Prevalence Of Arrhythmias Research Articles

Atrial and ventricular arrhythmias in young, lifelong and retired elite endurance athletes

Abstract Background Whilst endurance athletes are known to have an overall higher prevalence of atrial fibrillation (AF), the prevalence of other non-sustained and sustained atrial arrhythmias (AAs) and ventricular arrhythmias (VAs) remains poorly defined. Purpose We aimed to define the prevalence of non-sustained and sustained AAs (including AF) and VAs in a healthy cohort of young, lifelong and retired elite endurance athletes. We also sought to assess associations between arrhythmias, fitness and measures of cardiac structure. Methods Holter monitors in healthy endurance athletes (n=288) from an international cohort of elite endurance athletes (the Pro@Heart consortium) were analysed for the presence of sustained and non-sustained AAs and VAs. Athletes were sub-divided into young elite athletes (n=176) and former elite athletes (n=112) of which 60 were lifelong (≥2.5 hours/week) and 52 retired (<2.5 hours/week) athletes (determined by current high-intensity exercise activity). Each athlete underwent cardio-pulmonary exercise testing, echocardiography and contrast-enhanced cardiac MRI. Participants with known structural or electrical cardiac disease were excluded. Independent T-test / One-Way ANOVA (parametric data) or Mann-Whitney U / Kruskal-Wallis Tests (non-parametric data) assessed for differences between the groups. Results Young athletes (n=176, 70.5% male) were significantly fitter with a greater degree of cardiac remodelling as compared with lifelong (n=60, 63.3% male) and retired (n=52, 82.7% male) athletes (Figure 1). The prevalence of non-sustained AAs (young: 4.0% vs lifelong: 66.7% vs retired: 61.5%, p<0.001), sustained AAs (young: 0.6% vs lifelong: 8.3% vs retired: 15.4%, p<0.001) and non-sustained VAs (young: 1.7% vs lifelong: 18.3% vs retired: 23.1%, p<0.001) was higher in lifelong and retired athletes compared with young athletes (Figure 2). Non-sustained VAs were predominately monomorphic (85%), short and moderate rate (median duration 2.8 seconds and heart rate 154 beats per minute). No athletes developed sustained VAs and/or sudden cardiac arrest. Young athletes had less VAs that were multifocal in origin compared with lifelong and retired athletes (young: 29.5%, lifelong: 37.3%, retired: 53.5%, p=0.027). There was no difference in prevalence of any arrhythmia between lifelong and retired athletes. There were no significant correlations between arrhythmias and fitness or cardiac imaging parameters. Conclusion Healthy athletes have a significant prevalence of non-sustained atrial and ventricular arrhythmias and sustained atrial arrhythmias that is more prevalent in older athletes. In older athletes, the prevalence of arrhythmias is similar regardless of whether athletes are actively engaged in training or retired suggesting that pro-arrhythmic remodelling in athletes is sustained, not immediately reversible and may be minimally responsive to detraining.Arrhythmias and cardiac imagingArrhythmias amongst athlete groups

Concomitant left atrial appendage occlusion and transcatheter aortic valve replacement among patients with atrial fibrillation: an updated systematic review and meta-analysis

Abstract Background Atrial fibrillation (AF) is a prevalent arrhythmia in patients undergoing transcatheter aortic valve replacement (TAVR). Left atrial appendage occlusion (LAAO) has emerged as a viable strategy to prevent stroke in selected patients with AF. While both devices can be implanted simultaneously during a single procedure, the safety and efficacy of this approach remain uncertain. Purpose This study aims to evaluate the efficacy and safety of concomitant LAAO in patients with AF and aortic valve disease undergoing TAVR. Methods We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies that compared concomitant TAVR and LAAO with isolated TAVR. The study's primary outcomes were all-cause mortality, stroke or transient ischemic attack (TIA), and major bleeding. We established a minimum follow-up time of six months. Results Three studies met our eligibility criteria, including one randomized controlled trial and two observational studies. The meta-analysis included 570 patients, 249 (44%) who underwent LAAO and TAVR, with a mean follow-up of 16.3 months. In the overall population, there was no significant difference between the groups in all-cause mortality (relative risk [RR] 0.95; 95% confidence interval [CI] 0.67-1.35; p = 0.78; figure 1A), major bleeding (RR 1.15; 95% CI 0.75-1.77; p = 0.51; 1B), and stroke or TIA (RR 0.70; 95% CI 0.33-1.45; p = 0.33; figure 1C). Conclusion In conclusion, concomitant LAAO and TAVR did not demonstrate discernible clinical differences compared to isolated TAVR in patients with AF and aortic valve disease. We recommend that this therapeutic approach be individualized until more robust data become available.

Low conduction velocity is a key factor for localisation of reentrant drivers for atrial fibrillation

Abstract Background Atrial Fibrillation (AF) is a prevalent cardiac arrhythmia globally, associated with heightened risks of stroke, dementia, and heart failure. Catheter ablation, the sole curative therapy for AF, yields suboptimal success rates for persistent AF cases. Understanding the mechanisms and dynamics of AF remains challenging, hindering treatment advancements. Novel ablation strategies aimed at targeting substrates harbouring AF reentrant drivers (RD), such as low-voltage ablation and rotor-based ablation, have yet to demonstrate superiority over the gold standard ablation strategy – pulmonary vein isolation. Purpose The purpose of the study is to integrate in-silico 3D left atrial (LA) simulations and explainable artificial intelligence (AI) to pinpoint key factors for RD localisation in persistent AF, aiming to improve the mechanistic understanding of AF and help develop a more effective ablation strategy. Methods 3D LA models were derived from magnetic resonance images of 41 patients and combined with atrial cell electrophysiology models. Persistent AF was initiated in each patient-specific LA model with fast pacing, and five functional features (action potential duration (APD), conduction velocity (CV), wavelength, APD spatial gradient, CV spatial gradient, and wavelength spatial gradient) and three structural features (fibrotic density, fibrotic entropy, and image intensity ratio) were evaluated. A random forest AI model was trained to classify phase singularities corresponding to the RDs (PS-RD) in five distinct tissue classes (total LA tissue, healthy tissue, fibrotic border zone, dense fibrotic tissue, and PS-RD tissue) based on the functional and structural features. Shapley additive explanations (SHAP) analysis was then used to find the most influential feature in the AI model’s decision process. Results Simulations of the patient-specific LA models revealed that RDs were typically localised in regions with the lowest atrial CV, which often coincided with patches of dense fibrotic tissue. In a five-fold cross-validation, the random forest AI model achieved high accuracy in classifying PS-RD regions: a mean ROC AUC of 0.99 ± 0.010, a mean F1 score of 0.86 ± 0.034, a mean recall of 0.95 ± 0.058, and a mean precision score of 0.79 ± 0.085. The further SHAP analysis revealed that low CV was the key determinant in classifying the PS-RD regions. Conclusion Our study combined AF computational modelling and explainable AI to identify the key factors in RD localisation. Both the computational and AI models concluded that low CV was the most important determinant in localising RDs. These findings provide mechanistic evidence for the efficacy of ablation strategies that target low CV atrial areas for persistent AF patients.

Impact of rhythm control strategy on outcomes in patients with first diagnosed atrial fibrillation in an 11-year real-world registry

Abstract Background Atrial fibrillation (AF) is a highly prevalent arrhythmia with a high burden of disease. This sub-study of the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) sought to evaluate clinical characteristics, treatment strategies and outcomes in patients with first diagnosed AF (FDAF). Methods Patients with AF presenting to the emergency department (ED) of an University Hospital between June 2009 and March 2020 were consecutively enrolled. Follow-up was performed for all-cause mortality, stroke, major bleeding and myocardial infarction (MI). Outcomes were were related to patients with FDAF or pre-existing AF, as well as assigned treatement strategy (rhythm vs. rate control). The trial was registered at ClinicalTrials.gov Identifier: NCT05995561. Results Overall 2,758 (27%) of all patients presented with FDAF. Compared to FDAF, patients with pre-existing AF showed higher all-cause mortality HR 1.41 (95%CI 1.28-1.55, p<0.0001) and major bleeding events 1.29 (95% CI 1.06-1.56, p=0.0098). Non-implementation of rhythm control in FDAF was seen in 2,079 cases (75.4%) and was associated with an excess of all-cause mortality HR 1.66 (95%CI 1.30-1.99, p<0.0001) and incident MI HR 1.79 (95% CI 1.03-3.09, p=0.0385). A non-implementation of rhythm control remained an independent predictor for all-cause mortality and MI even after adjustment for significant univariate variables aHR: 1.34 (95%CI: 1.04-1.72, p=0.0234) and aHR: 1.79 (95%CI: 1.03-3.09, p=0.0385). Conclusion Real-world data from FDAF patients presenting in the setting of an ED showed a potential benefit regarding mortality and MI for rhythm control strategy. Further research is needed to validate this hypothesis.

Implantable loop recorders in children and adolescents with Brugada syndrome: the YoungBruLoop study

Abstract Background Young (<18 years of age) patients with Brugada syndrome (BrS) are often underrepresented in BrS studies and their management, especially related to syncopal episodes, remains unclear. Purpose To describe the arrhythmia prevalence and clinical implication derived from continuous rhythm monitoring by implantable loop recorder (ILR) among patients younger than 18 years of age, and to assess the etiology behind syncope of undetermined origin. Methods A total of 147 BrS patients with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n=77, 52%) and adolescents (age 13 to 18 years; n=70, 48%). Results Mean age was 11.3 years (36.1% females, 21.1% spontaneous type I ECG). Forty-six patients (31.2%) underwent ILR implant due to syncope. Over a median follow-up of 3.6 years, an arrhythmic event was recorded in 22.4% of patients and in the vast majority of cases it was of non-ventricular origin (44% atrial, 47% bradyarrhythmias). Predictors of arrhythmias at univariate Cox Regression analysis were spontaneous type I ECG (HR 2.1 - 95%C.I. 1.1-4.1), history of syncope (HR 3.1 - 95%CI 1.5-6.3) and age >12 years (HR 2.0 - 95%C.I. 1.0-3.3). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were related to fever in half of cases. In patients with recurrent syncope, the prevalence of truly arrhythmic syncope was 17.8%, and it was due to brady-, atrial- and ventricular arrhythmias in 40%, 20% and 40% of cases, respectively. Conclusions Continuous rhythm monitoring with ILRs in BrS pediatric patients detects a broad range of heart rhythm disturbances including life-threatening arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type I ECG and in half of cases are fever-related. Despite the young age, brady- and atrial arrhythmias are overall frequent and represent the cause of arrhythmic syncope in 60% of patients. Young BrS patients with syncope of undetermined origin may benefit from ILR implant.

Identification and Functional Investigation of SOX4 as a Novel Gene Underpinning Familial Atrial Fibrillation

Background: Atrial fibrillation (AF) signifies the most prevalent supraventricular arrhythmia in humans and may lead to cerebral stroke, cardiac failure, and even premature demise. Aggregating strong evidence points to genetic components as a cornerstone in the etiopathogenesis of familial AF. However, the genetic determinants for AF in most patients remain elusive. Methods: A 4-generation pedigree with idiopathic AF and another cohort of 196 unrelated patients with idiopathic AF as well as 278 unrelated healthy volunteers were recruited from the Chinese population of Han ethnicity. A family-based whole-exome sequencing examination followed by a Sanger sequencing assay in all research subjects was implemented. The functional impacts of the identified SOX4 mutations were explored via a dual-reporter assay. Results: Two new heterozygous SOX4 mutations, NM_003107.3: c.211C>T; p.(Gln71*) and NM_003107.3: c.290G>A; p.(Trp97*), were observed in the family and 1 of 196 patients with idiopathic AF, respectively. The two mutations were absent in the 278 control individuals. The biochemical measurements revealed that both Gln71*- and Trp97*-mutant SOX4 failed to transactivate GJA1 (Cx43). Moreover, the two mutations nullified the synergistic activation of SCN5A by SOX4 and TBX5. Conclusions: The findings first indicate SOX4 as a gene predisposing to AF, providing a novel target for antenatal genetic screening, individualized prophylaxis, and precision treatment of AF.

New mapping algorithm SHIM (SVD, Hilbert Identifying Method) for the extraction of phase singularities and spiral waves in cardiac arrhythmias

Background and ObjectiveAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide. The effectiveness of AF ablation is restricted primarily by inaccuracies in the voltage-map videos (VMVs) acquired through multielectrode catheters. We introduce an innovative algorithm improving map quality and pinpointing the precise locations of action potential singularities. MethodsThe methodology relies on three key operations: singular value decomposition (SVD), Hilbert transform, and identifying the ridge of singularities SHIM (SVD, Hilbert, Identifying Method). To check its feasibility, this approach was used to analyze record sources from two distinct origins: a) cultures of cardiac cells, and b) real-world atrial fibrillation (AF) measurements. Efficacy is exemplified through four illustrative cases, two involving cultures of cardiac cells exposing action potential spirals, and two clinical cases involving basket catheter voltage-map videos. Resolution goodness is measured by a new method of the ratio of the peak’s height divided by the average width at half maximum or the width of the ridge-of-peaks cross-section. ResultsIn the first sample, the driving rotor became evident only following the SVD procedure stage, and its stable center became more pronounced after the H and I stages. In the case of spiral splitting, SHIM extracted all the individual tiny spiral centers. In the VMVs obtained from the basket catheters, even when the image sharpness was suboptimal, distinct singularity ridges were easily discernible with peak intensities larger than 1. ConclusionThe cumulative impact of the three stages of our analysis suggests that our novel method may excel in identifying problematic sources more effectively than previously utilized systems.

Arrhythmias in adult patients after Rastelli surgery: a single-centre experience.

Rastelli surgery is used for the correction of several CHDs. Although late-onset cardiac arrhythmias have emerged as a major complication after corrective surgeries, there is a paucity of data on arrhythmias after Rastelli surgery. This retrospective cohort study was conducted on patients who had undergone Rastelli surgery and have been followed at the adult CHD clinic at our hospital. A total of 55 patients (36.4% female, age 22.2 ± 6.4 years) were followed for a median period of 24.2 (20.6-31.0) years. Tachyarrhythmias occurred in 21 (38.4 %) patients (n = 15 for atrial tachycardia, 5 for ventricular tachycardia, and 1 for both atrial and ventricular tachycardia). Older age at surgery was significantly associated with the risk of tachyarrhythmias (P = 0.022). Bradyarrhythmia occurred in 12 (21.8%) patients and consisted of perioperative AV block (n = 5), late AV block (n = 1), and sinus node dysfunction (n = 6). Nine (16.4%) patients underwent catheter ablation. The mechanisms of atrial arrhythmias include cavotricuspid isthmus-dependent and surgical scar-dependent intra-atrial reentrant tachycardias. Among the three patients who underwent ablation for ventricular tachycardia, all circuits were dependent on the scar at the base of the right ventricle to pulmonary artery conduit. Median survival free from any event (arrhythmia, death, or heart failure) was 31.6 (28.1-35.1) years after Rastelli surgery. The prevalence of arrhythmias late after Rastelli surgery is substantial and increases in the second decade after surgery. Older age at surgery is associated with a higher prevalence of arrhythmias.

Minimalist approach to left atrial appendage occlusion through three-dimensional intracardiac echocardiography: Procedural steps and single-center experience

Atrial fibrillation (AF), the most prevalent arrhythmia worldwide, is associated with an annual risk of ischemic stroke of up to 5%, with approximately 98% of thrombi originating from the left atrial appendage (LAA). Direct oral anticoagulants or vitamin K antagonists remain the gold standard for preventing systemic thromboembolism in patients with AF. LAA occlusion (LAAO) is an alternative stroke prevention technique for patients with AF who cannot tolerate long-term anticoagulation. Percutaneous LAAO typically employs a multimodal imaging approach with contrast fluoroscopy and transesophageal echocardiography (TEE) for visualization, device selection and deployment, and complication monitoring. TEE is also used for follow-up imaging. However, it necessitates general anesthesia or deep sedation and is associated with a high risk of adverse events. Three-dimensional intracardiac echocardiography (3D ICE) has been proposed as a viable alternative to TEE for LAAO procedures. In this review, we summarized the current evidence regarding ICE guidance in LAAO procedures. We also presented a case series of consecutive patients presenting at our center who underwent LAAO, which was performed by a single operator using a minimalist approach of moderate sedation, 3D ICE, and same-day discharge. We also presented a summary of the minimalist approach to LAAO using 3D ICE and detailed procedural steps of 3D ICE catheter manipulation for successful LAAO intervention.

Cardiopulmonary Fitness and Personalized Exercise Prescription in Patients With Hypertrophic Cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) are generally restricted regarding participation in competitive sports based on the potential risk of sudden cardiac death and malignant arrhythmias. As a result, they are often inactive and experience the negative consequences of a sedentary lifestyle. Hence, the need arises to strike the right balance between these 2 extremes through personalized exercise prescription. The aims of this study were (1) to assess the characteristics of patients with HCM practicing regular aerobic physical activity compared with sedentary patients; (2) to perform a personalized moderate-intensity exercise prescription and evaluate its effects. Patients with HCM were evaluated through clinical assessment, ECG, ambulatory ECG monitoring, echocardiography, and cardiopulmonary testing. A personalized moderate-intensity exercise prescription was performed, and the same investigations were repeated. Physically active patients with HCM demonstrated better cardiopulmonary functional capacity than sedentary patients (oxygen consumptionpeak/kg 32.9±7.4 versus 25.2±7.4 mL/min per kg P≤0.0001, ventilation/carbon dioxide production slope 26.7±4.3 versus 29.9±5.2 P=0.004), with similar prevalence of ventricular arrhythmias (P=0.43). Sedentary subjects showed a borderline higher prevalence of obesity (P=0.07) than physically active subjects. Moderate-intensity exercise prescription led to improved cardiopulmonary fitness without occurrence of adverse events. Patients with HCM practicing regular aerobic exercise have a better functional capacity in the absence of relevant events than sedentary patients. Conversely, a sedentary lifestyle led to a deterioration of cardiopulmonary functional capacity and fitness. The tailored moderate-intensity personalized exercise prescription appears to be a feasible approach in carefully selected patients with HCM to counterbalance the negative effects of sedentary behavior without significant major events.

The management of new-onset atrial fibrillation in critical illness: an update on current therapeutic options.

New-onset atrial fibrillation (NOAF) is the most prevalent arrhythmia among critically ill patients, correlating with heightened morbidity and mortality rates. Current evidence for managing NOAF in this patient population is limited. Numerous meta-analyses have been conducted to assess the efficacy of atrial fibrillation treatments in acute settings, including rate or rhythm control strategies, anticoagulation, and intensive care interventions. The employment of β-blockers for rate control appears to confer greater benefits in critically ill patients. However, the advantage of anticoagulation remains ambiguous because of bleeding risks, which is partly attributed to the scarcity of evidence in the complex context of critical illness. Approximately one-third of patients with transient atrial fibrillation face recurrence within a year. Therefore, vigilant posthospitalization follow-up and monitoring should be considered for high-risk patients to detect atrial fibrillation recurrence. Long-term anticoagulation strategies should be tailored to individual patient profiles, weighing the risks of thromboembolism. Factors predicting atrial fibrillation recurrence include age, the burden of atrial fibrillation, and atrial size. There are significant knowledge gaps concerning NOAF in critically ill patients, highlighting the need for further research, particularly randomized clinical trials.

Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms

The frequency and clinical phenotypes of cardiotoxic events in chimeric antigen receptor (CAR) T-cell recipients remain poorly understood given that landmark approval trials typically exclude patients with high-risk cardiovascular profiles and data from nontrial settings are scarce. To summarize the prevalence of adverse cardiovascular events among adults receiving CAR T-cell therapies for advanced hematologic malignant neoplasms. MEDLINE, Embase, Cochrane Library, and Google Scholar were systematically searched from database inception until February 26, 2024. Observational studies were included if they comprised adult CAR T-cell recipients with advanced hematologic malignant neoplasms and if they systematically evaluated cardiovascular complications. Extraction of prespecified parameters related to the patient population, study design, and clinical events was performed at the study level by 2 independent reviewers in accordance with the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Meta-analysis of single proportions was conducted using random-effect models with Freeman-Tukey double arcsine transformations to calculate pooled prevalence estimates. Sensitivity analysis was performed using generalized linear mixed models with logit transformations. Ventricular and supraventricular arrhythmias, heart failure events, reduction in left ventricular ejection fraction, myocardial infarction, and cardiovascular and all-cause mortality. Thirteen studies comprising 1528 CAR T-cell recipients (median [IQR] age, 61 [58.7-63.0] years; 1016 males [66%]; 80% patients with lymphoma) were included. The median (IQR) duration of follow-up was 487 (294-530) days. On random-effects meta-analysis, we observed a pooled prevalence of 0.66% (95% CI, 0.00%-2.28%) for ventricular arrhythmia, 7.79% (95% CI, 4.87%-11.27%) for supraventricular arrhythmia, 8.68% (95% CI, 2.26%-17.97%) for left ventricular dysfunction, 3.87% (95% CI, 1.77%-6.62%) for heart failure events, 0.62% (95% CI, 0.02%-1.74%) for myocardial infarction, and 0.63% (95% CI, 0.13%-1.38%) for cardiovascular death. The pooled prevalence of all-cause mortality was 30.01% (95% CI, 19.49%-41.68%). Sensitivity analyses generated similar findings. This meta-analysis found a low prevalence of ventricular arrhythmia, myocardial infarction, and cardiovascular death among CAR T-cell recipients over a short-term to midterm follow-up. Left ventricular dysfunction and supraventricular arrhythmia were the most commonly reported cardiovascular complications, suggesting that cardiovascular surveillance strategies should focus on decreases in ejection fraction and supraventricular arrhythmia.

Smart watch applications in atrial fibrillation detection: Current state and future directions.

Atrial fibrillation (Afib) is a prevalent chronic arrhythmia associated with severe complications, including stroke, heart failure, and increased mortality. This review explores the use of smartwatches for Afib detection, addressing the limitations of current monitoring methods and emphasizing the potential of wearable technology in revolutionizing healthcare. Current Afib detection methods, such as electrocardiography, have limitations in sensitivity and specificity. Smartwatches with advanced sensors offer continuous monitoring, improving the chances of detecting asymptomatic and paroxysmal Afib. The review meticulously examines major clinical trials studying Afib detection using smartwatches, including the landmark Apple Heart Study and ongoing trials such as the Heart Watch, Heartline, and Fitbit Heart Study. Detailed summaries of participant numbers, smartwatch devices used, and key findings are presented. It also comments on the cost-effectiveness and scalability of smartwatch-based screening, highlighting the potential to reduce healthcare costs and improve patient outcomes. The integration of wearable technology into healthcare can lead to earlier diagnosis, improved patient engagement, and enhanced cardiac health monitoring. Despite ethical considerations and disparities, the potential benefits outweigh the challenges. This review calls for increased awareness, collaboration with insurance companies, and ongoing research efforts to optimize smartwatch accuracy and encourage widespread adoption of Afib detection. With insights from major trials, this review serves as a comprehensive reference for healthcare professionals and policymakers, guiding future strategies in the early diagnosis and management of atrial fibrillation.

Persistent hypertension induces atrial remodeling and atrial fibrillation through DNA damage and ATM/CHK2/p53 signaling pathway

Atrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, with hypertension emerging as an independent risk factor. Previous literature has established associations between DNA damage response (DDR) and autophagy in relation to the pathogenesis of AF. The aim of this study was to evaluate the effect of atrial DNA damage response in persistent hypertension-induced atrial electrical and structural remodeling, and to further explore the potential therapeutic targets. Patient samples, spontaneous hypertensive rats (SHR) and angiotensin II (Ang II)-challenged HL-1 cells were employed to elucidate the detailed mechanisms. Bioinformatics analysis and investigation on human atrial samples revealed a critical role of DDR in the pathogenesis of AF. The markers of atrial DNA damage, DDR, autophagy, inflammation and fibrosis were detected by western blot, immunofluorescence, monodansyl cadaverine (MDC) assay and transmission electron microscopy. Compared with the control group, SHR exhibited significant atrial electrical and structural remodeling, abnormal increase of autophagy, inflammation, and fibrosis, which was accompanied by excessive activation of DDR mediated by the ATM/CHK2/p53 pathway. These detrimental changes were validated by in vitro experiments. Ang II-challenged HL-1 cells also exhibited significantly elevated γH2AX expression, and markers related to autophagy, inflammation as well as structural remodeling. Additionally, inhibition of ATM with KU55933 (a specific ATM inhibitor) significantly reversed these effects. Collectively, these data demonstrate that DNA damage and the subsequently overactivated ATM/CHK2/p53 pathway play critical roles in hypertension-induced atrial remodeling and the susceptibility to AF. Targeting ATM/CHK2/p53 signaling may serve as a potential therapeutic strategy against AF.

Clinical characteristics and outcomes in middle-aged Fontan patients

BackgroundMiddle-aged Fontan patients are underrepresented in contemporary studies. The purpose of this study was to describe the clinical characteristics and outcomes in middle-aged patients with Fontan palliation. MethodsAll adults with Fontan palliation were divided into ‘middle-aged’ group (>40 years of age at baseline encounter), and ‘young adult’ group. Clinical characteristics were assessed across multiple domains (atrial arrhythmias, heart failure, and hepatorenal function). Clinical outcomes were assessed as composite outcome of death/heart transplant. ResultsOf 455 adults (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, and worse hepatorenal function. Of 63 patients in the middle-aged group, 26 (41 %) patients died, and 4 (6 %) patients underwent heart transplant. The middle-aged group had a higher 5-year cumulative incidence of death/transplant (45 % versus 21 %, p < 0.001), and 10-year cumulative incidence of death/transplant (64 % versus 29 %, p < 0.001) compared to the young adult group. Higher pulmonary artery wedge pressure (hazard ratio 1.18 [1.09–1.27]), and higher model for end-stage liver disease excluding international normalized ratio score (hazard ratio 1.07, [1.03–1.14]), were associated with death/transplant. ConclusionsAbout 14 % of adults with Fontan palliation were middle-aged, and these patients had higher prevalence of cardiovascular comorbidities, hepatorenal dysfunction, and mortality. These data underscore the need for better risk stratification strategies to identify patients at risk for adverse outcomes and allow for early referral for transplant evaluation in this emerging subpopulation. Clinical summaryThe purpose of this study was to describe the clinical characteristics (comorbidities and end-organ dysfunction) and outcomes (death/transplant) in middle-aged patients with Fontan palliation. Of 455 patients (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, worse hepatorenal function, and higher risk of death/transplant. The correlates of death/transplant were higher pulmonary artery wedge pressure and hepatorenal dysfunction. These data underscore the need for better risk stratification in this emerging population.

Embryological Classification of Arrhythmogenic Triggers Initiating AtrialFibrillation.

Atrial fibrillation (AF) is a prevalent multifactorial arrhythmia associated with specific single-nucleotide polymorphisms (SNPs). Pulmonary vein (PV) isolation is an established treatment for AF; however, recurrence risk remains caused by AF triggers beyond the PVs. Understanding the embryological origins of these triggers could improve treatment outcomes. This study aimed to investigate the association between embryologically categorized AF triggers, clinical and genetic backgrounds, and postablation prognosis. In cohort 1, comprising 3,067 patients with AF undergoing PV isolation, the clinical characteristics and outcomes were analyzed. Among them, 815 patients underwent genetic analysis using AF-associated SNPs (cohort 2). Patients were delineated based on the developmental origin of the AF triggers: common PV, sinus venosus (SV), and primitive atrium (PA). SV-origin extra-PV AF triggers occurred in 20.3% (n=622) of patients, whereas PA-origin triggers occurred in 11.9% (n=365) of patients in cohort 1. Multivariate analysis of cohort 2 revealed that female sex, lower body mass index, absence of hypertension, rs2634073 near PITX2, and rs6584555 in NEURL1 were associated with SV-AF, whereas nonparoxysmal AF and rs2634073 near PITX2 were predictors of PA-AF. The PA group had a significantly higher arrhythmia recurrence rate after repeated procedures than the common PV (HR: 1.75; 95%CI: 1.34-2.29; P< 0.001) and SV-AF (HR: 1.31; 95%CI: 1.19-1.45; P< 0.001) groups with more de novo AF triggers. However, the incidence of adverse events did not differ significantly among the 3 groups. SV-derived AF triggers may have hereditary factors with a favorable postablation prognosis, whereas PA-derived triggers are linked to AF persistence and poor ablation response. Variants near PITX2 may play a pivotal role in extra-PV triggers.

The interaction between neutrophils and atrial myocytes in the occurrence and development of atrial fibrillation

BackgroundAtrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias, strongly associated with neutrophils. However, the underlying mechanism remain unclear. This study aims to explore the interaction between neutrophils and atrial myocytes in the pathogenesis of AF.MethodsPatch-clamp was employed to record the action potential duration (APD) and ion channels in HL-1 cells. Flow cytometry was used to assess the differentiation of neutrophils. The mRNA and protein levels of CACNA1C, CACNA2D, and CACNB2 in HL-1 cells were detected.ResultsHigh-frequency electrical stimulation resulted in a shortening of the APD in HL-1 cells. Flow cytometry demonstrated that neutrophils were polarized into N1 phenotype when cultured with stimulated HL-1 cells medium. Compared to control neutrophils conditioned medium (CM), cocultured with TNF-α knockout neutrophils CM prolonged APD and the L-type Ca (2+) channel (LTCC) of HL-1 cells. Additionally, the expression of CACNA2D, CACNB2 and CACNA1C in HL-1 cells were upregulated. Compared with CACNA1C siRNA-transfected HL-1 cells treated with TNF-α siRNA-transfected neutrophils CM, the APD and LTCC of CACNA1C siRNA-transfected HL-1 cells were shortened in control N1 neutrophil CM. The APD and LTCC of control HL-1 cells were also shortened in control N1 neutrophil CM, but prolonged in TNF-α siRNA-transfected neutrophils CM.ConclusionThese findings suggest that neutrophils were polarized into N1 phenotype in AF, TNF-α released from N1 neutrophils contributes to the pathogenesis of AF, via decreasing the APD and LTCC in atrial myocytes through down-regulation of CACNA1C expression.

Linking Sleep Disorders to Atrial Fibrillation: Pathways, Risks, and Treatment Implications.

Sleep is a complex biobehavioural process essential for overall health, with various dimensions including duration, continuity, timing, and satisfaction. This study investigated the intricate relationships between common sleep disorders such as insomnia and obstructive sleep apnoea (OSA) and their impact on atrial fibrillation (AF), a prevalent arrhythmia with significant health implications. Using a comprehensive review of the current literature, this study examined the pathophysiological mechanisms linking sleep disorders to cardiovascular risks, focusing on autonomic nervous system disturbances, inflammation, and oxidative stress associated with OSA. These findings indicate that sleep disorders significantly elevate the risk of AF through mechanisms such as increased sympathetic activity and structural cardiac remodelling. Additionally, this study highlights the potential benefits of treating sleep disorders, particularly with continuous positive airway pressure (CPAP) therapy, in reducing AF recurrence and improving cardiovascular outcomes. This conclusion emphasises the importance of integrated therapeutic approaches that address both sleep disorders and AF to enhance patient outcomes and quality of life. Future research should explore these connections to develop more effective and holistic treatment strategies.

Integrative multi-omics summary-based mendelian randomization identifies key oxidative stress-related genes as therapeutic targets for atrial fibrillation and flutter.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with substantial morbidity and mortality. Oxidative stress (OS) has been implicated in the pathogenesis of AF, suggesting that targeting OS-related genes could offer novel therapeutic opportunities. This study aimed to identify causal OS-related genes contributing to AF through a comprehensive multi-omics Summary-based Mendelian Randomization (SMR) approach. This study integrated data from genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) to explore the relationships between oxidative stress-related (OS-related) genes and AF risk. Genes associated with oxidative stress and AF were obtained from the Nielsen et al. study (discovery) and the FinnGen study (replication). The SMR analysis and HEIDI test were utilized to assess causal associations, followed by Bayesian co-localization analysis (PPH4 > 0.5) to confirm shared causal variants. Multi-omics data were employed to analyze the associations within mQTL-eQTL pathways. A two-sample MR analysis was conducted for sensitivity verification. The significance of findings was determined using a false discovery rate (FDR) < 0.05 and p_HEIDI > 0.01. At the DNA methylation level, 19 CpG sites near 7 unique genes were found to have causal effects on AF and strong co-localization evidence support (PPH4 > 0.70). At the gene expression level, six oxidative stress-related genes from eQTLGen and three from GTEx (v8), including TNFSF10, CDKN1A, ALOX15, TTN, PTK2, ALB, KCNJ5, and CASQ2, were found to have causal effects on AF in the sensitivity and co-localization analyses (PPH4 > 0.50). At the circulating protein level, both ALAD (OR 0.898, 95% CI 0.845-0.954, PPH4 = 0.67) and APOH (OR 0.896, 95% CI 0.844-0.952, PPH4 = 0.93) were associated with a lower risk of AF, and APOH was validated in the replication group. After integrating the multi-omics data between mQTL and eQTL, we identified two oxidative stress-related genes, TTN and CASQ2. The methylation of cg09915519 and cg10087519 in TTN was associated with higher expression of TTN and a lower risk of AF, which aligns with the negative effect of TTN gene expression on AF risk. TTN may play a protective role in AF. This study identified several OS-related genes, particularly TTN, as having causal roles in AF, which were verified across three-omics pathways. The findings underscore the importance of these genes in AF pathogenesis and highlight their potential as therapeutic targets. The integration of multi-omics data provides a comprehensive understanding of the molecular mechanisms underlying AF, paving the way for targeted therapeutic strategies.

Diet and risk of atrial fibrillation: a systematic review.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Comprehensive modification of established AF risk factors combined with dietary interventions and breaking deleterious habits has been shown to reduce AF burden and recurrence. Numerous AF risk factors, such as diabetes, obesity or hypertension can be partially related to dietary and lifestyle choices. Therefore, dietary interventions may have potential as a therapeutic approach in AF. Based on available data, current guidelines recommend alcohol abstinence or reduction to decrease AF symptoms, burden, and progression, and do not indicate the need for caffeine abstention to prevent AF episodes (unless it is a trigger for AF symptoms). Uncertainty persists regarding harms or benefits of other dietary factors including chocolate, fish, salt, polyunsaturated and monounsaturated fatty acids, vitamins, and micronutrients. This article provides a systematic review of the association between AF and both dietary patterns and components. Additionally, it discusses potentially related mechanisms and introduces different strategies to assess patients' nutrition patterns, including mobile health solutions and diet indices. Finally, it highlights the gaps in knowledge requiring future investigation.