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

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

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.

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

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 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

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 ± ± ± ±

Surgical Bioprosthesis Age % < 5 years < 5 years 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 21mm mm 59.7 >25mm >25mm12.0 Implanted THV Size 23mm 23mm72 26mm 26mm28 Access Transfemoral67 Transapical33

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

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

1-Year All-Cause Mortality TF vs. TA 13.2% TF 14.0% TA Mortality (%) No. at Risk TF TA Months Overall Log-Rank p-value = 0.83

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.

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

Functional Outcomes NYHA Class p = NS p < No. Patients

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

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

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

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

Moderate / Severe Regurgitation % Baseline30D1YRBaseline30D1YR MitralTricuspid p = p = NS p = p = NS No. of Evaluable Echos

No. Patients 21mm >21mm Year All-Cause Mortality and Quality of Life by Surgical Valve Size (Labeled) No. at Risk 21mm >21mm Log-Rank p-value = % 11.1% Death (%) Time in Months patients were missing data on labeled surgical valve size Mean [95% CI] p=NS for all between group comparisons p< for change in each group in 1 year Surgical Valve Size 21mm Surgical Valve Size >21mm

1-Year All-Cause Mortality and Quality of Life by Residual Gradient at Discharge No. at Risk MG ≥ 20 mmHg MG < 20 mmHg Log-Rank p-value = % 8.3% Death (%) Time in Months Discharge Mean Gradient ≥ 20 mmHg Discharge Mean Gradient < 20 mmHg No. Patients MG ≥ 20 mmHg MG < 20 mmHg Mean [95% CI] p=NS for all between group comparisons p< for change in each group in 1 year

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.

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

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

BACKUP SLIDES

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