Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation

CAD occurs when the arteries that supply blood to the heart become blocked as a result of
plaque buildup. In severe cases, CAD can cause chest pain, shortness of breath, and heart
attack. After a heart attack, some people may develop a leak in the mitral valve of the
heart. This condition is known as ischemic mitral regurgitation (IMR), and it can cause blood
to flow backward into the heart. If left untreated, severe IMR can lead to heart failure or
serious heart rhythm irregularities, known as arrhythmias. People with severe mitral valve
leakage routinely undergo one of two surgical procedures to fix the mitral valve: a mitral
valve repair procedure, in which a surgical ring is used to repair the valve; or a mitral
valve replacement procedure, in which the damaged valve is replaced with a new one.
Currently, there is no consensus in the medical community as to which procedure is more
beneficial. The purpose of this study is to determine whether people with severe mitral valve
regurgitation should undergo a mitral valve repair procedure or a mitral valve replacement
procedure.

This study will enroll people with CAD who have severe mitral regurgitation. At a baseline
study visit, participants will undergo a physical examination; blood collection;
neurocognitive tests; and questionnaires regarding medical history, medication history, and
quality of life. In the operating room, participants will be randomly assigned to undergo
either the mitral valve repair procedure or the mitral valve replacement procedure. Blood,
urine, and tissue samples may be collected from participants after the surgery; this is
optional and will only be done with prior approval from participants. All participants will
attend study visits at Day 30 and Months 6, 12, and 24. At each visit, participants will take
part in a medication history review, a physical examination, an echocardiogram, a
cardiopulmonary exercise test, neurocognitive tests, and quality of life surveys.

Inclusion Criteria:

- Chronic severe ischemic mitral regurgitation (often with tethering as a major
mechanism) in the judgment of the clinical site echocardiographer, assessed by
transthoracic echocardiogram. Assessment of mitral regurgitation will be performed
using an integrative method (Zoghbi W. et al. J. American Society of Echocardiography.
2003:16:777-802. see appendix). Quantitative guidelines as proposed would be: ERO ≥
0.4 cmsq. If ERO < 0.4, then the degree of mitral regurgitation will be guided by
other color Doppler quantitative methods (jet area/left atrial area ratio, vena
contracta, supportive criteria in an integrated fashion

- Eligible for surgical repair and replacement of mitral valve

- CAD with or without the need for coronary revascularization

Exclusion Criteria:

- Any evidence of structural (chordal or leaflet) mitral valve disease or ruptured
papillary muscle

- Prior mitral valve repair

- Severe irreversible pulmonary hypertension in the judgment of the investigator

- Medically unable to undergo cardiopulmonary bypass (CPB)

- Inability to derive ERO and end-systolic volume index (ESVI) by transthoracic
echocardiography

- Planned concomitant intra-operative procedures (with the exception of tricuspid valve
repair, closure of patent foramen ovale [PFO] or atrial septal defect [ASD] or Maze
procedure)

- Clinical signs of cardiogenic shock at the time of surgery

- Treatment with long-term intravenous inotropic therapy at the time of surgery

- ST segment elevation myocardial infarction (MI) requiring intervention in the 7 days
before surgery

- Congenital heart disease (except PFO or ASD)

- Evidence of cirrhosis or liver synthetic failure

- Excessive surgical risk, as judged by the surgical investigator

- Recent history of psychiatric disease (including drug or alcohol abuse) that is likely
to impair compliance with the study, as judged by the investigator

- Therapy with an investigational intervention at the time of screening, or planning to
enroll in an additional investigational intervention study during participation in
this study

- Any concurrent disease with a life expectancy of less than 2 years

- Pregnant