Key result
Computational model reveals how six AF-associated mutations alter the probability of ectopy and re-entry.
Why the study?
The precise biophysical mechanisms responsible for the initiation and maintenance of AF remain unclear, despite the pulmonary veins being the primary anatomical site of initiation.
A novel computational model of the PV-LA junction demonstrates how specific ion channel mutations influence the electrophysiological substrate for atrial fibrillation initiation.
Links AF mutations to ectopic beats and reentry; leaves open translation to human risk stratification or therapy.
Atrial fibrillation (AF) is a common health problem with substantial individual and societal costs. The origin of AF has been debated for more than a century, and the precise, biophysical mechanisms that are responsible for the initiation and maintenance of the chaotic electrochemical waves that define AF, remains unclear. It is well accepted that the outlet of the pulmonary veins is the primary anatomical site of AF initiation, and that electrical isolation of these regions remains the most effective treatment for AF. Furthermore, it is well known that certain ion channel or transporter mutations can significantly increase the likelihood of AF. Here, we present a computational model capable of characterizing functionally important features of the microanatomical and electrophysiological substrate that represents the transition from the pulmonary veins (PV) to the left atrium (LA) of the human heart. This model is based on a finite element representation of every myocyte in a segment of this (PV/LA) region. Thus, it allows for investigation a mix of typical PV and LA myocytes. We use the model to investigate the likelihood of ectopic beats and re-entrant waves in a cylindrical geometry representing the transition from PV to LA. In particular, we investigate and illustrate how six different AF- associated mutations can alter the probability of ectopic beats and re-entry in this region.
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Jæger et al. (2021) studied Atrial fibrillation. Six different AF-associated mutations (computational model) was evaluated on Probability of ectopic beats and re-entrant waves. A computational model of the pulmonary vein to left atrium transition illustrated how six different AF-associated mutations alter the probability of ectopic beats and re-entry.
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