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

Inclusion Criteria:

1. Symptomatic functional MR (≥3+) due to cardiomyopathy of either ischemic or non-ischemic etiology determined by assessment of a transthoracic echocardiogram (TTE)and transesophageal echocardiogram (TEE) obtained within 60 days prior to enrollment, with MR severity and MR etiology confirmed by the Echocardiography Core Lab.
2. In the judgment of the HF specialist investigator at the site, the subject has been adequately treated per applicable standards, including for coronary artery disease, left ventricular dysfunction, mitral regurgitation and heart failure (e.g., with cardiac resynchronization therapy, revascularization, and/or optimal therapy as appropriate;
3. New York Heart Association (NYHA) Functional Class II, III or ambulatory IV.
4. The subject is extremely high risk for open mitral valve surgery due to comorbidities such that the calculated STS mortality risk is ≥ 8%, or the Local Site Heart Team concludes that comorbidities result in extremely high operative risk of stroke or death. A candidate who does not meet the STS mortality risk criterion of ≥ 8% can be included in the trial if the Local Site Heart Team (CT surgeon and HF specialist investigators) and the Central Eligibility Committee concur and document that the subject has extremely high operative risk of stroke or death from open mitral valve surgery for reasons not captured by the STS risk calculator. The local site surgeon's assessment of operative comorbidities not captured by the STS risk calculator must be documented in the case report form as well as in the subject's medical record.
5. The subject has had at least one hospitalization for heart failure in the 12 months prior to enrollment and/or BNP ≥400 pg/ml or NT-proBNP ≥1600 pg/ml measured within 90 days prior to enrollment.
6. 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. The Echocardiography Core Lab will confirm these findings prior to enrollment.
7. Creatinine Kinase-MB (CK-MB) obtained within prior 14 days < local laboratory ULN (Upper Limit of Normal)
8. Transseptal catheterization and femoral vein access is determined to be feasible by the MitraClip implanting investigator.
9. Age 18 years or older.
10. The subject or the subject's legal representative understands and agrees that should he/she be assigned to the Control group, he/she will be treated with medical therapy and conservative management without surgery and without the MitraClip, either domestically or abroad. If the subject would actively contemplate surgery and/or MitraClip if randomized to Control, he/she should not be enrolled in this trial.
11. 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:

1. The subject has severe LV dysfunction based on a transthoracic echocardiogram(TTE) obtained within 60 days prior to enrollment (severe LV dysfunction is defined as Left Ventricular End Systolic Dimension (LVESD) >60mm or Left Ventricular Ejection Fraction (LVEF) <20%) and confirmed by the Echocardiography Core Laboratory.
2. Evidence of an acute myocardial infarction within 30 days prior to enrollment.
3. Untreated clinically significant coronary artery disease requiring revascularization ortricuspid or aortic valve disease requiring surgery.
4. Cerebrovascular accident within 6 months prior to enrollment or severe symptomatic carotid stenosis (> 70% by ultrasound).
5. ACC/AHA Stage D heart failure.

6. Presence of any of the following:

   • Estimated pulmonary artery systolic pressure (PASP) > 70 mm Hg assessed by echocardiography or right heart catheterization
   • 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
7. Severe right ventricular failure identified by severely reduced/poor wall motion or severe tricuspid regurgitation.
8. Any percutaneous cardiac intervention or carotid surgery within 30 days prior to enrollment, or any cardiac surgery within 6 months prior to enrollment.
9. 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 prior to enrollment, or revision of any implanted rhythm management device within last 90 days prior to enrollment.
10. Mitral valve orifice area < 4.0 cm2 based on a transthoracic echocardiogram (TTE)within 60 days prior to enrollment, and confirmed by the Echocardiography Core Laboratory.
11. If leaflet tethering is present, vertical coaptation length is less than 2 mm based on a transesophageal echocardiogram (TEE) within 60 days prior to enrollment, and confirmed by the Echocardiography Core Laboratory.

12. Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in MR and confirmed by the Echocardiography Core Laboratory. This include, but are not limited to:

    • Evidence of calcification in the grasping area
    • Presence of a significant cleft in the grasping area
    • Lack of both primary and secondary chordal support in the grasping area
    • Leaflet mobility length < 1 cm
13. Hemodynamic instability defined as systolic pressure < 90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support or intra-aortic balloon pump or other hemodynamic support device.
14. Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.
15. Life expectancy < 12 months due to non-cardiac conditions.
16. Modified Rankin Scale ≥ 4 disability.
17. Status 1 heart transplant or prior orthotopic heart transplantation.
18. Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve, or any prior transcatheter mitral valve procedure.
19. Echocardiographic evidence of intracardiac mass, thrombus or vegetation, and confirmed by the Echocardiography Core Laboratory.
20. Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated).
21. Active infections requiring current antibiotic therapy.
22. Subjects in whom transesophageal echocardiography (TEE) is contraindicated or high risk.
23. Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically.
24. Pregnant or planning pregnancy within next 12 months.
25. Currently participating in an investigational drug or another device study that has not reached its primary endpoint. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
26. Subject belongs to a vulnerable population per investigator's judgment or subject has any kind of disorder that compromises his/her ability to give written informed consent and/or to comply with study procedures.