Mechanisms of pulmonary arterial hypertension-induced atrial fibrillation: insights from multi-scale models of the human atria.

This study aimed to use multi-scale atrial models to investigate pulmonary arterial hypertension (PAH)-induced atrial fibrillation mechanisms. The results of our computer simulations revealed that, at the single-cell level, PAH-induced remodelling led to a prolonged action potential (AP) (ΔAPD: 49.6 ms in the right atria (RA) versus 41.

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.

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.

Simplifying the Process of Going From Cells to Tissues Using Statistical Mechanics.

The value of digital twins for prototyping controllers or interventions in a sandbox environment are well-established in engineering and physics. However, this is challenging for biophysics trying to seamlessly compose models of multiple spatial and temporal scale behavior into the digital twin. Two challenges stand out as constraining progress: (i) ensuring physical consistency of conservation laws across composite models and (ii) drawing useful and timely clinical and scientific information from conceptually and computationally complex models.

Cardiac Conduction Velocity, Remodeling and Arrhythmogenesis.

Cardiac electrophysiological disorders, in particular arrhythmias, are a key cause of morbidity and mortality throughout the world. There are two basic requirements for arrhythmogenesis: an underlying substrate and a trigger. Altered conduction velocity (CV) provides a key substrate for arrhythmogenesis, with slowed CV increasing the probability of re-entrant arrhythmias by reducing the length scale over which re-entry can occur.

Impulse Data Models for the Inverse Problem of Electrocardiography.

Objective: To develop, train and test neural networks for predicting heart surface potentials (HSPs) from body surface potentials (BSPs). The method re-frames traditional inverse problems of electrocardiography into regression problems, constraining the solution space by decomposing signals with multidimensional Gaussian impulse basis functions.

Methods: Impulse HSPs were generated with single Gaussian basis functions at discrete heart surface locations and projected to corresponding BSPs using a volume conductor torso model.

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.

Virtual Overdose Response for People Who Use Opioids Alone: Protocol for a Feasibility and Clinical Trial Study.

Background: A recent quarterly report released by Alberta Health reports that on average 2.5 Albertans die every day from accidental overdose deaths, and that between April 1, 2020, and June 30, 2020, the province lost a total of 301 people. In Canada, between January 2016 and March 2020, a total of 16,364 people died due to opioid-related overdose.

Service delivery models for injectable opioid agonist treatment in Canada: 2 sequential environmental scans.

Background: Injectable opioid agonist treatment (iOAT) is an emerging evidence-based option in the continuum of care for opioid use disorder in parts of Canada. Our study objective was to identify and describe iOAT programs operating during the ongoing opioid overdose crisis.

Methods: We conducted 2 sequential environmental scans.

Closing the Loop: Validation of Implantable Cardiac Devices With Computational Heart Models.

Objective: Cardiovascular Implantable Electronic Devices (CIEDs) are used extensively for treating life-threatening conditions such as bradycardia, atrioventricular block and heart failure. The complicated heterogeneous physical dynamics of patients provide distinct challenges to device development and validation. We address this problem by proposing a device testing framework within the in-silico closed-loop context of patient physiology.

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.

Resonant model-A new paradigm for modeling an action potential of biological cells.

Organ level simulation of bioelectric behavior in the body benefits from flexible and efficient models of cellular membrane potential. These computational organ and cell models can be used to study the impact of pharmaceutical drugs, test hypotheses, assess risk and for closed-loop validation of medical devices. To move closer to the real-time requirements of this modeling a new flexible Fourier based general membrane potential model, called as a Resonant model, is developed that is computationally inexpensive.

Cardiac Electrical Modeling for Closed-Loop Validation of Implantable Devices.

Objective: Evaluating and testing cardiac electrical devices in a closed-physiologic-loop can help design safety, but this is rarely practical or comprehensive. Furthermore, in silico closed-loop testing with biophysical computer models cannot meet the requirements of time-critical cardiac device systems, while simplified models meeting time-critical requirements may not have the necessary dynamic features. We propose a new high-level (abstracted) physiologically-based computational heart model that is time-critical and dynamic.

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.

Predictive modeling of drug effects on electrocardiograms.

Whole electrocardiogram (ECG) waveform analysis is a technique for evaluating aggregate arrhythmic risks of drugs. In this paper, we propose methods for exploring changes to ECG morphology due to drug effects using Gaussian model parameters, and predict patient specific post-drug ECG based on pre-drug ECG. We evaluate the proposed methods using clinical ECG recordings from subjects under the effect of anti-arrhythmic drugs Dofetilide, Quinidine, Ranolazine, and Verapamil, from the ECGRVDQ database on PhysioNet.

A machine learning approach to reconstruction of heart surface potentials from body surface potentials.

Invasive cardiac catheterisation is a precursor to ablation therapy for ventricular tachycardia. Invasive cardiac diagnostics are fraught with risks. Decades of research has been conducted on the inverse problem of electrocardiography, which can be used to reconstruct Heart Surface Potentials (HSPs) from Body Surface Potentials (BSPs), for non-invasive cardiac diagnostics.

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.

Parametric Modeling of Electrocardiograms using Particle Swarm optimization.

The electrocardiogram (ECG) is commonly used to monitor or diagnose adverse heart conditions. While general ECG recordings are widely available, parametric ECG models have been proposed to generate ECG-like signals. Such ECG generators can create extended segments of specific beat morphology or cardiac rhythm, especially in disease states, which can be used to validate cardiac devices or evaluate ECG processing algorithms.

An intracardiac electrogram model to bridge virtual hearts and implantable cardiac devices.

Virtual heart models have been proposed to enhance the safety of implantable cardiac devices through closed loop validation. To communicate with a virtual heart, devices have been driven by cardiac signals at specific sites. As a result, only the action potentials of these sites are sensed.

A Parametric Computational Model of the Action Potential of Pacemaker Cells.

Objective: A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need.

Methods: The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable.

Depression Outcomes in Adults Attending Family Practice Were Not Improved by Screening, Stepped-Care, or Online CBT during a 12-Week Study when Compared to Controls in a Randomized Trial.

There is uncertainty regarding possible benefits of screening for depression in family practice, as well as the most effective treatment approach when depression is identified. Here, we examined whether screening patients for depression in primary care, and then treating them with different modalities, was better than treatment-as-usual (TAU) alone. Screening was carried out for depression using the 9-item Patient Health Questionnaire (PHQ-9), with a score of ≥10 indicating significant depressive symptoms.