Lanters E A H, van Marion D M S, Steen H, de Groot N M S, Brundel B J J M
Unit Translational Electrophysiology, Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Neth Heart J. 2015 Jun;23(6):327-33. doi: 10.1007/s12471-015-0699-0.
Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia accounting for one-third of hospitalisations. Treatment of AF is difficult, which is rooted in the progressive nature of electrical and structural remodelling, called electropathology, which makes the atria more vulnerable for AF. Importantly, structural damage of the myocardium is already present when AF is diagnosed for the first time. Currently, no effective therapy is known that can resolve this damage.Previously, we observed that exhaustion of cardioprotective heat shock proteins (HSPs) contributes to structural damage in AF patients. Also, boosting of HSPs, by the heat shock factor-1 activator geranylgeranylacetone, halted AF initiation and progression in experimental cardiomyocyte and dog models for AF. However, it is still unclear whether induction of HSPs also prolongs the arrhythmia-free interval after, for example, cardioversion of AF.In this review, we discuss the role of HSPs in the pathophysiology of AF and give an outline of the HALT&REVERSE project, initiated by the HALT&REVERSE Consortium and the AF Innovation Platform. This project will elucidate whether HSPs (1) reverse cardiomyocyte electropathology and thereby halt AF initiation and progression and (2) represent novel biomarkers that predict the outcome of AF conversion and/or occurrence of post-surgery AF.
心房颤动（AF）是最常见的与年龄相关的心律失常，占住院病例的三分之一。房颤的治疗很困难，其根源在于电重构和结构重构的进展性，即所谓的电病理学，这使得心房更容易发生房颤。重要的是，首次诊断房颤时心肌已经存在结构损伤。目前，尚无已知的有效疗法能够解决这种损伤。此前，我们观察到心脏保护热休克蛋白（HSPs）耗竭会导致房颤患者的结构损伤。此外，热休克因子-1激活剂香叶基香叶基丙酮增强热休克蛋白后，可在实验性心肌细胞和犬房颤模型中阻止房颤的起始和进展。然而，热休克蛋白的诱导是否也能延长房颤复律后的无心律失常间期仍不清楚。在这篇综述中，我们讨论了热休克蛋白在房颤病理生理学中的作用，并概述了由HALT&REVERSE联盟和房颤创新平台发起的HALT&REVERSE项目。该项目将阐明热休克蛋白是否（1）逆转心肌细胞电病理学，从而阻止房颤的起始和进展，以及（2）代表预测房颤转复结果和/或术后房颤发生情况的新型生物标志物。
