# Prognostic Value of Different Iron Status Definitions in Congestive Heart Failure: A Retrospective MIMIC-IV Analysis of Risk Stratification and Mortality

## TL;DR

This study shows that assessing iron status using a combined model of ferritin and TSAT improves risk prediction for heart failure patients compared to standard guidelines.

## Contribution

A combined Ferritin-TSAT model provides better risk stratification for CHF mortality than binary guideline definitions.

## Key findings

- Guideline-defined iron deficiency was linked to a 4.36-fold higher 1-year mortality risk in CHF patients.
- The combined Ferritin-TSAT model identified distinct subgroups with varying mortality risks, including hyperferritinemia and intermediate groups.
- The combined model outperformed binary definitions in distinguishing iron-replete and hyperferritinemic subgroups.

## Abstract

Background: Iron 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 μg/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 hospitalised CHF patients. Methods: This retrospective analysis used MIMIC-IV data from 1839 CHF patients. Iron status within 24 h of admission was categorised 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 ≥ 20%; High: ferritin ≥ 300 μg/L). Adjusted Cox models assessed mortality associations. Results: Guidelines-defined iron deficiency (33.66% 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. Conclusions: Iron 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 personalised therapies (e.g., IV iron for deficiency, investigation for hyperferritinemia) to enhance CHF outcomes.