Abstract
<title>Abstract</title> <p>Background Iron deficiency management in acute heart failure (AHF) relies on ferritin and transferrin saturation (TSAT), yet the prognostic significance of TSAT within the hyperferritinemic range (ferritin ≥ 300 ng/mL)—where patients are currently classified as iron-sufficient—has not been systematically examined in critically ill AHF populations. Methods We conducted a retrospective cohort study using the MIMIC-IV database (2008–2019), including 1,395 adult patients admitted to the intensive care unit (ICU) with AHF who had ferritin and TSAT measured within 48 hours of admission. Patients were classified into five iron metabolism phenotypes using European Society of Cardiology (ESC) guideline thresholds. The primary analysis compared HyperF+HighTSAT (ferritin ≥ 300 ng/mL, TSAT ≥ 20%, n = 306) versus HyperF+LowTSAT (ferritin ≥ 300 ng/mL, TSAT < 20%, n = 332). The primary outcome was in-hospital all-cause mortality, analyzed via multivariable logistic regression with sequential covariate adjustment (Model 0–3). Secondary outcomes included 28-day and 1-year mortality assessed by Cox proportional hazards models and Kaplan-Meier curves. Results In-hospital mortality showed a clear gradient across phenotypes: 6.6% (absolute iron deficiency), 11.9% (functional iron deficiency), 8.8% (normal iron), 14.8% (HyperF+LowTSAT), and 27.8% (HyperF+HighTSAT). Among the 638 hyperferritinemic patients, those with high TSAT had significantly higher in-hospital mortality than those with low TSAT (adjusted OR 1.71, 95% CI 1.06–2.75, P = 0.027). One-year survival was significantly worse in the high-TSAT group (adjusted HR 1.45, 95% CI 1.12–1.86, P = 0.004). Subgroup analyses showed consistent directional associations across all strata. Conclusions Among AHF patients classified as iron-sufficient by current ferritin-based criteria, an elevated TSAT (≥ 20%) identifies a subgroup with substantially increased in-hospital and 1-year mortality, independent of established illness severity markers.</p>