Nonmodifiable Risk Factors Predict Outcomes in Brugada Syndrome.

Area of Science:

• Cardiology
• Genetics
• Electrophysiology

Background:

• Risk stratification in Brugada syndrome (BrS) traditionally relies on dynamic factors like syncope and type 1 ECG patterns.
• The influence of nonmodifiable factors such as sex and genetic variations on BrS risk remains unclear.

Purpose of the Study:

• To identify nonmodifiable risk factors for life-threatening arrhythmic events (LAEs) in Brugada syndrome patients.
• To assess the clinical utility of these nonmodifiable risk factors in risk stratification.

Main Methods:

• Analysis of clinical and genetic data from 2,182 unrelated Italian BrS patients.
• Screening focused on the SCN5A gene and three pivotal single-nucleotide variations associated with BrS.
• Multivariable Cox proportional hazards model used to identify independent risk factors.

Main Results:

• Male sex, SCN5A missense and nonmissense mutations, and a polygenic risk score for BrS were independently associated with increased LAE risk.
• A derived nonmodifiable risk score identified three distinct risk profiles.
• Nonmodifiable risk independently predicted LAE at follow-up, alongside established predictors like prior LAE, syncope, and type 1 ECG pattern.

Conclusions:

• Male sex, SCN5A mutation type, and polygenic risk score are significant nonmodifiable risk factors in BrS.
• These nonmodifiable factors are independently associated with LAE risk, irrespective of clinical presentation or ECG pattern.
• The derived risk equation aids in calculating granular 5-year LAE risk, facilitating clinical decision-making.