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Treatment with Growth Hormone Receptor Antagonist in Acromegaly: Effect on Cardiac Structure and Performance

Departments of Molecular and Clinical Endocrinology and Oncology (R.P., R.S.A., M.C.D.M., M.Galdi., A.Ci., G.L., A.Co.), Clinical and Experimental Medicine (M.Galde., A.D.), "Federico II" University of Naples, 80131 Naples, Italy; and Pfizer Inc. (I.K., P.B.), New York, New York 10017

Address all correspondence and requests for reprints to: Rosario Pivonello, Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, via S. Pansini 5, 80131 Naples, Italy. E-mail: rpivone{at}tin.it.

Aim: The aim of the current study was to evaluate the effect of short-term (6 months) and long-term (18 months) treatment with pegvisomant on cardiac structure and performance in patients with acromegaly.

Patients: Seventeen patients (nine women, eight men, 27–61 yr) with active acromegaly entered and 12 completed the long-term study. After a baseline evaluation, including measurement of hemodynamic, biochemical, and hormonal parameters, and a standard Doppler echocardiography, treatment with pegvisomant was started at the initial dose of 10 mg/d, increasing by 5 mg/d every 6 wk on the basis of IGF-I levels until normalization or the achievement of a maximal dose of 40 mg/d.

Results: After short-term treatment, IGF-I levels were normalized in 10 of the 17 (59%) patients. Left ventricular mass index (LVMi) was significantly decreased without changes in diastolic and systolic performance. After long-term treatment, IGF-I levels were normalized in 10 of the 12 (83%) patients. Blood glucose and serum insulin levels were decreased compared with baseline. LVMi was further decreased compared with short-term treatment, so that the prevalence of left ventricle hypertrophy decreased from 50% at baseline to 17% after 18 months of treatment. Moreover, ejection fraction as well as early to late (atrial) peak velocity ratio (E/A) were significantly increased, whereas isovolumic relaxation time was significantly decreased compared with baseline, demonstrating an improvement of both diastolic and systolic function. A significant correlation was found between the change in IGF-I levels and that of left ventricular ejection fraction. In general, the prevalence of cardiac insufficiency was present in 13 of the 17 (76%) patients at baseline and in one (8%) patient after 18 months of treatment.

Conclusions: Long-term treatment with the GH receptor antagonist improves acromegalic cardiomyopathy by decreasing cardiac hypertrophy and enhancing diastolic and systolic function, and consequently partially or completely reverting the cardiac insufficiency.

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