Meshless Simulation of Multi-site Radio Frequency Catheter Ablation through the Fragile Points Method

Computational models for radio frequency catheter ablation (RFCA) of cardiac arrhythmia have been developed and tested in conditions where a single ablation site is considered. However, in reality arrhythmic events are generated at multiple sites which are ablated during treatment. Under such conditions, heat accumulation from several ablations is expected and models should take this effect into account. Moreover, such models are solved using the Finite Element Method which requires a good quality mesh to ensure numerical accuracy. Therefore, clinical application is limited since heat accumulation effects are neglected and numerical accuracy depends on mesh quality. In this work, we propose a novel meshless computational model where tissue heat accumulation from previously ablated sites is taken into account. In this way, we aim to overcome the mesh quality restriction of the Finite Element Method and enable realistic multi-site ablation simulation. We consider a two ablation sites protocol where tissue temperature at the end of the first ablation is used as initial condition for the second ablation. The effect of the time interval between the ablation of the two sites is evaluated. The proposed method demonstrates that previous models that do not account for heat accumulation between ablations may underestimate the tissue heat distribution

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: a computational study

Hyperactivity of the parasympathetic nervous system has been linked to the development of paroxysmal atrial fibrillation (AF). The parasympathetic neurotransmitter acetylcholine (ACh) causes a reduction in action potential (AP) duration (APD) and an increase in resting membrane potential (RMP), both of which contribute to enhance the risk for reentry. Research suggests that small-conductance calcium activated potassium (SK) channels may be an effective target for treating AF. Therapies targeting the autonomic nervous system, either alone or in combination with other drugs, have been explored and have been shown to decrease the incidence of atrial arrhythmias. This study uses computational modeling and simulation to examine the impact of SK channel block (SKb) and-adrenergic stimulation through Isoproterenol (Iso) on countering the negative effects of cholinergic activity in human atrial cell and 2D tissue models. The steady-state effects of Iso and/or SKb on AP shape, APD at 90% repolarization (APD90) and RMP were evaluated. The ability to terminate stable rotational activity in cholinergically-stimulated 2D tissue models of AF was also investigated. A range of SKb and Iso application kinetics, which reflect varying drug binding rates, were taken into consideration. The results showed that SKb alone prolonged APD90 and was able to stop sustained rotors in the presence of ACh concentrations up to 0.01 M. Iso terminated rotors under all tested ACh concentrations, but resulted in highly-variable steady-state outcomes depending on baseline AP morphology. Importantly, the combination of SKb and Iso resulted in greater APD90 prolongation and showed promising anti-arrhythmic potential by stopping stable rotors and preventing re-inducibility

Meshless electrophysiological modeling of cardiac resynchronization therapy—benchmark analysis with finite-element methods in experimental data

Computational models of cardiac electrophysiology are promising tools for reducing the rates of non-response patients suitable for cardiac resynchronization therapy (CRT) by optimizing electrode placement. The majority of computational models in the literature are mesh-based, primarily using the finite element method (FEM). The generation of patient-specific cardiac meshes has traditionally been a tedious task requiring manual intervention and hindering the modeling of a large number of cases. Meshless models can be a valid alternative due to their mesh quality independence. The organization of challenges such as the CRT-EPiggy19, providing unique experimental data as open access, enables benchmarking analysis of different cardiac computational modeling solutions with quantitative metrics. We present a benchmark analysis of a meshless-based method with finite-element methods for the prediction of cardiac electrical patterns in CRT, based on a subset of the CRT-EPiggy19 dataset. A data assimilation strategy was designed to personalize the most relevant parameters of the electrophysiological simulations and identify the optimal CRT lead configuration. The simulation results obtained with the meshless model were equivalent to FEM, with the most relevant aspect for accurate CRT predictions being the parameter personalization strategy (e.g., regional conduction velocity distribution, including the Purkinje system and CRT lead distribution). © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics. © 2022 The Author(s

Strong-form approach to elasticity: Hybrid finite difference-meshless collocation method (FDMCM)

We propose a numerical method that combines the finite difference (FD) and strong form (collocation) meshless method (MM) for solving linear elasticity equations. We call this new method FDMCM. The FDMCM scheme uses a uniform Cartesian grid embedded in complex geometries and applies both methods to calculate spatial derivatives. The spatial domain is represented by a set of nodes categorized as (i) boundary and near boundary nodes, and (ii) interior nodes. For boundary and near boundary nodes, where the finite difference stencil cannot be defined, the Discretization Corrected Particle Strength Exchange (DC PSE) scheme is used for derivative evaluation, while for interior nodes standard second order finite differences are used. FDMCM method combines the advantages of both FD and DC PSE methods. It supports a fast and simple generation of grids and provides convergence rates comparable to weak formulations. We demonstrate the appropriateness and robustness of the proposed scheme through various benchmark problems in 2D and 3D. Numerical results show good accuracy and h-convergence properties. The ease of computational grid generation makes the method particularly suited for problems where geometries are very complicated and known only imperfectly from images, frequently occurring in e.g. geomechanics and patient-specific biomechanics, where the proposed FDMCM method, after its extension to non-linear regime, appears to be a promising alternative to the traditional weak form-based numerical schemes used in the field

Modeling the impact of prostate edema on LDR brachytherapy: a Monte Carlo dosimetry study based on a 3D biphasic finite element biomechanical model

Prostate volume changes due to edema occurrence during transperineal permanent brachytherapy should be taken under consideration to ensure optimal dose delivery. Available edema models, based on prostate volume observations, face several limitations. Therefore, patient-specific models need to be developed to accurately account for the impact of edema. In this study we present a biomechanical model developed to reproduce edema resolution patterns documented in the literature. Using the biphasic mixture theory and finite element analysis, the proposed model takes into consideration the mechanical properties of the pubic area tissues in the evolution of prostate edema. The model's computed deformations are incorporated in a Monte Carlo simulation to investigate their effect on post-operative dosimetry. The comparison of Day1 and Day30 dosimetry results demonstrates the capability of the proposed model for patient-specific dosimetry improvements, considering the edema dynamics. The proposed model shows excellent ability to reproduce previously described edema resolution patterns and was validated based on previous findings. According to our results, for a prostate volume increase of 10–20% the Day30 urethra D10 dose metric is higher by 4.2%–10.5% compared to the Day1 value. The introduction of the edema dynamics in Day30 dosimetry shows a significant global dose overestimation identified on the conventional static Day30 dosimetry. In conclusion, the proposed edema biomechanical model can improve the treatment planning of transperineal permanent brachytherapy accounting for post-implant dose alterations during the planning procedure.This work was partly supported by the French Brittany Region and by the French ANR within the Investissements d'Avenir program (Labex CAMI) under reference ANR-11-LABX-0004 (Integrated project CAPRI) and through FOCUS project (ANR-16-CE19-0011)