Current and Future Management of Symptomatic Aortic Stenosis - PowerPoint PPT Presentation

Current and Future Management of Symptomatic Aortic Stenosis Alexander (Sandy) Dick, MD

Disclosures • None pertaining to this talk

Technique vs Technology SAVR vs TAVR

TAVR and SAVR Equivalency? • Mortality/Stroke • Morbidity – Vascular, PVL, PPM • Hemodynamics • Quality of life • Durability • Patient acceptance

Risk 6.2% High Risk ( STS >8% ) +++ Data Intermediate Risk 13.9% Partner II (STS 4-8%) Low Risk 79.9% CorValve Evolute R (STS <4%) Partner III Durability

Evolut R 2.0 • Self expanding Nitinol • Recapture, Reposition and Redeployment • Extended sealing skirt to reduce PVL

Lotus • Nitinol wire frame • Bovine tissue valve • Outer PU skirt • Mechanical expansion and locking

The PARTNER 2A Trial Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team Operable (STS ≥ 4%) Randomized Patients n = 2032 ASSESSMENT: Yes No Transfemoral Access Transfemoral (TF) Transapical (TA) / TransAortic (TAo) 1:1 Randomization (n = 1550) 1:1 Randomization (n = 482) TF TAVR Surgical AVR TA/TAo TAVR Surgical AVR VS. VS. (n = 775) (n = 775) (n = 236) (n = 246) Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years

Primary Endpoint (ITT) All-Cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) 50 Surgery HR [95% CI] = 0.89 [0.73, 1.09] p (log rank) = 0.253 TAVR 40 30 21.1% 20 16.4% 19.3% 8.0% 14.5% 10 6.1% 0 0 3 6 9 12 15 18 21 24 Months from Procedure Number at risk: Surgery 1021 838 812 783 770 747 735 717 695 TAVR 1011 918 901 870 842 825 811 801 774

Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) 50 Surgery HR [95% CI] = 0.87 [0.71, 1.07] TAVR p (log rank) = 0.180 40 30 21.0% 20 16.6% 18.9% 8.0% 14.0% 10 5.7% 0 0 3 6 9 12 15 18 21 24 Months from Procedure Number at risk: Surgery 944 826 807 779 766 743 731 715 694 TAVR 994 917 900 870 842 825 811 801 774

Primary Endpoint (ITT) All-cause Mortality or Disabling Stroke TAVR SAVR Relative Risk Ratio 0.92 Non-Inferiority p- n = 1011 n = 1021 Upper 1-sided 97.5%CI 1.09 value = 0.001 19.3% 21.1% Pre-specified non-inferiority margin = 1.2 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 Risk ratio (test/control) Favors TAVR Favors Surgery Primary Non-Inferiority Endpoint Met

Primary Endpoint Subgroup Analysis (ITT) TAVR (%) AVR (%) Hazard Ratio HR p-value for Subgroup n = 1011 n = 1021 (95% CI) (95% CI) interaction Overall 19.3 21.1 0.89 [0.73-1.09] Age 18.0 19.5 0.90 [0.69-1.17] 0.96 < 85 23.6 0.89 [0.65-1.20] 21.5 ≥ 85 Sex 16.9 20.3 0.81 [0.59-1.10] 0.37 Female 0.96 [0.74-1.25] 21.4 21.7 Male STS Score 15.8 18.4 0.84 [0.61-1.16] 0.60 ≤ 5 0.94 [0.73-1.21] 22.4 23.1 > 5 LV Ejection Fraction 19.1 21.5 0.84 [0.56-1.25] 0.27 ≤ 55 1.11 [0.81-1.53] 20.1 18.0 > 55 Mod or Severe Mitral Regurgitation 17.8 20.3 0.85 [0.67-1.08] 0.53 No 1.00 [0.64-1.57] 25.9 24.4 Yes Previous CABG 20.6 22.2 0.91 [0.73-1.13] 0.69 No 0.82 [0.53-1.27] 15.3 18.0 Yes Peripheral Vascular Disease 18.2 20.7 0.85 [0.67-1.09] 0.47 No 0.99 [0.71-1.40] 22.3 22.0 Yes 15 Foot Walk Test 17.7 20.9 0.82 [0.62-1.09] 0.43 ≤ 7 secs 0.97 [0.71-1.31] 20.7 20.8 > 7 secs Access Route 16.8 20.4 0.79 [0.62-1.00] 0.06 Transfemoral 1.21 [0.84-1.74] 27.7 23.4 Transthoracic 0.5 1.0 2.0 Favors TAVR Favors Surgery

TF Primary Endpoint (ITT) All-cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) 50 TF Surgery HR: 0.79 [95% CI: 0.62, 1.00] TF TAVR p (log rank) = 0.05 40 30 20.4% 20 15.9% 16.8% 7.7% 10 12.3% 4.9% 0 0 3 6 9 12 15 18 21 24 Months from Procedure Number at risk: TF Surgery 775 643 628 604 595 577 569 557 538 TF TAVR 775 718 709 685 663 652 644 634 612

TF Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) 50 TF Surgery HR: 0.78 [95% CI: 0.61, 0.99] TF TAVR p (log rank) = 0.04 40 30 20.0% 20 15.8% 16.3% 7.5% 10 11.7% 4.5% 0 0 0 3 6 9 12 15 18 21 24 Months from Procedure Number at risk: TF Surgery 636 624 600 591 573 565 555 537 722 TF TAVR 762 717 708 685 663 652 644 634 612

JACC, Feb1, 2017

Recommendation (Transcaval Favorable; Feasible; Unfavorable suitability) Basis for recommendation No unfavorable features. Target entry site lumbar vertebra L 2.5 Projection angles AP / Lateral Interposed & nearby structures No interposed structures. Aortic lumen diameter (+3/0/-3cm) 15 mm / 15 mm / 13 mm Target distance below renal artery 30 mm Target to aorto-iliac bifurcation 53 mm Covered stent bailout limb access & size L 4.0 mm / R 3.2 mm Working sheath distance to target 28 cm Mesenteric arteries Celiac patent; SMA patent. Caveat & Comments Exam more than 6 months old. Reviewers NHLBI Table version 2016-07 R Lederman read 2016-11-15

PARTNER SAPIEN Platforms Device Evolution SAPIEN XT SAPIEN SAPIEN 3 Valve Technology Sheath 22-24F 16-20F 14-16F Compatibility Available Valve Sizes 23 mm 26 mm 23mm 26mm 29mm* 20 mm 23 mm 26 mm 29 mm *First Implant Oct 30, 2012

Philippe Généreux et al. JACC 2012;60:1043-1052 American College of Cardiology Foundation

Other Clinical Endpoints (ITT) At 30 Days and 2 Years 30 Days 2 Years Events (%) TAVR Surgery TAVR Surgery p-value* p-value* (n = 1011) (n = 1021) (n = 1011) (n = 1021) 6.5 6.5 0.99 19.6 17.3 0.22 Rehospitalization MI 1.2 1.9 0.22 3.6 4.1 0.56 Major Vascular 7.9 5.0 0.008 8.6 5.5 0.006 Complications Life-Threatening / 10.4 43.4 <0.001 17.3 47.0 <0.001 Disabling Bleeding AKI (Stage III) 1.3 3.1 0.006 3.8 6.2 0.02 New Atrial Fibrillation 9.1 26.4 <0.001 11.3 27.3 <0.001 New Permanent 8.5 6.9 0.17 11.8 10.3 0.29 Pacemaker 0.4 0.0 0.05 1.4 0.6 0.09 Re-intervention 0.0 0.0 NA 1.2 0.7 0.22 Endocarditis *Event rates are KM estimates, p-values are point in time

The PARTNER 2A and S3i Trials Study Design Intermediate Risk Symptomatic Severe Aortic Stenosis Intermediate Risk ASSESSMENT by Heart Valve Team P2 S3i P2A n = 1078 n = 2032 ASSESSMENT: ASSESSMENT: Optimal Valve Transfemoral No Yes Delivery Access Access Transapical / Transapical / Transfemoral (TF) Transfemoral (TF) Transaortic (TA/TAo) TransAortic (TA/TAo) 1:1 Randomization 1:1 Randomization TF TAVR TA/TAo TAVR TF TAVR TA/Tao TAVR Surgical Surgical VS VS SAPIEN 3 SAPIEN 3 SAPIEN XT SAPIEN 3 AVR AVR Primary Endpoint: All-Cause Mortality, All Stroke, or Mod/Sev AR at One Year (Non-inferiority Propensity Score Analysis)

Primary Endpoint - Non-inferiority Death, Stroke, or AR ≥ Mod at 1 Year (VI) Weighted Difference -9.2% Non-Inferiority p- Upper 1-sided 95% CI -6.0% value < 0.001 Pre-specified non-inferiority margin = 7.5% -10 -8 -6 -4 -2 0 2 4 6 8 10 Favors TAVR Favors Surgery Primary Non-Inferiority Endpoint Met

Primary Endpoint - Superiority Death, Stroke, or AR ≥ Mod at 1 Year (VI) Weighted Difference -9.2% Superiority Testing p- Upper 2-sided 95.0% CI -5.4% value < 0.001 -10 -8 -6 -4 -2 0 2 4 6 8 10 Favors Surgery Favors TAVR Superiority Achieved

Other Unadjusted Clinical Outcomes At 30 Days and 1 Year (AT) 30 Days 1 Year Events (%) TAVR Surgery TAVR Surgery (n = 1077) (n = 944) (n = 1077) (n = 944) Re-hospitalization 4.6 6.8 11.4 15.1 0.3 1.9 1.8 3.1 MI 6.1 5.4 --- --- Major Vascular Complication 0.5 3.3 --- --- AKI (Stage III) Life-Threatening/Disabling 4.6 46.7 --- --- Bleeding 5.0 28.3 5.9 29.2 New Atrial Fibrillation 10.2 7.3 12.4 9.4 New Permanent Pacemaker 0.1 0.0 0.6 0.5 Re-intervention Endocarditis 0.2 0.0 0.8 0.7

Severity of PVR at 30 Days and All-cause Mortality at 2 Years (VI) 50 Moderate/Severe Overall Log-Rank p = 0.001 Mild Mod/Sev (reference = None/Trace) None/Trace 40 p (Log-Rank) < 0.001 All-Cause Mortality (%) 34.0% 30 Mild (reference = None/Trace) 20 p (Log-Rank) = 0.82 14.1% 10 13.5% 0 0 3 6 9 12 15 18 21 24 Months from Procedure Number at risk: Moderate/Sev 36 32 32 26 26 24 22 22 21 Mild 210 204 199 194 188 184 182 180 175 None/Trace 701 678 664 647 628 621 612 605 585

Paravalvular Regurgitation (VI) 3-Class Grading Scheme P < 0.001 P < 0.001 ≥ Moderate 0.6% 100% ≥ Moderate Mild 3.5% 8.0% Mild 80% 26.8% Severe 60% Moderate Mild None/Trace 40% 20% 0% TAVR Surgery TAVR Surgery No. of echos 30 Days 2 Years TAVR 872 600 Surgery 757 514

Paravalvular Regurgitation 3-Class Grading Scheme (VI) P < 0.001 P < 0.001 ≥ Moderate 100% 1.5% Mild 80% 39.8% 60% Severe Moderate Mild 40% None/Trace 20% 0% TAVR Surgery TAVR Surgery No. of echos 30 Days 1 Year P2A Surgery 755 610 S3i TAVR 992 875

Quality of Life • American TVT registry 2011-2016 in 31636 patients • KCCQ-OS – Baseline 42.3 (23.7) – 30 day 69.9 (27.6) – 1 yr 74.2 (31.9) Arnold et al; JAMA Cardiol. 2017 Feb 1