Management of iron deficiency in chronic heart failure
- Authors: Uskach T.M.1,2
-
Affiliations:
- Chazov National Medical Research Center of Cardiology
- Russian Medical Academy of Continuous Professional Education
- Issue: Vol 94, No 4 (2022)
- Pages: 572-578
- Section: Reviews
- URL: https://journals.rcsi.science/0040-3660/article/view/108242
- DOI: https://doi.org/10.26442/00403660.2022.04.201451
- ID: 108242
Cite item
Full Text
Abstract
Iron deficiency is frequent in patients with chronic heart failure (CHF) with a prevalence of 50%, and its frequency varies depending on the study groups. The presence of iron deficiency limits erythropoiesis, leading to the development of anemia over time in patients with CHF, regardless of gender, race, and left ventricular ejection fraction (LVEF). Observational studies demonstrate a higher prevalence of iron deficiency in women and in patients with higher NYHA (New York Heart Association) functional class, decreased LVEF, increased brain natriuretic peptide (NT-proBNP), or increased high-sensitivity C-reactive protein. Iron deficiency and anemia in patients with CHF are independently associated with a decreased exercise capacity, hospitalizations for CHF, an increase in overall mortality and mortality from cardiovascular diseases. The clinical significance of iron deficiency requires the need to diagnose iron metabolism in all patients with CHF. Current guidelines for the diagnosis and treatment of CHF indicate the need to determine the level of ferritin and saturation of transferrin in all patients with a suspected diagnosis of heart failure. The use of oral iron therapy in patients with CHF demonstrates its low efficacy in correcting this condition according to the clinical trials. At the same time the use of intravenous iron therapy is safe and improves symptoms, exercise capacity and quality of life in patients with heart failure with reduced ejection fraction and iron deficiency, which has been shown both in international placebo-controlled trials and meta-analyses. The use of iron carboxymaltose should improve CHF symptoms, exercise capacity and quality of life in patients with CHF and LVEF<45%. Intravenous iron therapy has also been shown to reduce readmissions for CHF in patients with an LVEF<50% who have recently been hospitalized for worsening CHF.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Tatiana M. Uskach
Chazov National Medical Research Center of Cardiology; Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: tuskach@mail.ru
ORCID iD: 0000-0003-4318-0315
д-р мед. наук, вед. науч. сотр. отд. заболеваний миокарда и сердечной недостаточности, проф. каф. кардиологии
Russian Federation, Moscow; MoscowReferences
- Kurz K, Lanser L, Seifert M, et al. Anaemia, iron status, and gender predict the outcome in patients with chronic heart failure. ESC Heart Fail. 2020;7:1880-90. doi: 10.1002/ehf2.12755
- Pasricha SR, Flecknoe-Brown SC, Allen KJ, et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust. 2010;193(9):525-32. doi: 10.5694/j.1326-5377.2010.tb04038.x
- Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. The Journal of Nutrition. 2001;131(2S-2):568S-80S. doi: 10.1093/jn/131.2.568S
- Fairbanks V. Iron deficiency. In: Beutler E. Williams hematology. Eds V Fairbanks, E Beutler. 6th ed. New York: McGraw-Hill, 2001; p. 295-470.
- Clark SF. Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol. 2009;25:122-8.
- Zimmermann MB. Hurrell RF. Nutritional Iron Deficiency. Lancet. 2007;370:511-20. doi: 10.1016/S0140-6736(07)61235-5
- Anand IS, Gupta P. Anemia and iron deficiency in heart failure: current concepts and emerging therapies. Circulation. 2018;138:80-98. doi: 10.1161/CIRCULATIONAHA.118.030099
- von Haehling S, Gremmler U, Krumm M, et al. Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: the PrEP Registry. Clin Res Cardiol. 2017;106(6):436-43. doi: 10.1007/s00392-016-1073-y
- Jacob C, Altevers J, Barck I, et al. Retrospective analysis into differences in heart failure patients with and without iron deficiency or anaemia. ESC Heart Fail. 2019;6(4):840-55. doi: 10.1002/ehf2.12485
- Baker JF, Ghio AJ. Iron homoeostasis in rheumatic disease Rheumatology. 2009;48(11):1339-44. doi: 10.1093/rheumatology/kep221
- Gomollón F, Gisbert JP. Anemia and inflammatory bowel diseases. World J Gastroenterol. 2009;15(37):4659-65. doi: 10.3748/wjg.15.4659
- Weiss G. Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta. 2009;1790(7):682-93. doi: 10.1016/j.bbagen.2008.08.006
- Klip IT, Comin-Colet J, Voors AA. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J. 2013;165:575-82. doi: 10.1016/j.ahj.2013.01.017
- Paterek A, Mackiewicz U, Mączewski M. Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities. J Cell Physiol. 2019;234(12):21613-29. doi: 10.1002/jcp.28820
- Muñoz M, Villar I, García-Erce JA. An update on iron physiology. World J Gastroenterol. 2009;15(37):4617-26. doi: 10.3748/wjg.15.4617
- Handelman GJ. Levin NW. Iron and anemia in human biology: a review of mechanisms. Heart Fail Rev. 2008;13(4):393-404. doi: 10.1007/s10741-008-9086-x
- Westenbrink BD, Visser FW, Voors AA, et al. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J. 2007;28(2):166-71. doi: 10.1093/eurheartj/ehl419
- Kemna EH, Tjalsma H, Willems HL, et al. Hepcidin: from discovery to differential diagnosis. Haematologica. 2008;93(1):90-7. doi: 10.3324/haematol.11705
- Viatte L, Vaulont S. Hepcidin, the iron watcher. Biochimie. 2009;91(10):1223-8. doi: 10.1016/j.biochi.2009.06.012
- Camaschella C. Iron deficiency. Blood. 2019;133:30-9. doi: 10.1182/blood-2018-05-815944
- Anderson GJ, Vulpe GD. Mammalian iron transport. Cell Mol Life Sci. 2009;66(20):3241-61. doi: 10.1007/s00018-009-0051-1
- Cairo G, Bernuzzi F, Recalcati S. A precious metal: iron, an essential nutrient for all cells. Genes Nutr. 2006;1(1):25-39. doi: 10.1007/BF02829934
- Iorio A, Senni M, Barbati G, et al. Prevalence and prognostic impact of non-cardiac co-morbidities in heart failure outpatients with preserved and reduced ejection fraction: a community-based study. Eur J Heart Fail. 2018;20:1257-66. doi: 10.1002/ejhf.1202
- Hinton PS, Sinclair LM. Iron supplementation maintains ventilatory threshold and improves energetic efficiency in iron-deficient nonanemic athletes. Eur J Clin Nutr. 2007;61(1):30-9. doi: 10.1038/sj.ejcn.1602479
- Anker SD, Comin Colet J, Filippatos G, et al. FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436-48. doi: 10.1056/NEJMoa0908355
- Cleland JG, Zhang J, Pellicori P, et al. Prevalence and outcomes of anemia and hematinic deficiencies in patients with chronic heart failure. JAMA Cardiol. 2016;1:539-47. doi: 10.1001/jamacardio.2016.1161
- Jankowska EA, Rozentryt P, Witkowska A, et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010;31:1872-80. doi: 10.1093/eurheartj/ehq158
- Makubi A, Hage C, Lwakatare J, et al. Prevalence and prognostic implications of anaemia and iron deficiency in Tanzanian patients with heart failure. Heart. 2015;101:592-9. doi: 10.1136/heartjnl-2014-306890
- Yeo TJ, Yeo PS, Ching-Chiew Wong R, et al. Iron deficiency in a multi- ethnic Asian population with and without heart failure: prevalence, clinical correlates, functional significance and prognosis. Eur J Heart Fail. 2014;16:1125-32. doi: 10.1002/ejhf.161
- Martens P, Nijst P, Verbrugge FH, et al. 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. doi: 10.1080/00015385.2017.1351239
- Cohen-Solal A, Damy T, Terbah M, et al. High prevalence of iron deficiency in patients with acute decompensated heart failure. Eur J Heart Fail. 2014;16(9):984-91. doi: 10.1002/ejhf.139
- Allain F, Loizeau V, Chaufourier L, et al. Usefulness of a personalized algorithm-based discharge checklist in patients hospitalized for acute heart failure. ESC Heart Fail. 2020;7(3):1217-23. doi: 10.1002/ehf2.12604
- World Health Organization (WHO). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization, 2011. Available at: http://www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed: 15.02.2022.
- Lynch S. Indicators of the iron status of populations: red blood cell parameters. Assessing the Iron Status of Populations: Including Literature Reviews: Report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level. Geneva Switzerland; 2004; Apr:6–8. Geneva (Switzerland): WHO, 2007.
- Fletcher A, Forbes A, Svenson N, Thomas DW. Guideline for the laboratory diagnosis of iron deficiency in adults (excluding pregnancy) and children. Br J Haematol. 2022;196(3):523-9. doi: 10.1111/bjh.17900
- Beverborg NG, Klip IT, Meijers WC, et al. Definition of iron deficiency based on the gold standard of bone marrow iron staining in heart failure patients. Circ Heart Fail. 2018;11(2):e004519. doi: 10.1161/CIRCHEARTFAILURE.117.004519
- Loncar G, Obradovic D, Thiele H, et al. Iron deficiency in heart failure. ESC Heart Fail. 2021;8(4):2368-79. doi: 10.1002/ehf2.13265
- Walters GO, Miller FM, Worwood M. Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol. 1973;26:770-2. doi: 10.1136/jcp.26.10.770
- Guyatt GH, Oxman AD, Ali M, et al. Laboratory diagnosis of iron-deficiency anemia. J Gen Intern Med. 1992;7:145-53. doi: 10.1007/BF02598003
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure Eur Heart J. 2021;42(36):3599-726. doi: 10.1093/eurheartj/ehab368
- Beck-da-Silva L, Piardi D, Soderet S, et al. IRON-HF study: a randomized trial to assess the effects of iron in heart failure patients with anemia. Int J Cardiol. 2013;168:3439-42. doi: 10.1016/j.ijcard.2013.04.181
- 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(19):1958-66. doi: 10.1001/jama.2017.5427
- Niehaus ED, Malhotra R, Cocca-Spofford D, et al. Repletion of iron stores with the use of oral iron supplementation in patients with systolic heart failure. J Card Fail. 2015;21(8):694-7. doi: 10.1016/j.cardfail.2015.05.006
- Lewis GD, Semigran MJ, Givertz MM, et al. Oral iron therapy for heart failure with reduced ejection fraction:design and rationale for oral iron repletion effects on oxygen uptake in heart failure. Circ Heart Fail. 2016;9(5):e000345. doi: 10.1161/CIRCHEARTFAILURE.115.000345
- von Haehling S, Ebner N, Evertz R, et al. Iron deficiency in heart failure: an overview. JACC Heart Fail. 2019;7:36-46. doi: 10.1016/j.jchf.2018.07.015
- Crichton RR, Danielson BG, Geisser P, et al. Iron therapy with special empasis on intravenous administration. 3nd ed. Bremen: UNI-Med, 2006; p. 96.
- Comin-Colet J, Lainscak M, Dickstein K, et al. The effect of intravenous ferric carboxymaltose on health-related quality of life in patients with chronic heart failure and iron deficiency: a subanalysis of the FAIR-HF study. Eur Heart J. 2013;34:30-8. doi: 10.1093/eurheartj/ehr504
- Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. CONFIRM- HF Investigators. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015;36:657-68. doi: 10.1093/eurheartj/ehu385
- van Veldhuisen DJ, Ponikowski P, van der Meer P, et al; EFFECT-HF Investigators. Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation. 2017;136:1374-83. doi: 10.1161/CIRCULATIONAHA.117.027497
- 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. doi: 10.1002/ejhf.473
- Okonko DO, Grzeslo A, Witkowski T. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol. 2008;51(2):103-12. doi: 10.1016/j.jacc.2007.09.036
- Filippatos G, Farmakis D, Colet JC, et al. Intravenous ferric carboxymaltose in iron-deficient chronic heart failure patients with and without anaemia: a subanalysis of the FAIR-HF trial. Eur J Heart Fail. 2013;15:1267-76. doi: 10.1093/eurjhf/hft099
- Ponikowski P, Kirwan BA, Anker SD, et al. AFFIRM-AHF Investigators. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020;396:1895-904. doi: 10.1016/s0140-6736(20)32339-4
- 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. doi: 10.1002/ejhf.823
- Khan MS, Usman MS, von Haehling S, et al. Ferric carboxymaltose for the treatment of iron-deficient heart failure patients: a systematic review and meta-analysis. ESC Heart Failure. 2020;7(6):3392-400. doi: 10.1002/ehf2.13146
![](/img/style/loading.gif)