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

Phase 3

Terminated

Conditions: Mitral Valve Insufficiency
Heart Failure

Interventions: Procedure: Surgical mitral valvuloplasty with placement of annular ring (SMVR)
Drug: Optimal medical therapy (OMT)

Registration Number: NCT00608140

Lead Sponsor: Duke University

Brief Summary: Mitral regurgitation (MR), also known as mitral insufficiency, is a condition in which the heart's mitral valve, located between two of the heart's main chambers, does not firmly shut, allowing blood to leak backwards within the heart. Improper functioning of the mitral valve disrupts the proper flow of blood through the body, resulting in shortness of breath and fatigue. When mild, MR may not pose a significant danger to a person's health, but severe MR may be associated with serious complications, such as heart failure, irregular heart rhythm, and high blood pressure. Although there are treatments for MR, including medication and surgery, more information is needed on the effectiveness of these treatments in people with significant MR. This study will compare the safety and effectiveness of corrective surgery added to optimal medical treatment (OMT) versus OMT alone in treating people with significant MR caused by an enlarged heart.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Surgical mitral valvuloplasty with placement of annular ring (SMVR)	Participants will receive optimal medical therapy plus surgical mitral valve repair with complete annular ring placement
1	Optimal medical therapy (OMT)	Participants will receive optimal medical therapy plus surgical mitral valve repair with complete annular ring placement
2	Optimal medical therapy (OMT)	Participants will receive optimal medical therapy alone
3	Surgical mitral valvuloplasty with placement of annular ring (SMVR)	Participants will receive optimal medical therapy plus 18-month delayed surgical mitral valve repair with complete annular ring placement
3	Optimal medical therapy (OMT)	Participants will receive optimal medical therapy plus 18-month delayed surgical mitral valve repair with complete annular ring placement

Primary Outcome Measures

Name	Time	Method
Effect of Adding SMVR to OMT Alone on LV Remodeling, Specifically LV End-systolic Volume Index (LVESVI)	Measured at Month 18

Secondary Outcome Measures

Name	Time	Method
Perioperative Mortality	Measured between Days 0 and 30 postsurgery
Peak VO2	Measured at Month 18
Change in 6-minute Walk Test	Measured at baseline and Month 18 but n/a	The 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No data were collected for this outcome measure and no analysis was performed.
Change in Minnesota Living With Heart Failure (MLHF) Score	Planned to be measured at baseline and Month 18 but n/a	Change in MLHF score. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Total Days Alive and Total Days Not Hospitalized	Measured at baseline and Month 18	Total days alive and not hospitalized by 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.
Total Mortality (All Causes)	Measured at Month 18	Total all-cause mortality at 18 months. However, the 2 patients enrolled did not meet the 18 month measurement of primary/secondary endpoints before the trial was terminated. No analysis was performed.

Trial Locations

Locations (9): Morehouse School of Medicine
🇺🇸
Atlanta, Georgia, United States
Minnesota Heart Failure Network
🇺🇸
Minneapolis, Minnesota, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Utah Health Sciences Center
🇺🇸
Murray, Utah, United States
Montreal Heart Institute
🇨🇦
Montreal, Quebec, Canada
University of Vermont - Fletcher Allen Health Care
🇺🇸
Burlington, Vermont, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States