This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Beeri, R. Articles by Levine, R. A. Search for Related Content PubMed PubMed Citation Articles by Beeri, R. Articles by Levine, R. A. Related Collections Remodeling Animal models of human disease Valvular heart disease CV surgery: valvular disease Chronic ischemic heart disease

(Circulation. 2007;116:I-288 – I-293.)
© 2007 American Heart Association, Inc.

Surgery for Valvular Heart Disease

Early Repair of Moderate Ischemic Mitral Regurgitation Reverses Left Ventricular Remodeling

A Functional and Molecular Study

Ronen Beeri, MD; Chaim Yosefy, MD; J. Luis Guerrero, BS; Suzan Abedat, MSc; Mark D. Handschumacher, BS; Robert E. Stroud, MS; Suzanne Sullivan, BS; Miguel Chaput, MD; Dan Gilon, MD; Gus J. Vlahakes, MD; Francis G. Spinale, MD, PhD; Roger J. Hajjar, MD; Robert A. Levine, MD

From the Cardiac Ultrasound Laboratory, Cardiovascular Research Center, and Cardiothoracic Surgery Department, Massachusetts General Hospital and Harvard Medical School (R.B., C.Y., J.L.G., M.D.H., S.S., M.C., G.J.V., R.J.H., R.A.L.), Boston, Mass; the Heart Institute, Hadassah-Hebrew University Medical Center (R.B., S.A., D.G.), Jerusalem, Israel; and the Cardiothoracic Surgery Department, Medical University of South Carolina (R.E.S., F.G.S.), Charleston, SC.

Correspondence to Robert A Levine, MD, Cardiac Ultrasound Laboratory, YAW5, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. E-mail rlevine{at}partners.org

Background— Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling.

Methods and Results— Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically.

Conclusions— Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI.

Key Words: mitral valve • myocardial infarction • regurgitation • remodeling • surgery