Arrhythmogenicity of fibro-fatty infiltrations

Figure 1. A comparison between simulated geometries and clinically observed ones. For clarity, a similar color scheme was used. Adipose tissue is the lightest color, myocytes the middle shade and fibrotic tissue has been given the darkest colour. In the simulation data (Fig. 1a and b), there was a = 40% adipose tissue and f = 9% fibrotic tissue for an adipose radius of 400 μm. The histological cut is from sheep data17 and has a scale bar which denotes 500 μm. Figure 1c shows one infiltrate which consists of individual adipocytes which can be seen as small circular shapes. Each circle in Fig. 1b accounts for the whole infiltrate and is not subdivided into individual adipocytes.

Figure 2. Conduction velocity at 240 ms periodical pacing for fibrotic and adipose tissue shows faster velocity decrease upon increase of fibrotic tissue in comparison with adipose tissue (a). The conduction velocity restitution curve of fibrotic and adipose tissue shows lower conduction velocities for fibrotic tissue than for adipose tissue during the whole stimulation range (b). Simulations were carried out in a tissue of area \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$76.8\times \mathrm{76.8\ }m{m}^{2}$$\end{document}76.8×76.8 mm2, where the radius of fibrotic cells equals 50 μm, and of adipose infiltrates equals 400 μm. The conduction velocities in normal tissue are consistent with the velocities obtained in previous modelling studies18,25 and experimental recordings38. Note however that there is no data available for conduction velocities in the presence of adipose infiltrates.

Figure 3. Period of spiral wave created by an S1S2 protocol for fibrotic and adipose textures with different percentages of non-conducting tissue (a) and with different sizes of adipose infiltrates in light blue (b). Simulations were carried out in a tissue of area \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$76.8\times \mathrm{76.8\ }m{m}^{2}$$\end{document}76.8×76.8 mm2, where the radius of fibrotic cells equals 50 μm, and of adipose infiltrates equals 400 μm (a). The detail plot was made with the same tissue dimensions and for 20% of non-conducting tissue (b). The points for fibrotic and adipose tissue are plotted in their respective colour from Fig. 3a, dark blue (pure fibrotic tissue) and orange (pure adipose tissue).

Figure 4. Generation of arrhythmia by high frequency pacing versus size of the fat infiltrates. The percentage of total in-excitable tissue is shown at which arrhythmia occurred and sustained for 1.68 s with a probability higher than 25% after 10 external stimuli with a period 240 ms (a). Detailed probability distribution for radius 50 μm and radius 400 μm (b). The peak of the distributions was found in Fig. 4a and was denoted by the same colour, green and red. Simulations were carried out in a tissue of area \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$76.8\times \mathrm{76.8\ }m{m}^{2}$$\end{document}76.8×76.8 mm2, where the radius of adipose infiltrates equals 400 μm.

Figure 5. Textures of fat-fibrotic tissue corresponding to the most probable onset of arrhythmias for various radii of ATI and different percentage of ATI and F (Fig. 5b: The lines approximate the maximum of arrhythmia onset probability similar to that of Fig. 4b). The dependency can be fitted linearly. An example of such fit for radius 250 μm is presented (a). The comparison of arrhythmogenicity of ATI and F for various ATI radii represented by the arrhythmogeneity index (c).

Figure 6. Initiation of arrhythmia using a burst pacing protocol for various ATI and F percentages. The left column shows activation maps for the first wave over a timespan of 300 ms. The white lines show the region activated during a time interval of 25 ms (from 75 ms till 100 ms). The gray scale pictures show the distribution of the transmembrane potential at given times t. Movies of all three simulations can be found in the supplementary information.

Figure 7. Schematic representation of arrhythmogenicity during fibro-fatty tissue remodelling. Further explanations can be found in the text.