Rare Cardiac Genetic Variation Is Associated With Postoperative Atrial Fibrillation.

IF 6.1 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Genomic and Precision Medicine Pub Date : 2026-09-30 DOI:10.1161/CIRCGEN.125.005688

Zhanlin Chen, Anirudha S Chandrabhatla, Anna Pfenniger, Tom Liu, Patrick M McCarthy, James L Cox, Stephen F Chiu, Rod Passman, Philip Greenland, Adam Gordon, S Chris Malaisrie, Gregory Webster

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引用次数: 0

Abstract

Background: New-onset postoperative atrial fibrillation (POAF) is a common surgical complication, yet the contribution of rare genetic variants to POAF is poorly characterized.

Methods: We conducted a cohort study including 49 913 adults who underwent surgery without a preoperative diagnosis of atrial fibrillation (AF). All participants had whole-genome sequencing linked to electronic health record data. Pathogenic or likely pathogenic (LP) variants were identified in 141 cardiac genes associated with early-onset AF. The primary outcome was POAF, defined as a new diagnosis of AF within 30 days of surgery; the secondary outcome was freedom from AF over 5 years. Multivariable regression and propensity-score matching were used to evaluate the associations between pathogenic/LP variants and POAF.

Results: Among 49 913 participants, 2298 underwent cardiac surgery and 47 615 underwent noncardiac surgery. The prevalence of pathogenic/LP variants was 6.0% in the cardiac surgery group (138/2298) and 4.1% in the noncardiac surgery group (1947/47 615). Overall, carriers of ≥1 pathogenic/LP variant had higher odds of POAF than noncarriers (6.6% versus 4.0%; odds ratio [OR], 1.8 [95% CI, 1.4-2.1]). In cardiac surgery, 36.0% of pathogenic/LP carriers (78/216) developed POAF versus 23.4% of noncarriers (492/2082; OR, 2.3 [95% CI, 1.4-3.2]), and in noncardiac surgery, POAF occurred in 3.8% of carriers (74/1947) versus 2.5% of noncarriers (1465/45 668; OR, 1.5 [95% CI, 1.2-1.9]). Pathogenic/LP variants in cardiomyopathy-only genes (n=589; OR, 1.8 [95% CI, 1.3-2.6]) or in genes associated with both cardiomyopathy and arrhythmia (n=1059; OR, 1.8 [95% CI, 1.4-2.3]) were significantly associated with POAF, whereas variants in arrhythmia-only genes (n=454; OR, 1.3 [95% CI, 0.8-2.1]) were not. Five-year freedom from AF was lower among pathogenic/LP variant carriers in both cardiac surgery (53% versus 64%; P=0.010) and noncardiac surgery (92% versus 94%; P=0.002).

Conclusions: Rare pathogenic/LP variants in cardiomyopathy genes were associated with risk of POAF and reduced AF-free survival over long-term follow-up across cardiac and noncardiac surgery.

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罕见的心脏遗传变异与术后心房颤动有关。

背景：术后新发心房颤动（POAF）是一种常见的外科并发症，然而罕见的基因变异对POAF的影响尚不清楚。方法：我们进行了一项队列研究，包括49913名术前未诊断为房颤（AF）的成年人。所有参与者都进行了与电子健康记录数据相关的全基因组测序。在141个与早发性房颤相关的心脏基因中鉴定出致病性或可能致病性（LP）变异。主要结局为POAF，定义为手术后30天内新诊断为房颤；次要终点是5年内无房颤。采用多变量回归和倾向评分匹配来评估致病性/LP变异与POAF之间的关系。结果：在49913名参与者中，2298人接受了心脏手术，47615人接受了非心脏手术。致病性/LP变异的患病率在心脏手术组为6.0%(138/2298)，在非心脏手术组为4.1%（1947/47 615）。总体而言，携带≥1个致病/LP变异的人患POAF的几率高于非携带者（6.6%比4.0%；比值比[OR]为1.8 [95% CI, 1.4-2.1]）。在心脏手术中，36.0%的致病/LP携带者（78/216）发生POAF，非携带者为23.4% (492/2082；OR, 2.3 [95% CI, 1.4-3.2])，在非心脏手术中，POAF发生在3.8%的携带者（74/1947）和2.5%的非携带者（1465/ 445668；OR, 1.5 [95% CI, 1.2-1.9]）。仅心肌病基因（n=589； OR, 1.8 [95% CI, 1.3-2.6]）或同时与心肌病和心律失常相关的基因（n=1059； OR, 1.8 [95% CI, 1.4-2.3]）的致病/LP变异与POAF显著相关，而仅心肌病基因的变异（n=454； OR, 1.3 [95% CI, 0.8-2.1]）与POAF无关。在心脏手术和非心脏手术中，致病/LP变异携带者的5年房颤自由度均较低（53%对64%，P=0.010）（92%对94%，P=0.002）。结论：在心脏和非心脏手术的长期随访中，心肌病基因中罕见的致病/LP变异与POAF的风险和af无生存期降低相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

9.20

自引率

5.40%

发文量

144

期刊介绍： Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.