Does the age of sudden cardiac death in family members matter in brugada syndrome?

Abstract

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.