Skip to main content
Log in

Clinical Potential of Growth Hormone in the Treatment of Congestive Heart Failure

  • Leading Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Substantial evidence supports a role for the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis in regulation of normal cardiac growth, structure and function. Moreover, experimental data suggest beneficial effects of GH and IGF-1 on contractility and peripheral resistance in rats with impaired cardiac function. An increased Ca++ responsiveness is one possible underlying cause for the improvement in contractility, although effects of GH and IGF-1 on apoptosis may also play a more long term role for cardiomyocyte survival.

Until recently, studies regarding GH treatment in heart failure were limited to case reports where administration dramatically improved cardiac function. In a small non-blind study of 7 patients with idiopathic dilated cardiomyopathy and congestive heart failure (CHF) without GH deficiency who received treatment with recombinant GH (somatropin) for 3 months, considerable improvement of cardiac function was reported. More recent studies have demonstrated beneficial effects in patients with CHF due to both ischaemic and idiopathic dilated cardiomyopathy, with improvements in haemodynamics when somatropin was added both as a maintenance therapy and as a short term infusion.

So far, 2 placebo-controlled studies with somatropin as adjunctive therapy in patients with CHF have been reported, although neither study could confirm previously reported improvement in systolic function and lowering of wall stress.

In summary, it is clear that further placebo-controlled clinical trials are mandatory to verify positive effects and to monitor long term safety when somatropin is administered as an agent in the treatment of CHF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. D’Ercole AJ, Stiles AD, Underwood LE. Tissue concentrations of somatomedin-C: Further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A 1984; 81: 935–9

    Article  PubMed  Google Scholar 

  2. Murphy LJ, Bell GI, Duckworth L, et al. Identification, characterization and regulation of a rat complementary deoxyribonucleic acid which encodes insulin-like growth factor 1. Endocrinology 1987; 121: 684–91

    Article  PubMed  CAS  Google Scholar 

  3. Isgaard J, Nilsson A, Vikman K, et al. Growth hormone regulates the level of IGF-1 mRNA in rat skeletal muscle. J Endocrinol 1989; 120: 107–12

    Article  PubMed  CAS  Google Scholar 

  4. Wåhlander H, Isgaard J, Jennische E, et al. Left ventricular insulin-like growth factor 1 mRNA increases in early renal hypertension. Hypertension 1992; 19: 25–32

    Article  PubMed  Google Scholar 

  5. Merola B, Cittadini A, Colao A, et al. Cardiac structure and functional abnormalities in adult patients with growth hormone deficiency. J Clin Endocrinol Metab 1993; 77: 1658–61

    Article  PubMed  CAS  Google Scholar 

  6. Amato G, Carella C, Fazio S, et al. Body composition, bone metabolism and heart structure and function in growth hormone (GH) deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993; 77: 1671–6

    Article  PubMed  CAS  Google Scholar 

  7. Caidahl K, Edén S, Bengtsson B-Å. Cardiovascular and renal effects of growth hormone. Clin Endocrinol (Oxf) 1994; 40: 393–400

    Article  CAS  Google Scholar 

  8. Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996; 334: 809–14

    Article  PubMed  CAS  Google Scholar 

  9. Osterziel KJ, Strohm O, Schuler J, et al. Randomised, double blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet 1998; 351: 1233–7

    Article  PubMed  CAS  Google Scholar 

  10. Isgaard J, Bergh C-H, Caidahl K, et al. A placebo controlled study of growth hormone in patients with congestive heart failure. Eur Heart J 1998; 19: 1704–11

    Article  PubMed  CAS  Google Scholar 

  11. Strömer H, Cittadini A, Douglas PS, et al. Exogenously administered growth hormone and insulin-like growth factor-1 alter intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation in the isolated isovolumic buffer-perfused rat heart. Circ Res 1996; 79: 227–36

    Article  PubMed  Google Scholar 

  12. Johannsson G, Oscarsson J, Rosén T, et al. Effects of 1 year of growth hormone therapy on serum lipoprotein levels in growth hormone deficient adults — influence of gender and Apo(a) and ApoE phenotypes. Arterioscler Thromb Vasc Biol 1995; 15: 2142–50

    Article  PubMed  CAS  Google Scholar 

  13. Donohue TJ, Dworkin LD, Lango MN, et al. Induction of myocardial insulin-like growth factor 1 gene expression in left ventricular hypertrophy. Circulation 1994; 89: 799–809

    Article  PubMed  CAS  Google Scholar 

  14. Isgaard J, Wåhlander H, Adams MA, et al. Increased expression of growth hormone receptor mRNA and insulin-like growth factor 1 mRNA in volume overloaded hearts. Hypertension 1994; 23: 884–8

    Article  PubMed  CAS  Google Scholar 

  15. Russell-Jones DL, Leach RM, Ward JPT, et al. Insulin-like growth factor-1 gene expression is increased in the right ventricle hypertrophy induced by chronic hypoxia in the rat. J Endocrinol 1993; 10: 99–102

    CAS  Google Scholar 

  16. Mathews LS, Engberg B, Norstedt G. Regulation of rat GH receptor gene expression. J Biol Chem 1989; 264: 9905–10

    PubMed  CAS  Google Scholar 

  17. Ymer SI, Herington AC. Developmental expression of the growth hormone receptor gene in rabbit tissues. Mol Cell Endocrinol 1992; 83: 39–49

    Article  PubMed  CAS  Google Scholar 

  18. Guron G, Friberg P, Wickman A, et al. Cardiac insulin-like growth factor 1 and growth hormone receptor expression in renal hypertension. Hypertension 1996; 27: 636–42

    Article  PubMed  CAS  Google Scholar 

  19. Cittadini A, Strömer H, Katz SE, et al. Differential cardiac effects of growth hormone and insulin-like growth factor-1 in the rat. Acombined in vivo and in vitro evaluation. Circulation 1996; 93: 800–9

    Article  PubMed  CAS  Google Scholar 

  20. Yang R, Bunting S, Gillett N, et al. Growth hormone improves cardiac performance in experimental heartfailure. Circulation 1995; 92: 262–7

    Article  PubMed  CAS  Google Scholar 

  21. Duerr RL, Huang S, Miraliakbar HR, et al. Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. J Clin Invest 1995; 95: 619–27

    Article  PubMed  CAS  Google Scholar 

  22. Isgaard J, Kujacic V, Jennische E, et al. Growth hormone improves cardiac function in rats with experimental myocardial infarction. Eur J Clin Invest 1997; 27: 517–25

    Article  PubMed  CAS  Google Scholar 

  23. Jin H, Yang R, Gillett N, et al. Beneficial effects of growth hormone and insulin-like factor-1 in experimental heart failure in rats treated with chronic ACE inhibition. J Cardiovasc Pharmacol 1995; 26: 420–5

    Article  PubMed  CAS  Google Scholar 

  24. Shen YT, Wiedmann RT, Lynch JJ, et al. GH replacement fails to improve ventricular function in hypophysectomized rats with myocardial infarction. Am J Physiol 1996; 271: H1721–7

    PubMed  CAS  Google Scholar 

  25. Shen YT, Woltmann RF, Appleby S, et al. Lack of beneficial effects of growth hormone treatment in conscious dogs during development of heart failure. Am J Physiol 1998; 274: H456–66

    PubMed  CAS  Google Scholar 

  26. Cittadini A, Grossman J, Napoli R, et al. Growth hormone attenuates early ventricular remodeling and improves cardiac function in rats with large myocardial infarction. J Am Coll Cardiol 1997; 29: 1109–16

    Article  PubMed  CAS  Google Scholar 

  27. Mayoux E, Ventura-Clapier R, Timsit J, et al. Mechanical properties of rat cardiac skinned fibers are altered by chronic growth hormone hypersecretion. Circ Res 1993; 72: 57–64

    Article  PubMed  CAS  Google Scholar 

  28. Tajima M, Weinberg EO, Bartunek J, et al. Treatment with growth hormone enhances contractile reserve and intracellular calcium transients in myocytes from rats with postinfarction heart failure. Circulation 1999; 99: 127–34

    Article  PubMed  CAS  Google Scholar 

  29. Volterrani M, Desenzani P, Lorusso R, et al. Hemodynamic effects of intravenous growth hormone in congestive heart failure. Lancet 1997; 349: 1067–8

    Article  PubMed  CAS  Google Scholar 

  30. Ito H, Hiroe M, Hirata Y, et al. Insulin-like growth factor-1 induces hypertrophy with enhanced expression of musclespecific genes in cultured rat cardiomyocytes. Circulation 1993; 87: 1715–21

    Article  PubMed  CAS  Google Scholar 

  31. Donath MY, Zapf J, Eppenberger-Eberhardt M, et al. Insulin-like growth factor 1 stimulates myofibril development and decreases smooth muscle I-actin of adult cardiomyocytes. Proc Natl Acad Sci USA 1994; 91: 1686–90

    Article  PubMed  CAS  Google Scholar 

  32. Freestone NS, Ribaric S, Mason WT. The effect of insulin-like growth factor-1 on adult rat cardiac contractility. Mol Cell Biochem 1996; 163/164: 223–9

    Article  PubMed  Google Scholar 

  33. Cuneo RC, Wilmshurst P, Lowy C, et al. Cardiac failure responding to growth hormone. Lancet 1989; I: 838–9

    Article  Google Scholar 

  34. Frustaci A, Perrone GA, Gentiloni N, et al. Reversible dilated cardiomyopathy due to growth hormone deficiency. Am J Clin Pathol 1992; 97: 503–11

    PubMed  CAS  Google Scholar 

  35. O’Driscoll JG, Green DJ, Ireland M, et al. Treatment of end-stage cardiac failure with growth hormone. Lancet 1997; 349: 1068

    Article  PubMed  Google Scholar 

  36. Genth-Zotz S, Zotz R, Geil S, et al. Recombinant growth hormone therapy in patients with ischemie cardiomyopathy. Effects on hemodynamics, left ventricular function and cardiopulmonary exercise capacity. Circulation 1999; 99: 18–21

    Article  PubMed  CAS  Google Scholar 

  37. Beer N, Tortoledo F, Beer R, et al. Beneficial effects of growth hormone in patients with chagas cardiomyopathy and dialated cardiomyopathy of unknown etiology, [abstract no. 2920]. Circulation 1997; 96Suppl. 1: I–521

    Google Scholar 

  38. Turner H, Wass JAH. Growth hormone in the treatment of dilated cardiomyopathy [letter]. N Engl J Med 1996; 335: 672

    Article  PubMed  CAS  Google Scholar 

  39. Frustaci A, Gentiloni N, Russo MA. Growth hormone in the treatment of dilated cardiomyopathy [letter]. N Engl J Med 1996; 335: 672–3

    Article  PubMed  CAS  Google Scholar 

  40. Beer N, Toledo F, Beer R, et al. Heart Failure ’97. Beneficial effects of growth hormone in patients with congestive heart failure, [abstract] Second International Meeting of the Working Group on Heart Failure. From Heart Failure 1997; Cologne, 294

  41. Saraste A, Pulkki K, Kallajoki, et al. Apoptosis in human acute myocardial infarction. Circulation 1997; 95: 320–3

    Article  PubMed  CAS  Google Scholar 

  42. Narula J, Haider N, Virmani R, et al. Apoptosis in myocytes in end-stage heart failure. N Engl J Med 1996; 335: 1182–9

    Article  PubMed  CAS  Google Scholar 

  43. Itoh N, Yonehara S, Ishii A, et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991; 66: 233–43

    Article  PubMed  CAS  Google Scholar 

  44. Nagata S, Goldstein P. The Fas death factor. Science 1995; 267: 1449–56

    Article  PubMed  CAS  Google Scholar 

  45. Kajstura J, Cheng W, Reiss K, et al. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest 1996; 74: 86–107

    PubMed  CAS  Google Scholar 

  46. Buerke M, Mohara T, Skurk C, et al. Cardioprotective effect of insulin-like growth factor-1 in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci USA 1995; 92: 8031–5

    Article  PubMed  CAS  Google Scholar 

  47. Buerke M, Prufer D, Ibe W, et al. Human growth hormone exerts cardioprotective effects in murine reperfusion injury [abstract #2116]. 70th Scientific Session of the American Heart Association, Orlando (FL): 1997 Nov

  48. Li Q, Li B, Wang X, et al. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress and cardiac hypertrophy. J Clin Invest 1997; 100: 1991–9

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jörgen Isgaard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isgaard, J., Bergh, CH. Clinical Potential of Growth Hormone in the Treatment of Congestive Heart Failure. BioDrugs 12, 245–250 (1999). https://doi.org/10.2165/00063030-199912040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-199912040-00002

Keywords

Navigation