Ferritin, Inflammation and Iron Deficiency in Acute Heart Failure - evidence from the EDIFICA cohort

Abstract

Aims: Ferritin is used to assess iron stores and guide therapeutic decisions regarding intravenous iron supplementation. However, in the context of acute heart failure (AHF), inflammation-driven ferritin upregulation might disrupt its correlation with iron stores, restricting iron bioavailability and amplifying the inflammatory response. Our aim was to assess the clinical and prognostic associations of ferritin levels in an AHF cohort and to determine whether the prognostic value of ferritin is influenced by the presence of infection, inflammatory activation, and other markers of iron deficiency. Methods and Results: The association between ferritin and clinical outcomes (180 days) in AHF was evaluated in a cohort of 526 patients from the EDIFICA registry. The median ferritin plasma concentration at admission was 180 pg/mL. Patients with higher ferritin levels at admission were men, exhibiting a high prevalence of CKD and alcohol consumption, and presenting with lower blood pressure and a higher incidence of clinical infection. Higher ferritin levels were associated with increased risk of the composite of HF hospitalization or cardiovascular death (Tertile 2: HR 1.52; 95%CI 1.04-2.21; p=.027; Tertile 3: HR 1.69; 95%CI 1.17-2.44; p=.005), independently of classical HF prognostic factors, inflammatory and iron-related markers. No significant associations were found between serum iron or transferrin saturation tertiles, iron status categories, or guideline-defined iron deficiency criteria and the primary composite outcome. Conclusions: Elevated ferritin levels are independently associated with poor prognosis in AHF. Low ferritin levels are associated with a favorable outcome and may not carry significant value in identifying ID in this population.