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Long-term effects of iron deficiency in patients with heart failure with or without anemia: the RAID-HF follow-up study

  • Harm Wienbergen
  • Otmar Pfister
  • Matthias Hochadel
  • Andreas Fach
  • Tina Backhaus
  • Oliver Bruder
  • Björn Andrew Remppis
  • Micha Tobias Maeder
  • Wolfgang von Scheidt
  • Matthias Pauschinger
  • Jochen Senges
  • Rainer Hambrecht
  • for the RAID-HF (Registry Analysis of Iron Deficiency-Heart Failure) Study Group
Original Paper

Abstract

Introduction

Iron deficiency (ID) has been recognized as a relevant comorbidity in heart failure with reduced ejection fraction (HFrEF); however, study data have shown that diagnostic and therapeutic efforts on ID are primarily performed in patients with anemia.

Methods

The RAID-HF registry investigated consecutive patients with ID and HFrEF in 11 heart centers in Germany and Switzerland. The present analysis focuses on 1-year follow-up data in patients with versus without anemia.

Results

In 505 patients with HFrEF and ID and 418 patients with HFrEF without ID 1-year follow-up was performed. Patients with ID had a higher long-term mortality compared to those without ID (19.5% vs. 13.7%, p = 0.02) and reported a lower quality of life. Only a minority of patients with ID (9.3%) received iron supplementation during long-term course, just 4.7% intravenously. Anemia was associated with an elevated mortality whereas ID versus no ID did not predict mortality in anemic patients (log-rank p = 0.78). However, in patients without anemia ID versus no ID predicted mortality (log-rank p = 0.002). In the adjusted analysis a significant interaction remained, with ID being a significant predictor of 1-year mortality in patients without anemia (HR 2.15, 95% CI 1.12–3.78), but not in anemic patients (HR 0.99, 95% CI 0.65–1.49).

Conclusions

RAID-HF demonstrates the impact of ID on long-term mortality and quality of life in patients with HFrEF and reveals an underuse of iron supplementation in current clinical practice. Particularly in patients without anemia the diagnosis of ID is of clinical relevance to identify patients at higher mortality risk.

Keywords

Iron deficiency Heart failure with reduced ejection fraction Anemia Iron supplementation 

Notes

Acknowledgements

The following centres participated in the RAID-HF registry: Germany: Elisabeth-Krankenhaus, Essen; Herz- und Gefäßzentrum Bad Bevensen; Klinikum Links der Weser, Bremen; Klinikum Nürnberg-Süd; Universitätsklinik Dresden; Universitätsklinik des Saarlandes, Homburg; Klinikum Lippe-Detmold. Switzerland: Universitätsspital Basel; Kantonsspital St. Gallen; Ospedale Regionale di Lugano; Kantonsspital Baden.

Funding

This work was supported by Vifor Pharma Germany and Vifor Pharma Switzerland.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B et al (2010) Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 31:1872–1880CrossRefPubMedGoogle Scholar
  2. 2.
    Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W et al (2013) Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 165(4):575–582CrossRefPubMedGoogle Scholar
  3. 3.
    Jankowska EA, rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B et al (2011) Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. J Card Fail 17:899–906CrossRefPubMedGoogle Scholar
  4. 4.
    Enjuanes C, Klip IT, Brugera J, Cladellas M, Ponikowski P, Banasiak W et al (2014) Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol 174:268–275CrossRefPubMedGoogle Scholar
  5. 5.
    Okonko DO, Grzeslo A, Witkowski T, Mandai AK, Slater RM, Roughton M et al (2008) 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 51:103–112CrossRefPubMedGoogle Scholar
  6. 6.
    Anker SD, Comin-Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H et al (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361:2436–2448CrossRefPubMedGoogle Scholar
  7. 7.
    Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V et al (2015) Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 36:657–668CrossRefPubMedGoogle Scholar
  8. 8.
    Beck-da-Silva L, Piardi D, Soder S, Rohde LE, Pereira-Barretto AC, de Albuquerque D et al (2013) IRON-HF study: a randomized trial to assess the effects of iron in heart failure patients with anemia. Int J Cardiol 168:3439–3442CrossRefPubMedGoogle Scholar
  9. 9.
    Anker SD, Kirwan BA, van Veldhuisen DJ, Filippatos G, Comin-Colet J, Ruschitzka F et al (2018) 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 20:125–133CrossRefPubMedGoogle Scholar
  10. 10.
    Hasenfuß G, Anker S, Bauersachs J, Böhm M, Hoppe UC, Pieske B et al (2013) Kommentar zu den Leitlinien der Europäischen Gesellschaft für Kardiologie (ESC) zur Diagnostik und Behandlung der akuten und chronischen Herzinsuffizienz. Kardiologe 7:105–114CrossRefGoogle Scholar
  11. 11.
    McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K et al (2012) 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. Eur Heart J 33:1787–1847CrossRefPubMedGoogle Scholar
  12. 12.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ et al (2016) 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 37:2129–2200CrossRefPubMedGoogle Scholar
  13. 13.
    Wienbergen H, Pfister O, Hochadel M, Michel S, Bruder O, Remppis BA et al (2016) 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 118:1875–1880CrossRefPubMedGoogle Scholar
  14. 14.
    World Health Organization. Worldwide prevalence of anaemia 1993–2005. WHO global database on anaemia. https://www.who.int. Accessed 16 Jun 2018
  15. 15.
    Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW et al (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147CrossRefPubMedGoogle Scholar
  16. 16.
    EuroQoL group (2017) EQ-5D instruments. https://www.euroqol.org/eq-5d-instruments/. Accessed 16 Jun 2018
  17. 17.
    Kaspar M, Fette G, Güder G, Seidlmayer L, Ertl M, Dietrich G et al (2018) Underestimated prevalence of heart failure in hospital inpatients: a comparison of ICD codes and discharge letter information. Clin Res Cardiol.  https://doi.org/10.1007/s00392-018-1245-z (Epub ahead of print) PubMedGoogle Scholar
  18. 18.
    Llorens P, Javaloyes P, Martín-Sánchez FJ, Jacob J, Herrero-Puente P, Gil V et al (2018) Time trends in characteristics, clinical course, and outcomes of 13,791 patients with acute heart failure. Clin Res Cardiol.  https://doi.org/10.1007/s00392-018-1261-z (Epub ahead of print) Google Scholar
  19. 19.
    Riedel O, Ohlmeier C, Enders D, Elsässer A, Vizcaya D, Michel A et al (2018) The contribution of comorbidities to mortality in hospitalized patients with heart failure. Clin Res Cardiol 107:487–497CrossRefPubMedGoogle Scholar
  20. 20.
    Jankowska EA, Kasztura M, Sokolski M, Bronisz M, Nawrocka S, Oleskowska-Florek W et al (2014) 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 35:2468–2476CrossRefPubMedGoogle Scholar
  21. 21.
    Haddad S, Wang Y, Galy B, Korf-Klingebeil M, Hirsch V, Baru AM et al (2017) Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure. Eur Heart J 38:362–372PubMedGoogle Scholar
  22. 22.
    von Haehling S, Gremmler U, Krumm M, Mibach F, Schon N, Taggeselle J et al (2017) Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry. Clin Res Cardiol 106:436–443CrossRefGoogle Scholar
  23. 23.
    Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA (2011) Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol 58:1241–1251CrossRefPubMedGoogle Scholar
  24. 24.
    van Veldhuisen DJ, Ponikowski P, van der Meer P, Metra M, Böhm M, Doletsky A et al (2017) Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 136:1374–1383CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Keating GM (2015) Ferric carboxymaltose: a review of its use in iron deficiency. Drugs 75:101–127CrossRefPubMedGoogle Scholar
  26. 26.
    Gutzwiller FS, Schwenkglenks M, Blank PR, Braunhofer PG, Mori C, Szucs TD et al (2012) 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 14:782–790CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM et al (2017) 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 317:1958–1966CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Tkaczyszyn M, Comin-Colet J, Voors AA, van Veldhuisen DJ, Enjuanes C, Moliner-Borja P et al (2018) Iron deficiency and red cell indices in patients with heart failure. Eur J Heart Fail 20:114–122CrossRefPubMedGoogle Scholar
  29. 29.
    Ebner N, Jankowska EA, Ponikowski P, Lainscak M, Elsner S, Sliziuk V et al (2016) 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 205:6–12CrossRefPubMedGoogle Scholar
  30. 30.
    Grote Beverborg N, van Veldhuisen DJ, van der Meer P (2018) Anemia in heart failure: still relevant? JACC Heart Fail 6:201–208CrossRefPubMedGoogle Scholar
  31. 31.
    Parikh A, Natarajan S, Lipsitz SR, Katz SD (2011) Iron deficiency in community-dwelling US adults with self-reported heart failure in the National Health and Nutrition Examination Survey III: prevalence and associations with anemia and inflammation. Circ Heart Fail 4:599–606CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R et al (2013) Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 368:1210–1219CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Harm Wienbergen
    • 1
  • Otmar Pfister
    • 2
  • Matthias Hochadel
    • 3
  • Andreas Fach
    • 1
  • Tina Backhaus
    • 1
  • Oliver Bruder
    • 4
  • Björn Andrew Remppis
    • 5
  • Micha Tobias Maeder
    • 6
  • Wolfgang von Scheidt
    • 7
  • Matthias Pauschinger
    • 8
  • Jochen Senges
    • 3
  • Rainer Hambrecht
    • 1
  • for the RAID-HF (Registry Analysis of Iron Deficiency-Heart Failure) Study Group
  1. 1.Bremer Institut für Herz- und Kreislaufforschung am Klinikum Links der WeserBremenGermany
  2. 2.Universitätsspital BaselBaselSwitzerland
  3. 3.Stiftung Institut für Herzinfarktforschung LudwigshafenLudwigshafen am RheinGermany
  4. 4.Elisabeth-Krankenhaus EssenEssenGermany
  5. 5.Herz- und Gefäßzentrum Bad BevensenBad BevensenGermany
  6. 6.Kantonsspital St. GallenSt. GallenSwitzerland
  7. 7.Klinikum Augsburg, Herzzentrum Augsburg-SchwabenAugsburgGermany
  8. 8.Klinikum Nürnberg, Paracelsus Medizinische PrivatuniversitätNurembergGermany

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