Effectiveness of Surgical Mitral Valve Repair Versus Medical Treatment for People With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure

It is estimated that approximately 4 out of 10 people with an enlarged heart due to heart
failure develop MR, referred to as secondary MR. This type of MR is caused by enlargement of
the left ventricle (LV), one of the heart's main chambers. In turn, the enlargement leads to
stretching of certain heart muscles around the mitral valve and of the valve itself. Symptoms
of secondary MR may include shortness of breath, fatigue, dizziness, swollen feet, cough, and
heart palpitations. Mitral valve repair or replacement surgery is sometimes considered as a
treatment option to restore proper heart function in people with secondary MR. Surgical
repair with placement of an artificial ring around the mitral valve can help to tighten the
valve and add benefit to non-surgical treatments for MR. However, although surgical placement
of the ring improves mitral valve function in most people, it is not known whether this
surgery helps people live longer and healthier lives. This study will compare the safety and
effectiveness of surgical mitral valvuloplasty with placement of an annular ring (SMVR) added
to optimal medical treatment (OMT) versus OMT alone in non-ischemic heart failure patients
with significant secondary MR.

Participation from baseline through follow-up in this study will last 18 months. All
potential participants will initially undergo a transesophageal echocardiogram to confirm the
presence of an abnormal mitral valve. Eligible participants will then undergo a number of
baseline tests, which will include cardiopulmonary exercise stress testing, a chest wall
echocardiogram, blood draw, 6-minute walk test, medical questionnaires, and a physical exam.
Next, participants will be randomly assigned to receive immediate open heart surgery with the
placement of a mitral valve ring, delayed surgery at least 18 months later, or OMT.
Participants assigned to receive immediate surgery will undergo the surgery 2 weeks after
baseline testing. Participants assigned to receive OMT will receive treatment with any of the
following medication regimens: combination of vasodilator therapy and diuretics, nitrates and
nifedipine, and beta-adrenergic blocker therapy. Follow-up visits for all participants will
occur at Months 1, 3, 6, 12, and 18 and will include repeat baseline testing. Long-term
survival status data may be collected beyond 18 months for some participants.

Inclusion Criteria:

- Symptomatic chronic heart failure, New York Heart Association (NYHA) class II to IIIb

- Left ventricular ejection fraction of 0.35 due to non-ischemic etiology

- Evidence by transthoracic echocardiography (TTE) of moderate or severe MR without
obvious primary mitral valve pathology

- Peak VO2 less than or equal to 22 ml/kg/min, as obtained at study entry

- Optimal heart failure therapy for at least 6 months prior to study entry

Exclusion Criteria:

- Significant coronary artery disease (greater than 75% lesion in any vessel) by
coronary angiography or by a history of a prior heart attack

- Heart failure due to active myocarditis, congenital heart disease, or obstructive
hypertrophic cardiomyopathy

- Significant ventricular arrhythmias not treated with an implantable defibrillator

- Primary MR due to significant chordal or leaflet abnormalities by TTE

- Other hemodynamically relevant stenotic or regurgitant valvular diseases

- Severe tricuspid regurgitation (TR) (moderate TR is allowed)

- Severe pulmonic regurgitation (PR) (moderate PR is allowed)

- Moderate to severe aortic regurgitation

- Any moderate to severe stenotic lesions using American Heart Association/American
College of Cardiology (AHA/ACC) criteria 31

- Dependence on chronic inotropic therapy

- Restrictive cardiomyopathy or constrictive pericarditis

- Severe right ventricular dysfunction

- Baseline creatinine greater than or equal to 3 mg/dL or renal replacement therapy
(chronic hemodialysis or peritoneal dialysis)

- Poor transthoracic sonographic windows precluding reasonable assessment of LV
endocardial borders from apical imaging on TTE

- Inability to perform the spirometric exercise testing

- Significant chronic lung disease that might interfere with the ability to interpret
the spirometric measurements, including home oxygen, forced expiratory volume in 1
second (FEV1) less than 1.0 L/min, or exertional hypoxemia with saturations less than
90%

- Any known neoplastic disease other than skin cancer

- Other terminal illness with a life expectancy less than 1 year

- Plan for percutaneous mitral valve procedure