Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: Implications for long-term cardiac safety

Abstract

Ventricular tachyarrhythmias may occur during intravenous arsenic trioxide (As 2O 3). This has not happened during oral As 2O 3. Sixteen patients were studied by electrocardiography and 24-hour Holter monitoring at baseline, during and after oral As 2O 3 (As 2O 3-ON, As 2O 3-OFF). QT and corrected QT (QTc) were significantly longer during As 2O 3-ON than in As 2O 3-OFF, but QT and QTc dispersions were comparable. The patients' 24-hour heart rates were higher during As 2O 3-ON than in As 2O 3-OFF. QTc intervals at each hour were longer during As 2O 3-ON than in As 2O 3-OFF. However, QTc prolongation of more than 30 milliseconds only occurred at one time point (2 hours) after oral As 2O 3, resulting in QTc of more than 500 milliseconds in 3 of 16 patients, all within 4 hours of oral As 2O 3. Although the standard deviation of normal RR interval was lower during As 2O 3-ON, ratios of low frequency to high frequency power for As 2O 3-ON and As 2O 3-OFF were comparable. No ventricular proarrhythmias were observed. These observations, due to the lower peak plasma arsenic reached during oral As 2O 3, may explain the relative cardiac safety of oral As 2O 3. © 2006 by The American Society of Hematology.