Defining Iron Deficiency in Patients With Heart Failure

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Researchers investigated the impact of varying iron deficiency definitions on its prevalence and association with prognosis in ambulatory patients with chronic heart failure.

Differing definitions of iron deficiency offer a wide range of results for patients who may or may not be diagnosed with iron deficiency and, in trials, the lack of definition specificity may understate the benefits of intravenous iron, while the lack of definition sensitivity may exclude patients who should receive intravenous iron. These research findings were published in the Journal of the American College of Cardiology.

Varying heart failure (HF) guidelines define iron deficiency as a serum ferritin <15, <30, or <100 ng/mL, or when ferritin is 100 to 299 ng/mL, transferrin saturation <20%, or serum iron ≤13 µmol/L. In an attempt to reduce misinterpretation caused by varying definitions, researchers analyzed how different definitions for iron deficiency affected its prevalence and impact on patient outcomes.  

This single-center multi-variable analyses study included 4422 patients with HF who were referred to Hull LifeLab, UK, from 2001 to 2019. The median age was 75 years (range, 68-82 years), 60% were men, 32% had reduced left ventricular ejection fraction, 46% had a transferrin saturation (TSAT) of <20%, 48% had a serum iron concentration of ≤13 µmol/L, and 57% had a serum ferritin concentration of <100 ng/mL.

In total, 68%  of patients fulfilled current guideline criteria for iron deficiency; of these, 35% had a TSAT >20%. Researchers found that iron deficiency was more common in women and patients with preserved ejection fraction, anemia, or more severe symptoms. Serum ferritin of <100 ng/mL was associated with lower mortality (hazard ratio [HR], 0.91; 95% CI, 0.81-1.01; P =.09).

Investigators noted limitations to their study. Certain biomarkers of interest were not measured and the soluble transferrin receptor test for iron deficiency is not widely used. Additionally, there was no information collected on the rate of intravenous iron, number of transfusions that some patients may have received, or the presence of genetic mutation. Finally, this was a single-center study including predominantly White participants, thus reducing its generalizability.

“Irrespective of how it is defined, [iron deficiency] is common in patients with HF,” the researchers stated. “When defined by current guideline criteria, [iron deficiency] was not associated with poor outcome; indeed, lower serum ferritin concentrations were associated with a better survival.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Masini G, Graham FJ, Pellicori P, et al. Criteria for iron deficiency in patients with heart failure. J Am Coll Cardiol. Published online February 1, 2022. doi:10.1016/j.jacc.2021.11.039