Majd A El-Harasis, Zachary T Yoneda, Katherine C Anderson, Fei Ye, Joseph A Quintana, J Roberto Martinez-Parachini, Gregory G Jackson, Bibin T Varghese, Diane M Crawford, Lili Sun, Hollie L Williams, Matthew J O'Neill, Giovanni E Davogustto, James L Laws, Brittany S Murphy, Kelsey Tomasek, Yan Ru Su, Emily McQuillen, Emma Metz, Carly Smith, Doug Stubbs, Dakota D Grauherr, Quinn S Wells, Gregory F Michaud, Pablo Saavedra, Juan Carlos Estrada, Travis D Richardson, Sharon T Shen, Arvindh N Kanagasundram, Jay A Montgomery, Harikrishna Tandri, Christopher R Ellis, George H Crossley, Prince J Kannankeril, Lynne W Stevenson, William G Stevenson, Steven A Lubitz, Patrick T Ellinor, Dan M Roden, M Benjamin Shoemaker
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The efficacy of AF ablation in these patients is unknown.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14573,"journal":{"name":"JACC. 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引用次数: 0
摘要
背景:罕见的致病性心肌病(CM)和心律失常变异患者可能会出现心房颤动(AF)。这些患者的房颤消融疗效尚不清楚:本研究测试了以下假设1) 任何 CM 或心律失常基因中存在致病变异的患者在房颤消融术后复发率都会增加;以及 2) 与特定基因组(致心律失常左心室 CM [ALVC]、致心律失常右心室 CM、扩张型 CM、肥厚型 CM 或通道病)相关的致病变异患者复发率都会增加:我们对接受房颤导管消融术和全外显子组测序的患者进行了一项前瞻性、观察性、队列研究。主要结果指标是在90天空白期后发生≥30秒的任何房性快速心律失常:在1366名参与者中,109人(8.0%)的CM或心律失常基因存在致病或可能致病(P/LP)变异。在多变量分析中,任何基因中出现 P/LP 变异与复发均无明显关系(HR 1.15;95% CI 0.84-1.60;P = 0.53)。与致心律失常右室CM、扩张型CM、肥厚型CM和通道病变基因组相比,ALVC基因组(主要是LMNA)中的P/LP变异与复发率升高有关(n = 10;HR 3.75;95% CI 1.84-7.63;P < 0.001)。与基因型阴性对照组相比,P/LP TTN 变体参与者(n = 46)的复发率没有差异(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具有罕见致病性 CM 或心律失常变异(包括 TTN)的患者使用房颤消融术。然而,ALVC 变异(如 LMNA)患者的心律失常复发风险可能明显更高。
Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes.
Background: 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.
Objective: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
期刊介绍:
JACC: Clinical Electrophysiology is one of a family of specialist journals launched by the renowned Journal of the American College of Cardiology (JACC). It encompasses all aspects of the epidemiology, pathogenesis, diagnosis and treatment of cardiac arrhythmias. Submissions of original research and state-of-the-art reviews from cardiology, cardiovascular surgery, neurology, outcomes research, and related fields are encouraged. Experimental and preclinical work that directly relates to diagnostic or therapeutic interventions are also encouraged. In general, case reports will not be considered for publication.