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

Europace. 2011 Jul;13(7):968-75. doi: 10.1093/europace/eur011. Epub 2011 Jan 26.


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, BrSSCN5A+) and 136 without an SCN5A mutation (patients without an SCN5A mutation, BrSSCN5A-)] 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 BrSSCN5A+ and BrSSCN5A-. Baseline P-wave durations were longer in BrSSCN5A+ than in BrSSCN5A-, but lengthened markedly in BrSSCN5A- during provocation testing. Atrial dimensions did not differ. Atrial ectopic beats occurred more often in BrSSCN5A-, and the proportion of patients experiencing one or more atrial ectopic beats was larger in BrSSCN5A- than in BrSSCN5A+.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrial Fibrillation / epidemiology*
  • Atrial Fibrillation / physiopathology
  • Brugada Syndrome / complications*
  • Brugada Syndrome / genetics*
  • Brugada Syndrome / physiopathology
  • Case-Control Studies
  • Electrocardiography
  • Electrocardiography, Ambulatory
  • Female
  • Heart Atria / pathology
  • Heart Atria / physiopathology
  • Heart Conduction System / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation / genetics*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Retrospective Studies
  • Risk Factors
  • Sodium Channels / genetics*


  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels