T-wave alternans and torsades de pointes in a patient with leukemia treated with arsenic trioxide

A man in his 30s with a history of acute promyelocytic leukemia (APL) treated with arsenic trioxide (10 mg/day) for 28 days was hospitalized with recurrent loss of consciousness. His magnesium, 1.24 mmol/l; potassium, 4.47 mmol/l; and ionized calcium, 1.18 mol/l. ECG (Figure 1) demonstrates sinus rhythm with a QTc of 820 ms, extended to the next QRS complex, resulting in pseudo slight QRS widening of the next beat, mimicking premature ventricular contractions in a bigeminal pattern. A prolonged but variable QTc and a distinct beat-to-beat alternating of opposite T-wave polarity with a repeating ABABAB pattern can be seen more clearly in leads V2 to V5 (Figure 1). This rare phenomenon is known as macrovolt T-wave alternans (TWA), which is associated with life-threatening ventricular arrhythmias owing to spatiotemporal heterogeneity of repolarization. Later, the telemetry tracing showed torsades de pointes (TdP) following R-on-T phenomenon (red arrowhead) on the basis of T-wave alternans (Figure 2). Cardioversion was attempted multiple times because of hemodynamic instability. Loading doses of intravenous magnesium sulfate were administered followed by infusion at 3.5 mg/min to maintain plasma magnesium concentration within the high-normal range. 12-lead ECG showing marked QT prolongation, and macroscopic T-wave alternans (black and red arrowheads), seen best in leads V2 to V5. The telemetry tracing showing torsades de pointes following R-on-T phenomenon (black arrowhead) on the basis of T-wave alternans. TWA is defined as a transient beat-to-beat oscillation in T-wave timing, axis, morphology and/or amplitude in sinus rhythm without associated QRS variability or clinically significant changes in the RR interval. It is considered an indicator of myocardial electrical instability and harbinger of life-threatening ventricular arrhythmias. Experimental evidence is that abnormal intracellular Ca2+ handling is the ionic basis for TWA.1,2 Increased and unstable cardiac Ca2+ dynamics and suppressed K+ channels (both IKr and IKs) lead to prolonged repolarization in ventricular myocytes, action potential duration alternans and beat-to-beat alternation during repolarization giving rise to TWA on the ECG. In conclusion, the treatment of relapsed APL with arsenic trioxide prolongs the QTc and increases the spacial heterogeneity of repolarization. These effects are associated with the occurrence of ventricular tachyarrhythmias, including TdP.3 Z.W. and Y.-T.Z. contributed to conception and literature search. Y.-T.Z. and F.X. contributed draft of the manuscript and revision. Z.W. contributed to design and approved the manuscript to be submitted. This manuscript is not under consideration elsewhere. Furthermore, none of the contents of the manuscript have been previously published. In addition, all of the authors have read and approved the manuscript. Written consent has been obtained from the patient for publication. None declared. All data relevant to the study are included in the article.