Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Statistics, Vanderbilt University, Nashville, Tennessee, USA.
JACC Clin Electrophysiol. 2024 Nov;10(11):2359-2370. doi: 10.1016/j.jacep.2024.06.035. Epub 2024 Sep 4.
Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF). The efficacy of AF ablation in these patients is unknown.
This study tested the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have increased recurrence following AF ablation; and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, or a channelopathy) have increased recurrence.
We performed a prospective, observational, cohort study of patients who underwent AF catheter ablation and whole exome sequencing. The primary outcome measure was ≥30 seconds of any atrial tachyarrhythmia that occurred after a 90-day blanking period.
Among 1,366 participants, 109 (8.0%) had a pathogenic or likely pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, the presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15; 95% CI 0.84-1.60; P = 0.53). P/LP variants in the ALVC gene group, predominantly LMNA, were associated with increased recurrence (n = 10; HR 3.75; 95% CI 1.84-7.63; P < 0.001), compared with those in the arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, and channelopathy gene groups. Participants with P/LP TTN variants (n = 46) had no difference in recurrence compared with genotype-negative-controls (HR 0.93; 95% CI 0.54-1.59; P = 0.78).
Our results support the use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN. However, patients with ALVC variants, such as LMNA, may be at a significantly higher risk for arrhythmia recurrence.
患有罕见致病性心肌病（CM）和心律失常变异的患者可能会出现心房颤动（AF）。这些患者的 AF 消融疗效尚不清楚。
本研究检验了以下假设：1）任何 CM 或心律失常基因的致病性变异患者，AF 消融后复发率增加；2）具有特定基因组（致心律失常性左心室 CM [ALVC]、致心律失常性右心室 CM、扩张型 CM、肥厚型 CM 或通道病）相关的致病性变异患者，复发率增加。
我们对接受 AF 导管消融和全外显子组测序的患者进行了前瞻性、观察性、队列研究。主要观察指标是在 90 天空白期后出现任何 30 秒以上的心房性心动过速。
在 1366 名参与者中，有 109 名（8.0%）在 CM 或心律失常基因中存在致病性或可能致病性（P/LP）变异。多变量分析显示，任何基因的 P/LP 变异与复发无显著相关性（HR 1.15；95%CI 0.84-1.60；P=0.53）。以 LMNA 为主的 ALVC 基因组的 P/LP 变异与复发增加相关（n=10；HR 3.75；95%CI 1.84-7.63；P<0.001），与致心律失常性右心室 CM、扩张型 CM、肥厚型 CM 和通道病基因组相比。与基因型阴性对照相比，P/LP TTN 变异患者（n=46）的复发率无差异（HR 0.93；95%CI 0.54-1.59；P=0.78）。
我们的研究结果支持对大多数患有罕见致病性 CM 或心律失常变异的患者（包括 TTN）进行 AF 消融。然而，具有 ALVC 变异（如 LMNA）的患者心律失常复发的风险可能显著增加。
