Percutaneous Mitral Valve Repair MitraClip: Procedure, Data, Patient Selection Chad Rammohan, MD FACC Director, Cardiac Cath Lab El Camino Hospital Mountain View, California
Mitral Regurgitation MitraClip Transseptal and procedural technique Degenerative MR 5 year EVEREST II (ACC 2014) Prohibitive surgical risk cohort Functional MR - COAPT
MR Etiology Normal Degenerative MR Prolapse Degenerative MR Flail Functional MR Ischemic vs. nonischemic
MitraClip Concepts Facilitates proper leaflet coaptation Mechanical solution to a mechanical problem Etiology Degenerative - Anchor flail and prolapsed leaflets (similar to chordal transfer/replacement) Functional - Coapt tethered leaflets to reduce time and force required to close valve Creates tissue bridge Porcine model, 6M
The MitraClip System MitraClip Device (Clip) Clip Delivery System MitraClip System Arm Steerable Guide Handle Gripper Delivery Catheter Handle Steerable Guide, Steerable Sleeve, and Delivery Catheter Stabilizer MitraClip Device (Clip)
MitraClip Features Venous puncture Standard Percutaneous Left Atrial Access Versatile Positioning Capabilities o Adaptability to varying patient anatomy Precise MitraClip Placement Control o Re-positioning capability Allows multiple tissue releases and grasps Allows optimal MR reduction Provides option to not deploy Clip
Echo Related Valve Anatomy Use of common anatomically based vocabulary reinforces clear communication 30 0 MEDIAL 60 0 FOSSA P3 A3 A2 P2 POSTERIOR AO A1 P1 30 0 ANTERIOR LAA LATERAL
Transseptal Crossing
Tenting: Junction Between the Muscular and Membranous Septum Imaging: Bi-caval
Tenting: Posterior - Mid Aspect of Fossa Imaging: Short Axis at the Base Line of coaptation
Tenting: Superior Aspect of Fossa Imaging: 4 Chamber or 5 Chamber, Height 3.5-4.0cm 3.5-4.0 cm 3.5-4.0 cm
Puncture and Cross Fossa Imaging: Short Axis at the Base
Steering to Valve Plane
Steering
Grasping
Grasping
Grasping Technique
Deployment
Worldwide Experience Study Population N* EVEREST I (Feasibility) Feasibility patients 55 EVEREST II (Pivotal) Pre-randomized patients 60 EVEREST II (Pivotal) EVEREST II (Pivotal) Non-randomized patients (High Risk Study) Randomized patients (2:1 Clip to Surgery) 78 279 184 Clip 95 Surgery REALISM (Continued Access) Non-randomized patients 899 Compassionate/Emergency Use Non-randomized patients 66 ACCESS Europe Phase I Non-randomized patients 567 ACCESS Europe Phase II Non-randomized patients 286 Commercial Use Commercial patients 16,953 Total 19,148 +95 surgery *Data as of 12/31/2014. Source: Abbott Vascular
Commercial MitraClip Implant Experience Treating Centers: 455 Patients 1 : 17,806 Implant Rate 1 : 96% Etiology 2 Functional MR 66% Degenerative MR 21% Mixed 13% Etiology 2 Mixed 13% DMR 21% FMR 66% 1. First-time procedures only. Includes commercial patients, ACCESS I and ACCESS II patients 2. Etiology not inclusive of U.S. cases as of 04/14/2014 Data as of 12/31/2014. Source: Abbott Vascular.
Global MitraClip Procedures Data on file at Abbott Vascular as of 12/31/2014
EVEREST II RCT Aug 2005 - Nov 2008 Randomized Cohort N=279 Treated MitraClip Patients N=178 Untreated n=6 MitraClip n=15 Surgery Treated Surgery Patients N=80 N=258 Treated Patients N=30 Withdrawals N=15 N=3 Missed Visits N=2 81% Clinical Follow-Up 5-Year Analysis (N=145) 79% Clinical Follow-Up 5-Year Analysis (N=63) Median follow-up 4.93 years. 1,007 total patient-years of follow-up.
Baseline Characteristics EVEREST II RCT Characteristic MitraClip N = 184 Surgery N = 95 p-value Age (mean), years 67 66 ns Male 63% 66% ns History of CHF 91% 78% 0.005 NYHA Functional Class III/IV 51% 47% ns Functional MR Etiology 26% 27% ns Coronary Artery Disease 47% 46% ns Prior Myocardial Infarction 22% 21% ns Previous Cardiovascular Surgery 22% 19% ns Atrial Fibrillation 34% 39% ns COPD (with or without home O 2 ) 15% 15% ns Moderate to Severe Renal Disease 3% 2% ns Diabetes 8% 11% ns LV Ejection Fraction (mean), % 60 61 ns LV End Systolic Dimension (mean), cm 3.7 3.5 ns
Site-Reported Adverse Events Through 5 Years EVEREST II RCT Adverse Event Rates (%) Per Patient-Year of Follow-up S M AE Categories Cardiac Vascular Neurologic Renal M: MitraClip S: Surgery M S M S M S M S M S Index Through 30 Days 30 Days Through 1 Year 1 Year Through 2 Years 2 Years Through 3 Years 3 Years Through 4 Years 4 Years Through 5 Years
Long-Term MitraClip Device Safety EVEREST II RCT Through 1 Year # (%) of patients 1 Year to 5 Years # (%) of patients Single Leaflet Device Attachment (SLDA) 10 (6.3%) 0 (0.0%) MV stenosis 1 (0.6%) 0 (0.0%) Device Embolization 0 (0.0%) 0 (0.0%) Based on N=158 who were implanted with 1 or 2 MitraClip devices
Kaplan-Meier Freedom From Mortality EVEREST II RCT MitraClip (N=178) 93.7% 92.3% 1 year Surgery (N=80) 81.2% 79.0% 5 years
Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery Group Surgery (N=80) MitraClip (N=178) 78.9% 97.4% 1 year 74.3% 92.5% 5 years EVEREST II RCT
Mitral Regurgitation Grade EVEREST II RCT All Treated Patients (N=258) MitraClip (N=178) MR 2+ at 1 and 5 Years Surgery (N=80) MR 2+ at 1 and 5 Years p < 0.005 p < 0.005 p < 0.005 p < 0.005 2+ 81% 82% 0+ 1+ 1+ 2+ 99% 98% 0+ 2+ 0+ 3+ 2+ 3+ 3+ 1+ 3+ 1+ 2+ 4+ 3+ 4+ 3+ 4+ 2+ 4+ 2+ Baseline 1 Year N=149 Baseline 5 Years N=106 Baseline 1 Year N=66 Baseline 5 Years N=41
NYHA Functional Class EVEREST II RCT All Treated Patients (N=258) MitraClip (N=178) NYHA I/II at 1 and 5 Years Surgery (N=80) NYHA I/II at 1 and 5 Years p < 0.005 p < 0.005 p < 0.005 p < 0.005 98% 91% 88% 98% I I I I II I II I II I II I III II III II III II III II IV IV III IV III IV Baseline 1 Year N=151 Baseline 5 Years N=106 Baseline 1 Year N=66 Baseline 5 Years N=42 N = survivors with paired data; p-values for descriptive purposes only
Long-Term Durability of Clinical Success 5-Year Outcomes in Patients Who Were Alive and Free From MR 3+/4+ and MV Surgery (or Re-Operation) at 1 Year EVEREST II RCT Clinical Success Groups Outcome MitraClip (N=97) Surgery (N=64) Freedom From Death at 5 Years 87% 90% Freedom From MV Surgery (or Re-operation) at 5 Years 94% 95% MR 2+ at 5 Years 86% 97% MR 1+ at 5 Years 47% 92% NYHA Class III/IV (%) Baseline 5 Years 47% 6% 40% 3% Mean Change in LVEDV From Baseline to 5 Years -27 ml -45 ml Mean Change in Diastolic SLAD From Baseline to 5 Years 0.0 cm -0.4 cm
EVEREST II RCT 5 Year Results The EVEREST II RCT is the longest prospective follow-up of two therapies for treating MR Clinical benefits provided by MitraClip and MV surgery are durable through 5 years Reduction in MR Severity Improvement in LV Volumes and Dimensions Improvements in NYHA Functional Class Low rate of adverse events from 1 year to 5 years in both groups Beyond 6 months, the rate of MV surgery is low in the MitraClip group
Improved Functional Status and Quality of Life in Prohibitive Surgical Risk Patients With Degenerative Mitral Regurgitation Following Transcatheter Mitral Valve Repair with the MitraClip System Lim et al.. JACC 2014 Jul 15;64(2):182-92. 141 high surgical risk DMR patients treated in the EVEREST Registries with 1-year follow-up available Prohibitive risk definition retrospectively applied by heart team Two cardiac surgeons experienced in MV surgery Cardiologist experienced in MV disease 127 patients were documented to meet prohibitive risk
Baseline Demographics and Comorbidities Characteristic Age (mean ± SD) Prohibitive Risk DMR N = 127 82 ± 9 years Patients over 75 years of age 84% Male Gender 55% Coronary Artery Disease 73% Prior Myocardial Infarction 24% Previous Cardiovascular Surgery 48% Atrial Fibrillation History 71% Prior Stroke 10% Diabetes 30% Moderate to Severe Renal Disease 28% Chronic Obstructive Pulmonary Disease 32% STS Mortality Risk (mean ± SD) [v2.73, replacement] 13.2 ± 7.3% SF-36 QoL Physical Component Score (mean ± SD) 32.0 ± 8.7 SF-36 QoL Mental Component Score (mean ± SD) 46.1 ± 12.5
Baseline Cardiac Comorbidities Characteristic Prohibitive Risk DMR N = 127 Congestive Heart Failure 98% NYHA Functional Class III or IV 87% LV Ejection Fraction (mean ± SD) 60.6 ± 9.5 % LV End Diastolic Volume (mean ± SD) LV Internal Diameter, systole (mean ± SD) 127.0 ± 40.5 ml 3.4 ± 0.8 cm
Percent MitraClip Implant Rate Prohibitive Risk DMR (N=127) 95.3% Implant Rate 100% 80% 4.7% 44.1% 0 MitraClip (N=6) 60% 1 MitraClip (N=56) 40% 20% 51.2% 2 MitraClips (N=65) 0%
CEC-Adjudicated Safety Events Prohibitive Risk DMR (N=127) Event (Non-Hierarchical) 30 Days 1 Year n % n % Death* 8 6.3% 30 23.6% Myocardial Infarction 1 0.8% 1 0.8% Non-elective CV Surgery for AEs 1 0.8% 1 0.8% Stroke 3 2.4% 3 2.4% New onset of permanent AF 0 0 0 0 Renal Failure 2 1.6% 5 3.9% Ventilation > 48 hours 4 3.1% 6 4.7% GI complication requiring surgery 1 0.8% 3 2.4% * No intra-procedural or cath lab deaths
Percent Patients Mitral Regurgitation Grade Through 1 Year Patients With Data Available at Follow-Up (Completers Analysis) 100 80 2+ 1+ 1+ 60 40 3+ 2+ 2+ MR 2+ in 83% of surviving patients at 1 year 20 0 4+ 3+ 3+ 4+ Baseline Discharge 1 Year
Percent Patients NYHA Functional Class Through 1 Year 100 80 II I 2+ I 60 40 III II 3+ II NYHA Class I/II in 87% of surviving patients at 1 year 20 0 IV III 4+ III Baseline 1 Year 2 Year
Hospitalizations For Heart Failure 1.00 0.80 0.60 0.67 73% Reduction p < 0.0001 0.40 0.20 0.18 0.00 1 Year Prior to MitraClip N = 127 1 Year Post Discharge N = 120
5 Year Prohibitive Risk: Summary MitraClip therapy safely reduces DMR in patients at prohibitive risk for MV surgery In this group of prohibitive risk DMR patients, MitraClip therapy provides meaningful clinical improvements Reduction of LV volumes Improvements in NYHA Functional Class Improvements in Quality of Life Reduction in Hospitalizations for Heart Failure
Degenerative MR FDA-approved indications: for the percutaneous reduction of significant symptomatic mitral regurgitation (MR 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at a prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit CMS National coverage decision
MR Etiology Normal Degenerative MR Prolapse Degenerative MR Flail Functional MR Ischemic vs. nonischemic
Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation COAPT Trial: Overview
Objective To evaluate the safety and effectiveness of the MitraClip System for treatment of functional mitral regurgitation (FMR 3+) in symptomatic heart failure subjects who are treated per standard of care and who have been determined by the site s local heart team as not appropriate for mitral valve surgery
Trial design 430 patients enrolled at up to 75 US sites Significant FMR ( 3+ by core lab) Symptomatic heart failure subjects who are treated per standard of care Determined by the site s local heart team as not appropriate for mitral valve surgery Specific valve anatomic criteria Randomize 1:1 MitraClip N=215 Control group Standard of care N=215 Clinical and TTE follow-up: Baseline, Treatment, 1-week (phone), 1, 6, 12, 18, 24, 36, 48, 60 months
Key Inclusion Criteria (i) Functional MR 3+ due to cardiomyopathy of either ischemic or non-ischemic etiology Symptomatic (NYHA class II, III or ambulatory IV) Local Site Heart Team (CT surgeon and HF specialist investigators) and the Central Eligibility Committee concur that surgery will not be offered as a treatment option and that medical therapy is the intended therapy for the subject, even if the subject is randomized to the Control group. Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012. COAPT TRIAL OVERVIEW NPL 03976 Rev E CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
Key Inclusion Criteria (ii) The subject has had at least 1 HF hospitalization in the 12 months prior to enrollment and/or a corrected BNP 300 pg/ml or nt-probnp 1500 pg/ml measured within 90 days prior to registration. Subject has been adequately treated per applicable standards for CAD, LV dysfunction, MR or HF (CRT, revascularization, and/or OMT). The primary regurgitant jet is non-commissural. If secondary MR jets exist, they must be considered clinically insignificant. CK-MB obtained within prior 14 days less than local laboratory upper limit of normal (ULN) Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012. COAPT TRIAL OVERVIEW NPL 03976 Rev E CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
Primary Endpoints Primary Effectiveness (min 1-year follow-up all pts) Recurrent heart failure hospitalizations Primary Safety (1 year) Composite of Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, and any device related complications requiring non-elective cardiovascular surgery at 12 months Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012. COAPT TRIAL OVERVIEW NPL 03976 Rev E CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
Patient Selection: Bottom Line Degenerative Functional Low Surgical Risk Surgical Mitral Valve Repair COAPT High Surgical Risk MitraClip COAPT