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This study presents a novel methodology for stratifying post-myocardial infarction patients at risk of ventricular arrhythmias using patient-specific 3D cardiac models derived from late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) images. The method integrates imaging and computational simulation with a simplified cellular automaton model, Arrhythmic3D, enabling rapid and accurate VA risk assessment in clinical timeframes. Applied to 51 patients, the model generated thousands of personalized simulations to evaluate arrhythmia inducibility and predict VA risk. Key findings include the identification of slow conduction channels (SCCs) within scar tissue as critical to reentrant arrhythmias and the localization of high-risk zones for potential intervention. The Arrhythmic Risk Score (ARRISK), developed from simulation results, demonstrated strong concordance with clinical outcomes and outperformed traditional imaging-based risk stratification. The methodology is fully automated, requiring minimal user intervention, and offers a promising tool for improving precision medicine in cardiac care by enhancing patient-specific arrhythmia risk assessment and guiding treatment strategies.

The availability of digital twins for the cardiovascular system will enable insightful computational tools both for research and clinical practice. This, however, demands robust and well defined models and methods for the different steps involved in the process. We present a vessel coordinate system (VCS) that enables the unanbiguous definition of locations in a vessel section, by adapting the idea of cylindrical coordinates to the vessel geometry. Using the VCS model, point correspondence can be defined among different samples of a cohort, allowing data transfer, quantitative comparison, shape coregistration or population analysis. Furthermore, the VCS model allows for the generation of specific meshes (e.g. cylindrical grids, ogrids) necessary for an accurate reconstruction of the geometries used in fluid simulations. We provide the technical details for coordinates computation and discuss the assumptions taken to guarantee that they are well defined. The VCS model is tested in a series of applications. We present a robust, low dimensional, patient specific vascular model and use it to study phenotype variability analysis of the thoracic aorta within a cohort of patients. Point correspondence is exploited to build an haemodynamics atlas of the aorta for the same cohort. The atlas originates from fluid simulations (Navier-Stokes with Finite Volume Method) conducted using OpenFOAMv10. We finally present a relevant discussion on the VCS model, which covers its impact in important areas such as shape modeling and computer fluids dynamics (CFD).

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically-consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions., Comment: Paper under revision