Transcatheter Mitral Valve Repair for the Treatment of Mitral Valve Regurgitation In Heart Failure (The EVOLVE-MR Trial)

Inclusion Criteria Study participants must meet ALL of the following inclusion criteria in order to be eligible for this study: 1. Male or female ≥18 years of age; 2. 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); 3. Left ventricular ejection fraction (LVEF) \>20%, as determined by transthoracic echocardiogram (TTE), and confirmed by the Echocardiography Core Lab (ECL); 4. Symptomatic heart failure as defined by NYHA class II, III or ambulatory IV and NT-proBNP as follows: * NT-proBNP \> 300 pg/mL in patients with sinus rhythm * NT-proBNP \> 600 pg/mL in patients with atrial fibrillation 5. 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/sacubitril), Ivabradine and aldosterone antagonist (as per the ACC/AHA Guidelines and Canadian Cardiovascular Society Heart Failure Guidelines or other therapies (including SGLT2 inhibitors) as judged by the HF specialist investigator on site and confirmed by the Clinical Eligibility Committee. 6. Clinical agreement amongst local investigators that the patient will not be offered surgical intervention; 7. 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; 8. 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; 9. 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 1) are NOT eligible for this study: 1. Life expectancy less than 12 months due to non-cardiac conditions; 2. ACC/AHA Stage D Heart Failure; 3. Left ventricular ejection fraction ≤ 25%; indexed left ventricular end-diastolic volume ≥100 ml/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 heart 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; Women are considered not of childbearing potential if they: 1. Have had a hysterectomy, a bilateral oophorectomy or tubal ligation prior to Baseline Visit. 2. Are postmenopausal defined as no menses for at least 1 year and have a serum FSH level of 40 IU/L. Women of childbearing potential must agree to use an effective method of birth control throughout the study. Acceptable means of birth control include: implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner. 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 is at 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 Glomerular 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.