Practical Guidance for Diagnosing and Treating Iron Deficiency in Patients with Heart Failure: Why, Who and How?

Abstract

Iron deficiency (ID) is a comorbid condition frequently seen in patients with heart failure (HF). Iron has an important role in the transport of oxygen, and is also essential for skeletal and cardiac muscle, which depend on iron for oxygen storage and cellular energy production. Thus, ID per se, even without anaemia, can be harmful. In patients with HF, ID is associated with a poorer quality of life (QoL) and exercise capacity, and a higher risk of hospitalisations and mortality, even in the absence of anaemia. Despite its negative clinical consequences, ID remains under-recognised. However, it is easily diagnosed and managed, and the recently revised 2021 European Society of Cardiology (ESC) guidelines on HF provide specific recommendations for its diagnosis and treatment. Prospective randomised controlled trials in patients with symptomatic HF with reduced ejection fraction (HFrEF) show that correction of ID using intravenous iron (principally ferric carboxymaltose [FCM]) provides improvements in symptoms of HF, exercise capacity and QoL, and a recent trial demonstrated that FCM therapy following hospitalisation due to acute decompensated HF reduced the risk of subsequent HF hospitalisations. This review provides a summary of the epidemiology and pathophysiology of ID in HFrEF, and practical guidance on screening, diagnosing, and treating ID.

Keywords: chronic heart failure; ferric carboxymaltose; guidelines; iron deficiency.

Figure 1

Role of iron in the body and detrimental impact of iron deficiency [20,21,31]. ATP, adenosine triphosphate; Fe-S, iron–sulphur; Hb, haemoglobin; TCA, tricarboxylic acid.

Figure 2

Causes of iron deficiency in heart failure [19,27,29,31,39,40,43,44,45,46]. DOAC, direct oral anticoagulant; EPO, erythropoietin; GI, gastrointestinal; IL, interleukin; PPI, proton-pump inhibitor; RES, reticuloendothelial system; TNF-α, tumour necrosis factor alpha.

Figure 3

Algorithm showing screening, diagnosing, treating and monitoring for iron deficiency in patients with HF (updated from McDonagh T et al. 2018 [48] in line with the 2021 ESC HF guidelines [3]). * TSAT = (concentration of serum iron/total capacity to bind iron) × 100. ^† Note: The use of ferric carboxymaltose has not been assessed in paediatric patients, and therefore treatment with ferric carboxymaltose is not advised in children less than 14 years of age. Full prescribing information can be found in the latest Summary of Product Characteristics [49]. Hb, haemoglobin; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ID, iron deficiency; IV, intravenous; LVEF, left ventricular ejection fraction; TSAT, transferrin saturation.

Figure 4

Screening and treatment of iron deficiency across the HFrEF continuum [3,48,53]. Iron deficiency determined by a ferritin <100 μg/L or TSAT <20% when ferritin is 100–299 μg/L; and anaemia determined by a Hb <13 g/dL in males and <12 g/dL in females. TSAT = (serum iron concentration/total iron-binding capacity) × 100. FCM, ferric carboxymaltose; Hb, haemoglobin; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; ID, iron deficiency; LVEF, left ventricular ejection fraction; TSAT, transferrin saturation.

Figure 5

Key primary and secondary outcome results from AFFIRM-AHF [16]. * AFFIRM-AHF primary endpoint narrowly missed statistical significance. AFFIRM-AHF, Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency; CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazard ratio; RR, rate ratio.