Heart Failure - Iron Deficiency With or Without Anemia

Publication Date: April 1, 2022

4. Initial and Serial Evaluation

4. Initial and Serial Evaluation

4.1.1. Initial Laboratory and Electrocardiographic Testing

1. For patients presenting with HF, the specific cause of HF should be explored using additional laboratory testing for appropriate management. ( B-NR , I )
2. For patients who are diagnosed with HF, laboratory evaluation should include complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, glucose, lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone to optimize management. ( C-EO , I )
3. For all patients presenting with HF, a 12-lead ECG should be performed at the initial encounter to optimize management. ( C-EO , I )
  1. Identifying the specific cause of HF is important, because conditions that cause HF may require disease-specific therapies. Depending on the clinical suspicion, additional diagnostic studies are usually required to diagnose specific causes such as ischemic cardiomyopathy, cardiac amyloidosis, sarcoidosis, hemochromatosis, infectious mechanisms (eg, HIV, COVID-19, Chagas), hypothyroidism, hyperthyroidism, acromegaly, connective tissue disorders, tachycardia-induced cardiomyopathy, Takotsubo, peripartum cardiomyopathy, cardiotoxicity with cancer therapies, or substance abuse would require specific management in addition to or beyond GDMT.
  2. Laboratory evaluation with complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, iron studies (serum iron, ferritin, transferrin saturation), and thyroid-stimulating hormone levels provides important information regarding patients’ comorbidities, suitability for and adverse effects of treatments, potential causes or confounders of HF, severity and prognosis of HF, and is usually performed on initial evaluation. Pertinent laboratory tests are repeated with changes in clinical condition or treatments (e.g., to monitor renal function or electrolytes with diuretics).
  3. Electrocardiography is part of the routine evaluation of a patient with HF and provides important information on rhythm, heart rate, QRS morphology and duration, cause, and prognosis of HF. It is repeated when there is a clinical indication, such as a suspicion for arrhythmia, ischemia or myocardial injury, conduction, or other cardiac abnormalities.

10. Comorbidities in Patients With HF

10. Comorbidities in Patients With HF

10.1. Management of Comorbidities in Patients With HF

Management of Anemia or Iron Deficiency

1. In patients with HFrEF and iron deficiency with or without anemia, intravenous iron replacement is reasonable to improve functional status and QOL. ( B-R , IIa )
2. In patients with HF and anemia, erythropoietin-stimulating agents should not be used to improve morbidity and mortality. ( B-R , III (harm) )
  1. Routine baseline assessment of all patients with HF includes an evaluation for anemia. Anemia is independently associated with HF disease severity and mortality, and iron deficiency appears to be uniquely associated with reduced exercise capacity. Iron deficiency is usually defined as ferritin level <100 μg/L or 100 to 300 μg/L, if the transferrin saturation is <20%. Intravenous repletion of iron has been shown to improve exercise capacity and QOL. The FAIR-HF (Ferric Carboxymaltose Assessment in Patients With Iron Deficiency and Chronic Heart Failure) trial showed significant improvement in NYHA classification, the 6-minute walk test, and QOL of 459 outpatients with chronic HF who received weekly intravenous ferric carboxymaltose until iron repletion. The improvement was independent of the presence of anemia. These findings were confirmed in 2 more recent trials. The IRONOUT HF (Iron Repletion Effects on Oxygen Uptake in Heart Failure) trial, however, showed no such improvement with oral iron supplementation. This is attributed to the poor absorption of oral iron and inadequacy of oral iron to replete the iron stores in patients with HF. Therefore, oral iron is not adequate to treat iron deficiency anemia in patients with HF. Although these trials were underpowered to detect reductions in hard clinical endpoints, 2 meta-analyses have suggested intravenous iron is associated with a reduction in cardiovascular death and hospitalizations. Most recently, the AFFIRM-AHF multicenter trial, which included 1132 patients with EF <50% hospitalized for HF, showed a decrease in hospitalization for HF with intravenous ferric carboxymaltose compared to placebo (RR, 0.74; 95% CI, 0.58–0.94) but no reduction in cardiovascular death.
  2. Anemia in patients with HF is associated with impaired erythropoietin production, with low levels found to be associated with worse long-term outcomes. Although small studies examining the use of erythropoietinstimulating agents for the treatment of anemia in patients with HF have suggested a trend toward improvement in functional capacity and reduction in hospitalization, a high-quality randomized trial of darbepoetin alpha in 2278 patients showed no benefit and an increase in thrombotic events, including stroke. A meta-analysis of 13 trials supports these findings. Accordingly, erythropoietin-stimulating agent therapy is not recommended for the treatment of anemia in patients with HF.

Recommendation Grading


  • ECG: Electrocardiogram
  • HF: Heart Failure
  • HFrEF: Heart Failure With Reduced Ejection Fraction
  • NYHA: New York Heart Association
  • QOL: Quality Of Life
  • RCT: Randomized Controlled Trial
  • RR: Relative Risk

Source Citation

Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022; https://doi.org/10.1016/j.jacc.2021.12.012.

Copublished in Circulation. 2022; https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063.


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