Key result
High fibrosis density with fibrocytes cuts conduction velocity ~82% in an in silico AF model.
Why the study?
Fibrosis is a hallmark of arrhythmogenic structural remodeling in AF, but the specific effects of diffuse fibrosis density and different fibrotic cell types on persistent AF dynamics remain unclear.
Does the type and density of fibrotic cells affect atrial fibrillation dynamics in a 3D human atrial model?
Does the type and density of fibrotic cells affect atrial fibrillation dynamics in a 3D human atrial model?
Computational modeling demonstrates that fibrocytes at high density in diffuse fibrosis significantly reduce conduction velocity and promote chaotic propagation patterns in persistent atrial fibrillation.
Caution against clinical adoption; extends in silico evidence on fibrocytes but leaves human translation open.
Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.
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Palacio et al. (2021) studied Persistent atrial fibrillation. Fibrotic cell types (fibroblasts, myofibroblasts, fibrocytes) and diffuse fibrosis density (6.25% vs 25%) was evaluated on Action potential duration, conduction velocity, and fibrillatory conduction patterns. High fibrosis density (25%) with fibrocytes in an in silico model of persistent AF generated the largest proarrhythmic effect, reducing conduction velocity by up to 82%.
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