A Review of Healthy and Fibrotic Myocardium Microstructure Modeling and Corresponding Intracardiac Electrograms

Figures

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  FIGURE 1. Electrical propagation in healthy cardiac tissue. (A) Extracellular field caused by the depolarization of cardiomyocytes when an excitation propagates from left to right (green arrows). Spatial transmembrane voltage distribution is color-coded on the membranes and shown in the bottom row. The leftmost cells are already depolarized an in the action potential plateau while those on the right are still at resting membrane voltage. (B) Symmetric unipolar electrogram measured at the surface of the cardiac tissue (pink). The initial positive wave (R-peak) is caused by the wavefront approaching the electrode (dark gray), the polarity changes when the wavefront passes underneath the electrode, and the S-peak is caused by the wavefront traveling away from the measuring electrode.

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  FIGURE 2. Bidomain simulation of a realistically deformed LASSO™ (Biosense Webster) catheter in a left atrium to study the genesis of different EGM morphologies in healthy myocardium. (A) The wavefront approaches the electrode pair 7–8 and activates both electrodes at the same time, the resulting bipolar electrogram with a reduced peak-to-peak amplitude (0.42 mV). (B) Several wavefronts approaching electrode pair 13–14, both unipolar electrograms are asymmetrical, lacking an S-peak; the resulting bipolar electrogram has a high peak-to-peak amplitude and a positive polarity. (C) The wavefront travels almost perpendicular to electrode pair 3–4; the electrodes are activated at different times, the resulting bipolar electrogram has negative polarity and a high peak-to-peak amplitude (7.45 mV).

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  FIGURE 3. Filter effects on electrograms measured in healthy myocardium. (A) Unipolar electrograms with different highpass filter values. (B) Effect of different highpass cut-off values on the unipolar electrogram amplitude. (C) Bipolar electrogram with different highpass cut-off values. (D) Effect of different highpass cut-off values on the bipolar electrogram amplitude.

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  FIGURE 4. Electrical propagation in fibrotic cardiac tissue, the composition is heterogeneous and includes cardiac myocytes (orange), myofibroblasts/fibroblasts (green) and collagen fibers (purple). Depolarization of cardiomyocytes when an excitation propagates from left to right (brown arrows). Dotted arrows represent a conduction block, while dashed arrows represent slowed conduction. As a result of the zig-zag propagation of the wavefront (white arrows), the unipolar electrogram morphology is not symmetric, is prolonged and shows multiple deflections.

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  FIGURE 5. Filter effect on electrograms measured in the proximity of a fibrotic area. (A) Unipolar electrograms with different highpass filter values. (B) Effect of different highpass cut-off values on the unipolar electrogram amplitude. (C) Bipolar electrogram with different highpass cut-off values. (D) Effect of different highpass cut-off values on the bipolar electrogram amplitude.

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  FIGURE 6. Sketches of a tissue cut for healthy and fibrotic tissue (top row). Fibrotic sketches represent different fibrotic patterns (diffuse, interstitial, patchy or compact). The bottom row depicts the homogenization assumption where a hexahedral mesh element of 100 μm × 100 μm × 100 μm represents several cardiac myocytes and has to assume one average set of properties that describes the electrophysiology of this group of cells. For fibrotic tissue, homogenization implies that one element contains different types of cells (cardiac myocytes and fibroblasts/myofibroblasts) and collagen. Also the electrophysiological characteristics of this piece of tissue has to be represented by one set of effective parameters.

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  FIGURE 7. Different fibrosis modeling methodologies and their corresponding unipolar and bipolar electrograms. Central fibrotic area (dashed line), the choice of the modeling approach affects the resulting uEGMs and biEGMs. (A) fibroblasts coupled to myocytes in the fibrotic region; (B) removing a share of elements in the fibrotic region from the computational domain; (C) severely reducing conductivity in a share of elements in the fibrotic region but the spatial transmembrane voltage gradients of fibrotic elements still contribute to the EGMs; (D) conductivity gradient from center of the fibrotic region to the surrounding healthy tissue. Absolute EGM amplitudes are smaller than in vivo due to the small size of the tissue patch.