Modeling Electrophysiological and Biomechanical Effects of Fibrosis at the Organ Scale

Axel Loewe
Karlsruhe Institute of Technology (KIT)


Abstract

Cardiac fibrosis is a key substrate for conduction abnormalities, arrhythmia maintenance, and impaired mechanical function. Because fibrotic remodeling spans spatial scales from microscopic collagen deposition and disrupted cell-to-cell coupling to macroscopic scar and diffuse structural remodeling, computational modeling has become an important tool for linking tissue structure to organ-scale functional consequences. This invited overview lecture will summarize current computational approaches for modeling fibrosis and its electrophysiological effects, such as conduction slowing, wavebreak, reentry, and electrogram fractionation, across scales. At the microscopic level, the lecture will review representations of fibrotic microstructure, including percolation-based models, cleft-based approaches, and other explicit representations of microscopic collagen barriers. At the macroscopic level, we will discuss phenomenological formulations such as reduced conductivity, non-conductive scar regions, and regionally defined remodeling. Stochastic methods for generating physiologically realistic fibrosis patterns, as well as links to patient-specific imaging and mapping data, will also be covered. The presentation will further address the incorporation of fibrosis-associated electrophysiological remodeling, including ion channel changes and altered cellular properties. Beyond the electrophysiological consequences of fibrosis, the lecture will review recent progress in modeling the biomechanical effects of fibrosis and scar, including increased stiffness, altered contractility, impaired chamber deformation, and changes in overall cardiac performance in electromechanical simulations. Emphasis will be placed on how the chosen representation of fibrosis influences predicted electrophysiological and biomechanical behavior at the organ scale. Finally, open challenges will be highlighted, including integration of imaging-derived structure with model formulations, balancing microstructural fidelity against data availability and computational cost, combining electrophysiological and mechanical remodeling in multiscale models, and establishing validation strategies that support both mechanistic insight and future clinical applicability.