Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model

Abstract

Ectopic beats are known to be involved in the initiation of a variety of cardiac arrhythmias. Although their location may vary, ectopic excitations have been found to originate from infarct areas, regions of micro-fibrosis and other heterogeneous tissues. However, the underlying mechanisms that link ectopic foci to heterogeneous tissues have yet to be fully understood. In this work, we investigate the mechanism of micro-reentry that leads to the generation of ectopic beats near infarct areas using a patient-specific heart model. The patient-specific geometrical model of the heart, including scar and peri-infarct zones, is obtained through magnetic resonance imaging (MRI). The infarct region is composed of ischemic myocytes and non-conducting cells (fibrosis, for instance). Electrophysiology is captured using an established cardiac myocyte model of the human ventricle modified to describe ischemia. The simulation results clearly reveal that ectopic beats emerge from micro-reentries that are sustained by the heterogeneous structure of the infarct regions. Because microscopic information about the heterogeneous structure of the infarct regions is not available, Monte-Carlo simulations are used to identify the probabilities of an infarct region to behave as an ectopic focus for different levels of ischemia and different percentages of non-conducting cells. From the proposed model, it is observed that ectopic beats are generated when a percentage of non-conducting cells is near a topological metric known as the percolation threshold. Although the mechanism for micro-reentries was proposed half a century ago to be a source of ectopic beats or premature ventricular contractions during myocardial infarction, the present study is the first to reproduce this mechanism in-silico using patient-specific data.

3D Electrophysiological Modeling of Interstitial Fibrosis Networks and Their Role in Ventricular Arrhythmias in Non-Ischemic Cardiomyopathy

“…The reentry mechanism in our simulations involved small activation waves propagating through narrow pathways in the fibrosis which survived long enough for the surrounding tissue to become re-excitable. Such mechanisms have been noted in previous theoretical studies on electrical percolation in excitable tissue [28,29], in the fibrotic atria [30], after myocardial infarction [31], and in our previous 2D NICM fibrosis study [13].…”

Perlin Noise Generation of Physiologically Realistic Patterns of Fibrosis

“…In the heart, arguably the best-understood organ from both a physiological and mathematical perspective, the importance of fibrosis microstructure has already been identified as a key issue [38,7]. Variability on the microscopic scale has been explored computationally in terms of density of obstruction for diffuse fibrosis [39,40], including the differential effects on excitation propagating in directions longitudinal or transverse to the fibre direction [41]. A recent work incorporated interstitial and diffuse fibrosis into a larger-scale model, using image data to inform density but without an attempt to explicitly capture the precise microfibrotic structure [17].…”

Factors Promoting Conduction Slowing as Substrates for Block and Reentry in Infarcted Hearts

“…3 B and 8 . In the case of fibrosis, source-sink mismatches as wavefronts propagate around and through these complex fibrotic patterns have been shown to result in unidirectional block ( 27 , 34 , 48 , 49 ). Microscopic tissue expansions, generated by fibrosis, effectively increase the local effective refractory period ( 12 , 28 , 29 ), meaning that conduction fails in fibrotic regions but propagates normally in surrounding healthy tissue, as highlighted in Fig.…”

“…Fibrosis was represented by including synthetic patterns of nonconducting tissue with different densities and random topologies into the isthmus/BZ of the geometrical models ( 27 , 34 ) (see Fig. 1 B ).…”