Transcatheter Aortic Valve Replacement with a Self-Expanding Prosthesis or Surgical Aortic Valve Replacement in Intermediate-Risk Patients:

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1 Transcatheter Aortic Valve Replacement with a Self-Expanding Prosthesis or Surgical Aortic Valve Replacement in Intermediate-Risk Patients: 1-Year Results from the SURTAVI Clinical Trial Nicolas M. Van Mieghem, MD, PhD, FACC, FESC For the SURTAVI Investigators

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Financial Relationship Consultant (fees paid to institution) Grant/Research Support & consulting Fees Company Medtronic Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, Acist, Claret, Terumo, PulseCath

Background Self-expanding transcatheter aortic valve replacement (TAVR) is preferred to medical therapy in patients with severe, symptomatic aortic stenosis (AS) deemed prohibitive for surgical

3 Background Self-expanding transcatheter aortic valve replacement (TAVR) is preferred to medical therapy in patients with severe, symptomatic aortic stenosis (AS) deemed prohibitive for surgical aortic valve replacement (SAVR) 1, and is superior in patients at high risk for operative mortality at 30 days. 2 The comparative efficacy of TAVR and SAVR has been less well studied in patients at lower surgical risk. The SURTAVI trial was conducted to determine whether TAVR with a self-expanding CoreValve or Evolut R is non-inferior to surgical AVR for all-cause mortality or disabling stroke at 24 months in patients with severe AS at intermediate surgical risk. 1 Popma J, Adams D, Reardon M, et al. J Am Coll Cardiol Adams D, Popma J, Reardon M, et al. New Engl J Med

Primary Endpoint timed to occur when 1400 subjects Subjects have been who followed had for not 12 months reached Analysis 24-month using modeling

4 4 Bayesian Analysis of the 24-Month Primary Endpoint A pre-specified interim analysis occurred when 1400 patients reached 12-month follow-up. Observed 24-month outcomes Interim were Bayesian used Analysis to inform of the 2Year modeling. Primary Endpoint timed to occur when 1400 subjects Subjects have been who followed had for not 12 months reached Analysis 24-month using modeling follow-up to include had all patient their data outcomes imputed using their last known event status. Combining imputed and observed data, the posterior distribution of the difference in 24-month event rates was calculated.

5 Primary Endpoint This Bayesian method demonstrated that the trial met its primary endpoint 1 1 Reardon M, Van Mieghem N, Popma J, et al. New Engl J Med 2017

6 6 Objective The 1-year follow-up for all 1,660 patients treated in SURTAVI is now complete Also complete is the 30-day follow-up for 275 patients who underwent TAVR as part of a non-randomized continued access study The purpose of this presentation is to report the outcomes for both of these patient cohorts

7 Study Timeline 2012 June SURTAVI First patient enrolled CoreValve: 23, 26, 29 mm (US) April 2015 Evolut R (US) June Sept Dec Jul Oct CoreValve: 23, 26, 29 mm (CAN, EU) CoreValve: 31 mm (US, CAN, EU) SURTAVI RCT 2 Yr Outcomes TCT 2018 SURTAVI Enrollment complete CAS First patient enrolled Evolut R: 23, 26, 29 mm CoreValve: 31 mm Primary endpoint assessment CAS Enrollment complete SURTAVI 1-Year follow-up complete 7

second generation valves SURTAVI CAS 59 sites 95.6% TF 0.

8 Study Features SURTAVI RCT 17 sites 65 sites 5 sites CoreValve (n=724) 94% TF 4% DA 2% SCA Evolut R (n=139) 16% second generation valves SURTAVI CAS 59 sites 95.6% TF 0.4% DA 4% SCA 93% second generation valves CoreValve (n=20) Evolut R (n=254) 8

Patient Flow Randomized Controlled Trial (RCT) 1746 patients Continued Access Study (CAS) 290 patients TAVR ITT group: N=879 15 not attempted: - 4 died - 6 withdrew consent - 5 physician withdrew

9 Patient Flow Randomized Controlled Trial (RCT) 1746 patients Continued Access Study (CAS) 290 patients TAVR ITT group: N= not attempted: - 4 died - 6 withdrew consent - 5 physician withdrew TAVR mitt* group: N=864 SAVR ITT group: N= not attempted: - 4 died - 43 withdrew consent - 23 physician withdrew - 1 lost to follow-up SAVR mitt* group: N= not attempted: - 1 died - 2 withdrew consent - 11 physician withdrew - 1 pending procedure TAVR attempted implant: N=275 2 not implanted 1 went to SAVR 2 surgical patients received TAVR 1 not implanted 2 went to TAVR 1 TAVR patient received SAVR 1 not implanted TAVR implanted group: N=863 SAVR implanted group: N=794 TAVR implanted group: N=274 *The modified intention-to-treat (mitt) population includes all subjects with an attempted procedure 9

10 Baseline Characteristics n (%) or mean ± SD RCT* SAVR (N=796) TAVR (N=864) Age, years 79.7 ± ± 6.2 Male sex 438 (55.0) 498 (57.6) Body surface area, m ± ± 0.2 STS PROM, % 4.5 ± ± 1.5 Logistic EuroSCORE, % 11.6 ± ± 7.6 Diabetes mellitus 227 (34.8) 295 (34.1) Serum creatinine >2 mg/dl 17 (2.1) 14 (1.6) Prior stroke 57 (7.2) 57 (6.6) Prior TIA 46 (5.8) 58 (6.7) Peripheral vascular disease 238 (29.9) 266 (30.8) Pre-existing IPG / ICD 72 (9.9) 87 (10.1) *mitt population; no significant difference in any baseline characteristics CAS TAVR (N=275) 79.0 ± (46.2) 1.9 ± ± ± (36.4) 2 (0.7) 16 (5.8) 8 (2.9) 71 (25.8) 19 (6.9) 10

11 Baseline Frailty, Disabilities and Comorbidities* n (%) or mean ± SD RCT* CAS SAVR (N=796) TAVR (N=864) TAVR (N=275) Body mass index <21 kg/m 2 21 (2.6) 20 (2.3) Falls in past 6 months 101 (12.7) 102 (11.8) 5 meter gait speed >6 s 403 (52.9) 428 (51.8) 6 minute walk test (meters) ± ± Grip strength below threshold 489 (63.0) 519 (62.5) Does not live independently 22 (2.8) 18 (2.1) Chronic lung disease (mod/severe) 106 (13.3) 115 (13.3) Home oxygen 21 (2.6) 18 (2.1) Cirrhosis of the liver 5 (0.6) 4 (0.5) Immunosuppressive therapy 68 (8.5) 64 (7.4) 7 (2.5) 23 (8.4) 116 (44.3) ± (66.7) 7 (2.5) 50 (18.2) 2 (0.7) 2 (0.7) 16 (5.8) *mitt population; no significant difference in any baseline characteristics 11

12 RESULTS 12

13 All-Cause Mortality or Disabling Stroke 30% All-Cause Mortality or Disabling Stroke 25% 20% 15% 10% 5% TAVR SAVR P-value (log-rank) = % 7.8% No. at Risk SAVR TAVR 0% Months Post-Procedure

14 All-Cause Mortality 30% 25% TAVR All-Cause Mortality 20% 15% 10% 5% SAVR P-value (log-rank) = % 6.5% No. at Risk SAVR TAVR 0% Months Post-Procedure

15 Disabling Stroke 30% Disabling Stroke No. at Risk SAVR TAVR 25% 20% 15% 10% 5% 0% TAVR SAVR P-value (log-rank) = Months Post-Procedure % 2.1% 15

16 All Stroke 30% 25% TAVR All Stroke 20% 15% 10% 5% SAVR P-value (log-rank) = % 5.2% No. at Risk SAVR TAVR 0% Months Post-Procedure

17 NYHA Functional Class % of Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% p=0.42 p<0.01 p= % 4.4% 54.7% 53.6% 40.0% 41.2% 0.3% 0.8% TAVR (N=860) Baseline SAVR (N=789) 0.2% 1.1% 0.4% 0.2% 5.6% 9.6% 4.2% 4.3% 30.7% 63.5% TAVR (N=822) 30 Days 36.4% 52.8% SAVR (N=708) 24.2% 25.6% 71.2% 70.0% TAVR (N=732) 1 Year SAVR (N=606) IV III II I 17

KCCQ Summary Score Over Time 100 KCCQ Summary Score 90 80 70 60 50 40 Baseline 30 Days 6 Months 12 Months Change from

18 KCCQ Summary Score Over Time 100 KCCQ Summary Score Baseline 30 Days 6 Months 12 Months Change from Baseline TAVR 18.4 ± ± ± 22.3 SAVR 5.9 ± ± ± 22.2 P < TAVR SAVR 18

19 6 Minute Walk Test Change from Baseline p<0.01 p< N=709 N=624 N=501 N= Day 12 Months TAVR SAVR Change is increase or decrease in meters walked in 6 minutes 19

20 Procedural Overview % or mean ± SD RCT SAVR (N=796) TAVR (N=864) General anesthesia, % Procedure time, min ± ± 32.7 Total time in cath lab or OR, min ± ± 61.3 Pre-procedure BAV NA 47.2 Post-dilatation NA 29.0 More than 1 valve implanted, % NA 6.7 Length of index procedure hospital stay, days Length of ICU stay, hours 9.8 ± ± 4.9 (n=778) 70.4 ± 96.2 (n=767) 48.6 ± 44.0 Aortic cross-clamp time, min 74.3 ± 30.4 NA CPB time, min 97.8 ± 39.3 NA CAS TAVR (N=275) ± ± ± 2.6 (n=225) 32.8 ± 32.3 NA NA 20

21 Clinical Outcomes at 30 Days RCT CAS SAVR (N=796) TAVR (N=864) P All-cause mortality or disabling stroke All-cause mortality Disabling stroke All stroke Life-threatening or major bleeding Transfusion of PRBCs* -n(%) 328 (41.2) 108 (12.5) <0.01 Acute kidney injury, stage <0.01 Major vascular complications <0.01 Permanent pacemaker implant <0.01 Atrial fibrillation <0.01 Myocardial infarction *Percentage rates, all others are Kaplan-Meier rates TAVR (N=275) (5.1)

22 Hemodynamics* TAVR had significantly better valve performance over SAVR at all follow-up visits (P<0.001) Aortic Valve Area, cm TAVR SAVR TAVR CAS Baseline Discharge 6 Months 1 Year AV Mean Gradient, mm Hg *Core lab adjudicated 22

23 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Total Aortic Regurgitation* 0.7% 6.8% 92.5% SAVR (N=707) None/trace Mild Moderate Severe 0.2% 3.2% 35.9% 60.6% TAVR (N=832) 0.7% 8.3% 91.0% SAVR (N=602) 5.2% 34.0% 60.8% TAVR (N=718) RCT Discharge RCT 1 Year * Implanted population, core lab adjudicated 23

24 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Total Aortic Regurgitation* 0.7% 6.8% 92.5% SAVR (N=707) None/trace Mild Moderate Severe 0.2% 3.2% 35.9% 60.6% TAVR (N=832) 1.1% 22.6% 76.3% TAVR (N=266) RCT Discharge CAS Discharge * Implanted population, core lab adjudicated 24

25 Conclusion 25 The 1-year results from the SURTAVI randomized trial demonstrate that TAVR with the self-expanding Evolut R or CoreValve has similar outcomes compared to SAVR in terms of all-cause mortality or disabling stroke in patients at intermediate surgical risk TAVR patients had a faster improvement in quality of life, as well as superior functional status which was maintained to 1 year The 30-day results from the Continued Access Study demonstrate that the combination of operator experience and next-generation technology lead to fewer complications and improved clinical outcomes for patients

26 Functional Status after Transcatheter and Surgical Aortic Valve Replacement A sub-analysis from the SURTAVI Trial Jeffrey J. Popma, MD For the SURTAVI Investigators

27 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Financial Relationship Institutional Grants Institutional Grants; Medical Advisory Board Institutional Grants Institutional Grants; Consultant Company Medtronic Boston Scientific Abbott Edwards

28 Background The SURTAVI trial has shown that transcatheter aortic valve replacement (TAVR) is an alternative to surgery (SAVR) in intermediate-risk patients with severe, symptomatic aortic stenosis 1. Of specific interest is the clinical recovery pattern that patients experience following TAVR and SAVR. There are 2 goals to this sub-analysis from SURTAVI: to characterize how and when patients recover functionality and quality of life following aortic valve replacement To identify recovery patterns specifically related to transcatheter vs. surgical treatment 1 Reardon M, Van Mieghem N, Popma J, et al. New Engl J Med 2017

29 Patient Flow 1,746 patients randomized TAVR ITT group: N=879 SAVR ITT group: N= not attempted: - 4 died - 6 withdrew consent - 5 physician withdrew 71 not attempted: - 4 died - 43 withdrew consent - 23 physician withdrew - 1 lost to follow-up TAVR mitt* group: N=864 SAVR mitt* group: N=796 2 not implanted 1 went to SAVR 2 surgical patients received TAVR 1 not implanted 2 went to TAVR 1 TAVR patient received SAVR TAVR implanted group: N=863 SAVR implanted group: N=794 *The modified intention-to-treat (mitt) population includes all subjects with an attempted procedure

30 Methods Measures of functional status and quality of life were collected at baseline, 30 days, 6 months, and 1 year following treatment Patients were divided according to treatment arm, and then further separated into 3 categories based on meters walked in 6 minutes at baseline: <150 meters meters >400 meters For these patient groups, changes in meters walked at each time point relative to baseline were analyzed. These functional changes were then correlated to quality of life scores, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)

31 Key Definitions Clinically meaningful improvement in functional status: either an increase in 40m walked in 6 minutes relative to baseline or a 10% relative improvement Meaningful improvement in KCCQ score: 10 points relative to baseline

32 Baseline 6 Minute Walk Test The 3 patient groups were well balanced between TAVR and SAVR, with the majority of patients walking between 150 and 400 meters at baseline Percent of Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 8.4% 10.3% 72.7% 71.4% 19.0% 18.3% TAVR SAVR >400 m m <150 m

33 Baseline Characteristics TAVR (N=864) SAVR (N=796) n (%) or mean ± SD <150 m N= m N=583 >400 m N=67 <150 m N= m N=493 >400 m N=71 Age, years 80.7 ± ± ± ± ± ± 5.1 Male sex 63 (41.4) 349 (59.9) 55 (82.1) 53 (42.1) 288 (58.4) 48 (67.6) Body surface area, m ± ± ± ± ± ± 0.2 STS PROM, % 4.8 ± ± ± ± ± ± 1.7 Diabetes mellitus 54 (35.5) 199 (34.1) 16 (23.9) 65 (51.6) 163 (33.1) 15 (21.1) Serum creatinine >2 mg/dl 5 (3.3) 9 (1.5) 0 (0.0) 3 (2.4) 7 (1.4) 2 (2.8) Prior stroke 7 (4.6) 40 (6.9) 7 (10.4) 15 (11.9) 27 (5.5) 6 (8.5) Prior TIA 14 (9.2) 30 (5.1) 5 (7.5) 8 (6.3) 33 (6.7) 0 (0) Peripheral vascular disease 52 (34.2) 171 (29.3) 17 (25.4) 41 (32.5) 150 (30.4) 16 (22.5) Pre-existing IPG/ICD 19 (12.5) 57 (9.8) 5 (7.5) 13 (10.3) 53 (10.8) 1 (1.4)

34 Baseline Cardiac Risk Factors TAVR (N=864) SAVR (N=796) n (%) or mean ± SD <150 m N= m N=583 >400 m N=67 <150 m N= m N=493 >400 m N=71 Coronary artery disease 88 (57.9) 370 (63.5) 42 (62.7) 69 (54.8) 333 (67.5) 37 (52.1) Prior CABG 17 (11.2) 96 (16.5) 15 (22.4) 16 (12.7) 92 (18.7) 13 (18.3) Prior PCI 28 (18.4) 126 (21.6) 15 (22.4) 19 (15.1) 113 (22.9) 14 (19.7) Prior myocardial infarction 17 (11.2) 87 (14.9) 12 (17.9) 16 (12.7) 70 (14.2) 11 (15.5) Congestive heart failure 149 (98.0) 552 (94.7) 62 (92.5) 124 (98.4) 475 (96.3) 68 (95.8) History of arrhythmia 51 (33.6) 187 (32.1) 20 (29.9) 45 (35.7) 153 (31.0) 16 (22.5) Atrial fibrillation / flutter 44 (28.9) 165 (28.3) 19 (28.4) 41 (32.5) 127 (25.8) 12 (16.9) NYHA III / IV 118 (77.6) 333 (57.1) 31 (46.3) 98 (77.8) 267 (54.2) 27 (38.0)

35 Baseline Frailty, Disabilities and Comorbidities* TAVR (N=864) n (%) or mean ± SD <150 m N= m N=583 >400 m N=67 <150 m N=126 SAVR (N=796) m N=493 >400 m N=71 Body mass index <21 kg/m 2 1 (0.7) 17 (2.9) 2 (3.0) 2 (1.6) 9 (1.8) 5 (7.0) Falls in the past 6 months 30 (19.7) 63 (10.8) 1 (1.5) 17 (13.5) 61 (12.4) 3 (4.2) Grip strength below threshold Does not live independently Moderate / severe lung disease 107 (73.3) 337 (60.2) 31 (48.4) 82 (67.2) 306 (63.2) 29 (42.0) 5 (3.3) 7 (1.2) 3 (4.5) 4 (3.2) 12 (2.4) 3 (4.2) 21 (13.8) 77 (13.3) 9 (13.4) 18 (14.3) 65 (13.2) 5 (7.0) Home oxygen 8 (5.3) 8 (1.4) 0 (0.0) 5 (4.0) 7 (1.4) 0 (0.0)

36 RESULTS

37 6 Minute Walk Test Change from Baseline The degree of improved functionality and the time course of recovery differed according to treatment modality p< p< N=709 N=624 N=501 N= Days 1 Year Change is increase or decrease in meters walked in 6 minutes TAVR SAVR

38 6 Minute Walk Test At 30 days, almost 50% of TAVR patients experienced clinically meaningful improvement in functional status, as compared to 30% of SAVR patients 100% % patients with meaningful improvement 80% 60% 40% 20% 0% 47.8% 51.0% 44.5% 32.0% N=709 N=624 N=528 N=501 TAVR SAVR 30 Days 1 Year

39 Follow-up 6 Minute Walk Test Patients with the most limited mobility at baseline were the most likely to experience a meaningful improvement in mobility after treatment. Patients with the best mobility at baseline didn t have a measurable change following treatment 100% 80% 60% 40% 20% 0% 84.5% 84.4% 75.8% 58.1% 45.0% 47.1% 41.9% 29.2% 25.0% 13.1% 13.8% 9.8% N=128 N=97 N=86 N=77 N=520 N=471 N=377 N=363 N=61 N=56 N=65 N=61 TAVR SAVR TAVR SAVR TAVR SAVR <150 m m >400 m 30 Days 1 Year

40 KCCQ Summary Score Patients with a meaningful improvement in functional status had a better quality of life at both 30 days and 1 year % patients with KCCQ improvement 10 points at 30 days 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 73.4% 54.5% 64.5% 35.5% N=338 N=484 N=166 N=547 Yes No Yes No TAVR SAVR Meaningful Improvement in Functional Status

41 KCCQ Summary Score % patients with KCCQ improvement 10 points at 1 year 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 77.8% 74.1% 62.4% 59.2% N=317 N=420 N=221 N=407 Yes No Yes No TAVR SAVR Meaningful Improvement in Functional Status

42 Summary TAVR patients had significantly better functional status than SAVR patients at both 30 days and 1 year following treatment. The group of patients deriving the most functional improvement from aortic valve replacement had the most limited mobility at baseline. Prior to treatment, approximately 20% of patients were unable to walk 150 meters in 6 minutes. They were more often female, in NYHA Class III / IV, and frail relative to the rest of the SURTAVI population. More than half of them showed a clinically meaningful improvement as a result of treatment, regardless of modality.

43 Summary Patients with a clinically meaningful improvement in functional status had better quality of life than those patients that did not have improved functionality We conclude that in intermediate surgical risk severe aortic stenosis patients, functional status recovered more quickly and to a greater extent in TAVR patients as compared to SAVR patients. This translated into better quality of life for these patients.

44 30-Day Outcomes in Patients with a Society of Thoracic Surgeons Predicted Risk of Mortality < 3% from the Evolut R FORWARD Study Eberhard Grube, MD, PhD For the Evolut R FORWARD Study Investigators

45 BACKGROUND Benefits of TAVR include shorter length of stay, less AKI, less AF, quicker quality of life recovery and better hemodynamics than surgery. 1,2 TAVR is now an appropriate alternative to surgical AVR in patient at intermediate risk. 3,4 The multicenter Evolut R FORWARD Study assessed 1038 patients with symptomatic aortic stenosis at increased surgical risk who underwent transcatheter aortic valve replacement (TAVR) with the Evolut R valve in a routine hospital setting. The 30-day mortality rate was 1.9% and disabling stroke was 1.8%. In anticipation of the reporting from current randomized trials evaluating TAVR in patients at lower surgical risk, we performed a post-hoc analysis in patients with an STS predicted risk of mortality < 3.0%. 1 Adams DH, et al. N Engl J Med 2014; 270: ; 2 Smith CR, et al. N Engl J Med 2011;364: ; Leon MB, et al. 2016; 374: ; 4 Reardon MJ, et al. N Engl J Med 2017;376:

BACKGROUND 30-Day All-Cause Mortality in Intermediate Risk Reardon MJ, et al, JAMA Cardiol 2016;1:945-9; Wenaweser P, et al, Eur Heart J 2013; 34: 1894-905; Lange, et al, J Am Coll Cardiol 2012; 59:

46 BACKGROUND 30-Day All-Cause Mortality in Intermediate Risk Reardon MJ, et al, JAMA Cardiol 2016;1:945-9; Wenaweser P, et al, Eur Heart J 2013; 34: ; Lange, et al, J Am Coll Cardiol 2012; 59: 280-7; Barbanti M, et al, Am J Cardiol 2016; 117: 820-7; Leon MB, et al, N Engl J Med 2016:374: ; Kodali S, et al., Eur Heart J 2016; 37: ; Reardon MJ, et al. N Engl J Med 2017; 376: ; Thourani VH, et al, Ann Thorac Surg 2015; 99:

CURRENT GUIDELINES RECOMMEND SURGERY FOR PATIENTS DEEMED AT LOW SURGICAL RISK 2017 ACC/AHA Focused Update 1 2017 ESC /EACTS Guidelines 2 Choice of

EuroSCORE I< 10% and no other risk factors not included in these scores, such as frailty, porcelain aorta, sequelae of chest radiation).

47 CURRENT GUIDELINES RECOMMEND SURGERY FOR PATIENTS DEEMED AT LOW SURGICAL RISK 2017 ACC/AHA Focused Update ESC /EACTS Guidelines 2 Choice of intervention in symptomatic aortic stenosis Class Level SAVR is recommended in patients at low surgical risk (STS or EuroSCORE II< 4% or logistic EuroSCORE I< 10% and no other risk factors not included in these scores, such as frailty, porcelain aorta, sequelae of chest radiation). I B 1 Nishimura R, et al. J Am Coll Cardiol 2017;70: ; 2 Baumgartner H, et al. Eur Heart J 2017; Aug 26. doi: /eurheartj/ehx391. [epub ahead of print] TCT

48 DEFINING LOW-RISK PATIENTS FOR TAVR Ongoing randomized trials define low risk as: 1. Heart Team agreement of low 30-day risk (STS PROM < 3%) 1 OR 2. Operative mortality < 2% for SAVR 2 1 Medtronic TAVR in low risk (NCT ); 2 PARTNER 3 (NCT ) 5

49 METHODS The Evolut R FORWARD Study documented the safety and effectiveness of TAVR in patients undergoing TAVR in a routine hospital setting. Patient eligibility not solely based on STS Score* Age 80 years OR High risk for SAVR where high risk is defined as: STS PROM 8% OR Heart Team agreement of risk for SAVR due to frailty or comorbidities Post-hoc analysis of patients with an STS < 3% *Per protocol. CE Marking for patients at intermediate surgical risk was received during the trial. Inclusion eligibility was determined per local Instructions for Use. 6

50 BASELINE CHARACTERISTICS Characteristic, mean ± SD or % STS < 3% N=257 STS 3% N=781 P Value Age, years 77.9 ± ± 5.4 <0.001 Female < BSA, m ± ± 0.2 <0.001 STS PROM, % 2.2 ± ± 4.7 <0.001 Logistic EuroSCORE, % 11.3 ± ± 12.0 <0.001 EuroSCORE II, % 3.3 ± ± 5.3 <0.001 NYHA Class 0.06 I II III IV

51 STS BASELINE FACTORS Characteristic, % STS Factors STS < 3% N=257 STS 3% N=781 P Value Diabetes mellitus < Serum creatinine >2 mg/dl < Dialysis Chronic lung disease (COPD) < Peripheral arterial disease < Cerebrovascular disease Previous CABG Previous PCI Previous MI Atrial fibrillation

52 NON-STS BASELINE FACTORS Characteristic, % STS < 3% N=257 STS 3% N=781 P Value Non-STS Factors Katz score < Frailty Porcelain aorta Pulmonary hypertension Implanted cardiac device Evidence of radiation damage Abnormal chest wall anatomy Severely atherosclerotic aorta

53 PROCEDURAL OUTCOMES STS < 3% N=257 STS 3% N=781 P Value Characteristic, % Anesthesia < General Local/conscious sedation Access < Iliofemoral Subclavian Direct aortic Pre-BAV Post-BAV EnVeo InLine sheath Implanted Valve Size mm mm mm More than 1 valve implanted

54 NYHA CLASSIFICATION 11

55 SAFETY OUTCOMES AT 30 DAYS Kaplan-Meier rates as %. 12

56 SUMMARY In this routine practice study, 25% of enrolled patients had an STS < 3%, yet they were considered at elevated operative risk: Nearly 30% were frail 40% had pulmonary hypertension >10% had porcelain aorta or significant aortic calcification Symptom improvement at 30 days was similar regardless of STS There were no differences in 30-day outcomes except major bleeding, which may be attributed to differences in vascular status as significantly more patients with an STS 3% had PVD. The Evolut R FORWARD Study did not assess low-risk patients. The feasibility of TAVR in low-risk patients needs to be confirmed in dedicated randomized trials. 13

LOW RISK TAVR. WHAT THE FUTURE HOLDS

LOW RISK TAVR. WHAT THE FUTURE HOLDS Michael J. Reardon, M.D. Professor of Cardiothoracic Surgery Allison Family Distinguish Chair of Cardiovascular Research Houston Methodist DeBakey Heart & Vascular