FIRST LARGE COHORT WITH A SUTURELESSAORTIC 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 improvement) @ 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 wallSino-tubular junction and the annulus diameter >1.3

Main In/Exclusion Criteria

Paris

Nurnberg

Hannove

r

Bad Oey

nha...

Leipzig Bern

Zabrze

Bordeaux

Leuve

n

Bochum

Eindho

ven

Lille

Oldenburg

Bad Beve

nsen

Braunsc

hweig

Leiceste

rAals

t

Munich

Nieuwegein

Graz

HamburgVien

na

Amsterdam

Essen

Nantes

0

20

40

60

80

100

120Enrollment : February 2010 – September 2013 5 year follow-up ongoing25 Centers in 8 European Countries658 operated patientsSurgical access: median sternotomy/minimally invasive access Available sizes: S, M, L, XL

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 > 1.3• 9 (5.7%)Withdrawn consent

Study Flow Chart

Patients Enrolledn = 815

Different prosthesis implantedn =30

Patients includedn = 628

1-year Follow-Upn = 549

Deathn =50

Explantn =12

Excluded before implant N=157 (not meeting Inclusion Criteria)

Patients with Perceval valve attempt

n = 658

Patient withdrawaln = 15

Patient lost to F-upn = 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

Demographic 658 patientsMean age (range) 78.3 ± 5.6 (61.6 ; 92.6)Males 234 (35.6%)Females 424 (64.4%)

40% of patients octagenarian

3.3%

30.1%58.7%

4.9%

NYHA I NYHA II NYHA III NYHA IV

NYHA ClassificationAge distribution

Patient demographics

7,3%

52,7%

40,0%

< 70 70-79 ≥80

Active Smokers

Cerebrovascular disease

Renal insufficiency

Chronic lung disease

Extracardiac arteriopathy

Diabetes*

Systemic hypertension

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

4.7%

11.4%

14.8%

15.7%

17.0%

29.0%

83.7%

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 approach OVERALL (N=658)

Median sternotomy 439 (66.7%)

Minimally invasive access Ministernotomy / Minithoracotomy

219 (33.3%)

S M L XL0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

12.8%

44.1%

38.8%

4.4%

Valve size

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)

Isolated Concomitant Cardiac Procedures

64.470.9

38.743.9

CPB Time (min)

X-Clamp Time (min)

Isolated Concomitant Cardiac Procedures

53.9

79.3

33.2

53.0

CPB Time (min)

X-Clamp Time (min)

Surgical Approach

Minimally Invasive Access (219)

Early (≤ 30 days)

n=628

Late @ 1 yr (>30 days)

n = 600n (%) n (%)

Any death 22 (3.5) 28 (4.6)

Cardiac deaths 16 (2.5) 12 (2.0)Non cardiac deaths 6 (0.9) 16 (2.7)

1 month 96.32 % (94,84 % - 97.79 %)3 months 94.06 % (92.02 % - 95.78 %)6 months 93.24 % (91.27 % - 95.22 %)9 months 92.58 % (90.52 % - 94.65 %)12 months 91.75 % (89.59 % - 93.92 %)

91.75%

Freedom From Overall Death Freedom From Cardiac Death

95.43%

1 month 97.43 % (96.19% - 98.67 %)3 months 96.61 % (95.18 % - 98.03 %)6 months 95.94 % (94.38 % - 97.5 %)9 months 95.6 % (93.97 % - 97.22 %)12 months 95.43 % (93.77% - 97.08 %)

Mortality

Early(≤ 30 days)

n = 628

Late @1 year (> 30 days)

n = 600

n (%) n (%)

Reintervention for bleeding 27 (4.3) 0 (0.0)

Explant 6 (0.9) 6 (1.0)

Primary PVL 5 (0.8) 2 (0.3)

Leading to explant 4 (0.4) 0 (0.0)

Stroke 14 (2.2) 5 (0.8)

Endocarditis 1 (0.2) 8 (1.3)

Leading to explant 0 (0.0) 5 (0.8)

Hemolysis (clinically significant) 1 (0.2) 1 (0.2)

SVD 0 (0.0) 0 (0.0)

Valve Thrombosis 0 (0.0) 0 (0.0)

AV block III leading to Pace Maker Implant 51 (8.1) 9 (1.5)

Morbidity

preoperative 12 months 0%

10%20%30%40%50%60%70%80%90%

100%

NYHA Class

IV III II I

NYHA III-IV: 63.2%

NYHA I-II: 89.9%

Clinical Status

Preoperative Discharge 3-6 months 12 months0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

0

5

10

15

20

25

30

35

40

45

50

0.700000000000002

1.5 1.5 1.5

45

10.3 8.9 9.2

EOA (cm2)

MPG (mmHg)

Hemodynamic data at 1 year

LV mass regression by follow-up interval in paired patients (n=126)

P <0.01

300

250

200

150

100

50

0Discharge (N=126) 3/6 Month (N=126) 12 Month (N=126)

MEA

N LV

MAS

S - 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 HarringerDepartment 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,GermanyMatthias 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, AustriaRainald Seitelberger

Hendrik Treede Universitäres Herzzentrum Hamburg GmbH, Hamburg, GermanyLeonard Conradi

Riccardo Cocchieri Amsterdam Medical Centre - AMC, Amsterdam, NetherlandBas De Mol

Jean-Christian Roussel Centre Hospitalier Universitaire,

Nantes, FrancePhilippe Despins Heinz G. Jakob Department of Thoracic & Cardiovascular Surgery,

University of Essen, West German Heart Center, Essen, Germany Daniel Wendt

Thierry FolliguetCardiac Medico-Surgical Department, Institute Mutualiste Montsouris, Paris, FranceKostantinos Zannis

Steffen Pfeiffer Cardiac Surgery, Paracelsus Medical University, Klinikum Nürnberg, Nuremberg, Germany Giuseppe Santarpino

Malakh Shrestha Cardio-thoracic, Transplantation & Vascular Surgery, Hannover Medical School, GermanySamir Sarikouch

Jan F. Gummert Klinik, Herz- und Diabeteszentrum, Bad Oeynhausen, Germany

Friedrich W. Mohr Herzzentrum der Universität Leipzig, Klinik fur Herzchirurgie, Leipzig, GermanyPascal Dohmen

Mario Stalder Inselspital, University of Bern, Bern, SwitzerlandEva Roost

Krzysztof FilipiakSilesian 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, GermanyMatthias 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

www.klinikum-nuernberg.de

Thank you!