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.

Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.

The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts.

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.

OpenEP: A Cross-Platform Electroanatomic Mapping Data Format and Analysis Platform for Electrophysiology Research.

Background: Electroanatomic mapping systems are used to support electrophysiology research. Data exported from these systems is stored in proprietary formats which are challenging to access and storage-space inefficient. No previous work has made available an open-source platform for parsing and interrogating this data in a standardized format.

Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology.

Aims: Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This in vitro experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia.

Methods And Results: Detailed ECG, surface electrogram, and panoramic optical mapping were performed in isolated rabbit hearts cooled to moderate (31°C) and severe (17°C) hypothermia.

Improved co-registration of ex-vivo and in-vivo cardiovascular magnetic resonance images using heart-specific flexible 3D printed acrylic scaffold combined with non-rigid registration.

Background: Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI).

Generation of a cohort of whole-torso cardiac models for assessing the utility of a novel computed shock vector efficiency metric for ICD optimisation.

Implanted cardiac defibrillators (ICDs) seek to automatically detect and terminate potentially lethal ventricular arrhythmias by applying strong internal electric shocks across the heart. However, the optimisation of the specific electrode design and configurations represents an intensive area of research in the pursuit of reduced shock strengths and fewer device complications and risks. Computational whole-torso simulations play an important role in this endeavour, although knowing which specific metric should be used to assess configuration efficacy and assessing the impact of different patient anatomies and pathologies, and the corresponding effect this may have on different metrics has not been investigated.

Conceptual Intra-Cardiac Electrode Configurations That Facilitate Directional Cardiac Stimulation for Optimal Electrotherapy.

Objective: Electrotherapy remains the most effective direct therapy against lethal cardiac arrhythmias. When an arrhythmic event is sensed, either strong electric shocks or controlled rapid pacing is automatically applied directly to the heart via an implanted cardioverter defibrillator (ICDs). Despite their success, ICDs remain a highly non-optimal therapy: the strong shocks required for defibrillation cause significant extra-cardiac stimulation, resulting in pain and long-term tissue damage, and can also limit battery life.

Ventricular Endocardial Tissue Geometry Affects Stimulus Threshold and Effective Refractory Period.

Background: Understanding the biophysical processes by which electrical stimuli applied to cardiac tissue may result in local activation is important in both the experimental and clinical electrophysiology laboratory environments, as well as for gaining a more in-depth knowledge of the mechanisms of focal-trigger-induced arrhythmias. Previous computational models have predicted that local myocardial tissue architecture alone may significantly modulate tissue excitability, affecting both the local stimulus current required to excite the tissue and the local effective refractory period (ERP). In this work, we present experimental validation of this structural modulation of local tissue excitability on the endocardial tissue surface, use computational models to provide mechanistic understanding of this phenomena in relation to localized changes in electrotonic loading, and demonstrate its implications for the capture of afterdepolarizations.

Normal interventricular differences in tissue architecture underlie right ventricular susceptibility to conduction abnormalities in a mouse model of Brugada syndrome.

Aims: Loss-of-function of the cardiac sodium channel NaV1.5 is a common feature of Brugada syndrome. Arrhythmias arise preferentially from the right ventricle (RV) despite equivalent NaV1.

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks.

Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic.

Bidomain Predictions of Virtual Electrode-Induced Make and Break Excitations around Blood Vessels.

Introduction And Background: Virtual electrodes formed by field stimulation during defibrillation of cardiac tissue play an important role in eliciting activations. It has been suggested that the coronary vasculature is an important source of virtual electrodes, especially during low-energy defibrillation. This work aims to further the understanding of how virtual electrodes from the coronary vasculature influence defibrillation outcomes.

Virtual electrodes around anatomical structures and their roles in defibrillation.

Background: Virtual electrodes from structural/conductivity heterogeneities are known to elicit wavefront propagation, upon field-stimulation, and are thought to be important for defibrillation. In this work we investigate how the constitutive and geometrical parameters associated with such anatomical heterogeneities, represented by endo/epicardial surfaces and intramural surfaces in the form of blood-vessels, affect the virtual electrode patterns produced.

Methods And Results: The steady-state bidomain model is used to obtain, using analytical and numerical methods, the virtual electrode patterns created around idealized endocardial trabeculations and blood-vessels.

Computational Representations of Myocardial Infarct Scars and Implications for Arrhythmogenesis.

Image-based computational modeling is becoming an increasingly used clinical tool to provide insight into the mechanisms of reentrant arrhythmias. In the context of ischemic heart disease, faithful representation of the electrophysiological properties of the infarct region within models is essential, due to the scars known for arrhythmic properties. Here, we review the different computational representations of the infarcted region, summarizing the experimental measurements upon which they are based.

Local Gradients in Electrotonic Loading Modulate the Local Effective Refractory Period: Implications for Arrhythmogenesis in the Infarct Border Zone.

Ectopic electrical activity that originates in the peri-infarct region can give rise to potentially lethal re-entrant arrhythmias. The spatial variation in electrotonic loading that results from structural remodelling in the infarct border zone may increase the probability that focal activity will trigger electrical capture, but this has not previously been investigated systematically. This study uses in-silico experiments to examine the structural modulation of effective refractory period on ectopic beat capture.

Structural heterogeneity modulates effective refractory period: a mechanism of focal arrhythmia initiation.

Reductions in electrotonic loading around regions of structural and electrophysiological heterogeneity may facilitate capture of focal triggered activity, initiating reentrant arrhythmias. How electrotonic loading, refractoriness and capture of focal ectopics depend upon the intricate nature of physiological structural anatomy, as well as pathological tissue remodelling, however, is not well understood. In this study, we performed computational bidomain simulations with anatomically-detailed models representing the rabbit left ventricle.