Ann Thorac Surg 2002;73:1769
© 2002 The Society of Thoracic Surgeons
Original article: cardiovascular
Invited commentary
Pedro J. del Nido, MDa
a Department of Cardiac Surgery, Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
e-mail: pedro.delnido{at}tch.harvard.edu
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The growth hormone and insulin-like growth factor I (GH-IGF-I) axis plays an important role in cardiac development and plays a trophic role on the heart. There is a high density of growth hormone receptors in cardiomyocytes, and locally produced IGF-I in response to exogenous growth hormone (GH) has been shown to improve contractility and leads to increased synthesis of contractile myofilaments and hypertrophy.
Growth hormone and insulin-like growth factor I axis has also been implicated in heart failure from a variety of etiologies both experimentally and in the clinical setting, where a putative role has been suggested. A number of clinical trials now completed and currently underway are attempting to determine the potential therapeutic benefits of growth hormone supplementation in adults with symptoms of congestive heart failure but who are not growth hormone deficient. The rationale for this approach is based on the observation that a relative growth hormone insensitivity develops as heart failure progresses, with high serum GH levels and low IGF-I levels. In children with dilated cardiomyopathy, growth hormone administration is proposed as a therapy that could promote hypertrophy and increase in muscle mass. Clinical trials are ongoing in pediatric patients with cardiomyopathy to evaluate the impact of exogenous growth hormone on cardiac function and symptoms of congestive heart failure.
The report by Tsai and associates showing similar findings in a group of children with isolated ventricular septal defect is consistent with previous reports describing the growth hormone insensitivity in children with congenital heart defects and symptoms of heart failure. However, the observation that GH and IGF-I levels gradually return towards normal following surgical repair is important because it supports the theory that GH insensitivity is a secondary phenomenon associated with heart failure, rather than a primary defect contributing to the progression to heart failure due to an inability to adapt to the increase in cardiac workload. To resolve this controversy more definitively, however, further studies monitoring GH-IGF-I serum levels before and after surgical repair, as well as correlating serum levels with actual tissue levels of these growth factors, may be necessary. Until further insight is gained into the mechanism of growth hormone insensitivity in children with congenital heart defects and symptoms of heart failure, a proposal for therapeutic GH supplementation in these patients may be premature.
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Change of serum growth factors in infants with isolated ventricular defect undergoing surgical repair
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Ann. Thorac. Surg. 2002 73: 1765-1768.
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