Modulation of cardiac arrhythmogenesis by spatially correlated fibrosis

Abstract

Cardiac fibrosis creates structural barriers that disrupt electrical propagation, precipitating arrhythmias. Computational models frequently approximate fibrosis using uncorrelated random noise, neglecting the complex micro-architecture of biological tissue. Here, we investigated how different histology-inspired fibrotic structures interact with propagating waves to modulate sustained reentry. We extended a Perlin noise-based generator — introducing a high-density composition mode and border zone support — to synthesize compact, diffuse, interstitial, and patchy patterns. These architectures were characterized using a set of morphological and topological descriptors and percolation theory. Subsequently, we conducted electrophysiological simulations across 2D and 3D domains using the monodomain formulation coupled with a detailed ventricular cellular model adapted to reproduce acute hypoxia. The results revealed that spatially correlated patterns possess higher percolation thresholds than uncorrelated noise, yielding distinct vulnerability profiles. Compact fibrosis, characterized by massive and dense clusters, anchored stable circuits with minimal wave fractionation, presenting the lowest relative reentry risk among the patterns. Conversely, diffuse fibrosis significantly fractionated wavefronts, creating multiple anchoring points and the highest reentry incidence. Interstitial and patchy architectures forced tortuous, zigzag conduction; notably, patchy fibrosis was the only pattern that exhibited increased arrhythmogenicity in 3D, utilizing its combination of elongated strands and dense macro-structures to stabilize scroll waves. Quantifying these topology-specific wave interactions provides a foundation to inform more accurate and geometry-conscious computational modeling of cardiac fibrosis and arrhythmogenesis.