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Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the T.O.S.CA. GHD Study.

ABSTRACT: Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD.One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6±1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6±1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay.GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p = .008 and -24%, p = .015, respectively), lower LV end-systolic wall stress (-21%, p = .03), higher RV performance (+18% in RV area change, p = .03), lower estimated systolic pulmonary artery pressure (-11%, p = .04), higher peak VO2 (+20%, p = .001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p = .002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (? = -1.92, SE = 1.67, p = .03), VE/VCO2 slope (? = 2.23, SE = 1.20, p = .02) and NT-proBNP (? = 2.48, SE = 1.02, p = .016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p < .001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF.GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality.

SUBMITTER: Arcopinto M

PROVIDER: S-EPMC5240983 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the T.O.S.CA. GHD Study.

Arcopinto Michele M Salzano Andrea A Giallauria Francesco F Bossone Eduardo E Isgaard Jörgen J Marra Alberto M AM Bobbio Emanuele E Vriz Olga O Åberg David N DN Masarone Daniele D De Paulis Amato A Saldamarco Lavinia L Vigorito Carlo C Formisano Pietro P Niola Massimo M Perticone Francesco F Bonaduce Domenico D Saccà Luigi L Colao Annamaria A Cittadini Antonio A

PloS one 20170117 1

<h4>Background</h4>Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD.<h4>Methods</h4>One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and ...[more]

PMID: 28095492

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Project description:ObjectiveThe aim of this study was to perform psychometric testing of the Growth Hormone Deficiency-Child Impact Measure (GHD-CIM): a patient-reported outcome (PRO) for children with GHD aged 9 to < 13 years and an observer-reported outcome (ObsRO) for parents/guardians of children who are unable to answer for themselves.MethodsA non-interventional, multicenter, clinic-based study was conducted in 30 private-practice and large institutional sites in the US and the UK. Psychometric analyses were conducted following an a priori validation statistical analysis plan.ResultsA preliminary examination of the data determined a PRO version for children aged 9 to < 13 years was not psychometrically sound and therefore the decision was made to have only an ObsRO measure of the GHD-CIM, which would be suitable for children aged 4 to < 13 years. The GHD-CIM ObsRO validity analyses included 98 parents/guardians. Factor analyses identified three domains: Physical Functioning (PHYS), Social Well-Being (SWB), and Emotional Well-Being (EWB). Internal consistency reliability was acceptable for all domains and for the overall score (Cronbach's alpha > 0.70), as was test-retest reliability for the SWB, EWB and overall (above 0.70). At least one convergent validity hypotheses for each domain and overall was proven (r > 0.40). Known-groups validity hypotheses for the EWB and SWB domains were significant (p < 0.05). Associated effect sizes ranged from - 0.40 to - 0.58, indicating that the GHD-CIM is sensitive to change. Anchor-based patient and clinician ratings of severity of disease suggest a preliminary minimally important difference of 5 points for the overall score, and 5 for PHYS, 7 for EWB, and 5 for SWB.ConclusionsThe GHD-CIM ObsRO was found to be a reliable and valid measure to assess disease-specific functioning, which will provide a more complete patient-centric picture to the growth hormone therapy experience in children.Trial registrationClinicalTrials.gov NCT02580032, first posted 20 October 2015.

Project description:BackgroundGrowth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64-82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved.Methods/designEvidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH < 6.7 mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (primary outcome; inferiority margin 0.55 SD), target height (TH) minus near FH, HRQoL, bone health index and lipid profiles (secondary outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario.DiscussionIf this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8-4.6 million (€2.05-5.24 million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects.Trial registrationEudraCT number: 2020-001006-39.

Dataset Information

Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the T.O.S.CA. GHD Study.

Publications

Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the T.O.S.CA. GHD Study.

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