Heijman Jordi, Algalarrondo Vincent, Voigt Niels, Melka Jonathan, Wehrens Xander H T, Dobrev Dobromir, Nattel Stanley
Department of Cardiology, Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Department of Medicine, Montreal Heart Institute and Université de Montréal, 5000 Belanger St. E., Montreal, Canada H1T 1C8 Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Cardiovasc Res. 2016 Apr 1;109(4):467-79. doi: 10.1093/cvr/cvv275. Epub 2015 Dec 23.
Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms for arrhythmia initiation and maintenance. However, it has become clear that the clinical factors predisposing to AF and the cellular and molecular mechanisms involved are extremely complex. Moreover, all AF-promoting and maintaining mechanisms are dynamically regulated and subject to remodelling caused by both AF and cardiovascular disease. Accordingly, the initial presentation and clinical progression of AF patients are enormously heterogeneous. An understanding of arrhythmia mechanisms is widely assumed to be the basis of therapeutic innovation, but while this assumption seems self-evident, we are not aware of any papers that have critically examined the practical contributions of basic research into AF mechanisms to arrhythmia management. Here, we review recent insights into the basic mechanisms of AF, critically analyse the role of basic research insights in the development of presently used anti-AF therapeutic options and assess the potential value of contemporary experimental discoveries for future therapeutic innovation. Finally, we highlight some of the important challenges to the translation of basic science findings to clinical application.
心房颤动（AF）是一个极为常见的临床问题，与发病率和死亡率的增加相关。目前的抗心律失常选择包括药物、消融和手术治疗，并且已显著改善了临床结局。然而，它们的疗效仍然欠佳，其应用受到各种潜在严重不良反应的限制。显然需要改进治疗选择。数十年的研究极大地扩展了我们对AF基本机制的理解。异位起搏和折返活动已被确定为心律失常起始和维持的主要机制。然而，已明确的是，易患AF的临床因素以及所涉及的细胞和分子机制极其复杂。此外，所有促进和维持AF的机制都受到动态调节，并会因AF和心血管疾病而发生重塑。因此，AF患者的初始表现和临床进展具有极大的异质性。人们普遍认为对心律失常机制的理解是治疗创新的基础，但尽管这一假设似乎不言而喻，但我们并未意识到有任何论文对AF机制的基础研究对心律失常管理的实际贡献进行过批判性审视。在此，我们回顾了对AF基本机制的最新见解，批判性地分析了基础研究见解在当前使用的抗AF治疗选择发展中的作用，并评估了当代实验发现对未来治疗创新的潜在价值。最后，我们强调了基础科学发现转化为临床应用的一些重要挑战。
