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Prolongation of the QT Interval and Ventricular Tachycardia in Patients Treated with Arsenic Trioxide for Acute Promyelocytic Leukemia
- Kazunori Ohnishi, MD;
- Hiroshi Satoh, MD; and
- Ryuzo Ohno, MD
- Hamamatsu University School of Medicine; Hamamatsu Shizuoka 431-3192, Japan (Ohnishi, Satoh) Aichi Cancer Center Hospital; Nagoya Aichi 464-8681, Japan (Ohno)
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IN RESPONSE:
The tachyarrhythmias seen in our study were not sustained tachycardia but were nonsustained ventricular tachycardia, accelerated idioventricular rhythm, or paroxysmal supraventricular tachycardia. Many cardiologists would not treat these arrhythmias with antiarrhythmic agents, especially if the patients were asymptomatic. We agree that excessive use of antiarrhythmic agents should be avoided.
In our study, the QTc interval was prolonged in all patients during arsenic trioxide therapy. However, the basic cardiac condition and the characteristics of ventricular arrhythmias differed somewhat from those expected in the long QT syndrome. First, the patients were heavily treated with chemotherapeutic agents, including anthracycline and all-trans retinoic acid. Cardiac damage was therefore likely to be universal before arsenic trioxide therapy, although echocardiographic abnormalities were indicated only in the single patient with previous myocardial infarction. We believe that arsenic trioxide is likely to have adverse effects in heavily pretreated patients.
Second, all of the nonsustained ventricular tachycardias in our study were monomorphic. If prolongation of the QT interval was the main mechanism for the ventricular arrhythmias, polymorphic ventricular tachycardia and torsade de pointes would have been expected. Ventricular tachycardia occurred in relation to QTc prolongation, but the degree of prolongation varied. In some cases, the arrhythmias were more closely associated with the increase in QTc dispersion. Therefore, the prolongation of the global QTc interval was not the only condition for arrhythmia; its spatial inhomogeneity could also have contributed.
In a study by Westervelt and colleagues (1), 3 of 10 patients receiving arsenic therapy (1 of whom became asystolic) died suddenly during the first cycle. Unnikrishnan and coworkers (2) reported that torsades de pointes developed in three patients with leukemia during treatment with arsenic trioxide. We continue to believe that clinicians should carefully monitor cardiac arrhythmias during arsenic trioxide therapy and that prophylactic therapy, including the reduction of the daily dosage of arsenic trioxide, should also be applied. We recommend a small dosage of mexiletine (150 to 300 mg/d) to avoid such adverse effects as liver dysfunction and nervous system disorders, which might be augmented by arsenic trioxide therapy.
Kazunori Ohnishi, MD
Hiroshi Satoh, MD
Hamamatsu University School of Medicine
Hamamatsu Shizuoka 431-3192, Japan
Ryuzo Ohno, MD
Aichi Cancer Center Hospital
Nagoya Aichi 464-8681, Japan
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
