The adjusted ferritin inflammation index: a novel metric for predicting mortality in heart failure with reduced and...

Iron deficiency is a prevalent comorbidity in patients with heart failure (HF) and is associated with adverse outcomes. Traditional markers such as ferritin and transferrin saturation may be misleading due to the confounding impact of systemic inflammation. This study aimed to develop and validate the Adjusted Ferritin Inflammation Index (AFII), a novel composite score integrating ferritin/C-reactive protein (CRP) ratio and albumin levels, to improve mortality risk stratification in HF patients.

This retrospective cohort study included 322 patients with HF and reduced or mildly reduced ejection fraction (HF with reduced ejection fraction: left ventricular ejection fraction ≤40%; HF with mildly reduced ejection fraction: left ventricular ejection fraction 41%-49%). Patients were evaluated for iron parameters between January 2017 and September 2023. Laboratory values (ferritin, CRP, and albumin) were obtained at admission for inpatients or at the first outpatient evaluation. Baseline characteristics were compared between survivors and deceased patients. Adjusted Ferritin Inflammation Index was derived using logistic regression and calculated as: AFII = (Albumin × -0.168) + (Ferritin/CRP × -0.012) + 6.958. The score was log-transformed (Base 2), and the optimal cut-off (2.1) was determined via receiver-operating characteristic curve analysis. Mortality predictors were assessed using Cox regression, and survival differences were analysed with Kaplan-Meier curves.

During a median follow-up of 41 months, 106 patients (32.9%) died. In multivariate Cox regression, AFII ≥ 2.1 independently predicted mortality (hazard ratio: 2.155; 95% confidence interval: 1.361-3.412; P = .001), along with New York Heart Association (NYHA) class, sodium, brain natriuretic peptide, and smoking. Ferritin and transferrin saturation were not associated with survival (P = .733 and P = .790, respectively). The AFII showed superior predictive performance [area under the curve (AUC): 0.713] compared with ferritin/CRP (AUC: 0.438) and albumin (AUC: 0.694). Kaplan-Meier analysis showed significantly reduced survival in patients with AFII ≥ 2.1 across the overall cohort (3-year survival: 54.9% vs 84.6%).

Adjusted Ferritin Inflammation Index is a novel inflammation-adjusted metric that independently predicts mortality in HF with reduced ejection fraction/HF with mildly reduced ejection fraction patients and outperforms traditional iron markers. Its use may enhance risk stratification and inform future strategies for iron deficiency management in HF.