ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Pediatric Cardiology
Multimodal Evidence Chain of Iron Overload, Inflammation, and Dysfunction: An Integrated Predictive Model of Early Cardiac Injury in Pediatric Transfusion-Dependent β-Thalassemia
Panyan Zhou
Caili Li
Xiaomei Gao
Caifen Ye
Mufang Huang
Heng Zhang
Zhuhai People's Hospital, Zhuhai, China
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Abstract
Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.
Summary
Keywords
B-TypeNatriuretic Peptide, Cardiac dysfunction, Iron Overload Mechanism, Transfusion-dependent β-thalassemia, Troponin I
Received
30 September 2025
Accepted
06 January 2026
Copyright
© 2026 Zhou, Li, Gao, Ye, Huang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Panyan Zhou
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