Catheter-based mitral valve repair MitraClip System

Transcription

1 Percutaneous Mitral Valve Repair: Results of the EVEREST II Trial William A. Gray MD Director of Endovascular Services Associate Professor of Clinical Medicine Columbia University Medical Center The Cardiovascular Research Foundation

2 Catheter-based mitral valve repair MitraClip System

3 Baseline

4 Post Procedure

5 Atrial view

6 evalve clip MV repair: clinical experience Study EVEREST I (Feasibility) * EVEREST II * EVEREST II EVEREST II (Pivotal) REALISM (Continued Access) European Experience Population Non-randomized Pre-randomization High Risk Registry Randomized patients (2:1 MitraClip to Surgery) High Risk & Non High Risk Total n MitraClip 95 Surgery ,115 MitraClip *Percutaneous Mitral Valve Repair Using the Edge-to-Edge Repair: Six months Results of the EVEREST Phase I Clinical trial, JACC 25;46: Percutaneous Mitral Repair with the MitraClip System: Safety and Midterm Durability in the Initial EVEREST Cohort, JACC 29; 54:

7 EVEREST II: randomized clinical trial Study design 279 Patients enrolled at 37 sites Significant MR (3+-4+) 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

8 EVEREST II: randomized clinical trial Key inclusion/exclusion criteria Inclusion Candidate for MV Surgery Moderate to severe (3+) or severe (4+) MR Symptomatic o >25% EF & LVESD 55mm Asymptomatic with one or more of the following o LVEF 25-6% o LVESD 4mm o New onset atrial fibrillation o Pulmonary hypertension ACC/AHA Guidelines JACC 52:e1-e142, 28 Exclusion AMI within 12 weeks Need for other cardiac surgery Renal insufficiency Creatinine >2.5mg/dl Endocarditis Rheumatic heart disease MV anatomical exclusions Mitral valve area <4.cm 2 Leaflet flail width ( 15mm) and gap ( 1mm) Leaflet tethering/coaptation depth (>11mm) and length (<2mm)

9 EVEREST II: randomized clinical trial Baseline demographics and co-morbidities Device (%) n=184 Control (%) n=95 P Age (mean) Male Congestive heart failure Coronary artery disease Myocardial infarction Angina Atrial fibrillation Cerebrovascular disease Peripheral vascular disease Cardiomyopathy Hypercholesterolemia Hypertension Moderate to severe renal disease Diabetes Previous cardiovascular surgery MR Severity: 3+ to 4+ MR Etiology: Degenerative / Functional 67.3 years / years / <.1 >.99 >

10 EVEREST II: randomized clinical trial 65 yrs demographic comparison EVEREST II RCT n=279 58% 28 STS Database Isolated 1 st Elective Operation for MR* Repair Replace High Volume Hospitals (>14/Yr) Age yrs (mean) % 45% 75 yrs 32% n/a n/a % NYHA Class III or IV 5% 26% 45% n/a CHF 86% 41% 58% n/a Hypertension 75% 6% 67% 43% Diabetes Mellitus 9% 13% 23% 6.5% COPD / Chronic Lung Disease n/a 15% 17% 29% n/a EF (mean) 6% 53% 55% 56%

11 EVEREST II: randomized clinical trial Primary endpoints Safety Major Adverse Event Rate at 3 days Per protocol cohort Superiority hypothesis Effectiveness Clinical Success Rate Freedom from the combined outcome of Death MV surgery or re-operation for MV dysfunction MR >2+ at 12 months Per protocol cohort Non-inferiority hypothesis Pre-Specified MAEs 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

12 EVEREST II: randomized clinical trial Additional analysis Intention to Treat Safety Major Adverse Event Rate at 3 days Effectiveness Freedom from the combined outcome of death, MV surgery >9 days or re-operation for valve dysfunction >9 days post Index procedure, and MR >2+ at 12 months Clinical Benefit (per protocol cohort) MR Severity Left Ventricular Function NYHA Functional Class Quality of Life (SF-36 Survey)

13 EVEREST II: Patient flow Per protocol cohort: Analysis of device performance Randomized Cohort n=279 Device Group n=184 Treated n=178 Randomized, not treated Device, n=6 Control, n=15 Control Group n=95 Treated n=8 (86% MV repair) Acute Procedural Success Not Achieved n=41 Acute Procedural Success Achieved n=137 Acute Procedural Success (APS) = MR 2+ at discharge Acute procedural success (APS)=MR 2 at discharge 3 days n=136 99% Clinical Follow-up 12 months n= % Clinical Follow-up 98% Echo Follow-up Investigational device limited by Federal (U.S.) law to investigational use only. PML2827 Rev. A 3/21 3 days n=79 99% Clinical Follow-up 12 months n=74 94% Clinical Follow-up 92% Echo Follow-up

14 EVEREST II: Patient flow Post MitraClip procedure Acute Procedural Success Not Achieved n=41 Acute Procedural Success Achieved n=137 No Additional Intervention n=11 2 nd MitraClip Procedure n=2 MV Surgery Post MitraClip Procedure n=28 MV Surgery Post MitraClip Procedure n=9 2 nd MitraClip Procedure n=3 n=37 81% Follow-up 96% MR 2+ at 12 months

15 EVEREST II: Primary endpoints Safety Major Adverse Events 3 days Per protocol cohort Effectiveness Clinical Success Rate * 12 months Device Group, n= % Device Group, n= % Control Group, n=79 p SUP <.1 p NI =.12 Control Group, n=74 57.% 87.8% Met superiority hypothesis Pre-specified margin = 6% Observed difference = 47.4% 97.5% LCB = 34.4% LCB=lower confidence bound UCB=upper confidence bound LCB = lower confidence bound UCB = upper confidence bound Met non-inferiority hypothesis Pre-specified margin = 31% Observed difference = 15.4% 95% UCB = 25.4% *Freedom * from the combined outcome of of death, MV death, surgery MV or surgery re-operation or re-operation for MV for dysfunction, MV dysfunction, MR >2+ at 12 months 18 MR 2+ at 12 months Investigational device limited by Federal (U.S.) law to investigational use only. PML2827 Rev. A 3/21

16 EVEREST II: Primary safety endpoint 3 Day MAE, non-hierarchical Per protocol cohort Death 2 (2.5%) Major Stroke 2 (2.5%) Re-operation of Mitral Valve 1 (1.3%) Urgent / Emergent CV Surgery 4 (5.1%) Myocardial Infarction Renal Failure Deep Wound Infection Ventilation >48 hrs 4 (5.1%) New Onset Permanent Atrial Fib Septicemia GI Complication Requiring Surgery 1 (.7%) All Transfusions 2 units* 12 (8.8%) 42 (53.2%) TOTAL % of Patients with MAE *p<.1 if include Major Bleeding only # Patients experiencing event Device Group 9.6% p<.1* Control Group (n=136) (n=79) 57.% (95% CI 34.4%, 6.4%) 19

17 EVEREST II: Safety and effectiveness Safety Major Adverse Events 3 days Intention to treat cohort Effectiveness Clinical Success Rate * 12 months Device Group, n=18 15.% Device Group, n= % Control Group, n=94 p SUP <.1 p NI =.5 Control Group, n= % 74.2% Met superiority hypothesis Pre-specified margin =2% Observed difference = 32.9% 97.5% LCB = 2.7% LCB=lower confidence bound UCB=upper confidence bound LCB = lower confidence bound UCB = upper confidence bound Met non-inferiority hypothesis Pre-specified margin = 25% Observed difference = 7.3% 95% UCB = 17.8% *Freedom from the combined outcome of death, MV surgery or re-operation for MV dysfunction, MR 2+ at 12 months * Freedom from the combined outcome of death, MV surgery or re-operation for MV dysfunction >9 days post Index procedure, MR >2+ at 12 months Investigational device limited by Federal (U.S.) law to investigational use only. PML2827 Rev. A 3/21 21

18 EVEREST II: MR reduction per protocol cohort 1% Device Group Control Group 8% 6% 3+/ % 3+/ % 4% 2% % 3+/ % Baseline 12 Months Baseline 12 Months n=137 n=119 n=8 n=67

19 EVEREST II: LV volume Per protocol cohort (pre-specified hypothesis) 2 16 Device Group n=118, matched data p< Control Group n=65, matched data p<.1 Volume (ml) 12 8 p=.5 Volume (ml) 12 8 p= LVEDV LVESV LVEDV LVESV Baseline 12 Months

20 EVEREST II: LV dimension Per protocol analysis (pre-specified hypothesis) Device Group n=118, matched data Control Group n=65, matched data 6 p<.1 6 p< Dimension (cm) p=.564 Dimension (cm) p= LVID diastole LVID systole LVID diastole LVID systole Baseline 12 Months

21 EVEREST II: NYHA functional class per protocol cohort Device Group Control Group Percent Patients I II III p<.1 I II 97.6% NYHA Class I/II I II III p<.1 I II 87.9% NYHA Class I/II IV Baseline 12 months Baseline 12 months n=124, Matched data n=66, Matched data IV III

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26 EVEREST II: Quality of life, SF-36 survey Per protocol cohort 3 Day Scores 12 Month Scores 6 5 Device Group p<.1 p<.1 Control Group P=.291 P= Device Group P<.1 P<.1 Control Group P=.57 P= Score PCS MCS n=12, matched pairs PCS MCS n=64, matched pairs PCS MCS n=11, matched pairs PCS MCS n=6, matched pairs Baseline 3 days 12 Months

27 EVEREST II: summary Safety & effectiveness endpoints met Safety: MAE rate at 3 days MitraClip device patients: 9.6% MV surgery patients: 57% Effectiveness: Clinical Success Rate at 12 months MitraClip device patients: 72% MV Surgery patients: 88% Clinical benefit demonstrated for MitraClip System and MV surgery patients through 12 months Improved LV function Improved NYHA Functional Class Improved Quality of Life Surgery remains an option after the MitraClip procedure