Medium Term Survival and Functional Status in Patients with Severe Aortic Stenosis Treated by Transcatheter Aortic Valvular Implantation in the PARTNER EU Trial Bernard De Bruyne, MD, PhD Cardiovascular Center Aalst OLV-Clinic Aalst, Belgium Room 135 Monday 01:00 PM to 01:14 PM
Disclosure Statement Nothing to disclose
Participating Investigators Participating Investigators Aalst OLV-Clinic IC: B. De Bruyne, Marc Vanderheyden CV: I. Degrieck, F. Casselman, H. Vanermen Essen - University Clinics-West German Heart Center IC: S. Sack, R. Erbel, H. Eggebrecht, P. Kahlert CV: M. Thielmann, D. Wendt, H. Jakob Paris - Hôpital Bichat IC: A. Vahanian, D. Himbert CV: P. Nataf, N. Al-Attar Rotterdam - Erasmus Medical Center IC: P. DeJaegere CV: A.P. Kappetein Frankfurt a.m. - J. W. Goethe University IC: V. Schächinger, S. Fichtlscherer CV: G. Wimmer-Greinecker, M. Doss London - Kings College Hospital IC: M. Thomas, P. MacCarthy CV: A. El-Gamel, O. Wendler Massy - Institut Hospitalier Jacques Cartier IC: T. Lefevre, M-C. Morice CV: P. Donzeau-Gouge, A. Farge, M. Romano Rouen - Charles Nicole Hôpital IC: A. Cribier, H. Eltchaninoff CV: J-P Bessou, Y-P Litzler Vienna - Medical University (AKH) IC: D. Glogar, H. Baumgartner CV: E. Wolner, P. Simon, W. Wisser, M.T. Kasimir Steering Committee: Wimmer-Greinecker, Schächinger, Lefevre, De Bruyne, Nataf, DeJaegere
Trial Overview & Methods Purpose Establish interventional cardiology/ cardiac surgery partnerships to identify, jointly screen and treat adult severe aortic stenosis patients by transfemoral or transapical TAVI Design Prospective, multicenter, non- randomized, observational trial of the Edwards SAPIEN THV Primary Safety Endpoint Freedom from death from the index procedure to 30 days and 6 months Primary Efficacy Endpoint Hemodynamic, QOL and NYHA improvement at 12 months Trial Conduct Enrollment period April 2007 January 2008 initiated in precommercialization period Investigator and Site Training 2 day didactic, simulator training, case observations 2 proctored cases each approach (TF/TA) Follow-up and Monitoring 30 day, 6, 12 and 18 month intervals 100% monitoring in progress Trial Oversite Echo Corelab Columbia University Medical Center, NYC ( Dr. L. Gillam) CEC and DSMB - independent committees to review safety & adjudicate events Administration- European Center for Cardiovascular Research (CERC), Paris 100% event adjudication in progress
Key Inclusion/Exclusion Criteria Inclusion Criteria Logistic EuroSCORE 20% and/or STS score 10 Comorbidities if EuroSCORE <20 Porcelain aorta, surgically unmanageable ascending aortic calcification Chest deformities that preclude open chest procedures Senile degenerative symptomatic aortic valve stenosis with a documented AVA < 0.8 cm², mean gradient > 40mmHg and/or jet velocity > 4.0 m/s Exclusion Criteria Evidence of an acute myocardial infarction within 14 days of the intended treatment Any therapeutic invasive cardiac procedure, other than BAV, performed within 30 days of the index procedure Native aortic annulus <16 mm or >25 mm (per baseline ECHO) Life expectancy <12 months due to non-cardiac co-morbid conditions Unprotected left main disease (>70%) Active infection or endocarditis Acute coronary insufficiency
Baseline Demographics ITT Transfemoral n = 61 Mean Age (yrs) 82.3 ± 5.2 (Range: 69.1-92.5) Gender Female: 61% Male: 39% NYHA I: 2% III: 68% II: 15% IV: 16% Mean Aortic Valve Area 0.7 ± 0.2 (Range: 0.3-1.2) Mean Gradient 47.3 ± 19.9 (Range: 10-120) Mean Ejection Fraction 52.7 ± 17.7 (Range: 15.0-86.1) Logistic EuroSCORE 25.7 ± 11.5 (Range: 6.4-65.5) Median = 24.4 STS Score 11.3 ± 6.1 (Range: 3.7-32.7) Transapical n = 69 81.9 ± 5.7 (Range: 67.7-93.3) Female: 51% Male: 49% I: 1% III: 68% II: 13% IV: 17% 0.7 ± 0.4 (Range: 0.3-2.7) 46.7 ± 18.6 (Range: 18-87) 53.0 ± 14.6 (Range: 17.3-77.0) 33.8 ± 14.4 (Range: 5.1-72.1) Median = 29.8 11.8 ± 6.8 (Range: 2-41)
70% 60% 50% 40% 30% 20% 10% 0% p = ns Coronary Artery Disease Comorbidities p=0.02 TF TA p = <0.0001 p=0.008 p=0.008 Mitral Disease Peripheral vascular Disease Prior CABG Carotid Disease p=0.04 55% 65% 42% 62% 16% 49% 19% 42% 13% 33% 6% 20% Prior Pacemaker N = 130 TA Cohort had greater comorbidities with higher: CAD, Mitral disease, PVD, Prior CABG, Carotid Disease, Prior Pacemaker At least one-third of patients enrolled had underlying: Systemic hypertension (71% TF, 77% TA) Pulmonary disease (48% TF, 35% TA) Chronic kidney disease (37% TF, 46% TA)
Study Flow Chart Signed Informed Consent 131 Screening failure = 1** INTENTION-TO-TREAT (ITT) Attempted Procedure TRANSFEMORAL 61* 130 TRANSAPICAL 69 Aborted Procedure (No valve implant attempted) 6 4 DEVICE IMPLANT PERFORMED Patient followed per protocol as intended (AI) 55 65 * One TF cross-over to TA analyzed is in TF cohort per PARTNER EU Trial Executive Committee ruling ** One screening failure active endocarditis - 131 patients signed informed consents
Cm² mmhg Percent Hemodynamics and Valve Performance 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 Mean Gradient and AVA 46.9 0.7 1.6 10 10.9 Baseline 30 Day 6 Months 1 Year EOA N= 84 78 51 39 Mean Gradient N= 108 85 65 57 Effective Orifice Area 1.5 1.5 12.2 Mean Gradient 50 45 40 35 30 25 20 15 10 5 0 Valve performs as intended with relief of severe stenosis and return to low gradients 64 62 60 58 56 54 52 50 48 54.2 53.2 LVEF 56.8 62.6 56.2 56.1 Baseline 30 Days 6 Months 1 Year TA N = 50 37 30 23 TF N = 46 37 29 29 Transfemoral Transapical 56.3 55.2
Total Aortic Insufficiency Total Aortic Insufficiency Transfemoral Aortic Insufficiency Transapical 2% 2% 0% 0% +4 Severe +4 Severe 0% 2% 0% 0% 6% 15% 6% 0 % +3 Moderate +3 Moderate 2% 16 % 0% 0% 46% 41% 28% 33 % +2 Mild +2 Mild 38% 27% 37% 13% 40% 32% 44% 29% 45% +1 Trace +1 Trace 35% 30% 40% 57% 6% 10% 22% 21% 0 (None) 0 (None) 25% 25% 23% 30% F-U Visit Discharge n=52 30 Day n=41 6 Month n=36 1 Year n=33 At one year post implant: 66%: 0 or 1+ Follow-up Visit Discharge n=48 30 Day n=44 6 Month n=30 1 Year n=23 At one year post implant: 87%: 0 or 1+
Functional Status
% of Patients Edwards SAPIEN TM THV - PARTNER EU: Functional Status and Medium Term Survival 1-Year NYHA Classification 100% 90% 80% 70% 60% 50% 40% 30% NYHA I NYHA II NYHA III NYHA IV N =120 20% 10% 0% N = 120 Baseline 30 Days 6 Months 89% of surviving patients in NYHA Class 1 or 2 1 Year Death Unknown
Nr of patients Edwards SAPIEN TM THV - PARTNER EU: Functional Status and Medium Term Survival 1-Year NYHA Classification 70 60 62 60 60 30 Days 6 months 50 46 1 year 40 34 30 20 10 19 11 9 3 0 3 17 19 15 2 0 Improved NYHA Unchanged NYHA Worsened NYHA Death Not reported N = 120 81% had improved NYHA class at 12 months
Quality of Life Overall Summary Score 90 80 70 67.6 78.3 72.1 60 50 48.3 50.3 49.2 40 30 20 10 0 N = 30 22 52 30 22 52 Baseline 1 Year Transfemoral Transapical Combined Linear (Combined) At 1 year post implantation, a large treatment effect is noted by a 22.9 point improvement
90 80 70 60 50 40 30 20 10 0 Quality of Life EQ-5D % Patients Reporting Problems 77 69 51 54 48 50 47 34 33 28 N = 51 51 51 50 51 50 50 50 51 49 Mobility Self-Care Usual Activities Pain/Discomfort Anxiety/Depression Baseline 1 Year At 1 year post implantation, a meaningful improvement in most activities of daily living is noted
Probabilty (event free) 0.0 0.2 0.4 0.6 0.8 1.0 18 Months - Arrhythmias Requiring Pacemaker N = 130 Transfemoral Freedom from Pacemaker = 98% Transapical Freedom from Pacemaker = 90% TF 30D: 0.98 6M: 0.98 1Y: 0.98 18M: 0.98 SE: 0.02 SE: 0.02 SE: 0.02 SE: 0.02 Nrisk: 52 Nrisk: 51 Nrisk: 45 Nrisk: 27 TA 30 D: 0.96 6M: 0.93 1Y: 0.93 18M: 0.9 SE: 0.03 SE: 0.04 SE: 0.04 SE: 0.05 Nrisk: 44 Nrisk: 30 Nrisk: 24 Nrisk; 14 1 6 Time (months) 12 18 30 day pacemaker in conventional AVR = 3.2% 8.5% ¹ 1. Dawkins et al. Permanent Pacemaker Implantation After Isolated AVR, Ann Thorac Surg, 2008, 85:108-12.
Survival at 18 months
Probabilty (event free) Edwards SAPIEN TM THV - PARTNER EU: Functional Status and Medium Term Survival Transfemoral Survival to 18 Months 0.0 0.2 0.4 0.6 0.8 1.0 30D: 0.92 SE: 0.04 Nrisk: 56 6M: 0.9 SE: 0.04 Nrisk: 55 1Y: 0.79 SE: 0.05 Nrisk: 47 Late Deaths (>30 days) (n = 12) 18 Month Survival = 71 ± 6% 18M: 0.71 SE: 0.06 Nrisk: 28 1 6 12 18 Time (months) Data Extract 07 August 09
Probabilty (event free) 0.0 0.2 0.4 0.6 0.8 1.0 Transapical Survival to 18 Months 18M: 0.43 SE: 0.06 (n = 26) Nrisk: 19 Late Deaths (>30 days) 18 Month Survival = 43±6 % 30D: 0.81 SE: 0.05 Nrisk: 56 6M: 0.58 SE: 0.06 Nrisk: 40 1Y: 0.49 SE: 0.06 Nrisk: 33 1 6 Time (months) 12 18 Data Extract 07 August 09
Survival KM Survival Estimate Between 6 and 18 months 1 0.8 0.6 0.4 0.2 Transapical Transfemoral 0 6 9 12 15 18 Only patients alive at 6 months TF n = 55, TA n = 40 Months post Procedure
Conclusions The PARTNER EU Trial is the first TAVI trial where implant approach (TF or TA) was determined jointly by interventional cardiologists and cardiac surgeons. Comparison of survival between TF and TA is problematic due to variability in baseline co morbidity. The Edwards SAPIEN TM THV valve shows excellent hemodynamic performance (AR 0 or 1 in the majority of patients), which translates into a marked improvement in functional status and physical and mental wellbeing. The Kaplan-Meier survival estimates between 6 to 18 months after implantation are very favorable with no signs of valve deterioration.