Brugada syndrome and atrial fibrillation: pathophysiology and genetics

Abstract

In 1992, the Brugada brothers described eight patients with a syndrome of ST segment elevation in electrocardiogram (ECG) leads V1–V3 accompanied by a right bundle branch block appearance and the risk of ventricular fibrillation and sudden cardiac death.1 One patient was an 8-year-old girl with an additional history of paroxysmal atrial fibrillation (AF). She had experienced her first paroxysm soon after birth while her first episode of syncope occurred at 8 years of age. Since this first description a dramatic variability in clinical presentation of the disease has transpired. A high prevalence of AF has, however, remained a feature.2 The first gene linked to the Brugada syndrome was SCN5A, which encodes the α-subunit of the NaV1.5 cardiac sodium channel responsible for the inward sodium current. A 20% yield of disease-associated variants has consistently been reported.2 More recently less common mutations in other genes have been associated with the Brugada syndrome including mutations in: GPD1L, involved in the transportation of cardiac sodium channels to the cell membrane; SCN1B and SCN3B, encoding β-subunits of NaV1.5; KCNE3 encoding a β-subunit of the channel responsible for the I (to) current; and CACNA1C and CACNB2b, which both encode subunits of the L-type calcium channel.3 Mutations in SCN5A have also been reported in association with familial AF.4 The prevalence of AF and atrial flutter in patients with Brugada syndrome is approximately 20%2 compared with 2.3% in the general population above the age of 40.5 Kusano et al . found that 70% of episodes of AF in their Brugada patients occurred at night, suggesting that nocturnal vagal activity and withdrawal of sympathetic activity may play an important role in arrhythmogenesis. Bradycardia …