TAVI Passed the Exam and is Ready for Clinical Use in Inoperable Patients Disclosures Research Funding and Speaking Honoraria: Edwards Lifesciences Inc Discussion will include unapproved and off-label devices, procedures, and indications Howard C. Herrmann, MD Professor of Medicine Director, Interventional Cardiology and Cardiac Catheterization Laboratories University of Pennsylvania Medical Center

30-40% Of Cardiologists’ AS Patients Go Untreated Severe Symptomatic Aortic Stenosis Percent of Cardiology Patients Treated No AVR AVR Under-treatment especially prevalent among patients managed by Primary Care physicians Update June 2008 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 10 10

Reasons for Failure to Operate AVR Offered but Declined by Patient: Preferred medical management 30% Chose balloon valvuloplasty 23 Wanted comfort care 16 No reason given 30 Physicians Failed to Offer: No discussion AVR in chart 32 No reason in chart 14 Co-morbidity 33 Age 9 Age and co-morbidity 7 Clinically stable 5 Charlson et al, J Heart Valve Dis 2006;15:312

Cohort B: Standard Rx patients Freedom from Mortality (%) Mortality vs. STS Score <10 (n=56) 10-15 (n=78) >15 (n=44) Freedom from Mortality (%) P (log rank) = 0.013 Months 13

PARTNER Study Design 2 Parallel Trials: Individually Powered n= 700 Symptomatic Severe Aortic Stenosis ASSESSMENT: High Risk AVR Candidate 3105 Total Patients Screened Total = 1058 patients 2 Parallel Trials: Individually Powered High Risk n= 700 Inoperable n=358 Standard Therapy (usually BAV) ASSESSMENT: Transfemoral Access Not In Study TAVI Trans femoral Primary Endpoint: All Cause Mortality over length of trial (Superiority) 1:1 Randomization VS WNA: The primary endpoint is for cohort B is All Cause Mortality over the length of the trial. The trial was not powered to show superiority at 1 year, and such an analysis has not been performed. ANH: I also updated the N’s for each arm as well as the total to match the data that was sent earlier. 14

All-cause mortality (%) HR [95% CI] = 0.54 [0.38, 0.78] P (log rank) < 0.0001 100 Standard Rx TAVI 80 60 50.7% All-cause mortality (%) 40 30.7% 20 ∆ at 1 yr = 20.0% NNT = 5.0 pts Months Numbers at Risk TAVI 179 138 122 67 26 Standard Rx 121 83 41 12

Mortality or Major Stroke HR [95% CI] = 0.58 [0.43, 0.78] P (log rank) = 0.0003 100 Standard Rx TAVI 80 51.3% 60 All-cause mortality or Major Stroke (%) 40 33.0% 20 ∆ at 1 yr = 18.3% NNT = 5.5 pts Months Numbers at Risk TAVI 179 132 118 56 25 Standard Rx 83 41 12

Mortality or Repeat Hosp HR [95% CI] = 0.46 [0.35, 0.59] P (log rank) < 0.0001 100 Standard Rx TAVI 80 71.6% 60 All-cause mortality or Repeat Hospitalization (%) 40 42.5% ∆ at 1 yr = 29.1% NNT = 3.4 pts 20 Months Numbers at Risk TAVI 179 117 102 56 22 Standard Rx 121 49 23 4

NNT to be alive at 1 year with >20 pt increase in KCCQ = 3!

PARTNER Cohort A to be presented at ACC 2011 What does the future hold? PARTNER Cohort A to be presented at ACC 2011 TAVI Yogi Berra: “The future ain’t what it used to be.” Former President George W. Bush: “We will know the future when we get there.”

Conclusions Our aging demographic means that a large number of patients with AS will be elderly and have co-morbidities that make open AVR high risk A large percentage (~30%) of patients with AS are sufficiently high risk or truly inoperable and do not receive AVR at all PARTNER demonstrated that TAVI markedly improves the survival and quality of life for these patients Together, these 2 groups (inoperable and high-risk) will result in the majority of patients with AS receiving TAVI in the future