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

Condition(s) targeted: Mitral Valve Insufficiency; Heart Failure

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

Phase: Phase 3

Status: Recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

Official(s) and/or principal investigator(s):
Kerry L. Lee, PhD, Principal Investigator, Affiliation: Duke University
Eugene Braunwald, MD, Study Chair, Affiliation: Harvard University

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.

Official title: Surgery Versus Medical Treatment Alone for Patients With Significant Mitral Regurgitation and Non-Ischemic Congestive Heart Failure: SMMART-HF

Study design: Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Effect of adding SMVR to OMT alone on LV remodeling, specifically LV end-systolic volume index (LVESVI)

Secondary outcome:

Peak VO2

Change in 6-minute walk test

Change in Minnesota Living with Heart Failure (MLHF) score

Total days alive and total days not hospitalized

Total mortality (all causes)

Perioperative mortality

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Morehouse School of Medicine, Atlanta, Georgia 30310, United States; Recruiting
Elizabeth Ofili, MD, Phone: 404-752-1970, Email: eofili@msm.edu
Brenda Lankford, RN, PhD, Phone: 404-756-1377, Email: blankford@msm.edu
Elizabeth Ofili, MD, Principal Investigator
Anekwe Onwuanyi, MD, Sub-Investigator

Brigham and Women's Hospital, Boston, Massachusetts 02115, United States; Recruiting
Lynne W. Stevenson, MD, Phone: 617-732-7406, Email: lstevenson@partners.org
Jerry Cornish, Email: jcornish@partners.org
Lynne W. Stevenson, MD, Principal Investigator
Michael Givertz, MD, Sub-Investigator
Marc Semigran, MD, Sub-Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Margaret M. Redfield, MD, Phone: 507-284-1281, Email: redfield.margaret@mayo.edu
Jilian Foxen, Phone: 919-284-1281, Email: foxen.jilian@mayo.edu
Margaret M. Redfield, MD, Principal Investigator
John Burnett, MD, Sub-Investigator
Horng Chen, MD, Sub-Investigator

Minnesota Heart Failure Network, Minneapolis, Minnesota 55415, United States; Recruiting
Steven R. Goldsmith, MD, Phone: 612-347-2875, Email: srg_hcmc@yahoo.com
Shari Mackedanz, RN, BSN, Phone: 612-347-5195, Email: shari.mackedanz@co.hennepin.mn.us
Steven R. Goldsmith, MD, Principal Investigator
Bradley Bart, MD, Sub-Investigator

Duke University Medical Center, Durham, North Carolina 27705, United States; Recruiting
Christopher O'Connor, MD, Phone: 919-880-6787, Email: oconn002@mc.duke.edu
Renee Story, Phone: 919-681-3398, Email: story003@mc.duke.edu
Christopher O'Conner, MD, Principal Investigator
Michael Felker, MD, MHS, Sub-Investigator
Larry Allen, MD, Sub-Investigator
Joseph Rogers, MD, Sub-Investigator
Carmelo Milano, MD, Sub-Investigator

Montreal Heart Institute, Montreal, Quebec H1T - 1C8, Canada; Recruiting
Jean Rouleau, MD, Phone: 514-343-6351, Email: jean.rouleau@umontreal.ca
Mady Benhaim, Phone: 514-376-3330, Ext: 3935, Email: mady.benhaim@umontreal.ca
Jean Rouleau, MD, Principal Investigator
Normand Racine, MD, Sub-Investigator

Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Douglas Mann, MD, Phone: 713-798-0285, Email: dmann@bcm.tmc.edu
Mary Soliz, Phone: 713-798-0270, Email: msoliz@bcm.tmc.edu
Douglas Mann, MD, Principal Investigator
Anita Deswal, MD, MPH, Sub-Investigator

University of Utah Health Sciences Center, Murray, Utah 84107, United States; Recruiting
David Bull, MD, Phone: 801-585-3936, Email: david.bull@hsc.utah.edu
Bev Campbell, Phone: 801-408-5715, Email: bev.campbell@intermountainmail.org
David Bull, MD, Principal Investigator
Dean Li, MD, Sub-Investigator
Dale Renlund, MD, Sub-Investigator

University of Vermont - Fletcher Allen Health Care, Burlington, Vermont 05401, United States; Recruiting
Martin LeWinter, MD, Phone: 802-847-2879, Email: martin.lewinter@vtmednet.org
Michaelanne Rowen, RN, Phone: 802-847-4746, Email: michaelanne.rowen@vtmednet.org
Martin LeWinter, MD, Principal Investigator
Markus Meyer, MD, Sub-Investigator
Richard Pratley, MD, Sub-Investigator
Peter VanBuren, MD, Sub-Investigator

Starting date: March 2008
Ending date: May 2010
Last updated: October 14, 2008