Prognostic implications of iron deficiency in patients with atrial fibrillation, with and without chronic heart failure

BACKGROUND: Iron deficiency (ID) is common in patients with atrial fibrillation/flutter (AF), but its prognostic implications and optimal diagnostic criteria, particularly in those with and without heart failure (HF), remain unclear. This study assessed the associations between different ID definitions and clinical outcomes in patients with AF.

METHODS: This Danish nationwide cohort study included 10 834 patients with AF who underwent iron studies between 2008 and 2019, stratified by HF status. ID was defined using four criteria: European Society of Cardiology (ESC) guidelines, ferritin <100 ng/mL, transferrin saturation (TSAT) <20% and serum iron ≤13 µmol/L. Associations between ID definitions and all-cause mortality, cardiovascular mortality and all-cause hospitalisation were evaluated using Cox regression models, adjusted for confounders.

RESULTS: Prevalence of ID varied substantially across definitions, ranging from 36.2% to 62.7%. Over a median follow-up of 31 months, TSAT <20% was associated with increased all-cause and cardiovascular mortality in both HF (HR 1.25, 95% CI 1.14 to 1.37 and HR 1.31, 95% CI 1.14 to 1.49, respectively) and patients without HF (HR 1.39, 95% CI 1.18 to 1.64 and HR 1.54, 95% CI 1.18 to 2.00, respectively). Similarly, serum iron ≤13 µmol/L was associated with higher all-cause and cardiovascular mortality in HF (HR 1.44, 95% CI 1.31 to 1.58 and HR 1.42, 95% CI 1.24 to 1.63, respectively) and patients without HF (HR 1.67, 95% CI 1.41 to 1.97 and HR 1.46, 95% CI 1.13 to 1.89, respectively). ID defined by ESC guidelines or ferritin <100 ng/mL was not associated with mortality in either group but was linked to higher all-cause hospitalisation in patients with HF (HR 1.15, 95% CI 1.08 to 1.23 and HR 1.16, 95% CI 1.09 to 1.23, respectively).

CONCLUSIONS: ID defined by TSAT <20% or serum iron ≤13 µmol/L is associated with increased mortality in patients with AF, irrespective of HF status, highlighting these criteria as clinically relevant for risk stratification.