Abstract
Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength - electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely.
Highlights
Atrial fibrillation (AF) is a cardiac arrhythmia characterized by rapid and irregular atrial activation
In our simulations of tissue strands, full electrical remodeling reduces the action potential duration (APD) at 1 Hz pacing from 228 ms to 135 ms, while at 5 Hz the APD is shortened from 134 ms to 103 ms
This reduction in the amount of APD shortening with faster pacing demonstrates the flatter APD restitution occurring with electrical remodeling
Summary
Atrial fibrillation (AF) is a cardiac arrhythmia characterized by rapid and irregular atrial activation. Such desynchronized activation may occur when multiple waves circulate the atria. Unlike ventricular fibrillation, where unsynchronized activation of the ventricles (the main pumping chambers of the heart) causes an immediate and typically fatal loss of blood pressure, atrial fibrillation may be a repetitive, even chronic, disease. AF is more prominent in the context of alterations in atrial tissue properties – due to disease, arrhythmias, or age – known as remodeling. AF itself leads to remodeling, causing electrophysiological (‘‘electrical’’), contractile, and structural changes [4]. AF can typically be reversed in its early stages, it becomes more difficult to eliminate over time due to such remodeling – the expression ‘‘AF begets AF’’ [5]
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