1. Michael Mack, M.D. Dallas, TX
Clinical Update of the Data from the Transapical Approach Clinical Trials
Michael Mack, M.D.
Dallas, TX

2. Conflict of Interest Disclosure
PARTNER US Pivotal Trial Executive Committee- Edwards Lifesciences (uncompensated)

3. Access For TAVI Femoral vein Femoral artery Left ventricular apex
Subclavian/axillary (left)
Ascending aorta

4. Access For TAVI Femoral vein Femoral artery Left ventricular apex
Subclavian/axillary (left)
Ascending aorta

5. Trial Enrollment- Dallas n=226

6. Baseline Demographics SOURCE Cohorts 1 & 2TF
(n=946)
TA/Other
(n=1398)
P-value
Age (yrs)
81.8 ± 6.6
80.6 ± 7.1
<0.0001
Pulmonary Disease
24.5%
26.1%
0.4115
Renal Dysfunction
24.8%
31.2%
0.0009
Logistic EuroSCORE
24.0
28.1
Peripheral Vascular Disease
10.3%
26.7%
CAD
47.8%
56.1%
Porcelain Aorta
4.8%
10.2%
Prior CABG
15.1%
25.5%
Mitral valve disease
21.4%
36.3%
Compliments
John Webb
Data Extract – 17MAY2010, 30JUL2010 7 7

7. Pooled SOURCE, Pooled Monitored, and Canadian Registries DemographicsTF
n=463 TA
n=575
Pooled Monitored
n=222
n=277
Canada
n=167
n=172
Age (yrs) 82 81 83 80
Male
45%
44%
34%
55%
35%
Baseline EF
7.9% (<30)
6.5% (<30)
51%
53%
56%
Prior CABG
18%
27%
26%
29%
39%
Prior PCI
23%
25%
22%
28%
30%
STS Score - 12 9 11
Compliments
John Webb 8

8. Is Mortality Higher with TA vs. TF ?
Author N TA TF
YES
Webb
168
18.2%
8.0%
Thomas
1038
10.3%
6.3% NO
Rodes-Cabau
339
11.3%
9.5%
Himbert 75
8.3%
7.8%

10. Canadian Special Access Registry
345 Edwards SAPIEN procedures
Transfemoral Approach
n=168 (49%)
Transapical Approach
n=177 (51%)
Age 81 ± 8 years
STS score 9.8 ± 6.4%

11. 24-month Follow-Up Survival Curves
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
76%
75%
78%
64%
% Survival
65%
64%
All patients
Transfemoral
Transapical 6 12 18 24
Months of follow-up

12. TA Results From TA Programs
Author/Center N
30 Day Mortality TA
One Year Survival
Walther
Leipzig
299
8.0%
80%
Pasic
Berlin
194
5.7%
Total
493
6.8%

13. n
175
Procedural Success
100%
Mortality – 30 Day
5.1%
Survival - 1 Year
82.6%

14. TA Results -Summary 11.8% 7% Total 1,747 10.5% 1,153 70% 76% 13.7%
Studies N TA
30 Day Mortality TF
One Year Survival
Registries
1,153
11.8% 7%
70%
76%
TF First
153
13.7%
9.3%
73%
79%
TA First
493
6.8% NA
80%
Total
1,747
10.5%
7.4%

15. TA Clinical Trial Outcomes: 30d Mortality
The only winning outcome in PARTNER is for both TF and TA to succeed.
By way of review:
- In TRAVERCE and REVIVAL II, 30-day TA survival was 85% and 82%, respectively; and, 1-yr survival was 61% and 56%.
- PARTNER EU, 30d survival was 81%; and, 6-mo survival was only 58%.
To assure success in PARTNER US, 30-day survival must range between 87% and 90%, to achieve a 1-yr survival of 65%.
If TA fails: (1) supreme irony that a trial called PARTNER has just one member crossing the finish line; (2) surgeon buy-in unlikely  IC-surgeon conflict (CMS reimbursement restrictive; fewer pts referred with inoperable AS as distinction between inoperability & high-risk is gray area; slows market adoption); (3) surgeon backlash, or anti-halo effect, against EW; (4) TA approval delayed indefinitely as a second TA clinical trial will be required in the presence of a commercial 18Fr TF device.
Clinical Trial
Compliments
John Webb

16. Is The Stroke Rate Lower With TA vs. TF?
Author N TA TF
YES
Webb
168
1.8%
5.3%
Himbert 75 0% 6% NO
Rodes-Cabau
339
1.7% 3%
Thomas
1038
2.6%
2.4%

17. Courtesy of Pr M. Gilard and Pr M. Laskar, CoPI FRANCE2 registry.
1662 consecutive patients in 33 centers January 1st 2010 to January
8.4%
27.4%
21.3%
Compliments
John Webb
Courtesy of Pr M. Gilard and Pr M. Laskar, CoPI FRANCE2 registry.

18. Courtesy of Pr M. Gilard and Pr M. Laskar, CoPI FRANCE2 registry.
Interim data to mid Nov 2010
n:759 TF
Edwards
CoreValve TA SC
Log. EuroSCORE
22,1
20,9
25,4
24,9
STS
13,5
14,1
15,5
14,0
Annulus Ø
21,4
23,0
21,8
23,6
Mortality TF
Edwards
CoreValve TA SC
at 30 days
7,8%
13,3%
9,2%
11,3%
at 6 months
15,4%
24,4%
17,2%
19,7%
Stroke
3.5%
2.4%
7.7%
Permanent PM
Edwards 9.4%
CoreValve 29.3%
8.4%
27.4%
21.3%
Courtesy of Pr M. Gilard and Pr M. Laskar, CoPI FRANCE2 registry.

19. PARTNER - Enrollment Timelines
April 17, 2007 – Cohort A and B enrollment commences (Transfemoral only)
April 6, 2008 – Transapical enrollment commences (Cohort A)
March 16, 2009 – Cohort B enrollment closes
August 28, 2009 – Cohort A enrollment closes

20. PARTNER Enrollment Cohort A RANDOMIZED Control n = 351 THV n = 348
Transfemoral
249
243
Transapical
102
105
NON-RANDOMIZED
Roll-in n = 41
CA* n = 345
Transfemoral 22
190
Transapical 19
155
* Continued access

21. PARTNER - Total Enrollment
TF TA
Total
Cohort A
Roll-in 21 19 40
Randomized
492
207
699
Cont Access (non-rand)*
190
155
345
Cohort B NA
358
Cont Access (rand) 91 74
Overall
1247
381
1628

22. PARTNER Baseline Characteristics*
Variable %
Cohort A-TF (test control)
Cohort A-TA (test control)
Cohort B-TF (test control)
Number of patients
450
182
430
Age (years)
Gender (male)
58.1
57.4
48.7
Diabetes
40.2
41.7
35.4
Hyperlipidemia
79.5
79.3
74.0
Hypertension
90.0
95.4
85.3
Smoking
42.6
56.6
46.9
Prior MI
25.3
31.4
25.2
Preliminary snapshot
Outcomes data blinded
*subset of all randomized patients
in cohort A (TF+TA) and cohort B (incl. CA)

23. PARTNER High Risk Co-Morbidities (1)*
Variable %
Cohort A-TF (test control)
Cohort A-TA (test control)
Cohort B-TF (test control)
Number of patients
450
182
430
Periph Vasc Disease
32.7
56.2
26.8
Hx CHF
97.6
96.6
97.0
NYHA Class III/IV
94.0
91.6
93.2
Prior CABG
59.5
69.8
Prior PCI
45.7
48.4
37.2
Prior BAV
15.9
25.6
Severe COPD (O2 dep)
7.1
9.7
23.8
*subset of all randomized patients
in cohort A (TF+TA) and cohort B (incl. CA)

24. Symetis ACURATE™ Device
Porcine Bioprosthesis (Labcor)

25. Symetis ACURATE™ Device
Delivery System: Release of the valve (unsheathing) 2 steps: step 1: Trigger – stabilization arms + upper crown step 2: Screw + Trigger – final release
Screw
Trigger

26. Acurate™ FIM trial postoperative outcome 30d-mortality rate [n]
respiratory
right heart failure (coronary)
unclear
5 / 12.5%
3 (pod 14,15,26) 1 (pod 0)
 1 (pod 19)
new PM (AV-block) [n]
1 / 2.5%
stroke rate [n]
2 / 5.0% 
temporary hemodialysis [n]
1 / 2.5% 
ventilation time [hours, median]
3.7

27. TAVI- TA Conclusions TA approach is more direct and simpler
TA is more invasive to the patient
TF and TA are complementary procedures
Percutaneous access and secure closure devices will facilitate TA approach
All approaches (TF, TA, Subclavian, DA) are worth pursuing at this point