Transferrin Saturation Provides Prognostic Information Beyond Ferritin in Hyperferritinemic Heart Failure: A MIMIC-IV Retrospective Cohort Study

Abstract Patients with heart failure and ferritin ≥ 300 ng/mL are classified as iron-sufficient and excluded from intravenous iron trials regardless of transferrin saturation (TSAT). We studied ICU-admitted, iron-tested adults with heart failure in MIMIC-IV whose iron panel was measured within 48 h of ICU admission, and classified them using European Society of Cardiology thresholds. Among 909 patients, 443 were hyperferritinemic. Comparing TSAT ≥ 20% with < 20%, 1-year mortality in the landmark cohort (n = 440) was 51.8% versus 31.4% (adjusted hazard ratio 1.84, 95% CI 1.34–2.53), and the association persisted after adjustment for guideline-directed medical therapy and log-ferritin (1.57, 1.12–2.20; P = 0.009). Ferritin alone was not associated with mortality. In-hospital and 28-day associations were directionally consistent, though they attenuated after additional adjustment for guideline-directed medical therapy and ferritin, and TSAT improved 1-year discrimination modestly (ΔC + 0.013). In this single-center retrospective cohort, high TSAT identified a subgroup of hyperferritinemic patients with higher 1-year mortality beyond ferritin concentration alone. Because iron parameters reflect a single early-ICU measurement and only 8.2% of eligible patients underwent iron testing, these observational findings do not imply a causal or therapeutic role for TSAT.