Advertisement

Heart Failure pp 171-178 | Cite as

Anemia and Iron Deficiency in Heart Failure

  • Otmar PfisterEmail author
Chapter
Part of the Cardiovascular Medicine book series (CVM)

Abstract

Anemia and iron deficiency (ID) are common co-morbidities in chronic heart failure (CHF) patients and are both independently associated with increased morbidity and mortality. Anemia affects one of three CHF patients and ID is present in half of CHF patients. While the treatment of anemia remains a challenge, ID has become a valid treatment target. ID is diagnosed when ferritin is lower than 100 ng/l, or between 100 and 299 ng/l with concurrent transferrin saturation below 20%. Correction of ID in CHF patients with or without anemia was shown to be safe and efficacious. It improves exercise capacity, quality of life and reduces the need for heart failure dependent hospitalisations. Current international guidelines recommend testing of all CHF patients for ID. If ID is diagnosed, intravenous iron substitution is recommended.

References

  1. 1.
    Groenveld HF, Januzzi JL, Damman K, van Wijngaarden J, Hillege HL, van Veldhuisen DJ, et al. Anemia and mortality in heart failure patients a systematic review and meta-analysis. J Am Coll Cardiol. 2008;52(10):818–27.PubMedCrossRefGoogle Scholar
  2. 2.
    Cleland JG, Zhang J, Pellicori P, Dicken B, Dierckx R, Shoaib A, et al. Prevalence and outcomes of anemia and hematinic deficiencies in patients with chronic heart failure. JAMA Cardiol. 2016;1(5):539–47.PubMedCrossRefGoogle Scholar
  3. 3.
    O'Meara E, Rouleau JL, White M, Roy K, Blondeau L, Ducharme A, et al. Heart failure with anemia: novel findings on the roles of renal disease, interleukins, and specific left ventricular remodeling processes. Circ Heart Fail. 2014;7(5):773–81.PubMedCrossRefGoogle Scholar
  4. 4.
    Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001;103(16):2055–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Westenbrink BD, Voors AA, de Boer RA, Schuringa JJ, Klinkenberg T, van der Harst P, et al. Bone marrow dysfunction in chronic heart failure patients. Eur J Heart Fail. 2010;12(7):676–84.PubMedCrossRefGoogle Scholar
  6. 6.
    van der Meer P, Lok DJ, Januzzi JL, de la Porte PW, Lipsic E, van Wijngaarden J, et al. Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients. Eur Heart J. 2008;29(12):1510–5.PubMedCrossRefGoogle Scholar
  7. 7.
    van der Putten K, Braam B, Jie KE, Gaillard CA. Mechanisms of disease: erythropoietin resistance in patients with both heart and kidney failure. Nat Clin Pract Nephrol. 2008;4(1):47–57.PubMedCrossRefGoogle Scholar
  8. 8.
    Abramov D, Cohen RS, Katz SD, Mancini D, Maurer MS. Comparison of blood volume characteristics in anemic patients with low versus preserved left ventricular ejection fractions. Am J Cardiol. 2008;102(8):1069–72.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    O'Meara E, Clayton T, McEntegart MB, McMurray JJ, Lang CC, Roger SD, et al. Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Circulation. 2006;113(7):986–94.PubMedCrossRefGoogle Scholar
  10. 10.
    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;27(12):1440–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Borenstein J. Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol. 2002;39(11):1780–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Ghali JK, Anand IS, Abraham WT, Fonarow GC, Greenberg B, Krum H, et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation. 2008;117(4):526–35.PubMedCrossRefGoogle Scholar
  13. 13.
    Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013;368(13):1210–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355(20):2085–98.PubMedCrossRefGoogle Scholar
  15. 15.
    Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010;363(12):1146–55.PubMedCrossRefGoogle Scholar
  17. 17.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891–975.PubMedCrossRefGoogle Scholar
  18. 18.
    Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116(23):4754–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997;89(3):1052–7.PubMedGoogle Scholar
  20. 20.
    Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG, et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol. 2006;48(12):2485–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J. 2013;165(4):575–82. e3PubMedCrossRefGoogle Scholar
  22. 22.
    Wienbergen H, Pfister O, Hochadel M, Michel S, Bruder O, Remppis BA, et al. Usefulness of iron deficiency correction in management of patients with heart failure [from the Registry Analysis of Iron Deficiency-Heart Failure (RAID-HF) registry]. Am J Cardiol. 2016;118:1875–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23.PubMedCrossRefGoogle Scholar
  24. 24.
    Jankowska EA, Malyszko J, Ardehali H, Koc-Zorawska E, Banasiak W, von Haehling S, et al. Iron status in patients with chronic heart failure. Eur Heart J. 2013;34(11):827–34.PubMedCrossRefGoogle Scholar
  25. 25.
    Sica DA. Pharmacotherapy in congestive heart failure: drug absorption in the management of congestive heart failure: loop diuretics. Congest Heart Fail. 2003;9(5):287–92.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    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(12):1241–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Comin-Colet J, Enjuanes C, Gonzalez G, Torrens A, Cladellas M, Merono O, et al. 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(10):1164–72.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Enjuanes C, Klip IT, Bruguera J, Cladellas M, Ponikowski P, Banasiak W, et al. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol. 2014;174(2):268–75.PubMedCrossRefGoogle Scholar
  30. 30.
    Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010;31(15):1872–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Niehaus ED, Malhotra R, Cocca-Spofford D, Semigran M, Lewis GD. 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Lewis GD, Semigran MJ, Givertz MM, Malhotra R, Anstrom KJ, Hernandez AF, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Bolger AP, Bartlett FR, Penston HS, O'Leary J, Pollock N, Kaprielian R, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol. 2006;48(6):1225–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Toblli JE, Lombrana A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007;50(17):1657–65.PubMedCrossRefGoogle Scholar
  35. 35.
    Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, et al. 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.PubMedCrossRefGoogle Scholar
  36. 36.
    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(2):236–42.PubMedGoogle Scholar
  37. 37.
    Drakos SG, Anastasiou-Nana MI, Malliaras KG, Nanas JN. Anemia in chronic heart failure. Congest Heart Fail. 2009;15(2):87–92.PubMedCrossRefGoogle Scholar
  38. 38.
    Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436–48.PubMedCrossRefGoogle Scholar
  39. 39.
    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(1):13–8.PubMedCrossRefGoogle Scholar
  40. 40.
    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;168(4):3439–42.PubMedCrossRefGoogle Scholar
  41. 41.
    Toblli JE, Di Gennaro F, Rivas C. Changes in echocardiographic parameters in iron deficiency patients with heart failure and chronic kidney disease treated with intravenous iron. Heart Lung Circ. 2015;24(7):686–95.PubMedCrossRefGoogle Scholar
  42. 42.
    Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, et al. 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(11):657–68.PubMedCrossRefGoogle Scholar
  43. 43.
    Avni T, Leibovici L, Gafter-Gvili A. Iron supplementation for the treatment of chronic heart failure and iron deficiency: systematic review and meta-analysis. Eur J Heart Fail. 2012;14(4):423–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Kapoor M, Schleinitz MD, Gemignani A, Wu WC. Outcomes of patients with chronic heart failure and iron deficiency treated with intravenous iron: a meta-analysis. Cardiovasc Hematol Disord Drug Targets. 2013;13(1):35–44.PubMedCrossRefGoogle Scholar
  45. 45.
    Filippatos G, Farmakis D, Colet JC, Dickstein K, Luscher TF, Willenheimer R, 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(11):1267–76.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Internal Medicine/Cardiology, University Hospital BaselUniversity of BaselBaselSwitzerland

Personalised recommendations