Next Generation Therapies: Aortic, Mitral and Beyond

Next Generation Therapies: Aortic, Mitral and Beyond Scott M Lilly, MD PhD Medical (Interventional) Director, Structural Heart Program Heart Summit, Lima OH August 26 th, 2017

Next Generation Therapies: Aortic, Mitral and Beyond

Origins of TAVR

Severe Symptomatic Aortic Stenosis: 50% 2-year Mortality Severe Symptomatic Aortic Stenosis: Percent Treated AVR No AVR Ross and Braunwald 1968, Circulation Bouma B J et al. Heart 1999;82:143-148 Iung B et al. European Heart Journal 2003;24:1231-1243 Pellikka, Sarano et al. Circulation 2005 Charlson E et al. J Heart Valve Dis 2006;15:312-321

CORE? STS 0-3 EuroScore 0-2 STS 4-8 EuroScore 3-5 STS > 8 EuroScore > 6 LOW INTERMED HIGH INOPERABLE < 70 yo, no comorbidities 80 years old, no comorbidities 80 years old Prior sternotomy SAVR SAPIEN What 1 o endpoint is appropriate?

Challenges to Success in Low-Risk Patients Procedural Considerations Have Greater Relevance Continue to reduce paravalvular leak Continue to reduce vascular complications Continue to reduce incidence of heart block Continue to reduce incidence of stroke Technological Considerations Require Broader Consideration More clinical experience to observe valve durability Valve-in-valve potential Access to coronary arteries

SAVR CORE SAPIEN U.S. Low Risk Trials LOW Risk TRIAL DESIGN ENDPOINTS PARTNER III STS < 4% N = 1300 50 Sites 1-yr MORTALITY STROKE REHOSPITALIZATION MDT Low-Risk STS < 3% N = 1200 80 Sites 2-yr MORTALITY STROKE Randomized TAVR v SAVR Both in early enrollment

Next Generation Therapies: Aortic, Mitral and Beyond

Mitral Valve Therapies European Survey on Valvular Heart Disease 92 Centers, 25 countries over 4 months Those not offered surgery were older, with more co-morbidities (diabetes, atheresclerotic vascular disease, lung disease), heart failure admissions, and overall comorbidity indices. At the time of intervention, comorbidities* may drive outcome more strongly than the valve disease itself.

Percutaneous Strategies: MitraClip Prolapse Restricted Motion EVEREST I and II Surgical Candidates COAPT Symptomatic or Asymptomatic RESHAPE-HF MVR Indication 10 Feldman and Young 2014, JACC

Percutaneous Strategies: MitraClip Surgical candidates (n = 279), with operative indication. 2:1 MitraClip:Surgery Compared to surgery, MitraClip had: Fewer adverse events (30-d) Comparable mortality Comparable symptomatic improvement Greater residual MR Higher rate of subsequent MV surgery (~20%) The goal of any therapy is simple to live longer or better. Patients with Moderate-Severe Mitral Regurgitation that are Poor Surgical Candidates 11 Feldman et al. 2011, 2015 NEJM; Feldman and Young 2014, JACC

MitraClip EVEREST II Trial Primary Endpoint* Freedom from Reoperation After 6-mo Compared to surgery, MitraClip had: Fewer adverse events (30-d) Comparable mortality Comparable symptomatic improvement Greater residual MR Higher rate of subsequent MV surgery (~20%) If procedural outcomes and reduction in residual MR can be improved, might a percutaneous approach be preferred? *Death, mitral valve surgery, 3-4+ mitral regurgitation 12 Feldman et al. 2015 NEJM

MitraClip FDA Approved The MitraClip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation due to primary abnormality of the mitral apparatus (degenerative MR) in patients who are at prohibitive risk for mitral valve surgery. What about Functional Mitral Regurgitation? COAPT Trial 13

Direct Mitral Annuloplasty Mitralign (Mitralign Inc) RFA-assisted puncture Place pledgets, draw together Accucinch (Guided Delivery Systems) Anchors below MV Nitinol wire to cinch Cardioband (Edwards) Above MV Sequential Anchors Feldman and Young 2014, JACC

Percutaneous Mitral Replacement Structural Considerations Varied pathophysiological states Annulus size, 3-dimensional anatomy Subvalvular apparatus Ventricular size, geometry, function Dynamic pressure environment Technical Considerations Securely fix prosthesis Avoid left ventricular outflow tract Avoid paravalvular leak Manage potential areas of stasis Implantation route and safety

SAPIEN Approved for Mitral Valve in Valve Clinical need, innovation Approved based on registry Requires existing bioprosthesis 16

Percutaneous Mitral Replacement Twelve (Medtronic) TA delivery Inner/Outer Stent Repositionable CardiaQ (Edwards) TA, TF delivery Supra-annular Repositionable Tendyne (Abbott) TA delivery Tethered to apex Repositionable Tiara (Neovasc) TA delivery Avoids LVOT No anchoring Herrmann 2015, CRF; De Backer et al 2014, Circ Cardiovasc Interv

Percutaneous Mitral Replacement Twelve (Medtronic) TA delivery Inner/Outer Stent Repositionable APPOLO Trial Severe symptomatic mitral regurgitation STS > 3% Candidate for bioprosthetic MVR Recruiting now

Next Generation Therapies: Aortic, Mitral and Beyond

Is the Tricuspid Valve Relevant? Arbulu et al., 1991 J Thorac Cardiovasc Surg 53 patients (IVDA) with right sided endocarditis Valvulectomy without replacement 16 (30%) died, 6 within 45 days 6 (11%) later with valve replacement due to refractory right sided heart failure Some tolerate, so do not 20

Tricuspid Regurgitation and Mortality 5,233 patients, TTE at VAMC, 4-year follow up Severe TR: 50% survival at ~2-yrs (47 days) Independent of PA pressures, LV or RV function 21 Nath et al., JACC 2004

Strategies for Percutaneous Intervention Cinch, Coapt, or Re-construct Cinch (Annular Reduction) Cerclage Plication Tensioning Re-Construct Valve-in-valve SVC-IVC Valves Coapt MitraClip Forma Anchor 22

Strategies for Percutaneous Intervention: Cinch TriAlign (MitrAlign) TriCinch (4Tech) Early US feasibility (SCOUT) *Early CE Mark Trials Hahn et al. 2017; Fortech, TVT 2015 23

Strategies for Percutaneous Intervention: Coapt MitraClip (Abbott) Forma Anchor (Edwards)* ~3:1 AS:PS *Early US feasibility Nickening et al. 2017; Campelo-Parada et al. 2015 24

Percutaneous Valve Replacement Native: Caval Valves IVC and/or SVC IVC caliber, landing zone Limited experience NYHA marginally improves Dedicated devices forthcoming Tricuspid Ring: VIV 64 year old female HOVER (US) TRICAVAL (Europe) 25

64 year old female Rheumatic Heart Disease 1982: Mitral valve replacement (Porcine) 1991: Mitral valve replacement (Mechanical) 1994: Mitral valve replacement (Mechanical) 1997: Mitral valve replacement (Mechanical), Aortic valve replacement (Mechanical), Tricuspid valve #34 Physio ring and Mitral valve cadaveric homograft in the tricuspid position Congestive cirrhosis, MELD 11, Childs-Pugh Class A NYHA IV, repeated paracenteses

Conclusions Percutaneous therapies for aortic, mitral and tricuspid valve disease are rapidly developing Heterogeneous population, different expectations Options for transcatheter therapies exist for nearly all patients with valvular heart disease Collaborative and multidisciplinary decision making can lead to the right therapies, for the right patient

Thank You Scott M Lilly, MD PhD Medical (Interventional) Director, Structural Heart Program 215-796-8304 scott.lilly@osumc.edu