Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome

作者：Amin Ahmad S; Boink Gerard J J; Atrafi Florence; Spanjaart Anne M; Asghari Roodsari Alaleh; Molenaar Remco J; Ruijter Jan M; Wilde Arthur A M; Tan Hanno L^*

来源：Europace, 2011, 13(7): 968-975.

DOI：10.1093/europace/eur011

• Atrial fibrillation
• Brugada syndrome
• SCN5A
• Sodium channel
• Conduction
• Excitability

Aims Brugada syndrome (BrS) is associated with increased risk for atrial fibrillation (AFib). However, the role of SCN5A mutations in the occurrence of AFib remains unclear. Cardiac sodium current reduction caused by SCN5A mutations may facilitate AFib by slowing intra-atrial conduction and inducing structural changes, but also prevent it by suppressing atrial ectopic activity. Here, we examined the relation between SCN5A mutations, atrial conduction velocity, atrial structural changes, and atrial ectopic activity in BrS.
Methods and results Data from 214 BrS patients [78 with an SCN5A mutation (patients with an SCN5A mutation, BrS(SCN5A+)) and 136 without an SCN5A mutation (patients without an SCN5A mutation, BrS(SCN5A-))] were collected. Intra-atrial conduction velocity was assessed by measuring P-wave durations at baseline and during sodium channel provocation testing. Atrial structural changes were assessed by measuring atrial dimensions using cardiac magnetic resonance imaging. Atrial ectopic activity was assessed by determining the incidence of atrial ectopic beats using 24 h Holter recordings. Clinical characteristics (including AFib occurrence) did not differ between BrS(SCN5A+) and BrS(SCN5A-). Baseline P-wave durations were longer in BrS(SCN5A+) than in BrS(SCN5A-), but lengthened markedly in BrS(SCN5A-) during provocation testing. Atrial dimensions did not differ. Atrial ectopic beats occurred more often in BrS(SCN5A-), and the proportion of patients experiencing one or more atrial ectopic beats was larger in BrS(SCN5A-) than in BrS(SCN5A+).
Conclusion In BrS, the presence of an SCN5A mutation is associated with intra-atrial conduction slowing and suppressed atrial ectopic activity. Intra-atrial conduction slowing may provide a plausible substrate for AFib maintenance, while reduced atrial ectopic activity may constitute inhibition of the trigger for AFib initiation.

• 出版日期2011-7