THE COREVALVE ReValving SYSTEM LEADING THE WAY TO PERCUTANEOUS AORTIC VALVE REPLACEMENT Laborde JC,MD Chief Physician Proctor, January 28, 2009 * CoreValve ® and REVALVING ® System are registered trademarks of CoreValve Inc, USA Questions to Industry

* CoreValve ® and REVALVING ® System are registered trademarks of CoreValve Inc, USA MY CONFLICTS OF INTEREST ARE Affiliation/Financial Relationship Company Grant/Research Support n/a Consulting Fees/Honoraria CoreValve, Stentys, Triplelay Major Stock Shareholder/Equity CoreValve, Stentys, Triplelay Royalty Income Devax Ownership/Founder n/a Intellectual Property Rights Stentys, Triplelay, Devax Other Financial Benefit n/a

Homograft – 1962 Porcine valve – 1965 Pericardial tissue valve – First CoreValve Transcatheter AVR by Retrograde Approach Laborde, Lal, Grube – July 12, 2004 First PVT Transcatheter AVR by Antegrade Approach Alain Cribier Mechanical heart valve – 1962 Surgery Transvascular Aortic Valve Replacement 2006 First CoreValve PERCUTANEOUS AVR by Retrograde Approach – Oct 12, 2006 Serruys, DeJaegere, Laborde First Edwards/PVT Transapical Beating Heart AVR Webb, Lichtenstein – Nov 29, First PVT animal implantation A. Cribier First Corevalve animal implantation JC. Laborde

Specifically designed for transcatheter delivery Specifically designed for transcatheter delivery Single layer porcine pericardium Single layer porcine pericardium Tri-leaflet configuration Tri-leaflet configuration Tissue valve sutured to frame Tissue valve sutured to frame Standard tissue fixation techniques Standard tissue fixation techniques 200M cycle AWT testing completed 200M cycle AWT testing completed Supra-annular valve function Intra-annular implantation and sealing skirt Porcine Pericardial Tissue Valve

Valve implantation Blood flow distribution during implantation No Ventricular Support No Rapid pacing 25F catheter : 8 mm 21F catheter : 7 mm 18F catheter : 6 mm Pre-closing with 10 F Prostar True percutaneous approach CoreValve System Technology Evolution CoreValve ReValving System Technology Evolution

* CoreValve ® and REVALVING ® System are registered trademarks of CoreValve Inc, USA Size 18French/6mm : smallest in the clinic  Pure percutaneous (femoral)  Accommodates subclavian and direct aorta access techniques  Local anesthesia possible  <2 hour procedure door to door  No ECC, no accelerated pacing, no obstruction of the aortic orifice CoreValve PAVR ReValving System Basic CharacteristicsFunction Hemodynamics > surgical tissue valves Durability Durability in vitro > surgical tissue valves Tissue Porcine pericardium  Widely available  Avoids BSE

* CoreValve ® and REVALVING ® System are registered trademarks of CoreValve Inc, USA CoreValve PAVR ReValving System Advanced Characteristics Repositioning capability  NOT a one-shot manipulation  During (stepwise) deployment  Distally before annulus contact  Proximally until frame release  Proximally after frame release

Reposition of the valve At 2/3 of implantation CoreValve System CoreValve ReValving System

Reposition of the valve After implantation CoreValve System CoreValve ReValving System

* CoreValve ® and REVALVING ® System are registered trademarks of CoreValve Inc, USA CoreValve PAVR ReValving System Advanced Characteristics Repositioning capability  NOT a one-shot manipulation  During (stepwise) deployment  Distally before annulus contact  Proximally until frame release  Proximally after frame release Retrieval capability  Any time before frame release  Requires use of new device

Retrieval of the valve At 2/3 of implantation CoreValve System CoreValve ReValving System

Current & Future UK accounts UNITED KINGDOM 1.London- Brompton Hospital 2.London- St. Georges Hospital 3.Leicester- Glenfield Hospital 4.Bristol- Bristol Royal Infirmary 5.Brighton- Brighton/Sussex University Hospital 6.Manchester - Wynthenshaw Hospital 7.Belfast- Royal Victoria Hospital 8.Leeds- Leeds General Infirmary 9.Glasgow- Glasgow Western Infirmary 10.Wolverhampton - Newcross hospital 11.Blackpool- Victoria Hospital 225 Pts Updated Jan 2009

PAVR Cases Post CE Mark Total # of Cases Total # of In-Training Cases Total # of Certified Cases Updated Dec 2008

18F Expanded Evaluation Registry Cases with 30-Day Follow-up by Case Type Site Reported and Non-Adjudicated 1265 Cases “captured” and follow-up status received In-Training Registry % « solo » centers Registry % Updated Dec 2008

Patient Demographics In-TrainingCertifiedTotal Mean ± SD or %N = 809N = 456N = 1265 Age (years) 80.9 ± ± ± 6.6 Logistic EuroSCORE (%) 21.3 ± ± ± 13.9 Female 55.2%54.9%55.1% NYHA I-II: 17.5% III-IV: 82.5% I-II: 15.5% III-IV: 84.5% I-II: 16.7% III-IV: 83.3% Aortic Valve Area (cm 2 ) 0.65 ± ± ± 0.18 Peak gradient (mm Hg) 79.0 ± ± ± 26.2 Mean gradient (mm Hg) 49.2 ± ± ± 16.5 LVEF(%) 52.8 ± ± ± 13.9

Patient Co-Morbidities / History In- Training CertifiedBoth Angina16.5%14.7%15.8% Ao. Aneurysm3.9%2.6%3.4% Atrial Fib25.6%34.0%28.7% Carotid AD12.3%14.7%13.2% CAD58.9%61.7%59.9% COPD25.6%22.2%24.4% CHF19.1%9.0%15.5% Cardiomyopathy7.1%5.0%6.3% Diabetes M25.3%26.6%25.8% Hyperlipidemia46.9%50.2%48.1% Hypertension63.7%67.0%64.9% Pulmonary Hypertension 25.7%34.0%28.8% In- Training CertifiedBoth Mediastinal Radiation 2.9%2.2%2.6% MI11.4%11.5% PVD22.9%24.4%23.4% Porcelain Aorta7.0%8.0%7.4% Renal Failure24.6%30.9%27.0% Stroke or TIA8.8%9.5%9.1% Pacemaker13.5%11.7%12.8% Defibrillator1.3%1.5%1.4% CABG19.8%24.6%21.5% Valvular Surgery3.7%4.3%3.9% PCI29.4%23.3%27.2%

Procedural Results In-Training (N = 809) Certified (N = 456) Both (N = 1265) Procedural success % mn Procedure Mean Time SD (minutes) 97.5 % 98.9 % 98.0 %

Mean Logistic Euroscore vs 30-Day Mortality In-Training (N = 809) Certified (N = 456) Both (N = 1265) 0 % % 8.3 % 9.7 % 21.3% 25.2% 22.7% LogisticEuroscore 30-DayMortality LogisticEuroscore 30-DayMortality LogisticEuroscore 30-DayMortality

≤ 30-Day Mortality In-Training (N = 809) Certified (N = 456) Both (N = 1265) 0 % % 8.3 % 9.7 %

≤ 30-Day Adverse Events* (Site Reported & Non-Adjudicated) In-TrainingCertifiedBoth CARDIAC Deaths † 5.4%3.9%4.9% Aortic Dissection 0.7%0.2%0.6% Cardiac Tamponade 3.5%2.2%3.0% Cardiac Perforation 2.3%1.8%2.1% Access Site Complication 2.5%0.7%1.8% Major Bleeding 5.1%3.3%4.4% Conversion to Surgery 0.6%0.9%0.7% Myocardial Infarction 0.9%0.4%0.7% Major Arrhythmia 9.1%4.6%7.5% Pacemaker 18.8%17.8%18.4% Renal Failure 1.9%1.5%1.7% Stroke 2.2% TIA 0.2%0.4%0.3% Structural Valve Dysfunction 0.0% Valve Migration 0.0% * Multiple events in same patients = data not cumulative † Includes deaths where cause is not known

Paired NYHA Comparison Baseline to 30-Day Follow-up

Paired Comparative Gradient Data at 30 Days

Paired Comparative Echo Data at 30 Days Baseline30-Day Follow-up Baseline30-Day Follow-up Baseline30-Day Follow-up In-TrainingCertifiedBoth Effective Orifice Area (cm 2 ) Mean SD Baseline30-Day Follow-up Baseline30-Day Follow-up Baseline30-Day Follow-up In-TrainingCertifiedBoth LVEF (%) Mean ｱ SD

Conclusions Results from the initial safety and efficacy trials have demonstrated transcatheter aortic valve implantation to be a potential alternative treatment for high risk and inoperable patients with symptomatic AVD Results from the Expanded Evaluation Registry further confirm this potential in a larger cohort of patients Randomized controlled trials will be needed to confirm what we are already doing and possibly extend this technology to lesser risk patients 24