Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling: Failure of Hypertrophic Compensation

Objectives We examined whether mitral regurgitation (MR) augments post-myocardial infarction (MI) remodeling. Background MR doubles mortality after MI, but its additive contribution to left ventricular (LV) remodeling is debated and has not been addressed in a controlled fashion. Methods Apical MIs were created in 12 sheep, and 6 had an LV-to-left atrial shunt implanted, consistently producing regurgitant fractions of ∼30%. The groups were compared at baseline, 1, and 3 months. Results Left ventricular end-systolic volume progressively increased by 190% with MR versus 90% without MR (p 2+ -ATPase levels (0.56 ± 0.03 vs. 0.76 ± 0.02, p Conclusions In this controlled model, moderate MR worsens post-MI remodeling, with reduced contractility. Pro-hypertrophic pathways are initially upregulated but subsequently fall below infarct-only levels and baseline; with sustained caspase 3 elevation, transformation to a failure phenotype occurs. Extracellular matrix turnover increases in MR animals. Therefore, MR can precipitate an earlier onset of dilated heart failure.