Biology subjects

Kassar, A.

Publications and source records attributed to Kassar, A..

3 recordsLinked to original sources

bioRxiv2025

Effect of Wall Motion Sampling on CFD-Derived Left Atrial Flow Metrics

The temporal resolution of medical imaging sequences used to drive patient-specific computational fluid dynamics (CFD) simulations remains limited, typically providing 10-20 frames per cardiac cycle. Therefore, temporal interpolation to reconstruct left atrial (LA) wall motion and boundary conditions is required, but its impact on hemodynamic predictions has not been systematically characterized. To investigate this, we constructed high-temporal-resolution reference wall-motion data using electromechanical (EM) simulations on five patient-specific atrial geometries with a history of atrial fibrillation. We then generated temporally downsampled datasets to emulate clinical frame rates (5, 10, 20, and 40 frames per cycle) and performed CFD simulations to isolate the effects of temporal undersampling on hemodynamic metrics. The focus was placed on kinetic energy, KE, and residence time, TR, particularly in the left atrial appendage (LAA), where thrombosis is most likely to occur. We employed an immersed boundary method to prescribe the wall motion and computed blood TR through a passive scalar transport equation. Results indicate that while global LA hemodynamic indices were marginally affected by the frame rate (errors < 9%), LAA metrics were more sensitive with errors up to 31% compared to reference values. The results based on 20 and 40 frames per cycle yielded favorable agreement with reference results, while 5-and 10-frame reconstructions showed larger, though not systematically biased, deviations from the reference. Importantly, patient ranking by blood-stasis indices was largely preserved. The analysis suggests that patientspecific LA reconstructions derived from dynamic CT imaging provide a reliable basis for estimating LAA blood-stasis indices. Higher frame rates ([≥] 20 per cycle) offer improved quantitative accuracy, while lower temporal resolutions may remain informative for patient stratification purposes, where relative ranking is more relevant than absolute accuracy.

bioengineering↗

bioRxiv2025

Systematic computational assessment of atrial function impairment due to fibrotic remodeling in electromechanical properties

Cardiac fibrosis is a pathological condition associated with many cardiovascular diseases. Atrial fibrosis leads to reduced atrial function, resulting in diminished blood flow and an increased risk of stroke. This reduced function arises from altered myocardial electrophysiological and mechanical properties. Identifying the relative importance of these fibrosis-associated properties can reveal the most significant determinants of left atrial function impairment. In this study, we used a computational framework to investigate the relative importance of various fibrosis-associated properties. Our model, a 3D electromechanical framework coupled with a 0D circulatory model, incorporated patient-specific geometries and fibrosis distributions from clinical imaging data. Nine parameters related to fibrotic remodeling (conduction velocity, ion channel expression levels, cell- and tissue-scale contractility, and stiffness) were analyzed using two sensitivity analysis schemes: a one-factor-at-a-time setup, allowing for the analysis of isolated effects, and a fractional factorial design, enabling the examination of combined effects. As output, we tracked various metrics derived from model-predicted pressure-volume loops. Impairment of L-type calcium current (ICaL) was most detrimental (up to 64% reduction in A-loop area). Conversely, reduced inward rectifier current (IK1) led to improved atrial function (up to 27% increase in A-loop area). Fractional factorial design analysis revealed that combination with other parameter changes blunted the impact of reduced ICaL but amplified the impact of reduced IK1. Further analysis of spatiotemporal distributions linked these effects to changes in intracellular calcium handling. Future research focusing on IK1 and ICaL could be highly significant for clinical and scientific advances. Modeling work can potentially help evaluate left atrial function among larger patient cohorts, focusing on strain analysis. Our work could also be extended to spatiotemporal simulations of blood flow and thrombosis, shedding light onto the mechanisms underlying atriogenic stroke. Author summaryCardiac fibrosis is a process where healthy heart muscle is replaced with non-conductive, non-contractile tissue. This change disrupts how the heart beats and contracts. In the left atrium, fibrosis is strongly linked to atrial fibrillation and a higher risk of stroke, the latter due to impaired pumping and altered blood flow. In this study, we used a detailed computer model of the heart, based on real patient-specific left atrial shapes and fibrosis patterns, to understand how different fibrosis-related changes affect atrial function. We tested nine features of the hearts electrical and mechanical behavior that are known to change during fibrosis, aiming to identify which ones have the most impact on the atrial function. We found that reducing the L-type calcium current -- an important signal for muscle contraction -- caused the greatest decrease in atrial performance. Surprisingly, reducing the inward rectifier potassium current actually improved it. These effects were tied to changes in calcium handling inside heart cells. Our findings highlight promising directions for future heart disease research and treatment.

systems biology↗

bioRxiv2024

Patient-specific multi-physics simulations of fibrotic changes in left atrial tissue mechanics impact on hemodynamics

Stroke is a leading cause of death and disability worldwide. Atrial myopathy, including fibrosis, is associated with an increased risk of ischemic stroke, but the mechanisms underlying this association are poorly understood. Fibrosis modifies myocardial structure, impairing electrical propagation and tissue biomechanics, and creating stagnant flow regions where clots could form. Fibrosis can be mapped non-invasively using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, fibrosis maps are not currently incorporated into stroke risk calculations or computational electro-mechano-fluidic models. We present multi-physics simulations of left atrial (LA) myocardial motion and hemodynamics using patient-specific anatomies and fibrotic maps from LGE-MRI. We modify tissue stiffness and active tension generation in fibrotic regions and investigate how these changes affect LA flow for different fibrotic burdens. We find that fibrotic regions and, to a lesser extent, non-fibrotic regions experience reduced myocardial strain, resulting in decreased LA emptying fraction consistent with clinical observations. Both fibrotic tissue stiffening and hypocontractility independently reduce LA function, but together, these two alterations cause more pronounced effects than either one alone. Fibrosis significantly alters flow patterns throughout the atrial chamber, and particularly, the filling and emptying jets of the left atrial appendage (LAA). The effects of fibrosis in LA flow are largely captured by the concomitant changes in LA emptying fraction except inside the LAA, where a multi-factorial behavior is observed. This work illustrates how high-fidelity, multi-physics models can be used to study thrombogenesis mechanisms in patient-specific anatomies, shedding light onto the links between atrial fibrosis and ischemic stroke. Key pointsO_LILeft atrial (LA) fibrosis is associated with arrhythmogenesis and increased risk of ischemic stroke; its extent and pattern can be quantified on a patient-specific basis using late gadolinium enhancement magnetic resonance imaging. C_LIO_LICurrent stroke risk prediction tools have limited personalization, and their accuracy could be improved by incorporating patient-specific information like fibrotic maps and hemodynamic patterns. C_LIO_LIWe present the first electro-mechano-fluidic multi-physics computational simulations of LA flow, including fibrosis and anatomies from medical imaging. C_LIO_LIMechanical changes in fibrotic tissue impair global LA motion, decreasing LA and left atrial appendage (LAA) emptying fractions, especially in subjects with higher fibrosis burdens. C_LIO_LIFibrotic-mediated LA motion impairment alters LA and LAA flow near the endocardium and the whole cavity, ultimately leading to more stagnant blood regions in the LAA. C_LI

bioengineering↗