Growth Hormone Therapy in Heart Failure: Where Are We Now?

Catherine Demers, MD, MSc, Robert S. McKelvie, MD, PhD

Disclosures

CHF. 2003;9(2) 

In This Article

Randomized, Controlled, Clinical Trials Evaluating the Role of GH in HF

Only three randomized, controlled clinical trials evaluating the effect of GH in patients with HF have been published ( Table II ).[47,48,49] In 50 patients with idiopathic dilated cardiomyopathy treated for 12 weeks, despite a significant increase in IGF-I and IGFBP-3, there were no changes in systolic wall stress, left ventricular cavity dimensions, or left ventricular ejection fraction, although there was a significant increase in left ventricular mass.[47] Another study evaluated 22 patients with dilated, ischemic, or valvular cardiomyopathies randomized to receive GH or placebo for 12 weeks.[48] IGF-I was significantly increased, but left ventricular ejection fraction at rest or with exercise, end-systolic diameter, end-diastolic diameter, left ventricular wall thickness, and left ventricular mass were not improved with rhGH, compared to placebo. Furthermore, cardiac index, stroke volume index, systemic vascular resistance, pulmonary artery pressure, and wedge pressure also remained unchanged after 3 months of therapy.[47] In an unblinded, randomized clinical trial, 22 patients with ischemic cardiomyopathy were randomized to GH or placebo for a duration of 6 months.[49] GH had no effect on the total perfusion score in the GH-treated group, as measured by gated single-photon emission-computed tomography imaging, or on left ventricular mass and left ventricular ejection compared to the placebo group, despite significant increases in IGF-I and IGFBP-3 levels. These studies involved a smaller daily dose of rhGH than the study by Fazio et al.,[38] where a doubled dose was administered every second day. The administration of GH every other day may be more optimal for the induction of IGF-I mRNA in the periphery.[48]

Osterziel et al.[47] reported that one patient with NYHA class IV symptoms at baseline treated with rhGH was withdrawn from treatment due to progressive left ventricular failure. One patient with known ventricular arrhythmia (Lown IV B) taking rhGH received an implantable cardioverter/defibrillator following hospital admission for sustained ventricular tachycardia, and another patient allocated to rhGH also received a defibrillator prior to active treatment for a syncopal episode that occurred during baseline testing. There were no significant adverse events reported for patients in the placebo group. Isgaard et al.[48] reported no serious side effects for patients treated with rhGH and placebo during the study. Finally, Smit et al.[49] reported that one patient was admitted with chest pain without evidence of myocardial infarction and two patients experienced a congestive heart failure exacerbation relieved by increased dosage of diuretics.

In these three studies, there were no significant improvements in exercise capacity, NYHA functional classification, plasma epinephrine, norepinephrine, aldosterone, renin activity, or angiotensin II. The lack of positive findings in these randomized clinical trials could be due to the small sample sizes, short duration of treatment, and the dose administered to patients with HF. Levels of plasma GH measured in cachectic heart failure patients are elevated, as well as other markers of catabolic state, such as cortisol and tumor necrosis factor levels, compared to noncachectic patients.[50] Patients with cachexia and HF present with characteristics suggestive of GH resistance, with increased levels of GH and a tendency to lower levels of IGF-I. GH resistance is also seen in states of malnutrition and critical illness.[51] Lack of response to GH therapy in cachectic HF patients with more severe disease may be associated with GH resistance.[51] This may suggest some "uncoupling" of the GH/IGF-I axis in some HF patients, but further study of this mechanism is needed in this population of patients.

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