Abstract 19882: Ventricular Assist Device Implantation Corrects Impairment of Growth Hormone/Insulin-like Growth Factor-1 Signaling in Patients with Advanced Heart Failure
Introduction: Heart failure (HF) is a clinical syndrome with complex metabolic derangements and progressive catabolic effects. Patients with HF have increased muscle atrophy and proteolysis which has been linked to impaired growth hormone (GH)/insulin-like growth factor (IGF)-1 axis signaling and insulin resistance. We hypothesized that implantation of a ventricular assist device (VAD) will reverse GH/IGF-1 axis dysfunction in patients with HF.
Methods: Serum was collected from 18 subjects with advanced HF before and after VAD implantation and 6 healthy control subjects. Clinical data were obtained from institutional medical records. Serum levels of insulin, GH, IGF-1 and IGFBP-3 were measured by ELISA and insulin resistance calculated using the HOMA-IR method.
Results: The control subjects had a mean age of 46±3.8 years and BMI of 25.7±0.9 kg/m2. The cohort with advanced HF had a mean age of 52.1±2.6 years, mean ejection fraction of 18±0.8% and mean VAD duration of 117±13.1 days. There was no difference in mean BMI after VAD. Serum levels of GH were increased (647±382.2 pg/ml in con vs 1370.9±254.3 pg/ml in HF, p=0.15) while IGF-1 and IGFBP-3 were decreased in HF (5867.7±1299.3 pg/ml in con vs 786.3±369.4 pg/ml in HF, p<0.05; 2912.6±326.6 ng/ml in con vs 1711.5±188.1 ng/ml in HF, p<0.05) compared to control subjects. After VAD implantation, IGF-1 serum levels increased 4-fold (2678.2±750.9 pg/ml after VAD, p<0.05) and IGFBP-3 increased mildly (2085.5±205.4 pg/ml after VAD, p=0.14), but no change was found in elevated levels of GH.
Conclusions: Our data demonstrate that hemodynamic improvement and mechanical unloading after VAD implantation leads to correction of growth hormone resistance and increased levels of the anabolic molecule IGF-1 in patients with advanced HF. These findings show the reversibility of metabolic abnormalities of impaired GH/IGF-1 signaling in patients with advanced HF.
- © 2010 by American Heart Association, Inc.