Role of growth hormone in chronic heart failure - Therapeutic implications

Congestive heart failure is a multiple aetiology, high prevalence, poor pro g prognosis cardiovascular disorder. Medical treatment of dilated cardiomyo pathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta -blockers have been shown to have favou rable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiol ogical processes such as the control of muscle mass and function, body comp osition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Rece ptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, G H may act directly on the heart or via the induction of local or systemic I GF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms . Patients with acromegaly have an increased propensity to develop ventricula r hypertrophy and cardiovascular diseases and, in addition, an impaired car diac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated upregulatio n of cardiac IGF-1 production and expression of GH and IGF-I receptors, imp lying that the local regulation of these factors is influenced by haemodyna mic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by chang es in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thicke ning, which leads to impaired cardiac performance; therefore, based on the evidence available for GK we would expect beneficial effects from the use o f GH in these patients. Several papers highlight the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH admin istration dramatically improves cardiac function. In small nonblind studies , both short and long term GH treatment have demonstrated beneficial effect s in patients with heart failure secondary to ischaemic or idiophatic cardi omyopathy. Recently, two randomised, placebo-controlled studies, did not sh ow significant GH-mediated improvement in cardiac performance in patients w ith dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failu re and explain the different responses to GH therapy seen in different pati ents. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.