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, asses sed at rest and during physical exercise by gated blood pool cardiac scinti graphy, in 30 patients with active acromegaly. OCT was initially given at a dose of 0.05-0.1 mg, 3 times daily, and the do se was subsequently increased to achieve GH/insulin-like growth factor I (I GF-I) normalization. Hormone normalization after treatment was considered w hen basal and/or oral glucose test-suppressed GH values were below 2.5 and 1 mu g/L, respectively, and IGF-I values were within the normal range for a ge. To evaluate the response to OCT treatment in terms of cardiac performan ce, the 30 patients were divided into 2 groups on the basis of normalized t in 13 patients) or nonnormalized tin 17 patients) circulating GH and IGF-I levels. At study entry, hypertension was found in 6 patients (20%), abnormal left v entricular diastolic filling was found in 12 patients (40%), and impaired l eft ventricular ejection fraction was found in 2 patients at rest (6.6%) an d in 18 patients at peak exercise (60%). Before OCT treatment, exercise dur ation 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 ICE-I levels was achieved in all patients, but normalization was obtained only in 13 of 30 patients. In patients achieving circulating GH and IGF-T n ormalization after OCT treatment but not in those with persistently elevate d hormone levels, a significant decrease in heart rate, bath at rest (from 75.7 +/- 3.3 to 66.5 +/- 2.9 beats/min; P < 0.01) and after exercise (from 157.5 +/- 4.9 to 123.7 +/- 4.1 beats/min; P < 0.01), and a significant incr ease 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 vent ricular ejection fraction was unchanged at rest but was significantly reduc ed 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 incre ased (from 128.5 +/- 4.9 to 141.2 +/- 5.4 mm Hg; P < 0.05). In these 17 pat ients, the ejection fraction response to exercise was significantly impaire d, 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 t o exercise at study entry, 6 developed an abnormal response after 1 yr. Lef t ventricular diastolic filling was unchanged by OCT treatment in all patie nts. Exercise duration (only in young patients from 7.5 +/- 0.5 to 9.3 +/- 0.7 min; P < 0.05) and exercise workload tin all 13 patients from 80.8 +/- 6.4 to 92.3 +/- 5.9 watts; P < 0.05) were significantly increased in the gr oup 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 o f basal or glucose-suppressed GH levels below 2.5 or 1 mu g/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 ventr icular ejection fraction either at rest or at peak exercise without signifi cant changes in diastolic filling. By contrast, the persistence for 1 yr of elevated hormone levels caused a significant increase in systolic blood pr essure and impaired cardiac performance. These data suggest that prolonged suppression of circulating GH and IGF-I levels could normalize cardiac perf ormance and probably reverse the poor prognosis for cardiovascular disease in acromegaly.