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

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.Peer ReviewedPostprint (published version

Modelagem computacional da eletrofisiologia cardíaca: o desenvolvimento de um novo modelo para células de camundongos e a avaliação de novos esquemas numéricos

The modeling of the electrical activity of the heart is of great medical and scientific interest, because it provides a way to get a better understanding of the related biophysical phenomena, allows the development of new techniques for diagnoses as well as new drugs. Unfortunately, the modern mathematical models are of high complexity and computational costly. This study aims to: 1) The development of a computer model for the electrophysiology of cardiac cells from the mouse Sinoatrial Node; 2) To compare different numerical techniques for solving the ordinary differential equations associated to the cardiac models. During the development of the model, optimization techniques were used for all curve fitting procedures and parameter tuning in order to reproduce the experimental measurements described in the literature. The performance of explicit and implicit methods are evaluated, as well as the impact of computational techniques for code optimizations.A modelagem da atividade elétrica do coração é de grande interesse médico-científico, pois possibilita uma melhor compreensão dos fenômenos biofísicos envolvidos na atividade cardíaca, permite o desenvolvimento de novas técnicas de diagnóstico e de novas drogas. Infelizmente, os modelos matemáticos modernos são de alta complexidade e computacionalmente muito custosos. Este trabalho tem como objetivos: 1) O desenvolvimento de um modelo computacional para a eletrofisiologia de células cardíacas do Nodo Sinoatrial de camundongos; 2) A comparação de diferentes técnicas numéricas para a resolução de equações diferenciais ordinárias associadas à modelagem da eletrofisiologia cardíaca. Para o desenvolvimento do modelo, técnicas de otimização são adotadas para as tarefas de ajuste de curvas e de estimativa de parâmetros, as quais visam a reprodução de medições experimentais descritas na literatura. Os desempenhos de métodos explícitos e implícitos são avaliados, assim como o impacto de técnicas computacionais para a otimização de código

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

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.Peer Reviewe