Dynamic trajectories of iron deficiency during hospitalization and their clinical and biomarker profiles in heart failure
T Toyota, M Sano, R Murai, Y Azumi, H Hayashi, S Ito, J Ooka, Y Sasaki, T Taniguchi, A Kobori, N Ehara, M Kinoshita, Y FurukawaAbstract
Background
Iron deficiency (ID) is highly prevalent in heart failure (HF) and is associated with adverse outcomes. However, most studies assess ID at a single time point, and the clinical and biological implications of dynamic changes during hospitalization remain insufficiently characterized.
Purpose
To characterize inpatient trajectories of ID in patients with HF, evaluate the influence of anemia on these trajectories, and examine their associations with inflammatory and iron-regulatory biomarkers as well as subsequent clinical outcomes.
Methods
We analyzed 276 hospitalized HF patients between April 2021 and December 2024 with hemoglobin and iron parameters at admission and discharge. ID was defined as ferritin <100 ng/mL, or ferritin 100–299 ng/mL with transferrin saturation (TSAT) <20%. Anemia was defined as hemoglobin <12 g/dL in women and <13 g/dL in men. Patients were classified into four ID trajectories: persistent ID, improved ID (ID at admission, and non-ID at discharge), incident ID (non-ID at admission, and ID at discharge), and persistent non-ID. Discharge IL-6 (pg/mL) and hepcidin-25 (ng/mL) were compared across trajectories. The primary outcome was a composite of all-cause death or HF rehospitalization from discharge. Multivariable Cox regression adjusted for age, sex, LVEF, eGFR, log NT-proBNP, and anemia.
Results
Among 276 patients, anemia at admission was present in 183 (66%). Trajectory distribution differed by anemia status (P<0.001), with persistent ID more frequently observed in anemic patients. During a median follow-up of 12.9 months, 70 composite events occurred. Discharge IL-6 differed significantly across trajectories (median [IQR], pg/mL): persistent non-ID 5.42 [3.22–11.53], improved ID 4.21 [2.85–8.38], incident ID 5.26 [4.93–10.70], persistent ID 6.58 [3.97–15.73] (P=0.009). Discharge hepcidin-25 also differed markedly (ng/mL): persistent non-ID 58.20 [36.83–84.03], improved ID 26.15 [12.62–47.45], incident ID 31.60 [6.20–35.00], persistent ID 8.75 [1.50–26.10] (P<0.001). In adjusted Cox analysis (reference: persistent non-ID), incident ID was associated with increased risk (HR 3.01, 95% CI 1.07–8.47, P=0.037), whereas improved ID (HR 1.15, 95% CI 0.63–2.11, P=0.654) and persistent ID (HR 0.81, 95% CI 0.43–1.55, P=0.525) were not significantly associated with outcomes.
Conclusion
Dynamic changes in iron status during hospitalization define biologically distinct HF phenotypes with differing inflammatory and iron-regulatory profiles. Incident ID at discharge identifies a small but high-risk subgroup, supporting repeated iron assessment during hospitalization for improved risk stratification.Iron Deficiency Trajectories in HF