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Multiparametric investigation of cardiac physiology is crucial for the diagnosis and therapy of heart disease. However, no method exists to simultaneously map multiple parameters that govern cardiac (patho)physiology from beating hearts in vivo. Here, we present a cardiac sensing platform that addresses this challenge, functioning with a wireless interface. Advanced fabrication and assembling strategies enable the heterogeneous integration of transparent microelectrodes, light-emitting diodes, photodiodes, and optical filters into a multilayer array structure on soft substrates. The microelectrodes exhibit superior electrochemical performance for measuring electrical potentials and excellent transparency for co-localized fluorescence measurement. The device shows excellent biocompatibility and records the fluorescence of calcium reporter with performance comparable to imaging cameras. Multiparametric in vivo mapping of electrical excitation, calcium dynamics, and their combined effects on cardiac excitation-contraction coupling is demonstrated during normal rhythm, arrhythmia, and treatment. This technology offers potential widespread use in cardiac research to support scientific discoveries and advance clinical life-saving diagnostics and therapies.

The rare dermatological condition X-linked ichthyosis (XLI) is associated with a substantially-increased risk of cardiac arrhythmias. Arrhythmias predispose to multiple serious health conditions, and there is a need to identify them at an early stage, ideally using non-invasive, convenient, cost-effective, and reliable wearable technology methods. We tested the feasibility of monitoring heart rhythms using an Apple Watch in five adult males from the United Kingdom diagnosed with XLI. Participants returned routine electrocardiogram (ECG) traces from the watch three times per week for eight weeks (plus any traces associated with 'watch alerts' indicating arrhythmic episodes) for cardiologist review. Participant feedback was also obtained on the perceived usability/wearability of the watch/app, and on the study requirements. Participants were generally happy with the study conduct, found the watch/app straightforward to use, and there was a > 95% data return rate. Minor protocol improvements were suggested. There were few issues reported with wearability of the watch. Three participants exhibited no ECG abnormalities, but two presented with ventricular ectopic beats (VEs). Only one watch 'alert' ECG was returned, and this was considered normal sinus rhythm, suggesting the possibility of 'false positive' calls. Based on our small sample, smartwatch-based screening for cardiac rhythm abnormalities in the high-risk male XLI population appears useful, feasible, and acceptable to patients and a larger-scale clinical trial is warranted. Potentially, such devices may be more suited to detecting persistent abnormalities rather than unpredictable, acute, arrhythmic episodes. The high VE burden in some participants with XLI is consistent with septal defects underlying arrhythmia risk., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: PDE2 (phosphodiesterase 2) is upregulated in human heart failure. Cardiac PDE2-transgenic mice are protected against contractile dysfunction and arrhythmias in heart failure but whether an acute elevation of PDE2 could be of therapeutic value remains elusive. This hypothesis was tested using cardiac PDE2 gene transfer in preclinical models of heart failure., Methods and Results: C57BL/6 male mice were injected with serotype 9 adeno-associated viruses encoding for PDE2A. This led to a ≈10-fold rise of PDE2A protein levels that affected neither cardiac structure nor function in healthy mice. Two weeks after inoculation with serotype 9 adeno-associated viruses, mice were implanted with minipumps delivering either NaCl, isoproterenol (60 mg/kg per day), or isoproterenol and phenylephrine (30 mg/kg per day each) for 2 weeks. In mice injected with serotype 9 adeno-associated viruses encoding for LUC (luciferase), isoproterenol or isoproterenol+phenylephrine infusion induced left ventricular hypertrophy, decreased ejection fraction unveiled by echocardiography, and promoted fibrosis and apoptosis assessed by Masson's trichrome and Tunel, respectively. Furthermore, inotropic responses to isoproterenol of ventricular cardiomyocytes isolated from isoproterenol+phenylephrine-LUC mice loaded with 1 μmol/L Fura-2AM and stimulated at 1 Hz to record calcium transients and sarcomere shortening were dampened. Spontaneous calcium waves at the cellular level were promoted as well as ventricular arrhythmias evoked in vivo by catheter-mediated ventricular pacing after isoproterenol (1.5 mg/kg) and atropine (1 mg/kg) injection. However, increased PDE2A blunted these adverse outcomes evoked by sympathomimetic amines., Conclusions: Cardiac gene therapy with PDE2A limits left ventricle remodeling, dysfunction, and arrhythmias evoked by catecholamines, providing evidence that increasing PDE2A activity acutely could prevent progression toward heart failure.

Background: Coronary microvascular dysfunction (CMD) is an important cause of angina with nonobstructive coronary arteries (ANOCA). It is unclear whether CMD is associated with arrhythmia., Aims: This study aimed to evaluate the prevalence of arrhythmias in patients with ANOCA and CMD compared to those in patients with ANOCA without CMD., Methods: In this observational study of the Coronary Microvascular Disease Registry (NCT05960474), patients with ANOCA who underwent invasive coronary functional assessment for CMD were included. The diagnosis of arrhythmia was based on 12-lead electrocardiography (ECG), or clinical diagnosis accompanied by ECG evidence within 1 year before CMD evaluation., Results: The study included 262 patients; 66 (25.2%) were CMD-positive. Patients with CMD were older, and there was no difference in history of heart failure and baseline left ventricular ejection fraction compared to those without CMD. Premature atrial contractions (PACs) (25.8% vs. 5.6%; p < 0.001), supraventricular tachycardia (SVT) (24.2% vs. 6.6%; p < 0.001), premature ventricular complexes (PVCs) (43.9% vs. 10.7%; p < 0.001), nonsustained ventricular tachycardia (NSVT) (28.8% vs. 3.1%; p < 0.001), and accelerated idioventricular rhythm (9.1% vs. 2.6%; = 0.02) were more common in CMD-positive patients. In a multivariate analysis adjusting for baseline differences and other variables clinically associated with arrhythmia, CMD was associated with PACs (odds ratio [OR]: 4.7; 95% confidence interval [CI]: 1.8-11.9), SVT (OR: 3.5; 95% CI: 1.5-8.6), PVCs (OR: 5.9; 95% CI: 2.6-13.0), and NSVT (OR: 9.5; 95% CI: 3.2-27.7)., Conclusion: Patients with ANOCA and CMD have a higher likelihood of arrhythmias, especially ventricular arrhythmias., (© 2024 Wiley Periodicals LLC.)

Aim: Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship. Our study focuses on the L-type calcium channel Ca v 1.2, a crucial component of the ventricular action potential and excitation-contraction coupling., Methods: We used circular dichroism (CD), 1 H- 15 N HSQC NMR, and trypsin digestion to determine the structural and stability properties of CaM variants. The affinity of CaM for Ca 2+ and interaction of Ca 2+ /CaM with Ca v 1.2 (IQ and NSCaTE domains) were investigated using intrinsic tyrosine fluorescence and isothermal titration calorimetry (ITC), respectively. The effect of CaM variants of Ca v 1.2 activity was determined using HEK293-Ca v 1.2 cells (B'SYS) and whole-cell patch-clamp electrophysiology., Results: Using a combination of protein biophysics and structural biology, we show that the disease-associated mutations D131E and Q135P mutations alter apo/CaM structure and stability. In the Ca 2+ -bound state, D131E and Q135P exhibited reduced Ca 2+ binding affinity, significant structural changes, and altered interaction with Ca v 1.2 domains (increased affinity for Ca v 1.2-IQ and decreased affinity for Ca v 1.2-NSCaTE). We show that the mutations dramatically impair Ca 2+ -dependent inactivation (CDI) of Ca v 1.2, which would contribute to abnormal Ca 2+ influx, leading to disrupted Ca 2+ handling, characteristic of cardiac arrhythmia syndromes., Conclusions: These findings provide insights into the molecular mechanisms behind arrhythmia caused by calmodulin mutations, contributing to our understanding of cardiac syndromes at a molecular and cellular level., (© 2025 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Historically, individuals with HCM have been restricted from vigorous competitive sports due to concerns for risk of sudden death. More recently, prospective data are emerging that individuals with HCM who participate in vigorous sports do not have increased arrhythmic risk compared to the less active, and series of athletes with HCM continuing to compete, while small, have not shown high risk. Guidelines are evolving, and while differences exist, all now recommend an individualized approach and shared decision-making for athletes with HCM wishing to return to play., Competing Interests: Declaration of competing interest Belinda Gray, None. Michael J Ackerman, consultant for Abbott, BioMarin Pharmaceuticals, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Illumina, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. Mark Link, None. Rachel Lampert, Honoria, Research support, Medtronic, Abbott-St Jude, Boston Scientific, advisory board, Medtronic (all ended 5/22)., (Copyright © 2024. Published by Elsevier Inc.)

A healthy heart shows intrinsic electrical heterogeneities that play a significant role in cardiac activation and repolarization. However, cardiac diseases may perturb the baseline electrical properties of the healthy cardiac tissue, leading to increased arrhythmic risk and compromised cardiac functions. Moreover, biological variability among patients produces a wide range of clinical symptoms, which complicates the treatment and diagnosis of cardiac diseases. Ischemic heart disease is usually caused by a partial or complete blockage of a coronary artery. The onset of the disease begins with myocardial ischemia, which can develop into myocardial infarction if it persists for an extended period. The progressive regional tissue remodeling leads to increased electrical heterogeneities, with adverse consequences on arrhythmic risk, cardiac mechanics, and mortality. This review aims to summarize the key role of electrical heterogeneities in the heart on cardiac function and diseases. Ischemic heart disease has been chosen as an example to show how adverse electrical remodeling at different stages may lead to variable manifestations in patients. For this, we have reviewed the dynamic electrophysiological and structural remodeling from the onset of acute myocardial ischemia and reperfusion to acute and chronic stages post-myocardial infarction. The arrhythmic mechanisms, patient phenotypes, risk stratification at different stages, and patient management strategies are also discussed. Finally, we provide a brief review on how computational approaches incorporate human electrophysiological heterogeneity to facilitate basic and translational research.

Quinidine, the first antiarrhythmic drug, was widely used during the 20th century. Multiple studies have been conducted to provide insights into the pharmacokinetics and pleiotropic effects of Class Ia antiarrhythmic drugs. However, safety concerns and the emergence of new drugs led to a decline in their use during the 1990s. Despite this, recent studies have reignited the interest in quinidine, particularly for ventricular arrhythmias, where other antiarrhythmics have failed. In conditions such as Brugada syndrome, idiopathic ventricular fibrillation, early repolarization syndrome, short QT syndrome, and electrical storms, quinidine remains a valuable asset. Starting from the European and American recommendations, this comprehensive review aimed to explore the various indications for quinidine and the studies that support its use. We also discuss the potential future of quinidine, including the necessary research to optimize its use and patient selection. Additionally, it addresses the imperative task of mitigating the iatrogenic burden associated with quinidine usage and confronts the challenge of ensuring drug accessibility., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bartter's and Gitelman's syndromes (BS/GS) are genetically determined kidney tubulopathies leading to electrolyte and neurohormonal abnormalities. Although considered benign entities, major adverse cardiovascular events may complicate both syndromes, in form of ventricular arrhythmias leading to palpitations, syncope or sudden cardiac death, microvascular cardiac dysfunction and exercise-induced myocardial contractile deficit. The mechanisms leading to cardiovascular complications are not only driven by chronic electrolyte abnormalities, i.e. chronic hypokalemia and hypomagnesemia, but also by neurohormonal alterations that can impair vascular tone and myocardial contractility. In presence of triggering factors, BS/GS patients may experience a spectrum of cardiac arrhythmias necessitating prompt diagnosis and treatment. The aim of this review is to explore the pathophysiological mechanisms of BS and GS, highlighting those responsible for cardiovascular involvement, and to analyze the spectrum of associated cardiovascular complications. This highlights the importance of an integrated shared management of GS/BS patients between Nephrologist and Cardiologist., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Myocardial disarray, an early feature of hypertrophic cardiomyopathy (HCM) and a substrate for ventricular arrhythmia, is poorly characterized in pre-hypertrophic sarcomeric variant carriers (SARC+LVH-). Using diffusion tensor cardiac magnetic resonance (DT-CMR) we assessed myocardial disarray and fibrosis in both SARC+LVH- and HCM patients and evaluated the relationship between microstructural alterations and electrocardiographic (ECG) parameters associated with arrhythmic risk., Methods and Results: Sixty-two individuals (24 SARC+LVH-, 24 HCM, and 14 matched controls) were evaluated with multi-parametric CMR including stimulated echo acquisition mode DT-CMR, and blinded quantitative 12-lead ECG analysis. Mean diastolic fractional anisotropy (FA) was reduced in HCM compared with SARC+LVH- and controls (0.49 ± 0.05 vs. 0.52 ± 0.04 vs. 0.53 ± 0.04, P = 0.009), even after adjustment for differences in extracellular volume (ECV) (P = 0.038). Both HCM and SARC+LVH- had segments with significantly reduced diastolic FA relative to controls (54 vs. 25 vs. 0%, P = 0.002). Multiple repolarization parameters were prolonged in HCM and SARC+LVH-, with corrected JT interval (JTc) being most significant (354 ± 42 vs. 356 ± 26 vs. 314 ± 26 ms, P = 0.002). Among SARC+LVH-, JTc duration correlated negatively with mean diastolic FA (r = -0.6, P = 0.002). In HCM, the JTc interval showed a stronger association with ECV (r = 0.6 P = 0.019) than with mean diastolic FA (r = -0.1 P = 0.72). JTc discriminated SARC+LVH- from controls [area under the receiver operator curve 0.88, confidence interval 0.76-1.00, P < 0.001], and in HCM correlated with the European Society of Cardiology HCM sudden cardiac death risk score (r = 0.5, P = 0.014)., Conclusion: Low diastolic FA, suggestive of myocardial disarray, is present in both SARC+LVH- and HCM. Low FA and raised ECV were associated with repolarization prolongation. Myocardial disarray assessment using DT-CMR and repolarization parameters such as the JTc interval demonstrate significant potential as markers of disease activity in HCM., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Myocardial fibrosis leads to cardiac dysfunction and arrhythmias in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain poorly understood. Here, RNA sequencing identifies Forkhead Box1 (FoxO1) signaling as abnormal in male HFpEF hearts. Genetic suppression of FoxO1 alters the intercellular communication between cardiomyocytes and fibroblasts, alleviates abnormal diastolic relaxation, and reduces arrhythmias. Targeted downregulation of FoxO1 in activated fibroblasts reduces cardiac fibrosis, blunts arrhythmogenesis and improves diastolic function in HFpEF. These results not only implicate FoxO1 in arrhythmogenesis and lusitropy but also demonstrate that pro-fibrotic remodeling and cardiomyocyte-fibroblast communication can be corrected, constituting an alternative therapeutic strategy for HFpEF., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Implantable cardioverter defibrillators (ICDs) reduce mortality associated with ventricular arrhythmia in high-risk patients with cardiovascular disease. Machine learning (ML) approaches are promising tools in arrhythmia research; however, their application in predicting ventricular arrhythmias in patients with ICDs remains unexplored. We aimed to predict and stratify ventricular arrhythmias requiring ICD therapy using 12-lead electrocardiograms (ECGs) in patients with an ICD., Methods and Results: This retrospective analysis included 200 adult patients who underwent ICD implantation at a single center. Patient demographics, clinical features, and 12-lead ECG data were collected. Unsupervised learning techniques, including K-means and hierarchical clustering, were used to stratify patients based on 12-lead ECG features. Dimensionality reduction methods were also used to optimize clustering accuracy. The silhouette coefficient was used to determine the optimal method and number of clusters. Of the 200 patients, 59 (29.5%) received appropriate therapy. The mean age of patients was 62.3 years, and 81.0% were male. The mean follow-up period was 2,953 days, with no significant intergroup differences. Hierarchical clustering into 3 clusters proved to be the most accurate (silhouette coefficient=0.585). Kaplan-Meier curves for these 3 clusters revealed significant differences (P=0.026)., Conclusions: We highlight the potential of ML-based clustering using 12-lead ECGs to help in the risk stratification of ventricular arrhythmia. Future research in a larger multicenter setting may provide further insights and refine ICD indications.

Background: Left ventricular (LV) myocardial contraction patterns can be assessed using LV mechanical dispersion (LVMD), a parameter closely associated with electrical activation patterns. Despite its potential clinical significance, limited research has been conducted on LVMD following myocardial infarction (MI). This study aims to evaluate the predictive value of cardiac magnetic resonance (CMR)-derived LVMD for adverse clinical outcomes and to explore its correlation with myocardial scar heterogeneity., Methods: We enrolled 181 post-MI patients (median age: 55.7 years; 76.8% male) who underwent CMR examinations. LVMD was calculated using the CMR-feature tracking (CMR-FT) technique, defined as the standard deviation (SD) of the time from the R-wave peak to the negative strain peak across 16 myocardial segments. Entropy was quantified using an algorithm implemented with a generic Python package. The primary composite endpoints included sudden cardiac death (SCD), sustained ventricular arrhythmias (VA), and new-onset heart failure (HF)., Results: Over a median follow-up of 31 months, LVMD and border zone (BZ) entropy demonstrated relatively high accuracy for predicting the primary composite endpoints, with area under the curve (AUC) values of 0.825 and 0.771, respectively. Patients with LVMD above the cut-off value (86.955 ms) were significantly more likely to experience the primary composite endpoints compared to those with lower LVMD values (p < 0.001). Multivariable analysis identified LVMD as an independent predictor of the primary composite endpoints after adjusting for entropy parameters, strain, and left ventricular ejection fraction (LVEF) (hazard ratio [HR]: 1.014; 95% confidence interval [CI]: 1.003-1.024; p = 0.010). A combined prediction model incorporating LVMD, BZ entropy, and LVEF achieved the highest predictive accuracy, with an AUC of 0.871 for the primary composite endpoints. Spearman rank correlation analysis revealed significant linear correlations between LVMD and entropy parameters (p < 0.001 for all)., Conclusions: Myocardial heterogeneity, as assessed by LVMD and BZ entropy, represents reliable and reproducible parameters reflecting cardiac remodeling following MI. LVMD has independent prognostic value, and the combination of LVMD and BZ entropy with the guideline-recommended LVEF as a unified model enhances the accuracy of forecasting the risk of primary combined endpoints in patients after MI., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the principles of the Helsinki. The studies involving human participants were reviewed and approved by the Institutional Review Committee of The Second Affiliated Hospital of Kunming Medical University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Arrhythmia of the heart is a dangerous and potentially fatal condition. The current widely used treatment is the implantable cardioverter defibrillator (ICD), but it is invasive and affects the patient's quality of life. The sonogenetic mechanism proposed here focuses ultrasound on a cardiac tissue, controls endogenous stretch-activated Piezo1 ion channels on the focal region's cardiomyocyte sarcolemma, and restores normal heart rhythm. In contrast to anchoring the implanted ICD lead at a fixed position in the myocardium, the size and position of the ultrasound focal region can be selected dynamically by adjusting the signals of every piezoelectric chip on the ultrasonic phased array, and it allows novel and efficient defibrillations. Based on the developed interdisciplinary electro-mechanical model of sonogenetic treatment, our analysis shows that the proposed ultrasound intensity and frequency will be safe and painless for humans and well below the limits established by the U.S. Food and Drug Administration., (© 2025 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood., Objective: We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression., Methods: After exposure to 20 Gy of x-rays in a single fraction, neonatal rat ventricular cardiomyocytes were analyzed 24 and 96 hours postradiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration in both monolayers and single cells. In addition, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and messenger RNA levels., Results: After irradiation with 20 Gy, neonatal rat ventricular cardiomyocytes exhibited increased beat rate and conduction velocity 24 and 96 hours after treatment. Messenger RNA and protein levels of ion channels were altered, with the most significant changes observed at the 96-hour mark. Upregulation of Cacna1c (Ca v 1.2), Kcnd3 (K v 4.3), Kcnh2 (K v 11.1), Kcnq1 (K v 7.1), Kcnk2 (K 2P 2.1), Kcnj2 (K ir 2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 ryanodin-rezeptor 2 and Slc8a1 Na + /Ca 2+  exchanger expression and altered properties 96 hours posttreatment. Fibroblast and myofibroblast levels remained unchanged., Conclusion: cSBRT modulates the expression of various ion channels, calcium handling proteins, and gap junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed after cSBRT., Competing Interests: Disclosures Dr Mages acknowledges educational support from Biotronik and Johnson & Johnson, while Dr Rahm acknowledges support from Boston Scientific, Johnson & Johnson, Abbott, and Medtronic. Dr Thomas has received lecture fees/honoraria from various pharmaceutical and medical device companies, including Abbott, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Medtronic, Novartis, Pfizer Pharma, Sanofi-Aventis, and ZOLL CMS. Dr Lugenbiel has received lecture fees from Bayer Vital, Pfizer Pharma, and Bristol Myers Squibb as well as educational support from Boston Scientific and fees/honoraria from Johnson & Johnson and Boston Scientific. The remaining authors have declared no relevant relationships. We declare that no artificial intelligence was used in preparation of the present manuscript., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Little is known about age and clinical intervention after implantable loop recorder (ILR) insertion. This study investigated the association between age and clinical intervention after ILR implantation., Methods and Results: Data were obtained from a multicenter registry of ILR in Korea (2017-2020, n = 795). ILRs were inserted with indications of unexplained syncope, recurrent palpitation, or cryptogenic stroke. The primary outcome was clinically actionable event that was a composite of the newly detected atrial fibrillation (AF), pacemaker or implantable cardioverter defibrillator (ICD) implantation, catheter ablation, and anticoagulation initiation. The mean age was 64.3 years, and the mean follow-up duration was 20.6 months. Clinically actionable events were observed in 322 (40.5%) patients. Compared to younger age (< 50 years), older age (≥ 50 years) showed higher prevalence of newly detected AF (3.7% vs. 15.8%; p = 0.001), pacemaker implantation (11.2% vs. 21.2%; p = 0.022), and initiation of anticoagulation (3.7% vs. 18.6%; p < 0.001). No significant differences were found in ICD implantation (1.9% vs. 1.3%; p = 0.996) or catheter ablation (3.8% vs. 6.0%; p = 0.512). The older age group more frequently experienced clinically actionable events compared to the younger age group (hazard ratio 2.52, 95% confidence interval: 1.86-3.41; p < 0.001). A significant association was found in the increase of age (per 1-year) and the risk of clinically actionable events (adjusted hazard ratio 1.03, 95% confidence interval 1.02-1.04; p < 0.001)., Conclusion: Advanced age is a significant risk factor for clinical intervention after ILR insertion. ILR should be considered more actively in older patients requiring prolonged rhythm monitoring., (© 2024 Wiley Periodicals LLC.)

In recent years, concerns have been raised regarding the safety of exposure to pyriproxyfen (PPF), a larvicide commonly used in drinking water reservoirs to control populations of disease-vector mosquitoes for human safety. These concerns are focused mainly on exposure by pregnant women, since studies have shown deleterious effects of PPF on embryonic development, mainly addressing the central nervous system. However, since previous studies showed reduced growth in embryos exposed to PPF, we hypothesize that PPF exposure impairs the cardiovascular system, responsible for ensuring appropriate blood supply, which leads to stunted growth. This study aimed to investigate the impact of PPF exposure on heart ventricular morphology, its influence on cell proliferation and apoptosis, as well as assess the impact on the functionality of the heart and on embryonic growth. Chicken embryos were used as a model and two sublethal concentrations were tested: 0.01 mg/L and 10 mg/L PPF. Thinning of cardiac tissue was evident in heart structures at 10 mg/L PPF. Furthermore, DNA double-strand breaks and reduced cell proliferation were observed, combined with decreased apoptosis suggesting cell cycle arrest, especially in the left ventricle for both concentrations. In addition, these PPF concentrations induced heart arrhythmia, although no changes in heart rate were observed. Embryos exposed to 0.01 mg/L showed reduced body and heart mass, crown-rump length, and thoracic perimeter, while head circumference was reduced in both exposed groups. Together, combining morphological, molecular, and physiological parameters, this study showed the cardiotoxic effects of PPF exposure and elucidated its impacts on embryonic growth., Competing Interests: Declarations. Conflict of interest: All authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This paper introduces a new advanced model for denoising and classification of ECG signals, focusing on the use of a hybrid filter and Bayesian optimization. The hybrid filter synergistically combines enhanced empirical mode decomposition (EEMD), Chebyshev Type II filters, Butterworth, Daubechies Wavelet, and Savitzky-Golay filters, leveraging their respective advantages for effective noise reduction while preserving the essential features of the ECG signal. We employ a multi-criteria Bayesian optimization process, using cross-correlation and mean squared error (MSE) as key metrics, to refine the filter parameters to further improve the signal quality. Additionally, we deploy a residual and parallel deep learning architecture adapted for the precise classification of cardiac conditions, such as arrhythmia and myocardial infarction. The results show a significant improvement in classification accuracy, from 96.63%-97.86% to 97.24%-98.62% after filtering, and reaching 98.03%-99.61% after optimization for arrhythmia. For myocardial infarction, accuracy increases from 96.29%-97.42% to 97.34%-98.44% after filtering, and from 98.13%-99.07% after optimization. This holistic and multi-criteria approach enhances the reliability of medical diagnostics and represents a significant advancement in the processing of biomedical signals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to describe our experience and outcome of ablation therapy for arrhythmias in pediatrics at a tertiary care center., Methods: Data was collected retrospectively from the hospital medical records. All pediatrics presenting to AUBMC between 2000 and 2020 who underwent cardiac ablation were included. The data collected included type of arrhythmia, ablation technique, age and weight at ablation, procedure complications, medications used, and outcome assessment., Results: We had 67 patients who underwent cardiac ablation. Of those, 60% were males with a mean age of 15 years. Structural heart disease was present in 6% of patients. Wolff-Parkinson-White syndrome (WPW) was most prevalent at 31%, followed by atrioventricular nodal reentrant tachycardia (AVNRT) at 24%, atrioventricular reentrant tachycardia (AVRT) at 16%, ventricular tachycardia (VT) at 10%, atrial fibrillation (AF) at 3%, and atrial tachycardia (AT) at 1%. The remaining 15% of patients presented with less common types of arrhythmias, including other supraventricular tachycardias (SVTs), retrograde dual atrioventricular nodal reentry, and premature ventricular contractions (PVC). Antiarrhythmic medications were started before the procedure in 59% of our population. Medication regimens postablation included beta-blockers (68%), type 1c antiarrhythmics (25%), calcium channel blockers (3%), ivabradine (2%), and amiodarone (2%). The completed procedures showed a success rate of 93%., Conclusion: Ablation of arrhythmias in pediatrics is an effective procedure in the treatment of childhood arrhythmias. More studies are needed on cardiac ablation in this age group and those with structural heart disease in the Middle East region., (© 2024 Wiley Periodicals LLC.)

Ryanodine receptor type 2 (RyR2) is the principal intracellular calcium release channel in the cardiac sarcoplasmic reticulum (SR). Pathological RyR2 hyperactivity generates arrhythmia risk in genetic and structural heart diseases. RYR2 gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia. In structural heart diseases (i.e., heart failure), posttranslation modifications render RyR2 channels leaky, resulting in pathologic calcium release during diastole, contributing to arrhythmogenesis and contractile dysfunction. Hence, RyR2 represents a therapeutic target in arrhythmogenic heart diseases. We provide an overview of the structure and function of RyR2, and then review US Food and Drug Administration-approved and investigational RyR2 inhibitors. A therapeutic classification of RyR2 inhibitors is proposed based on their mechanism of action. Class I RyR2 inhibitors (e.g., flecainide) do not change SR calcium content and are primarily antiarrhythmic. Class II RyR2 inhibitors (e.g., dantrolene) increase SR calcium content, making them less effective as antiarrhythmics but preferable in conditions with reduced SR calcium content such as heart failure.

Mendelian randomization (MR) uses genetic variants associated with an exposure (eg, high blood pressure) as instrumental variables to test causal effects on an outcome (eg, atrial fibrillation [AF]). By leveraging the random assortment of genetic variants during gamete formation, MR reduces biases like confounding and reverse causation. We screened 391 papers, examining 277 that applied MR to investigate arrhythmia and, in others, cardiovascular traits, lifestyle, behavioral traits, and body composition. Our analysis focused on MR studies of arrhythmia and cardiovascular traits. Key findings highlight high systolic blood pressure, low resting heart rate, elevated cardiac troponin I levels, coronary artery disease, and heart failure as risk factors for AF, whereas AF itself increases heart failure risk. As genetic data become more accessible, MR's relevance grows. Sensitivity analyses and integrating MR with other methodologies in a triangulation framework enhance the robustness of causal inferences by navigating different biases., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The complexity of cardiac electrophysiology procedures has increased significantly during the past 3 decades. Anesthesia requirements of these procedures can differ on the basis of patient- and procedure-specific factors. This manuscript outlines various anesthesia strategies for cardiac implantable electronic devices and electrophysiology procedures, including preprocedural, procedural, and postprocedural management. A team-based approach with collaboration between cardiac electrophysiologists and anesthesiologists is required with careful preprocedural and intraprocedural planning. Given the recent advances in electrophysiology, there is a need for specialized cardiac electrophysiology anesthesia care to improve the efficacy and safety of the procedures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Early repolarization (ER) is an electrocardiographic pattern characterized by J-point and ST-segment elevation, frequently observed in athletes. Initially deemed benign, recent studies suggest a possible association between ER and increased risks of cardiac arrhythmias and sudden cardiac death, necessitating a thorough examination of its clinical implications in athletes., Methods: A comprehensive literature review was conducted using MEDLINE (via PubMed) and EMBASE databases, focusing on articles related to ER in athletes. Search terms included "early repolarization," and relevant studies were selected based on their focus on athletic populations. A total of 22 articles were included for detailed analysis., Results: The review encompassed 22 studies with a combined total of 44,326 athletes, revealing an overall mean ER prevalence of 31.6 ± 17.6 (p < 0.001). Most common location in the inferolateral region at 32.28%. The prevalence varied significantly across studies, ranging from 7% to 89%, influenced by factors such as age, gender distribution, and athletic discipline. Male athletes exhibited a higher incidence of ER compared with females, and endurance athletes showed a greater prevalence than strength athletes., Conclusion: ER is notably prevalent among athletes, especially males and those engaged in endurance sports. Current studies do not establish a direct association between ER and increased mortality in athletes. Further research is essential to refine risk stratification criteria and develop appropriate management strategies to ensure athlete safety while maintaining optimal performance levels., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Epilepsy is an important cause of disability and mortality worldwide. It can be frequently misdiagnosed, and detailed history and relevant investigations are needed to differentiate epilepsy from syncope. Electroencephalogram is a key noninvasive assessment of neurological function, and the diagnostic yield is increased when performed for an extended period in the ambulatory setting with concurrent electrocardiogram and video monitoring. People living with epilepsy may be affected by a diverse range of ictal (seizure-associated) arrhythmias. The prevalence of detected arrhythmias in people living with epilepsy is anticipated to rise in the context of increasingly available wearable technology and improved survival. Ictal bradycardia and asystole sometimes observed in temporal lobe epilepsy may be associated with falls and injury that can be prevented by cardiac pacing; however, seizure control with medical therapy is still crucial. Sudden unexpected death in epilepsy is likely explained by a different mechanism, in particular central cardiorespiratory autonomic dysfunction sometimes associated with generalized tonic-clonic seizures. Channelopathies encompassing the heart-brain axis are increasingly recognized and may explain the overlap between certain epileptic and arrhythmogenic syndromes, with potential for targeted therapy in the future. The QT interval is prognostically significant in epilepsy, with various seizure types affecting the QT interval differently. Certain antiseizure medications may cause electrocardiogram abnormalities and arrhythmias although there remains limited clinical data. This State-of-the-Art Review describes our current understanding regarding the relationship between epilepsy and cardiac arrhythmias, as well as delineating areas of unmet need., Competing Interests: Funding Support and Author Disclosures Dr Paratz is supported by the Wilma Beswick Senior Research Fellowship, Department of Medicine at St Vincent’s Hospital Melbourne, University of Melbourne, a Heart Foundation Vanguard Grant, a Sylvia & Charles Viertel Foundation Clinical Investigator Grant and a Mamoma Foundation Fellowship. Dr Cook has a financial interest in Seer Medical Holdings Ltd and Epiminder Pty Ltd. Dr Paratz has received speaker fees from Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same heartbeat (eg, aortic valve closure during echocardiography with simultaneous electrocardiography). Here, we review the current knowledge on the role of the EMW as an independent parameter for ventricular arrhythmia-risk stratification. We (1) provide a standardized approach to echocardiographic EMW assessment, (2) define relevant cutoff values for both abnormal EMW negativity and positivity, (3) discuss pathophysiological underpinnings of EMW negativity, and (4) outline the potential future role of cardiac electromechanical relations in patients with proarrhythmic conditions., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Palpitations are common in pregnancy and warrant investigation. Palpitations may be caused by non-cardiac and cardiac causes. Patients with structural or functional abnormalities or inherited cardiovascular disease are more likely to develop arrhythmia, especially during pregnancy when the mother's body undergoes extensive physiological adaptations, which further contribute to an increased arrhythmia risk. While isolated ectopic beats do not require treatment, some heart rhythm disturbances can be life-threatening for mother and baby and mandate prompt intervention. Haemodynamically unstable patients should be electrically cardioverted. If the patient is stable, medical management is indicated, and early involvement of the pregnancy heart team can help facilitate appropriate treatment. In complex arrhythmia, consultation of an arrhythmia expert should be sought . Many anti-arrhythmics are safe in pregnancy, and it is important to reassure the pregnant patient of this., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Introduction: The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to a transvenous ICD in patients who meet the criteria for ICD implantation without concurrent need for cardiac pacing. The objective of this study is to examine the rates of and indications for S-ICD removal and extraction., Methods: A retrospective analysis of all patients who underwent S-ICD implantation between 2010 and 2022 at a single multihospital healthcare system was performed. The primary endpoint was S-ICD removal or extraction. Patient and device characteristics were abstracted from the electronic medical record. Univariate and multivariate analyses were completed to determine factors associated with S-ICD extraction., Results: A total of 372 patients (69.5% male; 48.6 ± 14.4 years old) underwent S-ICD implantation during the study period. There were 22 (5.9%) patients (81.8% male; 52.1 ± 13.2 years old) who underwent S-ICD extraction over a median follow-up period of 4.4 [2.0-6.5] years. The median length of time between implantation and extraction was 39.6 [8.3-64.6] months. The most common indications for S-ICD extraction were the need for bradycardia pacing (frequency among extractions, 18.2%), infection (22.7%), and inappropriate shocks due to oversensing (22.7%). A smoking history and higher body mass index were independently associated with S-ICD extraction., Conclusions: The overall rate of S-ICD extraction over 4.4 [2.0-6.5] years was 5.9%, with the most common indications for extraction being the need for bradycardia pacing, infection, and inappropriate shocks due to oversensing. A smoking history and high body mass index are associated with increased rates of S-ICD extraction. With appropriate patient selection for the S-ICD, the need to remove the device after implantation is low., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Voltage-gated sodium channels (VGSCs) are transmembrane protein complexes that are vital to the generation and propagation of action potentials in nerve and muscle fibers. The canonical VGSC is generally conceived as a heterotrimeric complex formed by 2 classes of membrane-spanning subunit: an α-subunit (pore forming) and 2 β-subunits (non-pore forming). Na V 1.5 is the main sodium channel α-subunit of mammalian ventricle, with lower amounts of other α-subunits, including Na V 1.6, being present. There are 4 β-subunits (β1-β4) encoded by 4 genes (SCN1B-SCN4B), each of which is expressed in cardiac tissues. Recent studies suggest that in addition to assignments in channel gating and trafficking, products of Scn1b may have novel roles in conduction of action potential in the heart and intracellular signaling. This includes evidence that the β-subunit extracellular amino-terminal domain facilitates adhesive interactions in intercalated discs and that its carboxyl-terminal region is a substrate for a regulated intramembrane proteolysis (RIP) signaling pathway, with a carboxyl-terminal peptide generated by β1 RIP trafficked to the nucleus and altering transcription of various genes, including Na V 1.5. In addition to β1, the Scn1b gene encodes for an alternative splice variant, β1B, which contains an identical extracellular adhesion domain to β1 but has a unique carboxyl-terminus. Although β1B is generally understood to be a secreted variant, evidence indicates that when co-expressed with Na V 1.5, it is maintained at the cell membrane, suggesting potential unique roles for this understudied protein. In this review, we focus on what is known of the 2 β-subunit variants encoded by Scn1b in heart, with particular focus on recent findings and the questions raised by this new information. We also explore data that indicate β1 and β1B may be attractive targets for novel antiarrhythmic therapeutics., (Copyright © 2024. Published by Elsevier Inc.)

Background: Smartphone electrocardiograms (iECGs) are an innovative method of capturing transient arrhythmias that are occasionally experienced by athletes. This study aimed to assess the accuracy of a 6-lead iECG compared with 12-lead ECG in athletes and those with known genetic heart disease (positive controls)., Research Design and Methods: Each participant had a resting 12-lead ECG (supine) and a 30 s 6-lead iECG (seated) taken within 2 h. Manual measurements of heart rate, QTc, and PR intervals, and QRS duration were completed using digital calipers. Bland-Altman analysis was used to assess the quantitative agreement of measurements., Results: The 6-lead readings for heart rate were faster than the 12-lead in athletes ( n  = 233) and positive controls ( n  = 49). All other measurements were shorter in the 6-lead. QTc mean difference was smaller in the positive controls (4.7 ± 26.0 ms) than in athletes (12.5 ± 25.0 ms). The largest difference was in PR intervals, both in athletes (12.8 ± 17.7 ms) and positive controls (7.6 ± 18.9 ms). QRS duration had the smallest mean difference (0.6 ± 9.0 ms in athletes, 1.0 ± 12.7 ms in positive controls)., Conclusions: The 6-lead readings had reasonable agreement with the 12-lead ECG. A 6-lead iECG is a reasonable option to opportunistically capture arrhythmias that may occur infrequently, but should not replace a 12-lead if available.

Background: Large language models (LLMs) such as Chat Generative Pre-trained Transformer (ChatGPT) excel at interpreting unstructured data from public sources, yet are limited when responding to queries on private repositories, such as electronic health records (EHRs). We hypothesized that prompt engineering could enhance the accuracy of LLMs for interpreting EHR data without requiring domain knowledge, thus expanding their utility for patients and personalized diagnostics., Methods: We designed and systematically tested prompt engineering techniques to improve the ability of LLMs to interpret EHRs for nuanced diagnostic questions, referenced to a panel of medical experts. In 490 full-text EHR notes from 125 patients with prior life-threatening heart rhythm disorders, we asked GPT-4-turbo to identify recurrent arrhythmias distinct from prior events and tested 220 563 queries. To provide context, results were compared with rule-based natural language processing and Bidirectional Encoder Representations from Transformer-based language models. Experiments were repeated for 2 additional LLMs., Results: In an independent hold-out set of 389 notes, GPT-4-turbo had a balanced accuracy of 64.3%±4.7% out-of-the-box at baseline. This increased when asking GPT-4-turbo to provide a rationale for its answers, a structured data output, and in-context exemplars, to a balanced accuracy of 91.4%±3.8% ( P <0.05). This surpassed the traditional logic-based natural language processing and BERT-based models ( P <0.05). Results were consistent for GPT-3.5-turbo and Jurassic-2 LLMs., Conclusions: The use of prompt engineering strategies enables LLMs to identify clinical end points from EHRs with an accuracy that surpassed natural language processing and approximated experts, yet without the need for expert knowledge. These approaches could be applied to LLM queries for other domains, to facilitate automated analysis of nuanced data sets with high accuracy by nonexperts., Competing Interests: Dr Narayan reports consulting for Abbott, Inc, UpToDate, Inc, and TDK, Inc; equity interest in Life Signals.ai and PhysCade, Inc; and intellectual property owned by the University of California Regents and Stanford University. Dr Rogers reports consulting for TDK, Inc. Dr Rodrigo holds equity interests in Corify Health Care. Dr Baykaner reports consulting honoraria to the institution from Abbott, Boston Scientific, and Daiichi Sankyo; no personal gain. P. Clopton reports consulting for the American College of Cardiology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The other authors report no conflicts.

Background -Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. In electrocardiogram (ECG) recordings abnormal durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality. Previous analyses of the National Health and Nutrition Examination Survey (NHANES) database for associations between smoking and ECG abnormalities were incomplete. To elucidate how smoking affects cardiac excitation, we assessed in a nationally representative sample (NHANES III) the association between serum cotinine and P duration, PR interval, PR segment, rate-corrected QT (QTc), QRS duration, and JT interval. Methods and Results-We analyzed data from 5,653 adults using survey-weighted multinomial logistic regression to estimate associations between tobacco use (> 15 ng/ml serum cotinine) and short (< 5th percentile) or long (> 95th percentile) ECG intervals, relative to reference (5-95th percentile). After adjustment for demographics, risk factors, and conduction-altering medications, smoking was associated with a higher odds of short PR interval, PR segment, and QRS, and long JT. Broader effects of smoking on ECG were also assessed by survey-weighted linear regression of continuous cotinine and ECG, which revealed cotinine inversely associated with PR segment and QTc. Over a 22-year follow-up, many ECG abnormalities predicted cardiovascular mortality in smokers, including long JT, QRS, and QTc, and short QRS, whereas only short JT predicted mortality in nonsmokers. Conclusions -Smoking increases likelihood for rapid atrioventricular and ventricular depolarization and slow ventricular repolarization, which may promote cardiac arrhythmia and mortality., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Objectives: Colorectal cancer is the second leading cause of cancer-related deaths in the U.S., and colonoscopy is a critical tool for colon cancer screening and diagnosis. Electrolyte disturbances and autonomic nervous system dysfunction that may occur due to bowel preparation and the colonoscopy procedure itself may play a role in the development of cardiac arrhythmia. This study aimed to assess the index of cardiac-electrophysiological balance (iCEB) to predict ventricular arrhythmia risk related to colonoscopy. Materials and Methods: Patients undergoing elective colonoscopy with a normal sinus rhythm were included. Electrocardiography (ECG) recordings both before bowel preparation and after the colonoscopy procedure were obtained. Values of the index of cardiac-electrophysiological balance (iCEB) were compared. Results: Among 36 patients, it was determined that the heart rate values of the patients before bowel preparation were higher than the heart rate values after colonoscopy [74.5 (60-108) bpm vs. 68.5 (53-108) bpm, p = 0.021]. The duration of QT interval increased (370.9 ± 27.8 ms vs. 398.7 ± 29.4 ms, p < 0.001) and the iCEB increased from 4.1 ± 0.5 to 4.5 ± 0.6 ( p < 0.001), indicating a significant post-procedural risk of ventricular arrhythmias. Conclusions: These findings suggest that routine iCEB assessment post-colonoscopy could identify high-risk patients requiring closer monitoring.

In 2024, we celebrate the 100th anniversary of Willem Einthoven receiving the Nobel Prize for his discovery of the mechanism of the electrocardiogram (ECG). Building on Einthoven's legacy, electrocardiography allows the monitoring of cardiac bioelectricity through solutions to the so-called forward and inverse problems. These solutions link local cardiac electrical signals with the morphology of the ECG, offering a reversible connection between the heart's electrical activity and its representation on the body surface. Inspired by Einthoven's work, researchers have explored the transition from monitoring to modulation of bioelectrical activity in the heart for the development of new anti-arrhythmic strategies, e.g. via optogenetics. In this review, we demonstrate the lasting influence that Einthoven has on our understanding of cardiac electrophysiology in general, and the diagnosis and treatment of cardiac arrhythmias in particular., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Ventricular arrhythmias (VAs), which can lead to sudden cardiac death, are the primary cause of mortality in patients with heart failure (HF). However, the precise mechanisms underlying these arrhythmias are not well understood. Recent studies have implicated tumour necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in pathological cardiac hypertrophy. Nevertheless, its role in isoproterenol (ISO)-associated VAs remains elusive., Methods and Results: We overexpressed TNIP3 in the myocardium using an adeno-associated virus 9 system, administered via tail vein injection. C57BL/6 mice received daily subcutaneous injections of ISO for two consecutive weeks to establish an HF model. We performed histopathology and electrophysiological studies to assess ventricular structural remodelling, electrical remodelling, and susceptibility to VAs. Additionally, RNA sequencing (RNA-Seq) and western blot analysis were conducted to elucidate the underlying mechanisms. The expression of TNIP3 was up-regulated following ISO treatment. TNIP3 overexpression significantly reversed ISO-induced cardiac dysfunction, fibrosis, electrical remodelling, and VAs susceptibility. Accordingly, RNA-Seq identifies that the inflammatory response takes an important role in ISO-induced Vas, and TNIP3 overexpression could alleviate ISO-induced cardiac proinflammatory response by promoting M1 to M2 macrophage polarization. Mechanistically, PI3K/Akt/NF-κB signalling is responsible for the protective effect of TNIP3 overexpression on ISO-induced HF. And PI3K/Akt signalling activation offset the protective effect of TNIP3 overexpression on ISO-induced cardiac inflammation and VAs., Conclusion: The findings of this study highlight the critical role of TNIP3 in ISO-associated cardiac remodelling and VAs, which are induced by the inhibited activation of the PI3K/Akt/NF-κB signalling pathway., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

It was widely accepted that malignant ventricular arrhythmias (VA) are the main direct initial cause for cardiac arrest and sudden cardiac death (SCD), but diverging data tended to demonstrate that asystole or pulseless activity were becoming the most prevalent cardiac rhythms at the time of cardiac arrest. We challenge here these conceptions and reinforce the persisting prominent role of VA in SCD., Competing Interests: Conflict of interest: None for any author., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Electrocardiogram (ECG) signals contain complex and diverse features, serving as a crucial basis for arrhythmia diagnosis. The subtle differences in characteristics among various types of arrhythmias, coupled with class imbalance issues in datasets, often hinder existing models from effectively capturing key information within these complex signals, leading to a bias towards normal classes. To address these challenges, this paper proposes a method for arrhythmia classification based on a multi-branch, multi-head attention temporal convolutional network (MB-MHA-TCN). The model integrates three convolutional branch layers with different kernel sizes and dilation rates to capture features across varying temporal scales. A multi-head self-attention mechanism dynamically allocates weights, integrating features and correlations from different branches to enhance the recognition capability for difficult-to-classify samples. Additionally, the temporal convolutional network employs multi-layer dilated convolutions to progressively expand the receptive field for extracting long-term dependencies. To tackle data imbalance, a novel data augmentation strategy is implemented, and focal loss is utilized to increase the weight of minority classes, while Bayesian optimization is employed to fine-tune the model's hyperparameters. The results from five-fold cross-validation on the MIT-BIH Arrhythmia Database demonstrate that the proposed method achieves an overall accuracy of 98.75%, precision of 96.60%, sensitivity of 97.21%, and F1 score of 96.89% across five categories of ECG signals. Compared to other studies, this method exhibits superior performance in arrhythmia classification, significantly improving the recognition rate of minority classes.

The automatic detection of arrhythmia is of primary importance due to the huge number of victims caused worldwide by cardiovascular diseases. To this aim, several deep learning approaches have been recently proposed to automatically classify heartbeats in a small number of classes. Most of these approaches use convolutional neural networks (CNNs), exploiting some bi-dimensional representation of the ECG signal, such as spectrograms, scalograms, or similar. However, by adopting such representations, state-of-the-art approaches usually rely on the magnitude information alone, while the important phase information is often neglected. Motivated by these considerations, the focus of this paper is aimed at investigating the effect of fusing the magnitude and phase of the continuous wavelet transform (CWT), known as the scalogram and phasogram, respectively. Scalograms and phasograms are fused in a simple CNN-based architecture by using several fusion strategies, which fuse the information in the input layer, some intermediate layers, or in the output layer. Numerical results evaluated on the PhysioNet MIT-BIH Arrhythmia database show the effectiveness of the proposed ideas. Although a simple architecture is used, their competitiveness is high compared to other state-of-the-art approaches, by obtaining an overall accuracy of about 98.5% and sensitivity and specificity of 98.5% and 95.6%, respectively.

Heart failure with preserved ejection fraction (HFpEF) is increasing at an alarming rate worldwide, with limited effective therapeutic interventions in patients. Sudden cardiac death (SCD) and ventricular arrhythmias present substantial risks for the prognosis of these patients. Obesity is a risk factor for HFpEF and life-threatening arrhythmias. Obesity and its associated metabolic dysregulation, leading to metabolic syndrome, are an epidemic that poses a significant public health problem. More than one-third of the world population is overweight or obese, leading to an enhanced risk of incidence and mortality due to cardiovascular disease (CVD). Obesity predisposes patients to atrial fibrillation and ventricular and supraventricular arrhythmias-conditions that are caused by dysfunction in the electrical activity of the heart. To date, current therapeutic options for the cardiomyopathy of obesity are limited, suggesting that there is considerable room for the development of therapeutic interventions with novel mechanisms of action that will help normalize sinus rhythms in obese patients. Emerging candidates for modulation by obesity are cardiac ion channels and Ca-handling proteins. However, the underlying molecular mechanisms of the impact of obesity on these channels and Ca-handling proteins remain incompletely understood. Obesity is marked by the accumulation of adipose tissue, which is associated with a variety of adverse adaptations, including dyslipidemia (or abnormal systemic levels of free fatty acids), increased secretion of proinflammatory cytokines, fibrosis, hyperglycemia, and insulin resistance, which cause electrical remodeling and, thus, predispose patients to arrhythmias. Furthermore, adipose tissue is also associated with the accumulation of subcutaneous and visceral fat, which is marked by distinct signaling mechanisms. Thus, there may also be functional differences in the effects of the regional distribution of fat deposits on ion channel/Ca-handling protein expression. Evaluating alterations in their functional expression in obesity will lead to progress in the knowledge of the mechanisms responsible for obesity-related arrhythmias. These advances are likely to reveal new targets for pharmacological modulation. Understanding how obesity and related mechanisms lead to cardiac electrical remodeling is likely to have a significant medical and economic impact. Nevertheless, substantial knowledge gaps remain regarding HFpEF treatment, requiring further investigations to identify potential therapeutic targets. The objective of this study is to review cardiac ion channel/Ca-handling protein remodeling in the predisposition to metabolic HFpEF and arrhythmias. This review further highlights interleukin-6 (IL-6) as a potential target, cardiac bridging integrator 1 (cBIN1) as a promising gene therapy agent, and leukotriene B4 (LTB4) as an underappreciated pathway in future HFpEF management.

Background: Evaluating myocardial function using cardiac magnetic resonance (CMR) feature tracking provides a comprehensive cardiac assessment, particularly a detailed evaluation for patients with repaired tetralogy of Fallot (rTOF). This study aimed to identify factors associated with arrhythmias in rTOF patients utilizing conventional CMR techniques, including myocardial strain measurements., Methods: This single-center, retrospective study included 245 rTOF patients who underwent CMR between 2017 and 2023. Patients were stratified based on the presence or absence of arrhythmias during follow-up. The biventricular strain was assessed using CMR-derived feature tracking. Demographic, clinical, and imaging data were collected, and statistical analyses were performed to identify factors associated with arrhythmic events., Results: The median age at surgery was 5.6 years (range 1-44 years), with the median age at CMR was 27.5 years (range 15-69 years). Over the follow-up period, 25 patients (10.2%) experienced atrial or ventricular arrhythmias. Univariate analysis revealed significant associations between arrhythmic events and older age at surgery and CMR, lower functional class, larger heart size on chest radiograph, and prolonged QRS duration (QRSd). Additionally, arrhythmias were associated with increased right ventricular (RV) volume, reduced RV and left ventricular (LV) ejection fraction (EF), and impaired strain values. Multivariate binary logistic regression, adjusting for age at surgery, NYHA class, QRSd, and cardiothoracic ratio, identified that a lower RV EF (adjusted odds ratio [aOR] 6.97), RV global radial strain (GRS) (aOR 6.68), RV global circumferential strain (GCS) (aOR 6.36), RV global longitudinal strain (GLS) (aOR 3.14), and LV GRS (aOR 3.02) were all significantly associated with arrhythmias., Conclusion: This study highlights the significant contribution of CMR-derived myocardial strain measurements in predicting arrhythmic events in patients with rTOF. In addition to conventional RV EF, strain metrics-particularly those of the right ventricle- emerged as strong, independent predictors of arrhythmias, offering valuable prognostic information for clinical management in this patient population. These findings underscore the importance of myocardial strain analysis as a complementary tool to conventional imaging in evaluating arrhythmic risk in rTOF patients., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethical approval and consent to participate, consent for publication: Electrocardiograms and chest radiographs correlated within 6 months of CMR were reviewed. The Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University approved the protocol for this study (COA no. Si 631/2023). Given the anonymous and retrospective nature of this study, written informed consent was not obtained from study subjects. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Aims: Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). The aim of the study is (i) to characterize the distribution of AAs in patients with IAS and (ii) evaluate the long-term clinical course of these patients., Methods and Results: An international multicentre study was performed and involved 28 centres in 16 countries. Inclusion criteria were (i) IAS and (ii) electrocardiographic documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained ventricular arrhythmias (VAs), or appropriate implantable cardioverter defibrillator (ICD) interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n = 355, 68%) and long QT syndrome (n = 93, 18%). The remaining patients (n = 71, 14%) presented with short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). Atrial arrhythmia was the first clinical manifestation of IAS in 52% of patients. More than one type of AA was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a two-fold increase in patients who experienced their first AA before the age of 20 (odds ratio 2.2, P = 0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs was reported in 2.8% of patients, strokes in 4.4%, and sinus node dysfunction in 9.6%., Conclusion: Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of VAs. The occurrence of stroke and sinus node dysfunction is not infrequently in this cohort., Competing Interests: Conflict of interest: G.C. has received honoraria from Bristol-Myers Squibb SA. Microport CRM, Biosense Webster, research grants from Boston Scientific Inc. J.T.-H. has been a consultant for Johnson and Johnson, Boston, MicroPort, Solid Bioscience, Cytokinetics, and Leo Pharma. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Athletes are predisposed to atrial arrhythmias but the association between intense endurance exercise training, ventricular arrhythmias (VAs), and sudden cardiac death is less well established. Thus, it is unclear whether the 'athlete's heart' promotes specific arrhythmias or whether it represents a more general pro-arrhythmogenic phenotype. Whilst direct causality has not been established, it appears possible that repeated exposure to high-intensity endurance exercise in some athletes contributes to formation of pro-arrhythmic cardiac phenotypes that underlie VAs. Theories regarding potential mechanisms for exercise-induced VAs include repeated bouts of myocardial inflammation and stretch-induced cellular remodelling. Small animal models provide some insights, but larger animal and human data are sparse. The current clinical approach to VAs in athletes is to differentiate those with and without structural or electrical heart disease. However, if the athlete's heart involves a degree of pro-arrhythmogenic remodelling, then this may not be such a simple dichotomy. Questions are posed by athletes with VAs in combination with extreme remodelling. Some markers, such as scar on magnetic resonance imaging, may point towards a less benign phenotype but are also quite common in ostensibly healthy athletes. Other clinical and invasive electrophysiology features may be helpful in identifying the at-risk athlete. This review seeks to discuss the association between athletic training and VAs. We will discuss the potential mechanisms, clinical significance, and approach to the management of athletes with VAs., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This State of the Future Review describes and discusses the potential transformative power of digital twins in cardiac electrophysiology. In this 'big picture' approach, we explore the evolution of mechanistic modelling based digital twins, their current and immediate clinical applications, and envision a future where continuous updates, advanced calibration, and seamless data integration redefine clinical practice of cardiac electrophysiology. Our aim is to inspire researchers and clinicians to embrace the extraordinary possibilities that digital twins offer in the pursuit of precision medicine., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Genetic testing is recommended in the diagnosis of short QT syndrome. This rare inherited lethal entity is characterized by structural normal hearts with short QT intervals in the electrocardiogram. Few families diagnosed with this arrhythmogenic disease have been reported worldwide so far, impeding a comprehensive understanding of this syndrome. Unraveling the origin of the disease helps to the early identification of genetic carriers at risk. However, only rare variants with a definite deleterious role should be actionable in clinical practice. Our aim was to perform a comprehensive update and reinterpretation, according to the American College of Medical Genetics and Genomics recommendations of all rare variants currently associated with short QT syndrome. We identified 34 rare variants. Reanalysis showed that only nine variants played a deleterious role associated with a definite short QT syndrome phenotype. These variants were located in the four main genes: KCNQ1, KCNH2, KCNJ2 or SLC4A3. Additional rare variants located in other genes were associated with other conditions with phenotypic shortened QT intervals, but not definite diagnosis of short QT syndrome. Periodically updating of rare variants, especially those previously classified as unknown, helps to clarify the role of rare variants and translate genetic data into clinical practice., Competing Interests: Declarations Ethical approval Not necessary. Consent to participate Not necessary. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Patients with anterior ST elevation myocardial infarction (STEMI) are vulnerable to life-threatening ventricular arrhythmia and arrhythmic death. This study aimed to investigate the predictive value of Tpeak-to-Tend (TpTe) and TpTe/QT ratio in patients with anterior STEMI on admission for the occurrence of in-hospital life-threatening ventricular arrhythmias and arrhythmic death., Methods: This observational cross-sectional research was performed on patients with anterior STEMI who showed up within 12 hours of the beginning of symptoms and received the initial percutaneous coronary intervention (pPCI). The primary study endpoints included the assessment of sustained ventricular arrhythmias and all-cause/arrhythmic deaths throughout the hospitalization. Data collection involved clinical history, vital signs monitoring, ECG measurements, LVEF evaluation, and performance of pPCI procedures., Results: The studied patients had a mean age of 53 ± 11 years. Patients with arrhythmic events displayed a significant rise in QT dispersion, TpTe, TpTe/QT, and arrhythmic death rates (P < 0.05). A multivariate logistic regression examination revealed that HR (with an OR of 1.037 and a 95% CI of 1.004 to 1.071, P = 0.027), TpTe (with an OR of 1.025 and a 95% CI of 1.004 to 1.047, P = 0.022), and TpTe/QT (with an OR of 5.464 and a 95% CI of 2.027 to 14.726, P = 0.001) were found to be significant predictors of arrhythmic events or mortality., Conclusion: In patients with anterior STEMI, TpTe and TpTe/QT ratio are significant predictors of in-hospital VA and arrhythmic death. Higher TpTe and TpTe/QT values are linked to a higher risk of these occurrences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: Arrhythmia occurs as a common heart vascular disease. Functional food is a rich source of natural compounds with significant pharmacological, The aim of this paper is to explore its effect on arrhythmia., Methods: By reviewing the literature and summarising the findings, we described the role of functional foods in the alleviation of cardiac arrhythmias from different perspectives., Results: Our study shows that functional foods have anti-arrhythmic effects through modulation of ion channels, oxidative stress, and Calmodulin-dependent protein kinase II., Conclusions: We summarize the mechanism of arrhythmia inhibition by the active ingredients of medicinal diets in this review article, intending to provide research ideas for dietary therapy to regulate arrhythmia., (© 2024 Wiley Periodicals LLC.)

Objectives: Hemodynamic gain index (HGI), a novel hemodynamic index obtained from cardiopulmonary exercise testing (CPX), is associated with adverse cardiovascular outcomes. However, its specific relationship with ventricular arrhythmias (VAs) is unknown. We aimed to assess the association of HGI with risk of VAs in a prospective study. Design: Hemodynamic gain index was estimated using heart rate and systolic blood pressure (SBP) responses ascertained in 1945 men aged 42-61 years during CPX from rest to maximum exercise, using the formula: [(Heart rate max x SBP max ) - (Heart rate rest x SBP rest )]/(Heart rate rest x SBP rest ). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for VAs. Results: Over a median follow-up duration of 28.2 years, 75 cases of VA were recorded. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of VA (HR 0.72, 95% CI: 0.55-0.95). The results remained consistent on adjustment for lifestyle factors and comorbidities (HR 0.72, 95% CI: 0.55-0.93). Comparing the top versus bottom tertiles of HGI, the corresponding adjusted HRs (95% CIs) were 0.51 (0.27-0.96) and 0.52 (0.28-0.94), respectively. The associations were attenuated on addition of CRF to the model. HGI improved risk discrimination beyond established risk factors but not CRF. Conclusions: Higher HGI is associated with a reduced risk of VAs in middle-aged and older Caucasian men, but dependent on CRF levels. Furthermore, HGI improves the prediction of the long-term risk for VAs beyond established risk factors but not CRF.

Background: Permanent pacemaker implantation (PPI) rates following transcatheter aortic valve replacement (TAVR) remain a concern. We assessed the PPI rates over time in patients implanted with an Evolut supra-annular, self-expanding transcatheter valve from the US STS/ACC TVT Registry., Methods: Patients who underwent TAVR with an Evolut R, Evolut PRO or Evolut PRO+ valve between July 2018 (Q3) and June 2021 (Q2) were included. PPI rates were reported by calendar quarter. In-hospital PPI rates were reported as proportions and 30-day rates as Kaplan-Meier estimates. A Cox regression model was used to determine potential predictors of a new PPI within 30 days of the TAVR procedure., Results: From July 2018 to June 2021, 54,014 TAVR procedures were performed using Evolut valves. Mean age was 79.3 ± 8.8 years and 49.2 % were male. The 30-day PPI rate was 16.6 % in 2018 (Q3) and 10.8 % in 2021 (Q2, 34.9 % decrease, p < 0.001 for trend across all quarters). The in-hospital PPI rate decreased by 40.1 %; from 14.7 % in 2018 (Q3) to 8.8 % in 2021 (Q2) (p < 0.001 for trend across all quarters). Significant predictors of a new PPI within 30 days included a baseline conduction defect, history of atrial fibrillation, home oxygen, and diabetes mellitus., Conclusion: From 2018 to 2021, TAVR with an Evolut transcatheter heart valve in over 50,000 patients showed a significant decreasing trend in the rates of in-hospital and 30-day PPI, representing the lowest rate of PPI in any large real-world registry of Evolut. During the same evaluated period, high device success and shorter length of stay was also observed., Competing Interests: Declaration of competing interest Dr. Harvey is a proctor and serves on the speakers' bureau and advisory board for Medtronic and Boston Scientific, is a proctor and serves on the speakers' bureau for Abiomed, and serves on the advisory board for Avail and Opsens; Dr. Puri is a consultant, speaker and proctor for Medtronic, consults for Centerline Biomedical, Boston Scientific, Abbott, Philips, Products & Features, Shockwave Medical, VDyne, VahatiCor, Advanced Nanotherapies, NuevoSono, TherOx, GE Healthcare, BioVentrix, Protembis, and has equity interest in Centerline Biomedical, VahatiCor and NuevoSono. Dr. Grubb has served as a consultant, speaker, proctor and advisory board member for Boston Scientific and Medtronic, as a member of the advisory board for Abbott, and as a principal investigator for Medtronic and a speaker for Edwards Lifesciences; Dr. Yakubov has received institutional research grants from Boston Scientific and Medtronic; Dr. Mahoney is a consultant and proctor for Medtronic, Abbott, and Edwards; Dr. Gada is a consultant to Abbott, Bard, Edwards LifeSciences and Medtronic; Dr. Coylewright has received research grants from Edwards Lifesciences and Boston Scientific; and has served on consulting/advisory boards for Medtronic, and Occlutech; Dr. Poulin has nothing to disclose; Dr. Chetcuti serves as a consultant for Boston Scientific and consultant and proctor for Medtronic; Dr. Sorajja reports grants and personal fees from Medtronic, grants and personal fees from Edwards Lifesciences, grants and personal fees from Abbott Vascular, personal fees from Anteris, personal fees from WL Gore, grants and personal fees from Boston Scientific, outside the submitted work; Dr. Rovin serves as a consultant, proctor and speaker for Abbott and Medtronic; Ms. Eisenberg is a shareholder and employee of Medtronic plc; Dr. Reardon has received fees to his institution from Medtronic for consulting and providing educational services., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Cold saline application through an irrigation catheter may induce reversible inhibition of submyocardial excitation, which may be used to identify in advance an ideal site for radiofrequency (RF) energy delivery around delicate areas., Methods: An open irrigation catheter was positioned vertically or parallel with 10-g contact on coronary perfusing porcine hearts and the contacted myocardium was cooled by cold saline at 4°C (20 mL/min). A temperature electrode was inserted 2 mm below the myocardial surface (intra-myocardial temperature at approximately 2 mm below the surface [Temp-BS]). Pacing threshold inside the ventricular wall was measured using an eight-pole electrode plunge needle inserted 5-8 mm close to the ablation catheter, and percent increase of the pacing threshold by the cold saline application (%increase-PT) was calculated., Results: During cooling, pacing at 10 V from the myocardial surface interrupted constant capture in 7/10 experiments in vertical and in 9/10 experiments in parallel ablation catheter contact. Minimum Temp-BS was not different in both catheter contact positions (25.9 ± 4.0°C in vertical vs. 25.4 ± 2.6°C in parallel). Large % increase-PT on the surface myocardium decreased as the myocardial depth became deeper, and > 150% increase was at a depth approximately 2-3 mm from the surface and > 120% increase around 6-7 mm from the surface. After cessation of cold saline application, the increased %increase-PT recovered to the pre-cooling values., Conclusions: Cold saline application through an irrigation catheter reversibly inhibited submyocardial excitation. This simple method may have the potential to pre-determine the ideal ablation site in sensitive areas of the heart, although further studies and technological adjustments are required before clinical use., (© 2024 Wiley Periodicals LLC.)

Introduction: The Medtronic Micra VR and Abbott AVEIR VR are the leadless pacemakers (LPM) currently available in the United States (US). Micra VR employs fixation tines and the AVEIR VR uses an active fixation helix. Micra VR requires fixation before electrical measurements are obtained, while R-waves may be mapped by AVEIR VR without fixation. Little comparative data is available for these LPMs. Accordingly, we compared the incidences of procedure-related major adverse clinical events (MACE) and device problems in the US for Micra VR and AVEIR VR during 2022-2024., Methods: We searched the FDA's Manufacturer and User Facility Device Experience (MAUDE) database for US reports of MACE and device problems that were filed from April 2022 to December 2023 for AVEIR VR, and from June 2022 to April 2024 for Micra VR. Totals for US-registered LPM implants were obtained from the manufacturers' product performance reports., Results: During the study period, 5990 AVEIR VR and 10 940 Micra VR implants were registered in the US. We found 305 MAUDE reports for AVEIR VR (5.1%), versus 541 MAUDE reports for Micra VR (4.9%) (p = .702). The incidence of MACE was 0.72% (43/5990) for AVEIR VR versus 0.59% (65/10 940) for Micra VR, (p = .387). The incidences of procedure-related death, cardiac perforation. cardiac arrest, emergency pericardial drainage or reparative surgery were similar for both LPMs (p > .05). Micra VR had more unacceptable thresholds requiring LPM replacement compared to AVEIR VR (95;0.9% vs. 24;0.4%; p = .001). AVEIR VR had a statistically higher incidence of device dislodgement during (32) and after (21) implant compared to Micra VR (53 (0.9%) vs. 46 (0.4%), p < .001)., Conclusions: Micra VR and AVEIR VR have similar procedural safety profiles, including the incidences of death and perforation. However, device problems differed significantly, possibly related to their design differences. Compared to Micra VR, AVEIR VR appears to have an advantageous threshold measurement capability but is more prone to device dislodgement., (© 2024 Wiley Periodicals LLC.)

Cardiac alternans (C-ALT) is a phenomenon of alternating strong and weak contractions in the heart and is considered a risk factor for the development of heart failure and arrhythmias. However, no model has been reported that can induce C-ALT in vitro using human cells, and the developmental mechanism of C-ALT has not been studied using human cells. In this study, we successfully induced C-ALT in vitro using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). By stimulating β-adrenergic receptor with isoproterenol on hiPSC-CMs cultured in atmospheric condition (with ~0.04% CO 2 ), contractility and calcium transient were observed to alternately increase and decrease with each beat. In contrast, C-ALT was not induced in hiPSC-CMs cultured at 5% CO 2 concentration. Since previous studies have linked C-ALT to problems with calcium regulation in the sarcoplasmic reticulum (SR), we exposed hiPSC-CMs to compounds that alter SR Ca 2+ loading and analyzed their contractile responses. The results showed that exposure to verapamil, thapsigargin, and ryanodine either suppressed or eliminated C-ALT. In contrast, omecamtiv mecarbil and blebbistatin, which alter contractility without SR Ca 2+ loading, did not induce or suppress C-ALT. These results suggest that C-ALT in hiPSC-CMs induced by isoproterenol may be due to abnormal regulation of the ryanodine receptor's opening and closing caused by excessive Ca 2+ load in the SR from β-adrenergic receptor stimulation., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)