Pang Zhihua, Ren Ying, Yao Zhuhua
Department of Cardiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China.
Front Cardiovasc Med. 2025 Jul 10;12:1578148. doi: 10.3389/fcvm.2025.1578148. eCollection 2025.
Atrial fibrillation (AF) is a complex arrhythmia driven by intricate pathophysiological mechanisms, with atrial fibrosis and inflammation emerging as central players in its initiation and perpetuation. Key pathways, including the renin-angiotensin-aldosterone system (RAAS), TGF-β/Smad signaling, and pro-inflammatory cytokine cascades (e.g., TNF-α/NF-κB, IL-6/STAT3), contribute to fibrotic remodeling and electrophysiological dysfunction. These pathways promote extracellular matrix deposition, fibroblast activation, and heterogeneous conduction, creating a substrate for AF maintenance. Contemporary therapeutic approaches predominantly target rhythm control via catheter ablation techniques and pharmacological interventions with antiarrhythmic agents. Nevertheless, the efficacy of anti-inflammatory approaches, such as corticosteroids and colchicine, remains uncertain due to limited robust clinical evidence, highlighting the need for further investigation. Advanced fibrosis quantification modalities, particularly late gadolinium-enhanced magnetic resonance imaging and electroanatomic mapping, have emerged as valuable tools for optimizing ablation strategies. Furthermore, emerging evidence highlights significant sex-based disparities in atrial fibrosis distribution and electrophysiological substrate characteristics, suggesting the potential for gender-specific therapeutic approaches. This comprehensive review systematically examines the pathophysiological roles of atrial fibrosis and inflammation in AF progression, with particular emphasis on their intricate bidirectional relationship. Through detailed elucidation of these mechanistic interactions, we aim to facilitate the development of novel therapeutic interventions to enhance clinical management of AF.
心房颤动（AF）是一种由复杂病理生理机制驱动的复杂心律失常，心房纤维化和炎症在其起始和持续过程中成为核心因素。包括肾素-血管紧张素-醛固酮系统（RAAS）、转化生长因子-β/Smad信号通路以及促炎细胞因子级联反应（如肿瘤坏死因子-α/核因子-κB、白细胞介素-6/信号转导和转录激活因子3）在内的关键通路，促成了纤维化重塑和电生理功能障碍。这些通路促进细胞外基质沉积、成纤维细胞活化和异质性传导，为房颤维持创造了条件。当代治疗方法主要通过导管消融技术和使用抗心律失常药物的药物干预来控制心律。然而，由于有力的临床证据有限，皮质类固醇和秋水仙碱等抗炎方法的疗效仍不确定，这凸显了进一步研究的必要性。先进的纤维化量化方法，特别是延迟钆增强磁共振成像和电解剖标测，已成为优化消融策略的有价值工具。此外，新出现的证据突出了心房纤维化分布和电生理基质特征方面存在显著的性别差异，提示了针对性别治疗方法的潜力。这篇综述系统地研究了心房纤维化和炎症在房颤进展中的病理生理作用，特别强调了它们复杂的双向关系。通过详细阐明这些机制相互作用，我们旨在促进新型治疗干预措施的开发，以加强房颤的临床管理。
