The somatotrophic system in patients with dilated cardiomyopathy: Relationof insulin-like growth factor-1 and its alterations during growth hormone therapy to cardiac function

OBJECTIVE Treatment with human recombinant growth hormone has yielded confl icting results in patients with congestive heart failure. In addition, grow th hormone resistance has been reported in severe heart failure. Therefore, the purpose of this study was to evaluate the somatotrophic axis and effec ts of growth hormone on haemodynamics in patients with heart failure due to dilated cardiomyopathy. DESIGN Randomized, double-blind, placebo-controlled trial. PATIENTS Fifty clinically-stable patients with moderate heart failure (mean left ventricular ejection fraction = 26 +/- 2%) due to dilated cardiomyopt hy were examined. MEASUREMENTS Patients were randomly assigned to treatment with placebo or 2 IU/d sc human recombinant growth hormone for a mean of 1 4 weeks. Cardiac size and function were evaluated by magnetic resonance ima ging. Central haemodynamics were obtained by right heart catheterization. M easurements of plasma noradrenaline, serum insulin-like growth factor-1, an d insulin-like growth factor binding protein-3 were performed by standard a ssays at baseline and at the end of the treatment period. RESULTS The severity of heart failure as determined by stroke volume, left ventricular end diastolic diameter and plasma noradrenaline concentrations correlated significantly to baseline serum insulin-like growth factor-1 lev els (each P<0.05). The growth hormone-induced increase of insulin-like grow th factor-1 predicted the changes in ejection fraction (P<0.05). A signific ant increase in ejection fraction of 7% was observed in patients whose insu lin-like growth factor-1 increased by more than the median increase in comp arison to the patients with an increase below the median (+ 4.0 +/- 2.3% vs . - 3.0 +/- 1.8%; P=0.03). CONCLUSIONS Serum levels of insulin-like growth factor-1, reflecting growth hormone secretion, are diminished in relation to the severity of heart fai lure in patients with dilated cardiomyopathy, Growth hormone induced increa ses of insulin-like growth factor-1 of more than 77 ng/l caused significant improvement of ejection fraction.