bioRxiv Science⌕ Search

Biology subjects

Berg, L. A.

Publications and source records attributed to Berg, L. A..

3 recordsLinked to original sources

MonoAlg3D: Enabling Cardiac Electrophysiology Digital Twins with an Efficient Open Source Scalable Solver on GPU Clusters

Modelling and simulation are essential in biomedicine, and specifically in computational cardiology. Reliable, efficient and accurate solvers are critical. This study presents an open source, GPU-based cardiac electrophysiology solver for scalable digital twin multiscale simulations (MO_SCPLOWONOC_SCPLOWAO_SCPLOWLGC_SCPLOW3D), incorporating conduction system calibration and performance optimization. The solver employs the monodomain equation coupled with the Purkinje network, solved via the finite volume method, featuring a GPU-based linear solver and concurrent simulation dispatch with MPI. We demonstrate a 10.94x speedup over a CPU-based solution and scalability by running 512 simulations on 128 compute nodes, completing all coarse-mesh simulations in less than 24 minutes and fine-mesh simulations in 303 minutes. We also demonstrate integration into a cardiac digital twin pipeline for personalisation based on clinical data. The proposed open source solver enhances computational efficiency and physiological fidelity, enabling large-scale, high-speed cardiac simulations. This work marks a significant step toward fast and scalable cardiac simulations on GPU architectures, with integration in a Digital Twin personalisation pipeline including the conduction system.

bioengineering↗

Towards prospective in-silico trials in atrial fibrillation: the case of polypharmacological SK and K2P channel block

BackgroundVirtual evaluation of medical therapy through human-based modelling and simulation can accelerate and augment clinical investigations. Treatment of the most common cardiac arrhythmia, atrial fibrillation (AF), requires novel approaches. ObjectivesTo prospectively evaluate and mechanistically explain novel pharmacological therapies for atrial fibrillation through in-silico trials, considering single and combined SK and K2P channel block. MethodsA large cohort of 1000 virtual patients was developed for simulations of AF and pharmacological action. Extensive calibration and validation with experimental and clinical data support their credibility. ResultsSustained AF was observed in 654 (65%) virtual patients. In this cohort, cardioversion efficacy increased to 82% (534 of 654) through combined SK+K2P channel block, from 33% (213 of 654) and 43% (278 of 654) for single SK and K2P blocks, respectively. Drug-induced prolongation of tissue refractoriness, dependent on the virtual patients ionic current profile, explained cardioversion efficacy (atrial refractory period increase: 133.0{+/-}48.4 ms for combined vs. 45.2{+/-}43.0 and 71.0{+/-}55.3 for single SK and K2P block, respectively). Virtual patients cardioverted by SK channel block presented lower K2P densities, while lower SK densities favoured the success of K2P channel inhibition. Both ionic currents had a crucial role on atrial repolarization, and thus, a synergism resulted from the polypharmacological approach. All three strategies, including the multi-channel block, preserved atrial electrophysiological function (i.e., conduction velocity and calcium transient dynamics) and thus, its contractile properties (safety). ConclusionIn-silico trials identify key factors determining efficacy of single vs combined SK+K2P channel block as effective and safe strategies for AF management.

bioengineering↗

In Silico Evaluation of Cell Therapy in Acute versus Chronic Infarction: Role of Automaticity, Heterogeneity and Purkinje in Human

Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. After demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI, and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation, and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement, and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars, and acute infarction. We conclude that homogeneity in injected cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.

bioengineering↗