Long-term effects of iron deficiency in patients with heart failure with or without anemia: the RAID-HF follow-up study
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.
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.
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).
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.
KeywordsIron deficiency Heart failure with reduced ejection fraction Anemia Iron supplementation
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.
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.
- 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
- 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
- 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.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.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.World Health Organization. Worldwide prevalence of anaemia 1993–2005. WHO global database on anaemia. https://www.who.int. Accessed 16 Jun 2018
- 16.EuroQoL group (2017) EQ-5D instruments. https://www.euroqol.org/eq-5d-instruments/. Accessed 16 Jun 2018
- 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
- 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
- 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.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
- 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
- 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