1. TCT 2015 | San Francisco | October 15, 2015 Transcatheter Aortic Valve Replacement for Failed Surgical Bioprostheses Danny Dvir, MD John G. Webb, MD and Michael J. Mack, MD on behalf of The PARTNER II Trial Investigators and The PARTNER Publications Office 1-Year Results from the PARTNER II Valve-in-Valve Registry

2. Disclosure Statement of Financial Interest ConsultantConsultant Edwards Lifesciences Medtronic Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany

3. Background and Aims Valve-in-valve (VIV) TAVR has emerged as a viable alternative for patients with failing surgical bioprosthetic valves.Valve-in-valve (VIV) TAVR has emerged as a viable alternative for patients with failing surgical bioprosthetic valves. We sought to assess the safety and efficacy of VIV TAVR with the Edwards SAPIEN XT transcatheter heart valve (THV) in patients with failed surgical bioprosthetic valves at high risk with reoperation.We sought to assess the safety and efficacy of VIV TAVR with the Edwards SAPIEN XT transcatheter heart valve (THV) in patients with failed surgical bioprosthetic valves at high risk with reoperation.

4. Methods Inclusion criteria:Inclusion criteria: –Symptomatic severe stenosis or regurgitation of a surgical aortic tissue valve –High-risk for re-operation (estimated surgical mortality or major morbidity ≥ 50%) –Suitable for 23mm or 26mm SAPIEN XT THV Exclusion criteria:Exclusion criteria: –Surgical valve labeled size < 21mm –Prosthetic valve in another position Angiogram, CT, Echo images and clinical data were screened on a weekly web conference callAngiogram, CT, Echo images and clinical data were screened on a weekly web conference call

5. Analysis Population N = 197 Analysis Population N = 197 Study Population PARTNER 2 Valve-in-Valve Registry N = 99 At 24 sites between June 2012 and April 2013 PARTNER 2 Valve-in-Valve Registry N = 99 At 24 sites between June 2012 and April 2013 2 patients withdrew consent prior to procedure Primary Endpoint: 1 Year Mortality PARTNER 2 Valve-in-Valve Extended Registry N = 100 At 34 sites between May 2013 and December 2013 PARTNER 2 Valve-in-Valve Extended Registry N = 100 At 34 sites between May 2013 and December 2013

6. CharacteristicOverall (n = 197) Age - Years 78.5 ± 11.0 Male - % 60.4 STS Score 9.7 ± 5.1 NYHA Class III/IV - % 95.4 CAD - % 70.6 COPD (O 2 Dependent) - % 7.1 CKD (Cr ≥ 2mg/dL) - % 12.7 Atrial Fibrillation - % 49.7 Permanent Pacemaker - % 25.9 Frailty - % 33.0 Baseline Patient Characteristics Demographics All values expressed as % or Mean ± Standard DeviationVIVRegistry (n = 97) Extended VIV Registry (n = 100) p-value 80.1 ± 9.377.0 ± 12.30.05 55.765.00.18 9.8 ± 5.19.5 ± 5.10.64 95.995.00.22 68.073.00.45 5.29.00.29 14.411.00.47 50.549.00.83 27.824.00.54 37.129.00.23

7. Surgical Bioprosthesis Age % < 5 years < 5 years8.1 5-10 years 5-10 years32.4 > 10 years > 10 years59.5 Mode of Degeneration Stenosis Stenosis54.2 Regurgitation Regurgitation22.4 Mixed Mixed23.4 Surgical Valve Type Bioprosthetic Stented Bioprosthetic Stented94.4 Stentless/Homograft Stentless/Homograft4.6 Unknown Unknown1.0 Valve and Procedure Characteristics Labeled Surgical Valve Size % 21mm 21mm28.3 23-25mm 59.7 >25mm >25mm12.0 Implanted THV Size 23mm 23mm72 26mm 26mm28 Access Transfemoral67 Transapical33

8. 1-Year All-Cause Mortality Mortality (%) No. at Risk All VIV Pts. 197181172169129 Months 13.4% at 1 Year All VIV Patients 4.1% at 30 Days

9. 1-Year All-Cause Mortality Mortality (%) No. at Risk VIV Registry 9785807761 VIV Extended Registry 10096929268 Months 19.7% VIV Registry 7.2% VIV Extended Registry Overall Log-Rank p-value = 0.008 9.3% at 30 Days 0% at 30 Days

10. 1-Year All-Cause Mortality TF vs. TA 13.2% TF 14.0% TA Mortality (%) No. at Risk TF13012111411285 TA 65 65 58 58 56 56 55 5543 Months Overall Log-Rank p-value = 0.83

11. Clinical Outcomes 30 Days and 1 Year Complication 30 Days 1 Year All-Cause Mortality 8 (4.1%) 26 (13.4%) Cardiac Mortality Cardiac Mortality 7 (3.6%) 17 (8.9%) Stroke (All) 5 (2.5%) 7 (3.7%) Rehospitalization 14 (7.3%) 22 (11.8%) All values are expressed as n (%) and percentages are Kaplan-Meier estimates at 30 days or 1 year.

12. Procedural Complications Complication n (%*) Coronary Obstruction 1 (0.5) Need for a second THV 3 (1.5) Major Bleeding 29 (14.8) Major Vascular Complications 6 (3.1) Pacemaker 3 (1.5) Acute Kidney Injury 16 (8.2) *Percentages are Kaplan-Meier estimates

13. Functional Outcomes NYHA Class 197181 95.5 11.6 12.0 p = NS p < 0.0001 158No. Patients

14. Functional & Quality of Life Outcomes Mean [95% CI] No. Patients 191181136 p < 0.0001 p = 0.20 No. Patients 191176144 Six Minute Walk Test Distance KCCQ Overall Summary Score p = 0.0014 p < 0.0001

15. Echocardiographic Outcomes Mean Gradient and Aortic Valve Area p < 0.0001 p = NS No. of Evaluable Echos 179164125 191176131 Mean ± SD mmHg cm²

16. Echocardiographic Outcomes p = NS p = 0.02 No. of Evaluable Echos 175162117 Mean [95% CI] LV Ejection Fraction p < 0.0001 p = 0.0002 175162117 Mean [95% CI] LV Mass index

17. Aortic Regurgitation (Total) 172162 p = NS p < 0.0001 101 No. of Evaluable Echos Nearly all post-procedure AR was Paravalvular.

18. Moderate / Severe Regurgitation % Baseline30D1YRBaseline30D1YR MitralTricuspid 16816497 p = 0.0002 p = NS p = 0.002 p = NS No. of Evaluable Echos 168163100

19. No. Patients 21mm514633 >21mm134124105 1-Year All-Cause Mortality and Quality of Life by Surgical Valve Size (Labeled) 5448454332 13712712112094 No. at Risk 21mm >21mm Log-Rank p-value =0.09 20.4% 11.1% Death (%) 0 10 20 30 40 50 Time in Months 036912 4 patients were missing data on labeled surgical valve size Mean [95% CI] p=NS for all between group comparisons p<0.0001 for change in each group in 1 year Surgical Valve Size 21mm Surgical Valve Size >21mm

20. 1-Year All-Cause Mortality and Quality of Life by Residual Gradient at Discharge 6459565441 120 11511010982 No. at Risk MG ≥ 20 mmHg MG < 20 mmHg Log-Rank p-value = 0.09 17.3% 8.3% Death (%) 0 10 20 30 40 50 Time in Months 036912 Discharge Mean Gradient ≥ 20 mmHg Discharge Mean Gradient < 20 mmHg No. Patients MG ≥ 20 mmHg615746 MG < 20 mmHg11811293 Mean [95% CI] p=NS for all between group comparisons p<0.0001 for change in each group in 1 year

21. Conclusions VIV TAVR SAPIEN XT THV – 1 Year Excellent freedom from death, stroke, and major adverse events.Excellent freedom from death, stroke, and major adverse events. Significant clinical benefit in terms of symptoms, functional status, 6min walk test and QOL.Significant clinical benefit in terms of symptoms, functional status, 6min walk test and QOL. Hemodynamic improvement and LVMi regression, increase in LVEF, decrease in MR / TR and low rates of AR.Hemodynamic improvement and LVMi regression, increase in LVEF, decrease in MR / TR and low rates of AR. Data raises important considerations regarding SAVR strategy in favor of implanting large surgical valves in the index surgery.Data raises important considerations regarding SAVR strategy in favor of implanting large surgical valves in the index surgery.

22. Clinical Implication Valve-in-Valve TAVR using SAPIEN XT is a beneficial therapeutic alternative to reoperation in patients with failed aortic bioprostheses.

23. Thank you to the dedicated study teams at all the PARTNER Sites! Special thanks to the participants in this writing group Danny Dvir John Webb Michael Mack Todd Dewey Kevin Greason Jonathon Leipsic Raj Makkar Craig Miller Rupa Parvataneni Augusto Pichard Lowell Satler Craig Smith Rakesh Suri Jonathon White Martin Leon

24. BACKUP SLIDES

25. High SAPIEN XT Implantation Will Decrease Post Procedural Gradients SAPIEN XT 23mm in Perimount #19 (courtesy of M. Simonato)