{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:14:58Z","timestamp":1783617298355,"version":"3.55.0"},"reference-count":36,"publisher":"Radcliffe Medical Media Ltd","issue":"3","license":[{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/legalcode"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Card Fail Rev"],"abstract":"<jats:p>There is an increasing awareness of the prevalence of iron deficiency in patients with heart failure (HF), and its contributory role in the morbidity and mortality of HF. Iron is a trace element necessary for cells due to its capacity to transport oxygen and electrons. The prevalence of iron deficiency increases with the severity of HF. For a long time the influence of iron deficiency was underestimated, especially in terms of worsening of cardiovascular diseases and developing anaemia. In recent years, studies with intravenous iron agents in patients with iron deficiency and HF showed new insights into the improvement of iron therapy. Additionally, experimental studies supporting the understanding of iron metabolism and the resulting pathophysiological pathways of iron have been carried out. The aim of this mini review is to highlight why iron deficiency is recognised as an important comorbidity in HF.<\/jats:p>","DOI":"10.15420\/cfr.2019.9.2","type":"journal-article","created":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T13:29:31Z","timestamp":1569677371000},"page":"173-175","source":"Crossref","is-referenced-by-count":15,"title":["Why is Iron Deficiency Recognised as an Important Comorbidity in Heart Failure?"],"prefix":"10.15420","volume":"5","author":[{"given":"Nicole","family":"Ebner","sequence":"first","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Centre Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"von Haehling","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Centre Goettingen, Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"1. Jelani QU, Katz SD. Treatment of anemia in heart failure: potential risks and benefits of intravenous iron therapy in cardiovascular disease. Cardiol Rev 2010;18:240-50. https:\/\/doi.org\/10.1097\/CRD.0b013e3181e71150; PMID: 20699672.","DOI":"10.1097\/CRD.0b013e3181e71150"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"2. Ebner N, von Haehling S. Iron deficiency in heart failure: a practical guide. Nutrients 2013;5:3730-9. https:\/\/doi. org\/10.3390\/nu5093730; PMID: 24064572.","DOI":"10.3390\/nu5093730"},{"key":"ref2","unstructured":"3. Toblli JE, Silverberg DS, Di Gennaro F, et al. Iron metabolism. In: Cardio-Renal Anaemia Syndrome CRAS. Basics and Clinical Aspects. 1st ed. Buenos Aires, Argentina: Publicaciones Latinoamericans, 2008;55-68."},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"4. Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol 2011;58:1241-51. https:\/\/doi.org\/10.1016\/j.jacc.2011.04.040; PMID: 21903058.","DOI":"10.1016\/j.jacc.2011.04.040"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"5. Klip IT, Comin-Colet J, Voors AA, et al. Iron deficiency in chronic heart failure: An international pooled analysis. Am Heart J 2013;165:575-82.e3. https:\/\/doi.org\/10.1016\/j. ahj.2013.01.017; PMID: 23537975.","DOI":"10.1016\/j.ahj.2013.01.017"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"6. Jankowska EA, von Haehling S, Anker SD, et al. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J 2013; 34: 816-29. https:\/\/doi. org\/10.1093\/eurheartj\/ehs224; PMID: 23100285.","DOI":"10.1093\/eurheartj\/ehs224"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"7. Gonz\u00e1lez-Costello J, Com\u00edn-Colet J, Lup\u00f3n J, et al. Importance of iron deficiency in patients with chronic heart failure as a predictor of mortality and hospitalizations: insights from an observational cohort study. BMC Cardiovasc Disord 2018;18:206. https:\/\/doi.org\/10.1186\/s12872-018-0942-x; PMID: 30382817.","DOI":"10.1186\/s12872-018-0942-x"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"8. McDonagh T, Damy T, Doehner W, et al. Screening, diagnosis and treatment of iron deficiency in chronic heart failure: putting the 2016 European Society of Cardiology heart failure guidelines into clinical practice. Eur J Heart Fail 2018;20:1664-72. https:\/\/doi.org\/10.1002\/ejhf.1305;","DOI":"10.1002\/ejhf.1305"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"9. Jankowska EA, Tkaczyszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail 2016;18:786-95. https:\/\/doi. org\/10.1002\/ejhf.473; PMID: 26821594.","DOI":"10.1002\/ejhf.473"},{"key":"ref9","unstructured":"10. Zhang S, Zhang F, Du M, et al. Efficacy and safety of iron supplementation in patients with heart failure and iron deficiency: a meta-analysis. Br J Nutr 2019;20:1-23. https:\/\/doi. org\/10.1017\/S000711451900014X; PMID: 30782220."},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"11. Qian C, Wei B, Ding J, et al. The Efficacy and safety of iron supplementation in patients with heart failure and iron deficiency: a systematic review and meta-analysis. Can J Cardiol 2016;32:151-9. https:\/\/doi.org\/10.1016\/j.cjca.2015.06.009; PMID: 26454467.","DOI":"10.1016\/j.cjca.2015.06.009"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"12. Klip IT, Comin-Colet J, Voors AA, et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 2013;165:575-82.e3. https:\/\/doi.org\/10.1016\/j.ahj.2013.01.017; PMID: 23537975.","DOI":"10.1016\/j.ahj.2013.01.017"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Iron deficiency in heart failure: an overview","DOI":"10.1016\/j.jchf.2018.07.015"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"14. Anker SD, Kirwan BA, van Veldhuisen DJ, et al. Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. Eur J Heart Fail 2018;20:125-33. https:\/\/doi. org\/10.1002\/ejhf.823; PMID: 28436136.","DOI":"10.1002\/ejhf.823"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"15. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation 2003;107:223-5. https:\/\/doi. org\/10.1161\/01.CIR.0000052622.51963.FC; PMID: 12538418.","DOI":"10.1161\/01.CIR.0000052622.51963.FC"},{"key":"ref15","unstructured":"16. von Haehling S, Anker SD. Iron deficiency in health and disease. In: Anker SD, von Haehling S (eds). Anaemia in chronic heart failure. 2nd ed. Bremen, Germany: UNI-MED Verlag AG, 2009;34-7."},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"17. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436-48. https:\/\/doi. org\/10.1056\/NEJMoa0908355; PMID: 19920054.","DOI":"10.1056\/NEJMoa0908355"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"18. Cohen LA, Gutierrez L, Weiss A, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 2010;116:1574-84. https:\/\/doi.org\/10.1182\/ blood-2009-11-253815; PMID: 20472835.","DOI":"10.1182\/blood-2009-11-253815"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"19. Anderson GJ, Vulpe CD. Mammalian iron transport. Cell Mol Life Sci 2009;66:3241-61. https:\/\/doi.org\/10.1007\/s00018-009- 0051-1; PMID: 19484405.","DOI":"10.1007\/s00018-009-0051-1"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"20. Ye H, Rouault TA. Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry 2010;49:4945-56. https:\/\/doi.org\/10.1021\/bi1004798; PMID: 20481466.","DOI":"10.1021\/bi1004798"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"21. Punnonen K, Irjala K, Rajam\u00e4ki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997;89:1052-57. PMID: 9028338.","DOI":"10.1182\/blood.V89.3.1052"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"22. Leszek P, Sochanowicz B, Szperl M, et al. Myocardial iron homeostasis in advanced chronic heart failure patients. Int J Cardiol 2012;159:47-52. https:\/\/doi.org\/10.1016\/j.ijcard.2011. 08.006; PMID: 21899903.","DOI":"10.1016\/j.ijcard.2011.08.006"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"23. Kasner M, Aleksandrov AS, Westermann D, et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol 2013;168:4652-7. https:\/\/doi.org\/10.1016\/j.ijcard.2013.07.185; PMID: 23968714.","DOI":"10.1016\/j.ijcard.2013.07.185"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"24. Willis WT, Gohil K, Brooks GA, Dallman PR. Iron deficiency: improved exercise performance within 15 h of iron treatment in rats. J Nutr 1990;120:909-16. https:\/\/doi.org\/10.1093\/ jn\/120.8.909; PMID: 2199635.","DOI":"10.1093\/jn\/120.8.909"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"25. Tobin BW, Beard JL. Interactions of iron deficiency and exercise training relative to tissue norepinephrine turnover, triiodothyronine production and metabolic rate in rats. J Nutr 1990;120:900-8. https:\/\/doi.org\/10.1093\/jn\/120.8.900","DOI":"10.1093\/jn\/120.8.900"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"26. Blayney L, Bailey-Wood R, Jacobs, A et al. The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria. Circ Res 1976;39:744-748. https:\/\/doi.org\/10.1161\/01.RES.39.5.744; PMID: 184977.","DOI":"10.1161\/01.RES.39.5.744"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"27. Ebner N, Jankowska EA, Ponikowski P. The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure. Int J Cardiol 2016;205:6-12. https:\/\/doi.org\/10.1016\/j. ijcard.2015.11.178; PMID: 26705670.","DOI":"10.1016\/j.ijcard.2015.11.178"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"28. Bekfani T, Pellicori P, Morris D, et al. Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life. Clin Res Cardiol 2019;108:203-11. https:\/\/doi. org\/10.1007\/s00392-018-1344-x; PMID: 30051186.","DOI":"10.1007\/s00392-018-1344-x"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"29. Dziegala M, Josiak K, Kasztura M, et al. Iron deficiency as energetic insult to skeletal muscle in chronic diseases. J Cachexia Sarcopenia Muscle 2018;9:802-815. https:\/\/doi. org\/10.1002\/jcsm.12314; PMID: 30178922.","DOI":"10.1002\/jcsm.12314"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"30. Altman NL, Patel A. Intravenous iron therapy in heart failure. Heart Fail Clin 2018;14:537-43. https:\/\/doi.org\/10.1016\/j. hfc.2018.06.003; PMID: 30266362.","DOI":"10.1016\/j.hfc.2018.06.003"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"31. Lewis GD, Malhotra R, Hernandez AF, 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 trial. JAMA 2017;317:1958-66. https:\/\/doi.org\/10.1001\/jama.2017.5427; PMID: 28510680.","DOI":"10.1001\/jama.2017.5427"},{"key":"ref31","unstructured":"32. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Rev Esp Cardiol (Engl Ed) 2016;69:1167. https:\/\/doi. org\/10.1016\/j.rec.2016.11.005; PMID: 27894487."},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"33. Mu\u00f1oz M, Olsen PS, Petersen TS, et al. Pharmacokinetics of ferric bepectate - a new intravenous iron drug for treating iron deficiency. Basic Clin Pharmacol Toxicol 2019. https:\/\/doi. org\/10.1111\/bcpt.13219; PMID: 30839153; epub ahead of press.","DOI":"10.1111\/bcpt.13219"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"34. Charles-Edwards G, Amaral N, et al. Effect of iron isomaltoside on skeletal muscle energetics in patients with chronic heart failure and iron deficiency: the FERRIC-HF II randomized mechanistic trial. Circulation 2019;139:2386-98. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.118.038516; PMID: 30776909.","DOI":"10.1161\/CIRCULATIONAHA.118.038516"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"35. Moliner P, Enjuanes C, Tajes M, et al. Association between norepinephrine levels and abnormal iron status in patients with chronic heart failure: is iron deficiency more than a comorbidity? J Am Heart Assoc 2019;8:e010887. https:\/\/doi. org\/10.1161\/JAHA.118.010887; PMID: 30760082.","DOI":"10.1161\/JAHA.118.010887"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"36. Pollock RF, Muduma G. A systematic literature review and indirect comparison of iron isomaltoside and ferric carboxymaltose in iron deficiency anemia after failure or intolerance of oral iron treatment. 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