The Burden of Iron Deficiency in Heart Failure: Therapeutic Approach

Journal of the American College of Cardiology

Volumn 71, Issue 7, 2018, Pages 782-793

  Rocha, Bruno M L ^a   Cunha, Gonçalo J L ^a   Menezes Falcão, Luiz F ^b,c  

^a Department of Neurology   (Portugal)

^b HOSPITAL DE SANTA MARIA   (Portugal)

^c INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

Author keywords

ferric carboxymaltose; heart failure; iron deficiency

Indexed keywords

FERRIC CARBOXYMALTOSE; FERRITIN; FERROUS SULFATE; IRON; IRON DEXTRAN; IRON SACCHARATE; PLACEBO; REACTIVE OXYGEN METABOLITE; TRANSFERRIN RECEPTOR;

ACUTE HEART FAILURE; ALGORITHM; CARDIAC MUSCLE; CARDIOVASCULAR MAGNETIC RESONANCE; CITRIC ACID CYCLE; CLINICAL DECISION MAKING; COST EFFECTIVENESS ANALYSIS; DISEASE BURDEN; DRUG SAFETY; ELECTROLYTE DISTURBANCE; HOSPITALIZATION; HUMAN; HYPERTENSION; HYPOPHOSPHATEMIA; HYPOTENSION; IRON DEFICIENCY; IRON DEFICIENCY ANEMIA; IRON THERAPY; MUSCULOSKELETAL DISEASE; NEW YORK HEART ASSOCIATION CLASS; PATHOPHYSIOLOGY; PREVALENCE; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SKIN MANIFESTATION; SUPPLEMENTATION; CLINICAL TRIAL (TOPIC); COST OF ILLNESS; HEART FAILURE; PROCEDURES; TRENDS;

ANEMIA, IRON-DEFICIENCY; CLINICAL TRIALS AS TOPIC; COST OF ILLNESS; HEART FAILURE; HOSPITALIZATION; HUMANS;

EID: 85044345240     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2017.12.027     Document Type: Review

References (66)

1. Mosterd, A., Hoes, A.W., Clinical epidemiology of heart failure. Heart 93 (2007), 1137–1146.
2. Christiansen, M.N., Køber, L., Weeke, P., et al. Age-specific trends in incidence, mortality, and comorbidities of heart failure in Denmark, 1995 to 2012. Circulation 135 (2017), 1214–1223.
3. Rocha, B.M., Menezes Falcão, L., Acute decompensated heart failure (ADHF): a comprehensive contemporary review on preventing early readmissions and postdischarge death. Int J Cardiol 223 (2016), 1035–1044.
4. Dokainish, H., Teo, K., Zhu, J., et al. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health 5 (2017), e665–e672.
5. Ponikowski, P., Voors, A.A., Anker, S.D., 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). Eur Heart J 37 (2016), 2129–2200.
6. Yancy, C.W., Jessup, M., Bozkurt, B., et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 70 (2017), 776–803.
7. Wish, J.B., Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol 1 Suppl 1 (2006), S4–S8.
8. Kalantar-Zadeh, K., Lee, G.H., The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease?. Clin J Am Soc Nephrol 1 Suppl 1 (2006), S9–S18.
9. Chapter 2: Use of iron to treat anemia in CKD. Kidney Int Suppl (2011) 2 (2012), 292–298.
10. Nanas, J.N., Matsouka, C., Karageorgopoulos, D., et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 48 (2006), 2485–2489.
11. Van Aelst, L.N.L., Abraham, M., Sadoune, M., et al. Iron status and inflammatory biomarkers in patients with acutely decompensated heart failure: early in-hospital phase and 30-day follow-up. Eur J Heart Fail 19 (2017), 1075–1076.
12. Leszek, P., Sochanowicz, B., Szperl, M., et al. Myocardial iron homeostasis in advanced chronic heart failure patients. Int J Cardiol 159 (2012), 47–52.
13. Enjuanes, C., Bruguera, J., Grau, M., et al. Iron status in chronic heart failure: impact on symptoms, functional class and submaximal exercise capacity. Rev Esp Cardiol (Engl Ed) 69 (2016), 247–255.
14. Jankowska, E.A., Kasztura, M., Sokolski, M., et al. 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 35 (2014), 2468–2476.
15. Jankowska, E.A., Rozentryt, P., Witkowska, A., et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 31 (2010), 1872–1880.
16. Klip, I.T., Comin-Colet, J., Voors, A.A., et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 165 (2013), 575–582.e573.
17. Tkaczyszyn, M., Comín-Colet, J., Voors, A.A., et al. Iron deficiency and red cell indices in patients with heart failure. Eur J Heart Fail, 2017 Apr 6 [E-pub ahead of print].
18. Wienbergen, H., Pfister, O., Hochadel, M., 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 118 (2016), 1875–1880.
19. 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 106 (2017), 436–443.
20. Enjuanes, C., Klip, I.T., Bruguera, J., et al. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol 174 (2014), 268–275.
21. Núñez, J., Comín-Colet, J., Miñana, G., et al. Iron deficiency and risk of early readmission following a hospitalization for acute heart failure. Eur J Heart Fail 18 (2016), 798–802.
22. 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 16 (2014), 984–991.
23. Levi, S., Rovida, E., The role of iron in mitochondrial function. Biochim Biophys Acta 1790 (2009), 629–636.
24. Jankowska, E.A., von Haehling, S., Anker, S.D., Macdougall, I.C., Ponikowski, P., Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J 34 (2013), 816–826.
25. Melenovsky, V., Petrak, J., Mracek, T., et al. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis. Eur J Heart Fail 19 (2017), 522–530.
26. Wilson, J.R., Fink, L., Maris, J., et al. Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance. Circulation 71 (1985), 57–62.
27. Martens, P., Verbrugge, F.H., Nijst, P., Dupont, M., Mullens, W., Limited contractile reserve contributes to poor peak exercise capacity in iron-deficient heart failure. Eur J Heart Fail, 2017 Sep 18 [E-pub ahead of print].
28. Dai, D.F., Johnson, S.C., Villarin, J.J., et al. Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circ Res 108 (2011), 837–846.
29. Maeder, M.T., Khammy, O., dos Remedios, C., Kaye, D.M., Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure. J Am Coll Cardiol 58 (2011), 474–480.
30. Triposkiadis, F., Karayannis, G., Giamouzis, G., Skoularigis, J., Louridas, G., Butler, J., The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J Am Coll Cardiol 54 (2009), 1747–1762.
31. Patel, V.B., Zhong, J.C., Grant, M.B., Oudit, G.Y., Role of the ACE2/angiotensin 1-7 axis of the renin-angiotensin system in heart failure. Circ Res 118 (2016), 1313–1326.
32. Patel, A.R., Kramer, C.M., Role of cardiac magnetic resonance in the diagnosis and prognosis of nonischemic cardiomyopathy. J Am Coll Cardiol Img 10 Pt A (2017), 1180–1193.
33. Nagao, M., Matsuo, Y., Kamitani, T., et al. Quantification of myocardial iron deficiency in nonischemic heart failure by cardiac T2* magnetic resonance imaging. Am J Cardiol 113 (2014), 1024–1030.
34. Núñez, J., Monmeneu, J.V., Mollar, A., et al. Left ventricular ejection fraction recovery in patients with heart failure treated with intravenous iron: a pilot study. ESC Heart Fail 3 (2016), 293–298.
35. Jankowska, E.A., Malyszko, J., Ardehali, H., et al. Iron status in patients with chronic heart failure. Eur Heart J 34 (2013), 827–834.
36. Okonko, D.O., Mandal, A.K., Missouris, C.G., Poole-Wilson, P.A., Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol 58 (2011), 1241–1251.
37. Xu, W., Barrientos, T., Mao, L., Rockman, H.A., Sauve, A.A., Andrews, N.C., Lethal cardiomyopathy in mice lacking transferrin receptor in the heart. Cell Rep 13 (2015), 533–545.
38. Ebner, N., Jankowska, E.A., Ponikowski, P., et al. The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure. Int J Cardiol 205 (2016), 6–12.
39. Jankowska, E.A., Rozentryt, P., Witkowska, A., et al. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. J Card Fail 17 (2011), 899–906.
40. Cooper, T.J., Anker, S.D., Comin-Colet, J., et al. Relation of longitudinal changes in quality of life assessments to changes in functional capacity in patients with heart failure with and without anemia. Am J Cardiol 117 (2016), 1482–1487.
41. Lewis, G.D., Malhotra, R., Hernandez, A.F., 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 317 (2017), 1958–1966.
42. Bregman, D.B., Morris, D., Koch, T.A., He, A., Goodnough, L.T., Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia. Am J Hematol 88 (2013), 97–101.
43. McDonagh, T., Macdougall, I.C., Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?. Eur J Heart Fail 17 (2015), 248–262.
44. Moore, R.A., Gaskell, H., Rose, P., Allan, J., Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data. BMC Blood Disord, 11, 2011, 4.
45. Anker, S.D., Comin Colet, J., Filippatos, G., et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361 (2009), 2436–2448.
46. Niehaus, E.D., Malhotra, R., Cocca-Spofford, D., Semigran, M., Lewis, G.D., Repletion of iron stores with the use of oral iron supplementation in patients with systolic heart failure. J Card Fail 21 (2015), 694–697.
47. Pisani, A., Riccio, E., Sabbatini, M., Andreucci, M., Del Rio, A., Visciano, B., Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrol Dial Transplant 30 (2015), 645–652.
48. Toblli, J.E., Lombraña, 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 50 (2007), 1657–1665.
49. Toblli, J.E., 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 24 (2015), 686–695.
50. Okonko, D.O., Grzeslo, A., Witkowski, T., 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 51 (2008), 103–112.
51. Beck-da-Silva, L., Piardi, D., Soder, S., et al. IRON-HF study: a randomized trial to assess the effects of iron in heart failure patients with anemia. Int J Cardiol 168 (2013), 3439–3442.
52. Ponikowski, P., van Veldhuisen, D.J., Comin-Colet, J., et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 36 (2015), 657–668.
53. van Veldhuisen, D.J., Ponikowski, P., van der Meer, P., et al. Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 136 (2017), 1374–1383.
54. Anker, S.D., Kirwan, B.A., van Veldhuisen, D.J., 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, 2017 Apr 24 [E-pub ahead of print].
55. Jankowska, E.A., 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 18 (2016), 786–795.
56. Keating, G.M., Ferric carboxymaltose: a review of its use in iron deficiency. Drugs 75 (2015), 101–127.
57. Avni, T., Bieber, A., Grossman, A., Green, H., Leibovici, L., Gafter-Gvili, A., The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc 90 (2015), 12–23.
58. Roger, S.D., Gaillard, C.A., Bock, A.H., et al. Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial. Nephrol Dial Transplant 32 (2017), 1530–1539.
59. Gutzwiller, F.S., Schwenkglenks, M., Blank, P.R., et al. Health economic assessment of ferric carboxymaltose in patients with iron deficiency and chronic heart failure based on the FAIR-HF trial: an analysis for the UK. Eur J Heart Fail 14 (2012), 782–790.
60. 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 4 (2017), 274–281.
61. Brock, E., Braunhofer, P., Troxler, J., Schneider, H., Budget impact of parenteral iron treatment of iron deficiency: methodological issues raised by using real-life data. Eur J Health Econ 15 (2014), 907–916.
62. Drozd, M., Jankowska, E.A., Banasiak, W., Ponikowski, P., Iron therapy in patients with heart failure and iron deficiency: review of iron preparations for practitioners. Am J Cardiovasc Drugs 17 (2017), 183–201.
63. Kalra, P.A., Bock, K., Meldal, M., Iron isomaltoside 1000: a new high dose option for parenteral iron therapy. Port J Nephrol Hypert 26 (2012), 13–24.
64. Goddard, A.F., James, M.W., McIntyre, A.S., Scott, B.B., for the British Society of Gastroenterology. Guidelines for the management of iron deficiency anaemia. Gut 60 (2011), 1309–1316.
65. Levy, I., Gralnek, I.M., Complications of diagnostic colonoscopy, upper endoscopy, and enteroscopy. Best Pract Res Clin Gastroenterol 30 (2016), 705–718.
66. Moliner, P., Jankowska, E.A., van Veldhuisen, D.J., et al. Clinical correlates and prognostic impact of impaired iron storage versus impaired iron transport in an international cohort of 1821 patients with chronic heart failure. Int J Cardiol 243 (2017), 360–366.