Heart Failure disease

In the aging society, heart failure (HF) is a problem of epidemic proportions, which projected to rise in the next decades imposing tremendous societal and economic costs. [5]

Iron deficiency is widely prevalent finding in patients with heart failure, observed on average in 50% of outpatients and up to 80% of acute patient. Iron metabolism disorders are widespread health problems on a global scale and range from iron deficiency to iron-overload. [13]

Heart failure

Heart failure (HF) is a complex syndrome in which the heart fails to circulate the required amount of blood and nutrients to meet the body’s demands. [2]

Iron Deficiency in those with chronic heart failure

Iron deficiency (ID) and anemia are among the most frequently observed commodities in HF, and both are independently associated with worse clinical status and outcomes. [3-4]  

Iron depletion frequently results from inadequate dietary intake or chronic blood loss. However, iron deficiency, which is the focus in this section, is inability to utilize the circulating iron or failure to meet excessive iron demands [7].

Incidence and prevalence

In the developed world, prevalence of iron deficiency in population varies from 10 to 16% depending on the sex and age [8]. Prevalence of iron deficiency anemia vary from 2.6 to 5% [6].

However, clinically, iron deficiency is present in up to 66% of HF patients and leads to reduced exercise tolerance, progressive HF, and increased mortality [8-10, 20].

Iron deficiency defined as depleted iron stores and unmet cellular iron demand was present in 37% of patients with chronic HF and up to 66% of patients with acute HF [8-10, 20].

ID is substantially more prevalent that anemia in HF, with a prevalence of reaching up to 59% even in non anemic ambulatory HF patients [14-18]

Prevalence of ID among non-anemic patients is even higher at 57% in men and 79% in women [19].

Symptoms of Iron Deficiency in Heart Failure

  • Lack of appetite
  • Hypo nutrition
  • GI tract congestion
  • Some medications

Treatments

Oral Iron supplements, such as ferrous fumarate, ferrous gluconate, and ferrous sulphate, are easily administrable and cheap option, but may lead to drug intolerance (mainly gastrointestinal discomfort), impaired diversity of microbiota, and counteractive action of hepcidin may prevent effective absorption of additional iron [11-12].

  1. Alnuwaysir RIS, Hoes MF, van Veldhuisen DJ, van der Meer P, Grote Beverborg N. Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology. J Clin Med. 2021 Dec 27;11(1):125. doi: 10.3390/jcm11010125. PMID: 35011874; PMCID: PMC8745653. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745653/
  2. Inamdar AA, Inamdar AC. Heart Failure: Diagnosis, Management and Utilization. J Clin Med. 2016 Jun 29;5(7):62. doi: 10.3390/jcm5070062. PMID: 27367736; PMCID: PMC4961993. - https://pubmed.ncbi.nlm.nih.gov/27367736/
  3. 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. PMID: 29967232. - https://pubmed.ncbi.nlm.nih.gov/29967232/
  4. Grote Beverborg N, van Veldhuisen DJ, van der Meer P. Anemia in Heart Failure: Still Relevant? JACC Heart Fail. 2018 Mar;6(3):201-208. doi: 10.1016/j.jchf.2017.08.023. Epub 2017 Nov 8. PMID: 29128254. - https://pubmed.ncbi.nlm.nih.gov/29128254/
  5. Theidel U, Väätäinen S, Martikainen J, Soini E, Hardt T, Doehner W. Budget impact of intravenous iron therapy with ferric carboxymaltose in patients with chronic heart failure and iron deficiency in Germany. ESC Heart Fail. 2017 Aug;4(3):274-281. doi: 10.1002/ehf2.12179. Epub 2017 Jul 3. PMID: 28772041; PMCID: PMC5542731. https://pubmed.ncbi.nlm.nih.gov/28772041/
  6. Gupta PM, Hamner HC, Suchdev PS, Flores-Ayala R, Mei Z. Iron status of toddlers, nonpregnant females, and pregnant females in the United States. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1640S-1646S. doi: 10.3945/ajcn.117.155978. Epub 2017 Oct 25. PMID: 29070559; PMCID: PMC5701724. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701724/#:~:text=In%20summary%2C%20according%20to%20the,%2C%20and%2016.3%25%2C%20respectively.
  7. Zhang H, Zhabyeyev P, Wang S, Oudit GY. Role of iron metabolism in heart failure: From iron deficiency to iron overload. Biochim Biophys Acta Mol Basis Dis. 2019 Jul 1;1865(7):1925-1937. doi: 10.1016/j.bbadis.2018.08.030. Epub 2018 Aug 26. PMID: 31109456. - https://pubmed.ncbi.nlm.nih.gov/31109456/
  8. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010 Aug;31(15):1872-80. doi: 10.1093/eurheartj/ehq158. Epub 2010 Jun 21. Erratum in: Eur Heart J. 2011 May;32(9):1054. PMID: 20570952. - https://pubmed.ncbi.nlm.nih.gov/20570952/
  9. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell. 2010 Jul 9;142(1):24-38. doi: 10.1016/j.cell.2010.06.028. PMID: 20603012. - https://pubmed.ncbi.nlm.nih.gov/20603012/
  10. Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM, Tang WHW, LaRue SJ, Redfield MM, Semigran MJ, Givertz MM, Van Buren P, Whellan D, Anstrom KJ, Shah MR, Desvigne-Nickens P, Butler J, Braunwald E; 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):1958-1966. doi: 10.1001/jama.2017.5427. Erratum in: JAMA. 2017 Jun 20;317(23):2453. doi: 10.1001/jama.2017.7019. PMID: 28510680; PMCID: PMC5703044. - https://pubmed.ncbi.nlm.nih.gov/28510680/
  11. Kortman GAM, Reijnders D, Swinkels DW. Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD. Hemodial Int. 2017 Jun;21 Suppl 1:S28-S36. doi: 10.1111/hdi.12553. Epub 2017 Mar 22. PMID: 28328083. - https://pubmed.ncbi.nlm.nih.gov/28328083/
  12. Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22;126(17):1981-9. doi: 10.1182/blood-2015-05-642223. Epub 2015 Aug 19. PMID: 26289639. - https://pubmed.ncbi.nlm.nih.gov/26289639/
  13. Del Pinto R, Ferri C. Iron deficiency in heart failure: diagnosis and clinical implications. Eur Heart J Suppl. 2022 Nov 12;24(Suppl I):I96-I99. doi: 10.1093/eurheartjsupp/suac080. PMID: 36380788; PMCID: PMC9653155. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9653155/
  14. Cleland JG, Zhang J, Pellicori P, Dicken B, Dierckx R, Shoaib A, Wong K, Rigby A, Goode K, Clark AL. Prevalence and Outcomes of Anemia and Hematinic Deficiencies in Patients With Chronic Heart Failure. JAMA Cardiol. 2016 Aug 1;1(5):539-47. doi: 10.1001/jamacardio.2016.1161. PMID: 27439011. - https://pubmed.ncbi.nlm.nih.gov/27439011/
  15. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010 Aug;31(15):1872-80. doi: 10.1093/eurheartj/ehq158. Epub 2010 Jun 21. Erratum in: Eur Heart J. 2011 May;32(9):1054. PMID: 20570952. - https://pubmed.ncbi.nlm.nih.gov/20570952/
  16. Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J. 2013 Apr;165(4):575-582.e3. doi: 10.1016/j.ahj.2013.01.017. Epub 2013 Feb 22. PMID: 23537975. - https://pubmed.ncbi.nlm.nih.gov/23537975/
  17. Klip IT, Jankowska EA, Enjuanes C, Voors AA, Banasiak W, Bruguera J, Rozentryt P, Polonski L, van Veldhuisen DJ, Ponikowski P, Comin-Colet J, van der Meer P. The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences. Eur J Heart Fail. 2014 Jun;16(6):655-62. doi: 10.1002/ejhf.84. Epub 2014 Mar 18. PMID: 24644024. - https://pubmed.ncbi.nlm.nih.gov/24644024/
  18. Yeo TJ, Yeo PS, Ching-Chiew Wong R, Ong HY, Leong KT, Jaufeerally F, Sim D, Santhanakrishnan R, Lim SL, M Y Chan M, Chai P, Low AF, Ling LH, Ng TP, Richards AM, Lam CS. 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 Oct;16(10):1125-32. doi: 10.1002/ejhf.161. Epub 2014 Sep 11. PMID: 25208495. - https://pubmed.ncbi.nlm.nih.gov/25208495/
  19. Cohen-Solal A, Damy T, Terbah M, Kerebel S, Baguet JP, Hanon O, Zannad F, Laperche T, Leclercq C, Concas V, Duvillié L, Darné B, Anker S, Mebazaa A. High prevalence of iron deficiency in patients with acute decompensated heart failure. Eur J Heart Fail. 2014 Sep;16(9):984-91. doi: 10.1002/ejhf.139. Epub 2014 Jul 28. PMID: 25065368. - https://pubmed.ncbi.nlm.nih.gov/25065368/
  20. Lewis GD, Semigran MJ, Givertz MM, Malhotra R, Anstrom KJ, Hernandez AF, Shah MR, Braunwald E. 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 May;9(5):e000345. doi: 10.1161/CIRCHEARTFAILURE.115.000345. PMID: 27140203; PMCID: PMC6078413. https://pubmed.ncbi.nlm.nih.gov/23537975/
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Could you be experiencing iron deficiency?

Iron deficiency can show up in many ways, like extreme fatigue, pale skin, or difficulty concentrating. Take our easy quiz to detect possible warning signs and take action early.
Check your Symptoms

How talk to your doctor about iron deficiency

Talking to your doctor about iron deficiency doesn’t have to be complicated. Share your symptoms and concerns, ask for a blood test to check your iron levels, and explore options for managing your health together. Early diagnosis can make a big difference.
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