Pulmonary vein flow split effects in patient-specific simulations of left atrial flow.

Disruptions to left atrial (LA) blood flow, such as those caused by atrial fibrillation (AF), can lead to thrombosis in the left atrial appendage (LAA) and an increased risk of systemic embolism. LA hemodynamics are influenced by various factors, including LA anatomy and function, and pulmonary vein (PV) inflow conditions. In particular, the PV flow split can vary significantly among and within patients depending on multiple factors. In this study, we investigated how changes in PV flow split affect LA flow transport, focusing for the first time on blood stasis in the LAA, using a high-fidelity patient-specific computational fluid dynamics (CFD) model. We use an Immersed Boundary Method, simulating the flow in a fixed, uniform Cartesian mesh and imposing the movement of the LA walls with a moving Lagrangian mesh generated from 4D Computerized Tomography images. We analyzed LA anatomies from eight patients with varying atrial function, including three with AF and either a LAA thrombus or a history of Transient Ischemic Attacks (TIAs). Using four different flow splits (60/40% and 55/45% through right and left PVs, even flow rate, and same velocity through each PV), we found that flow patterns are sensitive to PV flow split variations, particularly in planes parallel to the mitral valve. Changes in PV flow split also had a significant impact on blood stasis and could contribute to increased risk for thrombosis inside the LAA, particularly in patients with AF and previous LAA thrombus or a history of TIAs. Our study highlights the importance of considering patient-specific PV flow split variations when assessing LA hemodynamics and identifying patients at increased risk for thrombosis and stroke. This knowledge is relevant to planning clinical procedures such as AF ablation or the implementation of LAA occluders.

Fibrosis, atrial fibrillation and stroke: clinical updates and emerging mechanistic models.

The current paradigm of stroke risk assessment and mitigation in patients with atrial fibrillation (AF) is centred around clinical risk factors which, in the presence of AF, lead to thrombus formation. The mechanisms by which these clinical risk factors lead to thromboembolism, including any role played by atrial fibrosis, are not understood. In patients who had embolic stroke of undetermined source (ESUS), the problem is compounded by the absence of AF in a majority of patients despite long-term monitoring. Atrial fibrosis has emerged as a unifying mechanism that independently provides a substrate for arrhythmia and thrombus formation. Fibrosis-based computational models of AF initiation and maintenance promise to identify therapeutic targets in catheter ablation. In ESUS, fibrosis is also increasingly recognised as a major risk factor, but the underlying mechanism of this correlation is unclear. Simulations have uncovered potential vulnerability to arrhythmia induction in patients who had ESUS. Likewise, computational models of fluid dynamics representing blood flow in the left atrium and left atrium appendage have improved our understanding of thrombus formation, in particular left atrium appendage shapes and blood flow changes influenced by atrial remodelling. Multiscale modelling of blood flow dynamics based on structural fibrotic and morphological changes with associated cellular and tissue electrical remodelling leading to electromechanical abnormalities holds tremendous promise in providing a mechanistic understanding of the clinical problem of thromboembolisation. We present a review of clinical knowledge alongside computational modelling frameworks and conclude with a vision of a future paradigm integrating simulations in formulating personalised treatment plans for each patient.