Dofetilide-Induced Microvolt T-Wave Alternans.

Area of Science:

• Cardiology
• Clinical Electrophysiology
• Pharmacology

Background:

• Dofetilide is an antiarrhythmic agent targeting potassium channels.
• Dofetilide administration is linked to potential ventricular arrhythmias, including torsade de pointes.
• Microvolt T-wave alternans (TWA) is an ECG marker associated with malignant ventricular arrhythmias.

Purpose of the Study:

• To investigate whether dofetilide administration induces TWA in healthy subjects.
• To quantify the TWA changes over a 24-hour period post-dofetilide administration.

Main Methods:

• A cohort of 22 healthy subjects received a 500 μg dose of dofetilide.
• Electrocardiograms (ECG) were recorded at baseline and 15 time points over 24 hours.
• Computerized algorithms using the correlation method were employed for automatic TWA detection.

Main Results:

• TWA significantly increased in 21 out of 22 subjects after dofetilide administration.
• Peak TWA values rose from a median of 6 μV at baseline to a maximum of 32 μV.
• The increase in TWA occurred on average 5 hours post-administration, with levels returning closer to baseline later.

Conclusions:

• Dofetilide administration leads to a significant increase in the occurrence and magnitude of TWA in healthy individuals.
• The observed TWA elevation suggests a potential proarrhythmic effect of dofetilide.
• These findings highlight TWA as a sensitive indicator of dofetilide's electrophysiologic impact.