Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation

Abstract

One contribution of 25 to a Theme Issue 'The virtual physiological human: integrative approaches to computational biomedicine'. Mechanisms underlying the genesis of re-entrant substrate for the most common cardiac arrhythmia, atrial fibrillation (AF), are not well understood. In this study, we develop a multi-scale three-dimensional computational model that integrates cellular electrophysiology of the left atrium (LA) and pulmonary veins (PVs) with the respective tissue geometry and fibre orientation. The latter is reconstructed in unique detail from high-resolution (approx. 70 mm) contrast micro-computed tomography data. The model is used to explore the mechanisms of re-entry initiation and sustenance in the PV region, regarded as the primary source of high-frequency electrical activity in AF. Simulations of the three-dimensional model demonstrate that an initial break-down of normal electrical excitation wave-fronts can be caused by the electrical heterogeneity between the PVs and LA. High tissue anisotropy is then responsible for the slow conduction and generation of a re-entrant circuit near the PVs. Evidence of such circuits has been seen clinically in AF patients. Our computational study suggests that primarily the combination of electrical heterogeneity and conduction anisotropy between the PVs and LA tissues leads to the generation of a high-frequency (approx. 10 Hz) re-entrant source near the PV sleeves, thus providing new insights into the arrhythmogenic mechanisms of excitation waves underlying AF.

A mathematical model of the unidirectional block caused by the pulmonary veins for anatomically induced atrial reentry

“…But, the abrupt changes in geometry and myofiber orientation in the PV sleeves are regarded as the most significant contributors in generating reentry, which is the same as the anatomically induced reentry proposed in this paper. Similar arguments can be applied to computational simulations by Aslanidi et al [26,27] except the fact that conduction slowing occurs at the junction between the left superior pulmonary veins and the inter-pulmonary area.…”

“…Maybe the two reentries constitute AF together, or one instigates the prerequisite conditions for the other. From previous computational simulations of the two reentries with biologically detailed data [26][27][28][29][30], we observe that the two reentries can be initiated by the same cause such as conduction delay due to abrupt changes of fiber orientation. However, answers can be sought in mathematical analysis.…”

Recent progress in multi-scale models of the human atria

“…Data from [29,30]. (b) The canine atria and pulmonary vein region reconstructed from micro-CT data (i) (data from [32]) is of sufficient resolution to reconstruct orientation demonstrating the complexity of fibres in the pulmonary veins (ii) (data from [45,47]). RA = right atrium, LA = left atrium, PV = pulmonary veins, LSPV = left superior pulmonary vein.…”

Influence of left atrial geometry on rotor core trajectories in a model of atrial fibrillation

“…In addition, human atria exhibit fibrosis and scar outside the pulmonary veins (PV) to a considerable degree, which may contribute to the initiation mechanisms for AF in many patients [8]. A variety of computational models propose that fibre orientation, fibrosis and the geometry of LA together can play an important role for the generation of anisotropic conductivity [9,10].…”

“…In addition, human atria exhibit fibrosis and scar outside the pulmonary veins (PV) to a considerable degree, which may contribute to the initiation mechanisms for AF in many patients [8]. A variety of computational models propose that fibre orientation, fibrosis and the geometry of LA together can play an important role for the generation of anisotropic conductivity [9,10].Clinical studies show that LA size and diameter and the PV structural characteristics in isolation [11][12] are related with the outcome of catheter ablation and are useful as independent predictors of AF recurrence. In this paper, we investigate, using a computational model, and anatomically accurate LA geometries derived from persistent AF patients, the effect of geometry in isolation on the maintenance of localised fibrillatory propagation, the spatiotemporal evolution of rotors over time and their association with anatomical characteristics.…”