1. New Data from The PARTNER Trial
E Murat Tuzcu, MD
TCT 2012 | Miami, FL | October 24, 2012

2. Proctor for Edwards LifeSciences
Augusto D. Pichard, MD
Proctor for Edwards LifeSciences

3. PARTNER Trial Timelines
2006
2012
May ‘07
Aug ‘09
Mar ‘09
Aug ‘09
Mar ‘11
Dec ‘11
PARTNER IB - TF
Randomized CA Cohort B - TF
PARTNER IA - TF
Partner IA - TA
PARTNER CA – TA and TF
PARTNER IIB - TF
PARTNER IIA

4. Three-Year Outcomes in “Inoperable” Patients : The PARTNER Trial
Samir R. Kapadia, MD On behalf of The PARTNER Trial Investigators
TCT 2012 | Miami, FL | October 24, 2012

5. All Cause Mortality (ITT) Landmark Analysis
HR [95% CI] = 0.53 [0.41, 0.68]
p (log rank) <
Standard Rx
TAVR
HR [95% CI] = 2.03 [1.36, 3.04]
p (log rank) =
HR [95% CI] = 1.90 [1.05, 3.43]
p (log rank) = 0.03
∆ = 20.1%
∆ = 21.0%
∆ = 17.3%
All Cause Mortality (%)
50.8%
NNT = 5.0 pts
NNT = 5.8 pts
NNT = 4.8 pts
40.3%
35.1%
30.7%
17.8%
19.3% 6 12 18 24 30 36
Months
Numbers at Risk
Standard Rx
179
121 85 62 46 27 17
TAVR
138
124
110
101 88 70

6. Repeat Hospitalization (ITT)
Rehospitalization
Mortality or Rehospitalization
Standard Rx
HR [95% CI] = 0.39 [0.28, 0.54]
p (log rank) <
93.1%
88.0%
TAVR
26.8%
72.5%
75.7%
71.6%
31.5%
37.6%
33.4%
53.9%
27.5%
66.3%
Rehospitalization (%)
Mortality or Rehospitalization (%)
NNT = 3.7 pts
56.5%
26.9%
NNT = 3.2 pts
42.3%
44.1%
34.9%
NNT = 3.0 pts
NNT = 3.6 pts
NNT = 2.7 pts
27.0%
HR [95% CI] = 0.46 [0.36, 0.58]
p (log rank) <
NNT = 3.7 pts
Months
Months
Days Alive Out of Hospital Median [IQR]
TAVR 944 [ ]
Standard Rx 368 [ ]
p <.0001
Numbers at Risk
Standard Rx
179 86 49 30 19 11 7
TAVR
115
100 89 77 64

7. All Stroke (ITT) Stroke (%) Months TAVR
HR [95% CI] = 2.77 [1.24, 6.19]
p (log rank) =
Standard Rx
Stroke (%)
NNT = 9.8 pts
NNT = 12.2 pts
NNT = 17.5 pts
15.7%
13.7%
11.2%
∆ = 10.2%
∆ = 5.7%
∆ = 8.2%
Point-in-time at 2 yrs: p =
5.5%
5.5%
5.5%
Months
Numbers at Risk
TAVR
179
128
116
105 96 82 65
Standard Rx
118 84 62 46 27 17

8. Mean Gradient & Valve Area
EOA
Mean Gradient
Mean Gradient (mmHg)
Valve Area (cm²)
N =
Error bars = ± 1 Std Dev 8

9. PARTNER TF Continued Access (Non-randomized)
Susheel K. Kodali
TCT | Miami | October 22, 2012

10. Transfemoral Implants per Site
RCT-TF (27 sites) :
Median Enrollment: 8
Mean Enrollment: 15.7
NRCA-TF (27 sites) :
Median Enrollment: 35
Mean Enrollment: 40.1
Question: How homogeneous was the site enrollment in CAP-TF?
Responder: Marty or Craig
Answer: 22 sites enrolled TF patients in the NRCA phase. All sites had previous experience of TF during the RCT phase.

11. * Events adjudicated to one year
Mortality Following TF TAVR
2-Yr Death (%) 10 20 30 40 50
Time in Months 4 8 12 16 24
423
368
338
313
292
278
265
1080
948
767
604
304
272
183
Number at risk
PMA
NRCA
Log-Rank p= 0.010
HR: 1.31 [95% CI: 1.07, 1.62]
35.9%
29.5%
* Events adjudicated to one year

12. * Events adjudicated to one year
Stroke Following TF TAVR
2-Yr Stroke (%) 2 4 6 8 10
Time in Months 12 16 20 24
423
349
321
299
279
267
254
1080
916
743
580
292
264
177
Number at risk
PMA
NRCA
Log-Rank p= 0.036
HR: 1.58 [95% CI: 1.03, 2.43]
9.0%
5.8%
* Events adjudicated to one year

13. Conclusions
Procedural and long term mortality in the NRCA was similar (5.7% vs. 4.9%, p=0.54) (25.8% vs %, p=0.001);
Neurologic complications (stroke) were less frequent in the NRCA at 30 days (5.4% vs. 3.3%, p=0.06) and 1 year (4.8% vs. 7.3%, p=0.05) 13

14. Continued Access (Non-randomized): Transapical
Todd M. Dewey, MD
TCT | Miami | October 22, 2012

15. Transapical Enrollment per Site
Mean # pts enrolled:
PMA-TA (14 sites) = 7.4
NRCA-TA (22 sites) = 44.9

16. In-Hospital / 30 Day Outcomes
PMA Cohort
TA-TAVR
(n = 104)
NRCA Cohort
(n = 988)
p-value
All mortality – no. (%)
9.6
8.8
0.78
Cardiac mortality – no. (%)
5.8
5.6
0.93
Rehospitalization – no. (%)
4.8
4.6
0.91
Death or rehosp – no. (%)
14.4
13.2
0.72
Stroke or TIA - %
2.3
0.04
Stroke - %
2.1
0.02
I think we need to do either In-Hospital + 30 days

17. 2 Year Mortality following TA-TAVR
All-Cause Mortality (%) 10 20 30 40 50
Time in Months 4 8 12 16 24
104 85 79 73 68 63 60
988
808
638
456
194
171
116
Number at risk
PMA
NRCA
Log-Rank p= 0.160
HR: 1.27 [95% CI: 0.91, 1.77]
40.7%
33.6%

18. Conclusion
Transapical TAVR continues to be a safe, reproducible, and effective procedure
for the treatment of critical aortic stenosis in a high- risk population that are not candidates for transfemoral approach.

19. Low Flow Severe Aortic Stenosis
Howard C. Herrmann, MD University of Pennsylvania, Philadelphia, PA
TCT 2012 | Miami, FL | October 24, 2012

20. Results KM mortality for LF vs NF0%
10%
20%
30%
40%
50%
60%
70% 4 8 12 16 20 24
HR: 1.52 [95% CI: 1.24, 1.87]
Log-Rank p= <.001
47.2%
33.9%
ITT - Cohorts A & B
ITT - Cohorts A & B
2-Yr Death (%) 0%
10%
20%
30%
40%
50%
60%
70%
80% 4 8 12 16 20 24
HR: 1.07 [95% CI: 0.83, 1.37]
Log-Rank p= 0.616
48.9%
46.1%
LF LEF
LF NEF
LF (Low Flow)
NF (Normal Flow)
Months
Numbers at Risk
LF LEF LG
225
177
154
142
128
119
100
NF LEF NG
304
214
213
193
179
162
134
2-Yr Death (%)
ITT - Cohorts A & B 4 8 12 16 20 24
2-Yr Death (%) 0%
10%
20%
30%
40%
50%
60%
70%
HR: 0.97 [95% CI: 0.65, 1.44]
Log-Rank p= 0.886
48.0%
50.9%
LF LEF LG
LF LEF NG
Months
Numbers at Risk LF
530
422
368
336
308
282
235 NF
441
342
317
300
274
239
Months
Numbers at Risk
LF LEF LG
147
115
100 94 83 76 67
NF LEF NG 78 62 54 48 45 43 33

21. Sammy Elmariah, MD, MPH, FACC On Behalf of the PARTNER Investigators
Left Ventricular Function in High-Risk Patients with Aortic Stenosis The PARTNER Trial
Sammy Elmariah, MD, MPH, FACC
On Behalf of the PARTNER Investigators
TCT 2012 | Miami, FL | October 23, 2012

22. Change in LVEF over Time
P <
Left Ventricular Ejection Fraction (%)
NOTE: Please reserve this color scheme for comparisons between the two main treatment arms. Blue = TAVR, Yellow = SAVR or Standard Therapy
When comparing other subgroups, please use green, gray, orange, or other colors
ADD P-VALUES
10-14% point improvement in LVEF
1 year
Baseline
1 month
6 months

23. Multivariable Predictors of LVEF Improvement at 30-days
Hazard Ratio [95% CI]
p value
TAVR Arm
0.80 [0.36 – 1.79]
0.58
Baseline LVEF
0.91 [0.86 – 0.96]
0.0009
Age
1.10 [1.00 – 1.14]
0.054
*Model included age, gender, baseline LVEF, STS score, history of MI and PCI, moderate/severe MR, and moderate/severe paravalvular leak.
However, the predictors were different in the two arms indicating differential impact of baseline characteristics based on approach. In the TAVR arm, BMI, mean gradient, renal function and prior vascular intervention impacted survival. Whereas in the surgery arm, prior CABG, STS score, liver disease and presence of MR were significant factors.
ADD BASELINE GRADIENT TO MODEL FOR PAPER.

24. All Cause Mortality (ITT) LVEF Improvement at 30-days
Death from Any Cause (%) 10 20 30 40
Time in Days 60
120
180
240
300
360
420
480
540
600
660
720
137
130
124
107
104 97 90 84 75
138
134
128
121
119
113
109
106 86
112
100 93 91 89
111 88 78 67
Number At Risk
TAVR - No Improvement
TAVR - Improvement
SAVR - No Improvement
SAVR - Improvement
Log Rank P= 0.025
34.3%
21.4%
20.0%
27.6%

25. LVEF improved over 6-mo post TAVR and SAVR in those with EF 20-50%.
Conclusions
All-cause mortality rates at 1-year were similar regardless of baseline LVEF and type of aortic valve intervention (TAVR or SAVR).
LVEF improved over 6-mo post TAVR and SAVR in those with EF 20-50%.
Baseline LVEF predicted early improvement in LVEF.
All-cause mortality rates were increased in those who underwent TAVR and failed to demonstrate early improvement in LV function.
There was no relationship between baseline LVEF and NYHA functional recovery after TAVR or SAVR. 25

26. On behalf of The PARTNER Trial Investigators
Early and Late Outcomes of Transcatheter Valve-in-Valves for Failed Balloon Expandable Transcatheter Aortic Valves
Raj R. Makkar, MD
Cedars-Sinai Heart Institute, Los Angeles
On behalf of The PARTNER Trial Investigators
TCT 2012 | Miami, FL | October 24, 2012

27. Indication for TV-in-TV
Significant AR in 59 cases (97%)
2 cases implanted primarily for unstable device position (1 very high, 1 very low)

28. Echocardiographic Findings Mean and Peak Gradients
Peak Gradient - TV-in-TV
Mean Gradient - TV-in-TV
Peak Gradient - No TV-in-TV
Mean Gradient - No TV-in-TV
Gradient (mmHg)
Data from tab 34
Numbers at Risk
TV-in-TV 57 51 33 13 5
No TV-in-TV
2,369
2,078
1,415
873
333

29. Thirty Day Outcomes KM Estimates
%, n
TV-in-TV
No TV-in-TV
p value
Mortality
All Cause
10.1 (6)
5.9 (145)
0.21
Cardiovascular
8.4 (5)
4.2 (102)
0.13
Repeat Hospitalization
10.3 (6)
5.8 (136)
0.14
Stroke or TIA
5.0 (3)
3.8 (91)
0.60
Death from any cause or major stroke
13.4 (8)
8.0 (197)
0.16
Myocardial Infarction
0.0 (0)
0.8 (19)
0.49
Open Aortic Valve Replacement
0.6 (14)
0.56
Vascular Complications
10.0 (6)
13.1 (321)
0.47
Bradyarrhythmic Event
6.5 (156)
0.03
Permanent Pacemaker
11.7 (7)
5.4 (130)
Renal Failure (Dialysis required)
3.4 (2)
2.9 (69)
0.84
Dialysis lasting > 30 days
0.6 (15)
0.54
Data from tab 23
Note: P-value from the log rank test.

30. Conclusions (1)
TV-in-TV was performed 2.4% of time, mostly as a “rescue” for moderate or more valvular or paravalvular AR.
TV-in-TV is an effective treatment for acute failure of TAVR preventing open heart surgery in 98% of cases in this series.
Rescue TV-in-TV is associated with longer procedure times, frequent hemodynamic support requirement, increased radiation exposure, contrast use, total CK enzyme leaks and longer hospital stays
The two multivariate predictors of TV-in-TV were male gender and larger LVES dimensions 30

31. Conclusions (3)
At 2 years, in patients who underwent TV-in-TV for failed TAVR:
There was an increase in:
- All cause death
- Cardiac death
- Rehospitalization
There was no difference in:
- Stroke
- NYHA class 31

32. Outcomes in Women The PARTNER Trial
Mathew R. Williams, MD
on behalf of The PARTNER Trial Investigators
TCT | Miami | October 25, 2012

33. In-Hospital / 30d Outcomes
Female
Male
Outcome
TAVR (N = 147)
Surgery (N = 151)
p value
TAVR
(N = 201)
Surgery (N = 198)
p value for
Interaction
All mortality – %
6.8
13.2
0.06
6.0
12.1
0.03
0.94
Cardiac mortality – %
4.8
4.0
0.74
3.5
6.1
0.23
0.30
Rehospitalization – %
6.6
0.95
2.0
0.25
0.39
Death or rehosp - %
13.6
18.5
9.0
0.14
0.82
I would favor taking out the actual numbers and keeping only percentages. Makes the table a lot less crowded.
I kept a copy with both, but have simplified here.
MI and AKI were original on this slide, but I thought that seemed odd, since the mortality and rehospitalization data are the primary endpoints. So I moved MI and AKI over to the slide with Vascular Complications and Bleeding and new Pacemakers. Hope that’s ok. I can move it back, if you prefer.

34. Mortality Stratified by Treatment Female Subgroup – Pooled Cohort
HR: 0.67 [95% CI: 0.44, 1.00]
Log-Rank p= 0.049
40%
TAVR
SAVR
38.2%
30%
28.2%
All-Cause Mortality
20%
10% 0% 4 8 12 16 20 24
Months
Numbers at Risk
TAVR
147
132
123
118
112
106
103
AVR
153
110
101 97 94 89 83

35. Conclusions (1)
Subgroup analysis reveals significant differences in mortality between men and women undergoing TAVR
Although early mortality is similar in men and women undergoing TAVR (6.8% vs. 6.0%, p = NS), late mortality (2 year) is lower in women (28.6% vs. 37.5%, p=0.07).
This difference may be due to a larger number of co-morbid conditions in men despite similar risk scores.
Women have a survival benefit up to two years with TAVR compared to sAVR particularly if TF. This benefit was not seen in men.
While female gender may be a risk factor for surgical AVR, it does not appear to be a risk factor for women undergoing TAVR.

36. Conclusions (2)
Procedural complications including stroke and vascular complications occurred at different rates between men and women
Women undergoing TAVR had significantly higher rates of stroke than those undergoing surgery (5.4% vs. 0.7%, p=0.02). This was driven primarily by a higher stroke rate in the transfemoral arm (6.3% vs 0%, p<0.01). Among men there was no difference in strokes between TAVR and surgery (4.0% vs. 4.5%, p=0.98)
Major vascular complications were more common in women undergoing TAVR than men (15.0% vs 8.0%, p=0.04)
On multivariate analysis, assignment to TAVR did not impact mortality in either men or women. In men, late mortality was driven primarily by comorbidities