Arrhythmia Research Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
J Am Coll Cardiol. 2010 Feb 23;55(8):705-12. doi: 10.1016/j.jacc.2009.12.005.
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, represents a major burden to patients and health care systems through its sequelae of heart failure and stroke. Its age-dependent increase in prevalence has led to worrisome predictions of an expanding burden secondary to our aging population. This growing epidemic is further exacerbated by a current lack of highly effective therapies for the arrhythmia stemming from our incomplete understanding of its complex pathophysiology. Recent genetic studies, triggered in part by evidence of a hereditary component of AF, have begun to identify predisposing genes and offer further insights into the mechanisms of lone AF. A variety of ion channels and most recently a circulating hormone have been implicated. The apparent genetic diversity underlying the arrhythmia has served to emphasize the heterogeneity of factors that govern its initiation and maintenance. The different causative genes seem to predispose to AF through distinct putative mechanisms, including enhanced and delayed atrial action potential repolarization, cellular hyperexcitability, and conduction velocity heterogeneity. Classification of lone AF into mechanistic subgroups serves to emphasize its heterogeneity and has the potential to guide developmental and clinical treatment strategies. The frequent recalcitrant nature of the arrhythmia to contemporary pharmacological and invasive therapies may be overcome through an ability to identify, through genetics, the mechanistic subclass of AF for an individual patient. Proper identification of the culprit pathophysiology may permit administration of a targeted form of therapy that carries maximal efficacy and minimal risk in a manner consistent with the vision of pharmacogenomics.
心房颤动（AF）是最常见的持续性心律失常，通过心力衰竭和中风等后遗症给患者和医疗保健系统带来了沉重负担。其患病率随年龄增长而增加，这导致人们对因人口老龄化而导致负担不断扩大的情况感到担忧。由于我们对其复杂病理生理学的理解不完整，目前缺乏针对心律失常的高效治疗方法，这种不断增加的流行情况进一步恶化。部分由 AF 的遗传成分证据引发的最近的遗传研究已经开始确定易患基因，并为了解孤立性 AF 的机制提供了进一步的见解。多种离子通道，最近还有一种循环激素，都被牵连其中。心律失常的明显遗传多样性强调了控制其发生和维持的因素存在异质性。不同的致病基因似乎通过不同的假定机制导致 AF，包括增强和延迟心房动作电位复极、细胞过度兴奋和传导速度异质性。将孤立性 AF 分类为机制亚组有助于强调其异质性，并有可能指导开发和临床治疗策略。该心律失常常常对当代药理学和介入治疗具有抗性，这可能通过通过遗传学识别个体患者的 AF 机制亚组来克服。正确识别致病病理生理学可以允许以与药物基因组学相一致的方式，对每个患者进行靶向治疗，从而实现最大疗效和最小风险。
