Identifying Left Atrium and Left Atrial Appendage Prone to Thrombus Formation in Patients with Atrial Fibrillation Using Statistical Shape Modeling

Background: The morphology of the left atrium (LA) and left atrial appendage (LAA) is associated with LAA thrombus formation (LAAT) in patients with atrial fibrillation (AF). Statistical shape modeling (SSM) could be a comprehensive and objective method for evaluating LA/LAA shape, thereby improving LAAT risk assessment. Methods and results: In this individual-matched case-control study, 110 pairs of AF patients with or without LAAT were compared. Using SSM of cardiac computed tomography angiography images, we developed a LA/LAA shape deformation score (LADS). LADS was significantly higher in the LAAT group (4.0 +/- 5.0 vs.-4.0 +/- 6.5, P < 0.01) and independently associated with LAAT (odds ratio for each point increase in LADS: 1.31, 95 % confidence interval: 1.21-1.42, P < 0.01). LAAT risk assessment was significantly improved by the addition of LADS to clinical characteristics plus traditional structural parameters, evaluated by the area under the receiver- operating characteristic curve (0.879 vs 0.788, P < 0.01), net reclassification improvement (30.9 %, 95 % CI: 23.6-38.1 %, P < 0.05) and integrated discrimination improvement (18.5 %, 95 %CI: 16.8-20.3 %, P < 0.05). The predictive role of LADS in LAAT was confirmed by an unmatched external validation study including 406 patients with AF (19 cases with LAAT). Computational fluid dynamics analysis of 20 patients showed a significant association between LADS and endothelial cell activation potential, time-averaged wall shear stress, relative residence time, and blood velocity in the LAA. Conclusion: SSM-derived LADS was significantly associated with LAAT and improved LAAT risk assessment. The relationship between LAAT and LADS may be attributed to mechanisms involving endothelial dysfunction and blood stasis.