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

by Michele Arcopinto, Andrea Salzano, Francesco Giallauria, Eduardo Bossone, Jörgen Isgaard, Alberto M. Marra, Emanuele Bobbio, Olga Vriz, David N. Åberg, Daniele Masarone, Amato De Paulis, Lavinia Saldamarco, Carlo Vigorito, Pietro Formisano, Massimo Niola, Francesco Perticone, Domenico Bonaduce, Luigi Saccà, Annamaria Colao, Antonio Cittadini, T.O.S.CA. (Trattamento Ormonale Scompenso CArdiaco) Investigators

Background

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.

Methods

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.

Results

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 (β = -1.92, SE = 1.67, p = .03), VE/VCO₂ slope (β = 2.23, SE = 1.20, p = .02) and NT-proBNP (β = 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 2 and LVEF.

Conclusions

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.

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