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

Shunsuke Miyauchi; Takehito Tokuyama; Shinya Takahashi; Toru Hiyama; Yousaku Okubo; Sho Okamura; Shogo Miyamoto; Naoto Oguri; Taiichi Takasaki; Keijiro Katayama; Mutsumi Miyauchi; Yukiko Nakano

doi:10.1016/j.jacep.2023.01.029

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

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

Authors

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Division of Medicine, Health Service Center, Hiroshima University, Higashihiroshima, Japan.
² Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
³ Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁴ Division of Medicine, Health Service Center, Hiroshima University, Higashihiroshima, Japan.
⁵ Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁶ Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: nakanoy@hiroshima-u.ac.jp.

PMID: 37495324
DOI: 10.1016/j.jacep.2023.01.029

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atrial Appendage* / diagnostic imaging
Atrial Appendage* / pathology
Atrial Fibrillation* / complications
Atrial Fibrillation* / pathology
Atrial Fibrillation* / surgery
Fibrosis
Heart Diseases* / etiology
Humans
Ischemic Stroke* / complications
Ischemic Stroke* / pathology
Stroke* / epidemiology
Stroke* / etiology
Thrombosis* / diagnostic imaging
Thrombosis* / epidemiology
Thrombosis* / etiology