A His bundle pacing protocol for suppressing ventricular arrhythmia maintenance and improving defibrillation efficacy.

Background: The excitable gap (EG), defined as the excitable tissue between two subsequent wavefronts of depolarization, is critical for maintaining reentry that underlies deadly ventricular arrhythmias. EG in the His-Purkinje Network (HPN) plays an important role in the maintenance of electrical wave reentry that underlies these arrhythmias.

Objective: To determine if rapid His bundle pacing (HBP) during reentry reduces the amount of EG in the HPN and ventricular myocardium to suppress reentry maintenance and/or improve defibrillation efficacy.

Secretome of atrial epicardial adipose tissue facilitates reentrant arrhythmias by myocardial remodeling.

Background: Epicardial adipose tissue (EAT) accumulation is associated with cardiac arrhythmias. The effect of EAT secretome (EATs) on cardiac electrophysiology remains largely unknown.

Objective: The purpose of this study was to investigate the arrhythmogenicity of EATs and its underlying molecular and electrophysiological mechanisms.

Detection of focal source and arrhythmogenic substrate from body surface potentials to guide atrial fibrillation ablation.

Focal sources (FS) are believed to be important triggers and a perpetuation mechanism for paroxysmal atrial fibrillation (AF). Detecting FS and determining AF sustainability in atrial tissue can help guide ablation targeting. We hypothesized that sustained rotors during FS-driven episodes indicate an arrhythmogenic substrate for sustained AF, and that non-invasive electrical recordings, like electrocardiograms (ECGs) or body surface potential maps (BSPMs), could be used to detect FS and AF sustainability.

Tissue Preparation Techniques for Contrast-Enhanced Micro Computed Tomography Imaging of Large Mammalian Cardiac Models with Chronic Disease.

Structural remodeling is a common consequence of chronic pathological stresses imposed on the heart. Understanding the architectural and compositional properties of diseased tissue is critical to determine their interactions with arrhythmic behavior. Microscale tissue remodeling, below the clinical resolution, is emerging as an important source of lethal arrhythmia, with high prevalence in young adults.

The Purkinje network plays a major role in low-energy ventricular defibrillation.

Background: During ventricular fibrillation (VF), targeting the excitable gap (EG) of reentry throughout the myocardium with low-energy surface stimulation shows promise for painless defibrillation. However, the Purkinje network may provide alternative pathways for reentry to evade termination. This study investigates the role of the Purkinje network in painless defibrillation.

Low-energy, single-pulse surface stimulation defibrillates large mammalian ventricles.

Background: Strong electric shocks are the gold standard for ventricular defibrillation but are associated with pain and tissue damage. We hypothesized that targeting the excitable gap (EG) of reentry with low-energy surface stimulation is a less damaging and painless alternative for ventricular defibrillation.

Objective: The purpose of this study was to determine the conditions under which low-energy surface stimulation defibrillates large mammalian ventricles.

Stretchable Conductive Fabric for Cardiac Electrophysiology Applications.

Stretchable conductive fabric (SCF) is a durable nontoxic textile material coated or blended with conductive metals. Unlike solid metal, SCF effectively conducts electricity with low resistance and maintains conductance when stretched. Thus, we hypothesized that SCF electrodes are more suitable for cardiac electrophysiology applications in beating hearts than traditional solid metal electrodes.

Wide-area low-energy surface stimulation of large mammalian ventricular tissue.

The epicardial and endocardial surfaces of the heart are attractive targets to administer antiarrhythmic electrotherapies. Electrically stimulating wide areas of the surfaces of small mammalian ventricles is straightforward given the relatively small scale of their myocardial dimensions compared to the tissue space constant and electrical field. However, it has yet to be proven for larger mammalian hearts with tissue properties and ventricular dimensions closer to humans.

Acetylcholine Delays Atrial Activation to Facilitate Atrial Fibrillation.

Background: Acetylcholine (ACh) shortens action potential duration (APD) in human atria. APD shortening facilitates atrial fibrillation (AF) by reducing the wavelength for reentry. However, the influence of ACh on electrical conduction in human atria and its contribution to AF are unclear, particularly when combined with impaired conduction from interstitial fibrosis.

Wavelength and Fibrosis Affect Phase Singularity Locations During Atrial Fibrillation.

The mechanisms underlying atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, remain elusive. Atrial fibrosis plays an important role in the development of AF and rotor dynamics. Both electrical wavelength (WL) and the degree of atrial fibrosis change as AF progresses.

Role of the Purkinje-Muscle Junction on the Ventricular Repolarization Heterogeneity in the Healthy and Ischemic Ovine Ventricular Myocardium.

Alteration of action potential duration (APD) heterogeneity contributes to arrhythmogenesis. Purkinje-muscle junctions (PMJs) present differential electrophysiological properties including longer APD. The goal of this study was to determine if Purkinje-related or myocardial focal activation modulates ventricular repolarization differentially in healthy and ischemic myocardium.

Variability in pulmonary vein electrophysiology and fibrosis determines arrhythmia susceptibility and dynamics.

Success rates for catheter ablation of persistent atrial fibrillation patients are currently low; however, there is a subset of patients for whom electrical isolation of the pulmonary veins alone is a successful treatment strategy. It is difficult to identify these patients because there are a multitude of factors affecting arrhythmia susceptibility and maintenance, and the individual contributions of these factors are difficult to determine clinically. We hypothesised that the combination of pulmonary vein (PV) electrophysiology and atrial body fibrosis determine driver location and effectiveness of pulmonary vein isolation (PVI).

Complex interactions in a novel SCN5A compound mutation associated with long QT and Brugada syndrome: Implications for Na+ channel blocking pharmacotherapy for de novo conduction disease.

Background: The SCN5A mutation, P1332L, is linked to a malignant form of congenital long QT syndrome, type 3 (LQT3), and affected patients are highly responsive to the Na+ channel blocking drug, mexiletine. In contrast, A647D is an atypical SCN5A mutation causing Brugada syndrome. An asymptomatic male with both P1332L and A647D presented with varying P wave/QRS aberrancy and mild QTc prolongation which did not shorten measurably with mexiletine.

Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial Fibrillation.

Background: Recent studies have demonstrated conflicting mechanisms underlying atrial fibrillation (AF), with the spatial resolution of data often cited as a potential reason for the disagreement. The purpose of this study was to investigate whether the variation in spatial resolution of mapping may lead to misinterpretation of the underlying mechanism in persistent AF.

Methods And Results: Simulations of rotors and focal sources were performed to estimate the minimum number of recording points required to correctly identify the underlying AF mechanism.

Modelling methodology of atrial fibrosis affects rotor dynamics and electrograms.

Aims: Catheter ablation is an effective technique for terminating atrial arrhythmia. However, given a high atrial fibrillation (AF) recurrence rate, optimal ablation strategies have yet to be defined. Computer modelling can be a powerful aid but modelling of fibrosis, a major factor associated with AF, is an open question.

Novel Radiofrequency Ablation Strategies for Terminating Atrial Fibrillation in the Left Atrium: A Simulation Study.

Pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) is the cornerstone of atrial fibrillation (AF) therapy, but few strategies exist for when it fails. To guide RFA, phase singularity (PS) mapping locates reentrant electrical waves (rotors) that perpetuate AF. The goal of this study was to test existing and develop new RFA strategies for terminating rotors identified with PS mapping.

Opsin spectral sensitivity determines the effectiveness of optogenetic termination of ventricular fibrillation in the human heart: a simulation study.

Key Points: Optogenetics-based defibrillation, a theoretical alternative to electrotherapy, involves expression of light-sensitive ion channels in the heart (via gene or cell therapy) and illumination of the cardiac surfaces (via implanted LED arrays) to elicit light-induced activations. We used a biophysically detailed human ventricular model to determine whether such a therapy could terminate fibrillation (VF) and identify which combinations of light-sensitive ion channel properties and illumination configurations would be effective. Defibrillation was successful when a large proportion (> 16.

Disrupted calcium release as a mechanism for atrial alternans associated with human atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but our knowledge of the arrhythmogenic substrate is incomplete. Alternans, the beat-to-beat alternation in the shape of cardiac electrical signals, typically occurs at fast heart rates and leads to arrhythmia. However, atrial alternans have been observed at slower pacing rates in AF patients than in controls, suggesting that increased vulnerability to arrhythmia in AF patients may be due to the proarrythmic influence of alternans at these slower rates.

Fitting C² continuous parametric surfaces to frontiers delimiting physiologic structures.

We present a technique to fit C(2) continuous parametric surfaces to scattered geometric data points forming frontiers delimiting physiologic structures in segmented images. Such mathematical representation is interesting because it facilitates a large number of operations in modeling. While the fitting of C(2) continuous parametric curves to scattered geometric data points is quite trivial, the fitting of C(2) continuous parametric surfaces is not.

Feasibility of image-based simulation to estimate ablation target in human ventricular arrhythmia.

Background: Previous studies suggest that magnetic resonance imaging with late gadolinium enhancement (LGE) may identify slowly conducting tissues in scar-related ventricular tachycardia (VT).

Objective: To test the feasibility of image-based simulation based on LGE to estimate ablation targets in VT.

Methods: We conducted a retrospective study in 13 patients who had preablation magnetic resonance imaging for scar-related VT ablation.

Effects of mechano-electric feedback on scroll wave stability in human ventricular fibrillation.

Recruitment of stretch-activated channels, one of the mechanisms of mechano-electric feedback, has been shown to influence the stability of scroll waves, the waves that underlie reentrant arrhythmias. However, a comprehensive study to examine the effects of recruitment of stretch-activated channels with different reversal potentials and conductances on scroll wave stability has not been undertaken; the mechanisms by which stretch-activated channel opening alters scroll wave stability are also not well understood. The goals of this study were to test the hypothesis that recruitment of stretch-activated channels affects scroll wave stability differently depending on stretch-activated channel reversal potential and channel conductance, and to uncover the relevant mechanisms underlying the observed behaviors.

Computational cardiology: how computer simulations could be used to develop new therapies and advance existing ones.

This article reviews the latest developments in computational cardiology. It focuses on the contribution of cardiac modelling to the development of new therapies as well as the advancement of existing ones for cardiac arrhythmias and pump dysfunction. Reviewed are cardiac modelling efforts aimed at advancing and optimizing existent therapies for cardiac disease (defibrillation, ablation of ventricular tachycardia, and cardiac resynchronization therapy) and at suggesting novel treatments, including novel molecular targets, as well as efforts to use cardiac models in stratification of patients likely to benefit from a given therapy, and the use of models in diagnostic procedures.

Mechanisms of human atrial fibrillation initiation: clinical and computational studies of repolarization restitution and activation latency.

Background: Mechanisms of atrial fibrillation (AF) initiation are incompletely understood. We hypothesized that rate-dependent changes (restitution) in action potential duration (APD) and activation latency are central targets for clinical interventions that induce AF. We tested this hypothesis using clinical experiments and computer models.