Torsades de pointes in two patients on treatment with arsenic trioxide

Arsenic trioxide (As2O3) induces remission in relapsed or resistant promyelocytic leukemia. It has apoptotic and differentiating effects on other leukemic cell lines and is being studied in clinical trails on a wide range of malignancies. The patients, aged 29 and 79 years, were on treatment for relapsed acute myeloid leukemia and myelodysplastic syndrome respectively. Duration of As2O3 treatment at the onset of oscillating ventricular tachycardia (torsades de pointes-TdP) was 42 and 16 days, with cumulative doses of 840 and 320 mgs respectively. One patient had prior therapy with anthracyclines, cardiac ejection fractions were normal. Both patients developed peripheral neuropathy and were treated for sepsis and hypoxia. Serum electrolytes including potassium, magnesium and calcium were normal. During treatment QTc intervals showed serial increase. One patient died from the arrhythmia, the other responded to treatment and died from massive hemoptysis. TdP is reported in arsenic poisoning but not with treatment protocols. Arsenic causes T wave changes, QTc prolongation, and rarely heart blocks, T wave alternans and prominent U waves. Arsenic may induce TdP by direct action, through sympathetic input imbalance or by affecting Mg conductance. Arsenic induced TdP is resistant to chemical and electrical cardioversion; hence patients should be monitored for ‘impending’ TdP. Other causes of QTc prolongation should be corrected. Antiarrhythmics that prolong QTc intervals must be avoided in treatment.