STS 2015 John V. Conte, MD Professor of Surgery Johns Hopkins University School of Medicine On Behalf of the CoreValve US Investigators Transcatheter Aortic Valve Replacement or Surgical Aortic Valve Replacement in Patients With Prior Coronary Artery Bypass Grafting CoreValve US Pivotal Trial

STS 2015 Transcatheter aortic valve replacement (TAVR) has had a major impact on how high risk patients with AS are treated TAVR has demonstrated morbidity and mortality advantages over SAVR in many patient cohorts In patients with prior CABG there is no consensus in the literature whether TAVR or SAVR offers a benefit Background Adams DJ, Popma JJ, Reardon MJ, et al. N Engl J Med 2014;370: Greason KL, Verghese M, Suri RM, et al. Ann Thorac Surg 2014;98:1-7. Stortecky S, Brinks H, Wenaweser P, et al. Ann Thorac Surg 2011;92:

STS 2015 Subgroup analysis of patients in High Risk Arm of Corevalve Clinical Trial who had a prior CABG Analysis Goal: –To identify if there existed any morbidity or mortality benefits with TAVR vs. SAVR therapy Plan of Investigation 3

STS 2015 * Randomization stratified by intended access site Pivotal Trial Design 4

STS Fr delivery system 4 valve sizes (18-29 mm annular range) Transfemoral Subclavian Direct Aortic Study Device and Access Routes 5

STS 2015 Subgroup Disposition Patients with Prior CABG 6

STS 2015 Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Age, years 82.0 ± ± Men, % STS Predicted Risk of Mortality, % 7.3 ± ± NYHA Class III/IV Body surface area, m ± History of hypertension Peripheral vascular disease Cerebrovascular disease Diabetes mellitus Insulin requiring diabetes Prior stroke Chronic lung disease/ COPD STS severe chronic lung disease Baseline Demographics 7

STS 2015 Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Age, years 82.0 ± ± Men, % STS Predicted Risk of Mortality, % 7.3 ± ± NYHA Class III/IV Body surface area, m ± History of hypertension Peripheral vascular disease Cerebrovascular disease Diabetes mellitus Insulin requiring diabetes Prior stroke Chronic lung disease/ COPD STS severe chronic lung disease Baseline Demographics 8

STS 2015 Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Age, years 82.0 ± ± Men, % STS Predicted Risk of Mortality, % 7.3 ± ± NYHA Class III/IV Body surface area, m ± History of hypertension Peripheral vascular disease Cerebrovascular disease Diabetes mellitus Insulin requiring diabetes Prior stroke Chronic lung disease/ COPD STS severe chronic lung disease Baseline Demographics

STS 2015 Cardiac History 10 Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Years since CABG 12.6 ± ± Patients with LIMA grafts Previous PCI or more Total Previous Heart Surgeries Mitral valve surgery Balloon valvuloplasty Pre-existing IPG/ICD

STS Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Years since CABG 12.6 ± ± Patients with LIMA grafts Previous PCI or more Total Previous Heart Surgeries Mitral valve surgery Balloon valvuloplasty Pre-existing IPG/ICD Cardiac History

STS Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Years since CABG 12.6 ± ± Patients with LIMA grafts Previous PCI or more Total Previous Heart Surgeries Mitral valve surgery Balloon valvuloplasty Pre-existing IPG/ICD Cardiac History

STS Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Years since CABG 12.6 ± ± Patients with LIMA grafts Previous PCI or more Total Previous Heart Surgeries Mitral valve surgery Balloon valvuloplasty Pre-existing IPG/ICD Cardiac History

STS Characteristic, % or mean ± SD TAVR N=115 SAVR N=111P Value Years since CABG 12.6 ± ± Patients with LIMA grafts Previous PCI or more Total Previous Heart Surgeries Mitral valve surgery Balloon valvuloplasty Pre-existing IPG/ICD Cardiac History

STS 2015 Results

1-Year All-Cause Mortality Patients with Prior CABG 16

STS 2015 Outcomes with both therapies were excellent –SAVR O/E ratio 0.79 vs. STS PROM –TAVR O/E ratio 0.48 vs. STS PROM Prior to the beginning of the CoreValve US Pivotal Trial Heart Teams had no TAVR experience Clinical Results 17

STS 2015 Cox Multivariate Model created using baseline demographic, cardiac and procedural characteristics No single characteristic predictive of mortality Combinations of characteristics were tested Combination of Age >80 and STS PROM Score >7% was predictive of lower 1 year mortality (p=0.03) in TAVR pts Predictors of Mortality

STS 2015 Major Stroke Patients with Prior CABG 19

STS 2015 All-Cause Mortality or Major Stroke Patients with Prior CABG 20

STS 2015 MACCE Patients with Prior CABG 21

STS 2015 Index Procedural Events Procedural Events a TAVR N=115 SAVR N=111P Value Blood units transfused b 0.4 ± ± 3.1 <0.001 ≥ 1 unit b 19.1%73.9% <0.001 ≥ 2 units b 11.3%63.1% <0.001 Procedure time, min 66.9 ± ± 95.5 <0.001 Time in ICU, hours 73.9 ± ± Index LOS, days 7.3 ± ± 12.7 <0.001 a Data presented as mean ± SD or percentages and log-rank P values. 22 b Within the first 24 hours post-procedure.

STS 2015 Other Outcomes 23 Events a 1 Month1 Year TAVRSAVRP ValueTAVRSAVRP Value Major vascular complications Pacemaker implant < Life threatening or disabling bleeding < <0.001 Acute kidney injury a Data presented as Kaplan-Meier estimates and log-rank P values.

STS 2015 Paravalvular Regurgitation Patients with Prior CABG 24

STS 2015 NYHA Class Patients with Prior CABG 25

STS 2015 KCCQ Overall Summary Patients with Prior CABG 26

STS 2015 This is the first review to demonstrate an advantage of TAVR over SAVR in patients with prior CABG using prospective randomized data. –Trend towards improvement in the primary endpoint of mortality at 1 year –Significant differences in the composite endpoint of mortality or major stroke –Significant differences in MACCE Conclusions 27

STS 2015 No independent predictors of 1 yr mortality Combination of Age >80yrs and STS >7% demonstrated a survival advantage for TAVR at 1 year TAVR demonstrated several procedural advantages with significant reductions in healthcare utilization Conclusions

STS 2015 Technological evolutions which reduce : PVL Vascular access problems Pacemakers implantation will encourage a shift of re-operative pts to TAVR Previous CABG patients who may benefit from SAVR include: Young patients who might need more than 1 AVR Patients who need concomitant revascularization and a LIMA available Patients with poor access who require alternative access via sternotomy Implications

STS 2015 Thank You On Behalf of the CoreValve US Investigators