Department of Cardiology, Arrhythmia Unit, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain (D.C.); Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.F.-R., J.J.); Department of Cardiology, Arrhythmia Unit, Hospital Clínico Universitario San Carlos, Madrid, Spain (D.F.-R.); Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (D.F.-R., J.J.); and Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (J.J.).
Department of Cardiology, Arrhythmia Unit, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain (D.C.); Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (D.F.-R., J.J.); Department of Cardiology, Arrhythmia Unit, Hospital Clínico Universitario San Carlos, Madrid, Spain (D.F.-R.); Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (D.F.-R., J.J.); and Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (J.J.)
Pharmacol Rev. 2018 Jul;70(3):505-525. doi: 10.1124/pr.117.014183.
Atrial fibrillation is a highly prevalent cardiac arrhythmia and the most important cause of embolic stroke. Although genetic studies have identified an increasing assembly of AF-related genes, the impact of these genetic discoveries is yet to be realized. In addition, despite more than a century of research and speculation, the molecular and cellular mechanisms underlying AF have not been established, and therapy for AF, particularly persistent AF, remains suboptimal. Current antiarrhythmic drugs are associated with a significant rate of adverse events, particularly proarrhythmia, which may explain why many highly symptomatic AF patients are not receiving any rhythm control therapy. This review focuses on recent advances in AF research, including its epidemiology, genetics, and pathophysiological mechanisms. We then discuss the status of antiarrhythmic drug therapy for AF today, reviewing molecular mechanisms, and the possible clinical use of some of the new atrial-selective antifibrillatory agents, as well as drugs that target atrial remodeling, inflammation and fibrosis, which are being tested as upstream therapies to prevent AF perpetuation. Altogether, the objective is to highlight the magnitude and endemic dimension of AF, which requires a significant effort to develop new and effective antiarrhythmic drugs, but also improve AF prevention and treatment of risk factors that are associated with AF complications.
心房颤动是一种高发的心律失常，也是引起栓塞性脑卒中的最重要原因。虽然遗传研究已经确定了越来越多的与房颤相关的基因，但这些遗传发现的影响仍有待实现。此外，尽管经过了一个多世纪的研究和推测，房颤的分子和细胞机制仍未建立，房颤的治疗，特别是持续性房颤的治疗，仍然不尽人意。目前的抗心律失常药物与显著的不良事件相关，特别是致心律失常作用，这可能解释了为什么许多症状明显的房颤患者没有接受任何节律控制治疗。本综述重点介绍了房颤研究的最新进展，包括其流行病学、遗传学和病理生理学机制。然后，我们讨论了当今房颤抗心律失常药物治疗的现状，回顾了分子机制，以及一些新的心房选择性抗纤维颤药物的可能临床应用，以及正在作为上游治疗药物进行测试以预防房颤持续的靶向心房重构、炎症和纤维化的药物。总之，目的是强调房颤的巨大规模和地方性，这需要大力开发新的、有效的抗心律失常药物，但也要改善与房颤并发症相关的房颤预防和治疗风险因素。
