Cardiac cachexia and muscle wasting: definition, physiopathology, and clinical consequences

References

• Greenberg B, Kahn AM. Clinical assessment of heart failure. In: Bonow RO, Mann DL, Zipes DP, Libby P, Braunwald E, editors. Braunwald’s Heart Disease. A Textbook of Cardiovascular Medicine. Philadelphia: Elsevier Saunders; 2012:505–516.
   Google Scholar
• Anker SD, Chua TP, Ponikowski P, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation. 1997;96:526–534.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Curtis JP, Selter JG, Wang Y, et al. The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Intern Med. 2005;165:55–61.
   PubMed Web of Science ®Google Scholar
• Kalantar-Zadeh K, Block G, Horwich T, Fonarow GC. Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol. 2004;21:1439–1444.
   Google Scholar
• Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J. 2008;156:13–22.
   PubMed Web of Science ®Google Scholar
• Lavie CJ, de Schutter A, Alpert MA, Mehra MR, Milani RV, Ventura HO. Obesity paradox, cachexia, frailty, and heart failure. Heart Fail Clin. 2014;10:319–326.
   PubMed Web of Science ®Google Scholar
• Tacke M, Ebner N, Boschmann M, et al. Muscle wasting in patients with chronic heart failure: results from the studies investigating comorbidities aggravating heart failure (SICA-HF). Eur Heart J. 2013;34:512–519.
   Web of Science ®Google Scholar
• Kalantar-Zadeh K, Rhee C, Sim JJ, Stenvinkel P, Anker SD, Kovesdy CP. Why cachexia kills: examining the causality of poor outcomes in wasting conditions. J Cachexia Sarcopenia Muscle. 2013;4:89–94.
   PubMed Web of Science ®Google Scholar
• Letilovic T, Vrhovac R. Influence of additional criteria from a definition of cachexia on its prevalence-good or bad thing? Eur J Clin Nutr. 2013;67:797–801.
   Web of Science ®Google Scholar
• Martins T, Vitorino R, Moreira-Gonçalves D, Amado F, Duarte JA, Ferreira R. Recent insights on the molecular mechanisms and therapeutic approaches for cardiac cachexia. Clin Biochem. 2014;47:8–15.
   Web of Science ®Google Scholar
• Oreopoulos A, Kalantar-Zadeh K, McAlister FA, et al. Comparison of direct body composition assessment methods in patients with chronic heart failure. J Card Fail. 2010;16:867–872.
   Web of Science ®Google Scholar
• Ebner N, Elsner S, Springer J, von Haehling S. Molecular mechanisms and treatment targets of muscle wasting and cachexia in heart failure: an overview. Curr Opin Support Palliat Care. 2014;8:15–24.
   Web of Science ®Google Scholar
• Anker SD, Ponikowski P, Varney S, et al. Wasting as independent risk factor of mortality in chronic heart failure. Lancet. 1997;349:1050–1053.
   PubMed Web of Science ®Google Scholar
• Anker SD, Negassa A, Coats AJ, et al. Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet. 2003;361:1077–1083.
   PubMed Web of Science ®Google Scholar
• Evans WJ, Morley JE, Argiles J, et al. Cachexia: a new definition. Clin Nutr. 2008;27:793–799.
   PubMed Web of Science ®Google Scholar
• Christensen HM, Kistorp C, Schou M, et al. Prevalence of cachexia in chronic heart failure and characteristics of body composition and metabolic status. Endocrine. 2013;43:626–634.
   Web of Science ®Google Scholar
• Trullàs JC, Formiga F, Montero M, et al; RICA Investigators. Impact of weight loss on mortality in chronic heart failure: findings from the RICA registry. Int J Cardiol. 2013;168:306–311.
   Web of Science ®Google Scholar
• Morley JE, Abbatecola AM, Argiles JM, et al; Society on Sarcopenia, Cachexia and Wasting Disorders Trialist Workshop. The society on sarcopenia, cachexia and wasting disorders trialist workshop. Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc. 2011;12:403–409.
   PubMed Web of Science ®Google Scholar
• Pocock SJ, McMurray JJ, Dobson J, et al. Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme. Eur Heart J. 2008;29:2641–2650.
   PubMed Web of Science ®Google Scholar
• Mancini DM, Walter G, Reichek N, et al. Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation. 1992;85:1364–1373.
   PubMed Web of Science ®Google Scholar
• Lima AR, Martinez PF, Okoshi K, et al. Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure. Int J Exp Pathol. 2010;91:54–62.
   Web of Science ®Google Scholar
• Thibault R, Chanséaume S, Azarnoush K, et al. Mitochondrial protein synthesis is increased in oxidative skeletal muscles of rats with cardiac cachexia. Nutr Res. 2014;34:250–257.
   Web of Science ®Google Scholar
• Schulze PC. Protein catabolism and impairment of skeletal muscle insulin signalling in heart failure. Clin Sci. 2010;119:465–466.
   Web of Science ®Google Scholar
• Toth MJ. Impaired muscle protein anabolic response to insulin and amino acids in heart failure patients: relationship with markers of immune activation. Clin Sci. 2010;119:467–476.
   Web of Science ®Google Scholar
• Callahan DM, Toth MJ. Skeletal muscle protein metabolism in human heart failure. Curr Opin Clin Nutr Metab Care. 2013;16:66–71.
   Web of Science ®Google Scholar
• Mangner N, Matsuo Y, Schuler G, Adams V. Cachexia in chronic heart failure: endocrine determinants and treatment perspectives. Endocrine. 2013;43:253–265.
   Web of Science ®Google Scholar
• Yoshida T, Tabony AM, Galvez S, et al. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia. Int J Biochem Cell Biol. 2013;45:2322–2332.
   PubMed Web of Science ®Google Scholar
• Cunha TF, Bacurau AV, Moreira JB, et al. Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure. PLoS One. 2012;7:e41701.
   PubMed Web of Science ®Google Scholar
• Foletta VC, White LJ, Larsen AE, Leger B, Russell AP. The role and regulation of mafbx/atrogin-1 and murf1 in skeletal muscle atrophy. Pflugers Arch. 2011;461:325–335.
   Web of Science ®Google Scholar
• Gielen S, Sandri M, Kozarez I, et al. Exercise training attenuates murf-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study. Circulation. 2012;125:2716–2727.
   PubMed Web of Science ®Google Scholar
• Breitbart A, Auger-Messier M, Molkentin JD, Heineke J. Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting. Am J Physiol Heart Circ Physiol. 2011;300:H1973–H1982.
   Web of Science ®Google Scholar
• Damatto RL, Martinez PF, Lima AR, et al. Heart failure-induced skeletal myopathy in spontaneously hypertensive rats. Int J Cardiol. 2013;167:698–703.
   Web of Science ®Google Scholar
• Anker SD, Coats AJS. Cardiac cachexia. A syndrome with impaired survival and immune and neuroendocrine activation. Chest. 1999;115:836–847.
   PubMed Web of Science ®Google Scholar
• Martinez PF, Okoshi K, Zornoff LA, et al. Chronic heart failure-induced skeletal muscle atrophy, necrosis, and myogenic regulatory factors changes. Med Sci Monit. 2010;16:374–383.
   Web of Science ®Google Scholar
• Santos DP, Okoshi K, Moreira VO, et al. Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure. Growth Horm IGF Res. 2010;20:149–155.
   Web of Science ®Google Scholar
• Carvalho RF, Cicogna AC, Campos GE, et al. Myosin heavy chain expression and atrophy in rat skeletal muscle during transition from cardiac hypertrophy to heart failure. Int J Exp Pathol. 2003;84:201–206.
   Web of Science ®Google Scholar
• Von Haehling S, Steinbeck L, Doehner W, Springer J, Anker SD. Muscle wasting in heart failure: an overview. Int J Biochem Cell Biol. 2013;45:2257–2265.
   PubMed Web of Science ®Google Scholar
• Okutsu M, Call JA, Lira VA, et al. Extracellular superoxide dismutase ameliorates skeletal muscle abnormalities, cachexia, and exercise intolerance in mice with congestive heart failure. Circ Heart Fail. 2014;7:519–530.
   PubMed Web of Science ®Google Scholar
• Ciciliot S, Rossi AC, Dyar KA, Blaauw B, Schiaffino S. Muscle type and fiber type specificity in muscle wasting. Int J Biochem Cell Biol. 2013;45:2191–2199.
   PubMed Web of Science ®Google Scholar
• Sullivan MJ, Green HJ, Cobb FR. Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity. Circulation. 1991;84:1597–1607.
   PubMed Web of Science ®Google Scholar
• Szabó T, Postrach E, Mähler A, et al. Increased catabolic activity in adipose tissue of patients with chronic heart failure. Eur J Heart Fail. 2013;15:1131–1137.
   Web of Science ®Google Scholar
• Loncar G, Fulster S, von Haehling S, Popovic V. Metabolism and the heart: an overview of muscle, fat, and bone metabolism in heart failure. Int J Cardiol. 2013;162:77–85.
   PubMed Web of Science ®Google Scholar
• Boxall BW, Clark AL. Beta-blockers and weight change in patients with chronic heart failure. J Card Fail. 2012;18:233–237.
   Google Scholar
• Brasier AR, Recinos AR, Eledrisi MS. Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol. 2002;22:1257–1266.
   PubMed Web of Science ®Google Scholar
• Hansen PR, Rieneck K, Bendtzen K. Spironolactone inhibits production of proinflammatory cytokines by human mononuclear cells. Immunol Lett. 2004;91:87–91.
   PubMed Web of Science ®Google Scholar
• Werner C, Werdan K, Ponicke K, Brodde OE. Impaired beta-adrenergic control of immune function in patients with chronic heart failure: reversal by beta1-blocker treatment. Basic Res Cardiol. 2001;96:290–298.
   Web of Science ®Google Scholar
• Krack A, Sharma R, Figulla HR, Anker SD. The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J. 2005;26:2368–2374.
   Web of Science ®Google Scholar
• Yoshida T, Galvez S, Tiwari S, et al. Angiotensin II inhibits satellite cell proliferation and prevents skeletal muscle regeneration. J Biol Chem. 2013;288:23823–23832.
   Web of Science ®Google Scholar
• Springer J, Tschirner A, Haghikia A, et al. Prevention of liver cancer cachexia-induced cardiac wasting and heart failure. Eur Heart J. 2014;35(14):932–941.
   PubMed Web of Science ®Google Scholar
• Invernizzi M, Carda S, Cisari C; On behalf of Societa Italiana per lo Studio Della Sarcopenia e Della Disabilita Muscolo-Scheletrica (SISDIM). Possible synergism of physical exercise and ghrelin-agonists in patients with cachexia associated with chronic heart failure. Aging Clin Exp Res. 2014;26:341–351.
   Google Scholar
• Egerman MA, Glass DJ. Signaling pathways controlling skeletal muscle mass. Crit Rev Biochem Mol Biol. 2014;49:59–68.
   PubMed Web of Science ®Google Scholar
• Seiva FR, Ebaid GM, Castro AV, et al. Growth hormone and heart failure: oxidative stress and energetic metabolism in rats. Growth Horm IGF Res. 2008;18:275–283.
   PubMed Web of Science ®Google Scholar
• Yoshida T, Semprun-Prieto L, Sukhanov S, Delafontaine P. IGF-1 prevents Ang II-induced skeletal muscle atrophy via akt- and foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol. 2010;298:H1565.
   PubMed Web of Science ®Google Scholar
• Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323:236–241.
   PubMed Web of Science ®Google Scholar
• Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann D. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the studies of left ventricular dysfunction (SOLVD). J Am Coll Cardiol. 1996;27:1201–1206.
   PubMed Web of Science ®Google Scholar
• Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the vesnarinone trial (VEST). Circulation. 2001;103:2055–2059.
   PubMed Web of Science ®Google Scholar
• Yndestad A, Damas JK, Oie E, Ueland T, Gullestad L, Aukrust P. Systemic inflammation in heart failure – the whys and wherefores. Heart Fail Rev. 2006;11:83–92.
   PubMed Web of Science ®Google Scholar
• von Haehling S, Schefold JC, Lainscak M, Doehner W, Anker SD. Inflammatory biomarkers in heart failure revisited: much more than innocent bystanders. Heart Fail Clin. 2009;5:549–560.
   PubMedGoogle Scholar
• Bozkurt B, Kribbs SB, Clubb FJ Jr, et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation. 1998;97:1382–1391.
   PubMed Web of Science ®Google Scholar
• Sivasubramanian N, Coker ML, Kurrelmeyer KM, et al. Left ventricular remodeling in transgenic mice with cardiac restricted overexpression of tumor necrosis factor. Circulation. 2001;104:826–831.
   PubMed Web of Science ®Google Scholar
• Romeiro FG, Zornoff LAM, Okoshi K, Okoshi MP. Gastrointestinal changes associated to heart failure. Arq Bras Cardiol. 2012;98:273–277.
   Web of Science ®Google Scholar
• Sandek A, Bauditz J, Swidsinski A, et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1561–1569.
   PubMed Web of Science ®Google Scholar
• Arutyunov GP, Kostyukevich OI, Serov RA, Rylova NV, Bylova NA. Collagen accumulation and dysfunctional mucosal barrier of the small intestine in patients with chronic heart failure. Int J Cardiol. 2008;125:240–245.
   Web of Science ®Google Scholar
• Krack A, Richartz BM, Gastmann A, et al. Studies on intragastric pco2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure. Eur J Heart Fail. 2004;6:403–407.
   Web of Science ®Google Scholar
• Wrigley BJ, Lip GYH, Shantsila E. The role of monocytes and inflammation in the pathophysiology of heart failure. Eur J Heart Fail. 2011;13:1161–1171.
   PubMed Web of Science ®Google Scholar
• Valentova M, von Haehling S, Doehner W, Murin J, Anker SD, Sandek A. Liver dysfunction and its nutritional implications in heart failure. Nutrition. 2013;29:370–378.
   Web of Science ®Google Scholar
• Araújo JP, Lourenço P, Rocha-Gonçalves F, Ferreira A, Bettencourt P. Adiponectin is increased in cardiac cachexia irrespective of body mass index. Eur J Heart Fail. 2009;11:567–572.
   Web of Science ®Google Scholar
• Von Haehling S, Lainscak M, Springer J, Anker SD. Cardiac cachexia: a systematic overview. Pharmacol Ther. 2009;121:227–252.
   PubMed Web of Science ®Google Scholar
• Yoshida T, Semprun-Prieto L, Wainford RD, Sukhanov S, Kapusta DR, Delafontaine P. Angiotensin II reduces food intake by altering orexigenic neuropeptide expression in the mouse hypothalamus. Endocrinology. 2012;153:1411–1420.
   PubMed Web of Science ®Google Scholar
• Toth MJ, Gottlieb SS, Goran MI, Fisher ML, Poehlman ET. Daily energy expenditure in free-living heart failure patients. Am J Physiol. 1997;272:E469–E475.
   Google Scholar
• Tacke M, Ebner N, Boschmann M, et al. Resting energy expenditure and the effects of muscle wasting in patients with chronic heart failure: results from the studies investigating comorbidities aggravating heart failure (SICA-HF). J Am Med Dir Assoc. 2013;14:837–841.
   Web of Science ®Google Scholar
• Habedank D, Meyer FJ, Hetzer R, Anker SD, Ewert R. Relation of respiratory muscle strength, cachexia and survival in severe heart failure. J Cachexia Sarcopenia Muscle. 2013;4:277–285.
   Web of Science ®Google Scholar
• Melenovsky V, Kotrc M, Borlaug BA, et al. Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol. 2013;62:1660–1670.
   PubMed Web of Science ®Google Scholar
• Lavie CJ, Osman AF, Milani RV, Mehra MR. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. Am J Cardiol. 2003;91:891–894.
   PubMed Web of Science ®Google Scholar
• Tian M, Asp ML, Nishijima Y, Belury MA. Evidence for cardiac atrophic remodeling in cancer-induced cachexia in mice. Int J Oncol. 2011;39:1321–1326.
   PubMed Web of Science ®Google Scholar
• Okoshi MP, Okoshi K, Pai VD, Pai-Silva MD, Matsubara LS, Cicogna AC. Mechanical, biochemical, and morphological changes in the heart from chronic food restricted rats. Can J Physiol Pharmacol. 2001;79:754–760.
   Web of Science ®Google Scholar
• Okoshi K, Matsubara LS, Okoshi MP, et al. Food restriction-induced myocardial dysfunction demonstrated by the combination of in vivo and in vitro studies. Nutr Res. 2002;22:1353–1364.
   Web of Science ®Google Scholar
• Cicogna AC, Padovani CR, Okoshi K, Matsubara LS, Aragon FF, Okoshi MP. The influence of temporal food restriction on the performance of isolated cardiac muscle. Nutr Res. 2001;21:639–648.
   Web of Science ®Google Scholar
• Fioretto JR, Queiroz SS, Padovani CR, Matsubara LS, Okoshi K, Matsubara BB. Ventricular remodeling and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition. Am J Physiol. 2002;282:H1327–H1333.
   Google Scholar
• Sugizaki MM, Carvalho RF, Aragon FF, et al. Myocardial dysfunction induced by food restriction is related to morphological damage in normotensive middle-aged rats. J Biomed Sci. 2005;12:641–649.
   Web of Science ®Google Scholar
• Gut AL, Okoshi MP, Padovani CR, Aragon FF, Cicogna AC. Myocardial dysfunction induced by food restriction is related to calcium cycling and beta-adrenergic system changes. Nutr Res. 2003;23:911–919.
   Web of Science ®Google Scholar
• Okoshi MP, Okoshi K, Matsubara LS, et al. Myocardial remodeling and dysfunction are induced by chronic food restriction in spontaneously hypertensive rats. Nutr Res. 2006;26:567–572.
   Web of Science ®Google Scholar
• Okoshi K, Fioretto JR, Okoshi MP, et al. Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility. Braz J Med Biol Res. 2004;37:607–613.
   Web of Science ®Google Scholar
• Cicogna AC, Padovani CR, Okoshi K, Aragon FF, Okoshi MP. Myocardial function during chronic food restriction in isolated hypertrophied cardiac muscle. Am J Med Sci. 2000;320:244–248.
   Web of Science ®Google Scholar
• Gut AL, Sugizaki MM, Okoshi MP, et al. Food restriction impairs myocardial inotropic response to calcium and beta-adrenergic stimulation in spontaneously hypertensive rats. Nutr Res. 2008;28:722–727.
   Web of Science ®Google Scholar
• Molfino A, Papa A, Gasperini-Zacco ML, et al. Left ventricular mass correlates with lean body mass in patients with disease-associated wasting. J Cachexia Sarcopenia Muscle. 2014;5:251–252.
   Web of Science ®Google Scholar
• Nanas JN, Matsouka C, Karageorgopoulos D, et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol. 2006;48:2485–2489.
   PubMed Web of Science ®Google Scholar
• Arora NP, Ghali JK. Anemia and iron deficiency in heart failure. Heart Fail Clin. 2014;10:281–294.
   Web of Science ®Google Scholar
• Jankowska EA, Ponikowski P. Molecular changes in myocardium in the course of anemia or iron deficiency. Heart Fail Clin. 2010;6:295–304.
   PubMedGoogle Scholar
• Enjuanes C, Klip IT, Bruguera J, et al. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol. 2014;174:268–275.
   PubMed Web of Science ®Google Scholar
• Ebner N, Springer J, Kalantar-Zadeh K, et al. Mechanism and novel therapeutic approaches to wasting in chronic disease. Maturitas. 2013;75:199–206.
   PubMed Web of Science ®Google Scholar
• Lenk K, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle. 2010;1:9–21.
   PubMed Web of Science ®Google Scholar