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Cardiac electrophysiology (EP) has few women physicians.The purpose of this study was to determine temporal and geographical trends in the proportion of women EP operators in the United States.We extracted data from the Medicare Provider Utilization and Payment Database from 2013 to 2019 using procedure codes for atrial fibrillation (AF) ablation, supraventricular tachycardia/atrial flutter (SVT/AFL) ablation, and cardiac device implantation. The Medicare Provider Utilization and Payment Database excludes operators who perform ≤10 procedures annually for a given individual procedure code. The proportion of women operators was compared across the 7-year period.On average annually between 2013 and 2019, 5% (n = 187) of the 3524 EP operators were women. Procedure-specific analyses demonstrated a similarly low proportion of women EP operators across each procedure type. Despite a 137% increase in the total number of AF ablationists over the 7-year period, the proportion of women remained unchanged (P = .3966). The number of SVT/AFL ablationists and device operators remained constant over time as did the proportion of women operators (P = .9709 and .3583, respectively). In 2019, 10 states (20%) had no women EP operators who performed10 of any given EP procedure annually, 20 states (39%) had no women who performed10 of either AF or SVT/AFL ablation procedures annually, and 10 states (20%) had no women device operators who performed10 of any given type of device implantation annually.Women EP operators remain underrepresented, and the proportion of women is stagnant even in areas of major clinical growth such as AF ablation. One-fifth of states had no women operators who performed10 of any given EP procedure annually.

Introduction and objectives: There are scarce data on left atrial (LA) enlargement and electrophysiological features in athletes. Methods: Multicenter observational study in competitive athletes and controls. LA enlargement was defined as LA volume indexed to body surface area ≥ 34mL/m2. We analyzed its relationship with atrial electrocardiography parameters. Results: We included 356 participants, 308 athletes (mean age: 36.4±11.6 years) and 48 controls (mean age: 49.3±16.1 years). Compared with controls, athletes had a higher mean LA volume index (29.8±8.6 vs 25.6±8.0mL/m2, P=.006) and a higher prevalence of LA enlargement (113 [36.7%] vs 5 [10.4%], P

The bidomain equations form the state-of-the-art model of cardiac electrophysiology and describe normal or pathological propagation of the excitation wave through cardiac tissue. If based on mechanistic cell models and applied to anatomically realistic geometries, their discretization requires very fine resolutions both in space and time and renders the numerical solution an extremely challenging computational problem. In this paper, we address this challenge by combining space-time adaptive discretization with dynamic load balancing for parallel computing. We use multilevel finite element methods for the spatial adaptation of the mesh, embedded Rosenbrock time integration for an adaptive choice of step sizes, and non-overlapping domain decomposition for the parallelization. In order to further reduce the computational costs, we exploit the sparsity of local matrices during the assembly of global FEM matrices which ensure an optimal usage of memory. In numerical tests, we demonstrate the feasibility of our approach that a substantial reduction factor of computing time is achieved w.r.t the static grid computation and a good parallel efficiency is achieved.

Drug isomers may differ in their proarrhythmia risk. An interesting example is the drug sotalol, an antiarrhythmic drug comprising d- and l- enantiomers that both block the hERG cardiac potassium channel and confer differing degrees of proarrhythmic risk. We developed a multi-scale in silico pipeline focusing on hERG channel - drug interactions and used it to probe and predict the mechanisms of pro-arrhythmia risks of the two enantiomers of sotalol. Molecular dynamics (MD) simulations predicted comparable hERG channel binding affinities for d- and l-sotalol, which were validated with electrophysiology experiments. MD derived thermodynamic and kinetic parameters were used to build multi-scale functional computational models of cardiac electrophysiology at the cell and tissue scales. Functional models were used to predict inactivated state binding affinities to recapitulate electrocardiogram (ECG) QT interval prolongation observed in clinical data. Our study demonstrates how modeling and simulation can be applied to predict drug effects from the atom to the rhythm for dl-sotalol and also increased proarrhythmia proclivity of d- vs. l-sotalol when accounting for stereospecific beta-adrenergic receptor blocking.

Background Interatrial septal tachycardias (IAS-ATs) following atrial fibrillation (AF) ablation or cardiac surgery are rare, and their management is challenging. Objective The purpose of this study was to investigate the electrophysiological features and outcomes associated with catheter ablation of IAS-AT. Methods We screened 338 patients undergoing catheter ablation of ATs following AF ablation or cardiac surgery. Diagnosis of IAS-AT was based on activation mapping and analysis of response to atrial overdrive pacing. Results Twenty-nine patients (9%) had IAS-AT (cycle length [CL] 311 ± 104 ms); 16 (55%) had prior AF ablation procedures (median 3; range 1–5), 3 (10%) had prior surgical maze, and 12 (41%) had prior cardiac surgery (including atrial septal defect surgical repair in 5 and left atrial myxoma resection in 1). IAS substrate abnormalities were documented in all patients. Activation mapping always demonstrated a diffuse early IAS breakout with centrifugal biatrial activation, and atrial overdrive pacing showed a good postpacing interval (equal or within 25 ms of the AT CL) only at 1 or 2 anatomically opposite IAS sites in all cases. Ablation was acutely successful in 27 patients (93%) (from only the right IAS in 2, only the left IAS in 9, both IAS sides with sequential ablation in 13, and both IAS sides with bipolar ablation in 3). After median follow-up of 15 (6–52) months, 17 patients (59%) remained free from recurrent arrhythmias. Conclusion IAS-ATs are rare and typically occur in patients with evidence of IAS substrate abnormalities and prior cardiac surgery. Catheter ablation can be challenging and may require sequential unipolar ablation or bipolar ablation.

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.

Possible mechanisms of left-axis deviation (LAD) in the setting of left bundle branch block (LBBB) include differences in cardiac electrophysiology, structure, or anatomic axis.The purpose of this study was to clarify the mechanism(s) responsible for LAD in patients with LBBB.Twenty-nine patients with nonischemic cardiomyopathies and LBBB underwent noninvasive electrocardiographic imaging (ECGi), cardiac computed tomography, and magnetic resonance imaging in order to define ventricular electrical activation, characterize cardiac structure, and determine the cardiac anatomic axis.Sixteen patients had a normal QRS axis (NA) (mean axis 8° ± 23°), whereas 13 patients had LAD (mean axis -48° ± 13°; P.001). Total activation times were longer in the LAD group (112 ± 25 ms vs 91 ± 14 ms; P = .01) due to delayed activation of the basal anterolateral region (107 ± 10 ms vs 81 ± 17 ms; P .001). Left ventricular (LV) activation in patients with LAD was from apex to base, in contrast to a circumferential pattern of activation in patients with NA. Apex-to-base delay was longer in the LA group (95 ± 13 ms vs 64 ± 21 ms; P.001) and correlated with QRS frontal axis (RLAD in LBBB appears to be due to electrophysiological abnormalities rather than structural factors or cardiac anatomic axis.

Background Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear. Objective The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. Methods In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models. Results Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01–0.38] ms/%; P = .04) and increased local ARI dispersion (effect size –0.13 [–0.23 to –0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01). Conclusion Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias.

Chagas disease is caused by infection from the protozoan parasite Trypanosoma cruzi. Although it is endemic to Latin America, global migration has led to an increased incidence of Chagas in Europe, Asia, Australia, and North America. Following acute infection, up to 30% of patients will develop chronic Chagas disease, with most patients developing Chagasic cardiomyopathy. Chronic Chagas cardiomyopathy is highly arrhythmogenic, with estimated annual rates of appropriate implantable cardioverter-defibrillator therapies and electrical storm of 25% and 9.1%, respectively. Managing arrhythmias in patients with Chagasic cardiomyopathy is a major challenge for the clinical electrophysiologist, requiring intimate knowledge of cardiac anatomy, advanced training, and expertise. Endocardial-epicardial mapping and ablation strategy is needed to treat arrhythmias in this patient population, owing to the suboptimal long-term success rate of endocardial mapping and ablation alone. We also describe innovative approaches to improve acute and long-term clinical outcomes in patients with refractory ventricular arrhythmias following catheter ablation, such as bilateral cervicothoracic sympathectomy and bilateral renal denervation, among others.

Introduction: The authors present the results of the national cardiac electrophysiology registry of the Portuguese Association of Arrhythmology, Pacing and Electrophysiology (APAPE) and the Portuguese Institute of Cardiac Rhythm (IPRC) for 2017 and 2018. Methods: The registry is annual, voluntary, and observational. Data are collected retrospectively. Developments over the years and their implications are analyzed and discussed. Results: In the 22 electrophysiology centers, 3407 ablations were performed in 2017 and 3653 ablations in 2018. Atrial fibrillation (AF) ablation was the most frequently performed procedure: 1017 ablations in 2017 and 1222 procedures in 2018. Of the patients undergoing AF ablation, 63% were male, 60% were between 50 and 69 years old and 74% had paroxysmal AF. Clinically relevant complications were reported in 0.8% of the procedures. In 2017, 216 ventricular tachycardia or ventricular fibrillation (VT/VF) ablation procedures were performed in 15 centers. In 2018, 19 centers performed 249 TV/VF ablations. About 45% of VT/VF ablations were performed in patients with structural heart disease. Complications were reported in 3.2% of the procedures, including one death (0.2%). Conclusions: The national electrophysiology registry showed a sustained increase in the number of catheter ablations. In addition, procedural complexity increased and AF ablation assumed a dominant position among the procedures performed. Resumo: Objetivo: Apresentam-se os dados referentes ao Registo Nacional de Eletrofisiologia Cardíaca da Associação Portuguesa de Arritmologia, Pacing e Eletrofisiologia (APAPE) e Instituto Português do Ritmo Cardíaco (IPRC) para os anos de 2017 e 2018. Métodos: Trata-se de um registo anual, voluntário, observacional e retrospetivo. É analisada a evolução da atividade dos Centros de Eletrofisiologia tendo em conta o tipo de procedimentos realizados e são discutidas as potenciais implicações. Resultados: Nos 22 Centros de Eletrofisiologia em funcionamento foram realizadas 3407 ablações em 2017 e 3653 ablações em 2018. A ablação de fibrilhação auricular foi o procedimento mais frequente (1017 ablações em 2017 e 1222 em 2018). Dos doentes submetidos a ablação de fibrilhação auricular, 63% eram do sexo masculino, 60% apresentavam entre 50 e 69 anos de idade e 74% tinham arritmia paroxística. Foram reportadas complicações clinicamente relevantes em 0,8% dos procedimentos.Em 2017, foram efetuadas 216 ablações de taquicardia ventricular ou fibrilhação ventricular (TV/FV) em 15 centros. Em 2018, 19 centros realizaram 249 ablações de TV/FV. Cerca de 45% das ablações de TV/FV foram efetuadas em doentes com cardiopatia estrutural. Foram reportadas complicações em 3,2% dos procedimentos, incluindo um óbito (0,2%). Conclusão: A eletrofisiologia nacional mantém um crescimento no número de ablações por cateter. Além disso, verificou-se aumento na complexidade das ablações realizadas, assumido a ablação de fibrilhação auricular uma posição dominante entre os procedimentos efetuados.

Computational models of the heart, from cell-level models, through one-, two- and three-dimensional tissue-level simplifications, to biophysically-detailed three-dimensional models of the ventricles, atria or whole heart, allow the simulation of excitation and propagation of this excitation, and have provided remarkable insight into the normal and pathological functioning of the heart. In this article we present equations for modelling cellular excitation (i.e. the cell action potential) from both a phenomenological and a biophysical perspective. Hodgkin-Huxley formalism is discussed, along with the current generation of biophysically-detailed cardiac cell models. Alternative Markovian formulations for modelling ionic currents are also presented. Equations describing propagation of this cellular excitation, through one-, two- and three-dimensional idealised or realistic tissues, are then presented. For all types of model, from cell to tissue, methods for discretisation and integration of the underlying equations are discussed. The article finishes with a discussion of two tissue-level experimental imaging techniques - diffusion tensor magnetic resonance imaging and optical imaging - that can be used to provide data for parameterisation and validation of cell- and tissue-level cardiac models.

Atrial fibrillation is a common disease of increasing prevalence. Catheter ablation has evolved into an established therapeutic option that mainly aims to electrically isolate the pulmonary veins from atrial myocardium. The traditional method comprises point-by-point radiofrequency current ablation guided by electroanatomical mapping and has proven to be effective and safe in experienced hands. However, this approach is technically highly demanding and associated with a long learning curve, limiting its widespread utilization. To address these shortcomings, simplified ablation tools for pulmonary vein isolation are needed. In this context, balloon devices promise to ease the procedure by approaching the entire orifice of a targeted pulmonary vein in a single maneuver. This requires less catheter manipulation in the left atrium and often allows ablation of a large volume of tissue with a single application of ablative energy. Two balloon devices—one using cryoenergy, the other laser energy—have already been established in clinical routine and have demonstrated noninferiority when compared with radiofrequency ablation in large randomized trials. More balloon devices are on the verge of being introduced into clinical practice and bear the potential to expand the interventional electrophysiologist’s armamentarium when treating atrial fibrillation. The authors review the use of the established balloon devices available for atrial fibrillation ablation and provide a detailed outlook on upcoming balloon technologies, including 3 different balloons utilizing radiofrequency energy as well as a novel cryoballoon.

Background During the COVID-19 pandemic, attempts to conserve resources and limit virus spread have resulted in delay of nonemergent procedures across all medical specialties including cardiac electrophysiology. Many patients have delayed care and continue to express concerns about potential nosocomial spread of coronavirus. Objective To quantify risk of development of COVID19 due to in-hospital transmission related to an electrophysiology procedure, in the setting of preventive measures instituted in our laboratory areas. Methods We contacted patients by telephone who underwent emergent procedures in the electrophysiology lab during the COVID19 surge at our hospital (3/16/2020 to 5/15/2020, reaching daily census 450 COVID19 patients,) > two weeks after the procedure, to assess for symptoms of and/or testing for COVID-19, and assessed outcomes from medical record review. Results Of the 124 patients undergoing EP procedures in this period, none had developed documented or suspected coronavirus infection. 7 patients described symptoms of chest pain, dyspnea, or fever; 3 were tested for coronavirus and found to be negative. Of the remaining 4, 2 had a more plausible alternative explanation for the symptoms, and 2 had transient symptoms not meeting published criteria for probable COVID19 infection. Conclusion Despite a high hospital census of COVID-19 patients during the period of hospital stay for an electrophysiology procedure, there were no likely COVID-19 infections occurring in follow up of at least two weeks. With proper use of preventive measures as recommended by published guidelines, the risk of nosocomial spread of COVID-19 to patients in the electrophysiology lab is low., Graphical abstract

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.

Percutaneous epicardial access continues to have a growing role within cardiac electrophysiology. The classic approach has typically been with a Tuohy needle via a subxiphoid approach guided by fluoroscopic landmarks and tactile feedback. Recent developments have highlighted the role of the micropuncture needle, electroanatomic mapping, and real-time pressure sensors to reduce complications. Further, different access sites, such as the right atrial appendage, have been described and may offer a novel approach to percutaneous epicardial access. In addition, future directions of percutaneous access may involve direct visualization, near-field impedance monitoring, and real-time virtual imaging.

Managing arrhythmias from the left ventricular summit and interventricular septum is a major challenge for the clinical electrophysiologist requiring intimate knowledge of cardiac anatomy, advanced training and expertise. Novel mapping and ablation strategies are needed to treat arrhythmias originating from these regions given the current suboptimal long-term success rates with standard techniques. Herein, we describe innovative approaches to improve acute and long-term clinical outcomes such as mapping and ablation using the septal coronary venous system and the septal coronary arteries, alcohol ablation, coil embolization, and ablation of all early sites among others.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted healthcare 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 patients with arrhythmia. 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 serological 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.

Occult atrial fibrillation (AF) can be the underlying cause for cryptogenic stroke (CS). Implantable loop recorders (ILRs) have become an important tool for long-term arrhythmia monitoring in CS patients. Office-based ILR implantation by nonelectrophysiologist physicians is increasingly common. To report the real world diagnostic yield and accuracy of remote ILR monitoring in high risk CS patients, we retrospectively analyzed 145 consecutive patients with CS who underwent ILR implantation between October 2014 and October 2018 at New York University Langone Health. A certified device technician and an electrophysiologist adjudicated all transmissions. The yield and accuracy of Reveal LINQ Intra Cardiac Monitor (ICM), a fourth generation device, was compared to that of TruRhythm Detection algorithm (fifth generation device). AF was diagnosed in 17 patients (12%) over a mean follow-up of 28 ± 12 months. The median time to diagnosis was 7.4 ± 21.3 months. A total of 1,637 remote transmissions (scheduled- and auto-triggered alerts: 756; patient-triggered: 881) were adjudicated. The positive predictive value for AF episodes in the scheduled interrogations increased from 4% in the Reveal LINQ ICM to 16% in the TruRhythm LINQ. Of 881 patient-triggered transmissions, none were found to be true positive. In the Reveal LINQ ICM, for scheduled transmissions, primary causes of false positive (FP) were atrial ventricular premature complexes (80%). In the TruRhythm LINQ, for scheduled transmissions, primary cause of FP were T-wave over-sensing (87%). In conclusion, the real world diagnostic yield of ILR for patients with CS remains suboptimal, with at least 84% of AF alerts being FP. Patient-riggered events did not correlate with arrhythmia and the necessity of patient triggering in this population should be questioned. Expert interpretation of recordings is critical to assure accurate diagnosis.

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.

Introduction: Year-by-year analysis of the practice of cardiac electrophysiology in Portugal enables assessment of its development over time and of its position within the overall picture in Europe. Objective: We present the results of the National Registry of Cardiac Electrophysiology of the Portuguese Association for Arrhythmology, Pacing and Electrophysiology (APAPE) for 2015 and 2016. Methods: This is a voluntary, observational, annual registry collected retrospectively. Results: The data of the electrophysiological studies and ablations related to the referred years are presented. Conclusion: Changes in these data over the years are analyzed and the relation of the Portuguese data in the European panorama and possible implications are discussed. Resumo: Introdução: O conhecimento da atividade efetuada num país permite posicioná-lo dentro da comunidade onde se insere. Objetivo: Apresentam-se os dados referentes ao registo nacional de eletrofisiologia cardíaca da Associação Portuguesa de Arritmologia, Pacing e Eletrofisiologia (APAPE) relativo aos anos de 2015 e 2016. Métodos: Trata-se de um registo de dados anual, voluntário, observacional, com colheita retrospetiva de dados. Resultados: São apresentados os dados dos estudos eletrofisiológicos e de ablações relativos aos anos referidos. Conclusão: Analisam-se a sua evolução ao longo dos anos e a posição relativa dos dados nacionais em relação ao panorama europeu e eventuais implicações.

Background Stereotactic body radiation therapy (SBRT) has been shown to be effective in treating patients with refractory ventricular tachycardia. Objective The purpose of this study was to describe outcomes for SBRT in advanced heart failure patients admitted for repeated implantable cardioverter-defibrillator (ICD) therapies who were refractory to standard treatments. Methods SBRT simulation, planning, and treatments were performed using standard techniques with collaboration from a radiation oncologist, electrophysiologist, and cardiac imaging specialist. Patients were treated with single-fraction 25 Gy while awake. Efficacy was assessed by total durations in seconds of ventricular tachycardia, frequency of antitachycardia pacing (ATP), and quantity of shocks before and after treatment as recorded by an ICD. Results A total of 10 patients (mean age 61 years; 3 female) were included. Etiologies of heart failure were ischemic in 40% (4/10) and nonischemic in 60% (6/10). Among 8 patients with available ICD data, the total reduction in seconds of detected VT was 69% (pretreatment 1065 seconds/month vs posttreatment 332 seconds/month). The total reduction in ATP sequences was 48% (17.3 pretreatment and 8.9 posttreatment). Reduction in total ICD shocks after SBRT was 68% (2.9 shocks/month pretreatment and 0.9 shocks/month posttreatment). When excluding a single nonresponder, there was a significant reduction in VT seconds (94%; P = .04) and a trend toward ICD shock reduction (90%; P = .07) post-SBRT. Conclusion Noninvasive treatment with SBRT was feasible and modestly effective at reducing VT burden in the critically ill. This suggests that SBRT treatment may be a useful palliation for electrical storm.

Atrial dysfunction has been widely considered a marker or consequence of other cardiac conditions rather than the cause itself. Here, we propose the term atrial failure as a clinically relevant entity, defined as any atrial dysfunction causing impaired heart performance, symptoms, and worsening quality of life or life expectancy. Aspects of the etiology, mechanisms, and consequences of atrial failure are discussed. Recent advances in cardiac electrophysiology and imaging have improved our understanding of the highly complex atrial anatomy and function, underlying the paramount importance of the atria in optimal heart performance. It is time to reappraise the concept of the failing atrium as a primary cause or aggravating factor of the symptoms in many of our patients. The concept of atrial failure may foster basic and translational research to gain a better understanding of how to identify and manage atrial dysfunction.

Access to the epicardial space is fundamental to several cardiac procedures. While traditional indications include catheter ablation of ventricular arrhythmias and accessory pathways, novel indications include left atrial appendage occlusion, esophageal protection, mapping and ablation during atrial fibrillation procedures, implantation of epicardial pacing leads, and phrenic nerve displacement to facilitate safe ablation of atrial and ventricular arrhythmias. Accessing the epicardial space safely is a major challenge requiring intimate knowledge of cardiac anatomy, extensive training, and expertise. Over the past years, multiple technological advances have led to significant improvements in epicardial access success and safety. Important examples of such advances include CO2 insufflation through the coronary sinus or the right atrial appendage, pressure sensor needle, computed tomography, cardiac magnetic resonance, and electroanatomic mapping–guided epicardial access. In addition, we provide special maneuvers to minimize inadvertent right ventricular perforation.

Operator splitting methods constitute a powerful strategy to solve problems in the field of cardiac electrophysiology. In particular, it has been shown that operator splitting methods of order higher than two are more efficient than lower-order methods when solving problems involving simulations of the bidomain and monodomain models. An example of such problems is given by the Niederer problem, a well-defined benchmark in cardiac tissue electrophysiology. In this study, we present some fourth-order operator splitting methods, having real and complex coefficients, and compare their performance when applied to the Niederer benchmark as well as a variant with a stiffer cell model.

Cardiac digital twins (Cardiac Digital Twin (CDT)s) of human electrophysiology (Electrophysiology (EP)) are digital replicas of patient hearts derived from clinical data that match like-for-like all available clinical observations. Due to their inherent predictive potential, CDTs show high promise as a complementary modality aiding in clinical decision making and also in the cost-effective, safe and ethical testing of novel EP device therapies. However, current workflows for both the anatomical and functional twinning phases within CDT generation, referring to the inference of model anatomy and parameters from clinical data, are not sufficiently efficient, robust and accurate for advanced clinical and industrial applications. Our study addresses three primary limitations impeding the routine generation of high-fidelity CDTs by introducing; a comprehensive parameter vector encapsulating all factors relating to the ventricular EP; an abstract reference frame within the model allowing the unattended manipulation of model parameter fields; a novel fast-forward electrocardiogram (Electrocardiogram (ECG)) model for efficient and bio-physically-detailed simulation required for parameter inference. A novel workflow for the generation of CDTs is then introduced as an initial proof of concept. Anatomical twinning was performed within a reasonable time compatible with clinical workflows ( 4h) for 12 subjects from clinically-attained magnetic resonance images. After assessment of the underlying fast forward ECG model against a gold standard bidomain ECG model, functional twinning of optimal parameters according to a clinically-attained 12 lead ECG was then performed using a forward Saltelli sampling approach for a single subject. The achieved results in terms of efficiency and fidelity demonstrate that our workflow is well-suited and viable for generating biophysically-detailed CDTs at scale.

Unipolar electrograms are voltage signals that reflect time-varying extracellular currents. Bipolar electrograms provide differential extracellular voltages along an axis and resemble a local directional derivative. Both are based on the fundamental concept of electric fields in tissues. Omnipolar electrograms are derived from a clique, a group of nearby electrodes that generate bipolar signals from multiple directions. They are electrode and catheter-orientation independent. • Omnipolar electrograms provide wavefront characteristics, such as amplitude, timing, direction, and speed, in physiologically relevant directions located at the center of the electrode clique. This enables determinations of a maximal bipolar voltage amplitude termed OT Vmax, the generalization of peak-to-peak in the presence of directionality, and is not affected by catheter orientation and is less sensitive to electrode distance for small cliques. • Specialized catheters and three-dimensional mapping system software enable omnipolar electrograms and derived quantities to be generated and displayed in real-time. • Omnipolar electrograms during atrial fibrillation are significantly less influenced by directional factors, allowing for robust and consistent substrate assessment. • Mapping the ventricles using an equispaced electrode grid catheter and omnipolar electrograms can provide reliable substrate assessment within infarcted and noninfarcted regions of the ventricles to aid in determining ablation targets, such as a lesion gap or an isthmus.

This article represents an overview of the basic concepts of cardiac electrophysiology. This relatively new field became a subspecialty of cardiology in the mid-1990s due to the rapid development of equipment that allowed the study and cure of cardiac arrhythmias percutaneously. Simultaneously, technology provided the field with percutaneous cardiac implantable electronic devices designed to protect patients from life-threatening bradyarrhythmias and tachyarrhythmias. Recently, the field has focused on the ablative treatment of atrial fibrillation, the most common arrhythmia facing an aging population, and the diagnosis and management of many inherited arrhythmias through advances in understanding of their genetic cause.

Autonomic dysregulation in cardiovascular disease plays a major role in the pathogenesis of arrhythmias. Cardiac neural control relies on complex feedback loops consisting of efferent and afferent limbs, which carry sympathetic and parasympathetic signals from the brain to the heart and sensory signals from the heart to the brain. Cardiac disease leads to neural remodeling and sympathovagal imbalances with arrhythmogenic effects. Preclinical studies of modulation at central and peripheral levels of the cardiac autonomic nervous system have yielded promising results, leading to early stage clinical studies of these techniques in atrial fibrillation and refractory ventricular arrhythmias, particularly in patients with inherited primary arrhythmia syndromes and structural heart disease. However, significant knowledge gaps in basic cardiac neurophysiology limit the success of these neuromodulatory therapies. This review discusses the recent advances in neuromodulation for cardiac arrhythmia management, with a clinical scenario-based approach aimed at bringing neurocardiology closer to the realm of the clinical electrophysiologist.

The potential role of cardiac MR imaging in the diagnosis, risk-stratification, and treatment of patients with cardiac arrhythmias is rapidly evolving. Beyond substrate identification and characterization, it is now feasible to perform MR imaging-based noninvasive virtual programmed stimulation to identify potential ablation targets. The next phase of MR imaging-guided electrophysiology may involve intraprocedural guidance of electrophysiologic interventions using real-time MR imaging. This review discusses the spectrum of MR imaging applications in electrophysiology ranging from those that are established in clinical practice to those that are in the experimental phase of development.

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.

Prolonged QT intervals are a major risk factor for ventricular arrhythmias and a leading cause of sudden cardiac death. Various drugs are known to trigger QT interval prolongation and increase the proarrhythmic potential. Yet, how precisely the action of drugs on the cellular level translates into QT interval prolongation on the whole organ level remains insufficiently understood. Here we use machine learning techniques to systematically characterize the effect of 30 common drugs on the QT interval. We combine information from high fidelity three-dimensional human heart simulations with low fidelity one-dimensional cable simulations to build a surrogate model for the QT interval using multi-fidelity Gaussian process regression. Once trained and cross-validated, we apply our surrogate model to perform sensitivity analysis and uncertainty quantification. Our sensitivity analysis suggests that compounds that block the rapid delayed rectifier potassium current I Kr have the greatest prolonging effect of the QT interval, and that blocking the L-type calcium current I CaL and late sodium current I NaL shortens the QT interval. Our uncertainty quantification allows us to propagate the experimental variability from individual block-concentration measurements into the QT interval and reveals that QT interval uncertainty is mainly driven by the variability in I Kr block. In a final validation study, we demonstrate an excellent agreement between our predicted QT interval changes and the changes observed in a randomized clinical trial for the drugs dofetilide, quinidine, ranolazine, and verapamil. We anticipate that both the machine learning methods and the results of this study will have great potential in the efficient development of safer drugs.

Cardiac electrophysiology has progressed in great strides since the electrical activity of the heart was first discovered in 1842 and documented using electrocardiography. Optical imaging of cardiac electrophysiology, or optocardiography, has seen many advances in recent years including panoramic imaging of the heart, alternating transillumination to image transmural electrical activity, optogenetic models and customizable 3D printed optical mapping systems. Most of these techniques were adopted from other fields of study and refined for cardiac electrophysiology purposes. The future of this field could see similar adaptations of photoacoustic tomography, structured light technology and optical coherence tomography contributing to optocardiography.

Background Nowadays, transvenous lead extraction (TLE) is considered an essential technique in lead management strategy. Since 2011, a multidisciplinary approach was undertaken in our centre involving electrophysiologists, cardiac surgeons and anaesthesiologists to improve cross- unit cooperation and minimize complications and mortality. The present paper reports procedural outcomes and complications of our lead extraction experience. Methods We retrospectively collected and analysed data from all consecutive patients undergoing cardiac implantable electronic device leads TLE at the IRCCS Centro Cardiologico Monzino between January 2011 and November 2017. Results One-hundred fifty patients (111 males, 68 ± 13 years) underwent extraction procedures. The most common extraction indication were infections (86.7%) and TLE was carried out by laser-based approach in 88 (58.6%) patients, by mechanical dilating sheaths in 58 (38.7%) patients and by a combined approach (TLE + open surgical intervention) in 4 (2.7%) patients. Procedural success was obtained in 146 (97.3%) cases with only 3 (2.0%) major complications with 2 cases of structural injury with tamponade requiring emergent median sternotomy. Open surgery extraction was required in 4 patients, after an attempt to TLE, due to leads strict adhesion to cardiac or vascular structures, whereas in 5 (3.3%) cases, the treatment of choice was a combined approach consisting in transvenous leads extraction followed by planned surgery. Conclusions TLE is a complex procedure that sometimes leads to fatal complications. In our single center experience, a multidisciplinary approach involving electrophysiologist, cardiac surgeon, anaesthesiologist in an operating room allows a safer approach and major complications treatment.

The theory of bioelectrodes describes the rules governing the passage of electrical charge between electrodes and electrolytes. In this review, we explain the basis of bioelectrodes with focus on clinical electrophysiology. The central concept is the double-layer capacitance that forms in the interface between the electrode and tissue. This phenomenon controls charge transfer between electrodes and tissues and contributes to detrimental effects such as electrode polarization and motion artifacts. Many methods critical to the practice of electrophysiology, including fractally coated pacemaker leads, biphasic stimuli, signal filtering, and the use of nonpolarizable electrodes, are devised to mitigate these problems. Our goal is to provide a robust and intuitive background on these topics for practicing electrophysiologists to help them better understand how catheters and leads work and to assist them with optimizing and troubleshooting electrophysiology systems.

Cardiac arrhythmias are a leading cause of cardiovascular death. It has long been accepted that life-threatening cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, and sudden cardiac death) are more likely to occur in the morning after waking. It is perhaps less well recognized that there is a circadian rhythm in cardiac pacemaking and other electrophysiological properties of the heart. In addition, there is a circadian rhythm in other arrhythmias, for example, bradyarrhythmias and supraventricular arrhythmias. Two mechanisms may underlie this finding: (1) a central circadian clock in the suprachiasmatic nucleus in the hypothalamus may directly affect the electrophysiology of the heart and arrhythmogenesis via various neurohumoral factors, particularly the autonomic nervous system; or (2) a local circadian clock in the heart itself (albeit under the control of the central clock) may drive a circadian rhythm in the expression of ion channels in the heart, which in turn varies arrhythmic substrate. This review summarizes the current understanding of the circadian rhythm in cardiac electrophysiology, arrhythmogenesis, and the underlying molecular mechanisms.

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.

Background Low-density lipoprotein receptor-related protein 5 (LRP5) has been intensively studied as a co-receptor for β-catenin-dependent Wnt signaling. Emerging evidences have demonstrated β-catenin-independent functions of LRP5. However, the biological role of LRP5 in the mammalian heart is largely unknown. Methods and results Conditional cardiac-specific Lrp5 knockout (Lrp5-CKO) mice were generated by crossing Lrp5flox/flox mice with αMHC/MerCreMer mice. Lrp5-CKO mice consistently displayed normal cardiac structure and function. Telemetric electrocardiogram recordings revealed a short QT interval in Lrp5-CKO mice, which was tightly linked to the striking abbreviation of action potential duration (APD) in ventricular myocytes. The analysis of whole-cell currents indicated that a reduction in activity and protein expression of L-type calcium channel (LTCC), rather than other ion channels, contributed to the abnormality in APD. Furthermore, we showed that Lrp5 ablation induced a significant convergence of CaV1.2α1c proteins to the endoplasmic reticulum. Consequently, increased proteasomal degradation of these proteins was observed, which was independent of the Wnt/β-catenin signaling pathway. Conclusions LRP5 directly modulates the degradation of LTCC to control cardiac QT interval. These findings provide compelling evidence for the potential role of LRPs in cardiac electrophysiology.

Background Sorting nexin 17 (SNX17) is a critical cytoplasmic adaptor protein that regulates endosomal trafficking of membrane proteins to determine their recycling and/or degradation. The potential role of SNX17 in cardiovascular pathophysiology has not been reported. Methods and results Cardiac arrhythmias were monitored using standard limb lead II electrocardiograph, and cardiac performances were determined by echocardiography in a rat model of myocardial infarction (MI) created by left anterior descending coronary artery ligation. We found that SNX17 was substantially downregulated in ischemic myocardium. The downregulation contributed to the cardiac electrical disturbances and contractile dysfunction as SNX17 replacement mitigated the detrimental alterations of MI hearts. Specifically, silence of SNX17 expression using RNA interference caused intracellular Ca2+ overload as revealed by the abnormal rise of resting [Ca2+]i and deceleration of Ca2+ decay, whereas SNX17 overexpression using vectors elicited the opposite effects. Moreover, the protein level of SERCA2a was significantly decreased by silencing SNX17. Immunohistochemistry indicated that SNX17 and SERCA2a were co-localized, and co-immunoprecipitation revealed the binding between the phox-homology domain of SNX17 and SERCA2a protein. Furthermore, lysosome inhibitor chloroquine prevented SNX17 silencing-induced reduction of SERCA2a protein level. Conclusion Abnormal downregulation of SNX17 contributes to ischemic damages of cardiac electrophysiology and contractile function. SNX17 is an endogenous anti-arrhythmic factor acting by preserving functional SERCA2a protein in MI thereby offering a new strategy for the management of MI to alleviate ischemic myocardial injuries.

Cardiomyopathy is the leading cause of mortality in the world and economic burdens on national economies. A cardiac patch approach aims at regenerating an infracted heart by providing healthy functional cells to the injured region via a film carrier substrate, and providing mechanical and electrical support. Selenium acts as an important element in the prevention and treatment of cardiovascular diseases but their health-related effects have not been fully explored. Limitation is the fact that cardiac electrophysiology was only globally personalized, thus missing the potential localized pathological features in vivo. The epidemiological aspects of plasma levels of selenium and other lipid parameters in cardiomyopathy patients (30 nos) from South Tamilnadu, India were studied. The epidemiological data showed significant differences between plasma selenium, Glutathione per oxidase (Gpx) and High reactive-C Protein in cardiomyopathy patients when compared to the control. As a novel approach, in the present study chitosan-Selenium nanoparticles (SeNPs) film was used to produce electrical conductivity in the cardiac patches. The prepared chitosan-SeNPs film was characterized by Scanning Electron microscopy with Energy Dispersive X ray spectrum (SEM-EDX). The electrical and mechanical properties of the chitosan-SeNPs film were also studied. The chitosan-SeNPs film had compression of elastic modulus (67.1% elongation) and tensile strength of 419 kPa. The electrical conductivity of chitosan-SeNPs film was measured as 0.0055S cm−1. The H9C2 cells were very well grown in chitosan-SeNPs film and proliferated. In our study, we confirm the potential of SeNPs-chitosan film for use as substrates to grown cellular behavior via electrical stimulation, mechanical strength and as biocompatible film for cardiac tissue engineering applications.

Uncertainty and physiological variability are ubiquitous in cardiac electrical signaling. It is important to address the uncertainty and variability in cardiac modeling to provide reliable and realistic predictions of heart function, thus ensuring trustworthy computer-aided medical decision-making and treatment planning. Statistical techniques such as Monte Carlo (MC) simulations have been applied to uncertainty quantification and propagation in cardiac modeling. However, MC simulation-based methods are computationally prohibitive for complex cardiac models with a great number of parameters and governing equations. In this paper, we propose to use the Generalized Polynomial Chaos (gPC) expansion in combination with Galerkin projection to analytically quantify parametric uncertainty in ion channel models of mouse ventricular cell, and further propagate the uncertainty across different organizational levels of cell and tissue. To identify the most significant parametric uncertainty in cardiac ion channel and cell models, variance decomposition-based sensitivity analysis was first performed. Following this, gPC was integrated with deterministic cardiac models to propagate uncertainty through ion current, ventricular cell, 1D cable, and 2D tissue to account for the stochasticity and cell-to-cell variability. As compared to MC, the gPC in this work shows the superior performance in terms of computational efficiency. In addition, the gPC models can provide a measure of confidence in model predictions, which can improve the reliability of computer simulations of cardiac electrophysiology for clinical applications.

Background: This study assessed anxiety and depression in children with permanent pacemakers (PPM) and quality of life of their parents. Methods: Ninety children (63.3% males and 36.6% females) and their parents were included in the study and were divided into three groups. The control group (Group 1) included 30 normal healthy children (57% males and 43% females), the PPM group (Group 2) included 30 age-matched children (70% males and 30% females) with PPM and structurally normal heart, while the Group 3 included 30 children (63% males and 37% females) with PPM and congenital heart disease (PPM + CHD). Psychological assessment of children and their parents was carried out using an interview-based questionnaires. Results: Psychiatric disorders were more prevalent in PPM + CHD group including depression (P = 0.04), anxiety (P = 0.02) and lower parents’ QoL (P = 0.01). The PPM group had higher depression and lower parents’ QoL than the control group. Family income was independent factor for depression (r2 = −6.3, with P

Sinus rhythm surrogates for critical isthmus sites are highly desirable because the vast majority of VT is hemodynamically unstable. While many ablation strategies to decrease the arrhythmogenicity of scar have been shown to be effective, the predominant method for electroanatomic mapping relies on a voltage-based depiction of scar and abnormal electrograms. A functional prioritization of slow conduction, distinct from late activation, is feasible in clinical practice with the creation of isochronal late activation maps. Regions of slow conduction are easily visualized with isochronal displays of baseline intrinsic rhythm activation and deceleration zones, where isochrones crowd, have been observed to have strong correlation with successful ablation sites. Automated annotation of the offset of local electrograms was developed to create the propagation maps to incorporate electrogram width and completion of local activation. Simple conduction velocity estimates where three isochrones are seen within a 1 cm radium confirm that deceleration zones harbor conduction velocity of

BACKGROUND Implantable loop recorders (ILRs) are EGM monitors allowing continuous EGM monitoring for up to 3 years. This enables providers to capture arrhythmias that may occur infrequently and briefly despite carrying significant implications for a patient. In patients with hypertrophic cardiomyopathy (HCM), 1-3s runs of non-sustained ventricular tachycardia (NSVT) has been associated with an increased risk of sudden cardiac death (SCD). ILRs can be used to detect these arrhythmias and aid in risk stratifying HCM patients according to their SCD risk. While these devices are effective at recording such arrhythmias, their ability to automatically identify and label them can be improved. Here, we enrolled 33 patients with HCM to test a novel ILR with bluetooth enabled technology (Abbott ConfirmRx). Using EGM data captured from 3 years of follow up, we applied a deep neural network to improve the automated signal labelling. METHODS AND RESULTS We trained a recently published deep neural network (DNN) to identify cardiac rhythms in 4 categories: supraventricular tachycardia, ventricular tachycardia, sinus bradycardia and atrial fibrillation. We trained this model using a dataset consisting of raw EGM transmissions from ILRs in 33 patients with HCM. EGM interpretations by an RN and MD electrophysiologist were used as the gold standard. Transmissions were spliced into 20 second segments and annotated as one of the 4 aforementioned categories. 762 EGM annotated segments were provided in random order to the DNN to train a model to classify raw EGM readings. Next, we tested the model using 327 new EGM segments to evaluate its classification accuracy (figure 1). Our results (table 1) show that the DNN achieved an overall arrhythmia identification accuracy of 98.2%. The model's sensitivity in identifying supraventricular tachycardia, ventricular tachycardia and atrial fibrillation was 97.2%, 84.2% and 100% respectively. CONCLUSION Automated labelling of EGM signals recorded by ILRs can be improved with the use of novel DNNs. Our DNN-based model achieved an overall classification accuracy of 98.2%. These data suggest that DNNs can serve as one method of improving ILR data acquisition and analysis. This may increase the clinical utility of these tools at detecting brief and paroxysmal but yet concerning arrhythmias such as NSVTs in patients with HCM.