Spiral-wave instability in a medium with a gradient in the fibroblast density: A computational study

Fibrosis, a process of fibroblast proliferation in cardiac tissue, is a major concern for patients with diseases like ischemia, heart failure, and cardiomyopathy, because of its arrhythmogenic effects. Fibroblasts, in appreciable densities, are known to affect the electrical-wave dynamics in cardiac tissue, because the coupling of fibroblasts with myocytes modulates the electrophysiological properties of the myocytes. Furthermore, in fibrotic hearts, the distribution of fibroblasts can be heterogeneous, so the density of fibroblasts can vary from wounded regions (like infarcted or ischemic zones) to normal regions of the heart. Such gradients in the fibroblast density (GFD) induce spatial variation in the electrophysiological properties of the tissue, and the latter can initiate and affect the dynamics of pathological waves like spiral waves. We study the effects of GFDs on the dynamics of spiral waves by using a state-of-the-art mathematical model for human-ventricular tissue. We find that, in the presence of GFDs, spiral waves are unstable, i.e., a stable spiral wave breaks into multiple spiral waves. We find that GFDs induce spatial variations in the local spiral-wave frequency ω in the medium. Such a variation in ω leads to anisotropic thinning of the spiral arm that gives way to spiral-wave breaks. We also study the factors that enhance the instability of the spiral waves in the medium with GFD. Finally, we show that the presence of GFD can spontaneously lead to spiral waves, via high-frequency pacing, in the medium.