Atrial fibrosis is one of the main manifestations of atrial cardiomyopathy, an array of electrical, mechanical and structural alterations associated with atrial fibrillation (AF), stroke and heart failure. Atrial fibrosis can be both a cause and a consequence of AF and, once present, it accelerates the progression of AF. The pathophysiological mechanisms leading to atrial fibrosis are diverse and include stretch-induced activation of fibroblasts, systemic inflammatory processes, activation of coagulation factors and fibrofatty infiltrations. Importantly, atrial fibrosis can occur in different forms, such as reactive and replacement fibrosis. The diversity of atrial fibrosis mechanisms and patterns depends on sex, age and comorbidity profile, hampering the development of therapeutic strategies. In addition, the presence and severity of comorbidities often change over time, potentially causing temporal changes in the mechanisms underlying atrial fibrosis development. This Review summarizes the latest knowledge on the molecular and cellular mechanisms of atrial fibrosis, its association with comorbidities and the sex-related differences. We describe how the various patterns of atrial fibrosis translate into electrophysiological mechanisms that promote AF, and critically appraise the clinical applicability and limitations of diagnostic tools to quantify atrial fibrosis. Finally, we provide an overview of the newest therapeutic interventions under development and discuss relevant knowledge gaps related to the association between clinical manifestations and pathological mechanisms of atrial fibrosis and to the translation of this knowledge to a clinical setting.

心房纤维化是心房心肌病的主要表现之一，房性心肌病是与心房颤动 （AF）、中风和心力衰竭相关的一系列电、机械和结构改变。心房纤维化既可以是 AF 的原因，也可以是 AF 的结果，一旦出现，它会加速 AF 的进展。导致心房纤维化的病理生理机制多种多样，包括拉伸诱导的成纤维细胞激活、全身炎症过程、凝血因子激活和纤维脂肪浸润。重要的是，心房纤维化可以以不同的形式发生，例如反应性和替代性纤维化。心房纤维化机制和模式的多样性取决于性别、年龄和合并症，阻碍了治疗策略的制定。此外，合并症的存在和严重程度通常会随着时间的推移而变化，可能导致心房纤维化发展机制发生时间变化。本文总结了心房纤维化的分子和细胞机制、其与合并症的关系以及性别相关差异的最新知识。我们描述了心房纤维化的各种模式如何转化为促进 AF 的电生理机制，并批判性地评估了量化心房纤维化的诊断工具的临床适用性和局限性。最后，我们概述了正在开发的最新治疗干预措施，并讨论了与心房纤维化的临床表现和病理机制之间的关联以及将这些知识转化为临床环境相关的知识空白。