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

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

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

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

All Cause Mortality (ITT) Landmark Analysis HR [95% CI] = 0.53 [0.41, 0.68] p (log rank) < 0.0001 Standard Rx TAVR HR [95% CI] = 2.03 [1.36, 3.04] p (log rank) = 0.0005 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

Repeat Hospitalization (ITT) Rehospitalization Mortality or Rehospitalization Standard Rx HR [95% CI] = 0.39 [0.28, 0.54] p (log rank) < 0.0001 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) < 0.0001 NNT = 3.7 pts Months Months Days Alive Out of Hospital Median [IQR] TAVR 944 [233-1096] Standard Rx 368 [147-1096] p <.0001 Numbers at Risk Standard Rx 179 86 49 30 19 11 7 TAVR 115 100 89 77 64

All Stroke (ITT) Stroke (%) Months TAVR HR [95% CI] = 2.77 [1.24, 6.19] p (log rank) = 0.0094 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 = 0.0137 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

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

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

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.

* 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

* 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

Conclusions Procedural and long term mortality in the NRCA was similar (5.7% vs. 4.9%, p=0.54) (25.8% vs 18.0%, 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

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

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

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

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%

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.

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

Results KM mortality for LF vs NF 0% 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

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

Change in LVEF over Time P < 0.0001 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

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.

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%

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

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

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)

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

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.

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

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

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

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.

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

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.

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