Transcatheter Mitral Valve Repair for the Treatment of Mitral Valve Regurgitation In Heart Failure (The EVOLVE-MR Trial)
Transcatheter Mitral Valve Repair for the Treatment of Mitral Valve Regurgitation In Heart Failure (The EVOLVE-MR Trial)
The study compares the effectiveness of treatment with MitraClip to medical therapy in
 improving the reduction of cardiovascular morbidity and functional capacity at 12 months, in
 patients with moderate functional mitral regurgitation.
Primary Objective To compare the effectiveness of treatment with MitraClip to medical therapy
 in improving left ventricular remodelling (indexed left ventricular end-diastolic
 volume,(LVEDVi)) and functional capacity (distance walked on a 6MWT) at 12 months, in
 patients with moderate functional mitral regurgitation Secondary Objectives

 -  To evaluate the effects of MitraClip and medical therapy on change from baseline in
 mitral regurgitation severity at 12 months

 -  To evaluate the effects of MitraClip and medical therapy on change from baseline in
 quality of life at 12 months Exploratory Objectives To evaluate the effects of MitraClip
 and medical therapy on functional class, biomarkers, clinical events, parameters of
 physical activity, echocardiographic parameters and health economic assessments.
Inclusion Criteria:

 -  Study participants must meet ALL of the following inclusion criteria in order to be
 eligible for this study:

 1. Moderate (2+,2-3+) functional mitral regurgitation due to cardiomyopathy of
 either ischemic or non-ischemic etiology as determined by transthoracic
 echocardiogram (TTE), and confirmed by the Echocardiography Core Lab (ECL);

 2. Left ventricular ejection fraction > 20%, as assessed by any one of the following
 methods: echocardiography, contrast left ventriculography, gated blood pool scan
 or cardiac magnetic resonance imaging (MRI) and evidence of LV dilatation defined
 as a baseline LVEDV of 75-110 ml/m2 measured by echocardiography;

 3. Symptomatic heart failure as defined by NYHA class II, III or ambulatory IV and
 NT-pro BNP > 800ug/mL (sinus rhythm) or 1000ug/mL (AFIB);

 4. Treatment and compliance with medical therapy for heart failure for at least 30
 days;

 Optimal medical therapy is defined by:

 a. Maximum tolerated beta-blocker, angiotensin converting enzyme inhibitor (ACE)
 or angiotensin receptor blocker (ARB), Entresto (valsartan/sacubatril) and
 aldosterone antagonist (as per the ACC/AHA Guidelines as judged by the HF
 specialist investigator on site and confirmed by the Central Eligibility
 Committee).

 5. Clinical agreement amongst local investigators that the patient will not be
 offered surgical intervention;

 6. The primary regurgitant jet, in the opinion of the MitraClip implanting
 investigator, can successfully be treated by the MitraClip. Treatment of
 commissural mitral regurgitation may be treated at the discretion of the
 operator. All major jets contributing the secondary MR will be treated with the
 MitraClip;

 7. Ability to perform a six-minute walk test (6MWT) without substantial physical
 limitations and without use of a walker or wheelchair and distance walked in 6
 minutes of ≤ 450m;

 8. Ability and willingness to give written informed consent and to comply with the
 requirements of the study.

 Exclusion Criteria:

 -  Study participants meeting any of the following exclusion criteria by the day of
 randomization (visit 2) are NOT eligible for this study:

 1. Life expectancy less than 12 months due to noncardiac conditions;

 2. ACC/AHA Stage D Heart Failure;

 3. Left ventricular ejection fraction ≤ 20%; indexed left ventricular end-diastolic
 volume > 110ml/m2

 4. Severe (3-4+, 4+) secondary mitral regurgitation with an indication for
 intervention

 5. Hypotension (systolic pressure <90 mm Hg) or requirement for inotropic support or
 mechanical hemodynamic support;

 6. United Network for Organ Sharing (UNOS) status 1 heart transplantation (Canadian
 Cardiac Transplantation Network, CCTN, status 4) or prior orthotopic hear
 transplantation;

 7. Untreated clinically significant coronary artery disease requiring
 revascularization;

 8. CABG within prior 30 days;

 9. Percutaneous coronary intervention within prior 30 days;

 10. Severe Chronic Obstructive Pulmonary Disease (COPD) requiring continuous daytime
 home oxygen or chronic oral corticosteroid therapy;

 11. Previous surgical mitral valve bioprosthesis, mitral annuloplasty, or
 transcatheter mitral valve procedure;

 12. Positive pregnancy test, or woman of child bearing potential not using highly
 effective methods of contraception;

 13. Mitral valve area <4.0 cm2 as assessed by planimetry of the mitral valve;

 14. Subjects in whom trans-esophageal echocardiography is contraindicated or high
 risk;

 15. Mitral leaflet anatomy which may preclude MitraClip implantation:

 1. Perforated mitral leaflets or clefts, lack of primary or secondary chordal
 support;

 2. Severe calcification in the grasping area;

 3. Rheumatic valve disease.

 16. Stroke or transient ischemic event within 30 days before randomization;

 17. Modified Rankin Scale >4 disability;

 18. Need for emergent or urgent surgery for any reason or any planned cardiac surgery
 within the next 12 months;

 19. Severe renal impairment defined as an Estimated Glomelular Filtration Rate (eGFR)
 <30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease
 (MDRD) formula;

 20. Severe anemia requiring transfusional support or therapy with erythropoietin;

 21. Physical evidence of uncontrolled right-sided congestive heart failure with
 echocardiographic evidence of moderate or severe right ventricular dysfunction;

 22. Aortic valve disease requiring surgery or transcatheter intervention;

 23. Significant tricuspid valve disease requiring surgical intervention or very
 severe tricuspid regurgitation with evidence of right ventricular dysfunction;

 24. Active infection requiring antibiotic therapy;

 25. Active endocarditis or active rheumatic heart disease or leaflets degenerated
 from rheumatic disease;

 26. Echocardiographic evidence of intracardiac mass, thrombus or vegetation;

 27. Any condition making it unlikely the patient will be able to complete all
 protocol procedures (including compliance with guideline directed medical
 therapy) and follow-up visits;

 28. Presence of any of the following:

 1. Pulmonary artery systolic pressure (PASP) > 70 mm Hg confirmed by right
 heart catheterization;

 2. Infiltrative cardiomyopathies.

 29. Any other condition(s) that would compromise the safety of the patient as judged
 by the site principal investigator.