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
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 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 2014 2 Adams D, Popma J, Reardon M, et al. New Engl J Med 2014 3
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.
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 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
Study Timeline 2012 June SURTAVI First patient enrolled CoreValve: 23, 26, 29 mm (US) 2015 2016 2017 2018 2019 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
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 TAVR mitt* group: N=864 SAVR ITT group: N=867 71 not attempted: - 4 died - 43 withdrew consent - 23 physician withdrew - 1 lost to follow-up SAVR mitt* group: N=796 15 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
Baseline Characteristics n (%) or mean ± SD RCT* SAVR (N=796) TAVR (N=864) Age, years 79.7 ± 6.1 79.9 ± 6.2 Male sex 438 (55.0) 498 (57.6) Body surface area, m 2 1.9 ± 0.2 1.9 ± 0.2 STS PROM, % 4.5 ± 1.6 4.4 ± 1.5 Logistic EuroSCORE, % 11.6 ± 8.0 11.9 ± 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 ± 6.1 127 (46.2) 1.9 ± 0.2 4.1 ± 1.5 9.1 ± 6.5 100 (36.4) 2 (0.7) 16 (5.8) 8 (2.9) 71 (25.8) 19 (6.9) 10
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) 260.9 ± 117.9 254.1 ± 115.8 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) 252.2 ± 117.3 174 (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
RESULTS 12
All-Cause Mortality or Disabling Stroke 30% All-Cause Mortality or Disabling Stroke 25% 20% 15% 10% 5% TAVR SAVR P-value (log-rank) =0.55 8.5% 7.8% No. at Risk SAVR TAVR 0% 0 2 4 6 8 10 12 Months Post-Procedure 796 723 678 864 813 772 13
All-Cause Mortality 30% 25% TAVR All-Cause Mortality 20% 15% 10% 5% SAVR P-value (log-rank) =0.91 6.7% 6.5% No. at Risk SAVR TAVR 0% 0 2 4 6 8 10 12 Months Post-Procedure 796 739 692 864 821 783 14
Disabling Stroke 30% Disabling Stroke No. at Risk SAVR TAVR 25% 20% 15% 10% 5% 0% TAVR SAVR P-value (log-rank) =0.13 0 2 4 6 8 10 12 Months Post-Procedure 796 723 678 864 813 772 3.3% 2.1% 15
All Stroke 30% 25% TAVR All Stroke 20% 15% 10% 5% SAVR P-value (log-rank) =0.14 6.9% 5.2% No. at Risk SAVR TAVR 0% 0 2 4 6 8 10 12 Months Post-Procedure 796 697 653 864 789 747 16
NYHA Functional Class % of Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% p=0.42 p<0.01 p=0.66 5.0% 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 Baseline TAVR 18.4 ± 22.8 21.9 ± 22.3 20.6 ± 22.3 SAVR 5.9 ± 27.0 21.3 ± 22.3 20.5 ± 22.2 P <0.01 0.61 0.88 TAVR SAVR 18
6 Minute Walk Test Change from Baseline p<0.01 p<0.01 40 30 20 10 0-10 -20 35.4 37.0 17.8 N=709 N=624 N=501 N=528 30 Day 12 Months -14.4 TAVR SAVR Change is increase or decrease in meters walked in 6 minutes 19
Procedural Overview % or mean ± SD RCT SAVR (N=796) TAVR (N=864) General anesthesia, % 100 76 Procedure time, min 203.7 ± 69.1 52.3 ± 32.7 Total time in cath lab or OR, min 295.5 ± 81.6 190.8 ± 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 ± 8.0 5.7 ± 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) 52.7 41.2 ± 25.2 153.9 ± 51.2 40 36.7 2.9 3.2 ± 2.6 (n=225) 32.8 ± 32.3 NA NA 20
Clinical Outcomes at 30 Days RCT CAS SAVR (N=796) TAVR (N=864) P All-cause mortality or disabling stroke 3.8 2.8 0.26 All-cause mortality 1.6 2.1 0.50 Disabling stroke 2.4 1.2 0.06 All stroke 5.4 3.3 0.03 Life-threatening or major bleeding 9.1 12.0 0.05 Transfusion of PRBCs* -n(%) 328 (41.2) 108 (12.5) <0.01 Acute kidney injury, stage 2-3 4.4 1.6 <0.01 Major vascular complications 1.1 5.9 <0.01 Permanent pacemaker implant 6.5 25.6 <0.01 Atrial fibrillation 43.1 12.7 <0.01 Myocardial infarction 0.9 0.8 0.88 *Percentage rates, all others are Kaplan-Meier rates TAVR (N=275) 0.4 0.0 0.4 1.5 6.6 14 (5.1) 1.8 3.6 16.1 12.6 0.4 21
Hemodynamics* TAVR had significantly better valve performance over SAVR at all follow-up visits (P<0.001) Aortic Valve Area, cm 2 2.5 2.0 1.5 1.0 0.5 0.0 TAVR SAVR 47.7 47.0 0.78 0.77 TAVR CAS 2.13 2.14 2.14 1.82 1.80 1.78 12.4 11.1 11.6 8.9 8.3 8.3 Baseline Discharge 6 Months 1 Year 60.0 50.0 40.0 30.0 20.0 10.0 0.0 AV Mean Gradient, mm Hg *Core lab adjudicated 22
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
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
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
Functional Status after Transcatheter and Surgical Aortic Valve Replacement A sub-analysis from the SURTAVI Trial Jeffrey J. Popma, MD For the SURTAVI Investigators
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
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
Patient Flow 1,746 patients randomized TAVR ITT group: N=879 SAVR ITT group: N=867 15 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
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 150 400 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)
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
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 150-400 m <150 m
Baseline Characteristics TAVR (N=864) SAVR (N=796) n (%) or mean ± SD <150 m N=152 150 400 m N=583 >400 m N=67 <150 m N=126 150 400 m N=493 >400 m N=71 Age, years 80.7 ± 5.8 80.1 ± 6.1 77.7 ± 6.1 79.3 ± 6.8 79.7 ± 6.2 79.2 ± 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 2 1.9 ± 0.2 1.9 ± 0.2 1.9 ± 0.2 1.9 ± 0.3 1.9 ± 0.2 1.9 ± 0.2 STS PROM, % 4.8 ± 1.5 4.4 ± 1.5 3.3 ± 1.2 5.0 ± 1.7 4.4 ± 1.6 3.8 ± 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)
Baseline Cardiac Risk Factors TAVR (N=864) SAVR (N=796) n (%) or mean ± SD <150 m N=152 150 400 m N=583 >400 m N=67 <150 m N=126 150 400 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)
Baseline Frailty, Disabilities and Comorbidities* TAVR (N=864) n (%) or mean ± SD <150 m N=152 150 400 m N=583 >400 m N=67 <150 m N=126 SAVR (N=796) 150 400 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)
RESULTS
6 Minute Walk Test Change from Baseline The degree of improved functionality and the time course of recovery differed according to treatment modality 40 35.4 p<0.01 37 p<0.01 30 20 17.8 10 0-10 -20 N=709 N=624 N=501 N=528 30 Days 1 Year -14.4 Change is increase or decrease in meters walked in 6 minutes TAVR SAVR
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
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 150-400 m >400 m 30 Days 1 Year
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
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
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.
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.
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
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: 1790-8; 2 Smith CR, et al. N Engl J Med 2011;364:2187-98; Leon MB, et al. 2016; 374: 1609-20; 4 Reardon MJ, et al. N Engl J Med 2017;376:1321-31. 2
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: 280-7; Barbanti M, et al, Am J Cardiol 2016; 117: 820-7; Leon MB, et al, N Engl J Med 2016:374:1609-20; Kodali S, et al., Eur Heart J 2016; 37:2252-62; Reardon MJ, et al. N Engl J Med 2017; 376: 1321-31; Thourani VH, et al, Ann Thorac Surg 2015; 99: 55-61. 3
CURRENT GUIDELINES RECOMMEND SURGERY FOR PATIENTS DEEMED AT LOW SURGICAL RISK 2017 ACC/AHA Focused Update 1 2017 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;70:252-289; 2 Baumgartner H, et al. Eur Heart J 2017; Aug 26. doi: 10.1093/eurheartj/ehx391. [epub ahead of print] TCT 2015 4 4
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 (NCT02825134); 2 PARTNER 3 (NCT02675114) 5
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
BASELINE CHARACTERISTICS Characteristic, mean ± SD or % STS < 3% N=257 STS 3% N=781 P Value Age, years 77.9 ± 6.9 83.0 ± 5.4 <0.001 Female 53.7 68.6 < 0.001 BSA, m 2 1.8 ± 0.2 1.7 ± 0.2 <0.001 STS PROM, % 2.2 ± 0.5 6.6 ± 4.7 <0.001 Logistic EuroSCORE, % 11.3 ± 7.5 19.3 ± 12.0 <0.001 EuroSCORE II, % 3.3 ± 3.1 6.4 ± 5.3 <0.001 NYHA Class 0.06 I 2.0 1.3 II 31.0 25.1 III 59.5 65.2 IV 7.5 8.5 7 7
STS BASELINE FACTORS Characteristic, % STS Factors STS < 3% N=257 STS 3% N=781 P Value Diabetes mellitus 19.1 33.5 < 0.001 Serum creatinine >2 mg/dl 0.4 7.4 < 0.001 Dialysis 0.4 3.3 0.006 Chronic lung disease (COPD) 15.0 30.2 < 0.001 Peripheral arterial disease 9.8 27.1 < 0.001 Cerebrovascular disease 20.2 15.9 0.11 Previous CABG 7.8 11.6 0.09 Previous PCI 26.8 28.2 0.68 Previous MI 10.6 16.8 0.02 Atrial fibrillation 26.3 37.0 0.002 8
NON-STS BASELINE FACTORS Characteristic, % STS < 3% N=257 STS 3% N=781 P Value Non-STS Factors Katz score < 0.001 0 2 4.7 4.9 3 4 3.1 8.5 5 6 92.2 86.7 Frailty 28.6 35.7 0.04 Porcelain aorta 7.1 4.1 0.06 Pulmonary hypertension 40.8 47.7 0.06 Implanted cardiac device 11.7 12.0 0.88 Evidence of radiation damage 3.5 1.4 0.03 Abnormal chest wall anatomy 2.0 0.6 0.06 Severely atherosclerotic aorta 10.5 11.5 0.69 9
PROCEDURAL OUTCOMES STS < 3% N=257 STS 3% N=781 P Value Characteristic, % Anesthesia < 0.001 General 47.9 30.7 Local/conscious sedation 52.1 69.3 Access < 0.001 Iliofemoral 99.2 97.6 Subclavian 0.4 1.9 Direct aortic 0.4 0.3 Pre-BAV 40.1 47.2 0.05 Post-BAV 37.7 31.6 0.07 EnVeo InLine sheath 86.9 89.3 0.30 Implanted Valve Size 0.02 23 mm 4.8 6.5 26 mm 31.7 38.2 29 mm 63.5 55.3 More than 1 valve implanted 0.0 1.3 0.13 10
NYHA CLASSIFICATION 11
SAFETY OUTCOMES AT 30 DAYS Kaplan-Meier rates as %. 12
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