Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure.
OBJECTIVE
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.
Abbate
Antonio
A
Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy. abbatea@yahoo.com
Biondi-Zoccai
Giuseppe G L
GG
Bussani
Rossana
R
Dobrina
Aldo
A
Camilot
Debora
D
Feroce
Florinda
F
Rossiello
Raffaele
R
Baldi
Feliciano
F
Silvestri
Furio
F
Biasucci
Luigi M
LM
Baldi
Alfonso
A
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001344:Autopsy; D046508:Culture Techniques; D005260:Female; D006333:Heart Failure / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016015:Logistic Models; D008297:Male; D032342:Muscle Cells / Q000473:pathology; D009203:Myocardial Infarction / Q000401:mortality* / Q000473:pathology*; D011336:Probability; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013997:Time Factors; D020257:Ventricular Remodeling / Q000502:physiology*