Left Ventricular Diastolic Filling Pattern at Doppler Echocardiography and Apoptotic Rate in Fatal Acute Myocardial Infarction

Abstract

Heart failure is a complex syndrome characterized by impaired emptying and/or impaired filling of the heart chambers. The use of parameters of diastolic function has provided novel tools for risk stratification and management of patients with heart failure. This study evaluated the potential correlation between apoptosis at time of death and left ventricular (LV) diastolic function after acute myocardial infarction. We selected, at routine postmortem examination, 14 subjects who died 10 to 62 days after an acute myocardial infarction and had an available echocardiographic report from the most recent hospital admission. The apoptotic rate was calculated at the region bordering the infarct, using co-localization of in situ end-labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3. Transthoracic echocardiographic studies were retrospectively reevaluated and pulse-wave Doppler spectra of mitral inflow were analyzed. LV diastolic function was assessed by measuring the ratio of E peak velocity to A peak velocity and E-wave deceleration time; a ratio of E peak velocity to A peak velocity >or=2 and deceleration time <115 ms were considered a restrictive filling pattern. A restrictive pattern was found in 4 cases (29%). All subjects with a restrictive pattern were symptomatic for New York Heart Association class IV heart failure (100% vs 20%, p = 0.015) and had larger transverse heart diameters at pathology (p = 0.014). The apoptotic rate in the peri-infarct region was significantly higher in patients with a restrictive versus nonrestrictive diastolic pattern (13%, 10 to 14, vs 3%, 1 to 6, p = 0.014). At multivariable analysis that included the restrictive pattern, class IV heart failure, and cardiac diameters, the restrictive pattern remained an independent predictor of increased apoptosis (p = 0.030). In conclusion, patients with severe postinfarction LV diastolic dysfunction had significantly higher rates of cardiomyocyte loss by apoptosis, which may partly explain their unfavorable outcome.