CHA2DS2-VASc and CHA2DS2-VA scores are often used to demonstrate thromboembolic risk in nonvalvular atrial fibrillation. Elevated whole blood viscosity is an independent risk factor for ischemic stroke.

This study aimed to ascertain the correlation between whole blood viscosity and CHA2DS2-VASc/CHA2DS2-VA scores.

This study was performed retrospectively in a tertiary cardiac facility, encompassing 150 patients.

The study's results demonstrate that whole blood viscosity, concerning both high shear rate and low shear rate variables, are statistically significant in forecasting the likelihood of elevated CHA2DS2-VA and CHA2DS2-VASc scores. (AUC: 0.690, 0.693; p: <0.001; 0.647, 0.665; p: <0.05).

Whole blood viscosity had a substantial correlation with the CHA2DS2-VASc/CHA2DS2-VA scores in patients with atrial fibrillation and may be used to evaluate thromboembolism risk, akin to these scores.

Recent studies have indicated an association between periodontitis and atrial fibrillation (AF), although the underlying mechanisms remain unclear. Porphyromonas gingivalis (P ginigivalis) is a causative agent of periodontal disease and is highly pathogenic. This study focused on P gingivalis and aimed to investigate the relationship among periodontitis, atrial translocation of P gingivalis, and atrial fibrosis and AF.

An experiment was conducted using P gingivalis-infected C57BL/6J mice, in which P gingivalis was inoculated into the pulp of the molars. Immunohistochemistry was used to visualize the localization of P gingivalis, and loop-mediated isothermal amplification was employed to detect P gingivalis DNA in the left atrium. AF inducibility was examined by intracardiac stimulation. Moreover, left atrial appendage specimens were obtained from 68 patients with AF. A periodontal examination was conducted before the surgery, and the periodontal epithelial surface area and periodontal inflamed surface area, which are quantitative indices used to determine the clinical severity of periodontitis, were measured. The bacterial number of P gingivalis in human atrial tissue was analyzed via quantitative polymerase chain reaction. Atrial fibrosis was assessed using Azan-Mallory staining.

The translocation path of P gingivalis from the dental granuloma to the left atrium via the circulatory system was demonstrated by immunohistochemistry and loop-mediated isothermal amplification in P gingivalis-infected mice, which showed a higher degree of atrial fibrosis (21.9% versus 16.3%; P=0.0003) and a higher AF inducibility (30.0% versus 5.0%; P=0.04) than the control mice. Upregulation of galectin-3 and transforming growth factor-beta 1 in the left atrium was observed in P gingivalis-infected mice. Moreover, immunohistochemistry revealed that P gingivalis was also present in human atrial tissue. The number of P gingivalis in the human atrial tissue was positively correlated with periodontal epithelial surface area (ρ=0.35; P=0.004), periodontal inflamed surface area (ρ=0.52, P<0.0001), and the degree of atrial fibrosis (ρ=0.38; P=0.002).

P gingivalis translocation to the left atrium correlates with the clinical severity of periodontitis, which may exacerbate atrial fibrosis and AF. Atrial translocation of P gingivalis is a potential pathway explaining the causal relationship between periodontitis and AF.

This study aimed to evaluate whether tirzepatide is associated with a reduced atrial fibrillation (AF) burden in patients with type 2 diabetes (T2D).

A retrospective cohort study was conducted using the TriNetX database. Adults with both AF and T2D diagnosed between January 2022 and February 2025 were included. The primary outcome was a composite of cardioversion, intravenous antiarrhythmic drug use, and AF ablation. Secondary outcomes included each component of the composite, heart failure, ischemic stroke, and all-cause mortality. Propensity score matching and Cox models were used. Subgroup analyses were conducted based on AF type, coronary artery disease, chronic kidney disease, heart failure, and obesity.

After matching, 11,194 patients were analyzed. Tirzepatide use was associated with a significantly lower risk of the primary outcome (HR: 0.65; 95 % CI: 0.55-0.76; P < 0.001). Significant findings were also observed across all secondary outcomes, including cardioversion, intravenous antiarrhythmic therapy, atrial fibrillation ablation, heart failure, ischemic stroke, and all-cause mortality. These associations remained consistent across prespecified subgroups and multiple sensitivity analyses.

Tirzepatide was significantly associated with reduced AF burden in patients with T2D and AF. These findings suggest a potential therapeutic role, supporting further prospective evaluation. Condensed abstract Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown metabolic and cardiovascular benefits, but its impact on AF burden remains unclear. Using the TriNetX database, this study analyzed 11,194 patients with AF and T2D and found that tirzepatide use was significantly associated with a lower two-year risk of cardioversion, intravenous antiarrhythmic drug use, and AF ablation (HR: 0.65; 95 % CI: 0.55-0.76; P < 0.001). These findings suggest that tirzepatide may offer therapeutic benefits in this high-risk population, warranting further investigation through randomized clinical trials.

Stroke is an injury occurring due to a sudden interruption of blood supply to the brain. It is the leading cause of disability worldwide and the second most prevalent cause of mortality. The objective of this study is whether momentous inflammatory and coagulation markers may have a correlation with each other in stroke patients.

Sixty stroke patients and twenty sex-age matched normal controls were sampled. Interleukin (IL)-6, IL-1β, sP-selectin, and high-sensitivity C-reactive protein (hsCRP), key inflammatory markers, were selected and measured by ELISA, and tissue factor gene expression level was evaluated by real-time PCR in peripheral blood mononuclear cells.

The serum levels of sP-selectin, IL-1β, IL-6, and hsCRP increased significantly in patients (P-value < 0.05). In the patient group, a significant correlation was observed between these inflammatory markers and coagulant tissue factor gene expression in peripheral blood mononuclear cells (P-values < 0.05), while it was not significant in the control group.

This study proposed that the main inflammatory markers in connection with tissue factor may play a role in the occurrence of thrombosis in stroke patients. Therefore, targeting and inhibiting the key inflammatory factors along with existing anticoagulants may greatly reduce the complications associated with stroke.

Atrial fibrillation (AF) is increasingly recognized not merely as an arrhythmia, but as a clinical manifestation of atrial cardiomyopathy (AtCM)-a progressive, multifaceted disease of the atrial myocardium involving structural, electrical, mechanical, and molecular remodeling. AtCM often precedes AF onset, sustains its perpetuation, and contributes to thromboembolic risk independently of rhythm status. Emerging evidence implicates diverse pathophysiological drivers of AtCM, including inflammation, epicardial adipose tissue, metabolic dysfunction, oxidative stress, ageing, and sex-specific remodeling. The NLRP3 inflammasome has emerged as a central effector in atrial inflammation and remodeling. Gut microbial dysbiosis, lipid dicarbonyl stress, and fibro-fatty infiltration are also increasingly recognized as contributors to arrhythmogenesis. AtCM is further linked to atrial functional valve regurgitation and adverse outcomes in AF. Therapeutically, substrate-directed strategies-ranging from metabolic modulation and immunomodulation to early rhythm control-offer promise for altering the disease trajectory. This review synthesizes mechanistic insights into AtCM and discusses emerging therapeutic paradigms that aim not merely to suppress arrhythmia but to modify the underlying substrate. Recognizing AF as a syndrome of atrial disease reframes management strategies and highlights the urgent need for precision medicine approaches targeting the atrial substrate.

Left atrial appendage thrombus (LAAT) is the predominant etiology of ischemic stroke in patients with atrial fibrillation (AF), and LAAT is optimally demonstrated by transesophageal echocardiography (TEE). The study aimed to assess patients with nonvalvular atrial fibrillation (NVAF) identified with thrombus using TEE compared to those without thrombus, utilizing the C-reactive protein/albumin ratio (CAR) as a sensitive biomarker.

This study was conducted retrospectively at a single center with 668 patients with NVAF who underwent TEE. Patients were divided into two groups based on the presence or absence of LAAT on TEE. The levels of CAR, C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were compared.

CAR was identified as an independent variable in patients with thrombus detected on TEE. (OR: 12.773, CI: 6.669-24.464, p < 0.001) Albumin was shown to have the highest area under the curve (AUC) value for thrombus prediction, followed by CAR, CRP, NLR, and PLR, in that order. (AUC: 0.999 CI: 0.993-1.000; 0.977 (0.962-0.987); 0.931 (0.909-0.949); 0.600 (0.562-0.937) p < 0.001, AUC: 0.574 CI: 0.535-0.612 p: 0.014).

Our study demonstrates that CAR serves as an independent predictor of LAAT and shows more dependability than other biomarkers such as NLR, CRP, and PLR.

The co-occurrence of diabetes mellitus (DM) and atrial fibrillation (AF) poses growing health risks in the United States (U.S.), with diabetes patients having a 34 % higher risk of AF. This study examines trends in DM and AF related mortality among individuals aged ≥ 25 years in the U.S. from 1999 to 2020. Data from the CDC WONDER database were analyzed calculating age-adjusted mortality rates (AAMRs) per 100,000 and annual percent change (APC), stratified by age, sex, race/ethnicity, urbanization, and region. Between 1999 and 2020, 419,036 deaths were recorded among U.S. adults (≥25 years) with comorbid AF and DM. The AAMR rose from 4.83 in 1999 to 15.91 in 2020, with an APC increase of 15.01 from 2018 to 2020. Older adults (≥65) had higher AAMRs than younger adults (25-64). Men (11.23) had higher rates than women (7.16). NH American Indian/Alaskan Natives (9.54) and Whites (9.16) had the highest AAMRs, while NH Asian/Pacific Islanders (6.04) had the lowest. Non-metropolitan areas (10.32) exceeded metropolitan areas (8.53). The Western U.S. (9.87) had the highest regional AAMR. Rising DM and AF-related deaths highlight a growing burden, particularly in men, NH American Indian/Alaskan Natives and Whites, and rural populations, necessitating targeted interventions.

Atrial fibrillation is the most common cardiac arrhythmia and is a major risk factor for ischemic stroke. Atrial fibrillation and ischemic stroke are major cardiovascular complications in cancer patients, who have a higher burden and worse outcomes than the general population. Clinical risk stratification scores for stroke and bleeding, commonly used in the general population to estimate thromboembolic and bleeding risk, respectively, are less well validated in cancer patients, who have historically been excluded in clinical trials. There is a lack of consensus opinion on how to effectively risk-stratify cancer patients based on the currently available tools and a need for cancer-specific scores that offer a tailored approach to each patient in order to more effectively stratify ischemic stroke and bleeding risk in this cohort of patients. Cancer-mediated physiologic changes and adverse effects of antineoplastic therapy have been implicated as etiologies of the increased risk for both atrial fibrillation and ischemic stroke. Risk stratifying scores such as CHA2DS2-VASc and HAS-BLED, commonly used in the general population, are less well validated in cancer patients. There is a need for cancer-specific scores that can more effectively stratify ischemic stroke and bleeding risk in cancer patients, although given the heterogeneity of cancers, whether a "one score fits all" is uncertain.

Sleep architectural disruption is associated with atrial fibrillation (AF); however, associated autonomic influences remain unclear and it is unknown if this detriment persists during wakefulness. We hypothesize sleep disruption and autonomic dysfunction have diurnal patterning in patients with paroxysmal AF.

We analyzed data from the Sleep Apnea and Atrial Fibrillation Biomarkers and Electrophysiologic Atrial Triggers (SAFEBEAT) study designed to examine paroxysmal AF and sleep apnea, including simultaneous collection of continuous electrocardiogram monitoring (Heartrak Telemetry®) and actigraphy (Actiwatch GTX) for 7-21 days. Heart rate variability (HRV) measures in time-domain (standard deviation of normal-to-normal (NN) intervals (SDNN), coefficient of variation (CV)) and frequency-domain (low frequency power (LFP), high frequency power (HFP)) were used as surrogates of autonomic function and averaged per sleep/wake per day. A linear mixed-effects model assuming compound symmetry correlation structure was used to assess the relationship of HRV with actigraphy-derived sleep data.

The analytic sample (age 60.1 ± 12.0 years, body mass index 32.6 ± 6.7 kg/m2, 36% female, 75% White) included 100 participants with paroxysmal AF. Longer sleep latency was associated with lower HFP during wakefulness (coefficient - 0.0501, p = 0.031). Higher sleep efficiency was associated with increased SDNN (coefficient 0.0007, p = 0.014) and CV (coefficient 0.0167, p = 0.047). Higher arousal index was associated with increased CV (coefficient 0.0166, p = 0.007) and LFP (coefficient 0.0232, p = 0.003). During sleep, longer average awakenings duration was associated with increased LFP/HFP ratio (coefficient 0.1977, p < 0.001) and reduced HFP (coefficient - 0.1338, p < 0.001). Significant sleep-wake interactions were observed for sleep latency with HFP (p = 0.024), sleep efficiency with SDNN and CV (both p < 0.01), WASO with SDNN, CV, and LFP (all p < 0.05), and frequency of awakenings with CV and LFP (both p < 0.05).

Actigraphy-based measures of sleep disruption were associated with autonomic function alterations exhibiting diurnal variability in paroxysmal AF. Greater overall HRV and parasympathetic modulation were related to better sleep quality. Increased sympathetic activation was associated with sleep fragmentation. Results provide insights into differential autonomic dysfunction related to sleep disruption that may contribute to atrial arrhythmogenesis.

Background: Atrial fibrillation (AF) is the most common supraventricular arrythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. Population studies have also suggested an association between AF and cognitive impairment and dementia. The aim of this study is therefore to assess, in a population of AF patients on oral anticoagulant therapy, the association between circulating biomarkers involved in the pathogenesis of AF and the cognitive and motor performances of the enrolled patients. Methods: The Strat-AF study is an observational, prospective, single-center, hospital-based study enrolling elderly patients with AF. Results refer to 180 subjects who underwent a complete clinical, biohumoral, cognitive, and functional evaluation. Results: At multivariate logistic regression, Clot Lysis Time (CLT) and circulating levels of von Willebrand Factor (vWF) remained significantly associated with pathological performances at the Stroop test (expressed as execution time) [OR 95% CI 1.54 (1.02-2.35), p = 0.042 and 1.75 (1.08-2.82), p = 0.023, respectively]. With regard to the Short Physical Performance Battery (SPPB), the circulating levels of IL-8 remained significantly associated with the clinical endpoint [OR 95% CI 2.19 (1.13-4.25), p = 0.020]. Conclusions: Our results suggest a potential innovative tool able to identify AF patients at risk of worse prognosis in terms of cognitive and motor performances. The clinical relevance of these results is due to the fact that we have no efficient methods to predict a deterioration in the cognitive performance and, consequently, the possible onset of dementia in AF patients undergoing oral anticoagulant therapy.

Bruton tyrosine kinase (Btk) has long been known to play a key role in chronic lymphatic leukaemia, Waldenström macroglobulinaemia and other B-cell proliferative disorders. An impressive programme of drug discovery and clinical development led to the approval of covalent and non-covalent Btk inhibitors that became pillars of treatment of such malignancies. However, both a risk of cardiovascular events and the emergence of an elusive mutational landscape seem to complicate the clinical use of each Btk inhibitor. In this plain language mini-review, we show that the search for better Btk inhibitors is challenged by the ancestral origin of Btk, its homology with innocent kinases in cardiovascular system and unique phylogenetic-like modalities with which Btk can mutate upon exposure to one inhibitor or another. Whereas basic and clinical pharmacology is already at work to explore new avenues of Btk inhibition, phylogeny remains behind the curtain to steer achievements and failures in this field.

Atrial fibrillation (AF) is a prevalent and chronic cardiovascular disorder associated with various pathophysiological alterations, including atrial electrical and structural remodeling, disrupted calcium handling, autonomic nervous system dysfunction, aberrant energy metabolism, and immune dysregulation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in the pathogenesis of AF.

This discussion aims to elucidate the involvement of AF-related lncRNAs, with a specific focus on their role as miRNA sponges that modulate crucial signaling pathways, contributing to the progression of AF. We also address current limitations in AF-related lncRNA research and explore potential future directions in this field. Additionally, we summarize feasible strategies and promising delivery systems for targeting lncRNAs in AF therapy.

In conclusion, targeting AF-related lncRNAs holds substantial promise for future investigations and represents a potential therapeutic avenue for managing AF.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical, structural, and autonomic remodeling of the atria. AF is closely associated with elevated interleukin-6 (IL-6) levels, which contribute to atrial remodeling and the progression of AF. This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways, atrial fibrosis, electrical remodeling, and calcium mishandling. Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF, highlighting its potential as a therapeutic target. Future studies should focus on IL-6 blockade strategies to manage AF, aiming to improve patient outcomes.

Atrial fibrillation (AF) and dementia are increasingly prevalent in aging US populations. Their association raises public health concerns, emphasizing the need to understand mortality trends in older adults. This study examines AF and dementia-related mortality trends from 2000 to 2020.

Using the CDC WONDER Multiple Cause of Death database, we analyzed death certificates for individuals aged 65 and older, reporting age-adjusted mortality rates (AAMRs) per 100 000 persons. Trends were assessed through annual percent change (APC) analysis via Joinpoint regression, with stratifications by sex, race/ethnicity, urbanization, and Census regions.

A total of 400 103 AF and dementia-related deaths were recorded between 2000 and 2020. The AAMR increased markedly from 25.4 in 2000 to 70.4 in 2020. The overall AAMR showed a steady increase from 2000 to 2018 (APC: +4.2%; 95% CI: 2.5-5.5), with a sharper rise from 2018 to 2020 (APC: +9.5%; 95% CI: 4.5-12.2; p < 0.001). Mortality rates were comparable between men (AAMR: 44.4) and women (AAMR: 43.9). NH White individuals exhibited the highest AAMR (47.0), followed by NH Black (26.6), Hispanic (23.1), and NH Asian/Pacific Islander (18.0) populations. Nonmetropolitan areas had higher AAMRs (48.1) compared to metropolitan areas (43.5). Regionally, the Western US recorded the highest AAMR at 48.2, while state-level disparities showed a nearly threefold difference between the top 90th and bottom 10th percentiles.

Rising AF and dementia-related mortality rates among older adults highlight a need for targeted screening and intervention, particularly for high-risk demographics and underserved regions.

At its earliest appearance, atrial fibrillation (AF) is often unnoticed, asymptomatic, and/or merely device-detected. Widespread use of heart-rate monitoring technologies has facilitated such "nascent atrial fibrillation (nAF)" recognition. Consequently, clinicians face a growing number of patients affected by new-onset AF in the absence of a definite indication for anticoagulation due to several counterarguments: (1) a CHA2DS2-VA score ≤ 1 in otherwise apparently healthy subjects; (2) an uncertain embolic/hemorrhagic benefit/risk ratio with anticoagulation; (3) EKG demonstration and confirmation of AF; and (4) existence of a pathogenic mechanism other than atrial hypercoagulability. In this frustrating limitation of pharmacological options, cardiologists may miss a complete comprehension of drugs with proven anti-ictal potential, whose administration may serve both as a bridge strategy toward future anticoagulation and as a consolidative strategy paralleling anticoagulation. This review aims to summarize and elucidate such therapeutic strategies and their preventative mechanisms.

Obstructive sleep apnea (OSA) is known to contribute to the occurrence and recurrence of atrial fibrillation (AF). However, the mechanism remains unknown.

Chronic OSA rat model was established to elucidate the role of macrophages in OSA-induced AF. Moreover, to reveal the mechanisms underlying the abnormal polarization of macrophages induced by chronic OSA, co-culture cell model of macrophages and atrial myocytes was created.

Chronic OSA altered the pathological phenotype of atrial myocardial tissues, rendering it more susceptible to AF. Furthermore, chronic OSA promoted the polarization of M1 macrophages in the atrial tissue, and the AF susceptibility induced by chronic OSA was reversed upon clearance of macrophages. Then, we found that macrophages induced an atrial fibrillation-like phenotype in atrial myocytes, while atrial myocytes promoted M1 polarization of macrophages, under hypoxia/reoxygenation treatment. Moreover, hypoxia/reoxygenation upregulated the expression of hypoxia-inducible factor 1-α (HIF1α) in atrial myocytes, which subsequently promoted the expression of macrophage migration inhibitory factor (MIF) by binding to the promoter region. The increased expression of MIF further activated the expression of nuclear factor-kappa B (NF-κB) through interaction with CD74, ultimately leading to M1 macrophages polarization.

Increased polarization of M1-type macrophages was involved in the increased susceptibility to AF induced by OSA. In mechanism, OSA increased MIF expression by HIF1α in atrial myocytes. Then, MIF activated NF-κB expression by CD74 in macrophages, consequently driving the polarization of M1-type macrophages. Finally, M1 macrophages exacerbated atrial remodeling through the secretion of inflammatory cytokines, which contributed to the increased susceptibility to AF.

Atrial fibrillation (AF), a common cardiac arrhythmia, is associated with severe complications such as stroke and heart failure. Although the precise mechanisms underlying AF remain elusive, inflammation is acknowledged as a pivotal factor in its progression. Angiotensin II (AngII) is implicated in promoting atrial remodeling and inflammation. However, the exact pathways through which AngII exacerbates AF are still not fully defined. This study explores the key molecular mechanisms involved, including dysregulation of calcium ions, altered connexin expression, and activation of signaling pathways such as TGF-β, PI3K/AKT, MAPK, NF-κB/NLRP3, and Rac1/JAK/STAT3. These pathways are instrumental in contributing to atrial fibrosis, electrical remodeling, and increased susceptibility to AF. Ang II-induced inflammation disrupts ion channel function, resulting in structural and electrical remodeling of the atria and significantly elevating the risk of AF. Anti-inflammatory treatments such as RAAS inhibitors, colchicine, and statins have demonstrated potential in reducing the incidence of AF, although clinical outcomes are inconsistent. This manuscript underscores the link between AngII-induced inflammation and the development of AF, proposing the importance of targeting inflammation in the management of AF.

Many scoring systems are used to evaluate malnutrition, but there is no consensus on which scoring system would be more appropriate. We aimed to investigate the effect of malnutrition in patients with non-valvular atrial fibrillation (NVAF) and to compare three scoring systems.

A total of 2592 patients with non-valvular AF from 35 different centers in Turkey were included in this prospective study. All participants were divided into two groups: 761 patients who died and 1831 patients who were alive. The malnutrition status of all participants was evaluated with three scoring systems. The primary outcome was all-cause mortality. The mean age of the population was 68.7 ± 11.1 years, and 55.5 % were female. According to Cox regression analysis, the geriatric nutritional risk index (GNRI) (HR = 0.989, 95 % CI: 0.982-0.997, p = 0.007), controlling nutritional status (CONUT) score (HR = 1.121, 95 % CI: 1.060-1.185, p < 0.001), and prognostic nutritional index (PNI) (HR = 0.980, 95 % CI: 0.962-0.999, p = 0.036) were found to be significant mortality predictors. ROC curve analysis indicated GNRI (AUC = 0.568), CONUT (AUC = 0.572), and PNI (AUC = 0.547) had moderate predictive values. Kaplan-Meier analysis showed that increasing the risk class based on GNRI (p < 0.001) and CONUT (p < 0.001) was associated with decreased survival, while PNI staging had no statistically significant effect (p = 0.266).

Malnutrition, determined by three scoring systems, was found to be an independent predictor of all-cause mortality in NVAF patients. Nutritional examination may provide useful information for prognosis and risk stratification in patients with NVAF.

There is growing evidence that eicosapentaenoic acid (EPA) uptake has beneficial effects on various cardiovascular diseases. However, electrophysiological actions of EPA remain poorly documented. To investigate the potential antiarrhythmic effects of EPA, mice were fed a high-fat diet (HFD) or an HFD supplemented with EPA for eight weeks. Electrocardiogram (ECG) recordings in combined with esophageal electrical stimulation revealed that HFD-fed mice exhibited bradycardia, reduced P-wave amplitude, and prolonged P-wave duration. Atrial fibrillation (AF) was induced in 100 % of HFD mice, which was only in 50 % of EPA-supplemented mice with significantly shorter durations. HFD-fed mice showed decreased expression of Cav1.2-mRNA, increased expression of Kv1.5-mRNA, elevated expression of inflammatory cytokines (IL-1β, TNF-α, and IL-10), and larger fibrotic area in atrial tissue, which were all reversed by EPA supplementation. These findings suggest that long-term dietary intake of EPA may help maintain normal atrial function and structure, thereby reducing the risk of AF.

Atrial fibrillation (AF) remains the most common arrhythmia worldwide, but its pathophysiology remains complex and multifactorial. As obesity has increased over the past couple of decades, much interest has been generated about its relationship with other diseases. As a result, the interplay between AF and obesity has been rigorously investigated as risk factor modification has become more important for the management of AF. In this review, we discuss the epidemiology of AF and obesity, the pathophysiology connecting these two diseases, and how obesity affects the management of AF.

Atrial fibrillation (AF), the most common type of heart arrhythmia, is recognized as an independent risk factor for stroke. Fortunately, catheter ablation (CA) offers an effective treatment option for AF patients. However, numerous studies have reported suboptimal outcomes, as AF recurrence rates often remain elevated even after CA. Consequently, there exists a need for early identification of patients prone to recurrence, necessitating anti-inflammatory and/or antiarrhythmic treatment post-CA. The discovery and application of markers associated with AF recurrence could significantly aid in this early identification process. In this review, we present an overview of AF recurrence markers from three distinct perspectives (biochemical, imaging, and electrocardiographic markers).

The relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. The purpose of this study was to investigate the role of KCa3.1 in the migration of macrophages from EAT to adjacent atrial tissue during rapid pacing.

Part 1: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + clodronate liposome (CL) group. Part 2: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + TRAM-34 group. HL-1 cells and RAW264.7 cells were co-cultured to explore the specific migratory mechanism of macrophages.

Depleting EAT macrophages significantly reduced macrophage infiltration in the adjacent atrium and the induction of AF in canines with rapid atrial pacing. TRAM-34 significantly inhibited the migration of macrophages from EAT to the adjacent atrium and electrical remodelling in canines with rapid atrial pacing. Compared with those of the control HL-1 cells, the secretion of CCL2 and the number of migrating macrophages in pacing HL-1 cells was significantly increased, which could be reversed by TRAM-34. Further in vitro experiments showed that KCa3.1 regulated CCL2 secretion through the p65/STAT3 signalling pathway.

Inhibiting myocardial KCa3.1 reduced the migration of EAT macrophages to adjacent atrial muscles caused by rapid atrial pacing, thereby decreasing vulnerability to AF. The mechanism by which KCa3.1 regulates CCL2 may be related to the p65/STAT3 signalling pathway.

Background: The impact of Celiac Disease (CD) is not only limited to the intestinal system, but extraintestinal manifestations may also be seen. In this context, cardiac manifestations have recently been the focus of attention. This study aimed to evaluate myocardial repolarization properties in CD patients by assessing the frontal QRS-T Angle (fQRS-T) on electrocardiography (ECG). Methods: A total of 302 patients, including 150 CD patients and 152 control group patients, were included in the study. ECG parameters, including fQRS-T, QRS interval, and QTc interval, were calculated for each patient and compared between the groups. In addition, the relationship of these ECG parameters with disease duration was also analyzed. Results: The median disease duration was 38.5 (16 to 96) months in the CD group. Significantly wider QRS interval (92 (86 to 96) vs. 83 (76.3 to 93), p < 0.001) and fQRS-T (23 (13 to 37) vs. 18 (6.3 to 27), p < 0.001) values were observed in the CD group. Among CD patients, those with longer disease duration (>38.5 months) exhibited significantly wider QRS intervals (94 (88 to 98) vs. 88 (84 to 94), p < 0.001) and frontal QRS-T angles (29 (14 to 47) vs. 16 (10 to 25), p < 0.001) compared to those with shorter disease duration. A positive correlation between the disease duration and fQRS-T was also demonstrated (r = 0.478, p < 0.001). Multivariable logistic regression identified QRS interval (OR: 1.060, 95% CI: 1.032-1.088, p < 0.001) and frontal QRS-T angle (OR: 1.028, 95% CI: 1.013-1.043, p < 0.001) as independent predictors of CD. Additionally, the QRS interval (OR: 1.066, 95% CI: 1.012-1.124, p = 0.016) and frontal QRS-T angle (OR: 1.021, 95% CI: 1.003-1.038, p = 0.021) were significant predictors of longer disease duration. A linear regression analysis confirmed that disease duration was a stronger predictor of frontal QRS-T angle widening (B: 0.389, 95% CI: 0.102-0.677, p < 0.001) compared to age (B: 0.184, 95% CI: 0.123-0.245, p = 0.008). Conclusions: In this study, we demonstrated that chronic inflammation secondary to CD may have negative effects on cardiac repolarization and that this effect is closely related to disease duration.

The rate at which atrial fibrillation (AF) patients experience a return of symptoms after catheter ablation is significant, and there are multiple risk factors involved. This research intends to perform a meta-analysis to explore the risk factors connected to the recurrence of AF in patients following catheter ablation.

The PubMed, Cochrane Library, WOS, Embase, SinoMed, CNKI, Wanfang, and VIP databases were explored for studies from January 1, 2000 to August 10, 2021, and research meeting the established inclusion requirements was chosen. Two authors separately gathered details regarding the study structure. The strength of the link between various risk factors and AF returning after CA was evaluated using odds ratios. All statistical evaluations were conducted with RevMan5.3 software.

In total, 44 articles and 62,674 patients were included. The OR for AF recurrence in patients with diabetes was 2.04 compared with the reference group (95% CI 1.51-2.76, p < 0.00001); that of lower left ventricular ejection fraction was 1.38 (95% CI 1.25-1.52, p < 0.00001); that of female was 1.34 (95% CI 1.18-1.52, p < 0.00001); that of increased age was 1.03 (95% CI 1.02-1.04, p < 0.00001); that of persistent AF was 1.72 (95% CI 1.58-1.87, p < 0.00001); that of AF duration over 2 years was 1.17 (95% CI 1.08-1.26, p < 0.00001); that of increased left atrial diameter (LAD) was 1.12 (95% CI 1.08-1.17, p < 0.00001); that of larger left atrial volume index (LAVi) was 1.02 (95% CI 1.01-1.03, p < 0.00001); that of higher hs-CRP was 1.19 (95% CI 1.04-1.36, p = 0.04); that of early recurrence (ER) was 3.22 (95% CI 2.74-3.77, p < 0.00001); and that of long ablation duration was 1.00 (95% CI 0.98-1.02, p = 0.72). Heterogeneity and slight publication bias were observed for each factor.

Evidence indicates that diabetes, low left ventricular ejection fraction, being female, older age, longer duration of atrial fibrillation, elevated high-sensitivity C-reactive protein levels, large left atrial dimension, large left atrial volume index, persistent atrial fibrillation, and exercise rehabilitation are factors that increase the chances of getting atrial fibrillation again after catheter ablation. However, the length of the ablation procedure does not relate to the recurrence of AF.

Although atrial fibrillation is the most common rhythm problem, the results of treatment to restore sinus rhythm are still not satisfactory. Nearly half of patients undergoing ablation relapse within one year. Therefore, triggered activities may not be the only cause. Inflammation is quite common in AF. In this study, we investigated the effect of PIV, an inflammatory marker, on recurrence.

A total of 157 patients who underwent ablation with cryo balloon were included in the study. One-year follow-up was evaluated for causes of recurrence.

When the inflammatory parameters between the two groups are analyzed, CRP (5.9 [5.0-6.9] vs 9.7 [7.6-11.9], p < 0.001), NL ratio (2.8 [2.5-3.0] vs 6.4 [5.0-6.8], p < 0.001), SII2 (618.5 [557.1-679.9] vs 1798.9 [1305.8-2292.1], p < 0.001), PIV (355.9 [313.4-398.4] vs 1832 [1317.8-2347.1], p < 001) were significantly higher in the AF recurrence group. ROC analysis showed that PIV had the best sensitivity and specificity.

Inflammation has been found to be a cause of AF recurrence and PIV is one of the best markers for this.

Current arrhythmia therapies such as ion channel blockers, catheter ablation, or implantable cardioverter defibrillators have limitations and side effects, and given the proarrhythmic risk associated with conventional, ion channel-targeted anti-arrhythmic drug therapies, a new approach to arrhythmias may be warranted. Measuring and adjusting the level of specific ions that impact heart rhythm can be a simple and low-complication strategy for preventing or treating specific arrhythmias. In addition, new medicines targeting these ions may effectively treat arrhythmias. Numerous studies have shown that intracellular and extracellular zinc concentrations impact the heart's electrical activity. Zinc has been observed to affect cardiac rhythm through a range of mechanisms. These mechanisms encompass the modulation of sodium, calcium, and potassium ion channels, as well as the influence on beta-adrenergic receptors and the enzyme adenylate cyclase. Moreover, zinc can either counteract or induce oxidative stress, hinder calmodulin or the enzyme Ca (2+)/calmodulin-dependent protein kinase II (CaMKII), regulate cellular ATP levels, affect the processes of aging and autophagy, influence calcium ryanodine receptors, and control cellular inflammation. Additionally, zinc has been implicated in the modulation of circadian rhythm. In all the aforementioned cases, the effect of zinc on heart rhythm is largely influenced by its intracellular and extracellular concentrations. Optimal zinc levels are essential for maintaining a normal heart rhythm, while imbalances-whether deficiencies or excesses-can disrupt electrical activity and contribute to arrhythmias.

Cardiac arrhythmia is a rising public health issue. The aim of this study was to determine the associations of atrial fibrillation (AF) and heart block with cardiovascular disease (CVD) incidence and all-cause mortality.

We included 141,362 participants (mean age [49.3], 80.9% men) from the Kailuan study. Arrhythmias were diagnosed through a 12-lead electrocardiograph (ECG). Mortality and CVD events were ascertained through multiple sources, including a municipal social insurance institution, hospital records, death certificates, and regular active follow-ups. During a median follow-up of 12.5 years, 18,301 total deaths and 13,208 cases of CVD were documented. The multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing participants with AF to those without arrhythmia were 1.76 (1.61-1.93) for all-cause mortality, 2.11 (1.86-2.39) for CVD, 3.99 (3.33-4.79) for heart failure, and 1.56 (1.30-1.90) for stroke. Further, comparing participants with heart block to those without arrhythmia, the multivariable-adjusted HRs (95% CIs) were 1.31 (1.24-1.38) for all-cause mortality, 1.26 (1.18-1.35) for CVD, 1.40 (1.23-1.59) for heart failure, and 1.25 (1.15-1.37) for stroke. Additionally, there were generally stronger associations for AF and heart block with all-cause mortality and CVD in younger participants compared with their older counterparts (Ps-interaction ≤ 0.02) and a stronger association between AF and CVD in women compared with men (Ps-interaction ≤ 0.006).

AF and heart block were associated with a higher risk of subsequent adverse CVD events and mortality. Our findings highlight the importance of strategies for preventing cardiac arrhythmias to reduce the risk of CVD and mortality.

Many studies have shown that myocardial infarction (MI) is significantly associated with atrial fibrillation (AF), but the causal relationship between MI and AF has not been established. Therefore, we performed this Mendelian randomization (MR) study to investigate the relationship between MI and AF. We used a publicly available summary statistical dataset for MI based on genome-wide analysis studies (GWAS; ebi-a-GCST011364; 14,825 cases and 2680 controls) and a summary statistical dataset for AF based on an European GWAS (finn-b-I9_AF_REIMB; 10,516 cases and 116,926 controls). The 2-sample bidirectional MR analysis was performed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods. The causal effect of MI on AF was analyzed using 30 MI-specific single nucleotide polymorphisms (SNPs) that were characterized as instrumental variables (IVs) based on the GWAS data. The causal effect of MI on AF was confirmed by the IVW (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.27-1.58; P < .001), MR-Egger (OR: 1.49; 95% CI: 1.15-1.93; P = .005), and weighted median (OR: 1.42; 95% CI: 1.24-1.63; P < .001) analyses. Furthermore, in the reverse MR analyses, the causal effect of AF on MI was analyzed using 20 AF-specific SNPs that were screened as IVs. The causal effect of AF on MI was significant based on the results from the IVW method (OR: 1.05; 95% CI: 1.00-1.09; P = .033). In conclusion, the bidirectional MR analyses demonstrated a clear bidirectional causal association between MI and AF.

The incidence of new-onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long-term prognosis. The C2HEST score has been recently proposed to stratify the risk of NOAF. Pooled data on the performance of the C2HEST score are lacking.

Systematic review and meta-analysis of observational studies reporting data on NOAF according to the C2HEST score. We searched PubMed, Web of Science and Google scholar databases without time restrictions until June 2023 according to PRISMA guidelines. Meta-analysis of the area under the curve (AUC) with 95% confidence interval (95% CI) and a sensitivity analysis according to setting of care and countries were performed.

Of 360 studies, 17 were included in the analysis accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The prevalence of women ranged from 10.6 to 54.75%. The pooled analysis gave an AUC of .70 (95% CI .66-.74). A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95% CI 0.64-0.75). In the subgroup of patients with cardiovascular disease, the AUC was .71 (.69-.79). The C2HEST score performed similarly in Asian (AUC .72, 95% CI .68-.77), and in Western patients (AUC .68, 95% CI .62-.75). The best performance was observed in studies with a mean age <50 years (n = 3,144,704 with 25,538 NOAF, AUC .78, 95% CI .76-.79).

The C2HEST score may be used to predict NOAF in primary and secondary prevention patients, and in patients across different countries. Early detection of NOAF may aid prompt initiation of management and follow-up, potentially leading to a reduction of AF-related complications.

The aim of this study was to assess the association between adherence to Mediterranean diet and the presence of atrial fibrillation (AF) in a Northern Chinese population.

This study was a single center, case-control study. A total of 952 low risk participants in Beijing Anzhen Hospital from 2016 to 2021 were collected, including 476 patients with first diagnosed of atrial fibrillation and 476 age and sex matched controls. According to the food frequency questionnaire (FFQ), the alternate Mediterranean diet score (AMED) was calculated, which was 0-9 points, indicating the adherence to the Mediterranean diet from low to high.

The average age of the participants was 57.6 ± 9.1 years old, and 70.2% were men. After analyzing every component of AMED, vegetable consumption shows a negative correlation with the risk of AF, whereas alcohol consumption demonstrates a positive correlation with it (OR = 0.61, 95% CI 0.44-0.80, p < 0.001; OR = 1.99, 95% CI 1.48-2.58, p < 0.001). All patients were grouped according to AMED score. A significant inverse association between AMED and the risk of AF was observed. Compared with participants with AMED<4, the multivariable-adjusted ORs of AF were 0.75 (95% CI 0.55-1.06) for AMED 4-5 and 0.61 (95% CI 0.43-0.89) for AMED ≥6, with a trend in risk (p = 0.008). Results were consistent in stratified analyses of gender, age, BMI and smoking.

The Mediterranean diet was inversely associated with the risk of AF in this Northern Chinese population.

To assess the global burden of atrial fibrillation (AF) attributable to high body mass index (BMI) from 1990 to 2021 and analyze its spatiotemporal distribution characteristics.

An observational study based on GBD 2021 data.

Data on AF burden due to high BMI were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage change (EAPC) was calculated to evaluate temporal trends in age-standardized rates of deaths and disability-adjusted life years (DALYs) over 30 years.

In 2021, high BMI-related AF caused 27,000 deaths and 725,000 DALYs globally, a 376% increase since 1990. Females and the elderly (aged 70+) bore a higher burden. Upper-middle-income regions surpassed high-income regions in AF burden. Australasia had the highest age-standardized rates, while High-income Asia Pacific and South Asia had the lowest. South Asia showed rapid growth in age-standardized death rates.

The global burden of high BMI-related AF varies across regions and time, threatening global health, especially for females and the elderly. Targeted strategies are needed to reduce AF and obesity.

Background: Atrial fibrillation (AF) is affected by both environmental and genetic factors. Previous genetic association studies, especially genome-wide association studies, revealed a large group of AF-associated genes. However, little is known about the functions and interactions of these genes. Moreover, established genetic variants of AF contribute modestly to AF variance, implying that numerous additional AF-associated genetic variations need to be identified. Hence, a systematic network and pathway analysis is needed. Methods: We retrieved all AF-associated genes from genetic association studies in various databases and performed integrative analyses including pathway enrichment analysis, pathway crosstalk analysis, network analysis, and microarray meta-analysis. Results: We collected 254 AF-associated genes from genetic association studies in various databases. Pathway enrichment analysis revealed the top biological pathways that were enriched in the AF-associated genes related to cardiac electromechanical activity. Pathway crosstalk analysis showed that numerous neuro-endocrine-immune pathways connected AF with various diseases including cancers, inflammatory diseases, and cardiovascular diseases. Furthermore, an AF-specific subnetwork was constructed with the prize-collecting Steiner forest algorithm based on the AF-associated genes, and 24 novel genes that were potentially associated with AF were inferred by the subnetwork. In the microarray meta-analysis, six of the 24 novel genes (APLP1, CREB1, CREBBP, PRMT1, IRAK1, and PLXND1) were expressed differentially in patients with AF and sinus rhythm. Conclusions: AF is not only an isolated disease with abnormal electrophysiological activity but might also share a common genetic basis and biological process with tumors and inflammatory diseases as well as cardiovascular diseases. Moreover, the six novel genes inferred from network analysis might help detect the missing AF risk loci.

Kinase inhibitors (KIs) targeting oncogenic molecular pathways have revolutionized cancer therapy. By directly targeting specific tumor-driving kinases, targeted therapies have fewer side effects compared with chemotherapy. Despite the enhanced specificity, cardiovascular side effects have emerged with many targeted cancer therapies that limit long-term outcomes in patients with cancer. Endothelial cells lining all blood vessels are critical to cardiovascular health and are also exposed to circulating levels of systemic anticancer therapies. Both on- and off-target perturbation of signaling pathways from KIs can cause endothelial dysfunction, resulting in cardiovascular toxicity. As such, the endothelium is a potential source, and also a therapeutic target for prevention, of cardiovascular toxicity. In this review, we examine the evidence for KI-induced endothelial cell dysfunction as a mechanism for the cardiovascular toxicities of vascular endothelial growth factor inhibitors, BCR-Abl (breakpoint cluster region-Abelson proto-oncogene) KIs, Bruton tyrosine inhibitors, and emerging information regarding endothelial toxicity of newer classes of KIs.

Introduction Coronary artery bypass grafting (CABG) carries the risk of postoperative arrhythmias. Our study focusses on the efficacy of dexamethasone in both on-pump CABG (ONCAB) and off-pump CABG (OPCAB). Methods This single center randomized control trial was conducted from July 1st, 2018 to January 20th, 2019 in patients undergoing conventional ONCAB and OPCAB at the National Cardiovascular Center Harapan Kita (NCCHK). All arrhythmia incidents were recorded postoperatively with routine monitoring done every hour until the patient was discharged. Results One hundred and twenty patients were included in the study and arrhythmias occurred in 24.2% of patients. In the ONCAB groups, there was an association between dexamethasone versus placebo in reducing the incidence of arrhythmias (p = 0.02; OR 0.23 [0.064-0.831]). However, in patients who underwent OPCAB, there was no association between dexamethasone administration and the incidence of arrhythmias (p = 0.347; OR 0.55 [0.157-1.931]). Patients on dexamethasone in both ONCAB and OPCAB groups showed a significant decrease in IL-6, CRP, and procalcitonin (p = 0.001 for all). Overall, arrhythmic subjects had significantly higher levels of inflammatory markers IL-6 (p = 0.013), CRP (p = 0.025), and procalcitonin (p = 0.001). Conclusion Dexamethasone reduced postoperative arrhythmias, likely by modulating systemic inflammation, as shown by the decrease in inflammatory markers in ONCAB patients compared to those given a placebo.

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. The prevalence of both AF and dementia is steadily rising and is expected to rise further in the coming decades. There is increasing evidence to suggest an association between AF and various degrees of cognitive dysfunction, from mild cognitive impairment to severe dementia. In this review, we aimed to discuss the epidemiological aspects, pathophysiological mechanisms, role of neuroimaging, impact of treatment modalities, and clinical and socioeconomic impact of this association. Numerous observational studies and meta-analyses have revealed this association to exist in AF patients with and without a history of stroke, and the association also persists after adjusting for shared risk factors such as hypertension and diabetes mellitus. Various pathophysiological mechanisms have been proposed for this association, including silent cerebral infarcts, cerebral microbleeds, cerebral hypoperfusion, inflammation, and atherosclerosis. While neuroimaging findings have been utilized to suggest some of these pathophysiological mechanisms, more studies are needed to further elucidate this and to determine the potential role of neuroimaging in altering anticoagulation and other treatment decisions. Anticoagulants have shown effectiveness in reducing the rate of cognitive decline in AF patients; however, their role in low-risk AF patients remains under investigation. Even though AF patients receiving catheter ablation may have post-operative cognitive dysfunction in the short term, long-term follow-up studies have shown an improvement in cognitive function following ablation. Cognitive decline in AF patients often occurs with greater functional decline and other psychosocial impairments such as depression and anxiety and future research on this association must incorporate aspects of social determinants of health and associated outcomes.

Aim: The aim of this study is to investigate the value of inflammatory markers for atrial fibrillation (AF) recurrence prediction after cryo-balloon ablation (CA).Materials & methods: The study included 399 patients divided into two groups by AF recurrence after CA. Inflammatory markers including uric acid/albumin ratio (UAR), systemic immune inflammation index (SIII) and CRP/albumin ratio (CAR) were evaluated.Results: UAR, SIII, and CAR were independently associated with the risk of recurrence in AF patients following CA. In ROC curve analysis, CAR had a greater area under curve (AUC:0.73) value than either SIII (AUC:0.68) or UAR (AUC:0.64).Conclusion: Our study results indicate that CAR compared with SIII and UAR had a greater predictive value than others inflammatory markers in predicting AF recurrence post-CA.

Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias and has a significant economic and social burden. Whether it is associated with lifestyle behaviors and socioeconomic status is currently poorly understood. This study aimed to explore the relationship among these factors and determine the role of inflammatory cytokines.

We investigated the causal effects of lifestyle behaviors and socioeconomic status on AF using bidirectional two-sample Mendelian randomization (MR). Instrumental variables were obtained from a publicly available genome-wide association study. A two-step MR was conducted to determine the mediating role of 91 inflammatory cytokines. Inverse variance weighted was used as the main method with four supplementary MR methods. To obtain more robust results, several sensitivity analyses were conducted.

The results indicated that seven of the lifestyle behaviors [smoking initiation, vegetable intake, coffee consumption (cups/day), dozing, lifetime smoking index, napping, and alcohol abuse] were potential risk factors for AF. One socioeconomic status, education attainment (years of education), was causally associated with a decreased risk of AF. Moreover, we found that thymic stromal lymphopoietin, CD40l receptor, C-X-C motif chemokine 6, and C-X-C motif chemokine 11 levels mediated the causal effect, at proportions of 13.6%, 4.1%, 4.3%, and 6.9%, respectively.

Our findings provide insight into the relationship between lifestyle behaviors, socioeconomic status, and AF. Inflammatory cytokines are potential mediators of this relationship.

Atrial fibrillation has an estimated prevalence of 1.5-2%, making it the most common cardiac arrhythmia. The processes that cause and sustain the disease are still not completely understood. An association between atrial fibrillation and systemic, as well as local, inflammatory processes has been reported. However, the exact mechanisms underlying this association have not been established. While it is understood that inflammatory macrophages can influence cardiac electrophysiology, a direct, causative relationship to atrial fibrillation has not been described. This study investigated the pro-arrhythmic effects of activated M1 macrophages on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes, to propose a mechanistic link between inflammation and atrial fibrillation.

Two hiPSC lines from healthy individuals were differentiated to atrial cardiomyocytes and M1 macrophages and integrated in an isogenic, pacing-free, atrial fibrillation-like coculture model. Electrophysiology characteristics of cocultures were analysed for beat rate irregularity, electrogram amplitude and conduction velocity using multi electrode arrays. Cocultures were additionally treated using glucocorticoids to suppress M1 inflammation. Bulk RNA sequencing was performed on coculture-isolated atrial cardiomyocytes and compared to meta-analyses of atrial fibrillation patient transcriptomes.

Multi electrode array recordings revealed M1 to cause irregular beating and reduced electrogram amplitude. Conduction analysis further showed significantly lowered conduction homogeneity in M1 cocultures. Transcriptome sequencing revealed reduced expression of key cardiac genes such as SCN5A, KCNA5, ATP1A1, and GJA5 in the atrial cardiomyocytes. Meta-analysis of atrial fibrillation patient transcriptomes showed high correlation to the in vitro model. Treatment of the coculture with glucocorticoids showed reversal of phenotypes, including reduced beat irregularity, improved conduction, and reversed RNA expression profiles.

This study establishes a causal relationship between M1 activation and the development of subsequent atrial arrhythmia, documented as irregularity in spontaneous electrical activation in atrial cardiomyocytes cocultured with activated macrophages. Further, beat rate irregularity could be alleviated using glucocorticoids. Overall, these results point at macrophage-mediated inflammation as a potential AF induction mechanism and offer new targets for therapeutic development. The findings strongly support the relevance of the proposed hiPSC-derived coculture model and present it as a first of its kind disease model.