Three-Dimensional Impulse Propagation in Myocardium

Abstract

I mpulse propagation in the heart depends on the excitability of individual cardiomyocytes, impulse transmission between adjacent myocytes, and the 3-dimensional (3D) arrangement of those cells. These factors operate across a wide range of spatial scales, and normal function at each level ensures that electric activation spreads across the cardiac chambers in a stable rhythm, which triggers efficient contraction. Perturbation of this function can give rise to rhythm disturbance and reentrant activation. The conditions necessary for reentrant arrhythmia have been known in a general sense Abstract: Impulse propagation in the heart depends on the excitability of individual cardiomyocytes, impulse transmission between adjacent myocytes, and the 3-dimensional arrangement of those cells. Here, we review the role of each of these factors in normal and aberrant cardiac electric activation, with particular emphasis on the effects of 3-dimensional myocyte architecture at the tissue scale. The analysis draws on findings from in vivo and in vitro experiments, as well as biophysically based computer models that have been used to integrate and interpret these experimental data. It indicates that discontinuous arrangement of myocytes and extracellular connective tissue at the tissue scale can give rise to current source-to-sink mismatch, spatiotemporal distribution of refractoriness, and rate-sensitive electric instability, which contribute to the initiation and maintenance of reentrant cardiac arrhythmia. This exacerbates the risk of rhythm disturbance associated with heart disease. We conclude that structure-based, multiscale computer models that incorporate accurate information about local cellular electric activity provide a powerful platform for investigating the basis of reentrant cardiac arrhythmia. However, it is important that these models capture key features of structure and related electric function at the tissue scale. (Circ Res. 2013;112:834-848.)Key Words: electric anisotropy ■ electrophysiology ■ fibrosis ■ infarct border zone ■ myocardial architecture ■ normal activation ■ reentrant arrhythmia

Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo

“…Atrial wall thickness variation may influence AF activation patterns25; particularly, tissue thickness variation has been demonstrated to possibly lead to drifting and localization of reentrant drivers in a human atrial model. Moreover, development and progression of atrial fibrosis is widely accepted as one of the most important substrates for AF perpetuation by inducing marked local conduction abnormalities 4, 5. Recent clinical studies in AF patients using in vivo late gadolinium–enhanced MRI suggest that the extent and distribution of atrial fibrosis is a reliable predicator of catheter ablation success 6, 9.…”

“…15, 28 Atrial 3D geometry with a resolution of 180 μm 3 including accurate wall thickness, myofiber orientations, and transmural fibrosis, was integrated with the adapted cellular model into a 3D computer model. Electrical conductivities were set at an anisotropic ratio of 9:1, which led to ≈3:1 regional anisotropic ratio for conduction velocities along the long axis of the cell and allowed the proper reproduction of the experimentally mapped conduction velocities as utilized by previous atrial modeling studies 4, 15. Fibrosis and simulated ablation lesion lines were modeled as nonconducting tissue 4, 29.…”

“…Electrical conductivities were set at an anisotropic ratio of 9:1, which led to ≈3:1 regional anisotropic ratio for conduction velocities along the long axis of the cell and allowed the proper reproduction of the experimentally mapped conduction velocities as utilized by previous atrial modeling studies 4, 15. Fibrosis and simulated ablation lesion lines were modeled as nonconducting tissue 4, 29. The simulated activation time maps were interpolated, smoothed, and visualized on the epicardial surface mesh of the human atria.…”

“…Current ablation strategies for persistent/permanent AF or AF with concurrent cardiac diseases are disappointing, with a <30% long‐term success rate for single‐ablation procedures 1, 2, 3. This inadequate success rate may be because of the lack of basic understanding of the underlying atrial functional and structural substrates that sustain AF directly in human hearts4, 5, 6, 7 and emphasizes the need for quantitative tools to evaluate human atrial 3‐dimensional (3D) structural features in both clinical and experimental settings.…”

“…Large‐animal structural models, such as sheep15, 16 and goats,17 have been used to investigate myofiber structure and surface geometry of the intact atria and progress has been made in defining the mechanisms of AF in animal models 4, 18. However, the interspecies difference in atrial structure and physiology may diminish the translational applications of these models to human AF 7.…”