Search

Rhythm control is a cornerstone of atrial fibrillation (AF) management. Shorter time between diagnosis of AF and receipt of catheter ablation is associated with greater rates of therapy success. Previous work considered diagnosis-to-ablation time as a binary or categorical variable and did not consider the unique risk profile of patients after a referral for ablation was made. The purpose of this study was to comprehensively assess the impact of diagnosis-to-ablation and referral-to-ablation time on postprocedural outcomes at a population level. This observational cohort study included patients who received catheter ablation to treat AF in Ontario, Canada. Patient demographics, medical comorbidities, AF diagnosis date, ablation referral date, and ablation date were collected. The primary outcomes of interest included a composite of death and hospitalization/emergency department visit for AF, heart failure, or ischemic stroke. Multivariable Cox models assessed the impact of diagnosis-to-ablation and referral-to-ablation times on the primary outcome. Our cohort included 7472 patients who received ablation for de novo AF between April 1, 2016, and March 31, 2022. Median [interquartile range] diagnosis-to-ablation time was 718 [399–1274] days and median referral-to-ablation time was 221 [117–363] days. Overall, 911 patients (12.2%) had the composite endpoint within 1 year of ablation. Increasing diagnosis-to-ablation time was associated with a greater incidence for the primary outcome (hazard ratio [HR]1.02; 95% confidence interval [CI] 1.01–1.02 per month). Increasing referral-to-ablation time did not impact the primary outcome (HR 1.00; 95% CI 0.98–1.01 per month). Delays between AF diagnosis and ablation referral may contribute to adverse postprocedural outcomes and provide an opportunity for health system quality improvements. [Display omitted] [ABSTRACT FROM AUTHOR]

Rapid technologic development and expansion of procedural expertise have led to widespread proliferation of catheter-based electrophysiology procedures. It is unclear whether these advances come at cost to patient safety. This meta-analysis aimed to assess complication rates after modern electrophysiology procedures during the lifetime of the procedures. A comprehensive search was performed to identify relevant data published before May 30, 2023. Studies were included if they met the following inclusion criteria: prospective trials or registries, including comprehensive complications data; and patients undergoing atrial fibrillation ablation, ventricular tachyarrhythmia ablation, leadless cardiac pacemaker implantation, and percutaneous left atrial appendage occlusion. Pooled incidences of procedure-related complications were individually assessed by random effects models to account for heterogeneity. Temporal trends in complications were investigated by clustering trials by publication year (2000–2018 vs 2019–2023). A total of 174 studies (43,914 patients) met criteria for analysis: 126 studies of atrial fibrillation ablation (n = 24,057), 25 studies of ventricular tachyarrhythmia ablation (n = 1781), 21 studies of leadless cardiac pacemaker (n = 8896), and 18 studies of left atrial appendage occlusion (n = 9180). The pooled incidences of serious procedure-related complications (3.49% [2000–2018] vs 3.05% [2019–2023]; P <.001), procedure-related stroke (0.46% vs 0.28%; P =.002), pericardial effusion requiring intervention (1.02% vs 0.83%; P =.037), and procedure-related death (0.15% vs 0.06%; P =.003) significantly decreased over time. However, there was no significant difference in the incidence of vascular complications over time (1.86% vs 1.88%; P =.888). Despite an increase in cardiac electrophysiology procedures, procedural safety has improved over time. [ABSTRACT FROM AUTHOR]

Premature ventricular contraction (PVC) burden is a risk factor for heart failure and cardiovascular death in patients with structural heart disease. Long-term electrocardiographic monitoring can have a significant impact on PVC burden evaluation by further defining PVC distribution patterns. This study aimed to ascertain the optimal duration of electrocardiographic monitoring to characterize PVC burden and to understand clinical characteristics associated with frequent PVCs and nonsustained ventricular tachycardia in a large US cohort. Commercial data (iRhythm's Zio patch) from June 2011 to April 2022 were analyzed. Inclusion criteria were age >18 years, PVC burden ≥5%, and wear period ≥13 days. PVC burden cutoffs were determined on the basis of AHA/ACC/HRS guidelines for very frequent PVCs (10,000–20,000 during 24 hours). Patients were assigned to categories by PVC densities: low, <10%; moderate, 10% to <20%; and high, ≥20%. Mean measured error was assessed at baseline and daily until the wear period's end for overall PVC burden and different PVC densities. Analysis of 106,705 patch monitors revealed a study population with mean age of 70.6 ± 14.6 years (33.6% female). PVC burden was higher in male patients and those >65 years of age. PVC burden mean error decreased from 2.9% at 24 hours to 1.3% at 7 days and 0.7% at 10 days. Number of ventricular tachycardia episodes per patient increased with increasing PVC burden (P <.0001). Extending ambulatory monitoring beyond 24 hours to 7 days or more improves accuracy of assessing PVC burden. Ventricular tachycardia frequency and duration vary by initial PVC density, highlighting the need for prolonged cardiac monitoring. [ABSTRACT FROM AUTHOR]

• Back pain is one of the most common problems experienced by patients due to, limitation of movement and immobilization of the affected leg after the electrophysiology study procedure. • The limitation of movement after the procedure negatively affects the comfort and satisfaction of patients. • Back massage with frankincense and myrrh oil increased overall comfort, physical comfort, the psychospiritual comfort. • Massage with frankincense and myrrh oil can be recommended as a complementary and integrative treatment to improve comfort in patients who are to undergo cardiac electrophysiological study. Back pain is one of the most common problems experienced by patients after the cardiac electrophysiological study procedure. In addition, limitation of movement after the procedure negatively affects the comfort and satisfaction of patients. The aim of this study was to determine the effect of back massage with frankincense and myrrh oil on back pain severity and comfort in patients who were to undergo cardiac electrophysiological study. This is a randomized controlled study with a pretest–posttest design. This study was conducted from October 2020 to March 2021, at the angio unit of a heart hospital at a university in Turkey. The study was completed with 30 patients in each group, a total of 90 people. Data were collected using a patient information form, a Visual Analogue Scale (VAS) and the General Comfort Questionnaire (GCQ). The intervention group and the placebo group received back massage with frankincense and myrrh essential oil and with jojoba fixed oil respectively. No intervention was applied to the control group. There was no statistically significant difference between the post-procedure VAS values according to the groups. Except for sociocultural comfort, there were significant differences between the groups in terms of GCQ total scores and subscales at the first and last follow-up. Back massage with frankincense and myrrh oil increased overall comfort, physical comfort, the psychospiritual comfort. Additional research with a rigorous design is needed to determine its effect on pain. [ABSTRACT FROM AUTHOR]

Anaesthetists play a key role in the management of patients in the cardiac catheterization laboratory (cath lab), both for elective and emergency procedures. Safe and effective provision of anaesthesia relies on a thorough appreciation of the setup of the cath lab and an understanding of the ever-increasing range of procedures carried out in the angiography suite. This article provides an overview of general considerations for working in this challenging environment within the hospital, as well as outlining key cardiology subspecialties and their requisites for the anaesthetist: electrophysiology, structural, interventional, devices and mechanical circulatory support. [ABSTRACT FROM AUTHOR]

[Display omitted] • The healthcare system is a significant contributor to global warming. • Cardiac electrophysiology mainly uses high-tech single-use medical devices. • Worldwide complex supply chain for medical treatment, particularly medical devices. • The complex supply chain has led to device shortages. • Reprocessing of medical devices labelled single use could be part of the solution. • All stakeholders must engage sustainability efforts. Sustainability in healthcare, particularly within the domain of cardiac electrophysiology, assumes paramount importance for the near future. The escalating environmental constraints encountered necessitate a proactive approach. This position paper aims to raise awareness among physicians, spark critical inquiry and identify potential solutions to enhance the sustainability of our practice. Reprocessing of single-use medical devices has emerged as a potential solution to mitigate the environmental impact of electrophysiology procedures, while also offering economic advantages. However, reprocessing remains unauthorized in certain countries. In regions where it is possible, stringent regulatory standards must be adhered to, to ensure patient safety. It is essential that healthcare professionals, policymakers and manufacturers collaborate to drive innovation, explore sustainable practices and ensure that patient care remains uncompromised in the face of environmental challenges. Ambitious national/international programmes of disease prevention should be the cornerstone of the strategy. It is equally vital to implement immediate actions, as delineated in this position paper, to bring about tangible change quickly. [ABSTRACT FROM AUTHOR]

Atrial myopathy may underlie the progression of atrial fibrillation (AF) from a treatable disease to an irreversible condition with poor ablation outcomes. Electrophysiological methods to unmask areas prone to re-entry initiation could be key to defining latent atrial myopathy. Consecutive patients referred for AF ablation were prospectively included at four institutions. Decrement evoked potential mapping (DEEP) was performed in eight left atrial sites and five right atrial sites, from two different pacing locations (endocardially from the left atrial appendage, epicardially from the proximal coronary sinus). The electrograms (EGMs) during S1 600 ms drive and after an extra stimulus (S2 at +30 ms above atrial refractoriness) were studied at each location and assessed for decremental properties. Follow-up was 12 months. Seventy-four patients were included and 85% had persistent AF. A total of 17,614 EGMs were individually analysed and measured. Nine percent of the EGMs showed DEEP properties (local delay of >10 ms after S2) with a mean decrement of 33±26 ms. DEEPs were more frequent in the left atrium than the right atrium (9.4% vs 8.0%; p<0.001) and more prevalent in persistent AF patients than paroxysmal AF patients (9.8% vs 4.6% p=0.001). Atrial DEEPs were more frequently unmasked in normal bipolar voltage areas and by epicardial pacing than endocardial pacing (9.6% vs 8.4%, respectively; p=0.004). Within the left atrium, the roof had the highest prevalence of DEEP EGMs. DEEP mapping of both atria is useful for highlighting areas with a tendency for unidirectional block and re-entry initiation. Those areas are more easily unmasked by epicardial pacing from the coronary sinus and more prevalent in persistent AF patients than in paroxysmal AF patients. [ABSTRACT FROM AUTHOR]

The article focuses on the antiarrhythmic drugs. It is reported that antiarrhythmic agents are medications used to treat abnormal heart rhythms, or arrhythmias and works by suppressing the mechanisms that cause arrhythmias, including automaticity, triggered activity, and re-entry. It is further reported that these drugs are commonly used in the perioperative period and should be carefully considered before initiating treatment, as they can have both therapeutic and adverse effects.

The article offers information on the Perioperative arrhythmias which are extremely common, usually transient and typically require no intervention. Topics discussed include the majority of perioperative arrhythmias do not require treatment with antiarrhythmic drugs; three main mechanisms of arrhythmogenesis such as automaticity, triggered rhythm and re-entry; and mentions that inappropriate use of antiarrhythmic drugs can increase morbidity and mortality.

Numerical simulations in electrocardiology are often affected by various uncertainties inherited from the lack of precise knowledge regarding input values including those related to the cardiac cell model, domain geometry, and boundary or initial conditions used in the mathematical modeling. Conventional techniques for uncertainty quantification in modeling electrical activities of the heart encounter significant challenges, primarily due to the high computational costs associated with fine temporal and spatial scales. Additionally, the need for numerous model evaluations to quantify ubiquitous uncertainties increases the computational challenges even further. In the present study, we propose a non-intrusive surrogate model to perform uncertainty quantification and global sensitivity analysis in cardiac electrophysiology models. The proposed method combines an unsupervised machine learning technique with the polynomial chaos expansion to reconstruct a surrogate model for the propagation and quantification of uncertainties in the electrical activity of the heart. The proposed methodology not only accurately quantifies uncertainties at a very low computational cost but more importantly, it captures the targeted quantity of interest as either the whole spatial field or the whole temporal period. In order to perform sensitivity analysis, aggregated Sobol indices are estimated directly from the spectral mode of the polynomial chaos expansion. We conduct Uncertainty Quantification (UQ) and global Sensitivity Analysis (SA) considering both spatial and temporal variations, rather than limiting the analysis to specific Quantities of Interest (QoIs). To assess the comprehensive performance of our methodology in simulating cardiac electrical activity, we utilize the monodomain model. Additionally, sensitivity analysis is performed on the parameters of the Mitchell-Schaeffer cell model. Unlike conventional techniques for uncertainty quantification in modeling electrical activities, the proposed methodology performs at a low computational cost the sensitivity analysis on the cardiac electrical activity parameters. The results are fully reproducible and easily accessible, while the proposed reduced-order model represents a significant contribution to enhancing global sensitivity analysis in cardiac electrophysiology. • Non-intrusive surrogate model is introduced for cardiac electrophysiology models. • Spatial and temporal evolution of solutions are deemed as quantities of interest. • Uncertainty quantification is performed on stochastic processes. • Sensitivity analysis is conducted on monodomain-Mitchell-Schaeffer model parameters. [ABSTRACT FROM AUTHOR]

PoAF is the most common complication after cardiac surgery and may occur in patients with pre-existing arrhythmogenic substrate. Characterization of this substrate could aid in identifying patients at risk for PoAF. We therefore compared intra-atrial conduction parameters and electrogram morphology between patients without and with early- (≤5 days after surgery) and late- (up to 5 years) postoperative atrial fibrillation (PoAF). Epicardial mapping of the right and left atrium and Bachmann's Bundle (BB) was performed during sinus rhythm (SR) in 263 patients (207male, 67 ± 11 years). Unipolar potentials were classified as single, short or long double and fractionated potentials. Unipolar voltage, fractionation delay (time difference between the first and last deflection), conduction velocity (CV) and conduction block (CB) prevalence were measured. Comparing patients without (N = 166) and with PoAF (N = 97), PoAF was associated with lower CV and more CB at BB. Unipolar voltages were lower and more low-voltage areas were found at the left and right atrium and BB in PoAF patients. These differences were more pronounced in patients with late-PoAF (6%), which could even occur up to 5 years after surgery. Although several electrophysiological parameters were related to PoAF, age was the only independent predictor. Patients with de novo PoAF have more extensive arrhythmogenic substrate prior to cardiac surgery compared to those who remained in SR, which is even more pronounced in late-PoAF patients. Future studies should evaluate whether intra-operative electrophysiological examination enables identification of patients at risk for developing PoAF and hence (preventive) therapy. [Display omitted] • PoAF is associated with pre-existing substrate, consisting of conduction slowing, lower unipolar voltages and more LVAs. • Patients with late-PoAF have even more pronounced arrhtyhmogenic substrates prior to cardiac surgery. • This substrate is particularly located at Bachmann's Bundle, although clear differences in electrophysiological parameters are also present at the left and right atrium. • The first episode of late-PoAF could even occur up to 5 years after surgery and occurred only in patients who also developed early-PoAF. [ABSTRACT FROM AUTHOR]

Action potential duration (APD) restitution curve and its maximal slope (Smax) reflect single cell-level dynamic instability for inducing chaotic heart rhythms. However, conventional parameter sensitivity analysis often fails to describe nonlinear relationships between ion channel parameters and electrophysiological phenotypes, such as Smax. We explored the parameter–phenotype mapping in a population of 5000 single-cell atrial cell models through interpretable machine learning (ML) approaches. Parameter sensitivity analyses could explain the linear relationships between parameters and electrophysiological phenotypes, including APD 90 , resting membrane potential, Vmax, refractory period, and APD/calcium alternans threshold, but not for Smax. However, neural network models had better prediction performance for Smax. To interpret the ML model, we evaluated the parameter importance at the global and local levels by computing the permutation feature importance and the local interpretable model-agnostic explanations (LIME) values, respectively. Increases in I CaL , I NCX , and I Kr , and decreases in I K1 , I b,Cl , I Kur , I SERCA , and I to are correlated with higher Smax values. The LIME algorithm determined that I NaK plays a significant role in determining Smax as well as I to and I Kur. The atrial cardiomyocyte population was hierarchically clustered into three distinct groups based on the LIME values and the single-cell simulation confirmed that perturbations in I NaK resulted in different behaviors of APD restitution curves in three clusters. Our combined top-down interpretable ML and bottom-up mechanistic simulation approaches uncovered the role of I NaK in heterogeneous behaviors of Smax in the atrial cardiomyocyte population. [ABSTRACT FROM AUTHOR]

[Display omitted] • A computer-aided method for detecting and delineating intracardiac electrograms during arrhythmia substrate analysis. • A computationally efficient fully convolutional neural network with a wide receptive field to capture long-term temporal context. • Demonstrating reliable performance on a complex and highly challenging clinical dataset. • Comprehensive exploratory analysis of design and intrinsic regularization techniques that contribute to the model's performance. • Does not require extensive preprocessing or manual adjustment of parameters typical for this field. Automated segmentation of intracardiac electrograms and extraction of fundamental cycle length intervals is crucial for reproducible arrhythmia substrate analysis conducted during electrophysiology procedures. The objective of this study is to develop a robust, computationally efficient end-to-end model for the precise electrogram multi-channel delineation using a highly imbalanced dataset. A temporal deep convolutional neural network (CNN) based on the UNet architecture incorporating convolutional layers of varying dilation rates was implicitly regularized through data augmentations (DAs), a domain specific Tversky loss function, and distinct labelling strategies for segments comprising atrial fibrillation (AF). An exploratory study utilizing Bayesian search was conducted to optimize architectural and loss function hyperparameters. The impact of dilated convolutions, data augmentations, and labelling strategies on the performance and generalization capability was assessed through an ablation study. The performance of different models was evaluated using a cross-validation procedure and two independent test datasets derived from two separate patient cohorts containing 326, 84, and 97 electrograms encompassing sinus rhythms, abnormal complexes during ongoing tachycardias, and stimulation protocols. A UNet model with optimized loss hyperparameters, a dilated receptive field, and atrial fibrillation (AF) annotated as a positive class (D-UNet-L) achieved an average Sørensen-Dice coefficient (SDC) of 84.9 % on recordings with regular atrial beats across test datasets, surpassing the performance of models without loss optimization (81.5 %), without dilated kernels (81.3 %), and with inversed AF labelling (77.5 %). Notably, the highest average accuracy (Acc) of 95.8 % for AF recordings was obtained by a model trained on negatively assigned AF segments, outperforming D-UNet-L (88.9 %), the model without loss optimization (81.5 %), and the model without dilated kernels (81.3 %). The reference D-UNet-L model exhibited overall root-mean-square errors of 8.3 and 9.0 ms across test datasets. Additionally, 61.5 % and 20.8 % of delineations exhibited absolute errors below 5 ms and 10 ms, respectively. Disabling data augmentation (DAs) resulted in a 2.7 % decrease in validation SDC and a 5.3 % increase in training SDC." Generalization capability across independent datasets was improved by employing exponentially weighted Tversky loss. The model's segmentation performance on longer sequences with atrial fibrillation was improved by incorporating dilated convolution kernels. Noise-aware and morphology data augmentations effectively mitigated overfitting potential in a limited training dataset. Label noise introduced by annotating atrial fibrillation sequences into a positive class strengthened regularization of the model, particularly in its ability to identify regular beats. However, it also negatively impacted performance on F-waves. The proposed method diminishes the dependence on manual measurements in complex electrophysiology measurements and enhances utilization of the collected electrophysiology data. The findings underscore the substantial impact of intrinsic regularization techniques and establish guidelines to facilitate methodological decision-making processes. [ABSTRACT FROM AUTHOR]

Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP 1 1 https://opencarp.org/. Plank et al. (2021) and the Python-based carputils 2 2 https://git.opencarp.org/openCARP/carputils. framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments. • Open-source framework for standardizing cardiac electrophysiology simulations. • Built upon cardiac electrophysiology modeling community standard software, the openCARP simulator and the carputils framework. • Simplifies model calibration, avoids calibration errors, leading to valid and reproducible cardiac electrophysiology studies. • Efficient streamlining and automation of cardiac electrophysiology modeling studies, ensuring quality and credibility of in silico studies. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2 J2 (CYP2J2) is primarily expressed extrahepatically and is the predominant epoxygenase in human cardiac tissues. This highlights its key role in the metabolism of endogenous substrates. Significant scientific interest lies in cardiac CYP2J2 metabolism of arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, to regioisomeric bioactive epoxyeicosatrienoic acid (EET) metabolites that show cardioprotective effects including regulation of cardiac electrophysiology. From an in vitro perspective, the accurate characterization of the kinetics of CYP2J2 metabolism of AA including its inhibition and inactivation by drugs could be useful in facilitating in vitro-in vivo extrapolations to predict drug-AA interactions in drug discovery and development. In this review, background information on the structure, regulation and expression of CYP2J2 in human heart is presented alongside AA and EETs as its endogenous substrate and metabolites. The in vitro and in vivo implications of the kinetics of this endogenous metabolic pathway as well as its perturbation via inhibition and inactivation by drugs are elaborated. Additionally, the role of CYP2J2-mediated metabolism of AA to EETs in cardiac electrophysiology will be expounded. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is a genetic disorder known for its characteristic electrocardiogram (ECG) patterns and increased risk of sudden cardiac death. Brugada phenocopy (BrP) presents similar ECG patterns but is distinguished by its reversible nature when the underlying conditions are resolved. This article delineates the intricacies of BrP, emphasizing its etiology, clinical presentation, diagnosis, treatment, and prognosis. The article categorizes BrP based on various underlying causes, including metabolic disturbances, myocardial infarction, and mechanical compression, among others. It also underscores the critical importance of differentiating BrP from BrS to avoid misdiagnosis and inappropriate treatment, such as unnecessary implantation of cardioverter-defibrillators. The reversible aspect of BrP underlines the necessity for an etiology-specific approach to treatment, which not only prevents cardiac death but also highlights the significance of understanding the dynamic nature of ECG patterns. Through an exploration of case studies and current research, this review advocates for increased awareness and further investigation into BrP. It aims to enhance the diagnostic accuracy and management strategies, thereby improving the prognosis for patients presenting with Brugada-like ECG patterns. The review culminates in a call for further research to close existing knowledge gaps and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Obesity is a significant risk factor for arrhythmic cardiovascular death. Interactions between epicardial adipose tissue (EAT) and myocytes are thought to play a key role in the development of arrhythmias. In this review, the authors investigate the influence of EAT on arrhythmogenesis. First, they summarize electrocardiographic evidence showing the association between increased EAT volume and atrial and ventricular conduction delay. Second, they detail the structural cross talk between EAT and the heart and its arrhythmogenicity. Adipose tissue infiltration within the myocardium constitutes an anatomical obstacle to cardiac excitation. It causes activation delay and increases the risk of arrhythmias. Intercellular electrical coupling between cardiomyocytes and EAT can further slow conduction and increase the risk of block, favoring re-entry and arrhythmias. Finally, EAT secretes multiple substances that influence cardiomyocyte electrophysiology either by modulating ion currents and electrical coupling or by stimulating fibrosis. Thus, structural and paracrine cross talk between EAT and cardiomyocytes facilitates arrhythmias. [ABSTRACT FROM AUTHOR]

Spurred by federal legislation, professional organizations, and patients themselves, patient access to data from electronic cardiac devices is increasingly transparent. Patients can collect data through consumer devices and access data traditionally shared only with health care providers. These data may improve screening, self-management, and shared decision-making for cardiac arrhythmias, but challenges remain, including patient comprehension, communication with providers, and sustained engagement. Ways to address these challenges include leveraging visualizations that support comprehension, involving patients in designing and developing patient-facing digital tools, and establishing clear practices and goals for data exchange with health care providers. [ABSTRACT FROM AUTHOR]

Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (I Kr). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through I Kr blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca2+ current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium. [ABSTRACT FROM AUTHOR]

Patients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population. Using nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA. We identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06–1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93–1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04–1.47; SA with CPAP, OR:1.08, 95%-CI:0.93–1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07–1.65; SA with CPAP, OR:1.14, 95%-CI:0.94–1.39). SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP. [ABSTRACT FROM AUTHOR]

We present a new explicit local space–time adaptive framework to decrease the time required for monodomain simulations for cardiac electrophysiology. Based on the localized structure of the steep activation wavefront in solutions to monodomain problems, the proposed framework adopts small time steps and a tree-based adaptive mesh refinement scheme only in the regions necessary to resolve these localized structures. The time step and mesh adaptation selection process is fully controlled by a combination of local error indicators. The main contributions of this work consist in the introduction of a primal symmetric interior penalty formulation of the monodomain model and an efficient algorithmic strategy to manage local time stepping for its temporal discretization. In a first serial implementation of this framework, we report that our new scheme is between 50% and 95% faster (in wall clock time) compared to an optimized implementation of a commonly used numerical scheme without significant loss of solution accuracy, showing that this framework is a promising candidate to accelerate monodomain simulations of cardiac electrophysiology. Preliminary studies of a parallel version of the proposed scheme alongside a novel load balancing strategy are found in the appendix and show that, although the scaling of the proposed scheme is limited, the new strategy remains faster than an optimized implementation of a classic operator splitting scheme. • Efficient space-time adaptive scheme via SIPG formulation of the monodomain model • Local formulation of space and time error indicators to control time steps and AMR • High precision in relevant problem setups while still being computationally efficient • Preliminary strategy for distributed memory parallelization with limited scalability [ABSTRACT FROM AUTHOR]

The reconstruction of epicardial and endocardial extracellular potentials (EEP) by noninvasive methods has become a significant topic in cardiac electrophysiology over recent years. It is of great importance for the diagnosis of arrhythmia and for guidance of radiofrequency ablation, based on the difference in potentials between different locations on the heart's surface. In this study, we propose a non-local regularization of total variation (TV) in a low-rank (LR) and sparse decomposition framework, suitable for the rank-deficient problem of EEP reconstruction. LR and sparse decomposition can be utilized to extract the spatial-temporal information resulting from the sparse properties of EEP data, and the non-local similarities in the LR part can be a constraint for a non-local total variation regularization. The proposed method is implemented in simulated myocardial infarction (MI), interventional, and clinical premature ventricular contraction (PVC) experiments to verify its feasibility and reliability. Compared with the existing LR and TV methods, the proposed method performs better at potential reconstruction as well as PVC localization, particularly in the boundary of the MI region, while the results of this method are also consistent with those of invasive measurements using an EnSite 3000 system in the clinical experiment. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways. [ABSTRACT FROM AUTHOR]

The first workshop on Novel Optics-based approaches for Cardiac Electrophysiology (NOtiCE) was held in Florence Italy in 2018. Here, we learned how optical approaches have shaped our basic understanding of cardiac electrophysiology and how new technologies and approaches are being developed and validated to advance the field. Several technologies are being developed that may one day allow for new clinical approaches for diagnosing cardiac disorders and possibly intervening to treat human patients. In this review, we discuss several technologies and approaches to optical voltage imaging with voltage-sensitive dyes. We highlight the development and application of fluorinated and long wavelength voltage-sensitive dyes. These optical voltage sensors have now been applied and well validated in several different assays from cultured human stem cell-derived cardiomyocytes to whole hearts in-vivo. Imaging concepts such as dual wavelength ratiometric techniques, which are crucial to maximizing the information from optical sensors by increasing the useful signal and eliminating noise and artifacts, are presented. Finally, novel voltage sensors including photoacoustic voltage-sensitive dyes, their current capabilities and potential advantages, are introduced. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic poses a significant stress on health resources in Australia. The Heart Rhythm Council of the Cardiac Society of Australia and New Zealand aims to provide a framework for efficient resource utilisation balanced with competing risks when appropriately treating patients with cardiac arrhythmias. This document provides practical recommendations for the electrophysiology (EP) and cardiac implantable electronic devices (CIED) services in Australia. The document will be updated regularly as new evidence and knowledge is gained with time. [ABSTRACT FROM AUTHOR]

We introduce Branched Latent Neural Maps (BLNMs) to learn finite dimensional input–output maps encoding complex physical processes. A BLNM is defined by a simple and compact feedforward partially-connected neural network that structurally disentangles inputs with different intrinsic roles, such as the time variable from model parameters of a differential equation, while transferring them into a generic field of interest. BLNMs leverage latent outputs to enhance the learned dynamics and break the curse of dimensionality by showing excellent in-distribution generalization properties with small training datasets and short training times on a single processor. Indeed, their in-distribution generalization error remains comparable regardless of the adopted discretization during the testing phase. Moreover, the partial connections, in place of a fully-connected structure, significantly reduce the number of tunable parameters. We show the capabilities of BLNMs in a challenging test case involving biophysically detailed electrophysiology simulations in a biventricular cardiac model of a pediatric patient with hypoplastic left heart syndrome. The model includes a 1D Purkinje network for fast conduction and a 3D heart-torso geometry. Specifically, we trained BLNMs on 150 in silico generated 12-lead electrocardiograms (ECGs) while spanning 7 model parameters, covering cell-scale, organ-level and electrical dyssynchrony. Although the 12-lead ECGs manifest very fast dynamics with sharp gradients, after automatic hyperparameter tuning the optimal BLNM, trained in less than 3 h on a single CPU, retains just 7 hidden layers and 19 neurons per layer. The resulting mean square error is on the order of 1 0 − 4 on an independent test dataset comprised of 50 additional electrophysiology simulations. In the online phase, the BLNM allows for 5000x faster real-time simulations of cardiac electrophysiology on a single core standard computer and can be employed to solve inverse problems via global optimization in a few seconds of computational time. This paper provides a novel computational tool to build reliable and efficient reduced-order models for digital twinning in engineering applications. The Julia implementation is publicly available under MIT License at https://github.com/StanfordCBCL/BLNM.jl. [ABSTRACT FROM AUTHOR]

Human cardiac slices have emerged as a promising model of the human heart for scientific research and drug testing. Retaining the normal tissue architecture, a multi-cell type environment, and the native extracellular matrix, human cardiac slices faithfully replicate organ-level adult cardiac physiology. Previously, we demonstrated that human cardiac tissue slices cultured for 24 h maintained normal electrophysiology. In this project, we further optimized the organotypic culture condition to maintain normal electrophysiology of the human cardiac slices for 4 days. The prolonged culture of human cardiac tissue slices demonstrated here enables the study of chronic drug effects, gene therapies, and gene editing. To achieve greater control of the culture environment, we have also developed an automated, self-contained heart-on-a-chip system. The culture system supports media circulation, oxygenation, temperature control, electrical stimulation, and static mechanical loading. The culture parameters can be individually adjusted to establish the optimal culture condition to achieve long-term culture and to minimize tissue dedifferentiation. The development of the heart-on-a-chip technology presented here further encourages the use of organotypic human cardiac slices as a platform for pre-clinical drug testing and research in human cardiac physiology. [ABSTRACT FROM AUTHOR]

Abstract In this work, we propose a mathematical model of the cardiac electrophysiology which takes into account time delays in signal transmission, in order to capture the whole activities of macro- to micro-scale transport processes, and use this model to analyze the propagation of electrophysiological waves in the heart. The propagation of electrical activity in the heart is mathematically modeled by a modified bidomain system. As transmembrane potential evolves, the domain has anisotropical properties which are transposed into intracellular and extracellular conductivity. The new bidomain system is a multi-scale, stiff and strongly nonlinear coupled reaction–diffusion model in the shape of a set of ordinary differential equations coupled with a set of partial differential equations with multiple time delays. First, the mathematical models are introduced. Afterward the existence and uniqueness of solution of the state equation are proved as well as stability result. A numerical calculation is performed by using a coupling Lattice Boltzmann Method. [ABSTRACT FROM AUTHOR]

To compare the effects of sevoflurane and propofol on the porcine cardiac conduction system. A prospective, comparative study of electrophysiological properties of anaesthetics agents in an experimental porcine model. A total of 36 hybrid Landrace-Large White pigs. After premedication with 20 mg kg−1 of intramuscular ketamine, anaesthesia was induced with 4.5 mg kg−1propofol intravenously. In 18 consecutive animals, anaesthesia was maintained with propofol (13 mg kg−1 hour−1) and in the remaining 18 animals with 2.66% sevoflurane. The femoral artery and vein were canalized for invasive monitoring, analytical blood gas sampling and intracardiac catheter insertion. Following instrumentation and after a period of stabilization, a customary electrophysiological evaluation was performed. We compared the electrophysiology of the sinus and atrioventricular node (AV) node under sevoflurane or propofol anaesthesia, and the effects of both anaesthetics on atrial and ventricular refractoriness. There was a significant difference in sinus node recovery time between sevoflurane and propofol (907 ± 231 versus 753 ± 146 ms, p = 0.02). Sevoflurane in comparison with propofol significantly prolonged specialized AV conduction times, represented by an increased Wenckebach cycle length (272 ± 54 versus 235 ± 40 ms, p = 0.03) and AV nodal refractoriness (327 ± 34 versus 287 ± 30 ms, p = 0.002). In addition, sevoflurane prolonged ventricular refractoriness (298 ± 27 versus 255 ± 38 ms, p = 0.007) and the QT corrected interval (0.50 ± 0.05 versus 0.46 ± 0.09 ms, p = 0.005). Sevoflurane in comparison with propofol, depresses several parameters of sinus and AV nodal function and prolongs the ventricular refractoriness of the porcine cardiac conduction system. These findings should be taken into consideration for the choice of anaesthetic agents in clinical and experimental settings. [ABSTRACT FROM AUTHOR]

Abstract Objective The objective of the present investigation was to explore the possible effect of the 5-HT3 receptor antagonist tropisetron on the expression levels of the inflammatory factors interleukin 6 (IL-6), creatine kinase isoenzyme (CK-MB), soluble growth stimulating gene 2 protein (sST2) and immunoglobulin E (IgE), as well as the cardiac action potential in septic rats. Methods The cecal ligation and perforation (CLP) method was utilized to construct abdominal infarction in rats. A total of 68 male adult Sprague Dawley rats were used, including 40 for assessing survival and 28 for detecting the expression levels of IL-6 and IgE, myocardial injury, cardiac dysfunction and the cardiac action potential. These 28 rats were divided into the sham (6 rats), sham + Tropisetron (6 rats), CLP (8 rats) and CLP + Tropisetron (8 rats) groups. Twenty-four hours after establishment of the sepsis rat model, immunohistochemistry was used to analyze 5-HT3 receptor protein expression, and enzyme-linked immunosorbent assay (ELISA) was employed to monitor the serum levels of IL-6, CK MB, sST2 and IgE. Furthermore, the structure of the myocardium in various groups was examined by H&E staining. Results The levels of IL-6, CK-MB, sST2 and IgE in the sepsis group were significantly higher than those of the sham group (P < 0.01). Furthermore, the heart rate in the sepsis group was lower than that of the sham group (P < 0.01), and the time of atrial ventricular action potential in the sepsis group was longer than that of the sham group (P < 0.05). In addition, immunohistochemical analyses showed that the area, intensity and index of 5-HT3 receptor in the sepsis group were significantly lower than those of the sham group (P < 0.01). Importantly, the 5-HT3 receptor antagonist Tropisetron exhibited significant inhibitory effects IL-6, CK-MB, sST2 and IgE expression levels, and inductive effects on atrial ventricular action potential in the sepsis group. Conclusions Sepsis leads to systemic inflammatory reaction, resulting in myocardial injury, structural changes and immune imbalance. The inhibitory effect of tropisetron on inflammation, and the regulatory inflammatory disorder by the efferent vagus nerve may be one of the important mechanisms leading to cardiac electrophysiological changes in sepsis. [ABSTRACT FROM AUTHOR]

Abstract Background Higenamine (HG) is an active compound derived from Aconiti root with a cardiotonic effect. It has been approved by the Chinese SFDA for clinical trials due to its effect as a potent inotropic and chronotropic agent in the heart. However, the direct mode of action of HG on cardiac electrophysiology is unclear. Methods The experiments were performed at both cell levels and the isolated organ. The major cardiac ion currents and the action potential duration (APD) were measured using patch-clamps in single guinea-pig left ventricular myocytes. ECG was recorded in isolated guinea pig hearts. Results In the left ventricular myocytes, HG increased I Ca-L and I Ks in concentration- and voltage-dependent manners in the left ventricular myocytes. It potentiated the I Ca-L and I Ks simultaneously for synchronization. The EC 50 values were 0.27 μM and 0.64 μM for the I Ca-L and I Ks , respectively. HG (0.1 μM, 0.5 μM and 1 μM) had no effect on the I Kr and I Na. HG slightly prolonged APD at lower concentrations, and shortened the APD at higher concentrations. HG can induce the delayed after depolarization (DAD), which showed some pro-arrhythmic effect. In the isolated perfused heart, HG increased the heart rate via an action on the sinoatrial node cells, but did not induce cardiac arrhythmias, even at high concentrations. The EC 50 value for the sinoatrial node that controls the heart rate was 0.13 μM. The sinoatrial node cells appeared to be more sensitive than ventricular myocytes to HG. The effects of HG on ventricular cells and sinoatrial node cells were both mediated through stimulation of β1-AR. Conclusion We show for the first time that HG produced a predominant action on the sinoatrial node. HG appears to control the cardiac electrophysiology through its predominant effect on the sinoarial node cells, without induction of the ectopic activity that causes cardiac arrhythmias. Thus, HG might be useful for the treatment of bradycardia. [ABSTRACT FROM AUTHOR]

Abstract We consider Isogeometric Analysis (IGA) for the numerical solution of the electrophysiology of the atria, which in this work is modeled by means of the bidomain equations on thin surfaces. First, we consider the bidomain equations coupled with the Roger–McCulloch ionic model on simple slabs. Here, our goal is to evaluate the effects of the spatial discretization by IGA and the use of different B-spline basis functions on the accuracy of the approximation, in particular regarding the accuracy of the front velocity and the dispersion error. Specifically, we consider basis functions with high polynomial degree, p , and global high order continuity, C p − 1 , in the computational domain: our results show that the use of such basis functions is beneficial to the accurate approximation of the solution. Then, we consider a realistic application of the bidomain equations coupled with the Courtemanche–Ramirez–Nattel ionic model on the two human atria, which are represented by means of two NURBS surfaces. Highlights • Isogeometric Analysis is used as solver for the cardiac electrophysiology. • The bidomain equations model the electric wave propagation on atrial surfaces. • A numerical dispersion study for Isogeometric Analysis is performed. • The electrophysiology problem is solved on both atria with a realistic ionic model. [ABSTRACT FROM AUTHOR]

Abstract Sudden cardiac death is a leading cause of death worldwide, mainly caused by highly disturbed electrical activation patterns in the heart. Currently, murine models are the most popular model to study underlying molecular mechanisms of inherited or acquired cardiac electrical abnormalities, although the numerous electrophysiological discrepancies between mouse and human raise the question whether mice are the optimal model to study cardiac rhythm disorders. Recently it has been uncovered that the zebrafish cardiac electrophysiology seems surprisingly similar to the human heart, mainly because the zebrafish AP contains a clear plateau phase and ECG characteristics show alignment with the human ECG. Although, before using zebrafish as a model to study cardiac arrhythmogenesis, however, it is very important to gain a better insight into the electrophysiological characteristics of the zebrafish heart. In this review we outline the electrophysiological machinery of the zebrafish cardiomyocytes, with a special focus on the intracellular Ca2+ dynamics and excitation-contraction coupling. We debate the potential of zebrafish as a model to study human cardiovascular diseases and postulate steps to employ zebrafish into a more 'humanized' model. [ABSTRACT FROM AUTHOR]

The efficient solution of coupled PDEs/ODEs problems arising in cardiac electrophysiology is of key importance whenever interested to study the electrical behavior of the tissue for several instances of relevant physical and/or geometrical parameters. This poses significant challenges to reduced order modeling (ROM) techniques –such as the reduced basis method –traditionally employed when dealing with the repeated solution of parameter dependent differential equations. Indeed, the nonlinear nature of the problem, the presence of moving fronts in the solution, and the high sensitivity of this latter to parameter variations, make the application of standard ROM techniques very problematic. In this paper we propose a local ROM built through a k -means clustering in the state space of the snapshots for both the solution and the nonlinear term. Several comparisons among alternative local ROMs on a benchmark test case show the effectivity of the proposed approach. Finally, the application to a parametrized problem set on an idealized left-ventricle geometry shows the capability of the proposed ROM to face complex problems. [ABSTRACT FROM AUTHOR]

Background Studies have shown regional and functional selectivity of cardiac postganglionic neurones indicating there might exist a similar heterogeneity in spinal segmental preganglionic neurones, which requires further investigation. Methods Right and left sympathetic chains were electrically stimulated from T6 to T1 in the innervated isolated rabbit heart preparation ( n  = 18). Sinus rate, left ventricular pressure, retrograde ventriculo-atrial conduction, monophasic action potential duration, effective refractory period, ventricular fibrillation threshold and electrical restitution were measured. Results Right sympathetic stimulation had a greater influence on heart rate (T1-T2: right; 59.9 ± 6.0%, left; 41.1 ± 5.6% P  < 0.001) and left stimulation had greater effects on left ventricular pressure (T1-T2: right; 20.7 ± 3.2%, left; 40.3 ± 5.4%, P  < 0.01) and ventriculo-atrial conduction (T1-T2: right; −6.8 ± 1.1%, left; −15.5 ± 0.2%) at all levels, with greater effects at rostral levels (T1-T3). Left sympathetic stimulation caused shorter monophasic action potentials at the base (T4-T5: right; 119.3 ± 2.7 ms, left; 114.7 ± 2.5 ms. P  < 0.05) and apex (T4-T5: right; 118.8 ± 1.2 ms, left; 114.6 ± 2.6 ms. P  < 0.05), greater shortening of effective refractory period (T4-T5: right; −3.6 ± 1.3%, left; −7.7 ± 1.8%. P  < 0.05), a steeper maximum slope of restitution (T4-T5 base: right; 1.3 ± 0.2, left; 1.8 ± 0.2. P  < 0.01. T4-T5 apex: right; 1.0 ± 0.2, left; 1.6 ± 0.3. P  < 0.05) and a greater decrease in ventricular fibrillation threshold (T4-T5: right; −22.3 ± 6.8%, left;-39.0 ± 1.7%), with dominant effects at caudal levels (T4-T6). Conclusions The preganglionic sympathetic efferent axons show functionally distinct pathways to the heart. The caudal segments (T4-T6) of the left sympathetic chain had a greater potential for arrhythmia generation and hence could pose a target for more focused clinical treatments for impairments in cardiac function. [ABSTRACT FROM AUTHOR]

Model personalization requires the estimation of patient-specific tissue properties in the form of model parameters from indirect and sparse measurement data. Moreover, a low-dimensional representation of the parameter space is needed, which often has a limited ability to reveal the underlying tissue heterogeneity. As a result, significant uncertainty can be associated with the estimated values of the model parameters which, if left unquantified, will lead to unknown variability in model outputs that will hinder their reliable clinical adoption. Probabilistic estimation of model parameters, however, remains an unresolved challenge. Direct Markov Chain Monte Carlo (MCMC) sampling of the posterior distribution function (pdf) of the parameters is infeasible because it involves repeated evaluations of the computationally expensive simulation model. To accelerate this inference, one popular approach is to construct a computationally efficient surrogate and sample from this approximation. However, by sampling from an approximation, efficiency is gained at the expense of sampling accuracy. In this paper, we address this issue by integrating surrogate modeling of the posterior pdf into accelerating the Metropolis-Hastings (MH) sampling of the exact posterior pdf. It is achieved by two main components: (1) construction of a Gaussian process (GP) surrogate of the exact posterior pdf by actively selecting training points that allow for a good global approximation accuracy with a focus on the regions of high posterior probability; and (2) use of the GP surrogate to improve the proposal distribution in MH sampling, in order to improve the acceptance rate. The presented framework is evaluated in its estimation of the local tissue excitability of a cardiac electrophysiological model in both synthetic data experiments and real data experiments. In addition, the obtained posterior distributions of model parameters are interpreted in relation to the factors contributing to parameter uncertainty, including different low-dimensional representations of the parameter space, parameter non-identifiability, and parameter correlations. [ABSTRACT FROM AUTHOR]

Preclinical drug screens are not based on human physiology, possibly complicating predictions on cardiotoxicity. Drug screening can be humanised with in vitro assays using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, in contrast to adult ventricular cardiomyocytes, iPSC-CMs beat spontaneously due to presence of the pacemaking current I f and reduced densities of the hyperpolarising current I K1 . In adult cardiomyocytes, I K1 finalises repolarisation by stabilising the resting membrane potential while also maintaining excitability. The reduced I K1 density contributes to proarrhythmic traits in iPSC-CMs, which leads to an electrophysiological phenotype that might bias drug responses. The proarrhythmic traits can be suppressed by increasing I K1 in a balanced manner. We systematically evaluated all studies that report strategies to mature iPSC-CMs and found that only few studies report I K1 current densities. Furthermore, these studies did not succeed in establishing sufficient I K1 levels as they either added too little or too much I K1 . We conclude that reduced densities of I K1 remain a major flaw in iPSC-CMs, which hampers their use for in vitro drug screening. [ABSTRACT FROM AUTHOR]

We propose a mathematical approach for the analysis of drugs effects on the electrical activity of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) based on multi-electrode array (MEA) experiments. Our goal is to produce an in silico tool able to simulate drugs action in MEA/hiPSC-CM assays. The mathematical model takes into account the geometry of the MEA and the electrodes' properties. The electrical activity of the stem cells at the ion-channel level is governed by a system of ordinary differential equations (ODEs). The ODEs are coupled to the bidomain equations, describing the propagation of the electrical wave in the stem cells preparation. The field potential (FP) measured by the MEA is modeled by the extracellular potential of the bidomain equations. First, we propose a strategy allowing us to generate a field potential in good agreement with the experimental data. We show that we are able to reproduce realistic field potentials by introducing different scenarios of heterogeneity in the action potential. This heterogeneity reflects the differentiation atria/ventricles and the age of the cells. Second, we introduce a drug/ion channels interaction based on a pore block model. We conduct different simulations for five drugs (mexiletine, dofetilide, bepridil, ivabradine and BayK). We compare the simulation results with the field potential collected from experimental measurements. Different biomarkers computed on the FP are considered, including depolarization amplitude, repolarization delay, repolarization amplitude and depolarization-repolarization segment. The simulation results show that the model reflect properly the main effects of these drugs on the FP. [ABSTRACT FROM AUTHOR]

Computational models of heart electrophysiology achieved a considerable interest in the medical community as they represent a novel framework for the study of the mechanisms underpinning heart pathologies. The high demand of computational resources and the long computational time required to evaluate the model solution hamper the use of detailed computational models in clinical applications. In this paper, we present a multi-front eikonal algorithm that adapts the conduction velocity (CV) to the activation frequency of the tissue substrate. We then couple the eikonal new algorithm with the Mitchell–Schaeffer (MS) ionic model to determine the tissue electrical state. Compared to the standard eikonal model, this model introduces three novelties: first, it evaluates the local value of the transmembrane potential and of the ionic variable solving an ionic model; second, it computes the action potential duration (APD) and the diastolic interval (DI) from the solution of the MS model and uses them to determine if the tissue is locally re-excitable; third, it adapts the CV to the underpinning electrophysiological state through an analytical expression of the CV restitution and the computed local DI. We conduct series of simulations on a 3D tissue slab and on a realistic heart geometry and compare the solutions with those obtained solving the monodomain equation. Our results show that the new model is significantly more accurate than the standard eikonal model. The proposed model enables the numerical simulation of the heart electrophysiology on a clinical time scale and thus constitutes a viable model candidate for computer-guided radio-frequency ablation. [ABSTRACT FROM AUTHOR]

Numerical simulation of the propagation of electrical signals in the heart is a very demanding application. In fact, very fine meshes and small time steps are currently required to capture the phenomena. In this paper, we propose and explore a very high-order scheme specifically designed for this application. Its numerical properties are detailed and the different choices on both the scheme’s definition and implementation are discussed and justified. Numerical results show the importance of considering very high-order schemes, even for classical tests such as the propagation of planar or spiral waves. [ABSTRACT FROM AUTHOR]

Background Cardiac arrhythmias are one of the main causes of death in ChCP and other dilated cardiomyopathies. Previous studies demonstrated that ventricular arrhythmias are associated with the presence of autoantibodies with beta-adrenergic activity, Ab-β. Objectives The aim of this study was to investigate whether Ab-β, present in chronic chagasic patients (ChCP), induce cardiac arrhythmias in the pharmacological type-2 long QT syndrome model (LQTS-2). Methods/results The LQTS2 was established by perfusion of Tyrode saline solution with a potassium channel blocker E-4031 (5 μM) in isolated rabbit hearts or in rabbit cardiac strips, in order to record ECG or action potential, respectively. Autoantibodies from ChCP activating (Ab-β) or not (Ab-NR) cardiac beta 1-adrenergic receptors were used. Ab-β, but not Ab-NR, were able to significantly shorten QT, QTc and increase Tpeak-Tend interval in the LQTS-2. A positive correlation between higher QTc and Tpeak-Tend was found after Ab-β perfusion in the same model. In addition, in the LQTS-2 model, in almost 75% (11/15) of the hearts perfused with Ab-β, ventricular and atrio-ventricular electrical disturbances were observed. Atenolol abolished all Ab-β-induced arrhythmias. Ab-β, when perfused in a cellular LQTS-2, drastically reduced the action potential duration and evoked early afterdepolarization (EAD's), while Ab-NR did not modulate the AP properties in the LQTS-2. Conclusion The results indicate that Ab-β were able to induce cardiac arrhythmias and EAD's. This phenomenon can explain, at least in part, the cellular mechanism of Ab-β-induced arrhythmias. Furthermore, atenolol is effective for the treatment of Ab-β-induced arrhythmias. [ABSTRACT FROM AUTHOR]

Introduction The Göttingen minipig is a promising model for pharmacological safety assessment and for translational research in cardiology. We have examined the main ion currents in cardiomyocytes of the minipig heart. Methods Cardiac cells were isolated from different cardiac regions (endo-, mid- and epicardial left ventricle and right ventricle) from Göttingen minipigs and examined using the whole cell patch clamp technique combined with pharmacological interventions. Results The inward rectifier (I K1 ), the delayed rectifier (I K ), with the rapid and slow components, (I Kr , I Ks ) and the L-type Ca 2 + channel (I Ca,L ) were identified in the different regions of the heart, whereas the Ca 2 + -independent transient outward current (I to1 ) was observed in only a few cells. I K1 was similar in the cardiac regions with a slightly lower value in the epicardial cells. I Ks was smaller in epi- and endo-cardial regions. Discussion The equivalents of the main human cardiac ion currents are present in the minipig cardiomyocytes with the exception of the Ca 2 + -independent I to1 . The study provides further evidence that the minipig is a valid model for investigating cardiovascular pharmacology. [ABSTRACT FROM AUTHOR]

An efficient and fast visualization algorithm is important for analyzing a large volume of physical data conformed to 3D anatomical geometry that evolves with time (i.e., 4D data). Such 4D visualization helps to study the evolution of cardiac excitation waves in normal and pathological conditions and understand the mechanisms underlying the genesis and maintenance of cardiac arrhythmias. However, due to limited hardware resources, so far we have not found any report about real time methods to visualize a large volume of 4D data of virtual heart simulation data. In this study, we propose a GPU-based method to address this issue, our method consists of two phases, and the first is the data compression phase, implementing an improved hierarchical vector quantization method with N-nearest neighbor searching strategy in GPU, which reduces compression time dramatically. In the second phase, the compressed data is directly decompressed in GPU and rendered with ray casting method. What is more, an adaptive sampling strategy and empty space skipping methods are further used to accelerate the rendering process, resulting in a high rendering speed. The proposed method has been evaluated for the visualization of large time-varying cardiac electrophysiological simulation data by using our simulation datasets and has achieved promising results. For about 27G bytes dataset, our method can render the data with above 35 frames per second (FPS), which exceeds the real-time frame rate for interactive observing. It significantly decreases the time in the compression phase and achieves real time rendering speed with high image quality in the visualization phase, which demonstrates the accuracy and efficiency of our method. [ABSTRACT FROM AUTHOR]