Effect of Early Versus Late Onset Mitral Regurgitation on Left Ventricular Remodeling in Ischemic Cardiomyopathy in an Animal Model

ABSTRACT Background Patients surviving a myocardial infarction have progressive cardiac dysfunction and ventricular remodeling. Mitral regurgitation is often diagnosed in these patients, and is a risk factor that portends poor prognosis. Whether such post-infarction mitral regurgitation magnifies adverse left ventricular remodeling is unclear, which was studied in an animal model. Methods Forty-one adult rats were induced with myocardial infarction by left coronary artery ligation and assigned to three groups: (group 1) myocardial infarction only; (group 2) myocardial infarction with severe mitral regurgitation introduced after 4 weeks; and (group 3) myocardial infarction with severe mitral regurgitation introduced after 10 weeks. Valve regurgitation was introduced by advancing a trans-apical, ultrasound guided needle into the mitral valve anterior leaflet. Animals were survived to 20 weeks from the index procedure, with biweekly cardiac ultrasound, and invasive hemodynamics and histology at termination. Results At 20 weeks, end diastolic volume was largest in the groups with mitral regurgitation, compared to the group without the valve lesion (group 1: 760.9±124.6μl, group 2: 958.0±115.1μl, group 3: 968.3±214.9μl). Similarly, end systolic volume was larger in groups with regurgitation (group 1: 431.2±152.6μl, group 2: 533.2±130.8μl, group 3: 533.1±177.5μl). In the infarction only group, left ventricular remodeling was maximal until 6 weeks and plateaued thereafter. In groups with mitral regurgitation, left ventricular remodeling was significantly elevated upon the onset of regurgitation and persisted. Conclusions Mitral regurgitation is a potent driver of adverse cardiac remodeling after a myocardial infarction, irrespective of the timing of its onset.