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Abstract：
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.
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, P=0.038; RA: +0.94±0.38 μm, P=0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, P<0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 μm, P=0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 μm, P<0.001) and extracellular matrix content (LA: +3.07±1.29%, P=0.016), and a higher capillary density (LA: +0.13±0.06, P=0.007) and size (LA: +0.46±0.22 μm, P=0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 μm, P<0.001; RA: +2.86 μm, P<0.001), extracellular matrix content (LA: +3.53%, P<0.001; RA: +6.40%, P<0.001) and fibroblast density (LA: +4.38%, P<0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 μm, P=0.008; RA: +2.58 μm, P<0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, P=0.002; RA: OR, 1.54, P=0.004), with persistent AF (LA: OR, 1.22, P=0.036) or heart failure (LA: OR, 1.62, P<0.001). Hypertrophic features were more common in men (LA: OR=1.33, P=0.002; RA: OR, 1.54, P=0.004).
CONCLUSIONS: Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men.
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, P=0.038; RA: +0.94±0.38 μm, P=0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, P<0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 μm, P=0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 μm, P<0.001) and extracellular matrix content (LA: +3.07±1.29%, P=0.016), and a higher capillary density (LA: +0.13±0.06, P=0.007) and size (LA: +0.46±0.22 μm, P=0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 μm, P<0.001; RA: +2.86 μm, P<0.001), extracellular matrix content (LA: +3.53%, P<0.001; RA: +6.40%, P<0.001) and fibroblast density (LA: +4.38%, P<0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 μm, P=0.008; RA: +2.58 μm, P<0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, P=0.002; RA: OR, 1.54, P=0.004), with persistent AF (LA: OR, 1.22, P=0.036) or heart failure (LA: OR, 1.62, P<0.001). Hypertrophic features were more common in men (LA: OR=1.33, P=0.002; RA: OR, 1.54, P=0.004).
CONCLUSIONS: Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men.
摘要：
背景：心房心肌病（atCM）是一种新兴的心血管疾病预后因素。纤维化重塑，心肌细胞肥大，和毛细血管密度是atCM的标志。病因因素和心房颤动（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。
结果：我们检查了左心房（LA，n=95）和右心房（RA，n=76）来自接受心脏手术的欧洲患者队列的附件。在麦胚凝集素/CD31/波形蛋白染色后进行组织学atCM特征的定量。AF的贡献，心力衰竭,性别,用多元线性回归模型确定年龄和组织学特征。持续性房颤与子宫内膜纤维化增加相关(LA:+1.13±0.47μm,P=0.038;RA:+0.94±0.38μm,P=0.041),而总的细胞外基质含量没有。男性有较大的心肌细胞（LA：1.92±0.72μm，P<0.001)，而女性有更多的子宫内膜纤维化（LA：+0.99±0.56μm，P=0.003)。心力衰竭患者表现出更多的子宫内膜纤维化（LA：1.85±0.48μm，P<0.001）和细胞外基质含量（LA：3.07±1.29％，P=0.016),和更高的毛细管密度（LA：0.13±0.06，P=0.007）和大小（LA：0.46±0.22μm，P=0.044)。组织学特征的模糊k均值聚类确定了atCM的2种亚型：1以增强的子宫内膜纤维化为特征（LA：3.17μm，P<0.001;RA:+2.86μm,P<0.001)，细胞外基质含量（LA：+3.53%，P<0.001;RA:+6.40%,P<0.001）和成纤维细胞密度（LA：+4.38%，P<0.001)，和1以心肌细胞肥大为特征（LA：1.16μm，P=0.008;RA:+2.58μm,P<0.001)。纤维化atCM患者更常见为女性(LA：比值比[OR]，1.33,P=0.002;RA:OR,1.54,P=0.004),持续性房颤(LA:OR,1.22，P=0.036）或心力衰竭（LA：OR，1.62,P<0.001)。肥厚特征在男性中更常见(LA:OR=1.33,P=0.002;RA:OR,1.54,P=0.004)。
结论：纤维化atCM与女性有关，持续性房颤,心力衰竭,而肥厚特征在男性中更为常见。
结果：我们检查了左心房（LA，n=95）和右心房（RA，n=76）来自接受心脏手术的欧洲患者队列的附件。在麦胚凝集素/CD31/波形蛋白染色后进行组织学atCM特征的定量。AF的贡献，心力衰竭,性别,用多元线性回归模型确定年龄和组织学特征。持续性房颤与子宫内膜纤维化增加相关(LA:+1.13±0.47μm,P=0.038;RA:+0.94±0.38μm,P=0.041),而总的细胞外基质含量没有。男性有较大的心肌细胞（LA：1.92±0.72μm，P<0.001)，而女性有更多的子宫内膜纤维化（LA：+0.99±0.56μm，P=0.003)。心力衰竭患者表现出更多的子宫内膜纤维化（LA：1.85±0.48μm，P<0.001）和细胞外基质含量（LA：3.07±1.29％，P=0.016),和更高的毛细管密度（LA：0.13±0.06，P=0.007）和大小（LA：0.46±0.22μm，P=0.044)。组织学特征的模糊k均值聚类确定了atCM的2种亚型：1以增强的子宫内膜纤维化为特征（LA：3.17μm，P<0.001;RA:+2.86μm,P<0.001)，细胞外基质含量（LA：+3.53%，P<0.001;RA:+6.40%,P<0.001）和成纤维细胞密度（LA：+4.38%，P<0.001)，和1以心肌细胞肥大为特征（LA：1.16μm，P=0.008;RA:+2.58μm,P<0.001)。纤维化atCM患者更常见为女性(LA：比值比[OR]，1.33,P=0.002;RA:OR,1.54,P=0.004),持续性房颤(LA:OR,1.22，P=0.036）或心力衰竭（LA：OR，1.62,P<0.001)。肥厚特征在男性中更常见(LA:OR=1.33,P=0.002;RA:OR,1.54,P=0.004)。
结论：纤维化atCM与女性有关，持续性房颤,心力衰竭,而肥厚特征在男性中更为常见。
