Percutaneous Mitral Valve Therapies Jeffrey J. Popma, MD Director, Interventional Cardiology Clinical Services Beth Israel Deaconess Medical Center Associate Professor of Medicine Harvard Medical School Boston, MA 1
Conflict of Interest Statement Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization(s) listed below. Physician Name Company/Relationship Jeffrey J. Popma, MD Research Grants: Cordis, Boston Scientific, Medtronic, Abbott-Guidant, ev3, LabCoat Medical Advisory Board: Cordis, Boston Scientific, Abbot Vascular 2
Transcatheter Mitral Valve Mitral Valve Pathology Mitral Valve Therapies Edge-edge repair Chordal Shortening Coronary Sinus Annuloplasty Direct Annuloplasty MV Replacement 3
Edge-to to-edge Evalve MitraClip Chordal Shortening Cardiosolutions Mitra-Spacer NeoChord Valtech VChordal Device Landscape 211 Percutaneous MV Repair Coronary sinus Annuloplasty Cardiac Dimensions Carillon Edwards Monarch Viacor PTMA Cerclage annuloplasty MV replacement EndoValve CardiAQ Valtech Cardiovalve ValveXchange Direct Annuloplasty Mitralign Bident GDS Accucinch ReCor (US) Quantum Cor (RF) Valtech Cardioband Micardia encor In patients 4
First Question: Degenerative or Functional? FED FED+ Forme Fruste Barlow s + ++ +++ ++++ Leaflet Tissue Adams et al. Eur Heart J 21;31:1958-1967 5
Second Question: What is the Surgical Risk (STS PROM)? FED FED+ Forme Fruste Barlow s Increasing Repair Difficulty Adams et al. Eur Heart J 21;31:1958-1967 6
Percutaneous Methods for Mitral Valve Repair Functional MR Leaflet Coaptation Edge-to to-edge Repair Alfieri Stitch Annular Reshaping Cinching Annuloplasty 7
Percutaneous Mitral Valve Repair MitraClip System 8
The MitraClip: Global Experience (through 4/2/211) ~3,135 patients at ~8 hospitals in EU and 4 clinical trial sites in Iceland the U.S. have been treated Sweden Finland with the MitraClip device Norway Estonia Russia Study EVEREST I 55 n Ireland United Kingdom Netherlands Germany Belgium Denmark Luxembourg Poland Latvia Lithuania Russia Belarus Ukraine Kazakhstan Czech Rep. Slovakia EVEREST II Roll-in 6 EVEREST II HRR 78 EVEREST II Randomized REALISM (Continued Access) 184 571 Commercial use (EU) 2187 Portugal Morocco Spain Andorra Algeria 5 KM France 5 Miles Liechtenstein Switzerland Tunisia Italy San Marino Austria Slovenia Croatia Malta Libya Hungary Bosnia & Serbia Montenegro Herzegovina Macedonia Albania Greece Romania Bulgaria Moldova Source: Abbott Vascular Cyprus Egypt Turkey Lebanon Israel Syria Jordan Georgia Azerbaijan Armenia Iraq Saudi Arabia Iran 9
EVEREST II Randomized Clinical Trial 279 Patients enrolled at 37 sites Significant MR (3+-4+) 73% DMR, 27% FMR Specific anatomical criteria Randomized 2:1 Device Group MitraClip System N=184 Control Group Surgical Repair or Replacement N=95 Echocardiography Core Lab and Clinical Follow-Up Baseline, 3 days, 6 months, 1 year, 18 months, and annually through 5 years Feldman T et al. NEJM 211;364:1395-46 46
EVEREST II RCT: Patient Flow Randomized Cohort n=279 Device Group n=184 Treated n=178 Randomized, not treated Device, n=6 Control, n=15 Surgical Group n=95 Treated n=8 (86% MV repair) Acute Procedural Success Not Achieved n=41 (23.%) 2 of 41 no implant Acute Procedural Success Achieved n=137 (77.%) Per Protocol 28 had MV surgery 9 had MV surgery 37/178 total (2.8%) Acute Procedural Success (APS) = MR 2+ at discharge 3 days n=136 99% Clinical Follow-up 12 months n=134 98.5% Clinical Follow-up 98% Echo Follow-up Feldman T et al. NEJM 211;364:1395-46 46 3 days n=79 99% Clinical Follow-up 12 months n=74 94% Clinical Follow-up 92% Echo Follow-up 11
EVEREST II RCT: Primary Safety Endpoint Per Protocol Cohort 3 Day MAE, non-hierarchical Death Major Stroke Re-operation of Mitral Valve Urgent / Emergent CV Surgery Myocardial Infarction Renal Failure Deep Wound Infection Ventilation >48 hrs New Onset Permanent Atrial Fib Septicemia GI Complication Requiring Surgery All Transfusions 2 units TOTAL % of Patients with MAE p<.1 if include Major Bleeding only # Patients experiencing event Device Group (n=136) 1 (.7%) 12 (8.8%) 9.6% Feldman T et al. NEJM 211;364:1395-46 46 Control Group (n=79) 2 (2.5%) 2 (2.5%) 1 (1.3%) 4 (5.1%) 4 (5.1%) 42 (53.2%) 57.% p<.1 (95% CI 34.4%, 6.4%) 1 12
Percent Patients (%) 1 8 6 4 2 EVEREST II: Mitral Regurgitation Grade Baseline, 1 and 2 Years (matched) 2+ 3+ 4+ + 1+ 2+ 3+ 4+ Baseline 1 Year 2 Years (N=122) (N=122) (N=122) Percutaneous Intention to Treat 1+ 2+ 3+ 4+ Percent Patients (%) 1 8 6 4 2 2+ 3+ 4+ + 1+ 2+ 3+ Baseline 1 Year 2 Years (N=56) (N=56) (N=56) Surgery + 1+ 2+ Within group difference (p<.5); Between group difference at 1 year (p<.5); Between group difference at 2 year (p<.5) Ted Feldman, ACC 211 Late Breaking Trial 13
EVEREST II: LV Volumes Baseline, 1 and 2 Years (matched) Intention to Treat Within group difference (p<.5) Between group difference at 1 year (p<.5) Between group difference at 2 year (p<.5) LV End Diastolic Volume 16 LVEDV (ml) 14 12 157 133 124 1 158 18 119 16 11 8 6 14 LVESV (ml) 18 LV End Systolic Volume 12 1 6 4 4 2 2 BL 1 Yr 2 Yrs Percutaneous N=117 BL 1 Yr 2 Yrs Surgery N=55 8 62 57 55 6 55 5 BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs Percutaneous N=117 Ted Feldman, ACC 211 Late Breaking Trial Surgery N=55 14
EVEREST II: Kaplan-Meier Freedom from Death Intention to Treat 1. Freedom from Death.8.6.4.2 Surgery = 95.% Percutaneous = 94.9% p=.95 Surgery = 91.1% Percutaneous = 89.8% p=.78 Surgery Percutaneous. At Risk: Percutaneous Surgery 18 36 54 72 9 18 Days from Index Procedure Days 6m 1yr 1.5yr 2yr 3yr 184 166 163 153 133 52 95 78 74 71 63 25 Ted Feldman, ACC 211 Late Breaking Trial 15
EVEREST II: Landmark Analysis of Kaplan-Meier Freedom from MV Surgery (Percutaneous)/Re-operation (Surgery) Intention to Treat 1. Freedom From Surgery (Device) or Reoperation (Surgery).8.6.4.2 Surgery = 98.7% Percutaneous = 96.3% p=.32 Surgery = 97.3% Percutaneous = 95.6% p=.52 Surgery Percutaneous. 18 36 54 72 9 18 Days from Index Procedure At Risk: Percutaneous Surgery Days 184 95 6m 1yr 1.5yr 2yr 3yr 138 131 124 19 44 77 72 69 61 24 Ted Feldman, ACC 211 Late Breaking Trial 16
EVEREST II: NYHA Functional Class At Baseline, 1 and 2 Years (matched) Intention to Treat Within group difference (p<.5) Between group difference at 1 year (p<.5) Between group difference at 2 year (p<.5) 1 Percent (%) 8 I I I II 1 I I II II III III Baseline 1 Year 2 Years (N=56) (N=56) (N=56) I 8 II 6 6 4 4 III II 2 II IV Baseline (N=127) 2 1 Year (N=127) 2 Years (N=127) III IV Percutaneous Ted Feldman, ACC 211 Late Breaking Trial Surgery 17
EVEREST II RCT MitraClip Arm MR Reduction by Etiology DMR Cohort FMR Cohort 1% 2+ 2+ 8% 1+ 34.5% 1+ 4.6% 6% 3+/4+ 1+-2+ 11.5% 3+/4+ 1+-2+ 12.5% 4% 2+ 36.8% 2+ 25.% 2% % 3+/4+ 17.2% 3+/4+ Baseline 12 Months Baseline 12 Months n=135 n=87 n=49 n=32 21.9% Ted Feldman, TCT 21 18
EVEREST II RCT MitraClip Arm Left Ventricular Function by Etiology LV End Diastolic and End Systolic Volumes DMR Cohort n=88, matched data FMR Cohort n=3, matched data 16 p<.1 16 P=.2 Volume (ml) 12 8 p=.2 Volume (ml) 12 8 p=.4 4 4 LVEDV LVESV LVEDV LVESV Baseline 12 Months Ted Feldman, TCT 21 19
EVEREST II RCT MitraClip Arm NYHA Functional Class by Etiology DMR Cohort n=93, matched data FMR Cohort n=31, matched data 1 I p<.1 p<.1 Percent Patients 8 6 4 2 II III I II 97.8% NYHA Class I/II II III I II 96.7% NYHA Class I/II IV Baseline 12 months Baseline 12 months IV Ted Feldman, TCT 21 2
EVEREST II High Surgical Risk Cohort Enrollment EVEREST II High Surgical Risk Cohort N = 372 EVEREST II High Surgical Risk Trial N = 78 Enrolled REALISM High Surgical Risk Trial^ N = 294 Enrolled 1 Year N = 78 1 Year N = 133 EVEREST II High Surgical Risk Cohort With 1 Year Follow-Up N = 211 Ted Feldman. EuroPCR 211 EVEREST HR defined by predicted surgical mortality 12% using STS risk calculator or surgeon estimate from co- morbuidities ^ ACCESS EU high risk defined by EuroSCORE 2% 21
EVEREST II High Surgical Risk Cohort Mitral Regurgitation Grade Ted Feldman. EuroPCR 211 22