Risk factors for cardiac events in patients with Brugada syndrome A PRISMA-compliant meta-analysis and systematic review

Introduction: Inconsistent results have been reported about the risk stratification of patients with Brugada syndrome. We have summarized the evidence regarding the strength of association between 6 risk factors (family history of sudden cardiac death [SCD] or syncope, inducible ventricular arrhythmias on electrophysiology study [EPS], spontaneous type 1 Brugada electrocardiogram [ECG], male sex, family history of SCD, and sodium voltage-gated channel alpha subunit 5 [SCN5A] gene mutation) and subsequent cardiac events in Brugada syndrome patients. Methods: Pubmed, Ovid, Embase, and the Cochrane Library were searched for studies published between January 1992 and March 2016. Only prospective studies (27 studies, 4494 patients) that reported estimates with 95% confidence intervals (CIs) of cardiac events for the 6 risk factors were included. Results: Family history of SCD or syncope (risk ratio [RR] 4.97, 95% CI 3.96-6.23, P< 0.001), inducible ventricular arrhythmia on EPS (RR 3.56, 95% CI 1.30-9.74, P= 0.01), and spontaneous type 1 Brugada ECG (RR 4.07, 95% CI 2.23-7.41, P< 0.001) were associated with an increased risk of future cardiac events. Spontaneous type 1 Brugada ECG was associated with an elevated risk of future cardiac events in patients without a family history of SCD. Conclusions: Inducible ventricular arrhythmias on EPS, spontaneous type 1 Brugada ECG, and family history of SCD or syncope indicate a high risk of future cardiac events in patients with Brugada syndrome. Spontaneous type 1 Brugada ECG significantly increased the risk of future cardiac events in patients without family history of SCD.