Genetics of atrial fibrillation-practical applications for clinical management: if not now, when and how?
Genetics of atrial fibrillation-practical applications for clinical management: if not now, when and how?
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DOI：
10.1093/cvr/cvab153
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发表时间：
2021-06-16
影响因子：
10.8
通讯作者：
Schnabel RB
中科院分区：
文献类型：
--
作者：
Kany S;Reissmann B;Metzner A;Kirchhof P;Darbar D;Schnabel RB
预计在未来几十年内，房颤（AF）的患病率和经济负担将增加一倍以上。除了抗凝和治疗伴随的心血管疾病外，与心率控制方法相比，早期和标准化的心律控制治疗可减少心血管结局，有利于安全地恢复和维持窦性心律。目前控制房颤节律的疗法包括抗心律失常药物（AAD）和导管消融（CA）。然而，个体患者的反应是高度可变的，一些患者在抗心律失常治疗的长时间内保持无AF，而另一些患者需要在数周内重复AF消融。房颤节律控制治疗的有限成功部分与对病理生理机制的不完全理解以及我们无法预测个体患者的反应有关。因此，一个主要的知识缺口是预测哪些房颤患者可能对节律控制方法有反应。在过去的十年中，在确定AF的遗传结构方面取得了巨大的进展，确定了与家族性（早发性）AF相关的心脏离子通道、信号分子和心肌结构蛋白的罕见突变。相反，全基因组关联研究已经确定了100多个遗传基因座的常见变异，多基因风险评分的发展已经确定了高风险个体。尽管回顾性研究表明，对AAD和CA的反应部分受到常见遗传变异的调节，但开发综合临床和遗传风险评分可能会将遗传数据转化为AF患者的床边护理。鉴于房颤流行的经济影响，即使治疗效果的微小变化也可能导致患者和医疗保健系统的实质性改善。
The prevalence and economic burden of atrial fibrillation (AF) are predicted to more than double over the next few decades. In addition to anticoagulation and treatment of concomitant cardiovascular conditions, early and standardized rhythm control therapy reduces cardiovascular outcomes as compared with a rate control approach, favouring the restoration, and maintenance of sinus rhythm safely. Current therapies for rhythm control of AF include antiarrhythmic drugs (AADs) and catheter ablation (CA). However, response in an individual patient is highly variable with some remaining free of AF for long periods on antiarrhythmic therapy, while others require repeat AF ablation within weeks. The limited success of rhythm control therapy for AF is in part related to incomplete understanding of the pathophysiological mechanisms and our inability to predict responses in individual patients. Thus, a major knowledge gap is predicting which patients with AF are likely to respond to rhythm control approach. Over the last decade, tremendous progress has been made in defining the genetic architecture of AF with the identification of rare mutations in cardiac ion channels, signalling molecules, and myocardial structural proteins associated with familial (early-onset) AF. Conversely, genome-wide association studies have identified common variants at over 100 genetic loci and the development of polygenic risk scores has identified high-risk individuals. Although retrospective studies suggest that response to AADs and CA is modulated in part by common genetic variation, the development of a comprehensive clinical and genetic risk score may enable the translation of genetic data to the bedside care of AF patients. Given the economic impact of the AF epidemic, even small changes in therapeutic efficacy may lead to substantial improvements for patients and health care systems.
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影响因子：
30.8
作者：
Ellinor, Patrick T.;Lunetta, Kathryn L.;Glazer, Nicole L.;Pfeufer, Arne;Alonso, Alvaro;Chung, Mina K.;Sinner, Moritz F.;de Bakker, Paul I. W.;Mueller, Martina;Lubitz, Steven A.;Fox, Ervin;Darbar, Dawood;Smith, Nicholas L.;Smith, Jonathan D.;Schnabel, Renate B.;Soliman, Elsayed Z.;Rice, Kenneth M.;Van Wagoner, David R.;Beckmann, Britt-M;van Noord, Charlotte;Wang, Ke;Ehret, Georg B.;Rotter, Jerome I.;Hazen, Stanley L.;Steinbeck, Gerhard;Smith, Albert V.;Launer, Lenore J.;Harris, Tamara B.;Makino, Seiko;Nelis, Mari;Milan, David J.;Perz, Siegfried;Esko, Tonu;Koettgen, Anna;Moebus, Susanne;Newton-Cheh, Christopher;Li, Man;Moehlenkamp, Stefan;Wang, Thomas J.;Kao, W. H. Linda;Vasan, Ramachandran S.;Noethen, Markus M.;MacRae, Calum A.;Stricker, Bruno H. Ch;Hofman, Albert;Uitterlinden, Andre G.;Levy, Daniel;Boerwinkle, Eric;Metspalu, Andres;Topol, Eric J.;Chakravarti, Aravinda;Gudnason, Vilmundur;Psaty, Bruce M.;Roden, Dan M.;Meitinger, Thomas;Wichmann, H-Erich;Witteman, Jacqueline C. M.;Barnard, John;Arking, Dan E.;Benjamin, Emelia J.;Heckbert, Susan R.;Kaeaeb, Stefan
通讯作者：
Kaeaeb, Stefan
肉瘤蛋白滴定中的罕见截断变体与家族性和早期心房颤动相关。
影响因子：
16.6
作者：
Ahlberg G;Refsgaard L;Lundegaard PR;Andreasen L;Ranthe MF;Linscheid N;Nielsen JB;Melbye M;Haunsø S;Sajadieh A;Camp L;Olesen SP;Rasmussen S;Lundby A;Ellinor PT;Holst AG;Svendsen JH;Olesen MS
通讯作者：
Olesen MS
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
DOI：
10.1038/nrcardio.2013.53
发表时间：
2013-06
期刊：
Nature reviews. Cardiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.9
作者：
Choe, Won-Seok;Kang, Jun Hyuk;Lim, Hong Euy
通讯作者：
Lim, Hong Euy