心力衰竭、女性性别和心房颤动是人类心房心肌病的主要驱动因素：来自 CATCH ME 联盟的结果。
Heart Failure, Female Sex, and Atrial Fibrillation Are the Main Drivers of Human Atrial Cardiomyopathy: Results From the CATCH ME Consortium.
机构信息
Department of Physiology, Cardiovascular Research Institute Maastricht University Maastricht Maastricht The Netherlands.
Maastricht Centre for Systems Biology University Maastricht Maastricht The Netherlands.
出版信息
J Am Heart Assoc. 2023 Nov 21;12(22):e031220. doi: 10.1161/JAHA.123.031220. Epub 2023 Nov 20.
BACKGROUND
Atrial cardiomyopathy (atCM) is an emerging prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are hallmarks of atCM. The contribution of etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been quantified. This study aimed to evaluate the association between histological features of atCM and the clinical phenotype.
METHODS AND RESULTS
We examined left atrial (LA, n=95) and right atrial (RA, n=76) appendages from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed following wheat germ agglutinin/CD31/vimentin staining. The contributions of AF, heart failure, sex, and age to histological characteristics were determined with multiple linear regression models. Persistent AF was associated with increased endomysial fibrosis (LA: +1.13±0.47 μm, =0.038; RA: +0.94±0.38 μm, =0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, <0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 μm, =0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 μm, <0.001) and extracellular matrix content (LA: +3.07±1.29%, =0.016), and a higher capillary density (LA: +0.13±0.06, =0.007) and size (LA: +0.46±0.22 μm, =0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 μm, <0.001; RA: +2.86 μm, <0.001), extracellular matrix content (LA: +3.53%, <0.001; RA: +6.40%, <0.001) and fibroblast density (LA: +4.38%, <0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 μm, =0.008; RA: +2.58 μm, <0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, =0.002; RA: OR, 1.54, =0.004), with persistent AF (LA: OR, 1.22, =0.036) or heart failure (LA: OR, 1.62, <0.001). Hypertrophic features were more common in men (LA: OR=1.33, =0.002; RA: OR, 1.54, =0.004).
CONCLUSIONS
Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men.
背景
心房心肌病（atCM）是心血管疾病中一个新兴的预后因素。纤维性重塑、心肌细胞肥大和毛细血管密度是 atCM 的特征。病因和心房颤动（AF）对不同 atCM 表型发展的贡献尚未量化。本研究旨在评估 atCM 的组织学特征与临床表型之间的关联。
方法和结果
我们检查了来自接受心脏手术的欧洲队列的 95 名患者的左心房（LA）和 76 名患者的右心房（RA）附件。用小麦胚凝集素/CD31/vimentin 染色法对 atCM 的组织学特征进行定量。使用多元线性回归模型确定 AF、心力衰竭、性别和年龄对组织学特征的贡献。持续性 AF 与内膜下纤维化增加有关（LA：+1.13±0.47 μm，=0.038；RA：+0.94±0.38 μm，=0.041），而细胞外基质含量则不然。男性的心肌细胞更大（LA：+1.92±0.72 μm，<0.001），而女性的内膜下纤维化更多（LA：+0.99±0.56 μm，=0.003）。心力衰竭患者的内膜下纤维化（LA：+1.85±0.48 μm，<0.001）和细胞外基质含量（LA：+3.07±1.29%，=0.016）更高，毛细血管密度（LA：+0.13±0.06，=0.007）和大小（LA：+0.46±0.22 μm，=0.044）更高。组织学特征的模糊 k-均值聚类确定了 2 种 atCM 亚型：1 种以增强的内膜下纤维化（LA：+3.17 μm，<0.001；RA：+2.86 μm，<0.001）、细胞外基质含量（LA：+3.53%，<0.001；RA：+6.40%，<0.001）和成纤维细胞密度（LA：+4.38%，<0.001）为特征，1 种以心肌细胞肥大（LA：+1.16 μm，=0.008；RA：+2.58 μm，<0.001）为特征。纤维化 atCM 患者中女性更为常见（LA：比值比[OR]，1.33，=0.002；RA：OR，1.54，=0.004），持续性 AF（LA：OR，1.22，=0.036）或心力衰竭（LA：OR，1.62，<0.001）更为常见。肥大特征在男性中更为常见（LA：OR=1.33，=0.002；RA：OR，1.54，=0.004）。
结论
纤维性 atCM 与女性、持续性 AF 和心力衰竭有关，而肥大特征在男性中更为常见。
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