Body mass index as a determinant of scar formation post-AF ablation: Insights from DECAAF II.

INTRODUCTION: Obesity is implicated in adverse atrial remodeling and worse outcomes in patients with atrial fibrillation. The objective of this study is to assess the effect of body mass index (BMI) on ablation-induced scar formation on late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR). METHODS: We conducted an analysis of DECAAF II participants who underwent LGE-CMR scans to measure scar formation 3 months after catheter ablation. Ablation parameters and lesion delivery were not dependent on BMI. The effect of BMI on ablation success was explored. RESULTS: Our analyses included 811 patients. Comorbidities were more prevalent in obese patients. Baseline left atrial volume was higher in obese individuals, 118, 126, 135, 140, and 143 mm3 for normal weight, overweight, obese grade 1, 2, and 3, respectively (p < .001). BMI was associated with scar formation (R = -0.135, p < .001), with patients with Class 3 obesity having the lowest percentage of ablation-induced scar, 11.1%, 10.3%, 9.5%, 8.8%, 6.8% by ascending BMI group. There was an inverse correlation between BMI and the amount of fibrosis covered by ablation scar, 24%, 23%, 21%, and 18% by ascending BMI group (p = .001). For the fibrosis-guided ablation group, BMI was associated with residual fibrosis (R = 0.056, p = .005). CONCLUSION: Obese patients have lower ablation scar formation, covered fibrosis, and more residual fibrosis postablation compared to nonobese patients, regardless of ablation parameters including impedance drop.

Atrial fibrillation versus non-atrial fibrillation coronary embolism.

BACKGROUND: Coronary embolism (CE) is an uncommon cause of non-atherosclerotic acute myocardial infarction (AMI). Although atrial fibrillation (AF) is the main cause of CE, evidence of clinical, biochemical, echocardiographic, angiographic findings and outcomes of AF CE is lacking. METHODS: We retrospectively analyzed 85 consecutive patients with CE that was diagnosed based on criteria encompassing clinical, angiographic and diagnostic imaging findings. We classified patients according to AF CE or non-AF CE. RESULTS: Forty-five patients presented with AF CE (53%). Patients with AF CE were older (76 ± 12 vs. 63 ± 14 years; p < 0.001) and had more often chronic kidney disease (24% vs. 5%; p = 0.01). AF CE had lower estimated glomerular filtration rate at admission (59 ± 18 vs. 77 ± 16 ml/min/1.73 m2; p < 0.001) and higher brain natriuretic peptide levels (512 ± 417 vs. 210 ± 479 pg/ml; p = 0.02). Coronary arteriography revealed a higher incidence of coronary artery obstruction in the AF CE group (73% vs. 38%; p = 0.001) without differences in interventional management. The AF CE group showed higher left atrial volume index (LAVI) (42 ± 15 vs. 25 ± 12 ml/m2; p < 0.001) and showed lower left atrium ejection fraction (LAEF) (32 ± 17 vs. 49 ± 17%; p = 0.001). In the multivariable analysis AF CE (OR 10 [95% CI 1.04-95; p = 0.046]) and LAEF (OR 0.94 [95% CI 0.88-0.99; p = 0.02]) were associated with worse in-hospital outcomes. Moreover, in the multivariable analysis, prior stroke (OR 12.5 [95% CI 1.1-137; p = 0.04]) and LAVI (OR 1.1 [95% CI 1.03-1.14; p = 0.003]) were independently associated with worse long-term outcomes. CONCLUSION: AF CE has specific characteristics compared to non-AF-CE and it is associated with more in-hospital events. Furthermore, atrial cardiopathy is associated with worse in-hospital and long-term outcomes in this setting.

Development of an Extended Cardiovascular SOFA Score Component Reflecting Cardiac Dysfunction with Improved Survival Prediction in Sepsis: An Exploratory Analysis in the Sepsis and Elevated Troponin (SET) Study.

INTRODUCTION: The cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score does not correspond with contemporary clinical practice in sepsis or identify impaired cardiac function. Our aim was to develop a modified cardiovascular SOFA component that reflects cardiac dysfunction and improves the SOFA score's 30-day mortality discrimination. METHODS: A cohort of sepsis patients from a previous study was divided into a training (n = 250) and test cohort (n = 253). Nine widely available measures of cardiovascular function were screened for association with 30-day mortality using natural cubic spline. High-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) and heart rate (HR) were transformed into ordinal variables (0-4 points). The presence of atrial fibrillation (AF) was assigned two points. The SOFA score was extended by adding the variable points in different weights and combinations. The best-performing cardiac-extended model (CE-SOFA) was evaluated in the test cohort. Improved prognostic discrimination and calibration were assessed using logistic regression, area under receiver operating characteristic curves (AUC), Net Reclassification Improvement (NRI) index, and DeLong and Hoshmer-Lemeshow tests. RESULTS: In the training cohort, all differently weighted and combined models using hs-cTnT, NT-proBNP and AF points added to the SOFA score showed improved discriminative ability (AUC 0.67-0.75) compared to the SOFA score (AUC 0.62; NRI P < .001; DeLong P ≤ .001). In the test cohort, CE-SOFA demonstrated improved 30-day mortality discrimination compared to the SOFA score (AUC 0.72 vs 0.68), exhibiting good calibration and significantly improved discrimination using the NRI index (P = .009) but not the DeLong test (P = .142). CONCLUSIONS: The CE-SOFA model reflects cardiac dysfunction and improves 30-day mortality discrimination in sepsis. External validation is the next step to further substantiate a revised cardiovascular component in a future SOFA 2.0.

Evaluation of posterior mitral isthmus ablation in the absence of a vein of Marshall.

BACKGROUND AND AIMS: Achieving acute and durable mitral isthmus (MI) block remains challenging using radio frequency (RF)-catheter ablation alone. Vein of Marshall (VoM) ethanolisation results in chemical damage along the mitral isthmus resulting in the creation of a durable transmural lesion with a very high rate of procedural block. However, no studies have systematically assessed the efficacy of MI ablation alone when no anatomical VoM is present. METHODS: Thirty seven patients without VoM evidenced after careful angiographic examination were included. Ablation parameters and result were compared to a matched control group in whom the posterior MI line was performed without assessing the presence of the VoM. RESULTS: MI block was achieved in 36 out of 37 patients without VoM (97%), with endocardial ablation only in 5/37 (14%) and combined endocardial and CS ablation in 32/37 patients (86%). There was a significant difference in occurrence of block between patients without a VoM and the control group (97,3% vs. 65% respectively, p<0,01), with a trend towards less needed RF (26 (IQR 20-38) vs 29 (IQR 19-40) tags (p=0.8), 611 (IQR 443-805) vs 746 (IQR 484-1193) seconds (p=0.08)). CONCLUSION: The absence of a Vein of Marshall is associated with a very high rate of procedural block during posterior mitral isthmus ablation. The higher rate of MI block in this specific population would also suggest the crucial role of the Vein of Marshall (when present) in resistant MI block.

Multielectrode Catheter-Based Pulsed Field Ablation of Persistent and Long-Standing Persistent Atrial Fibrillation.

BACKGROUND AND AIMS: Rhythm control of non-paroxysmal atrial fibrillation (AF) is significantly more challenging, as a result of arrhythmia perpetuation promoting atrial substrate changes and AF maintenance. We describe a tailored ablation strategy targeting multiple left atrial (LA) sites via a pentaspline pulsed field ablation (PFA) catheter in persistent AF sustained beyond 6 months (PerAF>6m) and long-standing persistent AF (LSPAF). METHODS: The ablation protocol included the following stages: pulmonary vein antral and posterior wall isolation plus anterior roof line ablation (Stage 1); electrogram-guided substrate ablation (Stage 2); atrial tachyarrhythmia regionalization and ablation (Stage 3). RESULTS: Seventy-two [age:68±10years, 61.1%males; AF history: 25 (18-45) months] patients with PerAF>6m (52.8%) and LSPAF (47.2%) underwent their first PFA via the FarapulseTM system. LA substrate ablation (Stage 1 and 2) led to AF termination in 95.8% of patients. AF organized into a left-sided atrial flutter (AFlu) in 46 (74.2%) patients. The PFA catheter was used to identify LA sites showing diastolic, low-voltage electrograms and entrainment from its splines was performed to confirm the pacing site was inside the AFlu circuit. Left AFlu termination was achieved in all cases via PFA delivery. Total procedural and LA dwell times were 112±25min and 59±22 min, respectively. Major complications occurred in 2 (2.8%) patients. Single-procedure success rate was 74.6% after 14.9±2.7 months of follow-up; AF-free survival was 89.2%. CONCLUSIONS: In our cohort, PFA-based AF substrate ablation led to AF termination in 95.8% of cases. Very favorable clinical outcomes were observed during >1year of follow-up.

Common SYNE2 Genetic Variant Associated With Atrial Fibrillation Lowers Expression of Nesprin-2α1 With Downstream Effects on Nuclear and Electrophysiological Traits.

BACKGROUND: Atrial fibrillation GWAS (genome-wide association studies) identified significant associations for rs1152591 and linked variants in the SYNE2 gene encoding Nesprin-2, which connects the nuclear membrane with the cytoskeleton. METHODS: Reporter gene vector transfection and CRISPR-Cas9 editing were used to identify the causal variant regulating the expression of SYNE2α1. After SYNE2 knockdown or SYNE2α1 overexpression in human stem cell-derived cardiomyocytes, nuclear phenotypes were assessed by imaging and atomic force microscopy. Gene expression was assessed by RNAseq and gene set enrichment analysis. Fura-2 AM staining assessed calcium transients. Optical mapping assessed action potential duration and conduction velocity. RESULTS: The risk allele of rs1152591 had lower promoter and enhancer activity and was significantly associated with lower expression of the short SYNE2α1 isoform in human stem cell-derived cardiomyocytes, without an effect on the expression of the full-length SYNE2 mRNA. SYNE2α1 overexpression had dominant negative effects on the nucleus with its overexpression or SYNE2 knockdown leading to increased nuclear area and decreased nuclear stiffness. Gene expression results from SYNE2α1 overexpression demonstrated both concordant and nonconcordant effects with SYNE2 knockdown. SYNE2α1 overexpression had a gain of function on electrophysiology, leading to significantly faster calcium reuptake and decreased assessed action potential duration, while SYNE2 knockdown showed both shortened assessed action potential duration and decreased conduction velocity. CONCLUSIONS: rs1152591 was identified as a causal atrial fibrillation variant, with the risk allele decreasing SYNE2α1 expression. Downstream effects of SYNE2α1 overexpression include changes in nuclear stiffness and electrophysiology, which may contribute to the mechanism for the risk allele's association with AF.

Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis.

BACKGROUND: Currently, there are no reliable methods for predicting and preventing atrial fibrillation (AF) in its early stages. This study aimed to identify plasma proteins associated with AF to discover biomarkers and potential drug targets. METHODS: The UK Biobank Pharma Proteomics Project examined 2923 circulating proteins using the Olink platform, forming the basis of this prospective cohort study. The UK Biobank Pharma Proteomics Project included a randomly selected discovery cohort and the consortium-selected replication cohort. The study's end point was incident AF, identified using International Classification of Diseases, Tenth Revision codes. The association between plasma proteins and incident AF was evaluated using Cox proportional hazard models in both cohorts. Proteins present in both cohorts underwent Mendelian randomization analysis to delineate causal connections, utilizing cis-protein quantitative trait loci as genetic tools. The predictive efficacy of the identified proteins for AF was assessed using the area under the receiver operating characteristic curve, and their druggability was explored. RESULTS: Data from 53 032 participants were included in this study. Incident AF cases were identified in the discovery cohort (1894; 5.5%) within a median follow-up of 14.5 years and in the replication cohort (451; 10.6%) within a median follow-up of 14.4 years. Twenty-one proteins linked to AF were identified in both cohorts. Specifically, COL4A1 (collagen IV α-1; odds ratio, 1.11 [95% CI, 1.04-1.19]; false discovery rate, 0.016) and RET (proto-oncogene tyrosine-protein kinase receptor Ret; odds ratio, 0.96 [95% CI, 0.94-0.98]; false discovery rate, 0.013) demonstrated a causal link with AF, and RET is druggable. COL4A1 improved the short- and long-term predictive performance of established AF models, as evidenced by significant enhancements in the area under the receiver operating characteristic, integrated discrimination improvement, and net reclassification index, all with P values below 0.05. CONCLUSIONS: COL4A1 and RET are associated with the development of AF. RET is identified as a potential drug target for AF prevention, while COL4A1 serves as a biomarker for AF prediction. Future studies are needed to evaluate the effectiveness of targeting these proteins to reduce AF risk.

Incidence and Outcomes of Patients With Early Cardiac Complications After Intracerebral Hemorrhage: A Report From VISTA.

BACKGROUND: The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of clinical trial data. METHODS: We used the Virtual International Stroke Trials Archive to investigate the incidence of cardiac complications within 30 days post-ICH or acute ischemic stroke (AIS). These complications included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/atrial flutter, other arrhythmia/ECG abnormalities, and cardiorespiratory arrest. We used propensity score matching to compare the incidence of patients with stroke-heart syndrome in patients with ICH with those following AIS. Factors associated with 90-day mortality were evaluated using multivariate logistic regression analysis in the ICH cohort. RESULTS: We pooled data from 8698 participants recruited in acute stroke trials (mean age, 68±12 years; 56% male), of whom 914 (11%) were patients with ICH. Among the patients with ICH, 123 (13%) had stroke-heart syndrome in patients with ICH. Following propensity score matching, a total of 1828 patients (914 for each of the cohorts) were analyzed. While the overall incidence of cardiac events tended to be lower in the ICH group compared with the AIS group (the cumulative incidence freedom from the event, 86.3% [95% CI, 84.1-88.6] versus 83.6% [95% CI, 81.2-86.0]; P=0.100), the incidences cardiac events other than atrial fibrillation/atrial flutter were comparable between the 2 matched groups. The incidence of atrial fibrillation/atrial flutter was significantly lower in the ICH group than in the AIS group (P<0.001). The multivariate-adjusted analysis found that stroke-heart syndrome in patients with ICH was associated with 90-day mortality (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]; P<0.001). CONCLUSIONS: Cardiac events are common and negatively affect prognosis in patients with ICH, just as seen in AIS.

Quality of Life Evaluation in Patients with Paroxysmal Atrial Fibrillation.

BACKGROUND: To estimate quality of life (QoL) in patients with paroxysmal atrial fibrillation (AF) using the SF-36 Health Status Survey. MATERIALS AND METHODS: In a single-center study involving 6,630 patients, we defined a group of 97 patients having an incidental finding of atrial fibrillation (AF). The control group included 99 patients from the same primary cohort, but without paroxysmal AF. The two study groups matched closely in anthropometric parameters and comorbidity. All patients underwent standard laboratory and instrumental research methods. In the primary visit, at the time of AF detection, we evaluated the patients QoL using the classical SF-36 Health Status Survey. At the second visit (6±0.5 months follow-up) and third visit (12±0.5 months follow-up), we re-evaluated the QoL using the SF-36 Health Status Survey. RESULTS: The absolute majority (95/97; 98%) of patients of the main group had a special variant of extrasystoles, namely the early atrial "P on T" type (versus 4.0% incidence in the control group) [OR 846 (382;187,000)]. The main group showed a significantly greater frequency of supraventricular extrasystoles. At the 1st visit, there was no group differences in QoL scores between the main and control groups (p>0.05). However, at 6 and 12 months follow-up, metrics of physical and mental health differed significantly between groups stratified by low and high QoL (p<0.05). The asymptomatic patients with paroxysmal AF and high compliance in oral anticoagulant therapy showed higher physical activity and social functioning. CONCLUSIONS: Paroxysmal AF in asymptomatic patients is a predictor for declining QoL during 12 months follow-up in patients with cardiovascular pathology. The paroxysmal AF patients who had high compliance of oral anticoagulant therapy proved to have improved physical activity and social functioning.

Electro-metabolic coupling in atrial fibrillation: A deeper understanding of the metabolic driver.

Atrial fibrillation (AF), the most common sustained heart rhythm abnormality, disrupts the normal link between electrical activity and atrial muscle contraction; this disruption is termed "excitation-contraction uncoupling". It weakens atrial contractions and contributes to the development and persistence of AF. In addition to electrical dysfunction, AF is increasingly recognized as a metabolic disorder. Metabolic remodeling may reportedly precede electrophysiological, contractile, and structural changes in AF. Both clinical observations and experimental studies have underscored the critical importance of metabolic homeostasis, and its disturbance is considered a key initial factor in the development of AF. Research in this field has progressed, and a consensus has emerged that metabolic status (energy flux) and electrophysiological signaling (ion flux) are interactively regulated, highlighting the concept of "electro-metabolic coupling." Their uncoupling or decompensation constitutes a common pathological basis of AF. Despite growing recognition of the importance of metabolic balance, the role of electro-metabolic coupling in AF remains unclear. Thus, this review aimed to discuss 1) a comprehensive understanding of electro-metabolic alterations post-AF, 2) the pivotal role of metabolic homeostasis in AF pathogenesis, and 3) the mutual regulation of electro-metabolic signaling, along with potential therapeutic strategies targeting these imbalances.

Brain lesion and echocardiogenic predictors of newly detected atrial fibrillation in acute ischemic stroke.

OBJECTIVES: Atrial fibrillation (AF) is one of the notorious risk factors in acute ischemic stroke (AIS), and the use of anticoagulants has been shown to be effective in preventing ischemic stroke in AF patients. Therefore, identifying AF in AIS patients has become increasingly important. However, the impact of brain imaging and cardiac indices on the development of new AF after stroke remains unclear. METHODS: A consecutive series of AIS patients who were admitted to the Ulsan University Hospital between January 2013 and December 2019 were identified. Patients with relevant ischemic brain lesions on MRI were included, and those without echocardiography data were excluded. We included and classified the AF patients who had the disease prior to or during hospitalization or met the criteria for cryptogenic stroke (CS). Differences in baseline characteristics, stroke risk factors, stroke severity, insular lesion, and echocardiographic data were investigated among each group. RESULTS: A total of 850 patients were enrolled in the study, comprising 231 patients with AF detected after stroke (AFDAS), 287 patients with known AF (KAF), and 350 patients with CS. Compared with KAF, patients with AFDAS had a lower prevalence of underlying coronary heart disease and stroke history. They had greater right insular cortex lesions and lesser left atrial enlargement in unadjusted analysis. Following adjusted analysis, the involvement of the right insular cortex was found to be associated with the AFDAS patient group (odds ratio, 1.57). When compared to the CS group, AFDAS patients were older, experienced more severe initial strokes, and had similar rates of pre-stroke anticoagulation prescription. Additionally, they demonstrated a higher prevalence of both insular lesions, increased left atrium volume index, reduced ejection fraction, and elevated e/e' ratio. After adjustment, age, initial stroke severity, insular involvement, left atrium volume index, ejection fraction, and e/e' ratio were found to be significant. CONCLUSIONS: These results suggest that the right insular cortex lesion on acute stroke may be a cause of AFDAS.

Utility of smart watch in expediting diagnosis of cold drink-triggered atrial fibrillation: a case report.

BACKGROUND: Patients presenting to the emergency department with recent palpitations are a diagnostic challenge when the arrhythmia and its symptoms have resolved prior to arrival. Newer smart watch technology, adept at detecting atrial fibrillation, can assist in the diagnostic evaluation of transitory palpitations. We report a case of cold drink-triggered atrial fibrillation whose diagnosis would not have been possible without the assistance of the patient's smart watch. CASE PRESENTATION: A middle-aged man without cardiac history developed sudden rapid, irregular palpitations with shortness of breath while drinking a glass of cold juice. He activated his smart watch with 1-lead electrocardiography technology which detected rapid atrial fibrillation. He sought medical care, but while waiting, his symptoms-then 90 min in duration-spontaneously resolved. His initial diagnostic evaluation documented only sinus rhythm, as did several follow-up evaluations with cardiology the next several weeks. Had it not been for his smart watch, the etiology of his transitory palpitations would have remained undiagnosed. His physicians encouraged trigger avoidance. In the following months, he avoided rapid ingestion of cold drink, taking instead small sips. The atrial fibrillation has not recurred. CONCLUSIONS: The case illustrates the valuable contribution of smart watch technology in the diagnostic evaluation of patients with short-lived palpitations. The case also educates clinicians about cold drink and food as a trigger of paroxysmal atrial fibrillation. This trigger, like alcohol, can be modified. Cold drink trigger avoidance has been reported by patients to reduce atrial fibrillation recurrence and is a low-risk, cost-effective strategy that is often successful.

Global burden of atrial fibrillation attributable to high body mass index from 1990 to 2021: findings from the Global Burden of Disease Study 2021.

OBJECTIVES: 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. STUDY DESIGN: An observational study based on GBD 2021 data. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The validity and reliability of the Arabic version of the EQ-5D in atrial fibrillation patients in a conflict country: a study from Syria.

BACKGROUND: The EQ-5D is one of the most commonly used tools to establish health-related quality of life (QoL). EQ-5D data in atrial fibrillation (AF) patients in the Middle East are lacking. OBJECTIVES: This study aims to evaluate the reliability and validity of the Arabic version of the EQ-5D in AF inpatients in Syria. METHODS: The study involved patients admitted to the emergency department of Tishreen's University Hospital in Latakia with AF as the primary diagnosis between the 1st of June 2021 and the 1st of June 2023. Arabic versions of the EQ-5D, EQ-VAS and SF36 questionnaires were administered to patients. Validation was done using convergent, discriminant, and known-groups validity, while reliability was conducted using EQ-5D retesting within 2-4 weeks. RESULTS: 432 participants were included in the study with a mean ± standard deviation of 63 ± 15. Males represented 242 (56%) of the participants. All hypotheses relating EQ-5D responses to external variables were satisfied. All three validation hypotheses demonstrated that the EQ-5D had the convergent, discriminant and known group validity to assess QoL in this cohort. The intraclass correlation coefficient (ICC) for test-retest reliability ranged between 0.74 and 0.88, while Cohen's κ ranged between 0.72 and 0.86. Cronbach's α value for internal consistency was 0.73. CONCLUSION: The Arabic version of EQ-5D was valid and reliable in measuring QoL in AF inpatients in Syria. This validation opens the door for more widespread use of the EQ-5D in Arabic-speaking regions, facilitating better-informed healthcare decisions and improving patient care strategies in Syria and other Middle Eastern countries.

Detection of atrial fibrillation after stroke due to large or small vessel disease: systematic review and meta-analysis.

BACKGROUND: Emerging evidence indicates a frequent occurrence of atrial fibrillation (AF) detection among patients with established causes of ischemic stroke unrelated to AF. This systematic review and meta-analysis aimed to evaluate AF detection rates in stroke patients with large or small vessel disease, considering the AF detection modality and duration of cardiac rhythm monitoring. AIMS: We conducted a comprehensive search of PubMed and Scopus databases up to March 2, 2024, to identify randomized controlled trials, non-randomized prospective studies, and retrospective studies assessing the frequency of AF detection in stroke patients with large or small vessel disease. The primary outcome of interest was the rate of AF detection. We utilized inverse-variance weights to produce the pooled prevalence (effect size-ES) and 95% confidence interval (CI) of patients diagnosed with post-stroke AF. SUMMARY OF REVIEW: In the analysis of 14 eligible studies encompassing 4,334 patients, AF was identified in 154 out of 2,082 patients with strokes attributed to small or large-vessel disease, yielding a pooled prevalence of 6.27% (ES; 95% confidence interval [CI]: 3.18-10.17, I2=87.83%). Among patients with large-vessel disease strokes, AF was diagnosed in 79 out of 1,042 patients, accounting for a pooled prevalence of 5.07% (ES;95% CI: 1.30-10.33, I2=77.05%). Similarly, among those with small-vessel disease strokes, AF was detected in 75 out of 1,040 patients, with a pooled prevalence of 5.03% (ES; 95% CI: 1.96-9.06, I2=78.05%). CONCLUSIONS: AF is often found in ischemic stroke patients with large or small-vessel disease. Detection rates increase with longer cardiac rhythm monitoring. The safety and benefits of oral anticoagulation for these AF episodes are uncertain.

Identification of senescence-related genes for potential therapeutic biomarkers of atrial fibrillation by bioinformatics, human histological validation, and molecular docking.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Effectiveness of a Triple Antiarrhythmic Drug Strategy for Arrhythmia Recurrence after Persistent Atrial Fibrillation Ablation.

BACKGROUND AND OBJECTIVE: Treating recurrent atrial arrhythmias after persistent atrial fibrillation (PeAF) ablation is often challenging. This single-center, prospective study aimed to observe the effectiveness of different combinations of oral antiarrhythmic drugs (AADs) in reverting to sinus rhythm (SR) in patients with recurrent atrial arrhythmias after PeAF ablation. METHODS: Forty-five patients who experienced recurrent atrial arrhythmias after PeAF ablation were included. Based on their medication regimens, patients were divided into two groups, with the study group being a triple-drug group (digoxin combined with amiodarone/ propafenone and ß-blocker), and the control group being a non-triple-drug group. RESULTS: The rate of reversion to SR was significantly higher in the study group (n = 29) than in the control group (n = 16) at 3 weeks (34.48% vs. 0%, p < 0.01) and 1 month (44.84% vs. 6.25%, p = 0.02) after initiating AADs. No patients with asymptomatic bradycardia were observed in either group. CONCLUSIONS: For patients with recurrent atrial arrhythmias after PeAF ablation, a regimen of low-dose digoxin combined with amiodarone/propafenone and ß-blocker may effectively improve short-term reversion rates.

Senescent CD8+ T cells: a novel risk factor in atrial fibrillation.

AIMS: Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms. METHODS AND RESULTS: Single-cell RNA sequencing and multicolor flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (p < 0.0001) and the left atria (p < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, p < 0.05) and postprocedural recurrence (hazard ratio = 22.955, p < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping. CONCLUSIONS: An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.