1. 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

2. 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:
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: (*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: 10 10

3. 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
Age and co-morbidity 7
Clinically stable 5
Charlson et al, J Heart Valve Dis 2006;15:312

4. 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

5. 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

6. All-cause mortality (%)
HR [95% CI] = 0.54 [0.38, 0.78]
P (log rank) <
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

7. Mortality or Major Stroke
HR [95% CI] = 0.58 [0.43, 0.78]
P (log rank) =
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

8. Mortality or Repeat Hosp
HR [95% CI] = 0.46 [0.35, 0.59]
P (log rank) <
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

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

11. 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.”

12. 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