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The following is a summary of “Nonmodifiable Risk Factors Predict Outcomes in Brugada Syndrome,” published in the November 2024 issue of Cardiology by Kukavica et al.      

Risk assessment in Brugada syndrome (BrS) has focused on dynamic factors like unexplained syncope and spontaneous type 1 electrocardiogram (ECG) patterns. Still, the impact of nonmodifiable factors such as sex and genetics remains unclear.  

Researchers conducted a retrospective study to identify nonmodifiable risk factors for life-threatening arrhythmic events (LAEs) in BrS.  

They analyzed clinical and genetic data from 2,182 Italian patients with BrS, assessing sodium voltage-gated channel alpha subunit 5 (SCN5A) gene mutations and 3 single-nucleotide variations (SNVs) associated with BrS (rs11708996, rs10428132, rs9388451) using multivariable Cox proportional hazards models.  

The results showed that male sex (HR: 3.6; 95% CI: 1.9-6.9; P=0.0001), missense SCN5A mutations in BrS -enriched domains (HR: 2.3; 95% CI: 1.2-4.3; P=0.008), nonmissense SCN5A mutations (HR: 3.2; 95% CI: 1.8-5.7; P<0.001), and a polygenic risk score for BrS (HR: 1.3; 95% CI: 1.0-1.6; P=0.041) were independently linked to a higher risk of LAEs since birth. Nonmodifiable risk was also associated with LAEs during follow-up (HR: 1.8; 95% CI: 1.1-2.7; P=0.014). Classical predictors, such as previous LAEs (HR: 13.8; 95% CI: 8.1-23.7; P<0.0001), unexplained syncope (HR: 4.1; 95% CI: 2.4-6.8; P<0.0001), and spontaneous type 1 ECG pattern (HR: 2.1; 95% CI: 1.2-3.8; P=0.010), were also significant.  

They concluded that male sex, specific SCN5A mutations, and polygenic risk scores were nonmodifiable risk factors that predict LAEs in BrS.  

Source: jacc.org/doi/abs/10.1016/j.jacc.2024.07.037