Iron deficiency is an important pathogenic factor affecting the severity and progression of chronic heart failure. Until now, iron deficiency diagnosis was based on the assessment of transferrin saturation and serum ferritin. Unfortunately, these standard measures of iron status are unreliable in the acute clinical settings (such as in acute heart failure)1. Either inflammation or oxidative stress may artificially increase ferritin concentrations, regardless of actual iron status, and artificial transferrin saturation elevations could occur due to catabolism and malnutrition2,3.
In this study, prevalence of iron deficiency was assessed in 165 patients with acute heart failure. A definition of iron deficiency from the FAIR-HF trial was used, based on low-serum hepcidin (<14.5 ng/mL) and high-serum soluble transferrin receptor (≥1.59 mg/L)4. This definition was utilised to investigate whether iron deficiency would predict poor outcome in this setting. The primary endpoint was all-cause death, with 12 months of follow up.
The prevalence of depleted iron store (low-serum hepcidin) and depleted utilised iron (high-serum soluble transferrin receptor) was very common (46 and 66%, respectively). Iron deficiency was found in 107 patients (65%). Low hepcidin and high soluble transferrin receptor was found in 61 patients (37%).
Iron deficiency, diagnosed based on both low-serum hepcidin and high soluble transferrin receptor, resulted in the highest 12-month mortality risk compared with patients with preserved iron status (41% [95% confidence interval 29–53%] vs 0%, respectively; p<0.001). When all definitions of iron deficiency were included in a multivariate analysis, only iron deficiency defined as both low-serum hepcidin and high soluble transferrin receptor, remained an independent significant predictor of 12-month mortality.
Importantly, indices of iron status were only weakly, if at all, associated with haemoglobin. Iron deficiency defined as depleted iron stores and iron availability allows for the identification of acute heart failure patients with particularly poor outcomes independent of haemoglobin levels. Iron therapy may offer an attractive therapeutic option for targeting abnormal iron metabolism in those with acute heart failure.