Effects of 1-year treatment with octreotide on cardiac performance in patients with acromegaly(365 views) Colao A, Cuocolo A, Marzullo P, Nicolai E, Ferone D, Florimonte L, Salvatore M, Lombardi G
Keywords: Growth Hormone, Octreotide, Somatomedin C, Acromegaly, Adult, Article, Clinical Article, Drug Effect, Drug Efficacy, Exercise, Female, Growth Hormone Blood Level, Heart Left Ventricle Ejection Fraction, Heart Left Ventricle Function, Heart Performance, Heart Scintiscanning, Human, Hypertension, Priority Journal, Adolescent, Aged, Human Growth Hormone, Insulin-Like Growth Factor I, Middle Aged, Ventricular Function,
Affiliations: Depts. of Molec. and Clin. E., Nucl. Med. Ctr. of the Natl. C., Federico II University of Naples, Naples, Italy
Dept. of Biomorphological and F., Federico II University of Naples, Naples, Italy
Dept. of Molec. and Clin. E., Federico II University, via S. Pansini 5, 80131 Naples, Italy
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Bertoni, P. D., Morandi, G., Impaired left ventricular diastolic function in acromegaly: An echocardiographic study (1987) Acta Cardiol, 42, pp. 1-10
Rodrigues, E. A., Caruana, M. P., Lahiri, A., Nabarro, J. D. N., Jacobs, H. S., Raftery, E. B., Subclinical cardiac dysfunction in acromegaly: Evidence for a specific disease of heart muscle (1989) Br Heart J, 62, pp. 185-194
Sacc, L., Cittadini, A., Fazio, S., Growth hormone and the heart (1994) Endocr Rev, 15, pp. 555-573
L pez-Velasco, R., Escobar-Morreale, H. F., Vega, B., Cardiac involvement in acromegaly: Specific myocardiopathy or consequence of systemic hypertension (1997) J Clin Endocrinol Metab, 82, pp. 1047-1053
Bonow, R. O., Bacharach, S. L., Green, M. V., Impaired left ventricular diastolic filling in patients with coronary artery disease: Assessment with radionuclide angiography (1981) Circulation, 64, pp. 315-323
Bonow, R. O., Vitale, D. F., Bacharach, S. L., Frederick, T. M., Kent, K. M., Green, M. V., Asynchronous left ventricular regional function and impaired global diastolic filling in patients with coronary artery disease: Reversal after coronary angioplasty (1985) Circulation, 71, pp. 297-307
Arrighi, J. A., Soufer, R., Left ventricular diastolic function: Physiology methods of assessment and clinical significance (1995) J Nucl Cardiol, 2, pp. 525-543
Nabarro, J. D. N., Acromegaly (1987) Clin Endocrinol (Oxf), 26, pp. 481-512
Bengtsson, B. A., Ed n, S., Ernest, I., Oden, A., Sj gren, B., Epidemiology and long term survival in acromegaly (1988) Acta Med Scand, 223, pp. 327-335
Lamberts, S. W. J., Van Der Lely, A. -J., De Herder, W. W., Hofland, L. J., Octreotide (1996) N Engl J Med, 34, pp. 246-254
Bates, A. S., Van't Hoff, W., Jones, J. M., Clayton, R. N., An audit of outcome of treatment in acromegaly (1993) Q J Med, 86, pp. 293-299
Padayatty, S. J., Perrins, E. J., Belchetz, P. E., Octreotide treatment increases exercise capacity in patients with acromegaly (1996) Eur J Endocrinol, 134, pp. 554-559
Effects of 1-year treatment with octreotide on cardiac performance in patients with acromegaly
The aim of the study was to investigate the effects of 1-yr treatment with octreotide (OCT) on left ventricular diastolic and systolic function, assessed at rest and during physical exercise by gated blood pool cardiac scintigraphy, in 30 patients with active acromegaly. OCT was initially given at a dose of 0.05-0.1 mg, 3 times daily, and the dose was subsequently increased to achieve GH/insulin-like growth factor I (IGF-I) normalization. Hormone normalization after treatment was considered when basal and/or oral glucose test-suppressed GH values were below 2.5 and 1 μg/L, respectively, and IGF-I values were within the normal range for age. TG evaluate the response to OCT treatment in terms of cardiac performance, the 30 patients were divided into 2 groups on the basis of normalized (in 13 patients) or nonnormalized (in 17 patients) circulating GH and IGF-I levels. At study entry, hypertension was found in 6 patients (20%), abnormal left ventricular diastolic filling was found in 12 patients (40%), and impaired left ventricular ejection fraction was found in 2 patients at rest (6.6%) and in 18 patients at peak exercise (60%). Before OCT treatment, exercise duration ranged from 6-10 min, and exercise workload ranged from 50-125 watts. After 1-yr treatment with OCT, a significant decrease in circulating GH and IGF-I levels was achieved in all patients, but normalization was obtained only in 13 of 30 patients. In patients achieving circulating GH and IGF-I normalization after OCT treatment but not in those with persistently elevated hormone levels, a significant decrease in heart rate, both at rest (from 75.7 ± 3.3 to 66.5 ± 2.9 beats/min; P < 0.01) and after exercise (from 137.5 ± 4.9 to 123.7 ± 4.1 beats/min; P < 0.01), and a significant increase in left ventricular ejection fraction, both at rest (from 56.5 ± 1.8% to 66.5 ± 2.2%; P < 0.01) and after exercise (from 52.6 ± 2.4% to 67.1 ± 1.7%; P < 0.01), were found. In the 17 patients who had persistently high circulating GH and IGF-I levels after 1 yr of OCT treatment, left ventricular ejection fraction was unchanged at rest but was significantly reduced after exercise compared to the basal value (from 64.9 ± 2.4% to 57.2 ± 2.6%, P < 0.01); systolic blood pressure at rest was significantly increased (from 128.5 ± 4.9 to 141.2 ± 5.4 mm Hg; P < 0.05). In these 17 patients, the ejection fraction response to exercise was significantly impaired, mostly in those less than 40 yr of age (from 11.6 ± 3.2% to -0.3 ± 5.6%; P < 0.05). In particular, among 9 patients who had a normal response to exercise at study entry, 6 developed an abnormal response after 1 yr. Left ventricular diastolic filling was unchanged by OCT treatment in all patients. Exercise duration (only in young patients from 7.5 ± 0.5 to 9.3 ± 0.7 min; P < 0.05) and exercise workload (in all 13 patients from 80.8 ± 6.4 to 92.3 ± 5.9 watts; P < 0.05) were significantly increased in the group of patients with normalized GH and IGF levels, but not in the remaining 17 (from 7.6 ± 0.4 to 7.5 ± 0.4 min and from 89.9 ± 5.5 to 84.4 ± 4.5 watts, respectively). In conclusion, the results of the present study indicate that suppression of basal or glucose-suppressed GH levels below 2.5 or 1 μg/L, respectively, together with normalization of plasma IGF-I levels for 1 yr are followed by a significant improvement, but not complete normalization, of left ventricular ejection fraction either at rest or at peak exercise without significant changes in diastolic filling. By contrast, the persistence for 1 yr of elevated hormone levels caused a significant increase in systolic blood pressure and impaired cardiac performance. These data suggest that prolonged suppression of circulating GH and IGF-I levels could normalize cardiac performance and probably reverse the poor prognosis for cardiovascular disease in acromegaly.
Effects of 1-year treatment with octreotide on cardiac performance in patients with acromegaly