Cardiomyocyte Apoptosis is Related to Left Ventricular Dysfunction and Remodelling in Dilated Cardiomyopathy, But is not Affected by Growth Hormone Treatment

BACKGROUND AND AIMS: Cardiomyocyte apoptosis (CA) is a common feature of end-stage heart failure. We examined whether CA is associated with cardiac dysfunction and remodelling in heart failure due to dilated cardiomyopathy and studied the effect of human growth hormone (hGH) on CA. METHODS AND RESULTS: We studied 38 patients, included in a phase III multi-center, randomised, double-blind and placebo-controlled trial of biosynthetic hGH treatment in dilated cardiomyopathy, at baseline and after 14 weeks treatment. Twenty-six patients received hGH and 12 received placebo. CA was quantified in endomyocardial biopsies using the TUNEL assay. CA correlated with left ventricular size (r=0.43, p=0.007). Compared to patients with CA below the median of 0.53%, patients with CA above the median had significantly larger left ventricular volumes and lower ejection fractions (EF) by echocardiography (median (interquartile range)) 200 ml (84) vs. 257 ml (134) and 27% (11) vs. 23% (9). Expression of the Fas receptor was associated with a high rate of CA. hGH treatment significantly increased serum IGF-1 levels, but it had no effect on CA or cardiac structure and function. CONCLUSION: CA is related to left ventricular enlargement and dysfunction in dilated cardiomyopathy. CA is not affected by short-term treatment with hGH.