Prognostic impact of iron deficiency in new-onset chronic heart failure: Danish Heart Failure Registry insights

Aims: Iron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition. This study evaluates the prevalence and the prognostic impact of ID using different criteria on all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF. Methods: In this nationwide registry-based cohort, we explored four definitions of ID: the current European Society of Cardiology (ESC) guidelines [ferritin <100 ng/mL or ferritin 100–299 ng/mL and transferrin saturation (TSAT) <20%], ferritin level <100 ng/mL, TSAT < 20% and serum iron ≤13 μmol/L. Patients were identified through the Danish Heart Failure Registry. Results: Of 9477 new-onset chronic HF patients registered in the Danish Heart Failure Registry from April 2003 to December 2019, we observed ID prevalence rates ranging from 35.8% to 64.3% depending on the ID definition used. Among patients with ID defined by iron ≤13 μmol/L or TSAT < 20%, 26% and 15.5%, respectively, did not meet the ESC guidelines definition for ID. Conversely, 11% of patients meeting the ESC criteria exhibited serum iron >13 μmol/L and TSAT > 20%. Regardless of anaemia status, ID defined by TSAT < 20% or serum iron ≤13 μmol/L was associated with all-cause mortality [non-anaemic, hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.30–1.89 and HR: 1.47, 95% CI: 1.24–1.73; anaemic, HR: 1.22, 95% CI: 1.07–1.38 and HR: 1.25, 95% CI: 1.09–1.44, respectively] and cardiovascular mortality (non-anaemic, HR: 2.21, 95% CI: 1.59–3.06 and HR: 1.47, 95% CI: 1.12–1.95; anaemic, HR: 1.37, 95% CI: 1.11–1.69 and HR: 1.28, 95% CI: 1.02–1.61, respectively), as well as increased risk of first hospitalization for HF (non-anaemic, HR: 1.28, 95% CI: 1.09–1.1.50 and HR: 1.27, 95% CI: 1.10–1.46; anaemic, HR: 1.25, 95% CI: 1.08–1.44 and HR: 1.22, 95% CI: 1.05–1.42, respectively). ID defined by ESC guidelines was associated with all-cause and cardiovascular mortality only in non-anaemic patients (HR: 1.41, 95% CI: 1.18–1.1.70 and HR: 1.58, 95% CI: 1.18-2.12.). Furthermore, the ESC guideline definition was associated with increased risk of first hospitalization for HF, regardless of anaemia status (non-anaemic, HR: 1.26, 95% CI: 1.08–1.1.47; anaemic, HR: 1.34, 95% CI: 1.17–1.53). Conclusions: ID, when defined by TSAT < 20% or serum iron ≤13 μmol/L, is associated with increased risk of all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF, regardless of anaemia status. Conversely, ID defined as ESC guidelines is associated with all-cause and cardiovascular mortality only in non-anaemic patients.