Cardiovascular effects of depot long-acting somatostatin analog sandostatin LAR in acromegaly

Cardiovascular disease is the most severe complication of acromegaly accoun ting for the increased mortality of these patients. Recently, the slow-rele ase form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection ev ery 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 mu g/L) in 39-75% of patients, and normalization of insulin-like grow th factor (IGF)-I levels for age in 64-88% of patients, with an excellent p atients' compliance. The aim of the present study was to investigate the early effect of OCT-LAR treatment on the left ventricular (LV) structure and performance in 15 som atostatin analog-naive patients with acromegaly (GH, 94.8 +/- 24.9 mU/L; IG F-I, 757.9 +/- 66.6 mu g/L), focusing on the early effect of GH and IGF-I s uppression on the heart. Cardiac structure was investigated by echocardiogr aphy, whereas LV performance was investigated by gated-blood-pool scintigra phy, before and after 3 and 6 months of treatment with OCT-LAR. OCT-LAR was initially administered im, at a dose of 20 mg every 28 days, fo r 3 months. In six patients, the dose was then increased to 30 mg every 28 days to achieve disease control, which was considered when fasting and/or g lucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, toge ther with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of G H (to 12.9 +/- 3.0 mU/L) and IGF-I levels (to 340.3 +/- 40.2 mu g/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression wa s 52.8 +/- 4.4%, and serum GH/IGF-I levels were normalized in 9 patients. A significant decrease of LV mass index (LVMi), interventricular septum thic kness, and LV posterior wall thickness was observed in all 15 patients afte r 3 and 6 months of OCT-LAR treatment: LVMi was decreased by 19.1 +/- 2.0% without any difference in patients with (19.9 +/- 2.7%) or without disease control (17.8 +/- 3.3%). Among the 11 patients with LV hypertrophy, 6 norma lized their LVMi aRer treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest (<50%) wa s found in 5 patients (33.3%), whereas an impaired response of LVEF at peak exercise (<5% increase of basal value) was found in 9 patients (60%). A si gnificant increase in LVEF, both at rest (from 51.6 +/- 2.6 to 58.1 +/- 1.7 %, P < 0.01) and at peak exercise (from 51.6 +/- 2.3 to 60.2 +/- 2.4%, P < 0.001) was found in patients with las compared with those without) disease control (from 55.2 +/- 3.8 to 58.0 +/- 4% and from 61.8 +/- 4.6 to 61.8 +/- 3.4%, respectively). Among the 5 patients with inadequate LVEF at rest, al l but 1 regained a normal LVEF after 6 months of treatment; whereas, among the 9 patients with an impaired response of the LVEF at peak exercise, 3 pa tients normalized, 4 improved, and 2 impaired their responses after treatme nt. The percent of IGF-I suppression was significantly correlated with the percent increase of resting LVEF (r = 0.644, P < 0.01). Exercise duration ( from 6.0 +/- 0.7 to 7.3 +/- 0.7 min) and capacity (from 69.0 +/- 8.2 to 80 +/- 7.8 watts) were increased in the 15 patients considered as a whole, but the improvement in the exercise response was significant only in patients with disease control (P < 0.01 and P < 0.05, respectively) who also had an increase in the peak ejection rate (P = 0.03). No change in hemodynamic par ameters, either at rest or at peak exercise, was found after treatment with OCT-LAR in the 15 patients. In conclusion, the results of the present study demonstrate that OCT-LAR im injections every 28 days induces a sustained suppression of GH levels and IGF-I levels in all acromegalic patients, allowing achievement of disease c ontrol in 60% of patients after 6 months of treatment. The sustained suppre ssion of IGF-I levels was followed by a significant reduction of LVMi in al l patients already after 3 months of treatment, with recovery of LV hypertr ophy in 6 of 11 patients. In contrast, LV performance was significantly imp roved only in patients achieving normalization of their hormone levels. The se data suggest that the treatment with OCT-LAR, by inducing a rapid suppre ssion of circulating GH and IGF-I levels, could produce an early improvemen t of the cardiac abnormalities of acromegaly, thus contributing to reversal of the poor prognosis for cardiovascular diseases of these patients.