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Impact of Iron Deficiency on Clinical Outcomes in Congestive Heart Failure: A Retrospective Analysis of Risk Stratification and Mortality

Hourani, A. Z. O.; Sürmeli, A. D.

2025-03-06 cardiovascular medicine
10.1101/2025.03.05.25323191 medRxiv
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BackgroundIron deficiency (ID) is prevalent in congestive heart failure (CHF), worsening outcomes. While European guidelines recommend screening using ferritin and transferrin-saturation (TSAT), inconsistent diagnostic criteria, especially regarding functional deficiency (ferritin 100-299 {micro}g/L + TSAT <20%) and hyperferritinemia, limit prognostic accuracy. This study evaluated iron status definitions, including guideline criteria and a combined Ferritin-TSAT model, for predicting 365-day mortality in hospitalized CHF patients. MethodsThis retrospective analysis used MIMIC-IV data from 1,839 CHF patients. Iron status within 24h of admission was categorized using: 1) Guideline ID vs. non-ID; 2) Ferritin categories; 3) TSAT categories; 4) Combined Ferritin-TSAT model (Low: guideline ID; Intermediate: ferritin 100-299 + TSAT [&ge;]20%; High: ferritin [&ge;]300 {micro}g/L). Adjusted Cox models assessed mortality associations. ResultsGuidelines-defined iron deficiency (33.65% prevalence) independently associated with higher 1-year mortality (56.1% vs. 29.4%; adjusted HR 4.36, 95%CI 3.35-5.34). The combined Ferritin-TSAT model showed significant prognostic value, differentiating true iron deficiency (reference) from hyperferritinemia (adjusted HR 0.50 vs. iron deficiency) and intermediate group (adjusted HR 0.36 vs. ID), indicating varying risk relative to the most deficient group. This combined model better distinguished hyperferritinemic and iron-replete subgroups than the binary guideline definition. ConclusionIron status, including deficiency and hyperferritinemia, independently predicts 1-year mortality in CHF. While guideline iron deficiency is a strong predictor, a combined Ferritin-TSAT classification offers finer risk stratification by identifying distinct phenotypes (true deficiency, hyperferritinemia, intermediate). Nuanced iron-status assessment could improve prognostic evaluation and guide personalized therapies (e.g., IV iron for deficiency, investigation for hyperferritinemia) to enhance CHF outcomes. Prospective validation is needed.

Published in Journal of Clinical Medicine (predicted rank #7) · training set

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