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Objective: Growth hormone (GH) resistance with a reduction of insulin-like growth factor-I (IGF-I) serum concentrations seems to be implicated in the catabolic process associated with chronic heart failure (CHF). However, data concerning the prognostic value of these alterations in CHF patients without cachexia are scant. In this study, we aimed to determine in CHF patients the prognostic value of IGF-I/GH ratio and its relationships with N-terminal brain natriuretic peptide (NT-proBNP), a known marker of prognosis in these patients., Design: We enrolled 82 non-cachectic patients, mean age 61+/-13 years, with ejection fraction <40% and predischarge New York Heart Association (NYHA) functional classes II-IV. All patients underwent clinical examination, two-dimensional echocardiography and NT-proBNP, GH and IGF-I measurement with log IGF-I/GH ratio calculation. Mortality and clinical status was documented at follow-up (18.4+/-8.1 months)., Results: During follow-up 17 patients died of cardiac causes. Non-survivors were at baseline in higher NYHA class (P<0.05) and showed higher values of NT-proBNP (P<0.001) than survivors; differently IGF-I, and log IGF-I/GH ratio were lower (P<0.05). At Cox multivariate analysis, NT-proBNP (P<0.001) and IGF-I/GH ratio (P<0.05) were independent predictors of death., Conclusions: High NT-proBNP levels and low IGH-I/GH ratio may be useful to stratify CHF patients at higher risk of cardiac death.

Exercise-induced impairment of left ventricular (LV) ejection fraction is common in patients with acromegaly and normal resting systolic function. This study aimed to clarify whether diastolic dysfunction plays a role in the abnormal adaptation to exercise in these patients. Forty-eight patients with active acromegaly underwent LV radionuclide angiography at rest and during exercise. Doppler echocardiography was also performed to assess LV mass index and diastolic function by combined analysis of mitral and pulmonary flow velocity curves. LV ejection fraction at peak exercise was related to rest ejection fraction (r = 0.78; P < 0.001), peak filling rate (r = 0.55; P < 0.01), LV mass index (r = -0.56; P < 0.001), and the difference between duration of diastolic reverse pulmonary vein flow and mitral flow at atrial contraction (Delta duration) (r = -0.54; P < 0.01). At stepwise regression analysis, rest ejection fraction and Delta duration were the only variables that independently influenced (P < 0.001) ejection fraction at peak exercise. Diastolic dysfunction is important in determining cardiac performance during exercise in patients with acromegaly and normal resting systolic function. Combined analysis of pulmonary vein and mitral flow velocity curves allows the identification of impaired LV diastolic function in such patients.

To characterize mitral and aortic valve abnormalities we performed M-mode, two-dimensional, and pulsed Doppler echocardiography in 42 patients with active acromegaly, 22 patients cured of acromegaly, and 64 controls pair-matched with the patients for sex and age. The overall prevalence of valve abnormalities was higher in both the active patients (86% vs. 24%; P < 0.0001) and the cured patients (73% vs. 9%; P < 0.0001) than in controls. Left ventricular hypertrophy was higher in active (81% vs. 29%; P < 0.0001), but not in cured (41% vs. 14%; P = 0.09) patients than in controls. Cardiac valve abnormalities were associated with left ventricular hypertrophy in both patients and controls, without any difference between them. Conversely, among subjects without left ventricular hypertrophy, mitral and aortic abnormalities were only present in the patients (75% of active and 54% of cured), but not in controls (3% of active controls and 0% of cured controls). In conclusion, patients with active acromegaly and those cured of the disease have a high prevalence of mitral and aortic abnormalities. The persistence of valve disease in patients with cured acromegaly is likely to be correlated with the persistence of left ventricular hypertrophy, which should be carefully and continuously monitored as an aspect of the risk of cardiac dysfunction in these patients.

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-onset acromegaly are ameliorated by suppressing GH/IGF-I levels for 6 months.

Background: Patients with mild heart failure show a reduction in preload reserve mechanism during volume expansion. At this time, the effects of volume expansion on left ventricular (LV) diastolic filling in this subset of patients have not been well characterized., Methods: We evaluated the effects of acute volume loading on Doppler parameters of LV filling in 10 healthy control subjects and in 12 patients with idiopathic dilated cardiomyopathy (DCM). In patients with DCM, the effects of losartan on diastolic adaptation to volume load were also investigated., Results: During volume loading, the healthy control subjects showed a decrease in isovolumic relaxation time (F = 5.3, P <.05) but an increase in the LV peak filling rate (F = 52.9, P <.001) and velocity time integral of both systolic (F = 72.8, P <.001) and diastolic (F = 4.6, P <.05) pulmonary venous flow. In patients with DCM, isovolumic relaxation time decreased more than in control subjects (F = 8.1, P <.01), and the deceleration time of the early mitral wave was reduced (F = 26.3, P <.001). Furthermore, the duration of pulmonary venous flow reversal exceeded that of mitral flow at atrial contraction (F = 28.5, P <.001). After treatment with losartan, the deceleration time of early mitral wave remained unchanged, and the duration of pulmonary venous flow reversal at atrial contraction did not exceed that of mitral flow; thus, a significant treatment effect was detectable (F = 5.6, P <.05; and F = 6.6, P <.05, respectively)., Conclusions: Control subjects respond to volume load with enhancement in early LV filling, whereas patients with DCM show an increase of LV filling pressure. Diastolic adaptation to volume load improves in patients with DCM after treatment with losartan.

Increased cardiovascular morbidity and mortality were reported in GH deficiency (GHD), and GH replacement can ameliorate cardiac abnormalities of adult GHD patients. To test the potential progression of untreated GHD on the cardiovascular risk and cardiac function, cardiovascular risk factors, cardiac size, and performance were prospectively evaluated in 15 GHD patients (age, 18-56 yr) who were treated with recombinant GH at the dose of 0.15-1.0 mg/d, 15 GHD patients (age, 18-56 yr) who refused GH replacement, and 30 healthy subjects (age, 18-53 yr). Electrocardiogram, systolic and diastolic blood pressure, and heart rate measurement, serum IGF-I, total cholesterol, low- and high-density lipoprotein (LDL, HDL) cholesterol, triglycerides, and fibrinogen level assay, echocardiography, and equilibrium radionuclide angiography were performed basally and after 12 months. At study entry, low IGF-I levels, unfavorable lipid profile, and inadequate cardiac and physical performance were found in GHD patients compared with controls. After 12 months of GH treatment, IGF-I levels normalized; HDL-cholesterol levels, left ventricular (LV) mass index (LVMi), left ventricular ejection fraction (LVEF) at peak exercise, peak filling rate, exercise duration and capacity significantly increased; total- and LDL-cholesterol levels significantly decreased. After 12 months in GH-untreated GHD patients, IGF-I levels remained stable, and HDL-cholesterol levels, LVEF both at rest and at peak exercise, and exercise capacity were further reduced; total- and LDL-cholesterol levels increased slightly. LVEF at rest and its response at peak exercise normalized in 60 and 53.3%, respectively, of GH-treated patients and in none of the GH-untreated patients. In conclusion, 12 months of GH replacement normalized IGF-I and improved lipid profile and cardiac performance in adult GHD patients. A similar period of GH deprivation induced a further impairment of lipid profile and cardiac performance. This finding strongly supports the need of GH replacement in adult GHD patients.