Mexiletine Reduces Arrhythmic Events in Long QT Syndrome 3

Study Questions:

Does mexiletine prevent arrhythmic events (AEs) in patients with long QT syndrome type 3 (LQT3)?

Methods:

This was a retrospective study of 34 patients with LQT3 confirmed by genetic analysis. An AE was defined as sudden cardiac death, aborted sudden death, an appropriate implantable cardioverter-defibrillator discharge, or cardiac syncope. Patients served as their own controls. AEs were compared on and off mexiletine.

Results:

The median age at which treatment with mexiletine (mean dose 8 mg/kg/day, median duration of therapy 36 months) was initiated was 22 years and the mean duration of follow-up was 59 months. The median QTc shortened significantly from a baseline of 509 ms to 457 ms on mexiletine. Compared to periods of time off mexiletine, during treatment with mexiletine, there were significant reductions in the proportion of patients with AEs (22% vs. 3%), the mean number of AEs per patient (0.43 vs. 0.03), and the annual rate of AEs (10.3% vs. 0.7%).

Conclusions:

Mexiletine is highly effective in reducing the risk of AEs in patients with LQT3.

Perspective:

LQT3 is present in approximately 10% of patients with LQTS, is associated with a high risk of AEs, and is caused by a gain-of-function mutation in the sodium channel gene SCN5a. The electrocardiogram marker of LQT3 is a late, but normal-appearing T wave. AEs in LQT3 typically occur at rest and the efficacy of beta-blockers has been uncertain. The sodium channel blocker mexiletine has been known to shorten the QTc in patients with LQT3. The present study is important because it provides the first clinical evidence that mexiletine reduces the risk of AEs in LQT3.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Prevention, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD & Pediatrics and Arrhythmias

Keywords: Arrhythmias, Cardiac, Atrial Fibrillation, Death, Sudden, Cardiac, Defibrillators, Implantable, Electrocardiography, Long QT Syndrome, Mexiletine, Primary Prevention, Sodium Channel Blockers, Syncope


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