Prevalence and Prognostic Significance of Exercise-Accentuated J-Point Elevation in Brugada Syndrome

The clinical significance of accentuation of precordial J-point elevation during exercise in Brugada syndrome (BrS) remains unclear.

This study sought to determine the prevalence and prognostic significance of accentuation of J-point elevation during exercise in a large single-center BrS cohort.

In this retrospective study, 141 consecutive patients referred for BrS evaluation (95 with type 1 BrS pattern-BrS1 cohort, 46 without type 1 pattern but with loss-of-function sodium voltage-gated channel alpha subunit 5 variants-SCN5A cohort) who underwent exercise stress testing (EST) from January 1, 2000, through October 31, 2025 were included. Two blinded cardiologists reviewed all tracings. An exercise-accentuated BrS phenotype was defined as J-point elevation increase ≥1 mm in V1/V2 during exercise. Cardiac events included arrhythmic syncope, cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks. Firth penalized logistic regression was used for unadjusted and adjusted analyses.

Overall, 41 patients (29%) demonstrated an exercise-accentuated BrS phenotype, emerging near peak exercise (median 90% age-predicted maximum heart rate). The phenotype was highly reproducible on serial testing (88% of follow-up ESTs). Exercise-accentuated phenotype was not associated with overall cardiac events (unadjusted OR: 1.83 [0.84-3.99]; P = 0.13; adjusted OR: 1.22 [0.47-3.21]; P = 0.69). However, it was strongly associated with exertion-triggered cardiac events (unadjusted OR: 10.50 [2.94-37.50]; P < 0.001; adjusted OR: 10.04 [2.76-36.53]; P < 0.001), independent of sex, exercise workload, and baseline type 1 pattern. Consistent results were noted in SCN5A variant-positive patients.

Exercise-induced accentuation of J-point elevation reproducibly identifies a subset of BrS patients at risk for exertional cardiac events. These findings support the inclusion of EST in the evaluation of patients with a clinical diagnosis or genetic susceptibility to BrS and may inform exercise-related risk counseling.