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

J Am Coll Cardiol. 2003 Mar 5;41(5):753-60. doi: 10.1016/s0735-1097(02)02959-5.


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 (>or=10 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 >or=10 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.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Apoptosis / physiology*
  • Autopsy
  • Culture Techniques
  • Female
  • Heart Failure / mortality*
  • Heart Failure / pathology*
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Logistic Models
  • Male
  • Muscle Cells / pathology
  • Myocardial Infarction / mortality*
  • Myocardial Infarction / pathology*
  • Probability
  • Risk Factors
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Time Factors
  • Ventricular Remodeling / physiology*