QT and corrected QT prolongation as early markers of cardiac iron overload in pediatric transfusion-dependent thalassemia: A systematic review and meta-analysis

Transfusion-dependent thalassemia (TDT) is a major health problem across the thalassemia belt. Although regular transfusions extend survival, they cause cardiac iron overload (CIO). Cardiac magnetic resonance imaging T2-star (MRI T2*) is the gold standard for detecting myocardial siderosis, but it remains costly and has limited availability. QT and corrected QT (QTc) intervals have been proposed as simple, inexpensive alternatives, yet pediatric evidence is limited. This systematic review aims to assess the association between QT and QTc prolongation and CIO in pediatric TDT. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines (PROSPERO ID: CRD420251051029). Searches were performed in PubMed, EBSCO, Scopus, ProQuest, ScienceDirect, and Google Scholar for studies published between January 2015 and January 2025. Keywords included "β-thalassemia," "transfusion-dependent thalassemia," "pediatric,", "iron overload," "QT interval," "QTc interval," "cardiac MRI T2*," and "serum ferritin." Eligible studies reported QT/QTc intervals in pediatric TDT with CIO confirmed by MRI T2* and/or serum ferritin. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were pooled using a random-effects model, with subgroup and sensitivity analyses. Seven studies involving 619 children were included; six provided data for meta-analysis. Both QT (mean difference [MD] 18.23 ms; 95% confidence interval [CI] 12.05-24.41; P < 0.00001) and QTc intervals (MD 21.15 ms; 95% CI 15.88-26.42; P < 0.00001) were significantly prolonged in the CIO group. Subgroup analyses confirmed consistent findings with low heterogeneity. QT and QTc prolongation are strongly associated with CIO in pediatric TDT.