Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) and COAPT CAS (COAPT)

• ClinicalTrials.gov Identifier: NCT01626079
• Recruitment Status: Active, not recruiting
• First Posted: June 22, 2012
• Results First Posted: May 6, 2020
• Last Update Posted: September 28, 2022
• Sponsor: Abbott Medical Devices
• Information provided by (Responsible Party): Abbott Medical Devices

Study Description

Brief Summary:

The purpose of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial is to confirm 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. This randomized controlled trial will provide the opportunity to strengthen or add labeling claims regarding safety and clinical benefits of the MitraClip System for symptomatic heart failure patients with moderate-to-severe or severe functional mitral regurgitation.

Approximately 610 subjects will be randomized at up to 100 investigational sites with approximately 305 subjects targeted to receive the study device. COAPT study completed recruiting subjects in June 2017.

As part of the COAPT trial, a subset of patients will be registered in the cardiopulmonary exercise (CPX) sub-study. The objective of this sub-study is to evaluate the exercise responses in a sub-cohort of COAPT subjects who receive MitraClip device (Device group) compared to the Control group who do not receive MitraClip device. (Note: the CPX Sub-study subjects will contribute to the analyses of the COAPT primary and secondary endpoints)

As an extension of the COAPT RCT trial, COAPT CAS study will be conducted after COAPT enrollment is complete under the same investigational device exemption (IDE(G120024)). The objective of this study is to evaluate the MitraClip® NT System for the treatment of clinically significant 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. The anticipated Study Completion Date is July 2024. COAPT CAS completed recruiting subjects in March 2019.

Condition or disease	Intervention/treatment	Phase
Mitral Regurgitation; Mitral Valve Regurgitation; Treatment of Functional Mitral Regurgitation in Symptomatic Heart Failure Subjects; Heart Failure	Device: MitraClip System	Not Applicable

Detailed Description:

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).

As part of the COAPT trial, a subset of patients (at least 50 up to 100 in total) will be registered in the CPX Sub-study, which is designed as a prospective, randomized (1:1 ratio to the MitraClip or no MitraClip device), parallel-controlled, multicenter study registering approximately 50-100 subjects in up to 50 qualified US sites from the COAPT trial. Subjects registered and randomized in the CPX Sub-study will contribute to the total enrollment approximately of 610 subjects in the COAPT trial. Roll-in subjects will not participate in the CPX Sub-study.

The COAPT CAS study is designed as a prospective, multicenter, single arm, continued access registry study. A maximum of 800 subjects (anticipated) will be registered from up to 75 sites in the United States. The enrollment will end once pre-market approval (PMA) of the proposed expanded indication of MitraClip System is obtained. Active follow-up of patients will be performed through 12 months with scheduled visits at 30 days and 12 months. The national Trans catheter Valve Therapy Registry (TVT Registry) will be used for data collection through 12 months. Annual follow-up data from 2 years through year 5 post-implant will be obtained by linkage to the Centers for Medicare and Medicaid Services (CMS) Claims database.

COAPT CAS data may be used to support the PMA application of the labeling claims for the treatment of moderate to severe or severe FMR in symptomatic heart failure subjects. This single arm registry will provide valuable new information regarding use of the MitraClip® NT System under more "real world" conditions.

COAPT study completed recruiting subjects in June 2017. COAPT CAS completed recruiting subjects in March 2019. A total of 162 subjects were enrolled in the COAPT CAS Group.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 776 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: 614 in the Randomized Group for COAPT Trial and 162 Subjects in the COAPT CAS Group
• Primary Purpose: Treatment
• Official Title: A Clinical Evaluation of the Safety and Effectiveness of the MitraClip® System for the Treatment of Functional Mitral Regurgitation in Symptomatic Heart Failure Subjects (COAPT Recruitment Closed). COAPT CAS (Recruitment Closed)
• Actual Study Start Date: August 2012
• Actual Primary Completion Date: March 2019
• Estimated Study Completion Date: July 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: MitraClip System; Percutaneous mitral valve repair using MitraClip System	Device: MitraClip System; Percutaneous mitral valve repair using MitraClip System; Other Names: MitraClip device; MitraClip
No Intervention: Control Group; Patients with mitral regurgitation managed non-surgically based on standard hospital clinical practice.
Experimental: COAPT CAS Group; Percutaneous mitral valve repair using MitraClip System	Device: MitraClip System; Percutaneous mitral valve repair using MitraClip System; Other Names: MitraClip device; MitraClip

Outcome Measures

Primary Outcome Measures :

1. Primary Safety Endpoint - Percentage of Participants With Freedom From Device Related Complications at 12 Months [ Time Frame: 12 months ]

   Percentage of Participants with Freedom from Device related Complications at 12 Months.

   Composite of Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, and any device related complications requiring non-elective cardiovascular surgery.

2. Primary Effectiveness Endpoint [ Time Frame: 24 months ]
   Recurrent HF hospitalizations (HFH) through 24 months, analyzed when the last subject completes 12-month follow-up

Secondary Outcome Measures :

1. Recurrent Heart Failure (HF) Hospitalization (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
   Number of recurrent Heart Failure hospitalization events at 12 months.
2. New York Heart Association (NYHA) Functional Class (COAPT CAS Study Analysis) [ Time Frame: 12 months ]

   The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

   Class I - No symptoms and no limitation in ordinary physical activity Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms Class IV - Severe limitations.

3. New York Heart Association (NYHA) Functional Class (COAPT CAS Study Analysis) [ Time Frame: 30 days ]

   The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

   Class I - No symptoms and no limitation in ordinary physical activity Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms Class IV - Severe limitations.

4. Quality of Life (QOL) (COAPT CAS Study Analysis) Quality of Life (QoL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: 12 months ]
   The Kansas City Cardiomyopathy Questionnaire is a 23-item, self administered instrument that quantifies physicalfunction, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possiblesubscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies thefollowing six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical FunctionDomain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQSymptom Stability Domain, Clinical Summary Score and Overall Summary Score. Clinical Summary Scoreincludes total symptom and physical function scores to correspond with NYHA Classification. Overall SummaryScore includes the total symptom, physical function, social limitations and quality of life scores.
5. Quality of Life (QOL) (COAPT CAS Study Analysis) Quality of Life (QoL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: 30 days ]
   The Kansas City Cardiomyopathy Questionnaire is a 23-item, self administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score. Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification. Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.
6. Six Minute Walk Test (6MWT Distance or 6MWD) (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
   The Six Minute Walk Test (6MWT) is a practical simple test that requires a 100-ft hallway but no exerciseequipment or advanced training for technicians. This test measures the distance that a patient can quickly walk ona flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of allthe systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation,peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific informationon the function of each of the different organs and systems involved in exercise or the mechanism of exerciselimitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses thesubmaximal level of functional capacity.
7. Six Minute Walk Test (6MWT Distance or 6MWD) (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
   The Six Minute Walk Test (6MWT) is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.
8. Mitral Regurgitation (MR) Severity (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
   MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2
9. Mitral Regurgitation (MR) Severity (COAPT CAS Study Analysis) [ Time Frame: 30 days ]

   MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

   MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

10. Major and/or Life Threatening Bleeding (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
11. Major and/or Life Threatening Bleeding (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
12. Major Vascular Complications (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
13. Major Vascular Complications (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
14. Renal Complication With Requirement for Dialysis (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
15. Renal Complication With Requirement for Dialysis (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
16. Transient Ischemic Attack (TIA) (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
17. Transient Ischemic Attack (TIA) (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
18. Stroke (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
19. Stroke (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
20. Myocardial Infarction (MI) (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
21. Myocardial Infarction (MI) (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
22. Death and Primary Cause of Death (COAPT CAS Study Analysis) [ Time Frame: 12 months ]
23. Death and Primary Cause of Death (COAPT CAS Study Analysis) [ Time Frame: 30 days ]
24. Percentage of Patients Free From the Composite of All-cause Death, Stroke, MI, or Non-elective Cardiovascular Surgery for Device Related Complications in the Device Group [ Time Frame: 30 days post-procedure in the Device group ]
    The percentage of patients free from the composite endpoint as described above.
25. Number of Deaths at 12 Months (All Cause Mortality) [ Time Frame: 12 months ]
    Death from any cause mortality at 12months.
26. Number of Participants With Mitral Regurgitation Severity Grade of 2+ or Lower at 12 Months [ Time Frame: 12 months ]

    MR severity grade of 2+ or lower at 12 months MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

    MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

27. Change in Distance Walked on the 6 Minute Walk Test (6MWT Distance or 6MWD) [ Time Frame: 12 months over baseline ]
    The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.
28. Change in Quality of Life (QoL) as Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: 12 months over baseline ]

    Paired data looking at difference between the baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and 12 month KCCQ score.

    The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

    Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

    Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

29. Change in Left Ventricular End Diastolic Volume (LVEDV) [ Time Frame: 12 months over baseline ]
    Paired data comparing the Change in LVEDV at baseline vs 12 months
30. Number of Participants With New York Heart Association (NYHA) Functional Class I/II [ Time Frame: 12 months ]

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA CLASS)

    Class I: Patients with cardiac disease but without resulting limitations of physical activity.

    Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.

    Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

31. Recurrent Hospitalizations - All Cause [ Time Frame: 24 Months ]
    Number of Recurrent Hospitalizations for any cause within 24 months.
32. Death or HF Hospitalization Within 24 Months (Finkelstein-Schoenfeld Analysis of All-Cause Death or Recurrent HF Hospitalization Through 24 Months) [ Time Frame: 24 months ]

    The win ratio is a useful method for providing an estimate of the treatment effect when composite endpoints are analyzed as the analysis accounts for clinical significance of the outcomes of interest. For example, in the composite of death and recurrent HF hospitalizations through 24 months, subjects in the Device and Control groups were formed into matched pairs, where each pair of subjects was classified into 1 of 5 outcomes scenarios:

    A. Death in Device group first B. Death in Control group first C. More HF hospitalizations in the Device group (or in the case of a tie, the first HF hospitalization in the Device group occurs first) D. More HF hospitalization in the Control group (or in the case of tie, the first HF hospitalization in the Control group occurs first) E. None of the above In this way, the number of "Winners" in the Device group was NW = NB + ND while the number of "Losers" in the Device group was NL = NA + NC. The "Win Ratio" was then calculated as NW/NL.

33. Death and Primary Cause of Death (COAPT CAS Study Analysis) [ Time Frame: 2 years ]
    The COAPT study is still on-going. Only the Primary and major secondary endpoints have been entered. Rest of the results will be entered when the study ends in July 2024.
34. Death and Primary Cause of Death (COAPT CAS Study Analysis) [ Time Frame: 3 years ]
35. Death and Primary Cause of Death (COAPT CAS Study Analysis) [ Time Frame: 4 years ]
36. Death and Primary Cause of Death (COAPT CAS Study Analysis) [ Time Frame: 5 years ]
37. Myocardial Infarction (MI) (COAPT CAS Study Analysis) [ Time Frame: 2 years ]
38. Myocardial Infarction (MI) (COAPT CAS Study Analysis) [ Time Frame: 3 years ]
39. Myocardial Infarction (MI) (COAPT CAS Study Analysis) [ Time Frame: 4 years ]
40. Myocardial Infarction (MI) (COAPT CAS Study Analysis) [ Time Frame: 5 years ]
41. Stroke (COAPT CAS Study Analysis) [ Time Frame: 2 years ]
42. Stroke (COAPT CAS Study Analysis) [ Time Frame: 3 years ]
43. Stroke (COAPT CAS Study Analysis) [ Time Frame: 4 years ]
44. Stroke (COAPT CAS Study Analysis) [ Time Frame: 5 years ]
45. Recurrent Heart Failure (HF) Hospitalization (COAPT CAS Study Analysis) [ Time Frame: 2 years ]
46. Recurrent Heart Failure (HF) Hospitalization (COAPT CAS Study Analysis) [ Time Frame: 3 years ]
47. Recurrent Heart Failure (HF) Hospitalization (COAPT CAS Study Analysis) [ Time Frame: 4 years ]
48. Recurrent Heart Failure (HF) Hospitalization (COAPT CAS Study Analysis) [ Time Frame: 5 years ]
49. Kaplan-Meier Freedom From All-cause Mortality [ Time Frame: 24 months ]
    Death from any cause within 24 months - no of events

Other Outcome Measures:

1. Device or Procedure-Related Adverse Events [ Time Frame: Within and after 30 days of the procedure ]
   Device or procedure-related adverse events are defined as adverse events that are adjudicated by the Clinical Events Committee as possibly, probably or definitely device and/or procedure-related, regardless of the temporal relationship to the MitraClip procedure. Device or procedure-related adverse events will be broken down into those that occur within 30 days of the procedure and those that occur after 30 days of the procedure. Examples of device-related adverse events are: myocardial perforation, Single Leaflet Device Attachment, embolization of the MitraClip device or MitraClip System components, iatrogenic atrial septal defect, mitral valve stenosis, need for mitral valve replacement instead of repair due at least in part to the MitraClip procedure or the presence of the MitraClip device.
2. Implant Rate [ Time Frame: Day 0 ]
   Defined as the rate of successful delivery and deployment of the MitraClip device(s) with echocardiographic evidence of leaflet approximation and retrieval of the delivery catheter
3. Device Procedure Time [ Time Frame: Day 0 ]
   Defined as the time elapsed from the start of the transseptal procedure to the time the Steerable Guide Catheter is removed
4. Total Procedure Time [ Time Frame: Day 0 ]
   Defined as the time elapsed from the first of any of the following: intravascular catheter placement, anesthesia or sedation, or transesophageal echocardiogram (TEE), to the removal of the last catheter and TEE
5. Device Time [ Time Frame: Day 0 ]
   Defined as the time the Steerable Guide Catheter is placed in the intra-atrial septum until the time the MitraClip Delivery System (CDS) is retracted into the Steerable Guide Catheter
6. Fluoroscopy Duration [ Time Frame: Day 0 ]
   Defined as the duration of exposure to fluoroscopy during the MitraClip procedure
7. MR Severity Grade [ Time Frame: Baseline ]

   MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

   MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

8. MR Severity Grade [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]

   MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

   MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

9. MR Severity Grade [ Time Frame: 6 months ]

   MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

   MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

10. MR Severity Grade [ Time Frame: 12 months ]

    MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

    MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

11. MR Severity Grade [ Time Frame: 24 months ]

    MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below

    MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR 2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR 3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2 MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2

12. MR Severity Grade [ Time Frame: 3 years ]
    MR Severity Grading was done by Quantitative Doppler Echocardiography and subjects were graded as below MR 1+ - Regurgitant Volume < 30 ml, Right ventricular EF <30%, Effective regurgitant orifice area < 20 mm^2 MR2+ - Regurgitant Volume 30-44 ml, Right ventricular EF 30-39%, Effective regurgitant orifice area 20-29 mm^2 MR3+ - Regurgitant Volume 45-59 ml, Right ventricular EF 40-49 %, Effective regurgitant orifice area 30-39 mm^2MR 4+ - Regurgitant Volume >= 60 ml, Right ventricular EF >=50%, Effective regurgitant orifice area >=40 mm^2
13. MR Severity Grade [ Time Frame: 4 years ]
14. MR Severity Grade [ Time Frame: 5 years ]
15. Effective Regurgitant Orifice Area [ Time Frame: Baseline ]
    Effective Regurgitant Orifice area is defined as = Regurgitant flow / Regurgitant velocity
16. Effective Regurgitant Orifice Area [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
    Effective Regurgitant Orifice area is defined as = Regurgitant flow / Regurgitant velocity
17. Effective Regurgitant Orifice Area [ Time Frame: 6 months ]
    Effective Regurgitant Orifice area is defined as = Regurgitant flow / Regurgitant velocity
18. Effective Regurgitant Orifice Area [ Time Frame: 12 months ]
    Effective Regurgitant Orifice area is defined as = Regurgitant flow / Regurgitant velocity
19. Effective Regurgitant Orifice Area [ Time Frame: 24 months ]
    Effective Regurgitant Orifice area is defined as = Regurgitant flow / Regurgitant velocity
20. Effective Regurgitant Orifice Area [ Time Frame: 3 years ]
    Effective Regurgitant Orifice area is defined as = Regurgitant flow / Regurgitant velocity
21. Effective Regurgitant Orifice Area [ Time Frame: 4 years ]
22. Effective Regurgitant Orifice Area [ Time Frame: 5 years ]
23. Regurgitant Volume [ Time Frame: Baseline ]
    Regurgitant Volume is calculated by subtracting the inflow volume across the mitral valve during diastole from the Left Ventricular Outflow Tract (LVOT) stroke volume during systole.
24. Regurgitant Volume [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
    Regurgitant Volume is calculated by subtracting the inflow volume across the mitral valve during diastole from the Left Ventricular Outflow Tract (LVOT) stroke volume during systole.
25. Regurgitant Volume [ Time Frame: 6 months ]
    Regurgitant Volume is calculated by subtracting the inflow volume across the mitral valve during diastole from the Left Ventricular Outflow Tract (LVOT) stroke volume during systole.
26. Regurgitant Volume [ Time Frame: 12 months ]
    Regurgitant Volume is calculated by subtracting the inflow volume across the mitral valve during diastole from the Left Ventricular Outflow Tract (LVOT) stroke volume during systole.
27. Regurgitant Volume [ Time Frame: 24 months ]
    Regurgitant Volume is calculated by subtracting the inflow volume across the mitral valve during diastole from the Left Ventricular Outflow Tract (LVOT) stroke volume during systole.
28. Regurgitant Volume [ Time Frame: 3 years ]
    Regurgitant Volume is calculated by subtracting the inflow volume across the mitral valve during diastole from theLeft Ventricular Outflow Tract (LVOT) stroke volume during systole.
29. Regurgitant Volume [ Time Frame: 4 years ]
30. Regurgitant Volume [ Time Frame: 5 years ]
31. Regurgitant Fraction [ Time Frame: Baseline ]
    Regurgitant fraction is the percentage of blood that regurgitates back through the aortic valve to the left ventricle due to aortic insufficiency, or through the mitral valve to the atrium due to mitral insufficiency.
32. Regurgitant Fraction [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
    Regurgitant fraction is the percentage of blood that regurgitates back through the aortic valve to the left ventricle due to aortic insufficiency, or through the mitral valve to the atrium due to mitral insufficiency.
33. Regurgitant Fraction [ Time Frame: 6 months ]
    Regurgitant fraction is the percentage of blood that regurgitates back through the aortic valve to the left ventricle due to aortic insufficiency, or through the mitral valve to the atrium due to mitral insufficiency.
34. Regurgitant Fraction [ Time Frame: 12 months ]
    Regurgitant fraction is the percentage of blood that regurgitates back through the aortic valve to the left ventricle due to aortic insufficiency, or through the mitral valve to the atrium due to mitral insufficiency.
35. Regurgitant Fraction [ Time Frame: 24 months ]
    Regurgitant fraction is the percentage of blood that regurgitates back through the aortic valve to the left ventricle due to aortic insufficiency, or through the mitral valve to the atrium due to mitral insufficiency.
36. Regurgitant Fraction [ Time Frame: 3 years ]
    Regurgitant fraction is the percentage of blood that regurgitates back through the aortic valve to the left ventricledue to aortic insufficiency, or through the mitral valve to the atrium due to mitral insufficiency.
37. Regurgitant Fraction [ Time Frame: 4 years ]
38. Regurgitant Fraction [ Time Frame: 5 years ]
39. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: Baseline ]
    Left Ventricle End-diastolic volume is the amount of blood that is in the left ventricle before the heart contracts.
40. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
    Left Ventricle End-diastolic volume is the amount of blood that is in the left ventricle before the heart contracts.
41. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 6 months ]
    Left Ventricle End-diastolic volume is the amount of blood that is in the left ventricle before the heart contracts.
42. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 12 months ]
    Left Ventricle End-diastolic volume is the amount of blood that is in the left ventricle before the heart contracts.
43. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 24 months ]
    Left Ventricle End-diastolic volume is the amount of blood that is in the left ventricle before the heart contracts.
44. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 3 years ]
    Left Ventricle End-diastolic volume is the amount of blood that is in the left ventricle before the heart contracts.
45. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 4 years ]
46. Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 5 years ]
47. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: Baseline ]
    Left Ventricular End-systolic volume (LVESV) is the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. LVESV is the lowest volume of blood in the left ventricle at any point in the cardiac cycle.
48. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
    Left Ventricular End-systolic volume (LVESV) is the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. LVESV is the lowest volume of blood in the left ventricle at any point in the cardiac cycle.
49. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 6 months ]
    Left Ventricular End-systolic volume (LVESV) is the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. LVESV is the lowest volume of blood in the left ventricle at any point in the cardiac cycle.
50. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 12 months ]
    Left Ventricular End-systolic volume (LVESV) is the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. LVESV is the lowest volume of blood in the left ventricle at any point in the cardiac cycle.
51. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 24 months ]
    Left Ventricular End-systolic volume (LVESV) is the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. LVESV is the lowest volume of blood in the left ventricle at any point in the cardiac cycle.
52. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 3 years ]
    Left Ventricular End-systolic volume (LVESV) is the volume of blood in the left ventricle at the end of contraction,or systole, and the beginning of filling, or diastole. LVESV is the lowest volume of blood in the left ventricle at anypoint in the cardiac cycle.
53. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 4 years ]
54. Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 5 years ]
55. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: Baseline ]
56. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
57. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 6 months ]
58. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 12 months ]
59. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 24 months ]
60. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 3 years ]
61. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 4 years ]
62. Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 5 years ]
63. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: Baseline ]
64. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
65. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 6 months ]
66. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 12 months ]
67. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 24 months ]
68. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 3 years ]
69. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 4 years ]
70. Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 5 years ]
71. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline ]
72. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
73. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 6 months ]
74. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 12 months ]
75. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 24 months ]
76. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 3 years ]
77. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 4 years ]
78. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 5 years ]
79. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: Baseline ]
80. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
81. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 6 months ]
82. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 12 months ]
83. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 24 months ]
84. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 3 years ]
85. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 4 years ]
86. Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 5 years ]
87. Mitral Valve Area [ Time Frame: Baseline ]
88. Mitral Valve Area [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
89. Mitral Valve Area [ Time Frame: 6 months ]
90. Mitral Valve Area [ Time Frame: 12 months ]
91. Mitral Valve Area [ Time Frame: 24 months ]
92. Mitral Valve Area [ Time Frame: 3 years ]
93. Mitral Valve Area [ Time Frame: 4 years ]
94. Mitral Valve Area [ Time Frame: 5 years ]
95. Mean Mitral Valve Gradient [ Time Frame: Baseline ]
    The normal area of the mitral valve orifice is about 4-6 cm2 when the mitral valve area goes below 2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient (mitral valve gradient) across the mitral valve. This gradient may increase by the rise in heart rate or cardiac output.
96. Mean Mitral Valve Gradient [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
    The normal area of the mitral valve orifice is about 4-6 cm2 when the mitral valve area goes below 2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient (mitral valve gradient) across the mitral valve. This gradient may increase by the rise in heart rate or cardiac output.
97. Mean Mitral Valve Gradient [ Time Frame: 6 months ]
    The normal area of the mitral valve orifice is about 4-6 cm2 when the mitral valve area goes below 2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient (mitral valve gradient) across the mitral valve. This gradient may increase by the rise in heart rate or cardiac output.
98. Mean Mitral Valve Gradient [ Time Frame: 12 months ]
    The normal area of the mitral valve orifice is about 4-6 cm2 when the mitral valve area goes below 2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient (mitral valve gradient) across the mitral valve. This gradient may increase by the rise in heart rate or cardiac output.
99. Mean Mitral Valve Gradient [ Time Frame: 24 months ]
    The normal area of the mitral valve orifice is about 4-6 cm2 when the mitral valve area goes below 2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient (mitral valve gradient) across the mitral valve. This gradient may increase by the rise in heart rate or cardiac output.
100. Mean Mitral Valve Gradient [ Time Frame: 3 years ]
     The normal area of the mitral valve orifice is about 4-6 cm2 when the mitral valve area goes below 2 cm2, thevalve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient (mitral valvegradient) across the mitral valve. This gradient may increase by the rise in heart rate or cardiac output.
101. Mean Mitral Valve Gradient [ Time Frame: 4 years ]
102. Mean Mitral Valve Gradient [ Time Frame: 5 years ]
103. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: Baseline ]
104. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
105. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: 6 months ]
106. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: 12 months ]
107. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: 24 months ]
108. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: 3 years ]
109. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: 4 years ]
110. Systolic Anterior Motion of the Mitral Valve (Present or Absent) [ Time Frame: 5 years ]
111. Cardiac Output [ Time Frame: Baseline ]
     The amount of blood the heart pumps through the circulatory system in a minute.
112. Cardiac Output [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
     The amount of blood the heart pumps through the circulatory system in a minute.
113. Cardiac Output [ Time Frame: 6 months ]
     The amount of blood the heart pumps through the circulatory system in a minute.
114. Cardiac Output [ Time Frame: 12 months ]
     The amount of blood the heart pumps through the circulatory system in a minute.
115. Cardiac Output [ Time Frame: 24 months ]
     The amount of blood the heart pumps through the circulatory system in a minute.
116. Cardiac Output [ Time Frame: 3 years ]
117. Cardiac Output [ Time Frame: 4 years ]
118. Cardiac Output [ Time Frame: 5 years ]
119. Forward Stroke Volume [ Time Frame: Baseline ]
     Stroke volume is the amount of blood ejected from the ventricle with each cardiac cycle. It can be readily calculated by subtracting the end-systolic volume from the end-diastolic volume.
120. Forward Stroke Volume [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ]
     Stroke volume is the amount of blood ejected from the ventricle with each cardiac cycle. It can be readily calculated by subtracting the end-systolic volume from the end-diastolic volume.
121. Forward Stroke Volume [ Time Frame: 6 months ]
     Stroke volume is the amount of blood ejected from the ventricle with each cardiac cycle. It can be readily calculated by subtracting the end-systolic volume from the end-diastolic volume.
122. Forward Stroke Volume [ Time Frame: 12 months ]
     Stroke volume is the amount of blood ejected from the ventricle with each cardiac cycle. It can be readily calculated by subtracting the end-systolic volume from the end-diastolic volume.
123. Forward Stroke Volume [ Time Frame: 24 months ]
     Stroke volume is the amount of blood ejected from the ventricle with each cardiac cycle. It can be readily calculated by subtracting the end-systolic volume from the end-diastolic volume.
124. Forward Stroke Volume [ Time Frame: 3 years ]
125. Forward Stroke Volume [ Time Frame: 4 years ]
126. Forward Stroke Volume [ Time Frame: 5 years ]
127. Kaplan-Meier Freedom From the Components of the Primary Safety Composite [ Time Frame: 12 months in Device group ]
     Freedom from the components of the primary safety composite of device related complications including Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, or any device related complications requiring non-elective cardiovascular surgery at 12 months will be the primary measure of safety.
128. Kaplan-Meier Freedom From the Components of the Primary Safety Composite [ Time Frame: 24 months in Device group ]
     Freedom from the components of the primary safety composite of device related complications including Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, or any device related complications requiring non-elective cardiovascular surgery at 12 months will be the primary measure of safety.
129. Kaplan-Meier Freedom From the Components of the Primary Safety Composite [ Time Frame: 3 years in Device group ]
     Freedom from the components of the primary safety composite of device related complications including Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, or any device related complications requiring non-elective cardiovascular surgery at 12 months will be the primary measure of safety.
130. Kaplan-Meier Freedom From the Components of the Primary Safety Composite [ Time Frame: 4 years in Device group ]
131. Kaplan-Meier Freedom From the Components of the Primary Safety Composite [ Time Frame: 5 years in Device group ]
132. Kaplan-Meier Freedom From the Primary Safety Composite [ Time Frame: 24 months in Device group ]
     Freedom from the primary safety composite of device related complications including Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, or any device related complications requiring non-elective cardiovascular surgery at 12 months will be the primary measure of safety.
133. Kaplan-Meier Freedom From the Primary Safety Composite [ Time Frame: 3 years in Device group ]
     Freedom from the primary safety composite of device related complications including Single Leaflet DeviceAttachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratoryconfirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, or any device related complicationsrequiring non-elective cardiovascular surgery at 12 months will be the primary measure of safety.
134. Kaplan-Meier Freedom From the Primary Safety Composite [ Time Frame: 4 years in Device group ]
135. Kaplan-Meier Freedom From the Primary Safety Composite [ Time Frame: 5 years in Device group ]
136. Kaplan-Meier Freedom From All-cause Mortality [ Time Frame: 24 months ]
     Kaplan-Meier survival rate for all cause mortality at 24 months
137. Kaplan-Meier Freedom From All-cause Mortality [ Time Frame: 3 years ]
     Kaplan-Meier survival rate for all cause mortality at 36 months
138. Kaplan-Meier Freedom From All-cause Mortality [ Time Frame: 4 years ]
139. Kaplan-Meier Freedom From All-cause Mortality [ Time Frame: 5 years ]
140. Kaplan-Meier Freedom From Cardiovascular Mortality [ Time Frame: 12 months ]
     Kaplan-Meier survival rate for Cardiovascular mortality.
141. Kaplan-Meier Freedom From Cardiovascular Mortality [ Time Frame: 24 months ]
     Kaplan-Meier survival rate for Cardiovascular mortality.
142. Kaplan-Meier Freedom From Cardiovascular Mortality [ Time Frame: 3 years ]
     Kaplan-Meier survival rate for Cardiovascular mortality.
143. Kaplan-Meier Freedom From Cardiovascular Mortality [ Time Frame: 4 years ]
144. Kaplan-Meier Freedom From Cardiovascular Mortality [ Time Frame: 5 years ]
145. Kaplan-Meier Freedom From the First HF Related Hospitalization [ Time Frame: 12 months ]
146. Kaplan-Meier Freedom From the First HF Related Hospitalization [ Time Frame: 24 months ]
147. Kaplan-Meier Freedom From the First HF Related Hospitalization [ Time Frame: 3 years ]
148. Kaplan-Meier Freedom From the First HF Related Hospitalization [ Time Frame: 4 years ]
149. Kaplan-Meier Freedom From the First HF Related Hospitalization [ Time Frame: 5 years ]
150. Kaplan-Meier Freedom From the First Cardiovascular Hospitalization [ Time Frame: 12 months ]
151. Kaplan-Meier Freedom From the First Cardiovascular Hospitalization [ Time Frame: 24 months ]
152. Kaplan-Meier Freedom From the First Cardiovascular Hospitalization [ Time Frame: 3 years ]
153. Kaplan-Meier Freedom From the First Cardiovascular Hospitalization [ Time Frame: 4 years ]
154. Kaplan-Meier Freedom From the First Cardiovascular Hospitalization [ Time Frame: 5 years ]
155. Kaplan-Meier Freedom From the First HF Related Hospitalization or All-cause Mortality [ Time Frame: 12 months ]
156. Kaplan-Meier Freedom From the First HF Related Hospitalization or All-cause Mortality [ Time Frame: 24 months ]
     Survival rate from the first HF related hospitalization or all-cause mortality.
157. Kaplan-Meier Freedom From the First HF Related Hospitalization or All-cause Mortality [ Time Frame: 3 years ]
158. Kaplan-Meier Freedom From the First HF Related Hospitalization or All-cause Mortality [ Time Frame: 4 years ]
159. Kaplan-Meier Freedom From the First HF Related Hospitalization or All-cause Mortality [ Time Frame: 5 years ]
160. NYHA Functional Class [ Time Frame: Baseline ]

     Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

     Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due to symptoms Class IV: Severe limitations

161. NYHA Functional Class [ Time Frame: 30 days ]

     Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

     Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due to symptoms Class IV: Severe limitations

162. NYHA Functional Class [ Time Frame: 6 months ]

     Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

     Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due to symptoms Class IV: Severe limitations

163. NYHA Functional Class [ Time Frame: 12 months ]

     Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

     Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due to symptoms Class IV: Severe limitations

164. NYHA Functional Class [ Time Frame: 24 months ]

     Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity:

     Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due to symptoms Class IV: Severe limitations

165. NYHA Functional Class [ Time Frame: 3 years ]

     Measure Description: The New York Heart Association (NYHA) Classification provides a simple way of classifyingthe extent of heart failure. It classifies patients in one of four categories based on their limitations during physicalactivity:

     Class I: No symptoms and no limitation in ordinary physical activity Class II: Mild symptoms (mild shortness ofbreath and/or angina) and slight limitation during ordinary activity Class III: Marked limitation in activity due tosymptoms Class IV: Severe limitations

166. NYHA Functional Class [ Time Frame: 4 years ]
167. NYHA Functional Class [ Time Frame: 5 years ]
168. Six-Minute Walk Test Distance (6MWD) [ Time Frame: Baseline ]
     Six-Minute Walk Test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk test distance (6 MWD) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
169. 6MWD [ Time Frame: 30 days ]
     Six-Minute Walk Test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk test distance (6 MWD) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
170. 6MWD [ Time Frame: 6 months ]
     Six-Minute Walk Test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk test distance (6 MWD) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
171. 6MWD [ Time Frame: 12 months ]
     Six-Minute Walk Test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk test distance (6 MWD) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
172. 6MWD [ Time Frame: 24 months ]
     Six-Minute Walk Test is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6-minute walk test distance (6 MWD) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
173. Change in 6MWD From Baseline [ Time Frame: Between baseline and 30 days ]
174. Change in 6MWD From Baseline [ Time Frame: Between baseline and 6 months ]
175. Change in 6MWD From Baseline [ Time Frame: Between baseline and 12 months ]
176. Change in 6MWD From Baseline [ Time Frame: Between baseline and 24 months ]
177. Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL Scores [ Time Frame: Baseline ]

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

178. KCCQ QoL Scores [ Time Frame: 30 days ]

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

179. KCCQ QoL Scores [ Time Frame: 6 months ]

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

180. KCCQ QoL Scores [ Time Frame: 12 months ]

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

181. KCCQ QoL Scores [ Time Frame: 24 months ]

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

182. Change in KCCQ QoL Scores From Baseline [ Time Frame: Between baseline and 30 days ]

     Paired data looking at difference between the baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and 30 days KCCQ score.

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

183. Change in KCCQ QoL Scores From Baseline [ Time Frame: Between baseline and 6 months ]

     Paired data looking at difference between the baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6 months KCCQ score.

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

184. Change in KCCQ QoL Scores From Baseline [ Time Frame: Between baseline and 12 months ]

     Paired data looking at difference between the baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and 12 months KCCQ score.

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

185. Change in KCCQ QoL Scores From Baseline [ Time Frame: Between baseline and 24 months ]

     Paired data looking at difference between the baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and 24 months KCCQ score.

     The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores: KCCQ Symptom Domain, KCCQ Physical Function Domain, KCCQ Quality of Life Domain, KCCQ Social Limitation Domain, KCCQ Self-efficacy Domain, KCCQ Symptom Stability Domain, Clinical Summary Score and Overall Summary Score.

     Clinical Summary Score includes total symptom and physical function scores to correspond with NYHA Classification.

     Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores.

186. SF-36 QoL Scores [ Time Frame: Baseline ]
     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
187. SF-36 QoL Scores [ Time Frame: 30 days ]
     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
188. SF-36 QoL Scores [ Time Frame: 6 months ]
     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
189. SF-36 QoL Scores [ Time Frame: 12 months ]
     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
190. SF-36 QoL Scores [ Time Frame: 24 months ]
     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
191. Change in SF-36 QoL Scores From Baseline [ Time Frame: Between baseline and 30 days ]
     Paired data looking at difference between the baseline SF-36 and 30 days SF-36. The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
192. Change in SF-36 QoL Scores From Baseline [ Time Frame: Between baseline and 6 months ]

     Paired data looking at difference between the baseline SF-36 and 6 months days SF-36.

     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).

193. Change in SF-36 QoL Scores From Baseline [ Time Frame: Between baseline and 12 months ]

     Paired data looking at difference between the baseline SF-36 and 12 month SF-36.

     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).

194. Change in SF-36 QoL Scores From Baseline [ Time Frame: Between baseline and 24 months ]

     Paired data looking at difference between the baseline SF-36 and 24 months SF-36.

     The 36-Item Short Form Health Survey questionnaire (SF-36) is a very popular instrument for evaluating Health-Related Quality of Life. with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. There are two distinct concepts measured by the SF-36: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).

195. Mitral Valve Surgery (Including Type of Surgery), New Use of CRT, New Use of Single or Dual Chamber Pacemaker, Permanent LVAD Implant, Heart Transplant, Additional MitraClip Device Intervention in Device Group [ Time Frame: Through 5 years ]
196. De Novo MitraClip Device Intervention in Control Group [ Time Frame: Through 5 years ]
197. Responder Analysis for 6MWD [ Time Frame: 12 months ]
     Where responder is defined as alive and experiencing an improvement of 24 meters and 50 meters (difference in proportion of responders between Device and Control groups)
198. Responder Analysis for 6MWD [ Time Frame: 24 months ]
     Where responder is defined as alive and experiencing an improvement of 24 meters and 50 meters (difference in proportion of responders between Device and Control groups)
199. Responder Analysis for LVEDV Index [ Time Frame: 12 months ]
     Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)
200. Responder Analysis for LVEDV Index [ Time Frame: 24 months ]
     Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)
201. Responder Analysis for LVEDV Index [ Time Frame: 3 years ]
     Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)
202. Responder Analysis for LVEDV Index [ Time Frame: 4 years ]
     Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)
203. Responder Analysis for LVEDV Index [ Time Frame: 5 years ]
     Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)
204. Responder Analysis for QoL (KCCQ) [ Time Frame: 12 months ]
     Where responder is defined as alive and experiencing an improvement of 5 points (difference in proportion of responders between Device and Control groups)
205. Responder Analysis for QoL (KCCQ) [ Time Frame: 24 months ]
     Where responder is defined as alive and experiencing an improvement of 5 points (difference in proportion of responders between Device and Control groups)
206. Each Subscale for QoL (KCCQ) [ Time Frame: 12 months ]
     difference in means between Device and Control groups for the Kansas City Cardiomyopathy Questionnaire (KCCQ) for the physical limitation and symptom stability scores.
207. Each Subscale for QoL (KCCQ) [ Time Frame: 24 months ]
     difference in means between Device and Control groups for the Kansas City Cardiomyopathy Questionnaire (KCCQ) for the physical limitation and symptom stability scores.
208. Length of Index Hospitalization for MitraClip Procedure (Device Group) [ Time Frame: Before MitraClip procedure on day 0 ]
     Length of stay in the hospital for the MitraClip Index procedure (device group)
209. Number of Hospitalizations and Reason for Hospitalization (i.e. Heart Failure, Cardiovascular, Non-cardiovascular) [ Time Frame: 12 months ]
     in each of the Device and Control groups
210. Number of Hospitalizations and Reason for Hospitalization (i.e. Heart Failure, Cardiovascular, Non-cardiovascular) [ Time Frame: 24 months ]
     in each of the Device and Control groups
211. Number of Days Alive and Out of Hospital [ Time Frame: From the time of randomization to 12 months ]
     mean no of days alive and out of hospital in both Device and Control groups
212. Number of Days Alive and Out of Hospital [ Time Frame: From the time of randomization to 24 months ]
     mean Number of days alive and out of hospital for the Device and Control groups
213. Number of Days Alive and Out of Hospital [ Time Frame: From the time of randomization to 3 Years ]
     Mean Number of days alive and out of hospital for the Device and Control groups
214. Number of Days Alive and Out of Hospital [ Time Frame: From the time of randomization to 4 Years ]
     difference in medians between Device and Control groups
215. Number of Days Alive and Out of Hospital [ Time Frame: From the time of randomization to 5 Years ]
     difference in medians between Device and Control groups
216. Number of Days Hospitalized From the "Treatment" Visit [ Time Frame: 12 months ]
     mean Number of days hospitalized from the "Treatment" visit for the Device and Control groups
217. Number of Days Hospitalized From the "Treatment" Visit [ Time Frame: 24 months ]
     mean Number of days hospitalized from the "Treatment" visit for the Device and Control groups
218. Number of Days Hospitalized From the "Treatment" Visit [ Time Frame: 3 Years ]
     mean Number of days hospitalized from the "Treatment" visit for the Device and Control groups
219. Number of Days Hospitalized From the "Treatment" Visit [ Time Frame: 4 Years ]
     difference in medians between Device and Control groups
220. Number of Days Hospitalized From the "Treatment" Visit [ Time Frame: 5 Years ]
     difference in medians between Device and Control groups
221. Proportion of Alive Time in Hospital [ Time Frame: 12 months ]
     summarized and compared between Device and Control groups
222. Proportion of Alive Time in Hospital [ Time Frame: 24 months ]
     summarized and compared between Device and Control groups
223. Proportion of Alive Time in Hospital [ Time Frame: 3 years ]
     summarized and compared between Device and Control groups
224. Proportion of Alive Time in Hospital [ Time Frame: 4 years ]
     summarized and compared between Device and Control groups
225. Proportion of Alive Time in Hospital [ Time Frame: 5 years ]
     summarized and compared between Device and Control groups
226. Proportion of Subjects Living in the Baseline Location [ Time Frame: 12 months ]
     Subjects living in the baseline location include : home, retirement home, nursing facility and other location.
227. Proportion of Subjects Living in the Baseline Location [ Time Frame: 24 months ]
     Subjects living in the baseline location include : home, retirement home, nursing facility and other location.
228. Proportion of Subjects Living in the Baseline Location [ Time Frame: 3 years ]
229. Proportion of Subjects Living in the Baseline Location [ Time Frame: 4 years ]
230. Proportion of Subjects Living in the Baseline Location [ Time Frame: 5 years ]
231. Mitral Valve Replacement Rates [ Time Frame: 12 months ]
     Subjects with mitral valve replacements in the Device and Control groups
232. Mitral Valve Replacement Rates [ Time Frame: 24 months ]
     Subjects with mitral valve replacements in the Device and Control groups
233. Mitral Valve Replacement Rates [ Time Frame: 3 years ]
     summarized and compared between Device and Control groups
234. Mitral Valve Replacement Rates [ Time Frame: 4 years ]
     summarized and compared between Device and Control groups
235. Mitral Valve Replacement Rates [ Time Frame: 5 years ]
     summarized and compared between Device and Control groups
236. New Onset of Permanent Atrial Fibrillation [ Time Frame: 12 months ]
237. New Onset of Permanent Atrial Fibrillation [ Time Frame: 24 months ]
238. New Onset of Permanent Atrial Fibrillation [ Time Frame: 3 years ]
239. New Onset of Permanent Atrial Fibrillation [ Time Frame: 4 years ]
240. New Onset of Permanent Atrial Fibrillation [ Time Frame: 5 years ]
241. Mitral Stenosis [ Time Frame: 12 months ]
     Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory
242. Mitral Stenosis [ Time Frame: 24 months ]
     Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory
243. Mitral Stenosis [ Time Frame: 3 years ]
     Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory
244. Mitral Stenosis [ Time Frame: 4 years ]
     Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory
245. Mitral Stenosis [ Time Frame: 5 years ]
     Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory
246. Clinically Significant Atrial Septal Defect (ASD) That Requires Intervention [ Time Frame: 12 months ]
247. Clinically Significant Atrial Septal Defect (ASD) That Requires Intervention [ Time Frame: 24 months ]
248. Clinically Significant Atrial Septal Defect (ASD) That Requires Intervention [ Time Frame: 3 years ]
249. Clinically Significant Atrial Septal Defect (ASD) That Requires Intervention [ Time Frame: 4 years ]
250. Clinically Significant Atrial Septal Defect (ASD) That Requires Intervention [ Time Frame: 5 years ]
251. Device-related Complications in Device Group Subjects and Control Group Subjects Who Undergo the MitraClip Procedure [ Time Frame: Through 5 years ]
252. Brain Natriuretic Peptide (BNP) or N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP Levels) [ Time Frame: Baseline ]
253. BNP or NT-proBNP Levels [ Time Frame: 30 days ]
254. BNP or NT-proBNP Levels [ Time Frame: 12 months ]
255. Modified Rankin Scale Score [ Time Frame: Baseline ]

     MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

     0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead

256. Modified Rankin Scale Score [ Time Frame: 30 days ]

     MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

     0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead

257. Modified Rankin Scale Score [ Time Frame: 6 months ]

     MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

     0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead

258. Modified Rankin Scale Score [ Time Frame: 12 months ]

     MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

     0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead

259. Major Bleeding [ Time Frame: 30 days ]
     Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding Academic Research Consortium (BARC) definition
260. Prolonged Ventilation [ Time Frame: 30 days ]
     Defined as pulmonary insufficiency requiring ventilatory support for greater than 48 hours post-catheterization
261. Average Dosages of Guideline Directed Medical Therapy (GDMT) [ Time Frame: Baseline ]
262. Average Dosages of GDMT [ Time Frame: 30 days ]
263. Average Dosages of GDMT [ Time Frame: 6 months ]
264. Average Dosages of GDMT [ Time Frame: 12 months ]
265. Average Dosages of GDMT [ Time Frame: 24 months ]
266. Average Dosages of GDMT [ Time Frame: 3 years ]
267. Average Dosages of GDMT [ Time Frame: 4 years ]
268. Average Dosages of GDMT [ Time Frame: 5 years ]
269. The Number of Subjects With Changes in GDMT Dosage From Baseline [ Time Frame: Between baseline and 30 days ]
270. The Number of Subjects With Changes in GDMT Dosage From Baseline to 6 Months [ Time Frame: Between baseline and 6 months ]
271. The Number of Subjects With Changes in GDMT Dosage From Baseline and 12 Months [ Time Frame: Between baseline and 12 months ]
272. The Number of Subjects With Changes in GDMT Dosage From Baseline and 24 Months [ Time Frame: Between baseline and 24 months ]
273. The Number and Reasons for Any Changes in GDMT and GDMT Dosage From Baseline [ Time Frame: Between baseline and 3 years ]
274. The Number and Reasons for Any Changes in GDMT and GDMT Dosage From Baseline [ Time Frame: Between baseline and 4 years ]
275. The Number and Reasons for Any Changes in GDMT and GDMT Dosage From Baseline [ Time Frame: Between baseline and 5 years ]
276. The Number of Subjects With Change in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 30 days ]
277. The Number of Subjects With Any Changes in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 6 months ]
278. The Number of Subjects With Any Changes in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 12 months ]
279. The Number of Subjects With Any Changes in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 24 months ]
280. The Number and Reasons for Any Changes in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 3 years ]
281. The Number and Reasons for Any Changes in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 4 years ]
282. The Number and Reasons for Any Changes in GDMT From Baseline That Result in a Greater Than 100% Increase or Greater Than 50% Decrease in Dose [ Time Frame: Between baseline and 5 years ]
283. Cardiopulmonary Exercise (CPX) Testing [ Time Frame: Baseline ]

     A substudy endpoint will utilize peak oxygen consumption oxygen uptake (VO2) as a parameter for cardiopulmonary exercise testing on a total of at least 50 and up to 100 subjects.

     The CPX analysis variables are:

     • Peak VO2 (ml/kg/min) - CPX Sub-study endpoint, descriptive analysis only, not powered for statistical significance
     • Exercise duration (min)
     • Peak workload (watts)
     • Maximum heart rate during exercise (beats/min)
     • Peak VE (l/min)
     • Respiratory Exchange Ratio (RER, VCO2/VO2)
     • VE/VCO2 slope
     • Ventilatory Threshold (ml/kg/min)
     • Borg scale
     • Exercise termination reason
     • Type of exercise (treadmill vs cycling)
284. Cardiopulmonary Exercise (CPX) Testing [ Time Frame: 12 months ]

     A substudy endpoint will utilize peak oxygen consumption oxygen uptake (VO2) as a parameter for cardiopulmonary exercise testing on a total of at least 50 and up to 100 subjects.

     The CPX analysis variables are:

     • Peak VO2 (ml/kg/min) - CPX Sub-study endpoint, descriptive analysis only, not powered for statistical significance
     • Exercise duration (min)
     • Peak workload (watts)
     • Maximum heart rate during exercise (beats/min)
     • Peak VE (l/min)
     • Respiratory Exchange Ratio (RER, VCO2/VO2)
     • VE/VCO2 slope
     • Ventilatory Threshold (ml/kg/min)
     • Borg scale
     • Exercise termination reason
     • Type of exercise (treadmill vs cycling)
285. Cardiopulmonary Exercise (CPX) Testing: Mean Changes in Peak VO2 [ Time Frame: Between baseline and 12 months ]

     Mean changes in peak VO2 (ml/kg/min) will be summarized at 12 months from baseline for the subset of patients who complete a CPX test at baseline and 12 months. A comparison of change from baseline between Device and Control groups will be presented.

     The CPX analysis variables are:

     • Peak VO2 (ml/kg/min) - CPX Sub-study endpoint, descriptive analysis only, not powered for statistical significance
     • Exercise duration (min)
     • Peak workload (watts)
     • Maximum heart rate during exercise (beats/min)
     • Peak VE (l/min)
     • Respiratory Exchange Ratio (RER, VCO2/VO2)
     • VE/VCO2 slope
     • Ventilatory Threshold (ml/kg/min)
     • Borg scale
     • Exercise termination reason
     • Type of exercise (treadmill vs cycling)
286. Health Economic Data [ Time Frame: Through 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Symptomatic functional MR (≥3+) due to cardiomyopathy of either ischemic or non-ischemic etiology determined by assessment of a qualifying transthoracic echocardiogram (TTE) obtained within 90 days and transesophageal echocardiogram (TEE) obtained within 180 days prior to subject registration, with MR severity based principally on the TTE study, confirmed by the Echocardiography Core Lab (ECL). The ECL may request a transesophageal echocardiogram (TEE) to confirm MR etiology.

   Note: Functional MR requires the presence of global or regional left ventricular wall motion abnormalities, which are believed to be the primary cause of the MR. If a flail leaflet or other evidence of degenerative MR is present, the subject is not eligible even if global or regional left ventricular systolic dysfunction is present.

   Note: Qualifying TTE must be obtained after the subject has been stabilized on optimal therapy including Guideline Directed Medical Therapy (GDMT) and at least 30 days after:

   1. a greater than 100% increase or greater than 50% decrease in dose of GDMT
   2. revascularization and/or implant of Cardiac Resynchronization Therapy device (CRT or CRT-D) or reprogramming of an implanted CRT or CRT-D that results in increased biventricular pacing (from <92% to ≥92%)
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 GDMT). The Eligibility Committee must also concur that the subject has been adequately treated.
3. New York Heart Association (NYHA) Functional Class II, III or ambulatory IV.
4. The Local Site Heart Team (CT surgeon and HF specialist investigators) and the Central Eligibility Committee concur that surgery will not be offered as a treatment option and that medical therapy is the intended therapy for the subject, even if the subject is randomized to the Control group.

5. The subject has had at least one hospitalization for heart failure in the 12 months prior to subject registration and/or a corrected brain natriuretic peptide (BNP) ≥300 pg/ml or corrected n-Terminal pro- brain natriuretic peptide NT-proBNP ≥1500 pg/ml measured within 90 days prior to subject registration ("corrected" refers to a 4% reduction in the BNP or NT-proBNP cutoff for every increase of 1 kg/m2 in BMI above a reference BMI of 20 kg/m2).

   Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on GDMT and at least 30 days after:

   1. a greater than 100% increase or greater than 50% decrease in dose of GDMT
   2. revascularization and/or implant of Cardiac Resynchronization Therapy device (CRT or CRT-D) or reprogramming of an implanted CRT or CRT-D that results in increased biventricular pacing (from <92% to ≥92%).

6. Left Ventricular Ejection Fraction (LVEF) is ≥20% and ≤50% within 90 days prior to subject registration, assessed by the site using any one of the following methods: echocardiography, contrast left ventriculography, gated blood pool scan or cardiac magnetic resonance imaging (MRI).

   Note: The method must provide a quantitative readout (not a visual assessment).

7. The primary regurgitant jet is non-commissural, and in the opinion of the MitraClip implanting investigator can be successfully be treated by the MitraClip. If a secondary jet exists, it must be considered clinically insignificant.
8. Creatine Kinase-MB (CK-MB) obtained within prior 14 days < local laboratory Upper Limit of Normal (ULN).
9. Transseptal catheterization and femoral vein access is determined to be feasible by the MitraClip implanting investigator.
10. Age 18 years or older.
11. 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 registered in this trial.
12. 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.
13. Left Ventricular End Systolic Dimension (LVESD) is ≤ 70 mm assessed by site based on a transthoracic echocardiographic (TTE) obtained within 90 days prior to subject registration.

For the CPX Sub-study: Subjects have to meet the COAPT study eligibility criteria to be registered in the CPX Sub-study.

COAPT CAS study Inclusion Criteria:

1. Subjects must meet all of the above COAPT RCT inclusion criteria, and must have national Medicare coverage by the Centers for Medicare and Medicaid Services (CMS).

Exclusion Criteria:

1. Chronic Obstructive Pulmonary Disease (COPD) requiring continuous home oxygen therapy or chronic outpatient oral steroid use.
2. Untreated clinically significant coronary artery disease requiring revascularization.
3. Coronary artery bypass grafting (CABG) within 30 days prior to subject registration.
4. Percutaneous coronary intervention within 30 days prior to subject registration.
5. Transcatheter aortic valve replacement (TAVR) within 30 days prior to subject registration.
6. Tricuspid valve disease requiring surgery or transcatheter intervention.
7. Aortic valve disease requiring surgery.
8. Cerebrovascular accident within 30 days prior to subject registration.
9. Severe symptomatic carotid stenosis (> 70% by ultrasound).
10. Carotid surgery or stenting within 30 days prior to subject registration.
11. American College of Cardiology /American Heart Association (ACC/AHA) Stage D heart failure.

12. Presence of any of the following:

    • Estimated pulmonary artery systolic pressure (PASP) > 70 mm Hg assessed by site based on echocardiography or right heart catheterization, unless active vasodilator therapy in the cath lab is able to reduce the pulmonary vascular resistance (PVR) to < 3 Wood Units or between 3 and 4.5 Wood Units with v wave less than twice the mean of the pulmonary capillary wedge pressure
    • 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.
13. Physical evidence of right-sided congestive heart failure with echocardiographic evidence of moderate or severe right ventricular dysfunction as assessed by site.
14. Implant of any Cardiac Resynchronization Therapy (CRT) or Cardiac Resynchronization Therapy with cardioverter-defibrillator (CRT-D) within the last 30days prior to subject registration.
15. Mitral valve orifice area < 4.0 cm2 assessed by site based on a transthoracic echocardiogram (TTE) within 90 days prior to subject registration.

16. Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in MR by the MitraClip. This evaluation is based on transesophageal echocardiogram (TEE) evaluation of the mitral valve within 180 days prior to subject registration and includes:

    • Insufficient mobile leaflet available for grasping with the MitraClip device
    • 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
17. 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.
18. Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.
19. Life expectancy < 12 months due to non-cardiac conditions.
20. Modified Rankin Scale ≥ 4 disability.
21. Status 1 heart transplant or prior orthotopic heart transplantation.
22. Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve, or any prior transcatheter mitral valve procedure.
23. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
24. Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated).
25. Active infections requiring current antibiotic therapy.
26. Subjects in whom transesophageal echocardiography (TEE) is contraindicated or high risk.
27. Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically.

28. Pregnant or planning pregnancy within next 12 months.

    Note: Female patients of childbearing age should be instructed to use safe contraception (e.g. intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches hormonal vaginal devices, injections with prolonged release.

29. 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.
30. 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.

For the CPX Sub-study: Subjects who have any contraindications to CPX and are not capable of performing CPX per investigator's assessment should not be registered in the CPX Sub-study.

COAPT CAS study Exclusion Criteria:

1. Subjects must not meet any of the above COAPT RCT exclusion criteria.

.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, Arizona

Banner Good Samaritan Medical Center

Phoenix, Arizona, United States, 85006

Scottsdale Healthcare Hospitals

Scottsdale, Arizona, United States, 85258

United States, California

Scripps Green Hospital

La Jolla, California, United States, 92037

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

El Camino Hospital

Mountain View, California, United States, 94040

University California Davis Medical Center

Sacramento, California, United States, 95817

Kaiser Permanente - San Francisco Hospital

San Francisco, California, United States, 94115

Stanford Hospital and Clinics

Stanford, California, United States, 94305

United States, Colorado

University of Colorado Hospital

Denver, Colorado, United States, 80045

United States, Connecticut

Hartford Hospital

Hartford, Connecticut, United States, 06106

Yale - New Haven Hospital

New Haven, Connecticut, United States, 06510

United States, District of Columbia

Medstar Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

Morton Plant Hospital

Clearwater, Florida, United States, 33756

Mount Sinai Medical Center

Miami, Florida, United States, 33140

Florida Hospital Orlando

Orlando, Florida, United States, 32803

Sarasota Memorial Hospital

Sarasota, Florida, United States, 34239

Tallahassee Memorial Hospital

Tallahassee, Florida, United States, 32308

Tampa General Hospital

Tampa, Florida, United States, 33606

United States, Georgia

Piedmont Hospital Atlanta

Atlanta, Georgia, United States, 30309

Emory University Hospital

Atlanta, Georgia, United States, 30322

United States, Hawaii

The Queen's Medical Center

Honolulu, Hawaii, United States, 96813

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

Rush University Medical Center

Chicago, Illinois, United States, 60612

Evanston Hospital

Evanston, Illinois, United States, 60201

United States, Indiana

St. Vincent Heart Center of Indiana

Indianapolis, Indiana, United States, 46290

United States, Iowa

Iowa Heart Center

Des Moines, Iowa, United States, 50266

United States, Kansas

University of Kansas Hosp Authority

Kansas City, Kansas, United States, 66160

Via Christi

Wichita, Kansas, United States, 66866

United States, Kentucky

St. Joseph's Hospital - Lexington, KY

Lexington, Kentucky, United States, 40504

Jewish Hospital

Louisville, Kentucky, United States, 40245

United States, Louisiana

Ochsner Clinic Foundation

New Orleans, Louisiana, United States, 70121

United States, Maine

Maine Medical Center

Portland, Maine, United States, 04102

United States, Maryland

University of Maryland Baltimore

Baltimore, Maryland, United States, 21201

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Michigan

University of Michigan Hospitals

Ann Arbor, Michigan, United States, 48109

Henry Ford Hospital

Detroit, Michigan, United States, 48202

William Beaumont Hospital

Royal Oak, Michigan, United States, 48073-6796

United States, Minnesota

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States, 55407

University of Minnesota

Minneapolis, Minnesota, United States, 55455

Mayo Foundation for Med Edu And Research

Rochester, Minnesota, United States, 55905

United States, Missouri

Saint Luke's Hospital

Kansas City, Missouri, United States, 64111

Barnes Jewish Hospital

Saint Louis, Missouri, United States, 63110

United States, Montana

St. Patrick Hospital

Missoula, Montana, United States, 59802

United States, Nebraska

Nebraska Heart Institute Heart Hospital

Lincoln, Nebraska, United States, 68526

United States, New Jersey

Cooper University Hospital

Camden, New Jersey, United States, 08103

Morristown Medical Center

Morristown, New Jersey, United States, 07960

United States, New York

North Shore

Manhasset, New York, United States, 11030

NYU Langone Medical Center

New York, New York, United States, 10016

Mount Sinai Medical Center

New York, New York, United States, 10029

Columbia University Medical Center / New York Presbyterian Hospital

New York, New York, United States, 10032

NYP Weill Cornell Medical Center

New York, New York, United States, 10065

St. Francis Hospital

Roslyn, New York, United States, 11576

United States, North Carolina

Carolinas Medical Center

Charlotte, North Carolina, United States, 28203

Duke University Medical Center

Durham, North Carolina, United States, 27710

Vidant Medical Center

Greenville, North Carolina, United States, 27834

United States, Ohio

The Christ Hospital

Cincinnati, Ohio, United States, 45219

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Ohio State University Medical Center

Columbus, Ohio, United States, 43210

Riverside Methodist Hospital

Columbus, Ohio, United States, 43214-3907

United States, Oklahoma

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, United States, 73120

United States, Oregon

Providence St. Vincent Medical Center

Portland, Oregon, United States, 97225

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Hospital of University Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Temple University Hospital

Philadelphia, Pennsylvania, United States, 19140

UPMC Presbyterian

Pittsburgh, Pennsylvania, United States, 15213

Pinnacle Health at Harrisburg Hospital

Wormleysburg, Pennsylvania, United States, 17043

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29403

United States, Tennessee

St. Thomas Hospital

Nashville, Tennessee, United States, 37205

United States, Texas

Seton Medical Center Austin

Austin, Texas, United States, 78705

Baylor Heart and Vascular Hospital

Dallas, Texas, United States, 75204

UT Southwestern Medical Center

Dallas, Texas, United States, 75235

Houston Methodist Hospital

Houston, Texas, United States, 77030

Memorial Hermann Hospital

Houston, Texas, United States, 77030

United States, Utah

Intermountain Medical Center

Murray, Utah, United States, 84107

United States, Virginia

University of Virginia

Charlottesville, Virginia, United States, 22908

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States, 23284

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, United States, 24014

United States, Washington

Swedish Medical Center Cherry Hill Campus

Seattle, Washington, United States, 98122

Canada, British Columbia

St Paul's - Providence Health Care

Vancouver, British Columbia, Canada, V6Z 1Y6

Canada, Ontario

Hamilton Health Sciences

Hamilton, Ontario, Canada, L8L 2X2

St Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Canada, Quebec

Montreal Heart Institute

Montreal, Quebec, Canada, H1T 1C8

Canada

University of Alberta

Edmonton, Canada

Sponsors and Collaborators

Abbott Medical Devices

Investigators

• Principal Investigator: Michael Mack, MD; Baylor Health Care System
• Principal Investigator: Gregg Stone, MD; MOUNT SINAI HOSPITAL
• Principal Investigator: William T Abraham, MD; The Ohio State University Heart Center
• Principal Investigator: JoAnn Lindenfeld, MD; Vanderbilt University Medical Center

  Study Documents (Full-Text)

Documents provided by Abbott Medical Devices:

Study Protocol  [PDF] October 12, 2016

Statistical Analysis Plan  [PDF] June 4, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Giustino G, Camaj A, Kapadia SR, Kar S, Abraham WT, Lindenfeld J, Lim DS, Grayburn PA, Cohen DJ, Redfors B, Zhou Z, Pocock SJ, Asch FM, Mack MJ, Stone GW. Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial. J Am Coll Cardiol. 2022 Nov 15;80(20):1857-1868. doi: 10.1016/j.jacc.2022.08.803.

Brener MI, Grayburn P, Lindenfeld J, Burkhoff D, Liu M, Zhou Z, Alu MC, Medvedofsky DA, Asch FM, Weissman NJ, Bax J, Abraham W, Mack MJ, Stone GW, Hahn RT. Right Ventricular-Pulmonary Arterial Coupling in Patients With HF Secondary MR: Analysis From the COAPT Trial. JACC Cardiovasc Interv. 2021 Oct 25;14(20):2231-2242. doi: 10.1016/j.jcin.2021.07.047.

Kosmidou I, Lindenfeld J, Abraham WT, Rinaldi MJ, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Gaba P, Rogers JH, Shahim B, Redfors B, Zhang Z, Mack MJ, Stone GW. Sex-Specific Outcomes of Transcatheter Mitral-Valve Repair and Medical Therapy for Mitral Regurgitation in Heart Failure. JACC Heart Fail. 2021 Sep;9(9):674-683. doi: 10.1016/j.jchf.2021.04.011. Epub 2021 Aug 11.

Arnold SV, Stone GW, Jain SS, Mack MJ, Saxon JT, Zhang Z, Lindenfeld J, Abraham WT, Cohen DJ; COAPT Investigators. Prognostic Importance of Health Status Versus Functional Status in Heart Failure and Secondary Mitral Regurgitation. JACC Heart Fail. 2021 Sep;9(9):684-692. doi: 10.1016/j.jchf.2021.04.012. Epub 2021 Aug 11.

Shahim B, Ben-Yehuda O, Chen S, Redfors B, Madhavan MV, Kar S, Lim DS, Asch FM, Weissman NJ, Cohen DJ, Arnold SV, Liu M, Lindenfeld J, Abraham WT, Mack MJ, Stone GW. Impact of Diabetes on Outcomes After Transcatheter Mitral Valve Repair in Heart Failure: COAPT Trial. JACC Heart Fail. 2021 Aug;9(8):559-567. doi: 10.1016/j.jchf.2021.03.011.

Kar S, Mack MJ, Lindenfeld J, Abraham WT, Asch FM, Weissman NJ, Enriquez-Sarano M, Lim DS, Mishell JM, Whisenant BK, Rogers JH, Arnold SV, Cohen DJ, Grayburn PA, Stone GW. Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure: COAPT Trial. Circulation. 2021 Aug 10;144(6):426-437. doi: 10.1161/CIRCULATIONAHA.120.053061. Epub 2021 May 27.

Gertz ZM, Herrmann HC, Lim DS, Kar S, Kapadia SR, Reed GW, Puri R, Krishnaswamy A, Gersh BJ, Weissman NJ, Asch FM, Grayburn PA, Kosmidou I, Redfors B, Zhang Z, Abraham WT, Lindenfeld J, Stone GW, Mack MJ. Implications of Atrial Fibrillation on the Mechanisms of Mitral Regurgitation and Response to MitraClip in the COAPT Trial. Circ Cardiovasc Interv. 2021 Apr;14(4):e010300. doi: 10.1161/CIRCINTERVENTIONS.120.010300. Epub 2021 Mar 15.

Mack MJ, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant BK, Grayburn PA, Rinaldi MJ, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Rogers JH, Marx SO, Cohen DJ, Weissman NJ, Stone GW; COAPT Investigators. 3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure. J Am Coll Cardiol. 2021 Mar 2;77(8):1029-1040. doi: 10.1016/j.jacc.2020.12.047.

Lindenfeld J, Abraham WT, Grayburn PA, Kar S, Asch FM, Lim DS, Nie H, Singhal P, Sundareswaran KS, Weissman NJ, Mack MJ, Stone GW; Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Investigators. Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial. JAMA Cardiol. 2021 Apr 1;6(4):427-436. doi: 10.1001/jamacardio.2020.7200.

Saxon JT, Cohen DJ, Chhatriwalla AK, Kotinkaduwa LN, Kar S, Lim DS, Abraham WT, Lindenfeld J, Mack MJ, Arnold SV, Stone GW. Impact of COPD on Outcomes After MitraClip for Secondary Mitral Regurgitation: The COAPT Trial. JACC Cardiovasc Interv. 2020 Dec 14;13(23):2795-2803. doi: 10.1016/j.jcin.2020.09.023.

Kosmidou I, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant BK, Kipperman RM, Boudoulas KD, Redfors B, Shahim B, Zhang Z, Mack MJ, Stone GW. Transcatheter Mitral Valve Repair in Patients With and Without Cardiac Resynchronization Therapy: The COAPT Trial. Circ Heart Fail. 2020 Nov;13(11):e007293. doi: 10.1161/CIRCHEARTFAILURE.120.007293. Epub 2020 Nov 12.

Giustino G, Lindenfeld J, Abraham WT, Kar S, Lim DS, Grayburn PA, Kapadia SR, Cohen DJ, Kotinkaduwa LN, Weissman NJ, Mack MJ, Stone GW. NYHA Functional Classification and Outcomes After Transcatheter Mitral Valve Repair in Heart Failure: The COAPT Trial. JACC Cardiovasc Interv. 2020 Oct 26;13(20):2317-2328. doi: 10.1016/j.jcin.2020.06.058.

Hahn RT, Asch F, Weissman NJ, Grayburn P, Kar S, Lim S, Ben-Yehuda O, Shahim B, Chen S, Liu M, Redfors B, Medvedofsky D, Puri R, Kapadia S, Sannino A, Lindenfeld J, Abraham WT, Mack MJ, Stone GW. Impact of Tricuspid Regurgitation on Clinical Outcomes: The COAPT Trial. J Am Coll Cardiol. 2020 Sep 15;76(11):1305-1314. doi: 10.1016/j.jacc.2020.07.035.

Grayburn PA, Sannino A, Cohen DJ, Kar S, Lim DS, Mishell JM, Whisenant BK, Rinaldi MJ, Kapadia SR, Rajagopal V, Crowley A, Kotinkaduwa LN, Lindenfeld J, Abraham WT, Mack MJ, Stone GW. Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial. J Am Coll Cardiol. 2020 Sep 1;76(9):1007-1014. doi: 10.1016/j.jacc.2020.07.010.

Arnold SV, Stone GW, Mack MJ, Chhatriwalla AK, Austin BA, Zhang Z, Ben-Yehuda O, Kar S, Lim DS, Lindenfeld J, Abraham WT, Cohen DJ; COAPT Investigators. Health Status Changes and Outcomes in Patients With Heart Failure and Mitral Regurgitation: COAPT Trial. J Am Coll Cardiol. 2020 May 5;75(17):2099-2106. doi: 10.1016/j.jacc.2020.03.002. Epub 2020 Mar 16.

Tang GHL. Echocardiographic Understanding of Secondary Mitral Regurgitation in Transcatheter Mitral Valve Repair: More to Learn. J Am Coll Cardiol. 2019 Dec 17;74(24):2980-2981. doi: 10.1016/j.jacc.2019.11.001. Epub 2019 Dec 9. No abstract available.

Asch FM, Grayburn PA, Siegel RJ, Kar S, Lim DS, Zaroff JG, Mishell JM, Whisenant B, Mack MJ, Lindenfeld J, Abraham WT, Stone GW, Weissman NJ; COAPT Investigators. Echocardiographic Outcomes After Transcatheter Leaflet Approximation in Patients With Secondary Mitral Regurgitation: The COAPT Trial. J Am Coll Cardiol. 2019 Dec 17;74(24):2969-2979. doi: 10.1016/j.jacc.2019.09.017. Epub 2019 Sep 28.

Baron SJ, Wang K, Arnold SV, Magnuson EA, Whisenant B, Brieke A, Rinaldi M, Asgar AW, Lindenfeld J, Abraham WT, Mack MJ, Stone GW, Cohen DJ; COAPT Investigators. Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial. Circulation. 2019 Dec 3;140(23):1881-1891. doi: 10.1161/CIRCULATIONAHA.119.043275. Epub 2019 Sep 29.

Arnold SV, Chinnakondepalli KM, Spertus JA, Magnuson EA, Baron SJ, Kar S, Lim DS, Mishell JM, Abraham WT, Lindenfeld JA, Mack MJ, Stone GW, Cohen DJ; COAPT Investigators. Health Status After Transcatheter Mitral-Valve Repair in Heart Failure and Secondary Mitral Regurgitation: COAPT Trial. J Am Coll Cardiol. 2019 May 7;73(17):2123-2132. doi: 10.1016/j.jacc.2019.02.010. Epub 2019 Mar 17.

Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Rinaldi M, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Marx SO, Cohen DJ, Weissman NJ, Mack MJ; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23.

Mack MJ, Abraham WT, Lindenfeld J, Bolling SF, Feldman TE, Grayburn PA, Kapadia SR, McCarthy PM, Lim DS, Udelson JE, Zile MR, Gammie JS, Gillinov AM, Glower DD, Heimansohn DA, Suri RM, Ellis JT, Shu Y, Kar S, Weissman NJ, Stone GW. Cardiovascular Outcomes Assessment of the MitraClip in Patients with Heart Failure and Secondary Mitral Regurgitation: Design and rationale of the COAPT trial. Am Heart J. 2018 Nov;205:1-11. doi: 10.1016/j.ahj.2018.07.021. Epub 2018 Aug 1.

• Responsible Party: Abbott Medical Devices
• ClinicalTrials.gov Identifier: NCT01626079
• Other Study ID Numbers: 11-512
• First Posted: June 22, 2012
• Results First Posted: May 6, 2020
• Last Update Posted: September 28, 2022
• Last Verified: September 2022

Keywords provided by Abbott Medical Devices:

Functional Mitral Regurgitation; Mitral Valve Regurgitation; Symptomatic Heart Failure; Functional MR; MitraClip; Mitral Valve Insufficiency; Cardiopulmonary exercise testing; COAPT CAS; COAPT Continued Access Study; MitraClip NT

Additional relevant MeSH terms:

Heart Failure; Mitral Valve Insufficiency; Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases