Time-dependent responses to provocative testing with flecainide in the diagnosis of Brugada syndrome

Abstract

Background: Time-dependent variability of electrocardiogram (ECG) in patients with Brugada syndrome could affect the interpretation of provocative testing.

Objective: The aim of this study was to characterize ECG changes during and after flecainide infusion.

Methods: We studied 59 consecutive patients. The ECG was continuously analyzed during the first 30 minutes of provocative testing, and a single ECG was recorded 60 minutes later. We analyzed CYP2D6 and CYP3A5 variants affecting flecainide metabolism and performed blinded measurements at lead II.

Results: At baseline, ECG patterns were classified as follows: type II in 31 patients (53%), type III in 15 (25%), and normal ECG in 13 (22%). Because of induction of type I ECG, the percentage of responders progressively increased with longer recording time periods (6.8% in 10 minutes vs 11.9% in 20-30 minutes vs 18.6% in 90 minutes; P < .01). Four patients displayed a late response, which was evidenced 90 minutes after the initiation of provocative testing. QRS width differentially increased between responders and nonresponders (P < .01), with a maximum QRS width of 110 ms during the first 30 minutes being effective for identifying possible late responders (sensitivity 100%; specificity 85.6%; positive predictive value 88%; negative predictive value 100%). The incidence of CYP2D6 variants was lower in late responders than in early or delayed responders (0% vs 75% vs 100%; P = .04), while a homogeneous distribution of CYP3A5*3/*3 was observed in our population.

Conclusion: Response to flecainide exhibits time-dependent variability of ECG patterns and intervals. Longer periods of ECG recording increase the recognition probability of type I ECG.

Keywords: Brugada syndrome; Cytochrome P450; Electrocardiogram; Flecainide; Provocative testing.