The SCN5A R558 allele, present in one-third of the population, thus constitutes a risk factor for lone AF and may increase susceptibility to sodium channel blocker-induced proarrhythmia.
In view of the pleiotropic effects of SCN5A mutations, the purpose of this study was to examine a cohort of patients with familial atrial fibrillation (AF) for mutations in the SCN5A gene.
The purpose of this study was to describe the first family associating LQT-3 and AF due to a gain-of-function mutation in SCN5A and assess the usefulness of the sodium blocker flecainide in individuals with both phenotypes.
We describe the development of a Brugada ECG together with sinus- and ventricular arrest after intravenous flecainide for atrial fibrillation in a patient in whom eventually a SCN5a mutation was identified.
Furthermore, several of the arrhythmogenic diseases, such as long-QT syndrome, Brugada syndrome, and AF, reported to be associated with mutations in SCN5A, are thoroughly described.
Screening of SCN5A-the gene encoding the α-subunit of the cardiac sodium channel-has indicated that disturbances of the sodium current may play a central role in the mechanism of lone AF.
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.
Variations in the gene encoding for the major sodium channel (Na(v)1.5) in the heart, SCN5A, has been shown to cause a number of arrhythmia syndromes (with or without structural changes in the myocardium), including the long-QT syndrome (type 3), Brugada syndrome, (progressive) cardiac conduction disease, sinus node dysfunction, atrial fibrillation, atrial standstill, and dilated cardiomyopathy.
Of 15 SCN5A mutation carriers in our study, 14 (93%) manifested arrhythmia: supraventricular arrhythmia (13 of 15), including sick sinus syndrome (5 of 15) and atrial fibrillation (9 of 15), ventricular tachycardia (5 of 15), and conduction disease (9 of 15).