Role of Device Therapy in FMR: Challenges and Opportunities Ori Ben-Yehuda, MD, FACC Clinical Trials Center Cardiovascular Research Foundation & Columbia University

I have no relevant financial relationships ORI BEN-YEHUDA, MD   I have no relevant financial relationships

FMR: More complicated than AS

Spectrum of Mitral Regurgitation Mitral valve Left Atrium Chordae Tendnae Functional Mitral Regurgitation (FMR) Left ventricle Papillary muscles Degenerative Mitral Regurgitation (DMR) LV Dysfunction Dilated Annulus (Non-ischemic or ischemic dilated cardiomyopathy) LA Dysfunction Dilated Annulus (Chronic atrial fibrillation, hypertension) Etiologies: Advanced Barlow’s Disease Fibroelastic deficiency Leaflet prolapse due to: Leaflet deformities or lesions Ruptured/ elongated chordae Papillary muscle rupture Etiologies Loss of leaflet coapation due to: annular enlargement Papillary muscle displacement causing leaflet tethering/tenting Benjamin MM et al. Curr Cardiol Rep 2014;16:517

Functional MR: Role of Tethering Levine et al. Curr Cardiol Rep 2002;4:125-9

CTSN: MR Recurrence with Repair N Engl J Med 2016; 374:344-353

Transcatheter Valve Implanation (Piazza. PCR London Valve)

The Challenges with TMVR for FMR LV Dysfunction Advanced stage of disease- very high risk Are we selecting patients that are too advanced? Complex anatomy- D shaped annulus Risk of PVL Sizing Low flow compared with Aortic Valve- risk of thrombosis LVOT Obstruction Conduction system issues, coronary risk

Transcatheter Mitral Valve Repair: Many Options Leaflet repair MitraClip Pascal Percutaneous Annuloplasty Coronary sinus annuloplasty Carillon Direct annuloplasty Cardioband Mitralign Millipede MVRx Basal ventriculoplasty GDS Chordal replacement NeoChord Harpoon

EVEREST II: 5 year results

EVEREST II: MR Recurrence but good functional outcome Mitral Regurgitation NYHA Class Feldman T et al. JACC 2015

Carillion Cardiac Dimension Indirect annuloplasty with nitinol device anchored into the coronary sinus to reduce annulus dimensions Transgiugular approach 500 pts treated for commercial use 66 pts implanted in trial FMR Safe (Death @30d 0% device related) Results @12 mo 1 grade of MR reduction 1 NYHA Class improvement (from III to II)

Valtech Cardioband Direct annuloplasty with supra annular fixation of a band with anchors Transseptal approach ~100 pts treated FMR Death @30d 4% Effective significant reduction of septo lateral dimension average up to 30% significant MR reduction < 2 in 92% @discharge Sustained results @12 mo MR < 2, 91% NYHA I/II, 70%

Cardioband Study Demographics (N=54) No. (%) or Mean Variable 71 ± 8 Age (years) Male 41 Female 13 Gender 7 (1-33) Euroscore II (%) 82 Baseline NYHA Class of III or IV (%) 33 21 Ischemic Non Ischemic 61 ± 6 LVEDD (mm) AvgSD 33 ± 11 EF (%) AvgSD 18 (32%) 11 (20%) 41 (74%) 13(23%) Prev CABG COPD Moderate to Severe Renal Failure Severe Pulmonary Hypertension Afib

Reported Major Safety Events at 30 Days 30 Day Events* Patients Experiencing Event, # (%) All Patients N=54 Death 2 (3.7%) Hemorrhagic Stroke** 1 (1.9%) Need for elective Mitral Operation** Ischemic attack Major Bleeding Complications Renal Failure Myocardial Infarction 0 (0%) Respiratory Failure Cardiac Tamponade * VARC Guidelines (European Heart Journal, 2012, 33:2403-2414) ** Part of the Death case

Annuloplasty: Significant Reduction in Septo Lateral (A-P) Dimension 30% average reduction in A-P *P<0.01 37±4 (29-46) 26±4 (18-35)

30% average reduction in A-P Annular Reconstruction by Significant Reduction in Septo Lateral (A-P) Dimension 30% average reduction in A-P *P<0.01 37±4 (29-46) 26±4 (18-35)

Septo-Lateral (A-P) Dimension (mm) over time

91% patients with MR≤2+ At 12 Months By Core Lab* at Discharge 84% MR ≤ 2+ at 1 Month 91% MR ≤ 2+ at 6 Months 90% MR ≤ 2+ at 12 Months *Dr. Paul Grayburn – Baylor University

Annuloplasty: Significant Reduction in Septo Lateral (A-P) Dimension 30% average reduction in A-P *P<0.01 37±4 (29-46) 26±4 (18-35)

Cardioband: Functional Improvement at 12 Months 6MWT P<0.05 MLHFQ P<0.01 NYHA Class P<0.01 343 41 II I 68% NYHA I/II Meters Walked MLHFQ Score % of population II 272 20 III III Baseline 12 Months Baseline 12 Months N = 15 N = 20 N = 23

The complementary role of transcatheter techniques annuloplasty mitraclip replacement Stand-alone Annuloplasty: early treatment FMR Stand-alone Mitraclip: FMR with asymmetric tethering (IMR) Combined Annuloplasty and MitraClip: Advanced FMR MV Replacement: Advanced FMR (Adapted from F Maisano)

Future Directions and Dilemmas COAPT- enrollment increasing Will it create a new standard Need more efficient trials COAPT light? Achievable but clinically relevant endpoints MR reduction not enough Heart Failure Hospitalizations, Exercise Capacity, QoL, Actigraphy Repair vs. Replacement Patient selection