FIRST LARGE COHORT WITH A SUTURELESS AORTIC VALVE: THE 1 YEAR FOLLOW-UP OF 628 CONSECUTIVE PATIENTS FROM AN INTERNATIONAL MULTICENTER PROSPECTIVE TRIAL Theodor Fischlein, Bart Meuris, Kavous Hakim-Meibodi, Martin Misfeld, Thierry Carrel, Marian Zembala, Sara Gaggianesi, Francesco Madonna, François Laborde, Axel Haverich on behalf of the Cavalier Trial Investigators The Perceval Sutureless valve is currently not approved for sale in US

T. Fischlein, B. Meuris, and F. Laborde are consultant for Sorin Group The trial was funded by Sorin Group Disclosure

Study Design Prospective, non-randomized, multi-center trial Primary endpoints: Safety (mortality and morbidity) and Effectiveness (clinical status end haemodynamic performance 1 year Clinical Event Committee (CEC) for independent review and adjudication of adverse events Yearly follow up to 5 years PERCEVAL

Inclusion Criteria Male/female ≥ 65 years old Aortic valve stenosis or steno-insufficiency Eligible to AVR with biological prosthesis Willing to sign informed consent Willing to undergo all medical follow-ups echocardiography examinations laboratory tests Exclusion criteria Preexisting valve prostheses (mitral, pulmonary or tricuspid) Double/triple valve replacement Simultaneous cardiac procedures (except septal myectomy and/or coronary bypass) Active endocarditis/myocarditis Congenital bicuspid valve Aneurysmal dilation or dissection of the ascending aortic wall Sino-tubular junction and the annulus diameter >1.3 Main In/Exclusion Criteria

CAVALIER Trial - Study Overview

MAIN REASONS FOR NOT RECEIVING PERCEVAL 66 (42%) Valve size not available 16 (10%) Congenital Bicuspid valve 12 (8%) Ratio STJ/Annulus > (5.7%)Withdrawn consent MAIN REASONS FOR NOT RECEIVING PERCEVAL 66 (42%) Valve size not available 16 (10%) Congenital Bicuspid valve 12 (8%) Ratio STJ/Annulus > (5.7%)Withdrawn consent Study Flow Chart Patients Enrolled n = 815 Different prosthesis implanted n =30 Patients included n = year Follow-Up n = 549 Death n =50 Explant n =12 Excluded before implant N=157 (not meeting Inclusion Criteria) Patients with Perceval valve attempt n = 658 Patient withdrawal n = 15 Patient lost to F-up n = 2

The Perceval Valve Valve Features Bovine pericardium Double-sheet design Eyelets for guiding suture positioning Self-Anchoring Frame Self-expanding, Ni-Ti alloy Anatomical design to fit Valsalva sinuses Double-ring geometry Carbofilm™ coating

Demographic658 patients Mean age (range)78.3 ± 5.6 (61.6 ; 92.6) Males234 (35.6%) Females424 (64.4%) 40% of patients octagenarian NYHA ClassificationAge distribution Patient demographics

Mean STS Score ± SD: 7.2 ± 7.4 (Min - Max: 0.8 – 50.0) Preoperative risk factors n=658 * Insulin dependent diabetes: 9.6%

Surgical approachOVERALL (N=658) Median sternotomy 439 (66.7%) Minimally invasive access Ministernotomy / Minithoracotomy 219 (33.3%) XL size implants started in July 2012 Concomitant Cardiac Procedures 194 / 658 (29.5%) CABG 154 (23.4%) Septal myectomy 22 (3.3%) Afib treatment 20 (3.0%) Tricuspid valve repair 7(1.1%) Congenital defect closure 3 (0.5%) Other 4 (0.6%) Note: Patients may have more than one concomitant surgical procedures Surgical details

Median Sternotomy (439) Surgical Approach Minimally Invasive Access (219)

Early (≤ 30 days) n=628 1 yr (>30 days) n = 600 n (%) Any death 22 (3.5)28 (4.6) Cardiac deaths 16 (2.5)12 (2.0) Non cardiac deaths6 (0.9)16 (2.7) 1 month96.32 % (94,84 % %) 3 months94.06 % (92.02 % %) 6 months93.24 % (91.27 % %) 9 months92.58 % (90.52 % %) 12 months91.75 % (89.59 % %) 91.75% Freedom From Overall DeathFreedom From Cardiac Death 95.43% 1 month97.43 % (96.19% %) 3 months96.61 % (95.18 % %) 6 months95.94 % (94.38 % %) 9 months95.6 % (93.97 % %) 12 months95.43 % (93.77% %) Mortality

Early (≤ 30 days) n = 628 year (> 30 days) n = 600 n (%) Reintervention for bleeding27 (4.3)0 (0.0) Explant6 (0.9)6 (1.0) Primary PVL5 (0.8)2 (0.3) Leading to explant4 (0.4)0 (0.0) Stroke 14 (2.2)5 (0.8) Endocarditis1 (0.2)8 (1.3) Leading to explant0 (0.0)5 (0.8) Hemolysis (clinically significant)1 (0.2) SVD0 (0.0) Valve Thrombosis0 (0.0) AV block III leading to Pace Maker Implant51 (8.1)9 (1.5) Morbidity

Clinical Status

Hemodynamic data at 1 year

LV mass regression by follow-up interval in paired patients (n=126) P < Discharge (N=126)3/6 Month (N=126)12 Month (N=126) MEAN LV MASS - g

Conclusion High implant success rate (95%) Very promising outcomes, with a low rate of cardiac mortality, stroke, major paravalvular leaks, and valve explants, despite the risk profile of the of patients (40% octagenarians; mean STS score 7.2) Early (2.5%) and one year (4.6%) cardiac mortality rates are favorable/comparable to those reported in the literature Proved suitability of the Perceval Valve in the conventional full sternotomy as well as the minimally invasive approach Clinical status (NYHA class) improved to at least one class in 77.5% of patients and remained stable during the FU Transvalvular gradient reduction was significant and stable resulting in a improvement in left ventricular mass (p<0.01) up to 1 year

Wolfang Harringer Department of Thoracic and Cardiovascular Surgery, Klinikum Braunschweig, Braunschweig, Germany Ulrike Carstens-Fitz Tom J. Spyt Regional Cardiothoracic Unit, Genfield General Hospital, Leicester, United Kingdom Jan Gerhard Wimmer-Greinecker Herz und Gefäßzentrum, Bad Bevensen,Germany Matthias Machner Erwin S.H. Tan Catharina Ziekenhuis, Eindhoven, Netherlands Filip P.A. Casselman OLV Clinic - Department of Cardiovascular and Thoracic Surgery, Aalst, Belgium Alaaddin Yilmaz Saint Antonius Hospital, Nieuwegein, Netherlands Uday Sonker Sabine Bleiziffer German Heart Center, Munich, Germany Peter J. Oberwalder Medical School Graz, Department of Cardiac Surgery, Graz, Austria Alfred A. Kocher Department Cardiothoracic Surgery, Medical University, Vienna, Austria Rainald Seitelberger Hendrik Treede Universitäres Herzzentrum Hamburg GmbH, Hamburg, Germany Leonard Conradi Riccardo Cocchieri Amsterdam Medical Centre - AMC, Amsterdam, Netherland Bas De Mol Jean-Christian Roussel Centre Hospitalier Universitaire, Nantes, France Philippe Despins Heinz G. Jakob Department of Thoracic & Cardiovascular Surgery, University of Essen, West German Heart Center, Essen, Germany Daniel Wendt Thierry Folliguet Cardiac Medico-Surgical Department, Institute Mutualiste Montsouris, Paris, France Kostantinos Zannis Steffen Pfeiffer Cardiac Surgery, Paracelsus Medical University, Klinikum Nürnberg, Nuremberg, Germany Giuseppe Santarpino Malakh Shrestha Cardio-thoracic, Transplantation & Vascular Surgery, Hannover Medical School, Germany Samir Sarikouch Jan F. Gummert Klinik, Herz- und Diabeteszentrum, Bad Oeynhausen, Germany Friedrich W. Mohr Herzzentrum der Universität Leipzig, Klinik fur Herzchirurgie, Leipzig, Germany Pascal Dohmen Mario Stalder Inselspital, University of Bern, Bern, Switzerland Eva Roost Krzysztof Filipiak Silesian University Center for Heart Disease, Zabrze, Poland Tomasz Niklewski Xavier Roques Hopital Cardiologique Du Haut- Lévêque, Pessac, France Willem J. Flameng Cardiac Surgery, U.Z. Gasthuisberg, Leuven, Belgium Axel M.M. Laczkovics Ruhr University of Bochum, Department of Cardiothoracic Surgery, Bochum, Germany Matthias Bechtel Alain G. Prat Centre Hospitalier Regional Universitaire, Lille, France Carlo Banfi Otto E Dapunt Klinikum Oldenburg, Department of Cardiovascular Surgery, Oldenburg, Germany Harald C. Eichstaedt Acknowledgments

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