第一部分 外科方法心脏部分去神经化预防冠状动脉旁路移植术后房颤：一项随机对照研究
摘要
背景：冠状动脉旁路移植术（coronary artery bypass grafting，CABG）后新发心房颤动（postoperative atrial fibrillation，POAF）是一种常见的并发症，会增加短期和长期临床不良预后的风险。目前预防POAF的方法有限，亟需开发出更高效、安全同时具备可普及性的干预方式。本研究拟探索CABG术中通过切断左侧Marshall韧带和切除右侧Waterston脂肪垫的部分去神经化方法，是否能预防POAF的发生。
方法：本研究是一项单中心、前瞻性、随机对照临床研究，招募于2022年8月至2023年12月期间在本中心行单纯CABG的患者，然后按1:1的比例随机分为干预组（CABG + 心脏部分去神经化）和对照组（仅CABG）。术后所有患者通过穿戴连续心电监测的设备，记录术后POAF发生情况，直到手术后第6天。所有患者在出院后30天完成短期的随访。主要终点是术后6天POAF的发生率，次要终点包括经济效益评估和安全性评估。
结果：本试验最终按计划共计入组430名患者，其中女性患者79名（18.4%）；平均年龄为61.9 ± 7.8岁。与对照组相比，干预组术后6天POAF发生率显著降低（18.1% vs. 31.6%，P = 0.001；相对危险度[risk ratio,RR]：0.57，95%置信区间[confidence interval，CI]：0.41-0.81)。为了进一步验证该结果的可靠性，通过Kaplan-Meier生存曲线的敏感性分析也显示，干预组POAF的发生率显著降低(风险比[hazard ration, HR]：0.53，95% CI：0.36-0.79，P = 0.002)。次要终点中安全性评估显示两组间无差异，经济效益评估显示干预组术后医疗费用降低。
结论：这项随机对照临床试验发现，心脏部分去神经化是一种预防单纯CABG术后POAF发生的有效方法，并且围术期没有额外并发症发生，能为心脏外科医生预防CABG后POAF的发生提供一种可行的干预方式。
 

第二部分 房颤患者与正常患者心外膜脂肪组织的单细胞转录图谱
摘要
背景：诸多研究表明，心外膜脂肪组织（epicardial adipose tissue，EAT）的调控在心房颤动（atrial fibrillation，AF）的发生发展中起到重要作用。然而，二者关联背后的细胞和分子生物学机制仍有待阐明。
方法：我们对来自两组受试者共9个EAT样本进行了单细胞核RNA测序：一组是因冠心病行冠状动脉旁路手术的非瓣膜性AF患者（n = 6），另一组是术前无合并AF病史的对照组窦律患者（n = 3）。然后在两组间进行了多种比较分析，包括细胞组成分析、细胞转录组变化、基因共表达网络分析、细胞间通讯分析以及功能分析。
结果：总共92734个单细胞核在无监督聚类分析中分为12个群，涵盖了所有已知脂肪组织内的细胞类型。AF组和对照组之间的差异表达分析显示，位于X和Y染色体上的一些基因（包括XIST和TSIX）存在显著差异，同时与免疫细胞功能相关的通路也明显上调。与对照组相比，AF患者EAT的细胞组成和转录组存在明显差异，尤其集中于B细胞。通过对不同B细胞亚群的信号通路进行比较后，发现AF组衰老的IL4R+幼稚B细胞更多地参与细胞死亡、脂肪酸代谢、葡萄糖代谢和炎症反应过程，可能是EAT参与AF发生发展中的重要环节。对不同的浆细胞亚群进行分析后，发现AF组与对照组之间抗体表达水平有显著差异，IgG可能在AF发病中发挥作用。
结论：本研究对正常和AF患者构建了全球首个完整的人类EAT单细胞核转录组图谱，从而为开发通过靶向调节EAT来治疗AF的新策略提供了依据。
 

第三部分 心外膜脂肪组织和房颤相关的机制和干预：总结和展望
摘要
心房颤动（房颤）是最常见的心律失常之一，其发病率高且会增加死亡、卒中等不良心血管事件的风险。按照房颤发生的时间，可将其分为术前房颤和术后新发房颤。已有研究表明，心外膜脂肪组织在房颤的发生发展中起到重要作用，由此也出现相关的干预靶点和措施。本文拟从心外膜脂肪组织的角度，总结与房颤相关的机制和干预研究，并提出展望，以供临床医师参考。
 

Part I Partial Cardiac Denervation to Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting：The pCAD-POAF Randomized Clinical Trial
Abstract
Background: Following coronary artery bypass grafting (CABG), postoperative atrial fibrillation (POAF) is a frequent complication that raises the risk of both short- and long-term clinical adverse outcomes. Efficient approaches to prevent POAF after CABG are still needed. This study aimed to investigate whether partial cardiac denervation, achieved by cutting off the ligament of Marshall (LOM) and resecting the fat pad along the Waterston groove, can reduce the risk of POAF following CABG.
Methods: This single-center, prospective, randomized clinical trial enrolled adult patients scheduled for isolated CABG in our center from August 2022 to December 2023. Participants were randomized into the intervention group (CABG plus partial cardiac denervation) and the control group (CABG only) in a 1:1 pattern. All participants were continuously monitored for the incidence of POAF until day 6 after the operation. The follow-up visits were 30 days after discharge.The primary outcome was the incidence of POAF in 6 days. Secondary outcome included economic and safety evaluation.
Results: The trial enrolled 430 patients as planned (79 [18.4%] female; mean [SD] age, 61.9 [7.8] years). Compared with the control group, the 6-day incidence of POAF was significantly lower in the intervention group (18.1% vs. 31.6%; P = 0.001; risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.41-0.81). To further support these results, a sensitivity analysis performed with Kaplan-Meier survival curves also showed a significant reduction in the occurrence of POAF in the intervention group (hazard ratio [HR]: 0.53, 95% CI: 0.36-0.79, P = 0.002). Safety assessments showed no difference between the 2 groups, while economic assessments showed that postoperative medical cost was reduced in the intervention group.
Conclusions: This randomized clinical trial found that partial cardiac denervation was an effective procedure to reduce the occurrence of POAF after isolated CABG without additional postoperative complications. These results suggest that partial cardiac denervation may be a good option for cardiac surgeons to consider for preventing POAF after CABG.
 

Part II Single-nucleus Atlas of Epicardial Adipose Tissue in Patients with Atrial Fibrillation and Normal Condition
Abstract
Background: Numerous recent evidence suggested a role of epicardial adipose tissue (EAT) in the development of Atrial Fibrillation (AF). However, the cellular and molecular mechanisms underlying the association remain elusive.
Methods: We performed single-nucleus RNA sequencing on nine EAT samples collected from 2 groups of subjects: patients with nonvalvular AF undergoing coronary bypass surgery for coronary artery disease (n=6), and a control group of patients without concomitant AF (n=3). Comparative analyses were performed between the groups, including cellular compositional analysis, cell type–resolved transcriptomic changes, gene coexpression network analysis, intercellular communication analysis, and functional analysis.  
Results: Unsupervised clustering of 92734 nuclei identified 12 clusters, encompassing all known cell types in the adipose tissue. Pseudobulk differential expression analysis between the AF and control groups revealed pronounced differences in a select subset of genes located on the X and Y chromosomes, including XIST and TSIX. Subsequent pathway analysis identified that the most significantly impacted pathways were those associated with immune cell functions. Meanwhile, differences in cellular composition and transcriptomic profiles, particularly concerning B cells, were observed between normal and AF conditions, highlighting distinct immune cell dynamics. By comparing the signaling pathways of different B cell subsets, it was found that aging IL4R+ naive B cells in AF group were more involved in the processes of cell death, fatty acid metabolism, glucose metabolism and inflammation, which may be an important part of EAT involvement in the occurrence and development of AF. After analysis of different plasma cell subsets, it was found that the antibody expression level was significantly different between the AF group and the control group, and IgG may play a role in the pathogenesis of AF.
Conclusions: We have constructed a comprehensive single-nucleus transcriptomic atlas of human EAT under both normal and AF conditions. Our study provides a valuable foundation for the development of novel therapeutic strategies aimed at treating AF by targeting and modulating EAT function.
 

Part III Mechanisms and Interventions Associated with Epicardial Adipose Tissue and Atrial Fibrillation: Summary and Prospects
Abstract
Atrial fibrillation (AF) is one of the most common arrhythmias, with a high incidence and an increased risk of cardiovascular adverse events such as death and stroke. According to the occurrence time of atrial fibrillation, it can be divided into preoperative atrial fibrillation and postoperative new-onset atrial fibrillation. Previous studies have shown that epicardial adipose tissue plays an important role in the occurrence and development of atrial fibrillation, and relevant intervention targets and measures have also emerged. From the perspective of epicardial adipose tissue, this review summarizes the mechanism and intervention research related to atrial fibrillation, prospect for future developments, and provide certain reference for clinicians.