Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting (CABG) Versus CABG Alone in People With Moderate 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. CABG is one treatment option for people with CAD. During a CABG procedure, a healthy
artery or vein from another part of the body is connected to the blocked coronary artery.
Blood flow is then routed around the blockage to the heart.

After a heart attack, some people may have a leak in the mitral valve of the heart. This
condition is known as ischemic mitral regurgitation (IMR) and is associated with poor health
outcomes, including worsening heart failure. In people with severe mitral valve leakage, the
CABG procedure and a mitral valve repair procedure are routinely performed together;
however, in people with only moderate valve leakage, there is no consensus in the medical
community as to whether the mitral valve repair procedure is beneficial at the time of CABG.
The purpose of this study is to determine whether people with moderate mitral valve
regurgitation should undergo a mitral valve repair procedure in addition to CABG or undergo
CABG alone.

This study will enroll people with CAD who require a CABG procedure and have moderate 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 CABG surgery and the mitral valve repair procedure or
only CABG surgery. 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 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:

- Moderate mitral regurgitation 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 between 0.2 cmsq to 0.39 cmsq. If ERO < 0.2, 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

- CAD that is amenable to CABG and a clinical indication for revascularization

- Age ≥ 18 years

Exclusion Criteria:

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

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

- Planned concomitant intra-operative procedures (with the exception of closure of
patent foramen ovale [PFO] or atrial septal defect [ASD]or Maze procedure or left
atrial appendage excision)

- Prior surgical or percutaneous mitral valve repair

- Contraindication to cardiopulmonary bypass (CPB)

- Clinical signs of cardiogenic shock at the time of surgery

- Treatment with chronic intravenous inotropic therapy at the time of surgery

- Severe, irreversible pulmonary hypertension in the judgment of the investigator

- 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

- Recent history of psychiatric disease (including drug or alcohol abuse) that is
likely to impair compliance with the study, in the judgment of 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
the study

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

- Pregnancy at the time of randomization