Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation

• Published in: PloS one Vol. 12; no. 8; p. e0183690
• Main Authors: Husser, Daniela, Ueberham, Laura, Hindricks, Gerhard, Büttner, Petra, Ingram, Christie, Weeke, Peter, Shoemaker, M. Benjamin, Adams, Volker, Arya, Arash, Sommer, Philipp, Darbar, Dawood, Roden, Dan M., Bollmann, Andreas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.08.2017; Public Library of Science (PLoS)
• Subjects: Ablation; Analysis; Atrial fibrillation; Atrial Fibrillation - surgery; Biology and Life Sciences; Cardiac arrhythmia; Care and treatment; Catheter ablation; Catheter Ablation - methods; Catheters; Current carriers; EKG; Fibrillation; Genes; Genetic screening; Genetic variation; Health aspects; Heart; Heart diseases; Humans; Impact analysis; Medical instruments; Medicine and Health Sciences; Mutation; Myocardium - metabolism; Patient outcomes; Physical Sciences; Physiological aspects; Radio frequency; Radiofrequency ablation; Research and Analysis Methods; Rhythm; Sodium; Sodium Channels - genetics; Treatment Outcome; Germany; United States > US; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183690

Rare variants of genes encoding the cardiac sodium channel and associated compounds have been linked with atrial fibrillation (AF). Nevertheless, current expert consensus does not support genetic testing in AF, which is in part based on the fact that "there is no therapeutic impact derived from AF genetic test results". However, there are no studies available supporting this recommendation. Consequently, this study analyzed the impact of rare variants affecting the cardiac sodium channel on rhythm outcome of AF catheter ablation. In 137 consecutive patients with lone AF enrolled in the Leipzig Heart Center AF ablation registry, screening for mutations in SCN5A, SCN1B - 4B, CAV3, GPD1L, SNTA1 and MOG1 was performed. We identified 3 rare non-synonymous variants in SCN5A, 5 in SCN1B, 1 in SCN4B, 1 in CAV3, 6 in GPD1L, 3 in SNTA1 and 3 in MOG1 (16%). Variant carriers were otherwise comparable with non-variant carriers. Analysis of AF recurrence rates after radiofrequency AF catheter ablation by serial 7-day Holter ECG monitoring between 3 and 12 months revealed no difference between groups, i.e. 45% in variant carriers vs. 49% in non-variant carriers. Rare variants in genes encoding the cardiac sodium channel and associated compounds are frequently found in lone AF but were not found to impact the outcome of AF catheter ablation. This finding supports current recommendations not to screen for rare variants for the ablation outcome in AF. Nevertheless, it may at least be helpful for understanding AF mechanisms and larger studies are needed to further explore the possible association between genotype and response to AF therapies.