Anaemia, iron deficiency and heart failure in 2020: facts and numbers

Vijay K Chopra, Stefan D Anker, Vijay K Chopra, Stefan D Anker

Abstract

Anaemia is defined by WHO as Hb < 13.0 g/dL in male adults and <12.0 g/dL in female adults. It is a common comorbidity in patients of heart failure with both HFrEF and HFpEF. The incidence ranges between 30% and 50%, though in certain communities, it is likely to be higher still. Elderly age, severe heart failure, poor nutrition, and elevation of inflammatory markers are associated with a higher incidence of anaemia. However, the commonest contributing factor to anaemia in HF is iron deficiency. In a Canadian study of 12 065 patients, the incidence of absolute ID was 21% in anaemic patients. Many other western studies have also quoted incidences varying between 35% and 43%. The earlier attempts to improve outcomes by supplementation with Erythropoietic-stimulating factors were unsuccessful and resulted in a higher incidence of thrombotic events. Iron deficiency (ID) has emerged as an important factor in patients of HF, even in those without anaemia and worsens outcomes. It is defined as Ferritin levels below 100 mcg/L or 100-299 μg/L with transferrin saturation of <20%. Attempts to correct ID by oral supplementation have been unsuccessful as seen in IRON-HF and IRONOUT-HF trials. FAIR-HF and CONFIRM-HF conclusively established the role of IV Iron in improving exercise capacity and quality of life in patients with HFrEF. ESC guidelines have given a class IC indication for testing all heart failure patients for ID, and an IIaA recommendation for its correction by IV ferric carboxymaltose was found to be deficient. Ongoing trials will establish the role of IV iron in improving mortality and in HFpEF patients and in patients with acute heart failure.

Keywords: Heart failure with preserved ejection fraction; Intravenous.

Conflict of interest statement

VKC reports no conflict of interest. SDA reports receiving fees from Abbott Vascular, Bayer, Boehringer Ingelheim, Cardiac Dimension, Impulse Dynamics, Novartis, Servier, and Vifor Pharma, and grant support from Abbott Vascular and Vifor Pharma.

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

References

    1. Nutritional anaemias . Report of a WHO scientific group. Geneva, World Health Organization, 1968. (WHO Technical Report Series, No. 405).
    1. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new‐onset heart failure. Circulation 2003; 107: 223–225.
    1. Adams KF Jr, Patterson JH, Oren RM, Mehra MR, O'Connor CM, Piña IL, Miller AB, Chiong JR, Dunlap SH, Cotts WG, Felker GM. Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA‐HFP) Registry. Am Heart J 2009; 157: 926–932.
    1. Komajda M, Anker SD, Charlesworth A, Okonko D, Metra M, di Lenarda A, Remme W, Moullet C, Swedberg K, Cleland JGF, Poole‐Wilson PA. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 2006; 27: 1440–1446.
    1. Von Haehling S, Schefold JC, Hodoscek LM, Doehner W, Mannaa M, Anker SD, Lainscak M. Anaemia is an independent predictor of death in patients hospitalized for acute heart failure. Clin Res Cardiol 2010; 99: 107–113.
    1. Martens P, Minten L. Prevalence of underlying gastrointestinal malignancies in iron‐deficient heart failure. ESC Heart Fail 2019. Feb; 6: 37–44.
    1. Goh, V. J. , Tromp J., Teng T.H. K., Tay W. T., van der Meer P., Ling L. H., Siswanto B. B., Hung C.L., Shimizu W., Zhang S., Narasimhan C., Yu C. M., Park S. W., Ngarmukos T., Liew H. B., Reyes E., Yap J., MacDonald M., Richards M. A., Anand I., Lam C. S.P., on behalf of the ASIAN‐HF investigators , (2018) Prevalence, clinical correlates, and outcomes of anaemia in multi‐ethnic Asian patients with heart failure with reduced ejection fraction. ESC Heart Failure 2018, : 570–578.
    1. Al‐JarallahM RR, Al‐Zakwani I, Dashti R, Bulbanat B, Sulaiman K, Alsheikh‐Ali AA, Panduranga P, Al Habib KF, Al Suwaidi J, Al‐Mahmeed W. Incidence and impact of cardiorenal anaemia syndrome on all‐cause mortality in acute heart failure patients stratified by left ventricular ejection fraction in the Middle East. ESC Heart Fail 2019. Feb; 6: 103–110.
    1. Chien SC, Lo CI, Lin CF, Sung KT, Tsai JP, Huang WH, Yun CH, Hung TC, Lin JL, Liu CY, Hou CJY, Tsai IH, Su CH, Yeh HI, Hung CL. Malnutrition in acute heart failure with preserved ejection fraction: clinical correlates and prognostic implications. ESC Heart Fail 2019. Oct; 6: 953–964.
    1. Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12065 patients with new‐onset heart failure. Circulation 2003. Jan 21; 107: 223–225.
    1. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin‐Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJV, Anker SD, Ponikowski P. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 2010; 31: 1872–1880.
    1. Von Haehling S, Gremmler U, Krumm M, Mibach F, Schön N, Taggeselle J, Dahm JB, Angermann CE. Prevalance and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: the PrEP registry. Clin Res Cardiol 2017; 106: 436–443.
    1. Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol 2006; 290: G199–G203 Cross Ref PubMed.
    1. Crielaard BJ, Lammers T, Rivella S. Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov 2017; 16: 2400–2423.
    1. Andrews NC. Closing the iron gate. N Engl J Med 2012; 366: 376–377.
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González‐Juanatey JR, Harjola VP, Jankowska EA, Jessup M. for the Authors/Task Force Members; Document Reviewers2016 ESC Guidelines 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: 891–975.
    1. Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E, Brosh D, Laniado S, Schwartz D, Yachnin T, Shapira I, Gavish D, Baruch R, Koifman B, Kaplan C, Steinbruch S, Iaina A. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalization. J Am Coll Cardiol 2000; 35: 1737–1744.
    1. Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, Maggioni AP, McMurray J, O'Connor C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen D, RED‐HF Committees and Investigators (2013) Treatment of anaemia with darbepoetin alfa in systolic heart failure. N Engl J Med 368:1210‐1219. Cross Pub Med
    1. Beck‐da‐Silva L, Piardi D, Soder S, Rohde LE, Pereira‐Barretto AC, de Albuquerque D, Bocchi E, Vilas‐Boas F, Moura LZ, Montera MW, Rassi S, Clausell N. Iron‐HF study. A randomized trial to assess the effects of iron in heart failure with anemia. Int J Cardiol 2013; 168: 3439–3442.
    1. 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, for the NHLBI Heart Failure Clinical Research Network , 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: 1958–1956.
    1. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole‐Wilson PA, Ponikowski P, FAIR‐HF Trial Investigators . Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361: 2436–2448.
    1. Ponikowski P, Van Veldhuisen DJ. Beneficial effects of long‐term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency CONFIRM‐HF. Eur Heart J 2015. Mar 14; 36: 657–668.
    1. Van Veldhuisen DJ, Ponikowski P, van der Meer P, Metra M, Böhm M, Doletsky A, Voors AA, Macdougall IC, Anker SD, Roubert B, Zakin L. for EFFECT‐HF InvestigationsEffect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 2017; 136: 1374–1383.
    1. 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: 786–795.
    1. Anker S. D, Kirwan B.A., van Veldhuisen D.J., Filippatos G, Comin‐Colet J, Ruschitzka F, Lüscher TF, Arutyunov GP, Motro M, Mori C, Roubert B. (2018) Effects of ferric carboxymaltose on hospitalizations and mortality rates in iron‐deficient heart failure patients: an individual patient data meta‐analysis. Eur J Heart Fail 20: 125‐133.
    1. 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: 840–855.
    1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR. 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 foundation/American Heart Association Task Force on Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2017; 70: 776–803.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel