Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Heart Rhythm. 2022 Dec;19(12):2033-2041. doi: 10.1016/j.hrthm.2022.07.030. Epub 2022 Aug 5.
Epicardial adipose tissue (EAT) accumulation is associated with the progression of atrial fibrillation. However, the histological features of EATs are poorly defined and their correlation with atrial fibrosis is unclear.
The purpose of this study was to identify and characterize EAT subgroups in the persistent atrial fibrillation (PeAF) cohorts.
EATs and the corresponding left atrial appendage samples were obtained from patients with PeAF via surgical intervention. Adipocyte markers, that is, Uncoupling Protein 1, Transcription Factor 21, and CD137, were examined. On the basis of expression of adipocyte markers, patients with PeAF were categorized into subgroups by using unsupervised clustering analysis. Clinical characteristics, histological analyses, and outcomes were subsequently compared across the clusters. External validation was performed in a validation cohort.
The ranking of feature importance revealed that the 3 adipocyte markers were the most relevant factors for atrial fibrosis compared with other clinical indicators. On the k-medoids analysis, patients with PeAF could be categorized into 3 clusters in the discovery cohort. The histological studies revealed that patients in cluster 1 exhibited statistically larger size of adipocytes in EATs and severe atrial fibrosis in left atrial appendages. Findings were replicated in the validation cohort, where severe atrial fibrosis was noted in cluster 1. Moreover, in the validation cohort, there was a high degree of overlap between the supervised classification results and the unsupervised cluster results from the k-medoids method.
Machine learning-based cluster analysis could identify subtypes of patients with PeAF having distinct atrial fibrosis profiles. Additionally, EAT whitening (increased proportion of white adipocytes) may be involved in the process of atrial fibrosis.
心外膜脂肪组织（EAT）的积累与心房颤动的进展有关。然而，EAT 的组织学特征尚未得到明确界定，其与心房纤维化的相关性也不清楚。
本研究的目的是在持续性心房颤动（PeAF）患者中确定和描述 EAT 亚组。
通过手术干预从 PeAF 患者中获取 EAT 和相应的左心耳样本。检查脂肪细胞标志物，即解偶联蛋白 1、转录因子 21 和 CD137。根据脂肪细胞标志物的表达，通过无监督聚类分析将 PeAF 患者分为亚组。随后比较了各个亚组的临床特征、组织学分析和结局。在验证队列中进行了外部验证。
特征重要性的排名显示，与其他临床指标相比，这 3 种脂肪细胞标志物是与心房纤维化最相关的因素。在 k-medoids 分析中，PeAF 患者可在发现队列中分为 3 个亚组。组织学研究表明，亚组 1 中的患者 EAT 中的脂肪细胞体积较大，左心耳中的心房纤维化严重。在验证队列中也得到了证实，其中亚组 1 中观察到严重的心房纤维化。此外，在验证队列中，监督分类结果与 k-medoids 方法的无监督聚类结果之间存在高度重叠。
基于机器学习的聚类分析可以识别具有不同心房纤维化特征的 PeAF 患者亚组。此外，EAT 变白（白色脂肪细胞比例增加）可能参与了心房纤维化的过程。
