Flecainide for the Treatment of Andersen-Tawil Syndrome

Abstract

Background: Andersen-Tawil syndrome type 1 (ATS1) is a rare arrhythmogenic disorder resulting from loss-of-function mutations in KCNJ2. Although the use of flecainide has been proposed to treat and prevent life-threatening arrhythmic events in ATS1, it has only been tested in small case series with limited follow-up. We performed a multicenter cohort study to determine the impact of flecainide on ATS.

Objectives: This study aimed to assess the efficacy and safety of flecainide in reducing ventricular arrhythmia and related symptoms in patients with ATS1.

Methods: Clinical and genetic data from consecutive ATS1 patients from 9 centers were collected and entered into a database at UCSF Medical Center, San Francisco, California, USA, and pooled for analysis.

Results: The study included 31 ATS1 patients with a median age of 27 years (Q1-Q3: 24-38 years). The median follow-up time was 4.2 years (Q1-Q3: 1.6-9.7 years), and the median daily dose of flecainide was 150 mg (Q1-Q3: 100-200 mg). A positive exercise treadmill test was defined as any ventricular arrhythmia other than occasional single premature ventricular contractions, and was seen in 16 of 18 patients before treatment. This decreased to 5 of 18 patients with flecainide (OR: 0.13; P = 0.035). One episode of nonsustained ventricular tachycardia was observed on exercise treadmill test during flecainide treatment, compared with 6 observed during pretreatment. The ventricular arrhythmia score, defined as the most severe arrhythmia on Holter monitoring, improved in 66% of patients (mean improvement 0.62 ± 1.6 U; P = 0.005). Premature ventricular contraction burden decreased by 84.8% (71.5%-100%), from 22.3% at baseline to 3.8% with flecainide (P < 0.001). While on flecainide, symptomatic patients had a 77.7% chance of becoming symptom-free (95% CI: 56.2%-100%). Most patients (21/25, 84%) reported no side effects. One patient experienced a VT storm while treated with flecainide but tolerated a lower dose with a good response.

Conclusions: These data demonstrate that flecainide treatment may be effective and well-tolerated in ATS1 patients. The occurrence of an arrhythmic storm in 1 patient underscores the potential for toxicity and mandates careful dose titration monitored by rest and exercise electrocardiogram for QRS widening.

Keywords: Andersen-Tawil syndrome; arrhythmia; flecainide.