Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure

OBJECTIVES The purpose of this study was to evaluate a potential correlation between apoptotic rate (AR), post-infarction left ventricular (LV) remodeling, and clinical characteristics in subjects who died late (greater than or equal to10 days) after an acute myocardial infarction (AMI) with evidence of persistent occlusion of the infarct-related artery at autopsy. BACKGROUND Apoptosis contributes to myocardiocyte loss in cardiac disease and may have a pathophysiologic role in post-infarction LV remodeling. METHODS The AR was calculated at the site of infarction and in remote unaffected LV regions, using co-localization of in situ end labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3, in 14 subjects who died within two months. after AMI. Correlation between AR and clinical characteristics such as age, site of AMI, transmural extension, multivessel coronary disease, and signs and/or symptoms of heart failure (HF); at the time of initial hospitalization for AMI or subsequently before death, was assessed using non-parametric statistical tests. Parameters of LV remodeling including diameters, free wall thickness, diameter-to-wall-thickness ratio, and mass were measured at gross examination at autopsy. Values are expressed as median (interquartile range). RESULTS Among clinical variables, early symptomatic post-infarction HF (9 cases, 64%) was associated with nearly fourfold increased AR at the site of infarction (26.2% [24.5% to 28.8%] vs. 6.4% [1.9% to 13.3%], p = 0.001). Moreover, AR both at the site of infarction and in unaffected regions was significantly correlated with parameters of progressive LV remodeling (p < 0.05). CONCLUSIONS Our data show that in patients dying greater than or equal to10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF. (C) 2003 by the American College of Cardiology Foundation.