心房颤动中的心脏代谢基质修饰：肠促胰素类治疗与导管消融时代的肥胖与心外膜脂肪组织

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中文摘要

心房颤动（AF）日益被视为一种全身性和心房性心脏代谢疾病的电学表现，而非孤立的肺静脉触发灶疾病。肥胖、胰岛素抵抗、高血压、睡眠呼吸障碍、射血分数保留的心力衰竭以及内脏脂肪堆积可促进心房牵张、炎症、纤维化、自主神经失衡和传导异质性。心外膜脂肪组织（EAT），尤其是左心房周围脂肪库，可能通过旁分泌、炎症、纤维化和浸润性途径，在全身代谢功能障碍与心房心肌病之间提供局部机制性桥梁。这一框架具有直接的治疗意义。结构化减重、心肺适能、减少饮酒和全面的危险因素管理可降低AF负荷并改善节律控制结局，尽管获益幅度因人群和试验设计而异。肠促胰素类治疗为基质修饰引入了一条可能重要的药理学途径。司美格鲁肽和替尔泊肽可产生显著减重以及有利的心血管和心力衰竭效应，而新兴的观察性和前瞻性数据提示其可降低AF发生率和消融后复发。然而，关于降低消融后复发的证据仍以非随机研究为主，且易受残余混杂、治疗选择效应和健康使用者偏倚的影响。因果关系、不依赖体重的抗心律失常效应、相对于消融的最佳时机以及停药后的持久性仍未解决。观察性钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂数据支持进一步研究心脏代谢途径用于节律控制，尽管随机证据尚未一致显示获益。本综述整合了机制、影像、生活方式、药理学和电生理证据，并提出一个实用模型，其中导管消融与心脏代谢基质修饰是互补策略。

英文摘要

Atrial fibrillation (AF) is increasingly understood as the electrical expression of a systemic and atrial cardiometabolic disease rather than an isolated disorder of pulmonary-vein triggers. Obesity, insulin resistance, hypertension, sleep-disordered breathing, heart failure with preserved ejection fraction, and visceral adiposity promote atrial stretch, inflammation, fibrosis, autonomic imbalance, and conduction heterogeneity. Epicardial adipose tissue (EAT), particularly the peri-left-atrial depot, may provide a local mechanistic bridge between systemic metabolic dysfunction and atrial cardiomyopathy through paracrine, inflammatory, fibrotic, and infiltrative pathways. This framework has direct therapeutic implications. Structured weight loss, cardiorespiratory fitness, alcohol reduction, and comprehensive risk-factor management can reduce AF burden and improve rhythm-control outcomes, although the magnitude of benefit varies across populations and trial designs. Incretin-based therapies have introduced a potentially important pharmacologic route to substrate modification. Semaglutide and tirzepatide produce substantial weight loss and favorable cardiovascular and heart-failure effects, while emerging observational and prospective data suggest lower AF incidence and post-ablation recurrence. However, evidence for reduced post-ablation recurrence remains predominantly non-randomized and is susceptible to residual confounding, treatment-selection effects, and healthy-user bias. Causality, weight-independent antiarrhythmic effects, optimal timing relative to ablation, and durability after treatment withdrawal remain unresolved. Observational sodium-glucose cotransporter-2 (SGLT2) inhibitor data support further investigation of cardiometabolic approaches to rhythm control, although randomized evidence has not consistently demonstrated benefit. Our review integrates mechanistic, imaging, lifestyle, pharmacologic, and electrophysiological evidence and proposes a practical model in which catheter ablation and cardiometabolic substrate modification are complementary strategies.