A placebo-controlled study of growth hormone in patients with congestive heart failure

Isgaard, Jörgen; Bergh, Claes‐Håkan; Caidahl, Kenneth; Lomsky, Milan; Hjalmarson, Å; Bengtsson, Bengt‐Åke

doi:10.1053/euhj.1998.1123

Cited by 177 publications

(111 citation statements)

References 22 publications

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“…3,4 Earlier studies have shown that GH supplementation may have beneficial effects on myocardial structure and function in some patients with CHF, [5][6][7] although neutral results of randomized trials have also been reported. 8,9 Elevated serum GH with normal or low IGF-1 levels was observed in cachectic patients with CHF. 10,11 These findings indicate that the GH/IGF-1 axis may be related to LV dysfunction and the resultant cachexia.…”

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confidence: 99%

Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

et al. 2001

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Background-Ghrelin is a novel growth hormone (GH)-releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). Methods and Results-Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 g/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo (PϽ0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo (PϽ0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (ϩ10% versus ϩ3%, PϽ0.05). They showed significantly higher cardiac output (315Ϯ49 versus 266Ϯ31 mL · min Ϫ1 · kg Ϫ1 , PϽ0.05) and LV dP/dt max (5738Ϯ908 versus 4363Ϯ973 mm Hg/s, PϽ0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15Ϯ3% to 19Ϯ3%, PϽ0.05). Conclusions-Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.

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Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

et al. 2001

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“…When patients with heart failure of different etiologies were analyzed, no effect of chronic GH administration on either cardiac function or neuroendocrine activation was observed. 14 One reason for these contradictory findings might be the heterogeneous origin of heart failure. An alternative explanation is the possible involvement of cardiomyocyte apoptosis occurring after myocardial infarction, 15 which might have been suppressed by GH and IGF-1, 16 suggesting a possible specific effect of GH in ischemic heart failure.…”

Section: Discussionmentioning

confidence: 99%

Cardiac and Renal Effects of Growth Hormone in Volume Overload–Induced Heart Failure

et al. 2002

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“…[17][18][19][20] With a series of 7 patients with DCM, Fazio et al 17 observed significant improvement in most measures of cardiac geometry and systolic function in response to GH therapy. Other investigators, however, noted only increased LV mass in response to GH, without significant changes in cardiac function or exercise capacity.…”

Section: Effects Of Gh In Human Cardiac Failurementioning

confidence: 99%

“…Other investigators, however, noted only increased LV mass in response to GH, without significant changes in cardiac function or exercise capacity. [18][19][20] Findings among adults with cardiac failure attributable to other causes, primarily myocardial ischemia, are similarly equivocal. 21,22 In several of those studies, increased LV mass was correlated with the magnitude of elevation of IGF-1 levels after initiation of GH treatment, [19][20][21] whereas others found that patients with low baseline IGF-1 levels were less likely to benefit from GH.…”

Section: Effects Of Gh In Human Cardiac Failurementioning

confidence: 99%

“…7,[13][14][15][16] Fazio et al 17 suggested that GH therapy may improve cardiac function among adults with DCM, although data from other human studies are equivocal. [18][19][20][21][22] On the basis of the importance of the GH/IGF-1 axis in the maintenance of normal myocardial function and data from experimental models and adults with heart failure, we hypothesized that GH might provide a pharmacologic means of improving LV energetics and normalizing the neurohormonal milieu, thus optimizing cardiac function, among children with DCM. To determine the efficacy and safety of GH in the treatment of pediatric DCM, we undertook a prospective, single-center, randomized, partially blinded, crossover trial among subjects 1 to 19 years of age with DCM and cardiac dysfunction of Ն6-month duration.…”

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Recombinant Human Growth Hormone Treatment for Dilated Cardiomyopathy in Children

et al. 2004

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ABSTRACT. Objective. Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure among children and is often progressive despite maximal medical therapy. Heart failure is characterized by a number of neurohormonal abnormalities, including derangements in the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) signaling axis. Decreased serum levels of GH, which acts on cardiac myocytes primarily through IGF-1, are associated with impaired myocardial growth and function, which can be improved with restoration of GH/IGF-1 homeostasis. In animal models and among human adults with heart failure attributable to DCM, treatment with GH results in acquisition of left ventricular (LV) mass and improved LV function, through a combination of mechanisms. We undertook this study to determine the effects of recombinant human GH on LV function and mass among children with stable LV dysfunction attributable to DCM.Methods. We performed a prospective, single-center, randomized, partially blinded, crossover trial among children 1 to 19 years of age with DCM and cardiac dysfunction of >6-month duration. After enrollment, patients were randomly assigned to receive treatment for 6 months with either conventional therapy (determined by the patient's primary cardiologist) plus recombinant human GH (0.025-0.04 mg/kg per day), administered as daily subcutaneous injections, or conventional therapy alone. Patients were then crossed over to the other treatment strategy for 6 months. The primary outcome measure was change in LV shortening fraction (SF). Other echocardiographic indices of LV function, somatic growth, and somatotropic/thyroid hormone levels were also monitored.Results. Only 8 of an intended 15 patients were enrolled, because of a combination of factors. Two patients withdrew during the study as a result of declining LV function requiring transplantation. LV SF did not change significantly during GH treatment, although both LV SF and LV SF z score were higher 6 months after cessation of GH treatment than at baseline. LV ejection fraction increased during GH therapy to a degree that approached significance. Height and weight percentiles for age increased significantly during GH therapy and remained higher 6 months after treatment. Annualized height velocity during GH treatment (13.7 ؎ 3.3 cm/year, >97th percentile for all patients) was significantly higher than that after GH discontinuation (3.2 ؎ 3.5 cm/year). Serum levels of IGF-1 and IGF-binding protein-3 were significantly higher after 6 months of GH treatment and 6 months after discontinuation of GH treatment than at baseline. There were no adverse events related to GH treatment.Discussion. In this prospective, single-center, randomized, partially blinded, crossover trial, recombinant human GH was administered to 8 pediatric patients with stable chronic heart failure secondary to DCM. Because of unanticipated difficulty enrolling eligible patients, the study was underpowered to detect changes in our primary outcome measure of the magnitude we project...

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A placebo-controlled study of growth hormone in patients with congestive heart failure

Cited by 177 publications

References 22 publications

Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

Cardiac and Renal Effects of Growth Hormone in Volume Overload–Induced Heart Failure

Recombinant Human Growth Hormone Treatment for Dilated Cardiomyopathy in Children

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