Pulmonary Veins Function as Echo Chambers in Persistent Atrial Fibrillation: Circuitous Re-Entry Generates Outgoing Wavefronts.

Background: Although the substrate in persistent atrial fibrillation (PeAF) is not limited to the pulmonary veins (PVs), PV isolation (PVI) remains the cornerstone ablation strategy.

Objectives: The aim of this study was to describe the mechanism of outgoing wavefronts (WFs) originating in the PV sleeves during PeAF.

Methods: Eleven patients presenting for first-time PeAF ablation were recruited (mean age 63.

Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.

Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown.

Image-Based Tools and Analysis for Human RVOT/RV Structures.

The right-ventricular (RV) outflow tract (RVOT) and the transition to the RV free wall are recognized sources of arrhythmia in human hearts. However, we do not fully understand myocardial tissue structures in this region. Human heart tissue was processed for optical clarity, labelled with wheat-germ agglutin (WGA) and anti-Cx43, and imaged on a custom-built line scanning confocal microscope.

Beatwise ECG Classification for the Detection of Atrial Fibrillation with Deep Learning.

Atrial fibrillation (AF) is the most common, sustained cardiac arrhythmia. Early intervention and treatment could have a much higher chance of reversing AF. An electrocardiogram (ECG) is widely used to check the heart's rhythm and electrical activity in clinics.

Extended-volume image-derived models of coronary microcirculation.

Objective: Recent advances in tissue clearing and high-throughput imaging have enabled the acquisition of extended-volume microvasculature images at a submicron resolution. The objective of this study was to extract information from this type of images by integrating a sequence of 3D image processing steps on Terabyte scale datasets.

Methods: We acquired coronary microvasculature images throughout an entire short-axis slice of a 3-month-old Wistar-Kyoto rat heart.

Multimodal imaging shows fibrosis architecture and action potential dispersion are predictors of arrhythmic risk in spontaneous hypertensive rats.

Hypertensive heart disease (HHD) increases risk of ventricular tachycardia (VT) and ventricular fibrillation (VF). The roles of structural vs. electrophysiological remodelling and age vs.

Non-Contact Intracardiac Potential Mapping Using Mesh-Based and Meshless Inverse Solvers.

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters has been used to identify ablation targets in persistent AF but is limited by poor contact and inadequate coverage of the left atrial cavity. In this paper, we investigate the accuracy with which atrial endocardial surface potentials can be reconstructed from electrograms recorded with non-contact catheters.

Intracardiac Inverse Potential Mapping Using the Method of Fundamental Solutions.

Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters can identify ablation targets in persistent AF, but is limited by poor contact and inadequate coverage. To investigate the accuracy of inverse mapping of endocardial surface potentials from electrograms sampled with noncontact basket catheters.

A novel system for mapping regional electrical properties and characterizing arrhythmia in isolated intact rat atria.

Detailed global maps of atrial electrical activity are needed to understand mechanisms of atrial rhythm disturbance in small animal models of heart disease. To date, optical mapping systems have not provided enough spatial resolution across sufficiently extensive regions of intact atrial preparations to achieve this goal. The aim of this study was to develop an integrated platform for quantifying regional electrical properties and analyzing reentrant arrhythmia in a biatrial preparation.

It's clearly the heart! Optical transparency, cardiac tissue imaging, and computer modelling.

Recent developments in clearing and microscopy enable 3D imaging with cellular resolution up to the whole organ level. These methods have been used extensively in neurobiology, but their uptake in other fields has been much more limited. Application of this approach to the human heart and effective use of the data acquired present challenges of scale and complexity.

Electrocardiographic Imaging of Repolarization Abnormalities.

Background Dispersion and gradients in repolarization have been associated with life-threatening arrhythmias, but are difficult to quantify precisely from surface electrocardiography. The objective of this study was to evaluate electrocardiographic imaging (ECGI) to noninvasively detect repolarization-based abnormalities. Methods and Results Ex vivo data were obtained from Langendorff-perfused pig hearts (n=8) and a human donor heart.

Evidence of structural and functional plasticity occurring within the intracardiac nervous system of spontaneously hypertensive rats.

Plasticity is a fundamental property of neurons in both the central and peripheral nervous systems, enabling rapid changes in neural network function. The intracardiac nervous system (ICNS) is an extensive network of neurons clustered into ganglionated plexi (GP) on the surface of the heart. GP neurons are the final site of neuronal control of heart rhythm, and pathophysiological remodeling of the ICNS is proposed to feature in multiple cardiovascular diseases, including heart failure and atrial fibrillation.

Cardiac intramural electrical mapping reveals focal delays but no conduction velocity slowing in the peri-infarct region.

Altered electrical behavior alongside healed myocardial infarcts (MIs) is associated with increased risk of sudden cardiac death. However, the multidimensional mechanisms are poorly understood and described. This study characterizes, for the first time, the intramural spread of electrical activation in the peri-infarct region of chronic reperfusion MIs.

Shift of leading pacemaker site during reflex vagal stimulation and altered electrical source-to-sink balance.

Key Points: Vagal reflexes slow heart rate and can change where the heartbeat originates within the sinoatrial node (SAN). The mechanisms responsible for this process - termed leading pacemaker (LP) shift - have not been investigated fully. We used optical mapping to measure the effects of baroreflex, chemoreflex and carbachol on pacemaker entrainment and electrical conduction across the SAN.

Reconstruction of coronary circulation networks: A review of methods.

Building anatomically accurate models of the coronary vascular system enables potentially deeper understandings of coronary circulation. To achieve this, (a) images at different levels of vascular network-arteries, arterioles, capillaries, venules, and veins-need to be obtained through suitable imaging modalities; and (b) from images, morphological and topological information needs to be extracted using image processing techniques. While there are several modalities that enable the imaging of large vessels, microcirculation imaging-capturing vessels having diameter lesser than 100 μm-has to date been typically confined to small regions of the heart.

Quantitative descriptions of extended volume cardiac tissue architecture from multiple large hearts.

The arrangement of cardiac cells into strand and sheet-like structures within the heart wall, confers important electrical properties onto heart tissue. Unraveling cardiomyocyte architecture in both healthy and diseased hearts is fundamental to understanding the mechanisms generating normal rhythm and arrhythmia. We analyzed five extended volume serial image stacks of normal pig left ventricular tissue.

Loss of Side-to-Side Connections Affects the Relative Contributions of the Sodium and Calcium Current to Transverse Propagation Between Strands of Atrial Myocytes.

Atrial fibrillation (AF) leads to a loss of transverse connections between myocyte strands that is associated with an increased complexity and stability of AF. We have explored the interaction between longitudinal and transverse coupling, and the relative contribution of the sodium (I) and calcium (I) current to propagation, both in healthy tissue and under diseased conditions using computer simulations. Two parallel strands of atrial myocytes were modeled (Courtemanche et al.

A Machine Learning Aided Systematic Review and Meta-Analysis of the Relative Risk of Atrial Fibrillation in Patients With Diabetes Mellitus.

Meta-analysis is a widely used tool in which weighted information from multiple similar studies is aggregated to increase statistical power. However, the exponential growth of publications in key areas of medical science has rendered manual identification of relevant studies increasingly time-consuming. The aim of this work was to develop a machine learning technique capable of robust automatic study selection for meta-analysis.

Segmentation of histological images and fibrosis identification with a convolutional neural network.

Segmentation of histological images is one of the most crucial tasks for many biomedical analyses involving quantification of certain tissue types, such as fibrosis via Masson's trichrome staining. However, challenges are posed by the high variability and complexity of structural features in such images, in addition to imaging artifacts. Further, the conventional approach of manual thresholding is labor-intensive, and highly sensitive to inter- and intra-image intensity variations.

How Accurate Is Inverse Electrocardiographic Mapping? A Systematic In Vivo Evaluation.

Background: Inverse electrocardiographic mapping reconstructs cardiac electrical activity from recorded body surface potentials. This noninvasive technique has been used to identify potential ablation targets. Despite this, there has been little systematic evaluation of its reliability.

Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation.

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart.

Development of 3-D Intramural and Surface Potentials in the LV: Microstructural Basis of Preferential Transmural Conduction.

Introduction: Extracellular potentials measured on the heart surfaces are used to infer events that originate deep within the heart wall. We have reconstructed intramural potentials in three dimensions for the first time, and compare these with epicardial and endocardial surface potentials and cardiac microstructure.

Methods And Results: Extracellular potentials from intramural point stimulation were measured from a high density 3-D electrode array in the in vivo pig LV.

Early embryo loss, morphology, and effect of previous immunization against androstenedione in the ewe.

In a naturally mated cycle, ova and viable embryo number as well as embryo size were assessed on Day 4, 10, 14, 18, and 30 of gestation in Romney ewes (n = 38-44 per gestational group). For Days 4-18 of gestation, embryos were recovered by flushing the reproductive tract after slaughtering of the ewe. Ovulation rate was determined by counting the number of corpora lutea present on both ovaries.

Reduced ovulation rate, failure to be mated and fertilization failure/embryo loss are the underlying causes of poor reproductive performance in juvenile ewes.

A ewe that is mated as a juvenile (producing a lamb at 1 year of age) will produce an average of only 0.6 lambs to weaning, compared to an average of 1.2 lambs in adult ewes.

Comparison of diffusion tensor imaging by cardiovascular magnetic resonance and gadolinium enhanced 3D image intensity approaches to investigation of structural anisotropy in explanted rat hearts.

Background: Cardiovascular magnetic resonance (CMR) can through the two methods 3D FLASH and diffusion tensor imaging (DTI) give complementary information on the local orientations of cardiomyocytes and their laminar arrays.

Methods: Eight explanted rat hearts were perfused with Gd-DTPA contrast agent and fixative and imaged in a 9.4T magnet by two types of acquisition: 3D fast low angle shot (FLASH) imaging, voxels 50 × 50 × 50 μm, and 3D spin echo DTI with monopolar diffusion gradients of 3.