Influence of Fibrosis Amount and Patterns on Ventricular Arrythmogenesis and Pumping Efficacy: Computational Study
Authors: Tekle Abrha Abebe , Lim Ki Moo 
Published: March 2020

Abstract
Background and aims: Clinical and computational studies have reported that spatial fibrosis pattern and fibrosis amount play a significant role in ventricular arrhythmogenicity. Nonetheless, the underlying mechanisms of arrhythmogenicity of fibrosis are not known accurately. In addition, we believe that the effect of different fibrosis types and fibrosis amount on the cardiac mechanical performance requires a further investigation. Therefore, this study investigated the effect of spatial distribution of fibrosis and fibrosis amount on the electrical and mechanical performance of the left ventricle (LV). Methods: We employed a human ventricular model that simulates both the electrophysiological and the mechanical contraction characteristics of the ventricle. The electrophysiological conduction model mimics the exchange of ions through the plasma membrane of myocardial cells whereas the mechanical contraction model simulates the mechanical cardiac response. Seventy-five fibrosis distributions comprising diffuse, patchy, and compact fibrosis types that contain 10%–50% fibrosis amount were generated to cover a wide range of fibrosis cases. The spatial fibrosis distribution in the human ventricular model was quantified using fibrosis entropy (FE) metric. Then, electrophysiological simulations under reentry conditions induced using the S1-S2 protocol were conducted to investigate the correlation between different patterns of fibrosis and ventricular arrhythmogenicity. Finally, we compared the mechanical response by conducting mechanical simulations to examine the influence of the fibrosis amount and spatial distribution of fibrosis on the pumping efficacy of the LV by extracting the calcium information from the electrophysiological simulation. Results: We observed that the spatial patchy fibrosis distribution was more chaotic (higher mean FE) than those of the compact and diffuse types. The electrical simulation results revealed that the ventricular arrhythmogenicity of diffuse fibrosis depends on the fibrosis amount and marginally on the spatial distribution of fibrosis. Meanwhile, the ventricular arrhythmogenicity of the compact and patchy fibrosis types is reliant on the spatial distribution of fibrosis than on the fibrosis amount. The average number of phase singularities in the electrical simulations with compact fibrosis was higher than those with patchy and diffuse fibrosis. As a result, compact fibrosis resulted a lower stroke volume (SV) of the LV, whereas the diffuse fibrosis resulted in a higher SV of the LV. The reduction in the stroke volume (SV) of the LV was linearly correlated to the electrical instabilities induced by the fibrosis amount and spatial distribution of fibrosis. Conclusion: The increase in the amount of diffuse, patchy and compact fibrosis in the myocardium increased the electrical instability and likely decreased the pumping efficacy of LV. Moreover, the effect fibrosis pattern on ventricular arrhythmogenesis was more significant in compact and patchy fibrosis types than in diffuse fibrosis.