Anabolism to Catabolism: Serologic Clues to Nutritional Status in Heart Failure

  • Laura Murphy
  • Alastair Gray
  • Emer JoyceEmail author
Biomarkers of Heart Failure (J. Grodin & W.H.W. Tang, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Biomarkers of Heart Failure


Purpose of Review

Malnutrition, sarcopenia, and cachexia are areas of increasing interest in the management of patients with heart failure (HF). This review aims to examine the serological markers useful in guiding the physician in identification of these patients.

Recent Findings

Traditional nutritional biomarkers including albumin/prealbumin, iron, and vitamin D deficiencies predict poor prognosis in malnutrition and HF. Novel biomarkers including ghrelin, myostatin, C-terminal agrin fragment, and adiponectin have been identified as possible substrates and/or therapeutic targets in cardiac patients with sarcopenia and cachexia, though clinical trial data is limited to date.


Increased focus on nutritional deficiency syndromes in heart failure has led to the use of established markers of malnutrition as well as the identification of novel biomarkers in the management of these patients, though to date, their usage has been confined to the academic domain and further research is required to establish their role in the clinical setting.


Malnutrition Sarcopenia Cachexia Frailty Heart failure 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart disease and stroke Statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603. Scholar
  2. 2.
    Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6(3):606–19. Scholar
  3. 3.
    Crespo-Leiro MG, Anker SD, Maggioni AP, Coats AJ, Filippatos G, Ruschitzka F, et al. European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail. 2016;18(6):613–25. Scholar
  4. 4.
    Raposo André T, Lopes-Santos A. I GN. Cardiac Cachexia syndrome. Eur Med J Cardiol. 2017;5(1):101–7.Google Scholar
  5. 5.
    Goyal P, Almarzooq ZI, Horn EM, Karas MG, Sobol I, Swaminathan RV, et al. Characteristics of Hospitalizations for Heart Failure with Preserved Ejection Fraction. Am J Med. 2016;129(6):635.e15–26. Scholar
  6. 6.
    McNallan SM, Chamberlain AM, Gerber Y, Singh M, Kane RL, Weston SA, et al. Measuring frailty in heart failure: a community perspective. Am Heart J. 2013;166(4):768–74. Scholar
  7. 7.
    Vidan MT, Sanchez E, Fernandez-Aviles F, Serra-Rexach JA, Ortiz J, Bueno H. FRAIL-HF, a study to evaluate the clinical complexity of heart failure in nondependent older patients: rationale, methods and baseline characteristics. Clin Cardiol. 2014;37(12):725–32. Scholar
  8. 8.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56. Scholar
  9. 9.
    Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Van Gossum A, Klek S, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr (Edinburgh, Scotland). 2015;34(3):335–40. Scholar
  10. 10.
    Tevik K, Thurmer H, Husby MI, de Soysa AK, Helvik AS. Nutritional risk screening in hospitalized patients with heart failure. Clin Nutr (Edinburgh, Scotland). 2015;34(2):257–64. Scholar
  11. 11.
    Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiencydagger. Eur Heart J. 2015;36(11):657–68. Scholar
  12. 12.
    Lin H, Zhang H, Lin Z, Li X, Kong X, Sun G. Review of nutritional screening and assessment tools and clinical outcomes in heart failure. Heart Fail Rev. 2016;21(5):549–65. Scholar
  13. 13.
    Kruizenga HM, Seidell JC, de Vet HC, Wierdsma NJ, van Bokhorst-de van der Schueren MA. Development and validation of a hospital screening tool for malnutrition: the short nutritional assessment questionnaire (SNAQ). Clin Nutr (Edinburgh, Scotland). 2005;24(1):75–82. Scholar
  14. 14.
    Hajahmadi M, Shemshadi S, Khalilipur E, Amin A, Taghavi S, Maleki M, et al. Muscle wasting in young patients with dilated cardiomyopathy. J Cachexia Sarcopenia Muscle. 2017;8(4):542–8. Scholar
  15. 15.
    • Iwakami N, Nagai T, Furukawa TA, Sugano Y, Honda S, Okada A, et al. Prognostic value of malnutrition assessed by controlling nutritional status score for long-term mortality in patients with acute heart failure. Int J Cardiol. 2017;230:529–36. This study highlights the importance of assessing nutritional status in acute HF patients due to the significant association with increased mortality identified in this group. CrossRefPubMedGoogle Scholar
  16. 16.
    Sargento L, Satendra M, Almeida I, Sousa C, Gomes S, Salazar F, et al. Nutritional status of geriatric outpatients with systolic heart failure and its prognostic value regarding death or hospitalization, biomarkers and quality of life. J Nutr Health Aging. 2013;17(4):300–4. Scholar
  17. 17.
    • Lewis GD, Malhotra R, Hernandez AF, SE MN, Smith A, Felker GM, et al. Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical TrialOral Iron for Heart FailureOral Iron for Heart Failure. JAMA. 2017;317(19):1958–66. The results for IV iron have previously been promising with improvements in exercise capacity in HF patients however, this study examines the use of oral iron and found it to be of little benefit in the treatment group. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Chiarantini D, Volpato S, Sioulis F, Bartalucci F, Del Bianco L, Mangani I, et al. Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure. J Card Fail. 2010;16(5):390–5. Scholar
  19. 19.
    Chung CJ, Wu C, Jones M, Kato TS, Dam TT, Givens RC, et al. Reduced handgrip strength as a marker of frailty predicts clinical outcomes in patients with heart failure undergoing ventricular assist device placement. J Card Fail. 2014;20(5):310–5. Scholar
  20. 20.
    Adejumo OL, Koelling TM, Hummel SL. Nutritional risk index predicts mortality in hospitalized advanced heart failure patients. J Heart Lung Transplant : the official publication of the International Society for Heart Transplantation. 2015;34(11):1385–9. Scholar
  21. 21.
    Santilli V, Bernetti A, Mangone M, Paoloni M. Clinical definition of sarcopenia. Clin Cases Mineral Bone Metab : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases. 2014;11(3):177–80.Google Scholar
  22. 22.
    Fulster S, Tacke M, Sandek A, Ebner N, Tschope C, Doehner W, et al. Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Eur Heart J. 2013;34(7):512–9. Scholar
  23. 23.
    Yost G, Bhat G. Relationship between handgrip strength and length of stay for left ventricular assist device implantation. Nutr Clin Pract : official publication of the American Society for Parenteral and Enteral Nutrition. 2017;32(1):98–102. Scholar
  24. 24.
    Anker SD, Sharma R. The syndrome of cardiac cachexia. Int J Cardiol. 2002;85(1):51–66.CrossRefGoogle Scholar
  25. 25.
    Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, et al. Cachexia: a new definition. Clin Nutr (Edinburgh, Scotland). 2008;27(6):793–9. Scholar
  26. 26.
    Farkas J, von Haehling S, Kalantar-Zadeh K, Morley JE, Anker SD, Lainscak M. Cachexia as a major public health problem: frequent, costly, and deadly. J Cachexia Sarcopenia Muscle. 2013;4(3):173–8. Scholar
  27. 27.
    Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet (London, England). 1997;349(9058):1050–3. Scholar
  28. 28.
    Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr (Edinburgh, Scotland). 2003;22(3):321–36.CrossRefGoogle Scholar
  29. 29.
    Heberton GA, Nassif M, Bierhals A, Novak E, LaRue SJ, Lima B, et al. Usefulness of psoas muscle area determined by computed tomography to predict mortality or prolonged length of hospital stay in patients undergoing left ventricular assist device implantation. Am J Cardiol. 2016;118(9):1363–7. Scholar
  30. 30.
    Bibas L, Saleh E, Alkharji S, Chetrit J, Mullie L, Cantarovich M, et al. Sarcopenia and mortality after heart transplantation. Can J Cardiol. 2017;33(10):S71–S2. Scholar
  31. 31.
    Kumar A, Ansari BA, Kim J, Suri A, Gaddam S, Yenigalla S, et al. Axial muscle size as a strong predictor of death in subjects with and without heart failure. J Am Heart Assoc. 2019;8(4):e010554. Scholar
  32. 32.
    Rossignol P, Masson S, Barlera S, Girerd N, Castelnovo A, Zannad F, et al. Loss in body weight is an independent prognostic factor for mortality in chronic heart failure: insights from the GISSI-HF and Val-HeFT trials. Eur J Heart Fail. 2015;17(4):424–33. Scholar
  33. 33.
    Tsuchida K, Fujihara Y, Hiroki J, Hakamata T, Sakai R, Nishida K, et al. Significance of Sarcopenia Evaluation in Acute Decompensated Heart Failure. Skeletal Muscle Mass Index versus Fat-Free Mass Index. Int Heart J. 2018;59(1):143–8. Scholar
  34. 34.
    Narumi T, Watanabe T, Kadowaki S, Takahashi T, Yokoyama M, Kinoshita D, et al. Sarcopenia evaluated by fat-free mass index is an important prognostic factor in patients with chronic heart failure. Eur J Int Med. 2015;26(2):118–22. Scholar
  35. 35.
    Melenovsky V, Kotrc M, Borlaug BA, Marek T, Kovar J, Malek I, et al. Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol. 2013;62(18):1660–70. Scholar
  36. 36.
    Kuzuya M, Izawa S, Enoki H, Okada K, Iguchi A. Is serum albumin a good marker for malnutrition in the physically impaired elderly? Clin Nutr (Edinburgh, Scotland). 2007;26(1):84–90. Scholar
  37. 37.
    Bharadwaj S, Ginoya S, Tandon P, Gohel TD, Guirguis J, Vallabh H, et al. Malnutrition: laboratory markers vs nutritional assessment. Gastroenterol Rep (Oxf). 2016;4(4):272–80. Scholar
  38. 38.
    Lourenço P, Silva S, Friões F, Alvelos M, Amorim M, Couto M, et al. Low prealbumin is strongly associated with adverse outcome in heart failure. Heart. 2014;100(22):1780–5. Scholar
  39. 39.
    von Haehling S, Ebner N, Evertz R, Ponikowski P, Anker SD. Iron deficiency in heart failure: an overview. JACC Heart failure. 2019;7(1):36–46. Scholar
  40. 40.
    Cappellini MD, Comin-Colet J, de Francisco A, Dignass A, Doehner W, Lam CS, et al. Iron deficiency across chronic inflammatory conditions: international expert opinion on definition, diagnosis, and management. Am J Hematol. 2017;92(10):1068–78. Scholar
  41. 41.
    Boulton FE. The myoglobin content of human skeletal muscle. Br J Haematol. 1973;25(2):281.PubMedGoogle Scholar
  42. 42.
    Stugiewicz M, Tkaczyszyn M, Kasztura M, Banasiak W, Ponikowski P, Jankowska EA. The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications. Eur J Heart Fail. 2016;18(7):762–73. Scholar
  43. 43.
    Martens P, Nijst P, Verbrugge FH, Smeets K, Dupont M, Mullens W. Impact of iron deficiency on exercise capacity and outcome in heart failure with reduced, mid-range and preserved ejection fraction. Acta Cardiol. 2018;73(2):115–23. Scholar
  44. 44.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. Scholar
  45. 45.
    Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, et al. Effects of vitamin D on cardiac function in patients with chronic HF: the VINDICATE study. J Am Coll Cardiol. 2016;67(22):2593–603. Scholar
  46. 46.
    Sanders KM, Scott D, Ebeling PR. Vitamin D deficiency and its role in muscle-bone interactions in the elderly. Curr Osteoporos Rep. 2014;12(1):74–81. Scholar
  47. 47.
    Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the longitudinal aging study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766–72. Scholar
  48. 48.
    Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab. 2007;92(6):2058–65. Scholar
  49. 49.
    Costanzo S, De Curtis A, Di Castelnuovo A, Persichillo M, Bonaccio M, Pounis G, et al. Serum vitamin D deficiency and risk of hospitalization for heart failure: prospective results from the Moli-sani study. Nutr Metab Cardiovasc Dis : NMCD. 2018;28(3):298–307. Scholar
  50. 50.
    Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail. 2007;13(6):422–30. Scholar
  51. 51.
    Tuegel C, Bansal N. Heart failure in patients with kidney disease. Heart. 2017;103(23):1848–53. Scholar
  52. 52.
    Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP, et al. The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis : the official journal of the National Kidney Foundation. 2004;43(5):861–7.CrossRefGoogle Scholar
  53. 53.
    Maurer MS, Horn E, Reyentovich A, Dickson VV, Pinney S, Goldwater D, et al. Can a left ventricular assist device in individuals with advanced systolic heart failure improve or reverse frailty? J Am Geriatr Soc. 2017;65(11):2383–90. Scholar
  54. 54.
    Jenkins R, Mandarano L, Gugathas S, Kaski JC, Anderson L, Banerjee D. Impaired renal function affects clinical outcomes and management of patients with heart failure. ESC heart failure. 2017;4(4):576–84. Scholar
  55. 55.
    KDOQI. Clinical practice guidelines and clinical practice recommendations for Anemia in chronic kidney disease. Am J Kidney Dis : the official journal of the National Kidney Foundation. 2006;47(5 Suppl 3):S11–145. Scholar
  56. 56.
    Zhou Y, Hellberg M, Svensson P, Hoglund P, Clyne N. Sarcopenia and relationships between muscle mass, measured glomerular filtration rate and physical function in patients with chronic kidney disease stages 3-5. Nephrol Dialysis Transplant : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018;33(2):342–8. Scholar
  57. 57.
    Pereira RA, Cordeiro AC, Avesani CM, Carrero JJ, Lindholm B, Amparo FC, et al. Sarcopenia in chronic kidney disease on conservative therapy: prevalence and association with mortality. Nephrol Dialysis Transplant : official publication of the European Dialysis and Transplant Association - European Renal Association. 2015;30(10):1718–25. Scholar
  58. 58.
    Anker SD, Ponikowski PP, Clark AL, Leyva F, Rauchhaus M, Kemp M, et al. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J. 1999;20(9):683–93. Scholar
  59. 59.
    Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, et al. Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004;59(3):242–8. Scholar
  60. 60.
    Bian AL, Hu HY, Rong YD, Wang J, Wang JX, Zhou XZ. A study on relationship between elderly sarcopenia and inflammatory factors IL-6 and TNF-alpha. Eur J Med Res. 2017;22(1):25. Scholar
  61. 61.
    Yoshihisa A, Kanno Y, Watanabe S, Yokokawa T, Abe S, Miyata M, et al. Impact of nutritional indices on mortality in patients with heart failure. Open heart. 2018;5(1):e000730. Scholar
  62. 62.
    Castellano G, Affuso F, Conza PD, Fazio S. The GH/IGF-1 Axis and heart failure. Curr Cardiol Rev. 2009;5(3):203–15. Scholar
  63. 63.
    Anker SD, Volterrani M, Pflaum CD, Strasburger CJ, Osterziel KJ, Doehner W, et al. Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone. J Am Coll Cardiol. 2001;38(2):443–52.CrossRefGoogle Scholar
  64. 64.
    Cittadini A, Saldamarco L, Marra AM, Arcopinto M, Carlomagno G, Imbriaco M, et al. Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction. J Clin Endocrinol Metab. 2009;94(9):3329–36. Scholar
  65. 65.
    Bhandari SS, Narayan H, Jones DJ, Suzuki T, Struck J, Bergmann A, et al. Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure. Eur J Heart Fail. 2016;18(3):281–9. Scholar
  66. 66.
    Hassfeld S, Eichhorn C, Stehr K, Naegele H, Geier C, Steeg M, et al. Insulin-like growth factor-binding proteins 2 and 3 are independent predictors of a poor prognosis in patients with dilated cardiomyopathy. Heart. 2007;93(3):359–60. Scholar
  67. 67.
    Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007;146(2):104–15.CrossRefGoogle Scholar
  68. 68.
    Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1):245–84. Scholar
  69. 69.
    Kalicinska E, Wojtas K, Majda J, Doehner W, von Haehling S, Banasiak W, et al. Anabolic deficiencies in men with systolic heart failure: do co-morbidities and therapies really contribute significantly? Aging Male : the official journal of the International Society for the Study of the Aging Male. 2013;16(3):123–31. Scholar
  70. 70.
    Wu HY, Wang XF, Wang JH, Li JY. Testosterone level and mortality in elderly men with systolic chronic heart failure. Asian J Androl. 2011;13(5):759–63. Scholar
  71. 71.
    Jankowska EA, Filippatos G, Ponikowska B, Borodulin-Nadzieja L, Anker SD, Banasiak W, et al. Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure. J Card Fail. 2009;15(5):442–50. Scholar
  72. 72.
    Jankowska EA, Biel B, Ponikowska B, Borodulin-Nadzieja L, Petruk-Kowalczyk J, Banasiak W, et al. 679 Reduction in serum testosterone deteriorates exercise capacity in men in the course of chronic heart failure. Eur J Heart Fail Suppl. 2007;6(S1):148. Scholar
  73. 73.
    Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006;114(17):1829–37. Scholar
  74. 74.
    Loncar G, Springer J, Anker M, Doehner W, Lainscak M. Cardiac cachexia: hic et nunc. J Cachexia Sarcopenia Muscle. 2016;7(3):246–60. Scholar
  75. 75.
    Serra-Prat M, Palomera E, Roca M, Puig-Domingo M. Long-term effect of ghrelin on nutritional status and functional capacity in the elderly: a population-based cohort study. Clin Endocrinol. 2010;73(1):41–7. Scholar
  76. 76.
    Nagaya N, Uematsu M, Kojima M, Date Y, Nakazato M, Okumura H, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation. 2001;104(17):2034–8.CrossRefGoogle Scholar
  77. 77.
    Steinbeck L, Ebner N, Valentova M, Bekfani T, Elsner S, Dahinden P, et al. Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Eur J Heart Fail. 2015;17(12):1283–93. Scholar
  78. 78.
    Araujo JP, Lourenco P, Rocha-Goncalves F, Ferreira A, Bettencourt P. Adiponectin is increased in cardiac cachexia irrespective of body mass index. Eur J Heart Fail. 2009;11(6):567–72. Scholar
  79. 79.
    Szabo T, Scherbakov N, Sandek A, Kung T, von Haehling S, Lainscak M, et al. Plasma adiponectin in heart failure with and without cachexia: catabolic signal linking catabolism, symptomatic status, and prognosis. Nutr Metab Cardiovasc Dis : NMCD. 2014;24(1):50–6. Scholar
  80. 80.
    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(6):H1973–H82. Scholar
  81. 81.
    Lenk K, Schur R, Linke A, Erbs S, Matsumoto Y, Adams V, et al. Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model. Eur J Heart Fail. 2009;11(4):342–8. Scholar
  82. 82.
    • Vest AR, Chan M, Deswal A, Givertz MM, Lekavich C, Lennie T, et al. Nutrition, Obesity, and Cachexia in Patients With Heart Failure: A Consensus Statement from the Heart Failure Society of America Scientific Statements Committee. J Card Fail. 2019;25(5):380–400. This article suggests an approach to the assessment of HF patients (both inpatients and outpatients) with malnutrition in combination with either cachexia and obesity and a management strategy for each cohort. CrossRefPubMedGoogle Scholar
  83. 83.
    Rozentryt P, von Haehling S, Lainscak M, Nowak JU, Kalantar-Zadeh K, Polonski L, et al. The effects of a high-caloric protein-rich oral nutritional supplement in patients with chronic heart failure and cachexia on quality of life, body composition, and inflammation markers: a randomized, double-blind pilot study. J Cachexia Sarcopenia Muscle. 2010;1(1):35–42. Scholar
  84. 84.
    Aquilani R, Viglio S, Iadarola P, Opasich C, Testa A, Dioguardi FS, et al. Oral amino acid supplements improve exercise capacities in elderly patients with chronic heart failure. Am J Cardiol. 2008;101(11a):104e–10e. Scholar
  85. 85.
    Forbes SC, Little JP, Candow DG. Exercise and nutritional interventions for improving aging muscle health. Endocrine. 2012;42(1):29–38. Scholar
  86. 86.
    Gould DW, Lahart I, Carmichael AR, Koutedakis Y, Metsios GS. Cancer cachexia prevention via physical exercise: molecular mechanisms. J Cachexia Sarcopenia Muscle. 2013;4(2):111–24. Scholar
  87. 87.
    Lenk K, Erbs S, Hollriegel R, Beck E, Linke A, Gielen S, et al. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Prev Cardiol. 2012;19(3):404–11. Scholar
  88. 88.
    Clark AL, Coats AJS, Krum H, Katus HA, Mohacsi P, Salekin D, et al. Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial. J Cachexia Sarcopenia Muscle. 2017;8(4):549–56. Scholar
  89. 89.
    Anker SD, Negassa A, Coats AJ, Afzal R, Poole-Wilson PA, Cohn JN, 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 (London, England). 2003;361(9363):1077–83. Scholar
  90. 90.
    Khawaja T, Chokshi A, Ji R, Kato TS, Xu K, Zizola C, et al. Ventricular assist device implantation improves skeletal muscle function, oxidative capacity, and growth hormone/insulin-like growth factor-1 axis signaling in patients with advanced heart failure. J Cachexia Sarcopenia Muscle. 2014;5(4):297–305. Scholar
  91. 91.
    Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436–48. Scholar
  92. 92.
    Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015;16(9):740–7. Scholar
  93. 93.
    Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation. 2003;107(25):3133–40. Scholar
  94. 94.
    Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the randomized Etanercept worldwide evaluation (RENEWAL). Circulation. 2004;109(13):1594–602. Scholar
  95. 95.
    Everett Brendan M, Cornel Jan H, Lainscak M, Anker Stefan D, Abbate A, Thuren T, et al. Anti-inflammatory therapy with Canakinumab for the prevention of hospitalization for heart failure. Circulation. 2019;139(10):1289–99. Scholar
  96. 96.
    Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, et al. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 2009;54(10):919–27. Scholar
  97. 97.
    Iellamo F, Volterrani M, Caminiti G, Karam R, Massaro R, Fini M, et al. Testosterone therapy in women with chronic heart failure: a pilot double-blind, randomized, placebo-controlled study. J Am Coll Cardiol. 2010;56(16):1310–6. Scholar
  98. 98.
    Stout M, Tew GA, Doll H, Zwierska I, Woodroofe N, Channer KS, et al. Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. Am Heart J. 2012;164(6):893–901. Scholar
  99. 99.
    Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335–45. Scholar
  100. 100.
    Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W, et al. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation. 2004;110(24):3674–9. Scholar
  101. 101.
    Katakami N, Uchino J, Yokoyama T, Naito T, Kondo M, Yamada K, et al. Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer. 2018;124(3):606–16. Scholar
  102. 102.
    Ebner N, von Haehling S. Unlocking the wasting enigma: highlights from the 8th Cachexia conference. J Cachexia Sarcopenia Muscle. 2016;7(1):90–4. Scholar
  103. 103.
    Polkey MI, Praestgaard J, Berwick A, Franssen FME, Singh D, Steiner MC, et al. Activin type II receptor blockade for treatment of muscle depletion in chronic obstructive pulmonary disease. A randomized trial. Am J Respir Crit Care Med. 2019;199(3):313–20. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyMater Misericoridiae University HospitalDublinIreland
  2. 2.Heart Failure and Cardiac TransplantationMater Misericordiae University HospitalDublin 7Ireland

Personalised recommendations