Prevalent Sustained Arrhythmia Research Articles

Advancing Atrial Fibrillation Research: The Role of Animal Models, Emerging Technologies and Translational Challenges

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, presenting a significant global healthcare challenge due to its rising incidence, association with increased morbidity and mortality, and economic burden. This arrhythmia is driven by a complex interplay of electrical, structural, and autonomic remodelling, compounded by genetic predisposition, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, AF management remains suboptimal, with ongoing debates surrounding rhythm control, rate control, and anticoagulation strategies. Animal models have been instrumental in elucidating AF mechanisms, facilitating preclinical research, and advancing therapeutic development. This review critically evaluates the role of animal models in studying AF, emphasizing their utility in exploring electrical, structural, and autonomic remodelling. It highlights the strengths and limitations of various models, from rodents to large animals, in replicating human AF pathophysiology and advancing translational research. Emerging approaches, including optogenetics, advanced imaging, computational modelling, and tissue engineering, are reshaping AF research, bridging the gap between preclinical and clinical applications. We also briefly discuss ethical considerations, the translational challenges of animal studies and future directions, including integrative multi-species approaches, omics technologies and personalized computational models. By addressing these challenges and addressing emerging methodologies, this review underscores the importance of refining experimental models and integrating innovative technologies to improve AF management and outcomes.

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.

Pulsed Field Energy in Atrial Fibrillation Ablation: From Physical Principles to Clinical Applications.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

Atrial fibrillation: real-life experience of a rhythm control with electrical cardioversion in a community hospital

BackgroundAtrial fibrillation is the most prevalent sustained cardiac arrhythmia. Electrical cardioversion, a well-established part of the rhythm control strategy, is probably underused in community settings. Here, we describe its use, safety, and effectiveness in a cohort of patients with atrial fibrillation treated in rural settings.MethodsIt is a retrospective cohort study. Data on all procedures from January 1, 2016, till December 1, 2022, in Tarusa Hospital, serving mostly a rural population of 15,000 people, were extracted from electronic health records. Data on the procedure’s success, age, gender, body mass index, comorbidities, previous procedures, echocardiographic parameters, type and duration of arrhythmia, anticoagulation, antiarrhythmic drugs, transesophageal echocardiography, and settings were available.ResultsAltogether, 1,272 procedures in 435 patients were performed during the study period. The overall effectiveness of the procedure was 92%. Effectiveness was similar across all prespecified subgroups. Electrical cardioversion was less effective in patients undergoing the procedure for the first time (86%, 95% CI: 82-90) compared to repeated procedures (95%, 95% CI: 93-96), OR 0.39 (95% CI: 0.26-0.59). Complications were encountered in 13 (1.02%) procedures but were not serious.ConclusionsElectrical cardioversion is an immediately effective procedure that can be safely performed in community hospitals, both in inpatient and outpatient settings. Further studies with longer follow-up are needed to investigate the rate of sinus rhythm maintenance in these patients.

Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.Graphical

Therapeutic advances in atrial fibrillation based on animal models.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia among humans, with its incidence increasing significantly with age. Despite the high frequency of AF in clinical practice, its etiology and management remain elusive. To develop effective treatment strategies, it is imperative to comprehend the underlying mechanisms of AF; therefore, the establishment of animal models of AF is vital to explore its pathogenesis. While spontaneous AF is rare in most animal species, several large animal models, particularly those of pigs, dogs, and horses, have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic options. This review aims to provide a comprehensive discussion of various animal models of AF, with an emphasis on the unique features of each model and its utility in AF research and treatment. The data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

Safety and efficacy of anticoagulation for atrial fibrillation in cirrhotic patients

Abstract Introduction Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and increases thromboembolism risk. AF is more prevalent in patients with cirrhosis and cirrhotics are at higher risk for ischemic stroke from thromboembolic mechanisms such as AF. Cirrhotics have complex pathophysiology of coagulation which can lead to bleeding diathesis or hypercoagulability. Cirrhotics have been excluded from major trials of anticoagulants (AC), thus there are currently no guidelines for AC in cirrhotics with AF. We aim to investigate how the incidence of ischemic stroke, major bleeding, hospitalizations, and mortality vary in patients with AF and cirrhosis between AC choices including no AC. Methods De-identified electronic health records from a U.S. health system between March 2013 and December 2022 were reviewed to identify patients with International Classification of Diseases (ICD) diagnoses of both AF and cirrhosis and who also had Creatinine, Bilirubin, and INR values within 6 months of their second diagnosis (either AF or cirrhosis). Model for End-stage Liver Disease (MELD) scores were calculated from these values and patients were followed from the first date of their second diagnosis. Incidences of ICD-coded ischemic stroke, ICD-coded bleeds, Current Procedural Terminology (CPT) coded transfusions, all-cause mortality, and hospitalizations were recorded. Propensity score weighting between AC and non-AC groups balanced covariates (Table 1). Bivariate analyses for outcomes were conducted between AC and non-AC groups and among warfarin, DOAC, and injectable AC subgroups. Results 1,205 patients with AF and cirrhosis were included. 605 patients were prescribed AC (50.2%), 384 were prescribed DOACs (63.5%), 275 were prescribed Warfarin (45.4%), and 131 (21.7%) were prescribed injectable AC. After propensity weighting, patients prescribed AC had similar rates of bleed (p=0.607), transfusion (p=0.225), and death (p=0.779) but decreased rates of ischemic stroke (p=0.001) and number of hospitalizations (p<0.001) compared to non-AC patients. Patients prescribed DOACs had similar rates of bleed (p=0.529), ischemic stroke (p=0.108), number of hospitalizations (p=0.870), and death (p=0.230) but decreased rates of transfusion (p<0.001) compared to patients on other forms of AC. Patients prescribed warfarin had similar rates of death (p=0.230) and decreased rates of bleed (p=0.013) but increased rates of transfusion (p<0.001), ischemic stroke (p<0.001), and number of hospitalizations (p = 0.024) (Table 2). Conclusions Patients with AF and cirrhosis receiving AC experienced decreased rates of ischemic stroke and number of hospitalizations compared to patients who did not receive AC. Among AC subgroups, patients prescribed DOACs had lower rates of transfusion compared to other AC therapies while patients prescribed warfarin had increased rates of transfusion, ischemic stroke, and number of hospitalizations compared to other AC therapies.

Association between cardiovascular risk factors and atrial fibrillation.

The most prevalent sustained arrhythmia in medical practice, atrial fibrillation (AF) is closely associated with a high risk of cardiovascular disease. Nevertheless, the risk of AF associated with cardiovascular risk factors has not been well elucidated. We pooled all published studies to provide a better depiction of the relationship among cardiovascular risk factors with AF. Studies were searched in the MEDLINE, Web of Science, and EMBASE databases since initiation until January 15, 2022. Prospective cohort studies assessing the relationship a minimum of single cardiovascular risk factors to AF incidence were included if they contained adequate data for obtaining relative risks (RR) and 95% confidence intervals (CI). Random-effects models were utilized to perform independent meta-analyses on each cardiovascular risk factor. PROSPERO registry number: CRD42022310882. A total of 17,098,955 individuals and 738,843 incident cases were reported for data from 101 studies included in the analysis. In all, the risk of AF was 1.39 (95% CI, 1.30-1.49) for obesity, 1.27 (95% CI, 1.22-1.32) per 5 kg/m2 for increase in body mass index, 1.19 (95% CI, 1.10-1.28) for former smokers, 1.23 (95% CI, 1.09-1.38) for current smokers, 1.31 (95% CI, 1.23-1.39) for diabetes mellitus, 1.68 (95% CI, 1.51-1.87) for hypertension, and 1.12 (95% CI, 0.95-1.32) for dyslipidemia. Adverse cardiovascular risk factors correlate with an increased risk of AF, yet dyslipidemia does not increase the risk of AF in the general population, potentially providing new insights for AF screening strategies among patients with these risk factors. https://www.crd.york.ac.uk/PROSPERO/, PROSPERO identifier (CRD42022310882).

L1 cell adhesion molecule may be a protective molecule for atrial fibrillation in patients with valvular heart disease

BackgroundAtrial fibrillation (AF) is the most prevalent sustained arrhythmia. L1 cell adhesion molecule (L1CAM) served as a crucial regulator of signaling pathways. This research sought to examine the clinical value and functions of soluble L1CAM in the serum of AF patients. MethodsIn total, 118 patients (valvular heart disease patients [VHD, total: n = 93; AF: n = 47; sinus rhythm (SR): n = 46] and healthy controls [n = 25]) were recruited in this retrospective study. Plasma levels of L1CAM were detected by enzyme-linked immunosorbent assays. The Pearson's correlation approach, as applicable, was used for analyzing the correlations. The L1CAM was shown to independently serve as a risk indicator of AF in VHD after being analyzed by the multivariable logistic regression. To examine the specificity and sensitivity of AF, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used. A nomogram was developed for the visualisation of the model. We further evaluate the prediction model for AF using calibration plot and decision curve analysis. ResultsThe plasma level of L1CAM was substantially decreased in AF patients as opposed to healthy control and SR patients (healthy control = 46.79 ± 12.55 pg/ml, SR = 32.86 ± 6.11 pg/ml, AF = 22.48 ± 5.39 pg/ml; SR vs. AF, P < 0.001; control vs. AF, P < 0.001). L1CAM was significantly and negatively correlated with LA and NT-proBNP (LA: r = −0.344, P = 0.002; NT-proBNP: r = −0.380, P = 0.001). Analyses using logistic regression showed a substantial correlation between L1CAM and AF in patients with VHD (For L1CAM, Model 1: OR = 0.704, 95%CI = 0.607–0.814, P < 0.001; Model 2: OR = 0.650, 95% CI = 0.529–0.798, P < 0.001; Model 3: OR = 0.650, 95% CI = 0.529–0.798, P < 0.001). ROC analysis showed that inclusion of L1CAM in the model significantly improved the ability of other clinical indicators to predict AF. The predictive model including L1CAM, LA, NT-proBNP and LVDd had excellent discrimination and a nomogram was developed. The model had good the calibration and clinical utility. ConclusionL1CAM was shown to independently serve as a risk indicator for AF in VHD. In AF patients with VHD, the prognostic and predictive effectiveness of models incorporating L1CAM was satisfactory. Collectively, L1CAM may be a protective molecule for atrial fibrillation in patients with valvular heart disease.

Whole-Exome Sequencing Implicates Neuronal Calcium Channel with Familial Atrial Fibrillation

Background: Atrial Fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, responsible for considerable morbidity and mortality. The heterogenic and complex pathogenesis of AF remains poorly understood, which contributes to the current limitation in effective treatments. We aimed to identify rare genetic variants associated with AF in patients with familial AF. Methods and results: We performed whole exome sequencing in a large family with familial AF and identified a rare variant in the gene CACNA1A c.5053G > A which co-segregated with AF. The gene encodes for the protein variants CaV2.1-V1686M, and is important in neuronal function. Functional characterization of the CACNA1A, using patch-clamp recordings on transiently transfected mammalian cells, revealed a modest loss-of-function of CaV2.1-V1686M. Conclusion: We identified a rare loss-of-function variant associated with AF in a gene previously linked with neuronal function. The results allude to a novel link between dysfunction of an ion channel previously associated with neuronal functions and increased risk of developing AF.

Identification of Differentially Expressed Genes and Pathways in Human Atrial Fibrillation by Bioinformatics Analysis.

IntroductionAtrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, but the molecular mechanisms underlying AF are not known. We aimed to identify the pivotal genes and pathways involved in AF pathogenesis because they could become potential biomarkers and therapeutic targets of AF.MethodsThe microarray datasets of GSE31821 and GSE41177 were downloaded from the Gene Expression Omnibus database. After combining the two datasets, differentially expressed genes (DEGs) were screened by the Limma package. MicroRNAs (miRNAs) confirmed experimentally to have an interaction with AF were screened through the miRTarBase database. Target genes of miRNAs were predicted using the miRNet database, and the intersection between DEGs and target genes of miRNAs, which were defined as common genes (CGs), were analyzed. Functional and pathway-enrichment analyses of DEGs and CGs were performed using the databases DAVID and KOBAS. Protein–protein interaction (PPI) network, miRNA- messenger(m) RNA network, and drug-gene network was visualized. Finally, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the expression of hub genes in the miRNA–mRNA network.ResultsThirty-three CGs were acquired from the intersection of 65 DEGs from the integrated dataset and 9777 target genes of miRNAs. Fifteen “hub” genes were selected from the PPI network, and the miRNA-mRNA network, including 82 miRNAs and 9 target mRNAs, was constructed. Furthermore, with the validation by RT-qPCR, macrophage migration inhibitory factor (MIF), MYC proto-oncogene, bHLH transcription factor (MYC), inhibitor of differentiation 1 (ID1), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were upregulated and superoxide Dismutase 2 (SOD2) was downregulated in patients with AF compared with healthy controls. We also found MIF, MYC, and ID1 were enriched in the transforming growth factor (TGF)-β and Hippo signaling pathway.ConclusionWe identified several pivotal genes and pathways involved in AF pathogenesis. MIF, MYC, and ID1 might participate in AF progression through the TGF-β and Hippo signaling pathways. Our study provided new insights into the mechanisms of action of AF.

Revealing the Influences of Sex Hormones and Sex Differences in Atrial Fibrillation and Vascular Cognitive Impairment.

The impacts of sex differences on the biology of various organ systems and the influences of sex hormones on modulating health and disease have become increasingly relevant in clinical and biomedical research. A growing body of evidence has recently suggested fundamental sex differences in cardiovascular and cognitive function, including anatomy, pathophysiology, incidence and age of disease onset, symptoms affecting disease diagnosis, disease severity, progression, and treatment responses and outcomes. Atrial fibrillation (AF) is currently recognized as the most prevalent sustained arrhythmia and might contribute to the pathogenesis and progression of vascular cognitive impairment (VCI), including a range of cognitive deficits, from mild cognitive impairment to dementia. In this review, we describe sex-based differences and sex hormone functions in the physiology of the brain and vasculature and the pathophysiology of disorders therein, with special emphasis on AF and VCI. Deciphering how sex hormones and their receptor signaling (estrogen and androgen receptors) potentially impact on sex differences could help to reveal disease links between AF and VCI and identify therapeutic targets that may lead to potentially novel therapeutic interventions early in the disease course of AF and VCI.

Polypharmacy and major adverse events in atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Polypharmacy has been defined as the daily use of more than 4 drugs, by an individual, regardless of the condition(s) they have been prescribed for and their efficacy. The burden of polypharmacy pertains to adverse drug reactions, disability, frequent and longtime hospitalization and long-term mortality. The prevalence of polypharmacy exceeds 10% in most adult age groups and particularly in the elderly. At the same time, atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, afflicting more than 8% of the elderly and those with multiple comorbidities. Purpose The purpose of this study was to examine the association between the presence of polypharmacy and outcomes among AF patients. Methods This is a retrospective analysis among 1140 patients enrolled in the MISOAC-AF trial. All cause- and cardiovascular- mortality have been defined as primary endpoints. Independent clinical predictors of polypharmacy and of major adverse outcomes were identified via bootstrapped multivariate logistic and Cox regression analysis, respectively. Results The mean number of prescribed medications at patients’ discharge was 3.9 ± 1.6 and polypharmacy (use of more than 4 medications daily) was found in 36.9% of the patients. Smoking (p = 0.036), dyslipidemia (p &amp;lt; 0.001), coronary artery disease (p &amp;lt; 0.001), heart failure (HF; p = 0.003) and chronic kidney disease (p &amp;lt; 0.001) were independent predictors of polypharmacy among AF paients. Kaplan–Meier survival analysis showed that AF patients with polypharmacy have significantly greater risk of CV death (p = 0.040), while Cox regression analysis indicated polypharmacy as an independent predictor for all-cause and CV- mortality [adjusted hazard ratios: 1.31(1.03 - 1.67) and 1.39(1.05 - 1.84), respectively] and for the composite outcome of AF- or HF- related hospitalization or CV death [adjusted hazard ratio: 1.31 (1.05 - 1.63)]. Conclusion This study highlights the implications of polypharmacy in the context of AF, a prevalent, chronic, life-threatening condition. Investigating polypharmacy is quite relevant in the era of pharmacovigilance, contributing to rational pharmacotherapy with regard to cardiovascular conditions and beyond. Abstract Figure. Mortality rates by polypharmacy presence

Coordination of a remote mHealth infrastructure for atrial fibrillation management during COVID-19 and beyond: TeleCheck-AF

During the coronavirus 2019 (COVID-19) pandemic, outpatient visits for patients with atrial fibrillation (AF), were converted into teleconsultations. As a response to this, a novel mobile health (mHealth) intervention was developed to support these teleconsultations with AF patients: TeleCheck-AF. This approach incorporates three fundamental components: 1) “Tele”: A structured teleconsultation. 2) “Check”: An app-based on-demand heart rate and rhythm monitoring infrastructure. 3) “AF”: comprehensive AF management. This report highlights the significant importance of coordination of the TeleCheck-AF approach at multiple levels and underlines the importance of streamlining care processes provided by a multidisciplinary team, using an mHealth intervention, during the COVID-19 pandemic. Moreover, this report reflects on how the TeleCheck-AF approach has contributed to strengthening the health system in maintaining management of this prevalent sustained cardiac arrhythmia, whilst keeping patients out of hospital, during the pandemic and beyond.

Predictors of Outcomes in Patients with Atrial Fibrillation: What Can Be Used Now and What Hope Is in the Future

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia affecting over 30 million patients worldwide with astronomical figures for progression over the next few decades. In this comprehensive review, we have sought to accumulate the factors that determine outcomes of AF. Patient factors such as age, sex, and ethnicity have a vital impact on the incidence and progression of AF, including outcomes of catheter ablation. While the above are non-modifiable, we also provide detailed associations of potentially modifiable comorbidities such as hypertension, congestive heart failure, valvular heart disease, diabetes mellitus, obesity, obstructive sleep apnea, conduction system disorders, and substance abuse with AF. Beyond patient factors, some parameters related to the AF itself can determine outcomes—such as duration of AF, whether it is paroxysmal or persistent AF and certain critical electrocardiographic patterns that suggest a higher risk of AF recurrence. Imaging modalities such as echocardiography, computed tomography, and cardiac magnetic resonance provide invaluable insights into the progression of AF. We describe the various pharmacological and non-pharmacological strategies for AF management with a peek at some futuristic approaches. While each one of these variables could lend themselves for a separate review, we attempted to provide an overview of the most critical predictors of AF outcomes to equip the readers with the latest know-how of the management of AF.

Prevalence and associated factors of undiagnosed atrial fibrillation among end-stage renal disease patients on maintenance haemodialysis: a cross-sectional study

BackgroundAtrial fibrillation (AF) is the most prevalent sustained arrhythmia worldwide and it aggravates cardiovascular morbidity and mortality; however, this is largely under-diagnosed. Moreover, among end-stage renal disease patients on haemodialysis, AF is substantially more common and serious. The researchers conducted this study to assess the prevalence of, and the factors correlated with AF in Jordanian haemodialysis patients.MethodsIn a cross-sectional analysis conducted from October 2018 to February 2019 in four tertiary hospitals, the researchers enrolled all consenting patients aged 18 years or older who were on haemodialysis for at least three months prior to the study. We screened for AF clinically by pulse palpation, precordial auscultation, by an automated blood pressure monitor and an electrocardiogram. The researchers reported qualitative variables as counts and frequencies, while continuous variables were summarised using the mean or median where necessary. We used multiple logistic regression with backward selection to identify independent risk factors of AF.ResultsA total of 231 patients were enrolled; mean age was 54.8 ± 15.6 years (from 20 to 86), and 44.3% of them were women. The prevalence of AF was found to be 7.8% (95% CI, 4.8–12.2), with no gender disparity. Age (adjusted odds ratio [AOR] = 1.05; 95% CI, 1.01–1.10; p = 0.031), history of ischaemic heart disease (AOR = 3.74; 95% CI, 1.09–12.34; p = 0.033), history of smoking (AOR = 0.15; 95% CI, 0.02–0.60; p = 0.019), and low interdialytic weight gain (AOR = 0.50: 95% CI, 0.25–0.91; p = 0.031) were independently correlated to AF.ConclusionsThe prevalence of AF among patients on maintenance haemodialysis is high, but largely undiagnosed. AF is generally associated with advancing age, history of ischaemic heart disease, lower interdialytic weight gain, and history of smoking. We suggest routine check-up of AF in this high-risk group of patients as anticoagulant therapy if indicated may prevent serious complications. However, there is a need for large-scale cohort studies and for the creation of regional chronic kidney disease and dialysis registries in the Middle East region.

Irregular pacing of ventricular cardiomyocytes induces pro-fibrotic signalling involving paracrine effects of transforming growth factor beta and connective tissue growth factor.

Atrial fibrillation is the most prevalent sustained arrhythmia associated with arrhythmic ventricular contractions, incident heart failure, increased morbidity and mortality. The relationship between arrhythmic contractions and ventricular remodelling is incompletely understood. The aim of this study was to characterize the influence of irregular contractions on pro-fibrotic signalling in neonatal rat ventricular cardiomyocytes (NRVM). Neonatal rat ventricular cardiomyocytes were paced via field stimulation at 3 Hz for 24 h. Irregularity was created by pseudorandomized variation of stimulation intervals and compared to regular pacing. Treatment of neonatal cardiac fibroblasts (NCF) with medium of irregularly paced NRVM increased protein expression of collagen I (206 ± 62%, P = 0.0121) and collagen III (51 ± 37%, P = 0.0119). To identify the underlying mechanism, expression of pro-fibrotic connective tissue growth factor (CTGF) and transforming growth factor beta (TGF-β) was assessed. In irregularly paced NRVM, increased protein expression of CTGF (80 ± 22%, P = 0.0035) and TGF-β (122 ± 31%, P = 0.0022) was associated with enhanced excretion of both proteins into the medium. Electron paramagnetic resonance spectroscopy revealed an increased production of reactive oxygen species (46 ± 21%, P = 0.0352) after irregular pacing accompanied by increased 8-hydroxydeoxyguanosine staining (214 ± 53%, P = 0.0011). Irregular pacing was associated with elevated mRNA levels of anti-oxidative superoxide dismutase 1 (25 ± 7%, P = 0.0175), superoxide dismutase 3 (20 ± 7%, P = 0.0309), and catalase (20 ± 7%, P = 0.046). These data demonstrate that irregular pacing is an important inductor of pro-fibrotic signalling in NRVM involving paracrine effects of CTGF and TGF-β as well as increased oxidative stress. Thus, irregularity of the heart beat might directly be involved in the progression of maladaptive remodelling processes in atrial fibrillation.

Clinical scores used for the prediction of negative events in patients undergoing catheter ablation for atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults. Catheter ablation (CA) is one of the most important management strategies to reduce AF burden and AF-associated complications. In order to stratify the risk of adverse events and to predict treatment success in AF patients undergoing CA, several risk stratification scores had been developed during the last decade. The aim of this review is to provide an overview of the most important clinical risk scores predicting rhythm outcomes, electro-anatomical substrate and mortality in AF.

Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes.

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia found in clinical practice. AF rarely exists as a single entity but rather as part of a diverse clinical spectrum of cardiovascular diseases, related to structural and electrical remodeling within the left atrium, leading to AF onset, perpetuation, and progression. Due to the high overall prevalence within the AF population arterial hypertension plays a significant role in the pathogenesis of AF and its complications. Fibroblast proliferation, apoptosis of cardiomyocytes, gap junction remodeling, accumulation of collagen both in atrial and ventricular myocardium all accompany ageing-related structural remodeling with impact on electrical activity. The presence of hypertension also stimulates oxidative stress, systemic inflammation, rennin-angiotensin-aldosterone and sympathetic activation, which further drives the remodeling process in AF. Importantly, both hypertension and AF independently increase the risk of cardiovascular and cerebrovascular events, e.g., stroke and myocardial infarction. Given that both AF and hypertension often present with limited on patient wellbeing, treatment may be delayed resulting in development of complications as the first clinical manifestation of the disease. Antithrombotic prevention in AF combined with strict blood pressure control is of primary importance, since stroke risk and bleeding risk are both greater with underlying hypertension.

Association between hepatic steatosis and serum liver enzyme levels with atrial fibrillation in the general population: The Study of Health in Pomerania (SHIP)

BackgroundHepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample. MethodsWe analyzed data from 3090 women and men, aged 20–81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software. ResultsThe prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF. ConclusionsOur findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF.