Abstract
Cachexia in patients with chronic heart failure (CHF) has been recognized for a long time; however, it has not received much attention until recently. Cardiac cachexia, a common and serious complication of CHF, is associated with very poor prognosis. Several studies have demonstrated that increased neurohormonal and immune abnormalities may play a crucial role in the pathophysiology of cardiac cachexia. Hormonal and catabolic/anabolic imbalances of the body are likely to be responsible for the development of cachexia in CHF. Recently, ghrelin, a novel growth hormone-releasing peptide, has been widely noticed to have potential in the treatment of severe CHF and cardiac cachexia. However, further research will be necessary to identify the exact pathways involved and to find the best therapeutic strategies of using ghrelin to fight the wasting process.
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References and Recommended Reading
Katz AM, Katz PB: Diseases of the heart in the works of Hippocrates. Br Heart J 1962, 24:257–264.
Anker SD, Ponikowski P, Varney S, et al.: Wasting as independent risk factor of survival in chronic heart failure. Lancet 1997, 349:1050–1053. In this manuscript, the authors validated that weight loss of more than 6% should be used to define the presence of cardiac cachexia.
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, 334:809–814.
Osterziel KJ, Strohm O, Schuler J, et al.: Randomised, doubleblind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet 1998, 351:1233–1237.
Isgaard J, Bergh CH, Caidahl K, et al.: A placebo-controlled study of growth hormone in patients with congestive heart failure. Eur Heart J 1998, 19:1704–1711.
Nagaya N, Miyatake K, Uematsu M, et al.: Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 2001, 86:5854–5859.
Nagaya N, Uematsu M, Kojima M, et al.: Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 2001, 104:1430–1435. These authors were the first to perform chronic subcutaneous administration of ghrelin in CHF rats. The results suggest that ghrelin reverses weight loss in CHF and improves left ventricular function and remodeling in CHF.
Nagaya N, Moriya J, Yasumura Y, et al.: Effect of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 2004, 110:3672–3679. This open study with historic controls was the first application of ghrelin in human patients with cardiac cachexia.
Freeman LM, Roubenoff R: The nutrition implications of cardiac cachexia. Nutr Rev 1994, 52:340–347.
Anker SD, Coats AJS: Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest 1999, 115:836–847.
Cowie MR, Mosterd A, Wood DA, et al.: The epidemiology of heart failure. Eur Heart J 1997, 18:208–225.
The CONSENSUS Trial Study Group: Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987, 316:1429–1435.
The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991, 325:293–302.
Garg R, Yusuf S: Overview of randomized trials of angiotensin converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995, 273:1450–1456.
McGovern PG, Pankow JS, Shahar E, et al.: Recent trends in acute coronary heart disease: mortality, morbidity, medical care, and risk factors. N Engl J Med 1996, 334:884–890.
Blackburn GL, Gibbons GW, Bothe A, et al.: Nutrition support in cardiac cachexia. J Thorac Cardiovasc Surg 1977, 73:489–496.
Anker SD, Negassa A, Coats AJS, et al.: Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitor: an observational study. Lancet 2003, 361:1077–1083. In this manuscript, the authors validated that weight loss of more than 6% should be used to define the presence of cardiac cachexia.
Anker SD, Swan JW, Volterrani M, et al.: The influence of muscle mass, strength, fatigability, and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure. Eur Heart J 1997, 18:259–269.
Anker SD, Ponikowski PP, Clark AL, et al.: Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J 1999, 20:683–693.
Anker SD, Clark AL, Teixeira MM, et al.: Loss of bone mineral in patients with cachexia due to chronic heart failure. Am J Cardiol 1999, 83:612–615.
Ponikowski P, Piepoli M, Chua TP, et al.: The impact of cachexia on cardiorespiratory reflex control in chronic heart failure. Eur Heart J 1999, 20:1667–1675.
Ponikowski P, Francis DP, Piepoli MF, et al.: Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation 2001, 103:967–972.
King D, Smith ML, Chapman TJ, et al.: Fat malabsorption in elderly patients with cardiac cachexia. Age Ageing 1996, 25:144–149.
Poehlman ET, Sceffers J, Gottlieb S, et al.: Increased resting metabolic rate in patients with congestive heart failure. Ann Intern Med 1994, 121:860–862.
Obisesan TO, Toth MJ, Kendall D: Energy expenditure and symptom severity in men with heart failure. Am J Cardiol 1996, 77:1250–1252.
Von Haehling S, Jankowska EA, Anker SD: Tumor necrosis factor-alpha and the failing heart—pathophysiology and therapeutic implications. Basic Res Cardiol 2004, 99:18–28.
Anker SD, Chua TP, Swan JW, et al.: Hormonal changes and catabolic/anabolic imbalance in chronic heart failure: the importance for cardiac cachexia. Circulation 1997, 96:526–534.
Niebauer J, Volk HD, Kemp M, et al.: Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 1999, 353:1838–1842.
Rauchhaus M, Clark AL, Doehner W, et al.: The relationship between cholesterol and survival in patients with chronic heart failure. J Am Coll Cardiol 2003, 42:1933–1940.
Leyva F, Anker SD, Godsland IF, et al.: Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 1998, 19:1814–1822.
Anker SD, Doelner W, Rauchhaus M, et al.: Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 2003, 107:1991–1997.
Gennari R, Alexander JW, Boyce ST, et al.: Effects of the angiotensin converting enzyme inhibitor enalapril on bacterial translocation after thermal injury and bacterial challenge. Shock 1996, 6:95–100.
Obisesan TO, Toth MJ, Donaldson K, et al.: Energy expenditure and symptom severity in men with heart failure. Am J Cardiol 1996, 77:1250–1252.
Anker SD, Clark AL, Kemp M, et al.: Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. J Am Coll Cardiol 1997, 30:997–1001.
Moriwaki H, Tajika M, Miwa Y, et al.: Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer. J Gastroenterol 2000, 35(Suppl 12):13–17.
Heymsfield SB, Casper K: Congestive heart failure: clinical management by use of continuous nasoenteric feeding. Am J Clin Nutr 1989, 50:539–544.
Otaki M: Surgical treatment of patients with cardiac cachexia. An analysis of factors affecting operative mortality. Chest 1994, 105:1347–1351.
Witte KKA, Clark AL, Cleland JGF: Chronic heart failure and micronutrients. J Am Coll Cardiol 2001, 37:1765–1774.
Brady JA, Rock CL, Hornerffer MR: Thiamine status, diuretic medications, and the management of congestive heart failure. J Am Diet Assoc 1995, 94:541–545.
Anand I, Chandrashekhan Y, De Giuli F, et al.: Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure. Cardiovasc Drugs Ther 1998, 12:291–299.
Herbaczynska-Cedro K, Kosiewicz-Wasek B, Cedro K: Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction. Eur Heart J 1995, 16:1044–1049.
Coats AJ, Adamopoulos S, Meyer TE, et al.: Effects of physical training in chronic heart failure. Lancet 1990, 335:63–66.
Piepoli M, Flather M, Coats AJS: Overview of studies of exercise training in chronic heart failure: the need for a prospective randomized multicentre European trial. Eur Heart J 1998, 19:830–841.
Schulze PC, Gielen S, Schuler G, Hambrecht R: Chronic heart failure and skeletal muscle catabolism: effect of exercise training. Int J Cardiol 2002, 85:141–149.
Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators: A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001, 345:1667–1675.
Young JB, Dunlap ME, Pfeffer MA, et al.: Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction. Circulation 2004, 110:2618–2626.
Song Yao-Hua, Li Y, Du J, et al.: Muscle-specific expression of IGF-1 blocks angiotensin-induced skeletal muscle wasting. J Clin Invest 2005, 115:451–458.
Hryniewicz K, Androne AS, Hudaihed A, Katz SD: Partial reversal of cachexia by beta-adrenergic receptor blocker therapy in patients with chronic heart failure. J Card Fail 2003, 9:464–468.
Pugh PJ, Jones RD, West JN, et al.: Testosterone treatment for men with chronic heart failure. Heart 2004, 90:446–447.
O’Driscoll JG, Green DJ, Ireland M, et al.: Treatment of endstage cardiac failure with growth hormone. Lancet 1997, 349:1068.
Anker SD, Volterrani M, Pflaum CD, et al.: Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone. J Am Coll Cardiol 2001, 38:443–452.
Cicoria M, Kalra PR, Anker SD: Growth hormone resistance in chronic heart failure and its therapeutic implications. J Card Fail 2003, 9:219–226.
Kojima M, Hosoda H, Date Y, et al.: Ghrelin is a growthhormone-releasing acylated peptide from stomach. Nature 1999, 402:656–660.
Nagaya N, Uematsu M, Kojima M, et al.: Elevated circulating level of ghrelin in cachexia associated with chronic heart failure. Relationships between ghrelin and anabolic/catabolic factors. Circulation 2001, 104:2034–2038.
Baldanzi G, Filigheddu N, Cutrupi S, et al.: Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002, 159:1029–1037.
Strassburg S, Springer J, Anker SD. Muscle wasting in cardiac cachexia. Int J Biochem Cell Biol 2005, 37:1938–1947.
Anker SD, Steinborn W, Strassburg S. Cardiac cachexia. Ann Med 2004, 36:518–529.
Sharma R, Coats AJ, Anker SD. The role of inflammatory mediators in chronic heart failure: cytokines, nitric oxide, and endothelin-1. Int J Cardiol 2000, 72:175–186.
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Akashi, Y.J., Springer, J. & Anker, S.D. Cachexia in chronic heart failure: Prognostic implications and novel therapeutic approaches. Curr Heart Fail Rep 2, 198–203 (2005). https://doi.org/10.1007/BF02696650
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DOI: https://doi.org/10.1007/BF02696650