SEE PAGE 2893 C ontinued growth in atrial fibrillation (AF)– related morbidity and mortality raises the demand for therapies to prevent or delay AF onset and progression. The transition from paroxysmal to persistent AF commonly occurs through the evolution of an arrhythmogenic atrial substrate, characterized by structural remodeling processes consisting of atrial dilation, fibrosis, and altered cellular ultrastructure, which lead to conduction disturbances that maintain AF. Intervening in this process provides the basis for so-called upstream therapies that halt AF onset or delay its transition to more persistent forms. Activation of the renin-angiotensin-aldosterone system (RAAS), in particular angiotensin II (Ang-II), promotes structural remodeling and is up-regulated in AF (1,2). Pharmacological agents that intervene in this process are obvious candidates as upstream mediators of atrial arrhythmogenic remodeling. In preclinical models, treatment with angiotensinconverting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) has demonstrated encouraging results, and human trials support their efficacy in the primary prevention of AF (3,4).

中文翻译：

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治疗心房颤动的上游靶点*

参见第 2893 页 C 心房颤动 (AF) 相关的发病率和死亡率的持续增长提高了对预防或延迟 AF 发作和进展的治疗的需求。从阵发性房颤到持续性房颤的转变通常是通过致心律失常的心房基质的演变发生的，其特征是由心房扩张、纤维化和细胞超微结构改变组成的结构重塑过程，这会导致维持房颤的传导障碍。干预这个过程为所谓的上游疗法提供了基础，这些疗法可以阻止 AF 发作或延迟其向更持久形式的转变。肾素-血管紧张素-醛固酮系统 (RAAS)，特别是血管紧张素 II (Ang-II) 的激活促进结构重塑，并在 AF 中上调 (1,2)。干预这一过程的药物制剂显然是房性心律失常重构的上游介质。在临床前模型中，血管紧张素转换酶抑制剂 (ACEi) 或血管紧张素受体阻滞剂 (ARB) 的治疗显示出令人鼓舞的结果，人体试验支持它们在 AF 一级预防中的功效 (3,4)。