Clinical and electrocardiographic profiles of index and familial cases in non-spontaneous brugada syndrome
B Lage Garcia, A M Pinto, L Pinheiro, E Mata, M Castro, M Tinoco, S Ribeiro, L Calvo, A LourencoAbstract
Background
Brugada syndrome (BrS) is frequently diagnosed either after clinical presentation in index patients (IN) or through familial screening (FAM). Differences between these populations, particularly in non-spontaneous BrS, remain incompletely characterised.
Purpose
To evaluate differences in phenotype and clinical course between IN and those diagnosed through FAM in non-spontaneous BrS.
Methods
Retrospective, single-center observational study including 227 patients with BrS identified either IN or FAM, between 2014 and 2025. Basal electrocardiogram (ECG) was obtained in all patients. Individuals with a spontaneous type 1 Brugada ECG pattern were excluded. Diagnosis of BrS required the presence of type 1 ECG pattern, following provocative test or positive genetic test, if belonging to a family with genetically confirmed BrS. IN and FAM patients were compared regarding baseline characteristics and events during follow-up. Chi-square, Student’s T-test and Mann-Whitney U tests were used for group comparisons.
Results
A total of 227 patients were included, of whom 140 (61.7%) were identified through FAM. The cohort was predominantly male (55.1%), with a mean age at diagnosis of 46.1±14.9years. IN patients were diagnosed at a significantly younger age than those identified through FAM (MD-8.9 years, p<0.001). Female sex was significantly more frequent among FAM (57.1% vs 25.3%, p<0.001). The prevalence of syncope at presentation did not differ between IN and FAM cases (p=0.79), nor did the presence of a family history of sudden cardiac death (p=0.99). A sodium channel blocker test was positive in 90.3% of patients, most commonly using ajmaline. Genetic testing identified a pathogenic variant in 21.6%, while results were inconclusive in 12.8%. IN patients demonstrated significant differences in several electrocardiographic parameters, including a lower frontal QRS axis (30.8° vs 44.7°, p=0.01) and differences in selected QRS amplitude measurements (R DI, S DI, R DIII, S DIII, R aVR, S aVL, and R V1; all p<0.05). No differences were observed in PR interval, QRS duration, or QTc interval. Intraventricular conduction abnormalities were more frequent among IN patients (42.5% vs 15.0%, p<0.001), whereas first-degree atrioventricular block was similar between groups (p=0.62). During a mean follow-up of 621.4±334.5 months, Cardioverter Defibrillator implantation rates were comparable between IN and FAM cases (11.5% vs 10.7%, p=0.86). Implantable loop recorders were more frequently used in IN patients (19.5% vs 8.7%, p=0.018). Rates of syncope (3.5%), ventricular arrhythmias (0.9%), and mortality (0.9%) were low and did not differ between groups.
Conclusions
In non-spontaneous BrS, IN and FAM cases may be associated with distinct demographic and electrocardiographic profiles. Further validation in larger cohorts is warranted to confirm these findings.For image description, please refer to the figure legend and surrounding text.