Cardiovascular Medicine

Kardiovaskuläre Medizin / Médecine cardiovasculaire

supplementum 20 ad cardiovascular Medicine 2011;14(5) 25 May 2011 www.cardiovascmed.ch

Jahrestagung der schweizerischen gesellschaft für Kardiologie (sgK)

gastgesellschaften: schweizerische gesellschaft für sportmedizin (sgsm) schweizerische gesellschaft für pädiatrische Kardiologie (sgpK) schweizerische gesellschaft für herz- und thorakale gefässchirurgie (sghc) schweizerische hypertonie gesellschaft (shg) swiss cardiovascular therapists (sct) schweizerischer verein für pflegewissenschaften (vfp)

assemblée annuelle de la société suisse de cardiologie (ssc)

sociétés invitées: société suisse de médecine du sport (ssms) société suisse de cardiologie pédiatrique (sscp) société suisse de chirurgie cardiaque et vasculaire thoracique (sscc) société suisse d’hypertension (ssh) swiss cardiovascular therapists (sct) association pour les sciences infirmières (apsi)

Basel, 8.–10. Juni 2011

official journal of the swiss society of cardiology, the swiss society of hypertension, the swiss society of angiology and the swiss society of paediatric cardiology impressum

Cardiovascular Medicine www.cardiovascmed.ch Official journal of the Swiss Society of Cardiology, the Swiss Society of Hypertension, the Swiss Society of Angiology and the Swiss Society of Paediatric Cardiology Kardiovaskuläre Medizin / Médecine cardiovasculaire

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G A I C editors

Editors in chief Section editors: Section editors: Section editors: Editors Thomas F. Lüscher, Zürich Images in cardiovascular The new compound The interesting ECG Paul Erne, Luzern René Lerch, Genève medicine Jérôme Biollaz, Lausanne Michael Kühne, Basel Augusto F. Gallino, Bellinzona Alain Delabays, Morges Georg Noll, Zürich Jürg Schläpfer, Lausanne Lukas Kappenberger, Lausanne Deputy editors Michel Zuber, Luzern Bernhard Meier, Bern Georg Noll Section editor: Section editors: Matthias Pfisterer, Basel Jan Steffel The new device Evidence-based Hans Rickli, St. Gallen Haran Burri, Genève cardiology Christian Seiler, Bern Stephan Windecker, Bern Heiner Bucher, Basel Bernard Waeber, Lausanne Jens Hellermann, Altstätten Jörg Muntwyler, Kloten editorial Board

D. Atar, Oslo F. Cosentino, Rom D. Keller Lang, Zürich J. Philippe, Genève U. Sigwart, Genève E. Battegay, Zürich H. Darioli, Lausanne P. Kaufmann, Zürich O. Ratib, Genève L. Spieker, Grenchen O. Bertel, Zürich J. Deanfield, London B. Kwak-Chanson, Genève T. J. Resink, Basel P. Suter, Zürich M. G. Bianchetti, Bellinzona F. Eberli, Zürich M. Lachat, Zürich P. Rickenbacher, Bruderholz S. Ulrich, Zürich P. Bösiger, Zürich E. Eckhout, Lausanne R. Lehmann, Zürich W. Riesen, St. Gallen E. Valsangiacomo, Zürich F. R. Bühler, Basel U. Eriksson, Wetzikon F. Mach, Genève M. Roffi, Genève P. M. Vanhoutte, Hongkong M. Burnier, Lausanne D. Gämperli, Zürich M. Maeder, St. Gallen F. Ruschitzka, Zürich G. Vassalli, Lausanne P. Buser, Basel W. Häfeli, Heidelberg W. Maier, Zürich H. Saner, Olten/Bern G. K. von Schulthess, Zürich P. G. Camici, London D. Hayoz, Lausanne C. Marone, Bellinzona U. Scherrer, Lausanne L. von Segesser, Lausanne T. Carrel, Bern K. Jäger, Basel F. H. Messerli, New York, USA J. Schwitter, Zürich D. Shah, Genève R. Corti, Zürich A. Jaussi, Yverdon-les-Bains T. C. Moccetti, Lugano G. Zünd, Zürich R. Jenni, Zürich P. Mohacsi, Bern J. J. P. Kastelein, Amsterdam S. Osswald, Basel Z. S. Katusic, Rochester, USA G. Pedrazzini, Lugano impressum

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vorträge / présentations orales

Freie Mitteilungen 1 / communications libres 1

Mitral and repair 4 S

Freie Mitteilungen 2 / communications libres 2

Basic research 6 S

Freie Mitteilungen 3 / communications libres 3

Stent 8 S

Freie Mitteilungen 4 / communications libres 4

Risk factors 10 S

Freie Mitteilungen 5 / communications libres 5

Heart failure: new insights 12 S

Freie Mitteilungen 6 / communications libres 6

Acute coronary syndrome 15 S

Freie Mitteilungen 7 / communications libres 7

Imaging: technology, prognostics and “unusual exertion diseases” 17 S

Freie Mitteilungen 8 / communications libres 8

Clinical cases 20 S

Freie Mitteilungen 9 / communications libres 9

Pacing and ICD 23 S

Freie Mitteilungen 10 / communications libres 10

Basic research 26 S

Freie Mitteilungen 11 / communications libres 11

Coronary heart disease and auricular occlusion 28 S

Freie Mitteilungen 12 / communications libres 12

Clinical cases 30 S

Freie Mitteilungen 13 / communications libres 13

Aortic revalving and aortic dissection 33 S

Freie Mitteilungen 14 / communications libres 14

Imaging 35 S

Freie Mitteilungen 15 / communications libres 15

Arrhythmias and ablation 37 S

Cardiovascular Medicine 2011;14(5): Suppl 20 2 S inhalt / sommaire

poster / posters

Moderierte poster / posters modérés

P190–P207 39 S postergruppe 1 / groupe de posters 1

Pathophysiology / Molecular biology 46 S postergruppe 2 / groupe de posters 2

Rhythmology and pacemakers 51 S postergruppe 3 / groupe de posters 3

Congestive heart failure, valvular heart disease 57 S postergruppe 4 / groupe de posters 4

Coronary artery disease, PCI 64 S postergruppe 5 / groupe de posters 5

Risk factors, hypertension, epidemiology, rehabilitation, thromboembolism 72 S postergruppe 6 / groupe de posters 6

Cardiac imaging 77 S postergruppe 7 / groupe de posters 7

Clinical cardiology 86 S postergruppe 8 / groupe de posters 8

Cardiac surgery 92 S erstautorenverzeichnis / liste des premiers auteurs

100 S

Cardiovascular Medicine 2011;14(5): Suppl 20 3 S Freie mitteilungen 1 – communications libres 1 Mitral and aortic valve repair

28 29 Acute haemodynamic changes after percutaneous Correction of mitral regurgitation by MitraClip in non- repair responders to cardiac resynchronization therapy improves symptoms and promotes reverse remodeling O. Gaemperli, D. Sürder, P. Biaggi, D. Hürlimann, I. Buehler, D. Bettex, C. Felix, J. Grünenfelder, R. Corti (Zürich, Lugano, CH) A. Auricchio, W. Schillinger, S. Meyer, F. Maisano, R. Hoffmann, Aims: Percutaneous mitral valve repair (MVR) using the Evalve G. Ussia, G.B. Pedrazzini, J. van der Heyden, S. Fratini, C. Klersy, MitraClip device has recently been developed. This method O. Franzen for the PERMIT-CARE delivers a clip via atrial trans-septal puncture grasping the mitral Introduction: Moderate to severe functional mitral regurgitation leaflets and thereby creating a double orifice valve. The aim of the (MR) may persist after cardiac resynchronization therapy (CRT), present study was to assess immediate hemodynamic changes contributing to less/no response to CRT. Percutaneous repair with after MVR with the MitraClip device using right heart the MitraClip (MC; Abbott Vascular, Menlo Park, CA) has be catheterization. proposed as an additional therapeutic option in select patients Methods: Patients with moderate to severe (3+) and severe (4+) (pts) with significant MR (>2+). The Percutaneous Mitral Valve mitral regurgitation (MR) due to functional (62%), degenerative Repair in Cardiac resynchronization Therapy (PERMIT- CARE) an (26%) or mixed (12%) disease were selected. MitraClip investigator-initiated survey, evaluated the safety and efficacy of implantation was performed under general anesthesia with the MC, and the effect of this treatment on symptoms and left fluoroscopy and echocardiographic guidance. Hemodynamic ventricular remodeling as well as morbidity and mortality in CRT variables were obtained before and after MVR using standard non-responders. right heart catheterization and oximetry. Methods: Fifty-one severely symptomatic CRT non-responders Results: A total of 42 consecutive non-surgical patients (age, 72 (70 ± 9years, 86% male, 73% ischemic etiology) underwent MC ± 15 years, EuroSCORE 26 ± 15) underwent percutaneous MVR treatment to correct persistent moderate-to severe MR (MR >2+: between May 2009 and September 2010. Mean ejection fraction 100%). Mean logistic EuroSCORE was 29.7%. Most pts (92%) was 46 ± 18% and 35 (83%) patients were in NYHA functional had CRT with cardioverter-defibrillator backup (33 ± 26 months). class III–IV.Acute procedural success (reduction in mitral Changes in NYHA functional class, degree of MR, LV ejection regurgitation (MR) to grade 2+ or less) was achieved in 38 (90%) fraction (EF), and LV end-diastolic/end-systolic volumes (EDV/ patients. Mitral valve clipping reduced mean pulmonary capillary ESV) before and after (3, 6, 12 months) MC were recorded. wedge pressure (PCWP) (from 17 ± 7 to 12 ± 4 mm Hg), PCWP Mortality including cause of death was collected. v-wave (from 24 ± 12 to 16 ± 6 mm Hg) and, mean pulmonary Results: MR was judged to be moderate-to-severe in 46% and artery pressure (PAP) (from 30 ± 12 to 23 ± 5 mm Hg), and severe in 54%. In most pts, MR reduction was achieved with increased cardiac output (from 5.0 ± 1. 8 to 6.9 ± 1. 9 L/min) and either 1 (49%) or 2 MC (46%). There were 2 peri-procedural cardiac index (CI) (from 2.8 ± 1. 1 to 3.8 ± 1. 2 L/min/m2) (all p deaths.Table 1 shows the effect of MC on MR, NYHA functional <0.05). No changes in mean arterial pressure and left ventricular class, LVESV, LVEDV, and LVEF. Median follow-up was 14 months filling pressures were recorded. Hemodynamic response to MVR (25th-75th 8–17months). Overall 30-day mortality was 4.2%. was similar in patients with degenerative versus functional MR. There were 9 additional deaths (sudden: 1; cardiac: 5; non- Conclusion: In a heterogenous population with functional and cardiac: 3) during follow-up.The overall mortality rate during degenerative MR, percutaneous MVR with the Evalve MitraClip follow-up was 19.9 per 100 person years (95%CI 10.3–38.3). system lowers PCWP and PAP by 21% and 20%, respectively, Mortality primarily occurred within 6 months of treatment. and increases CI by 31%. Non-survivors were more frequently older, had more frequently a previous valvular surgery, a much higher logistic Euroscore and STS, much higher mean value of NT-pro-BNP, longer QRS duration, and a more dilated heart. Re-hospitalization occurred in 5 patients and was related acute HF de-compensation in 2. Conclusions: MR treatment with MC in CRT non-responders is feasible, safe, and a significant proportion of patients demonstrated improved functional class, increased LVEF and reduced ventricular volumes, thus complementing CRT. Prospective studies are warranted to evaluate appropriate timing of MR treatment with MC after CRT as well as long-term morbidity, mortality and clinical benefit.

30 Foldoplasty is a new and simplified technique for mitral valve repair that confers excellent long-term outcomes P. O. Myers, A.W. El Bardissi, M. Cevasco, L.H. Cohn (Boston, US) Objectives: Quadrangular resection with sliding valvuloplasty is currently the most common technique used for repair of the posterior leaflet of the prolapsed mitral valve. Folding valvuloplasty is a simplified repair that does not involve resection and reduces the effective height of the posterior leaflet. Here we describe the long term outcome of patients who underwent folding valvuloplasty at our institution.

Cardiovascular Medicine 2011;14(5): Suppl 20 4 S Freie mitteilungen 1 – communications libres 1 Mitral and aortic valve repair

Methods: From 2002–2010, 161 consecutive patients underwent occurred, but there was a moderate para- and transprosthetic folding valvuloplasty at our institution. Primary endpoints included regurgitation in one patient. In two patients an implantation of long-term survival, freedom from reoperation, and permanent pacemaker was required (7.7%). echocardiographic evidence of recurrent MR. Conclusion: Our results confirmed thefi ef cacy of the Perceval S Results: Median age was 61 ± 14 and 68 (42%) patients were sutureless aortic valve during short to mid-term follow up. male with 146 (90%) patients having greater than moderate- Shortening the cross-clamp and ECC times may help to improve severe MR. CPB and X-clamp times were 117 ± 40 and 83 ± 29, clinical outcome. respectively. In addition to folding valvuloplasty, mitral rings were used in 96% (n = 155) of patients with a median size of 38 mm (IQR 34 mm, 38 mm). There was 1 operative mortality. Long-term 32 follow-up was available for all patients at a mean of 3.0 ± 1. 9 Mitral valve repair in Marfan syndrome with a years. NYHA class decreased significantly from 2.0 ± 0.9 to specific focus on prophylactic aortic root replacement 1. 1 ± 0.4 (p <0.0001). Two patients required reoperative mitral valve repair in the follow-up period. Postoperative echocardio- S. Cherian, J. Jolou, A. Mohammed, H. Muller, M. Cikirikcioglu, grams were obtained in 142 (88%) patients at a mean of 1. 6 ± 1. 2 A. Kalangos (Genève, CH) years. Grade of MR decreased significantly from 3.8 ± 0.5 Objective: Mitral regurgitation (MR) could be the first (severe) to 0.8 ± 0.8 (trace-mild), (p <0.0001) with only five manifestation in Marfan Syndrome, even before the onset of patients (3%) having moderate MR at follow-up. aortic dilatation and aortic regurgitation (AR). We aimed to assess Conclusions: Folding valvuloplasty is durable and provides the efficacy of mitral valve repair using a biodegradable excellent structural and symptomatic results in patients with mitral annuloplasty ring, and to analyse the role of prophylactic aortic prolapse. Given the ease and reproducibility of this technique, root replacement in Marfan syndrome. it should be offered as a suitable alternative to quadrangular Methods: A10-year (2000 to 2009) retrospective analysis of a resection. single surgeon’s experience included 27 Marfan patients (22 males, 5 females), aged between 7 to 60 years (mean 35.3), with BSA ranging from 1 to 2.6 (mean 2.04). Pre-operative MR was Grade III or more in 27, NYHA Class was Grade II or more in 25, mean LVESD was 4.93, and LVEDD was 6.38. Mechanisms of mitral regurgitation were anterior prolapse in 4, posterior prolapse in 3, and bileaflet prolapse in 20. All patients underwent mitral annuloplasty using Bioring, with quadrangular resection in 12, artificial chordae in 16, chordal shortening in 5, secondary chordal transfer in 3, and anterior or posterior commissural closure in 11. Pre-operative AR was Grade 2 or less in 13, with mean diameters of aortic root, and ascending of 3.4 cms, and 3.2 cms respectively. 14 patients with aortic root diameter greater than the physiologic range for their corresponding BSA underwent prophylactic valve sparing aortic root replacement. Follow-up was complete in 26 patients, ranging from 1 to 9 years (mean 4.7 years). Results: Post-operative MR was Grade 0 in 18, and Grade I in 9, with no further progression during follow-up. Post-operative LVESD improved in 26 patients (mean 3.7), and LVEDD improved in 23 (mean 5.05). AR improved in 12 out of 13 patients, and NYHA class improved in 25. Aortic root replacement was required in 1 patient at 2 years for progressive root dilatation. There were no post-operative deaths. Conclusions: Marfan patients with mitral regurgitation can be successfully repaired, with good mid-term results. Simultaneous prophylactic aortic root replacement is safe and effective in preventing late complications.

33 31 Mitral valve repair using an intra-annular Sutureless Perceval S aortic valve replacement: annuloplasty ring first experience with the new device S. Cherian, J. Jolou, P. Myers, H. Muller, M. Licker, V. Göber, E. Roost, L. Englberger, T.P. Carrel, M. Stalder M. Cikirikcioglu, A. Kalangos (Genève, CH) (Bern, CH) Background: Since annular dilatation is a vital component of Background and aim of the study: The Sutureless Perceval S mitral regurgitation (MR), annular support is necessary to provide aortic valve is a new generation of Nitinol-stented bioprosthesis, adequate repair, and to optimize long-term results.We aimed to designed to replace a dysfunctional aortic valve using analyse the results of a new intra-annular annuloplasty ring in conventional open-heart surgery. Primary objective of this clinical patients undergoing mitral valve repair for various mitral trial was to assess the safety and effectiveness of this device. pathologies. A clinical and echocardiographic follow up was performed at Materials and methods: Between 2003 and 2010, 337 patients discharge, after 3 to 6 and 11 to 13 months. with MR underwent mitral valve repair using the biodegradable Methods: From April 2009 to December 2010, we implanted the Bioring annuloplasty ring (Bioring, Switzerland), that was inserted Perceval S aortic valve in 26 (mean age: 77 ± 5 years, 18 female, into the mitral annulus within the sub-endocardial plane, using 8 male) patients.All patients suffered from severe aortic stenosis an intra-annular implantation technique.The etiologies for MR (mean gradient 53 ± 15 mm Hg). Mean logistic EuroSCORE was included rheumatic disease in 115, Barlow’s disease in 90, 8.5 ± 4.3%. The implanted valve size was 21, 23 and 25 mm in congenital malformations in 61, mitral degeneration in 27, 38.5, 42.3 and 19.2% of patients, respectively. Coronary bypass ischemic mitral disease in 23, endocarditis in 13, Marfan grafting was performed in 10 patients (38.5%). syndrome in 7, and trauma in 1. Mean age of patients was 38.3 Results: Mean aortic cross-clamp and ECC times were 35 ± 11 years (range 1 to 85), and comprised of 182 males (54%). min and 52 ± 15 min, respectively. During postoperative The average implantation time was noted, and compared to hospitalisation 2 patients died (7.7%, not device related) and that of supra-annular annuloplasty rings. no death or reoperation occurred within follow up.Atotal of 15 Results: Moderate to severe MR was present in all patients patients was examined at 3 to 6 months following implantation, pre-operatively, which reduced to no, trivial or mild regurgitation in and 9 after 11 to 13 months. No migration of the device had 320 (94.9 %) at a mean follow-up period of 4.2 years (range

Cardiovascular Medicine 2011;14(5): Suppl 20 5 S Freie mitteilungen 1 – communications libres 1 Mitral and aortic valve repair

1–8 years). There were 4 deaths (1.18% mortality), with a 30-day None of the patients had ischemic complications associated with mortality of 2 (0.6%). Mitral valve re-operation was necessary in iatrogenic injury to the underlying coronary vasculature. 13 (3.8 %) rheumatic patients, at a median period of 6.7 months Conclusion: The intra-annular annuloplasty ring is safe, quick to from the time of initial repair. Implantation time was 10–12 implant, with advantages over supra-annular rings, and it provides minutes shorter than that for supra-annular rings. No post- acceptable mid-term results. operative anticoagulation was required in any of the patients.

Freie mitteilungen 2 – communications libres 2 Basic research

44 In vitro characterisation and induction of cultured in various DM (fig. B and C). Preliminary data show cardiomyogenic differentiation in mouse and human upregulation of the cardiac-specific genes cTnI. (fig B), and to cardiac stem cells a lesser extent actinin (fig. C) in selected cell subpopulations. Conclusions: Adult mouse and human harbours stem A. Spicher, P. Vogt, G. Vassalli (Lausanne, CH) cells that can be expanded for many passages, form Aim: Recent data suggest the adult mammalian heart harbours cardiospheres, and can be induced to express cardiac-specific cardiac stem cells (CSCs) endowed with regenerative potential. genes in vitro. These cells are of interest to heart regeneration. This study was aimed at assessing the growth characteristics, marker expression, and differentiation potential of mouse and human CSCs. 45 Methods: CSCs were derived from whole mouse hearts or human atrial appendage samples. Mouse cells expressing stem Pharmacological inhibition of nicotinamide cell antigen-1 (Sca-1) were sorted using magnetic immunobeads. phosphoribosyltransferase reduces neutrophil- Human cells were either sorted for the stem cell marker c-kit, the mediated injury in a mouse model of myocardial endothelial/vascular markers CD31 and CD164, or the stromal ischaemia/reperfusion progenitor-associated markers NG2, CD106 and CD318 using F. Montecucco, I. Bauer, V. Braunersreuther, S. Bruzzone, magnetic immunobeads. Human cell clones were isolated and A. Poggi, E. Mannino, G. Pelli, K. Galan, M. Bertolotto, expanded. Alternatively, CSCs were obtained using the primary S. Lenglet, A. Garuti, C. Montessuit, R. Lerch, C. Pellieux, explant technique. Marker expression was assessed by flow N. Vuilleumier, F. Dallegri, R. Mostoslavsky, F. Patrone, F. Mach, cytometry. Cardiomyogenic differentiation was induced by A. Nencioni (Genève, CH; Genva, IT; Boston, US) switching cells from growth medium to various differentiation Introduction: Nicotinamide phosphoribosyltransferase (Nampt) media (DM; see figure: Legend to the graphs). Cardiomyogenic is a key enzyme for nicotinamide adenine dinucleotide (NAD+) differentiation was assessed by real-time RT-PCR for cardiac- biosynthesis, which appears to fuel inflammatory processes. specific genes including Nkx2.5, MLC2v, troponin I (cTnI), actinin. Here, we investigated the potential effects of Nampt and its Results: Mouse Sca-1+ CD31- CSCs were expanded for more pharmacological inhibition with FK866 in a mouse myocardial than 25 passages.They were able to form free-floating spherical ischemia/reperfusion model. aggregates (cardiospheres) typical of stem/progenitor cells.When Methods: In vivo and ex vivo, left coronary artery ligature was cultured in DM, CSCs upregulated cardiac genes (Nkx2.5, performed in C57Bl/6 mice. Coronary occlusion was maintained MLC2v, and to a lesser extent cTnI). This effect was more for 30 min, followed by different times (up to 24 h) of reperfusion. pronounced in cardiosphere-derived cells (CDCs) than in cells not FK866 (Nampt inhibitor) or vehicle was administered forming cardiospheres. Clonogenic human CSCs derived from intraperitoneally 5 minutes and 12 h after coronary occlusion. c-kit+, CD31+ or CD146+ cells showed two distinct phenotypes: Infarct size was assessed histologically. Serum Nampt, cardiac an endothelial-like phenotype (CD31+ CD146+) and a stromal troponin I (cTnI), CXCL1, CXCL2, and CCL2 were determined by progenitor phenotype (CD90+ CD106+ CD31- CD146-). Both ELISA. In vitro, neutrophil chemotaxis and reactive oxygen phenotypes shared CD13, CD29, CD44, CD54 and CD105 species (ROS) production, CXCL8 (human homolog of murine expression. Human clones formed cardiospheres (fig.A). RT-PCR CXCL2) synthesis by human peripheral blood mononuclear cells analysis of CDCs showed upregulation of primitive genes (Mesp1, (PBMCs) and Jurkat cells were determined. SIRT6 was silenced Nanog, Sox2) consistent with cardiospheres being comprised of by RNA-interference. partially de-differentiated cells. Human CSCs sorted based on Results: Treatment with FK866 reduced myocardial infarct size, positive or negative NG2, CD106 and CD318 expression were neutrophil infiltration and reactive oxygen species generation within infarcted hearts.The benefit of FK866 was not shown in the Langendorff model (without circulating leukocytes), suggesting a direct involvement of these cells. Sera from FK-treated mice showed reduced circulating levels of neutrophil chemoattractant CXCL2 and impaired capacity to prime neutrophil migration. CXCL8 (human CXCL2 functional homolog) was also reduced by FK866, as well as by sirtuin inhibitors and SIRT6 silencing, implying a pivotal role for this NAD ± dependent deacetylase. Conclusion: Nampt inhibition appears as a new strategy to dampen CXCL2-induced neutrophil recruitment and thereby reduce neutrophil-mediated tissue injury.

46 Survival mechanisms of the myocardium challenged by cardiotoxic cancer therapies C. Zuppinger, M. Chiusa, P. Trütsch, S. Hool, T. Suter, S. Zbinden (Bern, CH) Introduction: Many of the cellular signaling pathways targeted by new cancer therapeutics are also important for the homeostasis of the myocardium and can have significant cardiovascular side effects.We studied the response of primary cardiac microvascular endothelial cells to anthracyclines (doxorubicin) or anti-angiogenic

Cardiovascular Medicine 2011;14(5): Suppl 20 6 S Freie mitteilungen 2 – communications libres 2 Basic research

therapy (sunitinib), and if factors released from these cells 48 improve the survival of cardiomyocytes in culture. IL-8-mediated angiogenic responses of endothelial Methods: Adult rat ventricular cardiomyocytes (ARVM) were cells to lipid-antigen activation of iNKT cells depend isolated by retrograde perfusion and cultured in serum-free on EGFR transactivation medium. Cardiac microvascular endothelial cells (CMEC) were isolated and cultured until confluence in medium with 20% serum E. Kyriakakis, M. Philippova, M. Cavallari, G. De Libero, and with 0.5% serum before treatment for 24 hours. Protein P. Erne, T. Resink (Basel, Luzern, CH) quantification was performed by Western Blot, gene expression Introduction: Invariant Natural Killer T (iNKT) cells are a unique by real-time, PCR, VEGF release was measured by a rat specific T cell subset that is CD1d-restricted and specific for glycolipids, VEGF ELISA-kit, cell death was measured by LDH- and MTT- including the marine sponge α-galactosylceramide (α-GalCer) and assay, and mitochondrial respiration by oxymetry. unidentified self-molecules. In advanced atherosclerotic plaques, Results: Treatment with anthracyclines at a clinically relevant focal collections of inflammatory cells correlate with areas of concentration (0.5–1 micromolar) led to VEGF A release through intraplaque neovascularization. We recently reported that iNKT HIF-1 α stabilization and the expression of pro-neuregulin-1 cells might facilitate intraplaque neovascularisation in an in CMEC.Treatment with sunitinib (7.5–30 nM) resulted in a interleukin-8 (IL-8)-dependent manner. Here we investigated significant increase in cell death both in CMEC and ARVM.In further participating signal transduction mechanisms. ARVM sunitinib caused a significantly decreased activity of Methods: EC were treated with conditioned medium derived from mitochondrial complex I and II already at 7. 5 nM of sunitinib as human iNKT cells activated (CM+) or not (CM-) by αGalCer and measured by high resolution oxymetry. ARVM did not answer to assayed for behavioural characteristics and signalling molecules doxorubicin-induced stress conditions by the release of VEGF. related to migration or . Preliminary data on the presence of VEGF-receptors in Results: CM+ stimulated phosphorylation of EGFR (epidermal cardiomyocytes demonstrated VEGFR2 (Flk-1) protein in ARVM, growth factor receptor) and several intracellular signalling but not VEGFR1 (Flt-1). Stimulation with recombinant VEGF-A, effectors including focal adhesion kinase (FAK), Src, extracellular- but not with VEGF-B, resulted in an activation of the MAPK- signal-regulated kinase, c-Jun N-terminal kinase, p38-mitogen pathway in ARVM as assessed phospho-specific antibodies. activated protein kinase and signal transducer and activator of Treatment with recombinant neuregulin-1 increased the transcription 1 and 3, suggesting activation of multiple signalling expression of the anti-apoptotic proteins bcl-2, GATA-4 and pathways. CM ± induced EGFR phosphorylation was blocked by ErbB2. EGFR-inhibition or IL-8 immunodepletion of CM+. Of the Conclusion: These results indicate that the angiogenic and signalling effectors activated by CM+ only FAK and Src were survival factors VEGF-A and neuregulin-1 are produced by CMEC sensitive to EGFR-inhibition or IL-8-immunodepletion. Functional challenged by cardiotoxic cancer therapy. The combined use of responses of EC to CM+, namely acquisition of angiogenic anti-angiogenic targeted therapies and anthracyclines may impair morphology, migration in 2D-wound assay and angiogenesis in a this crucial signaling crosstalk between endothelial cells and 3D-model in vitro were abolished by EGFR inhibitors cetuximab, cardiomyocytes and lead to further damage in the myocardium. gefitinib or lapatinib. Conclusion: IL-8-dependent activation of angiogenic behaviour in EC in response to lipid-antigen activation of iNKT may occur 47 via transactivation of EGFR and subsequent FAK/Src signalling. Impaired stimulation of glucose transport in cardiac EGFR inhibition represents a novel therapeutic modality aimed myocytes exposed to free fatty acids and VLDL at plaque stabilization through the control of neovascularization within developing atherosclerotic plaques. M. Asrih, M.C. Brulhart-Meynet, R. James, R. Lerch, I. Papageorgiou, C. Pellieux, C. Montessuit (Genève, CH) Aims: The Western diet is characterized by overconsumption of 49 fatty and sugary food, leading to a worldwide epidemic of obesity The single nucleotide connexin37 1019C >T and type II diabetes, termed “diabesity”. Diabesity increases not polymorphism is associated with drug-resistant only the prevalence but also the severity of myocardial infarction. idiopathic atrial fibrillation Stimulation of glucose transport in response to insulin or metabolic stress is an important determinant of cardiac myocytes S. Carballo, A. Pfenniger, K. Galan, P. -F. Keller, D. Carballo, function and survival, in particular during ischemia-reperfusion F. Mach, R.W. James, D. Shah, B.R. Kwak (Genève, CH) episodes and in infarction. The impact of the dyslipidemia present Background and objective: Atrial fibrillation (AF), the most in diabesity on stimulated glucose transport in cardiac myocytes common sustained cardiac arrhythmia, is thought to depend on a remains unknown. combination of abnormal impulse formation and conduction at the Methods: Isolated adult rat cardiac myocytes were chronically ostia of pulmonary veins (PV), where sheets of cardiomyocytes exposed to free fatty acids (FFA) or to Very Low Density and vascular smooth muscle cells (VSMCs) interdigitate. Lipoproteins (VLDL). Insulin- and metabolic stress (oligomycin)- However, the molecular mechanisms underlying this regional stimulated glucose transport (GluT) and related cell signaling specificity remain to be discovered. Connexins (Cx) are gap were analyzed. junction proteins playing an essential role in electrical propagation Results: Exposure of cardiomyocytes to FFA reduced both in the heart. Cx40 is expressed by endothelial cells, VSMCs and insulin- and oligomycin-stimulated GluT and increased fatty acid atrial cardiomyocytes, whereas Cx37 is found in endothelial cells oxidation. The reduction in insulin-stimulated GluT was associated and VSMCs only. Several polymorphisms have been described in with impaired insulin signaling and overexpression of SOCS-1, a both Cx genes, which may affect their expression or function and protein known to hinder proximal insulin signaling. In contrast the thus contribute to the arrhythmogenicity of the PVs.The sought reduction of oligomycin-stimulated GluT could not be explained to investigate an association between several single nucleotide by a reduced activity of the cellular energy sensing system, as polymorphisms and idiopathic AF. assessed from the maintained phosphorylation state of AMPK Methods: DNA was extracted from the peripheral blood of a total (the “cell fuel gauge”). Inhibition of fatty acid oxidation at the of 92 patients suffering from drugresistant, highly symptomatic, level of mitochondrial acylcarnitine uptake restored oligomycin- predominantly idiopathic/lone AF who were referred to the stimulated, but not insulin-stimulated, GluT, suggesting that Geneva University Hospitals for a percutaneous catheter ablation. inhibition of OSGT occurs downstream of energy gauging and is Ninety-four control subjects were matched for age, sex, caused by some intermediate(s) of fatty acid oxidation. Similarly, hypertension, diabetes, dyslipidemia and smoking. Genotyping of exposure of cardiomyocytes to VLDL reduced both insulin- and the Cx40 -44G>A and +71A>G polymorphisms and of the Cx37 oligomycin-stimulated GluT. Inhibition of cellular lipoprotein lipase 1019C>T polymorphism was performed by PCR and RFLP restored both stimulated glucose transport activities, indicating assays. that FFA released from VLDL by lipolysis mediate the effects of Results: Analysis of the two Cx40 polymorphisms showed an VLDL on cardiomyocytes. almost complete linkage disequilibrium of the -44G/+71A and Conclusions: Free and VLDL-derived fatty acids impair metabolic -44A/+71G alleles.The overall genotype distribution in the control stress-stimulated glucose transport in cardiomyocytes by a group was - 44GG/+71AA = 64.9%, -44AG/+71AG = 30.9% and mechanism that is mediated by a fatty acid oxidation intermediate. -44AA/+71GG = 4.3%, with no significant difference in the Thus, in vivo, the myocardium would be more susceptible to drug-resistant AF group (p = 0.88). The specific genotype ischemia and reperfusion injury in the clinical context of diabesity distribution of the Cx37 1019C>T polymorphism in the control because of reduced metabolic stress-stimulated glucose uptake.

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group was 1019CC = 47.9%, 1019CT = 31.9% and 1019TT = gene polymorphism. The effects of this polymorphism on Cx37 20.2%. This distribution was significantly different in the drug- channel function and regulation are currently being determined resistant AF group: 1019CC = 46.7%, 1019CT = 44.6% and and this may lead to a novel therapeutic approach for AF in which 1019TT = 8.7% (p = 0.04). cell-cell communication is targeted. Conclusions: Our study describes for the first time an association of drug-resistant idiopathic AF with the Cx37 1019C>T

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64 65 Vascular healing response five years after Benefits of drug-eluting stents in diabetic patients implantation of first generation drug-eluting stents: with large coronary artery stenting the SIRTAX LATE optical coherence study M. Wanitschek, R. Jeger, A. Hvelplund, D. Kurz, D. Weilenmann, L. Räber, S. Baumgartner, H. Garcia Garcia, T. Pilgrim, J. Justiz, P. Eberli, P. Bonetti, H.Alber, S. Galatius, M. Pfisterer, C. Kaiser B. Kalesan, P. Wenaweser, A. Moschovitis, R. Vogel, B. Meier, for the BASKET-PROVE-Investigators P. Jüni, P. -W. Serruys, S. Windecker (Bern, CH; Rotterdam, NL; Background: Drug-eluting stents (DES) reduce restenosis rates Biel, CH) especially in patients with diabetes mellitus (DM) and small Aim: Stent strut protrusion, malapposition and uncoverage have . Less is known about the effect and safety of been identified as risk factors for the occurrence of stent DES in DM patients with large coronary arteries (≥3.0 mm). thrombosis.Their prevalence during longterm follow-up is Methods: BASKET-PROVE, a prospective multicenter trial, unknown. The objective was to assess stent strut protrusion, enrolled 2314 patients in need for large coronary artery stenting coverage and apposition five years after implantation of sirolimus- (≥3.0 mm) only, irrespective of clinical indication, and randomized eluting (SES) and paclitaxel-eluting stents (PES) by optical them 2:1 to DES versus bare-metal stents (BMS). In an a priori coherence tomography (OCT) as part of the SIRTAX LATE study. planned secondary analysis, outcomes were evaluated in patients Method/Results: A total of 95 consecutive patients underwent with versus without DM with a primary endpoint of major adverse OCT at 5 year in one randomly selected lesion per patient and cardiac events (MACE: cardiac death, myocardial infarction, 88 patients were suitable for the final analysis.The OCT analysis target-vessel revascularization (TVR)) up to 2 years. A Cox was assessed by analysts blinded for stent type. Statistical proportional-hazard model was used to evaluate the relative risk analysis was performed using a hierarchical Bayesian random- for DM and NON-DM patients receiving either DES or BMS. effects model. The analysis was performed in 41 SES patients Results: DM was known in 363 (16%) patients. Compared to with 6,380 struts, and in 47 PES patients with 6,782 struts.Atotal NON-DM patients, those with DM were older, had more risk of 196 struts were uncovered in SES (1.5%) compared to 185 factors (except smoking) and more severe coronary disease. struts in PES lesions (1.0%, weighted difference 0.5%, 95% CI MACE-free survival was very similar for DM patients with DES as –0.5 to 1. 6, P = 0.32). In SES lesions 269 malapposed struts were for NON-DM patients with DES (HR 0.9 (0.5–1.7)), whereas that observed (1.2%) versus 140 in PES lesions (0.7%, weighted of NON-DM patients with BMS was worse (HR versus NON-DM difference 0.5%, 95% CI 0.03 to 1. 6, p = 0.23). Protruding struts with DES 1. 6(1.1–2.3)) and worst for DM patients with BMS (HR were more frequent among SES (n = 114, 0.8%) than PES versus NON-DM with DES 3.1(1.8–5.3)).These results were patients (n = 24, 0.1%, weighted difference 0.7%, 95% CI 0.3 driven by differences in TVR rates whereas rates of cardiac death to 1. 3, p <0.01). and myocardial infarction between DES and BMS were minimal. Conclusion: Longterm follow-up of first generation DES show Conclusions: BASKET-PROVE documents the beneficial no significant differences in strut coverage and malapposition long-term effect in safety and efficacy of DES also in DM patients between SES and PES but a higher rate of protruding struts with with large coronary artery stenting, a finding which contrasts to SES.The persistence of uncovered struts, and the differential in the comparatively bad outcome of DM patients treated with BMS. protruding struts suggests that vascular healing is not completed five years after implantation of first generation DES.

66 Impact of stent thrombosis on clinical outcomes revascularization (TLR) – was performed according to stent type among patients undergoing percutaneous coronary and association with ST. intervention with newer generation drug-eluting stents Results: Through one year, TLF associated with ST was more common with R-ZES than EES (RR 2.44, 95% CI 1. 02–5.87, G. Stefanini, B. Kalesan, P. Jüni, P. Vranckx, S. Silber, P = 0.05), which was mainly driven by a higher risk of clinically- P. Wenaweser, B. Meier, P. W. Serruys, S. Windecker indicated TLR associated with ST (RR 7. 04, 95% CI 1. 60–30.9, (Bern, CH; Hasselt, BE; München, DE; Rotterdam, NL) P = 0.01). There was a trend towards a higher risk of target-vessel Aim: Stent thrombosis (ST) is a rare but serious complication MI associated with ST among R-ZES treated patients (RR 2.26, of percutaneous coronary interventions, potentially resulting in 95% CI 0.70-7.33, P = 0.17), and no difference for cardiac death myocardial infarction (MI) or death. Although ST was more associated with ST (RR 1. 01, 95% CI 0.25–4.01, P = 0.99). common with zotarolimus-eluting (ZES) than everolimus-eluting Overall, the higher risks of TLF and TLR associated with ST were stents (EES) in the RESOLUTE All Comers trial, clinical fully compensated by numerically fewer TLF (RR 0.87, 95% outcomes through one year showed similar rates of mortality and CI 0.64–1.17, P_for interaction = 0.03) and TLR (RR 0.84, 95% MI. The aim of this analysis was to further investigate the impact CI 0.52–1.35, P_for interaction = 0.007) not associated with ST of ST on clinical outcomes in this large-scale all-comers trial. among R-ZES treated patients. Methods: The RESOLUTE All Comers trial included a total of Conclusions: Higher rates of ST with ZES than EES failed to 2292 patients.Ablinded clinical events committee reviewed all translate into differences in overall clinical outcomes.This adverse events contributing to the primary outcome target lesion observation is explained by the low rate of ST and the failure (TLF) and independently adjudicated their association compensatory effect of events not associated with ST.Therefore, with Academic Research Consortium definite or probable ST. ST should not be considered an independent endpoint outside A stratified analysis of TLF and its components – cardiac death, the overall clinical context. target-vessel MI, and clinically-indicated target lesion

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67 Long-term comparison of everolimus-eluting stents Methods: To define the importance of coronary disease with sirolimus-eluting stents in patients with acute progression, all 442 patients of the BASKET trial with successful coronary syndromes complete revascularization by stenting documented by lack of events up to 6 months and no ischemic perfusion defects (PD) L. Räber, G. Stefanini, S. Baldinger, S. Baumgartner, 6 months after the intervention (rest/stress SPECT study) were M. Schmutz, P. Wenaweser, A. Khattab, T. Pilgrim, followed prospectively and invited to undergo a 2nd SPECT study L. Büllesfeld, R. Vogel, B. Kalesan, C. Seiler, B. Meier, after 5 years. At baseline, patients were randomized 2:1 to DES P. Jüni, S. Windecker (Bern, CH; Rotterdam, NL) or bare-metal stents (BMS). Events and PDs were analyzed for Background: The long-term safety and efficacy of everolimus- target-vessel (TV) vs remote-vessel origin (remote indicating eluting stents (EES) has not been established among patients disease progression) and compared between patients with DES with acute coronary syndrome (ACS). Moreover, EES have not vs BMS. been directly compared with sirolimus-eluting stents (SES) in Results: During follow-up, 97/428 (22,6%) patients had 148 large scale clinical trials.We therefore compared the long-term clinical events: 43 (10%) died, 34 (8%) suffered a myocardial clinical outcome among ACS patients treated with either EES or infarct and 71 (17%) needed revascularization. Event rates were SES. significantly higher in TV versus remote areas (14.3% vs 9,8%, Methods: All ACS patients undergoing percutaneous coronary p = 0.019). Remote infarcts or revascularizations were not intervention (PCI) with EES between 12/2006 and 03/2009 different between DES and BMS patients (10.6% versus 8.3%; (N = 903) were identified, and clinical outcome compared with p = 0.5) A 2nd SPECT study performed in 206/331 (62%) patients 843 ACS patients treated with SES.The spectrum of ACS without follow-up events (125 did not consent) showed 48 (23,3%) (N = 1746 patients) comprised unstable angina (UA, 7%), new PDs, which were asymptomatic in 67% of patients. Remote Non-ST- elevation myocardial infarction (NSTEMI, 58%) and PDs accounted for 18/48 (37,5%) PDs with similar rates for DES ST-elevation myocardial infarction (STEMI, 34%). Using and BMS patients (9.2% vs 7. 7%, p = 0.8). propensity score matching, we obtained a total of 1,410 ACS Conclusions: In addition to 23% of patients with very late clinical patients with 705 matched pairs of patients treated with EES and events after successful stenting, another 23% had new PDs, of SES.The median follow-up was 1. 4 years. Hazard ratios which a majority was asymptomatic. These findings occurred in comparing EES and SES were calculated using Cox regression remote areas in more than one third of cases, similarly after DES analysis. and BMS implantation, indicating relevant symptomatic and silent Results: The median duration of prescribed dual antiplatelet disease progression. This underscores the importance of 2nd therapy was 12.0 months in both groups.The composite of death, prevention after stenting. MI or target vessel revascularization (TVR) occurred in 13.8% of EES and 17.7% of SES patients with ACS (HR = 0.72, 95% CI 0.54–0.95, p = 0.02). The difference in favor of EES was driven 69 by a lower rate of TVR (8.8% vs. 5.7%, p = 0.04), whereas rates of death (8.8% vs. 7. 2%, p = 0.10) or MI (3.3% vs. 2.1%, p = 0.10) Implantation of a cell-polymer biograft for cardiac were similar.The risks of ARC definite (0.4%. vs 1. 8%, p = 0.03) function stabilisation and definite or probable stent thrombosis (3.4%. vs 6.1%, G. Guex, A. Frobert, S. Cook, G. Fortunato, E. Körner, p = 0.02) were lower with EES than SES up to 3 years. C. Fouassier, T.P. Carrel, H. Tevaearai, M.-N. Giraud Conclusion: Among ACS patients, EES is associated with (Bern, Freiburg, St. Gallen, CH) improved efficacy and safety during long-term follow-up to Introduction: Progress in tissue engineering for myocardial 3 years. regeneration is conditioned by the creation of a suitable environment in which cells can grow and organise themselves into a functional tissue.We designed micro-fibrous scaffolds 68 enriched with oxygen and investigated the hypothesis that Importance of symptomatic and silent coronary artery epicardial implantation of bone marrow-derrived mesenchymal disease progression very late after successful coronary stem cells (MSC) seeded on our oxygen coated Polycaprolactone stent implantation (PCL) matrix would induce functional benefits. Methods: Microfibrous PCL non-wovens were produced by M.J. Zellweger, C. Kaiser, R. Jeger, F. Bader, J. Müller-Brand, electrospinning and surface-coated by an RF plasma process P. Buser, H.P. Brunner, M. Pfisterer for the BASKET Investigators (CO_2/C_2H_4 gas). Bone marrow-derived MSC were Background: To assess the safety of drug-eluting stents (DES), characterised by FACS and 2 Mio cells were cultured on the long-term follow-up studies have been mandated. However, 10x15 mm patches for 7- 10 days. Cell mortality was assessed by during very late follow-up, ischemic events may be due to LDH release, viability and morphology by MTT staining and SEM coronary disease progression rather than due to late stent-related imaging respectively. Two weeks post LAD ligation, Lewis rats problems.

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showing reduced ejection fraction (EF of 48 ± 8%) were encapsulation or inflammation. Patches were permanently glued randomized into 4 groups: MSC seeded patches glued onto the onto the myocardium, no adhesion to other organs occurred. infarcted area with Tisseel fibrin glue (n = 7), non-seeded patches When compared to pre-treatment, MSC seeded patches induced (n = 8), glue only (n = 4) and sham operation (n = 5). Treatments a stabilisation of EF after 4 weeks (48 ± 10% and 47 ± 7% were applied via a second intercostal left thoracotomy. respectively). Non-seeded patches did not induce a stabilisation Echocardiography and pressure-volume loops were recorded (EF of 46 ± 8% and 39 ± 4% respectively, p = 0.02). after 28 days. Histological analyses are under investigation. Conclusions: Our preliminary data demonstrate that epicardial Results: CD90+, CD45- and CD31- MSC largely spread on the implantaion of MSC-oxygen enriched PCL biografts is safe and matrix and formed a monolayer prior to implantation. All animals reverses functional alterations observed in hearts after chronic survived the entire experimental procedure. We showed that PCL myocardial infarction. Further anlyses will confirm eventual effect patches allowed for a safe implantation without signs of rejection, on myocardial regeneration.

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70 Chronic hypoxemia induces systemic vascular Results: The study population was divided in quartiles by means dysfunction in humans of baseline oxygen arterial saturation (SaO2: <83%; 84–86%; 87–89%; ≥; 90%). FMD in the subgroup with the highest SaO S. Rimoldi, E. Rexhaj, M. Villena, U. Scherrer, C. Sartori, 2 (SaO2 ≥90%) was significantly greater than in the 3 other Y. Allemann (Bern, Lausanne, CH; La Paz, BO) subgroups (P <0.0001, fig. 1A) and similar to the one of matched Background: Cardiac and pulmonary diseases associated with healthy subjects living at low altitude. Oxygen administration chronic hypoxemia represent a leading cause of morbidity and significantly improved, but not completely normalized FMD in the mortality in Western countries.While cardiovascular disease three lower quartiles subgroups, whereas it had no detectable contributes importantly to this problem, the mechanisms effect in the subgroup of subjects in the highest quartile underlying vascular dysfunction in these patients remain unclear. (P = 0.02, fig. 1B). Mountain dwellers are characterized by chronic hypoxemia and Conclusions: Here we provide the first direct evidence that often do not display additional cardiovascular risk factors, thereby chronically hypoxemic subjects display endothelial dysfunction providing a unique opportunity to examine the independent that is only partially restored by oxygen administration suggesting effects of chronic hypoxemia on vascular function. We recently that chronic hypoxemia per se contributes to vascular dysfunction. showed that chronically hypoxemic mountain dwellers display Moreover, the present data indicate that there exists a cut-off systemic vascular dysfunction and hypothesized that oxygen value for the detrimental vascular effects of chronic hypoxemia administration improves endothelial function in these subjects. because in subjects with a SaO2 ≥90%, FMD was normal and Methods: We assessed endothelium-dependent (flow-mediated comparable to matched subjects living at low altitude.We vasodilation, FMD) in 33 mountain dwellers born and permanently speculate that in chronically hypoxemic patients, in addition to living at high altitude (3600 m) without any additional treating traditional cardiovascular risk factors, improving arterial cardiovascular risk factors, before and after a 1-hour oxygenation has favourable effects on cardiovascular morbidity administration of 100% oxygen by a face mask. and mortality.

71 Endocannabinoid plasma levels are independent artery disease (CAD). It is possible that soluble mediators predictors of coronary endothelial dysfunction in obesity released by the adipose tissue such as the endocannabinoids (ECs) have regulatory functions on the coronary vasomotor tone A. Quercioli, Z. Pataky, G.M. Vincenti, F. Montecucco, and induce the development of CAD. A. Thomas, C. Staub, Y. Seimbille, A. Golay, O. Ratib, Methods: Myocardial blood flow (MBF) responses to cold pressor E. Harsch, F. Mach, T. Schindler (Genève, CH) test (CPT) and pharmacologic vasodilation were measured with Objectives: We investigated the effects of increasing body weight positron emission tomography and 13N-ammonia. ECs were and the endocannabinoid system on the coronary circulatory extracted from plasma and analysed on mass spectrometry. function in individuals without any cardiovascular risk factor. Study participants were divided, based on their body mass index Background: Obesity is known to be an independent predictor (BMI, kg/m2), in: control, 20 < BMI <25 (n = 21); overweight, of endothelial dysfunction as a functional precursor of coronary 25 < BMI <30 (n = 26) and obese, BMI >30 (n = 30).

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Results: We found significant correlations between BMI and Conclusion: After introduction of smoking ban in enclosed public insulin resistance (HOMA) (r = 0.58, SEE = 0.45; p <0.0001) and places we observed a rapid, significant, and enduring reduction BMI and anandamide (AEA) (r = 0.46, SEE = 5.12; p <0.0001). of hospitalizations due to STEMI among residents of the canton Endothelium-related change in MBF during CPT from rest Ticino, southern of Switzerland. (DeltaMBF) progressively declined in overweight and obese groups as compared to control (0.2 ± 0.2 and 0.07 ± 0.1 vs. 0.3 ± 0.2, respectively), while the hyperaemic MBFs were significantly 73 lower in the overweight and obesity group compared with the Population attributable coronary risk is mainly driven control group (1.96 ± 0.4 and 2.1 ± 0.4 vs. 2.4 ± 0.5 p <0.05 ml/g/ by LDL-cholesterol: similar observations in two distinct min, respectively), without differing significantly between the healthy populations overweight and obesity groups.The EC AEA was comparable between overweight and controls, while it significantly increased M. Romanens, F. Ackermann, I. Sudano, T. Szucs, W. Riesen, in obesity; conversely, the 2-arachidoylglycerol (2-AG) increased M. Schwenkglenks (Olten, Zürich, Basel, St. Gallen, CH) in the obese group, although this increase did not achieve Aim: To determine population attributable coronary risk for major statistical significance. On multivariate analysis, increases in coronary risk factors and to derive the potential to reduce global plasma levels of 2-AG and AEA were independent predictors of coronary risk. coronary endothelial and arteriolar vascular smooth muscle cell Methods: We compared not randomly selected subjects from self dysfunction, respectively, in the obese population. referred CORDICARE (COR) and physician referred KARDIOLAB Conclusions: Increased ECs plasma levels are independently (KAR) patients for 10 year coronary risk determined by Swiss associated with abnormal coronary circulatory function in obesity. guidelines (AGLA) and by reclassification (posttest risk derived As an impairment of coronary circulatory function may reflect an from total plaque area of carotid arteries). The potential for risk early abnormal functional stage of the CAD process, increases in factors to reduce global coronary risk was estimated by ECs plasma levels may emerge as a novel and endogenous substituting measured results by ideal values of risk factors. We cardiovascular risk factor in obesity which needs experimental calculated the risk reduction attributable to achievement of all and clinical validation. AGLA goals, and for single risk factors: smokers became non-smokers, diabetic patients became non-diabetic patients, HDL level, if not already reached, was increased to 1. 5 mmol/l, 72 similarly, LDL level was decreased to 2.0 mmol/l, systolic blood Reduced hospitalization for ST-elevation myocardial pressure (BP) was decreased to 130 mm Hg and then 10 year infarction after introduction of smoking ban in public risk was recalculated for every subject. places in canton Ticino, southern Switzerland Results: COR included N = 892 (48% female), mean age 59 ± 9 years, KAR included N = 548 (34% female), mean age 57 ± 9 M. Di Valentino, S. Muzzarelli, A. Rigoli, C. Limoni, F. Barazzoni, years. COR vs KAR: less smokers (11% vs 28%), less diabetic G.B. Pedrazzini, A. Gallino (Bellinzona, Basel, Lugano, CH) patients (3% vs 9%), higher systolic BP (133 ± 15 vs 128 ± 19) Background: Second-hand smoke increases the risk of STEMI. and higher HDL (1.6 ± 1. 4 vs 1. 4 ± 0.4), lower AGLA coronary risk This study is aimed to assess the impact of smoking ban in public (6.6 ± 6.9 vs 8.3 ± 8.6%), lower posttest risk (13.2 ± 13.8 vs places on frequency of hospitalizations due to STEMI in canton 16.4 ± 16.5 %). Percent risk reduction for COR and KAR were Ticino, which was the first Swiss area applying this law. Canton reduced: all AGLA treatment goals achieved (–47% vs –71%), Ticino is located in southern Switzerland with a population of AGLA LDL goals achieved (–29% vs –36%), LDL ≤2.0 mmol/l around 330.000 individuals and represents a well defined (–51% vs –52%), no smokers (–7% vs –14%), HDL >1.49 mmol/l geographical and political area with its own public medical system (–14% vs –27%), blood pressure ≤130 mm Hg (–8% vs –7%), no isolated from the rest of the country. diabetes (–2% vs –4%). Methods: We compared the annual frequency of hospitalizations Conclusions: Achieving LDL ≤2.0 mmol/l would be the single due to STEMI during the pre-legislation (2004 to 2006),and the most important intervention to reduce coronary risk (risk reduction post-legislation- period (2007 to 2008), based on the coded by 50%). By achieving all AGLA goals, 10 year risk would fall from hospital discharge registry (ICD-10 codes). 13% to 7% in COR and from 16% to 5% in KAR. COR and KAR Results: The annual frequency of hospitalizations for STEMI was subjects are predominantly at low risk according to AGLA, at of 249, 298 and 288 (mean 278) during the three pre-legislation intermediate risk after reclassification, and could become true low year, respectively. This was consistent with a mean annual risk through intensified intervention. frequency of 278 during the three pre-legislation years. The frequency of hospitalizations due to STEMI dropped to 216 and 221, during the first and second post-legislation year.This was 74 correspond to a 22.4% (p <.0001) and 20.6% (p <.0002) Eccentric endurance exercise economically improves reduction in hospitalizations for STEMI during the two year of glucose tolerance the post-legislation period as compared to the mean frequency of the pre-legislation period (fig. 1). M. Zeppetzauer, C. Saely, P. Rein, A. Vonbank, H. Drexel (Feldkirch, AT) The interplay of muscle contraction with an external force can result in one of three types of muscle activity: shortening or “concentric” when muscle contraction is stronger than the external force; lengthening or “eccentric” when the external force is stronger; and isometric when both forces are equal. Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its effects on glucose metabolism are unclear.We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 meters; the distance was covered three to five times a week. Standard oral glucose tolerance tests were performed at baseline and after the two months periods of eccentric and concentric exercise, respectively; the area under the glucose curve was used as a measure of glucose tolerance. Energy expenditure was assessed for each hiking period. Both eccentric and concentric endurance exercise significantly improved glucose tolerance versus baseline (by 4.1%; p = 0.136 and 6.2%; p = 0.023, respectively). Of note,

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adjustment for energy expenditure per exercise unit (127 ± 22 Method: The time course of fasting level of CRP, IL-6, IL-8, IP-10, kcal/unit with eccentric and 442 ± 78 kcal/unit with concentric MCP-1 TNFα, VEGF sIL-1RI, sIL-1RII at baseline day 0 and at exercise) revealed a significantly greater improvement of glucose postoperative day 1,2,3,4,5,6,7 were measured on all consecutive tolerance per kcal spent with eccentric than with concentric patients undergoing elective off pump coronary bypass surgery. exercise (0.1123 mg.h.dl-1.kcal-1 versus 0.0245 mg.h.dl-1.kcal-1; Exclusion criteria were the use of anti-inflammatory medications, p = 0.038). We conclude that eccentric endurance exercise history of inflammatory disease, acute infection, acute myocardial economically improves glucose tolerance. It therefore is a infarction, use of antibiotics within two weeks of surgery. promising new exercise modality for individuals who are not able Result: Out of 69 patients 17 had BMI ≥30 kg/m2. Homeostasis or not willing to participate in more strenuous exercise regimens. model assessment of insulin resistance did not differ between the eccentric exercise, concentric exercise, glucose tolerance, energy two groups, mean 2.65 and 2.43 respectively. There was no expenditure, hiking. difference between the two groups and the course of IL-6, IL-8, IP-10, MCP-1 TNF α, VEGF.There was a significant increase CRP, sIL-1RI, sIL-1RII in the group with ≥30 kg/m2 BMI. 75 Conclusion: Plasma interleukin-1 (IL-1) an immune system Study of obesity-dependent secretion of adipokines activator is modulated in part through the simultaneous after off pump coronary bypass surgery appearance of inhibitors, including S IL-1RI and S IL-1RII. Both SIL1RI and SIL1RII are higher preoperative and postoperative H. Loeblein, S. Thalmann, O. Dzemali, K. Graves, U. Schurr, in patients ≥30 kg/m2 BMI. The increased release of IL-1RI and A. Haeusler, D. Odavic, G. Siniscalchi, M. Genoni, C. Meier sIL-1RII by obese patients(normal value 1. 6 ± 0.05 and 4.7 ± 0.06 (Zürich, CH) ng/ml) is consistent with the hypothesis that adipose tissue is Objective: It has been shown that obese patients have a associated with chronic, low-level activation of the immune heightened state of inflammation. This study was undertaken to system and a higher inflammatory response after coronary examine the postoperative time course of the serum inflammatory bypass surgery. The much higher increase in CRP level on markers and anti-inflammatory mediators [C-Reactive Protein postoperative day number 2 in obese patients suggest also that (CRP), Interleukin -6, Interleukin -8, IP-10 (interferon-γ induced these patients have a higher post interventional circulating levels protein ), TNF-α (Tumor-Nekrose-Faktor α), Vascular Endothelial of inflammatory markers. Growth Factor (VEGF), MCP1(Monocyte chemotactic protein-1), soluble IL-1 type I receptor (sIL-1RI), soluble IL-1 type II receptor (sIL-1RII)] in response to off pump coronary bypass surgery stratified by body mass index (BMI).

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76 The predictive value of normal cardiovascular on at least one minor criterion as defined by the Task Force magnetic resonance scans in patients with suspected Criteria. Patients were classified according to their initial scan arrhythmogenic right ventricular cardiomyopathy – results as either “normal” or “abnormal”. Scans were abnormal An outcome study if RV end-diastolic volume (RVEDV) was increased, and/or RV ejection fraction (RVEF) was decreased, and/or RV regional wall M. Deac, J. Wong, F. Alpendurada, K. Prasad motion abnormalities were observed (RV RWMA), and/or late (Morges, CH; London, UK) gadolinium enhancement of the LV (LV LGE) or RV (RV LGE) Objective: To assess the accuracy of cardiovascular magnetic was present. Cut-off values for normal versus abnormal volumes resonance (CMR) scans in predicting future major adverse and ejection fraction were based on previously published cardiovascular events(MACE) in patients with suspected reference ranges from our institution. The primary end-point was arrhythmogenic right ventricular cardiomyopathy (ARVC). a composite of all cause-mortality, life-threatening arrhythmias, Background: ARVC is a genetic disease that affects young appropriate ICD discharge, and unplanned hospital admission patients prone to sudden cardiac death. The incomplete for cardiovascular events. Positive (PPV) and negative predictive penetrance of this disorder means that there is a large values (NPV) of abnormal and normal scans for MACE were heterogeneity in the clinical expression of the disease, thus calculated. rendering the final diagnosis ofVC AR extremely challenging.With Results: 211 patients (57%) had normal baseline scans. Patients the constant increase in referrals to CMR centers of patients with with abnormal scans were older (47.4 yrs ± 14) and more often suspected ARVC, there is a clear need today to identify within this male (63.7%) than those with normal scans (40.6 yrs ± 16, 43.1% “every-day” patient population, a group of patients who will be at males). 51 patients reached a primary end-point. While the PPV an increased risk of MACE. of each of the CMR variables (RVEDV, RVEF, RV RWMA, LGE) Methods: Between 2002 and 2005, we studied 368 consecutive for predicting MACE was low (ranging from 16.9% to 25%), the patients referred for CMR assessment of suspected ARVC, based NPV of each of these imaging variables was strong, and ranged

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between 86.9% and 89.7%. The overall NPV of a normal scan 78 for predicting future adverse outcomes was 89.1%. Why and how do patients with heart failure die? Conclusion: The data confirm the value of CMR in a “real-life” Insights from the TIME-CHF trial patient population with suspected ARVC.Anormal CMR scan allows to reliably predict a long-term major cardiovascular P. Rickenbacher, M. Pfisterer, T. Burkard, W. Kiowski, event-free outcome. F. Follath, D. Burckhardt, R. Schindler, H.-P. Brunner- La Rocca for the TIME-CHF Investigators Background: There is a paucity of information on specific cause 77 (COD; e.g. witnessed arrhythmia) and mode of death (MOD; Septal strain patterns reveal ventricular asynchrony e.g. sudden death), particularly in patients (pts) with heart failure and regional differences in contractility in patients with (HF) and preserved ejection fraction (HFPEF) and in the elderly. asynchronous heart failure Methods: To get more insights into these questions, all pts of the multicenter TIME-CHF trial who died were reanalysed for COD B.W.L. De Boeck, G.E. Leenders, J. Lumens, M.J. Cramer, (cardiovascular (CV), cardiac, vascular, non-CV, unknown) and F. W. Prinzen, T. Delhaas (Luzern, CH; Utrecht, Maastricht, NL) MOD (CV, cardiac (sudden, circulatory failure), vascular, non-CV, Introduction: Response to CRT is believed to depend both on unknown) according to the ACME system (EHJ 1996;17:1390). intra-ventricular asynchrony as well as on (regional) contractility TIME-CHF was a randomized controlled multicenter trial disturbances or scarring.Asynchronous activation due to left comparing a standard symptom-guided with an intensified, bundle branch block (LBBB) is associated with a complicated NT-BNP guided medical therapy in 622 pts ≥60 years with sequence of systolic shortening and stretching of the symptomatic HF NYHA ≥II, a history of HF hospitalization <1 year interventricular septum. We hypothesized this septal strain and an elevated NT-BNP level. Pts were prospectively stratified pattern (SSP) to be determined both by asynchrony as well according to ejection fraction ≤45% (“HFREF”,n = 499) vs >45% as by contractility / scarring in the septum and lateral wall. (“HFPEF”,n = 123) and age 60-75 years (“<75”,n = 242) vs Methods: In 132 CRT- candidates with systolic heart failure and ≥75 years (“>75”,n = 380). LBBB-like ECG-morphology (65 ± 10 years, 93 male, 19 NYHA Results: During the 18-month follow-up 132 (21%) pts died. IV, 69 ischemic, LVEF 19 ± 6%; QRS-width 170 ± 23 ms), Baseline characteristics differed significantly between pts who the longitudinal SSP was assessed by speckle tracking died and survivors in HFREF and HFPEF, whereas mortality was echocardiography. Left ventricular (LV) volumes, ejection fraction not different: HFREF 21%, HFPEF 22% (p = 0.83). COD in pts (LVEF) and amount of scar were derived from 2-D with HFPEF was more often non-CV (33% vs 16%, p <0.05), echocardiographic images.To investigate the single and particularly renal failure (11% vs 1%, p <0.01), but did not differ combined effects of asynchrony and regional myocardial in cardiac, other vascular or unknown cause from HFREF pts. contractility / scarring on SSP and LV-function, we utilized the HFREF pts experienced more cardiac MOD (75% vs 56%, p CircAdapt computer model of the human heart and circulation. <0.05), due to a significant difference in sudden deaths (25% vs Results: In the study population, three characteristic SSPs were 7%, p <0.05), whereas circulatory failure, vascular and non-CV identified (fig: upper panels): SSP-1 = double-peaked shortening modes were equally distributed. The two age groups differed also (n = 28); SSP-2 = early systolic shortening followed by prominent in baseline characteristics, with a somewhat higher mortality in holo-systolic stretching (n = 34); and SSP-3 = pseudonormal pts >75 vs <75: 24% vs 17% (p = 0.06). However, no significant shortening with subtle late systolic stretch (n = 70). Similar SSPs differences in COD or MOD were found between the 2 age could be reproduced by the CircAdapt model (fig: welo r panels). groups. Simulating asynchronous activation alone (i.e., RV- septum-LV Conclusions: Despite similar 18-month mortality rates, important lateral wall activation time of 0-25-75 ms) resulted in SSP-1.This differences in COD and MOD were found only between pts with transformed into SSP-2 by additionally imposing hypocontractility/ HFREF and HFPEF, but not between the 2 age groups. HFPEF scarring in the septum and into SSP-3 when imposing lateral wall pts died more often for non-CV causes/renal failure than HFREF hypocontractility/scarring. Limited asynchrony (25ms septal-lateral pts and MOD was more often sudden in HFREF pts, whereas activation delay) and severe global LV hypocontractility also circulatory failure was observed similarly in both pt groups.“Why” resulted in SSP-3. In the CRT- candidates, response to CRT and “how” pts with HF die is of relevance for pts and their decreased progressively from SSP-1 to SSP-3 (increase in physicians and this information may help to not only better LVEF for SSP-1: 14 ± 9%, for SSP-2 8 ± 7%, for SSP-3 3 ± 7%). understand the pathophysiology and natural history of HF but Patients with SSP-3 revealed more scar (2 [2-5] segments) also target therapy in these pts. compared to SSP-1 (0 [0-1]) and SSP-2 (0 [0-1]), both p <0.05. Conclusions: In CRT candidates, septal strain patterns incorporate combined information on the amount of ventricular 79 asynchrony and the extent of contractility disturbances as Long-term outcome of NT-proBNP-guided versus established determinants of CRT response. symptom-guided therapy in chronic heart failure: results from the TIME-CHF trial M.T. Maeder, S. Van Wijk, F. Nietlispach, H. Rickli, W. Estlinbaum, P. Erne, P. Rickenbacher, M. Peter, M. Pfisterer, H.P. Brunner-La Rocca (St. Gallen, CH; Maastricht, NL; Basel, Liestal, Luzern, Bruderholz, Wolhusen, CH) Introduction: N-terminal-proB-type natriuretic peptide (NT- proBNP)-guided therapy may improve outcome in patients with chronic heart failure (HF) and reduced left ventricular ejection fraction (EF), especially in younger patients. However, it is unclear if these effects persist after discontinuation of NT-proBNP-guided strategy. Methods: 499 HF patients aged ≥60 years with EF ≤45% were randomized to intensified, NT-proBNP-guided versus symptom- guided therapy. Patients were a priori divided in two age groups (i.e. 60–74 y and ≥75 y). Treatment strategies according to guidelines were intensified based on group allocation during 12 months. 354 of 382 patients (93%) being alive at 18 months agreed for long-term follow-up which was continued up to 5½ years. The 1° endpoint was survival free of all-cause hospitalizations, 2° endpoints were survival free of HF hospitalization and all-cause mortality. Results: The effects of NT-proBNP-guided therapy observed during the first 18 months did not change significantly during further follow-up. Similarly to the first 18 months, the 1° endpoint

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(HR [hazard ratio] = 0.87; 95%-CI, 0.71–1.06; p = 0.16) and Results: All-cause mortality occurred in 36%, 40%, 39% and all-cause mortality (HR = 0.85; 95%-CI 0.64–1.13; p = 0.25) were 56% of patients with RVEF ≥40%, 30–39%, 20–29% and <20% not significantly reduced by NT-proBNP-guided therapy but there respectively. Compared with RVEF ≥40%, unadjusted hazard was a demonstrable benefit on the disease specific 2° endpoint ratios (HR) and 95% confidence intervals (CI) for all-cause HF hospitalization free survival (HR = 0.70; 95%-CI, 0.55–0.90; mortality associated with RVEF 30–39%, 20–29% and <20% p = 0.005). In patients aged 60–74 y, the positive effects seen were 1. 19 (0.90–1.57; P = 0.220), 1. 13 (0.84–1.51; P = 0.423) and during the first 18 months were maintained during long-term 1. 97 (1.43–2.73; P <0.001) respectively. Respective multivariable- follow-up (1° endpoint: HR = 0.72, p = 0.05; HF hospitalization adjusted HR’s (95% CI’s) for all-cause mortality were 1. 19 free survival HR = 0.52, p = 0.004; all-cause mortality HF = 0.62, (0.88–1.60; P = 0.261), 1. 00 (0.73–1.39; P = 0.982) and 1. 70 p = 0.06). No positive effect of NT-proBNP-guided therapy could (1.14–2.53; P = 0.009). Adjusted HR’s (95% CI’s) associated with be found in patients aged ≥75 y (1° endpoint: HR = 1. 02, p = 0.89; RVEF <20% (versus ≥40%) for cardiovascular mortality and HF hospitalization free survival HR = 0.84, p = 0.22; all-cause HF mortality were 1. 79 (1.17–2.76; P = 0.008) and 1. 97 (1.02–3.83; mortality HR = 1. 01, p = 0.95). This difference between age P = 0.045) respectively. RVEF had no independent association groups was related to positive effects of NT-proBNP-guided with sudden cardiac death, all-cause or HF hospitalization. therapy in patients with less than 2 co-morbidities (1° endpoint: Conclusions: Abnormally low RVEF is a significant independent HR = 0.62, p = 0.02; HF hospitalization free survival: HR = 0.36, predictor of mortality, but not of HF hospitalization, in older adults p = 0.001; all-cause mortality: HR = 0.39, p = 0.01), whereas no with systolic HF. Measurement of RVEF should be considered in treatment effects were seen in those with 2 or more co- these patients, and when available, should be used to stratify morbidities. patients for prognostic and therapeutic purposes. Conclusion: The positive effects of NT-proBNP guided HF therapy seen at 18 months in younger patients and those with little co-morbidities were maintained during long-term follow-up. 81 Patients aged ≥75y and those with significant co-morbidities did Ventilator inefficiency in heart failure with normal left not benefit long-term. ventricular ejection fraction: role of changes in pulmonary capillary wedge pressure during exercise

80 M.T. Maeder, D.M. Kaye (St. Gallen, CH; Melbourne, AU) Right ventricular ejection fraction and outcomes Introduction: Patients with heart failure (HF) and reduced left in elderly heart failure patients ventricular fraction (LVEF; HFREF) are well characterized by abnormalities of the ventilatory response to exercise including P. Meyer, M. Mujib, M.A. Feller, R.V. Desai, C. Adamopoulos, low peak oxygen consumption (peak VO_2) and a high slope of M. Banach, M. Lainscak, I. Aban, M. White, W.S. Aronow, the relationship between minute ventilation and carbon dioxide P. Deedwania, A.E. Iskandrian, A. Ahmed (Genève, CH; production (VE/VCO_2 slope). Recently several of these Birmingham, Allentown, US; Thessaloniki, GR; Lodz, PL; parameters have been documented in patients with HF and Golnik, SI; Montreal, CA; New York, San Francisco, US) a normal LVEF (HFNEF) although their pathophysiological Introduction: Reduced right ventricular ejection fraction (RVEF) significance in this group remains uncertain. The diagnosis of is associated with poor outcomes in patients with chronic systolic HFNEF is challenging and is essentially based upon the presence heart failure (HF). Although, most HF patients are older adults, of a normal sized left with a normal LVEF and the little is known about the relationship between low RVEF and demonstration of an abnormal distensibility, which can be done outcomes in systolic HF patients in older adults. using exercise right heart catheterisation. We aimed to compare Methods: Of the 2008 β-Blocker Evaluation of Survival Tr ial the VE/VCO_2 slope between patients with HFREF, HFNEF, and (BEST) participants with systolic HF (left ventricular ejection healthy controls, and to assess the association between exercise fraction, ≤35%) and data on baseline RVEF estimated by haemodynamics and the VE/VCO_2 slope in subjects with normal gated-equilibrium radionuclide ventriculography, 822 were ≥65 LVEF in order to evaluate the potential diagnostic utility of the VE/ years. Using RVEF ≥40% (n = 308) as reference, we examined VCO_2 slope in this setting. association of RVEF 30–39% (n = 214), 20–29% (n = 206) and Methods: We studied 36 patients with advanced HFREF, 10 <20% (n = 94) with outcomes using Cox regression models. patients with HFNEF, and eight asymptomatic controls (LVEF 24 ± 8, 68 ± 5, 64 ± 8%; peak VO_2 12.7 ± 3.7, 15.1 ± 4.9, 26.5 ± 12.5 ml/kg/min) undergoing cardiopulmonary exercise testing and right heart catheterisation. Subjects with normal LVEF (ie, the control and HFNEF groups) underwent exercise right heart catheterisation. Results: The VE/VCO_2 slope in the HFREF, HFNEF, and control groups was 42 ± 11, 34 ± 5, and 28 ± 3 respectively (p = 0.001). In subjects with normal LVEF, higher increase in PCWP per work rate per kilogram body weight (r = 0.66), lower peak exercise partial pressure of arterial carbon dioxide (PaCO2; r = –0.51) and lower peak exercise tidal volume (r = –0.55) were associated with higher VE/VCO_2 slope. Conclusions: In patients with HFNEF, the VE/VCO2 slope is intermediate between asymptomatic controls and HFREF patients. In subjects with normal LVEF, abnormalities in dead space ventilation (low peak exercise tidal volume) and ventilator control (low peak PaCO2) are related to the VE/VCO_2 slope which is as expected from its equation. However, there is also a significant association between a higher VE/VCO_2 slope and a more rapid increase in PCWP during exercise, indicating that the VE/VCO_2 slope may assist in the diagnosis of HFNEF in subjects with normal LVEF and may be a useful follow-up parameter in those with an established diagnosis of HFNEF.

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82 (p <0.001). NT-proBNP (AUC 0.85, 95% CI 0.81–0.89) predicted Trends in pre-hospital delay and door-to-balloon time all-cause mortality independently of and more accurately than in patients with ST-elevation myocardial infarction both cTnT (AUC 0.66, 95% CI 0.58-0.74, p <0.001) and the undergoing percutaneous coronary intervention in TIMI risk score (AUC 0.79, 95% CI 0.74–0.84, p <0.001). Net Switzerland 2000–2010 reclassification improvement (TIMI vs. additionally NT-proBNP) was 0.188 (p <0.009), and integrated discrimination improvement D. Radovanovic, P. Urban, G.B. Pedrazzini, H. Rickli, P. Erne was 0.100 (p <0.001). for the AMIS Plus Conclusions: Use of NT-proBNP improves the early diagnosis Background: Current guidelines for reperfusion therapy in and risk stratification of patients with suspected AMI. patients with acute ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) recommend door-to-balloon time (DTB) of less than 90 minutes, even for patients transferred from non-PCI hospitals.The aim of this study was to examine the trends in delay time to intervention during the last 11 years. Methods: Using data from the AMIS Plus registry, we analyzed the temporal trends in pre-hospital delay and DTB time in STEMI patients who underwent PCI between 2000 and 2010. Results: From 10,408 STEMI patients treated in 66 Swiss hospitals who underwent PCI, 2385 (23%) were female, aged 67.2 y (12.3 y) and 8023 (77%) were male patients, aged 61.7 y (12.5 y). 30% of patients were transferred for intervention. Median pre-hospital delay (IQR25, 75) was 180min (101, 410 min). In female patients, pre-hospital delay was significantly longer compared to male patients: 210 min (120, 460 min) versus 180 min (96, 398 min; p <0.001). The time between symptom onset and admission decreased over the 11 years: from 180 min (105, 482 min) in 2000 to 170 min (100, 392 min) in 2010 (p = 0.05) but the gender gap was unchanged. Median DTB time was shorter in male than in female patients: 61min (25, 120 min) versus 68 min (28, 131; p = 0.001), and decreased for the total population from 84 60min (30, 155 min) in 2000 to 53 min in 2010 (20, 90 min; High-sensitive cardiac Troponin in the distinction p <0.001) due to the decrease of DTB time in female patients of acute myocardial infarction from acute cardiac over the 11-year period from 80min (34, 238 min) to 65min (22, non-coronary disease 99 min). In total, 62% of the females and 66% of the males were treated within 90 min (p = 0.003). Male gender was a significant P. Haaf, B. Drexler, T. Reichlin, R. Twerenbold, M. Reiter, predictor for undergoing PCI <90 min (OR 0.85; 95% CI 0.77, J. Meissner, C. Meune, C. Balmelli, S. Osswald, C. Müller 0.95). However, the guidelines recommendation was achieved by (Basel, CH; Paris, FR) 66% of STEMI patients who underwent PCI in 2000, and by 75% Introduction: We hypothesized that high-sensitive cardiac in 2010 (p <0.001). Crude in-hospital mortality was 4.1% and troponin (hs-cTnT) and its early change are useful in 5.5% for MACCE but these did not significantly change over the distinguishing acute myocardial infarction (AMI) from acute study period (p = 0.45, p = 0.64 respectively). Admission year cardiac non-coronary disease and allocating early coronary after adjusting for age and gender was not a significant predictor angiography. of in-hospital mortality (OR 1. 04; 95%CI 0.99–1.08; p = 0.057). Conclusion: Although time to treatment of STEMI patients in Switzerland during the last 11 years decreased > 10%, it did not translate into a significant reduction of in-hospital mortality in this patient population.

83 N-terminal pro B-type natriuretic peptide in the early diagnosis and risk stratification of suspected acute myocardial infarction P. Haaf, C. Balmelli, T. Reichlin, R. Twerenbold, M. Reiter, J. Meissner, C. Meune, B. Drexler, S. Osswald, C. Müller (Basel, CH; Paris, FR) Introduction: Myocardial ischemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release.As ischemia precedes necrosis in acute myocardial infarction (AMI), we hypothesized that NT-proBNP might be useful in the early diagnosis and risk stratification of patients with suspected AMI. Methods: In a prospective multicenter study, NT-proBNP was measured at presentation in 658 consecutive patients with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists. Patients were followed long-term regarding mortality. Results: AMI was the adjudicated final diagnosis in 117 patients (18%). NT-proBNP levels at presentation were significantly higher in AMI as compared to patients with other final diagnoses (median 886 pg/ml vs. 135 pg/ml, p <0.001). The diagnostic accuracy of NT-proBNP for AMI as quantified by the area under the ROC curve (AUC) was 0.79 (95% confidence interval (CI) 0.75–0.83). When added to cardiac troponin T (cTnT), NT-proBNP significantly increased the AUC from 0.88 (95% CI 0.84–0.93) to 0.91 (95% CI 0.88-0.94,_p = 0.033). Cumulative 24-month mortality rates were 0% in the first, 1. 3% in the second, 8.3% in the third and 23.3% in the fourth quartile of NT-proBNP

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Methods: In a prospective, international multicenter study, hs-cTnT was measured in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain. Final diagnosis was adjudicated by two independent cardiologists. Results: AMI was the adjudicated final diagnosis in 127 patients (14%), cardiac non-coronary disease in 124 (14%). Patients with AMI had higher median presentation values of hs-cTnT (0.113 ug/l [0.049–0.246 ug/l] versus 0.012 ug/l [0.006–0.034 ug/l]; p <0.001) and higher absolute changes of hs-cTnT in the first hour (0.019 ug/l [0.007–0.067 ug/l] versus 0.001 ug/l [0–0.003 ug/l]; p <0.001) than patients with cardiac non-coronary disease. Adding changes of hs-cTnT in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver operating characteristics curve of 0.94 (95% confidence interval 0.90–0.96). An algorithm using ST-elevation, presentation values and changes of hs-cTnT values in the first hour accurately separated patients with AMIand cardiac non-coronary disease. Decision curve analysis showed the superiority of the combined use of hs-cTnT and its early absolute change in identifying patients with a need for early coronary angiography while leading to a considerable reduction in unnecessary coronary angiographies. Conclusion: The duration of reanimation and initial presentation Conclusions: The combined use of hs-cTnT at presentation and with PEA or asystole are the major determinants of adverse its early absolute change excellently discriminates between outcome in patients with acute coronary syndromes and cardiac patients with AMI and cardiac non-coronary disease.This arrest. distinction is mandatory to appropriately allocate early coronary angiography. 86 Use of glycoprotein IIb/IIIa inhibitors might be 85 associated with increased mortality in patients Outcome of patients with acute coronary syndromes with non-ST-elevation ACS and out-of hospital cardiac arrest F. Cuculi, D. Radovanoic, B. Seifert, S. Windecker, S. Toggweiler, D.J. Müller, M. Frank, M. Freuler, F. Duru, G.B. Pedrazzini, P. Urban, P. Erne (Oxford, UK; Zurich, Bern, R. Corti, T.F. Lüscher (Zürich, CH) Lugano, Meyrin, Luzern, CH) Introduction: Data about outcome after out-of hospital cardiac Background: The role of GP-IIb/IIIa inhibitors (GPI) in unselected arrest in patients with acute coronary syndromes (ACS) is quite ACS populations is unclear. sparse.We aimed to identify predictors of adverse cardiovascular Methods: Using data from the AMIS Plus registry, we analyzed and neurologic outcome. MACE rates – defined as composite endpoint of death, re- Methods: All patients who presented with ACS undergoing infarction and stroke and bleeding rates between patients with- coronary angiography at the University Hospital Zurich between and without GPI. Very high-risk patients (age >80, cardiogenic July 2007 and December 2009 were included for analysis. shock and/or CPR prior to admission) were analyzed separately. In-hospital outcome of patients with and without cardiac arrest was evaluated. Results: A total of 1252 patients with ACS were analyzed of whom 93 (7.5%) presented with cardiac arrest. Patients with cardiac arrest presented more frequently with ST elevation myocardial infarction (STEMI) and culprit vessel was more frequently the left anterior descending (LAD) or the left main coronary artery. In-hospital mortality was 1. 8% for patients without cardiac arrest, but 28% for patients with cardiac arrest (p <0.001). As shown in table 1, pulseless electrical activity (PEA) or asystole as initial rhythm and prolonged reanimation were factors associated with higher mortality in patients with cardiac arrest. These factors were also associated with adverse neurologic outcome (table 2).

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Results: Between January 2000 and December 2009 a total of patients with NT-proBNP <1000 ng/l, but 17% for those with 27238 ACS patients were registered in the AMIS Plus registry. NT-proBNP ≥1000 ng/l (p = 0.036). The Figure shows long-term Data were available for 16347 PCI treated patients and 8533 outcome of patients with NT-proBNP <1000 and ≥1000 ng/l. (52%) received with GPI. Patients with GPI were younger (61.5 Conclusion: NT-proBNP strongly predicts short- and long-term + 12 vs.63.0 + 12.6 years, p <0.001) and more likely to have a outcome in patients undergoing acute left main coronary artery STEMI (65.7 vs. 61.5%, p <0.001). MACE rates were lower for GPI stenting. Mortality in such patients is high, but those with treated STEMI patients (5.2 vs. 6.3 %, p = 0.021) but higher for NT-proBNP <1000 ng/l may have a favourable short- and GPI treated Non-ST- ACS patients compared to those without GPI long-term prognosis. (4.7 vs. 3.2 %, p = 0.005). Bleeding rates were significantly higher in GPI treated STEMI (3.5 vs. 2.1%, p <0.001), non-ST- ACS (2.9 vs. 1. 3 %, p <0.001) and very high-risk patients (8.0 vs. 2.4%, p <0.001). Adjusted OR did not show a significant difference for GPI treated STEMI and very high-risk patients but MACE was increased in GPI treated Non-ST- ACS patients (OR 1. 77 (95%CI 1. 29–2.44); p <0.001). Conclusions: While unadjusted analysis suggests a benefit of GPI in STEMI patients, this benefit is not significantte af r adjustment for confounding factors and in Non-ST- ACS patients use of GPI is even associated with significantly increased rates of MACE and in-hospital mortality.

87 The prognostic value of N-terminal proBNP in patients with acute coronary syndromes undergoing left main PCI L. Jaberg, S. Toggweiler, D. Müller, C.A. Wyss, W. Maier, L. Altwegg, J. Alibegovic, O. Gaemperli, U. Landmesser, T.F. Lüscher, R. Corti (Zürich, CH) Introduction: Patients undergoing acute left main (LM) coronary artery revascularization have a high mortality. We aimed to determine the prognostic value of N-terminal proBNP (NT- proBNP) in such patients. Methods: We reviewed medical records of all patients undergoing acute LM PCI between January 2005 and December 2008. We analyzed the clinical characteristics and the short- and long-term outcome in relation to NT-proBNP at admission. Results: A total of 71 patients with a median age of 69 years (69% male) were analyzed. Median NT-proBNP was 1364 ng/l, ranging from 46 to 70000 ng/l. In univariate analysis, age, log NT-proBNP (HR 3.51, 95% CI: 1. 55–7.97, p = 0.003) and LV-EF (HR 0.95, 95% CI: 0.91 – 0.99, p = 0.007) were significant predictors for all-cause mortality (Table). Receiver operating characteristic (ROC) curves were used to further evaluate the predictive value of NT-proBNP.The area under the curve was 0.763 for in-hospital mortality. An NT-proBNP of 1000 ng/l yielded a sensitivity of 100% and a specificity of 45% to identify patients who will die in-hospital and was therefore able to identify a subgroup with low mortality. In-hospital mortality was 0% for

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88 In vivo fluorine-19 MR angiography in a mouse model Methods: All experiments were performed on a Varian 9.4 T R.B. van Heeswijk, Y. Pilloud, U. Flögel, J. Schwitter, M. Stuber horizontal bore animal spectrometer.The study was approved (Lausanne, CH; Düsseldorf, DE) by the local animal ethics committee. Preparation of a 10% CE emulsion was carried out as previously described [2]. A CE Introduction: Magnetic resonance angiography (MRA) is dilution series was created to determine the detection limit of the commonly performed using gadolinium (Gd), which might be optimized F19 MRA method. Next, male balb/c mice (n = 7) were dangerous to people with renal insufficiency, or using time-of-flight anesthetized and injected with 12 ul/g of the CE emulsion. After (TOF)-derived imaging, which is susceptible to distortions due to acquisition of anatomic H1 gradient echo (GRE) images (30x30x2 the flowing blood it highlights.Therefore, a flow-independent mm2, 128x128), F19 GRE I maging at the same anatomical level angiographic technique without Gd may be most valuable.To was repeated (64x64, 512 averages, acquisition time = 21 min). address this need, we propose MR imaging of a compound that, The F19 contrast-to-noise ratio (CNR) was measured in several after intravenous injection, is only present in the lumen blood- places. pool. Perfluorocarbons such as perfluoro-15-crown-5-ether (CE) Results and discussion: The F19 images clearly, selectively and are excellent candidates for this lumen imaging: they are exclusively visualized the blood pool at different anatomical levels chemically inert, are non-toxic and are in several phase 3 FDA with high contrast (fig. 1b,d,f). These F19 images consistently trials [1], which also opens up the outlook for translation into the co-registered with the corresponding anatomy on the proton human setting. For these reasons, we have developed a images.The average CNR in the descending aorta and portal fluorine-19 (F19) MRA methodology using CE emulsions,ve ha vein was ~15, while it was ~50 in the heart. tested it in vitro and have, for the first time, explored its utility for angiography in vivo.

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Conclusion: Intravenously administered F19 is well-suited for a 89 selective and exclusive visualization of the vasculature and the Influence of microbubble shell design on attachment heart chambers in vivo. The high CNR and long intravascular efficiency in targeted ultrasound molecular imaging containment makes 19F MRI a promising alternative flow- independent angiographic MR technique. Since perfluoro-15- E. Khanicheh, M. Mitterhuber, K. Kinslechner, J. Lindner, crown-5-ether is safe, a translation into the human setting may B. Kaufmann (Basel, CH; Oregon, US) be possible. Introduction: Ultrasound molecular imaging relies on ligand- [1] J Ruiz-Cabello et al. NMR Biomed (2010) [2] U Flögel et al. mediated specific taat chment of microbubbles to the vascular Circ 118:p140 (2008) endothelium. Attachment efficiency has been reported to be low, and thus there is interest in the development of novel micro- bubble shell designs that yield better targeting efficiency. We hypothesized that the use of longer versus shorter polyethylene glycol arms for ligand attachment to microbubbles yield better targeting efficiency. Methods: Two different lipid-shelled microbubbles bearing biotin-tipped polyethyleneglycol spacer arms with a molecular weight of 2000 or 3400 (MB2000, MB3400) were prepared. Microbubble number, size and surface area was determined. Site density of biotin molecules available for ligand binding and site density of antibody ligands after conjugation was determined using fluorescence labeling techniques.To assess potential differences in circulation time between the two different preparations, microbubbles were injected intravenously as a bolus in wild type mice (n = 5), and contrast-specific images of the adductor muscle of the hindlimb were taken at a non-destructive mechanical index at 30sec intervals for 15 min. To assess in vivo attachment efficiency, contrast enhanced ultrasound molecular imaging with the two different microbubbles bearing an antibody to to P-Selectin (MB2000PSel, MB3400PSel) and microbubbles bearing a control antibody (MBCtr) was performed in a mouse model of TNF-α induced hindlimb muscle inflammation (n = 16). Results: The site density of biotin molecules available for ligand binding was similar for MB 2000 (15000/micrometer2) and MB 3400 (20000/micrometer2). The site density of antibodies after conjugation was not different between MB2000 and MB3400 (5700/ micrometer2 for both). The circulation time was identical between the two microbubble species.Targeted ultrasound molecular imaging demonstrated specific signal enhancement for MB2000PSel and MB3400PSel (1.5 ± 0.9 and 2.5 ± 1. 1; p <0.01 vs MBCtr; 0.5 ± 0.3), which was significantly higher in MB3400PSel than in MB2000PSel (p <0.01). Conclusion: Polyethylene glycol arm spacer length has a significant impact onta at chment efficiency of targted microbubbles, with longer spacer arms resulting in better attachment efficiency.

90 The prognostic value of cardiac hybrid imaging combining SPECT with CCTA A.P. Pazhenkottil, J.R. Ghadri, R.R. Buechel, B.A. Herzog, R.N. Nkoulou, M. Wolfrum, M. Fiechter, L. Husmann, S.M. Küest, O. Gaemperli, P. A. Kaufmann (Zürich, CH) Introduction: Although cardiac hybrid images fusing single- photon emission computed tomography (SPECT) myocardial perfusion imaging with coronary computed tomography angiography (CCTA) provide important complementary diagnostic information for coronary artery disease (CAD) assessment, no prognostic data exist on the predictive value of cardiac hybrid imaging. Hence, the aim of this study was to assess the prognostic value of cardiac hybrid imaging, Methods: Follow-up was obtained in 324 patients of 335 consecutive patients (97%) undergoing a one day stress/rest 99mTc-tetrofosmin SPECT and a CCTA for evaluation of CAD. Hard events (all-cause death and nonfatal myocardial infarction) and combined major adverse cardiac events (MACE: hard events, unstable angina requiring hospitalisation, coronary revascularizations) were determined using Kaplan-Meier method for the following groups: 1) Stenosis by CCTA and matching reversible SPECT defect; 2) Unmatched CCTA and SPECT finding; 3) Normal finding by CCTA and SPECT. Cox proportional hazard regression was used to identify independent predictors for cardiac events. Results: At a median follow-up of 2.8 ± 1. 0 years, 69 MACE occurred in 47 patients, including 20 hard events.Acorresponding matched hybrid image finding was associated with a significantly higher incidence of hard events (p <0.005) and proved to be an independent predictor for MACE. The annual hard event rate was

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6.0%, 2.8%, and 1. 3% for patients with matched, unmatched, mechanism is not known. We speculated that in CMS patients and normal findings. exercise intolerance is related to pulmonary fluid accumulation Conclusions: Cardiac hybrid imaging integrating SPECT and/or left ventricular dysfunction. with CCTA allows risk stratification in patients with known or Methods: To test this hypothesis we assessed extra-vascular suspected CAD. A matched defect on hybrid image is a strong water accumulation (ultrasound lung comets, ULC), predictor of MACE. pressure (right ventricular to right atrial pressure gradient, RV-RA pressure gradient) and left ventricular function (echocardiography) in 15 patients with CMS and 20 control subjects at rest and during exercise (50 W) at 3600 m. To evaluate the role of hypoxemia in this setting, we repeated these measurements during a 1-hour inhalation of 100% oxygen. Results: Exercise rapidly induced pulmonary interstitial fluid accumulation in all but one (14/15) patients with CMS and further aggravated the pre-existing hypoxemia. In contrast, in healthy high-altitude dwellers exercise did not induce fluid accumulation in the vast majority (16/20) of subjects (P = 0.002 vs. CMS) and did not alter arterial oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and hypoxemia in CMS patients was accompanied by a more than 2-times larger increase of pulmonary artery pressure than in controls (P <0.001), but no evidence of left ventricular dysfunction. Oxygen inhalation markedly attenuated the exercise-induced pulmonary 91 hypertension (P <0.01) and interstitial fluid accumulation Exercise induces rapid interstitial lung water (P <0.05, fig. 1) in patients with CMS, but had no detectable accumulation in patients with exaggerated pulmonary effects in controls (fig. 1). vasoreactivity Conclusions: These findings ovpr ide the first direct evidence S. Rimoldi, E. Rexhaj, D. Hutter, L. Pratali, M. Villena, that exercise induces rapid interstitial lung fluid accumulation U. Scherrer, C. Sartori, Y. Allemann (Bern, Lausanne, CH; and hypoxemia in patients with CMS that appear to be related Pisa, IT; La Paz, BO) to exaggerated . We suggest that this problem contributes to exercise intolerance in patients with CMS Background: Circumstantial evidence suggests that in healthy and speculate that in patients suffering from other forms of subjects exaggerated pulmonary hypertension may cause lung chronic hypoxic pulmonary hypertension exercise-induced fluid accumulation. Chronic mountain sickness (CMS) is pulmonary fluid accumulation also contributes to exercise characterized by exaggerated hypoxemia and pulmonary intolerance. vasoreactivity and exercise intolerance, but the underlying

92 Cardiac adaptation in ultra endurance training may ventricular noncompaction (LVNC). Findings were compared to cause pathologic findings – Advanced echocardiographic 23 age- and gender matched controls. study in 39 Ironman triathletes Results: The average age was 38 ± 9 years (12 females). There was no difference in body weight, body surface area, systolic and A.M. Bernheim, M. Zuber, M. Pfyffer, B. Knechtle, A. Fäh-Gunz, diastolic blood pressure (BP), LV ejection fraction (see table), and A. Linka, G. De Pasquale, B. Seifert, B. Naegeli, C.H. Attenhofer right ventricular fraction area change. IM ATHL showed athlete’s Jost (Zürich, Othmarsingen, St. Gallen, Winterthur, CH) hearts with dilated atria and eccentric left ventricular hypertrophy Introduction: Ultra endurance events such as the ironman (IM) as shown in the table and figure (left panel). There was no triathlon are increasingly popular in athletes (ATHL).The IM difference in global longitudinal strain, but there was a significant triathlon consists of a 3.8km swimming, a 180.2 km cycling, increase in peak systolic apical rotation in IM ATHL. In 4 IM ATHL and a 42.2 km run. Thus, these ATHL have a seemingly healthy with negative family history of heart disease there was a positive combination of muscle strengthening and endurance training. LVNC criterion of a 2:1 ratio; see figure (right panel). Grade I There are few data in the literature on echocardiographic findings diastolic dysfunction was present in 8 IM ATHL (20%) and in 1 in these ATHL. control (4%; p = 0.14). No IM ATHL had known arterial Methods: Thirty-nine IM ATHL were screened with an advanced hypertension but diastolic dysfunction correlated best with a echocardiographic exam including tissue Doppler imaging and higher diastolic BP (p = 0.0007), and less so with age (p = 0.03), 2D-speckle tracking analyzing longitudinal global strain of the left systolic BP (0.035) and left ventricular muscle mass index ventricle (LV) and LV twist mechanics the day before the IM (p = 0.045). triathlon. Additionally, we searched for positive criteria for left

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(CMR) parameters in predicting future major adverse cardio- vascular events (MACE). Background: ARVC is one of the commonest causes of sudden cardiac death amongst people younger than 30. Establishing the diagnosis still remains a difficult task. It is therefore essential to identify within a population with suspected ARVC, a subset who will indeed be at a higher risk of developing the disease, and at HR = heart rate at rest; BMI = body mass index; LVEF = left ventricular a higher risk of MACE. Imaging criteria that are most commonly ejection fraction; LVEDVI = left ventricular end-diastolic volume index; studied with respect to this entity include right ventricular volumes LAVI = left atrial volume index; RAVI = right atrial volume index; (RVEDV), ejection fraction (RVEF) and regional wall motion LV GS = left ventricular global strain (normal >–18%). abnormalities (RV RWMA). We sought to determine which of these robust CMR imaging parameters could better predict worse clinical outcomes. Methods: 368 consecutive patients referred between 2002 and 2005 for CMR assessment of suspected ARVC were included. Patients were required to have at least one minor criterion for ARVC as defined by the Task Force Criteria. Patients with known cardiomyopathies were excluded. For each patient, baseline RVEDV, RVEF, the presence of RV RWMA, as well as the presence or absence of late gadolinium enhancement (LGE) was assessed. Cut-off values for normal versus abnormal RVEDV and RVEF were based on previously published reference ranges from our institution. The primary end-point was a composite of all cause-mortality, life-threatening arrhythmias, appropriate ICD discharge, and unplanned hospital admission for cardiovascular events. Cox proportional hazards analysis was performed to assess the excess risk of adverse outcomes associated with each CMR variable. Results: The average age was 45.3 ±16 years; 190 were males Conclusion: In ultra endurance ATHL, hearts are enlarged; (51.9%). 65 patients (17. 7%) had increased RVEDV, 93 had diastolic dysfunction is not rare (20%) and best related to diastolic decreased RVEF (25.2%), 59 patients (16.6%) presented with BP. LV twist mechanics in IM ATHL show enhanced apical RV RWMA, 20 (9.7%) had LVLGE, and 4 (0.02%) had RVLGE. rotation. One positive noncompaction criterion was found in 51 patients reached the primary end-point. An abnormality in any 10% of IM ATHL. Ultra endurance training may not only lead to of the CMR variables was associated with a trend towards an physiological changes. increased risk of adverse outcomes. However, in this patient cohort, a decreased RVEF was the only single significant predictor of MACE [HR = 1. 83 (95% CI 1. 03–3.23; p value = 93 0.039)]. Prognostic cardiovascular magnetic resonance Conclusion: In this “everyday” cohort of patients referred for predictors of adverse outcomes in patients with CMR assessment of suspected ARVC, a decreased RVEF is suspected arrhythmogenic right ventricular significantly associated with an increased risk of MACE. cardiomyopathy M. Deac, J. Carpenter, D. Dawson, S. Prasad (Morges, CH; London, UK) Objective: To determine from everyday referrals of patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC), the accuracy of cardiovascular magnetic resonance

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117 There is life in the old dog yet: an astonishing reason segments showed only minor signs of atherosclerosis.The for cardiac death ascending aorta has a tree bark pattern and was enlarged up to 5 cm. Aortic wall was circumferentially thickened (fig. 2). P. K. Haager, R. Rodriguez, U. Bucher, H. Rickli (St. Gallen, CH) Microscopic analysis yield severe plasma cell infiltration. A 52 year old male was admitted with ongoing chest pain CCS IV Post mortem diagnosis was dead due to cardiogenic shock at a secondary care hospital. ECG at admission demonstrated caused by subtotal stenosis of both coronary ostia evoked by global ischemia. The patient was hypotensive and tachycardic. tertiary syphilis. Syphilis is a sexually transmitted disease caused Noradrenalin and oxygen were delivered. Situation deteriorated with ventricular tachycardia, defibrillation, intubation and need for mechanical ventilation. Patient was announced for immediate coronary angioplasty at a tertiary care hospital. Meanwhile, repeat ventricular tachycardia with need for defibrillation and ongoing mechanical resuscitation (CPR) occurred. The patient was transferred and angiography was done with ongoing CPR. The coronary angiogram demonstrated severe left main stenosis (fig. 1) without further narrowing. PCI and stent implantation was successfully performed. Transoesophageal echo ruled out aortic dissection, but circumferential wall thickening was recognized. Unfortunately, metabolic situation was intractable and the patient died more than one hour after CPR started. Autopsy was performed and demonstrated severe stenosis of the right and left (now successfully stented) coronary ostia. The remaining vessel

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by the spirochetal bacteria Treponema pallidum. Signs and transporter activity, caused by mutation of the SLC22A5 gene. symptoms vary depending on which of the four stages its Incidence is about 1 in 40000 newborns. Diagnosis is usually presents in. Cardiovascular syphilis is a rare (10%) form of tertiary made at age 1 to 7. Three forms of PCD are described. In the form syphilis. People are not infectious within this stage. Most common associated with cardiomyopathy, the disease is progressive and complication is syphilitic aortitis which may result in aneurysm patient die from heart failure if not treated. Substitution of formation. In 1999, 12 million people worldwide are believed to be L-Carnitin leads to a dramatic improvement of disease course. infected, 90% of cases within the developing world. Switzerland This case underlines the crucial role of etiologic diagnostics in faces a rapidly growing number of infections: 642 in 2006, 1113 in this reversible form of DCM. Early diagnostics and therapy are 2010 (+73%; 71% male). Most cases are seen in Zürich, Genève, critical for the prognosis of the patient. This is furthermore an Vaud and Bern. The exact reason is unknown. It is discussed example of a role played by CMR in the diagnostic work-up of whether negligent carelessness in consideration of improved HIV heart failure and its follow-up under therapy. therapy may play a role.

119 118 Gitelman syndrome revealed by a Brugada ECG Reversible congestive heart failure associated with pattern primary carnitin deficiency: report of a case and review D. Marino, M. Di Valentino, J. Klimusina, H. Zwahlen, of the literature A. Gallino, A. Menafoglio (Bellinzona, CH) S. Perruchoud, D. Locca, S. Di Bernardo, J. Schwitter Introduction: Bartter and Gitelman syndrome are inherited (Lausanne, CH) diseases due to mutations of genes encoding the sodium A 5-year-old previously healthy boy was admitted for abdominal transporter located in the nephron and characterized by pain and vomiting. Physical examination showed tachypnoe hypokalemia, hypomagnesemia, metabolic alkalosis, (32/min), hepatomegaly and painful palpation of the upper right hyperreninemia. Brugada syndrome is an inherited disease due to abdominal quadrant. Laboratory tests were normal except for mutations of genes encoding cardiac ion channels, mainly sodium elevated ammonium (202 mcmol/l). Chest X-ray was performed, channel. It is characterized by a typical ECG pattern of ST- showing cardiomegaly and interstitial edema. Transthoracic segment elevation in V1-V3 (type 1, diagnostic for the disease) echocardiography revealed dilated left cavities and LV and an increased risk of sudden cardiac death. Sometimes the hypertrophy together with a diffuse hypokinesia and LVEF of ECG is atypical (type 2 and 3) and convert to diagnostic type 1 30–40%. Diuretics and ACE-inhibitors were introduced. At that after drug challenge or electrolyte imbalance. time, the differential diagnosis for the DCM included myocarditis, Case report: A 30 years-old man presented with a history of congenital or genetic, metabolic or autoimmune disease.The atypical chest pain and muscle weakness. Clinical examination next day, the boy underwent cardiac magnetic resonance (CMR) was uneventful. The personal and family history was negative for examination, showing a severe dilatation of the LV with an cardiovascular disease, syncope or sudden death. ECG revealed end-diastolic diameter of 50 mm and a volume of 150 ml. a typical Brugada pattern type 1 (fig. 1). The echocardiography LVEF was 20% with diffuse LV hypokinesia (fig. 1). No late showed a structurally normal heart. The blood examination enhancement was present after Gadolinium injection, ruling revealed a severe hypokalemia at 2.1 mmol/l (n.v. 3.5–5 mmol/l), out myocarditis. Further laboratory metabolic analysis indicated normal serum calcium and magnesium, slight metabolic alkalosis severely decreased total and free carnitin levels and low renal (pH 7. 46, HCO3–30 mmol/l¸ pCO2 5,72 kPa), low urinary calcium carnitin reabsorption, corroborating the diagnosis of primary excretion (2 mmol/l) and high reninemia of 147. 3 ng/l (n.v. 3.6– carnitin deficiency (PCD). Carnitin substitution was initiated. The 20 ng/l). Based on the above findings a diagnosis of Gitelman clinical condition rapidly improved. No symptoms of heart failure syndrome was assumed. A treatment with spironolactone 200 mg/ were present anymore. A follow-up CMR performed 9 months day and diclofenac 150 mg/day was begun. The serum K was later confirmed the recovery. LV end-diastolic volume decreased repeatedly measured between 3.0 and 3.5 mmol/l, the weakness from 150 ml to 66 ml, LVEF increased from 20% to 55% (fig. 2). disappeared and ECG showed a non specific Brugada tepat rn Late enhancement was absent after Gadolinum injection (fig. 3). type 2 (fig. 2). The typical Brugada ECG on the admission was Carnitin is required for the transport of fatty acids from the cytosol into mitochondria during lipid breakdown. 75% of carnitin is obtained from food, 25% is endogenously synthesized. PCD is an autosomal recessive disorder resulting from impairment of a

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most likely provoked by the severe hypokalemia, as has been rarely reported. Conclusion: This case illustrate a Bartter or, most likely a Gitelman syndrome which was eventually diagnosed on the basis of the ECG alterations typical for Brugada syndrome.These ECG alterations made us search for possible electrolyte disturbances. The severe hypokalemia on laboratory analysis prompted further investigations leading to nephrological diagnosis.Adiagnostic test with ajmaline to confirm the Brugada syndrome was not be performed due to the refusal by the patient.

120 Electrical storm in a patient with aortic and endocarditis C. Hottkowitz, P. Ammann, G.R. Kleger, A. Kuenzli, M.T. Maeder (St. Gallen, Kreuzlingen, CH) A 44-year-old man was admitted after a one week’s history of fever, malaise, and headaches. Lumbar puncture revealed evidence of bacterial meningitis, and blood cultures were positive for Staphyloccocus aureus. Because of a systolic murmur a transthoracic echocardiogram was performed showing a heavily calcified right coronary cusp of the aortic valve and severe aortic regurgitation. In addition, there was a large and mobile structure (VSD) was identified (fig. 2D, asterisk). The patient underwent originating from the septal tricuspid annulus.Treatment with urgent surgery, and large aortic and tricuspid valve vegetations flucloxacillin/ tobramycin was instituted. A few hours later were confirmed. There was a perimembranous VSD partly filled ventricular tachycardia was seen on the telemetry electrocardio- with purulent material which extended to both sides of the VSD to gram (ECG). Intubation, administration of amiodarone and the aortic and tricuspid vegetations.After extensive debridement repeated attempts of electrical cardioversion were required to the aortic valve was replaced by a bioprosthesis, the tricuspid achieve rhythm control. During the tachycardia, the ECG showed valve was reconstructed, and the VSD was closed. While a right bundle branch block/inferior axis morphology (200 bpm; atrioventricular block is common in patients with invasive infective fig. 1A), while the ECG in normal sinus rhythm showed first endocarditis ventricular tachycardia is extremely rare.The degree atrioventriuclar block and incomplete left bundle branch morphology of the tachycardia suggested an origin at the base block (fig. 1B). Emergency coronary angiography revealed normal of the left ventricle but the exact mechanism remains unknown. coronary arteries without evidence of embolisation. Septic coronary embolism was ruled out. This case highlights the Transesophageal echocardiography showed a functionally malignancy of this disease and the need for very careful bicuspid aortic valve with a large and calcified structure monitoring once invasive infective endocarditis is suspected. originating from the previous right coronary cusp with several filiform vegetations (fig. 2A and C, triangles). This structure was directly adjacent to the septal tricuspid annulus where a large, 121 highly mobile vegetation was originating from (fig. 2B and C, arrows). In addition, a small subvalvular ventricular septal defect Two large intracardiac fibromas in nevoid-basal cell carcinoma (Gorlin syndrome): outcome of conservative treatment during a 9 year follow-up R. Weber, L. Weibel, E.R. Valsangiacomo Büchel, A. Rauch, A. Oxenius, D. Stambach, C.H. Attenhofer Jost (Zürich, Schwerzenbach, CH) Case report: The currently 9 year old patient (pt) was diagnosed to have a cardiac tumor as a fetus.At the age of 38 weeks of gestation, the incidental finding of a heart tumor was made by ultrasound. Emergency echocardiography at birth showed 2 tumors with the larger one of 3 cm obstructing the left ventricular inflow and outflow.There was normal systolic function of both ventricles. Surgical excision was recommended but declined by the parents.Additional findings at that time were pulmonary hypertension and mild laryngomalacia. The etiology of the tumor was unknown. Rhabdomyoma was suspected. Screening for tuberous sclerosis was negative. The cardiac tumors located epicardially were consistent with a hamartoma. As the family declined surgical intervention, the pt was followed with yearly

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also had subcutaneous, radio-opaque nodules at the back of his left forearm (fig. 2). There was a 3/6-systolic murmur at the right sternal border with increasing intensity during inspiration. Neck veins were distended with an estimated central venous pressure of 12 cm H20. A chest x-ray showed a “tent”-like cardiomegaly and bilateral pleural effusions but no pulmonary congestion. Transthoracic echocardiography revealed a large pericardial effusion but no signs of cardiac tamponade, a grossly dilated and hypertrophied right ventricle with impaired systolic function, severe tricuspid insufficiency and systolodiastolic D-shaping of the . No interatrial septal defect was present and all pulmonary veins seemed to drain into the left . Right ventricular systolic pressure was at 55 mm Hg above right atrial pressure. On right heart catheterization pulmonary resistance was 12.45 WU with an increased echocardiographic and clinical exams.The history of the father transpulmonary gradient of 41 mm Hg.There was no acute and the sister with mandicular cysts, as well as the presence of hemodynamic response on pulmonary vasodilator testing with macrocephaly, frontal bossing and palmo-plantar pits in the index ilomedin. The patient was diagnosed with limited cutaneous pt were suggestive of basal cell nevus syndrome (BCNS). In systemic sclerosis (SSc) with severe pulmonary hypertension. 2010, a dermatology review including histopathology revealed Clinical hallmarks of SSc were formerly labeled with the acronym multiple basal cell carcinomas. Genetic analysis identified a CREST for Calcinosis cutis, Raynaud phenomenon, Esophageal mutation in the patient and his father thus confirming the dysmotility, Sclerodactyly and Teleangiectasia. Patients with this diagnosis of BCNS.The impressive echocardiographic findings disease are at highest risk of developing pulmonary arterial in 2010 at the age of 9 years with the 2 heart tumors are shown in hypertension (PAH) among all patients with connective tissue figure 1 (small apical tumor measuring 20x25x30 mm; large tumor disease.The prevalence of PAH in SSc is around 15–20% and in the basal/mid anterior septum measuring 40x45x45 mm). carries a poor prognosis. Echocardiography is of importance for Cardiac MRI confirmed the finding of a cardiac fibroma with screening and detection of PAH due to connective tissue disease. typical late gadolinium enhancement as shown in figure 2 (arrow). An annual echocardiography is recommended in all these There is currently no intraventricular gradient. patients. Once PAH has been detected, right heart catheterization Now, at the age of 9 years, the pt has no cardiac symptoms, the is mandatory. Treatment options for PAH include bosentan, 24 hour ECG is unremarkable. Within the last years, the size of sildenafil and prostanoids. the cardiac tumors has only increased slightly. Summary: Cardiac tumors are rare in infancy. They are more common in genetic disorders such as neurofibromatosis, tuberous sclerosis, familial myxomas and -as in this pt- in BCNS also known as Gorlin syndrome.The heart tumors in BCNS are usually fibromas which can calcify and enlarge. Surgically excision is usually advised as a cardiac fibroma can cause heart failure, chest pain, ventricular tachycardia or death. The family of this pt has declined any intervention so far. Recently reported novel pharmacologic treatment targeting the hedgehog pathway appears to have antitumor activity in pt with BCNS and may represent an alternative therapy in this pt.

122 Digital ulcers, calcinosis cutis and cardiomegaly C. Müller Jampen, S. Oertle, T. Geiser, M. Schwerzmann (Bern, Ostermundigen, CH) A 53-year old immigrant from Eritrea was referred for cardiologic evaluation of progressive shortness of breath. He was thought to have severe left-sided valvular disease due to a systolic murmur and cardiomegaly. He was in functional class NYHA III. He had had pulmonary tuberculosis more than 20 years ago. On clinical examination his blood pressure was 105/70 mm Hg on both arms, he had a regular pulse with 80 bpm and was afebrile (36.5 °C). His resting saturation while breathing ambient air was 92%. A closer look at his fingertips showed small ulcers (fig. 1) and he

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123 Changes of renal function over time in patients function with CRT is unknown. Aim of this study was to evaluate with cardiac resynchronisation therapy renal function over time, both in CRT patients with normal and impaired renal function at baseline. L. Hitz, D. Theuns, M. Kühne, C. Sticherling, L. Jordaens, Methods: The study cohort consisted of 284 patients from S. Osswald, B. Schaer (Basel, CH; Rotterdam, NL) 2 university hospitals in whom a CRT- defibrillator was implanted Background: In subgroup analyses of large trials, no benefit of and in whom creatinine values at implant and at least after one a defibrillator has been shown in patients with advanced renal year were available.The glomerular filtration rate (GFR) (mL/ failure, questioning implantation in these patients. However, min/1.73 m²) was calculated using the extensively validated cardiac resynchronisation therapy (CRT) patients might MDRD formula. Patients were stratified using the 4 categories experience increased kidney perfusion and thus improvement of the MDRD scheme (normal up to severely impaired renal of pre-renal kidney failure. The magnitude of changes in renal function). Transitions from one category to another were

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determined. A clinically significant change was defined as >9 mL/ 125 min/1.73 m² in both directions. Finally, mortality according to the Baseline QRS morphology: a tool to predict categories at baseline was calculated. biventricular systolic function response to cardiac Results: The majority of patients were male(75%), age was resynchronization therapy 61 ± 12 years, ejection fraction 24 ± 8%, dilated cardiomyopathy was present in 51%, ischemic heart disease in 46% and G. Domenichini, G. Boriani, C. Valzania, H. Sunthorn, M. Biffi, miscellaneous pathologies in 3%. The device was implanted for H. Foulkes, G. Gavaruzzi, H. Burri (Genève, CH; Bologna, IT) primary prevention in 76%. Mean MDRD levels were 64 ± 29 ml/ Introduction: Predicting response to cardiac resynchronization min/1.73 m² at implant, 60 ± 24 after 1 year, and 56 ± 24 after therapy (CRT) remains a challenge.We evaluated the role 2 years, respectively (comparison of baseline to 1-year follow-up, of baseline QRS morphology to predict response in terms P = 0.13; comparison of baseline to 2-year follow-up, P = 0.005). of improvement in biventricular ejection fraction (EF). Significantly more patients exhibited a further impairment of GFR, Methods: Consecutive patients (pts) undergoing CRT both regarding a change in the MDRD category (p 0.02) as well implantation underwent radionuclide angiography at baseline and as a decrease in GFR of >10 ml/min/1.73 m² (p 0.01). Further after 6 months follow-up.The relationship between baseline QRS details are shown in table 1. During a mean follow-up 45 ± 30 morphology and mechanical dyssynchrony using phase analysis months, 21% of patients died (59/284). Mortality in MDRD was evaluated. Changes in left and right ventricular EF (LVEF and categories 1 + 2 was 15%, in 3 + 4 33%, respectively (P = <0.01). RVEF) were analyzed with regard to baseline QRS morphology. Conclusion: In a majority of CRT patients renal function is Results: We enrolled 56 pts (42 males, age 67 ± 11 years): 32 impaired at baseline. Despite resynchronization, GFR (as with left bundle branch block (LBBB), 4 with right bundle branch measured by MDRD) does not improve but deteriorates further block (RBBB) and 20 with non-specific intraventricular conduction over time. Mortality correlates with baseline GFR. delay (NSCD). No significant differences in left ventricular dyssynchrony were observed between pts with LBBB, NSCD and RBBB.Atotal of 48 pts completed follow-up. Pts with LBBB had significantly greater improvement in LVEF compared to those with NSCD (+10.5 ± 10.2% vs. +3.9 ± 7. 6%, p = 0.012). Response (defined as ≥5% increase in LVEF) was observed in 68% of LBBB vs. 24% of NSCD pts (p = 0.006). None of the RBBB pts were responders. RVEF was significantly improved in LBBB pts (+4.7 ± 8.9%, p = 0.009), but not in NSCD and RBBB pts (+0.2 ± 5.8%, p = 0.85). Finally, at multivariate analysis, LBBB was the only predictor of LVEF response (OR, 7. 45; 95% CI 1. 80–30.94; p = 0.006), but not QRS duration or extent of mechanical dyssynchrony. Conclusions: Presence of a LBBB is a marker of a positive response to CRT in terms of LVEF and RVEF improvement, irrespective of QRS duration or extent of mechanical dyssynchrony. Pts with NSCD and RBBB show significantly less 124 benefit from CRT than those with LBBB. Dronedarone exerts anti-thrombotic effects A. Breitenstein, S.H.M.Sluka, A. Akhmedov, G.G. Camici, J. Steffel, F. Duru, T.F. Lüscher, F. C. Tanner (Zürich, CH) 126 Background: Dronedarone is a benzofuran derivative with an Characterisation and financial impact of patients electropharmacologic profile resembling that of amiodarone, but with unused implantable cardioverter defibrillator less thyreoid-related and pulmonary side-effects. In a subgroup 5 years after implantation analysis of the ATHENA trial, there was a significant reduction in T. Reichlin, M. Kühne, C. Sticherling, S. Osswald, B. Schär hospitalisations for acute coronary syndromes in patients under (Basel, CH) dronedarone-treatment. Whether this is due to its antiarrhythmic Background: Implantable cardioverter-defibrillators (ICDs) are effect or possible anti-thrombotic properties is unknown. increasingly used for primary and secondary prevention of Methods and results: Male C57Bl6 mice were treated with sudden cardiac death. However, a substantial fraction of ICD dronedarone (200 mg/kg body weight once daily via oral gavage; patients will never receive appropriate ICD therapy, and long-term n = 7) or vehicle (0.5% methylcellulose; n = 7) for two weeks. 24 follow-up data on ICD patients are rare.The aim of our study was hours after the last application, arterial thrombus formation was to determine amount of and predictors for non-use as well as measured by a carotid artery photochemical injury model, a well financial impact of patients with unused ICDs5 years after established in vivo thrombosis model. Arterial flow was monitored implantation. via a Doppler flow probe, and thrombotic occlusion was defined Methods: We prospectively enrolled 322 consecutive ICD by a flow of less then 0.1 ml/min for more than 1 minute. The patients. Baseline data were collected at device implantation and investigator performing the thrombosis model was blinded all patients were followed-up for 101 ± 30 months (range 60–187 regarding the treatment. Dronedarone, at clinically relevant months) regarding first appropriate ICD-therapy, inappropriate plasma concentrations (1231 ± 0.014 ng/ml), inhibited carotid shocks and device replacement. artery thrombus formation in vivo (n = 7; P <0.05) without Results: After 5 years of follow up, 139 patients (43%) were affecting initial blood flow (n = 7; P = NS). Coagulation parameters free of appropriate ICD therapy. Patients with unused ICD were including prothrombin-time (PT) and activated partial plasma younger (median 57 vs. 63 years, p <0.001), more often had thrombin-time (aPTT) as well as total platelet number did not indication for primary prevention (34% vs. 21%, p = 0.01) and differ in controls as compared to dronedarone-treated mice had higher baseline ejection fraction (35% vs. 30%, p = 0.02). (n = 7; P = NS). Conclusions: Dronedarone impairs arterial thrombus formation in vivo. This action occurs within the range of dronedarone concentration measured in patients, and thus represents a possible explanation for the reduction in hospitalisations for acute coronary syndromes in patients under dronedarone treatment. Further investigation is necessary to elucidate the mechanisms responsible for this pleiotropic effect.

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In multivariable analysis, age <60 years, negative electrophysiol- ogical studies prior to implantation and implantation after 1. 1. 2000 were independent predictors for non-use. Of the patients with unused ICD after 5 years, 35 (25%) had experienced at least one episode of inappropriate ICD shock. A total number of 207 devices (1.5 devices per patient) was needed for the 139 patients within 5 years, accounting for around 43000 $ per patient. Conclusions: Nearly half of ICD patients seen in daily practice do not have appropriate ICD therapy within 5 years after implantation, highlighting the medical and economic need for improved patient selection. Conclusion: A simple 2-step algorithm evaluating QRS width and changes in negativity in lead I can accurately diagnose loss of RV capture in CRT.

128 Mid-term follow-up of the Sprint Fidelis® ICD lead S. Frey, U. Bucher, M. Kühne, R. Widmer, C. Sticherling, P. Ammann, S. Osswald, B. Schaer (Basel, St. Gallen, CH) Background: In October 2007, problems with an unusually high rate of lead fractures in Medtronic Sprint Fidelis leads (SFL) became apparent and the lead was withdrawn from the market. Worldwide, experts recommended a close follow-up of affected patients, but no prophylactic lead replacement. Industry- independent data on the long-term performance of the SFL in Switzerland have not been presented yet. Methods: All patients in whom a SFL was implanted in two large Swiss centers were identified. Pacing and high-voltage impedance of the RV-lead were regularly measured, but for the purpose of this study considered only at implant and then in intervals of ± 6 months.The rate of lead replacement due to overt lead malfunction (i.e. inappropriate discharge or recurrent lead noise) 127 or to unacceptably high impedances without lead noise was registered. In all patients, the lead integrity alert (LIA) was A novel ECG algorithm for diagnosing loss of left activated. ventricular capture in cardiac resynchronization Results: We identified 166 patients with an implanted SFL. Due therapy to incomplete data, had 9 (5%) patients were excluded and thus V. Ganière, V. Niculescu, G. Domenichini, C. Stettler, 157 studied. Age of the patients was 60 ± 13 years, 22% were P. Defaye, H. Burri (Genève, CH; Grenoble, FR) female. Follow-up was 49 ± 15 months. 10 leads (6.4%) were Background: The prerequisite for cardiac resynchronization replaced after 40 ± 15 months (range 15–58), one due to overt therapy (CRT) is biventricular capture, that may be verified by malfunction and 9 by decision of the treating cardiologist due to analysis of the surface ECG. Few algorithms exist, and have only high impedance values judged unacceptably.The cumulative been tested in patients with apical leads. 4-yearlead survival was 95.6%. The patient with lead malfunction Methods: We analyzed the ECG limb leads of 51 CRT patients experienced a severe electric storm with >50 shocks (stable during biventricular (BV), right ventricular (RV) and left ventricular impedance over time, but sudden rise from 500 to 2000 ohm (LV) capture, to devise a simple algorithm that may accurately 5 days before the storm, no short VV-intervals seen 3 months indicate changes in ventricular capture. earlier, LIA alarm activated, but not audible for the patient). No Results: A number of parameters differed significantly between LIA trigger due to elevated VV-intervals was observed in any the 3 pacing modes (P <0.001 for all comparisons): QRS axis patient. Rise of RV impedance 300 omega over time (suggestive (see figure), duration, amplitude and negativity in lead I.An of a probable lead problem in the near future) in patients without algorithm evaluating QRS narrowing and increasing negativity in lead replacement was observed in only 1 patient. The Kaplan- lead I was devised (see figure). For diagnosing loss of LV capture, Meier curve of lead survival is shown in the figure. the algorithm had a sensitivity of 88%, specificity of 95%, positive Conclusion: The Sprint Fidelis lead exhibits an impaired and negative predictive values of 85% and 96% respectively. mid-term performance regarding lead integrity. Fortunately, the The algorithm performed well both in patients with RV apical majority of leads that had to be replaced showed no overt (accuracy 90%, n = 17) as well as septal leads (accuracy 94%, malfunction with serious sequelae for the patients. n = 34).

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135 endothelial cells was highly decreased, suggesting that KLF2 Mice generated by assisted reproductive acts as a transcription factor for this gap junction protein. technologies, a model organism for the study Conclusions: High laminar shear stress in vivo or in vitro of epigenetic mechanisms of vascular dysfunction upregulates the expression of KLF2 and of the anti-atherogenic in vivo protein Cx37.Therefore, this effect of shear stress on Cx37 expression may participate in the overall protective effect of high E. Rexhaj, S. Rimoldi, A. Giacobino, P. Dessen, P. Nicod, laminar flow on the endothelium. C. Sartori, U. Scherrer (Lausanne, Genève, CH) Background: Environmental influences acting early in life predispose to premature cardiovascular disease.Assisted 137 reproductive technologies (ART) involve the manipulation of early High-density lipoprotein stimulates endothelial CAT-1 embryos at a time when they may be particularly vulnerable to expression and l-arginine uptake: a novel mechanism external disturbances.We recently found that vascular function leading to endothelial-protective effects of high-density in both children and mice conceived by ART is defective. In mice, lipoprotein that is profoundly altered in patients with this vascular dysfunction is transmitted to their progeny, coronary disease suggesting an epigenetic mechanism. Methods: To test this hypothesis, we assessed vascular function C. Besler, V. Makrides, K. Heinrich, M. Riwanto, K. Huggel, and the vascular DNA methylation pattern of imprinted genes and D. Pöhlmann, F. Verrey, T.F. Lüscher, U. Landmesser (Zürich, CH) the eNOS gene promoter in male ART and control mice.We then Background: Endothelial nitric oxide (NO) is a major regulator tested the effects of a histone deacetylase inhibitor on these of vascular homeostasis and exerts potent anti-atherogenic variables. effects. High-density lipoprotein (HDL) from healthy subjects Results: As expected, ART mice displayed marked mesenteric- (HDL-HS) stimulates endothelial NO synthase (eNOS)-dependent artery endothelial dysfunction in vitro and arterial hypertension in NO production; however, the underlying mechanisms remain to vivo. Most importantly, the methylation pattern of imprinted genes be further defined. In the present study we therefore H19 (P <.01, vs. ctrl), Gtl2 (P <.01, vs. ctrl), Peg3 (P = .02, vs. ctrl) characterized the effects of HDL-HS and HDL from patients with and of the eNOS promoter (P = .01, vs. ctrl) was altered in the coronary disease (HDL-CAD) on cationic amino acid transporter-1 aorta of ART mice.The dysmethylation of the eNOS gene (CAT-1), the main endothelial L-arginine transporter, and promoter in ART mice was of functional importance, since it was endothelial uptake of L-arginine, the substrate of eNOS. associated with decreased eNOS expression in carotid arteries Methods: HDL-HS (n = 25) and HDL-CAD (n = 25) was isolated and decreased NOx plasma concentration (9.1 ± 10.4 vs. 32.3 ± by sequential ultracentrifugation. The effects of HDL on 9.6 uM, X ± SD, P <.001, ART vs. ctrl). DNA dysmethylation can endothelial mRNA and protein expression of CAT- 1 were be reversed by histone deacetylase inhibitors. Administration of determined, and cellular localization of CAT- 1 was examined by such an inhibitor (Butyrate, 2 mg/kg/d, i.p. for 2 wks) to male ART confocal microscopy. NO production was measured by electron mice normalized the vascular methylation pattern of imprinted spin resonance spectroscopy. Endothelial L-arginine uptake was genes H19, Gtl2 and Peg3 (all P <.05 vs. vehicle), of the eNOS determined using L-[3H]arginine.The role of CAT- 1 for HDL- promoter (P = .04 vs. vehicle) and NOx plasma concentration induced endothelial L-arginine uptake and NO production was (29.0 ± 12.4 uM, P <.001 vs. vehicle). The normalization of the determined after inhibition of CAT- 1 by siRNA, N-ethylmaleimide vascular DNA methylation pattern by Butyrate was associated (NEM) or lysine. with normalization of the vascular function in ART mice and Results: HDL-HS substantially increased endothelial CAT- 1 prevention of the transmission of this defect to their progeny. expression on mRNA and protein level. Notably, inhibition of Conclusion: ART induces premature systemic vascular endothelial scavenger receptor (SR)-BI with a blocking antibody dysfunction in mice by an epigenetic mechanism. ART mice and PD98059, an inhibitor of extracellular-signal regulated kinase represent a model organism for the study of epigenetic (ERK) 1/2, prevented stimulation of CAT- 1 protein expression by mechanisms of vascular dysfunction. We speculate that HDL-HS. Moreover, HDL-HS induced endothelial membrane epigenetic mechanisms also play a role in ART- induced vascular translocation of CAT- 1 and increased caveolar association of dysfunction and predisposition to premature cardiovascular CAT- 1 and eNOS.Total and CAT- 1 mediated endothelial L-arginine disease in humans. uptake were stimulated by HDL-HS. Importantly, inhibition of CAT- 1 profoundly reduced the effect of HDL-HS on endothelial NO production. In marked contrast, HDL-CAD did not stimulate 136 endothelial expression and membrane translocation of CAT- 1 Shear stress modulates the expression of the and rather inhibited endothelial L-arginine uptake. vasoprotective protein Cx37 in endothelial cells Conclusion: The present study demonstrates for the first time that HDL from healthy subjects stimulates expression and A. Pfenniger, E. Sutter, S. Cuhlmann, P. C. Evans, R. Krams, membrane translocation of CAT- 1 in endothelial cells via the HDL B.R. Kwak (Genève, CH; London, UK) receptor SR-BI and the ERK1/2 signaling pathway, resulting in Introduction: Connexin37 (Cx37) is a gap junction protein increased L-arginine uptake. Of note, stimulation of CAT- 1 by essential for cell-cell communication in endothelial cells (ECs). Its HDL is critical for the capacity of HDL to augment endothelial expression is lost in ECs overlying atherosclerotic plaques. NO production. In contrast, HDL from patients with CAD fails to Moreover, the deletion of Cx37 in ApoE-/- mice increases their increase endothelial CAT- 1 expression and L-arginine uptake, susceptibility to atherosclerosis, which suggests that Cx37 has providing a novel mechanism for impaired vasoprotective effects anti-atherogenic properties. High laminar shear stress is known to of HDL in these patients. be vasculoprotective partly through the induction of KLF2. As the promoter region of the Cx37 gene contains KLF consensus binding sites, we hypothesize that shear stress, through the 138 modulation of KLF2, may affect Cx37 expression in ECs. Torcetrapib impairs endothelial function in Methods and results: We observed that Cx37 is highly hypertension expressed in the straight region of the common carotid artery of ApoE-/- mice, whereas it is reduced at carotid bifurcation. Shear M. Hermann, B. Simic, S. Shaw, C. Dörries, C. Besler, stress-modifying vascular casts were placed around the right T.F. Lüscher, F. Ruschitzka (Zurich, Bern, CH) common carotid artery of ApoE-/- mice and Cx37 expression in Background: A marked increase of HDL notwithstanding, the response to flow was assessed by en face immunofluorescence. cholesterol ester transfer protein (CETP) inhibitor torcetrapib We found that Cx37 expression is downregulated in regions of was associated with an increase in all-cause mortality in the altered flow (either low laminar or oscillatory shear stress), but is ILLUMINATE trial. As underlying mechanisms remain elusive, conserved in regions of high laminar flow. To further study the the present study was designed to delineate potential off-target mechanisms involved, the mouse endothelial cell line bEnd.3 was effects of torcetrapib. exposed to shear stress in vitro. After 24hrs of high laminar shear Methods and results: Spontaneously hypertensive rats (SHR) stress (30 dynes/cm2) Cx37 and KLF2 expression were increased and Wistar-Kyoto rats (WKY), were treated with torcetrapib when compared to static condition. Interestingly after effective (100 mg/kg/day; SHR-T and WKY-T) or placebo (SHR-P,WKY-P) silencing of KLF2 by transfection with siRNA, Cx37 expression for 3 weeks. Blood pressure transiently increased during the first was reduced and diffusion of Propidium Iodide between

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3 days of torcetrapib administration in SHR and returned to Methods and results: In human aortic vascular smooth muscle baseline thereafter despite continued drug administration. cells (AoSMC) cLDL (10–300 ug/ml) induced tissue factor (TF) Acetylcholine-induced endothelium-dependent relaxations of and plasminogen activator inhibitor type 1 (PAI-1) expression by aortic rings were markedly impaired, and eNOS mRNA and 3.5- and 3-fold, respectively (n = 4; p <0.01 for each mediator). protein were down-regulated after 3 weeks of torcetrapib cLDL also enhanced basal and TNF-α induced expression of TF treatment in SHR (P <0.0001, P <0.01 and P <0.05, resp. vs and PAI-1 expression in human aortic endothelial cells (n = 4; SHR-P). Torcetrapib reduced NO release in cultured aortic p <0.02 for each mediator). These effects were paralleled by endothelial cells (P <0.01 vs vehicle-treated cells) and increased an enhanced TF activity in both cell types (n = 4; p <0.01). In generation of reactive oxygen species in of SHR-T contrast, native LDL (nLDL) had no effect on expression or (P <0.05, vs SHR-P). Vascular reactivity to endothelin-1 (ET-1) activity of TF and PAI-1. In both cell types, cLDL induced TF and aortic ET-1 tissue content were increased in SHR-T (P <0.05 and PAI-1 expression at the transcriptional level via the mitogen- vs SHR-P). Importantly, the ETA/B-receptor antagonist bosentan activated protein kinases p38 and ERK (n = 3; p <0.05) as well as normalized endothelial function in SHR-T (P <0.05). the transcription factor NFkappaB (n = 4, p <0.05). In line with Conclusions: Torcetrapib induces a sustained impairment of these findings, intravenous administration of cLDL (2 mg/kg body endothelial function, decreases eNOS mRNA, protein as well as weight) accelerated arterial thrombus formation in a murine NO release, stimulates vascular ROS and endothelin production, photochemical carotid artery injury model as compared to an effect that is prevented by chronic ETA/B-receptor blockade. treatment with nLDL (2 mg/kg body weight) or vehicle (PBS) These unexpected off-target effects of torcetrapib need to be (n = 8; p <0.05 versus nLDL and control). ruled out in the clinical development of novel CETP-inhibitors, Conclusions: These data demonstrate that cLDL, at particularly before a large patient population at increased physiologically relevant concentrations, exerts potent pro- cardiovascular risk is exposed to these compounds. thrombotic effects in human vascular cells and enhances thrombus formation in vivo. This observation may be relevant for understanding the markedly increased incidence of fatal acute thrombotic events in patients with end-stage renal disease and the development of new LDL targeting therapies in these patients.

140 Tissue factor deencryption is required for normal development and haemostasis S.H.M. Sluka, A. Akhmedov, G.G. Camici, T.F. Lüscher, F. C. Tanner (Zürich, CH) Blood coagulation needs to be tightly regulated to assure proper hemostasis without the development of thrombosis.The activity of tissue factor (TF), the key initiator of coagulation, can be regulated by disulfide isomerisation which switches TF between a cryptic and an active form. Cys186-Cys209 disulfide bond formation leads to TF deencryption and thereby significantly increases TF’s affinity for factor VIIa binding.To investigate the role of TF activation in vivo, cystein 209 of murine TF was mutated into glycin in order to generate C209G-TF mice.These mice are called cryptic TF mice, since the homozygous mice cannot form the disulfide bridge required for TF activation and TF thus resides in its cryptic form. 17% of the offspring from heterozygous breeding pairs was homozygous for cryptic TF, which is significantly less than expected according to Mendelian distribution. Homozygous cryptic TF males suffered from early lethality, which occurred in about 50% of cases within six to twelve weeks of age.These mice showed macroscopic and microscopic signs of bleeding in heart, lung, and brain as well as secondary inflammatory changes. If not affected by early lethality, 139 homozygous cryptic TF males could age almost normally, but Carbamylated low-density lipoprotein induces exhibited prolonged tail bleeding times, lower hemoglobin arterial thrombus formation: role of tissue factor concentrations, and higher reticulocyte counts at one year of age. and plasminogen activator inhibitor type 1 expression In contrast to male mice, homozygous cryptic TF females were less affected by disease and early lethality; their survival rated did E.W. Holy, F. O. Owala, A. Akhmedov, T.F. Lüscher, not significantly differ from those of wild-type females. Despite of F. C. Tanner (Zürich, CH) this, homozygous cryptic TF females developed uterine bleedings Background: Cardiovascular disease is the major cause of death when bred with homozygous cryptic TF males, but not with in patients with chronic renal failure. Carbamylation of low-density wild-type males.These studies indicate that deencryption of TF lipoproteins (cLDL) in human serum by urea-derived cyanate is required for normal embryonic development and a balanced alters protein structure and is thought to promote vascular hemostasis.The latter is particularly important in organs exhibiting inflammation and dysfunction during end-stage renal disease. high tissue factor levels such as lung, heart, brain and uterus. However, it it is not known whether cLDL exerts prothrombotic effects in vascular cells and whether cLDL affects arterial thrombus formation in vivo.

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141 artery disease (CAD; n = 13; mean age: 60 ± 9 years) compared Revascularization in patients with suspected ACS: with healthy subjects with angiographically normal coronary diagnostic performance of multiple biomarkers including arteries (n = 14; mean age: 59 ± 11 years). Secondly, we hs-Troponin T and myeloid-related protein 8/14. determined the expression levels of pro-inflammatory surface The MyRiAD study molecules in each monocyte subset and each patient group. Results: Total monocyte counts were 334 ± 87/ul in CAD vs. 304 L. Altwegg, K. Yonekawa, C.A. Wyss, A. Brauchlin, ± 81/ul in controls (NS). An example of flow-cytometric analysis is G. Schulthess, P. Krayenbühl, R. Corti, U. Landmesser, shown in figure A. Quantitative data in the two groups are shown A. von Eckardstein, M. Hersberger, M. Neidhart, S. Gay, in Figure B (please note different scales for different monocyte I. Novopashenny, R. Wolters, M.B. Wischnewsky, T.F. Lüscher, subsets). Classical (non-mature) CD14+CD16- monocytes (Mo1), W. Maier (Zürich, CH; Bremen, DE) which normally account for nearly 90% of all monocytes, were Introduction: Timely revascularization is crucial for prognosis in decreased, whereas nonclassical (mature) monocytes (Mo3), acute coronary syndromes (ACS). Next to clinical presentation which are believed to include macrophage precursors, were and ECG, biomarkers represent the key diagnostic tools therefore. increased in CAD patients vs. healthy subjects (p <0.05). Recently, the incremental value of high sensitive (hs-) Troponin T Mo3 monocytes were characterized by high expression of the has been shown. We have suggested myeloid-related protein 8/14 chemokine receptor CX3CR1, which mediates monocyte (MRP 8/4), a marker of phagocyte activation, as an indicator for migration into plaques. Intermediate monocytes (Mo2) were plaque rupture and ACS. The MyRiAD Study (Myeloid-Related similar in CAD and controls. CD14-CD16+ cells (dendritic cell Protein in Evaluation of Acute Chest Pain in the Emergency precursors) tended to be increased in CAD patients (NS). Mo1 Departement) reports on the performance of hs-Troponin T monocytes in CAD patients expressed increased levels (p <0.05) and MRP 8/14 along with established and emerging markers of CX3CR1 and CCR2, two chemokine receptors involved in for indicating revascularization in ACS. atherogenesis. Similar trends were observed in all monocyte Methods: Inclusion criteria were presentation with any sign subsets. or symptom suggestive of ACS and regular biomarker testing Conclusions: Stable CAD is associated with expansion of the indicated by the physician in charge.Atotal of 403 consecutive circulating pool of mature monocytes. In addition, non-mature patients (pts) were enrolled. Hs-Troponin T, MRP 8/14, fatty acid monocytes in CAD patients express increased levels of the binding protein (FABP), myeloperoxidase (MPO), the routine chemokine receptors CX3CR1 and CCR2. These data suggest markers of myocardial necrosis, as well as nT-proBNP, were that mature monocytes may be a selective target for therapeutic measured with currently available commercial assays at intervention, thus preventing adverse effects of indiscriminate admission and serially, if applicable.The diagnostic performance monocyte suppression. was adjudicated according to the composite endpoint need for any coronary revascularization and cardiac death during hospitalization. Results: The composite endpoint was met in 32.8%, no events were observed in 67.2% of pts. In all pts with events, except 2 (1.5%) who died before, full angiographic documentation was available, as well as in 14.8% of pts without event. Event pts presented with STEMI in 50.8% and in 49.2% with NSTEMI/UAP. Conclusion: Hs-Troponin T, a marker of myocardial necrosis, best indicated the need for coronary revascularization or cardiac death in ACS pts.With current assay technology, neither the potential marker of plaque rupture MRP 8/14, nor biomarkers associated with miscellaneous pathways, reached a comparable diagnostic performance.

142 143 Circulating mature monocytes (macrophage precursors) are increased in patients with stable Transcatheter left atrial appendage occlusion coronary artery disease in atrial fibrillation: comparison of non-dedicated versus dedicated Amplatzer devices G. Vassalli, T. Tallone, G. Soldati, G.B. Pedrazzini, T. Moccetti (Lugano, CH) S. Gloekler, M. Schmid, A.M. Saguner, A. Khattab, A. Wahl, Introduction: Monocytes are central mediators in inflammation P. Wenaweser, S. Windecker, B. Meier (Bern, CH) and atherosclerosis.They circulate in blood and eventually Introduction: In patients with atrial fibrillation (AF), >90% of migrate into atherosclerotic plaques where they give rise to embolic strokes originate from the left atrial appendage (LAA). macrophages and dendritic cells. Different monocyte subsets Transcathether occlusion of the LAA is an alternative to oral with distinct roles in homeostasis and inflammation veha been anticoagulation (OAC). The aim of this study was to compare described based on the expression of the CD14 and CD16 procedural and follow-up results of transcatheter occlusion of the surface markers.While these subsets have been well LAA with non-dedicated Amplatzer devices (NDA, mainly septal characterized in mice, little data are available in humans. occluders) to those with a new dedicated device, the Amplatzer Methods: We developed a four-color flow cytometry protocol for cardiac plug (ACP). analysis of human blood monocyte subsets using monoclonal Methods: Amplatzer occluders are popular because of their antibody (mAb) to HLA-DR, CD14 (scavenger receptor), CD16, safety, low thrombogenicity, and facile applicability. When used and ten additional molecules involved in atherogenesis. Firstly, for LAA occlusion, however, they have a significant risk for we determined monocyte subsets in patients with stable coronary embolization. This led to an LAA-dedicated device, the Cardiac

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Plug, featuring an adapted mold and retention hooks. In an B). We compared early and late outcomes and assessed the observational single-center study, 64 consecutive patients with AF association of the reconstruction method and long-term survival. (32 with NDAs, 2002–2008, and 32 with ACPs, 2009–2010) were Results: The mean age was 66 and 67 years in groups A and B, compared. Device implantation was performed via femoral venous respectively. Operative mortality was 3.0% and 4.1%, and the and transseptal access under local anesthesia. After the incidence of perioperative myocardial infarction in the LAD procedure, OAC was stopped. Acetylsalicylic acid 100 mg/d and territory was 4.0% and 4.1% in groups A and B, respectively. clopidogrel 75 mg/d were prescribed for ≥5 and 1 months, There was no significant difference in early operative outcomes respectively. TEE and neurological examination were performed (P >0.05). Actuarial 5-year survival was 78.6% and 87.1% and after 3–6 months. 10-year survival was 45.4% and 49.4% in groups A and B, Results: Despite unfavorable baseline characteristics (higher respectively. Cox hazard proportional analysis showed that the age, CHADS-2-Score and co-morbidities) of the ACP group, reconstruction method did not have a significant impact on procedural results were superior in comparison to the NDA group. long-term survival. Total fluoroscopy time was 19 vs 28 minutes (p = 0.03), amount Conclusions: Extensive LAD endarterectomy and reconstruction of contrast agent 226 vs 424 ml (p <0.001), early device is a safe and feasible technique of revascularization for diffuse embolization 0% vs 13% (p = 0.02), tamponade 0% vs 6% coronary artery disease.The reconstruction method should be (p = 0.16), and technical implantation success 100% vs 84% chosen based on the availability of conduits and length of the (p <0.001). At 3–6 months follow-up, no cerebrovascular accidents arteriotomy. or mobile thrombi on the devices were found in either group. In the NDA group, 1 clinically silent systemic embolization of the device into the descending aorta was noted. In the ACP group, 145 1 silent pericardial effusion was seen and treated conservatively. Low perioperative mortality, good survival and During long-term follow-up, in the NDA group (mean 6.3 ± 1. 3 quality of life following CABG surgery in octogenarians years, 197 patient-years), 1 systemic embolic event occurred from a thrombus on the device (femoral occlusion). Five patients (16%) F. Sorrentino, G. Franciosi, T. Torre, M. Faeli, S. Riva Muzio, died because of nonrelated reasons. In the ACP group, follow-up F. Siclari (Lugano, CH) was 13 ± 4 months (34 patient-years) without mortality or embolic Objective: Aim of our study was to assess outcome and quality events. of life in octogenarians undergoing CABG surgery. Conclusion: The LAA-adapted ACP improved safety and early Methods: We retrospectively reviewed 158 consecutive patients results of LAA occlusion with Amplatzer devices. Long-term aged eighty years and older, mean age 82.6[2.32] (M/F 94/64) results after LAA occlusion with Amplatzer devices show excellent operated for isolated CABG from September 1999 to August efficacy with regard to stroke prevention. 2010 at our Institution. Data were collected from charts, general practitioners, direct questioning and SF36 questionnaire. Long term survival was assessed over a ten years interval with a mean 144 follow up 46.5 [32.7] months. Quality of life was evaluated by Extensive endarterectomy and reconstruction SF-36 self assessment administered to survivors. Values are of the left anterior descending artery: early and late expressed as mean [SD = standard deviation]. outcomes Results: Follow up was complete in 98.7% of patients. Overall early mortality (30 days) was 6.32 % (10/158). Mortality by group P. O. Myers, M. Tabata, P. S. Shekar, G.S. Couper, of urgency was 3.3%, 6.3%, and 16.6% respectively for elective, Z.I. Khalpey, S.F. Aranki (Boston, US) urgent and emergent procedures.Actuarial survival was 84%, Objectives: Coronary endarterectomy has been shown to be an 74.7%, and 43 % respectively at three, five and ten years. Major effective adjunctive technique of revascularization for diffuse Morbidity included: Re thoracotomy 6.3%, Myocardial infarction coronary artery disease.Along arteriotomy and reconstruction of 3.7%, Hemofiltration 3.9%, Stroke 1. 89%, Sternal infection 0.6%. the left anterior descending artery (LAD) is occasionally required Postoperative delirium 8.2%. Median ICU-stay was 2 days. for complete extraction of the atherosclerotic plaque.The aim of Median hospital stay was 8 days. Direct home discharge was this study was to examine early and late results of this technique attained by 31% of patients. Currently, patients who live and compare two different reconstruction methods. independently at home are 81 (75%); living in nursing home Methods: We retrospectively reviewed 224 consecutive patients independently are 3(2.7%); living in nursing home dependently who underwent extensive LAD endarterectomy and reconstruction are 15 (14%); living at home dependently are 7(6.5%) and two between January 1992 and March 2010. For reconstruction, patients are untraceable(1.8%). Quality of life assessed by SF-36 101 patients underwent saphenous vein patch and LAD grafting questionnaire showed both physical and mental indexes similar to (group A) and 123 patients had LIMA on-lay patch grafting (group the general population; respectively 48.8 [22.6] and 51.37 [18.1] vs 49.0 and 49. Recurrence of symptoms leading to invasive treatment, i.e. PTCA was 3/108 ( 2.7%). Conclusions: Bypass surgery in octogenarians has a low early mortality and morbidity. Long term survival and the high quality of life justifies surgery in this group of patients.

146 The EuroSCORE and its ability to predict: analysis of 5734 patients of a single institution D. Reineke, A. Kadner, R. Pop, B. Gahl, M. Czerny, F. Schönhoff, E. Krähenbühl, L. Englberger, M. Stalder, T.P. Carrel (Bern, CH) Introduction: The aim of our study was to analyse the EuroSCORE’s ability to predict outcome and to evaluate its single parameters as to their contributing value in a single center. Methods: Retrospectively, 5734 consecutive adult patients undergoing cardiac surgery between January 2004 and December 2009 were analyzed according to their calculated EuroSCORE and their observed in house mortality. Univariate and multivariate statistical analysis was done on each of the EuroSCORE’s 17 items. Sensitivity and specificity were assessed with ROC methodology. Results: All variables showed correlation with death in bivariable analysis except neurological deficit and .age Reasons for death correlated merely in 23% with EuroSCORE variables.While renal

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disease, recent myocardial infarction, post infarction VSD, active Discussion: The EuroSCORE is still a very reliable scoring myocarditis, intervention on the thoracic aorta and neurological system. Its ability to predict death is good. With an area under the deficit had no impact on mortality (p >0.05) all other variables curve of, 0.8 results were comparable to other centers. Already were associated with increased risk of death (p <0.05) in well known independent risk factors for death confirmed validity in multivariable logistic regression. ROC techniques on additive and this analysis.As such, EuroSCORE may welI serve as a reliable logistic EuroSCORE showed an area under the curve of 0.8. and valid tool in the current era.

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152 153 Conservative or surgical strategy? Repolarization abnormalities due to cardiac memory A difficult clinical decision making in a patient with idiopathic left fascicular ventricular tachycardia M. Balmelli, M. Di Valentino, J. Klimusina, A. Gallino, A. Menafoglio (Bellinzona, CH) C. Park, H. Sunthorn, D. Carballo, N. Tran, D. Shah A 65 year old female patient with rheumatic valvular disease (Genève, CH) underwent mechanical mitral valve replacement (Björk-Shiley Cardiac memory (CM), also called Chatterjee phenomenon, is 29 mm; (BS)) due to severe mitral stenosis in 1981. Few years characterized by transient negative T- waves during sinus rhythm later the patient was informed that her BS mechanical mitral valve on the surface electrocardiogram (ECG). This phenomenon belonged to a production batch at risk of rupture. The patient reflects a change in ventricular repolarisation induced by and her doctor were advised to consider re-operation with prolonged abnormal electrical activation (eg, cardiac pacing). replacement. The asymptomatic patient could not make a We report the case of a 28 year-old patient with repolarisation decision until 1994 when she underwent surgical replacement abnormalities due to CM in response to idiopathic left fascicular with implantation of a Carbo-Medics mechanical valve (29 mm). ventricular tachycardia (ILFVT). A 28 years-old male, in good As a complication of this second operation, the patient developed general health without structural heart disease, complained of five an invalidating left hemiparesis, possibly associated with episodes of palpitations over a 2 year period, which were never peri-operative embolisation from a giant left atrium(Ø 7. 8 cm). She documented. He consulted a cardiologist because the last almost completely recovered from this cerebral complication only episode lasted for 15 hours. Electrocardiography(ECG) in sinus after intensive rehabilitation. Over the following 14 years, the rhythm soon after spontaneous cardioversion showed negative patient did clinically well, and TTE showed normal functioning of T- waves in leads II, III, AVF and V4-V6, which were absent in a the mechanical mitral valve, an increase of the giant left atrium, comparative ECG 2 years prior.ADoppler echocardiogram and and the appearance of progressive aortic valve stenosis. During a 24-hour holter monitoring were normal. An electrophysiologic the last 18 months, the patient has complained of mild stress study with programmed stimulation under isoproterenol infusion dyspnea without angina or syncope; on clinical examination there induced a sustained tachycardia with a right bundle branch block was a hoarse 5/6 systolic aortic murmur, well audible metallic pattern and left-axis deviation compatible with an idiopathic left clicks of mitral valve and systolic murmur on the left lower sternal fascicular ventricular tachycardia (IFLVT).The tachycardia was border.TTE revealed normal function of mitral valve prosthesis, successfully ablated with radiofrequency current applied in the severe aortic valve stenosis (peak and mean systolic gradient basal mid inferoseptal left ventricle segment. The T- waves 110 mm Hg and 65 mm Hg) normal LVEF,and severe dilatation abnormalities shown in the initial ECG are probably related to of left atrium (Ø 11cm) with compression of right atrium (fig.A) abnormal cardiac activation during IFLVT; the T- wave vector with moderate tricuspid regurgitation and pulmonary arterial shows the same direction as the QRS vector during the hypertension (PAPs 65 mm Hg). ventricular tachycardia, with negative T- waves observed in inferior What therapeutic approach should be chosen in this complex and V4-V6 leads. In the differential diagnosis of T- wave inversion situation?: in young adults, CM due to tachyarrhythmias must be considered 1) Aortic valve replacement , tricuspid valve reconstruction and when hypertrophic cardiomyopathy, myopericarditis or cardiac surgical reduction of the giant left atrium ischemia have been excluded. 2) Aortic valve replacement 3) Aortic valve re-valving (trans-apical or trans-femoral) in order to avoid the major risk of re-operation 4) Conservative strategy since the patient is only mildly symptomatic despite of the severity of the aortic stenosis This case well illustrates the dilemma of consulting the patients with previous complications and underlines the difficulties of clinical decision making in these cases

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154 continuous murmur on the back and at the left sternal border. Sinus tales and a right heart›s challenge During a standard exercise treadmill testing, she reported chest pain at peak exercise, accompanied by >2 mm ST-segment H. Abbühl, T. Comberg, L. Günkel, N. Jander depression in V4-6. Transthoracic echocardiography showed (Basel, CH; Bad Krozingen, DE) normal biventricular size and function with no regional wall motion After an introducing overview to sinus valsalva aneurysms, their abnormalities at rest. There was no evidence of a residual PDA. natural course and associated complications – an own case with She had a tricuspid aortic valve with mild regurgitation. Doppler- difficult clinical decision making and follow up is presented. flow signals were observed in the interventricular septum (fig. 1). A 73 yrs old patient was sent to the cardiac center by his Because of the positive exercise test and the suspicion of cardiologist for a second opinion: he had a large sinus valsalva coronary fistulas, coronary angiography was performed. On aneurysm (SVA) of the right coronary sinus (59 mm) protruding angiography, the left circumflex cornary and the right coronary into the right ventricle, and a severe mitral regurgitation due to a artery (RCA) had their origin at the usual cusp in the aortic root, prolaps of P1 and P2 segments, with good left ventricular function but the left anterior descending coronary artery (LAD) was and normal diameters; the patient was completely asymptomatic. retrogradely perfused via contralateral collaterals from the RCA A therapy with losartan and a βblocker was proposed. Three years (fig. 2). The origin of the LAD could be selectively intubated with a later the aneurysm was slightly progredient (60 mm), the other catheter in the anterior aspect of the main pulmonary artery.An findings were stable and the patient still asymptomatic. A cardiac anomalous origin of a coronary artery from the pulmonary artery CT revealed sclerotic coronary arteries without significant is a rare congenital malformation. The most common of these obstruction and a statin was added to the therapy. Again 4 yrs anomalies is the origin of the left main coronary artery from the later, the increasing SVA (74 mm) now led to right ventricular pulmonary artery (ALCAPA), followed by the origin of the single outflow tract (RVOT) obstruction (RVOT gradient 94 mm Hg) and RCA and the LAD from the pulmonary artery. In children with at right heart catheterisation the cath could not pass besides the ALCAPA, fatal left ventricular infarction, congestive heart failure SVA into RVOT and pulmonary artery. Due to a supposed risk of and sudden cardiac death are common. These adverse events SVA rupture or right ventricular failure in a 80 yrs old otherwise are less severe or even absent with only the LAD originating from healthy man, an interdisciplinary team proposed the indication for the pulmonary artery, most likely because less myocardium is aortic root operation and mitral valve reconstruction. Before put in jeopardy. Due to the patient’s symptoms and evidence of operation the measured RVOT gradient was 102 mm Hg – to our myocardial ischemia, an attempt to improve retrograde LAD knowledge the highest published RVOT gradient caused by SVA coronary artery flow by percutaneous occlusion of its pulmonary obstruction so far. Operation, postoperative complications and origin – thereby preventing coronary steal into the low pressure course and resulting hemodynamics are presented. – was planed, but failed. The patient is now Discussion: Indications for intervention as well as different scheduled for cardiac surgery with re-insertion of the LAD into the treatment options (surgical, interventional) and published follow aorta. Congenital heart disease has different facets. In case of up’s are discussed. symptoms, previously non recognized congenital malformations may be present.

155 “Congenital” chest pain J. Robert, T. Rutz, A. Kadner, J.-P. Pfammatter, B. Meier, S. Windecker, M. Schwerzmann (Bern, CH) A 27-year-old woman was referred to the Grown-up congenital heart disease clinic with chest pain on exertion for several months. By the age of 12, she had undergone surgical ligation of a patent (PDA). She had 2 uneventful pregnancies, 2 and 4 years ago. On auscultation, there was a

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156 157 Unexplained large left ventricular aneurysm Demonstration of left-to-right shunt reduction with intra-aortic baloon pump in ventricular septal defect J. Klimusina, M. Di Valentino, A. Menafoglio, G.B. Pedrazzini, complicating myocardial infarction F. Faletra, L.K. von Segesser, A. Gallino (Bellinzona, Lugano, Lausanne, CH) A. Testuz, M. Roffi, E. Khabiri, K. Bendjelid, R. Bonvini A 62 years-old woman, without previous history of cardiovascular (Genève, CH) diseases was admitted to our institution due to symptomatic Introduction: While intra-aortic balloon pump (IABP) is widely episodes of monomorphic non-sustained ventricular tachycardia used in various situations of heart failure with reduced cardiac (VT). She has undergone radiotherapy and chemotherapy after ouput, it also has a role in case of ventricular septal defect (VSD) left mastectomy for breast cancer 20 years ago. Resting ECG complicating myocardial infarction (MI). In this particular situation revealed right bundle branch block with left anterior hemiblock the main aim of IABP is reduction of left ventricular afterload, thus and episodes of non-sustained VT of left ventricular (LV) origin diminishing the degree of the left-to-right shunt, finally resulting in (Panel A). Echocardiography showed the presence of large LV an increased effective systemic cardiac output. IABP might thus antero-lateral aneurysm (57x41 mm), and preserved function of allow stabilization of the hemodynamic status, finally allowing the remaining LV segments with ejection fraction of 35% (Panel postponing surgical VSD closure, and possibly reducing mortality. B, arrows). Subsequently performed coronary angiography This case aims to demonstrate hemodynamic contribution of demonstrated normal coronary arteries. Searching for the IABP in VSD complicating MI. possible explanations of the nature of the aneurysm magnetic Case report: A 79-year-old man with no previous cardiovascular resonance imaging (MRI) was performed. It showed transmural history presented to the emergency department with subacute late gadolinium enhancement (LGE) of the entire akynetic inferior myocardial infaction associated with mild signs of aneurysmal wall, consistent with transmural scar (Panel C, systemic hypoperfusion. A transthoracic echocardiography (TTE) arrows). Considering possible surgical resection the patient revealed a large akinesis of the inferior wall of the left ventricle underwent CT angiography for better understanding of anatomical with preserved left ventricular ejection fraction (LVEF), as well as relationship of aneurysm with the coronary tree. It showed intact a large VSD in the inferior mid portion of the venticular septum. arteries without any wall lesions (Panel D). Both 3D CT volume The coronary angiography confirmed sub-acute occlusion of the rendering modality and CT slices (panel E and F), however, mid portion of a dominant circumflex artery (LCX). Complete showed that the aneurysm involved not only the left, but also invasive shunt evaluation allowed to calculate a significant the right ventricle in its antero-apical region (arrows). Several left-to-right shunt, with a Qp/Qs of 3.1.Activation of the IABP 1:1 speculations concerning the aetiology were discussed. A silent contributed to reduction of the pulmonary output, as well as the myocardial infarction was a diagnostic option, however, the shunt (Qp/Qs = 2.4, 22% reduction), corresponding to an effective aneurysm did not match with a specific coronary territory and improvement of systemic cardiac output from 2.1 l/min “off-pump” coronary walls of the entire tree were free of any atherosclerotic to 2.4 l/min “on-pump” (= 12% of improvement) (cf. fig.). plaque (Panel D). Radiotherapy induced myocardial damage Discussion: In case of VSD complicating MI, invasive shunt was the most probable diagnosis considered the past history of measument is challenging and prone to errors, and usual cardiac radiotherapy. However, the patient’s recordings revealed that output measurment methods (Thermodilution, Fick) cannot easily radiotherapy was performed in supraclavicular and axillary be used for monitoring. Our data demonstrate the hemodynamic regions, without mediastinal application. Another possible cause contribution of IABP in VSD complicating MI as only seldom of LV bulging could be a diverticulum. However, its wall should reported before. Improvement of systemic cardiac output in this contain , myocardium and and display situation is obtained through systemic afterload reduction, leading normal contraction. In our case, on the contrary, MRI showed to significant shunt reduction. Hemodynamic stabilisation of akynetic region with transmural LGE, which is consistent with a the patient is the main purpose and, if obtained, may allow scar.Thus, the origin of the aneurysm remained unknown. We postponing the definitive surgical VSD closure and possibily restrained from surgical resection due to involvement of both reduce mortality. ventricles.The patient received defibrillator combined with pharmacological treatment. On the follow-up visit she was asymptomatic, without any episodes of VT.

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158 characteristics between the three groups.The VARC combined Single-centre transcatheter aortic-valve implantation safety endpoint (all-cause mortality, major stroke, peri-procedural experience reported according to the criteria newly myocardial infarction, life-threatening bleeding, and kidney injury established by the Valve Academic Research RIFLE stage 3) was comparable for all three groups (no PCI: Consortium 21.4%; concomitant PCI: 16.2%, staged PCI 13.0%; p = 0.527). Conclusion: In this single-center experience of elderly patients B.E. Stähli, R. Bünzli, J. Grünenfelder, T.F. Lüscher, with severe aortic stenosis undergoing TAVI, the prevalence of V. Falk, R. Corti, W. Maier, L. Altwegg (Zürich, CH) CAD was high and had no impact on clinical outcomes. Staged or Introduction: Transcatheter aortic valve implantation (TAVI) for concomitant percutaneous coronary revascularization appeared severe aortic stenosis (AS) in high-risk individuals has become an feasible and safe. accepted treatment option with steadily increasing success rates and outcome.Yet, current results are difficult to compare given the lack of standardized definitions. Here we report a single centre 160 TAVI experience according to the criteria newly established by Clinical outcome of high-risk patients with severe the Valve Academic Research Consortium (VARC). aortic stenosis and reduced left ventricular ejection Methods: TAVI was performed in 130 patients aged 83 [79–86] fraction undergoing conservative treatment years in median with severe AS and high surgical risk as or transcatheter aortic valve implantation estimated by a median logisticEuroSCORE of 23 [15–30]%. The Edwards SAPIEN (n = 50) and the Medtronic CoreValve (n = 80) P. Wenaweser, T. Pilgrim, S. Stortecky, A. Kadner, A. Bütikofer, were implanted by the appropriate access, which was trans- L. Büllesfeld, B. Eberle, T.P. Carrel, B. Meier, S. Windecker femoral in 97 (75%) and trans-apical in 33 (25%) of the patients, (Bern, CH) respectively. Median follow-up was 232 [41–489] days.Thirty-days Aims: In patients with severe aortic stenosis, a reduction in left and 1- year outcome is reported according to the VARC-Criteria. ventricular ejection fraction (LVEF)importantly affects prognosis Results: Both, procedural and 30-day device success, were high in patients treated conservatively, and significantly increases (98.5% and 92.3%, respectively). Combined major adverse event peri-interventional risk in patients undergoing surgical aortic rate (VARC safety endpoint) was 20.8% with a mortality of 11.5%. valve replacement (SAVR). Transcatheter aortic valve implantation Major vascular complications (11. 5%), life-threatening or disabling (TAVI) has been introduced as an alternative to SAVR for bleeding (8.4%), and acute kidney injury (6.2%) were frequently high-risk patients.We investigated clinical outcomes of high-risk observed. Less common were myocardial infarction (1.5%), and patients with severe aortic stenosis undergoing conservative stroke (0.8%). Prosthetic valve associated complications were management or TAVI, stratified by LVEF. commonly observed at 1 year, with new supraventricular or Methods and results: Among 334 patients referred with severe ventricular arrhythmias (60%), new left bundle branch block aortic stenosis between July 2007 and September 2010 and (20.0%), or permanent pacemaker implantation within 30 days increased risk for SAVR, 78 patients were allocated to a after the procedure (34.7%) accounting for most of them. conservative strategy, whereas 256 patients underwent TAVI. Overall 1-year survival was 80% with 67.9% of the patients living Seven patients from the conservative group crossed over to either independently at home.The efficacy endpoint (composed of TAVI (n = 5) or SAVR (n = 2) and have been excluded from the survival and freedom of therapy failure) was met in 61.7%. present analysis. LVEF was severely reduced (≤30%) among Conclusions: Applying the newly established VARC standardized 23 patients (32%) treated conservatively and 35 patients (14%) definitions for outcome reporting of TAVI procedures, TAVI undergoing TAVI. There were no significant differences between appears to be an effective, less invasive treatment option in high patients with and without severely reduced LVEF in terms of age, risk patients with severe AS. gender, BMI, history of coronary artery disease, prior CABG, previous myocardial infarction or stroke, and atrial fibrillation. However, patients with LVEF ≤30% had a s higher risk as 159 estimated by logistic EuroSCORE compared with patients with The impact of coronary artery disease on clinical LVEF >30% regardless of treatment strategy (conservative group: outcomes in patients undergoing transcatheter 38.4 ± 14.4% versus 23.2 ± 11.2%, p <0.001; TAVI group: 41.3 ± aortic valve implantation 16.5% versus 22.3 ± 12.8%, p <0.001). At 30 days, there was no significant difference between patients with and without severely T. Pilgrim, S. Windecker, S. Stortecky, C. Huber, G. Erdös, reduced LVEF with regard to mortality (5.7% versus 6.8%, p = A. Kadner, F. Meuli, A. Khattab, B. Meier, T.P. Carrel, 0.58), stroke (5.7% versus 3.6%, p = 0.41), or VARC combined P. Wenaweser (Bern, CH) safety endpoint (25.7% versus 19.0%, p = 0.24). During mid-term Background: Aortic valve stenosis is frequently associated follow-up (mean/median time of follow-up 386/297 days), mortality with coronary artery disease (CAD) in patients referred for was increased among patients with severely reduced LVEF transcatheter aortic valve implantation (TAVI). Similar risk factors treated conservatively (log rank p = 0.007), whereas no difference such as male gender, hypertension, hypercholesterolemia and in survival as a function of LVEF was observed among patients smoking suggest a similar pathogenesis.The impact of undergoing TAVI (log rank = 0.23). concomitant or staged PCI on clinical outcome in patients with Conclusion: Among elderly high-risk patients with severe aortic significant CAD undergoing TAVI is not well established. We stenosis, survival was impaired among patients with severely therefore investigated the prevalence of CAD and the impact of reduced LVEF treated conservatively but not among patients concomitant or staged PCI on clinical outcome in a consecutive undergoing TAVI. These findings suggest that patients with cohort of patients undergoing TAVI. severely reduced LVEF may disproportionally benefit from Methods and results: Between July 2007 and September 2010, minimal-invasive aortic valve replacement therapy. a total of 256 consecutive patients undergoing TAVI were included in a prospective single center registry. Coronary artery disease as assessed by coronary angiography was defined as >50% 161 stenosis in at least one coronary artery and observed in 167 Retrospective evalulation of a 3-dimensional planning (65.2%) patients. Patients with combined AS and CAD had system for transcatheter aortic valve implantation a significantly higherev pr alence of hypercholesterolemia (p <0.001), diabetes (p = 0.02) and peripheral vascular disease M. Gessat, S. Jacobs, T. Frauenfelder, L. Altwegg, (p <0.001) and had a higher peri-interventional risk as assessed S. Sündermann, J. Grünenfelder, R. Corti, V. Falk (Zürich, CH) by logistic EuroSCORE (26.7 ± 15.7 versus 21.1 ± 12.4, p = Introduction: Optimal imaging of the aortic root for transcatheter 0.004). There was no difference in the prevalence of angina at aortic valve implantation (T-AVI) is still missing. Exact sizing baseline (30.5% versus 27.0%, p = 0.33). Unadjusted mid-term of the aortic annulus and precise determination of the size of survival up to two years revealed no difference in survival the prosthesis may reduce the risk of obstruction of the coronary between patients with or without CAD undergoing TAVI (log rank arteries or embolization of the valve and may impact clinical p = 0.986). 37 TAVI patients underwent concomitant PCI (14.4%) outcome regarding onset of block (AVB) at the time of TAVI, 23 patients underwent PCI (9.0%) prior to or aortic insufficiency (AI). TAVI, and 196 patients had no intervention (76.6%) at all. There Method: 28 patients who underwent T- AVI, retrograde template were no significant differences with respect to baseline based planning was performed. This includes image acquisition

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based on Dyna CT-scan to create a virtual 3D model of the aortic signals/HITS.Assessed procedural steps were defined as: root. Three dimensional models of the T- AVI Prosthesis (Edwards instrumentation prior to valvuloplasty/IN, balloon-valvuloplasty/BV, Sapien) were virtually implanted into the 3D models of the aortic deployment of prosthesis/DP and post-implantation/PI including root. The operator could switch between valves and adjust their re-dilatation. Cerebral-embolic-load/CEL was related to duration virtual position in order to identify an optimal choice and of each procedural step comparing access route and method of placement. During the procedure, distances between the implant device deployment. Data are given as median (min, max), and and arbitrary points on the anatomy could be measured in order comparisons used nonparametric testing (significance vele l, to predict critical parameters for the implantation. p <0.05). Results: For 28 patients, who underwent T- AVI, retrograde Results: Deployment of prosthesis had the highest CEL (p template based planning was performed. This includes creation <0.05). During instrumentation prior valvuloplasty CEL was of a virtual 3D model of the ascending aorta from preoperatively almost as large, however, HITS were recorded at a much lower acquired DynaCT images.Three dimensional models (templates) density over time. Hemispheric CEL did not differ significantly. of the prosthesis (Edwards Sapien) were virtually implanted into CEL was comparable between the type of access routes. Only the 3D model and the optimal valve size was selected. The during post-implantation a larger CEL was released in TF than in planning decision coincided with the actually implanted valve size TA. Self-expanding devices had a higher CEL due to increased in 17 cases (61%). In 71% of these cases, no complications were HITS during deployment of prosthesis and post-implantation. reported. Three cases (18%) of Aortic Insufficiency (AI) and two The incidence of in-hospital death, stroke or delirium in this cases (12%) of AV-Block were among these patients. In two cohort was 0/44. patients who received a 26 mm implant, planning recommended Conclusions: Embolic load does not differ in type of access a 23 mm valve. In both cases, AVB III° occurred. In two patients route, however in the post-deployment phase a significant who received a 23 mm implant, planning recommended a 26 mm increase in HITS is noted after TF implantation. Rationale might valve. In one of these cases, paravalvular leakage led to an AI. In be twofold. First a higher rate of post-deployment device dilatation seven cases, planning suggested, that the 26 mm valve would still and second the retrieval of the delivery system. In regards of be too small. In all seven cases, postoperative AI was diagnosed. deployment method, the SE devices show a significant increase Conclusion: The study shows a correlation between two of CEL during deployment of prosthesis and post-implantation. frequent complications and a mismatch between implant Both might be due to beating heart deployment, increased aortic selection with and without a template based planning tool; T- AVI wall friction or retraction of the deployment system. Our results planning including 3D analysis of radiology images and implant are in line with previous MRI findings of substantial cerebral templates might be of clinical impact. ischemic lesions.

163 Reasons for reoperation after successfully treated acute aortic dissection type A S. Roost-Krähenbühl, S. Maksimovic, D. Reineke, L. Englberger, H. Brinks, M. Czerny, A. Weber, J. Schmidli, T.P. Carrel, M. Stalder (Bern, CH) Objective: Outcome of patients with acute aortic dissection type A (AADA) has improved over the last decade.Aim of this study was to evaluate the long-term outcome and re-intervention rate in patients with AADA. Method: All 325 patients admitted for AADA from January 1999 and December 2009 at our institution were included in this study. All in-hospital data was assessed. Patients who were discharged from our unit were followed in our outpatient clinic with clinical 162 and CT/MRI scan evaluation. All re-interventions were Cerebral embolic load during transcatheter aortic prospectively assessed. valve implantation Results: In-hospital mortality was 11.6% (38/325). 269 patients were discharged and followed in our outpatient clinic. Mean C. Huber, G. Erdös, R. Basciani, A. Kadner, H. Brinks, follow-up was 4.3 ± 3.1 years and was complete in 87% of V. Göber, M. Stalder, P. Wenaweser, S. Windecker, patients. 49 patients (18%) had 56 reoperations during the B. Eberle, T.P. Carrel (Bern, CH) observed period. In 15 patients aortic root replacement was done Background: In high-risk patients transcatheter aortic valve due to root aneurysm which resulted in aortic valve insufficiency implantation/TAVI is an attractive alternative to surgical aortic after primary root reconstruction. In 19 patients total arch valve replacement. An incidence of 0–6.3% of periprocedural replacement was done, in the majority of patients (11/19) as a stroke is reported. Clinically silent ischemic cerebral lesions have two step procedure prior to thoraco-abdominal aortic been documented by MRI in 66–84%. However, amount and replacement. Reason for isolated aortic arch replacement was pattern of cerebral embolic load as well as the relation to the transient neurological attack in 2 patients, infected prosthesis with procedural steps is unclear. pseudo-aneurysm (2 patients) and progressive dilatation of the Objective: Relating cerebral embolic load during TAVI to aorta in 4 patients. In 16 patients progressive aneurysm in the procedural steps. Comparing the transfemoral/TF and the descending aorta resulted in thoraco-abdominal aortic transapical/TA access as well as the type of device deployment replacement. Mortality for reoperation was 6.1% (3/49). balloon/BE vs. self-expanding/SE. Conclusion: In this study 18% of successfully treated AADA had Methods: In 44 patients (78 ± 6 y; logEuroScore 28 ± 15%; a re-intervention during the follow-up.This clearly emphasizes the nTF = 32; nTA = 12; nBE = 17; nSE = 27) transcranial Doppler importance of a structured follow-up in these patients. ultrasound recordings were analyzed for high-intensity transient

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175 hemorrhages occurred in 3 patients (21%) either subdurally Impact of chest x-ray before discharge in children (n = 1) or in choroid plexus (n = 2). Postoperative MRS could be after cardiac surgery – Prospective evaluation analyzed in seven patients.The ratios of choline/creatine (pre 0.58 vs. post 0.46, p = 0.018) and myoinositol/creatine (1.74 vs. D. Quandt, W. Knirsch, O. Niesse, T. Schraner, H. Dave, 1. 48, p = 0.043) decreased from before to after surgery, whereas O. Kretschmar (Zurich, CH) no significant difference was in ratio of lactate/creatine (0.28 vs. Introduction: Chest x-rays are performed routinely before 0.22, p = 0.398). Neurological assessment showed muscular discharge after cardiac surgery in many paediatric cardiac units. hypotonia (70%), but no focal neurological deficit or seizures. These radiographs contribute to radiation exposure, therefore Conclusions: Signs of generalized hypoxia in the WM are indications for chest x-rays should be restrictive. observed in all infants before cardiac surgery for CHD, but the Objective: To evaluate the diagnostic impact of routine chest extend of hypoxic brain alterations decreases after surgery. x-rays before discharge in children undergoing open heart surgery Hemorrhages are frequently observed, while cerebral strokes are and to analyze certain risk factors predicting pathologic findings. rare in our population. None of the observed pathologies was Methods: In a prospective single centre observational clinical accompanied by severe neurological symptoms. Further clinical study 128 consecutive children undergoing heart surgery (mean follow up after one year is necessary. age 28 months, range 0–17. 9years, 69 male) received a biplane chest x-ray 13 days (mean) after operation, before planned discharge. Pathologic findings in chest x-rays were defined as 177 infiltrate, atelectasis, pleural effusion, pneumothorax or signs Increased incidence of ischaemic cerebrovascular of fluid overload / pulmonary hypercirculation. Their therapeutic events in Ebstein anomaly emphasizes the importance consequences were documented. 109 asymptomatic children of identifying and treating interatrial shunt were included in the final analysis. Risk factors such as age, corrective versus palliative surgery, reoperation, sternotomy vs. C.H. Attenhofer Jost, J.A. Dearani, C. Scott, lateral thoracotomy and pulmonary complications (i.e. pulmonary H.M. Burkhart, H.M. Connolly (Zürich, CH; Rochester, US) infection, pleural effusion, atelectasis, pneumothorax) during Background: Paradoxical emboli leading to stroke in patients (pt) postoperative ICU (Intensive Care Unit) stay were analysed. with Ebsteinanomaly (EA) are rarely reported despite the Results: In only 5.5% (6/109) of these asymptomatic patients recognized high incidence of patent (PFO) and pathologic findings in routine chest x-ray before discharge were (ASD) with associated interatrial shunting found – pleural effusion (n = 1), atelectasis (n = 1), pneumothorax (IAS) in these pt. (n = 1), signs of fluid overload (n = 3). In only three of these cases Methods: Analysis of preoperative symptoms, cardiac findings (50%) subsequent non-invasive medical intervention (increasing and operative data of all 138 pt (89 females) undergoing cardiac diuretics) was needed. Five of these six patients have had surgery for EA at the age of >40 years at our center between complications during ICU stay. Risk factor analysis revealed 1975 and January 2010 were retrospectively analyzed. only pulmonary complications during ICU stay to be significantly Results: Age at surgery was 54 ± 8 years. Most pt were severely associated (p = 0.036) with pathologic x-ray findings before symptomatic: preoperative functional class was III or IV in 120pt. discharge. (87%) Preoperative stroke or transient ischemic attack was Conclusions: Routine chest x-rays before discharge can be reported in 21 pt (24%). Preoperative cyanosis was present omitted in asymptomatic children after cardiac surgery with an in 27 pt (20%), clubbing in 12 pt (9%). IAS was found by uneventful and straightforward perioperative course. Chest x-rays echocardiography and/or at operation in 87 (63%); 60 pt had an before discharge are warrantable if pulmonary complications ASD and 30 pt had a PFO.The best predictor of preoperative during ICU stay did occur as this is a risk factor for pathologic stroke was the presence of an ASD/PFO (p = 0.001). Stroke findings. occurred in 6 of 28 pt with a history of atrial fibrillation (p = 0.79), all having also an ASD or PFO.There was no association between stroke in EA pt and hypertension, hyperlipidemia, 176 or smoking (p = ns). Patients operated later more often had Cerebral magnetic resonance imaging before and a history of stroke (p = 0.02). after neonatal cardiac surgery for severe congenital Conclusion: Preoperative strokes are common in pt with EA heart disease and strongly correlate with the presence of ASD/PFO and age at surgery. In any pt with EA, ASD/PFO should be sought W. Knirsch, K. Batinic, R. Liamlahi, M. Makki, C. Kellenberger, aggressively and treatment options such as device closure or oral I. Scheer, M. Von Rhein, A. Schmitz, V. Bernet, M. Hug, anticoagulation evaluated. Besides, contrary to Ebstein repair in D. Hitendu, B. Latal (Zürich, CH) children where it is common to leave behind a small atrial septal Objectives: To determine the influence of neonatal cardiac fenestration at the time of surgery, this strategy should not be the surgery on brain metabolism in neonates with congenital heart case when operating on adults with Ebsteinanomaly. Even the disease (CHD) using cerebral magnetic resonance imaging (MRI) routine of leaving behind a small interatrial connection should be and spectroscopy (MRS). questioned. Methods: Cerebral MRI (3T scanner), including single voxel spectroscopy in white matter (WM) and basal ganglia, was performed before and after neonatal cardiac surgery in fourteen patients with severe cyanotic CHD.Twelve patients were treated for transposition of great arteries (TGA) by arterial switch, 2 for hypoplastic left heart syndrome by Norwood or hybrid transcatheter-surgical palliation. Results: Preoperative MRI was performed at median age of 6 days (range 1–12 d) before resp. 26 days (19–31 d) after neonatal cardiac surgery. Rashkind procedure was performed in 9 patients (75%) with TGA immediately after birth. Before surgery, all patients (100%) showed signs of generalized hypoxia with hyperintensity of the white matter (WM) on T2, with punctuate WM lesions in three patients (21%). Six patients (43%) showed hemorrhages either subdurally (n = 3) or in choroid plexus (n = 3). MRS was pathological in all patients with elevated brain lactate and decreased N-acetyl-aspartate (NAA) values. Only one patient (7%) with TGA had two small cerebral strokes after emergency shunt palliation due to closure of patent arterial duct. After surgery, hyperintensity of the WM decreased in most patients (54%). One patient (7%) had a new punctuate WM lesion. New

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178 increase, 95%-CI: 0.47–0.85) and heart rate–corrected flow Biodegradable remodeling annuloplasty ring to deceleration time in the descending aorta (OR = 1. 22 per 0.01 address atrioventricular valve regurgitation in s0.5 increase, 95%-CI: 1. 08–1.38) were independent predictors of common atrioventricular canal defects: CoA gradient ≥20 mm Hg (p <0.01 for both). A clinical prediction a multi-institutional global collaborative experience tree combining these variables reached a sensitivity and specificity of 90% and 76%, respectively (fig.). P. O. Myers, M. Cikirikcioglu, C. Baird, W. Mrowczynski, Conclusion: CMR derived minimal aortic cross-sectional area P. J. del Nido, M. Wojtalik, A. Kalangos and heart rate–corrected flow deceleration time in the descending (Boston, US; Genève, CH; Poznan, PL) aorta predict CoA gradient ≥20 mm Hg at subsequent Objective: Atrioventricular valve (AV) regurgitation is the most catheterization. The presented prediction tree based on cutoff common reason for late reoperation after common atrioventricular values is easy to use in clinical practice and may help to guide canal repair.The purpose of this report is to review a collaborative further diagnostic and therapeutic management of patients multi-institutational initial experience in using a novel investigated for CoA. biodegradable ring in AV valve repair in patients with common AV canal defects. Methods: From April 2004 to July 2009, 20 patients (mean age 9.2 ± 9.5 years, range 1–40 years) underwent operation for AV valve repair. 11 patients had partial AV canal and 9 had complete AV canal. 13 were reoperations after prior AV canal repair or other congenital cardiac operations.Amitral Bioring Kalangos (Bioring, Lonay, Switzerland) was used in 16 patients on the left AV valve (mean size 23.2 ± 3.6), and a tricuspid Bioring was used in 6 patients on the right AV valve (mean size 19.7 ± 3.4). Echocardiography was performed before discharge, at 6 months and thereafter once yearly. Results: There was one early death from biventricular failure. Early post-operative echocardiography showed a mean AV valve regurgitation grade of 0.5 ± 0.8 (3 patients with mild regurgitation, the remainder with trivial or none), a mean transvalvular gradient of 2.6 ± 2.6 mm Hg and an annulus of 26.1 ± 7. 5 mm for the left AV valve, and a regurgitation grade of 0.4 ± 0.9 (1 patient with moderate regurgitation, the remainder trivial or none) and a mean transvalvular gradient of 0.6 ± 1. 2 mm Hg for the right AV valve. During a mean follow-up of 42.1 ± 27.5 months (range 1–88 months), there were no late deaths. 2 patients required left AV valve reoperation for valve replacement, one for endocarditis and one for worsening regurgitation. In the remaining patients, the mean left AV regurgitation grade progressed to 1. 1 ± 0.9 (1 patient with moderate regurgitation, 2 with mild), with transvalvular gradients of 2.6 ± 1. 7 mm Hg and annulus dimensions of 33.6 ± 2.9 mm. The mean right AV regurgitation and gradients remained stable (0.5 ± 0.7 and 1. 0 ± 1. 4 mm Hg, respectively). Conclusions: The biodegradable annuloplasty ring showed satisfactory results in stabilizing the dilated AV annulus at mid-term follow-up, and represents a novel tool in the surgical armamentarium for valve repair, potentially increasing the stability of the repair without increasing the complexity of the operation, while allowing for annular growth in children.

180 179 Surgery of downstream aortic segments in Prediction of haemodynamic severity of coarctation: Marfan patients after previous aortic repair a magnetic resonance imaging based prediction tree F. Schoenhoff, S. Jungi, M. Czerny, E. Krähenbühl, S. Muzzarelli, A. Knauth Meadows, K. Gomes Ordovas, D. Reineke, J. Schmidli, A. Kadner, T.P. Carrel (Bern, CH) M. Hope, C. Higgins, J. Nielsen, T. Geva, J. Meadows (Basel, CH; San Francisco, New York, Boston, US) Objective: Patients with Marfan syndrome (MFS) frequently require interventions on the distal aorta.Aim of the current study Background: A published formula containing minimal aortic was to determine incidence and etiology of secondary surgical cross-section area and the flow deceleration pattern in the interventions in downstream aortic segments in MFS after descending aorta obtained by cardiovascular magnetic resonance previous aortic repair. (CMR) predicts severe coarctation of the aorta (CoA). However, Patients and methods: Data were prospectively collected from the existing formula is complicated to use in clinical practice and 86 MFS patients fulfilling Ghent criteria that underwent a total of has not been externally validated. Consequently, the clinical utility 136 operations and were followed at this institution between 1995 of this prediction model has been limited. and 2010. Objectives: To create a CMR based tree algorithm for predicting Results: Mean follow-up of survivors was 8.8 ± 6.8 y, mean CoA transcatheter systolic pressure gradient ≥20 mm Hg. time-to-re-operation was 5.5 ± 4.6 y. Thirty-day, 6 months, 1 year Methods: 79 consecutive patients who underwent both CMR and and late mortality was 3.5%, 5.8%, 7. 0% and 12.8%, respectively. cardiac catheterization for evaluation of native or recurrent CoA at Four out of these 11 deaths (36%) were due to aortic rupture the Children’s Hospital of Boston (CHB, n = 30) and the University during late follow-up. Seventy-eight patients (91%) primarily of California San Francisco (UCSF, n = 49) were retrospectively presented with root, ascending or arch lesions, whereas 7 reviewed. The published algorithm derived exclusively from data patients (8%) presented with thoracoabdominal lesions. Etiology obtained at CHB was first validated from data obtained at UCSF, at primary presentation was acute dissection in 36% [24 (77%) and diagnostic characteristics were determined. Next, pooled type A, 7 (23%) type B] and chronic dilative disease in 64%. data from both institutions were analyzed and a refined model Secondary arch replacement had to be performed in only 6% was created using logistic regression methods. Finally, recursive of patients in the non-dissected, but in 36% of the dissection partitioning was used to develop a clinical prediction tree focused group (p = 0.0005). In the non-dissection group, 11% of patients upon best fit of sensitivity and specificity at predictingve se re CoA. underwent surgery in downstream aortic segments [5 out of Results: Severe CoA was present in 48 patients (60%). Indexed 6 patients suffered from type B dissection in the meantime], minimal aortic cross-sectional area (OR = 0.63 per 10 mm/m2

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whereas in patients after acute dissection, 48% patients had to despite the wide availability of prophylactic surgery. The current undergo surgery on the distal aorta [42% of patients with type A data suggests that in patients with MFS, the need for repeated and 86% of those with type B dissection] (p = 0.0002). surgery in downstream aortic segments is not determined by the Conclusion: In a contemporary cohort of patients with MFS, a segment of the aorta that is initially involved but rather the third of the patients still presents initially with acute dissection presence or absence of acute dissection.

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181 Atrial remodeling and atrial arrhythmias in common complaints were syncope in 14 patients and palpitations non-elite male athletes in 12 patients. One patient presented with survived sudden cardiac death. During cardiac investigations, ventricular M. Wilhelm, L. Roten, H. Tanner, J.-P. Schmid, H. Saner tachycardia (VT) or ventricular fibrillation (VF) could be (Bern, CH) documented in 14 patients (of them 3 non-sustained VT). Nine Background: Endurance athletes have an increased risk of patients were treated with an ICD and three patients underwent developing atrial fibrillation (AF) at an age between 40 to 50 ablation for VT.Three patients died 10, 41 and 89 months after years. Signal-averaged P wave analysis has been used for initial presentation. identifying patients at risk for AF.The impact of lifetime training Conclusion: Patients with congenital left ventricular aneurysms hours on signal-averaged P wave duration and modifying factors and diverticula may rarely present with arrhythmic manifestations. has not been evaluated. In these patients, posterobasal or apical involvement is most Methods: Male non-elite athletes scheduled to participate in the commonly observed. These patients commonly have documented 2010 Grand Prix of Bern, a 10 Mile race, were invited. 492 VT/VF during cardiac screening and one third of the overall marathon and non-marathon runners applied for participation, cohort had hemodynamically significant VT/VF requiring ICD 70 were randomly selected, and 60 entered the final analysis. therapy. Subjects were stratified according to their lifetime training hours (average endurance and strength training hours per week x 52 x training years) in a low (<1500 hours), medium (1500 to 4500 183 hours), and high (>4500 hours) training group. The Swiss results of the international RealiseAF Results: Mean age was 42 ± 7 years. From low to high training registry: an observational, cross-sectional survey group, signal-averaged P wave duration increased from 131 ± 6 describing the characteristics, cardiovascular risk to 142 ± 13 ms (P = 0.026), and left atrial volume increased from and management of patients with atrial fibrillation 24.8 ± 4.6 to 33.1 ± 6.2 ml/m2 (P = 0.001). Parasympathetic tone, expressed as root of the mean squared differences of successive M. Zimmermann, L. Naditch-Brûlé, P. Steg normal-to-normal intervals (RMSSD) increased from 34 ± 13 to on behalf on the RealiseAF Swiss investigators 47 ± 16 ms (P = 0.002), and premature atrial contractions (PAC) Aim: RealiseAF is an international cross-sectional observational increased from 6.1 ± 7. 4 to 10.8 ± 7. 7 per 24 hours (P = 0.026). survey designed to obtain information on characteristics, Left ventricular mass increased from 100.7 ± 9.0 to 117. 1 ± 18.2 g/ cardiovascular (CV) risk and management of patients with Afib. m2 (P = 0.002). Left ventricular systolic and diastolic function and This report describes the results from the Swiss population. blood pressure at rest were normal in all athletes and showed no Methods and results: 402 patients (mean age 71.9 years; 64.1% differences between the training groups. Four athletes (6.7%) had male) were enrolled by 35 randomly selected physicians on the a history of paroxysmal AF, one athlete in the medium training basis of diagnosis of Afib during thefi of ce visit or a history of group and three athletes in the high training group (P = 0.252). documented Afib within the last 12 months.At enrollement, 68% Conclusions: In non-elite male athletes, lifetime training hours were in Afib, and 69.4% of the patients reported symptoms are associated with a prolongation of the signal-averaged P wave (279/402). AF was paroxysmal in 26.2% (105/401), persistent in duration and an increase in left atrial volume.The altered left atrial 24.7% (99/401) and permanent in 42.6% (171/401). Lone Afib substrate may facilitate the occurrence of AF.An increased atrial was present in 4.7% (19/402) and predisposing factors were ectopy and vagal tone may serve as triggering factors. identified in 17%. CV risk profile included family history of premature CV disease (15.4%), current smoking (8.5%), physical inactivity (64.7%), obesity (28.7%), hypertension (66.2%), 182 diabetes mellitus (18.2%), dyslipidemia (46.5%), heart failure Clinical characteristics and outcome of patients (32.7%), coronary artery disease (23.5%) and cerebrovascular with left ventricular aneurysms and diverticula disease (11%).The mean CHADS2 score was 1. 8 and 24.9% presenting with arrhythmic manifestations: (98/394) of the study population had been hospitalized in the experience of a tertiary care centre previous 12 months for a CV event including 5.8% for stroke (23/398), 2.8% for transient ischemic attack (11/391) and 1. 7% for L.M. Haegeli, E. Ercin, T. Wolber, C. Brunckhorst, F. Duru major bleeding (7/402). Catheter ablation had been performed in (Zürich, CH) the last 12 months in 3% (12/401). A rhythm-control strategy was Introduction: Congenital left ventricular aneurysms and chosen in 31.9% and a rate-control strategy was chosen in 55.6%. diverticula (LVA/D) are rare cardiac malformations, which can be SR or AF with HR ≤80 bpm, on the ECG the day of the visit was detected during childhood or later using echocardiography or observed in only 65% (29.9% SR, 35% Afib with HR ≤80 bpm). other imaging techniques. Some of these patients present with Vitamin K antagonist (VKA) was prescribed in 45.3% (174/384; ventricular arrhythmias.This study investigates the clinical 31.7% in CHADS2 = 0; 43.5% in CHADS2 = 1; 49.6% in CHADS2 characteristics and outcome of patients with LVA/D presenting ≥2); antiplatelets agents were prescribed in 15.1% (58/384). INR with arrhythmic manifestations. within last 6 months was performed in 80% of the cases with only Methods and results: Since 1990, 244 patients were diagnosed 48.5% of the values being in the target zone.These results are to have a congenital LVA/D at the University Hospital of Zurich. comparable to what was observed in the international registry The diagnosis was made using echocardiography after exclusion including 26 different countries worldwide. of coronary artery disease, local cardiac inflammatory process, Conclusion: In the RealiseAF Swiss registry: a) AFib was traumatic causes or cardiomyopathies. 30 patients (44 ± 21 years, associated with multiple CV risk factors; b) Afib patients were at 20 male) had arrhythmic manifestations at initial presentation. In high risk of CV events; c) antithrombotic prophylaxis was often five patients more than one LVA/D was found. Two simultaneous not applied in accordance to guidelines and d) rate-control was lesions were present in four patients and three in one patient. the most commonly used strategy.These results highlight the There was posterobasal, apical, anteroseptal and anterolateral need for better prevention of CV complications in Afib patients involvement in 12, 11, 4 and 4 patients, respectively. The most and for a better adherence to guidelines through education

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184 185 Feasibility and acute efficacy of radiofrequency De novo ablation for paroxysmal atrial fibrillation – ablation of cavotricuspid isthmus dependent atrial flutter Does induciblity of arrhythmia post PVI influence guided by real-time 3-dimensional echocardiography outcome? F. Regoli, F. Faletra, G. Nucifora, E. Pasotti, T. Moccetti, V. Sawhney, J. Tenkorang, A. Opel, R. Hunter, G. Thomas, C. Klersy, A. Auricchio (Lugano, CH; Pavia, IT) M. Earley, R. Schilling, S. Sporton (London, UK) Introduction: Whether real-time three-dimensional Introduction: Pulmonary vein isolation (PVI) alone is the transesophageal echocardiography (RT3DTEE) may guide a mainstay of catheter ablation for paroxysmal atrial fibrillation transcatheter radiofrequency ablation (RFA) procedure has not (PAF). It is not known whether, those patients whose AF persists been systematically investigated. Feasibility and acute efficacy or is inducible after PVI, gain an additional outcome benefit from of RT3DTEE-guided ablation of cavotricuspid isthmus (CTI) was additional lines.We examined the benefit of supplemental ablation evaluated. in these patients who have spontaneous AF or in whom AF is Methods: Seventy consecutive patients with CTI-dependent atrial induced immediately following PVI. flutter underwent CTI ablation. Procedural RT3DTEE monitoring Methods: 45 subjects with PAF who underwent induction of AF modality was assigned to patients who requested general or developed AF spontaneously during PVI were compared anaesthesia for the procedure (21 patients, 30%). In the other to control PAF patients matched by age, sex, structural heart patients (CON gp), the procedure was monitored according to disease and date of procedure. Wide area circumferential standard fluoroscopic approach. Of e,not procedural duration was radiofrequency ablation was performed in order to electrically considered skin-to-skin EP procedure duration, not inclusive of isolate the ipsilateral pulmonary veins in pairs. Outcome anaesthesiological preparation; adequate RFA applications (with measures were i) symptoms and ii) objective evidence of fixed temperature and power settings) were considered lesions arrhythmia (ECG, Holter monitoring and/or implantable loop lasting ≥60 seconds. recording) at a minimum of 6 months follow up. Discreet variables Results: RT3DTEE allowed visualization of the CTI in almost are expressed as count (%) and age as mean ± SD. every patient (20/21). Ablation catheter movement and contact Results: The table shows that subjects did not differ in terms of could be followed continuously and anatomic obstacles such as age, sex, presence of structural heart disease, symptoms and Eustachian ridge, prominent Eustachian valve, septal recess, or ECG confirmation of an atrial arrhythmia. The percentages of and (10) could be circumvented during RFA. patients (by arrhythmia type induced, mode of induction and Compared to CON, catheter ablation guided by RT3DTEE was ablation lines performed) who remained symptom-free and had equally effective to achieve CTI bidirectional block (100% in both ECG confirmation of absence of arrhythmia is also shown. groups) without complications. RT3DTEE shortened procedural Conclusions: Supplemental ablation following confirmation of time (73.5, interquartile range [IQR] 60.0–90.5 vs 115.0, IQR PVI during a de novo catheter ablation for PAF does not improve 85.0–135.8 minutes, p = 0.001), reduced radiation exposure outcome in terms of symptoms and ECG documentation of an (fluoroscopy time: 4.2, IQR 3.1–8.4 vs 19.3, IQR 12.9–36.4 atrial arrhythmia. minutes, p <0.001; fluoroscopy dose 575.4, IQR 451.3–1299.1 vs 3520.7, IQR 1783.5-6662.5 cGy cm2, p <0.001), and significantly reduced the number of RFA applications to achieve bidirectional isthmus block (7, IQR 6-10 vs 12 applications, IQR 10-22, p = 0.007). A strong learning curve was detected by comparing procedural data between the first and last patients treated with RT3DTEE approach (fig.). Conclusions: RT3DTEE-guided ablation of CTI was feasible and effective, conferring not only significant reductions of procedural time and radiation exposure, but also reduction in the number of RFA applications.

186 Combined radiofrequency ablation and left atrial appendage occlusion for patients with atrial fibrillation at risk for stroke C. Scharf, B. Nägeli, G. Sütsch, A. Fäh Gunz, D. Maurer, M. Pfyffer, C.H. Attenhofer Jost (Zürich, CH) Background: Radiofrequency ablation (RFA) of atrial fibrillation (AF) does not affect indication of anticoagulation in patients with CHADS score ≥2. Two left atrial appendage (LAA) occlusion systems (Watchman Cardiac Plug (WCP,Atritech) or AGA Ampatzer) have become available as an alternative to anticoagulation in AF.The purpose of the current study was to assess safety and efficacy of LAA occluder implantation with and without simultaneous RFA for AF. Methods and results: Implantation of a LAA occluder device (Watchman n = 25 and AGA n = 5) was performed during RFA for AF (group A, n = 15) or as the only procedure (group B, n = 15). During 57 ± 28 min (group A) and 55 ± 30 min (group B) of

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procedure time fluoroscopy was used for 12 ± 5 min (group A) in group B. As a consequence anticoagulation was stopped in and 15 ± 11 min (group B, p = ns). Acute complications occurred 10/14 (71%) patients in group A and in 8/13 (61%) patients in in 4 patients (2 in group A and B). Two patients had a transient group B (ns). One patient in group a had a sudden cardiac death neurologic deficit because of air embolism roin 1(g up A) and after 3 months and one suicide occurred. thrombus formation on the device in 1 (group A). Another two had Conclusion: Simultaneous RFA for AF during LAA occlusion did delayed pericardial tamponade after 1–3 days (group B, one with not increase complications. However morbidity and mortality after watchman and one with AGA occluder) with fatal outcome in one. LAA occluder device implantation is shows that these patients After 6 weeks the device showed complete occlusion of the LAA need careful observance. in 12 / 13 patients (92%) in group A and in 13/13 patients (100%)

moderierte poster – posters modérés

P190 Is oxidative stress one link to understand proteinuria in of the cryoballoon was performed using the guidewire and a transplant patients treated with mTOR-inhibitors? Effect of steerable sheath. After confirmation of PV occlusion by contrast different antioxidative strategies on albumin reabsorption injection, the freezing cycle was initiated with a standard in renal proximal tubule epithelial cells duration of 300 seconds. Each PV was treated with a minimum of 2 applications. If a PV could not be isolated using up to M. Oroszlan, N. Ligeti, P. Mohacsi (Bern, CH) 6 applications, a focal catheter was used to complete PVI. Background: We have previously shown that mTOR-inhibitors Phrenic nerve stimulation was performed during Cryo-PVI of the (mTOR-i) such as sirolimus and everolimus reduce the albumin right-sided PVs.The procedural endpoint was PVI confirmed by uptake in renal proximal tubule epithelial cells (PTEC) via an a circumferential mapping catheter. Follow-up was performed 1, angiotensin II (Ang II) -dependent manner (Transplant 3 and 6 months after the procedure, and then every 6 months. Immunology 2010). The underlying regulatory mechanisms still Results: Twenty-two patients (age 58 ± 10 years, ejection fraction remained unanswered. 0.59 ± 0.06, left atrial size 40 ± 3 mm) with paroxysmal AF Hypothesis: We hypothesize that oxidative stress contributes undergoing Cryo-PVI were included. The mean procedure time substantially to proteinuria and the following mechanisms are was 175 ± 41 min., the mean fluoroscopy time was 60 ± 28 min. suspected. I. mTOR-i induce oxidative stress. II. Elevated Of 89 targeted PVs, 75 PVs (84%) could be isolated using the oxidative stress through the renin angiotensin system (RAS): cryoballoon alone, the remaining 14 PVs (16%) were isolated Oxidative effects of Ang II are mediated by Ang II type 1 receptor using a focal catheter.After a single procedure, 13/22 patients (AT1R) and Ang II type 2 receptor (AT2R) can oppose it. (59%) were free from arrhythmia after a mean follow-up of 25 ± 5 Methods: Human renal PTEC line (human kidney-2 cells, HK-2) months.When including repeat procedures in 7/22 patients (32%) was used. Oxidative stress was measured by dichlorofluorescein- and a mean of 1. 4 ± 0.7 procedures per patient, 17 of 22 patients diacetate. Albumin receptor (cubilin and megalin), angiotensin (77%) remained in stable sinus rhythm. Late recurrences receptor (AT1R and AT2R) expression and albumin-uptake were (>12 months after the index procedure) were uncommon (9%). determined by cellular ELISA. The gene expression was Conclusion: Single-procedure efficacy of Cryo-PVI is determined by qRT- PCR. approximately 60% during a follow-up of 2 years. When including Results: I) mTOR-i resulted in increased reactive oxygen species repeat procedures in one third of the patients, the success rate is (ROS) production in PTEC.The loss of albumin receptors and the increased to 77%. reduced albumin uptake was prevented by antioxidants. II) RAS-blockade by the ACE-inhibitor, ramipril and/or the AT1R- blocker, losartan, prevented ROS production. The combination of P192 mTOR-i and an antioxidant drug, such as N-acetyl-cysteine (NAC) or the non-selective β-blocker, carvedilol, reduced oxidative P-wave signal averaged ECG to predict atrial stress markedly. mTOR-i-treated PTEC showed a significant fibrillation recurrence after radiofrequency decrease of AT2R expression. The AT1R expression remained pulmonary vein isolation unchanged. RAS-blockade resulted in decreased AT1R C. Blanche, N. Tran, F. Rigamonti, M. Zimmermann (Meyrin, CH) expression. Losartan monotherapy or in combination with ramipril Background: Recurrences of atrial fibrillation (AF)te af r evoked the effect via reduced gene expression of the AT1R. NAC radiofrequency catheter ablation (RCA) is frequent and is usually and carvedilol had neither an effect on AT1R nor on AT2R. caused by pulmonary vein (PV) re-conduction, foci outside the Conclusions: Antioxidants prevented the loss of albumin PV or by previous electrical remodelling with fibrosis.The present receptors and the impaired albumin uptake in mTOR-i treated study was conducted to determine the value of the signal- PTEC (as RAS-blockade, which was reported earlier). We averaged P-wave electrocardiogram (SAPW) to predict AF speculate that 1. mTOR-i downregulate AT2R expression and may recurrences after RCA in patients with paroxysmal or persistent induce oxidative stress via a RAS-independent way as well as AF. shifting thereby the phenotype of PTEC into a prooxidative state Methods: Forty-six patients (59 ± 11 years, 39 males, 7 females; and 2. RAS-blockade re-establishes a new balance between structural heart disease in 6/46; hypertension in 19/46; pro- (AT1R) and antioxidative (AT2R) actions favouring the antiarrhythmic drug therapy in 34/46) underwent sixty-five RCA antioxidative state by reducing AT1R expression. procedures for paroxysmal (n = 25) or persistent (n = 21) AF.A SAPW recording (Phi-Res analysis – Marquette Medical System; measurement of total filtered P wave duration, P wave integral, P191 RMS voltage of the terminal 20, 30 and 40 ms) was obtained Long-term follow-up 2 years after catheter ablation immediately after the ablation procedure (segmental PV isolation of paroxysmal atrial fibrillation using a single 28-mm ± left atrial lines and CFAE ablation in selected cases) and the cryoballoon patients were prospectively followed. Recurrence was defined M. Kühne, Y. Suter, T. Reichlin, B. Schaer, P. Ammann, as AF occurring after a blanking period of 2 months after the S. Osswald, C. Sticherling (Basel, St. Gallen, CH) procedure. Results: During a mean follow-up of 7. 3 ± 4.7 months, Background: Cryoballoon pulmonary vein (PV) isolation recurrences occurred in 42% (27/65; 11/34 paroxysmal AF, 16/31 (Cryo-PVI) has emerged as a novel technology for ablation persistent AF, p = 0.13). Among the various SAPW parameters, of atrial fibrillation (AF). Information on long-term follow-up only the total filtered P-wave duration (PFD) was statistically after Cryo-PVI is not available. different between patients with and those without recurrences: Methods: Cryo-PVI was performed using a single 28-mm 163 ± 23 ms vs 142 ± 21 ms respectively, p = 0.0003). PFD was cryoballoon ablation catheter (Arctic Front, Medtronic). Positioning also shorter in patients with paroxysmal AF compared to patients

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with persistent AF (140 ± 18 ms vs 162 ± 25 ms, p <0.0001). P194 A PFD of 140 ms was found to discriminate patients prone to Syncope due to digitalis intoxication recurrences over time (p = 0.003 according to Kaplan Meyer survival analysis, see figure) with a sensitivity of 78%,a M. Oberhaensli, S. Puricell, S. Cook, J. Schlaepfer, specificity of 47%, a positive predictive value of 51%, a negative J.-J. Goy (Fribourg, CH) predictive value of 75% and a total accuracy of 75%). Case description: An 83 years old woman was hospitalized Conclusion: A filtered P-wave duration > 140 ms is a powerful because of syncope type Adams-Stokes. In her medical history marker of AF recurrences after RCA. Prolonged PFD reflects inter we noted only essential hypertension treated with diuretics. She and/or intra-atrial conduction delay and is related to the extent of was started on digoxine 3 months before for some shortness of atrial scarring.Whether SAPW also reflects PV re-conduction breath, at a dose of 0.25 mg/day, 5 days a week. Her baseline after RCA remains to be determined. electrocardiogram was normal at that time. On admission, she was well oriented, and had a normal neurological status. BP was 110/75. Weight 56 kilograms. Pulse was irregular with a heart rate varying between 45 to 110 beats per minute Cardiac auscultation showed a 3/6 ejectional systolic murmur. Pulmonary status was normal. Electrocardiogram showed most of the electrocardiographic patterns of digitalis intoxication on the same electrocardiogram with depressed conduction (A-V block) and enhanced automaticity (ventricular tachycardia and bidirectional tachycardia) (fig. 1). Blood level of digoxine was 8.3 µmo/l. After normalization of the blood level of digoxine, symptoms recurred and electrocardiogram normalized.

Figure 1 Baseline electrocardiogram (continous recording). In I, II and III complete A-V block can be seen on the left (first 3 QRS complexes) followed by the beginning (fourth QRS from the left) of the typical form of ventricular tachycardia due to digitalis intoxication (fascicular tachycardia). In V1, V2, V3 this tachycardia (A-V dissociation present) lasts for 5 beats and is followed by a bidirectional tachycardia visible in V4, V5 and V6. This ECG is rare in that it shows in a few seconds most of the arrhythmias that digitalis can induced. P193 A pulsatile abdominal mass in the epigastric region G.M. Vincenti, L. Sekoranja, D. Carballo, R. Lerch, H. Müller (Geneva, CH) Case presentation: a 68-year-old patient was admitted with right- sided hemiplegia and dysarthria of acute onset. He was known for cardiovascular risk factors as hypertension and smoke. Physical examination on admission disclosed a pulsatile mass in the epigastric region, suspected to be an abdominal aortic aneurysm. Thoraco-abdominal computed tomography (CT) revealed an apical left ventricular (LV) protrusion through the diaphragm and midline thoraco-abdominal defect. Transthoracic echocardiography (TTE) showed left ventricular dilation with severe systolic dysfunction and confirmed an apical protrusion with a partially mobile apical thrombus.TTE repeated five ysda after anticoagulation therapy showed that the apical thrombus had disappeared. Coronary angiography revealed the absence of coronary lesions. Cardiac magnetic resonance imaging (cardiac- MRI) confirmed a LV diverticulum with midline thoraco-abdominal defect and a pericardial defect, suggestive for Cantrell’s P195 Syndrome. Influence of media consumption and physical Discussion: LV protrusion include aneurysms (congenital or activity on endothelial function and cardiac acquired), pseudoaneurysm, diverticula and hernias. Diverticula autonomic nervous modulation in children are distinguished by a thick wall and narrow communication with K. Khattab, N. Brugger, A. Trepp, N. Brügger, J.-P. Schmid, the ventricle while aneurysms have a thin wall (consisting of H. Saner, M. Wilhelm (Bern, CH) fibroelastic tissue and endocardium, without muscle tissue) and wide communication; in either case the pericardium remains Introduction: High media use is associated with increased intact. In contrast, cardiac hernias result from the herniation of cardiovascular mortality. However it remains unclear, whether ventricular or atrial tissue through a pericardial defect. In Cantrell’ high media use is an independent risk factor for cardiovascular s Syndrome the classical pentalogy include defects of abdominal disease (CVD) or aggravates other established risk factors such wall, sternum, diaphragm, pericardium and heart. Clinical as physical inactivity and unhealthy diet. Early stages of CVD presentation may vary and includes arrhythmias, congestive can be detected already in childhood. The aim of this study was heart failure,peripheral embolism, tamponade due to acute to determine the impact of media use and physical activity on rupture,sudden death or they can present as an incidental finding endothelial function and cardiac autonomic nervous modulation on routine chest X-ray (cardiomegaly, malposition of cardiac in children. silhouette or abnormal left cardiac border) in asymptomatic Method: We examined 60 children, age 10–14 years (mean age patients. Coronary angiography allows to exclude coronary artery 11.9 ± 0.9 years,), 26 boys and 34 girls in a prospective disease. Cardiac MRI is a sensitive method for detecting a LV observational cohort study.Aquestionnaire assessed media use protrusion but the distinction between aneurysm/diverticulum vs. (TV, PC and video games), physical activity and other CVD-risk hernia may be difficult. The treatment is surgery and sometimes factors. During three days a combined holter and movement the intraoperative and histopathologic examination may be the sensor was installed to evaluate heart rate variability and physical only method for diagnosis. activity, children kept a diary. Endothelial function was assessed Conclusions: our report is a rare case of Cantrell’s Syndrome noninvasively by peripheral arterial tonometry on two separate with congenital LV diverticulum, midline thoraco-abdominal defect days. and pericardial defect, with peripheral embolism (stroke) as Results: Mean time of physical activity was 617 min (SD ± 248 clinical presentation. min) per week. Physically active children showed higher reactive

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hyperaemia indices (RHI) of flow mediated vasodilatation than children compared to less active children spending more time children who were less active (RHI 1. 52 vs. 1. 19, SD ± 0.49 vs. with media (see fig.). 0.28, p = 0.02). Mean time spent with media use was 17.9 h (SD ± Conclusions: Physical activity has a positive effect on 13h) per week. There was no correlation between media use and endothelial function and increases nocturnal parasympathetic endothelial function in this population (RHI 1. 39 vs. 1. 33, SD ± nervous tone in 10–14 year old children. No significant correlation 0.4, n.s.).Ye t children with low activity and high media use had could be found between media consumption and endothelial significantly higher BMI than children with low activity andlow function. High media use combined with low physical activity was media use (BMI 19.6 vs. 16.6 ± 3.2 vs. 2.4 kg/m2, p = 0.006) and associated with highest BMI. Therefore physical activity may higher BMI than active children with low media use (BMI 19.6 vs. compensate negative effects of media use in 10–14 year old 17.2 ± 3.2 vs 2.3, p = 0.02). HRV-parameters indicating increased children and should become a central target of primary prevention vagal tone during sleep could be found in physically active programs.

P196 Traditional cardiovascular risk factors distribution achieves the treatment goals for individual risk factors. Never- and control in Switzerland: the EURIKA study theless, in a major part of the patients, a comprehensive CV risk management, is not achieved. R. Darioli, G. Plebani, A. Miserez (Lausanne, Zug, Basel, CH) Purposes: Despite the availability of the ESC guidelines on cardiovascular prevention, cardiovascular mortality is the P197 leading cause of death in Switzerland. The European Study on Cardiovascular Risk Prevention and Management in Daily Angiojet rheolytic thrombectomy in patients Practice (EURIKA, NCT00882336) investigated degree of control presenting with pulmonary embolism and cardiogenic of main CV risk factors in primary prevention of cardiovascular shock: a feasibility and safety pilot study disease (CVD). R. Bonvini, M. Roffi, H. Bounameaux, S. Noble, P. F. Keller, Methods: EURIKA study was conducted in 12 European H. Mueller, F. Sarasin, O. Rutschmann, K. Bendjelid, countries (Austria, Belgium, Sweden, France, Germany, Greece, M. Righini (Genève, CH) Norway, Russia, Spain, Switzerland, Turkey, UK). Patients aged Introduction: High-risk pulmonary embolism (PE), i.e., >50 years who were free of clinical CVD, but had at least one risk associated with hemodynamic instability, is an exceedingly high factor, were eligible for inclusion. Data recorded included smoking mortality condition. While systemic thrombolysis is considered the status, body mass index (BMI), lipid profiles, blood pressure and therapy of choice, percutaneous mechanical thrombectomy may the presence of diabetes. Cardiovascular risk was assessed represent an alternative treatment, especially if thrombolysis is by Systematic COronary Risk Evaluation (SCORE) methods. contraindicated. We report feasibility and safety of Angiojet- Treatment goals were evaluated in accordance with the Fourth Rheolytic-Thrombectomy (ART) in patients presenting with European Guidelines based on data from the physical high-risk PE. examination or from the blood sample.The target blood pressure Methods: The impact of ART in high-risk PE on hemodynamic values were <140/90 mm Hg and <130/80 mm Hg for DM and echocardiographic findings as well as on clinical outcomes patients.Target lipid levels were <5 mmol/L total cholesterol and was assessed in a pilot study. <3 mmol/L LDL cholesterol (LDLC), and <4.5 mmol/L total Results: 10 patients presenting with high risk PE – all of them in cholesterol and <2.5 mmol/L LDLC for diabetic patients. For cardiogenic shock – were included over an 18-months period. Six diabetic patients, target HbA1c was <6.5%. The target BMI was patients had contraindications for systemic thrombolysis. Eight <30 kg/m2. patients were intubated before ART, while six had experienced Results: In total, 667 patients (mean age: 65 years; 52.8% male) cardiac arrest prior to arrival in the catheterization laboratory. ART were evaluated in Switzerland and 7, 641 in total. 36.9% were high was technically successful in all cases and resulted in significant risk patients using SCORE >5% Calculation of SCORE risk was angiographic in eight and hemodynamic improvements in seven based on the following data: age, sex, systolic BP and total cases respectively. Intra-venous or intra-pulmonary thrombolysis cholesterol values at the study visit, and smoking status. 49.9% was administrated in four patients because of progressive clinical of patients were current smokers, 72% had hypertension, 62.3% deterioration during or after the procedure. No ART- related had dyslipidemia,, 31.4% had diabetes, and 44.7% presented a complications were detected and none of the patients had major BMI over 30 kg/m2 (obesity). Risk factors in patients receiving a cardiac or pulmonary complications during the procedure. Seven therapy were sufficiently controlled in 37.4% for hypertension (all patients died in the first 24-hourste af r the procedure: two from countries average (ACA) 38.8%), in 44.6% for dyslipidaemia (ACA multi-organ failure, one from post-anoxic cerebral edema, and 41.2%) and in 41.8 for diabetes (ACA 36.7%). Despite that 88.7% the remaining four from persisting right heart failure. The (ACA 92.2%) of the obese patients received a lifestyle advice, three survivors had favorable outcomes at one year. only 23.8% (ACA 24.7%) reached the target BMI. Conclusions: This pilot study confirms the safety and feasibility Conclusions: In Switzerland, the control of traditional of ART in patients presenting with PE and cardiogenic shock. cardiovascular risk factors is insufficient. A large proportion of However, the short-term mortality remained exceedingly high. asymptomatic patients with an intermediate to high CV risk (Clinical trial NCT00780767)

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P198 index (r = –0.66/r = –0.68), and higher diastolic left ventricular Living autologous tissue engineered heart valves – eccentricity index (r = 0.48/r = 0.49). In addition, higher delta-CS- A novel concept aiming at a minimally invasive approach A-BNP and delta-CS-A-NT-proBNP were related to lower partial pressure of arterial oxygen (r = –0.59/r = –0.72) and lower B. Weber, M.Y. Emmert, C. Brokopp, L. Baumgartner, estimated glomerular filtration rate (r=-0.54/r = –0.49). G. Zund, J. Grünenfelder, V. Falk, S.P. Hoerstrup (Zürich, CH) Conclusions: In patients with PAH, cardiac release of BNP and Introduction: Currently used substitutes are NT-proBNP is increased compared to controls. Cardiac release associated with several shortcomings, such as limited durability of BNP and NT-proBNP is related to measures of both right and thromboembolic complications.To overcome these ventricular strain and LV deformation as well as non-cardiac limitations, tissue engineering technologies have emerged in factors, highlighting a complex regulation of the cardiac release order to provide a living autologous valvular replacement with of B-type natriuretic peptides in PAH. regeneration and growth potential. Besides that, minimally invasive valve replacement procedures are rapidly evolving as alternative treatment option for patients with valvular heart disease. Here we first demonstrate the feasibility of combining these novel heart valve replacement approaches, (i) tissue engineering and (ii) minimally invasive implantation techniques, based on autologous cells and composite self-expandable biodegradable biomaterials. Methods: Tr ileaflet heart valves fabricated from biodegradable synthetic scaffolds, integrated in self-expanding stents and seeded with autologous vascular or stem cells were generated in-vitro using dynamic bioreactors. Subsequently, the stented tissue engineered heart valves (TEHV) were minimally invasively (transapically) implanted in the pulmonary position in sheep. In-vivo functionality was assessed by echocardiography and angiography up to 8 weeks post implantation. Tissue composition A of explanted TEHV and corresponding control valves was analyzed using histology, electron microscopy and extracellular matrix analysis. Results: The transapical implantations were successful in all animals.TEHV demonstrated in-vivo functionality with mobile but thickened leaflets. Histology revealed layered neo-tissues with endothelialized surfaces. Quantitative extracellular matrix analysis at 8 weeks showed higher values for DNA, collagen and glycosaminoglycans compared to native valves. Mechanical profiles rendered sufficient tissue strength, but less pliability independent of the cell source. Conclusion: This study demonstrates the principal feasibility of merging tissue engineering and minimally invasive valve replacement technologies and represents a fundamental step towards a future clinical realization of the entire heart valve tissue B engineering concept.

P199 P200 Cardiac release of B-type natriuretic peptides Exercise induced right ventricular overload in in pulmonary arterial hypertension patients with Contegra conduit: Is a diameter of 22 mm sufficient for adults? M.T. Maeder, D.M. Kaye (St. Gallen, CH; Melbourne, AU) Introduction: In patients with pulmonary arterial hypertension I.P.D. Fauchère, B.E. Stähli, P. Biaggi, M. Greutmann, (PAH), elevated concentrations of B-type natriuretic peptide R. Jenni, F. C. Tanner (Zürich, CH) (BNP) and N-terminal-proBNP (NT-proBNP) in peripheral plasma Introduction: The Contegra conduit, a bovine graft, is used for predict an adverse outcome.This may reflect an increased reconstruction of the right ventricular outflow tract in patients with cardiac release of these markers or alternatively a reduced congenital heart disease.This study was performed to evaluate if clearance.We therefore sought to characterize the plasma the Contegra conduit (maximal diameter = 22 mm) causes an concentrations and cardiac release of B-type natriuretic peptides exercise-induced stenosis in adults leading to pressure overload in PAH and investigate their determinants. of the right ventricle. Methods: Nine patients with PAH under established vasodilator Methods: Fourteen adult patients with a Contegra conduit therapy and nine control subjects [age 47 ± 15 vs. 53 ± 15 years, (diameter 20 or 22 mm) and 16 age-matched healthy controls p = 0.37; transpulmonary gradient, median (range), 35 (9-65) vs. were examined by quantitative Doppler-echocardiography at rest 6 (3-10), p = 0.001; pulmonary vascular resistance index, 1297 and during semi-supine exercise with 25 W increments every (156-1652) vs. 155 (70-235) dyn*sec*cm-5*m-2] underwent 2 minutes. Peak systolic velocity over the right ventricular outflow comprehensive transthoracic echocardiography immediately tract and peak tricuspid regurgitation velocity were measured followed by right heart catheterization. Samples were obtained using continuous wave Doppler echocardiography. Pressure from arterial and coronary sinus blood for measurement of BNP gradients were calculated using the simplified Bernoulli equation. and NT-proBNP in EDTA plasma. We calculated transcardiac Results: The maximal instantaneous systolic pressure gradient gradients of BNP and NT-proBNP (delta-CS-A-BNP, delta-CS-A- over the right ventricular outflow tract was significantly higher in NT-proBNP) defined as marker concentration in coronary sinus Contegra patients as compared to controls both at rest and during plasma minus marker concentration in arterial plasma as exercise (fig.). At 150 W, the pressure gradient reached 61.0 mm measures of cardiac peptide release. Hg in Contegra patients (p <0.001 vs control), while there was Results: Patients with PAH had significantly higher delta-CS-A- no significant increase in the control group (fig.). The maximal BNP [median (range), 96 (17- 815) vs. 31 (1-88) ng/L; p = 0.04] instantaneous systolic pressure difference between the right and delta-CS-A-NT-proBNP [45 (11-906) vs. 12 (7-57) ng/L; p = ventricle and the right atrium was 72 mm Hg in Contegra patients 0.01] compared to controls (fig.). There were correlations between (n = 5). Tr icuspid regurgitation was insufficient for calculating higher delta-CS-A-BNP and delta-CS-A-NTproBNP and higher pressure gradients in the majority of controls. Right atrial pressure pulmonary vascular resistance index (correlation coefficients, was 5 mm Hg in all individuals studied as estimated by the r = 0.42/r = 0.43), lower tricuspid annular plane systolic excursion diameter of the inferior vena cava and its respiratory variation. (r = –0.45/r = –0.46), lower left ventricular end-diastolic volume Conclusion: Patients with a Contegra conduit exhibit a highly significant increase in the maximal instantaneous systolic

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pressure gradient over the right ventricular outflow tract during P202 physical exercise.This observation demonstrates that the Phosphodiesterase-5 inhibition with Sildenafil Contegra conduit is undersized for adolescent or adult patients attenuates the pulmonary apoptosis and remodeling and does not allow a physiologic response to exercise leading to in chronic hypoxic rats pressure overload of the right ventricle. Hence, there is a need for larger heterograft conduits allowing a physiologic response to G. Milano, V. Rochemont, P. Bianciardi, M. Samaja, exercise in adolescent or adult patients. L.K. von Segesser (Lausanne, CH; Milano, IT) Background: We have recently demonstrated that daily reoxyenation during chronic hypoxia (CH) markedly improved recovery of the ventricular performance, attenuated the degree of apoptosis and right ventricle pressure without appreciable differences in myocardial hypertrophy. Unfortunately, the daily reoxygenation does not apply in clinical. Here, we investigated if the effects of Sildenafil were comparable or more effective to those induced by daily reoxygenation in a rat model of CH. Methods: Adult male Sprague-Dawley rats were exposed to CH (10% O2) with no treatment or with sildenafil administration (1.4 mg/kg/day, i.p.) for 2 weeks. Normoxic rats (N) breathing room air served as control. Hearts and lung were either subjected to or freeze-clamp for biochemical analyses or fixed with formalin for histological analyses.With a catheter inserted in the right ventricle and in the carotid artery, we measured the right and left ventricle pressures, respectively. Apoptosis was assessed using the TUNEL technique. Data are expressed as mean± SEM. Results: At the end of treatment, the RV systolic pressure was elevated in CH (P <0.001) while sildenafil (P <0.001)te at nuated this increase.The plasma level of NOx, an index of NO production, increased markedly in CH (P <0.001). In vivo P201 administration of sildenafil further increased the NOxve le l Safety and clinical utility of cardiovascular magnetic (P <0.05). Thus, whereas hypoxia increased NO production, resonance in neonates with congenital heart disease sildenafil enabled further increase of this parameter. Both RV/ B. Schaetzle, C.J. Kellenberger, A. Schmitz, M. Hug, LV+S ratio, an index of right hypertrophy, and Lung /body weight, E.R. Valsangiacomo Büchel (Zürich, CH) an index of pulmonary edema, were increased in CH with respect to normoxic hearts (P <0.001), whereas the treatment with Introduction: Cardiovascular magnetic resonance (CMR) is an sildenafil teat nuated the increase of these ratios (P <0.05). CH established advanced diagnostic modality in adult with congenital induced a approx. 2 fold increase in TUNEL-positive apoptotic heart disease (CHD). CMR is being increasingly used also in cells compared to N (P <0.001) both in heart and lung tissues. young children with complex CHD, as complement to Sildenafil teat nuated such increase (P <0.001 vs CH for both). echocardiography. We sought to evaluate the indications, safety The Western blot analysis revealed a significant increase in the and clinical impact of CMR performed in neonates with CHD. phosphorylation status of extracellular signal regulated kinase Methods: Clinical records and imaging reports of all patients ½ (ERK1/2) and endothelial NOS with Sildenafil versus N. younger than1 month, undergoing CMR between 2002 and 2010 The number of small pulmonary vessels (0–100 microm) was were retrospectively reviewed for diagnosis, indication for CMR, significantly increased in CH versus N and the treatment with complications and impact on clinical management. In all cases Sildenafil teat nuated this increase. CMR was performed as second-line diagnostic examination Conclusion: This study revealed that Sildenafil teat nuates complementing echocardiography. cell death induced by CH and induces a decline in the right Results: Seventy-eight CMR examinations were performed in ventricular hypertrophy with a parallel reduction in pulmonary 77 neonates. Mean age was 7 ± 8 days , weight 3064 ± 633 g. edema and remodeling. Diagnosis included aortic arch anomalies in 23 children, pulmonary atresia/multicentric lung perfusion in 16, complex CHD with single ventricle in 13, complex CHD with two ventricles in 10, pulmonary vein anomalies in 8, tetralogy of Fallot in 2 , tumour in P203 2 and 4 others. Correspondingly main indication for CMR was Thiamine supplementation in moderate congestive assessment of the aorta in 26 cases, pulmonary arteries in 21, heart failure: a randomized, double-blind, placebo- pulmonary veins in 15, complex congenital heart disease in 8, controlled, cross-over study myocardium in 3, ventricular size in 3, and two others. Mean A.W. Schoenenberger, R. Schoenenberger-Berzins, scanning time was 30 ± 12 min. The neonatal intensive care team C. Auf der Maur, P. M. Suter, A. Vergopoulos, P. Erne performed anaesthesia with mechanical ventilation in 57 cases, (Bern, Luzern, Zürich, CH) anaesthesiology staff in 21. No significant complications occurred Introduction: Diuretic treatment in congestive heart failure may during examination. In two patients in critical condition breath- lead to an increased urinary thiamine excretion and in long term holding was avoided and the images acquired during free thiamine deficiency which may further compromise cardiac breathing. CMR findings had a major impact on further clinical function. This study evaluated the effect of high dose thiamine management in 67/77 (87%) of the patients.The information supplementation in heart failure patients. obtained was crucial for following cardiac surgery in 54 cases, Methods: Ten patients with a left ventricular ejection fraction for catheter-guided intervention in 4; palliative care was decided in (LVEF) <40% and clinical signs of heart failure were randomly 9 neonates. In 7 children suspected diagnosis was confirmed and assigned to receive thiamine (300 mg per day) or placebo for in other 4 ruled out. 28 days.After a wash-out of 6 weeks, the patients crossed-over Conclusions: CMR can be effectively and safely performed in to a second treatment period. The primary outcome was a change neonates with CHD, at time of first diagnosis even in critically ill in echocardiographic measures. patients.The information obtained has a major clinical impact on Results: The mean age was 57.5 ± 9.1 years (range 44.9–75.4 further management and obviates other invasive and potentially years). During thiamine treatment the LVEF significantly increased harmful examinations. (from 29.0% to 31.7%, P = 0.025). The area of the right atrium significantly decreased (from 18.6 cm2 to 16.7 cm2, P = 0.026). Weight significantly decreased (from 81.8 kg to 81.0 kg, P = 0.015). There was a significant improvement of the 6-minutes walking test during thiamine treatment (from 542 m to 609 m, P = 0.017). No significant changes in these parameters were found during placebo treatment.

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Conclusions: This study suggests that thiamine supplementation has beneficial feef cts on cardiac function in patients with diuretic drugs for congestive heart failure. Subclinical thiamine deficiency is probably an underestimated issue in these patients. Larger studies investigating potential beneficial and harmfulfe ef cts of thiamine are required.

P204 Copeptin and sensitive cardiac troponin in the early diagnosis of acute myocardial infarction in patients with preexisting coronary artery disease M. Potocki, T. Reichlin, M. Noveanu, R. Twerenbold, M. Reiter, J. Meissner, K. Winkler, P. Haaf, S. Osswald, C. Mueller (Basel, CH; Barcelona, ES) Introduction: Chronically elevated levels of cardiac troponin (cTn) were found in more than 10% of patients with pre-existing coronary artery disease (CAD). These patients often suffer from acute chest pain and the early diagnosis of acute myocardial infarction (AMI) is particularly challenging. It is unknown whether copeptin, a novel marker quantifying endogenous stress, has additional value in patients with pre-existing CAD for the diagnosis of AMI. Methods: In this sub-analysis, we studied the data of 385 patients (72 [60–79] years; 77% male) with pre-existing CAD out of 1067 patients with symptoms suggestive of AMI. Measurement of copeptin, the Roche 4th generation standard assay (TnT) P205 and the Siemens sensitive cTnI-Ultra (TnI Ultra) assay were performed in a blinded fashion. Endogenous stress response in Tako-Tsubo Results: AMI was the final diagnosis in 76 patients with CAD cardiomyopathy and acute myocardial infarction (20%). Copeptin levels were significantly higher in AMI patients J. Meissner (Basel, CH) compared with patients having other diagnoses (26 pmol/l vs. Background: Since the clinical, electrocardiographic and 7 pmol/l, p <0.001). The combination of TnT and copeptin resulted laboratory presentation of Tako-Tsubo cardiomyopathy (TTC) in an area under the receiver-operating characteristic curve (AUC) and acute myocardial infarction (AMI) is similar, both entities are for the diagnosis of AMI of 0.94, which was significantly higher in general only distinguishable by coronary angiography. The than 0.87 for cTnT alone (p <0.001). The AUC was significantly purpose of this study was to examine the endogenous stress higher for the TnI Ultra assay than for the standard assay TnT response at presentation, quantified by the copeptin level, of and Copeptin (AUC for TnI Ultra, 0.94 vs. 0.87 for TnT and 0.75 patients with TTC and patients with AMI, as copeptin may be for Copeptin; p = 0.002 and p <0.001 respectively). Among the useful in the non-invasive differentiation between both diseases. patients with an initial sensitive TnI Ultra level below the 99th Methods: We compared the endogenous stress response at percentile (0.04 ug/l), copeptin was significantly higher in AMI initial presentation, quantified by the plasma copeptin levels, patients than in patients with other causes of chest pain (40 in 21 consecutive patients finally diagnosed with TTC and pmol/l vs. 7 pmol/l, p = 0.001). The combination of Copeptin and 21 patients finally diagnosed with AMI matched for sex and time TnI Ultra was able to improve the negative predictive value from since chest pain onset. 97% to 100% to rule out AMI. In patients with elevated TnI levels Results: The prevalence of cardiovascular risk factors and above the 99th percentile, Copeptin was significantly higher in initial cardiac troponin T levels were comparable in TTC and AMI. patients with AMI (26 pmol/l vs. 13 pmol/l, p = 0.024) but showed Copeptin levels were significantly welo r in patients with TTC as a substantial overlap, resulting in a low diagnostic accuracy with compared to patients with AMI (median 4.8 [IQR 3.5–13.5] pmol/L an AUC of 0.63 for the diagnosis of AMI. vs. 25.6 [IQR 12.1.–63.9] pmol/L, p = 0.002). The accuracy for Conclusion: Copeptin together with the standard TnT assay diagnosing TTC as quantified by the area under the receiver- improves the diagnostic accuracy to diagnose AMI in patients with operating-characteristics curve was significantly higher for pre-existing CAD. In the era of upcoming sensitive cTn, Copeptin could be an ideal partner in patients with initially negative sensitive cTn levels to rule out AMI. In contrast, Copeptin shows only a low diagnostic accuracy for the diagnosis of AMI in patients with chronically elevated sensitive cTn levels.

Cardiovascular Medicine 2011;14(5): Suppl 20 44 S moderierte poster – posters modérés

copeptin than for cardiac troponin T (0.782 vs. 0.549, p = 0.031). left ventricle with global systolic dysfunction (EF 35%). There was The optimal cut-off value for differentiation between TTC and AMI a large structure compressing the left atrium (LA) as well as a was found at a copeptin level of 7. 8 pmol/L (sensitivity 67% at a dense jet of paravalvular AR whose origin was unclear. Dynamic specificity of 86%, negative predictive value 72%, positive ECG changes with ST elevation (I-aVL) and deep ST depression predictive value 82%). (V4-V6) were noted in left lateral decubitus position. A 3D Conclusions: The endogenous stress response, quantified by a transoesophageal echocardiogram (TOE) demonstrated a very novel sensitive biomarker, seems to be different in patients with large posterior aortic pseudoaneurysm (9 x 8 cm) compressing TTC and AMI. Copeptin levels may be helpful in the non-invasive the LA, and communicating to the left ventricular outflow tract differentiation between TTC and AMI. (LVOT) through a large fistula with bidirectional flow. Furthermore, there was a 5x9 mm orifice on the left side of the aortic graft, 10 mm above the aortic valve, showing a dense systol ic flow to P206 the pseudoaneurysm and suggesting an avulsion of the left Aortic root replacement does not add additional coronary artery (fig. 1). A CT scan supported this diagnosis, surgical risk compared to isolated aortic valve showing the proximal end of the left coronary artery originating replacement from the wall of the pseudoaneurysm, 10 mm apart from the aortic tube graft (fig. 2). Due to hemodynamic instability, a surgical M. Muretti, S. Demertzis, S. Riva-Muzio, L. Vlad, correction was attempted, but due to refractory ventricular S. Matta, F. Siclari (Lugano, CH) dysfunction, the patient died despite successful repair. Peri- Background: Dilatation of the aortic root and / or ascending operative findings confirmed the imaging diagnosis. aorta is frequently documented in patients (pts) with indication for Conclusion: We report a case of rupture of the left coronary aortic valve replacement (AVR). With findings in the grey-zone of anastomosis 7 years after Bentall operation. This unique the formal criteria, indication for root replacement is still debated complication resulted in a large compressive pseudoaneurysm mainly due to the surgical risk potentially added to the risk of the with a para-aortic graft fistula to the LVOT.The dynamic ischemic AVR. We therefor analyzed our results to assess whether ECG changes as well as the global systolic dysfunction can be composite graft AVR (COMP) would add additional risk to an explained by extensive LV ischemia, the perfusion of the left isolated AVR (AVR). coronary being exclusively dependent on the intra-aneurysmal Patients and methods: A total of 406 pts (121 after COMP, 285 pressure. after AVR) operated upon between 10/99 and 08/10 was analyzed retrospectively. Pts with acute type A aortic dissections and/or use of deep hypothermic circulatory arrest were subsequently excluded leaving 84 pts with isolated COMP. Pre-, intra- and postoperative characteristics were compared by means of analysis of variance (ANOVA) or Chi square test. Logistic regression analysis was used for identifying predictive parameters for adverse postoperative outcomes.Values are expressed as mean/standard deviation. Results: The groups differed in favor to COMP with regard to mean age (AVR: 70/11, COMP: 60/11, p = .0001), prevalence of female pts (AVR: 43%, COMP: 19%, p = .0001), preoperative NYHA class (p = .001) and in favor of AVR with regard to the prevalence of endocarditis (AVR: 4%, COMP: 7%, p = .0015). Operative times and major outcome parameters are shown in figure 1. Not the group but female sex was an independent predictor of in-hospital mortality (p = 0.03), redo procedure and preop NYHA class had a borderline predictive value (p = 0.07 and 0.06 respect.). Conclusions: Even considering the differences between the groups and despite the expected longer ECC and x-clamp times COMP was not associated with increased mortality and morbidity in this series.

P207 Aortic pseudo-aneurysm due to de-insertion of the left coronary artery 7 years after Bentall operation P. Monney, C. Pellaton, M. Nasratullah, S.D. Qanadli, E. Ferrari, X. Jeanrenaud (Lausanne, CH) Case: A 65 year old male smoker with hypertension was referred for exertional dyspnea and orthopnea progressing over 3 weeks, with a new aortic regurgitation (AR) murmur. He was previously operated for a type A aortic dissection 11 years earlier (Vaskutek 26 mm graft and aortic valve resuspension), with a re-operation 4 years later for the de-insertion of the proximal graft anastomosis (Bentall operation with Carboseal 25 mm graft). On admission, high jugular venous pressure, pulmonary oedema and 3/6 AR murmur were noted. ECG showed mild anterolateral ST depression; troponin was 2.2 mcg/l and NTproBNP was 16 600 ng/l. The patient developed acute respiratory failure with facial cyanosis when lying down for central catheter insertion and was intubated. Transthoracic echocardiogram showed a mildly dilated

Cardiovascular Medicine 2011;14(5): Suppl 20 45 S postergruppe 1 – groupe de posters 1 pathophysiology / Molecular Biology

P208 P210 Dietary α-linolenic acid inhibits arterial thrombus Carbamylated low density lipoprotein impairs formation, tissue factor expression, and platelet nitric oxide induced vascular relaxation activation F. O. Owala, E.W. Holy, G.G. Camici, H. Greutert, E.W. Holy, M. Forestier, A. Akhmedov, E.K. Richter, B.E. Stähli, T.F. Lüscher, F. C. Tanner (Zürich, CH) F. Leiber, T.F. Lüscher, F. C. Tanner (Zürich, CH) Introduction: LDL carbamylation has emerged as a potentially Background: The plant-derived n-3 fatty acid (n-3 FA) α-linolenic important cause of cardiovascular complications in smokers and acid (ALA) may constitute an attractive cardioprotective patients with chronic renal failure. Hypothesis: Carbamylated LDL alternative to fish-derived n-3 FA. However, the effect of dietary (cLDL) impairs nitric oxide (NO) induced relaxation in mouse ALA on tissue factor (TF) and arterial thrombus formation remains aorta. unknown. Methods: Native LDL (nLDL) was carbamylated with potassium Methods and results: Male C57Bl/6 mice were fed a high ALA cyanate and the degree of carbamylation measured by or low ALA diet for 2 weeks.Arterial thrombus formation was chromatography. TBARS assay was performed to confirm the delayed in mice fed a high ALA diet as compared to those on a absence of LDL oxidation. Aortic rings were suspended in organ low ALA diet (n = 7; p <0.005). High dietary ALA impaired arterial chambers for isometric tension recording and the responses TF expression, TF activity and NFkappaB activity (n = 7; p <0.05); recorded in the presence or absence of 100 ug/ml nLDL or 100 plasma clotting times and plasma thrombin generation did not ug/ml cLDL during submaximal contraction to norepinephrine differ (n = 5; p = NS). In cultured human vascular smooth muscle (10-7 mol/L). and endothelial cells ALA inhibited TF expression and activity Results: LDL oxidation was neither detected in cLDL nor nLDL. (n = 4; p <0.01). Inhibition of TF expression occurred at the cLDL inhibited maximal endothelium-dependent relaxations to transcriptional level via the MAP kinase p38 in smooth muscle acetylcholine as compared to vessels treated with nLDL (68.53 ± cells and p38, ERK1/2, and JNK1/2 in endothelial cells. In 5.29% vs 87.04 ± 1. 68%; p = 0.003; n = 11) or controls (68.53 ± addition to its effect on TF, dietary ALA also impaired platelet 5.29% vs. 85.51 ± 2.42%; p = 0.009; n = 11). Similarly, cLDL aggregation to collagen and thrombin (n = 5; p <0.005). ALA inhibited receptor-independent relaxations to the calcium decreased collagen and thrombin induced activation of the ionophore A23187 (63.14 ± 3.40% vs. 85.35 ± 2.33%; n = 6; MAP kinase p38 in platelets. p = 0.003 vs control). In contrast, endothelium-independent Conclusions: ALA impairs arterial thrombus formation, TF relaxations to sodium nitroprusside were not affected by cLDL expression, and platelet activation, and thereby represents an (n = 11; p = n.s. vs. control). Indomethacin did not alter attractive nutritional intervention with direct dual anti-thrombotic endothelium-dependent relaxations to acetylcholine in vessels effects. treated with cLDL nor in controls (n = 5; p = n.s. for each group). In contrast, PEG-SOD and PEG-catalase blunted the inhibitory effect of cLDL on relaxations to acetylcholine (n = 5; p = 0.005) P209 without affecting the response of control vessels (n = 5; p = n.s.). PI3K/p110α inhibition differentially regulates cLDL induced the generation of superoxide anions in mouse vascular smooth muscle and endothelial cell aorta (3.02 ± 0.55 vs. 6.00 ± 1. 06 nmol/min/mg; n = 10; activation: implications for drug-eluting stent design p = 0.02 vs control). Conclusions: cLDL impairs endothelium-dependent relaxations E.W. Holy, F. O. Owala, G.G. Camici, H. Greutert, by stimulating the generation of superoxide resulting in a T.F. Lüscher, F. C. Tanner (Zürich, CH) decreased NO bioavailability. This observation may be important Objectives: To evaluate the impact of p110α inhibition on vascular for understanding the high cardiovascular event rates in smokers smooth muscle (VSMC) and endothelial cell (EC) activation. and patients with chronic renal failure. Background: Impaired reendothelialization and stent thrombosis remain safety concerns associated with the use of drug- eluting stents DES, despite a reduction in restenosis rates. P211 Phosphoinositide 3-kinase p110α (PI3K/p110α) controls crucial Recruitment of vascular repair cells via kinins cellular processes including proliferation and chemotaxis, thereby is impaired in coronary artery disease and diabetes representing an emerging drug target. However, its effect on vascular smooth muscle (VSMC) and endothelial cell (EC) K. Kuschnerus, N. Kränkel, M. Müller, S. Briand, T. Speer, activation remains unknown. C. Dörries, T.F. Lüscher, U. Landmesser (Zürich, CH) Methods: PI3K/p110α was inhibited by treatment with the small Background: In patients with coronary artery disease (CAD), molecule inhibitor PIK 75 or, alternatively, a specific siRNA. recruitment of circulating inflammatory cells from the blood to Proliferation and migration of VSMC and EC were assessed the vessel wall is enhanced, while recruitment of endothelial- by cell number and Boyden chamber, respectively. Endothelial repair promoting cells may be impaired. This disturbed balance senescence and dysfunction were evaluated by β-galactosidase is thought to promote the progression of atherosclerosis. Here assay, Western blots for expression of eNOS, TF, and PAI-1, and we assess the role of endothelial-derived kinins in selective organ chambers for isometric tension recording. recruitment of endothelial repair-promoting vs. pro-inflammatory Results: Inhibition of PI3K/p110α with PIK 75 or a specific siRNA cell types from patients with CAD, with or without type 2 diabetes selectively impaired proliferation and migration of VSMC while (T2D) and age-matched healthy controls (H) from the blood to the sparing EC completely. Treatment with PIK75 did not induce vessel wall. endothelial senescence nor inhibit eNOS expression or Methods and results: In H donors, B1 and B2 kinin receptors endothelium-dependent vascular relaxation. However, PIK 75 (B1R, B2R) were low expressed on CD14hi inflammatory inhibited both basal and TNF-α induced expression of TF and monocytes and high on Tie2+ angiogenic monocytes and KDR+ PAI-1. In contrast to PIK 75, both rapamycin and paclitaxel or CXCR4+ circulating progenitor cells (CPC). Consistently, the inhibited endothelial proliferation and migration; moreover they recruitment of healthy CXCR4+ CPC to human aortic endothelial induced expression of TF and PAI-1. cells (EC) in vitro and to the injured vessel wall in a carotid injury Conclusions: Inhibition of PI3K/p110α impairs proliferation mouse model was impaired when the B2R was inhibited by and migration of VSMC, but not EC. In addition to its potent icatibant, while no effect on CD14hi monocyte adhesion was antiproliferative and antimigratory effects on VSMC, targeting observed under B2R blockade. Closure of a scratch wound in an p110α inhibits the expression of prothrombotic mediators on EC. EC layer in vitro was accelerated by bradykinin (BK) stimulation Hence, PI3K/p110α inhibition may offer new options in DES during the adhesion phase of healthy PBMC and was blunted in design. the presence of B2R inhibitor. Endothelial recovery in a mouse carotid injury model was faster when wild type mouse bone marrow cells were injected, but reduced when the injected cells were obtained from B2R-deficient mice, independently of B2R expression on the recipient endothelium. B2R expression was significantly reduced on CXCR4+ CPC of CAD patients, and CAD CXCR4+ CPC adhesion to EC in vitro was less dependent on BK. No alterations in B1R or B2R expression or kinin-dependent

Cardiovascular Medicine 2011;14(5): Suppl 20 46 S postergruppe 1 – groupe de posters 1 α

adhesion were detected in CD14hi monocytes from CAD patients. the endogenous TF promotor. No homozygous alternatively Gap closure was less strongly accelerated by BK-mediated spliced TF pups were born from heterozygous alternatively adhesion in PBMC from nondiabetic CAD patients, and spliced TF mice.At embryonic day 9.5, however, a Mendelian completely blunted in CAD patients with T2D. distribution of genotypes was observed. Although it was highly Conclusion: Kinins facilitate the specific vascular recruitment of expressed in day 9.5 homozygous alternatively spliced TF endothelial-supportive leukocyte subtypes in healthy subjects, embryos, no pro-coagulant activity of alternatively spliced TF was while inflammatory cell types were recruited independently from detectable in a factor Xa generation assay. Histologically, on day kinins in our models. Reduced kinin receptor expression and kinin 8.5, vessels were filled with embryonic erythrocytes sensitivity of endothelial-supportive circulating cells might lead to and showed expression of α-smooth-muscle-actin (α-SMA) in their reduced recruitment in T2D and thereby underlie the decline wild-type as well as homozygous alternatively spliced TF of endothelial function and endothelial repair capacity, that likely embryos. On day 9.5, embryonic erythrocytes as well as α-SMA plays an important role for the atherosclerotic disease process. expression were reduced in vessels of alternatively spliced TF yolk sacs.At day 10.5, the alternatively spliced TF yolk sacs appeared pale and no intact blood vessels could be identified P212 both in an en-face preparation and histologically. These results CT-1 induces insulin resistance in cardiomyocytes indicate that alternatively spliced TF is not sufficient to allow proper embryonic development beyond day 9.5 and cannot M. Asrih, I. Papageorgiou, C. Montessuit (Genève, CH) rescue the vascular phenotype leading to embryonic death in Aims: Diabetes is a leading cause of mortality in western complete TF knock-out mice. Consistent with this observation, countries.This syndrome is mainly characterised by insulin the pro-coagulant activity of endogenously expressed resistance and high inflammatory state. Cardiotrophin-1 (CT-1), alternatively spliced TF cannot be detected. a member of Interleukine-6 (IL-6) family, is increased in the circulation of type II diabetic patients and contributes to inducing insulin resistance in adipocytes. However its effect on glucose metabolism in the heart remains unknown. Thus the aim of this work was to test whether CT-1 induces insulin resistance in cultured cardiomyocytes. Methods: Rat cardiomyocytes were cultured in presence or absence of 1nM CT-1.Thereafter glucose transport was measured in response to insulin or oligomycin, a mitochondrial ATP synthase inhibitor, used as a surrogate of metabolic stress. Intracellular signaling triggered by glucose transport stimuli was analyzed by Western-Blot. Results: Cardiomyocytes stimulated with increasing dose of insulin exhibited a dose response with a maximal response reached at 100nM of insulin. However, when treated with CT-1 the response of relative glucose transport was markedly reduced at all concentrations of insulin, indicating reduction in insulin responsiveness rather than in insulin sensitivity. CT-1 also P214 reduced oligomycin-stimulated glucose transport. Since Markers of plaque instability in the early diagnosis stimulation with insulin induces phosphorylation of the signaling of acute myocardial infarction intermediates Insulin Receptor (IR), Akt, and AS160, we have estimated their phosphorylation level by Western-Blot. T. Reichlin, N. Schaub, S. Steuer, R. Twerenbold, P. Haaf, Phosphorylation of IR, Akt on the residues Thr308 and Ser473, B. Drexler, J. Meissner, S. Osswald, C. Müller (Basel, Zürich, CH) and AS160 were lower in cardiotrophin-1 treated cardiomyocytes. Background: Plaque erosion and plaque rupture occur early To explain the mechanism of insulin resistance in cardiomyocytes in the pathophysiology of acute myocardial infarction (AMI). treated CT-1 we hypothesized a role for the pro-inflammatory Myeloperoxidase (MPO), Myeloid-related Protein 8/14 (MRP8/14) factor NFkB. In fact, phosphorylation of the pro-inflammatory and Pregnancy-associated plasma Protein-A (PAPP-A) have been factor was increased in cardiotrophin-1 treated cardiac myocytes proposed as markers of plaque instability. The aim of this study compare to untreated cardiomyocytes. was to investigate whether these markers of plaque instability Conclusion: Chronic exposure of cardiomyocytes to CT-1 leads might be useful in the early diagnosis of AMI. to a loss in the flexibility of myocardial glucose metabolism, by Methods: In a multicenter study MPO, MRP8/14, PAPP-A and mechanisms that remain to be investigated. Thus, increased level cardiac troponin T (cTnT) were measured in systemic circulation of CT-1 in diabetic patient could contribute to the development in 662 unselected patients presenting to the emergency of myocardial insulin resistance. department (ED) with chest pain. Final diagnoses were adjudicated by two independent cardiologists. Results: AMI was the final diagnosis in 18% of patients. Levels P213 of the three markers were significantly higher in patients with AMI compared to those with other causes of chest pain (median [IQR] Murine alternatively spliced tissue factor is not MPO 141 [95-315) vs. 105 [74–173] pmol/l, p <0.001; MRP8/ sufficient for embryonic development and does 14 4.3 [3.0–6.7] vs. 3.6 [2.6–5.0] mg/l, p = 0.009; PAPP-A 4.6 not trigger coagulation [4.0–9.2] vs. 4 [4–5.6] mIU/L, p <0.001). There was however a S.H.M. Sluka, A. Akhmedov, J. Vogel, T.F. Lüscher, substantial overlap between levels in AMI and non-AMI patients F. C. Tanner (Zürich, CH) and accordingly, the diagnostic performance of the markers as Tissue factor (TF) triggers blood coagulation and is crucially involved in embryonic development. It exists in two differentially spliced isoforms: the membrane bound full-length form and the more recently discovered soluble alternatively spliced form. Complete knock-out of TF causes embryonic lethality in mice due to defects in vessel development. The role of alternatively spliced TF in development is not known and its role in coagulation is still debated. Recently, however, a role of alternatively spliced TF in angiogenesis was described. It has not been examined yet whether alternatively spliced TF contributes to blood vessel formation in development and whether it has coagulant activity in a physiological setting.We generated an alternatively spliced TF knock-in mouse model replacing the endogenous TF gene by the alternatively spliced TF cDNA. This mouse lacks full length TF and instead expresses alternatively spliced TF under control of

Cardiovascular Medicine 2011;14(5): Suppl 20 47 S postergruppe 1 – groupe de posters 1 pathophysiology / Molecular Biology

assessed by the area under the receiver-operating curve to detect P216 AMI was poor (AUC MPO 0.62, MRP8/14 0.64, PAPP-A 0.62) and CB1 cannabinoid receptor antagonism inhibits significantly inferior compared to cTnT (AUC 0.85). None of the balloon-induced neointima formation in markers of plaque instability was able to improve the diagnostic atherosclerosis-prone mice accuracy provided by cTnT alone if the markers were combined (p >0.05 for all markers). F. Molica, F. Burger, C.Matter, S. Lenglet, G. Pelli, A. Zimmer, Conclusion: Markers of plaque instability measured in systemic P. Pacher, S. Steffens (Genève, Zürich, CH; Bonn, DE; circulation are slightly elevated in AMI patients, but do not seem Bethesda, US) helpful in the early diagnosis of AMI. Balloon-induced arterial injury stimulates vascular smooth muscle cell proliferation and inflammatory cell recruitment, which may result in restenosis of the diseased vessel. Increasing evidence suggests an increase of endocannabinoid levels in different pathological processes, leading to enhanced activation of their corresponding cannabinoid receptors, CB1 and CB2. The protective effects of CB1 receptor antagonism in atherosclerotic mice and in vitro inhibition of vascular smooth muscle cell proliferation and migration point to a potential interest of CB1 receptor blockade in restenosis.The objective of this study was to investigate the therapeutic benefit of the selective CB1 receptor antagonist AM281 in balloon-induced neointima formation. We performed left common carotid balloon distension injury in weight-matched (25–30 g) male apolipoprotein E-deficient (ApoE-/-) mice fed on high cholesterol (1.25%) diet for 8 weeks before the intervention. Littermates were randomly assigned to receive daily intraperitoneal injection of either the synthetic CB1 antagonist AM281 (10 mg/kg) or vehicle control (n = 6 per group), with the first injection given 30 minutes before balloon injury. After 7 days, we found significantly reduced numbers of medial nuclei (vehicle: 141. 1 ± 14.57; AM281: 86.44 ± 19.35; p = 0.0239) and intimal nuclei compared to vehicle treatment (vehicle: 44.94 ± 5.933; AM281: 29.94 ± 5.815; p = 0.0506) in injured vessels of AM281-treated mice, indicating reduced medial smooth muscle cells proliferation. Immunohistochemical analysis revealed significantly reduced staining for CD68-positive macrophages (vehicle: 3836 ± 1887; AM281: 987.3 ± 486.1; p = 0.0206) within dilated arteries of AM281-treated mice. Our data indicate a critical P215 role of CB1 receptors in neointima formation in response to acute The role for lipid rafts in T-cadherin interaction arterial injury. The putative effects of CB1 receptor inhibition on with hormone receptors in endothelial cells endothelium regeneration after injury remain to be investigated. K. Maslova, M. Philippova, M. Joshi, E. Kyriakakis, D. Pfaff, P. Erne, T. Resink (Basel, CH) P217 Introduction: T- cadherin (T-cad) is highly expressed in vascular Gender-specific long-term outcomes after endothelial cells (EC). Our recent findings show that T- cad drug-eluting versus bare-metal stent implantation overexpression in EC attenuates responsiveness to insulin via in large coronary arteries chronic activation of Akt and ensuing degradation of insulin- receptor substrate-1 (IRS-1). This study investigates the role A. Hvelplund, A. Süssenbacher, F. Nietlispach, B. Naegeli, for lipid rafts in T- cad interactions with insulin receptor (IR). G.B. Pedrazzini, B. Hornig, F. R. Eberli, H. Alber, S. Galatius, Methods: Human microvascular EC line HMEC-1 were stably C. Kaiser, M. Pfisterer for the BASKET-PROVE-Investigators transduced with respect to T- cad overexpression (T-cad+) or Background: Data on outcomes of women versus men after DES silencing (shT). Empty lentiviral vector or vector expressing implantation are controversial, partly because women differ from random shRNA was used as respective controls.Akt men with regard to disease presentation, higher age and smaller phosphorylation and IRS-1 levels in insulin (100 nM)-treated cells coronary artery size. were measured by immunoblotting. Filipin (3 µg/ml) was used to Methods: To address these uncertainties in a large prospective disrupt lipid raft/caveolae domains of the plasma membrane. Lipid trial with few exclusions where all patients were treated for large rafts were gradient-fractionated and distribution of proteins (T-cad, (≥3.0) vessels only, an a priori planned gender-specific analysis insulin receptor and caveolin-1) analysed by immunoblotting. was performed of BASKET-PROVE data. All 2314 patients T- cad/IR interactions were studied using co-precipitation randomized 2:1 to DES vs BMS were followed with a primary techniques. endpoint of 2-year major adverse cardiac events (MACE: cardiac Results: T- cad overexpression and silencing in EC attenuated death, infarction, target-vessel revascularization). A Cox- and amplified, respectively, both insulin-induced Akt proportional-hazard model was used to evaluate the relative phosphorylation and IRS-1 degradation. Filipin-pretreatment risk for women and men, respectively. of EC prevented modulatory effects of T- cad+/shT on insulin Results: The 565 (25%) women were older, more frequently signaling and normalized IRS-1 levels in T- cad+ or shT cells to hypertensive, non-smokers, witha history of heart failure, but less those in control EC. Both T- cad and IR are present in caveolin-rich frequently with a history of coronary disease and presented more fractions of the cell membranes. Co-precipitation experiments often with multivessel disease. No differences in randomization demonstrated interaction of T- cad with insulin receptor in EC. appeared: BMS were used in 31.7% women and 33.5% men Conclusions: The ability of T- cad to modulate insulin signaling in (p = 0.42). The overall 2-year rate of MACE was the same in EC depends on localization and physical interaction of T- cad and women (7.6%) as in men (7.6%) (p = 0.99) but women had a IR within lipid raft domains of the plasma membrane.These data greater benefit with DES compared to BMS: hazard rates of shed light on mechanisms whereby might T- cad contribute to 3.6 (2.0–6.6) vs 1. 7 (1.2–3.3) for men (p = 0.038 for interaction, progression of vascular insulin resistance in cardiovascular and significant by uni- and mulitvariably adjusted analyses). MACE metabolic diseases. rates were reduced in women from 15% (BMS) to 4% (DES) (p <0.0001) and in men from 10% to 6% (p = 0.003), respectively. Similarly, cardiac death/infarction rates were reduced by DES in women from 5.0% to 2.9% (p = 0.19) and in men from 4.6% to 2.8% (p <0.0001) and target-vessel revascularisation rates from 10.6% to 2.3% (p <0.0001) in women and from 7. 5% to 4.1% (p = 0.003) in men, respectively.

Cardiovascular Medicine 2011;14(5): Suppl 20 48 S postergruppe 1 – groupe de posters 1 pathophysiology / Molecular Biology

Conclusions: Women presented with a markedly different chronic activation of PI3-kinase/Akt signaling axis by T- cad baseline risk but had the same overall 2-year MACE rate as men. causes degradation of insulin receptor substrate IRS-1, which Compared to BMS, DES reduced the MACE rate more in women promotes a negative feedback loop in insulin signaling and than in men in need of large vessel stenting. renders a state of insulin insensitivity. In vivo, stress-induced upregulation of T- cad in the vascular endothelium (i.e. conditions of endothelial dysfunction) may restrict endothelial P218 responsiveness to insulin thereby causing vascular insulin Signal pathway cross-talk mediated by T-cadherin resistance. underlies vascular endothelial dysfunction in metabolic disease P220 M. Joshi, M. Phillippova, K. Maslova, D. Pfaff, E. Kyriyakakis, Characterization, differentiation and 3d formation P. Erne, T. Resink (Basel, Luzern, CH) of human mesenchymal stem cells for cardiovascular Introduction: T- cadherin (T-cad) is upregulated in atherosclerosis applications and in association with endothelial dysfunction. Genome-wide association studies suggest a role for T- cad also in progression of M.Y. Emmert, P. Wolint, B. Weber, C. Brokopp, L. Baumgartner, hypertension, which is associated with endothelial dysfunction, J. Grünenfelder, V. Falk, S.P. Hoerstrup (Zürich, CH) insulin resistance and increased risk of atherosclerosis.The PI3K/ Purpose: Mesenchymal stromal cells (MSCs) may be an ideal Akt/mTOR signalling axis is commonly used by insulin and T- cad cell source in treating heart disease. Here we establish clinical in endothelial cells (EC). Therefore we investigate the hypothesis relevant harvesting techniques, characterization, differentiation that T- cad constitutes a regulatory component of insulin signaling and expansion protocols in addition to 3D formation approaches pathways in EC. to make these cells ready for the clinical use. Methods: Human microvascular endothelial cells (HMEC-1) Methods and results: In our lab, we have established routine were stably transduced with respect to overexpression (T-cad sternal bone marrow puncture (n = 60) before cardiac surgery ± HMEC-1) or silencing of T- cad (shT-HMEC-1). HMEC-1 or hip puncture during trauma surgery to harvest human MSCs transduced with empty vector (E) or vector carrying non-target (n = 5). Bone marrow puncture can be safely performed and up to shRNA (shC) served as the respective controls. Cultures were 80 ml of human BM can be obtained per puncture. After harvest, treated with insulin (100 nM) for up to 30 mins and whole cell BM mononuclear cells are separated with the Ficoll gradient for lysates analyzed by immunoblotting for T- cad dependent effects further processing. Next, the cells are plated and only the on effector molecules of the insulin signalling cascade. adherent cells were taken for further analysis. (1. Quality criteria). Results: T- cad ± HMEC-1 exhibited blunted responsiveness Next, FACS analysis was performed (2. Quality criteria) and the to insulin, evidenced by decreased phosphorylation of IRS- cells were characterized for a typical MSC surface marker profile 1ser636/639, Aktser473, Aktthr308, mTORser2448 and including CD44+, CD90+, CD105+, CD106+, CD146+, GD2+, S6rpser240/244. The converse was true for shT-HMEC-1. CD31-, CD34-, CD45- and others (2. Quality Criteria). Finally, Constitutive levels of total IRS-1 were reduced in T- cad ± differentiation assays into all three lineages, including adipoietic, HMEC-1 but increased in shT-HMEC-1. In the presence of protein chondrogenic and osteogenic were performed for each sample (3. translation inhibitor, cycloheximide (5 µg/ml), T- cad ± HMEC-1 Quality criteria). After initial harvest and isolation of human MSCs, exhibited a more rapid degradation of IRS-1. In the presence of expansion of cells up to cell therapy relevant numbers (100 Mio either PI3K inhibitor LY 294002 (20 µM) or mTOR inhibitor cells) was possible up over a period of 8 weeks. Using modified rapamycin (10 nM) the level of total IRS-1 in T- cad ± HMEC-1 protocols of the hanging-drop culture method, human MSC was normalized to that in E-HMEC-1. derived 3D microtissues were successfully created with either Conclusion: T- cad upregulation in EC might contribute to 1500, 2500, 5000 or 10000 cells.After 48h hours the MTs display development of vascular insulin resistance by promoting a homogenous micro-architecture, were ready for further degradation of IRS-1 and thereby suppression of insulin signal processing such as catheter based injection into the heart. transduction via the PI3K/Akt/mTOR axis. Conclusion: Our data provide effective harvesting strategies and detailed characterization of human MSCs including quality criteria. Next, we demonstrate feasibility of MSC expansion to a P219 clinical relevant number. In addition, 3D microtissues represent a T-cadherin-dependent signaling in endothelial novel promising application format for cell therapy in terms of cell cells: A bridge between endothelial dysfunction, engraftment and survival after cell transplantation. angiogenesis and metabolic disease? M. Philippova, M.Joshi, E. Kyriakakis, K. Maslova, D. Pfaff, P221 P. Erne, T.Resink (Basel, Luzern, CH) T-cadherin modulates the angiogenic and Introduction: T- cadherin (T-cad), a GPI-anchored member of the lymphangiogenic potential of cutaneous squamous cadherin family, is widely expressed in the cardiovascular system. cell carcinomas Experimental, clinical and genomic studies suggest a role for T- cad in vascular disorders such as atherosclerosis, hypertension D. Pfaff (Basel, CH) and tumor angiogenesis. Insulin, a hormone that controls glucose Introduction: Important proangiogenic properties for metabolism, induces angiogenesis and NO-dependent EC-expressed T- cadherin (T-cad) have been identified. vasorelaxation via the PI3-kinase/Akt pathway.This axis is also Immunohistochemical and genomic studies also support a role, activated by T- cad in EC, raising the possibility that T- cad might albeit controversial, for T- cad in tumor cell biology.We explore modulate EC responses to insulin. consequences of altered T- cad expression on tumor cell Methods: Microvascular endothelial cell (EC) line HMEC-1 was behaviour and interactions with EC. transduced with lentiviral vectors expressing T- cad gene, T- cad Methods: Lentiviral vectors were generated to overexpress shRNA or respective control vectors. Insulin-induced angiogenic (T-cad+) and to silence (shT) T- cad protein in squamous cell sprouting and EC nitric oxide synthase (eNOS) activation carcinoma (SCC) cell line A431. Functional consequences were were analysed using EC-spheroid assay and immunoblotting, investigated in vitro using 3D-spheroid cultures and in vivo using respectively. a murine xenograft model. Results: T- cad overexpression in EC per se stimulated sprout Results: Paradoxically xenografts composed of either T- cad+ outgrowth from EC-spheroids. Insulin dose-dependently or shT A431 grew more rapidly than those composed of control enhanced activation of angiogenesis in spheroids of control vector transduced A431. shT A431 exhibited increased vector-transduced EC. However, in T- cad overexpressing or proliferation potential in vitro and in vivo. T- cad+ xenografts silencing EC-spheroids, angiogenic sprout outgrowth responses showed increased lymphangiogenic and angiogenic to insulin were respectively attenuated or enhanced. Similarly, microvascular density. This was due to the enhanced angiogenic T- cad overexpression or silencing respectively attenuated or potential of T- cad+ A431 as evidenced by their elevated VEGF enhanced insulin-induced activation of eNOS. expression (qPCR) in vitro and in vivo and by blockade of Conclusions: T- cad attenuates insulin-induced angiogenesis and angiogenesis in vitro with function blocking anti-VEGF antibodies. eNOS activation. These data match our recent findings that Metastatic potential was examined using an in vitro coculture

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model comprising suspensions of GFP-labelled A431 above uniform monolayers of vascular or lymphatic EC. shT A431 exhibited more efficient attachment to and transmigration across the EC monolayer. Studies on metastatic potential in vivo are ongoing. Conclusion: Expression levels of T- cad on SCC can markedly affect their proliferative and metastatic potentials (i.e. enhanced by downregulation) and their ability to recruit blood and lymph vessels (i.e. enhanced by upregulation). Our data may explain literature contradictions regarding expression levels of T- cad in different tumors in vivo.

P222 Vascular aging is exacerbated in the cerebral circulation as compared to the systemic one: implications for cerebrovascular disease Y. Shi, S. Keller, F. C. Tanner, T.F. Lüscher, G.G. Camici (Zürich, CH) Background: The progressively growing portion of aged people in western societies is a major healthcare challenge since aging per se is an independent risk factor for cerebrovascular disease. Some progresses were made in studying age-dependent vascular dysfunction of the peripheral circulation however, little is known concerning cerebral arteries.The present study was designed to assess age-induced vascular dysfunction of the basilar artery versus femoral artery in young 12-weeks (12W), middle aged 6-Months (6M) and old 2-years old (2Y) mice. Methods: Rings, mounted in myograph for isometric tension recording, were contracted with U46619 and exposed to increasing concentrations of acetylcholine. Endothelium- independent relaxations were studied with sodium nitroprusside (SNP). Results: In 12W mice, acetylcholine-induced relaxations in both femoral and basilar arteries were completely reversed by Methods: Ten uncoated NS and 6 TiNOX-coated NS (5–6 mm) L-NAME, an inhibitor of nitric oxide synthase, confirming the were implanted randomly in the iliofemoral artery of 6 mini-pigs. crucial role of nitric oxide (NO) as a vasoactive factor. In the After implantation, quantitative angiography (QA) was carried out femoral artery, acetylcholine-induced relaxations were impaired for calculation of artery and minimal luminal diameter. Follow-up by aging (12W vs. 6M vs. 2Y Emax% 71.41 ± 8.35, 63.15 ± 7. 27, was performed by QA and histomorphometry after 5 months. 43.72 ± 4.02). L-NAME reversed acetylcholine-induced-relaxation Results: No stent migration, no stent fracture and no thrombus in the young and middle-aged group, but not in the aged group, formation were observed. All stents were patent at follow-up. suggesting that NO-mediated-relaxation is impaired with aging. Based on the location of the stent (iliac/iliofemoral) and the More importantly this indicates that another endothelial derived stent-to-artery-ratio, stent segments (SS) were divided into relaxing factor (other than NO) compensates the blunted normally sized (stent-to-artery-ratio <1.4, n = 12) and oversized relaxation in femoral artery of aged mice. In addition, in middle- (stent-to-artery-ratio ≥1.4, n = 9), as recently proposed. All age and aged group SNP-induced dose response curves were SS expanded to their near nominal diameter during follow-up. shifted to the left, suggesting a hyperresponsiveness by smooth Normally sized SS increased their diameter by 6% and oversized muscles cells. In the basilar artery, acetylcholine-induced SS by 29%. A significant correlation between oversizing and relaxation was reduced in the middle-age group (12W vs. 6M angiographic respectively histomorphometric restenosis was Emax% 47.78 ± 4.43, 32.63 ± 2.97) and was partially reversed by observed. Restenosis rates were similar for uncoated NS and L-NAME suggesting that NO-mediated response is also impaired TiNOX-coated NS. in basilar artery. Unexpectedly, acetylcholine induced a Conclusions: TiNOX-coated NS are as safe and effective as paradoxical contraction in basilar artery of 2Y mice indicating a uncoated NS in the porcine iliofemoral artery.All stents further severe endothelial dysfunction which was not observed in the expand to near their nominal diameter during follow-up. femoral arteries of the same mice. In basilar artery dose- Oversizing is linearly and positively correlated with neointimal response-curves to SNP were comparable in the three differently proliferation and restenosis, which may not be reduced by aged groups. TiNOX-coating. Conclusion: Vascular endothelial functions are reduced with aging.And this process is exacerbated in cerebral arteries as compared to systemic ones. Future studies will be aimed at P224 elucidating the molecular mechanisms underlying the observed Myocardial velocities and 2d-strain in healthy effect. children before and immediately after a childhood Triathlon P. Schön, K. Petzuch, A. Kühn, C. Röhlig, J. Elmenhorst, P223 M. Schönfelder, R. Oberhoffer, J. Hess, M. Vogt (München, DE) Oversizing and restenosis with self-expandable Introduction or basis or objectives: There are many reports stents in iliofemoral arteries dealing with adults who practice endurance training. Knebel et. al. A.M. Saguner, T. Traupe, N. Hess, L. Raeber, N. Diehm, described 28 older (60–72 years) and 50 younger (22–59 years) O. Hess (Bern, CH) amateur athletes who participated in the Berlin Marathon. They found right ventricular functional changes as a sign of prolonged Aim: Uncoated self-expandable nitinol stents (NS) are commonly myocardial work load. The left ventricular systolic function was oversized in peripheral arteries.Yet, oversizing of NS may be preserved and there were no significant difference between older associated with increased restenosis.To provide further evidence, and young runners. However, few is known about the impact of NS were implanted in porcine iliofemoral arteries with a stent-to- endurance training on cardiac function in healthy children, and artery-ratio between 1. 0 and 2.3. Besides conventional uncoated the effects of sport competitions in children’s age.Aim of this NS, a novel self-expandable NS with an antiproliferative Titanium- study was to describe possible effects fo endurance competition nitride-oxide (TiNOX) coating was tested for safety and efficacy on cardiac function in children after the Munich children triathlon and in order to reduce restenosis. 2009.

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Methods: Colour tissue Doppler imaging and 2-dimensional function under stress is characterised by a decrease of E and E’ speckle tracking (S and E´ waves, indicative of systolic and velocity and an increase of A-velocity, resulting in an E/A inversion diastolic function, respectively), stroke volume and mitral peak which was consistent in all three doppler modalities. Data from inflow velocity (E wave) were recorded before and after the adults under stress show conflicting results: E and A increase triathlon competition in 24 boys and girls 8 to 16 years of age. under stress and E/E’ remains unchanged. Results: Our results indicate that after endurance stress children Conclusions: Endurance training seems to have a considerable have more pronounced changes of diastolic than of systolic heart effect on the ventricular function in children. For lack of function. They increase their cardiac output mainly by an increase comparable standard values in this group of age more data are in heart rate rather than in stroke volume.Velocity time integral required to asses the changes mentioned before. and global systolic 2-d strain were slightly reduced. The diastolic

postergruppe 2 – groupe de posters 2 rhythMology and paceMaKers

P225 P226 Occlusion of the right coronary artery during RFA Novel electroanatomic mapping tools (CARTO 3) at the cavotricuspid isthmus reduce procedure and fluoroscopy times during radiofrequency catheter ablation of atrial fibrillation C. Scharf, L. Dang, C.H. Attenhofer Jost, P. Levis (Zürich, CH) Case report: A 61 year old male patient without structural heart M. Kühne, Y. Suter, T. Reichlin, B. Schaer, P. Ammann, disease and normal stress test underwent pulmonary vein S. Osswald, C. Sticherling (Basel, St. Gallen, CH) isolation for paroxysmal atrial fibrillation under general Introduction: CARTO 3 (Biosense Webster, Diamond Bar, CA) anesthesia. During the intervention the patient was has emerged as a novel mapping tool permitting fast acquisition anticoagulated with iv heparin with an activated clotting time of anatomical information and accurate visualization of multiple (ACT) between 250 and 300 seconds. Because episodes of catheters during pulmonary vein isolation (PVI) of atrial fibrillation typical flutter were also observed, a cavotricuspid isthmus (AF). ablation in the right atrium was performed after the left atrial Methods: During the transition period from CARTO XP (XP) to procedure. During the ablation with a 3.5 mm irrigated tip CARTO 3 (C3), the last 25 patients in whom XP was used were electrode (EZ Steer Thermocool, Biosense Webster) with a compared to the first 25 patients in whom C3 was used during maximum of 35 Watts a tissue pop was audible.After interruption ablation of paroxysmal AF. Fast anatomical mapping (FAM) was of the radiofrequency delivery an ST elevation was noted in the used in all patients in the C3 group to create the three- inferior leads of the surface ECG (1). A coronary angiogram dimensional reconstruction of the left atrium. Radiofrequency (RF) showed a subtotal occlusion of the right coronary artery (RCA, energy delivery was performed using a bidirectional 3.5 mm-tip 2) with minor distal embolization, but normal left coronaries. open-irrigation RF ablation catheter (Thermocool, Biosense Balloon angioplasty with subsequent implantation of a drug Webster). The procedural endpoint was PVI confirmed by a eluting stent (Xience 2.9 x 18 mm) was performed. The location circumferential mapping catheter. of the ablation catheter during the tissue pop was found to be Results: Fifty consecutive patients (age 58 ± 9 years, ejection in very near proximity of the culprit lesion (3, 4). Immediate fraction 0.59 ± 0.05, left atrial size 41 ± 4 mm) with paroxysmal normalization of the ECG without rise of cardiac enzymes AF undergoing PVI using an electroanatomic mapping system were noted during an uneventful course of the hospitalisation. (CARTO XP or CARTO 3) were included. The mean procedure Conclusion: Occlusion of the right coronary artery is a rare time was 195 ± 49 min. in the XP group compared to 168 ± 37 complication of cavotricuspid isthmus ablation (4 cases published min. in the C3 group (p <0.05). The mean fluoroscopy time was up-to-date) despite the proximity of the RCA. Especially in 37 ± 17 in the XP group compared to 24 ± 11 in the C3 group patients under sedation or anesthesia immediate recognition of (p <0.05). The mean duration needed for creation of the ischemic changes in ECG and reopening of RCA is manadory to electroanatomical map in the XP group (with a mean of 62 ± 25 prevent myocardial damage. sampled points) was 21 ± 8 min. compared to 9 ± 4 min. for the FAM in the C3 group (p <0.01). The procedural endpoint of PVI was reached in all patients. Conclusion: Advances in electroanatomic mapping systems reduce procedure and fluoroscopy duration during PVI. Faster acquisition of the map, enhanced anatomical accuracy and visualization of multiple catheters (including all electrodes) with C3 may be the key factors.

P227 Predictors of bleeding complications after pulmonary vein isolation for atrial fibrillation F. Voss, M. Kühne, B. Schaer, S. Osswald, C. Sticherling (Basel, CH) Background: Patients with atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI) require effective anticoagulation to prevent thrombembolic complications. It is common practice to discontinue phenprocoumon and use low-molecular-weight heparin (LMWH) or heparin to bridge anticoagulation. The optimal management of anticoagulation is still unknown. Aim of this analysis was to identify predictors for post-procedural bleeding complications. Methods: We performed a retrospective analysis on 246 consecutive PVI at our center with regards to the periprocedural incidence of bleeding. Minor bleeding was defined as hematoma that did not require intervention and major bleeding was defined as hematoma that required an intervention or blood transfusion. In a multivariate regression analysis the following risk factors were

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analysed: Age, gender, CHADS2-Score, paroxysmal or persistent of QRS complex (p = 0.13) or the underlying cardiac disease AF, use of radiofrequency energy or cryoenergy, oral (p = 0.23). LV ejection fraction (LVEF) was severely depressed at anticoagulation, LMWH, aspirine and INR >2 at intervention. baseline (LVEF all pts 24 ± 8%, LVEF responders 24 ± 9%, Results: 183 consecutive patients (mean age 56y ± 10, male LVEF non-responders 25 ± 8%). Mean LVEF showed a significant 77%, paroxysmal AF 75%) underwent a total of 246 PVI- increase after CRT implantation in both groups (mean LVEF procedures using radiofrequency energy in 225 patients (91%) 33 ± 12% all pts, mean LVEF improvement 8 ± 15%). or cryoenergy in 21 patients (9%). Before the intervention, 192 Echocardiographic analysis revealed a significant reduction of patients (78%) were on phenprocoumon, 26 patients (11%) were LV endsystolic (median pre 59 mm vs post 49 mm, p <0.001) on aspirin, 3 patients (1.2%) were on phenprocoumon and aspirin, and enddiastolic (median pre 67 mm vs post 61 mm, p = 0.004) and 21 patients (8.5%) had no anticoagulation or antiplatelet diameter in the responder group while non-responders showed therapy. The INR was ≥2 in 67 (27%) patients at the day of the no significant reduction in LV size. procedure. There was one thromboembolic complication and 22 Conclusions: In our multicenter study VV-delay during intrinsic (9%) periprocedural bleeding complications.Three patients (1%) conduction and calculation of a ratio between intrinsic QRS suffered from a major bleeding complication that occurred early duration and intraoperative VV-delay did not predict response after intervention. All bleeding complications were groin problems. to CRT. In multivariate analysis, the use of aspirin was the only independent risk predictor for all bleedings (p = 0.012; OR 3.54 [CI 1. 31–9.53]), as well as for major bleedings (p = <0.001; P229 OR 31 [CI 1. 39–688]). The use of LMWH in patient with an Cardioversion of atrial fibrillation during ICD INR <2 was not associated with an increased risk for bleedings. implantation Conclusion: The incidence of major groin bleedings requiring on intervention in an unselected population undergoing PVI is 1%. M. Mutschelknauss, B. Schär, S. Osswald, M. Kühne, Particular care should be taken in patients receiving antiplatelet C. Sticherling (Basel, CH) therapy. It may be advisable to start oral anticoagulation and Aims: Restoration of sinus rhythm (SR) during ICD testing in discontinue antiplatelet therapy 2 weeks prior to the intervention. patients (pts) with atrial fibrillation (AF) may be beneficial but carries the potential risk of thrombembolic complications if the pts are not therapeutically anticoagulated. We aimed to analyze P228 short- and long-term efficacy and safety of concomitant Intraoperative VV-delay does not predict response conversion of AF at defibrillation threshold testing (DFT) during to cardiac resynchronization therapy ICD implantation. Methods: All pts from a prospective database referred for ICD M. Mutschelknauss, P. Ammann, B. Naegeli, D. Altmann, implantation between 02/2002 and 03/2010 were analyzed. DFT T. Reichlin, M. Kühne, B. Schär, S. Osswald, C. Hottkowitz, with an abbreviated protocol consisting of at least two ICD shocks C. Sticherling (Basel, St. Gallen, Zürich, CH) was performed. Oral anticoagulation (OAC) was interrupted at Background: A third of patients (pts) treated with cardiac least two days prior to ICD implantation. Success of cardioversion resynchronization therapy (CRT) are non-responders. To date, was defined as SR on surface ECG or intracardiac atrial no hemodynamic, clinical or echocardiographic predictors reliably electrogram (EGM) during postoperative ICD interrogation. identify non-responders. Aim of this multicenter study was to Follow-up visits including device interrogation were performed evaluate whether the intraoperative electrical interventricular at 1, 3, 6 months after ICD implantation and every six months delay (VV-delay) measured between the right ventricular (RV) thereafter. Any documented episode of AF lasting ≥30 seconds and left ventricular (LV) lead tip during intrinsic rhythm can predict was considered as AF recurrence. response to CRT. Results: During the study period (02/2002–03/2010) 555 pts Methods: Retrospective analysis of CRT database at three received an ICD at our institution. At time of implant 76/555 pts tertiary cardiac centres in Switzerland. VV-delay was measured at (14%) were in AF. Sixteen pts had to be excluded because of implant from the electrical delay of the local EGM between the tip insufficient ECG documentation. Thus, the study population of the RV and LV lead during intrinsic rhythm. A ratio (VV/QRS) consisted of 60 pts (53 male, mean age 67.7 ± 9.0 y). Median between VV-delay (ms) and intrinsic QRS duration (ms) was CHA2DS2-VASC score was 3 (IQR 3-4) and 55/60 pts (92%) calculated. Primary study endpoint was clinical improvement received oral anticoagulation with a mean INR of 1. 8 ± 0.6 at of at least one NYHA class; secondary endpoints were implant. In 37/60 pts (62 %) INR was <2.0 at implant. DFT echocardiographic parameters of LV dimension/function. during ICD implantation converted AF into SR in 48/60 pts (80%). Results: 146 CRT pts (105 male, mean age 66 ± 11 y) were Mean shock energy was 21 ± 6 Joules.Three months after analysed. 90/146 pts (62%) improved significantly teaf r CRT cardioversion 28/60 pts (47%) were in SR while 11/60 pts (18%) implantation while 56 pts (38%) remained clinically non- remained free from AF/atrial flutter recurrence after one year of responders. Amongst the responders 61/90 pts (68 %) improved FU. Success rate at 12 months showed no significant difference by one NYHA functional class while 29/90 pts (32%) improved between CRT (27/60 pts) and VVI/DDD (33/60 pts) recipients > one NYHA class. Responders (intrinsic QRS pre 159 ± 34 ms, (p = 0.37) and pts with (20/60 pts) and without amiodarone delta QRS pre/post 30 ± 26 ms) as well as non-responders therapy (p = 0.17). During a mean FU of 27 ± 25 months two pts (intrinsic QRS pre 165 ± 31 ms, delta QRS pre/post 31 ± 21 ms) suffered from transient ischemic attack within one month after ICD showed a significant narrowing of mean QRS duration (p = 0.14). implantation (7 and 12 d post-implant). INR in these two patients VV-delay displayed no significant difference between responders were 1. 4 and 3.2 at implantation. None of the 16 excluded pts and non-responders (p = 0.33). Mean VV/QRS ratio showed no showed symptoms of neurologic impairment during FU. significant correlation to clinical response (p = 0.95), narrowing Conclusion: The rate of concomitant AF cardioversion during DFT testing is 80%. Since only 18% remain in SR after one year and 3.3% of the pts experienced a thrombembolic complication continuation of meticulous OAC is paramount.

P230 Facilitation of AF by intermittent pacing mimicking pulmonary vein tachycardia is mediated by a shortening of ERP and shift of protective intermittent atrial capture towards higher pacing rates J. Tenkorang, F. Jousset, P. Ruchat, J. Vesin, P. Pascale, M. Fromer, S. Schaefer, S. Narayan, E. Pruvot (Lausanne, CH; San Diego, US) Introduction: We observed in humans and in an ovine model of pacing-induced atrial tachycardia (PIAT) that rapid atrial capture, repolarization alternans and atrial fibrillation (AF) were prevented

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by intermittent 2:1 capture mediated by decreased excitability. We ± 0.3 vs 0.7 ± 0.2 m/s, p <0.05). For all pts, LAA velocity was not hypothesize that long-term intermittent PIAT mimicking pulmonary correlated to the mean Va, but was weakly negatively correlated vein (PV) tachycardia promotes rapid atrial capture and AF to the LA volume (n = 82, R-squared = 0.1, p <0.05). Interestingly, beyond the baseline (BL) effective refractory period (ERP). LAA velocity showed a weak negative correlation with LA volume Methods: An ovine model of PIAT was developed using two in pts in AF (R-squared = 0.2, p = 0.03) but not in pts in SR (p = pacemakers (PM) with right atrial leads. One PM was used to NS). Exclusion of the CARTO-3 subgroup did not alter the results record broadband unipolar EGMs, and the other to deliver PIAT even though LA volume is known to be overestimated with FAM at decremental pacing CLs (400 beats, PCL 400–110 ms, 10 ms (no respiratory compensation). steps) and long term intermittent PIAT to promote atrial Conclusions: Bipolar voltages of the LAA cannot be used to remodelling (5s burst, 2s sinus rhythm) until sustained AF.The predict its contractility. Caution should be used regarding % of cumulative 2:1 capture and AF at each PCL between ERP interruption of anticoagulation after sinus rhythm restoration by and ERP+40ms were compared at BL, during (DR) and after CA in those with longstanding AF and dilated LA, as an increased remodelling (AR, before sustained AF). volume predicts poor LAA contractility. Results: Intermittent PIAT induced sustained AF after 3.8 ± 1. 6 weeks (n = 8 sheep). ERP of DR (125 ± 12 ms) and AR (116 ± 9 ms) decreased significantly compared to BL (140 ± 31 ms, p <0.05). The PCL range of 2:1 capture shifted progressively during DR and AR towards shorter values and paralleled the drop in ERP (fig.). PIAT induced no AF atwe BL.Ho ver, AF appeared during DR and AR and made up 15% and 16% of the burst pacing time respectively. The PCL range above ERP that triggered AF progressively increased from 20 ms during DR to 40 ms during AR. Conclusions: The facilitation of AF by intermittent PIAT mimicking salvos from PVs is heralded by a significant shortening of ERP and a progressive shift of protective 2:1 capture towards shorter PCLs as compared to BL.

P232 Influence of additional atrial lesions on arrhythmia termination following pulmonary vein – Linear ablation in a model of persistent atrial fibrillation L. Uldry, A. Forclaz, N. Virag, M. Hocini, J.-M. Vesin, P. Jais, L. Kappenberger, M. Haissaguerre (Lausanne, Tolochenaz, CH; Bordeaux, FR) Introduction: Ablation of persistent atrial fibrillation (PsAF) sequentially targets atrial structures contributing to AF maintenance until termination to sinus rhythm or atrial tachycardia. This model-based study investigated the influence of additional atrial lesions (AA) along the coronary sinus – inferior left atrium (CS) and around the orifice of left atrial appendage (LAA) on the process to AF termination. Methods: In a biophysical model of PsAF based on human MRI and a membrane kinetics model, the following ablation sequence was simulated: 1) pulmonary veins isolation, 2) roof line, 3) mitral P231 isthmus line and 4) cavo-tricuspid isthmus line. In addition AA Left atrial appendage contractility is predicted by were applied to assess their impact on each ablative step. left atrial volume but not amplitude of appendage Clusters of lesions with two density levels and locations were bipolar voltages simulated: 1) low density (20%) along CS, 2) high density (35%) along CS, 3) high density (35%) along CS and around LAA. AF J. Tenkorang, P. Carroz, P. Pascale, A. Forclaz, J. Schlaepfer, termination rates were assessed at each ablative step.Twenty M. Fromer, E. Pruvot (Lausanne, CH) simulations were performed for each group. Introduction: The left atrial appendage (LAA) is the main source Results: Pulmonary vein – linear ablation progressively increased of emboli in patients (pts) with atrial fibrillation (AF). Amplitude termination rates up to 85%. AA along the CS increased the of bipolar voltages (Va) is indicative of the state of the underlying termination rate to >90%. AA could convert AF to AT in 5–10% of myocardial tissue. It is not known whether Va of the LAA is simulations after the roof line, while no further AT was observed predictive of its contractile efficiency. following mitral isthmus line.Adding a second zone of AA at the Methods: 82 consecutive pts (53 paroxysmal AF, 60 male, age 57 ± 9 years) undergoing catheter ablation for AF (CA) were included. LAA velocity and heart rhythm were noted during transoesophageal echocardiography (TOE) performed within 24 hours prior to CA. Before ablation, a CARTO Merge-XP (Biosense, Webster) of the left atrial (LA) volume not including the pulmonary veins was constructed in 72 pts and a CARTO-3 fast anatomical map (FAM) in 11 pts. In each case, 5 evenly-spaced Va points were taken within the LAA. Regression analyses of the mean of the 5 Va points and of the LA volume were performed as a function of LAA velocity. Results: 26 pts were in AF and 56 were in sinus rhythm (SR) during the TOE. There was no difference in mean Va between the two groups (2.7 ± 1. 6 vs 2.9 ± 1. 8 mV, p = NS). Pts in AF at time of TOE were older (60 ± 7 vs 54 ± 10 years, p <0.05), had larger LA (117 ± 50 vs 90 ± 20 ml, p <0.05) and lower LAA velocity (0.5

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LAA base resulted in lower termination rates, except after the APs of the Epi-RV and the ST elevation and amplitude of the mitral isthmus line. T- wave respectively in anterior chest leads. Conclusions: This model-based study highlights that the Method: The diastolic potential and the duration of Epi-RV APs influence of additional atrial lesions is dependentev onpr ious were raised by steps of 5mV (from –85 to 0mV) and shortened by step in the ablation sequence: termination rates may therefore be steps of 10ms (from 249 to 25ms) respectively and the resulting either similar or worse. This suggests that additional atrial lesions ST elevation (measured at the J point) and amplitude of the T would be more beneficial if appliedte af r linear roof and mitral wave (at the peak) were measured in chest lead V2 of the isthmus ablation. simulated ECG. Results: Shortening of Epi-RV APs did not produce an ST elevation but an increase in the T wave amplitude limited to P233 leads V1 to V3. Panel A of the figure below shows that theT wave ST elevation in Brugada syndrome is linearly amplitude measured in lead V2 was linearly and negatively related to the diastolic potential of epicardial related to the duration of Epi-RV APs (R2 = 0.97, p <0.05). The action potentials of the right ventricle ST elevations in leads V1 to V3 were reproduced by raising the diastolic potential of Epi-RV APs. Panel B shows that the ST S. Chevallier, A. Forclaz, J. Tenkorang, E. Pruvot (Lausanne, CH) elevation measured in lead V2 was linearly related to the diastolic Background: Brugada syndrome (BrS) is a potentially life potential of Epi-RV APs (R2 = 0.99, p <0.05). threatening arrhythmic disorder, whose electrophysiological Conclusions: Using a realistic APs-based ECG program, mechanisms remain controversial. We recently showed, using shortening of APs of the Epi-RV did not reproduce the ST ECGsim, an interactive simulation program, to compute the elevation seen in BrS, but an increase in the amplitude of the 12-lead ECG based on a realistic 3D representation of epicardial ECG T wave.Anterior chest leads ST elevation was observed and endocardial action potentials (APs) that neither of the after raising the diastolic potential of the Epi-RV. As the debated repolarization and depolarization hypotheses from the relationship appeared linear, the amplitude of the ST elevation in literature reproduced the atypical RBBB pattern with ST elevation BrS might be used to estimate the severity of the underlying AP seen in BrS. Importantly, the ST elevations in leads V1 to V3 were alteration. Our findings suggest that BrS may also comprise only reproduced after raising the diastolic potential of a region alterations of cellular mechanisms involved in the maintenance (4cm diameter) covering the epicardial right ventricle free wall of diastolic potential. and outflow tract (Epi-RV). Our study is aimed at determining the relationship between the diastolic potential and the duration of

P234 Mechano-electrical contribution of ventricular Results: Step-CA (including PVI, CFAE, roof and mitral isthmus contractions to the complexity of atrial fibrillation lines) terminated 2/3 pers-AF into flutter. The mean contribution electrograms of the mechano-electrical feedback on AF complexity achieved 37%. The figure shows a representative example where the VC A. Buttu, S. Volorio, J.-M. Vesin, A. Forclaz, P. Pascale, component (2.03 Hz) has been removed from the ICV, resulting S. Narayan, E. Pruvot (Lausanne, CH; San Diego, US) in the atrial-ICV.All other components have been preserved. Introduction: Intracardiac organization indices (OI) have been Conclusions: Our preliminary findings suggest that by means used to track the efficiency of stepwise radiofrequency catheter of mechano-electrical feedback, VC contribute up to 37% of ablation (step-CA) of persistent atrial fibrillation (pers-AF). A the atrial complexity during pers-AF. It is also a first step in the better understanding of the components and complexity of AF elaboration of new organization indices free of ventricular electrograms (EGMs) is fundamental for tracking the organization contribution. of AF. It remains unknown whether ventricular contractions affect the complexity of AF EGMs by means of mechano-eletrical feedback. Our study is aimed at developing new methods to quantify the potential mechano-electrical contribution of ventricular contractions on AF complexity. Methods: During step-CA, a quadripolar catheter was placed into the right atrial appendage (RAA). Robust maximum positive peak detection was applied. The time difference between two adjacent peaks was regularly resampled resulting in the intra-cardiac variability (ICV) signal. ICV reflects the intrinsic atrial activation time variability as well as the potential mechano-electrical feedback of ventricular contractions (VC). A lowpass version impulses series of R wave locations was used as input to an adaptive interference canceller in order to suppress the VC contribution to ICV (VC-ICV).

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P235 ventricular systolic ejection fraction (64 ± 4 vs. 66 ± 5; P = 0.233) ECG periodic components as a promising tool for and mitral inflow E velocity to tissue Doppler e’ (E/e’) ratio (7.5 ± complexity assessment during stepwise ablation 1. 4 vs. 7. 8 ± 1. 3 P = 0.223). Male athletes showed a higher systolic of atrial fibrillation blood pressure at rest (123 ± 9 vs. 110 ± 11 mm Hg; P <0.001) and at peak exercise (180 ± 15 vs. 169 ± 7 mm Hg; P = 0.001). In A. Buttu, A. Viso, J. Van Zaen, J.-M. Vesin, A. Forclaz, P. Pascale, the frequency domain analysis of heart rate variability, male S.M. Narayan, E. Pruvot (Lausanne, CH; San Diego, US) athletes showed higher values of the low frequency (LF) power Purpose: Stepwise radiofrequency catheter ablation (step-CA) (81.3 ± 6.9 vs. 73.5 ± 9.0 n.u.; P <0.001) and lower values of the has become a treatment of choice for the restoration of sinus high frequency (HF) power (16.9 ± 7. 0 vs. 22.3 ± 8.5 n.u.; P rhythm (SR) in patients (pts) with long-standing persistent atrial <0.001). The sympatho-vagal balance, represented by the LF/HF fibrillation (pers-AF). Its success rate appears limited as the ratio, was significantly higher in male athletes (5.8 ± .2.8 vs 3.9 ± amount of ablation to achieve long term SR is unknown. Recently, 1. 9; P <0.001). Four athletes (3.3%) had at least one ducumented intracardiac organization indices (OI) of AF have been used to episode of paroxysmal AF, all were male (P = 0.045). track the efficiency of step-CA, with limited success. Our study is Conclusions: For a comparable amount of training and aimed at developing new OIs based on the relationships between performance, male athletes showed a more pronounced atrial harmonic components of atrial activity from the surface ECG and ventricular remodeling and a slightly altered, but not as a global assessment of AF complexity and organization during abnormal diastolic function. A higher blood pressure at rest and step-CA. Methods: 3 pts with pers-AF (age 62, AF duration 17 during exercise, and a higher sympathetic tone may be causal. months) underwent a step-CA. An adaptive tracking algorithm The altered left atrial substrate probably facilitated the occurrence was developed for estimating the instantaneous frequency of of AF. atrial activity on chest lead V1 (after QRST subtraction) and for extracting its fundamental and harmonic components.An adaptive organization index (AOI) was computed as the ratio P237 between the power of the extracted components and the total Long-term follow-up of patients after the power of the signal to evaluate the temporal evolution of AF “ablate and pace” procedure oscillations.The variance of the phase difference (PD) between the fundamental and harmonic components was used for H. Abbühl, M. Kühne, C. Sticherling, S. Osswald, B. Schär measuring AF regularity. Results: Step-CA terminated 2/3 pers-AF (Basel, CH) into flutter. Importantly, in the 2 terminated pts, the AOI did not Background: “A blate and pace” (A and P) is an established show any significant change during the step-CA (from pre- procedure for patients with drug-refractory atrial fibrillation (AF) ablation to CFAE), while the PD showed a gradual reduction and rapid ventricular response. It involves catheter ablation of the suggestive of increased coupling between the fundamental and AV node and implantation of a permanent DDD- (paroxysmal) the 1st harmonic. See figure. Conclusions: The PD and the AOI or VVI-pacemaker (permanent AF). A high amount of right- as measurements of complexity from the surface ECG appear as ventricular pacing has been shown to exhibit deleterious effect on promising methods for tracking the effect of step-CA on global AF ejection fraction (EF) in some patients (SAFE-PACE-study). Aim organization. This, however, needs to be validated on a larger of this study was to evaluate the long-term follow-up of the EF in population. these patients and to determine the need for biventricular pacing (CRT- P). Methods: Fifty-five consecutive patients who underwent Aand P at our hospital between 1/2001 and 5/2009 were identified. We had to exclude 9 patients in whom a CRT- P was implanted at the time of A and P, 4 patients with a follow-up of <12 months and 15 patients due to missing echocardiographic follow-up. In patients with several follow-up echocardiographies, the last one was considered. Results: Twenty-seven patients (15 female), age 69 ± 10 years, were included in the analysis. In 10 patients a VVI- and in 17 a DDD-pacemaker was implanted. EF at baseline was 52 ± 10%, with 5 (19%) patients having an EF ≤40% (range 32–40). Last echocardiographic follow-up, performed 51 ± 24 months after implant showed an EF of 53 ± 9% [with 2 patients having an EF of 40% at lowest] (p n.s.). In 5 patients, EF decline was ≥10% P236 (maximum 20%). No CRT- P-upgrade was necessary. In the Gender differences of atrial remodeling and atrial 9 patients who received a CRT- P at the time of A and P, EF arrhythmias in non-elite athletes changed from 28 ± 7% at baseline to 35 ± 12% (p = 0.2) at last echocardiographic follow-up performed 30 ± 25 months after M. Wilhelm, L. Roten, H. Tanner, J.-P. Schmid, H. Saner implant. (Bern, CH) Conclusion: In patients undergoing AV-nodal-ablation and Background: Endurance athletes have an increased risk of pacemaker insertion for drug-refractory atrial fibrillation, EF developing atrial fibrillation (AF) at an age between 40 to 50 years remains stable during long-term follow-up.Therefore, it does not with a striking male predominance.We hypothesized that male seem to be justified to implant a CRT- device prophylactically. athletes were more prone to atrial remodeling and investigated factors that promote the occurrence of AF. Methods: Non-elite athletes scheduled to participate in the 2010 P238 Grand Prix of Bern, a 10 Mile race, were invited. 873 marathon Left ventricular hypertrophy, late potentials and and non-marathon runners applied for participation, 140 female QRS dispersion in ultra endurance athletes compared and male athletes were randomly selected, and 120 of them to normal controls could be matched for age, lifetime training hours, race time and performance on a cardiopulmonary exercise test. Runners with B. Naegeli, G. De Pasquale, C. Scharf, B. Knechtle, M. Pfyffer, an elevated blood pressure (RR>140/90 mm Hg at rest) were M. Zuber, A.M. Bernheim, A. Linka, C.H. Attenhofer Jost excluded. (Zürich, St. Gallen, Othmarsingen, Winterthur, CH) Results: Mean age was 42 ± 7 years and mean race time was Background: Electrocardiographic (ECG) changes of 80 ± 13 minutes. Male athletes had a significantly longer depolarisation and repolarisation have been described in the signal-averaged P wave duration (136 ± 12 vs. 122 ± 10 ms; athlete’s heart. These ECG changes may occasionally be P <0.001) and a larger left atrium (56 ± 14 vs. 50 ± 10 ml; P = difficult to differentiate from arrhythmogenic right ventricular 0.008). Left atrial volume index showed no significant gender cardiomyopathy (ARVC) or hypertrophic cardiomyopathy. Data on differences (29 ± 7 vs. 30 ± 6 ml/m2; P = 0.973). In male athletes, prevalence of epsilon waves, QRS dispersion and late potentials left ventricular mass index was higher (107 ± 17 vs. 86 ± 16 g/m2; in athletes are limited. We thus examined the prevalence of these P <0.001), and deceleration time of the E wave was longer (182 ± findings in ironman triathletes, a good example of ultraendurance 29 vs. 162 ± 25 ms; P <0.001). There were no differences in left athletes (ATHL).

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Methods: Signal averaged ECG (SAECG) and a regular ECG as within normal limits in all athletes. ECG criteria for late potentials well as a complete transthoracic echocardiographic exam were were found in 4 ATHL, but also in 4 controls (p = 0.45); also no performed in 39 ATHL and compared to 23 age-and gender difference in QRS dispersion was found between the two groups. matched controls.All ECGs were screened for signs of ventricular No patient had epsilon waves or other signs of ARVC such as late potentials (VLP): QRS duration, late amplitude signal (LAS) negative T waves in the anterior precordial leads. duration; and mean root mean square voltage (RMS voltage). Conclusions: Apart from signs of LVH and an increased RMS Results: Average age was 39 years in ATHL and controls.Any voltage in the SAECG, there were no findings typical of ATHL ECG abnormality was found in 30 of 39 athletes versus 4 of 24 heart. The correlation of voltage criteria with LV muscle mass controls (p <0.0001). The results are shown in the Table. The most index LVMMI was confirmed; pathologic ECG suggestiveVC ofAR common ECG abnormality in ultraendurance ATHL were signs of with epsilon waves or negative precordial T waves are rarely LVH (see Table) using Sokolow amplitude criteria for LVH which found. Late potentials were not found to be helpful in correlated with echocardiographic LVMMI (p <0.0001 for LVH). PR differentiating athlete heart from a normal heart or interval tended to be longer in ATHL. Filtered QRS duration was cardiomyopathy as it can be found in both pt groups.

HR = heart rate; bpm; beats per minute; QRS dur = QRS duration; incomp RBBB = incomplete right bundle branch block; QTc = corrected QT interval; +LP = positive late potentials. Percentages are shown in parenthesis.

P239 P240 Elective cardioversion of atrial fibrillation via an Syncope remaining unexplained after a structured implanted cardioverter defibrillator – Safety work-up shares all the features of patient with and efficacy vasovagal events B. Schaer, M. Kühne, C. Sticherling, M. Mutschelknauss, L. Froidevaux, F. Sarasin, M. Louis Simonet, O. Hugli, S. Osswald (Basel, CH) B. Yersin, J. Schlaepfer, J. Sztajzel, C. Mischler, E. Pruvot Background: Even though ICDs are not designed to cardiovert (Lausanne, Genève, CH) atrial fibrillation (AF) or teflut r (AFlu), the energy delivered Purpose: we have shown that the application of a structured by dual-coil devices might be sufficient to do so Internal diagnostic work-up based on the ESC guidelines in patients with cardioversion thus could be an alternative to conventional syncope addressed to the emergency department improved the external cardioversion. Device longevity will not be affected by a likelihood of identifying a cause as compared to usual practice. single shock delivery, as cardioversion postpones the next regular We report here the clinical characteristics, recurrence and capacitor reformation by six months. mortality rates of the causes of syncope as diagnosed with the Methods: We prospectively performed cardioversion via the ICD structured diagnostic work-up. in 20 consecutive patients with persistent AF or AFlu, either at the Method and results: all patients with unexplained syncope time of device implant or during follow-up if considered clinically (un-SY) following a negative emergency department evaluation indicated by a cardiologist. Anticoagulation according to (i.e. history, physical examination, ECG and testing for orthostatic guidelines and sedation with etomidate were prerequisites.The hypotension) underwent alternatively a standardized set of amount of Joules used for cardioversion was left to the discretion sequential diagnostics tests based on the presence of an organic of the investigator, but only a single shock was allowed. This one heart disease and/or abnormal ECG and total number of being unsuccessful, external cardioversion was performed. syncope, or were managed by emergency department physicians All patients had dual-coil leads. in order to reflect usual practice. 173 consecutive patients (61 ± Results: Mean age of the patients was 71 ± 4 years, 18 were 20 y) were included in the intervention group, in whom a cause male, 11 had ischemic cardiomyopathy, and median diameter for syncope was established in 39% by the structured diagnostic of the left atrium (LA) was 59 (range 41–63). 18 patients were work-up (93/173 pts). The table below reports the clinical converted for AF, 2 for AFlu. In only five patients, cardioversion characteristics, recurrence and mortality rates at 1-year in was performed during implant. In 11 patients, the ICD was a the different groups of syncope causes. Patients with cardiac CRT device.With median 25.5 Joules (range 15–35 Joules) arrhythmias (CA) and carotid sinus hypersensitivity (CSH) were cardioversion was possible in 18/20 patients (90%). 2 patients with AF could not be converted with 25 and 36 Joules, their LA diameter being 58 and 63mm, respectively. In both, external cardioversion with 200 Joules was successful. Neither age, LA diameter nor the amount of Joules applied were predictors of success.There were also no complications noticed due to the procedure. Conclusion: Cardioversion of atrial fibrillation/flutter via their ICD is feasible and safe and thus can be recommended for such patients.

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older, with more coronary artery disease (CAD) and abnormal arrhythmogenic right ventricular cardiomyopathy (ARVC). ECG as compared to patients with vasovagal (VV), psychogenic Methods and results: A retrospective analysis was performed in pseudo-syncope (PPS) and unexplained syncope. Interestingly, 26 patients (median age of 40 years at diagnosis, 21 men) with the characteristics of unexplained syncope were similar to ARVC who underwent ICD implantation. Appropriate ICD therapy vasovagal patients including 1-year recurrence and mortality for ventricular arrhythmia occurred in 12 (46%) out of 26 patients rates. Death rate was low except for CA, and most syncope over a median (range) follow-up period of 10 (2.7, 37) years. In all recurrence occurred in the unexplained syncope and vasovagal patients with appropriate ICD therapy the ICD was originally groups. inserted for secondary prevention. Median (range) time from ICD Conclusions: in patients whose initial emergency department implantation to ICD therapy was 9 months (2 months; 8 years). evaluation was non contributive, syncope remained unexplained An ICD for secondary prevention of sudden cardiac death was in 60% of the cases despite the application of a structured implanted in 25 patients, and for primary prevention in one diagnostic work-up.The clinical characteristics of unexplained patient. History of heart failure was a significant predictor syncope were similar to vasovagal patients.As most recurrences of ICD therapy (p = 0.033). Left ventricular disease involvement occurred in these two groups, preventive counseling such as (p = 0.059) and age at implantation (p = 0.063) were borderline water intake and isometric maneuvers might be of clinical benefit. significant predictors. Those with syncope at time of diagnosis were significantly less likely to receive ICD therapy (p = 0.02). Invasive electrophysiological testing was not significantly P241 associated with appropriate ICD therapy. Predictors of appropriate ICD therapy in patients Conclusion: In our cohort of patients with ARVC, history of heart with arrhythmogenic right ventricular cardiomyopathy: failure was a significant predictor of appropriate ICD therapy, long-term experience of a tertiary care centre whereas left ventricular involvement and age at time of ICD implantation were of borderline significance. L.M. Haegeli, P. K. Schuler, T. Wolber, C. Brunckhorst, R. Jenni, T.F. Lüscher, F. Duru (Zürich, CH) Aim: To determine clinical, echocardiographical and electrophysiological predictors of appropriate implantable cardioverter defibrillator (ICD) therapy in patients with

postergruppe 3 – groupe de posters 3 congestive heart Failure, valvular heart disease

P242 Prognostic value of midregional pro-adrenomedullin Subsequent serial MR-proADM measurements on top of baseline compared to B-type natriuretic peptide in acute levels did not increased prognostic value. Serial measurements of decompensated heart failure BNP by contrast improved prognostic ability compared to baseline measurement alone (LRC 31.80 p <0.001). M. Noveanu, M. Potocki, T. Reichlin, T. Breidthardt, Conclusions: Prognostic ability of MR-proADM in ADHF is best R. Twerenbold, B. Drexler, C. Stelzig, N. Arenja, O. Hartmann, at ED presentation. Serial measurements of MR-proADM provide S. Osswald, C. Müller (Basel, CH; Henningsdorf, DE) no additional predictive value. Determination of MR-proADM on Background: B-type natriuretic peptide (BNP) reliably predicts top of BNP at ED presentation adds prognostic value and should outcome in patients with acute decompensated heart failure be recommended to improve risk stratification. (ADHF). Adrenomedullin (ADM), a vasodilator associated with presence and amount of microvascular dysfunction carries excellent prognostic properties in various diseases.ADM P243 measurements are however difficult to perform due to its ex-vivo Functional effects of longer-term application of instability. The aim of the current study was to assess prognostic urocortin 2 compared to enalapril in an animal model value of the more stable mid-regional fragment of ADM (MR- of severe heart failure proADM) at emergency department (ED) presentation and during course of hospitalization in ADHF patients. Serial measurements S. Meili-Butz, K. Bühler, D. John, T. Dieterle (Basel, CH) should indentify the time point with its best prognostic value and Background: Urocortin 2 (Ucn2), a member of the corticotropin- compare it to BNP. releasing factor (CRF)-related peptide family, induces potent Methods: This prospective multicenter study evaluated 277 acute and chronic beneficial hemodynamicfe ef cts via CRF patients (mean age 78 ± 10 years, 57% male) presenting with receptor 2 (CRFR2) stimulation in animal models of heart failure ADHF at the ED. Measurements of MR-proADM and BNP levels (CHF). However, no data are available on the hemodynamic were performed at ED presentation, 24 hours (h), 48 h and effects of chronic CRFR2 stimulation by Ucn2 compared to an discharge.The primary endpoint was all-cause mortality at established therapy of CHF, such as chronic ACE inhibition by 180 days. enalapril, in severe experimental CHF. Results: During follow-up 55 (20%) patients died. MR-proADM Methods: Experiments were performed in Dahl salt-sensitive rats. and BNP levels were higher in non-survivors at all time points Animals were fed a high salt diet (HSD) containing 4% NaCl to (all p <0.001). In survivors, treatment reduced MR-proADM and induce arterial hypertension, LV hypertrophy, LV dysfunction, and BNP levels during course of hospitalization (all p <0.001), while CHF. From the phase of LV dysfunction on (after 12 weeks of in non-survivors no change occured. Predictive value of MR- HSD), animals were treated with either Ucn2 (2.5 microg/kg body proADM for 180-day mortality was best at ED presentation (area under the ROC curve: 0.73; 95% CI 0.63–0.81 vs. 0.64; 95% CI 0.53–0.73 for BNP; p = 0.09) and remained nearly unchanged during course of hospitalization. Predictive value of BNP increased during hospitalization, reaching the best prognostic ability at hospital discharge (area under the ROC: 0.75; 95% CI 0.67–0.82, p = 0.02 vs. hospital presentation). Measurement of MR-proADM on top of BNP at ED presentation added incremental prognostic value (likelihood ratio chi-square [LRC] 28.9, p <0.001). Addition of BNP on top of MR-proADM resulted in no additional prognostic information (LRC 0.14, p = 0.969).

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weight, ip, bid) or enalapril (30 mg/kg body weight in drinking single predictors of 1-year mortality and patients were categorized water plus vehicle ip, bid). Animals underwent tail cuff blood to three risk groups: high risk group (BUN >27.5 mg/dl and age pressure (BP) measurements and echocardiographic analysis >86 years), intermediate risk group (BUN >27.5 mg/dl and age of LV dimension and function at baseline (prior to first treatment) ≤86 years) and low risk group (BUN ≤27.5 mg/dl). The Kaplan- and after 4 weeks of treatment. Meier curves showed a significant increase in mortality in the high Results: Results are given in the following table as mean ± SD. risk group compared with the lower risk groups (log-rank test Conclusion: Despite comparable BP reduction, longer-term p <0.001). The hazard ratio regarding 1-year mortality between CRF receptor 2 stimulation by Ucn2 in an animal model of patients identified as low and high risk was 2.0 (95% confidence hypertension-induced severe CHF improves LV function to a interval, 1. 7–2.4), with statistically significant differences between greater extent than enalapril without affecting survival. Data from all risk groups (p <0.001). The likelihood-based 95%-confidence this study suggest that longer-term administration of Ucn2 might set for the age- and the urea-threshold is contained in the represent a novel, safe, and beneficial approach to the treatment rectangular set defined by 25 mg/dl ≤ urea threshold ≤30.6 mg/dl of CHF. and 76 years ≤ age threshold ≤96 years. Conclusion: These results suggest that AHF patients at low, intermediate and high risk for death within 360 days can be P244 easily identified using patients demographic and laboratory Percutaneous mitral valve repair in high risk data obtained at presentation. Application of this simple risk patients – the Swiss experience after the first stratification algorithm may help to improve the management 100 patients of these patients. D. Sürder, G.B. Pedrazzini, T. Moccetti, E. Pasotti, F. Faletra, P. Erne, M. Zuber, P. Jamshidi, C. Auf der Maur, C. Kaiser, R. Jeger, D. Hürlimann, O. Gaemperli, P. Biaggi, D. Bettex, J. Grünenfelder, R. Corti (Lugano, Luzern, Basel, Zürich, CH) Introduction: Patients with severe mitral regurgitation (MR) and high operative risk remain frequently undertreated although their morbidity and mortality is usually high. We report on the experience gained after 100 patients in Switzerland with a novel technique of transvenous mitral valve reconstruction utilizing the MitraClip®-system. Methods: Patients with severe MR (>3+) and high operative risk (as defined by the logistic EuroScore or STS-Score) or declined for surgical repair were considered. Percutaneous MitraClip® implantation was performed in the cath-lab setting with trans- esophageal monitoring under general anesthesia. Results: Since 2009 we treated 100 high-risk patients with a mean age of 72 ± 13 years (67% male; logEuroScore 25 ± 17%, STS-Score 7 ± 7%; Mean ± SD) and a left ventricular ejection fraction of 45 ± 17% (Mean ± SD). The origin of the MR was functional in 57% and degenerative in 25% of the cases. In 17% of the patients the cause of the MR was mixed. Acute procedural success (APS) is defined as placement of 1 or more clips resulting in a discharge MR severity of ≤2+. APS could be demonstrated in 80% of the patients. In 44% of the patients with APS MR decreased to degree 1+. Median of ICU/CCU stay was 1 day, median of total hospital stay was 4 days and NYHA-class improved from 3.1 ± 0.5 to 2.2 ± 0.7 at 3 and 6 months. Discussion: In Switzerland 100 high-risk patients with severe MR have been successfully treated percutaneously with the MitraClip® system with an APS rate similar to previous reports. This new technique bears important potential in particular in those patients not qualifying for surgical repair due to high operative risk. Ongoing analysis are focussed on the influence of the origin of the MR on short and long term results of MitraClip® treatment as well as on the influence of MR grade at discharge on long term results. Clinical and echocardiographical long term results will be available at the time of the meeting.

P245 Risk stratification for 1-year mortality in acute heart failure: classification and regression tree analysis P246 N. Arenja, T. Breidthardt, W. Hochholzer, T. Socrates, C. Schindler, R. Twerenbold, R. Miriam, C. Heinisch, Acute and chronic cardiovascular effects of M. Potocki, M. Noveanu, T. Reichlin, S. Osswald, C. Mueller flavanol-rich chocolate in patients with heart failure (Basel, CH) I. Sudano, A.J. Flammer, M. Wolfrum, D. Périat, Background: Simple tools for risk stratification of patients with F. Enseleit, P. Kaiser, A. Hirt, T.F. Lüscher, F. Ruschitzka, acute heart failure (AHF) are an unmet clinical need, particularly G. Noll, R. Corti (Zürich, CH) regarding long-term mortality. Background: Recent studies indicated a beneficial feef ct of Methods: We prospectively enrolled 610 consecutive patients flavanol-rich cocoa on cardiovascular health, especially on presenting to the emergency department with AHF.The diagnosis vascular and platelet function, on blood pressure and insulin of AHF was adjudicated by two independent cardiologists.The resistance, most likely due to an increase in nitric oxide classification and regression tree (CART) analysis was used to bioavailability and a decrease in oxidative stress. Patients with develop a simple risk algorithm. This was internally validated by congestive heart failure (CHF) are characterized by impaired cross-validation. endothelial as well as increased platelet reactivity and oxidative Results: One-year follow-up was complete in all patients (100%). stress.Therefore, flavanol-rich chocolate might improve A total of 201 patients (33%) died within 360 days.The CART cardiovascular health in patients with CHF. analysis identified blood urea nitrogen (BUN) and age as the best

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Methods and results: Twenty patients with CHF were enrolled in of HF (odds-ratio [OR] = 2.54 [95%-CI 1. 57–4.10]), log10 of a double blind, randomized placebo controlled trial, comparing NT-BNP (2.79 per factor 10 [1.55–5.01]), presence of pacemaker the effect of flavanol-rich commercially available dark chocolate (2.35 [1.35–4.10]), systemic-inflammatory disease (3.13 [1.37– with cocoa-liquor free control chocolate on endothelial and 7. 13]), anemia (1.67 [1.06–2.63]), history of cancer (1.89 [1.07– platelet function, baroreceptor function, blood pressure and heart 3.33]), Charlson score (1.16 per score point [1.01–1.32]) and rate in the short-term (2 hours after ingestion of a chocolate bar) serum creatinine (1.06 per 10 µmol/l [1.00–1.13)] were the and long-term (4 weeks, two chocolate bars/day). Endothelial baseline characteristics associated with increased risk of death. function was assessed non-invasively by flow-mediated Mode of death was found to be cardiovascular (CV) in 77% vasodilatation (FMD) of the brachial artery. FMD significantly (sudden death 21%, circulatory failure 50%, vascular 6%), improved from 4.98 ± 1. 95% to 5.98 ± 2.32% two hours after non-CV in 18% and unknown in 5%. Pts who died experienced intake of flavanol-rich chocolate, and to 6.86 ± 1. 76% after a median of 4 AE (IQR 1-7) <60 days prior to death compared 4 weeks daily intake (measured after at least 12 hours to 0.7 (0.4–1.4) during randomly selected 60 days in pts who abstinence). Platelet adhesion significantly decreased from 3.9 ± survived (p <0.0001). This was true for HF related AE (1 [0-2] 1. 32% to 2.99 ± 1. 31% 2 hours after flavanol-rich chocolate intake, vs 0.1 [0–0.2]), CV AE (2 [1-3] vs 0.3 [0.1–0.6]), and non-CV AE an effect that was not sustained at 2 and 4 weeks. Cocoa-liquor (2 [0-4] vs 0.4 [0.2–0.8]); all p <0.0001. Pts who died were more free chocolate had no effect, neither on endothelial nor on platelet often hospitalized <60 days prior to death (median 1 [IQR 0–1]) function. Baroreceptor function, blood pressure and heart rate did than those surviving (0.1 [0.0–0.2]), p <0.0001. Significant not change in either group. differences were seen for CV, cardiac and HF related Conclusion: Flavanol-rich chocolate acutely improves vascular hospitalizations (p <0.0001), but not for non-CV hospitalizations function in patients with CHF.Asustained effect was seen after (p = 0.1). Frequency of AE varied between different modes of daily consumption over a 4 weeks period even after 12 hours death (fig., * p <0.05 vs pts alive). abstinence.These beneficial feef cts were paralleled by a inhibition Conclusions: In TIME-CHF, simple clinical and biological of platelet function in the presence of flavanol-rich chocolate only. variables were associated with death. In addition, pts who died were characterized by frequent AE and hospitalizations prior to death. Timely recognition of these factors might improve P247 identification, management and outcome in pts with HF. Baseline characteristics, adverse events and hospitalizations indicate an increased risk of death in patients with heart failure – an analysis of the P248 TIME-CHF trial Approaching cardiac transplantation with non- heartbeating donors: use of an isolated, rat-heart P. Rickenbacher, M. Pfisterer, T. Burkard, W. Kiowski, F. Follath, model to optimize ischaemic tolerance D. Burckhardt, R. Schindler, H.-P. Brunner-La Rocca for the TIME-CHF Investigators M. Dornbierer, M. Stadelmann, D. Clément, T.P. Carrel, Background: Risk factors for death in patients (pts) with heart H. Tevaearai, S. Longnus (Bern, Fribourg, CH; failure (HF) have been defined but vary with populations studied. Clermont-Ferrand, FR) Whether death is preceded by an increased rate of clincial events Introduction: Lack of donor organs currently limits the number has not been well characterized. of cardiac transplantations.Although use of non-heartbeating Methods: To further clarify these relations, baseline character- donors (NHBDs) could increase heart availability, these hearts istics as well as adverse events (AE) and hospitalizations within undergo a period of warm ischemia, which may cause irreversible 60 days preceding death were compared with those of the injury, precluding transplantation. Importantly, methods to extend survivors within a similar time period in the TIME-CHF study, ischemic tolerance could promote use of these hearts. However, a randomized controlled multicenter trial comparing a standard mechanisms responsible for irreversible warm ischemic injury and symptom-guided with an intensified, NT-BNP guided medical clinically-applicable approaches to reduce or limit this injury have therapy in 622 pts ≥60 years with symptomatic HF NYHA ≥II, not yet been fully characterized. Therefore, we aimed to establish a history of HF hospitalization <1 year and an elevated NT-BNP an ex vivo protocol to further characterize warm ischemia and to level. investigate the effects of mild hypothermia during ischemia on Results: During the 18-month follow-up, 132 (21%) of the pts ischemic tolerance. died. In multivariable analysis, coronary disease as primary cause Methods: Hearts isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer for 30 min aerobically in working-mode, subjected to global, no-flow ischemia and reperfused for 60 min. Ischemia was initiated by clamping preload and afterload lines and hearts were rapidly placed in a tissue bath to maintain desired temperature. At reperfusion, hearts were initially perfused in an unloaded mode for approximately one-third of the ischemic period and then switched to loaded mode for the remainder of reperfusion. Four ischemic periods were investigated: 37 °C for 20 or 30 min, and 32 °C for 40 or 55 min. Heart function, coronary perfusion and time to cardiac arrest were measured. Results: Our ex vivo preparation was used to examine contractile recovery in 37 hearts.After onset of ischemia, hearts continued to beat for 200 ± 52 sec at 37 °C and 307 ± 130 sec at 32 °C (all values are reported as mean ± standard deviation). Percent post-ischemic left contractile recovery after 60 min reperfusion, measured as RPP (peak systolic pressure-heart rate product), is presented below: Conclusions: We have established an ex vivo preparation that allows investigation of contractile recovery following a period of warm ischemia. Slightly reducing temperature during ischemia effectively improves ischemic tolerance. Further characterization of mechanisms associated with mild hypothermia is a promising approach to prolong ischemic tolerance and facilitate use of hearts from NHBDs for transplantation.

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P249 NT-proBNP provides incremental prognostic Results: Patients with abnormal echocardiography and elevated information in cardiac outpatients with and without NTpBNP had a mortality rate of 8.7% and an overall event rate echocardiographic findings of 20.2% (composite endpoint of overall mortality, myocardial infarction and hospitalization for heart failure) which was S. Toggweiler, O. Borst, M. Frank, D. Müller, F. Enseleit, significantly higher than in patients with abnormal M. Hermann, F. Ruschitzka, T.F. Lüscher, G. Noll (Zürich, CH) echocardiography and normal NTpBNP, in which no mortality Introduction: Outpatients frequently present with elevated (p = 0.011) and no events were observed (p <0.001). In patients natriuretic peptides in the absence of an obvious cardiac with a normal echocardiography, mortality was 1. 5% and 1. 8% abnormality or with normal natriuretic peptides despite for patients with normal and elevated NTpBNP, respectively echocardiographic findings.We aimed to determine the (p = 1. 000). Composite event rate was 1. 5% and 8.9% (p = 0.093), prognostic value of N-terminal pro B-Type Natriuretic Peptide respectively. Figure 1 shows Kaplan Meier estimates of event-free (NTpBNP) in outpatients with normal and abnormal survival in relation to NTpBNP and echocardiographic results. echocardiography. In multivariate analysis, NTpBNP was the most powerful predictor Methods: A total of 433 cardiovascular outpatients were included. of adverse cardiovascular events (HR 6.43, 95% CI 1. 53–27.00, The prognostic value of NTpBNP in patients with normal and p = 0.011, table 1). abnormal echocardiography during a 2-year follow-up was Conclusions: Patients with low NTpBNP have an excellent evaluated. prognosis irrespectively of echocardiographic findings.Therefore, determination of NTpBNP appears useful in assessing the clinical relevance of echocardiographic findings.

P250 Rapid progression of dilated cardiomyopathy in history. Genetic analysis revealed a novel mutation (c746 G>T) a young female with a new lamin A/C mutation: of the LMNA-gene. Mutation screening of the family members a case report and review of the literature is still pending. Conclusion: Our case demonstrates the importance of S.R. Schenker, S. Reineke, J. Seiler, C. Rieubland, considering the possibility of an inherited etiology when treating P. Mohacsi (Bern, CH) patients with DCM. Due to a highly variable penetrance or Background: Dilated cardiomyopathy (DCM) is the second most de-novo mutations there may be no or no obvious family history. common cause of heart failure after ischemic heart disease and Because of the high prevalence of Lamin A/C mutations and one of the leading indications for heart transplantation in patients the poor prognosis of symptomatic carriers, mutation screening below 40 years of age.The etiology of DCM remains unknown in should be considered carefully, especially in cases with a high about 40% of the cases. Familial dilated cardiomyopathy (FDC) is suspicion. Currently, there is no specific treatment, but due to an underrecognized form of DCM. It is estimated that in about the high incidence of sudden cardiac death placement of a ICD 20–25% of patients with DCM there is a familial etiology. Inherited should be considered early in the course of the disease. defects of the Lamin A/C, an important protein of the nuclear Identification of a mutation in the index patient allows genetic membrane, seem to play a major role in FDC. Moreover, and family counseling. symptomatic carriers of Lamin A/C mutations seem to have a worse prognosis than other patients with DCM due to cardiac arrhythmias (sudden cardiac death) and congestive heart failure. P251 Methods and results: We report the case of a 17- year- old female patient who was first diagnosed withve se re DCM when Effect of transcatheter aortic valve implantation presenting with dyspnea and a transient ischemic attack (most on neurohumoral activation and functional class likely cardio- embolic). She developed non- sustained ventricular S. Stortecky, T. Pilgrim, A. Kadner, C. Huber, B. Meier, tachycardia as well as a long 1st degree atrio-ventricular block T.P. Carrel, P. Wenaweser, S. Windecker (Bern, CH) and a left bundle branch block. A dual- chamber implantable Background: Severe aortic valve stenosis is often accompanied cardioverter-defibrillator (ICD) was therefore implanted in an by severe symptoms of congestive heart failure (CHF) restricting outside hospital. Despite optimal medical management and quality of life in elderly patients. Natriuretic peptides like B-type device upgrade to a cardiac resynchronization defibrillator she natriuretic peptide (BNP) and the N-terminal fragment (NT- developed rapid progression to end- stage heart failure and proBNP) are neurohumoral factors associated with increased underwent heart transplantation 5 months after her first wall stress.We assessed the effect of transcatheter aortic valve presentation. Her young age, rapid disease progression, delayed implantation (TAVI) on neurohumoral activation and functional intracardiac conduction and a subtle skeletal myopathy raised the class. suspicion of a genetic disease even without a positive family

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Methods and results: This prospective study included 72 1. 6 ± 2 days before TAVI and at discharge 6.9 ± 3 days after TAVI. patients (64% females; age 83 ± 5 years) with severe aortic Levels were significantly welo r after the intervention and left stenosis (AVA = 0.6 ± 0.2 cm2; pmean = 46 ± 15 mm Hg) under- ventricular ejection fraction improved compared to baseline going TAVI with a Medtronic CoreValve bioprosthesis (n = 62) measurements (table 1). Short-term clinical follow up (mean 41 ± or an Edwards Sapien Valve (n = 10). Baseline characteristics 16 days after TAVI) revealed an improvement of NYHA functional showed a mean logistic EuroScore of 22.3 ± 14.7%, 39 patients class (mean 2.6 ± 0.9 vs. 1. 4 ± 0.8, p <0.001) (54%) had preexisting coronary artery disease, 8 (11%) chronic Conclusion: Transcatheter aortic valve implantation results in a obstructive pulmonary disease, 50 (69%) arterial hypertension rapid decrease in neurohumoral activation, which is associated and 16 patients (22%) diabetes mellitus. Levels of the with an improvement of left ventricular function and symptoms neurohumoral factors BNP and NT- proBNP were measured of CHF.

P252 Quality of life in patients undergoing with deep recessi and a thickened non-compacted layer of the left percutaneous aortic valve implantation ventricular myocardium; Panels B-D: Parasternal short axis views of the 3 daughters, each with left ventricular diverticulae within S. Stortecky, T. Pilgrim, B. Meier, S. Windecker, the anterolateral left ventricular wall segments.The clinical course P. Wenaweser (Bern, CH) of the mother was complicated by worsening left ventricular Background: Transcatheter Aortic Valve Implantation (TAVI) has ejection fraction and worsening mitral regurgitation, while the emerged as treatment alternative to conventional surgery in high daughters were documented to have stable findings over a risk patients with symptomatic severe aortic stenosis.The follow-up period of 6 years. purpose of the present study was to assess changes in quality Conclusion: Isolated left ventricular diverticula may be an of life (QOL) in response to TAVI. abortive phenotypic presentation of left ventricular non Methods and results: This prospective study included 41 compaction. patients (63% females, age 82.5 ± 4.8years) with severe aortic valve stenosis (aortic valve area 0.6 ± 0.2 cm2) who underwent TAVI between 08/2007 and 10/2009. Thirty-six patients completed a full QOL-assessment during the preoperative and follow–up phase using the Short–Form–36 (SF-36) questionnaire. Preoperative QOL assessment showed a low SF-36 score with severe impairment of perceived QOL. Both physical (PH = 35.1 ± 17.2) and mental summary scores (MH = 42.9 ± 18) were significantly welo r score compared with the expected QOL scores in a healthy reference population aged >70 years (PH = 57.1, p <0.0001; MH = 68.8, p <0.0001). A mean of 267 ± 72 days after TAVI, QOL-follow up assessment revealed a remarkable increase in PH (68.5 ± 19.5; p <0.0001) and MH (59.8 ± 23.1, p <0.0001) to values closely matching a healthy reference population. Conclusion: Treatment of severe aortic stenosis by means of TAVI effectively alleviates symptoms and improves QOL in elderly patients at high risk for surgical aortic valve replacement.

P253 Left ventricular myocardial diverticula: An abortive form of left ventricular non-compaction cardiomyopathy? A. Brauchlin, R. Jenni, P. Biaggi, F. C. Tanner, M. Greutmann (Zürich, CH) Introduction: Left ventricular non compaction (LVNC) is a rare form of cardiomyopathy. Its etiology is not well defined. In some of the affected patients, however, recent studies have established mutations in sarcomeric protein genes that have previously been P254 found to be involved in other forms of cardiomyopathy. It may thus be possible that sarcomeric protein gene mutations can cause No diagnostic value of high sensitive troponin T different phenotypes of left ventricular myocardial abnormalities. as a marker for cardiac allograft rejection in long term Methods: We describe a familial cluster of left ventricular cardiac transplant survivors myocardial abnormalities with the index patient presenting with M. Ammon, R. Buechel, K. Glatz, T. Dieterle, P. Buser, the typical phenotype of LVNC. O. Pfister (Basel, CH) Results: After diagnosis of isolated LVNC in a 28-year old woman Background: Measurement of high sensitive troponin T her 3 daughters were referred to our center for the purpose of (hs tropT) enables the detection of low-level myocyte damage family screening. In all three daughters isolated diverticula within in various cardiac diseases.The diagnostic value of hs tropT to the left ventricular myocardium were found but none of the predict cardiac allograft rejection in long-term cardiac transplant daughters fulfilled the diagnostic criteria for LVNC. survivors remains unknown. Echocardiographic images are shown in figure 1: Panel A: Methods: In a cohort of heart transplanted patients hs tropT 4-chamber view of the index case with typical findings of LVNC together and BMP was prospectively measured prior to

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endomyocardial biopsy (EMB) and correlated to the degree jirovecii pneumonia, an invasive pulmonary aspergillosis. Both of histological cardiac allograft rejection according to the were successfully treated with cotrimoxazole and voriconazole, International Society of Lung and Heart Transplantation respectively. A few weeks later she again presented with fever, classification 2004 (ISHLT). Mild cardiacra allog ft rejection was diffuse petechia and severe pancytopenia. CMV viremia had defined as ISHLT grade 1R (former ISHLT 1990: 1a, 1b, 2). increased up to 24.8 Mio copies/ml, despite treatment with A hs tropT value above 0.014µg/l was considered positive. ganciclovir (GCV). CMV genotype revealed point mutation of Results: From February to December 2010, 40 consecutive the UL97 gene (A504V) associated with high grade resistance biopsies were performed in 21 patients. Patients were 51.1 years to GCV. She was therefore switched to foscarnet. CMV DNA old and mean time after transplantation was 9.9 years. The decreased to a 1000–3000 copies/ml range after 2 months, but prevalence of coronary artery disease (transplant vasculopathy) severe renal dysfunction developed and therefore foscarnet was was 30%. In 36.5% (15/40) EMB showed no signs of cellular discontinued. CMV viremia increased again to 398`327 copies/ml. rejection (ISHLT 0), whereas in the remaining 62.5% (25/40) EMB Leflunomide, an immunosuppressive drug used in rheumatoid revealed mild allograft rejection (ISHLT 1R). Overall, no moderate arthritis which is known to show activity against CMV, was (ISHLT 2R) or severe rejection (ISHLT 3R) was detected. Hs administered on a compassionate basis.Afew weeks later serum TropT was positive in 52.5% (21/40) of EMBs. In the absence of CMV DNA fell and remained stable, ranging between 3000–4000 rejection (ISHLT 0), hs tropT was positive in 53.3% (8/15) with a copies/ml. median value of 0.0345 µg/l (± 0.0280 interquartile range). In mild In conclusion, the additional immunosuppression that results from cellular rejection (ISHLT 1R), hs tropT was positive in 52% (13/25) CMV infection can place a patient at an increased risk for fungal with a median value of 0.0340 µg/l (±0.0035 interquartile range). and other opportunistic infections as demonstrated in this case. There was no significant correlation between positive hs tropT GCV-resistant-CMV is relatively rare but constitutes a challenge and ISHLT rejection status, serum creatinine or history of when the immune system is unable to control CMV-replication transplant vasculopathy. There was, however, a strong trend after transplantation. The experience in the use of Leflunomide in towards higher BNP values in patients with pos hs tropT the treatment of complex CMV syndromes is limited to casuistics, (p = 0.052). but may well expand its utility with broader application in future. Conclusion: There is no association between positive hs tropT and the grade of cardiac allograft rejection in long term cardiac transplant survivors. In particular, negative hs trop T does not P256 rule out mild cardiac rejection. Thus, hs tropT has no value in the Feasibility and safety of intramyocardial injection long-term management of transplanted patients and guidance using the myostar NOGA catheter in a sheep model of EMB. of myocardial infarction S. Perruchoud, D. Locca, E. Pruvot, P. Ruchat, I. Plaisance, P255 C. Gonzales, E. Eeckhout, I. Agarkova, T. Pedrazzini (Lausanne, CH) Walking the fine line in a patient with ganciclovir- resistant cytomegalovirus infection after stem cell Background/objective: The main goal of this study was to and heart transplantation develop a large animal model of myocardial infarction (MI) that would be suitable for assessing the potential of replacement C. Bösch, C. Garzoni, M. Martinelli, E. Negri, P. Mohacsi cell therapy for heart disease. Furthermore, we evaluated the (Bern, Frutigen, CH) feasibility to deliver injectable material using the NOGA cardiac Cytomegalovirus (CMV) infection remains one of the most navigation and injection system. In particular, the feasibility common complications affecting organ transplant recipients and and safety of LV mapping and intramyocardial injection was increases morbidity and mortality in terms of acute and/or chronic determined. Finally, we validated the use of tracing beads (TB) graft injury and dysfunction, as well as CMV-disease with organ to label the injection sites in order to facilitate cell tracking in manifestation. We report the case of a 56-year-old female with future experiments. restrictive cardiomyopathy secondary to systemic AL amyloidosis Materiels and methods: MI was produced in sheep by who received an autologous stem cell transplant and one year introducing a thrombogenic coil in a marginal branch of the left later orthotopic heart transplant. Due to high-risk constellation coronary artery.After stabilization, vascular access was provided for CMV (donor+/ recipient-) she received a 3 month course via the right carotid artery. LV mapping was performed and 0.2 ml of antiviral prophylaxis with valganciclovir (VGCV). One year of NaCl 0.9% containing 0.03% TB (Fluospheres®) were injected later she presented with fatigue, fever and myalgia. Acute in the free wall in 3 different sites.The animals experienced no cytomegalovirus syndrome was diagnosed with positive viral load major arrhythmias. Hearts were harvested at one and five weeks testing by PCR (CMV DNA of 33951 copies/ml) and treatment after injection. The whole myocardium was cut in 1 cm3-pieces was initiated with VGCV. Due to leucopenia and thrombocytopenia and fixed in embedding medium. Myocardium near the assumed treatment dose of VGCV intermittently required reduction. One injection sites was histologically analyzed for the presence of TB. month later she again returned with fever and chills. Further Results: Transthoracic echocardiography confirmed the presence extensive examinations revealed, apart from Pneumocystis of an akinetic anterior area after MI. The animals were stable for more than a year after MI. Mapping was readily achieved, showing the presence of anterolateral and anteroapical scar.TB were localized by microscopic examination in the expected area. Conclusions: A successful endovascular MI procedure was established in sheep leading to a chronic MI model. LV mapping and intramyocardial injections using NOGA myostar catheter in this model were feasible and safe. Injections sites were found at the expected location and facilitated by the presence of TB.These preliminary results highlight the interest of a sheep model of chronic MI for cardiac regenerative therapy.

P257 HeartWare left ventricular assist device: first clinical use at Berne, Switzerland M. Martinelli, L. Englberger, C. Bösch, E. Gygax, M. Stalder, P. Mohacsi (Bern, CH) Background: Continuous flow ventricular assist devices (VAD) have gained significant therapeutic importance in terminal heart failure (HF) since the clinical introduction of the 2nd Generation VAD HeartMate II. Further development of VADs targets long term support based on device durability, better survival with lower

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morbidity, patients (pts) VAD tolerance and better quality of life all information including coronary angiography. Findings (QoL). With such kind of VADs, outpatient management started to were validated in a second independent multicenter cohort be true reality. These VADs are still mainly used as bridge to (326 AHF patients, validation cohort). transplant. Outcome data are promising that in selected pts they Results: Among the 718 patients, 400 (56%) were adjudicated may become a real long-term alternative to hardly available heart to have ischemic AHF. BNP levels were significantly higher in transplantation (HTx). 2 selected pts received the smallest ischemic compared to non-ischemic AHF (median, 1097 pg/ml available permanent LVAD, the HeartWare Ventricular Assist [IQR 604–1525 pg/ml] vs median, 800 pg/ml [IQR 427–1317 pg/ Device (HVAD) as bridge to candidacy. Due to its magnetically ml], p <0.001). CTnT and s-cTnI were also significantly higher in levitated impeller, the miniaturized pump system offers better ischemic compared to non-ischemic AHF patients (median, device durability, less thrombogenicity and better pt comfort for 0.040 ug/L [IQR 0.010–0.306 ug/L] vs median, 0.018 ug/L [IQR individuals with lower body surface area. Keys for successful 0.010–0.060 ug/L], p <0.001; median, 0.024 ug/L [IQR 0.008– LVAD support are assessment of the INTERMACS-level, risk 0.106 ug/L] vs median, 0.016 ug/L [IQR 0.004–0.044 ug/L], stratification for RV Function, likelihood of restoration of vital p = 0.002). The diagnostic accuracy of BNP, cTnT and s-cTnI for organ function and patients understanding and willingness for the diagnosis of ischemic AHF as quantified by the area under VAD therapy as bridging (or destination) therapy. The first pt we the receiver operating characteristic curve (AUC) was low (AUC considered HVAD as bridge to candidacy indication was a 59 0.57, 95% Confidence interval (CI) 0.51–0.63; AUC 0.58, 95% CI year old woman with low body surface area (1.38 m²), post-CABG 0.52–0.64; AUC 0.61, 95% CI 0.54–0.67). These findings were and narrow intrathoracic space.After long standing mitral confirmed in the validation cohort. insufficiency she had “fixed” pulmonary hypertension (PHT) and Conclusions: At presentation to the ED, patients with ischemic HF NYHA Class IV.The second pt was a 69 year old man, AHF exhibit more extensive hemodynamic cardiac stress and suffering from end stage ischemic heart disease with advanced cardiomyocyte necrosis than patients with non-ischemic AHF. renal failure, mitral and tricuspidal regurgitation with 2° PHT and However, the overlap is substantial resulting in poor diagnostic NYHA III. RV function was moderately reduced. Not foreseeing accuracy. how post-implant performance will develop (renal failure, advanced age) we chose HVAD to offer him the comfort of a miniaturized device with promising durability and simplified P259 patient handling. Peri-/postoperative course: Both of our pts Chronic hypoxaemia and acute exercise-induced needed an attentive follow up. Main issues where changes in oxygenation do not have a clinically pharmacological RV support, optimization of volemia, renal relevant impact on circulating concentrations function, anticoagulation, wound & driveline care, infection of B-type natriuretic peptides management and patient instruction. After 3 to 4 weeks pts stabilized to proceed to outpatient care. Both pts had a M. Zurek, M.T. Maeder, M.H. Brutsche, C. Mueller remarkable amelioration of physical and psychical capacity, renal (Burgdorf, St. Gallen, Basel, CH) function and quality of life. Introduction: Experimental data indicate that hypoxia is a potent Conclusions: After having had severe HF, HVAD improved stimulus for myocardial release of B-type natriuretic peptide markedly both pts leading to reversed PHT and now eligible for (BNP). However, the existence of a significant association HTx. between hypoxaemia and BNP release in humans in vivo would critically challenge the role of BNP and the N-terminal part of its precursor peptide proBNP (NT-proBNP) as biomarkers for the P258 differentiation between cardiac and pulmonary causes of Quantifying cardiac haemodynamic stress and dyspnoea in patients presenting with acute shortness of breath. cardiomyocyte necrosis in ischaemic and non- Accordingly, the aim of the present study was to assess the ischaemic acute heart failure relationship between the partial pressure of arterial oxygen (PaO_2) and natriuretic peptide concentrations and the impact B. Drexler, C. Heinisch, C. Balmelli, J. Lassus, K. Siirilä-Waris, of acute exercise-induced changes in PaO_2 on circulating N. Arenja, T. Socrates, M. Noveanu, M. Potocki, C. Meune, natriuretic peptide concentrations. P. Haaf, T. Breidthardt, T. Reichlin, M. Nieminen, H. Veli-Pekka, Methods: In 157 consecutive patients with a broad range of S. Osswald, C. Müller (Basel, CH; Helsinki, FI; Paris, FR) cardiac and pulmonary function undergoing cardiopulmonary Background: The early and non-invasive differentiation of exercise testing for the evaluation of exercise intolerance (mean ischemic and non-ischemic acute heart failure (AHF) in the age 56 ± 15 years, 59% males), BNP, NT-proBNP, and PaO_2 Emergency Department (ED) is an unmet clinical need. were measured at rest and at peak exercise. Methods: We quantified cardiac hemodynamic stress using Results: Forty-nine patients had chronic hypoxaemia (defined as B-type natriuretic peptide (BNP) and cardiomyocyte necrosis PaO_2 below 10 kPa). There was no significant difference using two different cardiac troponin assays (cTnT, Roche, fourth between median (interquartile range) resting BNP [45(23-103) vs generation and sensitive cTnI (s-cTnI), Abbott-Architect) in 718 41(15-119) ng/L; p = 0.81] and NT-pro BNP [129(60-287) vs consecutive patients presenting to the ED with AHF (derivation 80(27-276) ng/L; p = 0.97] plasma concentration in patients with cohort). The diagnosis of ischemic AHF was adjudicated using hypoxaemia as compared with those without. There was no significant correlation between PaO_2 and BNP (r2 = 0.013) and NT-proBNP (r2 = 0.024) at rest. In addition, peak exercise BNP [60(28-127) vs 50(23-128) ng/L; p = 0.88] and NT-pro BNP [130(58-298) vs 87(32-276) ng/L; p = 0.94] plasma concentrations did not differ between patients with and without hypoxia at rest. There was no significant correlation between exercise-induced changes in PaO_2 and changes in BNP (r2 = 0.001) and NT-proBNP (r2 = 0.007) either. Conclusions: Among patients referred for cardiopulmonary exercise testing for evaluation of exercise intolerance, chronic hypoxaemia and exercise induced changes in PaO_2 are not associated with plasma concentrations of natriuretic peptides at rest and changes during exercise indicating that the spectrum of hypoxemia typically observed in practice is unlikely to affect plasma concentrations of natriuretic peptides in a clinically relevant manner.These findings strengthen the role of natriuretic peptides for the differentiation of cardiac versus non-cardiac including pulmonary causes of dyspnoea.

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P260 P261 The impact of anaemia on long-term clinical outcome The impact of blood transfusions on long-term in patients undergoing percutaneous coronary clinical outcome in patients undergoing intervention percutaneous coronary intervention T. Pilgrim, F. Vetterli, L. Räber, R. Binder, P. Wenaweser, T. Pilgrim, L. Räber, F. Vetterli, R. Binder, P. Wenaweser, A. Moschovitis, A. Khattab, L. Büllesfeld, R. Vogel, C. Seiler, A. Moschovitis, A. Khattab, L. Büllesfeld, R. Vogel, B. Meier, S. Windecker (Bern, CH) C. Seiler, B. Meier, S. Windecker (Bern, CH) Aims: There is conflicting evidence regarding the impact of Aims: Anemia is commonly encountered in patients with transfusion of packed red blood cells (PRBC) for anemia. We cardiovascular disease and has been associated with an adverse determined the incidence of peri-procedural transfusion of prognosis in patients undergoing PCI for coronary artery disease. PRBC in patients undergoing PCI with drug-eluting stents and We assessed the incidence of pre-procedural anemia in a investigated their impact on long-term survival. real-world setting of unselected patients undergoing PCI with Methods and results: We performed a retrospective analysis drug-eluting stents and investigated its impact on long-term of prospectively collected data from 6535 consecutive patients survival. undergoing PCI with drug-eluting stents between April 2002 Methods and results: We performed a retrospective analysis and March 2009. Laboratory values during hospitalization and of prospectively collected data from 6535 consecutive patients information on transfusion of blood products during the index undergoing PCI with drug-eluting stents between April 2002 hospitalization were retrieved from the local central hematology and March 2009. Follow-up was performed yearly with specific laboratory. Follow-up was performed yearly with specific questions addressing repeat hospital stay and major adverse questions addressing repeat hospital stay and major adverse cardiac events (MACE). Laboratory values were available in 6322 cardiac events (MACE). Laboratory values were available in 6322 patients (96.7%). After exclusion of 78 patients (1.2%) due to loss patients (96.7%). After exclusion of 78 patients (1.2%) due to to follow-up, a total of 6244 patients remained and were analyzed loss of follow-up, a total of 6244 patients were analyzed for the for the purpose of this study.The median and mean duration of purpose of this study.Transfusion of PRBCs occurred in 4.1% follow-up in this study cohort amounted to 1021 and 1010 days, of the overall patient population with a higher incidence in respectively. Anemia as defined by the WHO definition was patients with ACS (4.6% vs. 3.5%; p = 0.02). Patients receiving encountered in 21.7% of the patients with a significantly higher blood transfusions were older (p <0.001), more commonly female prevalence in patients with acute coronary syndromes (ACS) as (p <0.001), had a higher prevalence of renal insufficiency compared to patients with stable coronary artery disease (24.5% (p <0.001) and reduced left ventricular function (p <0.001), and vs. 18.6%; p <0.001). The overall patient population was divided more commonly presented with ACS at baseline (p = 0.016). in five categories based on hemoglobin values at baseline with All-cause death and myocardial infarction at one year occurred 20 g/l increments. Patients with lower hemoglobin levels on more frequently in patients receiving blood transfusions (27.5% admission were older, more commonly female, had a higher rate versus 5.8%, p <0.001). A stratified analysis of patients receiving of renal insufficiency and decreased systolic left ventricular blood transfusions by nadir hematocrit values demonstrated function, and presented more frequently with acute coronary more than doubling of the adverse events in patients with a nadir syndromes (p <0.001). The rate of all-cause death and non-fatal hematocrit level <25% and PRBC transfusion as compared to myocardial infarction was significantly higher among patients with the patient cohort with no transfusion (13.3% versus 5.1% for hemoglobin values on admission <100 g/l (25.2%) compared to Htc >30%, p = 0.01; and 37.3% versus 16.6% for Htc 26-30%, those with hemoglobin values ranging from 100 to 119 g/l (12.5%) respectively). In contrast, there was no significant difference and those with values ranging from 120 to 139 g/l (p <0.001). between patients with a nadir hematocrit ≤25% receiving PRBC Crude long-term survival without adjustment for baseline and those not receiving PRBC (28.7% versus 24.3%, p = 0.39). characteristics showed a steady decline up to four years that Long-term outcome was characterized by a steady decline of was most pronounced among patients in the lowest hemoglobin survival among patients who reveived >1 PRBC during PCI as category (4-year survival 60% in patients with hemoglobin compared to patients with no blood transfusion (65% versus values <100 g/l). This finding was maintained after adjustment 90% after 4 years). for baseline characteristics using a cox regression analysis. Conclusion: Blood transfusions were associated with impaired Conclusion: Anemia at baseline occurred in up to one quarter survival in this unselected patient population undergoing PCI in of patients and was associated with impaired survival in this the drug-eluting stent era, particularly among patients with a nadir unselected patient population undergoing PCI in the drug-eluting hematocrit less than 25%. stent era.

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P262 P263 The SYNTAX score predicts clinical outcomes in 5-years safety and efficacy data of the first the elderly with acute coronary syndrome treated progenitor cell based feasibility study in Switzerland with primary percutaneous coronary intervention – STIM F. Scherff, G. Vassalli, D. Sürder, A. Mantovani, C. Corbacelli, D. Sürder, G. Soldati, M. Gola, L. Ceriani, C. Crljenica, E. Pasotti, C. Klersy, A. Auricchio, T. Moccetti, G.B. Pedrazzini G. Astori, F. Faletra, M.G. Rossi, G.B. Pedrazzini, E. Pasotti, (Lugano, CH; Pavia, IT) T. Moccetti (Lugano, CH) Background: The SYNTAX score (SXscore), a comprehensive In 2002 the first in human administration of autologous bone angiographic scoring system based solely on the coronary marrow mononucleated cells (BM-MNC) after acute myocardial anatomy and lesion characteristics, has recently been shown to infarction (AMI) has been performed and recent randomized predict clinical outcomes in patients with left main or multivessel studies report that this therapy may improve remodelling of the disease, and in an all-comers population of patients undergoing left ventricle after the ischemic event. Stem cells Transplantation PCI. However, this score is not currently validated in patients wih in Ischemic Myocardium (STIM) is the first BM-MNC based myocardial infarction. The clinical SXscore (CSS) is calculated by prospective feasibility study in Switzerland and started in 2004. multiplying the SXscore to a modified ACEF score (age/ejection Study population: Patients with anterior AMI, successfully fraction +1 for each 10 mL the creatinine clearance <60 mL/min treated by percutaneous coronary intervention of the infarct- per 1. 73 m2). Here, we aimed to assess the predictive value of related artery (IRA) and left ventricular ejection fraction (LVEF) the SXscore and CSS in the elderly with acute coronary <50%. syndrome (ACS) treated with primary PCI. Methods: Methods: The SXscore was determined in a consecutive series – Aspiration of 50 ml bone marrow from the iliac crest. of 114 patients aged 73 or older treated with primary PCI for ACS – Isolation of the mononucleated cell fraction in the in-house cell at our institution during 2007–2008. Post-hoc analysis included processing facility by density gradient centrifugation. stratification of clinical outcomes atys 30da and post-discharge – Washing and resuspension of the BM-MNC in 10 ml 5% human outcomes at 1-year, according to 1 of 3 SXscore tertiles. albumin. Results: The 114 patients were subdivided into tertiles based on – Reinfusion of the BM-MNC in the IRA within an average the SXscore or CSS. Death rates at 30 days were higher in the of 2.7 days after AMI. highest tertile of SXscore (37% vs. 5%; p <0.001) or CSS (27.0% – Clinical and echocardiographical follow-up at day 0, 21, vs. 1. 4%; p <0.0001) compared with the lowest and intermediate at 4,12 months, 2,3,4 and 5 years after AMI tertiles as an aggregate group.The area under the curve-receiver – Safety and feasibility as 1° endpoint. operating characteristic (AUC-ROC) values were 0.77 and 0.82, Results: 23 patients (78% male, average age 55 ± 10 years) respectively, indicating high discriminatory power of the scores. have been successfully treated with intracoronary BM-MNC Rates of nonfatal major adverse cardiac/cerebrovascular events administration without any short-term periprocedural (MACCE) at 30 days were not different in the highest tertile of complications. LVEF raised from 41.5 ± 6.9% (mean ± SD) directly the SXscore compared with lower tertiles (5.7% vs. 3.8%; NS) after AMI (n = 23), to 48.5 ± 11.9%; at 4 months and respectively but were increased in the highest tertile of CSS (11. 8% vs. 1. 4%; to 50.6 ± 12.5% at 1 year. Left ventricular function remained then p = 0.026). In 30-day survivors, post-discharge death and MACCE stable along with the entire follow up: Mean LVEF at 2 years was rates at 1 year were not different among tertiles of SXscore but MACCE rates were increased in the highest tertile of CSS (12.1% vs. 3.1%; p = 0.03). MACCE-free survival curves for the highest vs. intermediate and lowest tertiles of SXscore are shown in the Figure. Conclusions: Our data demonstrate that both the SXscore and CSS have predictive value for short-term outcomes in the elderly with ACS treated with primary PCI. In addition, the CSS has predictive value for long-term MACCE rates post-discharge, reflecting the impact of comorbidities.Thus, the SXscore as a merely angiographic scoring system predicts risk in the specific subpopulation of old ACS patients treated with primary PCI.

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49.0 ± 11.1% (n = 22), at 3 years 49.7 ± 11.7% (n = 21) at 4 years 38%, and anatomical variants in 46%. Mean DAP of CA 51.4 ± 12.3% (n = 21) and at 5 years 49.4 ± 11.5% (n = 21). The decreased significantly with increasing operator`s experience improvement in LVEF could have been confirmed by the less (cases 1–100 vs. cases >200: 88.1 ± 42.9 Gy/cm2 vs. 67.3 ± 28.6 operator dependent G-SPECT analysis with a baseline LVEF Gy/cm2, p <0.05) but remained significantly higher than in of 41.0 ± 11.6% and a subsequent 7. 9% improvement to 48.9 ± transfemoral CA (50.2 ± 33.1Gy/cm2, p <0.05 vs. cases >200). 11.9% at 4 months. Furthermore G-SPECT analysis demonstrated Mean FT showed a similar decrease (7.6 ± 5.2min vs. 5.0 ± 2.0 a significant reduction of infarct size from 30.1 ± 13.5 % to min, p <0.05) but tended to remain higher compared with 20.1 ± 14.7%, an improvement of the SRS from 24.4 ± 11.2 % transfemoral CA (3.9 ± 3.3min, p = ns), whereas mean CV to 16.8 ± 13.4% as well as and improvement in SMS from 32.3 ± showed no significant decrease (122 ± 40. mlvs 112 ± 25 ml, 15.3% to 19.9 ± 15.9% and STS from 22.0 ± 10.2 % to 13.5 ± p = ns) and was similar to transfemoral CA (112 ± 33 ml, p = ns). 10.6%. Overall survival was 91% (n = 21) at 5 years. Among the Transradial PCI was attempted in 257 cases and successful in surviving population, no long-term complications such as cardiac 238 (93%). In patients undergoing transradial PCI mean DAP, FT, or non-cardiac tumor formation have been notified. and CV did not significantly decrease with increasing operator Discussion: Intracoronary treatment with BM-MNC after AMI is experience. However, compared with transfemoral PCI mean DAP feasible and seems to be safe in terms of short-term complication and FT tended to be higher in the transradial PCI population. rate as well as in terms of long-term patient safety. Transradial CA/PCI was not associated with any clinically relevant complication. Conclusion: The transradial approach represents an effective P264 and safe alternative to the transfemoral approach for routine CA/ Sealing pseudo-aneurysms of the femoral artery PCI. However, even in experienced operators performance of with saline injection – A new technique the transradial approach is associated with a significant learning curve. Moreover, transradial CA/PCI appears to be associated D. Périard, M.-A. Rey Meyer, D. Hayoz, S. Cook (Fribourg, CH) with a higher radiation exposure than transfemoral CA/PCI. Introduction: Pseudo-aneurysm (PA) of the femoral artery is the most frequent complication after diagnostic or therapeutic catheterization. PA usually manifests with large and painful P266 hematoma that might compress adjacent nerves and vein. Median levels and 99th percentiles of high-sensitive Among several therapeutic approaches, compression by injection troponin T in different groups of chest pain patients of saline around the neck is a recent and promising method. in the emergency department Aim: To explore compression with saline as an alternative treatment for iatrogenic femoral artery PA. T. Reichlin, R. Twerenbold, M. Reiter, S. Steuer, M. Potocki, Methods: From December 2009 to January 2011, all consecutive P. Haaf, S. Osswald, C. Mueller (Basel, Zürich, CH) patients with symptomatic PA were included in this study.After Background: The 99th percentile of troponin in healthy ultrasonic assessment, the PA neck was occluded by injection individuals has been defined as decision limit for the diagnosis of saline/lidocaïne (0.2%) mixture in the soft tissue at its vicinity, of acute myocardial infarction (AMI) in current guidelines.The followed by a short echo-guided compression. Outcome was median levels and 99th percentiles of troponin in different groups assessed at 1 and 30 days by duplex sonography. of patients presenting with chest pain in the real world however Results: Eleven patients with PA requiring immediate treatment are unknown. The introduction of sensitive troponin assays allows were included. All patients had at least one PA cavity. Besides, the accurate determination of median levels and 99th percentiles 4 patients had multiple pulsatile cavities and 7 patients had large of troponin in these patient groups. groin or abdominal hematoma, with either active bleeding, Methods: In a prospective, international multicenter study, compression of adjacent organ or hypotension. Three patients high-sensitive cardiac troponin T (hs-cTnT) was measured at had very short PA neck (table). The mean injected volume was admission in 1181 patients presenting to the emergency 47 ± 11 ml. The mean compression time until PA was closed was department with chest pain. The final diagnosis was adjudicated 6 ± 3 minutes.At 1 and 30 days, all PA remained occluded without by two independent cardiologists using all available medical any complication related to the procedure. records pertaining to the patient. The 99th percentile of the Conclusion: Saline injection to seal PA is feasible, safe and very hs-cTnT assay in healthy individuals is 14 ng/l. effective. The technique is rapid and well tolerated, and allows Results: The adjudicated final diagnosis was AMI in 187 patients – after a limited training – to close very large PA, even in case of (16%), unstable angina in 164 patients (14%), cardiac symptoms emergency. This new technique is more comfortable for the of origin other than coronary artery disease in 155 patients (13%), patient and the operator, and surely more economical than non-cardiac symptoms in 572 patients (48%), and symptoms of thrombin injection or surgical arterial suture. unknown origin in 103 patients (9%). Median levels of hs-cTnT at admission in these diagnostic groups were 115 ng/l, 11 ng/l, 13 ng/l, 6 ng/l and 9 ng/l, while the 99th percentile of hs-cTnT P265 observed in these groups were 5195 ng/l, 157 ng/l, 310 ng/l, First experience with the transradial approach 50 ng/l and 248 ng/l (p <0.001 for comparison). for routine coronary angiography and intervention in a Swiss moderate volume centre R. Nägele, P. Müller, K. Mayer, S. Schneiter, P. Bonetti (Chur, CH) Introduction: Transradial approach for coronary angiography (CA) and percutaneous coronary intervention (PCI) is associated with a low risk of complications and, thus, has emerged as an attractive alternative to the transfemoral approach. Currently, the transradial approach is rarely used in Switzerland. We sought to assess the feasibility, the learning curve and the limitations of routine transradial CA/PCI in a Swiss moderate volume center. Methods: After a dedicated 2-day training in a high volume center of excellence, 2 experienced operators started performing transradial CA/PCI at the Kantonsspital Graubuenden in July 2007. Patients with abnormal modified Allen test, prior coronary artery bypass surgery and renal failure were excluded. Dose area product (DAP), fluoroscopy time (FT) and contrast volume (CV) were collected and compared with data of patients undergoing transfemoral CA/PCI by the same operators during the same time period. Results: Transradial approach CA was attempted in 580 cases and was successful in 528 (91%). Reasons for transradial approach failure were puncture failure in 15%, arterial spasm in

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Conclusion: Real world chest pain patients, regardless of the absolute (Delta) change was 0.007 ug/l for hs-cTnT and 0.020 µg/l underlying cardiac or non-cardiac disease, have markedly higher for cTnI (both cut-off levels are roughly half of the 99th percentile levels of hs-cTnT compared to the reference values measured in of the respective cTn assay). Absolute changes were superior to healthy individuals. In especial, the 99th percentile of hs-cTnT in relative changes both in patients with low and elevated baseline non-cardiac chest pain patients is more than 3 times higher than cTn levels. the 99th percentile in healthy individuals, which is currently Conclusion: Absolute changes of cTn levels have a significantly recommended as decision limit in the diagnosis of AMI. These higher diagnostic accuracy for AMI than relative changes and observations are important when assessing chest pain patients seem therefore to be the preferred criteria to distinguish AMI in daily practice. from other causes of cTn elevations.

P268 Growth-differentiation factor-15 in the early diagnosis and risk stratification of acute chest pain T. Reichlin, N. Schaub, R. Twerenbold, J. Meissner, B. Drexler, S. Steuer, M. Noveanu, S. Osswald, C. Müller (Basel, Zürich, CH) Background: Growth-differentiation factor-15 (GDF-15) is a stress-responsive marker that might aid in the early diagnosis and risk-stratification in patients with suspected acute myocardial infarction (AMI). Methods: In a prospective, international multicenter study, GDF-15 and high sensitive cardiac troponin (hs-cTnT) were measured in 646 unselected patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists. Patients were followed long-term regarding mortality. Results: Acute myocardial infarction (AMI) was the adjudicated final diagnosis in 115 patients (18%). GDF-15 levels at P267 presentation were significantly higher in AMI as compared to patients with other diagnoses (median 1910 ng/l vs. 1110 ng/ml, Utility of absolute and relative changes in cardiac p <0.001). The diagnostic accuracy of GDF-15 at presentation for troponin concentrations in the early diagnosis the diagnosis of AMI as quantified by the area under the receiver of acute myocardial infarction operating characteristic curve (AUC) (0.69 (95% confidence T. Reichlin, A. Irfan, R. Twerenbold, M. Reiter, S. Steuer, interval (CI) 0.64–0.74) was lower compared to hs-cTnT at J. Meissner, S. Osswald, C. Mueller (Basel, Zürich, CH) presentation (AUC 0.96, 95% CI 0.94–0.98, p <0.001 for Background: Current guidelines for the diagnosis of acute myocardial infarction (AMI) require, among other criteria, a rise and/or fall in cardiac troponin (cTn) levels. It is unknown whether absolute or relative changes in cTn have higher diagnostic accuracy und should therefore be preferred. Methods: In a prospective observational multicenter study, we analyzed the diagnostic accuracy of absolute (Delta) and relative (Delta%) changes in cTn in 850 patients presenting to the emergency department with symptoms suggestive of AMI. Blood samples for the determination of high sensitive cardiac troponin T (hs-cTnT) and cardiac troponin I ultra (cTnI) were collected at presentation and after 1 and 2 hours in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Results: The area under the receiver operating characteristic curve (AUC) for diagnosing AMI was significantly higher for 2-hour absolute (Delta) vs. 2-hour relative (Delta%) cTn changes (AUC [95% Confidence Interval], hs-cTnT: 0.95 (0.92–0.98) vs 0.78 (0.71–0.84), p <0.001; cTnI: 0.95 (0.92–0.99) vs 0.73 (0.67–0.80), p <0.001). The ROC derived cut off value for 2-hour

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comparison). Cumulative 24-month mortality rates were 0.7%, Results: PCI due to myocardial infarction represented 0.0005% 6.3% and 21.1% in patients with normal (<1200 ng/l), moderately of all interventions performed during that time period. Mean age elevated (1200–1800 ng/l) and markedly elevated (>1800 ng/l) was 26.6 y ± 3.6 y and 82.1% (n = 23) of events occurred in men. levels of GDF-15 at admission (p <0.001). GDF-15 predicted Current smoking (82.1%) and a positive family history (46.4%) all-cause mortality independently of and more accurately than were the most frequent risk factors. 3 patients (10.7%) had hs-cTnT (AUC 0.85 (95% CI 0.81–0.90) vs.AUC 0.77 (95% CI undergone prior PCI for an acute MI. The most common 0.72–0.83), p = 0.04). Net reclassification improvement was 0.18 presenting symptom was retrosternal chest pain (85.7%) and (p = 0.002), the absolute integrated discrimination improvement STEMI was encountered in 64.3% of patients.The left anterior (IDI) was 0.06, yielding a relative IDI of 0.44 (p = 0.04). descending artery was involved in 67.9% of cases and the Conclusions: GDF-15 predicts mortality in unselected patients culprit lesion showed a mean degree of stenosis of 90.9%. with acute chest pain independently of and more accurately than Revascularization by PCI was performed in 20 patients (71.4%) hs-cTnT, but does not seem to help in the early diagnosis of AMI. of whom 14 (50%) were stented. MI could be linked to an underlying condition in 11 patients which was as follows: Kawasaki 3.6% (n = 1), PFO 3.6% (n = 1), hereditary P269 thrombophilia 14.3% (n = 4), familial mediteranean fever 3.6% Are bare-metal stents still a valid option in stenting (n = 1), septic embolism from endocarditis 3.6% (n = 1), cocaine of large coronary arteries? consumption 7. 1% (n = 2) and antiphospholipid antibody syndrome 3.6% (n = 1). Inhospital adverse events occurred in C. Kaiser, S. Galatius, P. Erne, F. R. Eberli, H. Alber, H. Rickli, 3 patients of whom 2 suffered from stent thrombosis.At 5 years G.B. Pedrazzini, B. Hornig, W. Kiowski, P. Bonetti, S. De Servi, only 2 patients had died – both from cardiac death. The M. Pfisterer for the BASKET-PROVE-Investigators secondary end point was achieved by 14.3% of the sample Background: Bare-metal stents (BMS) are often used in large at 5 years. vessel stenting in daily practice because the cost-effectiveness Conclusion: Myocardial infarction in young patients is an of drug-eluting stents (DES) is not proven here. However, data uncommon condition with a variety of possible aetiologies and of dedicated trials comparing DES with BMS in large coronary distinct risk factors. In-hospital and 5-year clinical outcome is arteries are lacking. excellent. Methods: To address this question, we compared the clinical outcomes of the BMS and the two DES arms of the BASKET- PROVE trial. In this prospective multicenter trial, 2314 patients in P271 need of large (≥3.0) vessel stenting were randomized irrespective Cost evaluation of cardiac magnetic resonance of indication 2:1 to DES (sirolimus- or everolimus-eluting 1:1) imaging versus coronary angiography for the versus BMS (Vision). The primary endpoint was the 2-year rate of work-up of coronary artery disease death from cardiac causes or nonfatal myocardial infarction, with target-vessel revascularization and major adverse cardiac events K. Moschetti, C. Pinget, S. Muzzarelli, O. Bruder, (MACE) as secondary endpoints. H. Mahrholdt, J. Schwitter (Lausanne, CH; Essen, DE) Results: Baseline variables were not different between 1549 DES Background: Among tests used to detect ischemia in patients and 765 BMS patients; 36% presented with stable, 33% with with known or suspected coronary artery disease (CAD), Cardiac unstable angina and 32% with acute infarction. After 2 years, the Magnetic Resonance (CMR) has recently emerged as a robust rate of death from cardiac causes or nonfatal myocardial infarction and reliable technique. Recent outcome studies demonstrated was lower in DES vs BMS patients (2.9% vs 4.8%, p <0.05). event rates as low as 0.3–0.5%/year in patients with a negative In addition, the use of DES reduced the target-vessel perfusion CMR test. Thus, CMR is increasingly used in daily revascularization rate (4.0% vs 10.3%, p <0.001) resulting in a routine in many sites. Nevertheless, invasive coronary lower MACE rate (7.7% vs 12.9%, p <0.001) compared to BMS. angiography (CA) remains the “gold standard” for the evaluation The benefits of DES were similar in both types of DES of CAD in most countries.This study focuses on two strategies investigated compared to BMS. for the work-up of known or suspected CAD: 1) a coronary Conclusions: Since DES showed superior efficacy and safety angiography to all patients or 2) a coronary angiography only to in a broad spectrum of patients in need of large coronary artery patients who are diagnosed positive for ischemia in a prior CMR. stenting, traditional BMS should be replaced by DES in these Objective: Assessing the costs of the two strategies for the situations. However, in patients with contraindications to DES for work-up of known or suspected CAD from a health care payer increased bleeding risk or inability to follow at least 6 months of perspective in Switzerland. dual anti-platelet therapy, BMS are still an option. Method & results: Using data of the European Cardiovascular Magnetic Resonance registry (EuroCMR registry, 20 hospitals, 11040 consecutive patients) we calculated the proportion of P270 patients who were diagnosed positive (20.6%), uncertain (6.5%), Acute coronary syndrome in patients younger than and negative (72.9%) after the CMR test among a study group 30 years – Incidence, aetiologies, baseline composed of 2717 patients with known or suspected CAD. No characteristics and long-term clinical outcome other medical test was performed to patients who were negative for ischemia. Positive diagnosed patients had a coronary S. Puricel, C. Lehner, M. Oberhänsli, T. Rutz, M. Togni, angiography. Those with uncertain diagnosis had additional A. Moschovitis, B. Meier, P. Wenaweser, S. Windecker, tests (84.7% stress echocardiography, 13.1% cardiac CT, 2.3% J.-C. Stauffer, S. Cook (Fribourg, Bern, CH) SPECT), the costs of these were added to the CMR strategy Introduction: Data on acute coronary syndrome (ACS) in costs. Using information from our outpatient invoicing department, young individuals are limited. Advanced atherosclerotic disease the costs for the different tests were assessed. Assuming that CA is unlikely. Therefore, unusual causes might been found in this is an outpatient test, we found an average cost per patient of CHF particular population. Moreover, the clinical outcome of these 1985 for the CMR strategy and CHF 2580 for the CA strategy. patients is unknown. We wanted to investigate the incidence, Since CA may also be an inpatient test, a sensibility analysis was clinical and angiographic characteristics, and long-term clinical performed. In this latter case, the cost per patient amounts to outcome in young patients suffering from myocardial infarction CHF 2408 for the CMR strategy and to CHF 4638 for the CA (MI) and referred at our institutions. strategy. Methods: From 1994 to 2010, 27 patients who were treated for Discussion: The study shows that CMR strategy costs at least acute coronary syndrome (28 events) were retrieved from our 25% less than the CA one for the Swiss health insurance system. database and followed by phone or physician visit. Data collected While lower in costs, CMR strategy is a non-invasive one, does were demographics, risk factors, ACS type, angiographic data, not expose to radiation, and yields additional information on LV laboratory results, initial coronary revascularization strategy, in function, viability, and anatomy of valves and great vessels. hospital and 5-year follow-up.The primary endpoint was 5-year Developing the use of CMR instead of CA might imply reductions all-cause mortality. The secondary endpoint was a composite in costs together with superior patient safety and comfort, and a of cardiac death, myocardial infarction and any repeat better utilization of resources at the hospital level. revascularization. Descriptive analysis focussed on reporting incidence and underlying aetiology.

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P272 15.8%, p = 0.67) and in-segment binary restenosis (6.6% vs. Randomised controlled clinical trial of the use 8.0%, p = 0.82) in the complex group. of autologous bone marrow derived progenitor cells Conclusions: In this all-comers randomized trial, major adverse to salvage myocardium in patients with acute anterior cardiovascular events were more frequent among complex than myocardial infarction simple patients.The newer generation ZES and EES proved to be safe and effective regardless of complexity with similar clinical D. Locca, T. Burchell, A. Flett, C. Yeo, R. De Palma, C. Knight, and angiographic outcomes for both stent types through one year. J. Schwitter, M. Rothman, J. Martin, A. Mathur (Lausanne, CH; London, UK) Background: REGENERATE AMI is a first in man trial. This is P274 a Randomised Controlled Clinical Tr ial assessing the use of How to perform quality control in modern autologous bone marrow derived progenitor cells to salvage interventional cardiology myocardium in patients with acute anterior myocardial infarction. Cells/placebo are infused 4–8 hours following a successful M. Zipponi, G.B. Pedrazzini, D. Sürder, E. Pasotti, F. Bomio, primary percutaneous coronary intervention (PPCI). This early A. Del Bufalo, A. Gallino, M. Giacchi, S. Musto D’Amore, time frame compared to previous stem cell trial was chosen in A. Auricchio, T. Moccetti (Lugano, CH) order to replicate the large improvements seen in animal models. Introduction: Assuring quality control in interventional cardiology Method: The main inclusion criteria were successful treatment is necessary both for medical and for economic reasons. Starting with stent deployment in the left anterior descending artery within from January 2012, with the introduction of SwissDRG, it 24 hours of STEMI and moderate to severe anterior regional wall becomes more and more a political issue, because the hospitals motion abnormality on Left ventricle angiography. Bone marrow can be directly exposed to competition. Actually, in their annually aspiration harvesting (100 ml) was performed after successful report, 3 types of complications are assessed: in hospital death, PPCI. Ficoll-Plaque technique was used for bone marrow emergency CABG and myocardial infarction (MI) during elective mononuclear cell (BM-MNC) isolation. Intracoronary infusion of angioplasty (PCI). However, there isn’t any standardization in BM-MNC versus placebo was performed <8 hours post PPCI. assessing these data and other important complications are not Cardiac magnetic resonance imaging (CMR) was performed adressed. Data of iatrogenic complications are usually acquired at 24 hours and at 3 months following the index admission. on an anonymous or retrospective basis.As a result a lot of Result: To date 44 patients were randomised. All patients had important data get lost. We present a new, active and prospective bone marrow successfully harvested, isolated and infused within approach to acquire data of complications. a mean time of 5.5 hours (SD 2.1). No major adverse cardiac Methods: Since 2009 a person, which is not directly involved in events (MACE) associated with the harvesting or infusion the procedures, has been charged to acquire and manage data of procedures during either the inpatient stay or at 3 months follow complications, which are collected actively during a daily meeting. up were recorded. We are currently blinded regarding stem cell or These data are inserted into the official patient documentation, in placebo infusion. our case into the “Cardioreport” linking the assessed complication Conclusion: Bone marrow harvest and intra coronary infusion to patient’s history, name and age and indication for invasive are feasible and safe in acute STEMI. This preliminary analysis procedure. Multiple entries are possible. suggests that if intra coronary stem cell infusion or biological Results: In 2010 we executed 2195 coronarographies, 1111 of therapy in acute MI becomes a recognized treatment the route of these were PCI, in 210 cases for STEMI. Allover 63 complications administration, the very early timing of delivery and bone marrow have been registered: aspiration are technically feasible and safe. – In a total of 7 cases intrahospital death occured, in 1 case after elective coronary angiography due to acute thrombosis of the left main stem after catheter manipulation (mortality rate (MR) P273 0.05%) and in 6 patients with STEMI. The MR after STEMI is The impact of patient and lesion complexity on therefore 2.9%. clinical and angiographic outcomes following – The rate of MI after elective PCI as defined by guidelines is revascularization with zotarolimus-eluting and 1. 17% (13 patients) everolimus-eluting stents: a sub-study of the resolute – emergency CABG after elective PCI occured in 1 case (0.09%) all comers trial – TIA/stroke was found in 7 cases (0.32%), 3 of them were TIA, 4 stroke. G. Stefanini, P. W. Serruys, S. Silber, A. Khattab, – major bleeding occured in 9 cases (0.41%); 12 patients P. Wenaweser, B. Meier, S. Windecker developed pseudoaneurysm (0.55%) (Bern, CH; Rotterdam, NL; München, DE) Discussion: Aim: To investigate the impact of patient and lesion complexity 1. Assuring the quality control of invasive procedures in on outcomes with newer generation zotarolimus-eluting (ZES) Cardiology is necessary both for medical and for economic and everolimus-eluting stents (EES). reasons. Methods: Patients enrolled in the RESOLUTE All Comers trial 2. Actually, the assessment of the quality is not standardized and were stratified into “complex” and “simple”, according to a a fair comparison between different interventional centers may prespecified definition of complexity (at least one ofthe following not be guaranteed. features at presentation: acute myocardial infarction within 72 hrs, 3. Prospective and continuous acquisition of complications could left ventricular ejection fraction <30%, serum creatinine ≥140 help to standardize recording of quality related data. µmol/L, treatment of bifurcations, saphenous vein grafts, arterial 4. Our method is feasible and effective in recording such sensible grafts, in-stent restenosis, unprotected left main lesions, >2 data requiring for an open discussion of all involved cardiologists. vessels treated, lesion length >27 mm, >1 lesion per vessel, lesions with thrombus, or lesions with total occlusion). Results: Out of 2,292 patients, 1,520 (66.3%) patients were P275 complex and treated with ZES (N = 764) or EES (N = 756). Event Aspirin resistance in clinical practice. Results rates were higher among complex patients and results did not from the The Antiaggregation Monitoring Registry differ between ZES and EES regardless of complexity. At one year, target lesion failure was 8.9% in ZES and 9.7% in EES M. Oberhänsli, D. Goy-Eggenberger, S. Puricel, S. Lehmann, treated complex patients (p = 0.66), and 6.8% in ZES and 5.7% M. Togni, J.-C. Stauffer, J.-J. Goy, S. Cook (Fribourg, CH) in EES treated simple patients (p = 0.55). Rates of cardiac death Background: Aspirin is the cornerstone therapy for patients (1.3% vs. 2.2%, p = 0.24), target-vessel myocardial infarction suffering from ischemic heart disease. Several studies indicate (4.3% vs. 4.4%, p = 0.90) and clinically-indicated target lesion aspirin ‘resistance’ rates ranging from 1% to 61% depending on revascularization (4.4% vs. 4.0%, p = 0.80) were similar for both the platelet aggregation tests and patient subgroups. stent types among complex patients. Definite or probable stent Aspirin ‘resistance’ still lacks a definition but is probably best thrombosis occurred in 20 (1.3%) complex patients with no defined by an effective inhibition of the COX pathway, the target difference between ZES (1.7%) and EES (0.9%, p = 0.26). of aspirin. Platelet aggregation tests directly using the trigger Angiographic follow-up showed similar results for ZES and EES (arachidonic acid) or dosing the end-product of this pathway in terms of in-stent % diameter stenosis (22.2 ± 15.4% vs. 21.4 ± (thromboxane B2) may therefore have a good correlation with

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effective aspirin efficacy. Studies using these tests showed very might be useful in the early diagnosis and risk stratification of low rates of aspirin ‘resistance’. patients with acute chest pain. Hypothesis: aspirin ‘resistance’ is rare in patients followed at our Methods: In a prospective, international multicenter study, BNP outpatient clinic. was measured in 1075 unselected patients with acute chest pain. Method: All patients seen at our outpatient clinic over a 3 month The final diagnosis was adjudicated by two independent period and chronically on aspirin were included in this registry. cardiologists. Patients were followed long-term regarding mortality. The patients were not aware that they will be tested. Results: AMI was the adjudicated final diagnosis in 168 patients Antiaggregation (ASP test) was estimated by the means of the (16%). BNP levels at presentation were significantly higher in AMI Multiplate analyzer using electrical impedance aggregometry as compared to patients with other diagnoses (median 224 pg/ml and arachidonic acid as trigger (Dynabyte, Munich, Germany). vs. 56 pg/ml, p <0.001). The diagnostic accuracy of BNP for the Area under the curve (AUC) was measured and the results diagnosis of AMI as quantified by the area under the receiver expressed as aggregation units. Normal values were 51–136 AU, operating characteristic curve (AUC) (0.74 (95% confidence partial antiaggregation defined as values between 30 and 50 AU interval (CI) 0.70–0.78) was lower compared to cardiac troponin T and complete antiaggregation was defined as <30 AU. at presentation (AUC 0.88, 95% CI 0.84–0.92, p <0.001). Results: 221 pts (183 men) with a mean age of 67 ± 11 year Cumulative 24-month mortality rates were 0.5% in the first, 2.1% were included in the registry. ASP test was <30 U (optimal in the second, 7. 0% in the third and 22.9% in the fourth quartile of antiaggregation) in 214 of 221 pts (96.8%) treated with aspirin. BNP (p <0.001). BNP predicted all-cause mortality independently 5 patients had values between 30 and 50 U (partial of and more accurately than cardiac troponin T: AUC 0.81 (95% antiaggregation) and 2 patients were above 50 U (no CI 0.76–0.86) vs.AUC 0.70 (95% CI 0.62–0.77, p <0.001). Net antiaggregation). reclassification improvement for BNP was 0.10 (p = 0.038), Conclusion: Aspirin resistance was rare in this cohort. More than and integrated discrimination improvement 0.068 (p = 0.011). 96% of our patients were within the therapeutic range for aspirin. Conclusions: BNP accurately predicts mortality in unselected patients with acute chest pain independently of and more accurately than cardiac troponin T, but does not seem to help in P276 the early diagnosis of AMI. CLO-CLO Study – Efficacy of dual-anti-platelet therapy with various clopidogrel molecules M. Oberhänsli, S. Puricel, S. Lehmann, G. Baeriswyl, J.-C. Stauffer, M. Togni, J.-J. Goy, S. Cook (Fribourg, CH) Background: Effective inhibition of platelet aggregation is of utmost importance in the prevention of thrombotic events during and after percutaneous coronary intervention (PCI). Dual- antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel (adenosine 5’-diphosphate (ADP)-receptor antagonist; CLO) is the current standard of care. Two new generic versions of CLO using a different salt of CLO than the original molecule (Plavix) have been launched in Switzerland. For these two molecules no clinical data on their potency and safety is actually available.The aim of our study is therefore to examine the efficacy of each CLO in patients treated by PCI with stent implantation. Method: 180 consecutive patients with acute coronary syndromes undergoing PCI with stent implantation were randomised. 60 patients were included in the interventional trial (population A) and 120 patients in the observational trial (population B). For the patients included in population A, a CLO P278 molecule was chosen in a random fashion (20 Plavix(R), 20 Percutaneous transfemoral aortic valve Clopidogrel-Sandoz(R), 20 Clopidogrel-Mepha(R)) and given with (SAPIEN Edwards) implantation for stenosed an initial loading dose of 600 mg and then 75 mg/d. After ten and and regurgitant mitroflow-valve Bioprotheses twenty days, the CLO molecule was changed in a random fashion A. Farshad Schneider, O. Bertel, P. Berdat, W. Amann without a new loading dose in order that each patient was treated (Zürich, CH) with each CLO molecule once.After 30 days, all patients received a ten day treatment of Prasugrel with a new loading dose. Platelet Introduction: Percutaneous transfemoral aortic valve function was assessed by the Multiplate analyzer ADP test(R) Implantation is a treatment option for patients with symptomatic (Dynabyte, Munich, Germany) and the results were expressed severe aortic stenosis who are at high surgical risk. Following this as area under the curve (AUC). Complete antiaggregation was indication, in our institution, we have successfully implanted defined as ADP <25 U, partial antiaggregation as ADP between balloon expandable Edwards Sapien (Edwards Lifesiences, Irvine 25 and 53 U and the complete absence of antiaggregation by California) aortic valves since 2008 in 80 Patients.The implant of values above 53 U. Platelet function was measured 6 hours after Edwards Sapien is also an option for patients with a degenerative administration of the loading dose and after ten days of each aortic valve Bioprothesis who are considered at high risk for the treatment. At the end, individual results were revealed and surgery. patients maintained on the drug with the best anti-platelet activity. Methods: We present the case histories of 3 patients in which Patients included in population B received a standard loading this treatment has been used for degenerating Bioprotheses. dose of 600 mg of Plavix and then 75 mg/d. Each patient had an an excessive operative risk (EuroSCORE Results: Results for the primary end point (effectiveness of ≥60), symptoms of heart failure (NYHA ≥III). Procedures were platelet inhibition after ten days of treatment with each CLO performed using femoral arteries. Balloon valvuloplasty under molecule) will be presented during the conference in June 2011. rapid pacing was carried out before valve implantation. The 26-mm Edwards Sapien Bioprotheses was inserted retrograd. In one Patient we implanted a stent because of the occlusion of the P277 ostium of the left coronary artery. Invasive and echocardiographic measurements were done before and after the valve implantation. B-type natriuretic peptide in the early diagnosis Results: In all patients TAVI was successful with immediate and risk stratification of acute chest pain decrease of transaortic peak-to-peak pressure. Major adverse P. Haaf, T. Reichlin, R. Twerenbold, M. Reiter, S. Steuer, cardiac and cerebrovascular events did not arise. NYHA S. Bassetti, C. Heinisch, B. Drexler, S. Osswald, C. Müller functional class improved in all patients and left ventricular (Basel, Schlieren, Olten, CH) ejection fraction increased. Introduction: Myocardial ischemia is a strong trigger of B-type Discussion: Our case histories demonstrate that the SAPIEN natriuretic peptide (BNP) release.As ischemia precedes necrosis EDWARDS balloon-expandable Bioprotheses can be safely and in acute myocardial infarction (AMI), we hypothesized that BNP effectively deployed in stenotic and regurgitant aortic valve

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Bioprotheses.The implantation is facilitated by the existing valve syndrome in 5 (23%), and chronic angina in 15 (68%). Right TRA structure. The immediate results show good hemodynamic status was used in all (21 pts, 95.5%) while in one patient where left with a low transvalvular gradient regurgitation. Long-term TRA was performed. The hydrophilic coating and the tapered favorable results are also to be expected. In the meantime, profile of the sheathless guide catheterwe allo d radial and SAPIEN EDWARDS balloon-expandable Bioprotheses are an brachial artery crossing without significant complications and acceptable alternative to surgery for patients with degenerative technical difficulties.The number of vessel treated by patient was aortic Bioprotheses with high preoperative surgical risk. In the 1. 31 ± 0.47 with 1. 68 ± 0.89 stent implanted per vessels (70% of elderly population, the bioprothetic can be considered a plausible drug-eluting stent). LAD, LCX, RCA and left main stem lesions valve choice in which the need of Anticoagulation can be avoided. respectively represented 44.5% (12), 7. 4% (2), 18.5% (5) and The dissection of the arteries is a possible complication of this 29.6% (8) of the treated lesions. Complex PCI corresponded to method. 70% of the procedures: rotablation was performed in 2 pts (9%), left main stem was the culprit lesion in 8 pts (36%), four pts (18%) had complex bifurcation lesion treated and one (5%) chronic total P279 occlusion was treated. Mean fluoroscopic time was 20.5 ± 7. 2 min Coronary collaterals and ischaemic burden and mean volume of contrast media was 256.2 ± 82.2 ml. of the myocardium Conclusion: This preliminary experience suggests that TRA using 7. 5 Fr sheathless guide catheter is an attractive alternative S.F. de Marchi, S. Streuli, P. Häfeli, S. Gloekler, C. Warncke, for complex PCI to transfemoral access using a 7F conventional S.Rimoldi, S. Stortecky, T. Traupe, H. Steck, C. Seiler (Bern, CH) guide catheter. Introduction: The aim of this study was to determine the amount of collateral flow needed to protect the myocardium from ischemia, and to assess independent determinants of ischemia P281 severity in a large cohort with quantitative assessment of Treatments with chemokine-binding protein collateral flow. Evasin-3 and -4 improve post-infarction myocardial Methods: 765 patients were included. The collateral flow index injury and cardiac remodeling in mice (CFI) was invasively measured as previously reported. The ST-segment shift in the intracoronary ECG (icST) was V. Braunersreuther, F. Montecucco, G. Pelli, K. Galan, quantitatively measured at 1 minute balloon occlusion using B. Delattres, J.-P. Vallée, S. Lenglet, A. Proudfoot, F. Mach customized tracing software. An icST >0.1 mV was defined as (Genève, CH) indicative for ischemia. The CFI-threshold that best separates Background: Chemokines are known to trigger and direct ischemic from non-ischemic myocardium was determined using leukocyte trafficking from the blood stream towards inflamed receiver-operator characteristics (ROC) curves. The factors tissues.They are implicated in several cardiovascular diseases, determining the amount of icST were assessed by stepwise such as atherosclerosis, stroke, myocardial infarction and multiple regression analysis. CFI, heart rate (HR), the reperfusion injury. Chemokine-binding proteins, called Evasins cardiovascular risk factors, and the coronary territories were have recently been identified from tick salivary glands and shown entered as test-variables. to inhibit chemokine-mediated leukocyte infiltration. In this study, Results: Median icST (interquartile range, in mV) were: 0.65 we investigated whether the anti-inflammatory treatment with (0.30–1.05) in LAD, 0.59 (0.30–1.01) in LCX, and 0.27 (0.09–0.54) Evasin-3 (CXC chemokine inhibitor) and Evasin-4 (CC chemokine in RCA. The CFI-cutoff points best discriminating ischemic from inhibitor) could influence post-infarction myocardial injury and non-ischemic myocardium were: 0.217 for all vessels, 0.222 for remodeling. LAD, 0.220 for LCX, and 0.210 for RCA. In multivariate analysis, Methods and results: C57Bl/6 mice were submitted in vivo to LAD, LCX, HR, and arterial hypertension were associated with left coronary artery permanent ligature for different times (up to higher, CFI and RCA with lower icST. 21 days). After coronary occlusion, intraperitoneal injection of Conclusions: On average, a CFI-value of 0.217 is sufficient to Evasin-3 or Evasin-4 reduced the infarct size as compared to protect the myocardium from ischemia during a brief coronary vehicle-treated control group.This beneficial feef ct was associated occlusion, being lower in the RCA territory. High collateral flow with a decrease in myocardial leukocyte infiltration and in and RCA-involvement exert a protective role, whereas LAD- and circulating levels of CXCL1 and CCL2. At 21 days, mouse survival LCX-involvement, arterial hypertension and a high HR constitute and cardiac function were improved by treatments with Evasins an ischemic burden for the myocardium. as compared to vehicle. Conclusion: In this study, we showed that treatments with Evasin-3 or Evasin-4 improved cardiac injury and remodeling in a P280 mouse model of chronic myocardial ischemia. Therefore, Evasins Complex percutaneous coronary interventions by might represent a promising therapeutic approach to reduce transradial approach using an atraumatic 7.5-french development of post-infarction heart failure in mice. sheathless catheter

S. Noble, R. Bonvini, P. F. Keller, M. Roffi (Genève, CH) P282 Introduction: Trans-radial approach (TRA) reduces bleeding Five year trends in interventional cardiology complications compared to transfemoral access during in Switzerland from 2006 to 2010 percutaneous coronary interventions (PCI). Failure of performing TRA and complications increase with the sheath size used, M.T. Maeder, G.B. Pedrazzini, M. Roffi, C. Kaiser, S. Cook, especially in case of small and tortuous radial arteries.The use R. Corti, P. Wenaweser, H. Rickli (St. Gallen, Lugano, Genève, of sheathless guide catheters, 1–2 French (Fr) sizes smaller in Basel, Fribourg, Zürich, Bern, CH) diameter than corresponding introducer sheaths, may reduce Background: The purpose of this study was to assess temporal these complications.We report our preliminary experience trends of major cardiovascular interventions including diagnostic performing complex intervention using a 7. 5 Fr sheathless guide coronary angiography (CA), percutaneous coronary intervention catheter (Asahi Intecc, Japan) by TRA. (internal diameter similar (PCI), transcatheter aortic valve implantation (TAVI) and other to a 7- Fr conventional guide catheter and external diameter interventions for structural heart disease in Switzerland over inferior to a 7Fr sheath). the last five years. Methods: We included all consecutive patients (pts) who Methods: Volume and type of endovascular procedures underwent TRA PCI performed with a 7. 5 Fr sheathless guide performed in all adult invasive cardiac intervention centres catheter between October 2009 and 2010 in our institution. In our in Switzerland were collected by means of a standardised database, we identified 22 patients for a total of 27 lesions treated questionnaire. The 2010 data are currently being collected in whom the operator felt safer using larger guiding catheters and will be available at the meeting. (i.e., 7 Fr) to perform the scheduled PCI. Results: As depicted in figure 1, the number of CA (+13.0%) and Results: Pts were male in 82% (18), mean age was 69.4 ± 10.9 PCI (+11. 5%) continued to increase from 2006 to 2009 with the years (range: 45–88 years). Pts were active smokers in 14% (3), PCI/CA ratio remaining relatively stable (2006: 46.3%; 2009: diabetic in 41% (9) and with high blood pressure in 68% (15). 45.7%). After both CA and PCI had seemingly reached a plateau Indications for PCI were STEMI in 2 pts (9%), acute coronary in 2007, the numbers further increased in 2008 and 2009. After its

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introduction in Switzerland in 2002, the use of drug-eluting stents P283 reached a maximum in 2006 (82%) and then stabilized at Muscle graft optimisation prior to implantation: 71–72%. Despite a levelling off in 2008, overall procedures for scaffold architecture and functionalisation influence closure of patent foramen ovale and atrial septal defect also cell differentiation increased (fig. 2). TAVI was introduced in 2007 (one centre) and underwent a dramatic expansion in 2008 (seven centres) and G. Guex, G. Fortunato, E. Körner, T.P. Carrel, H. Tevaearai, 2009 (eight centres; fig. 2). In addition, transcatheter mitral valve M.-N. Giraud (Bern, St. Gallen, CH) repair was introduced in 2009 (three centres; fig. 2). The 2010 Introduction: Cell therapies and associated paracrine effects for data will we presented at the meeting. heart regeneration have gained increasing interest. Epicardial Conclusions: Between 2006 and 2009, the numbers of CA, implantation of an engineered muscle-graft has been associated PCI and interventions for structural heart disease continued to with prolonged functional recovery of the ischemic hearts.These increase.The advent of TAVI has been rapidly embraced by Swiss observed effects are expected to originate from the cell secretion interventional cardiologists, and transcatheter mitral valve repair of cardioprotective, angiogenic or stem cell recruiting factors has also been introduced. The 2010 data will provide additional or by local delivery of these factors via functionalisation of the important insights into the latest developments of current practice implanted scaffold. In the present study we performed in vitro of interventional cardiology in Switzerland. studies to investigate the effects of scaffold architecture and surface functionalisation on muscle graft development and related cytokine secretion. Methods: Aligned and randomly oriented micron- (3.2 ± 0.8 um) or nano- (308 ± 178 nm) scaled fibrous polycaprolactone non-wovens were processed by electrospinning.A15 nm thick oxygen functional hydrocarbon coating was deposited at the surface by an RF plasma process (gas mixture: CO_2:C_2H_4 ratio 6:1; power input: 50 W; process duration: 20 minutes) and characterised by XPS. C2C12 muscle cells were grown on the matrices and analysed for viability, proliferation, orientation and myotube formation. Cell orientation was characterised by a cosine function, where S = 1 for aligned and S = 0 for randomly oriented cells. Cytokine secretion was assessed using antibody arrays. Results: The formation of a stable plasma polymer coating resulted in an 8–14% increased oxygen content on the matrix. On all scaffolds, cell viability varied from 40 to 60% relative to TCPS; cell growth rate fluctuated over 7 days from 0.6 to 2.2 times. Architectural cues highly influenced cell orientation. On aligned fibres, cells were highly oriented (S = 0.88 ± 0.02) as compared to randomly oriented fibres (S = 0.33 ± 0.2). Increased myotube formation was found on CO_2/C_2H_4 coated scaffolds. Graft contractility and cytokine secretion are under evaluation. Conclusion: We provide evidence that the combined application of architectural and chemical cues is most favourable for advanced muscle development. Fibre alignment and plasma coating seem to induce most pronounced cell differentiation. Ongoing growth factor release identification will further characterise this biograft and its possible promise for cardiac regeneration.

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P284 Blood pressure control in uncomplicated and complicated hypertension in Switzerland Switzerland. 300 randomly selected physicians provided data on 5 consecutive hypertensive patients showing up in their practices R. Brenner, B. Waeber, Y. Allemann (Bern, Lausanne, CH) for BP follow-up. BP was recorded in a seated position (three Introduction: For patients with uncomplicated hypertension, consecutive measurements, mean value of measurement 2 and blood pressure (BP) goal is <140/90 mm Hg. Complicated 3) and data on demographics and comorbidities were hypertension, defined as hypertension in patients with diabetes anonymously collected. mellitus, chronic kidney disease (CKD) with/without proteinuria or Results: 1376 patients were included in the analysis. 54% of the both, is associated with increased cardiovascular risk and study population were male, and mean age was 65.1 ± 11.9 years. therefore, more intensive BP lowering is recommended for this 26.4% of the patients had complicated hypertension. Overall, high-risk group (target <130/80 mm Hg). The BP control rate in mean BP was 137/82 mm Hg (fig.). BP was controlled at a level Switzerland, both in patients with uncomplicated and complicated of <140/90 mm Hg in 57% of the patients. For risk-adapted BP hypertension, is largely unknown. The goal of this study was goals, overall BP control decreased to 49% with a significantly therefore to assess and describe the control rates in treated better control rate in uncomplicated than in complicated hypertensive patients visiting their primary care providers. hypertension (59% vs 19%, p <0.001, *in the figure). In a Design and method: A cross-sectional visit-based survey of multivariate analysis, the presence of diabetes (OR 5.1, 95% ambulatory hypertensive patients was performed in 2009 in CI 3.7–7.1, p <0.001) or nephropathy (OR 3.3, 95% CI 2.0–5.5,

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p <0.001) was independently predictive for uncontrolled geographic regions provided data on 5 consecutive treated hypertension. hypertensive patients showing up in their practices for blood Conclusions: The data show that BP control in Switzerland is pressure follow-up. Data on demographics, comorbidities and poor, particularly in patients with complicated hypertension. Only current medication were anonymously collected. half of the patients reached their BP target. Nevertheless, control Results: Data from 1378 hypertensive patients was available. rates in Switzerland are higher than reported for other western 1. 6% of the patients had no pharmacological therapy, 33.9% European countries (31–46%), although comparisons between had a monotherapy and 64.5% had a combination therapy with reports is substantially limited by diverging methodologies. 71.6% of them taking at least one fixed dose combination. Overall, diuretics and angiotensin receptor blockers (ARB) were prescribed with the highest frequency (fig. 1), followed by βblockers and ACE inhibitors. In patients treated with monotherapy, ARBs were used preferentially (41.8%), followed by ACE inhibitors (21.5%) and β blockers (20.8%). The fixed combination therapy containing an ARB and a diuretic was most popular (fig. 2). Conclusion: In Switzerland, ARBs are the most prescribed antihypertensive drug class.This fact might reflect the efficient blood pressure lowering effect associated with the favorable adverse effect profile of this drug .class On the other hand, efficient marketing strategies may also influence the prescription habits. βblockers were the third most prescribed drug class in monotherapy as well as in combination. This is surprising since current guidelines recommend these agents with some restrictions. Fixed combinations are frequently prescribed in Switzerland, most probably because of greater efficiency, patient convenience and in order to improve adherence.The combination of an ARB with a diuretic is the most prescribed combination and it will be interesting to see how ACCOMPLISH and ASCOT- BPLA will influence these prescription habits.

P286 A survey of physician’s attitudes towards P285 the control of cardiovascular risk factors. Current antihypertensive therapy in Switzerland Swiss results of the EURIKA study R. Brenner, B. Waeber, Y. Allemann (Bern, Lausanne, CH) A. Miserez, G. Plebani, R. Darioli (Basel, Zug, Lausanne, CH) Introduction: Current guidelines recommend to begin Purpose: Since the publication of ESC 2007 guidelines, no pharmacological antihypertensive therapy either with information about patients reaching therapeutic targets and about monotherapy or, particularly in patients with high cardiovascular the physician’s management of CV risk factors in daily practice risk, with early low dose combination therapy. The Swiss has made available in Switzerland. The European Study on CV hypertension guidelines currently endorse four drug categories Risk Prevention and Management in Daily Practice (EURIKA, for first line antihypertensive therapy: inhibitors of the renin NCT00882336) investigated the use of CV risk assessments tools angiotensin system, calcium channel blockers (CCB), diuretics and guidelines, and explored factors limiting their use. and β blockers. Because the current antihypertensive prescription Methods: Cross-sectional study conducted in 12 countries practice of Swiss primary care providers is largely unknown, we across Europe. In this study was collected information from aimed to evaluate it accross all regions of Switzerland. physicians and their patients. Overall 806 physicians were Methods: A cross-sectional visit-based survey of ambulatory surveyed. Swiss physicians (n = 71) from all three speaking hypertensive patients was performed in 2009 in Switzerland. regions provided information about their demographic data, work 300 randomly selected physicians from the three main Swiss setting, assessment of patients with CV risk factors, use of risk calculation tools and clinical guidelines. Results: Participating physicians worked in urban (50.7%), suburban (22.5%) or rural (26.8%) areas; 70.4% were GP, 19.7% internists and 4.2% specialists (cardiology, endocrinology). A majority (62.3%) reported the use of global risk calculation tools. The preferred method was the use of written charts (74.4%), followed by software applications (30.2%). The most popular tools were the SCORE (ESC; 57.1%), Framingham (9.5%) and the European Hypertension Charts (28.6%). Reasons for not using risk tools included time constraints (38.5%), not being convinced of their usefulness (46.2%) and lack of knowledge (15.3%). A high percentage of physicians believed that the algorithms have limitations (83.8%); that they may lead to overlook other risk factors (89.5%), and/or that they lead to overestimate the cardiovascular risk (25.5%) and/or that they cannot be used to calculate risk in elderly patients (63.6%). The most commonly used clinical guidelines were those from the ESC (CVD Prevention in Clinical Practice [58.2%] and Management of Arterial Hypertension [44.8%]) or from local authorities (20.9%). In total, 7. 5% of the physicians reported not using guidelines. From these physicians, 80% reported there are too many guidelines. Conclusions: There is a significant room for improvement in the use of risk score calculation Time constraints, non-perception of usefulness and insufficient knowledge were common factors limiting the use of cardiovascular risk evaluation tools and assessment guidelines in Switzerland. Better compliance with risk assessment tools might reduce the high proportion of patients with poorly managed cardiovascular risk factors.

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P287 Aim: To evaluate the impact of educational factors on the Turner syndrome: analysis of incidence of “symptom-to-first-medical-contact” time in the state of Vaud area associated congenital heart disease and cardiovascular (Switzerland) in patients receiving primary PCI for STEMI. risk factors and their impact on outcome Method: Retrospective observational study of all STEMI patients (n = 402) extracted from our primary PCI hospital’s database C.H. Attenhofer Jost, D. Babovic-Vuksanovic, between 01-01-2009 and 06-31-2010.The main exclusion criteria C.G. Scott, C.R. Bonnichsen, H.M. Burkhart, were a “symptom-to-first-medical-contact” time >12 hours or other H.M. Connolly (Zürich, CH; Rochester, US) diagnosis at angiography. 352 patients were finally included. Background: In patients (pt) with Turner syndrome (TS), bicuspid Times at onset of symptoms and at admission were retrieved from aortic valve (BAV) and coarctation (COARCT) are the most the patients’ record files.The Swiss official education’s grading common associated congenital heart defects (CHD). However, system was used to classify patients into 2 educational levels. there is also an increased incidence of other CHD, common Results: A “symptom-to-first-medical-contact” time ≤2 hours had cardiovascular risk factors (CVRF) and growth hormone been recorded for a majority of patients with a High Education treatment. There are few data on the impact of these other factors Level (HEL) but only for a minority of patients with a Low on outcome. Education Level (LEL) (59.5% vs 41.4% respectively; p <0.05). In Methods: 80 pt with TS had an echocardiographic evaluation at a sub-group of patients (n = 88), the exact “symptom-to-call” time our center. In this pt group, we analyzed any present CHD, CVRF was available (median = 55 minutes). A “symptom-to-call” time and outcome by analysis of charts and echocardiographic reports. <55 minutes had been recorded for a majority of HEL but only Results: The median age at echocardiographic examination was for a minority of LEL (57.1% vs 35.9% respectively; p <0.05). 23 years (range: 0.5;67). Genetic analysis showed 36 pt (45%) Conclusion: In the state of Vaud, a High Education Level is with the karyotype 45X;. Any associated CHD was present in associated with shorter “symptom-to-first-medical-contact” and 26 pt (33%) including BAV in 19 pt (24%) and COARCT in 10 pt “symptom-to-call” times.Therefore, health education and (13%), less common were anomalous PV or intracardiac shunts. prevention should particularly focus on the population with a low A body mass index of >25 kg/m2 was found in 29 pt (36%), level of scholar education. hypertension in 18 pt (23%), hyperlipidemia in 16 pt (20%), definite or possible obstructive sleep apnea in 7 pt (9%) and a history of smoking in 4pt (5%). Growth hormone was administered ever in 27 pt (34%). Signs of aortopathy using the Z score were present in 50 pt (63%), only 16 of these had any associated CHD. COARCT or bicuspid AV. During follow-up, death occurred in 11 pt at an average age of 44 ± 12 years; in 5 pt death was due to a cardiac cause. Cardiovascular surgery was necessary in 16 pt (20%). Major adverse cardiac events (MACE) including cardiac death, cardiovascular surgery, stroke or acute myocardial infarction occurred in 20 pt (25%) and were best predicted by the presence of COARCT (p <0.0001), BAV (p = 0.003) see table. Treatment with growth hormone was not associated with an increased incidence of cardiac event. Aortic ectasia was best predicted by other CHD (p = 0.02; excluding pt with BAV and coarctation). Conclusion: In pt with TS, besides hypertension, other common cardiovascular risk factors include BMI >25 kg/m2, hyperlipidemia and OSAS. However, aortic ectasia and cardiovascular complications can not be predicted by cardiovascular risk factors or prior growth hormone treatment in these pt but by the presence of coarctation, bicuspid aortic valve or other congenital heart P289 disease. Adherence of vitamin K-antagonist guidelines in patients with acute coronary syndrome G. Sütsch, D. Radovanovic, P. Urban, O. Bertel, P. Erne, C. Scharf (Zürich, Genève, Luzern, CH) Background: Current guidelines (GL) emphasise a more aggressive use of Vitamin K-antagonist (VKA) in atrial fibrillation (AF). Aim: The purpose of this analysis was to assess the impact of the GL on patients (pts) with acute coronary syndrome (ACS). Methods: We screened all AMIS plus (Acute Myocardial Infarction in Switzerland) pts enrolled between 1999 and June 2010 (n = 28270 pts) and identified 1562 pts with AF.The CHAD2 and the CHAD2DS2CV score were calculated for 1198 pts. Finally, 822 pts could be included in the analysis. Results: Out of the 822 pts we identified 248 pts (33.1%) with a CHAD2 score >2. The corresponding figure for CHAD2DS2CV was nearby double (65.1%). VKF with or without dual platelet inhibition were administered in 114 pts (13.9%) with CHAD2 score and were similarly doubled with CHAD2DS2CV (28%). Conclusion: VKA is underused in pts with AF and ACS. The new GL uncover an even larger gap in daily practice.Apossible P288 explanation is the use of double antiplatelet inhibition. Does level of education compromise “symptom-to- first-medical-contact” time amongst STEMI patients? P290 S. Fournier, O. Müller, N. Lauriers, E. Eeckhout (Lausanne, CH) Background: One of the major objectives of the European “Stent Transportation noise and blood pressure For Life” initiative is to ensure equal access to percutaneous in a population-based sample of adults coronary intervention (PCI) for all STEMI patients. It is well known J. Dratva, H.C. Phuleria, M. Foraster, J.-M. Gaspoz, D. Keidel, that the “symptom-to-first-medical-contact” time stronglyfe af cts N. Künzli, L.-J. Sally Liu, M. Pons, E. Zemp, M.W. Gerbase, prognosis.The impact of educational factors on this critical time C. Schindler (Basel, CH; Barcelona, ES; Genève, Lugano, CH) period is poorly known. Background: There is abundant evidence for the association between traffic noise and ischemic heart disease, however

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studies are inconsistent for blood pressure and little is known on understanding of a link to autonomic function. We investigated if health effects from railway noise. routine use of these sprays at home was associated with reduced Objectives: The main aim was to investigate the effect of railway heart rate variability (HRV), a marker of autonomic dysfunction, and traffic noise exposure on blood pressure and, secondly, in the Swiss study on Air Pollution and Lung Diseases in Adults address potentially susceptible sub-samples. (SAPALDIA). Methods: Adjusted linear regression analyses were run on data Methods: 24-hour electrocardiograms were recorded in 580 from 6450 SAPALDIA 2 participants to assess the association of randomly selected SAPALDIA subjects ≥50 years of age and day- and nighttime railway and traffic noise (db(A)) with systolic participating in a detailed interview on cleaning activities and the (SBP) and diastolic blood pressure (DBP, mm Hg). Noise data use of spray products at home. Sixty five subjectsve ne r used any were provided by the Federal Office of Environment. Stratified spray or scented product and were considered the unexposed analyses by doctor diagnosed hypertension and diabetes were reference group. Exposure variables for analysis included: performed. cleaning sprays summarized as a composite score from 1 to 9; Results: Adjusted regression models yielded significant feef ct air freshening sprays and scented products, both with categories estimates for railway noise by day (SBP β = 0.061, 95%CI of <1, 1-3, and 4-7 days/week; and multiple types of sprays with 0.008–0.110; DBP β = 0.020, 95%CI –0.012–0.052) and night categories of any spray

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Conclusion: The fact that only 50% of the teams respectively whether BNP levels before EC are higher among patients who 42.7% of the competing players returned the questionnaire may experience AF recurrence within 30 days than among those with lead to the conclusion that the awareness of the problem is quite persistent sinus rhythm (SR). low. Most of the national teams show inhomogeneous screening Methods: 42 consecutive patients (30 men) with persistent AF concepts, which may be explained by different screening scheduled for elective EC were enrolled in a prospective study. concepts of regional clubs these athletes play regularly for. Apart Exclusion criteria were severe valve disease or a prosthetic heart from the relatively high rate of 82% of players who regularly valve, left ventricular ejection fraction <30%, recent change in any undergo an adequate cardiac screening the fact that 16 players medication and major co-morbidities. Baseline data were (13.1%) at this top level never went through a specific screening collected using a validated questionnaire. Venous blood was examination at all is alarming and should have consequences drawn before EC and processed immediately. BNP was assayed using an immunoassay (ABBOTT AG). Follow-up examinations were scheduled 4 weeks after EC. Changes in medications were strongly discouraged between the 2 visits. Prior to the follow-up visit, SR was confirmed using 24-hour Holter EKG. The same assay for BNP determination was used. AF recurrence was defined as a documented AF episode of at least 30 seconds. Results: Patients with AF recurrence (n = 13) showed similar baseline characteristics compared to patients with established SR with regard to age (69 vs. 65 years, p = 0.08), hypertension (69% vs. 52%, p = 0.30), body mass index (26 vs. 28 kg/m², p = 0.70) and renal function (creatinine: 86 vs 78 µmol/l, p = 0.13). Median (interquartile range) BNP levels prior to EC were 265 (216–580) and 398 (167–885) pg/ml in patients with persistent SR and those with subsequent AF recurrence, respectively (p = 0.50). During follow-up, median diastolic blood pressure (BP) was significantly lower in patients with persistent SR (89 (78–101) vs. 77 (71–86) mm Hg, p = 0.001) but not in patients with AF recurrence. Similarly, median BNP levels were significantly welo r after 4 weeks of follow-up in patients with persistent SR (265 (216–580) vs. 142 (94–329) pg/ml, p = 0.001) but not with AF recurrence P294 (398 (168–885) vs. 356 (265–547) pg/ml, p = 0.873). Systolic BP did not change in both groups. B-type natriuretic peptide and recurrence Conclusions: In this prospective study of AF patients undergoing of atrial fibrillation after electrical cardioversion EC, BNP did not differ among patients with persistent SR and T. Schön, Y. Suter, G. Völlmin, B. Kaufmann, D. Conen those with subsequent AF recurrence. Nevertheless, restoration (Basel, CH) of stable SR leads to lower diastolic BP and lower BNP levels, Background: Recurrence rate after electrical cardioversion suggesting hemodynamic improvements and/or reverse (EC) for persistent atrial fibrillation (AF) is high. B-type natriuretic remodeling in these patients. peptides (BNP) may be a promising clinical tool to identify patients at high risk for AF recurrence.We therefore assessed

P295 Can race result in Ironman triathletes be predicted Results: The average age was 38 ± 9 years (6 females). Resting by determination of body fat, skeletal muscle mass, heart rate was 54 ± 7 beats per minute. Body mass index was haematocrit or echocardiography? 22.6 ± 2 g/m2. PBF was only 15.3 ± 5.5%; the hematocrit was B. Knechtle, M. Pfyffer, M. Zuber, A.M. Bernheim, A. Linka, 43 ± 2%; SMM was 39 ± 6 kg. By echocardiography, left ventricular (LV) ejection fraction was 62 ± 6%, LV enddiastolic B. Seifert, G. De Pasquale, A. Fäh-Gunz, B. Naegeli, 2 C.H. Attenhofer Jost (St. Gallen, Zürich, Othmarsingen, CH) volume index 69 ± 14 ml/m and LV muscle mass index 99 ± 25 g/ m2.The IM total race time was 660 ± 28 min. Univariate predictors Introduction: The ironman (IM) triathlon consists of a 3.8 km (Spearman correlation) of IM total race time, LV muscle mass swimming, 180.2 km cycling, and a 42.2 km run. Thus IM index and LV end-diastolic volume index are shown in the table. triathletes (ATHL) are the prototype of ultra endurance athletes. Conclusion: In IM ATHL, good performance as measured by There are limited data on correlation of anthropometric measures total race time is best predicted by lower PBF and higher left with race time and echocardiographic findings in this population. ventricular muscle mass index; and partially predicted by LVEDVI. Methods: Thirty-four IM ATHL were screened the day prior to the Left ventricular changes compatible with athlete’s heart can not IM race, which 33 of these ATHL finished. Percent body fat (PBF), be predicted by age, amount of training (hours per week) and skeletal muscle mass (SMM) and hematocrit were measured and years of experience but correlate best with the percentage of a complete transthoracic echocardiographic exam performed. body fat and the skeletal muscle mass. Findings of echocardiography, IM race results and anthropometric measurements were correlated.

HR = heart rate at rest; bpm = beats per minute; BMI = body mass index; LVEF = left ventricular ejection fraction; LVEDVI = left ventricular enddiastolic volume index; LVMMI = left ventricular muscle mass index; PBF = percent body fat; SMM = skeletal muscle mass; total training per week (TPW); Hct = hematocrit; LAVI = left atrial volume index.

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P296 P297 Type 2 diabetes and the progression of visualized Population attributable stroke risk is usually low: atherosclerosis to clinical cardiovascular events similar observations in two distinct healthy populations C. Saely, P. Rein, A. Vonbank, K. Huber, H. Drexel (Feldkirch, AT) M. Romanens, F. Ackermann, I. Sudano, T. Szucs, W. Riesen, We aimed at prospectively evaluating to what extent pre-existing M. Schwenkglenks (Olten, Zürich, Basel, St. Gallen, CH) coronary artery disease (CAD) accounts for the increased Aim: To determine population attributable stroke risk for major long-term vascular event risk of patients with type 2 diabetes risk factors and to derive the potential to reduce stroke risk. (T2DM). We hypothesized that baseline CAD among patients with Methods: We compared not randomly selected subjects from self T2DM may account substantially for their increased referred CORDICARE (COR) and physician referred KARDIOLAB cardiovascular risk. Over 8 years we recorded vascular events in (KAR) patients for 10 year stroke risk determined by PROCAM 750 consecutive patients whose baseline CAD state was verified (European Journal of Clinical Investigation 2007;37:925–932). angiographically. The prevalence rates of CAD (87.8% vs. 80.4%; The potential for risk factors to reduce stroke risk was estimated p = 0.029) and of significant coronary stenoses ≥50% (69.5% vs. by substituting measured results by ideal values of risk factors. 58.4%; p = 0.010) as well as the extent of CAD, defined as the We calculated the risk reduction attributable to achievement of number of significant coronary stenoses (1.7 ± 1. 6 vs. 1. 4 ± 1. 5; two single risk factors: smokers became non-smokers, and p = 0.014) were higher in patients with T2DM (n = 164) than in systolic blood pressure (BP) was decreased to 130 mm Hg and non-diabetic subjects. During follow-up, T2DM strongly predicted then 10 year risk was recalculated for every subject. vascular events (n = 257) independently from the presence and Results: COR included N = 892 (48% female), mean age 59 ± 9 extent of baseline CAD (hazard ratio (HR) 1. 36 [1.03–1.81]; years, KAR included N = 548 (34% female), mean age 57 ± 9 p = 0.032); conversely, the presence and extent of baseline CAD years. COR vs KAR: less smokers (11% vs 28%), less diabetic predicted vascular events independently from T2DM (HRs 3.29 patients (3% vs 9%), higher systolic BP (133 ± 15 vs 128 ± 19) [1.93–5.64]; p <0.001 and 1. 37 [1.23–1.53]; p <0.001, respectively). and higher HDL (1.6 ± 1. 4 vs 1. 4 ± 0.4), lower AGLA coronary risk The overall risk increase conferred by T2DM was driven by the (6.6 ± 6.9 vs 8.3 ± 8.6), lower stroke risk (2.8 ± 3.2 vs 3.2 ± 3.4). extremely high 53.3% event rate of patients with both T2DM and Stroke risk for COR and KAR was reduced by achieved goals significant CAD at baseline; individuals with T2DM who did not (non smoking, blood pressure ≤130 mm Hg) to 2.1 ± 2.2 vs have significant CAD at baseline showed a significantly welo r 2.1 ± 2.1 (relative risk reduction –25% and –35%). event rate (22.0%; p <0.001). We conclude that T2DM and Conclusions: Achieving non smoking status and normal blood angiographically visualized coronary atherosclerosis are mutually pressure in all subjects would reduce stroke risk by about 25% independent predictors of vascular events.The overall risk and 35% respectively, but the absolute 10 year risk reduction in increase conferred by T2DM is driven by accelerated progression an already very low risk population remains modest. of pre-existing atherosclerosis to clinical cardiovascular events.

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P298 Cardiac function after repair of tetralogy of Fallot: How are the atria performing? C. Wohlmuth, E. Voser, C. Kellenberger, E.R. Valsangiacomo Büchel (Zürich, CH) Introduction: During the cardiac cycle the atria function as reservoir, conduit and active pump and are critical for ventricular filling. Knowledge about atrial performance in children and in congenital heart disease is scarce.We sought to evaluate right and left atrial size and function in patients with repaired tetralogy of Fallot (TOF). Methods: Cardiovascular magnetic resonance (CMR) was performed prospectively in 12 patients after TOF repair and with significant pulmonary regurgitation. The mean age was 16.7 ± 6.1 yrs, weight 50.9 ± 14.9 kg. The control group consisted of 10 healthy volunteers, age 18.8 ± 6.8 yrs, weight 52.3 ± 20.8 kg. Steady state free precession images were acquired in a short axis plane covering both atria and both ventricles.The atrial passive and active emptying volumes, atrial empting fraction, cyclic volume change, total atrial filling fraction and conduit volume were calculated from the volume/time curves obtained (fig. 1 and 2). Phase contrast cine images were acquired perpendicularly to the inflow of both AV-valves. Blood flow profile across the AV-valves (E/A ratio) was used to depict subjects with ventricular diastolic dysfunction. Data were compared between patients and controls, as well as between patients with normal and abnormal ventricular diastolic function. Results: In patients after TOF repair the right atrium showed an increased minimal volume at end-diastole (p <0.01) and increased minimal and maximal volumes during mid-diastole (p <0.05). Cyclic volume change (p <0.05), total atrial filling fraction (p <0.01) and passive emptying volume and fraction (p <0.05) were significantly decreased compared to controls. No significant difference was found for active emptying volume and fraction. In the left atrium the passive emptying fraction was the single decreased parameter (p <0.05) in the patient group. Patients with a reversed E/A ratio across the tricuspid valve,

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representing diastolic dysfunction of the right ventricle, presented P300 an increased conduit volume (p <0.05). Cyclic volume change, Evaluation of the left atrial appendage with real-time total atrial filling fraction, passive emptying volume and passive three-dimensional transesophageal echocardiography: empting fraction were slightly decreased, without reaching implications for catheter-based left atrial appendage statistical significance. closure Conclusion: Patients after TOF repair and with significant pulmonary regurgitation present an impaired right atrial function G. Nucifora, F. Faletra, F. Regoli, E. Pasotti, G.B. Pedrazzini, compared to controls. Right ventricular diastolic dysfunction T. Moccetti, A. Auricchio (Lugano, CH) causes even more distinctive changes of atrial parameters. Background: Precise knowledge of left atrial appendage (LAA) orifice size is crucial for correct sizing of LAA closure devices.Aim of the present study was to determine the incremental value of P299 real-time three-dimensional transesophageal echocardiography Echocardiographic assessment of the right heart: (RT3DTEE) for LAA orifice size assessment, compared to gender and body size matters two-dimensional transesophageal echocardiography (2DTEE), and to investigate the impact of presence/type of atrial fibrillation U. D’Oronzio, O. Senn, P. Biaggi, R. Jenni, F. C. Tanner, (AF) on LAA orifice size. M. Greutmann (Zürich, CH) Methods: 137 patients (38 controls, 31 with paroxysmal AF, 38 Introduction: Recently, guidelines have been published for with persistent AF and 30 with permanent AF) underwent 2DTEE the echocardiographic assessment of the right heart. These and RT3DTEE. Both techniques were used to measure LAA guidelines used pooled data from numerous, often small studies. orifice area. Sixty-four-slice CT was used as reference technique The proposed normal values for echocardiographic in 46 patients. measurements are however not stratified for gender or age and Results: 2DTEE underestimated LAA orifice area, compared are not indexed to biometric data such as body surface area to RT3DTEE (1.99 ± 0.94 cm2 vs. 3.05 ± 1. 27 cm2; p <0.001). (BSA). Our aim was therefore to assess the dependence of RT3DTEE showed higher correlation with CT for the assessment commonly used measurements of right heart dimension and of LAA orifice area, compared to 2DTEE (r = 0.92, p <0.001 function to age, gender and BSA. vs. r = 0.72, p <0.001, respectively). At Bland–Altman analysis, Methods: From our echocardiography database we identified RT3DTEE and 2DTEE underestimated LAA orifice area, all patients with structurally and functionally normal hearts who compared to CT. However, RT3DTEE showed smaller bias (0.07 underwent transthoracic echocardiograms between 2000 and cm2 vs. 0.72 cm2) and narrower limits of agreement (–0.71 to 0.85 2009. The following measurements, obtained from apical cm2 vs. –0.58 to 2.02 cm2) with CT, compared to 2DTEE. Among 4-chamber view were examined: Right ventricular (RV) AF patients, a progressive increase in LAA orifice area was enddiastolic area (Area-D), Right atrial long axis dimension observed with increasing frequency of AF (p <0.001; fig.). At (RA-Lx), fractional area change of the RV (FAC) and tricuspid multivariate analysis, presence/type of AF (β = 0.55, p <0.001) annular motion (TAM). Pearson correlation analysis and t-test and left atrial volume index (β = 0.40, p <0.001) were statistics were applied to investigate the associations between independently associated with LAA orifice area (table). echocardiographic measurements and anthropometrics. Conclusion: RT3DTEE is more accurate than 2DTEE for the Results: A total of 2296 subjects (mean age 44 ± 14 years, range assessment of LAA orifice size. A progressive increase in LAA 18–92 years, 49% males) were included. Mean BSA was 1. 8 ± orifice area is observed with increasing frequency of AF. 0.2 m2. There was no statistically significant correlation between RV-function (TAM and FAC) and age and only a weak, although statistically significant, correlation between RA and RV-size with age (coefficient of determination r2 = 0.01 and 0.001, respectively, p = 0.001 and <0.001). Figure 1 demonstrates that Area-D and RA-Lx were significantly welo r and FAC significantly higher in female subjects, while TAM was not significantly different between genders. The most striking difference was found for measurements of Area-D, where the mean difference between genders was 3.4 cm2 or 25%. There was a significant and positive correlation between Area-D and RA-Lx with BSA (correlation coefficient 0.47 and 0.41, respectively, p <0.0001 for both) but only a weak negative correlation for FAC (r = –0.15, p <0.0001) and a weak positive correlation for TAM (r = 0.08, p = 0.002). When dimensional and functional measurements were indexed to BSA, a significant gender fedif rence persisted for all measurements. Conclusions: Echocardiogaphic measurements of right heart dimension and systolic function are significantly different between genders, even when measurements are indexed to body surface area. This should be taken into account when defining normal values.

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P301 ml vs 83.3 ± 52.6 ml, p <0.001, respectively), while LAEF was Altered left ventricular geometry and torsional measured higher by RT3DE (42.8 ± 15.2% vs 34.2 ± 15.4%, mechanics in high altitude-induced pulmonary p <0.001, respectively). RT3DE measurements closely correlated hypertension: a 3-D echocardiographic study in terms of intraobserver (intra-class correlation r = 0.99, r = 0.99, r = 0.96, respectively) and interobserver variability (r = 0.97, B.W.L. De Boeck, S. Kiencke, C. Dehnert, K. Auinger, r = 0.98, r = 0.88, respectively). M. Maggiorini, P. Buser, B. Kaufmann (Basel, CH; Ulm, DE; Conclusion: LA volumes and EF as assessed by RT3DE Zürich, CH) correlate highly with CT measurements, albeit there is some Introduction: Reduced left ventricular (LV) twist has been bias between the imaging modalities. Most importantly, RT3DE reported in patients with long-standing pulmonary hypertension measurements using the novel dedicated LA analysis tool are and compensatory right ventricular hypertrophy. Ascent to high robust in terms of observer variability and thus suitable for altitude induces reversible increases in pulmonary pressure. follow-up analyses. We evaluated the effect of high altitude-induced pulmonary hypertension on LV geometry, volumes, systolic function and torsional mechanics. P303 Methods: 22 healthy volunteers were studied by Doppler and 3D Use of levosimendan as rescue therapy echocardiography at low altitude and after the second (“D3”) and in children with low cardiac output syndrom third night (“D4’) at high altitude (4559 m). Resting LV ejection fraction, end-diastolic and end-systolic volumes, sfericity (3D V. Amiet, M.-H. Perez, S. Di Bernardo, J. Cotting volume/length), and eccentricity (area 4Ch/area 2CH) were (Lausanne, CH) derived from axis-corrected 3D datasets and reconstructed Objective: Aim of post operative treatments after cardiac surgery true 4 and 2-chamber image planes, respectively. Global LV is to avoid low cardiac output syndrome (LCOS). Levosimendan, longitudinal and circumferential shortening (strain) and LV a new inotrope agent, has been demonstrated in adult patient to torsion were calculated by 3D speckle tracking echocardiography. be an effective treatment for this purpose when classical therapy Pulmonary pressure was estimated from the transtricuspid is not effective. It shows a positive effect on cardiac output, with pressure gradient (TRPG), LV preload from transmitral over fewer adverse effects and lower mortality than with dopamine. mitral annular E velocity (E/e’). There is very few data on its benefit in the paediatric population. Results: Compared to low altitude, exposure to high altitude The aim of this study is to evaluate the effect of levosimendan increased resting heart rate from 61 ± 11 to 76 ± 14 (D3) and 71 ± in cardiac children with LCOS. 13 (D4) bpm, cardiac index from 2.2 ± 0.5 to 2.5 ± 0.4 l/min/m2 Methods: Retrospective analysis of 25 children hospitalised in (both D3/D4) and TRPG from 21 ± 2 to 37 ± 9 mm Hg (both D3/ our PICU after cardiac surgery that demonstrated LCOS not D4, all p <0.01). LV preload (E/e’), volumes, and sfericity responding to classical catecholamine therapy and who received remained unaffected, but diastolic [1.04 ± 0.07 to 1. 09 ± 0.09 on levosimendan as rescue. LCOS parameters like urine output, D3&D4, p <0.05] and systolic [1.00 ± 0.06 to 1. 08 ± 0.1 (D3) and mixed venous oxygen saturation (SvO2), arterio-venous 1. 06 ± 0.07 (D4), p <0.05] eccentricity slightly increased, differences in CO2 (AVCO2) and plasmatic lactate were compared indicating mild D-shaping of the ventricle. LV systolic function before therapy and at 12, 24, 48 and 72 hours after the beginning (ejection fraction, global longitudinal and circumferential of the levosimendan infusion. We also analyzed the effect on the shortening) remained unchanged while LV torsion decreased from utilisation of amines (amine score), adverse events and mortality. 2.14 ± 0.85 to 1. 34 ± 0.68 and 1. 65 ± 0.54 degrees/cm on D3/D4, Results: After the beginning of levosimendan infusion, urine respectively (p <0.05). A weak but significant vein rse relation output (3.1 vs 5.3 ml/kg/h, p = 0.003) and SVO2 (56 vs 64 mm between torsion and systolic [r = 0.380, p <0.01] and diastolic Hg, p = 0.001) increase significantly during first 72 hours and at [r = 0.334, p <0.01] eccentricity was found. In addition, changes the same time plasmatic lactate (2.6 vs 1. 4 mmole/l, p <0.001), in systolic [r = –0.369 , p = 0.013] and diastolic [r = –0.329, AVCO2 (11 vs 8 mm Hg, p = 0.002) and amine score (63 vs 39, p = 0.032] eccentricity were also inversely related to torsional p = 0.007) decrease significantly. No side effects were noted changes.Arelation between (changes in) torsion and (changes during administration of levosimendan. In this group of patients, in) TRPG, heart rate or E/e’ could not be established. mortality was 0%. Conclusion: High altitude exposure is associated with mild Conclusion: Levosimendan is an effective treatment in children D-shaping of the ventricle and reduced ventricular torsion at after congenital heart surgery. Our study, with a greater sample unchanged global left ventricular function and preload. These of patient than other studies, confirms the improvement of cardiac data suggest a direct relation between LV geometry and torsional output already shown in other paediatric studies. mechanics.

P304 P302 Acute changes in circulating high-sensitive Assessment of left atrial volumes and function by Troponin T during exercise induced myocardial real-time three-dimensional echocardiography using ischaemia a novel dedicated analysis tool – Initial validation T. Reichlin, M. Zellweger, C. Maushart, M. Potocki, studies in comparison to CT R. Twerenbold, K. Roost, M. Pansini, F. Forrer, S. Osswald, A. Rohner, M. Brinkert, N. Kawel, R. Buechel, G. Leibundgut, C. Mueller (Basel, CH) H. Abbühl, M. Kühne, J. Bremerich, B. Kaufmann, S. Osswald, Background: Using a novel experimental high-sensitive assay, M. Handke (Basel, CH) a recent pilot study suggested that cardiac troponin I (cTnI) might Background: A novel real-time three-dimensional increase in the setting of exercise induced myocardial ischemia. echocardiography (RT3DE) analysis tool specifically designed Whether cTnT, which is a markedly larger molecule than cTnI, is for evaluation of the left atrium (LA) enables comprehensive similarly released during myocardial ischemia is unknown. The evaluation of LA size, global and regional function using a aim of our study was to determine whether a high sensitive cTnT dynamic 16-segment model. Aim of the study was the initial (hs-cTnT) assay can detect changes in circulating cTnT in the validation of this method using computed tomography (CT) as setting of exercise induced myocardial ischemia. method of reference. Method: Blood samples for measurement of hs-cTnT were Methods and results: The study population consisted of 34 obtained prospectively before, immediately after, as well as 2 and prospectively enrolled patients with clinical indication for 4 hours after bicycle stress testing in 251 consecutive patients pulmonary vein isolation. A dynamic polyhedron model of the referred for myocardial perfusion single-photon emission LA was generated using RT3DE. LA maximum and minimum computed tomography. The severity of inducible ischemia was volumes (LAmax / LAmin) and emptying fraction (LAEF) were categorized as none (summed difference score [SDS] <2), mild determined and compared to the results obtained by CT. High (SDS 2-7) and moderate-to-severe (SDS ≥8) blinded to hs-cTnT correlations between RT3DE and CT were found for LAmax results. (r = 0.92, p <0.001), LAmin (r = 0.95, p <0.001) and LAEF (r = Results: A moderate-to-severe ischemia was detected in 27 0.82, p <0.001). LAmax and LAmin were lower by RT3DE than by patients (11%), a mild ischemia in 75 patients (30%) and no CT (95.0 ± 44.7 ml vs 119.8 ± 50.5 ml, p <0.001 and 58.1 ± 41.3 ischemia was found in 149 patients (59%). By 2 and 4 hours, no

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relevant changes in hs-cTnT levels were observed (2h: median 0 for comparison). The diagnostic accuracy of hs-cTnT for the ug/l, IQR 0–0.002 ug/l; 4 h: median 0 ug/l, IQR –0.001 – 0.003 diagnosis of exercise induced myocardial ischemia as asses ug/l) in the overall cohort. Similarly, we found no differences in by the area under the receiver operating characteristics curve hs-cTnT changes between the three groups according to the however was only moderate (AUC 0.662, 95% confidence interval severity of ischemia (p = 0.10 and 0.50 for 2 h and 4 h). 0.61–0.71) Conclusion: Exercise-induced myocardial ischemia is not Conclusion: Although significantly elevated in patients with associated with a quantifiable increase in circulatingve le ls of exercise induced myocardial ischemia, baseline hs-cTnT levels hs-cTnT. are of only little diagnostic help in the detection of exercise induced myocardial ischemia.

P306 Assessment of beat-to-beat regularity of coronary motion S. Coppo, D. Locca, M. Stuber (Lausanne, CH) Introduction: For coronary magnetic resonance angiography (MRA), image data acquisition is subdivided into multiple segments, ECG-triggered and acquired over multiple cardiac cycles (1-3). However, such segmented data acquisition is strongly dependent upon precise geometrical repositioning of the heart among several consecutive cardiac cycles.This study therefore aims at measuring the beat-to-beat regularity of coronary motion on x-ray coronary angiograms to test the hypothesis that intervals with more precise geometric repositioning of the coronary arterial system do exist within the cardiac cycle. If tested positive, this may significantly challenge paradigms of contemporary coronary MRA methodology. Methods: Routine diagnostic cine breath-hold x-ray coronary P305 angiograms were acquired during catheterization, so patients Use of baseline levels of high sensitive Troponin T were not exposed to additional radiation and informed consent to detect exercise induced myocardial ischaemia was obtained from all participants. Images of the left coronary system were acquired in 9 patients who underwent elective T. Reichlin, M.J. Zellweger, C. Maushart, M. Potocki, coronary angiography for diagnostic purposes.The image matrix R. Twerenbold, N. Marti, M. Pansini, F. Forrer, S. Osswald, was 512x512 pixels with a 0.32 mm2 pixel size, a temporal C. Mueller (Basel, CH) resolution of 15 frames/s and synchronous ECG recording over Background: Patients with haemodynamically significant 3 consecutive heartbeats. In the left anterior descending coronary coronary artery stenosis experience recurrent episodes of artery (LAD) and the left coronary circumflex (LCX), bifurcations myocardial ischemia during exercise, which occasionally may were tracked during consecutive heartbeats using a user-assisted result in low level myocardial necrosis.The aim of our study was computer algorithm implemented in Matlab (The Mathworks, to determine whether the amount of low level myocardial necrosis Natick, MA, USA). The position of each bifurcation as a function as assessed by a high sensitive cardiac troponin T (hs-cTnT) of time after the R-wave of the ECG was computed and assay can be used for the detection of exercise induced investigated for beat-to-beat repositioning or irregularity. myocardial ischemia. Results: The irregularity of the beat-to-beat coronary bifurcation Method: Blood samples for measurement of hs-cTnT were position was very similar in all patients, resulting in a distinct obtained prospectively before testing in 481 consecutive patients temporal pattern (fig. 1) throughout the cardiac cycle. referred for myocardial perfusion single-photon emission Repositioning was always below 1. 6 mm while local minima were computed tomography. The severity of inducible ischemia was detected at end-systole and in mid-diastole, where repositioning categorized as none (summed difference score [SDS] <2), mild amounted to 0.7 mm or even less. During these intervals, the (SDS 2-7) and moderate-to-severe (SDS ≥8) blinded to hs-cTnT repositioning was significantly higher (student t-test: p <0.05) results. than immediately after the R-wave (early systole). Results: A moderate-to-severe ischemia was detected in 70 patients (15%), a mild ischemia in 159 patients (33%) and no ischemia was found in 252 patients (52%). Levels of hs-cTnT were significantly higher in patients with a higherve se rity of inducible myocardial ischemia (median [IQR] 0.012 [0.005–0.023] ug/l, 0.010 [0.005–0.017] ug/l and 0.006 [0.002–0.012] ug/l in patients with moderate-to-severe, mild and no ischemia, p <0.001

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Discussion: The repositioning of the coronary bifurcation Conclusion: Cardiovascular involvement in children with LSD is position is most precise at end-systole and during mid-diastole. especially relevant in MPS and PD. In FD in children, cardiac Since the duration of diastole is commonly more affected by RR anomalies are rare.Thus in MPS and PD, routine and repeat variability than that of systole, we posit that end-systolic imaging echocardiographic evaluation is necessary in children. may be preferable and may lead to an improved image quality and diagnostic value of coronary MRA in general. P308 Structural and functional adaption of the right P307 heart Echocardiographic findings in 30 children in ultra endurance athletes with various lysosomal storage disease A.M. Bernheim, M. Zuber, A. Linka, A. Fäh-Gunz, R. Weber, M. Rohrbach, M. Baumgartner, G. De Pasquale, B. Seifert, M. Pfyffer, B. Knechtle, E.R. Valsangiacomo Büchel, O. Kretschmar, B. Naegeli, C.H. Attenhofer Jost (Zürich, Othmarsingen, C.H. Attenhofer Jost (Zürich, CH) Winterthur, St. Gallen, CH) Background: Lysosomal storage diseases (LSD) can cause Background: Intensive endurance training may lead to structural cardiovascular involvement, especially thickening of cardiac and functional cardiac changes, an adaptive process known as valves, left ventricular hypertrophy (LVH), diastolic dysfunction the athlete’s heart. To date, research has primarily focused on left (DF), shortening of the PR interval and pulmonary hypertension. ventricular adaption to physical exercise, whereas data on Little is known about differences of cardiac involvement in involvement of the right heart has been sparse.The aim of the children between various LSD including Fabry disease (FD), present study was to evaluate alterations of the right-sided mucopolysacchardiosis (MPS), Pompe disease (PD), I-cell cardiac chambers in ironman (IM) triathlon participants. disease (ICD) and mucolipidosis (ML). Methods: An advanced echocardiographic examination, including Methods: Our echocardiographic database was searched for all standard Doppler, tissue Doppler imaging, and 2D speckle- children with the diagnosis of LSD; all echocardiographic data tracking strain echocardiography of right ventricular (RV) were analyzed as well as ECG tracings (PR interval), clinical longitudinal deformation in RV septal and lateral walls was findings and information on enzyme replacement therapy (ERT) performed in 39 IM athletes (ATHL) under resting condition the and bone marrow transplantation (BMT). day before the race. Echocardiographic data were compared to Results: LSD in children is rare with only 32 patients (19 females) 23 age- and gender-matched healthy controls. in our echocardiography data base.There were 21 pt with MPS Results: Echocardiographic findings in IM ATHL and controls are (6 pt with MPS I; 4 pt with MPS¨II, 3 with MPS III, 5 pt with MPS summarized in the table. IM ATHL had larger right-sided cardiac IV, and 3 pt with MPS VI), 6 pt with FD, 2 pt with mucolipidosis III, chambers than controls. In 5 IM ATHL (13%), RV apical ectasia 1 pt with ICD, and 2 pt with PD. ERT was given in 5 pt with MPS, was observed (figure). Five other ATHL showed a prominent 3 pt with FD and 1 pt with PD.Three pt with MPS had BMT.The , 2 among them additionally had RV sacculations results of the echocardiographic examinations are shown in the resembling changes usually observed in arrhythmogenic RV Table. Any valvular heart disease was present in 18 pt. Mitral cardiomyopathy (ARVC). There were significant differences in valve thickening was present in 18 pt, aortic valve thickening in RV systolic functional parameters. Apart from a higher tricuspid 16 pt. In children valvular heart disease is significantly lesste of n annular peak systolic exertion (TAPSE), apical segmental strain observed in FD than in MPS. Stenosis of the aortic valve was values were also higher in IM ATHL. We found no differences in observed in 3 pt, and of the mitral valve in 2 pt (all with MPS). RV diastolic function parameters, including E-, A-, E’-, A’ - Cardiac symptoms were reported only in 2 pt with MPS.Valvular abnormalities were more common than LVH (3 pt) which was seen in 2 pt with MPS and 1 pt with PD. In these pt, PR interval was not significantly different between the different diagnostic categories (p >0.05).

No. = number; LVMMI = left ventricular muscle mass index; EF = ejection fraction; LVH = left ventricular hypertrophy; P<0.05 is shown as *

The Figure shows a parasternal long-axis view image of a 14 year boy with MPS type II (Hunter) with typical thickening of the mitral valve (arrow); LA = left atrium; LV = left ventricle

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velocities, and the E/E’ ratio. However, systolic RV/RA pressure age at diagnosis was 3 years (range 0–37), 6 pts (42%) were gradients were higher in IM ATHL. All subjects were in sinus diagnosed within the first year of life and 3 pts (21%) in rhythm, their ECG showed no signs suggestive of ARVC. adulthood. Associated cardiac and non-cardiac abnormalities are Conclusions: In IM ATHL, right-sided cardiac chambers are summarized in table 1. Pulmonary hypertension was present in enlarged when compared to normal controls. Some structural half of all cases at time of diagnosis. In all pts the diagnosis was alterations may resemble ARVC. In addition, deformation imaging established by transthoracic echocardiography but most pts unmasked distinct functional changes with increased longitudinal underwent additional testing before surgery (cardiac 2D-strain in the apical segments of the right ventricle.When catheterization in 8, computed tomography in 7 and cardiac screening endurance ATHL, these echocardiographic changes magnetic resonance imaging in 6 pts). Surgical repair was have to be known. performed in 10 and surgery is planned in 2 pts. Median age at operation was 3 yrs (5 m–30 yrs). Systemic arterial blood supply to the right lung was closed surgically in 2 and interventionally in P309 1 patient. During a median follow-up time of 8.5 yrs (range 4–30 Monitoring of left atrial appendage closure yrs) no patient died. In 5 of 10 repaired pts (50%) significant with transesophageal echocardiography: obstruction/occlusion of pulmonary veins occurred during follow advantages and caveats up, necessitating redo surgery in 4. Pulmonary hypertension persisted in 3 pts (14%). At last follow up 10 patients (71%) were A. Fäh-Gunz, C.H. Attenhofer Jost, B. Naegeli, D. Maurer, in NYHA class I, 2 (14%) in NYHA class II and 2 (14%) in NYHA E. Straumann, P. Levis, F. W. Amann, G. Sütsch, M. Pfyffer, class III. C. Scharf (Zürich, CH) Conclusion: The majority of pts diagnosed with SS have Background: Percutaneous closure of the left atrial appendage associated cardiac and non-cardiac defects.While functional (LAA) is performed to prevent peripheral emboli in high-risk outcome after surgery is good, we found a high rate of residual patients(pt) with atrial fibrillation(afib). Transoesophageal pulmonary vein stenosis and a relatively high rate of persistence echocardiography(TOE) is used to guide implantation, but data of pulmonary hypertension. These findings mandate regular follow on its impact are limited. up these pts even after surgical repair. Methods: 2D- and 3D-TOE was performed immediately before, during and after LAA device closure. Number of LAA lobes were counted;, length and ostial diameter of the LAA were measured at 0°, 45°, 90° and 135° to size the device. Position of the device, coverage of the various LAA lobes, peridevice cleft, and compression of the Watchman device (Atritech; WD) were assessed during and after implantation. Results: In 34 pt (mean age: 67 ± 11 years; 24 men = 71%) device closure was planned. Indication for LAA closure was afib with systemic embolism in 8 pt (24%), a bleeding disorder in 3 pt (9%), in the other 23 pt strokes/TIAs despite oral anticoagulation. CHA2DS2-VASc-Score was 3.7 ± 1. 6 points. Implantation was not performed in 4 pt (12%) due to LAA thrombus (3 pt) and a multilobulated giant LAA (1 pt). Mean ostial size of the LAA was 22 ± 3 mm; length of LAA was 20.9 ± 5.9 mm. Of the 30 implanted pt; 23 (77%) received a WD and 7 pts (33%) a Cardiac plug (Amplatzer; CP). In 4 pts (13%, all WD), the size had to be changed during the procedure due to insufficient LAA coverage. In 12 pts (40%) repositioning was necessary due to incomplete P311 sealing on TOE. After implantation of the device, 7pt (WD 6pt, CP Diagnostic accuracy of pocket-sized handheld 1pt) showed non significant peridevice cleft of <5 mm, not related echocardiographs used by cardiologists in to device size( r = 0.064, p = 0.7). Size of the LAA occluder was the acute care setting 4.0 ± 2.4 mm larger than maximum measured diameter of the A. Testuz, H. Müller, P. -F. Keller, P. Meyer, L. Sekoranja, LAA (significant correlation; r = 0.81; p <0.0001).All devices were C. Vuille, H. Burri (Genève, CH) released only after stability testing. Complications included subacute dislodgement (without embolization) of a CP (1 pt), and Background: Handheld echocardiographs may be useful in the delayed tamponade after 24 hours (2 pt; one WD and one CP), acute care setting for patient triage as they are ultra-portable and one of them with fatal outcome. Small pericardial effusions were yield high quality 2D and color-Doppler images. However, small noted in 8 pt (27%). One pt had transient neurologic symptoms screen size and lack of pulsed-wave or continuous-wave Doppler due to air embolism. Peridevice flow was difficult to differentiate may limit diagnostic accuracy. from the transverse sinus which is an important caveat. Methods: Consecutive patients requiring an echocardiogram in Conclusions: Periprocedural guidance of LAA occluder the emergency room or intensive care unit in a single tertiary implantation by TOE has several advantages: 1. exclusion of centre were evaluated using a standard echocardiograph thrombi despite anticoagulation (9%), 2. device sizing, 3. (Philips ie33) with offline analysis by experienced cardiologists. detection of peridevice cleft and 4. stability assessment. After LAA Other cardiologists, blinded to the results, performed an device closure, development of pericardial effusion has to be echocardiogram using a handheld device (GE VScan) with excluded. bedside analysis of the images. Categorical parameters (grading of ventricular systolic function, valvular dysfunction and pericardial effusion) as well as likelihood of pre-defined clinical diagnoses P310 were compared. Results: A total of 46 patients were included (28 males, 68 ± 19 Scimitar syndrome – Clinical presentation, yrs). The results are shown in the table below. Agreement was management and outcome R. Hoop, A. Oxenius, M. Greutmann, E.R. Valsangiacomo Büchel (Zürich, CH) Introduction: Scimitar syndrome (SS) is defined as partial or complete anomalous pulmonary venous drainage of the right lung to the inferior vena cava with various additional features. Data on clinical presentation, cardiac comorbidities and outcome after surgical repair is sparse. Methods: All patients (pts) diagnosed with SS between 1979 and 2010 at our centre were reviewed. Our specific aim was to evaluate clinical presentation, therapeutic interventions and long-term outcome after surgery. Results: A total of 14 pts (42% males) were identified. Median

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particularly good for evaluation of left ventricular (LV) systolic Doppler (TVlat), myocardial performance index (MPI), and the function (abnormal in 55% of patients) and pericardial effusion rate of systolic RV pressure increase (dp/dt) measured at the (present in 13% of patients). tricuspid regurgitant signal. These parameters were compared to Conclusions: Handheld echocardiographs used by trained CMR derived RV ejection fraction (contiguous short axis slices, cardiologists provide accurate bedside evaluation of patients cine steady state free precession technique, manual contour in the acute care setting. tracing). Results: Mean RV ejection fraction was 47.1 ± 7. 8%. There was a significant correlation of FAC (mean 33 ± 9%, r = 0.47, p = 0.002) P312 and dp/dt (mean 992.9 ± 284, r = 0.33, p <0.05) with CMR Assessment of myocardial ischaemia and coronary derived RV function. A FAC >35% and dp/dt <1000 mm Hg/s arteries by cardiovascular magnetic resonance identified a RV ejection fraction <50% with a sensitivity of 84% in young adults after the arterial switch operation and 82%, and a specificity of 67% and 57%, respectively. The for transposition of the great arteries accuracy of dp/dt outperformed the other non-geometric parameters. D. Tobler, M. Greutmann, F. Verocai, M. Iwanochko, Conclusion: In patients with a subaortic RV, conventional R.M. Wald, A. Crean (Basel, Zürich, CH; Toronto, CA) measurements of RV function designed for a subpulmonary RV Background: In adults after the arterial switch operation (ASO), are less reliable.The old-fashioned, simple and geometry- current guidelines recommend regular non-invasive ischemia independent measurement of dp/dt provides an accurate estimate testing every 3–5 years given the uncertain course of this patient of RV function and should be used in these patients. group.This is generally performed by stress echocardiography or nuclear imaging techniques (MIBI). Our study examined the feasibility of using cardiovascular magnetic resonance (CMR) P314 as the principal screening modality. Pregnancy outcomes in women with heart defects Methods: Adult ASO survivors (≥18 years of age) were recruited from 2007–2010 at a tertiary centre in Switzerland prospectively. Patients underwent a combined CMR/MIBI protocol which included measurement of biventricular function, myocardial K. Khattab, C. Müller, J. Robert, A. Spreu, K. Scheibner, scar burden, coronary ostial assessment and myocardial L. Raio, M. Schwerzmann (Bern, CH) perfusion under vasodilator stress by both stress CMR (1st pass Introduction: Long-term outcome of congenital heart disease perfusion with gadolinium) and stress MIBI (technetium 99m). (CHD) has improved over the last decades.An increasing number Both stress studies were analysed visually for defects using the of women with CHD wish to become pregnant. Most of them are AHA 17 segment model of the left ventricle. Coronary ostia were at increased risk for maternal and fetal complications. Data about scored for assessability and normality of appearance. pregnancy outcomes in women with CHD in Switzerland in the Results: Nine patients completed the dual stress protocol and current era are missing. 1 patient underwent CMR and MIBI on separate days.There Method: 26 women with CHD, aged 29.9 ± 4.7 years, getting were no adverse side effects from the stress component of the pregnant in the years 2007–2009 were included in this procedure. The mean (±SD) right and left ventricular ejection observational, single centre, study. Primary endpoints were fractions were 50 ± 8% and 55 ± 6% respectively. Stress CMR maternal or foetal mortality within 6 months after delivery. was read as normal in all 10 patients with median summed stress, Secondary endpoints were urgent hospital admissions, the rates rest and difference scores of zero segments.Technetium MIBI of primary or secondary caesarean section, the APGAR score was reported as normal in 6 patients and probably normal in and birth weight. 1 patient. In the remaining 3 patients MIBI was mildly abnormal Results: There was no maternal or foetal mortality within the with stress-rest difference ≤; 3 segments and mainly fixed defects first 6 monthste af r delivery. There was 1 spontaneous abortion related to surgical repair.The median summed MIBI stress, rest in week 14 (4%). 6/26 (23%) women needed urgent hospital and difference scores were 0, 0 and 1 segment respectively. The admission during pregnancy: 1 for obstetric reason, 5 admissions coronary ostia were identified by CMR in all patients and thought for cardiac symptoms, one of them was in acute heart failure. to be clearly normal in 8 cases and probably normal in 2 cases. There were 6 primary caesarean sections, 3/26(11%) due to Myocardial scar identified by late gadolinium enhancement was obstetric reasons, 2/26 (11%) due to cardiac-related issues.There present in only 1 patient – this was concordant with MIBI which were 4 secondary caesarean sections, 3 for obstetric reasons showed a fixed defect in the right coronary artery territory. Nine (one with haemorrhagic complication), 1 due to acute heart patients had no evidence at all of myocardial scarring by late failure. Mean gestational week at delivery was 37.2 ± 5.7 weeks, gadolinium enhancement. one with extreme prematurity (at week 26, birth weight 700 g, Conclusion: ASO survivors in this study had little evidence of in a women with acute heart failure and a previous atrial switch significant myocardial ischemia, scar or coronary ostial procedure for complete transposition of the great arteries). Mean abnormality. Stress CMR may be a reasonable alternative to MIBI birth weight was 2973 ± 76 g. Three babies (14%) were small for in this young radiation-sensitive population and provides gestational age, 3 babies (14%) had a low birth weight (<2500 g). additional valuable information about the proximal coronary tree. The relative risk of low birth weight was 2.3 compared to the normal population of Switzerland. Mean APGAR at 1 minute was 7. 8 ± 1. 7. None of the offsprings had also CHD. On long term P313 follow-up (2 years in the case of the extreme premature baby), When right is left: assessment of systolic function none of the children shows developmental deficits. in patients with a subaortic right ventricle Conclusions: In the era, maternal and foetal mortality within 6 months after delivery is low in women with CHD. Nevertheless, K. Khattab, C. Müller, J. Robert, M. Schmid, C. Seiler, newborns of women with CHD are at increased risk of low birth A. Wahl, M. Schwerzmann (Bern, CH) weight and urgent hospital admissions of the mother are required Introduction: In adults with transposition of the great arteries in 1 of 4 cases. (TGA), the anatomical right ventricle (RV) serves as the subaortic ventricle, unless the patient underwent an arterial switch procedure. To assess systemic ventricular function in these P315 patients, echocardiographic parameters derived from studies Interventional interatrial shunt closure in with a subpulmonary RV are used. Their accuracy for a subaortic cyanotic adults with Ebstein›s malformation RV is unclear. Method: In 35 adults with a subaortic RV, we retrospectively M. Schwerzmann, A. Kadner, J.-P. Pfammatter, analyzed 49 echocardiograms and cardiac magnetic resonance P. Hildbrand, M. Hintermann, A. Wahl, S. Windecker, studies (CMR), performed within 1 month. Two patients had B. Meier (Bern, Brig, Solothurn, CH) congenitally corrected TGA, the other patients had complete Background: Ebstein’s malformation (EM) is a disorder of TGA and a previous atrial switch procedure. The following myocardial and tricuspid valvular development. Associated echocardiographic parameters of RV function were analysed: cardiac defects include a co-existing interatrial communication. Fractional area change (FAC); lateral tricuspid valve annular Age at presentation and severity of symptoms depend on systolic excursion (TAPSE) and motion velocities with tissue the anatomic severity of the malformation. Treatment

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recommendations focus on surgical interventions and anti- P317 arrhythmic management. In some adults with unrepaired EM, Aortopulmonary collaterals in neonates with interatrial right-to-left shunting as a result of pressure imbalance d-transposition of the great arteries (d-TGA)– between the atria or due to streaming of tricuspid regurgitant flow Clinical significance after arterial switch operation contributes to exercise intolerance and increases the risk of paradoxical embolism. It is unclear, whether shunt closure alone S. Navarini, C. Balmer, M. Hug, H. Dave, R. Prêtre, effectively alleviates symptoms in these patients or whether it will O. Kretschmar, W. Knirsch (Zürich, CH) exacerbate signs of right heart failure due to the abolition of a Objective: In patients with d-TGA enlarged bronchial arteries or hemodynamic “safety” valve. We hypothesized that hemodynamic major aortopulmonary collateral arteries (MAPCA) are common. testing identifies cyanotic adults with EM likely to benefit from Although clinically silent, the cardiac volume overload after shunt closure. surgical repair can lead to longer mechanical ventilation, inotropic Methods/Results: In 2009, 2 adults with EM (age 55–60 years) use and longer hospital stay. In addition, copious flow returning and resting saturations of 82–86% due to an interatrial shunt, from these vessels to the left atrium can impair the view on the underwent percutaneous shunt closure. In order to qualify for surgical field during cardiopulmonary bypass surgery. shunt closure, the following criteria were applied: Impaired Methods: We performed a 4-year retrospective monocentric exercise capacity with further desaturation during exercise, no study analyzing early clinical data in patients after arterial switch sustained arrhythmias, no severe tricuspid regurgitation, operation with MAPCAs complicating the postoperative course. unobstructed flow to the pulmonary arteries, no clinical signs of Results: In our institution 44 arterial switch operations were right heart failure, normal systolic function and an enddiastolic performed from 01.01. 2007 to 31.12.2010. Postoperatively 17 volume of >50 ml/m2 of the residual right ventricle on cardiac (39%) patients needed a cardiac catheterisation due to known MRI, and favorable response to temporary balloon occlusion of anomaly of the coronary arteries, pathologic signs for ischemia in the defect (i.e. no decrease in systemic blood pressure, no ECG, or prolonged postoperative course. 10 of these 17 patients elevation of right atrial pressure >20%, no decrease in right atrial (59%) had one or more MAPCAs, and 8 required transcatheter saturation >10%). Both procedures were done under fluoroscopy coil embolization. There was no significant difference in gender guidance.After shunt closure, resting oxygen saturation rose to and age. Catheterisation in patients with a hemodynamically >90% in both patients.After 12 months of follow-up, both patients relevant MAPCA was done between 7–53 (mean 18) days after described a sustained improvement in exercise capacity with switch operation without any major complications. Postoperative concomitant improvement on a cardiopulmonary exercise test. mean intubation time was 9.5 days, catecholamine use 9 days, One of the patients was able to re-practice gymnastics. Of note, and ICU stay 15 days. Overall hospital stay in patients with prior to the procedure, the patient was leaving home with a MAPCA coiling after arterial switch operation was 26 (mean, portable oxygenator. On follow-up echocardiography, there was range 15–81)days. One patient with a hydrocephalus internus no increase in RV diameter or tricuspid regurgitation and both requiring a ventriculo-peritoneal shunt after cerebral hemorrhagia patients had only minor increases in natriuretic peptides levels. stayed in hospital for 81 days. In all 8 patients cardiac Conclusion: Interventional interatrial shunt closure is safe and catheterisation resulted in complete MAPCA closure, but one effectively improves exercise capacity in selected cyanotic adults patient required an additional operation for stenosis of the left with EM. coronary artery. Conclusions: Hemodynamic relevant MAPCAs are quite common in patients after surgical repair of d-TGA. They can be P316 large enough to cause pulmonary volume overload with the Correlation of the right atrial volume with the right consequence of prolonged and complicated postoperative course. ventricular end-diastolic pressure Therefore, when facing this situation, an early postoperative work-up in the cathlab should be considered. W. Binder, C. Apitz, C. Bretschneider, A. Seeger, P. Martirosian, U. Kramer, M. Hofbeck, L. Sieverding (Tübingen, Giessen, DE) Introduction: The right ventricular end-diastolic pressure P318 (RVEDP) is an important parameter for the assessment of the Factors that impact end-of-life discussions in adult right ventricular function. It is determined invasively by cardiac congenital heart disease: patient and provider reports catheterization. The right atrium is directly subjected to the RVEDP through the open tricuspid valve. In case of elevated M. Greutmann, D. Tobler, M. Greutmann-Yantiri, J.M. Colman, pressure the right atrium is susceptible to dilation due to its A.H. Kovacs (Zürich, Basel, CH; Toronto, CA) thin-walled structure. This suggests that the right atrial volume Introduction: Previous research has shown that most adults with evaluated non-invasively by cardiovascular magnetic resonance congenital heart disease (CHD) are interested in discussing end imaging (CMR) can indicate chronic diastolic dysfunction of the of life (EOL) issues early in the disease course, yet few such right ventricle. discussions actually occur.We evaluated factors that impact EOL Methods: 35 patients with dilated right ventricle due to chronic discussions between adults with CHD and providers who care for pulmonary regurgitation were subjected to cardiac catheterization adults with CHD. and CMR to evaluate the necessity of Methods: Adult CHD outpatients completed a survey that replacement. In CMR the regurgitant fraction of the pulmonary assessed factors that might impact EOL discussions with their artery and the end-diastolic right ventricular volume were doctors. Background medical information was obtained by chart determined. In addition, the right atrial volume was assessed review. In parallel, providers within a national adult CHD network using ECG-gated cine steady state free precession (SSFP) were invited to complete a similar survey online. Responses were sequences for the acquisition of gapless slices in the axial plane: compared between the groups. In each slice the endocardium was manually contoured, and Results: Two hundred patients (52% male, age 35 ± 15 years) the resulting volumes were added according to the modified and 48 providers (primarily cardiologists) completed surveys. Simpson’s rule. Patients with tricuspid insufficiency were excluded Most providers (85%) reported that greater certainty about from the study. prognosis would help them discuss EOL issues. Providers worried Results: The normalization of the right atrial volume to body that they were unable reliably to estimate life-expectancy (89%) surface area resulted in the right atrial volume index (RAVI), and believed that patients were not ready for EOL discussions if which was on average 60.8 ± 20.1 ml/m2. Cardiac catheterization their life expectancies were >10 years (81%) or 5–10 years (67%). revealed a mean RVEDP of 10.4 ± 2.7 mm Hg, each of the values In contrast, only 25% of patients thought they were not ready to correlating well with the respective right atrial pressure (mean talk about the care they want if they get very sick; this patient 9.1 ± 2.6 mm Hg, r = 0.91, p <0.001). Furthermore, the correlation position was independent of disease complexity. The factors most between RVEDP and RAVI was shown to be statistically often reported by patients as facilitating discussion of EOL issues significant (r = 0.45, p = 0.007) despitete scat r of individual were trust in their doctors (88%) and belief that their doctors are values. good at taking care of CHD (81%).This parallels providers’ report Conclusions: The right atrial volume index determined by that a good relationship with patients (96%) and knowing patients cardiovascular magnetic resonance imaging correlates well with for a long time (85%) would help them discuss EOL issues. the right ventricular end-diastolic pressure. Hence it is a Patients indicated that EOL discussions would be hampered by parameter for diastolic dysfunction of the right ventricle that can their preference to concentrate on staying alive rather than to talk be assessed non-invasively.

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about death; this was reported more frequently by patients Methods: We performed a cross-sectional study including with CHD of great complexity than by those with CHD of mild 48 pubertal adolescents (13.6 ± 1. 5 yr), divided into two group. or moderate complexity (78% vs. 62%, p = 0.03). Twenty-four obese subjects (13.9 ± 1. 2 yr) with a mean BMI Conclusion: EOL discussions would be facilitated by improved z-score of 2.6 were compared to 24 lean control subjects (13.3 ± predictability of patients’ life expectancy. Providers worry about 1. 7 yr, mean BMI z-score of 0.0). Epicardial adipose tissue the readiness of patients, particularly those with longer life volume, as well as total, visceral, and subcutaneous abdominal expectancies, for EOL discussions; however, most CHD patients adipose tissue volumes were obtained in all children by MRI. are actually ready for such discussions.Atrusting patient-provider We measured fasting serum triglycerides, low- and high-density relationship is fundamental to facilitating EOL discussions. lipoproteins, total cholesterol, glucose and insulin levels. Office and 24-hour blood pressure measurements were collected. Results: Obese adolescents had higher epicardial fat volume P319 than controls (49.6 ± 18.0 cm3 vs 17.6 ± 6.7 cm3, p <.0005). Epicardial adipose tissue volume assessed by MRI EAT volume was strongly correlated to obesity indexes: BMI is increased in obese adolescents and correlates z-score (r = 0.790, p < .0005), waist circumference (r = 0.827, with cardiovascular risk factors p < .0005), and visceral abdominal fat volume (0.759, p < .0005). We also found a significant correlation between EAT volume and J. Wacker, N.J. Farpour-Lambert, D. Didier, A. Maggio, the following cardiovascular risk factors: fasting insulin (r = .583, M. Viallon, M. Beghetti (Genève, CH) p < .0005), HOMA-IR (r = .536, p < .0005), triglycerides (r = .534, Background: In adults, epicardial adipose tissue (EAT) is p < .0005), HDL-cholesterol (r = –.477, p = .001), and SBP 24h associated with metabolic syndrome and coronary artery disease. (r = .316, p = .036). Moreover, obese subjects with metabolic Epicardial fat thickness is increased in obese children, but there is syndrome had higher EAT volume than those without no data on total EAT volume and its relation to cardiovascular risk (63.5 ± 21.4 cm3 vs 44.9 ± 14.6 cm3, p = .026) factors in children. A positive association would sustain the early Conclusions: Epicardial adipose tissue volume is increased development of cardiovascular problems and the need for early in obese adolescents, and correlates with visceral fat and intervention. cardiovascular risk factors, in particular metabolic syndrome. Objectives: We sought to determine the volume of EAT in EAT may be associated to increased risk of cardiac event and adolescents and its relationship with obesity and other cardiovascular complications in adulthood, but further studies are cardiovascular risk factors. required.

P320 Reduced thickness of compacted myocardial layer: ± 0.05 cm in controls (p <0.0001), while maximal endsystolic a sensitive and specific echocardiographic criterion thickness of the compacted layer was significantly welo r than in for left ventricular non-compaction controls (0.53 ± 0.12 cm vs 1. 13 ± 0.22 cm; p <0.0001). The C. Gebhard, B.E. Stähli, M. Greutmann, R. Jenni, F. C. Tanner endsystolic ratio of non-compacted to compacted layer was 3.54 (Zürich, CH) ± 0.96 in patients with LVNC compared to 0.18 ± 0.06 in controls (p <0.0001). Endsystolic thickness of the compacted layer was Introduction: Left ventricular non-compaction (LVNC) is <8 mm in 40 cases and = 8 mm in 1 case with LVNC; conversely, characterized by a thickened myocardium with a non-compacted endsystolic thickness of the compacted layer was >8 mm in 40 inner and a compacted outer layer. A ratio of endsystolic thickness controls and = 8 mm in 1 control. The indexed ratio of septal wall of non-compacted to compacted layer >2 is an important thickness (M-mode) to compacted layer thickness was >0.64 diagnostic criterion. However, recent studies suggest that this (range = 0.64–1.85) in all patients with LVNC as opposed to criterion alone may be too sensitive. This study evaluates whether <0.63 (range = 0.27–0.63) in all controls.To differentiate LVNC the absolute thickness of the compacted layer could serve as an from normal hearts, an endsystolic thickness of the compacted additional criterion improving diagnostic accuracy. layer <8 mm has a sensitivity of 98% and a specifity of 100%, Methods: Echocardiography was performed in 41 patients and an indexed ratio of septal wall thickness to compacted layer with definite diagnosis of LVNC and in 41 age-matched controls thickness >0.64 has a specificity of 100% and a sensitivity of without cardiac disease.Absolute septal thickness (M-mode 100%. of parasternal long axis) as well as absolute thickness of Conclusion: Endsystolic thickness of the compacted layer non-compacted and compacted layers of affected ventricular <8 mm and indexed ratio of septal wall thickness to compacted segments (parasternal short axis) were measured. Mann- layer thickness >0.64 have a very high sensitivity and specificity Whitney-test was used for statistical analysis (SPSS 19). for the differentiation of LVNC from normal hearts.These critieria Results are indicated as mean ± SD. should be considered as additional parameters for the diagnosis Results: In patients with LVNC, maximal endsystolic thickness of LVNC. of the non-compacted layer was 1. 80 ± 0.41 cm compared to 0.19

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P321 resolved within 48 hours under anticoagulation therapy. TS has Tako-Tsubo syndrome: a cause of early recurrent been reported to be asymptomatic appearing frequently soon cardioembolic stroke after insular damage after stroke. The culprit stroke localisation frequently involved is the insular cortex which is known to cause dysautonomic and G. Moschovitis, P. Mayer-Melchiorre, A. Bersano, cardiovascular symptoms and possibly myocardial injury. In this M. Pons, C. Bassetti, C. Cereda (Lugano, CH) context, it may be speculated that TS could be induced by stroke Background: About ¼ of all ischemic strokes are of related autonomic disturbances. cardioembolic origin. Stress-mediated cardiomyopathy is a rare Conclusion: Stroke involving the insular cortex may induce TS: cause of acute left ventricular dysfunction which may be monitoring is mandatory. complicated by thrombus formation. We report the case of a first cardioembolic stroke involving the insular cortex developing few days later a recurrent contralateral ischemic stroke concomitant P322 with Tako-Tsubo syndrome (TS). A rare cause of dyspnoea and exercise Case report: A 70 year old female was referred to our center intolerance in a young patient with Evans syndrome complaining acute expressive aphasia. Her risk factors were only dislipidemia. She was cardio-pulmonal compensated. Cranial CT G. Moschovitis, R. Trunfio, J. Van Den Berg, T. Schmidhauser, scan confirmed an ischemia in the area of the leftarteria cerebri S. Regazzoni, M. Pons, F. Siclari (Lugano, CH) media involving the insular cortex. She was hospitalized in our Background: dyspnea and exercise intolerance are typical heart Stroke Unit for monitoring and treated with aspirine.After 3 days failure symptoms.We report the unusual presentation of a she presented an acute left arm paresis and non-painful thoracic Budd-Chiari syndrome in a patient with a known Evans syndrome discomfort. On the ECG T- wave negativity appeared on the which is in complete remission after treatment with corticosteroids anterior wall. Troponin-I increased to 0.34 ng/l. Transthoracic and monoclonal antibodies. ecocardiography showed a large acinetic area involving the Case description: a 26 year old woman was referred to our apical, anterior and inferior segments with a great thrombotic attention on february 2010 because of dyspnea on exercise formation; the systolic ejection fraction (EF) was estimated 40%. combined with epigastric discomfort and slight perimalleolar Anticoagulation therapy with Heparine e.v. was started. Medical bilateral pitting edema. Three years earlier she suffered from therapy included β-blocker and diuretic. After 48 hours the clinical an autoimmune haemolytic anemia and thrombocytopenia state improved. Echocardiography revealed an improvement of (Evans syndrome) with positive ANA, anti-histone and Lupus the global and regional EF, and a complete resolution of the anticoagulant antibodies, currently on remission after cortico- thrombus.After 1 week the EF was normal. Later on coronary steroid and Rituximab therapy. She was on anticonceptional pill. CT-scan showed normal coronary arteries.This finding enforced The physical exam revealed an hepatomegaly (confirmed by our diagnostic suspicion of a Tako-Tzubo (TS) cardiomyopathy. ultrasound), some ectatic paraombelical veins and perimalleolar Discussion: The plausible conclusion is that cerebral ischemia edema. The laboratory tests excluded hepatic dysfunction and the was of cardioembolic origin caused by LV thrombosis due to stress-induced TS cardiomyopathy. Surprisingly the thrombus

Figure 1 Transthoracic echocardiography showing a solid mass (M) Figure 1 protruding into the right atrium (RA) originating from the Transthoracic echocardiography: left ventricle (LV) with acinetic proximal part of the inferior vena cava (IVC), which appears apex and thrombus. LA = left atrium; RV = right ventricle; occluded. RV = right ventricle. LVOT = left ventricular outflow Ao = aorta. tract.

Figure 2 Figure 2 Subcostal view showing the occlusion (O) of the proximal part of After 2 days complete resolution of the thrombus under the IVC. The upper vena cava (UVC) appears enlarged and therapy. patent. In this view RA appears free.

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D-dimer were negative. Therefore a transthoracic echocardio- setting, an echocardiogram was performed to evaluate the graphy was requested to exclude low ejection fraction. The exam need for longer term mechanical circulatory support. revealed an occlusion of the proximal inferior vena cava (IVC) Figure 1 displays a transthoracic parasternal short axis view, with a solid mass protruding into the right atrium for about 2.5 cm showing complete obliteration of the left ventricle (LV) by (s. fig. 1), confirmed by Doppler analysis with flow inversion in the echodense material. There was no mitral or aortic valve opening IVC. On abdominal MR the intrahepatic segment of IVC appeared and no flow was detected on color Doppler. On figure 2 occluded and hypoplasic, the vena portae patent. After intensive concomitant complete thrombosis of the left atrium (LA) is interdisciplinary discussion the patient was successful treated visualized in the transesophageal bicaval view. The arterial by a combined approach (surgical and endovascular) under cannula was permeable with restoration of flow in the ascending prophylactic administration of corticosteroids, as well as an oral aorta.The right chambers were free of thrombus, with a very low anticoagulation therapy. The postoperative result was good and residual pulmonary flow. This extensive thrombosis of the left the patient could be discharged at home on 6 post-operative day. heart chambers occurred despite full dose anticoagulation as The CT scan 1 month later confirmed the good patency of the required for the ECMO circuit, and coexisted with a patent ECMO IVC and the reduction of the hepatomegaly. The histologic circuit and the absence of significant end-organ dysfunction. examination confirmed the diagnosis of “partiallyga or nized Twelve hours later, despite aggressive anticoagulation, the patient thrombotic material, without neoplastic tissue”. abruptly became unstable, with evidence of thrombus formation in Conclusion: in this case we describe the clinical course with the ECMO circuit and oxygenator failure. Efforts to restore support emphasis on diagnostic work-up including imaging and were unsuccessful. therapeutic management. Discussion: Clot formation is a well-known complication of ECMO.This case is unusual for the extent of the thrombosis documented by the echocardiograms and the striking contrast P323 between these findings and the preservation of stable Complete thrombosis of the left heart chambers hemodynamics, adequate ECMO flows and improving end-organ during mechanical circulatory support function. S. Reverdin, P. Meyer (Geneve, CH) Case presentation A 27 year-old drug-addicted male with a P324 history of relapsing endocarditis was admitted for acute heart Interatrial horseshoe thrombus trapped in a failure. One year prior to presentation he had undergone a Bentall patent foramen ovale procedure with an homograft combined with mitral valve repair. Upon presentation, transthoracic and transesophageal K.D. Till, U. Hufschmid, B.C. Friedli (Baden, CH) echocardiograms showed severe mitral and aortic regurgitations Introduction: Right heart thrombi in patients with pulmonary and an abscess of the mitral-aortic intervalvular fibrosa. The left embolism (PE) can be found with transthoracic echocardiography ventricle (LV) was severely dilated with a mildly reduced ejection (TTE) in 4-18%. The passage of a thrombus across a patent fraction. Blood cultures were positive for C. tuberculostaricum. foramen ovale (PFO) is rarely seen. Emergent replacement of the aortic homograft and mitral valve Case: A 38-year-old man hospitalized in the psychiatric clinic repair were performed, along with a patch reconstruction of the for several weeks because of a depressive episode presented aortic annulus.Attempts to wean cardio-pulmonary bypass were with dyspnea lasting for 3 days. Clinical examination showed unsuccessful, and the patient had to be placed on circulatory hypoxemia, tachycardia and normal blood pressure. D-dimer support with a veno-arterial, right atrium to ascending aorta and NT-proBNP levels were elevated, troponin T was normal. We extracorporeal membrane oxygenation (ECMO). After 3 days diagnosed PE with a saddle thrombus in the pulmonary artery of support, there was improving end organ function, without (fig. 1) in a CT angiography and started a therapeutic dosage lateralization on gross neurological examination, but no recovery of LV function based on invasive hemodynamics. In this stabilized

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of unfractionated heparin. TTE showed relevant pulmonary hypertension with right ventricular dysfunction (RVD), an atrial septum aneurysm and a biatrial U-shaped thrombus passing the a-v valves (fig. 2). The patient was immediately transferred for cardiac surgery. During induction of anaesthesia the patient had to be resuscitated mechanically because of hemodynamic instability. Transesophageal echocardiography showed the migrated thrombus in the aortic arch. An embolectomy of the right and left pulmonary artery along with a closure of a PFO was performed. Intraoperatively the thrombus was not detectable anymore. After surgery the patient developed acute ischemia of the upper left extremity. Thrombectomy of the subclavian and vertrebral artery restored perfusion. After a prolonged recovery the patient had no new neurological deficit and was discharged for cardiac rehabilitation. Right ventricular function had normalized. Discussion: The main role of TTE in non-high-risk PE is prognostic stratification to the intermediate or low-risk category. 1/4. Pulmonary systolic pressure was 40 mm Hg. HF with low In addition to RVD, TTE can identify right-to-left shunts through a voltage and increased left ventricular mass let us suspect a PFO and the presence of right heart thrombi, each indicating cardiac amyloidosis. Cardiac MR (CMR) corroborated this doubled mortality risk in PE. In our case the patient suffered from suspicion. Kinetics of gadolinium-chelates was positive for cardiac intermediate-risk PE. TTE was performed within 24 hours after amyloidosis and late enhancement images (LGE) typical for this diagnosis and showed a right heart thrombus trapped in a PFO disease, showing a circumferential, predominantly subendocardial during its transit from the right to the left atrium, producing pattern of enhancement (fig. 1). An endomyocardial biopsy was impending paradoxical embolism. Surgical embolectomy being diagnostic with amorphous interstitial deposits, positively stained the only efficient therapy, this underlines importance of TTE with Congo red (fig. 2) and apple-green under polarized light. at an early stage even in clinically intermediate-risk PE. Immuno-histochemical techniques showed neither light chains Conclusion: In high-risk PE emergency bedside TTE is Kappa or Lambda nor amyloid inflammatory protein. recommended for diagnostic purposes. In addition TTE is an Discussion: If a cardiac amyloidosis is suspected, the most important tool to detect complications of right heart thrombi even useful imaging modality is CMR with a LGE study. In a serie of in patients with clinically intermediate-risk PE. 33 patients with congestive HF, myocardial hypertrophy and restrictive filling pattern, sensitivity and specificity of CMR was 80% and 94% respectively. P325 Conclusion: In patients with congestive HF, microvoltage and Cardiac amyloidosis in patients with heart failure concentric hypertrophy, the differential diagnosis includes cardiac and myocardial hypertrophy, just think about it! amyloidosis. In this case, CMR is the most useful imaging modality. Definite diagnosis is only made by a tissue biopsy C. Sierro, J. Pasquier, S. Rotman, G. Girod, J. Schwitter stained with Congo red and by an immuno-histochemical study. (Sion, Lausanne, CH) Introduction: Heart failure (HF) is often caused by coronary artery disease or hypertension. Many other etiologies are known P326 such as cardiomyopathies, valvulopathies, infiltrative myocardial Bachmann bundle block due to primary diseases, pericardial or endocardial diseases, congenital cardiac lymphoma disorders, endocrine dysfunction, and toxics. Differential work-up of HF can be demanding. Case: A 60 years old male with treated C. Park, H. Muller, J. Peyrou, N. Schutz, M. Cikirikcioglu, hypertension had an echocardiography in 2005, showing D. Shah (Genève, CH) moderate concentric left ventricular hypertrophy (septum 12 mm, There are different muscular bridges providing interatrial posterior wall (PW) 11 mm, left ventricular mass 118 g/m2), connections between the atria across the septum. The considered as hypertensive cardiopathy. He was hospitalized in preferential connecting pathway is the Bachmann Bundle (BB) 2010 for biventricular, left predominant HF. NT-proBNP >3000 and block at its level can lead to interatrial block (IAB), defined ng/L. No neurological deficit. No inflammatory syndrome. Normal on the surface ECG as prolonged P-wave duration >110 ms.We immunofixation in blood and urin. Electrocardiogram (ECG) report the case of a 77-year old patient, with this very rare and showed a microvoltage with a precordial pseudo-infarct pattern, uncommon ECG changes related to primary cardiac lymphoma and echocardiography a concentric hypertrophy, an ejection infiltrating the interatrial septum. A 77-year-old immunocompetent fraction (EF) of 50%, a diastolic dysfunction grade 3/4, moderate woman was admitted for a 2 months history of worsening (2-3/4) mitral regurgitation (MR) and moderate pulmonary dyspnoea and recurrent position-dependent vertigo for 3 days. hypertension. HF was treated. After six months, EF was 60% and She was known for a past episode of heart failure attributed to diastolic dysfunction 2/4. Concentric hypertrophy was moderate to atrial flutter. Physical examination disclosed a cardiac systolic important (149 g/m2, septal and PW thickness 16 mm). MR was murmur grade 2/6 and oedema of the lower extremities.The ECG revealed sinus bradycardia with biphasic P waves in inferior and precordial leads and a delay of more than 200 ms suggestive of advanced interatrial block. Transthoracic echocardiography revealed the presence of a large right atrial mass involving the interatrial septum and the roof of the left atrium responsible for moderate tricuspid obstruction depending of the position of the patient and severe tricuspid regurgitation. The findings were confirmed on computed tomography demonstrating also partial obstruction of the superior vena cava. Rapid hemodynamic impairment with development of superior vena cava syndrome required high-risk emergency surgery. A large lobulated tumour, nearly completely occluding the right atrium was resected grossly by right atriotomy but unfortunately, the patient died due to multi-organ failure 2 days after the intervention. Definitive pathologic analysis showed diffuse large B Cell Lymphoma. IAB with biphasic P-wave is a potent precursor and predictor of atrial tachyarrhythmias. Our case showed a wide P-wave of 280 ms with an isoelectric line between the positive and negative deflection. The first positive deflectionly probab represents the cranio-caudal activation of the right atrium and the negative

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deflection corresponds to the delayed caudo-cranial activation of exertion during the previous month, with increasing intensity and the left atrium via the coronary sinus.The long isoelectric line frequency. Now, our patient was free of chest pain. (200 ms) is a consequence of very low voltage and a slowly The initial EKG demonstrated an isoelectric ST segment and conducting activation between the atria. This cardiac mass biphasic T waves biphasic from V2 to V4 (fig. 1). Troponin was infiltrating almost the totality of the interatrial septum and involving slightly elevated (0.21 ng/ml, n = 0.00–0.04). A coronarography the Bachmann bundle explains this rare ECG changes and is revealed a 95% stenosis of the mid portion of the left anterior probably the cause of the flutter observed in the patient. descending artery (LAD) (fig. 2, arrow) which was treated accordingly. Post procedure, the EKG showed deep inverted T waves in V2 and V3. The patient remained chest pain free until P327 discharge. Spontaneous coronary artery dissection: Discussion: The association of T waves abnormalities in the report of a case and review of the literature anterior leads with severe proximal LAD stenosis were first reported by Wellens’ group.Typically, T waves in V2 and V3 D. Zaugg Longchamp, M. Tapponnier, C. Stelios, present either with deep and symmetric wave (76%) or with E. Eeckhout, P. Vogt, D. Locca (Lausanne, CH) biphasic wave.They develop during a chest-pain free interval and A 31 year-old woman without cardiovascular risk factors (CRF) can remain for several weeks.The cardiac serum marker are was admitted to the emergency unit of our institution with 1 week normally not elevated. Because T waves inversions in precordial of typical chest pain without any significant electrocardiogram leads are found in numerous conditions, criteria have been (ECG) changes. Cardiac troponin I and creatine kinase were developed to facilitate in decision making.They include: prior raised to 1. 03 ug/l and 149 U/l. Transthoracic echocardiography chest pain, pattern during pain free state, no precordial Q waves, (TTE) was performed and showed a preserved left ventricular normal or slightly elevated cardiac serum markers, isoelectic or ejection fraction (LVEF) with a localised apical hypokinesia. The minimally elevated (<1 mm) ST segment, biphasic T waves or diagnosis of myocarditis was initially hypothesized. In order to rule symmetric deeply inverted T waves in V2 and V3. Angiography out an ischemic disorder a stress cardiac magnetic resonance remains the gold standard to diagnose and to treat severe (CMR) was performed within 12 hours following the patient proximal LAD lesions, as patients with Wellens’ syndrome are admission. CMR scan showed a border line LVEF and stress at high risk for anterior myocardial infarction. Literature revealed perfusion imaging highlighted a significant ischemia in the only one case of Wellens’ syndrome with mid LAD stenosis. anterior and infero-lateral walls (arrows fig. 1). An emergency Provocative diagnostic tests should be used cautiously, as coronary angiopraphy was performed showing smooth extensive anterior MI and fatal arrhythmias have been reported. unobstructed left main stem and clear dissection of the mid left Our patient had a one-month history of unstable angina and was anterior descending artery (LAD) associated with a mid circumflex free of chest pain upon arrival. The initial EKG showed isoelectric artery (Cx) dissection compatible with spontaneous coronary ST segments without Q waves. The T waves have typical biphasic artery dissection (SCAD). Due to sudden hemodynamic instability morphology in V2 and V3, which evolved into a deeply negative T and lateral ECG changes a stent was implanted in the Cx. Two wave pattern. Cardiac serum markers were minimally elevated. months later a repeated CMR scan showed a dilated LV with Coronary angiography demonstrated severe stenosis of the mid preserved LVEF but extended lateral and inferior subendocardial LAD. fibrosis.The repeated angiography failed to show any remaining Conclusion: Biphasic or inverted T waves in anterior leads coronary dissection in LAD and Cx territories. SCAD is an should alert “cardiology fellows” on call to potential severe LAD uncommon disease in the setting of acute coronary syndrome stenosis. Early catheterization is necessary to avoid fatal which may be present in stable or unstable angina and outcome. myocardial infarction. It has been especially described in post-partum period. To date optimal management of SCAD is not clearly defined. Possible options include medical therapy or invasive therapy. The rare literature published on that topic highlights the lack of agreement in detection and management of SCAD even if a large majority of patients who survive the acute phase have a good prognosis.This case reports uncommon clinical presentation of SCAD and highlighted the advantage of CMR imaging technique as a specific and accurate diagnostic tool in complex clinical feature to guide the therapy allowing tissular characterization and myocardial perfusion detection without any X-ray exposure.

P328 Wellens’ Syndrome: A T-wave warning against catastrophe? N. Tran, M. Padmalingam, A. Rezvan, D. Mullin, K. Kasper (Genève, CH; Philadelphia, Atlanta, US) Case: A 56 year-old postmenopausal Caucasian female with multiple risk factors was referred to our emergency department (ED) for chest pain on exertion. Symptoms started at rest and on

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P329 position, but the proximal portion was protruding accross the CS Management of preoperative ECMO support for erosion by 2 cm, which approximatively corresponds to the hemodynamic instability prior to arterial switch distance between the CS and the descending aorta. Microscopic operation analysis revealed inflammatory reaction not only around the CS and pericardial erosion, but also around the mediastinal A. Kadner, F. Schönhoff, D. Hutter, M. Pavlovic, hematoma and descending aorta suggesting that the erosion M. Schwerzmann, B. Wagner, J.-P. Pfammatter, developped for at least 7 days with a subsequent acute event T.P. Carrel (Bern, CH) (leak on the aorta) leading to death. The CS erosion occured in a Background: Extracorporeal membrane oxygenation (ECMO) bend where the centrifuge forces applied by the rods are has emerged as an effective method of mechanical support after important. Erosion by the PTMA device from within the vein was repair of congenital cardiac lesions in children with refractory listed among the potential major adverse event, but it never cardiac failure. However, experience with preoperative ECMO occured either in animal studies or in prior human implantations. support prior to arterial switch operation (ASO) is limited to a few cases and the management regarding potential preoperative “deconditioning” of the left ventricle due to reduced preload P331 on ECMO support is unclear.We report our experience and Shoulder pain after PFO closure: look at the management of a case of a newborn with TGA and intact Chiari network ventricular septum, who underwent preoperative ECMO support to the ASO. S. Chevallier, S. Cook (Fribourg, CH) Method/Results: A 2.8 kg newborn with TGA and intact Background: Percutaneous closure of patent foramen ovale ventricular septum had to undergo catheter septostomy for a (PFO) is being performed with increasing frequency in patients restrictive ASD. After failure of balloon atrial septostomy of the with cryptogenic stroke. Chiari›s network (CN) is a congenital aneurysmatic ASD and supportive therapy including inhaled nitric remnant connecting different parts of the atrium and found in oxide, emergency surgical atrial septectomy had to be performed about 2% of the general population. due to acute hemodynamic instability. Beside initial stabilization Method: A 26-year-old parturient was referred for investigations and amelioration of oxygen saturation was accomplished, after transient cerebral ischemia during delivery of her fourth progressive low-output-syndrom developed necessitating child. She has no known cardiovascular risk factor and no implantation of a centrifugal ECMO system on post-operative day contraception. Her medical history was only remarkable for 2. A centrifugal ECMO system was implanted and cardiac function monthly severe and invalidating migraine attack. was assessed by daily echocardiography with special attention to Transoesophageal echocardiography revealed atrial septal LV function and application of a weaning protocol. Arterial switch aneurysm with bi-directional shunt through a widely patent operation was performed after 4 days of ECMO support, the foramen ovale (PFO) (fig. 1). A closure of the PFO was performed infant was routinely weaned from the ECC and managened with with a 25 mm-Amplatzer device. inotropic support, which was completely weaned during the Results: Two month later, the patient was referred for subsequent days.The patient is doing well and is on no investigation of left shoulder pain that started a few days after medication. PFO closure. The pain was not reproducible by movement or Conclusions: Immediate ASO after ECMO support can be palpation. Transthoracic echocardiography ruled out pericardial successfully performed. No signs of “deconditioning” during the effusion and aortic erosion, and proved the stable position of the preoperative support time was observed allowing weaning from device.At 6-month routine transoesophageal echocardiographical ECC after ASO. Careful hemodynamic and echocardiographic follow-up, entrapment of one string of CN was observed in the assessment is necessary for determination of optimal duration of closure device (CD) (arrow fig. 2). Interestingly, shortly after the the preoperative stabilization period prior to the switch procedure. device implantation, the patient was free of recurrent migraine. Conclusion: We report a new problem after percutaneous PFO closure of CN entrapment against the atrial septum by the right P330 atrial disk of a 25mm-Amplatzer septal occluder device that was Erosion of successive tissue layers by associated with left shoulder pain and managed conservatively. percutaneous transvenous mitral annuloplasty device S. Noble, R. Vilarino, H. Muller, H. Sunthorn, M. Roffi (Genève, CH) An 83-year-old farmer with progressive dyspnea was admitted for acute heart failure. Transthoracic echocardiography (TTE) revealed functional (type IIIb) grade 3 mitral regurgitation (MR) and moderately decreased left ventricular ejection fraction (LVEF). Coronary angiogram demonstrated no significant lesions. Despite optimal medical therapy for 6 months, he remained in functional class III. Mitral valve repair using percutaneous implantation of the experimental Viacor PTMA device was performed. Under general anesthesia, with fluoroscopic and transesophageal echocardiography (TEE) guidance, PTMA catheter was inserted from the left subclavian vein to the coronary sinus (CS), and then advanced into the anterior interventricular vein. Into this catheter, two 120-mm rods were inserted to apply stiffnesses selectively to the P2 segment of the mitral valve, in order to reduce the septal-lateral dimension of the valve, improve leaflet coaptation, and reduce MR. Antero-posterior annulus diameter reduction was achieved and MR was reduced to grade 1. He was discharged at day 3 after having ruled out pericardial effusion by ETT and device migration by chest radiograph. At day 10, he self- medicated to temporarily relieve new onset of back pain. The day after, he experienced more intense back pain and was transferred to the emergency room in shock. Contrast induced thoraco- abdominal CT scan showed large hemothorax and an acute bleeding source on the descending aorta. Respecting the patient’s will, no surgery was attempted and he died 6 hours later. The autopsy showed perforation of the CS at 0.7 cm from the CS ostium, with subsequent perforation of the pericardium and descending aorta. PTMA device did not migrate from its final

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P332 (ACS) and A fib in the presence offi insuf cient anticoagulation Coronary vasospasm in a 6 years old girl: (INR 1. 6). Once in sinus rhythm, a coronary CT-scan was an unusual diagnosis performed showing that the left main trunk (LMT) was located between the aorta and pulmonary artery. CA showed a patent J. Wacker, Y. Aggoun, E. Golay, M. Beghetti, obtuse marginal and unchanged mid LAD lesion. In order to C. Tissot (Genève, CH) exclude an extrinsic compression of LMT, we undertook a Introduction: Syncope is a common complaint in the pediatric provocative test with dobutamine and atropine and simultaneous population, particularly in teenagers. Among cardiac causes of measurement of invasive coronary pressures (fractional flow syncope, the diagnosis of coronary artery anomalies remains reserve = FFR). After positioning the FFR wire in the mid LAD, we rare but can lead to serious complications. started the dobutamine infusion according to the local protocol. Case report: We report the case of a 6 years old girl who At 40 ug/Kg/min, heart rate has reached 180 bpm while blood presented with a one year history of syncope occurring during pressure was 220/120 mm Hg.At that moment the patient had exercise and emotion, with the frequency increasing during the typical chest pain in the absence of left main compression on CA, past 2 weeks to about twice a day. There were no other with a preserved TIMI 3 flow. After 150ug of intra-coronary complaints.Associated symptoms were palor, dyspnea and leg adenosine the FFR remained normal (baseline FFR: 0.94, at pain. Her past medical history is significant for spontaneous peak exercise 0.86). In view of these results, it was concluded closure of a perimembranous ventricular septal defect and her that the ACS episodes were not related to LMT compression but familial history is negative. The clinical exam is unremarkable. possibly to embolic events by A fib and insufficient The EKG is normal, with a corrected QT between 383–420 ms. anticoagulation. Cardiac enzymes showed an elevated CK-MB (263 U/l), elevated Conclusion: To confirm vain sively non-invasively or even NT pro-BNP (721 ng/l) but normal troponin level. Echocardio- invasively the external compression of the LMT arising from the graphy showed normal heart chambers size and function with right coronary sinus and located between the pulmonary artery normal-appearing coronary anatomy. The 24h EKG monitoring and the ascending aorta is very challenging. Since this rare showed significant ST segment depression followed by non congenital coronary malformation may be associated with sustained ventricular tachycardia during exercise. Coronary adverse events such as sudden cardiac death, the objectification CT-scan and coronary angiography showed no structural anomaly of the compression is critical before embracing treatments such of the coronary arteries.The cardiac MRI was normal, excluding as coronary artery bypass surgery or LMT stenting.This case the diagnosis of arythmogenic right ventricular dysplasia. A illustrates that an invasive stress test coupled with simultaneous second EKG monitoring showed torsade de pointe triggered by FFR measurement allows for confirmation or exclusion of this life an emotional stress with a prolonged QT interval (507 ms) that threatening condition. was at first attributed to an unusual form of long QT syndrome, and she was started on β blocker therapy. However, because of recurrent syncope on β-blocker, a myocardial scintigraphy with stress test was performed and showed abnormal captation in the anterior and apical regions, resolving with rest, compatible with myocardial ischemia, allowing us to evoke the diagnosis of coronary vasospasm. She was started on calcium antagonist with aggravation of the symptoms, reason why her treatment was changed for a β-blocker (nebivolol) and a dinitrate vasodilator associated with acetylsalicylic acid. Her evolution has been uneventful with no syncope for the last 6 months. Conclusion: Prinzmetal angina is seldom reported in the pediatric population. Calcium antagonists represent the gold standard in adults but had a controversial effect in our patient, with β-blocker being the most efficacious treatment.

P333 Recurrent acute coronary syndromes in a patient with anomalous left coronary originating from the right sinus of Valsalva N. Popova, R. Bonvini, M. Roffi, D. Carballo, S. Noble (Genève, CH) Case report: Congenital coronary anomalies are rare.We present the case of a 71-year-old patient with history of aortic valve replacement who presented with NSTEMI (peak CK 2000 U/l, troponin at 50 ug/l). Coronary angiography (CA) showed a single coronary artery originating from the right coronary sinus, an intermediate lesion of the mid LAD, and distal occlusion of the obtuse marginal branch of possible embolic cause in the presence of non-anticoagulated atrial fibrillation (A fib). The embolic origin was supported by the fact that the patient had also one ischemic lesion on cerebral MRI. No coronary CT scan could be performed at that time because the patient was in A fib.Two months later, he was re-admitted for acute coronary syndrome

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P334 P335 Outcome of cardiac surgery in Ebstein patients Surgical management of more than moderate over age 50 years: excellent survival and degree aortic insufficiency associated with improvement in cardiac symptoms ventricular septal defect: midterm results C.H. Attenhofer Jost, H.M. Connolly, C. Scott, H.M. Burkhart, A. Mohammed, S. Cherian, J. Jolou, Y. Aggoun, C.A. Warnes, J.A. Dearani (Zürich, CH; Zürich, Rochester, US) M. Cikirikcioglu, A. Kalangos (Genève, CH) Background: Data on management and surgical outcome of Objective: Ventricular Septal Defect (VSD) with Aortic patients (pt) with Ebstein’s anomaly (EA) over age 50 years are Regurgitation (AR) is a well-known association. Although early limited. VSD closure could prevent progression of associated AR, late Methods: 87 pt with EA (57 females = 64%) undergoing 89 presenting cases generally need additional techniques in order procedures cardiac surgery at our center at >50 years of age to address moderate to severe valve regurgitation. We aimed to between 1975 and January 2010 undergoing 89 procedures were assess the efficacy and durability of valve repair to treat moderate included in this retrospective study.All operative reports and to severe aortic insufficiency in this association. clinical charts were analyzed. Methods: A retrospective analysis of 20 consecutive patients Results: Age at EA diagnosis was 43 ± 19 years, mean age at (13 males, 7 females) with a mean age of 9.9 years (range 2–18) surgery 59 ± 8 years (range: 50–79). Preoperative symptoms operated by a single surgeon between 1996–2010.VSDs were included palpitations (69 pt), edema (30 pt), previous stroke/ subpulmonary (supracristal, doubly-committed, subarterial) in 10 transient ischemia attack (21 pt) and/or a history of heart failure patients, and subcristal in 10.The size of VSDs varied from 5 to (13 pt). Preoperatively, patients showed severe functional 18 mm as measured from the left ventricular aspect. AR was limitation; 79 pt (89%) had dyspnea on exertion NYHA class III or severe in 13 patients, and moderate to severe in 7. Transaortic IV.Atrial fibrillation was found in 10 pt; a pacemaker rhythm was approach for VSD closure was used in 18, and right present in 3 pt, one patient had a cardioverter defibrillator. ventriculotomy in 2. Patch closure was used in 10 cases, and Thirteen patients had previous cardiac surgery including ASD direct closure in other 10.Aortic valve repair was undertaken in 20 repair in 10 of these patients.Tricuspid valve replacement was patients employing techniques including Tr ussler in 10, free edge performed in 65 pt, and repair in 22 pt. Simultaneous cardiac triangular resection or plication in 12, cusp extension in 5, free procedures included closure of an interatrial communication in edge resuspension by a Gore-tex band in 2, tricuspidisation of a 54 pt, coronary artery bypass in 9 pt, ligation of accessory bicuspid valve in 1, and patch closure of a hole in 2. Five cases conduction tissue/MAZE procedure in 22 pt, 4 pt with mitral valve needed concomitant aortic annuloplasty. repair/replacement and other operations in 13 pt. There were Results: Follow-up was complete in all patients with a mean of 3 perioperative deaths (perioperative mortality 3%). Long-term 7. 9 years (range 3 months-14 years). There were no early or late follow-up was available in 81 of 86 survivors at 83 ± 68 months. mortalities. Postoperative echocardiography confirmed successful Improvement in functional class was reported in 67 of 81 pt VSD closure in all. AR improved in 19 patients (8 had no or trivial (83%). Postoperatively, only 8 pt (10%) remained in NYHA class AR, 11 had mild AR). Significant AR remained in 1 patient who III/IV. Fifteen pt died during follow-up (19%); best predictors of required aortic valve replacement on the 7th post-operative day. death was lack of postoperative improvement in functional class An additional 2 patients required aortic valve replacement at 3, (p = 0.02), a history of heart failure (p = 0.04) and diminished left and 4 years follow-up. ventricular ejection fraction of <50% (p = 0.04). Conclusions: Aortic valve repair with VSD closure in late Conclusion: Cardiac surgery in EA pt over age 50 years is often presenting patients provides good surgical outcomes.The choice complex. However, if it is performed at an experienced center for of the surgical repair technique employed depends on the severity congenital heart disease, perioperative mortality is low (3%) and and type of aortic cusp lesion, and is vital to ensure long-term long-term outcome shows impressive and sustained improvement efficacy of repair. in functional class.

P336 Controlled vascular endothelial growth factor Method and results: Human adipose-tissue stem cells (ASC) expression ensures safe angiogenesis and functional were transduced with retroviral vectors expressing either rat improvement in a model of myocardial infarction VEGF linked to the FACS-quantifiable surface marker CD8, or CD8 alone (CD8) as control. VEGF-expressing cells were then L. Melly, A. Marsano, U. Helmrich, M. Heberer, F. S. Eckstein, FACS-purified to generate populations producing either a specific T.P. Carrel, S. Cook, M.-N. Giraud-Flück, H. Tevaearai, A. Banfi (SPEC) or heterogeneous (ALL) VEGF levels. In a non-ischemic (Basel, Bern, CH) study, 107 cells of each group were injected into 5 sites of the left Introduction: Vascular Endothelial Growth Factor (VEGF) can ventricle of 15 nude rats.After 4 weeks, vessel density was induce normal or aberrant angiogenesis depending exclusively on increased 2–3 fold by both VEGF-producing groups. However, the amount secreted in the microenvironment, and not on its total ALL cells caused the development of numerous aberrant dose, as it remains localized in the matrix around each producing angioma-like structures, while SPEC cells induced only normal cell. To make this concept clinically applicable, we developed a and stable angiogenesis (fig. 1). To determine the safety and Fluorescent Activated Cell Sorting (FACS)-based technique to functional efficacy of this approach in cardiac ischemia, 70 nude rapidly purify transduced progenitors that homogeneously express rats underwent myocardial infarction by ligation of the left anterior a specific VEGFve le l from a heterogeneous primary population. descending artery.Two weeks later, heart failure was confirmed Here we aim at inducing safe and efficient angiogenesis in both by echocardiography and animals were randomized either to one normal and ischemic heart by cell-based expression of controlled of the 3 treatment groups (CD8, SPEC, ALL) with 107 cells, or VEGF levels. PBS, injected in 5 sites at the infarction border. Four weeks

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post-treatment, the ejection fraction was significantly worsened by Conclusion: Our data suggest that video assisted MIMVS treatment with either ALL VEGF (–13.4%) or control (CD8) cells through a right lateral mini-thoracotomy is a safe and efficient (–8.8%) as well as the PBS group (–8.0%) compared to SPEC first-line surgical choice, which facilitates combined cardiac VEGF cells (+1.7%). Further functional data of pressure-volume surgery and high valve repair rates (91.5%) at low risk. loops are being analyzed. Initial histology results confirm the induction of aberrant structures in the ALL group, which were completely prevented by SPEC cells similarly to the non-ischemic P339 tissue. Does a high body mass index affect the outcomes Conclusions: Controlled VEGF delivery by FACS-purified ASC is of minimally invasive mitral valve surgery? effective to reliably induce only normal vascular growth in the myocardium and is a promising novel strategy to achieve safe and D. Reser, T. Kofidis, J. Grünenfelder, V. Falk, S. Jacobs therapeutic angiogenesis to treat cardiac ischemia. (Zürich, CH) Introduction: Minimally invasive mitral valve surgery has evolved to a state-of-the-art procedure. However, it requires specialized P337 skills and shafted/endoscopic equipment in a restricted operative Minimally invasive aortic valve replacement with a field. There is still uncertainty as to whether obesity should deter sutureless prosthesis (3f Enable, ATS): a novel approach a surgeon from selecting the minimally invasive route. Our aim was to examine the effect of a high body mass index (>25 kg/m2) D. Reser, V. Falk, J. Grünenfelder (Zürich, CH) on the outcomes in video assisted minimally invasive mitral valve Introduction: Sutureless aortic valve prostheses are being surgery (MIMVS). established in modern cardiac surgery. They are implanted Methods: We conducted a retrospective database review through median sternotomy, transapically or percutaneously. Our of all patients undergoing MIMVS through a right lateral mini- aim was to evaluate the safety and benefits of the 3f Enable aortic thoracotomy between January 1st 2009 and December 31st prosthesis implanted minimal invasively through a right anterior 2010. mini-thoracotomy. Results: We identified a total of 153 consecutive patients and Methods: Case study of 5 patients undergoing aortic valve formed two groups: 75 patients had a body mass index >25 kg/m2 replacement with the 3f Enable sutureless, self-expanding, nitinol (25–36) 78 patients <25 kg/m2 (18–24). Age, Euroscore and stented, equine pericardial bioprosthesis through a right anterior gender were comparable between groups. Statistical analysis mini-thoracotomy (6–8 cm) in the second intercostal space. showed no significant differences between the groups comparing Results: Mean age was 70 years (±4), log Euroscore 5.6 the following variables: length of operation, CPB time, cross (±1.9). Median cross-clamp time was 71 minutes (62–80). No clamp time, successful valve reconstruction rate, conversion to intraoperative repositioning of the prosthesis was required. sternotomy, re-exploration for bleeding, ventilation time, ICU stay, Patients recovered fast without neurological complications, hospital stay, mortality, wound infection, stroke and need for reexploration for bleeding or wound infection. Mean ICU stay was transfusion. 43.8 hours (±40), hospital stay 9 days (±1.8), and ventilation time Conclusion: Our data suggest that a body mass index >25 kg/m2 16.8 hours (±16.5). No red blood cells were transfused and there is not a risk factor for a negative outcome in MIMVS.To the was no in-hospital mortality. One patient received a pacemaker contrary, these patients may profit from this approach because due to AV-Block III. Postoperative echocardiography revealed no it eliminates the need for sternotomy and the risk of subsequent paravalvular leak or major aortic insufficiency. There were no sternal wound infection in this high risk population. valve related adverse events. Conclusions: Our data suggest that the 3f Enable sutureless valve can be safely implanted through a right anterior mini- P340 thoracotomy. The minimal invasive approach may reduce the Outcomes of minimally invasive direct coronary need for red blood cell transfusions and facilitates patient bypass grafting recovery by eliminating sternotomy and the risk of subsequent deep wound infections. D. Reser, T. Kofidis, V. Falk, S. Jacobs (Zürich, CH) Introduction: Minimally invasive direct coronary artery bypass (MIDCAB) for revascularization of the left anterior descending P338 artery (LAD) through a left anterior mini-thoracotomy has become Operative outcomes of minimally invasive mitral a routine operation. Here we present our experience with valve surgery through a right lateral mini-thoracotomy 53 consecutive patients. Methods: All patients undergoing standard MIDCAB between D. Reser, T. Kofidis, S. Jacobs, V. Falk, J. Grünenfelder 1st 2009 and December 31st 2010 were included. Preoperative, (Zürich, CH) intraoperative, and postoperative data could be completed for all Introduction: Minimally invasive valve surgery has gained patients. Follow-up information about major cardiac and cerebral widespread acceptance in cardiac surgery. However, its adverse events (MACCE), and freedom of angina was collected. performance remains challenging for the surgeon: the operative Of these patients, 12 (22.6%) were scheduled for a hybrid field is restricted, and shafted instruments and/or endoscopes are procedure and received additional PCI with stenting. Four patients utilized. At our institution we use video assisted minimally invasive (7.5%) with multi-vessel disease with high predicted mortality for mitral valve surgery (MIMVS) as a standard approach in mitral conventional coronary artery bypass grafting (CABG) and the valve disease. Our aim was to examine the operative outcomes LAD as the major target vessel was classified to be suitable for of our MIMVS patients. MIDCAB. Methods: We conducted a retrospective database review of Results: Mean age was 66 years (±12.2), median Euroscore all patients undergoing MIMVS through a right lateral mini- 3.9. All patients were successfully operated without extracorporal thoracotomy between January 1st 2009 and December 31st bypass. One patient (1.8%) was converted to sternotomy. 22 2010. (41.5%) patients were directly extubated after the procedure. Results: We identified a total of 153 consecutive patients. Mean Median ICU stay was 1. 14 days (0–8), hospital stay 9.8 days age was 61 years (±12.4), median Euroscore 4.2 (1-12). There (2–49). No mortality, infarction or stroke occurred. One patient were 54 women in the group. Mean length of operation was 3.5h was treated with a wound infection. Reexploration for bleeding (±1.1), CPB time 150.3 minutes (±44.4) and aortic cross clamp was necessary in four patients (7.5%). Follow up was completed time 94.5 minutes (±27.8).In 140 patients (91.5%) the mitral valve in 22 patients (41.5%). One patient needed PCI with stenting of could be successfully reconstructed, 13 patients (8.5%) received the circumflex, another mitral valve repair after 18 months. a valve prosthesis. On 38 patients (24.8%) we additionally Conclusion: MIDCAB can be safely performed with low performed a cryoablation, on 7 (4.5%) a tricuspid valve repair postoperative mortality and morbidity. The short-term survival as and on 15 (9.8%) a closure of a patent foramen ovale. 6 patients well as freedom from MACCE and angina compare favourably (3.9%) had to be converted to median sternotomy (3 pulmonary with stenting and conventional surgery. vein injury, 1 valve not accessible after previous valve repair, 1 additional aortic valve regurgitation, 1 pleural adhesions).

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P341 Carpentier-Edwards pericardial valve (n = 110) were selected and The ideal distal anchoring point for neochordae compared to an individually matched group (logistic EuroScore, concomitant CABG, LVEF, valve size) of 110 patients after A. Weber, S. Hurni, S. Vandenberghe, A. Wahl, R. Vogel, mechanical bi-leaflet AVR (ATS/St.Jude Medical). Mean follow-up M. Keller, T.P. Carrel (Bern, CH) was 32.6 ± 24 months (range 2 to 120 months), mean age at Objective: Surgical treatment of mitral leaflet prolapse knows implant 50.6 ± 8.8 years (bioprostheses 51.7 ± 8.9 years; excellent outcomes with the use of neochordae. Upcoming mechanical valve 49.7 ± 8.6 years; p = 0.04). devices attempt the same treatment in a minimally invasive way Results: Survival was significantly reduced after biological AVR but are targeting the left ventricular (LV) apex as a distal (88.2% vs. 97.3%;p = 0.032). Freedom from all valve-related anchoring point, rather than the natural tip (PM). complications (bioprostheses 54.5%; mechanical valve 51.6%; In this study, we used cine cardiac magnetic resonance imaging p = ns) and freedom from reoperations (bioprostheses 100%; (CMR) to compare these two myocardial anchoring positions and mechanical valve 98%; p = ns) was comparable in both groups. their dynamic relation to the mitral leaflets. Average aortic mean (11. 2 ± 4.2 mm Hg vs. 10.5 ± 6.0 mm Hg, Methods: Eleven healthy volunteers (mean age 31 years; 6 p = 0.05) and peak (19.9 ± 6.7 mm Hg vs. 16.7 ± 8.0 mm Hg, females, mean EF 62%) were examined by CMR (3 Tesla, cine p = 0.03) gradients were higher after biological AVR. Regression steady free precession technique with retrospective gating), of LV-mass-index was higher after mechanical valve replacement whereby dedicated software enabled assessment of the (118.5 ± 24.9 g/m2 vs126.5 ± 38.5 g/m2; p = ns). Echocardio- physiological distances between three distal anchoring sites graphic valve prosthesis-patient mismatch (PPM) was higher (anterior PM, posterior PM, LV apex) and the plane of the mitral at follow up after biological AVR (0.876 ± 0.2 cm2/m2 vs. 1. 11 ± annulus at the level of leaflet coaptation. These distances were 0.4 cm2/m2; p = 0.01). measured in systole and diastole and the performance of virtual Conclusions: In this limited cohort of patients less than 60 years neochordae was analyzed for the three potential anchoring sites. of age, biological AVR was associated with reduced actuarial Results: Length difference between systole and diastole for the survival compared to mechanical valve implantation. Despite three measured distances were: 0.19 ± 0.11 cm (5.9 ± 3.4%) for similar valve-related event rates in both groups, better the anterior PM, 0.19 ± 0.09 cm (6.7 ± 3.6%) for the posterior PM hemodynamic performance of mechanical valves seems to and 1. 52 ± 0.18 cm (17. 8 ± 2.8%) for the left ventricular apex (p improve outcome.The later possibility of a transcatheter valve in <0.03). Virtual neochordae between the leaflet and LV apex were valve intervention once the tissue valve would degenerate does first adjusted in systole to achieve leaflet coaptation. They not justify the indication for biological AVR in younger patients. demonstrated that leaflet tear in diastole can only be avoided if the width of the attached leaflet is larger than the systole-diastole length difference. If, on the other hand, virtual neochordae are P343 adjusted in diastole to avoid leaflet tear, residual leaflet prolapse Are preoperative elevated inflammation parameters during systole can result. Since the systole-diastole length predictive for mortality in isolated coronary artery difference for PM anchored chordae is 10 times smaller than for by pass surgery apical chordae, there is strongly reduced risk of prolapse or tearing and the leaflet width is unimportant. Furthermore, if the G. Siniscalchi, H. Loblein, A. Häussler, D. Odavic, neochordae attached to the anterior mitral leaflet uses the LV R. Ploner, B. Seiffert, O. Dzemali, M. Genoni (Zürich, CH) apex as distal anchoring site, the angle α (fig. 1) between the Objective: It is shown that preoperative elevated inflammation aortic valve plane and this mitral leaflet is significantly reduced in markers can be used as a predictor of atherosclerosis. But the diastole and therefore increases the risk of systolic anterior value of these markers as never been studied during the post motion. operative period. This study was undertaken to see if these Conclusions: Anchoring of neochordae at the papillary muscles markers have a impact on post operative complication and should be preferred over the left ventricular apex. Further analysis outcome. of dilated hearts and papillary muscle displacement is necessary Methods: In this retrospective study the value of preoperative C to cover the whole spectrum of pathologies. Reactive Protein(CRP) and White Cell Count (WBC) elevation were analyzed in all patients undergoing coronary artery by pass surgery (CABG) during a period between 01.01. 2005 and 31.12.2009 in our centre. 933 patients. Results: Significant correlation between CRP elevation and prolonged intensive unite care unit stay (ICU ), (p <0.001) prolonged ventilation time (p <0.001), prolonged hospital stay (p <0.001), increased erythrocytes transfusion (p <0.001), increased renal insufficiency (p ≤0.001), post operative infection (p <0.001) and mortality (p <0.025). We are also be able to see a significant correlation between preoperative WBC elevation and prolonged ICU stay (p <0.001), CK MB (p <0.001), increased erythrocytes transfusion (p <0.001), infection rate (p <0.001), use of Intra-aortic balloon pump (IABP) (p <0.001), neurological complication (p ≤0.031) renal insufficiency p <0.001) and mortality (p <0.001). Taking in account all the variables CRP was independent risk for increase prolonged ICU days (p <0.001) increased ventilation time (p <0.001), hospital stay (p <0.001) and ck MB (p <0.018). P342 Conclusion: Our study shows that inflammation parameters such Patients less than 60 years of age following aortic as CRP and WBC are an important predictive marker for post valve replacement: comparison between pericardial operative complications and outcome. Elevated Morbidity and bioprostheses and mechanical aortic valve prostheses Mortality influenced the outcome negatively . If possible elective CABG cases should be operated very strictly only in patients with A. Weber, H. Noureddine, L. Englberger, F. Dick, T. Aymard, no elevated preoperatively inflammation markers. M. Czerny, D. Reineke, E. Roost, C. Huber, H. Tevaearai, T.P. Carrel, M. Stalder (Bern, CH) Background: Biological aortic valve replacement (AVR) in P344 patients less than 60 years of age is controversial and expected Syntax score in cardiac surgery – A tool for strategy event rates for survival and valve-related complications are not in coronary artery bypass grafting? clearly determined. Methods: Between 1/2000 and 12/2009, overall survival, G. Siniscalchi, H. Loblein, A. Häussler, M. Köhn, T. Syburra, valve-related events, and echocardiographic outcome were B. Seiffert, O. Dzemali, M. Genoni (Zürich, CH) analyzed in consecutive patients <60 years of age, who Objective: Numerous risk-stratification methods exist to predict underwent biological AVR. Those receiving a Perimount outcome in cardiac surgery. Recently Syntax score has been

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used to identify the complexity of coronary lesions by Conclusion: The bivariate analysis suggests that endoscopic incorporating coronary anatomy as it is intrinsic variables. harvesting leads to lower rates of SSI. In contrast, harvesting troponin subunit T has been shown to be readily released during from the lower limb was associated with an increased risk of SSI. myocardial injury; the level of troponin rise has also been shown Additional analyses including multiple regressions analyses to to predict prolonged ICU stay.We figure out to study a correlation adjust for confounding variables are required before between syntax score and the elevated level of cardiac enzymes recommending endoscopic harvesting to clearly prevent SSI. after off pump coronary bypass surgery (OPCAB). Methods: The data of 172 consecutive patients who underwent OPCAB between 01/2009 and 12/2009 in our centre were P346 retrospectively recognized. The patients were stratified into two Follow-up of last generation of stentless valve: groups: Syntax score (0-33) and Syntax >33. 43 female (21.8%) 140 Sorin Freedom Solo in aortic position and 154 male (78.2%) Results: In 119/ 172 patients,( 69%) Syntax score was >33 and T. Aymard, V. Göber, I. Bleul, A. Weber, A. Kadner, 53/ 172 (31%,) Syntax score was <33. The mean value in the L. Englberger, M. Stalder, H. Tevaearai, T.P. Carrel (Bern, CH) patient with >33 syntax score was 7. 7 ± 41 for the troponin, at Purpose: The Sorin Freedom Solo is a new generation of 24 h, 27.81 ± 42 for the CK masse MB at 24 h, and 466.6 ± 576 stentless bioprosthesis valve, designed for an entire supra- for the CK after 24 hours. In patients with a syntax score < than annular seating with one suture line implant technique.We aimed 33 the mean value for troponin was 2.2 ± 4, 27.4 ± 19 for the CK to review our experience and control the quality of our results in MB masse and 456 ± 342 for the CK. In our series, there was no terms of implantability, safety, mid-term hemodynamic significant interdependence of circulating troponin T, CK, CK Mb performance and clinic outcome. in postoperative period and grade of syntax score Methods: From January 2005 to December 2009, we implanted Conclusion: Our study showed no correlation in high Syntax the Sorin Solo bioprosthesis in aortic position in 140 patients. score levels and of elevated cardiac enzymes.The level of Patients with recent (<6 months) available clinical and SYNTAX Score has no influence in postoperative myocardial echocardiographic follow-up (>6 months) were reviewed. Patients’ damage in OPCAB.The worsening of coronary artery disease is profile, operative and early data were retrieved from our register. not correlated to myocardial damage after operation. We would Clinical and echocardiographic follow-up data were obtained from suggest using the Syntax score in cardiac surgery only as an the patient’s cardiologist and/or GP or from control in our additional tool in decision making for revascularization strategy, institution. and not as a predictor of potential postoperative myocardial Results: Of 140 patients, ninety-five were included (57.9% male, damage after off-pump coronary artery bypass grafting. 71.5 ± 8.6 years old, Log EuroSCORE: 10.5 ± 13.3). Aortic valve replacement was combined with another cardiac procedure in 52.6%. Mean size of implanted valves was 24.2 ± 2.2. Mean P345 aortic cross clamp time was 59.1 ± 22.8 min (47.9 ± 13.8 min for Prospective analysis of surgical site infection after isolated valve replacement). Postoperative heart block requiring endoscopic and open vein harvesting in coronary pacemaker implantation was low (4.2%). No other postoperative arterial bypass surgery in 1078 patients valve related complication was observed. Follow-up was 36.0 ± 13.9 months (clinical) and 32.5 ± 13.5 months (echographic D.T. Inderbitzin, O. Reuthebuch, B. Winkler, P. Matt, control). Mean pressure gradients was 10.4 ± 6.3 mm Hg (peak: F. Rüter, M. Grapow, F. S. Eckstein, A. Widmer (Basel, CH) 20.0 ± 11.4 mm Hg). Surface area of the prosthesis was 1. 9 ± 0.8 Introduction: Surgical site infection (SSI) after endoscopic cm2.Average NYHA score was 1. 4 ± 0.7 (2.5 ± 0.8 preoperative). and open vein harvesting in CABG is a rare, but devastating Conclusion: Mid-term hemodynamic performance of the Solo complication. We prospectively analyzed the incidence of stentless aortic bioprosthesis are encouraging and the clinical and potential risk factors for SSI in a 2 years follow-up. evolution after its implantation is good. Methods: From 1. 7. 2008–30.6.2010, data from all patients consecutively undergoing venous coronary arterial bypass grafting (CABG) were prospectively collected in a standardized P347 case report form, including age, gender, underlying diseases, Post-procedural stent shape analysis to elucidate location of venous harvest, endoscopic vs. open harvest. SSI was mechanisms of prosthetic valve associated defined as surgical site irritation with classic infectious cardinal complications after transcatheter aortic valve symptoms (dolor, rubor, calor). SSI-follow-up was accomplished implantation by phone call 1 and 6 months after surgery inquiring about cardinal symptoms of infection. Data were statistically analyzed M. Gessat, L. Altwegg, A. Plass, T. Frauenfelder, R. Corti, for potential risk factors for SSI in a bivariate analysis. J. Grünenfelder, V. Falk (Zürich, CH) Results: Totally 1078 patients (79.3% male, mean age 67.5 Introduction: Paravalvular aortic regurgitation (AR) and years) were included and 100% were analyzed. The overall conduction abnormalties such as left bundle branch block (LBBB) incidence of SSI at the harvest site was 2% (n = 22); 1. 3% (n = 8) and complete heart block (CHB) are considerably more frequent after endoscopic and 3% (n = 14) after open harvest. Harvesting in transcatheter aoric valve implantation (T-AVI) than in below the knee was found to be a highly significant risk factor for conventional aortic valve replacement (SAVR). In fact patients SSI (p 0.026 by Fishers Exact Test*) and endoscopic harvest (vs. receiving the self-expanding nitinol-based CoreValve show open) showed a clear tendency for less SSI (p 0.052*). Gender, highest rates of CHB, suggesting the stent design as a major age, body mass index and duration of surgery were no significant contributing factor.Thus, investigating stent deformation under the risk factors. (table) geometric constraints imposed by the aortic root anatomy and calcifications, might elucidate mechanisms leading to prosthetic valve associated complications. Methods: One-year-follow-up CTs of eight patients who had undergone T- AVI were acquired. Two cases had been diagnosed with postoperative AVB III° and AI II°, two cases with AVB III°, one case with LBBB and AI II°, one case with AI II°, and one case with neither notable AI nor arrhythmia. The implanted stents were extracted from the images.Areference model of an unconstrained CoreValve stent was created; deformation of the stent after implantation was modeled and visualized for each case.The maximum deformation of the stent was measured at its ventricular and aortal margins and the level of the natural annulus.The distance between the ventricular margin of the stent and the natural annulus was measured. Results: Deep implantation (implantation depth >1 cm) of the stent lead in all four cases to large deformations at the aortal margin of the stent (8.1 ± 1. 9 mm) and small deformations at the

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level of the natural annulus and the ventricular margin of the stent P349 (2.6 ± 1. 5 mm) with negligible reduction of the cross sectional Quantification of postoperative coronary bypass area at the annular level. All four cases with deep implantation flow using 3-Tesla magnetic resonance phase had AVB or LSB an AI of grade 2+. Three cases of high contrast imaging: comparison with intra-operative implantation (implantation depth <5 mm) showed moderate flow measurements deformations at the ventricular (3.5 ± 0.8 mm), aortal (4.5 ± 0.8 mm), and annular (3 ± 0.5 mm) levels and a notable reduction D. Reineke, V. Göber, H. Hoppe, M. Ith, O. Hess, M. Czerny, of the cross section area at the annular level. No AV blocks and E. Krähenbühl, M. Stalder, L. Englberger, T.P. Carrel (Bern, CH) one case of AI grade 2+ were found among these patients. Introduction: Evaluation of postoperative coronary bypass flow Conclusion: A novel approach to analysing the onset of using 3-Tesla magnetic resonance (MR) phase contrast and postoperative complications after T- AVI is presented. The comparison with intraoperative Doppler flow measurements. presented data is statistically not significant. veNe rtheless, a trend Methods: Fifty-six coronary bypasses (arteries: left internal towards cases with evenly distributed deformation showing fewer thoracic artery to left anterior descending artery n = 16, right complications than cases with large local deformation could be internal thoracic artery to right coronary artery n = 1; veins to right seen. This hypothesis will be further investigated in further coronary artery n = 18, marginal branch n = 7, circumflex branch studies. n = 7, diagonal branch n = 6, left anterior descending n = 1) were studied in 27 patients. In this prospective study, each bypass was studied intra-operatively using Doppler flow measurement. Within one week post surgery, patients were studied using a 3-Tesla MR scanner (Magnetom Verio, Siemens, Erlangen, Germany) using velocity encoded phase-contrast flow measurements. Results: Intra-operative Doppler flow measurements demonstrated regular flow patterns in all territories supplied. For all bypasses, MRI flow measurement results were as follows: median flow 60 ml/min (interquartile range (IQR): 37.5–78.5 ml/min). For comparison, the corresponding median intra-operative flow was 58 ml/min (IQR: 41–80 ml/min). There was a good agreement between intra-operative flow measurements and postoperative MRI flow measurements with a mean difference between the two methods of –1.02 ml/min and a range between limits of agreement of –67.37 – 65.33 ml/min. Linear regression analysis of pooled data revealed a highly significant correlation (p <0.001; R = 0.44). Discussion: This study demonstrates that postoperative 3-Tesla MR flow measurements agreed well with intra-operative Doppler results reconfirming coronary bypass patency. In the future, a broader application of this technique may facilitate follow-up post coronary bypass surgery possibly replacing empiric clinical judgment and angiography by an objective non invasive imaging.

P348 P350 Aortic valve replacement through the 4th intercostal space, is it possible and safe? Cardiovascular risk factors correlation with to syntax score, ejection fraction and B-type natriuretic T. Torre, R. Trunfio, G. Viganò, F. Sorrentino, S. Riva Muzio, peptide F. Siclari (Lugano, CH) H. Loeblein, O. Dzemali, M. Köhn, K. Graves, U. Schurr, Background: An antero-lateral minithoracotomy in the 4th A. Haeusler, D. Odavic, G. Siniscachi, M. Genoni (Zürich, CH) intercostal space has been proposed for aortic valve replacement (AVR) in alternative to other standard or mini-access approach. The risk factors for cardiovascular disease are well established. We retrospectively reviewed the operative results of two matched This study was undertaken to see if these factors are also groups of patients undergoing AVR with a sternotomy or this associated with syntax score, ejection fraction(EF) and level of minithoracotomy access. B-type natriuretic peptide (BNP). Methods: Between august 2003 and april 2010 109 consecutive Method: The data of 140 consecutive patients who underwent patients underwent a AVR of which 52 were operated through coronary bypass surgery between 1/2008–10/2008 were retrieved a 4th intercostal space thoracotomy (group M) and 57 through form our data bank. An association between cardiovascular risk a sternotomy approach (Group S). There was no difference factors [age, body mass index, total cholesterol, high density between the groups in terms of cardiovascular risk factor, sex, lipoprotein(HDL), low density lipoprotein(LDL), triglyceride(TG), mean age, Euroscore, BSA, mean ejection fraction, reoperation haemoglobin A1C(Hb1AC), hypertension, positive family history incidence and type of valvular lesion. Values are expressed as for cardiovascular disease and history of smoking] and syntax mean [SD = standard deviation] score, EF, BNP level was evaluated. Result: The average values were as follow: Syntax score 38.55, Results: There were no operative deaths. Conversion to 2 sternotomy was necessary in 2 group M patients. Cross clamping EF 54%, BNP 237 pg/ml, age 66, BMI 27 Kg/m , total cholesterol time (77.2 [17] vs. 44.4 [6.6] min), cardiopulmonary bypass time 4.6 mmol/l, HDL 1. 137 mmol/l, LDL 2.9 mmol/l, TG 1. 7 mmol/l, (131.7 [39.2] vs. 99.1 [4.6] and operative time (231.9 [50.2] vs. HgAIC 6.525. Of the 140 patients 64% were smokers or had a 161. 9 [32.3]) were significantly longer in group M (p <0.001). history of smoking , 80% had hypertension. There was no Ventilation time, ICU stay and length of hospital stay were similar. association between Syntax score and age, BMI, total cholesterol, In group M there were more reoperations for bleeding. No HDL, LDL, TG, HbA1C, hypertension, positive family history for statistically significant differences were observed between the two cardiovascular disease, smoking.We also found no association groups for postoperative atrial fibrillation, wound infections and between Syntax score and EF and between Syntax score and stroke. At a mean follow-up of 59.1 months all patients are BNP.Although ejection fraction and BNP were not found to have a alive and well; in group M 1 patient had to be reoperated for significant association with BMI, total cholesterol, HDL, LDL, TG, a paravalvular leak (6 months). QoL evaluation by SF-36 hypertension, positive family history for cardiovascular disease, questionnaire in group M showed a result better than the general smoking; there was a significant association ejection fraction and population in terms of physical and mental activity. BNP with level of HbA1C, CC= –.354 p = 0.003 and CC = 459 Conclusions: This study shows that the 4th intercostals space p = 0-001 respectively. Further, the level of BNP was also approach can be considered safe and longer operative times are significantly associated with increasing of age CC = 0.462, matched by a faster recovery. It represents an effective alternative P = 000, this association was not observed with ejection fraction. approach for AVR with the advantage of better cosmetic result Conclusion: Syntax score a tool currently used in angiographic and thoracic cage integrity by maintaining the possibility to grading the complexity of coronary artery disease in order to perform associated procedures. select the optimal technique of revascularization was not found to

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have a significant correlation with cardiovascular risk factors. was oversewn primarily in the right atrium. The patient had an There was a significant correlation between both BNP level and uneventful postoperative course and was discharged on the poor EF with higher HbA1C. BNP alone was associated with 5th postoperative day. increasing of age. Poor glycemic control outweighed other Conclusions: Although angiography is the definitive diagnostic cardiovascular risk factors in predicting a poor EF supporting imaging, the atypical presentation led to stepwise imaging to again the importance of good glycemic management and early reach the final diagnosis.To the best of our knowledge, this report cardiovascular screening of diabetic patients. is the first to comprehensively illustrate the characteristic appearance in a single patient by use of the full spectrum of noninvasive cardiac imaging modalities. P351 Triple valve repair in children with rheumatic heart disease: long-term experience P. O. Myers, M. Cikirikcioglu, C. Tissot, J.T. Christenson, M. Beghetti, A. Kalangos (Boston, US; Genève, CH) Objective: Tr iple valve replacement has poor early and long-term results, particularly in children. Little data is available on triple valve repair.We report our single-center long-term results on combined aortic, mitral and tricuspid valve repair in rheumatic children. Patients and methods: Ten children with severe rheumatic aortic, mitral and tricuspid regurgitation (mean age 12 ± 3 years) underwent triple valve repair over a 17 year period, using tailored cusp extension to repair the aortic valve, and ring annuloplasty and Carpentier’s techniques to repair the mitral and the tricuspid valves. Results: There were no early deaths. During a median follow-up of 58 months (range 3 months – 16 years), no late death occurred and 4 patients (40%) required reoperation at a median of 3 years (range 2.7–12 years), 1 for mitral valve replacement, 1 for aortic valve replacement and 2 for aortic and mitral valve replacement. Freedom from reoperation was 100% at 1 year, 63 ± 17% at 3, 5 and 10 years, and 47 ± 19% at 15 years. Conclusions: Tr iple valve repair, in this particularly challenging patient group, provided satisfactory initial and mid-term results, with a high burden of reoperation at the long-term, allowing a median of 3 years of growth and subsequent placement of a larger valve at the time of actual valve replacement. This strategy could be considered a good palliative surgical approach. P353 No-patch technique for complete common P352 atrioventricular canal repair Multi-modality Imaging in the evaluation P. O. Myers, M. Cikirikcioglu, A. Kalangos of aorta-right atrial tunnel (Boston, US; Genève, CH) P. O. Myers, F. Milas, S. Vlad, A. Panos Background: Although no-patch repair was the first described (Boston, US; Athènes, GR) surgical treatment for complete atrioventricular canal (CAVC) by Background: Aorta-right atrial tunnel is an extremely rare Lillihei in 1955, single or double-patch repairs, which are more congenital extracardiac vascular communication between heart complex, are currently more widely used. The objective of this chambers. We report on the imaging and management of a study was to assess the safety of directly closing both ventricular patient. and atrial septal components during the correction of CAVC. Case report: A 33 year old female patient presented Methods: Eight consecutive patients underwent no-patch repair Streptococcus viridans endocarditis following a fourth attempt between April 2007 and August 2008. The CAVC was closed at in vitro fertilization, which was treated with vancomycine for using pledgeted interrupted sutures placed on the right side of the 6 weeks.The physical examination was remarkable for a VSD crest, passed through the bridging leaflet and to the facing continuous murmur best heard at the right upper sternal border. part of the ostium primum defect, with closure of the left AV valve The echocardiogram showed a mass in the right atrium. Cardiac cleft. MRI showed that this mass contained turbulent blood flowing from the aorta to the right atrium. This mass was further defined by a coronary CT and angiography, which identified a posterior aorta-right atrial tunnel of 10 mm of maximal diameter, originating in the left sinus of Valsalva and draining to the RA adjacent to the opening of the coronary sinus.The coronary anatomy was normal. Stress echocardiography identified symptomatic lateral ischemia on exertion. The large size of this tunnel all the way the distal drainage in the right atrium did not allow for percutaneous occlusion with coils, and the patient was brought to the operating room for repair. On cardiopulmonary bypass, the distal opening of the tunnel was identified in the right atrium, behind a prominent network of fibers resembling the Eustachian valve, most likely responsible for the appearance as a mass on the echocardiogram and MRI. The aorta was transected and the proximal ostium of the tunnel was identified in the left sinus of Valsalva.The left main originated from the tunnel approximately 3 cm from the proximal ostium of the tunnel. A probe was advanced from the right atrium, within the tunnel, to the aorta to confirm the intramyocardial course of the tunnel. A circular patch of bovine pericardium was fashioned, which was sutured inside the tunnel, distal to the takeoff of the left main coronary artery.The distal tunnel ostium

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Results: The median age was 11 months (4–58). The median Results: Most frequently were post-cardiotomy effusions weight was 5.2 kg (4.4–8.6). The mean VSD size was 8.4 ± 1. 8 (42.2%), followed by neoplastic (17%), idiopathic-viral (11. 4%) mm. Cross-clamp was a mean of 52 ± 10 minutes.Two patients and posttraumatic-iatrogenic effusions (10.7%). Ascending aortic required concomitant right AV valve annuloplasty. There were no dissection and myocardial infarction with/without ventricular early deaths and all patients were in sinus rhythm. At discharge, rupture and severe dysfunction were in cause in 5.9%, respective no patient presented a significant residual VSD or LVOT 5.5% (s. fig. 1). Both entities are dramatic diseases with important obstruction. One patient presented mild left AV valve regurgitation surgical consequences and highest in-hospital mortality of 33%, and moderate right AV valve regurgitation; all others had no or respective 50%. Overall in hospital mortality was 15%. High early trivial regurgitation. There were no late deaths or reoperations. mortality rates of 19.1% and 17.2% were also observed in Conclusions: Surgical treatment of CAVC using the no-patch neoplastic and posttraumatic-iatrogenic effusions. Idiopathic, technique produces results comparable to modified single-patch post-cardiotomy and neoplastic pericardial effusions tend to repair, while reducing ischemic and bypass time. recidivate. Conclusions: In 58%, non post-cardiotomy, pericardial effusions were admitted to cardiac surgery for a more “invasive” pericardial P354 drainage.Actual guidelines (ESC 2004) propose a surgical Leg wound complications after saphenous vein approach in case of ruptured ventricular aneurysm and aortic harvesting for coronary artery bypass graft: dissection. Other indications are intra-pericardial blood clotting results from an ongoing prospective randomised trial and loculated effusions, making needle evacuation impossible. Diagnostic advantages, due to direct inspection and tissue R. Trunfio, S. Demertzis, M. Muretti, G. Viganò, F. Sorrentino, analysis, large access in acute pyo-pericardium and the option G. Franciosi, S. Riva Muzio, F. Siclari (Lugano, CH) to proceed an intra-pericardial drug instillation in neoplastic Background: Leg wound complications (LWC) after saphenous diseases are not mentioned and should kept in mind for treatment vein harvesting (SVH) prolong postoperative recovery, cause recommendations. Prognosis is harmful in case of pericardial patient discomfort and significant additional costs. Endoscopic hemorrhage and highest mortality rates of 50% are certainly due SVH is shown to decrease LWC but remains controversial to a pre-selection of acute life-threatening diseased patients. regarding quality and mid-term patency of the grafts. Patient and methods: From 02.2009 to 12.2010 a total of 170 consecutive patients (pts) were enrolled prospectively and randomized into one of the following groups: endoscopic SVH (ENDO, n = 49), open conventional (CONV, n = 79), open thermo-welding (OTHW, n = 42). In the latter group SVH was performed through multiple incisions (as in the CONV group) using the same thermo-welding forceps for cutting and coagulation as in the ENDO group.The leg wounds were evaluated at postop day 5 according to the ASEPSIS score, at 6 weeks and 6 months. Major adverse cardiac and cerebral events (MACCE: myocardial infarction, repeat revascularization, cerebrovascular accidents, death) were registered at XX. The incidence of LWC in the study period was compared to the incidence of LWC of the same time period of the year 2008. Comparisons were performed by ANOVA and/or Chi-square test and Kaplan-Meier analysis. Results: The incidence of significant LWC in the year prior to this study was 11% (24 out of 218 pts) compared to 2.9% (5 out of 170 pts) for the study period (p = 0.006). There were no statistically significant differences between the groups regarding the ASEPSIS score (ENDO: 1. 4 , CONV: 2.6, OTHW: 7. 5, p = 0.1), as well as the incidence and grade of LWC at 6 weeks and 6 P356 months (p = 0.6). The actuarial freedom from MACCE in the first Surgical correction of tracheo-esophageal 18 postop months was similar between the groups (ENDO: 96%, obstructions provides excellent freedom-from- CONV: 96%, OTHW: 94%, p = 0.89). re-intervention during long-term follow-up Conclusions: The increased and specific surveillance introduced by the study resulted in a highly significant reduction of LWC. C. Pawelczak, F. Schoenhoff, C. Friedli, M. Pavlovic, Freedom from MACCE at 18 months was high and similar J.-P. Pfammatter, C. Casaulta, T.P. Carrel, A. Kadner (Bern, CH) between the groups.The results so far do not favor one technique Objectives: Surgical correction of complex tracheo-esophageal over the other. obstructions due to vascular rings and slings has long been considered as ultima ratio. It was unclear whether patients would benefit in the long-term orif relief of symptoms was only P355 temporary. Aim of the current study was to provide long-term Etiologic spectrum of surgical pericardial effusion follow-up beyond infancy. drainage Patients and methods: Data were retrospectively collected from all patients that underwent surgery for complex tracheo- L. Niclauss, D. Delay, L.K. von Segesser (Lausanne, CH) esophageal obstructions due to vascular rings and slings at Objective: Surgical treatment of pericardial effusion, using this institution since 1992. different approaches, forms part of the standard cardiac surgeon’s Results: Twenty-seven patients were identified andov pr ided repertoire. Percutaneous approaches have replaced in some a mean follow-up of 9.4y.Two patients were lost to follow-up. extent the operative “standard”. Obvious advantages of the Diagnosis was double aortic arch (10 [40%]), right-sided aortic former are less traumatism, rapidity and availability as well as arch (6 [24%]), A. lusoria (3 [12%]), pulmonary artery sling (2 independency form complex infrastructures. However, surgical [8%]) and miscellaneous (4 [16%]). Tracheo- or bronchomalacia approaches may be advantageously and indicated in special was present in 10 [40%] and 3 [12%] patients, respectively. circumstances.The last ten year experience in a cardiac Two-thirds of patients (16 [64%]) suffered from associated cardiac surgery unit may be helpfully to define criteria, respecting actual defects.Two-thirds of patients (17 [67%]) had onset of symptoms guidelines, to opt for surgical pericardial drainage. shortly after birth whereas one-third (8 [33%]) presented later Methods: From January 2000 to December 2009 a total of in childhood. Diagnosis was made at an average age of 6 y 289 pericardial drainages in 273 patients by different surgical (0–14 y). Average time between onset of symptoms and referral approaches were performed. A retrospective study, analyzing for surgery was 4.1 y. Operative mortality was zero. Only 4 different etiologies, pre-operative clinical courses, surgical patients demonstrated residual symptoms during follow-up approaches and immediate postoperative courses (with or without leading to re-operation in 2 patients due to persistent dysphagia successive treatment), was realized in December 2010. and recurrent tracheal stenosis, respectively.

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Conclusion: Patients with complex tracheo-oesophageal lesions Methods: A 39-year-old man was hospitalised for stoke probably due to vascular malformations benefit from surgical intervention in due to paradoxal emboli. Echocardiography shows a PFO.A the long-term. The current data suggests that surgery is a viable catheter-based closure of the PFO was performed using the treatment option in this patient population and should not only be BioSTAR ® implant (33 mm). Correct positioning was controlled considered as a bail-out. with direct intra-cardiac echocardiography (AcuNavTM). Immediately after device deployment, the patient describes slight diffuse chest pain. Echocardiography shows correct positioning of P357 the device, with minimal pericardial effusion around the left atrial Advances in vacuum assisted closure therapy wall. The patient was discharged 48 hours later, with double oral for the treatment of poststernotomy mediastinitis: anti-platelet medication. An echocardiography was carried out five VAC-Instill system months later, because of persistent diffuse chest pain. A foreign body was found in the ascending aortic wall, at the level of the S. Karaca, A. Kalangos (Genève, CH) sino-tubular junction (fig. 1). The patient was admitted to the Background: Poststernotomy mediastinitis, also called deep cardiac surgery unit for surgical exploration. sternal wound infection, is one of the most feared complications Results: Initial surgical exploration, through a right atriotomy, in patients undergoing cardiovascular surgery. The incidence of showed correct positioning of the occluder with regard to the poststernotomy mediatinitis is fortunately very rare, between inter-auricular septum. PFO was closed correctly. After cardiac 1–3%, but shows a significant mortality, between 10–25%. The arrest, aorta was cross clamped and opened. Intra-aortic conventional forms of treatment involve surgical revision, open inspection revealed a perforation by a non absorbable metallic dressing and daily sternal lavage.Vacuum-assisted closure arm of the BioSTAR ® device close to the right coronary ostia therapy for treatment of sternal wound infection is a common (fig. 2). The device was complety ablated, aortic perforation was therapy since 1996. This wound-healing technique is based on a closed by a simple “X” stitch and the new iatrogenic intra-auricular local negative pressure which increases the microcirculation in sepal defect was closed by an autologous pericardial patch. the wound. The Vacuum-assisted closure (VAC) system has Postoperative echocardiography was normal and the patient recently been modified, allowing intermittent instillation of was discharged a day 10 after an uneventful course. antiseptic or antibacterial fluids into the wound. This VAC-Instill Conclusions: The BioSTAR ® occluder was designed to obtain therapy system is an innovative method that combines the a high percentage of bio-absorbable structures (90–95%). benefits of VAC and instillation therapy to help promote wound Avoidance or minimalization of foreign material implantation healing in cases of mediastinitis. and maintenance of a trans-septal access should be the main Methods: Eight patients (mean age 66 years) with suspected advantages. However, this case shows that severe complications, sternum infection underwent VAC-Therapy. The new VAC-instill like aortic root perforation, may be induced by the non absorbable system therapy, with intermittent instillation and lavage with part of the device (one metallic arm). The aortic root perforation antiseptic fluids, was applied immediately after diagnosis.The may occur during initial deployment or in consequence of antiseptic (Lavasept®) fluid instillation was 250cc every 8 hours progressive implant migration. Severe complications, even using regulated by the VAC-Instill system was changed every 4–5 days. new, potentially less invasive devices exists and should be keep Result: The VAC-Instill therapy lasted on average 18 ± 2 days, in mind, particularly in symptomatic patients. a median of 5–6 changes were necessary until the definitive closure of sternum. There were no deaths, and all patients could leave the hospital immediately after the closure of the sternum after 25 ± 2 days.The VAC-Instill therapy lasted on average 18 ± 2 days, a median of 5–6 changes were necessary until the definitive closure of sternum. There were no deaths, and all patients could leave the hospital immediately after the closure of the sternum after 25 ± 2 days. Conclusion: The new VAC–Instill system is useful in the treatment of mediastinitis, because it is a temporary wound care technique before reclosure of the sternum and intermittent instillation of antiseptic fluid supports the cleaning and drainage of the wound bed and the removal of infectious material.This method could open a new generation of treatment for poststernotomy mediastinitis.

P358 Aortic root perforation after BioSTAR® percutaneous closure of patent foramen ovale G.V. Vottero, L. Niclauss, M. Hurni, C. Marcucci, L.K. von Segesser (Lausanne, CH) Introduction: Percutaneous techniques are routinely used to close a patent foramen ovale (PFO). Complications remain rare, but have been described. In this case, a PFO was closed, using the “BioSTAR ® bio-absorbable septal repair implant”,provoking a perforation of the ascending aorta.

Cardiovascular Medicine 2011;14(5): Suppl 20 99 S erstautorenverzeichnis – liste des premiers auteurs

Die Ziffern beziehen sich auf die Seitenzahlen des Supplementums

Abbühl H 31 S, 55 S Greutmann M 84 S Naegeli B 55 S Schwerzmann M 83 S Altwegg L 28 S Guex G 9 S, 72 S Nägele R 66 S Shi Y 50 S Amiet V 79 S Navarini S 84 S Sierro C 88 S Ammon M 61 S Haaf P 15 S, 70 S Niclauss L 98 S Siniscalchi G 94 S Arenja N 58 S Haager PK 20 S Noble S 71 S, 90 S Sluka SHM 27 S, 47 S Asrih M 7 S, 47 S Haegeli LM 37 S, 57 S Noveanu M 57 S Sorrentino F 29 S Attenhofer Jost CH 35 S, 74 S, Hermann M 26 S Nucifora G 78 S Spicher A 6 S 92 S Hitz L 23 S Stähli BE 33 S Auricchio A 4 S Holy EW 27 S, 46 S Oberhaensli M 40 S, 69 S, Stefanini G 8 S, 69 S Aymard T 95 S Hoop R 82 S 70 S Stortecky S 60 S, 61 S Hottkowitz C 22 S Oroszlan M 39 S Sudano I 58 S Balmelli M 30 S Huber C 34 S Owala FO 46 S Sürder D 58 A, 65 S Bernheim AM 19 S, 81 S Hvelplund A 48 S Sütsch G 74 S Besler C 26 S Park C 30 S, 88 S Binder W 84 S Inderbitzin DT 95 S Pawelczak 98 S Tenkorang J 52 S, 53 S Blanche C 39 S Pazhenkottil AP 18 S Testuz A 32 S, 82 S Bonvini R 41 S Jaberg L 17 S Périard D 66 S Till KD 87 S Bösch C 62 S Joshi M 49 S Perruchoud S 21 S, 62 S Tobler D 83 S Brauchlin A 61 S Pfaff D 49 S Toggweiler S 16 S, 60 S Braunersreuther V 71 S Kadner A 90 S Pfenniger A 26 S Torre T 96 S Breitenstein A 24 S Kaiser C 68 S Philippova M 49 S Tran N 89 S Brenner R 72 S, 73 S Karaca S 99 S Pilgrim T 33 S, 64 S Tr unfio R 98 S Buttu A 54 S, 55 S Khanicheh E 18 S Popova N 91 S Khattab K 40 S, 83 S Potocki M 44 S Uldry L 53 S Carballo S 7 S Klimusina J 32 S Puricel S 68 S Cherian S 5 S Knechtle B 76 S Van Heeswijk RB 17 S Chevallier S 54 S, 90 S Knirsch W 35 S Quandt D 35 S Vassalli G 28 S Coppo S 80 S Kühne M 39 S, 51 S Quercioli A 10 S Vincenti GM 40 S Cuculi F 16 S Kuschnerus K 46 S Voss F 51 S Kyriakakis E 7 S Räber L 8 S, 9 S Vottero GV 99 S D’Oronzio U 78 S Radovanovic D 15 S Darioli R 41 S Locca D 69 S Regoli F 38 S Wacker J 85 S, 91 S De Boeck BWL 13 S, 79 S Loeblein H 12 S, 96 S Reichlin T 24 S, 47 S, 66 S, Wanitschek M 8 S de Marchi SF 71 S 67 S, 79 S, 80 S Weber A 94 S Deac M 12 S, 20 S Maeder MT 13 S, 14 S, 42 S, Rein P 75 S Weber B 42 S Di Valentino M 11 S 71 S Reineke D 29 S, 96 S Weber R 22 S, 81 S Domenichini G 24 S Marino D 21 S Reser D 93 S Wenaweser P 33 S Dornbierer M 59 S Martinelli M 62 S Reverdin S 87 S Wilhelm M 37 S, 55 S Dratva J 74 S Maslova K 48 S Rexhaj E 26 S Wohlmuth C 77 S Drexler B 63 S Mehta AJ 75 S Rickenbacher P 13 S, 59 S Meili-Butz S 57 S Rimoldi S 10 S, 19 S Zaugg Longchamp D 89 S Emmert MY 49 S Meissner J 44 S Robert J 31 S Zellweger MJ 9 S Melly L 92 S Rohner A 79 S Zeppetzauer M 11 S Fäh-Gunz A 82 S Meyer P 14 S Romanens M 11 S, 77 S Zimmermann M 37 S Farshad Schneider A 70 S Milano G 43 S Roost-Krähenbühl S 34 S Zipponi M 69 S Fauchère IPD 42 S Miserez A 73 S Zuppinger C 6 S Fournier S 74 S Mohammed A 92 S Saely C 77 S Zurek M 63 S Frey S 25 S Molica F 48 S Saguner AM 50 S Froidevaux L 56 S Monney P 45 S Sawhney V 38 S Montecucco F 6 S Schaer B 56 S Gaemperli O 4 S Moschetti K 68 S Schaetzle B 43 S Ganière V 25 S Moschovitis G 86 S Scharf C 38 S, 51 S Gebhard C 85 S Müller C 23 S Schenker SR 60 S Gessat M 33 S, 95 S Muretti M 45 S Scherff F 65 S Geyer R 75 S Mutschelknauss M 52 S Schoenenberger AW 43 S Gloekler S 28 S Muzzarelli S 36 S Schoenhoff F 36 S Göber V 5 S Myers PO 4 S, 29 S, 36 S, Schön P 50 S 97 S Schön T 76 S

Supplementum 20 der Zeitschrift «Cardiovascular Medicine» © 2011 by EMH Schweizerischer Ärzteverlag AG, Basel

Cardiovascular Medicine 2011;14(5): Suppl 20 100 S