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Iron Supplementation in Heart Failure

  • Heart Failure (F. Peacock and L. Zhang, Section Editors)
  • Published:
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Abstract

Purpose of Review

Iron deficiency is a common comorbidity in heart failure (HF) patients; it is detected in up to 50 % of patients with chronic HF and in up to 70% in patients with acute HF, often without concomitant anemia. HF patients are particularly susceptible to iron deficiency; disturbances in nutrition and gastrointestinal tract absorption, as well as excess blood loss may lead to absolute iron deficiency, while chronic inflammatory state associated with HF may lead to functional iron deficiency. As iron contributes to cardiac and peripheral muscle dysfunction, iron deficiency is associated with poor exercise capacity, quality of life, and long-term outcomes.

Recent Findings

The understanding of iron homeostasis in HF patients has improved considerably during last decade, and new molecules involved in iron metabolism, such as hepcidin, have been described. Guidelines recommend the monitoring of iron parameters in all HF patients. Iron supplementation has been shown to considerably improve patients’ symptoms, exercise tolerance, and quality of life, and also decrease the rate of rehospitalizations.

Summary

ID is common in HF patients regardless of concomitant anemia. Iron parameters should be measured in all HF patients, and iron supplementation should be considered when ID is detected, regardless of concomitant anemia. This review describes the current understanding of iron deficiency and considerations for its supplementation in HF patients.

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References

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

  1. 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;165(575–582):e573.

    Google Scholar 

  2. Cohen-Solal A, Damy T, Terbah M, Kerebel S, Baguet JP, Hanon O, Zannad F, Laperche T, Leclercq C, Concas V, Duvillie L, Darne B, Anker S, Mebazaa A. High prevalence of iron deficiency in patients with acute decompensated heart failure. Eur J Heart Fail. 2014;16:984–91.

    Article  CAS  PubMed  Google Scholar 

  3. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, von Haehling S, Doehner W, Banasiak W, Polonski L, Filippatos G, Anker SD, Ponikowski P. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. J Card Fail. 2011;17:899–906.

    Article  CAS  PubMed  Google Scholar 

  4. 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;31:1872–80.

    Article  CAS  PubMed  Google Scholar 

  5. Jankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, Banasiak W, Filippatos G, Anker SD, Ponikowski P. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Kell DB. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics. 2009;2:2.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131:568S–79S discussion 580S.

    CAS  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. • Jankowska EA, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J. 2013;34: 816–829. This is a very good review of the pathophysiology and diagnostics of iron deficiency.

  10. Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovasc Res. 2009;81:412–9.

    Article  CAS  PubMed  Google Scholar 

  11. von Haehling S, Jankowska EA, van Veldhuisen DJ, Ponikowski P, Anker SD. Iron deficiency and cardiovascular disease. Nat Rev Cardiol. 2015;12:659–69.

    Article  Google Scholar 

  12. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122:78–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Munoz M, Garcia-Erce JA, Remacha AF. Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis. J Clin Pathol. 2011;64:281–6.

    Article  CAS  PubMed  Google Scholar 

  14. Anderson GJ, Frazer DM, McLaren GD. Iron absorption and metabolism. Curr Opin Gastroenterol. 2009;25:129–35.

    Article  CAS  PubMed  Google Scholar 

  15. Handelman GJ, Levin NW. Iron and anemia in human biology: a review of mechanisms. Heart Fail Rev. 2008;13:393–404.

    Article  PubMed  Google Scholar 

  16. von Haehling S, Anker MS, Jankowska EA, Ponikowski P, Anker SD. Anemia in chronic heart failure: can we treat? What to treat? Heart Fail Rev. 2012;17:203–10.

    Article  CAS  Google Scholar 

  17. Franchini M, Montagnana M, Lippi G. Hepcidin and iron metabolism: from laboratory to clinical implications. Clin Chim Acta. 2010;411:1565–9.

    Article  CAS  PubMed  Google Scholar 

  18. • Jankowska EA, Kasztura M, Sokolski M, Bronisz M, Nawrocka S, Oleskowska-Florek W, Zymlinski R, Biegus J, Siwolowski P, Banasiak W, Anker SD, Filippatos G, Cleland JG, Ponikowski P. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J. 2014;35: 2468–2476. This study showed that iron deficiency is a marker of worse outcome in patients with acute heart failure.

  19. Maeder MT, Khammy O, dos Remedios C, Kaye DM. Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure. J Am Coll Cardiol. 2011;58:474–80.

    Article  CAS  PubMed  Google Scholar 

  20. Comin-Colet J, Enjuanes C, Gonzalez G, Torrens A, Cladellas M, Merono O, Ribas N, Ruiz S, Gomez M, Verdu JM, Bruguera J. Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anaemia status. Eur J Heart Fail. 2013;15:1164–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Enjuanes C, Klip IT, Bruguera J, Cladellas M, Ponikowski P, Banasiak W, van Veldhuisen DJ, van der Meer P, Jankowska EA, Comin-Colet J. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol. 2014;174:268–75.

    Article  PubMed  Google Scholar 

  22. Aung N, Ling HZ, Cheng AS, Aggarwal S, Flint J, Mendonca M, Rashid M, Kang S, Weissert S, Coats CJ, Richards T, Thomas M, Woldman S, Okonko DO. Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure. Int J Cardiol. 2013;168:1997–2002.

    Article  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. McDonagh T, Macdougall IC. Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral? Eur J Heart Fail. 2015;17:248–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC. Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol. 2011;8:485–93.

    Article  PubMed  Google Scholar 

  26. Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah AA, Wehrens XH, Deswal A. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012;59:998–1005.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Scharf RE. Management of bleeding in patients using antithrombotic agents: prediction, prevention, protection and problem-oriented intervention. Hamostaseologie. 2009;29:388–98.

    CAS  PubMed  Google Scholar 

  28. Weber CS, Beck-da-Silva L, Goldraich LA, Biolo A, Clausell N. Anemia in heart failure: association of hepcidin levels to iron deficiency in stable outpatients. Acta Haematol. 2013;129:55–61.

    Article  CAS  PubMed  Google Scholar 

  29. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Task Force for the D, Treatment of A, Chronic Heart Failure of the European Society of C, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P, Guidelines ESCCfP. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69.

    Article  CAS  PubMed  Google Scholar 

  30. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P, Investigators F-HT. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436–48.

    Article  CAS  PubMed  Google Scholar 

  31. •• Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh T, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD, Investigators C-H. 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: 657–668. A large trial showing the benefits of intravenous iron supplementation in heart failure patients.

  32. Jankowska EA, Malyszko J, Ardehali H, Koc-Zorawska E, Banasiak W, von Haehling S, Macdougall IC, Weiss G, McMurray JJ, Anker SD, Gheorghiade M, Ponikowski P. Iron status in patients with chronic heart failure. Eur Heart J. 2013;34:827–34.

    Article  CAS  PubMed  Google Scholar 

  33. Koulaouzidis A, Said E, Cottier R, Saeed AA. Soluble transferrin receptors and iron deficiency, a step beyond ferritin. A systematic review. J Gastrointestin Liver Dis. 2009;18:345–52.

    PubMed  Google Scholar 

  34. Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG, Tsagalou EP, Maroulidis GD, Alexopoulos GP, Kanakakis JE, Anastasiou-Nana MI. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol. 2006;48:2485–9.

    Article  PubMed  Google Scholar 

  35. Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol. 2006;1(Suppl 1):S4–8.

    Article  CAS  PubMed  Google Scholar 

  36. Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011;3:12–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sandek A, Bjarnason I, Volk HD, Crane R, Meddings JB, Niebauer J, Kalra PR, Buhner S, Herrmann R, Springer J, Doehner W, von Haehling S, Anker SD, Rauchhaus M. Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure. Int J Cardiol. 2012;157:80–5.

    Article  PubMed  Google Scholar 

  38. Sandek A, Swidsinski A, Schroedl W, Watson A, Valentova M, Herrmann R, Scherbakov N, Cramer L, Rauchhaus M, Grosse-Herrenthey A, Krueger M, von Haehling S, Doehner W, Anker SD, Bauditz J. Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia. J Am Coll Cardiol. 2014;64:1092–102.

    Article  PubMed  Google Scholar 

  39. Cohen-Solal A, Leclercq C, Deray G, Lasocki S, Zambrowski JJ, Mebazaa A, de Groote P, Damy T, Galinier M. Iron deficiency: an emerging therapeutic target in heart failure. Heart. 2014;100:1414–20.

    Article  CAS  PubMed  Google Scholar 

  40. Bolger AP, Bartlett FR, Penston HS, O’Leary J, Pollock N, Kaprielian R, Chapman CM. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol. 2006;48:1225–7.

    Article  CAS  PubMed  Google Scholar 

  41. Usmanov RI, Zueva EB, Silverberg DS, Shaked M. Intravenous iron without erythropoietin for the treatment of iron deficiency anemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency. J Nephrol. 2008;21:236–42.

    CAS  PubMed  Google Scholar 

  42. Gaber R, Kotb NA, Ghazy M, Nagy HM, Salama M, Elhendy A. Tissue Doppler and strain rate imaging detect improvement of myocardial function in iron deficient patients with congestive heart failure after iron replacement therapy. Echocardiography. 2012;29:13–8.

    Article  PubMed  Google Scholar 

  43. Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, Foldes G, Thum T, Majda J, Banasiak W, Missouris CG, Poole-Wilson PA, Anker SD, Ponikowski P. 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;51:103–12.

    Article  CAS  PubMed  Google Scholar 

  44. Filippatos G, Farmakis D, Colet JC, Dickstein K, Luscher TF, Willenheimer R, Parissis J, Gaudesius G, Mori C, von Eisenhart Rothe B, Greenlaw N, Ford I, Ponikowski P, Anker SD. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Maurer MS, Teruya S, Chakraborty B, Helmke S, Mancini D. Treating anemia in older adults with heart failure with a preserved ejection fraction with epoetin alfa: single-blind randomized clinical trial of safety and efficacy. Circ Heart Fail. 2013;6:254–63.

    Article  PubMed  Google Scholar 

  46. Kdoqi, National Kidney F. II. Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis. 2006;47:S16–85.

    Article  Google Scholar 

  47. Ishida JH, Johansen KL. Iron and infection in hemodialysis patients. Semin Dial. 2014;27:26–36.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. INSERM UMR-S942, Paris, France

    H. Tolppanen & A. Mebazaa

  2. Heart Center, Päijät-Häme Central Hospital, Lahti, Finland

    H. Tolppanen

  3. Department of Anesthesia and Critical Care, APHP, University Hospital Saint Louis Lariboisière, Paris, France

    A. Mebazaa

  4. University Paris Diderot, Sorbonne Paris Cité, Paris, France

    A. Mebazaa

Authors
  1. H. Tolppanen
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  2. A. Mebazaa
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Correspondence to H. Tolppanen.

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Dr. Tolppanen & Dr. Mebazaa have declared no conflicts of interests.

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This article is part of the Topical collection on Heart Failure.

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Tolppanen, H., Mebazaa, A. Iron Supplementation in Heart Failure. Curr Emerg Hosp Med Rep 4, 206–212 (2016). https://doi.org/10.1007/s40138-016-0117-y

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