Patchy fibrosis promotes trigger-substrate interactions that both generate and maintain atrial fibrillation.

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Cardiac Electrophysiology

Background:

• Fibrosis is mechanistically linked to cardiac arrhythmogenesis, particularly in atrial fibrillation (AF).
• Existing research highlights fibrosis's role in creating conduction barriers, promoting re-entry, and stabilizing rotors in AF.
• The specific mechanisms by which fibrosis generates AF triggers remain underexplored.

Purpose of the Study:

• To investigate the impact of fibrosis on the generation of AF triggers using computational models.
• To analyze trigger-substrate interactions in the presence of fibrosis within atrial tissue models.
• To elucidate the mechanisms by which fibrosis contributes to initiating and sustaining cardiac arrhythmias.

Main Methods:

• Application of an in-house computational framework to simulate atrial tissue models (2D and 3D).
• Inclusion of a reduced model for stochastic, spontaneous cellular triggers.
• Modeling of heterogeneous inter-cellular coupling to represent fibrotic changes.

Main Results:

• Fibrosis was shown to promote focal excitations by reducing electrotonic load on individual fiber strands.
• This reduction facilitates robust initiation of excitation within single strands, leading to full tissue focal excitation.
• Enhanced conduction block due to fibrosis can lead to trigger-substrate interactions, resulting in complex re-entrant patterns.

Conclusions:

• Fibrosis plays a significant role in promoting the emergence of focal excitations, a key trigger for AF.
• The study provides novel insights into how fibrosis creates the necessary triggers and substrate for arrhythmia induction and maintenance.
• Computational modeling effectively demonstrates the mechanistic link between fibrosis and the generation of cardiac arrhythmias.