A personalized real-time virtual model of whole heart electrophysiology

Computer models capable of representing the intrinsic personal electrophysiology (EP) of the heart in silico are termed virtual heart technologies. When anatomy and EP are tailored to individual patients within the model, such technologies are promising clinical and industrial tools. Regardless of their vast potential, few virtual technologies simulating the entire organ-scale EP of all four-chambers of the heart have been reported and widespread clinical use is limited due to high computational costs and difficulty in validation. We thus report on the development of a novel virtual technology representing the electrophysiology of all four-chambers of the heart aiming to overcome these limitations. In our previous work, a model of ventricular EP embedded in a torso was constructed from clinical magnetic resonance image (MRI) data and personalized according to the measured 12 lead electrocardiogram (ECG) of a single subject under normal sinus rhythm. This model is then expanded upon to include whole heart EP and a detailed representation of the His-Purkinje system (HPS). To test the capacities of the personalized virtual heart technology to replicate standard clinical morphological ECG features under such conditions, bundle branch blocks within both the right and the left ventricles under two different conduction velocity settings are modeled alongside sinus rhythm. To ensure clinical viability, model generation was completely automated and simulations were performed using an efficient real-time cardiac EP simulator. Close correspondence between the measured and simulated 12 lead ECG was observed under normal sinus conditions and all simulated bundle branch blocks manifested relevant clinical morphological features

Cell to whole organ global sensitivity analysis on a four-chamber heart electromechanics model using Gaussian processes emulators

Cardiac pump function arises from a series of highly orchestrated events across multiple scales. Computational electromechanics can encode these events in physics-constrained models. However, the large number of parameters in these models has made the systematic study of the link between cellular, tissue, and organ scale parameters to whole heart physiology challenging. A patient-specific anatomical heart model, or digital twin, was created. Cellular ionic dynamics and contraction were simulated with the Courtemanche-Land and the ToR-ORd-Land models for the atria and the ventricles, respectively. Whole heart contraction was coupled with the circulatory system, simulated with CircAdapt, while accounting for the effect of the pericardium on cardiac motion. The four-chamber electromechanics framework resulted in 117 parameters of interest. The model was broken into five hierarchical sub-models: tissue electrophysiology, ToR-ORd-Land model, Courtemanche-Land model, passive mechanics and CircAdapt. For each sub-model, we trained Gaussian processes emulators (GPEs) that were then used to perform a global sensitivity analysis (GSA) to retain parameters explaining 90% of the total sensitivity for subsequent analysis. We identified 45 out of 117 parameters that were important for whole heart function. We performed a GSA over these 45 parameters and identified the systemic and pulmonary peripheral resistance as being critical parameters for a wide range of volumetric and hemodynamic cardiac indexes across all four chambers. We have shown that GPEs provide a robust method for mapping between cellular properties and clinical measurements. This could be applied to identify parameters that can be calibrated in patient-specific models or digital twins, and to link cellular function to clinical indexes

The Effect of Ventricular Myofibre Orientation on Atrial Dynamics

Cardiac output is dependent on the tight coupling between atrial and ventricular function. The study of such interaction mechanisms is hindered by their complexity, and therefore requires a systematic approach. We have developed a four-chamber closed-loop cardiac electromechanics model which, through the coupling of the chambers with a closed-loop cardiovascular system model and the effect of the pericardium, is able to capture atrioventricular interaction. Our model simulates electrical activation and contraction of the atria and the ventricles coupled with a closed-loop model based on the CircAdapt framework. We include the effect of the pericardium on the heart using normal springs, scaling the local spring stiffness based on image-derived motion. The coupled model was used to study the impact of ventricular myofibre orientation on atrial dynamics by varying ventricular fibre orientation from –40∘ /+40∘ to –70∘ /+70∘. We found that steeper fibres increase atrioventricular valve plane motion from 1.0 mm to 14.0 mm, leading to a lower minimum left atrial (LA) pressure (–0.4 mmHg vs –1.1 mmHg) and greater venous return (LA maximum volume: 168 mL vs 182 mL), and that fibres angles –50∘ /+50∘ were consistent with a physiological atrial contraction and filling pattern. Our framework is capable of capturing complex interaction dynamics between the atria, the ventricles and the circulatory system accounting for the effect of the pericardium. Such simulation platform represents a useful tool to study both systolic and filling phases of all cardiac chambers, and how these get altered in diseased states and in response to treatment