Study population
From 1999 to 2020, a total of 138 consecutive patients with type-1 BrS were included and followed-up prospectively at Instituto do Coração, Faculdade de Medicina, Universidade de Sao Paulo, in Brazil.
All the patients signed an informed consent to the study, which was conducted in accordance with the Declaration of Helsinki and had the approval of our Institutional Review Board (Protocol #404214022).
A governmental funding (FAPESP) provided financial support for the genetic testing. A multicenter national survey on Inherited Channelopathy and Right Ventricular Cardiomyopathy was organized to provide genetic testing for patients from our and other institutions (Genetic of Brazilian Arrhythmias - GenBrA registry). All patients signed specific consent forms for genetic testing.
Patients were considered eligible if they presented with ST-segment elevation with type-1 morphology ≥2 mm in one or more standard precordial leads (SPL), V1 and/or V2 in the fourth intercostal space or high precordial leads (HPL), V1 and/or V2 in the second and third intercostal space, occurring either spontaneously or after provocative drug test with intravenous administration of sodium channel blockers (Ajmaline), according to the 2015 BrS Consensus.1
Subjects were classified into two groups: symptomatic (22 subjects) or asymptomatic (116 subjects), according to symptoms at the initial visit to the hospital. Symptoms were considered in cases of aborted SCD (9 subjects) or severe syncope (13 subjects). Severe syncope, presumably considered to be of arrhythmic origin, was defined as an abrupt loss of consciousness occurring without specific prodromes, syncope with seizures or a loss of consciousness during sleep with nocturnal agonal respiration. Asymptomatic group included all patients who had a non-phenocopy type-1 ECG pattern during routine examination or who underwent family screening. Seven patients were initially classified as symptomatic, but a vasovagal mechanism was evidenced during follow-up and then they were allocated in the asymptomatic group.
Baseline characteristics were obtained by periodic medical visits. The clinical variables of interest were age, gender, self-declared race, proband status, spontaneous or induced type-1 Brugada ECG pattern and clinical presentation at first diagnosis (symptomatic versus asymptomatic). A family history of early SCD was defined as an unexpected death before 45 years of age in the absence of known heart disease.
The following ECG parameters were accessed: PR and QRS intervals, early repolarization pattern in peripheral leads. Right ventricular outflow tract conduction delay (RVOTcd) signs were tested, including QRS fragmentation (QRS-f), aVR sign and deep S wave in lead 1. The PR and QRS intervals were measured in lead II and QRS duration was also measured in lead V2.9 QRS fragmentation was defined as 2 or more spikes within the QRS complex in leads V1 to V3.10 A positive aVR sign was defined with R wave ≥ 3mm or R/q ≥ 0.75, and a deep S wave in lead DI was considered if >0.1mV and/or duration > 40ms (Figure 1).11-13 The ECG was reviewed by L.S. and F.D. to ensure the presence of a type-1 ECG and to define de ECG parameters. Occasional disagreements were solved by consensus.
All the patients underwent exercise stress testing, transthoracic echocardiogram, and most underwent electrophysiology test. Cardiac magnetic resonance imaging, coronary angiography and cardiac tomography were performed according to medical judgement.
Follow-up visits were scheduled every 6 months. Follow-up time was defined from the first diagnostic ECG to the last evaluation or death. Patients were considered to have life-threatening arrhythmic events (LAE) if they presented with sustained VT/FV, aborted SCD and appropriate ICD therapies during the follow-up period (8 subjects).