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. 2023 Jul;9(7 Pt 2):1158-1168.
doi: 10.1016/j.jacep.2023.01.029. Epub 2023 Mar 22.

Relationship Between Fibrosis, Endocardial Endothelial Damage, and Thrombosis of Left Atrial Appendage in Atrial Fibrillation

Shunsuke Miyauchi  1 , Takehito Tokuyama  2 , Shinya Takahashi  3 , Toru Hiyama  4 , Yousaku Okubo  2 , Sho Okamura  2 , Shogo Miyamoto  2 , Naoto Oguri  2 , Taiichi Takasaki  3 , Keijiro Katayama  3 , Mutsumi Miyauchi  5 , Yukiko Nakano  6
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Free article

Relationship Between Fibrosis, Endocardial Endothelial Damage, and Thrombosis of Left Atrial Appendage in Atrial Fibrillation

Shunsuke Miyauchi et al. JACC Clin Electrophysiol. 2023 Jul.
Free article

Abstract

Background: Left atrial appendage (LAA) thrombus (LAAT) and ischemic stroke are considered important in atrial cardiomyopathy with progressive atrial fibrosis and endocardial endothelial damage.

Objectives: This study aimed to obtain histological evidence to clarify the association between LAA fibrosis and endocardial endothelial damage with LAAT, ischemic stroke, and clinical risk factors.

Methods: Ninety-six patients with atrial fibrillation (AF) scheduled to undergo LAA excision during surgery were enrolled. They underwent transesophageal echocardiography before the surgery to validate the LAA function/morphology and LAAT presence or absence. The resected LAAs were subjected to Azan-Mallory staining and CD31 immunohistochemistry to quantify the degree of fibrosis and endocardial endothelial damage staged as F1-F4 and E1-E4 per the quantiles.

Results: Patients with an LAAT and/or ischemic stroke history had higher fibrosis degrees (18.4% ± 9.9% vs 10.4% ± 7.0%, P < 0.0001) and lower CD31 expressions (0.27 [IQR: 0.05-0.57] vs 1.02 [IQR: 0.49-1.65]; P < 0.0001). Also, higher CHADS2 was associated with a higher degree of fibrosis and lower CD31 expression. Multivariate logistic regression analysis revealed that endothelial damage (E4) was associated with an LAAT and/or ischemic stroke history independent of AF type (paroxysmal or nonparoxysmal) with an OR of 3.47. Among patients with nonparoxysmal AF, fibrosis (F4, OR: 3.66), endothelial damage (E4, OR: 4.62), and LAA morphology (non-chicken-wing, OR: 3.79) were independently associated with LAAT and/or stroke. The degree of fibrosis correlated significantly with endothelial damage (R = -0.38, P = 0.0001).

Conclusions: These histological findings may be essential in considering the pathophysiology of LAAT and stroke within the atrial cardiomyopathy context.

Keywords: CHADS(2) score; atrial cardiomyopathy; atrial fibrillation; atrial fibrosis; endothelial damage; left atrial appendage thrombus.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the Japan Society for the Promotion of Science (JSPS, Tokyo, Japan) Grant-in-Aid for Young Scientists (Research Project number 22K16140) to Dr Miyauchi. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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