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

Abstract

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.