1. Transcatheter Aortic Valve Therapies
Mark Russo
Assistant Professor of Surgery
Co-Director, Center for Aortic Diseases

2. SUMMARY POINTS This is NOT experimental therapy
45,000 implants worldwide
In Germany, 20-25% of isolated AVRs are TAVI
Indications
Symptomatic, severe AS deemed inoperable
Shown to be clinically effective in a well-selected patients
RCT demonstrated an absolute 20% survival benefit
40%+ of OMM pts are dead at 6 months

3. ADVANCES IN THE RX OF STRUCTURAL HEART DISEASE
Cardiopulmonary Bypass
1977- Percutaneous Coronary Intervention
Transcatheter Valves

4. CHANGING TREATMENT PARADIGM
Treatment options: Significant unmet need
Delivery of care: “Heart team” concept
Tools available: Catalyze other percutaneous technologies for treatment of structure heart disease

5. The Problem of Aortic Stenosis

6. Helping to Solve a Grave Problem
Aortic stenosis is life threatening and progresses rapidly
Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1
“Surgical intervention [for severe AS] should be performed promptly once even…minor symptoms occur”1
1 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. 1998;113:
Latent Period
(Increasing Obstruction,
Myocardial Overload)
Survival, %
100 80 60 40 20 50 70
Age, y
Onset Severe Symptoms
Angina
Syncope
Average Survival, y
Failure 2 4 6

7. THE BURDEN OF AORTIC STENOSIS
In the US:
AS: ,500,000
Severe AS: 500,000
Severe, symptomatic AS: 250,000
AVRs performed annually: 85,000
>150,000 untreated AS patients

8. Addressing a Serious Unmet Need
At least 43-74% of patients with severe aortic stenosis (AS) do not have an AVR
1999
2006
2009
2005
2010
Patients, %
Aortic Valve Replacement (AVR)
No AVR

9. Dismal Outcomes with Severe Inoperable AS
5-Year Survival
Survival, % * * * * * †
* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. Accessed November 16, 2010.
† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.

10. Dismal Outcomes with Severe Inoperable AS
The predicted survival of inoperable patients with severe AS who are treated with standard non-surgical therapy is lower than with certain metastatic cancers.
5-Year Survival
Survival, % * * * * * †
* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. Accessed November 16, 2010.
† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.

11. Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1
Latent Period
(Increasing Obstruction,
Myocardial Overload)
Survival, %
100 80 60 40 20 50 70
Age, y
Onset Severe Symptoms
Angina
Syncope
Average Survival, y
Failure 2 4 6
Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1
1 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. 1998;113:

12. TAVI for Who? What is the Data to Support Use?

13. INDICATIONS Severe Symptomatic AS Inoperable – determined by a surgeon
Aortic Velocity > 40 m/sec
Mean Gradient > 4 mmHg
Valve Area < 1.0 cm2
Inoperable – determined by a surgeon
Mortality > 15%
Death or serious, irreversible morbidity > 50%
STS score > 8-10

14. The PARTNER Trial Protocol
Not in Study
Assessment
Transfemoral Access
Yes No
Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority)
Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority) TF
TAVR
(n = 179)
Standard Therapy
(Control) vs
1:1 Randomization
(n = 492) TA
(n = 207)
Primary Endpoint: All-Cause Mortality (1 yr) (Non-inferiority)
(n = 244)
AVR
(n = 248)
(n = 104)
(n = 103)
Cohort A
(n = 699)
Cohort B
(n = 358)
2 Cohorts
Individually Powered
(N = 1,057)
TA, transapical; TF, transfemoral.
Operability
Severe Symptomatic Native Aortic Valve Stenosis

15. PARTNER COHORT B
Source: NEJM, 2001

16. PARTNER COHORT B Mean Age: early 80s Mean STS Score: 11
Mean EuroScore: 12
NYSA III/IV - 90%
s/p CABG - 40%
COPD - 45%
O2 - 20%
PHTN - 40%
Radiation - 10%
Porcelain Aorta
Source: NEJM, 2001

17. PARTNER TRIAL – COHORT B 20% Reduction in Mortality
∆ at 1 yr = 20.0% NNT = 5.0 pts 20 40 60 80
100
Edwards SAPIEN THV
Standard Therapy
All-Cause Mortality, %
50.7%
HR [95% CI] = 0.51 [0.38, 0.68]
P (log rank) < .0001
30.7%
Months
Numbers at Risk
Edwards SAPIEN THV
179
138
124
103 60
Standard
Therapy
121 85 56 24
Source: NEJM, 2001

18. PARTNER TRIAL – COHORT B 20% Reduction in Mortality
∆ at 1 yr = 20.0% NNT = 5.0 pts 20 40 60 80
100
Edwards SAPIEN THV
Standard Therapy
All-Cause Mortality, %
50.7%
20% absolute reduction in mortality at 1 year
HR [95% CI] = 0.51 [0.38, 0.68]
P (log rank) < .0001
30.7%
Months
Numbers at Risk
Edwards SAPIEN THV
179
138
124
103 60
Standard
Therapy
121 85 56 24
Source: NEJM, 2001

20. Paravalvular Leaks Over Time

21. PARTNER TRIAL – COHORT B
Source: NEJM, 2001
NEJM, 2011

22. PARTNER TRIAL– COHORT B Quality of Life Benefits60 40 20 80
100 4 6 8 10 12 2
Standard Therapy
Edwards SAPIEN THV
∆ = 13.9 P < .001
∆ = 24.5 P < .001
KCCQ Score (Mean)
MCID, minimum clinically important difference.
MCID = 5 points
Months
Improvement in quality of life

23. CONCLUSIONS – PARTNER B
Standard therapy (including BAV in 83.8% of pts) did not alter the dismal natural history of AS; all-cause and cardiovascular mortality at 1 year was 50.7% and 44.6% respectively
Transfemoral balloon-expandable TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (5% after randomization in the intention-to-treat population)

24. Inoperability Operative mortality > 15%
Operative severe morbidity or death > 50%
STS score > 8
Previous cardiac surgery – multiple, s/p CABG
Home O2
PHTN
Radiation
Porcelain Aorta
Frailty

25. Fried Frailty Index Fried Phenotype of Frailty
Weight Loss (unintentional)
> 10 lb in previous year
Grip strength
Lowest 20% by sex/BMI
Exhaustion
Self-report (CES-D depression scale)
Walk time, 15 feet
Lowest 20% by sex/height
Low activity
Males < 383 kcal/week
Females < 270 kcal/week
Frailty: ≥ 3 criteria Intermediate/prefrail: 1 or 2 criteria
Fried LP, et al. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M156. 25

26. Approaches

27. Approaches Transfemoral Illiac Conduit Transapical Subclavian
Transaortic

28. TAVI - Transfemoral

29. TAVI - Transapical
Anterior Thoracotomy

30. TAVI - Transapical
Source: theheart.org

31. TAVI – LEFT SUBCLAVIAN APPROACH

32. TAVI-Transaortic