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Role of growth hormone in chronic heart failure. Therapeutic implications
M Volterrani1, F Manelli, M Cicoira
1Fondazione S. Maugeri, Cardiology Department, Gussago Medical Centre, Brescia, Italy. mvolterrani@fsm.it
Insights
Growth hormone (GH) may impact heart function, but its effectiveness in treating heart failure remains uncertain. Recent studies show mixed results, suggesting acquired GH resistance in severe heart failure may affect treatment outcomes.
Area of Science:
- Cardiology and Endocrinology
- Investigates the role of Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) in cardiovascular health.
Background:
- Congestive heart failure (CHF) is a prevalent cardiovascular disorder with a poor prognosis.
- Current treatments for CHF include diuretics, ACE inhibitors, and beta-blockers.
- GH and IGF-1 are crucial for muscle mass, body composition, and nutrient metabolism, with established roles in myocardial structure and function.
Purpose of the Study:
- To evaluate the potential beneficial effects of Growth Hormone (GH) in patients with heart failure.
- To explore the mechanisms by which GH and IGF-1 influence cardiac performance.
Main Methods:
- Review of existing literature on GH, IGF-1, and their effects on cardiac function.
- Analysis of studies involving patients with GH deficiency, acromegaly, and heart failure.
- Consideration of findings from animal models and clinical trials, including randomized, placebo-controlled studies.
Main Results:
- GH and IGF-1 receptors are present in cardiac myocytes, suggesting direct or indirect effects on the heart.
- GH administration improves cardiac function in patients with GH deficiency.
- Recent randomized trials showed no significant improvement in cardiac performance in dilated cardiomyopathy patients treated with GH, despite increased IGF-1 levels.
Conclusions:
- Acquired GH resistance may be a significant factor in severe heart failure, potentially explaining variable responses to GH therapy.
- The role and optimal use of GH in heart failure treatment require further investigation.
- Further research is needed to establish the place of GH treatment in managing heart failure.
Abstract:
Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases and, in addition, an impaired cardiac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thickening, which leads to impaired cardiac performance; therefore, based on the evidence available for GH we would expect beneficial effects from the use of 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 administration dramatically improves cardiac function. In small nonblind studies, both short and long term GH treatment have demonstrated beneficial effects in patients with heart failure secondary to ischaemic or idiophatic cardiomyopathy. Recently, two randomised, placebo-controlled studies, did not show significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failure and explain the different responses to GH therapy seen in different patients. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.