Sensitivity Analysis of In Silico Fluid Simulations to Predict Thrombus Formation after Left Atrial Appendage Occlusion

Abstract

Atrial fibrillation (AF) is nowadays the most common human arrhythmia and it is considered a marker of an increased risk of embolic stroke. It is known that 99% of AF-related thrombi are generated in the left atrial appendage (LAA), an anatomical structure located within the left atrium (LA). Left atrial appendage occlusion (LAAO) has become a good alternative for nonvalvular AF patients with contraindications to anticoagulants. However, there is a non-negligible number of device-related thrombus (DRT) events, created next to the device surface. In silico fluid simulations can be a powerful tool to better understand the relation between LA anatomy, haemodynamics, and the process of thrombus formation. Despite the increasing literature in LA fluid modelling, a consensus has not been reached yet in the community on the optimal modelling choices and boundary conditions for generating realistic simulations. In this line, we have performed a sensitivity analysis of several boundary conditions scenarios, varying inlet/outlet and LA wall movement configurations, using patient-specific imaging data of six LAAO patients (three of them with DRT at follow-up). Mesh and cardiac cycle convergence were also analysed. The boundary conditions scenario that better predicted DRT cases had echocardiography-based velocities at the mitral valve outlet, a generic pressure wave from an AF patient at the pulmonary vein inlets, and a dynamic mesh approach for LA wall deformation, emphasizing the need for patient-specific data for realistic simulations. The obtained promising results need to be further validated with larger cohorts, ideally with ground truth data, but they already offer unique insights on thrombogenic risk in the left atria.

Joint Analysis of Morphological Parameters and In Silico Haemodynamics of the Left Atrial Appendage for Thrombogenic Risk Assessment

“…is study has focused on studying the influence of LA/ LAA morphology and in silico haemodynamics on thrombus formation before the implantation of a LAAO device, which can lead to a better patient selection and personalised therapy choice. However, the developed modelling pipeline to create haemodynamics simulations has also shown [17][18][19][20][21] to be useful in determining the formation of thrombus after the implantation of LAAO devices (i.e., device-related thrombus). Unfortunately, the required follow-up data to perform such verification were not available in the analysed patients in this study.…”

“…Computational fluid dynamics (CFD) simulations with dynamic mesh movement of the mitral valve (MV) annulus ring were carried out by using ANSYS Fluent Solver 19.2 (Ansys, Inc., Pennsylvania, USA). In our study, we applied the boundary conditions (BCs) proposed by Mill et al [ 20 , 21 ]. They were defined as pressure inlet at the pulmonary veins (PVs) and as velocity outlet at the MV.…”

Non-Newtonian Blood Rheology Impacts Left Atrial Stasis in Patient-Specific Simulations

“…In fact, we previously showed that fixed-wall simulations and moving-wall simulations produce comparable values of blood residence time inside LAAs of the same geometry [28]. Furthermore, while previous CFD analyses indicate that LAA residence time correlates inversely with the LAA ejection fraction [28], this correlation is imperfect and additional factors such as LA volume, LAA morphology, PV flow profiles, and the MV have been associated to vortical patterns and residence time inside the LAA [60, 61, 21]. Of note, LAA morphology is a well-known stroke risk factor in patients with AF [11].…”

“…Since Shettigar et al [49] reported blood residence time to examine the washout of artificial ventricles, this quantity has been used to study the risk of intracardiac thrombosis [12,28,50]. Patient-specific computational fluid dynamics (CFD) analyses are emerging as a tool to help assess LAA thrombosis risk in AF patients [23] and after LAA occluder device implantation [21]. However, previous investigations have considered constant fluid viscosity, neglecting the non-Newtonian rheology of blood at low shear rates.…”

“…Intracavitary blood stasis and thrombogenesis risk can be quantified through blood residence time, i.e ., the time spent by blood particles inside a cardiac chamber [12], whose calculation requires detailed knowledge of the flow velocity field. Progress in computational fluid dynamics (CFD) algorithms and computer processing capacity now make it feasible to simulate blood flow in four-chamber domains [13], two-chamber domains (typically the left heart) [14, 15, 16], and single-chamber domains (typically the left ventricle) [17, 18, 19, 20, 21]. Some of these simulations include models of heart valve motion [19, 14, 16, 22] and some can resolve the intricate domain surface caused by endocardial trabeculation [22].…”