Transcatheter Mitral Valve Repair: today and tomorrow Sponsored by Abbott. Chairperson: M. Haude Panellists: A. Al Nooryani, M.

Transcription

1 Transcatheter Mitral Valve Repair: today and tomorrow Sponsored by Abbott Chairperson: M. Haude Panellists: A. Al Nooryani, M. Al Otaiby

2 Session objectives To learn about the clinical patient profile for TMVR To debate challenging cases on TMVR To learn about future developments in TMVR

3 Agenda 3 mn - Session objectives - M. Haude 9 mn - MitraClip NT therapy after 50,000 patients treated - M. Haude MitraClip NT: improving patient outcomes: 7 mn - Case direct myocardial revascularisation - A. Al Nooryani 8 mn - Discussion and audience interaction 7 mn - Case - functional mitral regurgitation - M. Al Otaiby 8 mn - Discussion and audience interaction 3 mn - Session evaluation and key learnings - M. Haude

4 MitraClip NT therapy after 50,000 patients treated

5 CONCEPT: TRANSCATHETER MITRAL VALVE REPAIR Double-orifice suture technique developed by Prof. Ottavio Alfieri First published results in 1998 illustrated proven benefit in selected pathologic conditions Dr. Fred St. Goar, interventional cardiologist had patient successfully treated with edge-to-edge surgery Conceived several ideas for percutaneous valve repair Founded Evalve 1999 in to develop minimally invasive approach to treat mitral regurgitation based on the Alfieri technique

6 MITRACLIP DEVICE Transcatheter repair of the MV Beating heart procedure no cardiopulmonary bypass Allows for real-time positioning and repositioning to optimize MR reduction Designed to preserve surgical options Femoral venous access Limited hospital length of stay compared to that after surgery

7 MitraClip Mitral Valve Surgery MitraClip Mitral Valve Surgery EVEREST II RANDOMIZED CONTROLLED TRIAL 5-YEAR RESULTS Sustained clinical benefits comparable to those seen after surgery Improvements in NYHA class: 6% of NYHA III/IV for MitraClip group vs 3% in Surgical group at 5 year Improvement in MR durable through 5 years Sustained NYHA Class improvement at 5 years - NYHA Functional Class at Baseline, 1 year and 5 year 98% 91% 88% 91% N=151 N=106 N=66 N=42 Sustained MR Reduction at 5 years - MR Severity at Baseline, at 1 year and 5 year 81% 82% 99% 98% Source: : EVEREST II 5years presented by T. Feldman at ACC 2014 Feldman et al. The EVEREST II RCT: 5-Year Results - J A C C V O L. 6 6, N O. 2 5 :

8 EVEREST II RANDOMIZED CONTROLLED TRIAL 5-YEAR RESULTS Freedom from death after the MitraClip procedure is comparable to surgery Feldman et al. The EVEREST II RCT: 5-Year Results - J A C C V O L. 6 6, N O. 2 5 :

9 Mitral Regurgitation Grade Reduction durable at one year p< ACCESS-EU REAL WORLD- CLINICAL EXPERIENCE % MR 2+ at 1 Year Demonstrated safety with low adverse event rates Description of Event (%) Death 3.4% (19/567) Stroke 0.7% (4/567 ) Myocardial Infarction 0.7% (4/567 ) Renal Failure 4.8%(27/567 ) Site Reported Safety Events at 30 Days Respiratory Failure 0.7% (4/567) Need for Resuscitation 1.8%(10/567) Cardiac Tamponade 1.1%(6/567) As assessed by sites (N=327, matched) Bleeding Complications 3.9% (22/567) Significant NYHA Functional Class Improvements durable at one year I II p< I Functional Improvement in 6-Minute Walk Test durable at one year p< meter improvement III II 79% NYHA Class I or II at 1 Year IV (N=343, matched) III IV (N=216, matched)) Data presented as mean ±95% confidence intervals (44.5, 74.6) Maisano - Percutaneous Mitral Valve Interventions in the Real World Early and 1-Year Results From the ACCESS-EU, A Prospective, Multicenter, Nonrandomized Post-Approval Study of the MitraClip Therapy in Europe - J Am Coll Cardiol 2013;62:

10 MITRACLIP IN SPECIFIC PATIENT POPULATIONS Patient groups in which significant clinical benefits have been reported: Degenerative MR, declined for surgery 1 Severe LV dysfunction refractory to medical therapy 2 Severe Heart Failure, despite optimal medical therapy 3 CRT non-responders 4 Bivalvular Disease: Severe Aortic Stenosis and Mitral Regurgitation 5 The following parameters should be taken into consideration by the Heart Team 6 : Moderate to severe or severe MR (Functional or Degenerative) Echocardiographic criteria for eligibility Level of surgical risk Greater than one year life expectancy 1. Reichenspurner, H. et al. Clinical Outcomes through 12 months in patients with Degenerative Mitral Regurgitation treated with the MitraClip device in the ACCESS-Europe Phase I trial. Eur J Cardiothoracic Surgery. 2013: 44:e Franzen O, Baldus S, Rudolph V, et al. Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: Emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. 2010; 31: Franzen et al. MitraClip Therapy In Patients With End-Stage Systolic Heart Failure. Eur J Heart Failure. 2011; 13: Auricchio et al. Correction of Mitral Regurgitation in Nonresponders To Cardiac Resynchronization Therapy By MitraClip Improves Symptoms And Promotes Reverse Remodeling. JACC 2011; 58: Rudolph V, Schirmer J, Franzen O, Schlu ter M, Seiffert M, Treede H, Reichenspurner H, Blankenberg S, Baldus S. Bivalvular transcatheter treatment of high-surgical-risk patients with coexisting severe aortic stenosis and significant mitral regurgitation. Int J Cardiol. 2013; 167(3): ESC/EACTS 2012 Guidelines on the management of valvular heart disease. Eur Heart J (2012) 33,

11 DEGENERATIVE MITRAL REGURGITATION, DECLINED FOR SURGERY ACCESS-EU DMR patients cohort: 117 elderly patients, 74% in NYHA class lll-lv Significant reduction in MR and clinical improvements reported at 12 months Implant rate of 94.9% MitraClip therapy reduced symptoms and enhanced quality of life in patients deemed inoperable or at high surgical risk Survival rate of 82.9% reported at 12 months Mitral Regurgitation Grade Reduction P= Significant NYHA Functional Class Improvements p< % MR 2+ at 1 Year I II III I II 80.8% NYHA Class I or II at 1 Year IV III As assessed by sites (N=71, matched) (N=78, matched) Reichenspurner, H. et al. Clinical Outcomes through 12 months in patients with Degenerative Mitral Regurgitation treated with the MitraClip device in the ACCESS-Europe Phase I trial. Eur J Cardiothoracic Surgery. 2013: July 17

12 SEVERE LEFT VENTRICULAR DYSFUNCTION REFRACTORY TO MEDICAL THERAPY 51 patients with MR 3+: adverse MV morphology and/or severe LV dysfunction in 69% Procedural success achieved in 96% of patients Reduction in MR, although moderate in most patients, was acceptable given high surgical risk and corresponding clinical benefits Mitral Regurgitation Grade Reduction P= Significant NYHA Functional Class Improvements p< % MR 2+ at discharge I II III I II 67% NYHA Class I or II at discharge IV III As assessed by sites (N=49) (N=49) Mitral valve repair using the MitraClip system was shown to be feasible in patients at high surgical risk primarily determined by an adverse mitral valve morphology and/or severe LV dysfunction. Franzen O, Baldus S, Rudolph V, et al. Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: Emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. 2010; 31:

13 SEVERE HEART FAILURE, DESPITE OPTIMAL MEDICAL THERAPY Retrospective analysis of 50 patients with LVEF 25%, MR >3+ and NYHA III or IV Significant clinical improvements reported at 6 months Cumulative survival at 6 months in NYHA-lll and NYHA-IV patients was 81.2% and 64.2% respectively Baseline characteristics 50 patients Age Years (mean±sd) 70±11 EuroSCORE (%) 34±21 FMR etiology (%) 100 Ischemic Cardiomyopathy (%) 56 NYHA lll-lv (%) 100 LVEF (%) 19±5 Patients with end-stage heart failure and marked LV dysfunction can be treated by the MitraClip as successful therapy promotes clinical benefits at 6 months. Franzen O, et al. MitraClip(R) therapy in patients with end-stage systolic heart failure. Eur J Heart Fail 2011; 13(5):

14 CRT NON-RESPONDERS (PERMIT-CARE ) Prospective survey of 51 CRT non-responders, with FMR and NYHA III or IV Implant rate of 95% At discharge 73% patients had an improved functional NYHA class; the proportion of NYHA I &II increased over time LVEF significantly increased at 6 and 12 months Reverse LV remodeling occurred even in the presence of MR 2+ - reduced LV volume in 70% of patients Auricchio A et al; PERMIT-CARE Investigators. Correction of Mitral Regurgitation in Nonresponders to Cardiac Resynchronization Therapy by MitraClip Improves Symptoms and Promotes Reverse Remodeling. J Am Coll Cardiol Nov 15;58(21):

15 BIVALVULAR DISEASE : SEVERE AORTIC STENOSIS AND MITRAL REGURGITATION 11 patients with bivalvular severe AS and MR 3+ treated with TAVR followed by MitraClip TAVR preceded MitraClip therapy in 10 patients; 3 patients underwent both interventions in single sessions Reduction in MR severity to 2+ or less in 10 patients; 100% of patients who underwent TAVR before MitraClip in separate session achieved MR 2+ Baseline characteristics 11 patients Mitral Regurgitation Grade Reduction p= Baseline characteristics Age Years (mean ± SD) 78±6 FMR ethiology (%) 45 LVEF (%) 36±13 NYHA lll-lv (%) 91 Logistic EuroSCORE (%) 25 Ischemic Cardiomyopathy (%) % MR 2+ Post MitraClip (N=7, TAVR before MitraClip therapy in separate sessions.) Complete transcatheter treatment of coexisting severe AS and significant MR in high-surgical-risk patients is technically feasible, regardless of which prosthesis and what access route is chosen for TAVR, and regardless of whether both procedures are performed in separate sessions or in a single session. Rudolph V, Schirmer J, Franzen O, Schlüter M, Seiffert M, Treede H, Reichenspurner H, Blankenberg S, Baldus S. Bivalvular transcatheter treatment of high-surgical-risk patients with coexisting severe aortic stenosis and significant mitral regurgitation. Int J Cardiol. 2013; 167(3):716-2

16 MITRACLIP INTERVENTION IMPROVES SURVIVAL MitraClip therapy is superior to conservative treatment and survival rates are comparable to surgery in high-surgical-risk patients with symptomatic MR (DMR and FMR) SWAANS Publication VELAZQUEZ Publication GIANNINI Publication 139 MitraClip patients compared to 53 Surgical patients and 59 OMT Patients 1 year mortality rates were 15% for MitraClip and Surgery vs 32.0% for OMT 239 optimally matched MitraClip and OMT patients with identical baseline characteristics OMT patients from the DUKE Echo Laboratory Database (85.000) 1 year mortality rates were 22.4% for MitraClip vs 32.0% for OMT 70 MitraClip patients compared to 90 OMT patients, only FMR 60 optimally matched patients Overall survival rates after 1 year: 89.7% vs 64.3% Swaans M Survival of Transcatheter Mitral Valve Repair Compared With Surgical and Conservative Treatment in High-Surgical-Risk Patients - J Am Coll Cardiol Intv 2014;7: Velazquez EJ, et al. - The MitraClip and survival in patients with mitral regurgitation at high risk for surgery: A propensity matched Comparison - Am Heart J 2015;0:1-10 Giannini C, et al. Comparison of Percutaneous Mitral Valve Repair Versus Conservative Treatment in Severe Functional Mitral Regurgitation - Am J Cardiol 2016;117:

17 ACC/AHA 2017 GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR HEART DISEASE Move the timing of intervention earlier in the disease course with the goal of preventing irreversible LV dysfunction, arrhythmias and pulmonary hypertension due to longstanding LV volume overload. 1 Transcatheter MV repair may be considered for severely symptomatic patients (NYHA class III/IV) with chronic severe primary MR (stage D) who have a reasonable life expectancy but a prohibitive surgical risk because of severe comorbidities. 2 Page Nishimura RA, Otto CM ACC/AHA valve guidelines: earlier intervention for chronic mitral regurgitation. Heart. 2014; retrieved: 2. Nishimura RA, Otto CM, Bonow RO AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(25). doi: /cir

18 ESC/EACTS 2017 GUIDELINES ON THE MANAGEMENT OF VALVULAR HEART DISEASE Indication for primary MR: Percutaneous edge-to-edge procedure may be considered in patients with symptomatic severe primary mitral regurgitation who fulfil the echocardiographic criteria of eligibility and are judged inoperable or at high surgical risk by the Heart Team, avoiding futility. (recommendation class llb, level of evidence C). 1 Page 22 When revascularization is not indicated and surgical risk is not low, a percutaneous edge-to-edge procedure may be considered in patients with severe secondary mitral regurgitation and LVEF >30% who remain symptomatic despite optimal medical management (including CRT if indicated) and who have a suitable valve morphology by echocardiography, avoiding futility. (recommendation class llb, level of evidence C). 1 Indication for secondary MR: In patients with severe secondary mitral regurgitation and LVEF <30% who remain symptomatic despite optimal medical management (including CRT if indicated) and who have no option for revascularization, the Heart Team may consider a percutaneous edge-to-edge procedure or valve surgery after careful evaluation for a ventricular assist device or heart transplant according to individual patient characteristics. (recommendation class llb, level of evidence C) Baumgartner H, Falk V, Bax JJ, et al ESC/EACTS Guidelines for the management of valvular heart disease: The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017;00:1-53. Page 25

19 WORLDWIDE CLINICAL EXPERIENCE Over patients have been treated with the MitraClip Therapy worldwide. 1 67% have functional mitral regurgitation (MR) 97% Implant Rate The use of the MitraClip is supported by a rigorous clinical trial program. 1 The majority is considered high risk* for mitral valve surgery 60% have functional MR MATTERHORN, RESHAPE-HF2 (Investigator Sponsored Studies) Currently Enrolling 1. Data as of November Source: Abbott Vascular. * Determination of high surgical risk based on: logistic EuroSCORE 20%, or STS calculated mortality 12%, or pre-specified high surgical risk co-morbidities specified in EVEREST II High Risk Study protocol.

20 COAPT TRIAL OVERVIEW Objective To evaluate the safety and effectiveness of the MitraClip System for the treatment of moderate-to-severe or severe functional mitral regurgitation (FMR) 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. Study Design & Duration Prospective, randomized, parallel-controlled, multicenter clinical evaluation of the MitraClip device for the treatment of clinically significant functional mitral regurgitation 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. Eligible subjects will be randomized in a 1:1 ratio to the MitraClip device (Device group) or to no MitraClip device (Control group). Subjects will have required follow-up evaluations at these time points post- Treatment visit: 1-week (phone contact), 30 days, 6 months, 12 months, 18 months, 24 months, and annually thereafter through 5 years. Enrollment A total of 610 subjects will be randomized with 305 subjects targeted to receive the study device. CIP : Version 7.0, April 22, 2016, approved by FDA May 11, 2016 for ~555 patients at up to 85 sites. CIP Version 8.0 submitted for ~610 patients at up to 100 sites. Source: Abbott Vascular

21 Study Title Study Investigator Study Design MATTERHORN J. Hausleiter RCT: Surgery vs. MitraClip for FMR or DMR with LV dysfunction RESHAPE-HF- 2 P.Ponikowski, S. Anker MITRACLIP EU INVESTIGATOR RCT: OMT vs MitraClip for FMR SPONSORED STUDIES Number of Patients to be Enrolled 210 (10+ sites) patients from Reshape-HF (10 sites) Enrolment status Primary Endpoint 65 SAFETY: Major adverse events (MAE) defined as composite of the following events within 30 days post intervention: death (all cause, cardiovascular), myocardial infarction, major bleeding, stroke, rehospitalization (all cause, cardiovascular), reintervention or non-elective cardiovascular surgery, renal failure (need for renal replacement therapy) deep wound infection, mechanical ventilation for more than 48 hours, gastrointestinal complication requiring surgery, new-onset permanent atrial fibrillation, septicemia, endocarditis / EFFICACY : Freedom from death, rehospitalization, reintervention, assist device, stroke 294 SAFETY: Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death Expect ed comple tion 2Q 19 4Q 18 Study Title Study Investigator Study Design Enrolment status Number of Patients to be Enrolled Primary Endpoint MITRA.FR J-F Obadia RCT: MitraClip vs. OMT in patients with severe FMR completed 288 (30 sites) All-cause mortality and unplanned hospitalizations for heart failure Source: Abbott Vascular

22 MITRACLIP NT Grippers material change from Elgiloy to Nitinol: Increased Gripper Drop Angle (85 ) (>120 ) Material and geometry changes enhance MitraClip NT steering Less user effort to straddle CDS Reduced M knob rotation to target & reduced A/P movement with M knob Less sleeve shortening Improved retraction of Clip into Guide Data on File at Abbott Vascular *Challenge as perceived by the users

23 MITRACLIP NT: 183 PATIENTS EXPERIENCE MitraClip NT Perceived Benefits Consistently Increase with Procedural Challenge* Data on File at Abbott Vascular *Challenge as perceived by the users

24 Conclusion: MitraClip has evolved as a valuable catheterbased treatment option in patients with both primary and secondary (functional) MR

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