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

Left atrial appendage (LAA) thrombus (LAAT) and ischemic stroke are considered important in atrial cardiomyopathy with progressive atrial fibrosis and endocardial endothelial damage. 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. 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. 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). These histological findings may be essential in considering the pathophysiology of LAAT and stroke within the atrial cardiomyopathy context.