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.......................................................................................................................................................................... decompensation, promote skeletal muscle dysfunction, and is associated with frailty, irrespective of anaemia.716718

It is recommended that all patients with HF are regularly screened for anaemia and iron deficiency with full blood count, serum ferritin concentration, and TSAT. The detection of anaemia and/or iron deficiency should prompt appropriate investigation to define their cause. Darbepoetin-alpha failed to reduce all-cause death or HF hospitalization and increased the risk of thromboembolic events in the only large-scale randomized trial in patients with HFrEF and mild to moderate anaemia.719 As a result, erythropoietin stimulating agents are not indicated for the treatment of anaemia in HF.

RCTs have shown that iron supplementation with i.v. ferric carboxymaltose is safe and improves symptoms, exercise capacity, and QOL of patients with HFrEF and iron deficiency.720723 Metaanalyses of RCTs showed also a reduction in the risk of the combined endpoints of all-cause death or CV hospitalization, CV death or HF hospitalization, CV death or recurrent CV or HF hospitalizations.724,725 The favourable effects of iron supplementation were independent from anaemia coexistence.726 In AFFIRM-AHF, patients hospitalized for HF with LVEF <50% and concomitant iron deficiency were randomized to i.v. ferric carboxymaltose or placebo, repeated at 6- and then 12-week intervals if indicated according to repeat iron studies.512 Administration of ferric carboxymaltose did not significantly reduce the primary composite outcome of total HF hospitalizations and CV death at 52 weeks (rate ratio 0.79, 95% CI 0.621.01, P = 0.059). However, it reduced the composite endpoint of first HF hospitalization or CV death (HR 0.80, 95% CI 0.660.98, P = 0.030) and total HF hospitalizations (rate ratio 0.74, 95% CI 0.580.94, P = 0.013).512 Therefore, iron supplementation with i.v. ferric carboxymaltose should be considered for the improvement of symptoms, exercise capacity, and QOL in patients with HF and LVEF <45%. It should also be considered for the reduction of HF rehospitalizations in patients with LVEF <50% recently hospitalized for worsening HF. Ongoing trials are expected to provide more evidence on the effects of ferric carboxymaltose in patients with HFpEF. In addition, large outcomes trials with other iron formulations are ongoing in HFrEF, HFpEF, and AHF.727 Oral iron therapy is not effective in iron repletion and did not improve exercise capacity in patients with HFrEF and iron deficiency.728 It is therefore not recommended for the treatment of iron deficiency in the patients with HF.

13.6 Kidney dysfunction

CKD and HF frequently coexist.471,707,729 They share common risk factors, such as diabetes or hypertension. CKD may worsen CV function causing hypertension and vascular calcification. HF may worsen renal function, through the effects of neurohormonal and inflammatory activation, increased venous pressure and hypoperfusion. Oxidative stress and fibrosis likely play a major role as pathogenic mechanisms in HF with CKD.730,731 While CKD and worsening renal function both appear more common in HFpEF as compared to in HFmrEF and HFrEF, perhaps due to shared pathophysiological mechanisms, they appear to be less associated with worse outcomes in HFpEF than in HFmrEF and HFrEF.732,733 CKD is a major independent determinant of increased mortality and morbidity in HF.471,734736 However, there are settings in which changes in serum creatinine are not associated with worse outcomes. When RAAS inhibitors, ARNI or SGLT2 inhibitors are started, the initial decrease in the glomerular filtration pressure may decrease GFR and increase serum creatinine. However, these changes are generally transient and occur despite improvement in patient outcomes and slower worsening of renal function in the long term. For instance, in EMPEROR-Reduced, the placebo-corrected eGFR dip induced by empagliflozin at week 4 was of 2.4 mL/min/1.73 m2 for patients with CKD and 2.7 mL/min/1.73 m2 for those without CKD, corresponding to a decrease from baseline of 5.2% and 3.8%, respectively. This was followed by a slower slope of eGFR decline and by a reduced rate of the composite kidney outcome with empagliflozin vs. placebo, with no difference between patients with or without CKD at baseline.109,737 Thus, with respect to the initiation of RAAS inhibitors, ARNI or SGLT2 inhibitors, a transient decrease in renal function should not prompt their interruption. An increase in serum creatinine of <50% above baseline, as long as it is <266 lmol/L (3 mg/dL), or a decrease in eGFR of <10% from baseline, as long as eGFR is >25 mL/min/1.73 m2, can be considered as acceptable (see section 5.3 and Supplementary Table 8). Also, with respect to diuretic therapy, small and transient rises in serum creatinine during treatment of acute HF are not associated with poorer outcomes when the patient is free of congestion.108,109,460462,471,729,737740 Randomized trials have shown that patients with HF and concomitant CKD are at higher risk of events but the beneficial effects of MT

Recommendations for the management of anaemia and iron deficiency in patients with heart failure

Recommendations Classa Levelb

It is recommended that all patients with HF be periodically screened for anaemia and iron deficiency with a full blood count, serum ferritin concentration, and TSAT. I C Intravenous iron supplementation with ferric carboxymaltose should be considered in symptomatic patients with LVEF <45% and iron deficiency, defined as serum ferritin <100 ng/mL or serum ferritin 100299 ng/mL with TSAT <20%, to alleviate HF symptoms, improve exercise capacity and QOL.720,722,724 IIa A Intravenous iron supplementation with ferric carboxymaltose should be considered in symptomatic HF patients recently hospitalized for HF and with LVEF <50% and iron deficiency, defined as serum ferritin <100 ng/mL or serum ferritin 100299 ng/mL with TSAT <20%, to reduce the risk of HF hospitalization.512 IIa B

HF = heart failure; LVEF = left ventricular ejection fraction; QOL = quality of life; TSAT = transferrin saturation. aClass of recommendation. bLevel of evidence. ESC 2021 Downloaded from academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026