A Semi-automatic Pipeline for Generation of Large Cohorts of Four-Chamber Heart Meshes.

Computational models for cardiac electro-mechanics have been increasingly used to further understand heart function. Small cohort and single patient computational studies provide useful insight into cardiac pathophysiology and response to therapy. However, these smaller studies have limited capability to capture the high level of anatomical variability seen in cardiology patients.

Additional coils mitigate elevated defibrillation threshold in right-sided implantable cardioverter defibrillator generator placement: a simulation study.

Aims: The standard implantable cardioverter defibrillator (ICD) generator (can) is placed in the left pectoral area; however, in certain circumstances, right-sided cans may be required which may increase defibrillation threshold (DFT) due to suboptimal shock vectors. We aim to quantitatively assess whether the potential increase in DFT of right-sided can configurations may be mitigated by alternate positioning of the right ventricular (RV) shocking coil or adding coils in the superior vena cava (SVC) and coronary sinus (CS).

Methods And Results: A cohort of CT-derived torso models was used to assess DFT of ICD configurations with right-sided cans and alternate positioning of RV shock coils.

Credibility assessment of patient-specific computational modeling using patient-specific cardiac modeling as an exemplar.

Reliable and robust simulation of individual patients using patient-specific models (PSMs) is one of the next frontiers for modeling and simulation (M&S) in healthcare. PSMs, which form the basis of digital twins, can be employed as clinical tools to, for example, assess disease state, predict response to therapy, or optimize therapy. They may also be used to construct virtual cohorts of patients, for in silico evaluation of medical product safety and/or performance.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

Aims: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT.

An automated near-real time computational method for induction and treatment of scar-related ventricular tachycardias.

Catheter ablation is currently the only curative treatment for scar-related ventricular tachycardias (VTs). However, not only are ablation procedures long, with relatively high risk, but success rates are punitively low, with frequent VT recurrence. Personalized in-silico approaches have the opportunity to address these limitations.

Effect of scar and pacing location on repolarization in a porcine myocardial infarction model.

Background: The effect of chronic ischemic scar on repolarization is unclear, with conflicting results from human and animal studies. An improved understanding of electrical remodeling within scar and border zone tissue may enhance substrate-guided ablation techniques for treatment of ventricular tachycardia. Computational modeling studies have suggested increased dispersion of repolarization during epicardial, but not endocardial, left ventricular pacing, in close proximity to scar.

Determining anatomical and electrophysiological detail requirements for computational ventricular models of porcine myocardial infarction.

Background: Computational models of the heart built from cardiac MRI and electrophysiology (EP) data have shown promise for predicting the risk of and ablation targets for myocardial infarction (MI) related ventricular tachycardia (VT), as well as to predict paced activation sequences in heart failure patients. However, most recent studies have relied on low resolution imaging data and little or no EP personalisation, which may affect the accuracy of model-based predictions.

Objective: To investigate the impact of model anatomy, MI scar morphology, and EP personalisation strategies on paced activation sequences and VT inducibility to determine the level of detail required to make accurate model-based predictions.

An in-silico assessment of efficacy of two novel intra-cardiac electrode configurations versus traditional anti-tachycardia pacing therapy for terminating sustained ventricular tachycardia.

The implanted cardioverter defibrillator (ICD) is an effective direct therapy for the treatment of cardiac arrhythmias, including ventricular tachycardia (VT). Anti-tachycardia pacing (ATP) is often applied by the ICD as the first mode of therapy, but is often found to be ineffective, particularly for fast VTs. In such cases, strong, painful and damaging backup defibrillation shocks are applied by the device.

High mean entropy calculated from cardiac MRI texture analysis is associated with antitachycardia pacing failure.

Background: Antitachycardia pacing (ATP), which may avoid unnecessary implantable cardioverter-defibrillator (ICD) shocks, does not always terminate ventricular arrhythmias (VAs). Mean entropy calculated using cardiac magnetic resonance texture analysis (CMR-TA) has been shown to predict appropriate ICD therapy. We examined whether scar heterogeneity, quantified by mean entropy, is associated with ATP failure and explore potential mechanisms using computer modeling.

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

Objective: Interstitial fibrosis is a pathological expansion of the heart's inter-cellular collagen matrix. It is a potential complication of nonischemic cardiomyopathy (NICM), a class of diseases involving electrical and or mechanical dysfunction of cardiac tissue not caused by atherosclerosis. Patients with NICM and interstitial fibrosis often suffer from life threatening arrhythmias, which we aim to simulate in this study.

Left ventricular endocardial pacing is less arrhythmogenic than conventional epicardial pacing when pacing in proximity to scar.

Background: Epicardial pacing increases risk of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) when pacing in proximity to scar. Endocardial pacing may be less arrhythmogenic as it preserves the physiological sequences of activation and repolarization.

Objective: The purpose of this study was to determine the relative arrhythmogenic risk of endocardial compared to epicardial pacing, and the role of the transmural gradient of action potential duration (APD) and pacing location relative to scar on arrhythmogenic risk during endocardial pacing.

Evaluation of a real-time magnetic resonance imaging-guided electrophysiology system for structural and electrophysiological ventricular tachycardia substrate assessment.

Aims: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model.

Methods And Results: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI.

Fibrosis Microstructure Modulates Reentry in Non-ischemic Dilated Cardiomyopathy: Insights From Imaged Guided 2D Computational Modeling.

Patients who present with non-ischemic dilated cardiomyopathy (NIDCM) and enhancement on late gadolinium magnetic resonance imaging (LGE-CMR), are at high risk of sudden cardiac death (SCD). Further risk stratification of these patients based on LGE-CMR may be improved through better understanding of fibrosis microstructure. Our aim is to examine variations in fibrosis microstructure based on LGE imaging, and quantify the effect on reentry inducibility and mechanism.

Modeling the Electrophysiological Properties of the Infarct Border Zone.

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.

Computational Modeling for Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF) patients with an electrical substrate pathology causing ventricular dyssynchrony. However 40-50% of patients do not respond to treatment. Cardiac modeling of the electrophysiology, electromechanics, and hemodynamics of the heart has been used to study mechanisms behind HF pathology and CRT response.

Mind the Gap: A Semicontinuum Model for Discrete Electrical Propagation in Cardiac Tissue.

Electrical propagation in cardiac tissue is a discrete or discontinuous phenomenon that reflects the complexity of the anatomical structures and their organization in the heart, such as myocytes, gap junctions, microvessels, and extracellular matrix, just to name a few. Discrete models or microscopic and discontinuous models are, so far, the best options to accurately study how structural properties of cardiac tissue influence electrical propagation. These models are, however, inappropriate in the context of large scale simulations, which have been traditionally performed by the use of continuum and macroscopic models, such as the monodomain and the bidomain models.

An efficient finite element approach for modeling fibrotic clefts in the heart.

Advanced medical imaging technologies provide a wealth of information on cardiac anatomy and structure at a paracellular resolution, allowing to identify microstructural discontinuities which disrupt the intracellular matrix. Current state-of-the-art computer models built upon such datasets account for increasingly finer anatomical details, however, structural discontinuities at the paracellular level are typically discarded in the model generation process, owing to the significant costs which incur when using high resolutions for explicit representation. In this study, a novel discontinuous finite element (dFE) approach for discretizing the bidomain equations is presented, which accounts for fine-scale structures in a computer model without the need to increase spatial resolution.

Parametrization strategies for matching activation sequences in models of ventricular electrophysiology.

Driven by recent advances in medical imaging, image segmentation and numerical techniques computer models of ventricular electrophysiology account for increasingly finer levels of anatomical and biophysical detail. However, considering the large number of model parameters involved parametrization poses a major challenge. A minimum requirement in combined experimental and modeling studies which aim at making specific predictions on a case by case basis is to achieve good agreement in activation and repolarization sequences between model and experiment or patient data.

Limitations of the homogenized cardiac Monodomain model for the case of low gap junctional coupling.

The cardiac Monodomain model is a mathematical model extensively used in studies of propagation of bioelectric wavefronts in the heart. To be able to use the model for complex and large cardiac simulations, such as the case of whole heart and 3D simulations, some parameters of the model that are known to physiologically vary in space, such as the intracellular conductivity, are traditionally kept constant at effective values. These effective values can be obtained via a mathematical procedure called homogenization.