Growth hormone resistance in chronic heart failure and its therapeutic implications

In recent years the administration of recombinant human growth hormone (GH) has received great attention. This review compares the potential of this therapeutic intervention in heart failure with that in other diseases where wasting is commonly seen. The pathophysiologic importance of GH and insulin-like growth factor (IGF)-I in these conditions will be discussed.

Abnormalities of the GH-IGF-I axis play an important role in the development of cachexia in chronic illnesses. GH resistance is a major determinant of the wasting process, acting through several different mechanisms: increased catabolism, impaired anabolism, and enhanced apoptosis in peripheral tissues. GH therapy has been evaluated in chronic heart failure (CHF); acquired GH resistance may explain the general lack of therapeutic success in the majority of studies. The assessment of plasma levels of GH, IGF-I, and, in particular, GH binding protein may help to guide dosing of GH for CHF patients.

GH resistance might be overcome by use of intermittent or higher doses of GH, or alternatively by combining GH with IGF-I. Randomized studies of GH therapy in catabolic states, with targeted dosing and longer duration of treatment are required to fully assess the safety and efficacy of this treatment approach.