0.11, P= 0.01). With regard to functional status and serum BNP levels of the patients, there was no significant difference between pre- and post-treatment. Conclusion: Our findins support that, moderate anthracycline doses may cause subclinical right ventricular dysfunction in adult. The long-term significance of this finding warrants further follow-up.

270 570 Heart failure: ventricular function P3358 Systolic and diastolic beneficial adaptation to an acute hemodynamic overload is impaired during myocardial ischemia: benefits of early reperfusion and ischemic preconditioning R. Ladeiras-Lopes, J. Ferreira-Martins, M. Pintalhao, A.L. Pires, R. Ferreira, R. Fontes Carvalho, P. Castro-Chaves, A. Leite-Moreira. Serviço de Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal Purpose: Systolic function adaptation to hemodynamic overload is already well characterized. However, its diastolic counterpart still remains largely unknown. Therefore, our objective was to study diastolic function response to acute mechanical overload in the normal cardiac muscle, in the presence of myocardial ischemia and after ischemic preconditionioning. Methods: Rabbit papillary muscles (modified Krebs solution, 0.2Hz, 1.8mM Ca 2+, 30 C) were acutely stretched from 92% Lmax to 100% Lmax (length at which maximal force is developed) under non-ischemic conditions (control: normoxia and presence of glucose; n=9), during an ischemia/reperfusion insult (IR: stretch during 15 minutes of ischemia followed by reperfusion; n=7) and after ischemic preconditioning (IP: stretch in muscles previously subjected to 2 cycles of 5 minutes ischemia followed by 10 minutes of reperfusion; n=8). Immediate and delayed responses to muscle stretch were evaluated. Results as mean ± standard error (p<0.05). Results: In the normal cardiac muscle (control), myocardial stretch caused an immediate (35.6±5.3%) and delayed increase in contractility (40.7±13.8%). Moreover, despite the immediate increase in myocardial passive tension (PT) induced by acute stretch (from 1.7±0.4 to 18.2±2.2 mn mm-2), latter there was a significant and time-dependent decrease in this parameter, down to 8.2±1.1 mn mm-2 (55%) at 60 minutes. On the contrary, in ischemic muscles (IR) this decrease in myocardial stiffness was blunted throughout the ischemic period. Upon reperfusion, both contractility and myocardial stiffness progressively returned to baseline levels. In the ischemic preconditioning (IP) group, after the acute overload there was a significant attenuation in the immediate increase in PT (13.1±2.7 in IP vs 18.2±2.2 mn mm-2 in control) and a normal adaptation of systolic function. Conclusion: After an acute overload there is an improvement in both systolic and diastolic function, with a significant and time-dependent decrease in myocardial stiffness. This adaptive mechanism is inhibited during ischemia and can be enhanced in ischemia preconditioned myocardium, which also highlights the possibility of its active modulation. P3359 Increased central venous pressure is a strong predictor of worsening renal function in patients with cardiovascular disease K. Damman, A.A. Voors, G. Navis, D.J. Van Veldhuisen, H.L. Hillege. University Medical Center, Groningen, Netherlands Background: Worsening renal function (WRF) is associated with increased mortality in patients with cardiovascular (CV) disease. Increased central venous pressure (CVP) is an independent determinant of renal impairment. The relationship between CVP and the occurrence of WRF in CV disease is unclear. Methods: We evaluated 361 patients with CV disease that underwent right heart catheterization and had serial serum creatinine measurements available. CVP, cardiac output (CO) and catheterization indications were extracted. Estimated glomerular filtration rate (GFR) was determined using the smdrd formula. WRF was defined as an increase 0.3 mg/dl in serum creatinine at any point in time. The primary outcome was the occurrence of WRF. Results: Mean age was 54±15 yr, 58% male. Mean egfr was 60±23 ml/min/1.73m 2,withameanCVPof7±6 mmhg and a CO of 5.3±1.7 L/min/m 2. Mean change in serum creatinine was 0.14±0.44 mg/dl, with a median follow up of 8.8 years. WRF occurred in 86 (24%) of patients. Baseline CVP above 8 mmhg (HR 1.69 ( ), P < 0.05) (Figure) was an independent predictors of WRF, next to egfr (hazard ratio (HR) 1.45 ( ), P < 0.001, per 10 ml/min/1.73m 2 decrease), age (HR 0.98 ( ), P < 0.05) and gender (HR 0.52 ( ), P<0.01), while diuretic use showed a trend with occurrence of WRF (HR 1.53 ( ), P = 0.07). Figure 1. CVP and WRF Conclusion: WRF occurred in 24% of patients with CV disease. Increased CVP is a strong independent predictor of WRF, next to egfr, age and gender. P3360 Heterogeneous cardiac response to high dose dobutamine magnetic resonance stress test in patient with left ventricular dysfunction G.D. Aquaro 1, V. Lionetti 2,C.Passino 1, P.G. Masci 1, V. Valenti 3, E. Strata 4,M.Emdin 1, M. Lombardi 1,A.Pingitore 5. 1 Fondazione Toscana Gabriele Monasterio, Pisa, Italy; 2 Scuola Superiore Sant Anna, Pisa, Italy; 3 La Sapienza Universita, Rome, Italy; 4 University of Florence, Florence, Italy; 5 CNR Istituto di Fisiologia Clinica, Pisa, Italy Background: Dobutamine (D) Magnetic Resonance (MR) stress test is diffusely used for assessing contractile reserve in patients with left ventricular (LV) dysfunction. Aim: to assess the effects of high D dose on LVvolumes and indices of global systolic function. Methods: Twelve patients (age 67±6) with non ischemic LV dysfunction underwent D-MR stress test. Seven subjects with normal systolic LV function served as control group. End-Diastolic (EDV), End-Systolic (ESV) LV volumes, LV ejection fraction (EF), LV stroke volumes (SV), cardiac output (CO) and heart rate (HR) were assessed at rest, low (20 mcg/kg/min) and peak (P) dose (40 mcg/kg/min). The ratio between systolic blood pressure (SBP) and ESV was used a a marker of inotropic response. Dysfunctioning patients were clustered in 2 groups: mild (M, EF 50<35%, n=5) and severe (S, EF 35%, n= 7) groups. Results: There we no major adverse effect during D. LV parameters are shown in figure. The reduction in EDV between rest and peak-d was higher in M than in N (-95±26 vs -18±29 ml p<0.003) and S (-95±26 vs -40±28ml p<0.03). Higher reduction in SV was evidenced in M than N (-37±18 vs +9.5±24 ml p<0.01) and S (-37±18 vs +3.4±11 ml p<0.006). Increase in SBP/EDV was lower in M than N(4.7±1.3 vs 2.6±1.2 mmhg/ml p<0.04) but higher in M than S (2.6±1.2 vs 0.09±0.11 mmhg/ml p<0.01). Augment in CO was lower in M tha n N (0.29±2.1 vs 4.6±2.7 L/min p<0.01) and S (0.29±2.1 vs 3.0±1.3 L/min). Figure 1 Conclusion: Cardiac response to high dose of D is characterized by reduction in LV volumes in all 3 groups. In M reduction in pre-load is not compensated by increase in inotropism and HR, whereas in S the pre-load persistence guarantees the maintenance of global LV systolic function. Peak D induce reduction of SV and CO in mild dysfunctioning LV. P3362 Randomised trial of carvedilol and metoprolol on left ventricular dyssynchrony in patients with dilated cardiomyopathy M.G. Kaya, B. Sarli, O. Gunebakmaz, M. Yarlioglues, T. Inanc, A. Dogan, A. Oguzhan, R. Topsakal. Erciyes University School of Medicine, Department of Cardiology, Kayseri, Turkey Background: There is limited data whether β-blockers can influence cardiac mechanical dyssynchrony in idiopathic dilated cardiomyopathy (IDC) patients. This is the first study comparing the effects of carvedilol and metoprolol on intraventricular dyssynchrony. We aimed to evaluate differential effects of carvedilol and metoprolol on LV remodeling and intraventricular dyssynchrony by using tissue Doppler echocardiography. Methods: Forty-eight patients with idiopathic dilated cardiomyopathy were randomısed to carvedilol or metoprolol. Of these, 43 IDC patients on standard heart failure therapy were evaluated with conventional and pulsed wave tissue Doppler echocardiography prior to and at 1 and 6 months after initiation of carvedilol (n=21) or metoprolol (n=22). Results: At the end of 6 months, intraventricular delay decreased from 66±5 to 57±9 ms(p<0.05) in carvedilol group and 68±6 to61±7 ms(p<0.05) in metoprolol group. The decrease in intraventricular delay was similar between two groups. LV ejection fraction increased from 31±7 to37±6 (p<0.05) in carvedilol

271 Heart failure: ventricular function / Heart failure models and mechanisms 571 group similar with metoprolol group (32±5to36±5, p<0.05). Also LV end-systolic and end-diastolic volumes were decreased closely in carvedilol and metoprolol groups. Improvements in LV reverse remodelling and mechanical dyssynchrony were coincident with reductions in NT-proBNP levels both in carvedilol and metoprol groups (1541±711 to 469±451, 1706±702 to 552±329, p<0.05, respectively). Conclusion: Both carvedilol and metoprolol similarly restores intraventricular and interventricular resynchronization and induces LV reverse remodeling in patients with idiopathic dilated cardiomyopathy and heart failure. P3363 Impact of time resolution of the full-volume data set in assessing left ventricular dyssynchrony using real-time three-dimensional echocardiography L. Badano, D. Muraru, R. Onut, D. Ermacora, M.T. Grillo, E. Zakja, P. Gianfagna, P.M. Fioretti. University Hospital, Department of Cardiopulmonary Sciences, Udine, Italy Background: Real-time three-dimensional echo (RT3DE) has been reported as a reliable technique to assess intra-left ventricular mechanical dyssynchrony (LVMD) in terms of systolic dyssynchrony index (SDI). However, current RT3DE scanners have limited time resolution (i.e. volumes per second or vps) of fullvolume data sets. Third generation RT3DE scanners offer the possibility of highresolution multi-beat acquisition of full-volume data sets. The aim of this study was to assess the impact of the temporal resolution of RT3DE full-volume data sets on the assessment of LVMD. Methods: 45 patients (16 showing LBBB at surface ecg, QRS= 167±17 ms) were studied using an advanced prototype of the Vivid E9 scanner (GE Healthcare, Horten, N) equipped with a 3V matrix probe. Two full-volume data-sets of the LV were obtained from apical approach using 2- and 4-beat acquisition modes. The data sets were randomly analysed using the 4D LV function package (TomTec Imaging Systems GmbH, Unterschleissheim, Germany) to obtain LV volumes and 16-segment SDI. Results: Patients showed a wide range of LV end-diastolic volumes (from 50 ml to 281 ml) and ejection fractions (from 27% to 70%). Temporal resolution of 2-beat 3D datasets was 23±3 vps vs. 44±7 vps of 4-beat datasets (p<0.0001). Bland- Altman analysis showed a systematic bias +1.1% (Limits of agreement from - 4.2% to +6.3%) with an overestimation of SDI obtained by 2-beat full-volume data sets. The difference between SDI measured on 4-beat and 2-beat datasets was significantly wider in LBBB pts (5.8±3.3% vs. 8.2±3.6%, respectively; p<0.047) than in pts with QRS < 120 ms (5.2±2.3% vs 5.9±2.9%, respectively; p= 0.044). Conclusions: Temporal resolution of the RT3DE dataset significantly impacts on the results of LVMD. The difference between low and high temporal resolution datasets is greater in pts with LBBB who are those in whom the results may have major clinical impact on management. P3364 Inert gas rebreathing: the effect of pulmonary shunt flow correction on the accuracy of cardiac output measurements in clinical practice F. Trinkmann, T. Papavassiliu, F. Kraus, H. Leweling, S.O. Schoenberg, M. Borggrefe, J.J. Kaden, J. Saur. Universitaetklinikum Mannheim, Mannheim, Germany Background: Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non-invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (QS). A reliable shunt correction requiring the hemoglobin concentration (chb) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to QS correction on the accuracy of IGR. Methods: CO determined by cardiac magnetic resonance imaging (CMR) served as reference values. The data was analyzed in four groups: PBF without correcting for QS (group A), shunt correction using the patients individual chb values (group B), a fixed standard chb of 14.0 g/dl (group C) and a gender-adapted standard chb for male (15.0 g/dl) and female (13.5 g/dl) probands each (group D). Results: 147 patients were analyzed. Mean CO by CMR was 5.2±1.4 l/min, mean CO by IGR was 4.8±1.3 l/min in group A, 5.1±1.3 in group B, 5.1±1.3 l/min in group C and 5.1±1.4 l/min in group D. The accuracy in group A (mean bias 0.5±1.1 l/min) was significantly lower as compared to groups B, C and D (0.1±1.1 l/min; p<0.01). Conclusion: IGR allows a reliable non-invasive determination of CO. Since PBF significantly increased the measurement bias, shunt correction should always be applied. A fixed chb of 14.0 g/dl can be used for both genders if the exact chb value is not known. Nevertheless, the individual value should be used if any possible. P3365 HEART FAILURE MODELS AND MECHANISMS The transcription factor Eya 4 is a new player in heart failure T. Williams, N. Burkard, C. Gebhard, M. Czolbe, F. Panther, J. Schonberger, O. Ritter. Department of Medicine I, University of Wuerzburg, Wuerzburg, Germany Introduction: We identified a mutation in human Eya4 causing dilated cardiomyopathy (DCM). This was the first time a transcription factor was identified as disease gene for DCM. Eya proteins are recruited to the DNA of target genes via an interaction with Six transcription factors. Only a few direct Eya-Six targets are known, including the cyclin-dependent kinase inhibitor p27kip1 (p27), which inhibits hypertrophic growth in adult cardiomyocytes. We hypothesized that the Eya-Six signalling cascade is also activated in acquired heart disease Methods and results: We investigated the role of Eya4 in acquired cardiac diseases in humans. We examined the correlation of p27 phosphorylation and Eya4 in cryosections of 16 failing human hearts and 6 normal human hearts. Immunocytochemical analysis revealed that Eya4 is distributed in the cytoplasm of control cardiomyocytes, while p27 resides mainly in the nucleus. In sections of human failing hearts, Eya4 was accumulated in the perinuclear region and p27 levels were significantly diminished, whereas phosphorylated p27 was evenly distributed in the cytoplasm. In a rat model for myocardial infarction immunofluorescence staining showed that Eya4 is translocated to the nucleus in a time-dependent manner. 16 min after experimental myocardial infarction there is a strong perinuclear accumulation of Eya4 in cardiomyocytes. An accumulation of Eya4 in the nucleus of myocytes was detectable 24h post infarction compared to the cytoplasmic distribution in control heart tissue. 8 weeks after MI Eya4 is completely relocated in the cytoplasm. We studied the effect of Eya4 overexpression on nuclear translocation in permanent mammalian cell lines and cardiac myocytes by immunofluorescence microscopy. 48h post transfection EGFP-tagged WT Eya4 was located in the cytoplasm and translocated to the nucleus after co-expression with DsRed-tagged Six1. Promoterstudies with a p27 promoter-luciferase (including Six1 consensus sites) vector also revealed that activated Eya4/Six1 act as suppressor of p27. Further transfection experiments demonstrated that Eya4/Six1 activation and subsequent p27 suppression increased expression of molecular markers for myocardial hypertrophy (β-mcc, ANP) and increased protein synthesis (3H-leucine incorporation). Discussion: In summary, we previously identified a mutation in Eya4 to cause DCM. We now provide evidence that the Eya4/Six1 signalling cascade is also activated in acquired heart disease. Eya4/Six1 seems to suppress p27 expression, which was shown to be an important inhibitor of the development of hypertrophy in postmitotic cardiomyocytes. P3366 IBP, a novel inhibitor of the calcineurin/nf-at cascade C. Gebhardt, F. Panther, N. Burkard, M. Czolbe, O. Ritter. Department of Medicine I, University of Wuerzburg, Wuerzburg, Germany Background: The calcineurin (Cn)/NF-AT signaling cascade plays a crucial role during T-cell activation and development of myocardial hypertrophy. We previously demonstrated that, in addition to NF-AT, Cn is translocated to the nucleus. We also developed a synthetic peptide (IBP) which inhibited the nuclear import of Cn without affecting calcineurin phosphatase activity. The antihypertrophic effect of IBP on the rat myocardium was shown in vivo and in vitro. Here we extended our studies on a potential use of IBP in the prevention of transplant rejection. Methods and results: Coimmunoprecipitation experiments revealed that the synthetic IBP peptide, which is identical to the nuclear localization sequence of calcineurin, disrupts importin/calcineurin interaction. We further demonstrated that inhibition of the importin/calcineurin interaction by the small competitive peptide (IBP) is sufficient to inactivate the calcineurin/nfat signalling cascade. Inhibitory effects of IBP on T-cell activation were analyzed by [H3]-thymidine incorporation (7135±2503 vs. 2957±1161 [%]) in activated T-cells in vitro (dentritic cells were used as antigen stimulation). To verify immunosuppressive effect of IBP in vitro, heterotopic heart transplantations were performed on rats. Following transplantation rats were treated with IBP (i.p. 130mg/kg/d) or peanut oil as control (i.p. 1 ml peanut oil/d) for 14 days. Time until transplant rejection was significantly prolonged in IBP treated animals compared to control group (12.2±1.5 day vs. 6±2.8 day; n=8; p<0.05). Conclusions: The synthetic inhibitory peptide IBP disrupts the calcineurin/nf- AT cascade by inhibition of Cn nuclear import. This suppresses T-cell activation in vitro and in vivo, thereby revealing a potential use of IBP as novel agent to protect donor organs from rejection.

272 572 Heart failure models and mechanisms P3367 Interleukin-1Trap, a novel interleukin-1 antagonist, inhibits apoptosis and ameliorates cardiac remodeling in experimental acute myocardial infarction A. Abbate, A. Varma, F.N. Salloum, I.M. Seropian, N.N. Hoke, B.W. Van Tassell. Virginia Commonwealth University, Richmond, United States of America Purpose: Interleukin-1 (IL-1) promotes apoptosis and cardiac remodeling after acute myocardial infarction (AMI). Interleukin-1 trap is a novel fusion protein that binds IL-1alpha and IL-1beta, thereby interfering with binding to the membrane receptor. The aim of our study was to evaluate the effects of the murine IL-1 trap on apoptosis and cardiac remodeling after experimental AMI in the mouse. Methods: Ischemia-induced apoptosis was studied in vitro in a primary mouse cardiomyocyte culture subjected to simulated ischemia-reperfusion. The role of the IL-1 trap in vivo was evaluated in ICR mice undergoing surgical coronary artery ligation to evaluate. Ten mice received IL-1 trap (5 mg/kg [n=5] or 30mg/kg [n=5]) and 10 received matching volume of NaCl 0.9% every 48 hours. Five mice underwent sham operation. All animals underwent transthoracic echocardiography before surgery and at 7 days. Results: In vitro IL-1 trap at 0.25 mg/ml was associated with a significant reduction in apoptosis compared to NaCl 0.9% (14±2% vs. 19±1%, p<0.05). Mice treated with IL-1 trap had more favorable cardiac remodeling with significantly smaller left ventricular end-diastolic diameter and greater fractional shortening at 7 days when compared to NaCl 0.9% (see figure), without a significant difference between the low and high dose groups. Conclusions: IL-1 trap is a novel IL-1 inhibitor that reduces ischemia-induced cardiomyocyte apoptosis and ameliorates cardiac remodeling after experimental AMI in the mouse model. P3368 Incident AF is a strong independent predictor of mortality and heart failure development in the elderly D. Zachariah 1,P.R.Kalra 1, P.R. Roberts 2,R.N.Foley 3. 1 Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom; 2 Southampton University Hospitals NHS Trust, Southampton, United Kingdom; 3 University of Minnesota, Minneapolis, United States of America Purpose: Atrial fibrillation (AF) has an increased prevalence at older ages and is generally a predictor of adverse outcome in patients with chronic heart failure (CHF). We sought to determine whether new onset AF was an independent predictor of development of CHF and mortality in an elderly population without overt cardiovascular disease (CVD).We also evaluated the risk of subsequent AF following first presentation with CHF. Method: We evaluated data from the Cardiovascular Health Study (CHS), a US prospective population-based cohort study (n=5795) of risk factors for coronary heart disease (CHD) and stroke (CVA) in adults 65 years.subjects underwent extensive baseline evaluation to identify the presence of CVD and CVD risk factors.the 1847 subjects found to have prior CV disease at baseline were excluded and the conditional impact of incident AF on subsequent CHF development and CVoutcome examined as a time dependent variable. CV events were evaluated as conditional, time-dependent antecedent associations of AF (see figure). Figure 1 Results: 4041 subjects (38.2% females;mean age 72.9±5.4 years) without baseline CVD were followed up for 10.3 years.during this time 16.7% developed AF.Adjusted HR for developing CHF following incident AF was 3.96 (95% CI ).Following presentation with CHF, adjusted HR for development of AF was 4.44 (95%CI ). Event rate per 1000 subject years following incident AF was:81 (95% CI 71 93) for CHF, 43 (95%CI 36 50)for CVA,and 161 (95% CI ) for death.the respective rates in the general population were:28 (95% CI 27-30) for CHF, 21 (95% CI 20 22) for stroke and 49 for death. Conclusion: Incident AF in a previously healthy elderly population is an independent predictor of death,adverse CV outcome and CHF.New onset CHF is a strong predictor of subsequent AF. P3369 Routine in-hospital care and prognosis of elderly patients with heart failure P. Le Corvoisier 1, B. Renaud 2, I. Mahe 3, J.F. Bergmann 3, D. Mottier 4,P.Maison 5, S. Letulle 6, J.L. Dubois-Rande 7, E. Paillaud 8, O. Montagne 6. 1 INSERM, clinical investigation center 006 and INSERM U955, Henri Mondor hospital, Creteil, France; 2 Emergency department, Henri Mondor hospital, Creteil, France; 3 Department of internal medicine, Lariboisiere-Fernand Vidal hospital, Paris, France; 4 Department of internal medicine and pneumology, Cavale Blanche hospital, Brest, France; 5 Department of clinical pharmacology, Henri Mondor hospital, Creteil, France; 6 Clinical investigation center 006, Henri Mondor hospital, Creteil, France; 7 Department of cardiology, Henri Mondor hospital, Creteil, France; 8 Department of internal medicine and geriatry, Henri Mondor hospital, Creteil, France Purpose: Most of the studies performed in heart failure (HF) patients have been conducted in middle-aged adults. However, patients with HF are mainly elderly patients in whom management is complicated by comorbid conditions. Little is known about the quality of care among this population. The aim of this study was to describe the in-hospital management in routine clinical settings and the prognosis of elderly patients with pulmonary oedema. Methods: All consecutive patients over 75 years of age presenting to 5 french emergency departments with acute pulmonary oedema were included in this observational study. During hospital stay, patients were evaluated without intervention on their management or their treatment. After discharge, their survival was followed for two years by phone calls. Results: 398 patients were enrolled during the 12 months of this study. 96% of these patients had at least one major comorbid condition and the prevalence of cognitive impairment was high (63% of patients with a Mini Mental State Examination <20). Admission in cardiology departments (33.7%) was associated with previous cardiologic assessment (OR: 2.32 [ ]), prior coronary artery disease (OR: 2.39 [ ]) and elevated troponin (OR: 1.67 [ ]). By contrast, cognitive impairment (OR: 0.39 [ ]) was associated with noncardiology department admission (66.3%). A preserved left ventricular ejection fraction ( 45%) was found in 70.5% of patients. Recommended treatments were under-prescribed at admission (48.1%) and were more likely to be delivered at discharge to patients admitted to cardiology departments (OR: 1.51 [ ]). In contrast, age over 85 years (OR: 0.64 [ ]), history of neurological disease (OR: 0.60 [ ]) and severe kidney disease (OR: 0.28 [ ]) were associated with a lower use of recommended medications. In-hospital mortality (11.0%) was not associated with department speciality. However, the two years mortality of patients treated with recommended medications at discharge was significantly reduced compared to patients treated with symptomatic drugs (OR: 0.68 [ ]). Similarly, the two years re-hospitalization rate was reduced in patients treated with recommended medications (OR: 0.42 [ ]). Conclusion: Routine cares of HF are dependant on non-cardiologic factors in this elderly population. These factors affect the prescription of recommended medications and influence the prognosis. Our findings suggest that the institution of protocols to standardize care could improve compliance with guidelines and longterm outcomes. P3370 Interleukin-6-Deficient mice resist development of experimental autoimmune cardiomyopathy provoked by beta1-adrenergic receptor L.-P. Ma 1,G.Premaratne 2,E.Bollano 2, C. Lindholm 3,M.Fu 2. 1 Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai, China, People s Republic of; 2 Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Gothenburg, Sweden; 3 University of Gothenburg, Gothenburg, Sweden Purpose: We studied the role of IL-6 in a mouse model of autoimmune cardiomyopathy induced by immunization with a synthetic peptide corresponding to the second extracellular loop of the β1ar (ECII). Methods: Twenty IL-6-deficient (IL-6-/-) mice and fifty-one wild type (WT) mice were immunized with β1ar ECII at 0, 1, 5, 9, 13 weeks and were observed until 25 weeks. Another forty-one WT mice and twenty IL-6-/- mice were used as control receiving vehicle in the same manner. Cardiac function and β1ar autoantibody were analysed by echocardiography and ELISA respectively. mrnas encoding for β1ar receptor signalling moleclues, cytokines and cardiomyocyte stretch markers were determined. Results: Cumulative mortality in WT immunized group (38.43%) was significant higher than other groups (IL-6-/- immunized 5%; WT control 2.44% and IL-6-/- control 0%). Compared to the IL-6-/- immunized and control mice, the WT immunized mice have shown significantly increased left ventricular end-systolic dimension (LVDs) and left ventricular end-diastolic dimension (LVDd) (P < 0.05 for both) and decreased fraction shortenings (FS) and circumferential fibers (CF) (P

273 Heart failure models and mechanisms 573 < 0.05 for both) in the end of experiment. Level of anti-β1ar antibody showed significantly higher in WT immunized mice than that in IL-6-/- mice and associated with decreased cardiac function. mrnas encoding for β1-adrenergic kinase (GRK2), B-type natriuretic peptide (BNP) and β1 adrenergic receptors in heart tissues from WT immunized group were increased. A significant positive correlation was found among enlarged left ventricular dimension, mrna expressions of BNP, β1ar and GRK2 and antibody titer, whereas a negative correlation was found between FS and antibody titer. Linear regression analysis showed linear correlation not only between FS and β1ar mrna but also between LVDd and BNP mrna. Moreover, there were significant differences in mrna level for both BNP and β1ar between WT immunized mice and other groups. Conclusions: Results demonstrate that immunization of mice with β1ar ECII was able to induce an early stage phenotype of cardiomyopathy. Moreover, IL-6 plays a key role in the induction of experimental autoimmune cardiomyopathy by β1ar. P3371 G-CSF induces reverse remodeling processes of hypertrophied hearts H. Moellmann 1,H.Nef 1,S.Voss 1,C.Troidl 2, M. Rauch 1, S. Szardien 1,S.Kostin 2, M. Weber 1,C.Hamm 1, A. Elsaesser 3. 1 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 2 Max-Planck- Institut fuer Herz und Lungenforschung, Bad Nauheim, Germany; 3 Klinikum Oldenburg, Oldenburg, Germany Background: The role of stem cells and their mobilization during reverse remodeling processes of hypertrophied hearts is yet not fully elucidated. Therefore, we investigated the influence of G-CSF therapy on left ventricular structure and function during hypertrophy regression in a mouse model of aortic banding and subsequent debanding. Material and Methods: Left ventricular hypertrophy was induced in 24 mice by transverse arch banding. After 8 weeks debanding was performed and mice were randomized into a G-CSF-group (300μg/kg/day for seven days after debanding) and a control group receiving saline injection. The success of G-CSF-treatment was confirmed by FACS analysis. Mice were euthanized 14 days after debanding. Functional parameters were assessed with echocardiography and cardiac MRI (7.05T). Morphologic alterations were examined by immunohistochemistry using a broad spectrum of specific antibodies. In order to examine the impact of stem cell mobilization, we performed a stem cell transplantation using an egfp-marked stem cell pool after prior sublethal irradiation. After 12 weeks the bone marrowtransplanted mice underwent the same experimental protocol with banding and debanding. Results: Transverse arch banding resulted in left ventricular hypertrophy (septum 0.99±0.03mm vs. 0.62±0.04mm; p<0.001), a marked fibrosis (relative collagen III-content 17.1±0.7% vs. 9.4±0.9%, p<0.001), and a reduction of the ejection fraction (64.5±2.7% vs. 77.3±1.5%; p<0.001). Histomorphometry showed a significant increased myocyte cross sectional area (351±22 μm 2 vs. 205±15 μm 2 ; p<0.001). G-CSF treatment was successful with an increase of sca-1+ cells in the peripheral blood (5.4±1.2% vs 1.8±0.3%; p<0.05). G-CSF treatment resulted in a significant increase of left ventricular ejection fraction after debanding in comparison to control (83.4±1.7% vs. 70.6±1.6%, p<0.001), a significant increase of capillary density (3420±299/mm 2 vs. 2586±144/mm 2,p<0.05), and a significantly stronger reduction of myocardial fibrosis (relative collagen III content 9.8±0.9% vs. 16.3±0.6%; p<0.001). These positive results were not accompanied by an increase of egfp+ cells in the myocardium during reverse remodeling processes. Conclusion: Aortic debanding lead to reverse remodeling processes in both groups. Treatment with G-CSF resulted in a decrease of fibrosis and an increase of capillary density and ejection fraction in comparison to control. These beneficial effects were independent from the stem cell mobilizing properties of G-CSF given the lack of an increase of (trans-)differentiated bone marrow derived cells in the myocardium. Myocardial sections were analyzed by WGA and CD45 immunohistochemistry, TUNEL, Sirius red and von Kossa staining, respectively. Western blot was performed following standard protocols. Results: AngII and PE neither affected survival nor cardiac function and evoked equal hypertrophy in WT and STAT3-KO hearts. In contrast, stimulation with Iso induced progressive LV dysfunction and dilation (FAC 27.8%, LVEDD 5.2mm vs. FAC 61.2%, LVEDD 4.3mm; p<0.01) and increased mortality (55% vs. 4%; p<0.001) in STAT3-KO but not in WT mice. Myocardial inflammation and fibrosis were increased in STAT3-KO hearts after 3 to 7 days of Iso stimulation. Experiments with STAT3; p47phox-dko, Tempol treatment and gp130/delta mice ruled out significant roles of oxidative stress and disturbance of gp130-dependent STAT3 activation in Iso-induced cardiac pathology. In response to acute Iso stimulation, STAT3-KO hearts exhibited impaired diastolic function (p<0.05), reduced ATP/ADP ratio, and increased lactate production compared to WT. Moreover, STAT3-KO myocardium exhibited pronounced calcium deposition, suggesting calcium overload as a mechanism of cardiomyocyte damage. Conclusion: Cardiomyocyte STAT3 is a key player in adaptive cardiac remodelling and preservation of LV function during chronic β-adrenergic stimulation. The control of myocardial metabolism and calcium homeostasis may represent important functions of cardiac STAT3. The identification of STAT3-dependent signalling targets offers new insight into the pathophysiology of heart failure and may lead to the definition of new therapeutic approaches. P3373 Mutations in the intermediate filament protein desmin severely compromise nanomechanical filament and network properties H. Baer 1, M. Schopferer 2,S.Sharma 1,N.Muecke 3, L. Kreplak 4, N. Willenbacher 2, H. Herrmann 3. 1 Medizinische Fakultaet Heidelberg, Heidelberg, Germany; 2 Technische Hochschule, Karlsruhe, Germany; 3 DKFZ, Heidelberg, Germany; 4 Dalhousie University, Halifax, Canada Mutations in the gene coding for the muscle-specific intermediate filament protein (IF) desmin are recognized to cause up to 1-2% of dilated cardiomyopathies. We could recently demonstrate that in contrast to prior expectations most of these mutations do not cause an incompetence of the mutant protein to assemble into bone fide IF proteins, neither in in vitro assays with purified recombinant proteins, nor in transfection analyses involving several tumour cell lines as well as cardiomyocytes. Desmin IFs are known to interconnect neighbouring myofibrils and to link the contractile apparatus to the cellular membrane (i.e. desmosomes), to other cellular organelles such as mitochondria and to the nucleus. Desmin IFs are therefore thought to be vital for intracellular mechanosensing as well as mechanotransduction. Altered intrinsic filament properties due to disease-mutants could impact on these functions. Therefore we set out to analyse whether mutations exhibiting preserved filament-formation capacities impact on the mechanical properties of desmin filaments. Using atomic force microscopy (AFM) we established a method to probe single filaments in order to assess their nanomechanical properties. In addition, bulk rheological properties of desmin networks in solution were analysed by oscillatory squeeze flow measurements via a Piezo Axial Vibrator and via commercial rheometers in order to measure (1) the bending stiffness of the filaments (i.e. the persistence length) and (2) their linear and non-linear viscoelastic properties. Analyses done on mutations located in the carboxy-terminal tail domain of desmin indicate that indeed some mutations lead to a diminished or even absent strain-stiffening of the desmin network. This finding indicates that these mutations are not able to increase their elastic modulus (to stiffen ) with increases in shear stress. This is expected to severly compromise their mechanical filament properties. Mechanical forces imposed on such mutant desmin filaments and filament networks would be expected to dissipate instead of being transmitted to intracellular targets such as the nucleus. Our findings confirm our hypothesis that indeed some desmin mutations impact only on higher order intrinsic filament properties of desmin. This points out to a novel molecular mechanism underlying the development of desminopathy. P3372 Cardiac STAT3 plays an important role in the protection against beta-adrenergic stress-related development of heart failure P. Fischer, B. Stapel, M. Hoch, S. Erschow, H. Drexler, D. Hilfiker-Kleiner. Medizinische Hochschule Hannover, Hannover, Germany Background: In the diseased heart, persistently heightened activation of neurohumoral circuits contributes to the progression of heart failure and increased mortality. As the level of cardiac STAT3 is reduced in failing human hearts we aim to determine its relevance for cardiac adaption to neurohumoral stress. Methods: Mice with cardiomyocyte-specific knockout of STAT3 (STAT3-KO) and wildtypes (WT) were exposed to continuous administration of sub-pressure doses of angiotensin II (AngII: 0.3 mg/kgbw/24h), phenylephrine (PE: 0.1 mg/kgbw/24h), or isoproterenol (Iso: 60 mg/kgbw/24h) for 2 weeks. Tempol (40 mg/kgbw) was given daily via i.p. injection. STAT3-KO mice with systemic knockout of the p47phox subunit of the NADPH oxidase (STAT3; p47phox-dko) and mice with a cardiomyocyte-specific mutation of the STAT3 binding site of the gp130 receptor (gp130/delta) were treated with Iso as described. Left ventricular (LV) function was assessed by echocardiography and invasive hemodynamics. P3374 Jun nh2-terminal kinase2 is involved in angiotensin ii-induced oxidative stress and cardiac dysfunction via toll-like receptor 4 S. Matsuda 1,S.Umemoto 2, H. Yoshino 1, T. Nakashima 1, S. Ito 3, H. Aoki 4, K. Yoshimura 5,T.Murata 6, M. Matsuzaki 1. 1 Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan; 2 Pharmaceutical Clinical Research Center,Yamaguchi University Hospital, Ube, Japan; 3 Shimonoseki Saiseikai General Hospital, Shimonoseki, Japan; 4 Cardiovascular Research Institute Kurume University, Kurume, Japan; 5 Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, Ube, Japan; 6 Science Research Center, Yamaguchi University, Ube, Japan Purpose: Toll-like receptor 4 (TLR4) is reported to be involved in cardiovascular events. Angiotensin II (AT II) also plays an important role in the development of cardiac hypertrophy and subsequent heart failure through the production of reactive oxygen species (ROS) in the heart. On the other hand, it is reported that the expression of Jun NH2-terminal Kinase2 (JNK2) depends on the level of ROS, and that TLR4 stimulates the upregulation of JNK2. However, the relationship between TLR4 and JNK2 by AT II stimulation in regulating oxidative stress and

274 574 Heart failure models and mechanisms cardiac function remains unknown. We investigated the effects of TLR4 on oxidative stress and the expression of JNK2 in the heart, and cardiac function in AT II-induced hyprtension in vivo. Methods: TLR4-/- and wild-type (WT) mice were randomized into AT II or NE treatment groups for 2 weeks. Systolic blood pressure (SBP) was obtained by tail-cuff plethysmography. We assessed left ventricular (LV) end-diastolic dimension, LV end-systolic dimension, fractional shortening (%FS), and the thickness of interventricular septum (IVS) as well as LV posterior wall (LVPW) calculated by the Teichholtz method. In addition, transmitral flow (TMF) calculated by the Doppler method were estimated based on transthoracic echocardiography under light anesthesia. To assess superoxide ( O 2 - ) content in the heart, we incubated frozen section of heart tissues with the dye hydroethidine staining by a laser scanning confocal microscope. The expression of JNK2 in the heart was evaluated with immunoblots. Results: Both AT II and NE equally and significantly increased SBP in both the WT and TLR4-/- mice compared with the control untreated mice throughout the experiments (p<0.05). In the WT mice, AT II induced an increase in the thickness of IVS and LVPW, and a decrease in %FS, and E/A ratio, whereas the TLR4- /- mice showed little effects of AT II on these indices. Furthermore, in the WT mice, AT II induced a 5-fold increase in. O2-content in the heart compared with the control mice, whereas only a 2-fold increase in O2-content was shown in the heart of the TLR4-/- mice. Moreover, in the WT mice, AT II induced a 2.5-fold increase in the expression of JNK2 in the heart, whereas there was little difference of the expression of JNK2 observed in the TLR4-/- mice by AT II treatment. On the contrary, NE treatment showed little effects on any indices in both the WT and TLR4-/- mice. Conclusions: TLR4 may be involved in cardiac dysfunction and hypertrophy via the activation of JNK2 and the increase in oxidative stress in AT II-induced hypertensioninvivo. P3375 Suppression of left ventricular lipin 1 mrna and corresponding phosphatidate phosphohydrolase 1 activity in experimental type 2 diabetic cardiomyopathy C. Burgdorf, L. Haensel, M. Heidbreder, O. Joehren, F. Schuette, H. Schunkert, T. Kurz. Universitaetsklinikum S-H, Campus Luebeck, Luebeck, Germany Recent studies suggest that lipin 1 regulates mammalian glycerolipid metabolism through its enzymatic phosphatidate phosphohydrolase 1 (PAP1) activity. PAP1 catalyzes the dephosphorylation of phosphatidate yielding diacylglycerol (DAG). Since alterations of glycerolipid homeostasis have been implicated in the pathogenesis of diabetic cardiomyopathy, we examined the expression pattern of lipin 1 and its enzymatic function in the myocardium of 8-month-old male Type 2 diabetic (fa/fa) Zucker diabetic fatty (ZDF) rats (n = 9) and genetically nondiabetic (fa/+) ZDF rats (n = 9). The presence of cardiac failure in diabetic ZDF-fa/fa rats at this stage has been shown previously. Expression of left ventricular (LV) lipin 1 mrna was markedly lower in ZDF-fa/fa rats compared to ZDF-fa/+ rats (0.12±0.01 vs. 0.18±0.03 mrna copies/gapdh mrna copies, p < 0.05) whereas atrial lipin 1 mrna expression was identical in both groups (0.04±0.01 mrna copies/gapdh mrna copies). Accordingly, activity of LV PAP1 was markedly reduced in ZDF-fa/fa rats (244±11 vs. 344±25 nmol DAG/h/mg protein, p < 0.01). Atrial PAP1 activity did not differ significantly between both groups (96±5 vs. 114±6 nmol DAG/h/mg protein). Notably, in both rat strains, enzymatic activities and mrna expression of lipin 1 were 2.5-fold to 4.5-fold higher in ventricular as compared to atrial tissue suggesting marked differences in the regional distribution pattern. Correlation analysis revealed a strong relation between PAP1 activity and lipin 1 mrna in myocardial tissue from ZDF rats (r = 0.99, p < 0.01) further supporting that lipin codes for PAP activity. Structural alterations such as increased LV collagen content or myocardial hypertrophy were not significantly augmented in ZDF-fa/fa hearts (percentage collagen content: 15±2 vs. 13±2% in ZDF-fa/+ hearts; heart weight to body weight ratio: 4.68±0.21 vs. 4.19±0.18 in ZDF-fa/+ rats). In conclusion, reduction of enzymatic PAP1 activity in LV myocardium from diabetic ZDF rats may result from a lack of endogenous lipin 1 protein abundance and may contribute to cardiac dysfunction in chronic diabetes. P3376 BNP gene transfer improves cardiac function after myocardial infarction and in hypertensive heart failure A.M. Moilanen 1, J. Rysa 1, E. Mustonen 1, A. Manninen 2, J. Aro 1, R. Serpi 1, H. Leskinen 1, H. Tokola 3, O. Vuolteenaho 4, H. Ruskoaho 1. 1 Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; 2 Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland; 3 Institute of Diagnostics, Department of Pathology, University of Oulu, Oulu, Finland; 4 Institute of Biomedicine, Department of Physiology, University of Oulu, Oulu, Finland Purpose: B-type natriuretic peptide (BNP) is an endogenous peptide produced under physiological and pathological conditions mainly by ventricular myocytes. It possesses natriuretic, diuretic, blood pressure lowering and antifibrotic actions that could mediate cardiorenal protection in cardiovascular diseases. However, these in vivo effects may be related to the hemodynamic effects of intravenous infusion of BNP. In the present study, we used human BNP (hbnp) gene transfer to determine direct structural and functional effects of BNP on left ventricular (LV) remodeling. Methods: BNP was overexpressed by using adenovirus mediated gene transfer in healthy rat hearts and in hearts during the remodeling process in response to pressure overload induced by angiotensin II and acute myocardial infarction (AMI). Adenovirus at dose infectious unit/animal was injected into the anterior wall of the left ventricle. The effects of BNP were analysed with echocardiography and histological analysis. The expression of BNP and the activation of underlying signaling pathways were also investigated. Results: In healthy heart, local adenoviral overexpression of hbnp resulted in decreased myocardial fibrosis by 34% (p<0.01) and increased capillary density by 9% (p<0.05) associated with 5.5-fold (p<0.001) increase in LV BNP peptide levels. Overexpression of hbnp improved fractional shortening (FS) by 22% (p<0.05) and ejection fraction (EF) by 19% (p<0.05) at 2 weeks post-infarction. Western blot assay analysis revealed that expression of SERCA2 and Thr17- phosphorylated phospholamban were increased by hbnp after AMI whereas the protein levels of p44/42 mitogen-activated protein kinase (MAPK) and p38 MAPK remained unchanged. Angiotensin II-induced LV hypertrophy was significantly attenuated by hbnp associated with decrease in LV collagen III mrna levels (p<0.01). Overexpression of hbnp also improved FS (20%, p<0.05) and EF (10%, p<0.05) in hypertensive LV hypertrophy induced by angiotensin II. Conclusions: These results indicate that direct BNP gene transfer into the left ventricular wall improves cardiac function and attenuates adverse post-infarction and hypertensive heart failure remodeling. The rescue of failing myocardium with BNP gene transfer may be a potential new therapy after myocardial infarction. P3377 carvedilol infusion before reperfusion improves left ventricular hemodynamic parameters at early stage in experimental model of acute myocardial infarction via inhibition of MCP-1 and MMP-2 activity G. Cimmino, B. Ibanez, S. Prat, R. Hutter, C. Giannarelli, J. Sanz, M.J. Garcia, V. Fuster, J.J. Badimon. Mount Sinai Hospital, New York, United States of America Background: Left ventricular (LV) remodeling after myocardial infarction (MI) contributes significantly to LV dilation and dysfunction, and disability and death. This process is complex, dynamic, and time dependent. Monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, T cells, and NK cells has been implicated in MI. It has important effects on macrophage recruitment and activation, cytokine synthesis, and myofibroblast accumulation in healing infarcts. Members of the matrix metalloproteinases (MMP) family play a central role in the degradation of extracellular matrix (ECM) at early stage during MI. Increased expression of MMP-2 in infarcted myocardium has been reported. β-blockers (β-bks) therapy are first line choice in the treatment of MI and heart failure but timing of administration and mechanisms responsible for their benefits are still unclear. We evaluated the effect of early (pre-reperfusion) carvedilol (CV) on LV remodeling in a model of acute MI. Methods: Acute MI was induced in Yorkshire pigs (n=23) by transient balloon occlusion (90 minutes) of the left anterior descending coronary artery. Animals were randomized to CV (5.25 mg n=12) or placebo (PL n=11) infused 30 min after occlusion. Five animals per group were sacrificed at 24 hours. Monocytes/macrophages infiltration, MCP-1, MMP-2, tissue MMP inhibitor (TIMP)-2 gene and protein expression, as well as MMP-2 activity, were quantified in the infarcted area. LV volumes, function, and salvaged myocardium (edematous minus infracted area) were measured by magnetic resonance at day 3 post-acute MI. Results: CV resulted in lower LV end diastolic volume (86+11ml) than PL ( ml; p=0.08). Salvaged myocardium was also increased by CV (20+4%) vs. PL (7+2%; p=0.04). A protective modulation of tissue gene and proteins involved in remodeling (significant down-regulation of MCP-1, MMP-2 and up-regulation of TIMP-2) as well as significant reduction of monocytes/macrophages infiltration was observed in CV group. Conclusions: Pre-reperfusion administration of β-blockers during acute MI significantly improves early LV remodeling. This seems to be secondary to improved MMPs/TIMPs balance and attenuated macrophage infiltration via downregulation of MCP-1. P3378 Sustained PKCbetaII inhibition restores both proteasome activity and protein quality control in two different heart failure models J.C.B. Ferreira 1,P.C.Brum 1, D. Mochly-Rosen 2. 1 University of Sao Paulo, Sao Paulo, Brazil; 2 Stanford University, Stanford, United States of America Protein quality control (PQC) dysfunction has been associated with posttranslational modifications, proteasome malfunction and misfolded proteins accumulation, which further culminates in cell death. The cellular mechanisms involved in PQC during heart failure progression have not been established. Using postmyocardial infarction model in rats, we found a progressive accumulation of oxidized and ubiquitinated proteins, increased HSP27 levels, ATP-dependent and independent proteasome dysfunction and augmented misfolded proteins during

275 Heart failure models and mechanisms 575 the ten weeks following myocardial infarction. During this period the rats transition to heart failure. We also show that a six-week treatment with biiv5-3, a biipkcspecific inhibitor peptide that our lab has previously designed, normalized cardiac proteasome function and restored PQC. In parallel, we observed increased survival and improved fractional shortening from 14±2% in control-treated animals to 27±2%.This sustained but mild inhibition of biipkc using biiv5-3 (60±8% inhibition of translocation and 62±9% inhibition of catalytic activity relative to controltreated animals) was selective; biiv5-3 treatment did not affect the activity of any other PKC isozymes, including apkc and the closely related, bipkc. Using another heart failure model, hypertensive Dahl salt-sensitive rats, we show that sixweek treatment with biiv5-3 also restored cardiac PQC. In contrast, treatment with the selective inhibitor of bipkc, an alternative splicing variant of biipkc, had no beneficial effects. Finally, we show in neonatal cardiomyocyte culture that biiv5-3 treatment abolished both ATP-dependent and independent proteasome inactivation induced by 10nM of phorbol ester (classical PKC activator). In conclusion, ourdata using two distinct in vivo models of heart failure and neonatal cardiomyocyte culture suggest that biipkc activation induces proteasome dysfunction and PQC disruption, contributing to the pathology associated with heart failure. P3379 Mechanism of inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-beta 1 in cultured cardiac fibroblast K.G. Shyu, B.W. Wang. Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Purpose: Transforming growth factor-β1 (TGF-β1) and endoglin play a causal role in promoting cardiac fibrosis. However, the effect of statin on TGF-β1 and endoglin is poorly understood. Atorvastatin has been demonstrated to have in vitro inhibitory effect on cardiac fibroblasts. However, the molecular mechanism and signaling pathway of atorvastatin to inhibit cardiac fibrosis is not known. Therefore, we sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after proinflammatory cytokine, TGF-β1 stimulation in cultured cardiac fibroblasts. Methods: Cultured cardiac fibroblasts were obtained from adult male Sprague- Dawley rat hearts. Different signaling pathway inhibitors were used. Western blots, real time polymerase chain reaction, gel sift and promoter activity assays were performed. Results: TGF-β1 stimulation increased endoglin protein and mrna expression and atorvastatin inhibited the induction of endoglin by TGF-β1. Phosphatidylinositol-3 kinase and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-β1. TGF-β1 induced phosphorylation of phosphatidylinositol-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of phosphatidylinositol-3 kinase and Akt induced by TGF-β1. The gel shift and promoter activity assay showed that TGF-β1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-β1. Conclusions: Phosphatidylinositol-3 kinase and Akt pathway mediates the inhibitory effect of atorvastatin on endoglin expression induced by TGF-β1. Our findings provide another evidence of pleiotropic effect of statin. Statin therapy may become another therapeutic strategy for controlling endoglin-associated pathologic cardiovascular disease in humans. P3380 Sarcoplasmic reticulum calcium leak accelerates development of heart failure X.H.T. Wehrens, J. Respress, S. Sarma, C. Reynolds, D.G. Skapura, R.J. Van Oort. Baylor College of Medicine, Houston, United States of America Background: In response to stress, the heart compensates by hypertrophic growth, which frequently progresses to heart failure. The initial hypertrophic response is associated with activation of several intracellular signaling pathways. Although there is a central role for calcium (Ca 2+ ) in hypertrophic signaling, the Ca 2+ source for activating these pathways remains elusive. Failing hearts are characterized by diastolic leakage of Ca 2+ from the sarcoplasmic reticulum (SR) due to increased activity of the intracellular Ca 2+ release channel/ryanodine receptor (RyR2). We hypothesized that pathological SR Ca 2+ leak through defective RyR2 accelerates HF development by activating Ca 2+ -dependent intracellular hypertrophic pathways. Methods and Results: Mice heterozygous for gain-of-function mutation R176Q/+ in RyR2 and wildtype (WT) mice were subjected to transverse aortic constriction (TAC), which causes pressure-overload. Cardiac function was evaluated using echocardiography before, and at 2, 4, and 8 weeks after TAC. Following pressurevolume loop measurements at 8 weeks post-tac, mice were sacrificed and routine histology was performed. Compared with WT mice, R176Q/+ mutant mice developed more pronounced contractile dysfunction induced by pressure overload. Ejection fraction was significantly lower in R176Q/+ mice compared withwt at 2, 4 and 8 weeks post-tac. Cardiac dimensions including end-diastolic diameter were larger in R176Q/+ than WT mice at 8 weeks post-tac. R176Q/+ mice displayed an enhanced hypertrophic response compared to WT mice as assessed by heart weight to body weight ratios, and cardiomyocyte crosssectional areas. QuantitativePCR revealed an increase in transcriptional activation of the cardiac stress genes brain natriuretic peptide (BNP) and alpha-skeletal actin (Acta1) inr176q/+ mice compared to WT mice 8 weeks after TAC. Finally, pressure overload resulted in an almost two-fold increase in expression of the exon 4 splice form of regulator of calcineurin-1 (RCAN1-4) in R176Q/+ mice compared to WT, reflecting enhanced calcineurin activity. Accordingly, calcineurin activity and phosphorylation of nuclear factor of activated T-cells (NFAT) were more increased in R176Q/+ TAC mice. Conclusion: Our results reveal that a gain-of-function mutation in RyR2 leads to enhanced activation of calcineurin and acceleration of heart failure development during pressure-overload. Therefore, enhanced Ca leak from the sarcoplasmic reticulum may adversely influence the pathogenesis of heartfailure. P3381 Influence of cardiac shape on left ventricular twist B.M. Van Dalen, F. Kauer, W.B. Vletter, O.I.I. Soliman, H.B. Van Der Zwaan, F.J. Ten Cate, M.L. Geleijnse. Erasmus MC - Thoraxcenter, Rotterdam, Netherlands Objectives: The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. Methods: The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age and gender matched healthy volunteers. DCM patients were divided into three subgroups of 15 patients according to LV ejection fraction (20-30%, 31-40%, and 41-50%). Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rotmax), and instantaneous LV peak systolic twist (Twistmax). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. Results: A parabolic relation between the sphericity index and apical Rotmax or Twistmax was identified in the total study population (R2 = 0.56, and R2 = 0.54, respectively, both P<0.001) and healthy volunteers (R2 = 0.39, and R2 = 0.25, respectively, both P<0.001), whereas these relations were linear in DCM patients (R2 = 0.40, and R2 = 0.43, respectively, both P<0.001) (Figure 1, open circles: healthy volunteers; closed circles: DCM patients). In the three LV ejection fraction subgroups of DCM patients these linear relationships remained observable. In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rotmax and Twistmax. Figure 1 Conclusion: LV apical rotation and twist are significantly influenced by LV configuration. Taken the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function. P3382 Beneficial effects of ivabradine on cardiac remodelling in the diabetic hypertensive heart are mediated through modulation of connective tissue growth factor E. Velkoska, R.G. Dean, K. Spencer, L.M. Burrell. The University of Melbourne, Melbourne, Australia Aim: We tested the hypothesis that heart rate reduction using the selective I f current inhibitor ivabradine would improve left ventricular (LV) function and structure in a rat model of diabetic hypertensive heart disease. Method: Spontaneously hypertensive rats with streptozotocin-induced diabetes (SHR-DM) received a subcutaneous infusion of either vehicle or ivabradine (6 mg/kg/day) for 8 weeks. Diabetic rats received 1-2 Units/day of insulin to maintain health. Non-diabetic SHR rats were used as controls. Blood pressure (BP) and heart rate (HR) were measured weekly using radiotelemetry, and cardiac function (MAP, LVEDP, tau, LV dp/dtmax/min) was assessed by catheterization at 8 weeks. LV fibrosis was assessed after picrosirius red staining, LV connective tissue growth factor (CTGF) gene and protein measured by RT-PCR and immunostaining, and LV angiotensin converting enzyme (ACE) was measured using in vitro autoradiography. Results: SHR rats with diabetes had an HbA1C of 12% and systolic BP of mmhg. The hypertensive diabetic heart was also characterized by LV

276 576 Heart failure models and mechanisms dysfunction (P<0.05), interstitial and perivascular fibrosis (both P<0.001), and overexpression of LV CTGF at both the gene and the protein level compared to non-diabetic SHR (P<0.05). After 8 weeks of treatment, ivabradine reduced HR by 10% (P<0.05) and improved systolic function by 15%(P<0.05) without any effect on BP. Ivabradine also reduced cardiac interstitial (33%, P<0.05) and perivascular fibrosis (22%, P<0.05), inhibited cardiac ACE activity by 30% (P<0.05), and significantly reduced CTGF at both the gene and the protein level (65%, P<0.05 and 93%, P<0.01 respectively). Conclusion: Ivabradine improves cardiac function and remodelling in a rat model of diabetic hypertensive heart disease. These effects most likely result from HR reduction which in turn may trigger inhibition of cardiac ACE, and suppression of the pro-fibrotic growth factor CTGF. These beneficial effects of ivabradine support testing pure heart rate reduction in patients with diabetic hypertensive heart disease. P3383 Effects of diabetes mellitus, pressure overload and their association on myocardial structure and function I. Falcao-Pires 1, N. Goncalves 1,C.Moura 1, K. Kupreishvili 2, I. Lamego 1, H.W.N. Niessens 2,J.C.Areias 1, A.F. Leite-Moreira 1. 1 Faculdade Medicina do Porto, Porto, Portugal; 2 VU University Medical Center, Amsterdam, Netherlands This study evaluated changes in passive properties, structural and functional mechanisms involved in cardiac injury induced by diabetes mellitus (DM), pressure overload or both. Experimentally, HT was established in rats by supra-renal aortic banding. six weeks later, DM was randomly induced by streptozotocin (65mg/kg, ip), resulting in 4 groups: SHAM, banded (BA), diabetic (DM) and banded-diabetic (DM-BA). On the 12th week myocardial function was assessed in LV papillary muscles at baseline function and in response to isoprenaline (ISO, M). BA increased LV mass and cardiomyocyte diameter. DM induced myocardial fibrosis and AGES deposition, prolonged contraction (tat, tps) and promoted a delayed, but faster, relaxation (thr, dl/dtmax) In SHAM, ISO (10-5 M) increased 86±26% active tension, 105±20% dt/dtmax and 167±29.9% dt/dtmin. Similar effects were observed in BA and DM animals. DM-BA had blunted inotropic and lusitropic responses to β-adrenergic stimulation, but did not present more structural damages than diabetes alone (Table 1). Table 1 Parameter SHAM (n=39) BA (n=35) DM (n=37) DM-BA (n=27) thr (ms) 159±6 149±3 181±4 ab 199±15 ab tat (ms) 96±3 94±2 109±2 ab 122±7 abc PS (%Lmax) 0.07± ± ± ±0.01 abc tps (ms) 102±3 101±2 116±3 ab 122±3 ab dl/dtmax (Lmax/s) 1.06± ± ± ±0.10 a dl/dtmin (Lmax/s) -1.66± ± ± ±0.27 a thr: time for half relaxation; tat: time to active tension; PS: peak isotonic shortening; dl/dtmax, dl/dtmin: maximum velocity of shortening and lengthening. Means ± SEM. P<0.05: a vs sham, bvsbaandcvsdm. Moreover, at a similar resting muscle length, ISO decreased passive tension by 12±3% in SHAM and 11±3% in BA, indicating an increase in myocardial distensibility, an effect absent in both diabetic groups. In conclusion, longstanding pressure overload increased LV mass, while DM induced structural myocardial damages by promoting AGES and collagen deposition, which might explain the abolition of ISO-induced increase in myocardial distensibility. The association of pressure overload and DM completely blunted the inotropic and lusitropic responses to ISO. This study presents novel mechanisms on the effects of pressure overload, DM and their association on myocardial structure and function. P3384 Spontaneous activation of hypertrophic pathways in the heart of a novel human relevant mouse model of diabetes S. Gibbons 1, Z. Hegab 1,M.Zi 1, S. Prehar 1, D. Oceandy 1, M. Goldsworthy 2, E. Cartwright 1,R.Cox 2, M. Mamas 1, L. Neyses 1. 1 The University of Manchester, Manchester, United Kingdom; 2 Medical Research Council, Mammalian Genetics Unit, Harwell Science and Innovation Centre, Oxford, United Kingdom Animal models are key in the exploration of the pathophysiological mechanisms and complications of diabetes mellitus (DM). Most current models have considerable limitations in that they do not faithfully replicate human forms of DM and toxins used to induce DM may have cardiovascular actions unrelated to DM. Recently, a novel human relevant mouse model of diabetes (GENA 348) was identified through the MRC mouse mutagenesis programme in which a point mutation in the glucokinase (hexokinase 4) gene results in severely impaired glucokinase function and significant hyperglycaemia. Similar loss of function mutations in the glucokinase are known to underlie Maturity Onset Diabetes of the Young Type 2 in humans. We studied the GENA 348 mouse to determine whether it expresses a cardiac phenotype and so can be used to study the pathophysiological mechanisms underlying the development of diabetic cardiomyopathy. Western blots of livers from GENA 348 showed a 74% reduction in glucokinase expression in the liver (P<0.05). 15 wild type (WT) and 8 Homozygote (HO) mutant GENA 348 mice had serial echocardiography performed at 3 and 6 months. At 3 months no evidence of cardiac hypertrophy or contractile dysfunction was demonstrated in HO compared to WT mice. By 6 months of age, echo demonstrated development of cardiac hypertrophy in HO mice characterised by a 16% increase in left ventricular mass/body weight (wt 4.28±0.15 vs HO 4.95±0.26, P<0.05), a 25% increase in dpw/dd (wt 23.3±1.0 vs HO 29.1±1.1, P<0.01), an 18% increase in left ventricular relative wall thickness (wt 0.45±0.01 vs HO 0.53±0.02, P<0.05) and a 16% increase in left ventricular diastolic posterior wall thickness (wt 1.1±0.04 vs HO 1.28±0.06, P<0.01). No differences in ejection fraction were observed. Western Blot analysis of cardiac tissue demonstrated 140% increase in Akt phosphorylation, a known mediator in the hypertrophic signaling cascade but no changes in phosphorylation of Erk1/2. Advanced Glycation End products (AGEs) mediate many of the complications of diabetes, we observed a 44% upregulation in RAGE (receptor for AGEs) expression. In conclusion, GENA348, a novel human relevant mouse genetic model of DM display cardiac hypertrophy with Akt activation and increased RAGE expression. Given that RAGE is known to activate PI3 kinase, which itself can phosphorylate Akt it is possible that the RAGE/PI3K/Akt pathway may provide the molecular mechanism associated with the cardiac phenotype. GENA 348 may thus provide a human relevant valuable tool to study the molecular determinants of DM related cardiovascular complications. P3385 Major cardiopulmonary defects of Caveolin-1 disrupted mice are caused by a dysfunctional endothelium C. Wunderlich, A. Schmeisser, M. Kasper, M. Forkmann, N. Steinbronn, A. Brandt, R.H. Strasser. Herzzentrum Dresden Universitaetsklinik, Dresden, Germany Recently generated Caveolin-1 deficient mice (cav-1-/-) display various physiological alterations such as severe heart failure and lung fibrosis. The underlying mechanism for the adverse cardiopulmonary phenotype remains to be illuminated. A plethora of biochemical and genetic data support the role of cav-1 as a negative regulator of agonist-mediated enos activation. Accordingly, constitutive enos hyperactivation was observed in cav-1-/-. Given the hyperactivated enos enzyme we hypothesized that disturbed enos signalling is involved in the evolution of the cardiopulmonary pathologies in cav 1-/-. By virtue of biochemical, morphologic und hemodynamic studies we analyzed cav 1-/- and respective wild types without and with oral supplementation of tetrahydrobiopterin (BH4) which acts as an essential enos cofactor. The present study provides evidence for an enhanced radical stress originating from the endothelium of cav-1-/-. BH4 administration to cav-1-/- resulted in significantly reduced superoxide formation, and as shown here for the first time in substantial improvements of both systolic and diastolic heart function and in a marked amelioration of the severe lung phenotype. Notably, the antioxidant tetrahydroneopterin which is not essential for enos function showed no effect. Taken together these novel findings indicate that a dysfunctional enos is of central importance in the genesis of the cardiopulmonary phenotype in cav-1-/- mice. Additionally, these findings are generally of paramount importance since they underline the deleterious role of an uncoupled enos in cardiovascular pathology and thus argue for an important interaction of the endothelium with the myocardial tissue. Additionally, our data suggest BH4 as an effective cure therewith suggesting a novel therapeutic strategy in this specific cardiomyopathy. P3386 Increased NADPH-oxidase activity and alterations in antioxidant enzymes in the right and left ventricle from human failing heart E. Borchi 1,V.Bargelli 1, F. Stillitano 1, C. Giordano 2,G.D Amati 2, E. Cerbai 1, C. Nediani 1. 1 University of Florence, Florence, Italy; 2 La Sapienza Universita, Rome, Italy Purpose: During pathophysiological conditions, the balance between reactive oxygen species (ROS) and antioxidants may shift towards a relative increase of ROS resulting in oxidative stress. Conflicting data are available on antioxidant defences in human failing heart and they are limited to the left ventricle. We aimed to investigate and compare a major source of ROS, a NADPH oxidase system, and antioxidant enzyme activities in the right (RV) and left (LV) ventricles of human failing hearts. Methods: The molecular and biochemical analyses were performed in RV and LV from non failing (NF) (n=5) and failing hearts secondary to idiopathic dilated cardiomyopathy or ischemic heart disease (n=13). NADPH oxidase activity, as major source of ROS, was determined by lucigenin-enhanced chemiluminescence and NOX2 and NOX4 gene expression by RT-PCR. The analysis of catalase (CAT), glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD) was performed by measuring their mrna (by real-time PCR) and protein levels (by Western blotting) as well as their enzymatic activities (by spectrophotometric methods). The level of lipid peroxidation was evaluated by measuring the contents of malonildialdheyde (MDA). Results: A significant increase in NADPH oxidase activity was found in both failing ventricles, more marked in RV. As for antioxidant enzymes, despite un-

277 Heart failure models and mechanisms 577 changed mrna or protein expression, the enzymatic activity of CAT and GPx was increased, whereas Mn-SOD activity appeared decreased. We attributed the changes in catalytic activity of these antioxidant enzymes to post-translational modifications (notably, tyrosine phosphorylation). The increase in NADPH oxidase activity positively and significantly correlated with the activation of both CAT and GPx. However, the slope of the linear correlation (m) was steeper in LV than in RV for GPx (LV: m = 2.416; RV: m = 1.485) and CAT (LV: m = 1.007; RV: m = 0.354). MDA levels, measured as an indirect index of oxidative stress, were significantly higher in the RV than LV. Conclusions: We concluded that in human failing RV and LV, oxidative stress was correlated to activation of antioxidant enzymes CAT and GPx. This activation appeared less evident in RV than LV. Thus, although qualitatively similar changes appeared in both the RV and LV of the same hearts, our data suggest a reduced protection of RV against oxidative stress damage and support the involvement of the right ventricle in the pathophysiology of heart disease. P3387 Heart failure and nucleocytoplasmic transport R. Cortes, E. Rosello-Lleti, M. Rivera Otero, L. Martinez-Dolz, A. Salvador, M. Portoles. Hospital La Fe, Valencia, Spain Purpose: The role of nucleus in the development of heart failure (HF) is unknown, so the objectives of this study were to analyze the effect of HF on the bidirectional nucleocytoplasmic transport. Therefore, we have determined the levels of the several proteins involved in this process: importin-β3 (IMP-β3), importin-α2 (IMP-α2), the exportin-1 (EXP-1), the exportin-4 (EXP-4), and Ran regulators (RanGAP1, RanGAP1u and RanBP1). Methods: A total of 53 human samples (mean age 49±12 years, 94% men) from ischemic (ICM, n=31) and dilated (DCM, n=16) patients undergoing heart transplant, and control donors (CNT, n=6) were analyzed by western blot techniques. Results: When we compared nucleocytoplasmic protein levels between HF and CNT hearts, we obtained that the four molecules (IMP- β3, IMP- α2, EXP-1, and EXP-4) were significantly increased in pathological samples (264±93 vs. 100±12 au, p<0.0001; 163±43 vs. 100±30 au, p=0.002; 293±130 vs. 100±24 au, p<0.0001; 169±69 vs. 100±25 au, p=0.001, respectively). Then, to compare protein levels according to etiology of HF, ICM hearts showed higher levels of IMP-β3 (250±89 vs. 100±12 au, p<0.0001), IMP-α2 (169±41 vs. 100±30 au, p=0.001), EXP-1 (278±137 vs. 100±24 au, p=0.007), and EXP-4 (181±68 vs. 100±25 au, p=0.014) than those in the CNT group. Furthermore, DCM hearts showed significant differences for IMP-β3 (292±95 vs. 100±12 au, p<0.0001), IMP-α2 (152±95 vs. 100±30 au, p=0.030) and EXP-1 (328±109 vs. 100±24 au, p<0.0001), compared to CNT group. There were not any significant differences in nuclear protein levels between the two etiologies of HF. Finally, we obtained that RanGAP1 and RaGAP1u were significantly increased according to etiology of HF: ICM (176±74 vs. 100±33 au, p=0.009; 151±72 vs. 100±25 au, p=0.009) and DCM (141±39 vs. 100±33 au, p=0.042; 150±48 vs. 100±25 au, p=0.003) compared to CNT hearts. But there were no differences for RanBP1. Conclusions: This study shows important alterations in the nucleocytoplasmic transport in heart failure, such as higher levels of importins, exportins and Ran regulators in ischemic and dilated human hearts compared to control group. This fact is closely related with the cardiomyocyte nucleocytoplasmic capability of repair in heart failure. P3388 Cardiac hypertrophy with ventricular preexcitation and glycogen accumulation in transgenic mice with activated polyamine catabolism M.J. Merentie 1,E.Pirinen 1, M. Hedman 2, J. Lipponen 3, A. Virkamaki 4,J.Kuusisto 2, S. Yla-Herttuala 1, M. Laakso 5. 1 A.I.Virtanen Institute for Molecular Sciences, Kuopio, Finland; 2 Kuopio University Hospital, Cardiology Unit, Kuopio, Finland; 3 Department of Physics, University of Kuopio, Kuopio, Finland; 4 Minerva Foundation Institute for Medical Research, University of Helsinki, Helsinki, Finland; 5 Department of Medicine, University of Kuopio, Kuopio, Finland Mutations in the human γ2 subunit of AMP -activated protein kinase (AMPK) are involved in the development of a hypertophic cardiomyopathy associated with excessive glycogen storage that results in the development of Wolff-Parkinson-White (WPW) syndrome, characteristic of which is ventricular preexcitation and tachycardias. Previously it has been shown, that spermidine/spermine N 1 -acetyltransferase (SSAT) transgenic mice exhibiting activated polyamine catabolism have increased heart weight and marked changes in energy metabolism. The aim of this study was to elucidate the cardiac function in SSAT transgenic mice. Echo- and electrocardiography (ECG) was performed in female SSAT (tg) and wild-type (wt) mice with high-resolution ultrasound designed for small animals. The ECG data was further analyzed with Kubios HRV analysis program. The renal perfusion was studied with high resolution CPS ultrasound. Blood pressure was measured with a tail-cuff system. Quantitative PCR was used to determine cardiac gene expression levels and microfluorometric analysis for glycogen content. The pumping ability of left ventricle (LV) was impaired in tg mice, since ejection fraction was significantly decreased (58±4 vs. 72±4%, p<0.001 t-test). Based on M-Mode measurements the LV mass (5.9±0.7 vs. 5.1±0.1 mg/g, p<0.05), LV end diastolic diameter (4.1±0.3 vs. 3.6±0.1 mm, p<0.01) and LV end systolic diameter (2.9±0.1 vs. 2.2±0.1 mm, p<0.001) were significantly increased. ECG recordings exhibited shorter PR interval (33.8±6.7 vs. 39.2±5.6 ms, p=0.09) and increased QRS duration (23.0±6.7 vs. 16.0±1.4 ms, p<0.01) in tg mice. Renal cortex perfusion was reduced in tg mice (0.82±0.05 vs. 0.95±0.03 cortex/artery ratio, p<0.01) and systolic and diastolic arterial blood pressure were decreased (94±16 vs. 128±6 mmhg, p<0.01; 58±12 vs. 89±6 mmhg, p<0.01, respectively). Glycogen content in the myocardium was increased (66±21 vs. 35±14 mmol/g protein, p<0.001) and cardiac AMPK γ2 subunit mrna level decreased in SSAT mice compared to wt mice (0.72±0.02 fold to wt, p<0.001). Activation of polyamine catabolism leads to downregulation of cardiac AMPK γ2 subunit and excessive cardiac glycogen resulting in left ventricular hypertrophy and preexcitation similar to WPW syndrome. P3389 Left ventricular torsion decreases after alcohol septal ablation in hypertrophic obstructive cardiomyopathy patients W. Brouwer, F.D.B. Tammer, I.K. Russel, T. Germans, M.J.W. Gotte, A.C. Van Rossum. VU University Medical Center, Amsterdam, Netherlands Objective: To determine the amount of left ventricular (LV) torsion in hypertrophic obstructive cardiomyopathy (HOCM) patients, before and 6 months after alcohol septal ablation (ASA). Background: Increased LV torsion, the overall twisting of the heart, has been observed in patients with localized (asymmetrical) hypertrophy (1) and concentric hypertrophy (2). Remote (non-septal) hypertrophy is frequently observed in HOCM patients with significant outflow tract obstruction (LVOT). ASA not only reduces the LVOT pressure gradient, but is also associated with regression of hypertrophy in non-septal regions (3). It is hypothesized that a reduction in cardiac mass modifies LV torsion. Methods: Eight symptomatic HCM patients (51±11years, 6 male) and 17 healthy subjects (38±13 years, 8 male) were studied. CMR cine imaging and tissue tagging prior to and 6 months after the ASA procedure was performed to determine LV mass and volume, and to calculate LV torsion (defined as the circumferentiallongitudinal shear angle) (4). Volume and torsion were compared before and after treatment using paired Student s T-test. Results: Significant regression in LV mass (from 219±95 g to 183±81 g, p=0.02) and LV end diastolic volume (EDV from 152±84 ml to 129±65 ml, p=0.04) occurred at follow-up. Torsion in patients was decreased after ASAtreatment (13.3±3.5 vs 11.7±5.2, p=0.03), but still increased compared to controls (11.7±5.2 vs 7.7±1.4, p=0.001). Conclusion: Torsion becomes reduced after alcohol septal ablation in HOCM patients. However, torsion still remains higher in HCM patients compared to healthy subjects. Discussion: ASA therapy in HOCM patients is associated with global reversed remodeling including a significant reduction in cardiac mass and volume. It can be hypothesized that restored perfusion due to reduced wall stress and wall thickness, contribute to an improvement in contractile function of predominantly the subendocardial myofibers. Improved subendocardial contraction counteracts subepicardial contraction and therefore reduces the amount of torsion. P3390 Exercise training delays cardiac dysfunction, inhibits autophagy and improves the fatty acid uptake on post-infarction left ventricular remodelling in the rabbit C.Y. Chen 1,B.C.Lee 2,H.C.Hsu 2,M.F.Chen 2. 1 National Taiwan University, Taipei, Taiwan; 2 National Taiwan University Hospital, Taipei, Taiwan Aims: We investigated the effect of exercise training on autophagy and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. Methods: Adult male New Zealand White rabbits (2.5 3 kg) were randomly assigned to one of two experimental groups: control (N) and MI (L). Myocardial infarction was induced by ligation of the left anterior descending coronary artery. After 4 weeks of MI, control and post-mi rabbits were assigned to either untreated (NE) or 4-weeks of a treadmill exercise protocol (LE; 30 min, 5 days/wk), then sacrificed. Results: Eight weeks of MI treatment resulted in a significant decrease in the LV ejection fraction (LVEF); whereas exercise training caused an improvement in the LVEF of MI rabbits (N vs L vs LE: 64.3±3.4, 40.1±3.6, 53.4±4.8%, respectively). The protein expression of autophagosomal membrane specific protein LC3II/LC3I in MI rabbit heart was 2.1 folds of the control group, and exercise training significantly decreased the LC3II/LC3I expression in the MI rabbit hearts. MI treatment caused downregulation of heart-type fatty acid binding protein (h-fabp) and total antioxidant capacity, and upregulation of lipid peroxidation and 3-nitrotyrosine in the heart tissue. The downregulation of h-fabp by MI treatment was reversed by exercise training. Exercise training had no effect on the regulation of lipid peroxidation and total antioxidant capacity in the MI heart. Conclusion: Collectively, we provide evidence that downregulation of autophagy and improvement of fatty acid uptake on exercise training could be, at least in

278 578 Heart failure models and mechanisms Figure 1. LC3 and fatty acid uptake in the heart part, compensatory mechanisms against deteriorating ventricular function in myoinfarcted heart. P3391 Depressed contractile function, SERCA-activity and reduced T-tubule density in myocytes isolated from the free left ventricular wall from patients with post-infarction heart failure M. Hoydal 1, I. Kirkeby-Garstad 1,A.Karevold 1,R.Haaverstad 1, A. Wahba 1,O.J.Kemi 2, Ø. Ellingsen 1, G.L. Smith 2,U.Wisloff 1 on behalf of Cardiac Exercise Research Group, Trondheim Norway. 1 Norwegian University of Science and Technology, Trondheim, Norway; 2 University of Glasgow, Glasgow, United Kingdom Purpose: Most cellular and molecular data for depressed cardiac function in man comes from well-established animal models and biopsies from transplant hearts (end-stage heart failure). These studies suggest impaired SERCA-2 activity and reduced T-tubule density as central mechanisms behind a failing heart. The aim of the present study was to determine SERCA-function in tissue samples, and contractile function, calcium handling and T-tubule density in cardiomyocytes isolated from free left ventricular wall in patients with- and without post-infarction heart failure (post-mi HF-patients) undergoing coronary artery bypass graft (CABG). Methods: 10 (63±6 years) patients without myocardial infarction and an EF>50 and 10 (69±5 years) post-mi HF-patients with EF<30 (NYHA 2-4) scheduled for CAGB were included. Small muscle biopsies were taken during the surgery. One small sample was processed for measurements of SERCA-activity whereas one was used for enzymatic cell isolation and one saved for molecular analysis. Tissue and cardiomyocytes were studied using fluorescence and confocal imaging. Results: Cardiomyocyte shortening was similar between groups at 0.5Hz (i.e. 30 beats/min), but in contrast to cardiomyocytes from heart with normal EF, we found a negative shortening-frequency relation in cardiomyocytes from failing hearts. At 2 Hz stimulation, cardiomyocyte shortening was clearly depressed (p<0.001) in post-mi HF. Diastolic calcium was increased (p<0.01), calcium amplitude 45% lower, and time to peak contraction and time to relaxation were slower at all stimulation frequencies (p<0.01) in cardiomyocytes from post-mi HF-patients. Synchrony of calcium release is closely linked to the density and organization of T- tubules in the cardiomyocyte. We found that the T-tubule density was reduced by 35% in myocytes from post-mi HF patients, which may contribute to the slower time to calcium release and lower amplitude. The rate of calcium removal via SERCA was 35% slower in tissue from post-mi HF-patients (p<0.01), which may explain the prolonged time to calcium removal and time to relenghtening in cardiomyocytes from failing hearts. Conclusion: This study demonstrate that patients selected for CAGB with post- MI HF have impaired cardiomyocyte function and depressed calcium handling. Reduced T-tubule density contributes to reduced calcium release and hence reduced cardiomyocyte shortening. Impaired SERCA function influence upon calcium removal and thereby relaxation during diastole. The findings substantiate that impaired SERCA-2 function and reduced T-tubule density is central mechanisms behind heart failure. P3392 Brain natriuretic peptide protects cardiac and skeletal muscle mitochondrial respiratory chain against Doxorubicin -induced deleterious effects through mitochondrial K-ATP channel opening A.P. Di Marco, J. Bouitbir, J. Zoll, S. Talha, A.L. Lang, I. Enache, V. Goldbarg, F. Piquard, B. Geny. Hopital Civil de Strasbourg, Strasbourg, France Objectives: The anticancer agent doxorubicin (DOX) induces oxidative stress via redox cycling of the drug on the mitochondrial respiratory chain. We hypothesized that brain natriuretic peptide (BNP) potential protection might be obtained through reduced oxydative stress, increased biogenesis and opening of mitochondrial KATP channels. Methods: Fifty-two rats were divided into 4 groups: the control group (n=10) received isotonic saline, the DOX group (n=14) received 20 mg/kg intraperitoneal doxorubicin, the DOX BNP group (n=16) received 5 mg/kg of BNP subcutaneously 1 hour before injection of 20 mg/kg doxorubicin, and the fourth group DOX-BNP-5HD (n=12) received 5 hydroxydecanoate (5HD), a specific inhibitor of mitochondrial ATP-sensitive (KATP) channels, 10 minute before BNP injection (5 mg/kg) followed by the administration of 20 mg/kg DOX 1 hour later. Analysis were performed 24 hours after DOX. Maximal oxidative capacities (Vmax) of the muscle and complexes I, II and IV of the mitochondrial respiratory chain were determined using glutamate-malate (Vmax), succinate (Vs) and TMPD-ascorbate, as substrates. Muscle superoxide anion content was determined by dihydroethidium staining. Expression of genes involved in mitochondrial biogenesis, oxidative stress and apoptosis was determined by q-rt-pcr. Results: DOX reduced Vmax (-25%, 22.5±1.94 and -40%,4.8±0.3; p<0.001 in the heart and gastrocnemius, respectively) as compared to control values (29.8±3.4 and 8.1±0.6 μmol O2/min/g dry weight). Vs and VTMPD were also impaired. DOX increased significantly DHE by 94% and 234%, reduced biogenesis (Sirt 3, PGC1) and antioxidant enzyme (SOD2) and increased apoptosis (Bax/Bcl2 ratio) in both muscles. 5HD counteracted the protective effects of BNP in the heart and in the gastrocnemius (Vmax 7.4±0.4 and 5.1±0.4 μmol O2/min/g dry weight in BNP and DOX-BNP-5HD groups). Similar data were observed concerning DHE and mitochondrial biogenesis and apoptosis. Conclusions: DOX significantly impaired the mitochondrial respiratory chain of the heart but also of the skeletal muscle, altering preferentially complex I and II activities. This was associated with increased oxidative stress and apoptosis and with reduced mitochondrial anti-oxydant defence and biogenesis. Preconditioning with BNP prevented such alterations likely by opening mitok-atp channels. Thus, stimulating the endocrine heart might be of value in patients with cancer, treated with DOX. P3393 Increased rho kinases (ROCKs) activity in patients with heart failure C.M. Yu 1,M.Dong 1,R.J.Li 1, M. Zhang 1, Q.H. Zhang 1,J.K.Liao 2. 1 The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China, People s Republic of; 2 Vascular Medicine Research Unit, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America Background: Rho-kinases (ROCKs) are the first and the best-characterized effectors of the small G-protein RhoA, and have been suggested to play a role in enhanced vasoconstriction in animal models of heart failure (HF). It is unknown whether ROCK activity is increased in patients with HF, which was examined in the current study. Methods: 178 HF patients and 35 matched controls were studied. HF patients were divided into 4 groups: HF with normal ejection fraction (EF) (55% EF) (n=70), HF with mildly reduced EF (40% EF<55%) (n=52), HF with moderately reduced EF (25% EF<40%) (N=40) and HF with severely reduced EF (EF<25%) (n=16). ROCKs activity was determined by phosphorylation of myosin binding subunit in leukocytes from peripheral blood. Results: ROCKs activity was significantly increased in HF patients than controls (2.92±0.87 vs 1.54±0.45, p<0.001). It was further increased in the HF patients with moderately (3.09±0.65) and severely (3.48±1.36) reduced EF groups than HF patients with normal (2.75±0.85) or mildly reduced (2.88±0.74) EF groups (all p<0.05). In univariate analysis, ROCKs activity correlate positively with EF on admission, heart rate, creatinine, white blood count, Six-minute Hall-Walk distance, smoking status, CHF status (acute or stable), presence of heart failure features on admission, dyspnea at rest, history of HF, as well as history of ischemic heart disease. Multiple linear regression analysis showed that dyspnea at rest (β=0.367, p=0.000), creatinine (β=0.254, p=0.003), smoking status (β=0.201, p=0.032) and EF (β=0.231, p=0.017) were independent predictors for ROCKs levels (R 2 =0.383). Conclusion: ROCKs activity was increased in HF patients, in particular those with EF<40%. The pathophysiological role of ROCKs activity in HF warrants further investigation. P3394 YB-1 prevents ventricular cardiomyocytes from TGFbeta induced apoptosis B. Meyering 1, S. Partsch 1, J. Heger 1, H.M. Piper 2,G.Euler 1. 1 Universitaet Giessen Physiologisches Institut, Giessen, Germany; 2 Heinrich-Heine University, Düsseldorf, Germany The transition of compensated hypertrophic growth to heart failure goes along with an enhanced expression of the apoptosis inducing cytokine TGFβ. In adult cardiomyocytes of rats, TGFβ induction results in activation of transcription factors from the SMAD and AP-1 families and causes apoptosis. We now generated an adenovirus (AdYB-1) for overexpression of YB-1, which is a SMAD signalling repressor, and analyzed its effect on apoptosis. Isolated cardiomyocytes of rat were infected with 1000 MOI (multiplicity of infection) of AdYB-1. After infection, overexpression of YB-1 mrna increased to 205±23% after 12 h and to 2506±633% after 24 h (n=6, p < 0.05). YB-1 protein expression increased to 150±13% after 12 h and to 1816±417% after 36 h (n=6, p < 0.05). Infection of cardiomyocytes with AdYB-1 or the control virus AdGFP for 24 h or 48 h did not influence mrna expression of SMAD isoforms as analyzed by realtime PCR. To investigate, if infection of cells with AdYB-1 has an influence on cell survival, we analyzed apoptosis and necrosis. The rate of apoptotic or necrotic cells did not increase when cardiomyocytes were infected with 1000 MOI AdYB-1 or AdGFP for 24 h (n=10) or 48 h (n=6). However, overexpression of YB-1 reduced apoptosis induction in TGFβ stimulated cardiomyocytes: When AdYB-1 infected cells were incubated with TGFβ (1ng/ml), the number of