Dofetilide-Induced Microvolt T-Wave Alternans

Dofetilide is an antiarrhythmic drug that selectively inhibits the rapid component of the delayed rectifier potassium current. The administration of dofetilide may cause ventricular arrhythmias and torsade de pointes. Electrocardiographic (ECG) microvolt T-wave alternans (TWA), an electrophysiologic phenomenon consisting in the beat-to-beat alternation of the T-wave amplitude requiring computerized algorithms to be detected, has also been associated to malignant ventricular arrhythmias. Aim of the present study was to evaluate if dofetilide induces TWA during the 24 hours following administration. The study population consisted of 22 healthy subjects ("ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects" database by Physionet) to whom a 500 μg-dose of dofetilide was administered. For each subject, 10 s ECG were acquired at baseline (0.5 hour before dofetilide administration) and at 15 time points during the 24 hours following the drug administration. ECG were then processed for automatic TWA detection by correlation method. In 21 subjects out of 22, after dofetilide administration, TWA significantly increased to a peak value (median TWA values went from 6 μV at baseline to a max 32 μV; p<; 0.05), on average after 5 hours, to then come back to values closer to baseline. Thus, in healthy subjects, dofetilide increases occurrence and levels (6 times baseline value on average) of TWA in the hours following its administration.