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. 2014 Sep 21;35(36):2468-76. doi: 10.1093/eurheartj/ehu235. Epub 2014 Jun 13.


Aim: Acute heart failure (AHF) critically deranges haemodynamic and metabolic homoeostasis. Iron is a key micronutrient for homoeostasis maintenance. We hypothesized that iron deficiency (ID) defined as depleted iron stores accompanied by unmet cellular iron requirements would in this setting predict the poor outcome.

Methods and results: Among 165 AHF patients (age 65 ± 12 years, 81% men, 31% de novo HF), for ID diagnosis we prospectively applied: low serum hepcidin reflecting depleted iron stores (<14.5 ng/mL, the 5th percentile in healthy peers), and high-serum soluble transferrin receptor (sTfR) reflecting unmet cellular iron requirements (≥1.59 mg/L, the 95th percentile in healthy peers). Concomitance of low hepcidin and high sTfR (the most profound ID) was found in 37%, isolated either high sTfR or low hepcidin was found in 29 and 9% of patients, and 25% of subjects demonstrated preserved iron status. Patients with low hepcidin and high sTfR had peripheral oedema, high NT-proBNP, high uric acid, low haemoglobin (P < 0.05), and 5% in-hospital mortality (0% in remaining patients). During the 12-month follow-up, 33 (20%) patients died. Those with low hepcidin and high sTfR had the highest 12-month mortality [(41% (95% CI: 29-53%)] when compared with those with isolated high sTfR [15% (5-25%)], isolated low hepcidin [7% (0-19%)] and preserved iron status (0%) (P < 0.001). Analogous mortality patterns were seen separately in anaemics and non-anaemics.

Conclusion: Iron deficiency defined as depleted body iron stores and unmet cellular iron requirements is common in AHF, and identifies those with the poor outcome. Its correction may be an attractive therapeutic approach.

Keywords: Acute heart failure; Hepcidin; Iron status; Mortality; Soluble transferrin receptor.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Analysis of Variance
  • Female
  • Heart Failure / blood
  • Heart Failure / mortality*
  • Hepcidins / deficiency
  • Humans
  • Iron Deficiencies*
  • Male
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Poland / epidemiology
  • Prevalence
  • Prospective Studies
  • Receptors, Transferrin / metabolism
  • Risk Factors


  • Hepcidins
  • Peptide Fragments
  • Receptors, Transferrin
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain