1. Axel Linke University of Leipzig Heart Center, Leipzig, Germany 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 (on behalf of the ADVANCE Investigators) UC201400445 EE

2. Potential Conflicts of Interest Speaker's name: Axel Linke, MD  I have the following potential conflicts of interest to report: Consultant: Medtronic, Inc. and St. Jude Medical Medtronic is the sponsor of the CoreValve ADVANCE study, and provided all statistical analyses and assisted in the graphical display of the data.

3. Transcatheter aortic valve implant (TAVI) enables treatment of aortic valve stenosis without open-heart surgery. 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 1-year patient outcomes from the ADVANCE study. ADVANCE | Background

4. Medtronic CoreValve ® System Porcine pericardial tissue valve sutured to a self expanding nitinol frame Supra-annular valve position preserves circularity at 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

5. ADVANCE | Methods 1,015 patients enrolled from March 2010 to July 2011 –5 year follow-up 44 centres - 12 countries in Western Europe, Asia and South America All centres had conducted at least 40 TAVI procedures prior to the study and had a Heart Team in place Clinical endpoints reported according to VARC I As-treated analysis

6. 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 ADVANCE | Endpoints

7. 100% of all patients were monitored All 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 of events utilized all available relevant source documents, including neuroimaging and systematic NIH Stroke Scale assessments Core laboratory for systematic review and assessment of EKGs and procedural angiograms Site reported echocardiographic data ADVANCE | Study Oversight

8. ADVANCE | Baseline Characteristics

9. ADVANCE | Procedural Results *measured by angiography

10. ADVANCE | Primary Endpoint *Kaplan-Meier Estimates

11. ADVANCE | 1-Year Stroke

12. ADVANCE | Additional VARC I Endpoints *Kaplan-Meier Estimates †New AKI that occurred outside of the 72 hr post-TAVI window are included

13. ADVANCE | 1-Year Survival

14. ADVANCE | Survival by EuroSCORE

15. ADVANCE | NYHA Symptom Status NYHA

16. ADVANCE | Valve Performance

17. Echo Assessment ADVANCE | Aortic Regurgitation

18. Echo Assessment ADVANCE | Paravalvular Leak

19. Echo Assessment ADVANCE | Transvalvular Regurgitation

20. ADVANCE | Survival by Aortic Regurgitation * *At discharge

21. ADVANCE | Summary and Conclusions Medtronic CoreValve ADVANCE is one of the largest “real world” TAVI trials performed in multiple experienced centres. One year outcomes continue to demonstrate – low 1-year mortality – low stroke rates at 1-year – low rates of AR and PVL at 1-year – mild AR with the same low mortality rate as those patients with no AR – improved valve performance