Pancreatic Iron Overload Is Associated With Early QTc Prolongation Before Myocardial Iron Deposition in...

This cross-sectional study evaluated the 12-lead electrocardiogram (ECG) corrected QT (QTc) interval as an accessible marker for organ-specific iron burden in adult patients with transfusion-dependent thalassemia (TDT).

We considered 273 adult TDT patients (37.48 ± 8.75 years; 53.8% females), enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. All patients underwent magnetic resonance imaging (MRI) for the quantification of hepatic, pancreatic, and myocardial iron ( $T_2^{*}$ technique) and the assessment of biventricular size and function, alongside a standard ECG within 3 months.

QTc interval showed a significant negative correlation with pancreatic $T_2^{*}$ (R = 0.220; p < 0.0001) and cardiac $T_2^{*}$ (R = -0.201; p = 0.001). A QTc > 425 ms predicted myocardial iron overload (MIO; $T_2^{*}$  < 20 ms). A significant stepwise prolongation of the QTc interval was observed across groups: no iron overload (405.45 ms), isolated pancreatic siderosis (421.76 ms), and combined pancreatic/myocardial siderosis (433.01 ms) (p = 0.001). In patients without MIO, a QTc > 416 ms predicted pancreatic siderosis ( $T_2^{*}$  < 26 ms) and a multivariable regression analysis confirmed pancreatic iron, female sex, and splenectomy as independent predictors of QTc duration.

The QTc interval may serve as an early "metabolic sensor" of multi-organ iron toxicity. A QTc > 416 ms is associated with pancreatic siderosis and possible cardiac risk before MRI detects cardiac iron. While QTc alone is unlikely to be sufficient for individual patient risk stratification, this inexpensive and widely available parameter may help inform decisions regarding advanced imaging.