Role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry

Colli-Franzone, P.; Gionti, Vincenzo; Pavarino, Luca F.; Scacchi, Simone; Storti, Cesare

doi:10.1016/j.mbs.2019.108228

Cited by 19 publications

(16 citation statements)

References 85 publications

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“…Comparably little is known about the properties of cardiac scar tissue, which differs significantly from normal myocardium in www.nature.com/scientificreports www.nature.com/scientificreports/ multiple aspects including structure and electrophysiological behavior. Most computational studies investigating electrical conduction in infarcted hearts model the intracellular space of scar tissue as insulated from the uninjured myocardium and focus on the effect of changes in the shape and location of the border zone, the degree of transmurality of the scar, and the remodeling of myocyte ion currents in the border zone 47,48 . Although scar tissue is composed of electrically passive cells and extracellular matrix, the assumption that it behaves simply as a barrier to conduction of electrical impulses is contradicted by an increasing number of studies 15,44,45 .…”

Section: Discussionmentioning

confidence: 99%

Connexin43 expression in bone marrow derived cells contributes to the electrophysiological properties of cardiac scar tissue

Vásquez

Mezzano

Kessler

et al. 2020

Sci Rep

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Cardiac pathologies associated with arrhythmic activity are often accompanied by inflammation. The contribution of inflammatory cells to the electrophysiological properties of injured myocardium is unknown. Myocardial scar cell types and intercellular contacts were analyzed using a threedimensional reconstruction from serial blockface scanning electron microscopy data. Three distinct cell populations were identified: inflammatory, fibroblastic and endocardial cells. While individual fibroblastic cells interface with a greater number of cells, inflammatory cells have the largest contact area suggesting a role in establishing intercellular electrical connections in scar tissue. Optical mapping was used to study the electrophysiological properties of scars in fetal liver chimeric mice generated using connexin43 knockout donors (bmpKO). Voltage changes were elicited in response to applied current pulses. Isopotential maps showed a steeper pattern of decay with distance from the electrode in scars compared with uninjured regions, suggesting reduced electrical coupling. The tissue decay constant, defined as the distance voltage reaches 37% of the amplitude at the edge of the scar, was 0.48 ± 0.04 mm (n = 11) in the scar of the bmpCTL group and decreased 37.5% in the bmpKO group (n = 10). Together these data demonstrate inflammatory cells significantly contribute to scar electrophysiology through coupling mediated at least partially by connexin43 expression.

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Section: Discussionmentioning

confidence: 99%

Connexin43 expression in bone marrow derived cells contributes to the electrophysiological properties of cardiac scar tissue

Vásquez

Mezzano

Kessler

et al. 2020

Sci Rep

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“…So far, only few papers have addressed a systematic uncertainty quantification (UQ) and propagation in cardiac electrophysiology models, despite the very rapid growth of cardiac modeling and the need to deal with multiple scenarios, towards model personalization. For instance, the role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry has been considered in Reference 75; the evaluation of cardiac mechanical markers (such as longitudinal and circumferential strains) to estimate the electrical activation times has been addressed in Reference 76. See, for example References 2,77, for a review of the possible sources of uncertainty in these models at different spatial scales.…”

Section: Discussionmentioning

confidence: 99%

Enabling forward uncertainty quantification and sensitivity analysis in cardiac electrophysiology by reduced order modeling and machine learning

Pagani

Manzoni

2021

Numer Methods Biomed Eng

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We present a new, computationally efficient framework to perform forward uncertainty quantification (UQ) in cardiac electrophysiology. We consider the monodomain model to describe the electrical activity in the cardiac tissue, coupled with the Aliev‐Panfilov model to characterize the ionic activity through the cell membrane. We address a complete forward UQ pipeline, including both: (i) a variance‐based global sensitivity analysis for the selection of the most relevant input parameters, and (ii) a way to perform uncertainty propagation to investigate the impact of intra‐subject variability on outputs of interest depending on the cardiac potential. Both tasks exploit stochastic sampling techniques, thus implying overwhelming computational costs because of the huge amount of queries to the high‐fidelity, full‐order computational model obtained by approximating the coupled monodomain/Aliev‐Panfilov system through the finite element method. To mitigate this computational burden, we replace the full‐order model with computationally inexpensive projection‐based reduced‐order models (ROMs) aimed at reducing the state‐space dimensionality. Resulting approximation errors on the outputs of interest are finally taken into account through artificial neural network (ANN)‐based models, enhancing the accuracy of the whole UQ pipeline. Numerical results show that the proposed physics‐based ROMs outperform regression‐based emulators relying on ANNs built with the same amount of training data, in terms of both numerical accuracy and overall computational efficiency.

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Section: Introductionmentioning

confidence: 99%

“…To overcome the limitations of medical imaging modalities, computational heart models have been widely used as a prediction tool for disease progression 5,19‐23 . Several MI heart models, such as in, 20‐23 have been developed and investigated using numerical simulation. In these models, border zone had been widely used as an intermediate role, where the conductivities and stiffness in this region have been modelled as a transitioning from infarct zone to normally perfused myocardium 20,21 .…”

Section: Introductionmentioning

confidence: 99%

The study of border zone formation in ischemic heart using electro‐chemical coupled computational model

Naim

Mokhtarudin

Lim

et al. 2020

Numer Methods Biomed Eng

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Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three‐dimensional LV through electro‐chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub‐regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time.

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Role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry

Cited by 19 publications

References 85 publications

Connexin43 expression in bone marrow derived cells contributes to the electrophysiological properties of cardiac scar tissue

Connexin43 expression in bone marrow derived cells contributes to the electrophysiological properties of cardiac scar tissue

Enabling forward uncertainty quantification and sensitivity analysis in cardiac electrophysiology by reduced order modeling and machine learning

The study of border zone formation in ischemic heart using electro‐chemical coupled computational model

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