title: 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: 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 < .001, respectively), independent of age, sex, NT-proBNP, peak VO2 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.
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Arcopinto
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Salzano
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giallauria
authors.affiliation: Dipartimento di Cardiologia e Cardiochirurgia, University Hospital "Scuola Medica Salernitana", Salerno, Italy.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bossone
authors.affiliation: Department of Internal Medicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Isgaard
authors.affiliation: IRCCS S.D.N., Naples. Italy.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marra
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bobbio
authors.affiliation: Divisione di Cardiologia, San Daniele del Friuli Hospital, Udine, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Vriz
authors.affiliation: Department of Internal Medicine, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: David N
authors.initials: DN
authors.lastname: Åberg
authors.affiliation: Cardiologia SUN, Monaldi Hospital, AO Colli, Second University of Naples, Naples, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Masarone
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Amato
authors.initials: A
authors.lastname: De Paulis
authors.affiliation: AORN "A. Cardarelli", Naples, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Saldamarco
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vigorito
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
authors.affiliation: Dipartimento di Scienze Biomediche Avanzate, Federico II University, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Niola
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università Magna Græcia, Catanzaro, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Bonaduce
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Saccà
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Divisione di Endocrinologia, Federico II University, Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Federico II University, Naples, Italy.|Interdisciplinary Research Centre in Biomedical Materials (CRIB), Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cittadini
mesh_terms: D002320:Cardiovascular Physiological Phenomena; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D015150:Echocardiography, Doppler; D015444:Exercise / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019382:Human Growth Hormone