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

• Type of Material: Article
• Authors: Takanori Kono, Emory University; Daisuke Onohara, Emory University; Alan Amedi, Emory University; Daniella Corporan, Emory University; Saimuralidhar Padala, Emory University
• Language: English
• Date: 2021-11-16
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 by The American Association for Thoracic Surgery
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.jtcvs.2021.11.024
• Title of Journal or Parent Work: The Journal of Thoracic and Cardiovascular Surgery
• Volume: 164
• Issue: 6
• Start Page: e333
• End Page: e347
• Grant/Funding Information: This work was funded by grants from American Heart Association (14SDG20380081, 17POST33661278, 19PRE34380625), National Institutes of Health (R01HL135145, R01HL133667, and R01HL140325), and infrastructure funding from the Carlyle Fraser Heart Center at Emory University Hospital Midtown, Atlanta, GA
• Keywords: heart failure; transcatheter mitral valve repair; left ventricular remodeling; Secondary mitral regurgitation; transcatheter mitral valve replacement; ischemic mitral regurgitation
• Research Categories: Health Sciences, Medicine and Surgery

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.