Presence of Left Atrial Fibrosis May Contribute to Aberrant Hemodynamics and Increased Risk of Stroke in Atrial Fibrillation Patients

Abstract

Atrial fibrillation (AF) patients are at high risk of stroke, with the left atrial appendage (LAA) found to be the most common site of clot formation. Presence of left atrial (LA) fibrosis has also been associated with higher stroke risk. However, the mechanisms for increased stroke risk in patients with atrial fibrotic remodeling are poorly understood. We sought to explore these mechanisms using fluid dynamic analysis and to test the hypothesis that the presence of LA fibrosis leads to aberrant hemodynamics in the LA, contributing to increased stroke risk in AF patients. We retrospectively collected late-gadolinium-enhanced MRI (LGE-MRI) images of eight AF patients (four persistent and four paroxysmal) and reconstructed their 3D LA surfaces. Personalized computational fluid dynamic simulations were performed, and hemodynamics at the LA wall were quantified by wall shear stress (WSS, friction of blood), oscillatory shear index (OSI, temporal directional change of WSS), endothelial cell activation potential (ECAP, ratio of OSI and WSS), and relative residence time (RRT, residence time of blood near the LA wall). For each case, these hemodynamic metrics were compared between fibrotic and non-fibrotic portions of the wall. Our results showed that WSS was lower, and OSI, ECAP, and RRT was higher in the fibrotic region as compared to the non-fibrotic region, with ECAP (p = 0.001) and RRT (p = 0.002) having significant differences. Case-wise analysis showed that these differences in hemodynamics were statistically significant for seven cases. Furthermore, patients with higher fibrotic burden were exposed to larger regions of high ECAP, which represents regions of low WSS and high OSI. Consistently, high ECAP in the vicinity of the fibrotic wall suggest that local blood flow was slow and oscillating that represents aberrant hemodynamic conditions, thus enabling prothrombotic conditions for circulating blood. AF patients with high LA fibrotic burden had more prothrombotic regions, providing more sites for potential clot formation, thus increasing their risk of stroke.

Left atrial epicardial adipose tissue is closely associated with left atrial appendage flow velocity in patients with nonvalvular atrial fibrillation

“…Compared with the non-LVZ group, the LAA-FV in the LVZ group was lower. This is consistent with the results of previous studies that show that there may be a correlation between atrial fibrosis and left atrial appendage velocity 13 , 14 . At present, TEE is the most widely used method to measure the function of the LAA, and it is considered the gold standard, but it is semi-invasive.…”

“…Epicardial adipose tissue (EAT) is in direct contact with the surface of the atrium and pulmonary vein and, like the myocardium, is supplied by the coronary artery 10 , which can play an important role in the occurrence and development of atrial fibrillation and stroke through a variety of mechanisms, such as fat infiltration, fibrosis and inflammation 11 , 12 . Previous studies have shown that myocardial fibrosis is closely related to the velocity of the left atrial appendage 13 , 14 . However, the relationship between epicardial adipose tissue and left atrial appendage velocity is rarely reported.…”

Assessment of Left Atrial Functions and Volume by Conventional Echocardiography in Patients with Atrial Arrhythmias

“…A recent research reports that LA wall fibrosis detected by delayed magnetic resonance imaging is inversely proportional to LA strain and strain rate and is associated with AF. [27] . Thus, structural and functional remodeling of LA in patients with AF may be the result of atrial pathology itself, independent of left ventricular dysfunction.…”

Exosomes from Bone Marrow Mesenchymal Stem Cells with Overexpressed Nrf2 Inhibit Cardiac Fibrosis in Rats with Atrial Fibrillation

“…Atrial fibrillation (AF) is an irregular rhythm of the heart which is mainly characterized by arrhythmia, pulse disorder, palpitation, dizziness, chest discomfort, and shortness of breath [ 1 ]. Further, the main histological feature for AF is atrial fibrosis which is often caused by deposition of excessive fibrinogen due to dysregulation of extracellular matrix metabolism [ 1 , 2 ]. Several previous studies have shown that apoptosis of atrial myocytes and atrial fibrosis lead to deceleration of atrial conduction velocity which mediates the occurrence and development of AF [ 3 , 4 ].…”