1. Three-year clinical and echocardiographic follow-up of aortic stenosis patients implanted with a self-expending bioprosthesis Sabine Bleiziffer German Heart Center, Munich, Germany Johan Bosmans University Hospital Antwerp, Antwerp, Belgium Ulrich Gerckens Gemeinschaftskrankenhaus Bonn, Bonn, Germany Peter Wenaweser University Hospital Bern, Bern, Switzerland Stephen Brecker St. George’s Hospital, London, United Kingdom Corrado Tamburino Ferrarotto Hospital, University of Catania, Catania, Italy Axel Linke University of Leipzig Heart Center, Leipzig, Germany (on behalf of the ADVANCE Investigators)

2. ADVANCE | Background Transcatheter aortic valve implant (TAVI) enables treatment of aortic valve stenosis using interventional techniques. The CoreValve ADVANCE study evaluated the clinical benefits of TAVI using the CoreValve system in a fully monitored, “real world” trial. This presentation reports for the first time the complete 3-year patient outcomes from the ADVANCE study. CoreValve ADVANCE Study 2

3. ADVANCE | Background Medtronic CoreValve ® System Porcine pericardial tissue valve sutured to a self expanding nitinol frame Supra-annular valve position preserves circularity at the level of valve function 18F catheter delivery system, with AccuTrak Stability Layer available in later cases 2 valve sizes were used in this study: 26 mm and 29 mm CoreValve ADVANCE Study 3

4. ADVANCE | Methods 1,015 patients enrolled from March 2010 to July 2011 –5 year follow-up planned 44 centres in 12 countries in Western Europe, Asia, and South America All centres conducted at least 40 TAVI procedures prior to the study and had a Heart Team in place Clinical endpoints reported according to VARC 1 As-treated analysis on attempted patients CoreValve ADVANCE Study 4 Patients Attempted Implant N = 996 Patients Attempted Implant N = 996 Patients Enrolled N = 1,015 Patients Enrolled N = 1,015 30-Day Follow-Up 943/944 (99.9%) 30-Day Follow-Up 943/944 (99.9%) 2-Year Follow-Up 723/747 (96.8%) 2-Year Follow-Up 723/747 (96.8%) 19 – No Implant Attempted  2 – deaths  17 – exits 19 – No Implant Attempted  2 – deaths  17 – exits 52 – Deaths 1 – Withdrawal 52 – Deaths 1 – Withdrawal 119 – Deaths 16 – Withdrawals 4 – Other Exits 119 – Deaths 16 – Withdrawals 4 – Other Exits 1-Year Follow-Up 804/825 (97.5%) 1-Year Follow-Up 804/825 (97.5%) 78– Deaths 2 – Withdrawals 1 – Other Exits 78– Deaths 2 – Withdrawals 1 – Other Exits 3-Year Follow-Up 651/678 (96.0%) 3-Year Follow-Up 651/678 (96.0%) 69– Deaths 2 – Withdrawals 1 – Other Exits 69– Deaths 2 – Withdrawals 1 – Other Exits

5. ADVANCE | Endpoints Primary Endpoint- Major Adverse Cardiac & Cerebrovascular Events (MACCE) at 30 days post procedure MACCE defined as a composite of All-cause Mortality Myocardial Infarction (Q-wave and non-Q-wave) Emergent Cardiac Surgery or Percutaneous Re-intervention Stroke Additional Clinical Endpoints (VARC I) Cardiovascular Mortality Bleeding Vascular Complications Acute Kidney Injury New Pacemaker Implantation CoreValve ADVANCE Study 5

6. ADVANCE | Study Oversight 100% of all patients monitored Primary endpoint events adjudicated by an independent clinical events committee consisting of TAVI-experienced interventional cardiologists and cardiac surgeons using VARC I definitions All cerebrovascular events adjudicated by an independent neurologist Adjudication utilized all available relevant source documents, including neuroimaging and systematic NIH Stroke Scale assessments Core laboratory evaluation of all EKGs and procedural angiograms Site reported echocardiographic data CoreValve ADVANCE Study 6

7. Characteristics N=1015% or mean ± SD% Age (yrs)81.1 ± 6.4Prior MI16.4 Male49.4Prior PCI31.5 Logistic EuroSCORE (%)19.4 ± 12.3Permanent Pacemaker12.9 NYHA III or IV79.6Prior CABG21.5 Diabetes31.4Cerebrovascular Disease13.1 CAD57.8COPD22.7 PVD19.7Pulmonary Hypertension13.1 Atrial Fibrillation33.4Renal Failure14.9 LVEF (%)53.3 ± 13.7 ADVANCE | Baseline Characteristics CoreValve ADVANCE Study 7

8. Procedural Parameters N=996% Successful vascular access, delivery & deployment of device & successful retrieval of the delivery system 97.5 Correct position of the device in the proper anatomical location98.7 Mean aortic valve gradient < 20 mmHg (discharge echo)96.2 One valve used96.0 Major Complications, Valve Related N=996% Annulus Rupture0.0 Valve Embolization0.2 Conversion to open AVR0.1 Coronary Compromised0.1 ADVANCE | Procedural Results CoreValve ADVANCE Study 8

9. Endpoint1 Month1 Year2 Years3 Years N=996%* MACCE8.021.030.138.5 All-cause Mortality4.517.625.533.7 Myocardial Infarction0.20.92.52.6 Emergent Cardiac Surgery or Percutaneous Re-intervention 1.31.61.92.4 Stroke3.04.45.66.5 Minor1.82.33.03.3 Major1.22.12.93.5 *Kaplan-Meier Estimates ADVANCE | Primary Endpoint CoreValve ADVANCE Study 9

10. Endpoint1 Month1 Year2 Year3 Year N=996%* Cardiovascular Mortality3.411.616.722.3 Bleeding29.032.033.835.3 Life Threatening or Disabling Bleeding4.04.95.66.1 Major Bleeding9.711.212.512.7 Minor Bleeding17.419.320.121.1 Vascular Complications20.721.822.0 Major10.912.012.3 Minor10.210.3 Acute Kidney Injury—Stage III † 0.40.6 New Pacemaker Implantation26.329.130.531.4 *Kaplan-Meier Estimates †New AKI that occurred outside of the 72 hr post-TAVI window are included ADVANCE | Additional VARC 1 Endpoints CoreValve ADVANCE Study 10

11. ADVANCE | 3-Year Survival

12. ADVANCE | Survival by log EuroSCORE

13. ADVANCE | 3-Year Stroke

14. ADVANCE | NYHA Symptom Status

15. ADVANCE | NYHA Paired Comparisons p-values are results of McNemar's test.

16. ADVANCE | Valve Performance

17. ADVANCE | Aortic Regurgitation

18. ADVANCE | Paravalvular Leak

19. ADVANCE | Paired Paravalvular Leak

20. ADVANCE | Transvalvular Leak

21. Based on echo at discharge ADVANCE | Survival by Aortic Regurgitation P-value (log rank) Overall Comparison = 0.009 Mild vs. Moderate/Severe = 0.069 AR-Mild vs. None = 0.669 Moderate/Severe vs. None = 0.004

22. ADVANCE | Summary and Conclusions CoreValve ADVANCE Study 22 ADVANCE is a large “real world” multicenter TAVI study reporting 3 year outcomes. Mortality remains low at 3 years and when stratified relative to EuroSCORE, patients with a EuroSCORE > 20 had only a 7.7% increase in mortality relative to all patients in the study Additional outcomes at 3 years continue to demonstrate: – excellent valve performance (large EOAs and low mean gradients) – low stroke rates – sustained moderate PVL rates and a trend towards mild PVL reducing over time