The State of TAVR -PARTNER: From Concept to Mortality Benefit Jeffrey W. Moses , MD Columbia University Medical Center Cardiovascular Research Foundation New York City Presenter Disclosure Information for U Minn Grand Rounds; Jeffrey W. Moses , M.D. Equity Relationship: Claret At Least 30% of Patients with Severe Symptomatic AS are “Untreated”! Severe Symptomatic Aortic Stenosis AVR Percent of Cardiology Patients Treated No AVR 100% 90% 80% 41 32 30 31 60 70% 45 48 60% 50% 40% 30% 68 70 69 59 55 52 Under-treatment especially prevalent among patients managed by Primary Care physicians 40 20% 10% 0% Bouma 1999 1. 2. 3. 4. Iung* 2004 Pellikka 2005 Charlson 2006 Bach 2009 Spokane (prelim) Vannan (Pub. Pending) Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-148 Iung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart Journal 2003;24:1231-1243 (*includes both Aortic Stenosis and Mitral Regurgitation patients) Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 2005 Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15:312-321 Potential Patients for Transcatheter Aortic Valve Therapy SEVERE AORTIC STENOSIS PT. REFUSALS BALLOON AORTIC VALVULOPLASTY NOT REFERRED ? ASYMPTOMATIC AORTIC VALVE REPLACEMENT SURGERY HIGH-RISK PATIENTS TAVR 2011 Technology Review Early Catheter-Based AV Designs The Davis valve (1965) The Andersen valve (1992) Alain Cibier Sketches (1990) 1 2 Systole 3 Diastole PVT-Edwards Percutaneous Heart Valve Cribier-Edwards Device First generation – polyurethane Second generation – bovine pericardium • equine pericardial valve • stainless steel stent • 23mm and 26mm diameters • balloon-expandable • AVA = 1.7-1.9 cm2 Dr. Alain Cribier First-in-Man PIONEER Percutaneous Transcatheter Implantation of an Aortic Valve Prosthesis for Calcific Aortic Stenosis First Human Case Description Alain Cribier, MD; Helene Eltchaninoff, MD; Assaf Bash, PhD; Nicolas Borenstein, MD; Christophe Tron, MD; Fabrice Bauer, MD; Genevieve Derumeaux, MD; Frederic Anselme, MD; François Laborde, MD; Martin B. Leon, MD Conclusions— Nonsurgical implantation of a Nov, prosthetic heart AHA; 2002 valve can be successfully achieved with immediate and midterm hemodynamic and clinical improvement. April 16, 2002 Sapien XT + NovaFlex Delivery System 18 Fr profile Transcatheter AVR Trans-apical Access Route Transfemoral Transapical TAVR 2011 The PARTNER Trial Published on-line September 22, 2010 @ NEJM.org and print October 21, 2010 On behalf of the Executive Committee, the Investigator Sites, and the courageous patients who participated in the PARTNER trial! PARTNER Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened Total = 1,057 patients N = 699 High Risk Inoperable 2 Parallel Trials: Individually Powered ASSESSMENT: Yes Transfemoral Access Transfemoral (TF) 1:1 Randomization ASSESSMENT: No Transfemoral Access Transapical (TA) 1:1 Randomization Yes No 1:1 Randomization N = 244 N = 248 N = 104 N = 103 N = 179 N = 179 TF TAVR AVR TA TAVR AVR TF TAVR Standard Therapy VS N = 358 VS Primary Endpoint: All-Cause Mortality at 1 yr (Non-inferiority) Not In Study VS Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority) Executive Committee Lars Svensson Craig Miller Murat Tuzcu Craig Smith Jeff Moses Marty Leon John Webb Michael Mack Transcatheter AVR Hybrid OR-Cath Lab A unique collaborative experience! Inoperable: Patient Characteristics - 1 TAVI Standard Rx n=179 n=179 83.1 ± 8.6 83.2 ± 8.3 0.95 45.8 46.9 0.92 11.2 ± 5.8 12.1 ± 6.1 0.14 26.4 ± 17.2 30.4 ± 19.1 0.04 NYHA I or II (%) III or IV (%) 7.8 92.2 6.1 93.9 0.68 0.68 CAD (%) 67.6 74.3 0.20 Prior MI (%) 18.6 26.4 0.10 Prior CABG (%) 37.4 45.6 0.17 Prior PCI (%) 30.5 24.8 0.31 Prior BAV (%) 16.2 24.4 0.09 CVD (%) 27.4 27.5 1.00 Characteristic Age - yr Male sex (%) STS Score Logistic EuroSCORE P value Inoperable: Patient Characteristics - 2 TAVI n=179 Standard Rx PVD (%) 30.3 25.1 0.29 COPD Any (%) O2 dependent (%) 41.3 21.2 52.5 25.7 0.04 0.38 Creatinine >2mg/dL (%) 5.6 9.6 0.23 Atrial fibrillation (%) 32.9 48.8 0.04 Perm pacemaker (%) 22.9 19.5 0.49 Pulmonary HTN (%) 42.4 43.8 0.90 Frailty (%) 18.1 28.0 0.09 Porcelain aorta (%) 19.0 11.2 0.05 Chest wall radiation (%) 8.9 8.4 1.00 Chest wall deformity (%) 8.4 5.0 0.29 Liver disease (%) 3.4 3.4 1.00 Characteristic n=179 P value 1ry Endpt - All Cause Mortality Standard Rx All-cause mortality (%) TAVI HR [95% CI] = 0.54 [0.38, 0.78] P (log rank) < 0.0001 Months Numbers at Risk TAVI Standard Rx 179 179 138 121 122 83 67 41 26 12 1ry Endpt - All Cause Mortality Standard Rx All-cause mortality (%) TAVI ∆ at 1 yr = 20.0% NNT = 5.0 pts 50.7% 30.7% Months Numbers at Risk TAVI Standard Rx 179 179 138 121 122 83 67 41 26 12 Clinical Outcomes at 30 Days & 1 Year 30 Days n=179 Outcome TAVI 1 Year n=179 Standard P-value Rx TAVI Standard P-value Rx Death All (%) Cardiovascular (%) 5.0 4.5 2.8 1.7 0.41 0.22 30.7 19.6 49.7 41.9 0.0004 <.0001 Repeat hospitalization (%) 5.6 10.1 0.17 22.3 44.1 <.0001 Death (all) or repeat hosp (%) 10.6 12.3 0.74 42.5 70.4 <.0001 6.7 0 1.7 5.0 1.7 0 0.6 1.1 0.03 . 0.62 0.06 10.6 0.6 2.2 7.8 4.5 0 0.6 3.9 0.04 1.00 0.37 0.18 8.4 3.9 0.12 33.0 50.3 0.001 0 0 0 0 . . 0.6 0 0.6 0 1.00 . Stroke or TIA All (%) TIA (%) Minor stroke (%) Major stroke (%) Death (all) or major stroke (%) Myocardial infarction All (%) Peri-procedural (% Clinical Outcomes at 30 Days & 1 Year 30 Days n=179 Outcome TAVI 1 Year n=179 Standard P-value Rx TAVI Standard P-value Rx Vascular complications All (%) 30.7 5.0 <.0001 32.4 7.3 <.0001 Major (%) 16.2 1.1 <.0001 16.8 2.2 <.0001 Acute kidney injury Creatinine >3 mg/dL (%) RRT (%) 0 1.1 1 1.7 1.00 1.00 1.1 1.7 2.8 3.4 0.45 0.50 Bleeding - major (%) 16.8 3.9 <.0001 22.3 11.2 0.007 BAV (%) 0.6 1.1 1.0 0.6 36.9 <.0001 Re-TAVI (%) 1.7 na 1.7 na 0 1.7 0.25 1.1 9.5 <.0001 0 0 . 1.1 0.6 0.31 New atrial fibrillation (%) 0.6 1.1 1.00 0.6 1.7 0.62 New pacemaker (%) 3.4 5.0 0.60 4.5 7.8 0.27 Cardiac re-intervention AVR (%) Endocarditis (%) Arrhythmias NYHA Class Over Time Survivors P < 0.0001 P < 0.0001 P < 0.0001 Percent P = 0.68 TAVI Standard Rx TAVI Standard Rx Baseline I TAVI Standard Rx 30 Day II 6 Month III IV TAVI Standard Rx 1 Year Treatment Visit PARTNER QOL Analyses TAVI not only adds years to life, but also, adds life to years! Cost-Effectiveness of TAVR vs. Control Lifetime Results $100,000 per LY Cost = $79,837 LE = 1.59 years ICER = $50,212/LYG $50,000 per LY TAVR 2011 Main Outcomes: High Risk Primary Endpoint: All-Cause Mortality at 1 Year 0.5 HR [95% CI] = 0.93 [0.71, 1.22] P (log rank) = 0.62 TAVR AVR 0.4 26.8 0.3 0.2 24.2 0.1 0 0 6 No. at Risk 12 18 24 Months TAVR 348 298 260 147 67 AVR 351 252 236 139 65 All-Cause Mortality Transfemoral (N=492) HR [95% CI] = 0.83 [0.60, 1.15] P (log rank) = 0.25 26.4 22.2 No. at Risk Months TAVR 244 215 188 119 59 AVR 248 180 168 109 56 All-Cause Mortality Transapical (N=207) HR [95% CI] = 1.22 [0.75, 1.98] P (log rank) = 0.41 29.0 27.9 No. at Risk Months TAVR 104 83 72 28 8 AVR 103 72 68 30 9 PARTNER 1A :30 Day Outcomes (AT) 18 Transfemoral 16 14 P=0.09 12 P=0.045 10 Transapical 9.5 8.2 8 6 4 15.4 10.9 8.7 7.6 7.0 5.4 3.7 2.5 4.4 1.4 2 0 TF AVR Death TF AVR Major Stroke TF AVR Death Stroke TA AVR Death TA AVR Major Stroke TA AVR Death Stroke NYHA Functional Class P < 0.001 Baseline 30 Days P = 0.05 P = 0.75 Patients Surviving, % P = 1.00 I 6 Months II III IV 1 Year Mean and Peak Gradient As-Treated Trial Arms (mmHg) Echo Findings Aortic Valve Gradients 80 Peak Gradient - AVR 70 Peak Gradient TAVR Mean Gradient - AVR 60 Mean Gradient TAVR 50 40 30 20 10 0 Baseline TAVR n = 327 AVR n = 301 30 Days TAVR n = 287 AVR n = 231 6 Months TAVR n = 246 AVR n = 170 1 Year TAVR n = 227 AVR n = 159 Paravalvular Aortic Regurgitation P < 0.001 P < 0.001 30 Days 6 Months 1 Year Patients, % P < 0.001 None Trace Mild Moderate Severe TAVR - The Future My Rosey Prophecy Surgery – The “PAST” In 5-10 years, most patients with severe AS requiring AVR will be treated using TAVR! TAVR – The “Future”