Computational Representations of Myocardial Infarct Scars and Implications for Arrhythmogenesis

Connolly, Adam; Bishop, Martin J.

doi:10.4137/cmc.s39708

Cited by 30 publications

(32 citation statements)

References 60 publications

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“…However, the induced PVC could still propagate further toward the distal end, where the tissue had recovered excitability, and reenter back around the scar [24]. In this work we have shown that conduction block can occur as a result of sourcesink mismatch rather than heterogeneities in AP duration or in the ERP.…”

Section: Unidirectional Conduction Blockmentioning

confidence: 79%

“…Recently, Connolly et al [24] have demonstrated that a premature stimulus capturing inside the isthmus may be blocked from propagating to the myocardium as the effective refractory period (ERP) was shown to be higher at the isthmus' proximal mouth. However, the induced PVC could still propagate further toward the distal end, where the tissue had recovered excitability, and reenter back around the scar [24].…”

Section: Unidirectional Conduction Blockmentioning

confidence: 99%

“…Each model included an idealized infarct region representing a scar with an isthmus with different widths [24]. A transition region consisting of BZ myocytes surrounding the isthmus and scar region was also included in the models.…”

Section: D Sheets With Idealized Scarmentioning

confidence: 99%

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Microscopic Isthmuses and Fibrosis Within the Border Zone of Infarcted Hearts Promote Calcium-Mediated Ectopy and Conduction Block

et al. 2018

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Ventricular tachycardia (VT) secondary to myocardial infarction (MI) remain a major cause of sudden death in adults. Premature ventricular complexes (PVCs), the first initiating beats of a portion of these arrhythmias, arise from triggered activity in the infarct border zone (BZ). At the cellular scale, spontaneous calcium release (SCR) events are a known cause of triggered activity and have been reported in cells that survive MI. At the tissue scale, fibrosis has been shown to play an important role in creating the substrate for VT. However, the interplay between SCR-mediated triggered activity and fibrosis upon VT formation in infarcted hearts has not been fully investigated. Here, we conduct in-silico experiments to assess how macroscopic and microscopic anatomical properties of the BZ can create a substrate for SCR-mediated VT formation. To study this question, we employ a stochastic subcellular-scale model of SCR events and action potential to simulate different cardiac preparations. Within 2D sheet models with idealized infarct scars and BZ we show that the probability of PVCs is higher, 55%, in preparations with thin conducting isthmuses (0.2 mm) transcending the scar. In an anatomically-detailed model of the rabbit ventricles with a realistic representation of intramural scars, we show that the heart's protective source-sink mismatch prevents ectopy. Furthermore, we demonstrate that fibrosis disrupts this antiarrhythmic mechanism making PVCs more likely. PVC probability is highest (≥25%) when fibrosis accounts for 60 and 90% of the BZ in the 2D sheet and the 3D anatomical model, respectively. Above these thresholds, PVC occurrence decreases because of: (1) the reduced number of myocytes in the BZ; (2) conduction block. Block is caused either by disconnection of BZ cells from the myocardium or due to source-sink mismatches at regions of rapid tissue expansion. Moreover, while outward propagation to healthy tissue may fail, PVCs traveling inward through the scar might encounter more favorable loading conditions. These PVCs may exit to the myocardium and reenter back at the region of block. Overall, our findings indicate that thin isthmuses and strands of myocytes interspersed with fibrosis can be arrhythmogenic. Ablation of these microscopic structures may prevent VT formation.

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Section: Unidirectional Conduction Blockmentioning

confidence: 79%

Section: Unidirectional Conduction Blockmentioning

confidence: 99%

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Microscopic Isthmuses and Fibrosis Within the Border Zone of Infarcted Hearts Promote Calcium-Mediated Ectopy and Conduction Block

et al. 2018

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“…Particularly, a shorter APD will also shorten the wavelength, making the formation of a sustained re-entrant circuit more likely. On the other hand, a longer APD at the BZ may be arrhythmogenic in the presence of an isthmus (Connolly and Bishop, 2016 ), where propagation is initially blocked, due to increased refractoriness, but might enter the isthmus creating a re-entrant circuit.…”

Section: Discussionmentioning

confidence: 99%

Modeling the Electrophysiological Properties of the Infarct Border Zone

et al. 2018

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Ventricular arrhythmias (VA) in patients with myocardial infarction (MI) are thought to be associated with structural and electrophysiological remodeling within the infarct border zone (BZ). Personalized computational models have been used to investigate the potential role of the infarct BZ in arrhythmogenesis, which still remains incompletely understood. Most recent models have relied on experimental data to assign BZ properties. However, experimental measurements vary significantly resulting in different computational representations of this region. Here, we review experimental data available in the literature to determine the most prominent properties of the infarct BZ. Computational models are then used to investigate the effect of different representations of the BZ on activation and repolarization properties, which may be associated with VA. Experimental data obtained from several animal species and patients with infarct show that BZ properties vary significantly depending on disease's stage, with the early disease stage dominated by ionic remodeling and the chronic stage by structural remodeling. In addition, our simulations show that ionic remodeling in the BZ leads to large repolarization gradients in the vicinity of the scar, which may have a significant impact on arrhythmia simulations, while structural remodeling plays a secondary role. We conclude that it is imperative to faithfully represent the properties of regions of infarction within computational models specific to the disease stage under investigation in order to conduct in silico mechanistic investigations.

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“…Connolly and Bishop 16 provide a detailed and nuanced overview of the many different computational strategies used to represent infarcted myocardium in simulations of cardiac electrophysiology. Given the recent surge of interest in the use of simulations conducted in patient-specific models reconstructed from clinical imaging data to derive useful insights for arrhythmia treatment, such as custom-tailored ablation planning, this is a timely and highly relevant review.…”

mentioning

confidence: 99%