# Multimodal evidence chain of iron overload, inflammation, and dysfunction: an integrated predictive model of early cardiac injury in pediatric transfusion-dependent β-thalassemia

## TL;DR

This study creates an early warning model for heart damage in children with β-thalassemia by combining imaging and blood markers.

## Contribution

The study introduces a novel integrated model combining T2* imaging, biomarkers, and strain measurements for early cardiac injury detection.

## Key findings

- The dysfunction group showed reduced GLS, elevated hs-cTnI and BNP, and shorter T2* values compared to controls.
- hs-cTnI, BNP, and T2* were identified as independent predictors of cardiac dysfunction.
- The combined three-factor model achieved excellent discrimination with an AUC of 0.914.

## Abstract

Despite standardized transfusion and chelation therapy, children with transfusion-dependent β-thalassemia (TDT) remain at high risk for cardiac dysfunction due to iron overload. Conventional ejection fraction assessment lacks sensitivity for early injury. This study evaluated multimodal indicators to develop a robust early-warning model.

A prospective cohort of 128 TDT children (3–16 years) underwent cardiac magnetic resonance (CMR) T2* imaging, echocardiography with global longitudinal strain (GLS), and measurement of circulating biomarkers including high-sensitivity cardiac troponin I (hs-cTnI), B-type natriuretic peptide (BNP), interleukin-6, and tumor necrosis factor-α. Children were classified into dysfunction and normal groups based on LVEF and GLS. Logistic regression identified predictors, and ROC analysis validated the integrated model.

The dysfunction group demonstrated reduced GLS, ventricular remodeling, elevated hs-cTnI and BNP, and significantly shorter T2* values compared with controls (p < 0.001). Inflammatory cytokines were also upregulated. Multivariate analysis identified hs-cTnI, BNP, and T2* as independent predictors. The combined three-factor model achieved excellent discrimination (AUC 0.914), outperforming single markers, with preserved calibration following bootstrap validation.

By linking iron overload, myocardial injury, inflammation, and structural dysfunction, this study proposes a clinically feasible integrated model for early cardiac risk detection in pediatric TDT. The approach supports precision monitoring and prevention of heart failure.

Iron overload drives cardiac dysfunction in children with TDT via inflammatory and myocardial injury pathways.Diagram illustrating the effects of iron overload, inflammation/injury, and volume overload on a heart. Iron overload is associated with MRI T2* imaging. Inflammation/injury involves biomarkers hs-cTnI, BNP, and IL-6. Volume overload is related to GLS (global longitudinal strain). A boy is shown wearing a shirt with a heart symbol.

Iron overload drives cardiac dysfunction in children with TDT via inflammatory and myocardial injury pathways.