Effects of different types of fibrotic remodelling in areas of low voltage on atrial fibrillation dynamics: an in-silico study

Abstract

Abstract Background Personalized computational models include the effects of personalised anatomy and atrial fibrillation (AF) remodelling in a framework that can be used to investigate patient-specific AF mechanisms and test treatment response, but modelling fibrosis remains an unresolved matter. The interpretation of regions exhibiting low voltage in electroanatomic mapping data at different pacing rates also remain unclear. However, these occurrences are correlated with fibrotic remodelling. We aimed to use patient-specific simulations to investigate the effects of fibrosis type on AF properties by modelling conduction velocity slowing, changes in ionic channels, and replacement fibrosis, incorporated in regions of low voltage identified through omnipolar mapping at different pacing rates. Methods Local activation times (LATs) voltage and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were collected in sinus rhythm with coronary sinus pacing at pacing interval (PIs) of 250ms and 600ms. For a total of 10 cases, personalised anatomical models were constructed for electrophysiology simulations, and analysed using an automated pipeline in python. For conductivity models, areas with peak omnipolar voltage (OV) below 0.5mV were assigned low conduction velocity. To incorporate ionic changes, the ionic properties were altered in fibrotic regions (peak OV < 0.5mV). In the simulations where replacement fibrosis was included through a probabilistic percolation method, percolation was modelled by using random number generator to probabilistically remove elements of low voltage. Pulmonary vein isolation was simulated in each model after 5s of AF, and wavefront propagation patterns were analysed to quantify the number of rotational areas or areas of wavefront break-up in 7 anatomical segments. Results The models with conductivity fibrotic remodelling demonstrated rotational drivers in more than two LA anatomical segments for both CS250ms pacing rate and CS600ms pacing rate across all 10 cases. The anterior wall exhibited the largest degree of rotational activity in 7 out of 10 cases for CS250ms pacing rate and in 9 out of 10 cases for CS600ms pacing rate (Figure A). The combination of percolation and conductivity remodelling also exhibited rotational activity on the anterior wall in 9 out of 10 cases at CS250ms pacing rate, and 7 out of 10 cases for CS600ms pacing rate. For the simulations where replacement fibrosis was included (percolation), both the roof and anterior wall exhibited the largest degree of rotational activity in 5 out of 10 cases at CS250ms pacing rate; while at CS600ms pacing rate, the posterior walled exhibited the majority of rotational activity in 7 cases (Figure B). All fibrosis models containing ionic changes terminated in more than half of the 10 cases for both pacing rates (CS250ms and 600). Conclusion The impact of low voltage on fibrotic remodelling causes complex effects on AF dynamics.