Mitral regurgitation worsens cardiac remodeling in ischemic cardiomyopathy in an experimental model

Objective: Mitral regurgitation (MR) developing concomitant with ischemic cardiomyopathy is a frequently diagnosed valvular lesion, for which an optimal therapeutic strategy is unknown. The contribution of MR to the ongoing cardiac remodeling from myocardial infarction (MI) remains controversial. We have developed a novel experimental model in which MI and severe MR can be independently introduced, to study the role of MR in chronic remodeling of the ischemic heart. Methods: A total of 98 rats were induced with MI+MR (group 1), MI (group 2), MR (group 3), or sham surgery (group 4). MR was induced by inserting a needle into the anterior mitral leaflet via the ventricular apex in a beating heart. MI was induced by ligating the left coronary artery. Biweekly ultrasound examinations were performed after surgery, and invasive hemodynamic assessments were performed in some rats at 2, 10, and 20 weeks. Results: At 2 weeks postsurgery, the mean end-diastolic volume was 432 +/- 103 mu L in ischemic hearts with MR, compared with 390 +/- 76.3 mu L in ischemic hearts without MR (a 10.76% difference). By 20 weeks, the mean volume was significantly greater in the former group (767 +/- 246 mu L vs 580 +/- 85 mu L; a 32.24% difference). At 2 weeks, mean end-systolic volume was 147 +/- 46.8 mu L in the ischemic hearts with MR and 147 +/- 45.7 mu L in those without MR. By 20 weeks, the mean volumes had increased to 357 +/- 136.4 mu L and 271 +/- 82.3 mu L, respectively (a 31.73% difference). Conclusions: MR in ischemic hearts significantly increased end-diastolic and end-systolic volumes of the left ventricle, indicating adverse cardiac remodeling and worse systolic function.