Scott M Lilly, MD PhD Medical (Interventional) Director, Structural Heart Program Heart Summit, Lima OH August 26th, 2017

Next Generation Therapies: Aortic, Mitral and Beyond

Next Generation Therapies: Aortic, Mitral and Beyond

Origins of TAVR

AVR No AVR

Severe Symptomatic Aortic Stenosis: Percent Treated

• 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

Severe Symptomatic Aortic Stenosis: 50% 2-year Mortality

LOW INTERMED HIGH INOPERABLE

SAV

R

SAP

IEN

STS > 8

EuroScore > 6 STS 4-8

EuroScore 3-5 STS 0-3

EuroScore 0-2

80 years old, no comorbidities

80 years old Prior sternotomy

< 70 yo, no comorbidities

CO

RE ?

What 1o endpoint is

appropriate?

Challenges to Success in Low-Risk Patients

• Continue to reduce paravalvular leak

• Continue to reduce vascular complications

• Continue to reduce incidence of heart block

• Continue to reduce incidence of stroke

More clinical experience to observe valve durability

Valve-in-valve potential

Access to coronary arteries

Technological Considerations Require Broader Consideration

Procedural Considerations Have Greater Relevance

U.S. Low Risk Trials

LOW Risk TRIAL DESIGN ENDPOINTS

SAP

IEN

SA

VR

C

OR

E

PARTNER III

MDT Low-Risk MORTALITY

STROKE

MORTALITY STROKE

REHOSPITALIZATION

STS < 3%

N = 1200 80 Sites

STS < 4%

N = 1300 50 Sites

Randomized TAVR v SAVR Both in early enrollment

2-yr

1-yr

Next Generation Therapies: Aortic, Mitral and Beyond

Mitral Valve Therapies

Those not offered surgery were older, with more co-morbidities (diabetes,

atheresclerotic vascular disease, lung disease), heart failure admissions,

and overall comorbidity indices.

European Survey on Valvular Heart Disease

92 Centers, 25 countries over 4 months

At the time of intervention, comorbidities* may drive outcome more strongly than the valve disease itself.

Percutaneous Strategies: MitraClip

10

Prolapse Restricted

Motion EVEREST I and II

COAPT

RESHAPE-HF

Feldman and Young 2014, JACC

Surgical Candidates

Symptomatic or Asymptomatic

MVR Indication

11 Feldman et al. 2011, 2015 NEJM; Feldman and Young 2014, JACC

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%)

Surgical candidates (n = 279), with operative

indication. 2:1 MitraClip:Surgery

The goal of any therapy is simple – to live longer or better.

Patients with Moderate-Severe Mitral Regurgitation that are Poor Surgical Candidates

Percutaneous Strategies: MitraClip

MitraClip EVEREST II Trial

12 Feldman et al. 2015 NEJM

After 6-mo Freedom from Reoperation Primary Endpoint*

*Death, mitral valve surgery, 3-4+ mitral regurgitation

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?

MitraClip FDA Approved

13

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

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

Technical Considerations

• Securely fix prosthesis

• Avoid left ventricular outflow tract

• Avoid paravalvular leak

• Manage potential areas of stasis

• Implantation route and safety

Structural Considerations

Varied pathophysiological states

Annulus size, 3-dimensional anatomy

Subvalvular apparatus

Ventricular size, geometry, function

Dynamic pressure environment

SAPIEN Approved for Mitral Valve in

Valve

• Clinical need, innovation

• Approved based on registry

• Requires existing bioprosthesis

16

Percutaneous Mitral Replacement

Herrmann 2015, CRF; De Backer et al 2014, Circ Cardiovasc Interv

Tiara (Neovasc)

• TA delivery • Avoids LVOT • No anchoring

Tendyne (Abbott)

• TA delivery • Tethered to apex • Repositionable

Twelve (Medtronic)

• TA delivery • Inner/Outer Stent • Repositionable

CardiaQ (Edwards)

• TA, TF delivery • Supra-annular • Repositionable

Percutaneous Mitral Replacement

APPOLO Trial

• Severe symptomatic mitral regurgitation

• STS > 3%

• Candidate for bioprosthetic MVR

• Recruiting now…

Twelve (Medtronic)

• TA delivery • Inner/Outer Stent • Repositionable

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

20

Some tolerate, so do not…

Tricuspid Regurgitation and Mortality

5,233 patients, TTE at VAMC, 4-year follow up

21 Nath et al., JACC 2004

Independent of PA pressures, LV or RV function

Severe TR: 50% survival at ~2-yrs (47 days)

Strategies for Percutaneous Intervention

22

Cinch (Annular Reduction) Cerclage Plication Tensioning

Coapt

MitraClip Forma Anchor

Re-Construct Valve-in-valve SVC-IVC Valves

Cinch, Coapt, or Re-construct

Strategies for Percutaneous Intervention: Cinch

TriAlign (MitrAlign) TriCinch (4Tech)

23 Hahn et al. 2017; Fortech, TVT 2015

*Early CE Mark Trials Early US feasibility (SCOUT)

Strategies for Percutaneous Intervention: Coapt

MitraClip (Abbott) Forma Anchor (Edwards)*

24 Nickening et al. 2017; Campelo-Parada et al. 2015

*Early US feasibility ~3:1 AS:PS

HOVER (US) TRICAVAL (Europe)

Percutaneous Valve “Replacement”

25

Native: Caval Valves Tricuspid Ring: VIV • IVC and/or SVC • IVC caliber, landing zone • Limited experience • NYHA marginally improves • Dedicated devices forthcoming

• 64 year old female…

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

Scott M Lilly, MD PhD Medical (Interventional) Director,

Structural Heart Program 215-796-8304

scott.lilly@osumc.edu

Thank You