Does the Age of Sudden Cardiac Death in Family Members Matter in Brugada Syndrome?

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta-analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random-effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty-two studies from 2004 to 2019 were included in this meta-analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82-1.51; P=0.489, I²=45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2-fold (pooled OR, 2.03; 95% CI, 1.11-3.73; P=0.022, I²=0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P=0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.