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

AimRare 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.Methods and resultsIn 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.ConclusionsRare 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.

研究目的：编码心脏钠通道（cardiac sodium channel）的基因及其相关复合物的罕见变异与心房颤动（atrial fibrillation，AF）相关。尽管如此，当前的专家共识并不支持对AF患者开展基因检测，该推荐的部分依据为“AF基因检测结果无法带来治疗获益”，但目前尚无研究支持这一推荐意见。因此，本研究探讨了影响心脏钠通道的罕见变异对AF导管消融术后节律结局的影响。

方法与结果
本研究纳入莱比锡心脏中心AF消融注册研究中的137例连续性孤立性心房颤动（lone AF）患者，对其SCN5A、SCN1B~SCN4B、CAV3、GPD1L、SNTA1及MOG1基因的突变进行筛查。本研究共检出3个SCN5A基因罕见非同义变异（non-synonymous variants）、5个SCN1B基因罕见变异、1个SCN4B基因罕见变异、1个CAV3基因罕见变异、6个GPD1L基因罕见变异、3个SNTA1基因罕见变异及3个MOG1基因罕见变异，总检出率为16%。变异携带者与非变异携带者的基线特征无显著差异。通过术后3~12个月期间连续7天动态心电图（Holter electrocardiogram, Holter ECG）监测，分析射频AF导管消融（radiofrequency AF catheter ablation）术后的AF复发率，结果显示两组复发率无显著差异：变异携带者组复发率为45%，非变异携带者组为49%。

结论
编码心脏钠通道的基因及其相关复合物的罕见变异在孤立性心房颤动患者中检出率较高，但未发现其对AF导管消融结局存在影响。该研究结果支持当前“无需为评估AF导管消融结局而筛查罕见变异”的推荐意见。尽管如此，该发现至少有助于阐明AF的发病机制，未来仍需开展更大样本量的研究，以进一步探讨基因型与AF治疗应答之间的潜在关联。