1Universitätsklinikum Mannheim I. Medizinische Klinik Mannheim, Deutschland; 2Universitätsklinikum Mannheim Med. Klinik IV Mannheim, Deutschland
Background:
Brugada syndrome (BrS) is a cardiac channelopathy associated with increased risk of sudden cardiac death (SCD) in typically young and otherwise healthy population. BrS is defined by its typical ST-elevation and repolarization abnormalities in right precordial electrocardiogram (ECG) leads. Clinical manifestation typically occurs in young adulthood, predominantly affecting men. Ventricular tachyarrhythmias (VTA) are frequently the initial manifestation of the disease. However, syncope or survived SCD due to documented VTA can also occur. Risk stratification becomes crucial as many patients diagnosed with BrS are asymptomatic at the time of diagnosis due to heightened awareness.
Objective:
This study analyzes clinical parameters of a large single-center cohort of BrS probands and affected family members to assess the risk of VTA and SCD during a long-term follow-up.
Methods:
All consecutive patients diagnosed with BrS between 1998 and 2023 were prospectively enrolled in the University Medical Center Mannheim BrS registry. Diagnosis was established in presence of spontaneous diagnostic ECG, drug-induced type 1-ECG and clinical symptoms or positive family history for BrS. Patients were divided in 3 subsets at the time of initial diagnosis: (i) BrS patients with definitive survived SCA/VTA (group 1), (ii) BrS patients with syncope (group 2), (iii) asymptomatic BrS patients (group 3). The occurrence of symptoms was assessed at each date of follow-up.
Results:
317 patients were included in the study. Of those, 26 patients (80 % male, mean age 37±8 years) with survived SCA comprised group 1 (G1). Group 2 (G2) included 79 patients (62 % male, mean age of 42±12,95 years) who experienced syncopal events and group 3 (G3) consisted of 212 asymptomatic BrS patients (63 % male, mean age 40±15,7 years). Median follow-up was 82 months (IQR 118). Type 1 ECG was observed in 26.9 % of cases in G1, as compared to 21.5 % in G2 and 23.4 % G3 (P=0.827) and was more common in patients with documented VTA. EPS was performed in 153 patients (42.3 % G1, 72.2 % G2, 40.1 % G3) and VF was inducible in 76 cases (55 % G1, 42 % G2 and 54 % G3). The distribution of inducibility did not statistically differ among the groups (P=0.65). Pathogenic or likely pathogenic variants were found in 107 patients. Variants in the SCN5A gene were most common (68 %), without statistically significant difference among the groups (P=0.4). 128 patients received an implantable cardioverter-defibrillator (ICD), 100 % G1, 62 % G2 and 25 % G3. During follow-up, a total of 21 arrhythmic events occurred: 38 % in G1, 9 % in G2, 2 % G3 (P<0.001). The annual risk of VTA was 0.74 % for all patients, 5.73 % in G1, 0.73 % in G2, and 0.1 % in G3 (P=0.002).
Conclusion:
Risk stratification in BrS remains complex. In our cohort of patients, spontaneous type-1 ECG and male sex showed to be important risk markers in BrS patients. However, up to one fourth of asymptomatic patients had spontaneous type 1 ECG at the time of diagnosis. Survived SCA and documented VTA were significant predictors for future cardiac events. Identification of asymptomatic patients with increased risk for VTA and SCD continues to be the holy grail of risk stratification in BrS.