The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Medical Modeling

Background:

• Atrial fibrillation (AF) involves electrical and structural remodeling, with fibrosis being a key feature.
• Fibrosis contributes to abnormal conduction and mechanical dysfunction in the atria.
• Fibrotic cells (fibroblasts, myofibroblasts, fibrocytes) influence fibrillatory dynamics.

Purpose of the Study:

• To assess the impact of diffuse fibrosis density and the interplay of fibrotic cell types on persistent AF dynamics.
• To investigate how varying fibrosis levels affect electrical propagation and AF complexity.

Main Methods:

• A 3D realistic human atria model was used, coupling cardiomyocytes with three fibrotic cell types.
• Low (6.25%) and high (25%) diffuse fibrosis densities were implemented in the left atrium.
• Analysis included action potential duration, conduction velocity, fibrillatory conduction patterns, and frequency analysis of virtual electrograms.

Main Results:

• Significant reduction in conduction velocity was observed, with higher densities causing greater reduction (up to 82% with fibrocytes).
• Increased fibrosis density intensified vulnerability to multiple re-entries, zigzag propagation, and chaotic activity.
• Fibrocytes demonstrated the most significant proarrhythmic effect, and high densities generated substantial dominant frequency gradients (up to 4.5 Hz).

Conclusions:

• Different fibrotic cell types and their density in diffuse fibrosis play a crucial role in the chaotic propagation patterns seen in persistent AF.
• Fibrosis density and specific cell composition significantly influence AF substrate and arrhythmogenesis.
• Computational modeling provides insights into the proarrhythmic mechanisms driven by fibrotic remodeling in the atria.