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

M. Arcopinto, A. Salzano, Francesco Giallauria, Eduardo Bossone, Jörgen Isgaard, A.M. Marra, Emanuele Bobbio, Olga Vriz, D.N. Aberg, Daniele Masarone, Amato De Paulis, Lavinia Saldamarco, A. C. Vigorito, P. Formisano, Massimo Niola, F. Perticone, D. Bonaduce, L. Saccà, A. Colao, Antonio Cittadini

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. © 2017 Arcopinto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Original languageEnglish
JournalPLoS One
Volume12
Issue number1
DOIs
Publication statusPublished - 2017

Fingerprint

heart failure
cardiac output
somatotropin
Growth Hormone
Heart Failure
Echocardiography
exercise test
Mortality
Doppler Echocardiography
gender
pulmonary artery
echocardiography
Licensure
Mountings
Insulin-Like Growth Factor I
Pulmonary Artery
multivariate analysis
Reproduction
arginine
Arginine

Cite this

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, M.; Salzano, A.; Giallauria, Francesco; Bossone, Eduardo; Isgaard, Jörgen; Marra, A.M.; Bobbio, Emanuele; Vriz, Olga; Aberg, D.N.; Masarone, Daniele; De Paulis, Amato; Saldamarco, Lavinia; Vigorito, A. C.; Formisano, P.; Niola, Massimo; Perticone, F.; Bonaduce, D.; Saccà, L.; Colao, A.; Cittadini, Antonio.

In: PLoS One, Vol. 12, No. 1, 2017.

Research output: Contribution to journalArticle

Arcopinto, M, Salzano, A, Giallauria, F, Bossone, E, Isgaard, J, Marra, AM, Bobbio, E, Vriz, O, Aberg, DN, Masarone, D, De Paulis, A, Saldamarco, L, Vigorito, AC, Formisano, P, Niola, M, Perticone, F, Bonaduce, D, Saccà, L, Colao, A & Cittadini, A 2017, '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', PLoS One, vol. 12, no. 1. https://doi.org/10.1371/journal.pone.0170058
Arcopinto, M. ; Salzano, A. ; Giallauria, Francesco ; Bossone, Eduardo ; Isgaard, Jörgen ; Marra, A.M. ; Bobbio, Emanuele ; Vriz, Olga ; Aberg, D.N. ; Masarone, Daniele ; De Paulis, Amato ; Saldamarco, Lavinia ; Vigorito, A. C. ; Formisano, P. ; Niola, Massimo ; Perticone, F. ; Bonaduce, D. ; Saccà, L. ; Colao, A. ; Cittadini, Antonio. / 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. In: PLoS One. 2017 ; Vol. 12, No. 1.
@article{cdf77eeabc9e4ffa9c2ba9becbd6dac7,
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. {\circledC} 2017 Arcopinto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
author = "M. Arcopinto and A. Salzano and Francesco Giallauria and Eduardo Bossone and J{\"o}rgen Isgaard and A.M. Marra and Emanuele Bobbio and Olga Vriz and D.N. Aberg and Daniele Masarone and {De Paulis}, Amato and Lavinia Saldamarco and Vigorito, {A. C.} and P. Formisano and Massimo Niola and F. Perticone and D. Bonaduce and L. Sacc{\`a} and A. Colao and Antonio Cittadini",
note = "Export Date: 21 March 2017 CODEN: POLNC References: Sacca, L., Heart failure as a multiple hormonal deficiency syndrome (2009) Circulation. Heart Failure., 2, pp. 151-156. , PMID: 19808331; Jankowska, E.A., Biel, B., Majda, J., Szklarska, A., Lopuszanska, M., Medras, M., Anabolic deficiency in men with chronic heart failure: Prevalence and detrimental impact on survival (2006) Circulation, 114, pp. 1829-1837. , PMID: 17030678; Rosen, T., Bengtsson, B.A., Premature mortality due to cardiovascular disease in hypopituitarism (1990) Lancet, 336, pp. 285-288. , PMID: 1973979; Colao, A., Di Somma, C., Cuocolo, A., Filippella, M., Rota, F., Acampa, W., The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: An observational, case-control study (2004) J Clin Endocrinol Metab, 89, pp. 5998-6004. , PMID: 15579750; Watanabe, S., Tamura, T., Ono, K., Horiuchi, H., Kimura, T., Kita, T., Insulin-like growth factor axis (insulin- like growth factor-I/insulin-like growth factor-binding protein-3) as a prognostic predictor of heart failure: Association with adiponectin (2010) Eur J Heart Fail, 12, pp. 1214-1222. , PMID: 20851819; Cittadini, A., Saldamarco, L., Marra, A.M., Arcopinto, M., ImbriacoM, C.G., Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction (2009) J Clin Endocrinol Metab, 94, pp. 3329-3336. , PMID: 19584187; Cittadini, A., Marra, A.M., Arcopinto, M., Bobbio, E., Salzano, A., Sirico, D., Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency: An extension of a randomized controlled single-blind study (2013) JACC. Heart Fail, 1, pp. 325-330. , PMID 24621936; Spielberger, C.D., Gorsuch, R.L., Lushene, R., Vagg, P.R., Jacobs, G.A., Manual for the state-trait anxiety inventory (1983) Consult Psychol Press, pp. 33-37; Zung, W.W., A self-rating depression scale (1965) Arch Gen Psych, 12, pp. 63-70; http://www.agenziafarmaco.gov.it/it/content/nota-39Wassermann, K., Hansen, J.E., Sue, D.Y., Whipp, B.J., (1987) Principles of Exercise Testing and Interpretation, pp. 2-8512. , Philadelphia: Lea & Febiger; Beaver, W.L., Wasserman, K., Whipps, B.J., A new method for detecting anaerobic threshold by gas exchange (1986) J Appl Physiol, 60, pp. 2020-2027. , PMID: 3087938; Lang, R.M., Badano, L.P., Mor-Avi, V., Afilalo, J., Armstrong, A., Ernande, L., Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American society of echocardiography and the european association of cardiovascular imaging (2015) J Am Soc Echocardiogr, 28, pp. 1-39. , PMID: 25559473; Boguszewski, M., Jansson, C., Rosberg, S., Albertsson-Wikland, K., Changes in serum insulin-like growth factor i (IGF-I) and IGF-binding protein-3 levels during growth hormone treatment in prepubertal short children born small for gestational age (1996) J Clin Endocrinol Metab, 81, pp. 3902-3908. , PMID: 8923836; Gitt, A.K., Wasserman, K., Kilkowski, C., Kleemann, T., Kilkowski, A., Bangert, M., Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death (2002) Circulation, 106, pp. 3079-3084. , PMID: 12473555; Arcopinto, M., Bobbio, E., Bossone, E., Perrone-Filardi, P., Napoli, R., Sacca, L., The GH/IGF-1 axis in chronic heart failure (2013) Endocr Metab Immune Dis Drug Targets, 13, pp. 76-91; Colao, A., Di Somma, C., Savanelli, M.C., De Leo, M., Lombardi, G., Beginning to end: Cardiovascular implications of growth hormone (GH) deficiency and GH therapy (2006) Growth Horm IGF Res, 16, pp. S41-S48; Marra, A.M., Arcopinto, M., Bossone, E., Ehlken, N., Cittadini, A., Grunig, E., Pulmonary arterial hypertensionrelated myopathy: An overview of current data and future perspectives (2015) Nutr Metab Cardiovasc Dis, 25, pp. 131-139. , PMID: 25455722; Niebauer, J., Pflaum, C.D., Clark, A.L., Strasburger, C.J., Hooper, J., Poole-Wilson, P.A., Coats, A.J., Anker, S.D., Deficient insulin-like growth factor i in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation (1998) J Am Coll Cardiol, 32 (2), pp. 393-397. , PMID: 9708466; Bhandari, S.S., Narayan, H., Jones, D.J., Suzuki, T., Struck, J., Bergmann, A., Squire, I.B., Ng, L.L., Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure (2015) Eur J Heart Fail, , Dec 15; Anker, S.D., Volterrani, M., Pflaum, C.D., Acquired growth hormone resistance in patients with chronic heart failure: Implications for therapy with growth hormone (2001) J Am Coll Cardiol, 38, pp. 443-452. , PMID: 11499736; Al-Obaidi, M.K., Hon, J.K., Stubbs, P.J., Plasma insulin-like growth factor-1 elevated in mild-to-moderate but not severe heart failure (2001) Am Heart J, 142, p. E10. , PMID: 11717621; Watanabe, S., Tamura, T., Ono, K., Insulin-like growth factor axis (insulin-like growth factor-I/insulinlike growth factor-binding protein-3) as a prognostic predictor of heart failure: Association with adiponectin (2010) Eur J Heart Fail, 12, pp. 1214-1222. , PMID: 20851819; Broglio, F., Fubini, A., Morello, M., Activity of GH/IGF-I axis in patients with dilated cardiomyopathy (1999) Clin Endocrinol, 50, pp. 417-430; Anwar, A., Gaspoz, J.M., Pampallona, S., Effect of congestive heart failure on the insulin-like growth factor-1 system (2002) Am J Cardiol, 90, pp. 1402-1405. , PMID: 12480057; Kontoleon, P.E., Anastasiou-Nana, M.I., Papapetrou, P.D., Hormonal profile in patients with congestive heart failure (2003) Int J Cardiol, 87, pp. 179-183. , PMID: 12559538; Corbalan, R., Acevedo, M., Godoy, I., Jalil, J., Campusano, C., Klassen, J., Enalapril restores depressed circulating insulin-like growth factor 1 in patients with chronic heart failure (1998) J Cardiac Fail, 4, pp. 115-119; Giustina, A., Veldhuis, J.D., Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human (1998) Endocrine Rev, 19, pp. 717-797; Mathews, L.S., Enberg, B., Norstedt, G., Regulation of rat growth hormone receptor gene expression (1989) J Biol Chem, 264 (17), pp. 9905-9910. , PMID: 2722883 Jun 15; Napoli, R., Guardasole, V., Matarazzo, M., Palmieri, E.A., Oliviero, U., Fazio, S., Sacc{\`a}, L., Growth hormone corrects vascular dysfunction in patients with chronic heart failure (2002) J Am Coll Cardiol, 39 (1), pp. 90-95. , PMID: 11755292 Jan 2; Bhandari, S.S., Narayan, H., Jones, D.J., Suzuki, T., Struck, J., Bergmann, A., Squire, I.B., Ng, L.L., Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure (2016) Eur J Heart Fail, 18 (3), pp. 281-289. , PMID: 26670643 Mar; Broglio, F., Benso, A., Gottero, C., Vito, L.D., Aimaretti, G., Fubini, A., Patients with dilated cardiomyopathy show reduction of the somatotroph responsiveness to GHRH both alone and combined with arginine (2000) Eur J Endocrinol, 142, pp. 157-163. , PMID: 10664524; Arcopinto, M., Isgaard, J., Marra, A.M., Formisano, P., Bossone, E., Vriz, O., IGF-1 predicts survival in chronic heart failure. Insights from the T.O.S.CA. (Trattamento Ormonale Nello Scompenso CArdiaco) registry (2014) Int J Cardiol, 176 (3), pp. 1006-1008. , PMID: 25037691 Oct 20; McKelvie, R.S., Moe, G.W., Ezekowitz, J.A., Heckman, G.A., Costigan, J., Ducharme, A., The 2012 Canadian Cardiovascular Society heart failure management guidelines update: Focus on acute and chronic heart failure (2013) Can J Cardiol., 29, pp. 168-181. , PMID: 23201056; Testa, G., Cacciatore, F., Galizia, G., Della-Morte, D., Mazzella, F., Gargiulo, G., Depressive symptoms predict mortality in elderly subjects with chronic heart failure (2011) Eur J Clin Invest, 41 (12), pp. 1310-1317. , PMID: 21615393 Dec; Mahajan, T., Crown, A., Checkley, S., Farmer, A., Lightman, S., Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life (2004) Eur J Endocrinol, 151, pp. 325-332. , PMID: 15362961; Arcopinto, M., Salzano, A., Isgaard, J., Cittadini, A., Hormone replacement therapy in heart failure (2015) Curr Opin Cardiol, 30, pp. 277-284. , PMID: 25807222; Rengo, G., Zincarelli, C., Femminella, G.D., Liccardo, D., Pagano, G., De Lucia, C., Myocardial β(2)Dadrenoceptor gene delivery promotes coordinated cardiac adaptive remodelling and angiogenesis in heart failure (2012) Br J Pharmacol, 166 (8), pp. 2348-2361. , PMID: 22452704 Aug; Givertz, M.M., Braunwald, E., Neurohormones in heart failure: Predicting outcomes, optimizing care (2004) Eur Heart J, 25 (4), pp. 281-282. , PMID: 14984914; Bossone, E., Limongelli, G., Malizia, G., Ferrara, F., Vriz, O., Citro, R., The T.O.S.CA. Project: Research, education and care (2011) Monaldi Arch Chest Dis, 76, pp. 198-203. , PMID: 22567736",
year = "2017",
doi = "10.1371/journal.pone.0170058",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - 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

AU - Arcopinto, M.

AU - Salzano, A.

AU - Giallauria, Francesco

AU - Bossone, Eduardo

AU - Isgaard, Jörgen

AU - Marra, A.M.

AU - Bobbio, Emanuele

AU - Vriz, Olga

AU - Aberg, D.N.

AU - Masarone, Daniele

AU - De Paulis, Amato

AU - Saldamarco, Lavinia

AU - Vigorito, A. C.

AU - Formisano, P.

AU - Niola, Massimo

AU - Perticone, F.

AU - Bonaduce, D.

AU - Saccà, L.

AU - Colao, A.

AU - Cittadini, Antonio

N1 - Export Date: 21 March 2017 CODEN: POLNC References: Sacca, L., Heart failure as a multiple hormonal deficiency syndrome (2009) Circulation. Heart Failure., 2, pp. 151-156. , PMID: 19808331; Jankowska, E.A., Biel, B., Majda, J., Szklarska, A., Lopuszanska, M., Medras, M., Anabolic deficiency in men with chronic heart failure: Prevalence and detrimental impact on survival (2006) Circulation, 114, pp. 1829-1837. , PMID: 17030678; Rosen, T., Bengtsson, B.A., Premature mortality due to cardiovascular disease in hypopituitarism (1990) Lancet, 336, pp. 285-288. , PMID: 1973979; Colao, A., Di Somma, C., Cuocolo, A., Filippella, M., Rota, F., Acampa, W., The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: An observational, case-control study (2004) J Clin Endocrinol Metab, 89, pp. 5998-6004. , PMID: 15579750; Watanabe, S., Tamura, T., Ono, K., Horiuchi, H., Kimura, T., Kita, T., Insulin-like growth factor axis (insulin- like growth factor-I/insulin-like growth factor-binding protein-3) as a prognostic predictor of heart failure: Association with adiponectin (2010) Eur J Heart Fail, 12, pp. 1214-1222. , PMID: 20851819; Cittadini, A., Saldamarco, L., Marra, A.M., Arcopinto, M., ImbriacoM, C.G., Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction (2009) J Clin Endocrinol Metab, 94, pp. 3329-3336. , PMID: 19584187; Cittadini, A., Marra, A.M., Arcopinto, M., Bobbio, E., Salzano, A., Sirico, D., Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency: An extension of a randomized controlled single-blind study (2013) JACC. Heart Fail, 1, pp. 325-330. , PMID 24621936; Spielberger, C.D., Gorsuch, R.L., Lushene, R., Vagg, P.R., Jacobs, G.A., Manual for the state-trait anxiety inventory (1983) Consult Psychol Press, pp. 33-37; Zung, W.W., A self-rating depression scale (1965) Arch Gen Psych, 12, pp. 63-70; http://www.agenziafarmaco.gov.it/it/content/nota-39Wassermann, K., Hansen, J.E., Sue, D.Y., Whipp, B.J., (1987) Principles of Exercise Testing and Interpretation, pp. 2-8512. , Philadelphia: Lea & Febiger; Beaver, W.L., Wasserman, K., Whipps, B.J., A new method for detecting anaerobic threshold by gas exchange (1986) J Appl Physiol, 60, pp. 2020-2027. , PMID: 3087938; Lang, R.M., Badano, L.P., Mor-Avi, V., Afilalo, J., Armstrong, A., Ernande, L., Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American society of echocardiography and the european association of cardiovascular imaging (2015) J Am Soc Echocardiogr, 28, pp. 1-39. , PMID: 25559473; Boguszewski, M., Jansson, C., Rosberg, S., Albertsson-Wikland, K., Changes in serum insulin-like growth factor i (IGF-I) and IGF-binding protein-3 levels during growth hormone treatment in prepubertal short children born small for gestational age (1996) J Clin Endocrinol Metab, 81, pp. 3902-3908. , PMID: 8923836; Gitt, A.K., Wasserman, K., Kilkowski, C., Kleemann, T., Kilkowski, A., Bangert, M., Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death (2002) Circulation, 106, pp. 3079-3084. , PMID: 12473555; Arcopinto, M., Bobbio, E., Bossone, E., Perrone-Filardi, P., Napoli, R., Sacca, L., The GH/IGF-1 axis in chronic heart failure (2013) Endocr Metab Immune Dis Drug Targets, 13, pp. 76-91; Colao, A., Di Somma, C., Savanelli, M.C., De Leo, M., Lombardi, G., Beginning to end: Cardiovascular implications of growth hormone (GH) deficiency and GH therapy (2006) Growth Horm IGF Res, 16, pp. S41-S48; Marra, A.M., Arcopinto, M., Bossone, E., Ehlken, N., Cittadini, A., Grunig, E., Pulmonary arterial hypertensionrelated myopathy: An overview of current data and future perspectives (2015) Nutr Metab Cardiovasc Dis, 25, pp. 131-139. , PMID: 25455722; Niebauer, J., Pflaum, C.D., Clark, A.L., Strasburger, C.J., Hooper, J., Poole-Wilson, P.A., Coats, A.J., Anker, S.D., Deficient insulin-like growth factor i in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation (1998) J Am Coll Cardiol, 32 (2), pp. 393-397. , PMID: 9708466; Bhandari, S.S., Narayan, H., Jones, D.J., Suzuki, T., Struck, J., Bergmann, A., Squire, I.B., Ng, L.L., Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure (2015) Eur J Heart Fail, , Dec 15; Anker, S.D., Volterrani, M., Pflaum, C.D., Acquired growth hormone resistance in patients with chronic heart failure: Implications for therapy with growth hormone (2001) J Am Coll Cardiol, 38, pp. 443-452. , PMID: 11499736; Al-Obaidi, M.K., Hon, J.K., Stubbs, P.J., Plasma insulin-like growth factor-1 elevated in mild-to-moderate but not severe heart failure (2001) Am Heart J, 142, p. E10. , PMID: 11717621; Watanabe, S., Tamura, T., Ono, K., Insulin-like growth factor axis (insulin-like growth factor-I/insulinlike growth factor-binding protein-3) as a prognostic predictor of heart failure: Association with adiponectin (2010) Eur J Heart Fail, 12, pp. 1214-1222. , PMID: 20851819; Broglio, F., Fubini, A., Morello, M., Activity of GH/IGF-I axis in patients with dilated cardiomyopathy (1999) Clin Endocrinol, 50, pp. 417-430; Anwar, A., Gaspoz, J.M., Pampallona, S., Effect of congestive heart failure on the insulin-like growth factor-1 system (2002) Am J Cardiol, 90, pp. 1402-1405. , PMID: 12480057; Kontoleon, P.E., Anastasiou-Nana, M.I., Papapetrou, P.D., Hormonal profile in patients with congestive heart failure (2003) Int J Cardiol, 87, pp. 179-183. , PMID: 12559538; Corbalan, R., Acevedo, M., Godoy, I., Jalil, J., Campusano, C., Klassen, J., Enalapril restores depressed circulating insulin-like growth factor 1 in patients with chronic heart failure (1998) J Cardiac Fail, 4, pp. 115-119; Giustina, A., Veldhuis, J.D., Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human (1998) Endocrine Rev, 19, pp. 717-797; Mathews, L.S., Enberg, B., Norstedt, G., Regulation of rat growth hormone receptor gene expression (1989) J Biol Chem, 264 (17), pp. 9905-9910. , PMID: 2722883 Jun 15; Napoli, R., Guardasole, V., Matarazzo, M., Palmieri, E.A., Oliviero, U., Fazio, S., Saccà, L., Growth hormone corrects vascular dysfunction in patients with chronic heart failure (2002) J Am Coll Cardiol, 39 (1), pp. 90-95. , PMID: 11755292 Jan 2; Bhandari, S.S., Narayan, H., Jones, D.J., Suzuki, T., Struck, J., Bergmann, A., Squire, I.B., Ng, L.L., Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure (2016) Eur J Heart Fail, 18 (3), pp. 281-289. , PMID: 26670643 Mar; Broglio, F., Benso, A., Gottero, C., Vito, L.D., Aimaretti, G., Fubini, A., Patients with dilated cardiomyopathy show reduction of the somatotroph responsiveness to GHRH both alone and combined with arginine (2000) Eur J Endocrinol, 142, pp. 157-163. , PMID: 10664524; Arcopinto, M., Isgaard, J., Marra, A.M., Formisano, P., Bossone, E., Vriz, O., IGF-1 predicts survival in chronic heart failure. Insights from the T.O.S.CA. (Trattamento Ormonale Nello Scompenso CArdiaco) registry (2014) Int J Cardiol, 176 (3), pp. 1006-1008. , PMID: 25037691 Oct 20; McKelvie, R.S., Moe, G.W., Ezekowitz, J.A., Heckman, G.A., Costigan, J., Ducharme, A., The 2012 Canadian Cardiovascular Society heart failure management guidelines update: Focus on acute and chronic heart failure (2013) Can J Cardiol., 29, pp. 168-181. , PMID: 23201056; Testa, G., Cacciatore, F., Galizia, G., Della-Morte, D., Mazzella, F., Gargiulo, G., Depressive symptoms predict mortality in elderly subjects with chronic heart failure (2011) Eur J Clin Invest, 41 (12), pp. 1310-1317. , PMID: 21615393 Dec; Mahajan, T., Crown, A., Checkley, S., Farmer, A., Lightman, S., Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life (2004) Eur J Endocrinol, 151, pp. 325-332. , PMID: 15362961; Arcopinto, M., Salzano, A., Isgaard, J., Cittadini, A., Hormone replacement therapy in heart failure (2015) Curr Opin Cardiol, 30, pp. 277-284. , PMID: 25807222; Rengo, G., Zincarelli, C., Femminella, G.D., Liccardo, D., Pagano, G., De Lucia, C., Myocardial β(2)Dadrenoceptor gene delivery promotes coordinated cardiac adaptive remodelling and angiogenesis in heart failure (2012) Br J Pharmacol, 166 (8), pp. 2348-2361. , PMID: 22452704 Aug; Givertz, M.M., Braunwald, E., Neurohormones in heart failure: Predicting outcomes, optimizing care (2004) Eur Heart J, 25 (4), pp. 281-282. , PMID: 14984914; Bossone, E., Limongelli, G., Malizia, G., Ferrara, F., Vriz, O., Citro, R., The T.O.S.CA. Project: Research, education and care (2011) Monaldi Arch Chest Dis, 76, pp. 198-203. , PMID: 22567736

PY - 2017

Y1 - 2017

N2 - 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. © 2017 Arcopinto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

AB - 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. © 2017 Arcopinto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

U2 - 10.1371/journal.pone.0170058

DO - 10.1371/journal.pone.0170058

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

ER -