Role of syncope in predicting adverse outcomes in patients with suspected Brugada syndrome undergoing standardized flecainide testing

Aims Sensitivity to flecainide testing results in suboptimal findings in patients with Brugada syndrome (BrS), leading to safety concerns. Because cardiac syncope effectively predicts outcomes in BrS, we aimed to explore its predictive value in a large cohort of negative and positive responders (NR and PR) to standard flecainide testing. Methods and results We analysed the data of 251 consecutive patients, 177 NR vs. 74 PR, to flecainide testing, performed according to standard recommendations. Cardiac syncope was defined as syncope presenting without prodromal symptoms and in the absence of any specific situation. Comparing PR with NR, there were no differences regarding age (39 +/- 15 vs. 44 +/- 13 years; P = 0.052), male gender (70.1% vs. 66.2%; P = 0.553), and family history of sudden cardiac death in relatives younger than 45 years (27% vs. 27%; P = 1). Cardiac syncope was more frequent in PR (12.2% vs. 4%; P = 0.022), and previous sudden cardiac arrest (SCA) was documented only in PR (5.4% vs. 0%; P = 0.007). During the follow-up period (6.2 +/- 3.3 years), one NR, who had previously experienced cardiac syncope, developed SCA 3 months after flecainide testing. Following resuscitation, a type I electrocardiogram was spontaneously recorded. The follow-up event rate was higher in patients with cardiac syncope, both in PR and in NR (P < 0.001 both). In a multivariate analysis, cardiac syncope was the unique variable that predicted adverse outcomes (hazard ratio 14.9, 95% confidence interval 1.84-121.25; P = 0.011). Conclusions In patients with false-negative responses to the provocative testing with flecainide, cardiac syncope predicts SCA, allowing a more extensive and individualized evaluation.