Simulation of diffuse and stringy fibrosis in a bilayer interconnected cable model of the left atrium.

AIMS: The aim of this study is to design a computer model of the left atrium for investigating fibre-orientation-dependent microstructure such as stringy fibrosis. METHODS AND RESULTS: We developed an approach for automatic construction of bilayer interconnected cable models from left atrial geometry and epi- and endocardial fibre orientation. The model consisted of two layers (epi- and endocardium) of longitudinal and transverse cables intertwined-like fabric threads, with a spatial discretization of 100 µm. Model validation was performed by comparison with cubic volumetric models in normal conditions. Then, diffuse (n = 2904), stringy (n = 3600), and mixed fibrosis patterns (n = 6840) were randomly generated by uncoupling longitudinal and transverse connections in the interconnected cable model. Fibrosis density was varied from 0% to 40% and mean stringy obstacle length from 0.1 to 2 mm. Total activation time, apparent anisotropy ratio, and local activation time jitter were computed during normal rhythm in each pattern. Non-linear regression formulas were identified for expressing measured propagation parameters as a function of fibrosis density and obstacle length (stringy and mixed patterns). Longer obstacles (even below tissue space constant) were independently associated with prolonged activation times, increased anisotropy, and local fluctuations in activation times. This effect was increased by endo-epicardial dissociation and mitigated when fibrosis was limited to the epicardium. CONCLUSION: Interconnected cable models enable the study of microstructure in organ-size models despite limitations in the description of transmural structures.

Simulated P wave morphology in the presence of endo-epicardial activation delay.

AIMS: Evidences of asynchrony between epicardial and endocardial activation in the atrial wall have been reported. We used a computer model of the atria and torso to investigate the consequences of such activation delay on P wave morphology, while controlling for P wave duration. METHODS AND RESULTS: We created 390 models of the atria based on the same geometry. These models differed by atrial wall thickness (from 2 to 3 mm), transmural coupling, and tissue conductivity in the endocardial and epicardial layers. Among them, 18 were in baseline, 186 had slower conduction in the epicardium layer and 186 in the endocardial layer. Conduction properties were adjusted in such a way that total activation time was the same in all models. P waves on a 16-lead system were simulated during sinus rhythm. Activation maps were similar in all cases. Endo-epicardial delay varied between -5.5 and 5.5 ms vs. 0 ± 0.5 ms in baseline. All P waves had the same duration but variability in their morphology was observed. With slower epicardial conduction, P wave amplitude was reduced by an average of 20% on leads V3-V5 and P wave area decreased by 50% on leads V1-V2 and by 40% on lead V3. Reversed, lower magnitude effects were observed with slower endocardial conduction. CONCLUSION: An endo-epicardial delay of a few milliseconds is sufficient to significantly alter P wave morphology, even if the activation map remains the same.

Multiparameter optimization of nonuniform passive diffusion properties for creating coarse-grained equivalent models of cardiac propagation.

The arrhythmogenic role of discrete cardiac propagation may be assessed by comparing discrete (fine-grained) and equivalent continuous (coarse-grained) models. We aim to develop an optimization algorithm for estimating the smooth conductivity field that best reproduces the diffusion properties of a given discrete model. Our algorithm iteratively adjusts local conductivity of the coarse-grained continuous model by simulating passive diffusion from white noise initial conditions during 3-10 ms and computing the root mean square error with respect to the discrete model. The coarse-grained conductivity field was interpolated from up to 300 evenly spaced control points. We derived an approximate formula for the gradient of the cost function that required (in two dimensions) only two additional simulations per iteration regardless of the number of estimated parameters. Conjugate gradient solver facilitated simultaneous optimization of multiple conductivity parameters. The method was tested in rectangular anisotropic tissues with uniform and nonuniform conductivity (slow regions with sinusoidal profile) and random diffuse fibrosis, as well as in a monolayer interconnected cable model of the left atrium with spatially-varying fibrosis density. Comparison of activation maps served as validation. The results showed that after convergence the errors in activation time were < 1 ms for rectangular geometries and 1-3 ms in the atrial model. Our approach based on the comparison of passive properties (<10 ms simulation) avoids performing active propagation simulations (>100 ms) at each iteration while reproducing activation maps, with possible applications to investigating the impact of microstructure on arrhythmias.