Selected Abstracts > Cardiovascular Disease > Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling

Title: Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling

J Am Coll Cardiol jan 2008;51:476-86

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 0.02). Pre-load-recruitable stroke work declined by 82  13% versus 25  16% (p 0.01) with MR, with decreased remote-zone sarcoplasmic reticulum Ca2-ATPase levels (0.56  0.03 vs. 0.76  0.02, p 0.001), and decreased isolated myocyte contractility. In remote zones, pro-hypertrophic Akt and gp130 were upregulated in both groups at 1 month, but significantly lower and below baseline in the MR group at 3 months. Pro-apoptotic caspase 3 remained high in both groups. Matrix metalloproteinase (MMP)-13 and membrane-type MMP-1 were increased in remote zones of MR versus infarct-only animals at 1 month, then fell below baseline. The MMP tissue inhibitors rose from baseline to 3 months in all animals, rising higher in the MI  MR-group border zone.

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.