Effects of Octreotide in Patients with Hypertrophic Obstructive Cardiomyopathy.

Demirtaş, Ertan; Sağ, Cemal; Kurşaklıoğlu, Hürkan; Uzun, Mehmet; Uzbay, Tayfun; Töre, Hasan Fehmi; Köse, Sedat; Genç, Celal; Demirkan, Deniz

doi:10.1536/ihj.39.173

Cited by 10 publications

(6 citation statements)

References 33 publications

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“…However, heart rate decreased, and LVEF at rest and ⌬LVEF increased only in patients with shorter disease duration. A direct cardiac effect of OCT on cardiac mass, as shown in patients with primary hypertrophic cardiomyopathy (39,40), or on heart rate via the conduction system (41) can be hypothesized. However, in a previous study we found similar results in a cohort of patients cured by surgery alone (42).…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Consequences of Early-Onset Growth Hormone Excess

Colao

Spinelli

Cuocolo

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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Acromegaly has relevant effects on the cardiovascular system, but few data deal with the early effects of GH and IGF-I excess. To study the early stage of acromegalic cardiomyopathy and give indirect evidence of the mechanisms underlying GH and IGF-I action on the human heart, 25 patients with uncomplicated acromegaly [15 young subjects with short-term (< or =5 yr) disease and 10 with long-term (>5 yr) disease] and 25 sex- and age-matched controls were studied. Cardiovascular risk parameters were studied by standard methods; cardiac morphology by M-mode and Doppler echocardiography, cardiac function at rest and at peak exercise by equilibrium radionuclide angiography, and vascular disease at common carotid arteries by Doppler ultrasonography. In the patient group these measurements were repeated after 6 months of treatment with octreotide-LAR (20-40 mg, im, every 28 d). Glucose, glycosylated hemoglobin, insulin, low density lipoprotein cholesterol, triglycerides, and fibrinogen levels were higher, and high density lipoprotein cholesterol levels were lower in acromegalic patients than in controls. Resting blood pressure was similar in patients and controls, whereas heart rate at rest and systolic blood pressure at peak exercise were higher in the patients. The left ventricular mass index was higher in acromegalic patients than in controls (123.3 +/- 8.9 vs. 81.5 +/- 4.3 g/m(2); P < 0.001); seven patients had left ventricular hypertrophy. Diastolic function was similar in the two groups. The ejection fraction at rest, but not at peak exercise, was significantly increased in the patients compared with controls. As a consequence the exercise-induced changes in the ejection fraction were lower in patients than controls (8.7 +/- 1.1% vs. 21.9 +/- 3.5%; P < 0.001). At common carotid ultrasonography, young patients with acromegaly had increased diastolic peak velocity and increased intima media thickness, even if neither patient nor controls had atherosclerotic plaques. Six months after OCT-LAR treatment, GH and IGF-I levels remarkably decreased in all patients; 8 (53.3%) achieved disease control. Insulin, total cholesterol, and fibrinogen levels reduced, whereas high density lipoprotein cholesterol levels increased. Both at rest and at peak exercise, heart rate significantly decreased, whereas systolic and diastolic blood pressures did not change. The left ventricular mass index was significantly reduced, but it was still higher than the control value (101.6 +/- 3.5 g/m(2); P < 0.01). The left ventricular ejection fraction at rest was significantly reduced, but its response at peak exercise was increased (16.3 +/- 2.4%), becoming similar to the control value. At common carotids, the intima media thickness of right and left arteries was significantly reduced as was the diastolic peak velocity without any change in systolic peak velocity. Short-term GH excess, despite causing enhanced cardiac performance at rest, reduces cardiac performance on effort and impairs vascular morphology. These deleterious effects of early-onse...

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Consequences of Early-Onset Growth Hormone Excess

Colao

Spinelli

Cuocolo

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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show abstract

“…In contrast with previous data of short-term follow-ups (28), no improvement in physical performance, both exercise duration and exercise workload, was observed in this study. A direct cardiac effect of octreotide, as shown on cardiac mass in patients affected with primary hypertrophic cardiomyopathy (46,47) or on heart rate via the conduction system (48), seems to be excluded by the evidence that the results were similar in patients controlled by surgery and in those controlled by octreotide.…”

Section: Discussionmentioning

confidence: 99%

Is the Acromegalic Cardiomyopathy Reversible? Effect of 5-Year Normalization of Growth Hormone and Insulin-Like Growth Factor I Levels on Cardiac Performance*

Colao¹,

Cuocolo

Marzullo³

et al. 2001

The Journal of Clinical Endocrinology & Metabolism

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Acromegalic patients are considered to be exposed to a doubled mortality rate, mostly for cardiovascular diseases. This open prospective study was designed to evaluate whether the impairment of cardiac performance could be reversed by the long-term suppression of GH and insulin-like growth factor I (IGF-I) levels. Eighteen patients with active acromegaly were studied before and 5 yr after surgery, followed by sc octreotide in 11 patients. Disease control (GH levels < or =1 microg/L after glucose load or < or =2.5 microg/L after fasting, respectively, together with normalized IGF-I levels for age) was achieved in seven patients after surgery and in six patients after 0.3--0.6 mg/day sc octreotide. Five patients were not controlled during the 5-yr follow-up. Cardiac performance at rest and at peak exercise was assessed by equilibrium radionuclide angiography at study entry and 5 yr after surgery alone or plus octreotide. Thirty-six sex- and age-matched healthy subjects served as controls. At study entry, patients had a lower left ventricular ejection fraction (LVEF) at peak exercise and LVEF exercise-induced changes, exercise duration, and capacity than controls (P < 0.001). After 5 yr of treatment, a significant decrease of resting heart rate (P = 0.03) and a significant increase of LVEF at peak exercise (P = 0.003) was found in patients achieving disease control. LVEF response at peak exercise worsened in none of the patients with controlled disease and in three patients with uncontrolled disease (60%) (chi(2) = 5.5; P = 0.02). Diastolic filling, exercise duration, and workload did not significantly change during the 5-yr follow-up. No difference was found between patients controlled by surgery alone or by surgery plus octreotide. This 5-yr prospective study demonstrated that the LVEF response at peak exercise improved in all patients achieving disease control, while it was worsened in 60% of uncontrolled ones. These results strengthen the need of a stable suppression of GH and IGF-I hypersecretion to restore a normal cardiac performance in acromegaly.

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“…Interestingly, in contrast with the changes in functional parameters that occurred only in patients achieving GH and IGF-I normalization, the reduction in LVMi was observed in all patients, independent from the normalization of hormone levels. It should be also considered that a decrease in LVM, after treatment with sc OCT, was reported in patients affected with primary hypertrophic cardiomyopathy (39,40), suggesting that the decrease of the LVM can be attributable not only to an endocrine mechanism, by decreasing circulating GH and IGF-I, but probably also to a direct autocrine and/or paracrine effect of OCT on the intracardiac GH/IGF-I axis.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Depot Long-Acting Somatostatin Analog Sandostatin LAR in Acromegaly*

Colao¹,

Marzullo²,

Ferone³

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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Cardiovascular disease is the most severe complication of acromegaly accounting for the increased mortality of these patients. Recently, the slow-release form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection every 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 μg/L) in 39–75% of patients, and normalization of insulin-like growth factor (IGF)-I levels for age in 64–88% of patients, with an excellent patients’ 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 somatostatin analog-naive patients with acromegaly (GH, 94.8 ± 24.9 mU/L; IGF-I, 757.9 ± 66.6 μg/L), focusing on the early effect of GH and IGF-I suppression on the heart. Cardiac structure was investigated by echocardiography, whereas LV performance was investigated by gated-blood-pool scintigraphy, 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, for 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 glucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, together with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of GH (to 12.9 ± 3.0 mU/L) and IGF-I levels (to 340.3 ± 40.2 μg/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression was 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 thickness, and LV posterior wall thickness was observed in all 15 patients after 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 normalized their LVMi after treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest (<50%) was 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 significant 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 (as 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, all 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 patients normalized, 4 improved, and 2 impaired their responses after treatment. 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 parameters, 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 control in 60% of patients after 6 months of treatment. The sustained suppression of IGF-I levels was followed by a significant reduction of LVMi in all patients already after 3 months of treatment, with recovery of LV hypertrophy in 6 of 11 patients. In contrast, LV performance was significantly improved only in patients achieving normalization of their hormone levels. These data suggest that the treatment with OCT-LAR, by inducing a rapid suppression of circulating GH and IGF-I levels, could produce an early improvement of the cardiac abnormalities of acromegaly, thus contributing to reversal of the poor prognosis for cardiovascular diseases of these patients.

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Effects of Octreotide in Patients with Hypertrophic Obstructive Cardiomyopathy.

Cited by 10 publications

References 33 publications

Cardiovascular Consequences of Early-Onset Growth Hormone Excess

Cardiovascular Consequences of Early-Onset Growth Hormone Excess

Is the Acromegalic Cardiomyopathy Reversible? Effect of 5-Year Normalization of Growth Hormone and Insulin-Like Growth Factor I Levels on Cardiac Performance*

Cardiovascular Effects of Depot Long-Acting Somatostatin Analog Sandostatin LAR in Acromegaly*

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