Clinical Outcomes Assessment of the MitraClip Therapy Percutaneous Therapy for High Surgical Risk Patients (COAPT)

Inclusion Criteria:

• Symptomatic (NYHA Functional Class II, III or ambulatory IV) functional mitral regurgitation(≥3+) determined by assessment of a TTE obtained within the prior 6 months of enrollment and mitral regurgitation severity is confirmed by the Echocardiography Core Lab
• Subject must have comorbidities such that a CT surgeon investigator at the site determines that medical factors preclude surgery based on a conclusion that the probability of death or serious morbidity, exceeds the probability of meaningful improvement and this conclusion is confirmed by the Eligibility Committee.
• In the judgment of an experienced cardiologist investigator at the site, the subject is likely to benefit from mitral regurgitation reduction, and this conclusion is confirmed by the Eligibility Committee
• The subject has been adequately treated per applicable standards, such as for coronary artery disease left ventricular dysfunction, mitral regurgitation or heart failure (e.g., cardiac resynchronization therapy revascularization optimal medical therapy).
• Left ventricular ejection fraction (LVEF) > 20% and left ventricular end-systolic dimension (LVESD) ≤ 60 mm based on an echocardiogram obtained within the prior 6 months
• The primary regurgitant jet originates from malcoaptation of the A2 and P2 scallops of the mitral valve. If a secondary jet exists, it must be considered clinically insignificant.
• Transseptal catheterization and femoral vein access is determined to be feasible.
• Age 18 years or older
• The subject or the subject's legal representative has been informed of the nature of the trial and agrees to its provisions including the possibility of randomization to the Control group and returning for all required post-procedure follow-up visits, and has provided written informed consent

Exclusion Criteria:

• Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR)
• Evidence of an acute myocardial infarction in the prior 90 days (defined as: Q wave or non-Q wave infarction having CK enzymes ≥ 2X the upper laboratory normal limit with the presence of a CK-MB elevated above the institution's upper limit of normal)
• Untreated clinically significant coronary artery disease requiring revascularization.
• Cerebrovascular accident within 6 months prior to randomization or severe carotid stenosis (> 70% by ultrasound)
• ACC/AHA Stage D heart failure
• Presence of any of the following:
• Severe TR or AR or moderate to severe AS (< 1.0 cm2)
• Estimated pulmonary artery systolic pressure (PASP) > 60 mm Hg assessed by echocardiography
• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or non ischemic etiology
• Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis)
• Hemodynamic instability requiring inotropic support or mechanical heart assistance
• Any percutaneous cardiac intervention or carotid surgery within the 30 days prior to randomization, or any cardiac surgery within the 6 months prior to randomization.
• Implant of any rhythm management device (i.e., pacemaker, Cardiac Resynchronization Therapy (CRT) Cardiac Resynchronization Therapy with cardioverter-defibrillator (CRT-D) or Implantable Cardioverter Defibrillator (ICD)) within the last 90 days or revision of any implanted rhythm management device within the last 90 days
• Mitral valve orifice area < 4.0 cm2
• If leaflet tethering is present, vertical coaptation length is less than 2 mm.
• Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in mitral regurgitation. This may include:
• Evidence of calcification in the grasping area of the A2 and/or P2 scallops
• Presence of a significant cleft of A2 or P2 scallops
• Lack of both primary and secondary chordal support
• Hemodynamic instability defined as systolic pressure < 90 mmHg without afterload reduction cardiogenic shock or the need for inotropic support or intra-aortic balloon pump
• Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months
• Life expectancy < 12 months due to non-cardiac conditions
• Modified Rankin Scale ≥ 4
• Status 1 heart transplant or prior orthotopic heart transplantation.
• Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve.
• Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
• Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic diseased (i.e., noncompliant, perforated).
• Active infections requiring current antibiotic therapy.
• Subjects in whom transesophageal echocardiography (TEE) is contraindicated
• A known hypersensitivity or contraindication to procedure medications which cannot be adequately managed medically
• Pregnant or planning pregnancy within next 12 months
• In the judgment of the Investigator, subjects in whom the presence of a permanent pacemaker or pacing leads would interfere with placement of the MitraClip device or the placement of the MitraClip device would disrupt the leads
• Currently participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational trials