Prolonged Corrected QT Interval as an Early Electrocardiographic Marker of Cyclophosphamide-Induced Cardiotoxicity in Pediatric Hematology and Oncology Patients.

BACKGROUND

Cyclophosphamide (CY) is associated with potentially fatal cardiotoxicity, yet no electrocardiographic indices have been established for early detection of CY-induced cardiomyopathy. This study aimed to determine whether corrected QT interval (QTc) prolongation can predict early onset of CY-related cardiac dysfunction in pediatric patients.

METHODS

We retrospectively analyzed 62 children who received high-dose CY therapy (≥100 mg/kg) for hematologic or oncologic diseases between 2010 and 2025. CY-induced cardiomyopathy was defined as a ≥10% reduction in the left ventricular ejection fraction to less than 50% or elevated brain natriuretic peptide/N-terminal pro-brain natriuretic peptide levels, according to the 2021 International Cardio-Oncology Society criteria. Resting 12-lead ECGs were obtained before and within 24 h of CY administration. QTc was calculated using the Fridericia and Bazett formulas, and ΔQTc (post-pre) was evaluated using logistic regression and receiver operating characteristic (ROC) analyses.

RESULTS

Seven (11.3%) patients developed CY-induced cardiomyopathy. QTc after CY administration and ΔQTc were significantly greater in the cardiomyopathy group (p < 0.001). In multivariate analysis, ΔQTc was independently associated with cardiomyopathy (odds ratio 2.21, 95% confidence interval [CI]: 1.26-3.90, p = 0.0060). ROC analysis revealed excellent predictive accuracy (area under the curve = 0.96), with a ΔQTc ≥30.5 ms yielding 100% sensitivity and 89.1% specificity. Progressive QTc prolongation was also observed from pre- to post-CY and at diagnosis in the affected patients.

CONCLUSIONS

QTc prolongation within 24 h of CY administration suggests subsequent CY-induced cardiomyopathy in children. ΔQTc may serve as an early, noninvasive marker for timely detection and intervention in CY-induced cardiotoxicity.