Immunohistochemical characteristics of local sites that trigger atrial arrhythmias in response to high-frequency stimulation.

Aims: The response to high frequency stimulation (HFS) is used to locate putative sites of ganglionated plexuses (GPs), which are implicated in triggering atrial fibrillation (AF). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS.

Methods And Results: Sixty-three atrial sites were tested with HFS in four Langendorff-perfused porcine hearts.

Atrial conduction velocity mapping: clinical tools, algorithms and approaches for understanding the arrhythmogenic substrate.

Characterizing patient-specific atrial conduction properties is important for understanding arrhythmia drivers, for predicting potential arrhythmia pathways, and for personalising treatment approaches. One metric that characterizes the health of the myocardial substrate is atrial conduction velocity, which describes the speed and direction of propagation of the electrical wavefront through the myocardium. Atrial conduction velocity mapping algorithms are under continuous development in research laboratories and in industry.

Left Atrial Enhancement Correlates With Myocardial Conduction Velocity in Patients With Persistent Atrial Fibrillation.

Background: Conduction velocity (CV) heterogeneity and myocardial fibrosis both promote re-entry, but the relationship between fibrosis as determined by left atrial (LA) late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMRI) and CV remains uncertain.

Objective: Although average CV has been shown to correlate with regional LGE-CMRI in patients with persistent AF, we test the hypothesis that a localized relationship exists to underpin LGE-CMRI as a minimally invasive tool to map myocardial conduction properties for risk stratification and treatment guidance.

Method: 3D LA electroanatomic maps during LA pacing were acquired from eight patients with persistent AF following electrical cardioversion.

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling.

We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting.

An audit of uncertainty in multi-scale cardiac electrophysiology models.

Models of electrical activation and recovery in cardiac cells and tissue have become valuable research tools, and are beginning to be used in safety-critical applications including guidance for clinical procedures and for drug safety assessment. As a consequence, there is an urgent need for a more detailed and quantitative understanding of the ways that uncertainty and variability influence model predictions. In this paper, we review the sources of uncertainty in these models at different spatial scales, discuss how uncertainties are communicated across scales, and begin to assess their relative importance.

Considering discrepancy when calibrating a mechanistic electrophysiology model.

Uncertainty quantification (UQ) is a vital step in using mathematical models and simulations to take decisions. The field of cardiac simulation has begun to explore and adopt UQ methods to characterize uncertainty in model inputs and how that propagates through to outputs or predictions; examples of this can be seen in the papers of this issue. In this review and perspective piece, we draw attention to an important and under-addressed source of uncertainty in our predictions-that of uncertainty in the model structure or the equations themselves.

Voltage during atrial fibrillation is superior to voltage during sinus rhythm in localizing areas of delayed enhancement on magnetic resonance imaging: An assessment of the posterior left atrium in patients with persistent atrial fibrillation.

Background: Bipolar electrogram voltage during sinus rhythm (V) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent atrial fibrillation (AF), but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance.

Objective: The purpose of this study was determine whether, given adequate temporal sampling, the spatial distribution of mean AF voltage (V) better correlates with delayed-enhancement magnetic resonance imaging (MRI-DE)-detected atrial fibrosis than V.

Methods: AF was mapped (8 seconds) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660 ± 28 points/map).

Determinants of new wavefront locations in cholinergic atrial fibrillation.

Aims: Atrial fibrillation (AF) wavefront dynamics are complex and difficult to interpret, contributing to uncertainty about the mechanisms that maintain AF. We aimed to investigate the interplay between rotors, wavelets, and focal sources during fibrillation.

Methods And Results: Arrhythmia wavefront dynamics were analysed for four optically mapped canine cholinergic AF preparations.

Rethinking multiscale cardiac electrophysiology with machine learning and predictive modelling.

We review some of the latest approaches to analysing cardiac electrophysiology data using machine learning and predictive modelling. Cardiac arrhythmias, particularly atrial fibrillation, are a major global healthcare challenge. Treatment is often through catheter ablation, which involves the targeted localised destruction of regions of the myocardium responsible for initiating or perpetuating the arrhythmia.

A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas.

Introduction: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation.

Analytical approaches for myocardial fibrillation signals.

Atrial and ventricular fibrillation are complex arrhythmias, and their underlying mechanisms remain widely debated and incompletely understood. This is partly because the electrical signals recorded during myocardial fibrillation are themselves complex and difficult to interpret with simple analytical tools. There are currently a number of analytical approaches to handle fibrillation data.

Characterisation of re-entrant circuit (or rotational activity) in vitro using the HL1-6 myocyte cell line.

Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia.

Concurrent micro- to macro-cardiac electrophysiology in myocyte cultures and human heart slices.

The contact cardiac electrogram is derived from the extracellular manifestation of cellular action potentials and cell-to-cell communication. It is used to guide catheter based clinical procedures. Theoretically, the contact electrogram and the cellular action potential are directly related, and should change in conjunction with each other during arrhythmogenesis, however there is currently no methodology by which to concurrently record both electrograms and action potentials in the same preparation for direct validation of their relationships and their direct mechanistic links.

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.

Rotor Tracking Using Phase of Electrograms Recorded During Atrial Fibrillation.

Extracellular electrograms recorded during atrial fibrillation (AF) are challenging to interpret due to the inherent beat-to-beat variability in amplitude and duration. Phase mapping represents these voltage signals in terms of relative position within the cycle, and has been widely applied to action potential and unipolar electrogram data of myocardial fibrillation. To date, however, it has not been applied to bipolar recordings, which are commonly acquired clinically.

A technique for visualising three-dimensional left atrial cardiac activation data in two dimensions with minimal distance distortion.

Electro-anatomic mapping and medical imaging systems, used during clinical procedures for treatment of atrial arrhythmias, frequently record and display measurements on an anatomical surface of the left atrium. As such, obtaining a complete picture of activation necessitates simultaneous views from multiple angles. In addition, post-processing of three-dimensional surface data is challenging, since algorithms are typically applicable to planar or volumetric data.

Automated fiducial point selection for reducing registration error in the co-localisation of left atrium electroanatomic and imaging data.

Registration of electroanatomic surfaces and segmented images for the co-localisation of structural and functional data typically requires the manual selection of fiducial points, which are used to initialise automated surface registration. The identification of equivalent points on geometric features by the human eye is heavily subjective, and error in their selection may lead to distortion of the transformed surface and subsequently limit the accuracy of data co-localisation. We propose that the manual trimming of the pulmonary veins through the region of greatest geometrical curvature, coupled with an automated angle-based fiducial-point selection algorithm, significantly reduces target registration error compared with direct manual selection of fiducial points.

A software platform for the comparative analysis of electroanatomic and imaging data including conduction velocity mapping.

Electroanatomic mapping systems collect increasingly large quantities of spatially-distributed electrical data which may be potentially further scrutinized post-operatively to expose mechanistic properties which sustain and perpetuate atrial fibrillation. We describe a modular software platform, developed to post-process and rapidly analyse data exported from electroanatomic mapping systems using a range of existing and novel algorithms. Imaging data highlighting regions of scar can also be overlaid for comparison.

An automated algorithm for determining conduction velocity, wavefront direction and origin of focal cardiac arrhythmias using a multipolar catheter.

Determining locations of focal arrhythmia sources and quantifying myocardial conduction velocity (CV) are two major challenges in clinical catheter ablation cases. CV, wave-front direction and focal source location can be estimated from multipolar catheter data, but currently available methods are time-consuming, limited to specific electrode configurations, and can be inaccurate. We developed automated algorithms to rapidly identify CV from multipolar catheter data with any arrangement of electrodes, whilst providing estimates of wavefront direction and focal source position, which can guide the catheter towards a focal arrhythmic source.

High-order spectral/ element discretisation for reaction-diffusion problems on surfaces: Application to cardiac electrophysiology.

We present a numerical discretisation of an embedded two-dimensional manifold using high-order continuous Galerkin spectral/ elements, which provide exponential convergence of the solution with increasing polynomial order, while retaining geometric flexibility in the representation of the domain. Our work is motivated by applications in cardiac electrophysiology where sharp gradients in the solution benefit from the high-order discretisation, while the computational cost of anatomically-realistic models can be significantly reduced through the surface representation and use of high-order methods. We describe and validate our discretisation and provide a demonstration of its application to modelling electrochemical propagation across a human left atrium.