Exercise testing in Brugada syndrome as a risk-stratification tool

Introduction Brugada Syndrome (BrS) is genetic disorder linked to ventricular arrythmias (VAs) and sudden cardiac death (SCD). Events often take place in situations of enhanced vagal tone, though adrenergically driven events have been reported. The precise role of exercise in the arrhythmogenicity of BrS is poorly understood. Existing evidence on its risks is limited, often stemming from case reports. The objective of this study was to explore the role of exercise testing (ET) in risk stratification of BrS. Methodology BrS (diagnosed as per guidelines) patients followed up at a tertiary centre were included. All patients underwent a maximal ET, with the chest leads placed in a high precordial position as previously described. Demographic, clinical, genotype (SCN5A) and outcome data was recorded. An abnormal ET included those patients with i) new (≥0.2mV) or augmented ST segment elevation in the precordial leads (exercise and/or recovery) seen in at least 3 consecutive beats and/or ii) VAs. Adverse outcome were defined as a composite endpoint comprising of device implantation, aborted cardiac arrest (CA) and/or death. Results The total cohort consisted of 111 individual (59.5% male, 44±17 years at diagnosis, 61.3% probands, 62 families, 10.8% athletes, median Shanghai Score 4 [IQR 4-5], 607 patient-years of follow-up, 16.1% SCN5A positive). Most (n=66, 59.5%) had an ajmaline provoked Type 1 Brugada pattern (in the context of a family history of BrS and/or arrhythmic syncope), followed by a spontaneous Type 1 pattern (n=37, 33.3%) and fever provoked (n=8, 7.2%) BrS ECG. 48 (43.2%) reported symptoms (24.3% syncope, 27.9% palpitations). A minority (n=8, 7.2%) reported marijuana use. A family history of SCD was frequently observed (n=36, 32.4%). A VT study was performed in 20 individuals (18.0%). 17 (15.3%) reached the composite endpoint (n=1 aborted CA, n=12 ICD for cardiogenic syncope, n=3 ICD for +ve VT study, n=1 PM for AVB). Th event rate was similar in both genders, irrespective of method of presentation (spontaneous vs drug / fever provoked ), ECG findings (HR, AVB, QRSD, ER, QRSF, LQRSV, TWI) and SCN5A genotype. A third had an abnormal ET (n=35, 31.8%). Denovo or augmented ST segment elevation was observed in 28 (25.2%) individuals. VAs were present in 13 (11.7%). Repolarisation changes and VAs during ET were associated with the composite endpoint, regardless of whether they occurred during exercise (p=0.011) or recovery (p=0.033). These phenomena were significant in males (p=0.006 [exertion] and p=0.026 [recovery]) but not in females, independent of SCN5A genotype. Conclusion A significant proportion of BrS patient developed ST segment changes or VAs during ET. These changes observed during exercise and/or recovery were significantly associated with adverse outcomes, suggesting that ET may contribute to risk stratification in BrS. Larger, longitudinal studies are warranted to validate this hypothesis.