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.
Highlights
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia
Even though we found significant difference in average endothelial cell activation potential (ECAP) and relative residence time (RRT) among the fibrotic and non-fibrotic regions of the left atrium (LA) wall (Table 2), we did not find strong association between the increased fibrotic burden and aberrant hemodynamics (R2 = 0.69, Figure 3), suggesting that our mechanistic explanation of the activation of endothelial cells and subsequent clot formation near the fibrotic region is a hypothesis that must be tested in future studies
Our results indicate that blood flow near the pulmonary veins (PVs) and the mitral valve (MV) depends more on the LA structure and local flow conditions at these locations, so fibrotic substrate near these regions are less likely to have aberrant hemodynamics and less clot prone
Summary
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. About 1–2% of individuals worldwide currently suffer from AF (Andrade et al, 2014), and its prevalence is expected to increase 2.5-fold in the four decades (Go et al, 2001). The left atrium appendage (LAA) has been identified as the most common site for clot formation, with ∼90% clots originating from the LAA causing stroke in AF patients (Kamp et al, 1999; Yaghi et al, 2015). Clinical and computational studies on LAA anatomy and blood flow have established that relatively low blood flow in the LAA explains the propensity to clot formation and eventual stroke events (Lee et al, 2014; Otani et al, 2016; Masci et al, 2019, 2020). In addition to the LAA, increased left atrium (LA) fibrotic burden has been associated with increased risk of stroke in clinical and imaging studies (Daccarett et al, 2011).
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