A computational model of fibrosis and the cardiac conduction system: the next generation of virtual heart models for research and teaching

The proliferation of fibrosis is observed in various cardiovascular diseases (CVDs) and has been linked to arrhythmias, the irregular rhythm of the heart. However, the precise mechanisms through which fibrosis promotes arrhythmia are not yet fully understood. Current computational models of fibrosis lack sophistication, failing to capture the underlying electrical heterogeneity. Developing an advanced computational model of fibrosis would enable detailed simulation studies and reveal novel mechanistic insights. Additionally, the cardiac conduction system (CCS) governs the normal excitation of the heart, and its remodelling can directly lead to arrhythmias. However, few, if any, computational models incorporate detailed electrophysiologically-anatomical representations of the CCS due to challenges in imaging and segmenting this system from anatomical data.

Atrial fibrillation (AF), the most prevalent sustained cardiac arrhythmia, becomes increasingly challenging to treat and manage as it progresses to a chronic condition, associated with electrical and structural remodelling. Fibrosis plays a significant role in this progression, particularly in the emergence of complex excitation patterns in chronic AF. The CCS is critical in the transmission of electrical excitation from the atria to the ventricles, making it a crucial factor in understanding how AF impairs cardiac function.

To underpin improved diagnostic and treatment strategies in the future, understanding the roles of fibrosis and the CCS in the development and progression of AF is essential. This project aims to develop a novel computational model of fibrosis, integrating it into a comprehensive whole-heart model with the CCS. The resulting tool will support future animal-free research and will be applied in his project to address fundamental questions regarding the mechanisms of AF.

The project brings together a team of computational modellers and experimentalists with a wealth of models, data, and experience to deliver on its objectives:

Objective 1: Develop and validate detailed and specific models that integrate electrophysiological and anatomical features of different forms of fibrosis, building upon our novel approach for modelling heterogeneous cellular coupling.

Objective 2: Investigate the fundamental mechanisms by which fibrosis promotes arrhythmia triggers and substrate using the developed model.

Objective 3: Explore how fibrosis contributes to trigger and substrate in AF by applying the models alongside reconstructed human atria and fibrosis maps.

Objective 4: Integrate these models into our whole-heart model and develop a robust simulation capable of considering structural remodelling and simulating normal and abnormal activation patterns.

Objective 5: Investigate the interaction between AF, the CCS, and ventricular function using the comprehensive whole-heart model.