ANEMIA AND HEART FAILURE
Abstract
The presence of anemia in patients with heart failure is a significant independent adverse prognostic factor. The etiology of anemia is multifactorial and the nature of heart failure itself, advanced age, and frequent comorbidities contribute to its development. Notably, absolute or functional iron deficiency, even in the absence of anemia, significantly diminishes the quality of life, increases hospitalization frequency, and raises mortality rates in patients with heart failure. The intricate etiology and pathophysiology of anemia present a challenge for the accurate interpretation of laboratory parameters of iron metabolism and necessitate a tailored therapeutic approach.
References
Safiri S, Kolahi AA, Noori M, Nejadghaderi SA, Karamzad N, Bragazzi NL, et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. J Hematol Oncol. 2021 Nov 4;14(1):185. doi: 10.1186/s13045-021-01202-2.
Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023 Jan 18;118(17):3272-87. doi: 10.1093/cvr/cvac013.
World Health Organization (WHO). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity; WHO/NMH/NHD/MNM/11.1. [Internet]. [Pristupljeno: May 30, 2024]. Dostupno: https://apps.who.int/iris/bitstream/handle/10665/85839/WHO_NMH_ NHD_MNM_11.1_eng.pdf.
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. 2021 Sep 21;42(36):3599-726. doi: 10.1093/eurheartj/ehab368.
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2024 Jan;26(1):5-17. doi: 10.1002/ejhf.3024.
Chopra VK, Anker SD. Anaemia, iron deficiency and heart failure in 2020: facts and numbers. ESC Heart Fail. 2020 Oct;7(5):2007-11. doi: 10.1002/ehf2.12797.
Anand I, McMurray JJ, Whitmore J, Warren M, Pham A, McCamish MA, et al. Anemia and its relationship to clinical outcome in heart failure. Circulation. 2004 Jul 13;110(2):149-54. doi: 10.1161/01.CIR.0000134279.79571.73.
Al-Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001 Oct;38(4):955-62. doi: 10.1016/s0735-1097(01)01470-x.
Komajda M, Anker SD, Charlesworth A, Okonko D, Metra M, Di Lenarda A, et al. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J. 2006 Jun;27(12):1440-6. doi: 10.1093/eurheartj/ehl012.
Cohen-Solal A, Philip JL, Picard F, Delarche N, Taldir G, Gzara H, et al; CARENFER Study Group. Iron deficiency in heart failure patients: the French CARENFER prospective study. ESC Heart Fail. 2022 Apr;9(2):874-84. doi: 10.1002/ehf2.13850.
Naito A, Obokata M, Kagami K, Harada T, Sorimachi H, Yuasa N, et al. Contributions of anemia to exercise intolerance in heart failure with preserved ejection fraction-An exercise stress echocardiographic study. Int J Cardiol Heart Vasc. 2023 Aug 20;48:101255. doi: 10.1016/j.ijcha.2023.101255.
Köseoğlu FD, Özlek B. Anemia and Iron Deficiency Predict All-Cause Mortality in Patients with Heart Failure and Preserved Ejection Fraction: 6-Year Follow-Up Study. Diagnostics (Basel). 2024 Jan 18;14(2):209. doi: 10.3390/diagnostics14020209.
Siddiqui SW, Ashok T, Patni N, Fatima M, Lamis A, Anne KK. Anemia and heart failure: a narrative review. Cureus. 2022 Jul 23;14(7):e27167. doi: 10.7759/cureus.27167.
Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure: Executive Summary: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):1757-80. doi: 10.1016/j.jacc.2021.12.011.
Cvetković Z. Suvajdžić-Vuković N. Epidemiologija i etiologija »nemaligne«anemije kod starih. In: Marisavljević D, Milošević DP, Nikolić-Žugić J, Čokić V, Prostan M, editors. Poremećaji i bolesti krvi i krvotvornih organa kod starih osoba. Beograd: Zavod za udžbenike; 2017. p. 320-31.
Masini G, Graham FJ, Pellicori P, Cleland JGF, Cuthbert JJ, Kazmi S, et al. Criteria for iron deficiency in patients with heart failure. J Am Coll Cardiol. 2022 Feb 1;79(4):341-51. doi: 10.1016/j.jacc.2021.11.039.
Kaiafa G, Kanellos I, Savopoulos C, Kakaletsis N, Giannakoulas G, Hatzitolios AI. Is anemia a new cardiovascular risk factor? Int J Cardiol. 2015;186:117-24. doi: 10.1016/j.ijcard.2015.03.159.
Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021 Jan 16;397(10270):233-48. doi: 10.1016/S0140-6736(20)32594-0.
Snook J, Bhala N, Beales ILP, Cannings D, Kightley C, Logan RP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut. 2021 Nov;70(11):2030-2051. doi: 10.1136/gutjnl-2021-325210.
Anand IS, Gupta P. Anemia and iron deficiency in heart failure: current concepts and emerging therapies. Circulation. 2018 Jul 3;138(1):80-98. doi: 10.1161/CIRCULATIONAHA.118.030099.
Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ Res. 2015 Mar 27;116(7):1254-68. doi: 10.1161/CIRCRESAHA.116.302317.
Röhrig G. Anemia in the frail, elderly patient. Clin Interv Aging. 2016 Mar 17;11:319-26. doi: 10.2147/CIA.S90727.
Cappellini MD, Comin-Colet J, de Francisco A, Dignass A, Doehner W, Lam CS, et al.; IRON CORE Group. Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management. 017 Oct;92(10):1068-78. doi: 10.1002/ajh.24820.
Rosenblum SL. Inflammation, dysregulated iron metabolism, and cardiovascular disease. Front Aging. 2023 Feb 3;4:1124178. doi: 10.3389/fragi.2023.1124178.
Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, et al; American Heart Association Council on the Kidney in Cardiovascular Disease and Council on Clinical Cardiology. Cardiorenal Syndrome: Classification, pathophysiology, diagnosis, and treatment strategies: A scientific statement from the American Heart Association. Circulation. 019 Apr 16;139(16):e840-78. doi: 10.1161/CIR.0000000000000664.
Xanthopoulos A, Papamichail A, Briasoulis A, Loritis K, Bourazana A, Magouliotis DE, et al. Heart failure in patients with chronic kidney disease. J Clin Med. 2023 Sep 21;12(18):6105. doi: 10.3390/jcm12186105.
Hullon D, Taherifard E, Al-Saraireh TH. The effect of the four pharmacological pillars of heart failure on haemoglobin level. Ann Med Surg (Lond). 2024 Jan 29;86(3):1575-1583. doi: 10.1097/MS9.0000000000001773.
Chatterjee B, Nydegger UE, Mohacsi P. Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT(1) antagonists. Eur J Heart Fail. 2000 Dec;2(4):393-8. doi: 10.1016/s1388-9842(00)00110-0.
Cvetković Z, Suvajdžić-Vuković N. Kasne komplikacije hematoloških bolesti i njihovog lečenja. In: Marisavljević D, Mihaljević B, Elezović I, Popović S, Suvajdžić-Vuković N, Vujić D, Janić D, Milenković P, Mostarica M, Bogdanović G, editors. Klinička hematologija. Beograd: Zavod za udžbenike; 2012. p. 1182-94.
Cvetković Z, Marković O, Mitrović M. Cardiotoxicity of antineoplastic therapy: Underlying mechanisms, clinical manifestations, and basic principles of cardio-oncology. Serbian J Med Chamb. 2023; 4(3):256-71. doi: 10.5937/smclk4-45065.
Aapro M, Beguin Y, Bokemeyer C, Dicato M, Gascón P, Glaspy J, et al.; ESMO Guidelines Committee. Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv96-110. doi: 10.1093/annonc/mdx758.
Savarese G, von Haehling S, Butler J, Cleland JGF, Ponikowski P, Anker SD. Iron deficiency and cardiovascular disease. Eur Heart J. 2023 May 7;44(18):1607. doi: 10.1093/eurheartj/ehad043.
Tziastoudi M, Pissas G, Golfinopoulos S, Filippidis G, Dousdampanis P, Eleftheriadis T, et al. Sodium-glucose transporter 2 (SGLT2) inhibitors and iron deficiency in heart failure and chronic kidney disease: a literature review. Life (Basel). 2023 Dec 13;13(12):2338. doi: 10.3390/life13122338.
Androne AS, Katz SD, Lund L, LaManca J, Hudaihed A, Hryniewicz K, et al. Hemodilution is common in patients with advanced heart failure. Circulation. 2003 Jan 21;107(2):226-9. doi: 10.1161/01.cir.0000052623.16194.80.
Tang YD, Katz SD. Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation. 2006 May 23;113(20):2454-61. doi: 10.1161/CIRCULATIONAHA.105.583666.
Mozaffarian D, Nye R, Levy WC. Anemia predicts mortality in severe heart failure: the prospective randomized amlodipine survival evaluation (PRAISE). J Am Coll Cardiol. 2003 Jun 4;41(11):1933-9. doi: 10.1016/s0735-1097(03)00425-x.
Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, et al; Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002 Oct 22;106(17):2194-9. doi: 10.1161/01.cir.0000035653.72855.bf.
Tim Goodnough L, Comin-Colet J, Leal-Noval S, Ozawa S, Takere J, Henry D, et al. Management of anemia in patients with congestive heart failure. Am J Hematol. 2017 Jan;92(1):88-93. doi: 10.1002/ajh.24595.
Babitt JL, Eisenga MF, Haase VH, Kshirsagar AV, Levin A, Locatelli F, et al.; Conference Participants. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2021 Jun;99(6):1280-1295. doi: 10.1016/j.kint.2021.03.020.
Anand I, Gupta P. How I treat anemia in heart failure. Blood. 2020 Aug 13;136(7):790-800. doi: 10.1182/blood.2019004004.
DeLoughery TG. Safety of Oral and Intravenous Iron. Acta Haematol. 2019;142(1):8-12. doi: 10.1159/000496966.
Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007 Oct 16;50(16):1561-9. doi: 10.1016/j.jacc.2007.07.016.
Beck-da-Silva L, Piardi D, Soder S, Rohde LE, Pereira-Barretto AC, de Albuquerque D, et al. IRON-HF study: a randomized trial to assess the effects of iron in heart failure patients with anemia. Int J Cardiol. 2013 Oct 9;168(4):3439-42. doi: 10.1016/j.ijcard.2013.04.181.
Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM, et al.; NHLBI Heart Failure Clinical Research Network. 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 May 16;317(19):1958-66. doi: 10.1001/jama.2017.5427.
Karavidas A, Troganis E, Lazaros G, Balta D, Karavidas IN, Polyzogopoulou E, et al. Oral sucrosomial iron improves exercise capacity and quality of life in heart failure with reduced ejection fraction and iron deficiency: a non-randomized, open-label, proof-of-concept study. Eur J Heart Fail. 2021 Apr;23(4):593-7. doi: 10.1002/ejhf.2092.
Gómez-Ramírez S, Brilli E, Tarantino G, Girelli D, Muñoz M. Sucrosomial® Iron: An updated review of its clinical efficacy for the treatment of iron deficiency. Pharmaceuticals (Basel). 2023 Jun 6;16(6):847. doi: 10.3390/ph16060847.
Fabiano A, Brilli E, Fogli S, Beconcini D, Carpi S, Tarantino G, et al. Sucrosomial® iron absorption studied by in vitro and ex-vivo models. Eur J Pharm Sci. 2018 Jan 1;111:425-31. doi: 10.1016/j.ejps.2017.10.021.
Girelli D, Ugolini S, Busti F, Marchi G, Castagna A. Modern iron replacement therapy: clinical and pathophysiological insights. Int J Hematol. 2018 Jan;107(1):16-30. doi: 10.1007/s12185-017-2373-3.
Barakat MF, Amin-Youseff G, Okonko DO. Oral sucrosomial iron in heart failure with a reduced ejection fraction. Eur J Heart Fail 2021 Apr;23(4):598-600. doi: 10.1002/ejhf.2176.
Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al.; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009 Dec 17;361(25):2436-48. doi: 10.1056/NEJMoa0908355.
Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, 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. 015 Mar 14;36(11):657-68. doi: 10.1093/eurheartj/ehu385.
Kalra PR, Cleland JGF, Petrie MC, Thomson EA, Kalra PA, Squire IB, et al.; IRONMAN Study Group. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022 Dec 17;400(10369):2199-209. doi: 10.1016/S0140-6736(22)02083-9.
Filippatos G, Ponikowski P, Farmakis D, Anker SD, Butler J, Fabien V, et al.; AFFIRM-AHF Investigators. Association between hemoglobin levels and efficacy of intravenous ferric subgroup analysis. Circulation. 2023 May 30;147(22):1640-53. doi: 10.1161/CIRCULATIONAHA.122.060757.
Jacob C, Altevers J, Barck I, Hardt T, Braun S, Greiner W. Retrospective analysis into differences in heart failure patients with and without iron deficiency or anaemia. ESC Heart Fail. 2019 Aug;6(4):840-55. doi: 10.1002/ehf2.12485.
Jankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, 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 Jul;18(7):786-95. doi: 10.1002/ejhf.473.
Anker SD, Kirwan BA, van Veldhuisen DJ, Filippatos G, Comin-Colet J, Ruschitzka F, 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 Jan;20(1):125-33. doi: 10.1002/ejhf.823.
Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, et al.; RED-HF Committees; RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013 Mar 28;368(13):1210-9. doi: 10.1056/NEJMoa1214865.
Mistry N, Hare GMT, Shehata N, Belley-Cote E, Papa F, Kramer RS, et al. Transfusion Thresholds for acute coronary syndromes-insights from the TRICS-III randomized controlled trial, systematic review, and meta-analysis. J Am Heart Assoc. 2023 Jan 3;12(1):e028497. doi: 10.1161/JAHA.122.028497.
Ding YY, Kader B, Christiansen CL, Berlowitz DR. Hemoglobin level and hospital mortality among icu patients with cardiac disease who received transfusions. J Am Coll Cardiol. 2015 Dec 8;66(22):2510-8. doi: 10.1016/j.jacc.2015.09.057.