遗传易感性如何影响房颤消融的有效性？

摘要(中文译文)

心房颤动（AF）是一种常见的心律失常，越来越多地采用导管消融治疗，但复发率仍然很高。遗传因素对房颤易感性和治疗反应均有影响。本综述总结了常见房颤相关变异、多基因风险评分和罕见单基因变异如何影响消融结果的证据。PITX2附近的4q25和ZFHX3内的16q22等位点的常见单核苷酸多态性易患房颤，但它们对消融成功的个体影响不大。多基因风险评分汇总了许多变体的小影响，并与心房传导异常和消融后更高的复发率有关，尽管它们尚未在临床实践中常规使用。在早发性或家族性房颤中，心肌病基因的致病性变异（如TTN）可能会导致心房心肌病，但不一定排除成功的消融，而LMNA突变与广泛的纤维化和不良预后有关。遗传变异影响心房电和结构重塑、异位触发分布、纤维化和自主神经张力，所有这些都会影响消融疗效。目前的指南不建议对大多数患者进行常规基因检测；然而，基因分型可以为选定人群的风险分层和随访提供信息。未来的工作应将多基因评分与临床危险因素相结合，探索基因型指导的手术策略和辅助治疗。我们还探讨了遗传易感性与血栓栓塞风险之间的关系，肥胖及其遗传决定因素与房颤永久性之间的相互作用，以及消融方式（射频、冷冻球囊和脉冲场消融）如何与遗传决定的底物相互作用。一种提出的临床算法将遗传评估集成到消融途径中。

Abstract

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia treated increasingly with catheter ablation, yet recurrence rates remain high. Genetic factors contribute to both AF susceptibility and response to therapy. This review summarizes evidence on how common AF-associated variants, polygenic risk scores, and rare monogenic variants influence ablation outcomes. Common single-nucleotide polymorphisms at loci such as 4q25 near PITX2 and 16q22 within ZFHX3 predispose to AF, but their individual effects on ablation success are modest. Polygenic risk scores aggregate small effects across many variants and have been linked to atrial conduction abnormalities and higher post-ablation recurrence, although they are not yet used routinely in clinical practice. In early-onset or familial AF, pathogenic variants in cardiomyopathy genes (eg, TTN) may create an atrial cardiomyopathy yet do not necessarily preclude successful ablation, whereas LMNA mutations are associated with extensive fibrosis and poor outcomes. Genetic variation affects atrial electrical and structural remodeling, ectopic trigger distribution, fibrosis, and autonomic tone, all of which influence ablation efficacy. Current guidelines do not recommend routine genetic testing for most patients; however, genotyping may inform risk stratification and follow-up in selected populations. Future work should integrate polygenic scores with clinical risk factors and explore genotype-guided procedural strategies and adjunctive therapies. We additionally address the relationship between genetic susceptibility and thromboembolic risk; the interplay among obesity, its genetic determinants, and AF perpetuation; and how ablation modalities (radiofrequency, cryoballoon, and pulsed-field ablation) may interact with a genetically determined substrate. A proposed clinical algorithm integrates genetic evaluation into the ablation pathway.

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