The Severity of Chronic Heart Failure due to Coronary Artery Disease Predicts the Endocrine Effects of Short- Term Growth Hormone Administration1

Abstract

Treatment with human recombinant GH has yielded conflicting results in patients with heart failure. As GH sensitivity may be important for treatment effects, the present study evaluated GH secretion and sensitivity in noncachectic patients with ischemic heart failure. Twenty clinically stable, male patients with moderate heart failure (mean New York Heart Association class, 2.0 ± 0.8; mean ejection fraction, 30.0 ± 8.4%) due to coronary artery disease were randomly assigned single blind to a low dose (group A; n = 10) and a high dose (group B; n = 10) group, receiving either 5μ g/kg·day recombinant human GH for 4 days followed by 10μ g/kg·day GH for another 4 days or 10 and 20 μg/kg·day GH, respectively. Cardiac function was assessed by echocardiography. Serum insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and 24-h urinary GH excretion as a measure of pituitary GH secretion were determined at baseline and on days 5 and 9. Baseline IGF-I and IGFBP-3 levels and GH excretion were significantly diminished compared to those in age-matched controls. There was a dose-dependent increase in IGF-I and IGFBP-3 during GH treatment. The increase in IGF-I induced by 10 μg/kg·day GH correlated positively to left ventricular ejection fraction (r = 0.59; P = 0.006) and inversely to left ventricular end-diastolic and end-systolic dimensions (r < –0.6 and P < 0.01 for both). In conclusion, GH secretion and serum levels of IGF-I and IGFBP-3 are diminished in patients with moderate ischemic heart failure. Left ventricular function determines the sensitivity of the GH/IGF-I system, measured as the IGF-I response to GH application. This finding suggests that individual dose adjustments may be an indispensable prerequisite for successful GH therapy in heart failure.