Mechanisms Of Arrhythmias Research Articles

HEART RHYTHM DISTURBANCES IN CONNECTIVE TISSUE DYSPLASIA

The article discusses the association between connective tissue dysplasia (CTD) and arrhythmias, particularly focusing on mitral valve prolapse as a potential risk factor for life-threatening ventricular arrhythmias and sudden cardiac death. Various studies emphasize the structural and mechanical abnormalities in the heart that contribute to arrhythmogenic phenotypes in CTD patients, such as fibrosis, mitral annular disjunction, and accessory chordae. Additionally, the text explores the role of autoantibodies, cardiac remodeling, and autoimmune processes in mediating rhythm disturbances and cardiac complications in CTD. The importance of ECG analysis, neural networks, and stress tests in detecting and monitoring arrhythmias in CTD patients is highlighted. The research underscores the significance of understanding the morphological basisand pathophysiological mechanisms of arrhythmias in CTD patients to improve therapeutic strategies and enhance patient outcomes.

Interplay of electrical and mechanical properties in transgenic rabbit models of long-QT and short-QT syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SNF Introduction Long-QT syndrome (LQTS) and short-QT syndrome (SQTS) are cardiac disorders primarily affecting electrical function but secondarily also impacting on mechanical features through electro-mechanical coupling (EMC). This study delves into in vivo and cellular electro-mechanical function and explores the impact of acute mechanical changes on the electrical phenotype, termed mechano-electrical coupling (MEC), in transgenic rabbit models. Aim This study aims to investigate the interrelationship between electrical and mechanical properties in LQTS and SQTS rabbit models, examining how acute mechanical alterations influence the electrical phenotype and exploring cellular electro-mechanical characteristics. Methods We examined 12-lead ECGs in LQT2, wildtype (WT), and SQT1 adult rabbits under various preload and afterload conditions. Additionally, patch-clamp and ionoptix experiments on isolated ventricular cardiomyocytes were conducted to investigate cellular electrical and mechanical characteristics. Results Baseline heart-rate corrected QTc intervals were prolonged in LQT2 (p<0.0001) and shortened in SQT1 (p=0.012) compared to WT. QT-dispersion was solely increased in LQT2 (p<0.05). Acute increase in preload and in afterload prolonged QTc intervals in all groups, while reduced preload shortened QTc intervals. MEC (mechano-induced ΔQTc) varied among genotypes; in LQT2, QTc changes were more significant than in WT (p<0.0001 with increased preload, p<0.001 with decreased preload, and p<0.05 with increased afterload). SQT1 showed a trend towards less pronounced changes compared to WT only after increased preload (p=0.11). At the cellular level, action potential duration was longer in LQT2 (p<0.001) and shorter in SQT1 (p<0.0001) compared to WT. While cardiomyocytes from WT and SQT1 showed similar Ca2+ transient durations at 1Hz, 0.5Hz, and 0.25Hz, in LQT2 cardiomyocytes Ca2+ transients were significantly prolonged at 0.5 (p<0.001) and 0.25Hz (p<0.05) in line with the pronounced APD prolongation. Additionally, LQT2 exhibited significantly more pro-arrhythmic Ca2+ oscillations, which may contribute to arrhythmia formation in LQT2s. Moreover, LQT2 exhibited a slower calcium transient upstroke velocity and a reduced cellular contraction velocity and peak sarcomere shortening at all frequencies, demonstrating a mechanical impairment compared to WT and SQTS cardiomyocytes. Conclusions Acute mechanical alterations induce electrical changes through MEC in LQT2, WT, SQT1 rabbits. The magnitude of these changes correlates with baseline QTc, exhibiting the most prominent effects in LQT2. Consistent findings between cellular electro-mechanical assessments and in vivo measurements underscore the significance of cardiomyocytes in unravelling the mechanisms behind EMC and MEC. This intricate interplay between electro-mechanical properties in cardiac disorders, highlighting the necessity of considering both aspects when investigating arrhythmia mechanisms.

Source-sink mismatch and conduction block: simulation study

Abstract Background Source-sink mismatch is one of the key concepts in arrhythmia mechanism such as relationship between pulmonary veins and the left atrium in atrial fibrillation. We sought to find the condition for conduction block in various geometries. Methods To simulate cardiac atrial tissue, the finite element method was used to discretize the governing equation in a 2D mesh. We evaluated under the following conditions: 6 sizes of source width (0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 mm), 64 types of angle (θ) at the junction (30-330 degrees), 3 conditions of conduction velocity (CV) (x0.5, x0.75, and x1 of normal CV of atrial myocardium). Results Conduction block was not observed with source width > 0.5 mm in any settings. In reduced CV condition, conduction block was not observed in θ < 300 degrees when source width > 0.3 mm. The higher CV, conduction block was observed in the narrower θ. In cases of CV of x1.0 and x0.75, conduction block was observed in θ < 180 degrees when source width < 0.3 mm. The smaller source width, conduction block was observed in the narrower θ. The wider θ, the easier conduction block occurred. Conclusion Conditions for conduction block due to source-sink mismatch are as follows: smaller source width, higher CV, and wider θ. Source with width > 0.5 mm may not be associated with source-sink mismatch in the atrial tissue. CV slowing by antiarrhythmic drugs can be effective in the aspect of source-sink mismatch.

Slow pathway ablation in pediatric patients: long-term outcomes in a high-volume center according to baseline electrophysiologic characteristics

Abstract Background Slow pathway ablation (SPA) in pediatric patients with documented paroxysmal supraventricular tachycardia (PSVT) has been proven safe and effective. Arrhythmia induction is often difficult in the pediatric population. Accordingly, empirical SPA is frequently adopted in this population. Real-world data about long-term outcomes of slow pathway ablation (SPA) in relation to tachycardia inducibility and electrophysiologic characteristics in pediatric patients with PSVT in a high-volume center are lacking. Purpose To compare long-term clinical outcomes of SPA in pediatric patients with and without intraprocedural documentation of DAVP and AV nodal reentrant tachycardia induction. Methods In this retrospective sigle-center study, all SPA procedures performed on pediatric patients (under 18 years) at our Institution since 2016 were considered. All patients had documented PSVT with short RP interval, no evidet ventricular pre-excitatio on surface ECG and normal echocardiography. Baseline EPS was performed to exclude the presence of concealed accessory pathway and isoproterenol infusion was used to exclude focal atrial tachycardias. According to intraprocedural EP characteristics, three group of patients were identified: Group 1 with AVNRT induction; Group 2 with dual atrioventricular nodal physiology (DAVP) and no tachycardia induction; Group 3 without DAVP. According to previous documentation of a short RP PSVT and after discussion with patients’ families, SPA was performed in all patients. The endpoint of the ablation was to eliminate slow pathway conduction and AV node re-entrant beat. Follow up visits were scheduled three and twelve months after ablation for all patients. Results 1734 patients underwent SPA since 2016 at our Institution. 1092 patients (73.4%) showed AVNRT induction during EPS (Group 1). 433 patients (14.2%) showed DAVP without tachycardia induction (Group 2). 209 patients (12.4%) didn’t show DAVP at EPS (Group 3). Age and gender were similar among the three groups. SPA was performed with acute procedural success in all patients. After 36-month median follow-up, freedom from palpitations was 98.5% in Group 1, 97.1% in Group 2 and 92.3% in Group 3. A survival analysis showed the best outcomes in group 1 and no significant difference in recurrence rate among the groups 2 and 3 (Figure 1). No permanent heart blocks, neither other major complication was observed. Conclusions When performed by experienced operators and in high-volume centers, SPA is a safe and effective procedure in pediatric patients with documented short RP PSVT. Success rate is highest with AVNRT induction and good without AVNRT induction, regardless of AV node dual conduction at baseline EPS. Such high success rate depends on careful exclusion of others arrhythmia mechanisms (i.e., focal atrial tachycardias, AV re-entrant tachycardias) that, although infrequent in children, are the main determinants of arrhythmia recurrences.

Long-term success and predictors of atrial arrhythmia recurrence following left atrial flutter ablation

Abstract Background In recent years, success rate of left atrial flutter (LAFL) ablation has witnessed improvement, attributed to enhanced comprehension of the arrhythmia mechanism and technological advancements. However, the recurrence rate and specific types of atrial arrhythmias, along with their potential predictors, remain inadequately understood. Purpose The aim of this study is to assess the factors influencing the efficacy, safety, and long-term success of radiofrequency (RF) ablation for LAFL. Methods Patients with sustained LAFL undergoing RF ablation were included in the study. LAFL mapping employed a combination of activation, voltage, and entrainment with 3D electroanatomical mapping. RF ablation targeted a protected isthmus of slow conduction, and if not localized, it involved creating lines of conduction block transecting the reentrant circuit or empirically created lines. Ablation success was defined as clean arrhythmia termination during RF application and no LAFL induction with pacing maneuvers. Follow-up included outpatient visits at 6 and 12 months. Ablation success at follow-up was defined as the absence of arrhythmia recurrence (≥30s) at regular outpatient or emergency department visits. Clinical and electrophysiological characteristics were analyzed and correlated with ablation success, complications, and freedom from arrhythmia recurrences at follow-up. Results The study included 104 consecutive patients undergoing LAFL ablation (67.5 ± 11.3 years, 67% male). Clinical characteristics comprised 12 with HFrEF, 44 with structural heart disease, 25 with valvular heart disease, 43 with previous pulmonary vein isolation (PVI) ablation, and 39 with significant left atrium enlargement. Simultaneous cavotricuspid isthmus ablation (CTI) was performed in 46 patients. LAFL cycle length was 293±68 ms, with more than one LAFL mechanism (2.0±0.8 mechanisms) demonstrated in 76 patients (73%). The most common LAFL mechanism was perimetral reentry (37%). LAFL was successfully ablated 83% of cases, with 7 patients experiencing complications (4 tamponades and 3 sinus node dysfunctions following LAFL termination). At a median follow-up of 28 months, 35 patients (34%) had AFL recurrence, and 15 of them required a second ablation procedure. No factor was associated with LAFL recurrence, except for a short LAFL cycle length (P=0.04) at the ablation procedure. Demonstration of more than one LAFL mechanism (P=0.48) or LAFL termination by focal or linear RF application (P=0.99) were not associated with AFL recurrences at follow-up. Conclusions Despite the relatively high efficacy of LAFL ablation, the rate of atrial arrhythmia recurrences at follow-up after a single procedure remains elevated, predominantly in the form of AFL rather than AF. Short LAFL cycle length at the index procedure appears to be a significant predictor of these recurrences. Arrythmia cycle length proved to be predictive factor of LAFL ablation success rate.Peri-veinal left AFL, LAT map, CranialPeri-veinal left AFL, LAT map, PA

Role of Machine Learning and Artificial Intelligence in Arrhythmias and Electrophysiology.

Machine learning (ML), a subset of artificial intelligence (AI) centered on machines learning from extensive datasets, stands at the forefront of a technological revolution shaping various facets of society. Cardiovascular medicine has emerged as a key domain for ML applications, with considerable efforts to integrate these innovations into routine clinical practice. Within cardiac electrophysiology, ML applications, especially in the automated interpretation of electrocardiograms, have garnered substantial attention in existing literature. However, less recognized are the diverse applications of ML in cardiac electrophysiology and arrhythmias, spanning basic science research on arrhythmia mechanisms, both experimental and computational, as well as contributions to enhanced techniques for mapping cardiac electrical function and translational research related to arrhythmia management. This comprehensive review delves into various ML applications within the scope of this journal, organized into 3 parts. The first section provides a fundamental understanding of general ML principles and methodologies, serving as a foundational resource for readers interested in exploring ML applications in arrhythmia research. The second part offers an in-depth review of studies in arrhythmia and electrophysiology that leverage ML methodologies, showcasing the broad potential of ML approaches. Each subject is thoroughly outlined, accompanied by a review of notable ML research advancements. Finally, the review delves into the primary challenges and future perspectives surrounding ML-driven cardiac electrophysiology and arrhythmias research.

A real-time signal processing software package for the electrophysiology laboratory.

Real-time signal processing has to date been difficult to implement in the clinical electrophysiology laboratory. To date, no open access software solutions are available in electrophysiology (EP) laboratories to facilitate real-time intraprocedural signal analysis. We aimed to develop an open access, scalable Python plug-in to allow real-time signal processing during human EP procedures. A Python-based plug in for the widely available EnsiteX mapping system was developed. This plug-in utilized the LiveSync feature of the system to allow real-time signal analysis. An open access library was developed to allow end-users to implement real-time signal analysis using this platform, implemented in the Python programming language https://github.com/anand9176/WaveWatch5000Public. We have developed and demonstrated the feasibility of a readily scalable and open-access Python-based plug in to an electroanatomic mapping system (EnSiteX) to allow real-time processing and display of electrogram (EGM) based information for the procedural electrophysiologist to view intraprocedurally in the electrophysiology laboratory. The availability, to the clinician, of traditional and novel EGM-based metrics at the time of intervention, such as atrial fibrillation ablation, allows for key mechanistic insights into critical unresolved questions regarding arrhythmia mechanism.

Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study.

Lethal arrhythmias in hypertrophic cardiomyopathy (HCM) are widely attributed to myocardial ischaemia and fibrosis. How these factors modulate arrhythmic risk remains largely unknown, especially as invasive mapping protocols are not routinely used in these patients. By leveraging multiscale digital twin technologies, we aim to investigate ischaemic mechanisms of increased arrhythmic risk in HCM. Computational models of human HCM cardiomyocytes, tissue, and ventricles were used to simulate outcomes of Phase 1A acute myocardial ischaemia. Cellular response predictions were validated with patch-clamp studies of human HCM cardiomyocytes (n = 12 cells, N = 5 patients). Ventricular simulations were informed by typical distributions of subendocardial/transmural ischaemia as analysed in perfusion scans (N = 28 patients). S1-S2 pacing protocols were used to quantify arrhythmic risk for scenarios in which regions of septal obstructive hypertrophy were affected by (i) ischaemia, (ii) ischaemia and impaired repolarization, and (iii) ischaemia, impaired repolarization, and diffuse fibrosis. HCM cardiomyocytes exhibited enhanced action potential and abnormal effective refractory period shortening to ischaemic insults. Analysis of ∼75 000 re-entry induction cases revealed that the abnormal HCM cellular response enabled establishment of arrhythmia at milder ischaemia than otherwise possible in healthy myocardium, due to larger refractoriness gradients that promoted conduction block. Arrhythmias were more easily sustained in transmural than subendocardial ischaemia. Mechanisms of ischaemia-fibrosis interaction were strongly electrophysiology dependent. Fibrosis enabled asymmetric re-entry patterns and break-up into sustained ventricular tachycardia. HCM ventricles exhibited an increased risk to non-sustained and sustained re-entry, largely dominated by an impaired cellular response and deleterious interactions with the diffuse fibrotic substrate.

Digital twins for cardiac electrophysiology: state of the art and future challenges.

Cardiac arrhythmias remain amajor cause of death and disability. Current antiarrhythmic therapies are effective to only a limited extent, likely in large part due to their mechanism-independent approach. Precision cardiology aims to deliver targeted therapy for an individual patient to maximize efficacy and minimize adverse effects. In-silico digital twins have emerged as apromising strategy to realize the vision of precision cardiology. While there is no uniform definition of adigital twin, it typically employs digital tools, including simulations of mechanistic computer models, based on patient-specific clinical data to understand arrhythmia mechanisms and/or make clinically relevant predictions. Digital twins have become part of routine clinical practice in the setting of interventional cardiology, where commercially available services use digital twins to non-invasively determine the severity of stenosis (computed tomography-based fractional flow reserve). Although routine clinical application has not been achieved for cardiac arrhythmia management, significant progress towards digital twins for cardiac electrophysiology has been made in recent years. At the same time, significant technical and clinical challenges remain. This article provides ashort overview of the history of digital twins for cardiac electrophysiology, including recent applications for the prediction of sudden cardiac death risk and the tailoring of rhythm control in atrial fibrillation. The authors highlight the current challenges for routine clinical application and discuss how overcoming these challenges may allow digital twins to enable asignificant precision medicine-based advancement in cardiac arrhythmia management.

Fibrosis modeling choice affects morphology of ventricular arrhythmia in non-ischemic cardiomyopathy.

Introduction: Patients with non-ischemic cardiomyopathy (NICM) are at risk for ventricular arrhythmias, but diagnosis and treatment planning remain a serious clinical challenge. Although computational modeling has provided valuable insight into arrhythmic mechanisms, the optimal method for simulating reentry in NICM patients with structural disease is unknown. Methods: Here, we compare the effects of fibrotic representation on both reentry initiation and reentry morphology in patient-specific cardiac models. We investigate models with heterogeneous networks of non-conducting structures (cleft models) and models where fibrosis is represented as a dense core with a surrounding border zone (non-cleft models). Using segmented cardiac magnetic resonance with late gadolinium enhancement (LGE) of five NICM patients, we created 185 3D ventricular electrophysiological models with different fibrotic representations (clefts, reduced conductivity and ionic remodeling). Results: Reentry was induced by electrical pacing in 647 out of 3,145 simulations. Both cleft and non-cleft models can give rise to double-loop reentries meandering through fibrotic regions (Type 1-reentry). When accounting for fibrotic volume, the initiation sites of these reentries are associated with high local fibrotic density (mean LGE in cleft models: p 0.001, core volume in non-cleft models: p = 0.018, negative binomial regression). In non-cleft models, Type 1-reentries required slow conduction in core tissue (non-cleftsc models) as opposed to total conduction block. Incorporating ionic remodeling in fibrotic regions can give rise to single- or double-loop rotors close to healthy-fibrotic interfaces (Type 2-reentry). Increasing the cleft density or core-to-border zone ratio in cleft and non-cleftc models, respectively, leads to increased inducibility and a change in reentry morphology from Type 2 to Type 1. Conclusions: By demonstrating how fibrotic representation affects reentry morphology and location, our findings can aid model selection for simulating arrhythmogenesis in NICM.

Pharmacological Management of Cardiac Arrhythmias in the Fetal and Neonatal Periods: A Scientific Statement From the American Heart Association: Endorsed by the Pediatric & Congenital Electrophysiology Society (PACES).

Disorders of the cardiac rhythm may occur in both the fetus and neonate. Because of the immature myocardium, the hemodynamic consequences of either bradyarrhythmias or tachyarrhythmias may be far more significant than in mature physiological states. Treatment options are limited in the fetus and neonate because of limited vascular access, patient size, and the significant risk/benefit ratio of any intervention. In addition, exposure of the fetus or neonate to either persistent arrhythmias or antiarrhythmic medications may have yet-to-be-determined long-term developmental consequences. This scientific statement discusses the mechanism of arrhythmias, pharmacological treatment options, and distinct aspects of pharmacokinetics for the fetus and neonate. From the available current data, subjects of apparent consistency/consensus are presented, as well as future directions for research in terms of aspects of care for which evidence has not been established.

Mechanism of Ventricular Tachycardia Occurring in Chronic Myocardial Infarction Scar.

Cardiac arrest is the leading cause of death in the more economically developed countries. Ventricular tachycardia associated with myocardial infarct is a prominent cause of cardiac arrest. Ventricular arrhythmias occur in 3 phases of infarction: during the ischemic event, during the healing phase, and after the scar matures. Mechanisms of arrhythmias in these phases are distinct. This review focuses on arrhythmia mechanisms for ventricular tachycardia in mature myocardial scar. Available data have shown that postinfarct ventricular tachycardia is a reentrant arrhythmia occurring in circuits found in the surviving myocardial strands that traverse the scar. Electrical conduction follows a zigzag course through that area. Conduction velocity is impaired by decreased gap junction density and impaired myocyte excitability. Enhanced sympathetic tone decreases action potential duration and increases sarcoplasmic reticular calcium leak and triggered activity. These elements of the ventricular tachycardia mechanism are found diffusely throughout scar. A distinct myocyte repolarization pattern is unique to the ventricular tachycardia circuit, setting up conditions for classical reentry. Our understanding of ventricular tachycardia mechanisms continues to evolve as new data become available. The ultimate use of this information would be the development of novel diagnostics and therapeutics to reliably identify at-risk patients and prevent their ventricular arrhythmias.

In Vivo Cardiac Electrophysiology in Mice: Determination of Atrial and Ventricular Arrhythmic Substrates.

Cardiac arrhythmias are a common cardiac condition that might lead to fatal outcomes. A better understanding of the molecular and cellular basis of arrhythmia mechanisms is necessary for the development of better treatment modalities. To aid these efforts, various mouse models have been developed for studying cardiac arrhythmias. Both genetic and surgical mouse models are commonly used to assess the incidence and mechanisms of arrhythmias. Since spontaneous arrhythmias are uncommon in healthy young mice, intracardiac programmed electrical stimulation (PES) can be performed to assess the susceptibility to pacing-induced arrhythmias and uncover the possible presence of a proarrhythmogenic substrate. This procedure is performed by positioning an octopolar catheter inside the right atrium and ventricle of the heart through the right jugular vein. PES can provide insights into atrial and ventricular electrical activity and reveal whether atrial and/or ventricular arrhythmias are present or can be induced. Here, we explain detailed procedures used to perform this technique, possible troubleshooting scenarios, and methods to interpret the results obtained. © 2024 Wiley Periodicals LLC. Basic Protocol: Programmed electrical stimulation in mice.

Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models.

Introduction: Sudden cardiac death (SCD) and ventricular fibrillation are rare but severe complications of many cardiovascular diseases and represent a major health issue worldwide. Although the primary causes are often acute or chronic coronary diseases, genetic conditions, such as inherited channelopathies or non-ischemic cardiomyopathies are leading causes of SCD among the young. However, relevant experimental models to study the underlying mechanisms of arrhythmias and develop new therapies are still needed. The number of genetically engineered mouse models with cardiac phenotype is growing, making electrophysiological studies in mice essential tools to study arrhythmogenicity and arrhythmia mechanisms and to test novel treatments. Recently, intracardiac catheterization via the jugular vein was described to induce and record ventricular arrhythmias in living anesthetized mice. Several strategies have been reported, developed in healthy wild-type animals and based on aggressive right ventricular stimulation. Methods: Here, we report a protocol based on programmed electrical stimulation (PES) performed in clinical practice in patients with cardiac rhythm disorders, adapted to two transgenic mice models of arrhythmia - Brugada syndrome and cardiolaminopathy. Results: We show that this progressive protocol, based on a limited number of right ventricular extrastimuli, enables to reveal different rhythmic phenotypes between control and diseased mice. In this study, we provide detailed information on PES in mice, including catheter positioning, stimulation protocols, intracardiac and surface ECG interpretation and we reveal a higher susceptibility of two mouse lines to experience triggered ventricular arrhythmias, when compared to control mice. Discussion: Overall, this technique allows to characterize arrhythmias and provides results in phenotyping 2 arrhythmogenic-disease murine models.

Analysis of the endocardial stage of treatment of tachyarhythmias after open interventions for atrial fibrillation. Experience of one center

AIM: To study EFI parameters and features of recurrent atrial tachyarrhythmias in patients who underwent surgical correction of AF.
 MATERIALS AND METHODS: from January 2013 to December 2021, 447 combined interventions were performed to eliminate AF using the labyrinth-3 and left atrial labyrinth techniques with correction of CHD (congenital heart disease) and/or coronary artery disease.
 Rhythm disturbances were detected in 57 (12.7%) patients at various follow-up periods. Endovascular interventions were performed in 39 patients. The average follow-up period after the endocardial stage was 34.37 (standard deviation 24.32) months. The median age of patients was 64 (58–67) years, 21 (54%) were men. The patients were divided into 2 groups: group 1 — after the classic biatrial (BA) labyrinth-3 — 23 (59%) patients, group 2 — after the left-atrial variant (LA) labyrinth-3 — 16 (41%) patients.
 At the endocardial stage, electrophysiological studies (EFI) were performed to clarify the mechanism of arrhythmia, and ablation eliminated tachyarrhythmia. EFI protocol: revision of the pulmonary veins, determination of the isolation of the posterior wall of the LA assessment of atrial arrhythmia, elimination of arrhythmia, control induction of arrhythmia after ablation. After repeated intervention, patients were observed in the operating clinic every 3 months.
 RESULTS: After the endocardial stage, a regular rhythm was determined in 19 (82.6%) patients of the BA group, 13 (92.9%) patients of the LA group (p = 0.914). Relapses in the form of AF were noted in 5 patients (4 — group 1 and 1 — group 2) group (p = 0.306) All relapses of tachyarrhythmia with an irregular cycle (AF) were detected in patients with AF before the endovascular stage In both groups, there were cases of restoration of conduction in the pulmonary veins — 10 (43.5%) patients after BA ablation and 1 (5.3%) patient after LA ablation. There are no recurrences of atrial arrhythmia after ablation of atrial flutter (arrhythmia with a stable cycle).
 CONCLUSION: The endocardial stage is highly effective and demonstrates subsequent freedom from atrial arrhythmia in patients who have tachycardia with a regular cycle after both methods of surgical ablation of AF. Recurrent tachyarrhythmia in the form of AF (irregular cycle) is associated with a low probability of maintaining a regular atrial rhythm after a repeated endocardial procedure, due to the presence of structural and electrophysiological changes in the atrial myocardium.

Simulation of cardiac arrhythmias in human induced pluripotent stem cell-derived cardiomyocytes.

The effects and mechanisms of cardiac arrhythmias are still incompletely understood and an important subject of cardiovascular research. A major difficulty for investigating arrhythmias is the lack of appropriate human models. Here, we present a protocol for a translational simulation of different types of arrhythmias using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and electric cell culture pacing. The protocol comprises the handling of ventricular and atrial hiPSC-CM before and during in vitro arrhythmia simulation and possible arrhythmia simulation protocols mimicking clinical arrhythmias like atrial fibrillation. Isolated or confluent hiPSC-CM can be used for the simulation. In vitro arrhythmia simulation did not impair cell viability of hiPSC-CM and could reproduce arrhythmia associated phenotypes of patients. The use of hiPSC-CM enables patient-specific studies of arrhythmias, genetic interventions, or drug-screening. Thus, the in vitro arrhythmia simulation protocol may offer a versatile tool for translational studies on the mechanisms and treatment options of cardiac arrhythmias.

The Potential Mechanisms of Arrhythmia in Coronavirus disease-2019.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.

Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.

The complexity of cardiac electrophysiology, involving dynamic changes in numerous components across multiple spatial (from ion channel to organ) and temporal (from milliseconds to days) scales, makes an intuitive or empirical analysis of cardiac arrhythmogenesis challenging. Multiscale mechanistic computational models of cardiac electrophysiology provide precise control over individual parameters, and their reproducibility enables a thorough assessment of arrhythmia mechanisms. This review provides a comprehensive analysis of models of cardiac electrophysiology and arrhythmias, from the single cell to the organ level, and how they can be leveraged to better understand rhythm disorders in cardiac disease and to improve heart patient care. Key issues related to model development based on experimental data are discussed, and major families of human cardiomyocyte models and their applications are highlighted. An overview of organ-level computational modeling of cardiac electrophysiology and its clinical applications in personalized arrhythmia risk assessment and patient-specific therapy of atrial and ventricular arrhythmias is provided. The advancements presented here highlight how patient-specific computational models of the heart reconstructed from patient data have achieved success in predicting risk of sudden cardiac death and guiding optimal treatments of heart rhythm disorders. Finally, an outlook toward potential future advances, including the combination of mechanistic modeling and machine learning/artificial intelligence, is provided. As the field of cardiology is embarking on a journey toward precision medicine, personalized modeling of the heart is expected to become a key technology to guide pharmaceutical therapy, deployment of devices, and surgical interventions.

Mechanistic insight into the functional role of human sinoatrial node conduction pathways and pacemaker compartments heterogeneity: A computer model analysis.

The sinoatrial node (SAN), the primary pacemaker of the heart, is responsible for the initiation and robust regulation of sinus rhythm. 3D mapping studies of the ex-vivo human heart suggested that the robust regulation of sinus rhythm relies on specialized fibrotically-insulated pacemaker compartments (head, center and tail) with heterogeneous expressions of key ion channels and receptors. They also revealed up to five sinoatrial conduction pathways (SACPs), which electrically connect the SAN with neighboring right atrium (RA). To elucidate the role of these structural-molecular factors in the functional robustness of human SAN, we developed comprehensive biophysical computer models of the SAN based on 3D structural, functional and molecular mapping of ex-vivo human hearts. Our key finding is that the electrical insulation of the SAN except SACPs, the heterogeneous expression of If, INa currents and adenosine A1 receptors (A1R) across SAN pacemaker-conduction compartments are required to experimentally reproduce observed SAN activation patterns and important phenomena such as shifts of the leading pacemaker and preferential SACP. In particular, we found that the insulating border between the SAN and RA, is required for robust SAN function and protection from SAN arrest during adenosine challenge. The heterogeneity in the expression of A1R within the human SAN compartments underlies the direction of pacemaker shift and preferential SACPs in the presence of adenosine. Alterations of INa current and fibrotic remodelling in SACPs can significantly modulate SAN conduction and shift the preferential SACP/exit from SAN. Finally, we show that disease-induced fibrotic remodeling, INa suppression or increased adenosine make the human SAN vulnerable to pacing-induced exit blocks and reentrant arrhythmia. In summary, our computer model recapitulates the structural and functional features of the human SAN and can be a valuable tool for investigating mechanisms of SAN automaticity and conduction as well as SAN arrhythmia mechanisms under different pathophysiological conditions.

Localized Re-Entry Is a Frequent Mechanism of De Novo Atypical Flutter

BackgroundLimited data exist about the origins and mechanisms of atypical atrial flutter that occurs in the absence of prior ablation or surgery. ObjectivesThe aims of this study were to report a large cohort of patients who presented for catheter ablation of de novo atypical flutters, to identify the most common locations and mechanisms of arrhythmia, and to describe outcomes after ablation. MethodsDemographic, electrophysiological, and outcome data were collected for patients who underwent ablation of de novo atypical flutter. ResultsThe mechanisms of 85 atypical flutters were identified in 62 patients and localized to the left atrium (LA) in 58 and right atrium (RA) in 27. In the LA, mechanisms were classified as macro–re-entry in 29 (50%) and localized re-entry in 29 (50%), whereas in the RA, mechanisms were macro–re-entry in 8 (30%) and localized re-entry in 19 (70%) (proportion of localized re-entry in the LA vs. RA, P = 0.08). Nine patients had both localized and macro–re-entrant atypical flutters. In the LA, localized re-entry was commonly found in the anterior LA, followed by the pulmonary veins and septum. In the RA, localized re-entry was found at various sites, including the lateral or posterior RA, septum, and coronary sinus ostium. During 39.4 months (Q1-Q3: 18.2-65.8 months) of follow-up, atrial arrhythmias occurred in 66% of patients after a single ablation and in 50% after >1 ablation. Among patients who underwent repeat ablation, compared with the index arrhythmia, different tachycardia circuits or arrhythmias were documented in 13 of 18 cases (72%). ConclusionsAtypical atrial flutters in patients without prior surgery or complex ablation are often due to localized re-entry (approximately 50% in the LA and a higher frequency in the RA). Other atrial tachycardias commonly occur during long-term follow-up following ablation, suggesting progressive atrial myopathy in these patients.