Transcather Aortic Valve Replacement Using the Self-Expanding Bioprosthesis: First Report Using STS/ACC Transcatheter Valve Therapy Registry CoreValve Data Jeffrey J. Popma, M.D. Beth Israel Deaconess Medical Center, Boston, MA

2 David Adams | Mt. Sinai, New York City Stan Chetcuti | University of MI, Ann Arbor James Hermiller | St. Vincent’s, Indianapolis Susheel Kodali | Columbia, New York City Jeffrey Popma | Beth Israel, Boston Michael Reardon | Methodist DeBakey, Houston Paul Sorajja | Abbott Northwestern Hospital, Minneapolis Wilson Szeto | University of PA, Philadelphia *not affiliated with the STS/ACC TVT-R Research and Publications Committee TVT CoreValve Collaborators

Funding Support and Disclaimer This research was conducted by Medtronic, independent of the STS and ACC, using a cohort of deidentified data for CoreValve cases from the STS/ACC TVT Registry. The views expressed in this presentation represent those of the author(s).

Disclosure Statement of Financial Interest Institutional Grants Medical Advisory Board Institutional Grants, Consultant Institutional Grants Medical Advisory Board Medtronic Boston Scientific Direct Flow Medical Abbot Vascular 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 The STS/ACC Transcatheter Valve Therapy (STS/ACC TVT) national registry was initiated in 2011 in collaboration with the FDA, the Center for Medicare and Medicaid Services and the Duke Clinical Research Institute The STS/ACC TVT Registry™ provides: – Data repository and reporting infrastructure to monitor the safety and effectiveness of TVT devices – Real world data to confirm consistent safety and effectiveness of TAVR to compare with results from controlled clinical trials. Carroll JD, et al. JACC 2013;62:

Objectives To report the 30-day and 1 year clinical outcome of patients treated with the CoreValve self-expanding bioprostheses in “real world” clinical practice To broadly compare these findings with the baseline characteristics and clinical results obtained in the US CoreValve Pivotal Trials

Methods Patients with severe aortic stenosis undergoing TAVR with the CoreValve bioprosthesis captured in the STS/ACC TVT Registry (TVT-R) Data were collected using standardized definitions harmonized with the STS National Database and the ACC NCDR Patient characteristics, procedural details, quality of life and clinical outcomes were collected Study inclusion: January 2014 to March patients treated at 214 clinical centers

TVT-R Patient Risk Assessment Risk TVT-R Risk Definition TVT-R N=6160 (%) Extreme Risk Technically inoperable, co-morbid, and debilitated patients 2422 (39.3) High Risk Predicted ≥8% risk of 30 day mortality based on STS risk model 3418 (55.5) Intermediate Risk Predicted 4-7% risk of 30 day mortality based on STS risk model 215 (3.5) Low Risk Predicted <4% risk of 30-day mortality based on STS risk model 34 (0.6)

US CoreValve Pivotal Trials – Extreme Risk Patients (N=639; 62%): ≥50% risk for mortality or irreversible morbidity at 30 days with SAVR 1 – High Risk Patients (N=391; 38%): ≥15% risk for mortality and <50% risk for death or morbidity at 30 days with SAVR 2 To broadly compare the results of TVT-R CoreValve data with outcomes documented in the US Pivotal Trials: Because different patient populations were enrolled in the TVT-R and US Pivotal studies, no statistical comparisons were made 1 Popma J. JACC 2014;63:1972–81. 2 Adams D. NEJM 2014; 370:

TVT-R CoreValve Baseline Characteristics Characteristic TVT R N=6160 ER/HR Pivotal N=1030 Age, years 81.1 ± ± 7.9 Body Surface Area, m ± ± 0.2 Male54.7%49.4% NYHA Class III/IV 83.7%89.4% STS PROM, % 8.7 ± ± 5.0 Diabetes Mellitus38.0%37.9% Insulin requiring diabetes14.5%14.7% Prior Stroke12.7%13.3% Peripheral Vascular Disease30.7%41.2% Chronic lung disease/COPD49.4%55.4%

TVT-R CoreValve Baseline Characteristics Characteristic TVT R N=6160 ER/HR Pivotal N=1030 Cardiac Surgery (Open Heart) 31.7%36.3% Balloon valvuloplasty11.7% 15.2% Coronary Artery Disease69.4% 79.1% Coronary Artery Bypass Surgery29.6% 35.8% Percutaneous Coronary Intervention 37.3% 35.2% Pre-Existing IPG/ICD 21.9% 24.9% Previous MI27.2% 29.0% Atrial Fibrillation / Atrial Flutter43.5% 44.8%

TVT-R CoreValve Frailty and Disability Characteristic TVT R N=6160 ER/HR Pivotal N=1030 Porcelain Aorta 5.1%3.6% Hostile Mediastinum6.6% 8.4% Severe STS Lung Disease16.6% 22.0% Immunosuppressive Therapy11.7% 12.7% BMI < 21 kg/m % 8.5% Albumin < 3.3 g/dL19.2% 16.9% 5-M gait speed >6 seconds74.6% 81.7%

TVT-R Etiology of Aortic Stenosis Valve Morphology Tricuspid, 88.0% Unicuspid, 0.1% Bicuspid, 2.9% Unknown, 9.0% Etiology Of Aortic Stenosis Degenerative, 94.8% Primary, 2.4% Congenital, 0.5% Endocarditis, 0.2% Rheumatic 0.9%

TVT-R CoreValve Echocardiographic Findings Assessment TVT R N=6160 ER/HR Pivotal N=1030 LVEF (%)52.3 ± ± 13.4 Aortic Valve Area (cm 2 )0.69 ± ± 0.23 Mean Gradient, mmHg)43.3 ± ± 15.2 Peak Velocity, m/sec4.1 ± ± 0.7 Aortic Regurgitation Grade* None22.6% 13.2% Trace/Trivial20.0%35.7% Mild37.6% 43.4% Moderate16.1% 7.6% Severe3.6% 0.1% *Based on site reported Echo for TVT-R and core lab reported for ER/HR pivotal

TVT-R CoreValve Procedural Overview Assessment TVT R (N=6160) ER/HR Pivotal (N=1030) General Anesthesia88.8% 95.2% Access Site Left/Right Iliofemoral89.4% 79.4% Left/Right Subclavian/Axillary5.3% 7.9% Direct Aortic4.6% 12.7% Valve size implanted 23 mm4.5%2.7% 26 mm22.7%34.2% 29 mm37.6%53.9% 31 mm35.1%9.2%

TVT-R CoreValve Procedural Overview Assessment TVT R N=6160 ER/HR Pivotal N=1030 Device Implanted Successfully98.0%96.8% More than 1 valve used5.4%6.6% Device Success*94.0%86.0% Valve-in-Valve, immediate intra- procedure 3.1%2.6% CardioPulmonary Bypass Used1.2%-- Conversion to Open Heart Surgery0.7%0.2% ICU hours 59.9 ± ± Length of Hospital Stay, days7.8 ± ± 7.8

TVT-R Corevalve 30 Day Outcomes Assessment TVT R N=6160 ER/HR Pivotal N=1030 All-Cause Mortality5.2%6.9% Any Stroke2.6%5.0% Myocardial Infarction0.6%1.2% Reintervention0.5%0.8% Endocarditis0.1% Major Vascular Complication1.1%7.5% Permanent pacemaker implanted22.0%20.2% Device Thrombosis0.0% Valve Related Readmission1.5%5.9%

TVT-R CoreValve 30 Day Mortality: 5.7% % % % % No Clear “Learning Curve” From Pivotal Trial to Commercial Use Despite Expansion to 214 Clinical Sites

TVT-R Mean Aortic Valve Gradients N ± ± ± ±5.0 Mean Gradient, mmHg

TVT-R CoreValve NYHA Functional Class

TVT-R CoreValve Total Aortic Regurgitation (N=6111)(N=5112)(N=3827)(N=401)

TVT-R Paravalvular Aortic Regurgitation (N=4730)(N=3533) (N=369)

TVT-R Corevalve One Year Clinical Outcomes TVT-R RegistryUS CoreValve Pivotal Events, % Overall N=380 ER All N=232 HR All N=144 ER/HR Pivotal N=1030 ER N=639 HR N=391 All-Cause Mortality Stroke or TIA Transient Ischemic Attack Any Stroke Myocardial Infarction Endocarditis Major Vascular Complication Device Thrombosis Aortic Valve Re-intervention Valve Related Readmission

TVT-R CoreValve Consistent with Pivotal Clinical Trials 1 Month 1 Year TVT Registry vs Clinical Trial TVT TAVR O/E Ratio = 0.60

TVT-R CoreValve Consistent with Pivotal Clinical Trials 25 TVT Registry vs Clinical Trial Extreme Risk High Risk

TVT-R CoreValve One Year KCCQ 40.9± ± ± ± ± ±22.8 Δ 26.8 ± 27.4 P< Δ 34.7 ± 27.8 P= KCCQ Quality of Life Summary Score N N

Limitations Risk categories  “Risk creep” not detected by conventional factors Potential underreporting of events Clinical site echocardiographic reporting Data compliance

Summary First report of 6160 patient treated with CoreValve self- expanding TAVR documenting “real world” commercial use in patients with symptomatic aortic stenosis Baseline characteristics confirm the high surgical risk of the TVT registry patients with aortic stenosis Early (30 day) and late (one year) clinically outcomes are broadly comparable to those patients enrolled in the Pivotal studies No detectable learning curve or safety issues were identified with commercial expansion

Conclusion The results of this study support the safety and efficacy of the self-expanding CoreValve bioprosthesis in “real world” commercial use in patients with severe aortic stenosis