Background: Acute heart failure (AHF) remains a major cause of morbidity and mortality, especially in hospitalized patients. Inotropic agents like dobutamine have long been used for hemodynamic support, yet concerns over adverse effects such as arrhythmias and increased myocardial oxygen consumption limit their safety. Levosimendan, a calcium sensitizer with vasodilatory properties, offers a potential alternative. This meta-analysis was conducted to evaluate the comparative safety and efficacy of levosimendan versus dobutamine in patients with AHF. Method: A systematic review and meta-analysis was conducted following PRISMA and AMSTAR 2 guidelines. Major databases including PubMed, Cochrane, Embase, and ScienceDirect were searched up to July 2025 without any language restrictions. Sixteen studies including 15 randomized controlled trials and 1 cohort study were evaluated for this study. Outcomes were pooled using a random effects model. Meta-regression was performed to assess the influence of baseline covariates. Result: In the pooled analysis of 16 studies, levosimendan showed a statistically significant reduction in mortality (RR: 0.59; P = 0.0009) compared to dobutamine. While systolic blood pressure and diastolic blood pressure remained comparable, levosimendan led to a marked reduction in pulmonary capillary wedge pressure and improved cardiac index, left ventricular ejection fraction, and mixed venous oxygen saturation. B-type natriuretic peptide and IL-6 levels also declined significantly in the levosimendan group. Adverse events such as hypotension and atrial fibrillation were slightly more frequent with levosimendan, while tachycardia and ischemic events were more common with dobutamine. Overall adverse event rates were similar. Conclusion: Levosimendan demonstrates favorable effects on mortality and key hemodynamic parameters in patients with AHF, especially those on β-blockers or with impaired left ventricular function. Although certain adverse effects like hypotension were more frequent, the overall safety profile remained comparable to dobutamine. These findings suggest levosimendan as a safer and more effective alternative in selected high-risk heart failure populations.

Abstract Aims Intracardiac echocardiography (ICE) is increasingly incorporated into atrial fibrillation (AF) ablation workflows, enabling real-time anatomic guidance and procedural precision. Nevertheless, ICE utilization shows substantial geographic variability, and its clinical benefit remains incompletely understood. This meta-analysis evaluated the efficacy, safety, and procedural performance of ICE-guided versus non–ICE-guided AF ablation. Methods and Results MEDLINE, the Cochrane Library, and Scopus were systematically searched through 3 August 2025. Three reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Random-effects models were used to pool data from 44 AF ablation studies comprising 482,043 patients. ICE guidance was associated with lower odds of any complication (OR 0.69; 95% CI 0.53–0.89), including significant reductions in cardiac tamponade (OR 0.58; 95% CI 0.53–0.62) and mortality (OR 0.21; 95% CI 0.16–0.27). ICE-guided ablation was also associated with shorter total procedure and fluoroscopy times, reduced radiation exposure, and lower contrast agent utilization. Atrial tachyarrhythmia (AT) recurrence did not differ between groups (OR 0.92; 95% CI 0.79–1.06). However, ICE use was associated with higher odds of first-pass pulmonary vein isolation (OR 1.62; 95% CI 1.09–2.41) and successful isolation of all pulmonary veins at the end of the procedure (OR 2.12; 95% CI 1.37–3.27), and lower odds of repeat ablation (OR 0.65; 95% CI 0.59–0.72). Conclusion ICE-guided AF ablation is associated with superior procedural safety and efficiency and a similar risk of AT recurrence compared to non–ICE-guided approaches.

Background While clinical differences between anterior (AC) and posterior (PC) circulation strokes are recognized, the underlying biological distinctions remain poorly defined, limiting the development of personalized therapies. This study aimed to delineate the unique clinical profiles and identify the distinct inflammatory signatures of AC versus PC ischemic strokes, thereby providing a biological basis for their classification as separate pathophysiological entities. Methods This retrospective cohort study analyzed 499 ischemic stroke patients (434 AC, 65 PC) admitted to a tertiary neurological center. Stroke subtype was confirmed by neuroimaging. A comprehensive comparative analysis was conducted on demographic characteristics, vascular risk factors, clinical severity via National Institutes of Health Stroke Scale (NIHSS) scores, and key laboratory parameters upon admission, with a focus on inflammatory markers (C-reactive protein and white blood cell count). Results The core innovation of this study is the discovery of a novel, divergent inflammatory signature: AC strokes were characterized by a systemic, C-reactive protein (CRP)-dominant response (14.97 vs. 8.65 mg/L, p < 0.001), whereas PC strokes exhibited a distinct, leukocyte-dominant profile (WBC count 10.80 vs. 9.36 × 10 9 /L, p < 0.001). This biological divergence was mirrored by a notable clinical dissociation, where PC strokes presented with significantly lower baseline NIHSS scores (8.31 vs. 13.47, p < 0.001), highlighting the insensitivity of standard severity scales to posterior-specific deficits. Furthermore, PC strokes were associated with older age and a higher rate of previous stroke, while AC strokes were more frequently linked to atrial fibrillation. Conclusion Our findings establish that AC and PC strokes are not merely anatomical variants but distinct pathophysiological entities, each possessing a unique biological fingerprint. The discovery of opposing inflammatory profiles, coupled with the clear dissociation from standard clinical severity scores, provides a compelling rationale to move beyond a “one-size-fits-all” approach in stroke care. This evidence lays a critical foundation for developing subtype-specific diagnostic biomarkers and targeted immunomodulatory strategies, representing a key translational step toward advancing precision medicine for stroke patients.

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion.

Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia and confers an elevated risk of major adverse cardiovascular events (MACEs). Emerging evidence indicates that metabolic dysregulation substantially influences the AF prognosis. The cardiometabolic index (CMI) and triglyceride-glucose (TyG) index are non-insulin-dependent surrogate markers of metabolic dysfunction that are readily obtainable in clinical practice. However, their comparative prognostic value for predicting MACEs in patients with AF has not been previously evaluated within the same cohort. This retrospective single-center cohort study enrolled 380 AF patients who received treatment at the Shanghai Jinyang Community Health Center between January 2022 and June 2025, with a maximum follow-up duration of 3 years. CMI and TyG were calculated from routinely collected baseline clinical and laboratory data. MACEs served as the primary endpoint. Predictive performance was examined using adjusted Cox regression with restricted cubic spline (RCS) to assess potential nonlinearity, along with Kaplan-Meier survival curves, receiver operating characteristic (ROC) curve-based discrimination analysis, machine learning approaches, and subgroup interaction testing. Incremental predictive benefit over the CHA2DS2-VASc score was further evaluated. A total of 53 patients (13.9%) experienced MACEs during follow-up. Baseline CMI and TyG values were statistically higher among patients with events (both P < 0.01). In multivariable Cox regression analyses, elevated CMI (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.89-5.58) and elevated TyG index (HR, 4.52; 95% CI, 1.83-11.12) emerged as independent predictors of MACEs. RCS analyses revealed nonlinear associations, with threshold effects at a CMI ≈ 0.85 and a TyG index ≈ 9.02. Their predictive ability was further supported by Kaplan-Meier and ROC curve analyses. Machine learning models, particularly extreme gradient boosting (XGBoost), demonstrated increased discrimination (area under the curve [AUC] reaching 0.93). Subgroup analyses revealed enhanced predictive performance in patients without heart failure, coronary artery disease, or diabetes, as well as in individuals aged ≥ 65 years. Incorporation of either the CMI or the TyG index into the CHA2DS2-VASc score yielded significant improvements in predictive accuracy, whereas adding both indices did not provide an additional benefit. CMI and the TyG index function as robust, independent predictors of 3-year MACEs in patients with atrial fibrillation, and may help identify metabolically impaired individuals who are not adequately captured by conventional risk scores. The TyG index, in particular, offers strong predictive accuracy combined with ease of measurement from routine laboratory tests, making it widely accessible across diverse healthcare settings. These simple, cost-effective indices enable the prompt recognition of high-risk patients and facilitate timely initiation of preventive interventions to reduce cardiovascular morbidity and mortality, serving as practical adjuncts to the CHA2DS2-VASc score for more precise risk stratification and personalized management of AF.

In the PRAGUE-25 study, the effect of lifestyle modification (LFM) in combination with antiarrhythmic drugs (AAD) in patients with atrial fibrillation (AF) and BMI 30-40 was smaller than that of catheter ablation (CA). The presented sub-analysis aims to assess the relationship between the actual weight reduction and the AF burden 12 months after randomization. Per-protocol analysis of the PRAGUE-25 trial. Patients in the LFM+AAD group were stratified into tertiles based on the extent of relative weight reduction, and a comparison of AF burden was performed between the LFM+AAD tertiles and the CA group. The study analyzed 83 LFM+AAD patients (age 60 ±9 years, 31% women, 54% paroxysmal AF, mean weight 109±17 kg) and 99 CA patients (age 60±9 years, 32% women, 56% paroxysmal AF, weight 109±15 kg). Within the LFM+AAD group, 28 patients achieved a weight reduction of >8.3% (-15.46±6.16 kg), 27 patients were between 3.1-8.1% (-6.56±2.28 kg), and 28 patients were <3.1% (+1.38±4.03 kg). Compared to the CA group, the AF burden at 12 months (0 [IQR 0-0]) was significantly higher in the second (3.5% [0; 52] and third (1[0; 47] LFM-ADD tertiles, but did not differ from CA in the first tertile (0% [0; 11.], p=0.17). In obese patients, the maintenance of SR on AADs is related to the level of weight reduction. The efficacy of AADs in obese patients with a significant weight loss at 12-months follow-up is close to catheter ablation, although the overall AF burden is still non-significantly higher.

Background Catheter ablation (CA) is a standard treatment for atrial fibrillation (AF); however, some patients experience worsening heart failure (WHF) afterward. The H 2 FPEF and HFA-PEFF scores are validated tools for HFpEF risk stratification, but their predictive value for WHF after CA in patients with preclinical heart failure (HF) remains unclear. Method This retrospective, single-center observational study included 257 AF patients with preserved left ventricular ejection fraction (LVEF) ≥50% and no history or symptoms of HF who underwent first-time CA between February 2017 and September 2022. Patients were classified as high HFpEF score group if they had H 2 FPEF score ≥6 or HFA-PEFF score ≥5. The primary endpoint was WHF: HF hospitalization, initiation of oral diuretics, or intravenous administration of diuretics. Results Among 257 patients, 54 (21.01%) were classified as high HFpEF score group. WHF incidence was significantly higher in the high HFpEF score group than in the low HFpEF score group (log-rank p &amp;lt; 0.001), while AF recurrence did not differ significantly (log-rank p = 0.546). In Firth's penalized logistic regression analysis, high HFA-PEFF score (HR 6.52, 95% CI 1.54–23.21, p = 0.014) and AF recurrence (HR 8.18, 95% CI 1.80–77.60, p = 0.005) appeared to be potential independent predictors of WHF. Conclusions In this exploratory analysis, the HFA-PEFF score potentially represent an independent predictor of WHF after CA in AF patients with preclinical HF and preserved LVEF.

BackgroundThis research assessed the causal influence of atrial fibrillation (AF) on depression.MethodsA two-sample Mendelian randomization (MR) approach was utilized along with data from additional databases. A genome-wide association study (GWAS) involving 463,010 participants allowed for the exploration of genetic variations associated with AF. Another GWAS with 215,644 individuals offered insights into the relationship between gene variants and depression. Data on the correlation between gene variants and depression were obtained from another GWAS encompassing 449,414 individuals. Effect sizes were assessed utilizing the inverse-variance weighted technique. Sensitivity analysis was conducted by weighted median, outlier, MR pleiotropy residual sum, weighted mode, and MR-Egger. A meta-analysis of the inverse-variance weighted (IVW) results from the two datasets was conducted.ResultsA significant association was found between genetically predicted AF and increased incidence of depression using 15 single nucleotide polymorphisms (SNPs) as markers. No evidence of gene pleiotropy was detected, as indicated by MR-Egger. Sensitivity analyses employing alternative Mendelian randomization techniques consistently yielded robust results. The combined odds ratio for depression was estimated at 29.19 (95% CI = 4.43-192.13, P < 0.001).ConclusionThis study found a causal relationship between genetically predicted AF and a heightened risk of depression.

Cardiovascular disease (CVD) remains a leading cause of global morbidity and mortality, and its initiation and progression are closely associated with multiple molecular mechanisms. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and antimicrobial proteins that are released by neutrophils during inflammation or infection. They play a crucial role in innate immune defense. However, when the dynamic balance of NETs is disrupted by excessive formation, persistent accumulation, or impaired clearance, NETs are no longer merely bystanders. Instead, they actively drive pathological processes in multiple CVDs and serve as a critical link between inflammation and cardiovascular injury. Given the central role of NETs in CVD pathogenesis, including atherosclerosis, myocardial ischemia–reperfusion injury, pulmonary arterial hypertension, atrial fibrillation, and heart failure, therapeutic strategies targeting NETs, such as inhibiting aberrant formation, enhancing clearance, or neutralizing toxic components, have emerged as promising approaches. In recent years, traditional Chinese medicine (TCM) and natural products have shown potential therapeutic value by modulating NET formation and promoting NET degradation, owing to their multitarget, multipathway regulatory effects. This article reviews the mechanisms by which NETs operate in CVDs and explores potential pathways through which TCM and natural active ingredients prevent and treat CVDs by regulating NETs. This review provides theoretical support for further research and clinical application.

Predicting irregularity: computational modelling of haemodynamics in atrial fibrillation.

This study was performed to evaluate the current status and to analyze the associated factors of intraoperative pain experience during radiofrequency ablation of atrial fibrillation (AF) with conscious sedation and analgesia. This cross-sectional observational study employed convenience sampling of AF patients underwent their first radiofrequency ablation. General information questionnaire, intraoperative status sheet, Wong-Baker faces pain rating scale, hospital anxiety and depression scale, and the Connor-Davidson Resilience Scale were employed for data collection and analysis. A total of 428 patients (mean age 66.5 ± 9.6years; 59.8% male) were enrolled in this study. At ablation start, 62.9% of patients had moderate pain. When ablating specific regions, moderate pain and severe pain was encountered in 76.2% and 11.7% patients, respectively. Female patients had higher pain score than male patients at the followed 3 time-points: ablation start, ablating specific regions, and sheaths removal (z =-2.923, -4.349, -2.385, respectively, all P < 0.05). A negative correlation between the interoperative pain scales and the psychological resilience scales was confirmed at the time-point of before sedation, during ablation, ablating specific regions, and sheaths removal (r=-0.161, -0.464, -0.773, -0.352, respectively, all P < 0.05). Multivariable logistic regression analysis revealed that the strength and resilience dimensions of psychological resilience were significant protective factors against pain during radiofrequency ablation, with low levels of strength and tenacity associated with 2.32-fold and 2.17-fold increased risks of moderate pain, respectively, while optimism and clinical factors showed no significant effects. Most of AF patients undergoing radiofrequency ablation with conscious sedation and analgesia experienced significant intraoperative pain experience, particularly when specific cardiac regions were ablated. Enhancing psychological resilience before the procedure may help reduce intraoperative pain scores. This trial is registered on Mar 17th, 2022, in the Chinese Clinical Trial Registry (ChiCTR2200057810).

While very high-power short-duration (vHPSD) ablation has been shown to be safe and effective for ablation of atrial fibrillation, the utility of vHPSD ablation for targeting premature ventricular complexes (PVCs) remains unclear. We aimed to describe our experience of PVC ablation using vHPSD ablation targeting areas with suboptimal catheter contact. We included 8 patients (mean age 66.5 ± 11.3 years, 77% female gender, mean LV ejection fraction 52.8 ± 8.2%, baseline PVC burden 23.3 ± 10.1% [range 9-41%]) with PVCs originating from intracavitary structures [LV papillary muscle(s) (n = 7), RV papillary muscle (n = 1)] which were successfully eliminated with vHPSD ablation using a temperature-controlled ablation catheter (QDOT-MICRO; Biosense Webster, Irvine, California, USA) with lesions delivered at 90 W for 4 seconds using QMODE+ mode. Mean QMODE+ lesions delivered in each patient was 28 ± 15.1 with a mean total QMODE+ RF time of 112 ± 60.4 seconds. There were no procedural complications. Durable PVC suppression was confirmed on post-ablation monitoring in all patients (mean post-ablation PVC burden < 1% [range 0-2.3%]). Ablation with vHPSD using a temperature-controlled radiofrequency ablation catheter can be safe and effective for PVC ablation in regions with poor catheter stability such as RV and LV papillary muscles.

Introduction: Ischemic preconditioning (IP) is a method that may help protect the human heart from injury during cardiac surgery. It is believed that IP prepares the heart for upcoming prolonged ischemia by activating local protective mechanisms. Objective: This prospective study aims to evaluate the degree of myocardial protection offered by IP compared to standard cold blood cardioplegia (CBC). Materials and Methods: Fifty patients with stable angina and coronary artery disease (CAD) scheduled for coronary artery bypass grafting (CABG) were randomized into two groups: IP (n=25) and control (n=25). In the IP group, two cycles of 2-minute ischemia followed by 3-minute reperfusion were applied before aortic cross-clamping. Blood samples were collected through a central venous catheter to measure creatine kinase-MB fraction (CK-MB), creatine phosphokinase (CPK), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Postoperative cardiac rhythm was also monitored. Results: The release of cTnI and lactate was significantly lower in the IP group compared to the control group (cTnI p &lt; 0.0001, CK-MB p = 0.005, CPK p = 0.005). However, there was no significant difference in LDH levels between the groups (p = 0.264). The need for defibrillation after cardiac arrest was lower in the IP group compared to the control group (18% vs. 40%). Conclusion: The role of IP in cardiac surgery remains uncertain. However, compared to CBC alone in low-risk CABG patients, IP as an adjunct to CBC reduced levels of cTnI, CK-MB, and CPK, and was associated with a lower incidence of postoperative atrial fibrillation.

The RUNX family of transcription factors is critical for heart development, physiology, and cardiovascular disease. However, current models of transcription factor binding seldom incorporate RNA modifications, and the latest methods that include them remain limited. This gap impedes accurate profiling of transcription factor affinities. In particular, the role of m6A-mediated mechanisms in regulating RUNX factors during cardiac fibrosis is still poorly understood. RNA sequencing of human atrial fibrillation tissues identified transcription factors with enriched expression associated with cardiac gene expression. Cardiac fibroblast-specific Ythdf1 conditional knockout mice (Postn-Cre × Ythdf1flox/flox), along with Cre and wild-type controls, were subjected to ISO/TAC treatment to induce cardiac fibrosis. AAV9 vectors carrying Postn promoter-driven shRNA targeting Runx1 were administered to ISO-treated mice to evaluate its role in cardiac fibrosis. Multi-omics approaches including MeRIP-seq, single-cell RNA-seq, RNA-seq, and ChIP-seq, combined with histological and biochemical analyses, were employed to elucidate the mechanism by which YTHDF1 regulates Runx1 expression. Runx1 was reconstituted in Ythdf1-deficient cardiac fibroblasts and mouse hearts to assess its effects on fibroblast proliferation and fibrosis. Runx1 expression was elevated in human atrial fibrillation samples, experimental cardiac fibrosis models, and TGF-β1-stimulated cardiac fibroblasts. Fibroblast-specific Runx1 knockdown attenuated cytoskeletal remodeling, suppressed fibroblast proliferation, and inhibited cardiac fibrosis. Mechanistically, Runx1 upregulation was associated with increased m6A methylation on its mRNA. Site-specific m6A modification at peak_21317 was essential for promoting YTHDF1 binding to Runx1 mRNA and enhancing its translation. This led to increased transcriptional activation of connective tissue growth factor (Ctgf), promoting cytoskeletal reorganization and collagen deposition. Importantly, epitranscriptomic inhibition of Runx1 ameliorated experimental cardiac fibrosis. Our study reveals a novel epitranscriptomic pathway wherein YTHDF1 recognizes m6A-modified Runx1 mRNA, enhancing its translation and thereby stimulating RUNX1-mediated Ctgf transcription. This process drives cytoskeletal remodeling, cardiac fibroblast proliferation, and fibrosis in an m6A-dependent manner. These findings offer new perspectives for developing preventive strategies against cardiac fibrosis. These results indicate that YTHDF1 and transcription factor RUNX1 mRNA and protein levels were up-regulated during human AF and pathological cardiac fibrosis, demonstrate a clinically relevant role for the YTHDF1/RUNX1 axis in mitigating AF and cardiac fibrosis, and suggesting that targeting RUNX1 m6A RNA methylation may serve as a promising therapeutic strategy for treating AF and cardiac fibrosis.

Atrial fibrillation (AF) is associated with an increased risk of stroke and hypercoagulability. Coagulation factors mediate remodeling processes via protease-activated receptors (PARs) in various organs.We evaluated whether inhibition of factor Xa (FXa) via rivaroxaban protects against atrial structural remodeling in goats with persistent AF and explored FXa and thrombin hypertrophic effect on human iPSC-derived cardiomyocytes (hiPSC-CMs).Three groups of goats were tested: CTRL AF (control AF, n = 10), RIVA AF (rivaroxaban treatment during AF, n = 11), and SHAM (no AF, n = 10). Pacing-induced AF was maintained for 16 weeks. AF stability, hemodynamics, and AF complexity were assessed. Atrial samples were collected for histological and gene expression analyses. hiPSC-CM were stimulated with PAR-1 agonist TRAP14, FXa, or thrombin with and without their inhibitors. Pro-hypertrophic and pro-inflammatory gene expression was assessed by qRT-PCR after 24 hours.Rivaroxaban inhibited thrombin generation in RIVA AF goats (baseline: 249 ± 42 nM vs. final: 69 ± 33 nM). Sixteen weeks of AF induced atrial myocyte hypertrophy in CTRL AF (13.5 µm [95% CI: 12.9, 14.0] vs. SHAM: 12.5 µm [95% CI: 12.0, 13.0]) and pro-hypertrophic (NPPA: fourfold; NPPB: 22-fold) and pro-fibrotic (COL1A1: threefold) gene expression. Rivaroxaban fully prevented hypertrophy (12.2 µm [95% CI: 11.7, 12.7]) and downregulated inflammatory signaling without altering hemodynamics and AF stability. In hiPSC-CM, thrombin and TRAP14 induced overexpression of the pro-hypertrophic genes NPPA and NPPB. The PAR1 antagonist, SCH79797, prevented thrombin-induced NPPA and NPPB upregulation.Prolonged rivaroxaban treatment reduces thrombin generation, preventing AF-induced atrial myocyte hypertrophy through inhibition of PAR-1 signaling.

Abstract Background Elevated pulmonary capillary wedge pressure (PCWP) is known to drive atrial fibrillation (AF). However, it remains unknown if non-invasive Cardiovascular Magnetic Resonance (CMR) - derived PCWP could predict the future risk of AF. This study investigated whether a CMR-derived measure of PCWP could predict future AF. Methods We enrolled 202 participants (mean age 76.2±4.2 years) from the LOOP study, each receiving implantable loop recorder (ILR) for continuous rhythm monitoring over 4 years. CMR imaging quantified left atrial volume (LAV) and left ventricular mass (LVM), allowing calculation of a validated sex-specific equation derived PCWP. Cox proportional hazards analysis identified independent variables associated with incident AF. Results Eighty-six participants (42.6%) manifested AF during follow-up. Individuals with AF exhibited significantly higher CMR-PCWP (16.1±2.8 vs. 14.7±2.3 mmHg, p&amp;lt;0.01) and greater LAV. Univariate regression highlighted that PCWP ≥16 mmHg was significantly associated with incident AF (hazard ratio 2.73). Stepwise Cox regression confirmed that PCWP ≥16 mmHg and the CHARGE-AF score remained independently associated with AF, with PCWP conveying higher hazard ratio (2.88, p&amp;lt;0.001). Kaplan-Meier analysis reinforced the importance of this threshold for AF onset, demonstrating a significantly increased probability of arrhythmia over time and emphasising its decisive clinical impact. Conclusion Elevated CMR-PCWP is associated with AF in older, high-stroke-risk individuals, underscoring the role of subclinical diastolic dysfunction in promoting arrhythmogenesis. Incorporating non-invasive PCWP assessment into routine CMR evaluation may enhance risk stratification, allowing prompt identification of at-risk patients and enabling earlier, precise, targeted measures for AF prevention.

Background: The optimal timing of initiating direct oral anticoagulants (DOACs) after ischemic stroke in patients with atrial fibrillation (AF) remains uncertain. Early initiation may reduce recurrent stroke risk but raise concerns about hemorrhagic complications. This study aimed to evaluate the efficacy and safety of early versus later anticoagulation after ischemic stroke in AF. Methods: We systematically searched PubMed, EMBASE, CENTRAL, and Scopus from inception to May 22, 2025, for randomized controlled trials (RCTs) comparing early (≤4 days) versus later (5-14 days) DOAC initiation post-stroke in AF. Primary outcomes were recurrent ischemic stroke, symptomatic intracerebral hemorrhage (sICH), and all-cause mortality. Data were pooled using MetaXL (version 5.3) with a random-effects model. Heterogeneity was assessed using the Chi-square test and I 2 statistic. Results: Five RCTs (n = 6810) were included. Early anticoagulation showed a non-significant reduction in recurrent ischemic stroke (OR 0.80, 95% CI: 0.59-1.09; I 2 = 1%) and no significant difference in sICH (OR 0.92, 95% CI: 0.45-1.85; I 2 = 0%) or all-cause mortality (OR 0.94, 95% CI: 0.78-1.14; I 2 = 0%). Across all outcomes, heterogeneity was low and findings were consistent. Conclusion: Early initiation of DOACs after ischemic stroke in AF appears safe and may modestly reduce stroke recurrence without increasing hemorrhagic or mortality risk. These findings support individualized decision-making and suggest that early anticoagulation is a reasonable strategy in appropriately selected patients.

It is observed that some atrial fibrillation (AF) patients develop right heart enlargement and severe right heart failure, which affect the prognosis. An abnormal right atrioventricular coupling index (RACI) indicates that AF has led to significant right atrial and right ventricular dysfunction. However, right atrial (RA) remodeling in AF patients is rarely assessed and data on the prognosis of RA is limited. This study aims to determine if the RACI can be used to predict the risk of long-term adverse outcomes in a cohort of patients with non-valvular AF after catheter ablation (CA). A total of 123 non-valvular AF patients who underwent CA in our center were enrolled in this retrospective study. Conventional and speckle tracking echocardiography (STE) were performed for AF patients before CA. Patients were followed up with until April 2025. The adverse outcomes were the composite of atrial tachyarrhythmia recurrence (ATa), stroke or transient ischemic attack (TIA), AF-associated hospitalization, pacemaker insertion and cardiovascular death. Logistic regression analysis was used to determine the optimal cutoff value of correlates for predicting adverse events. The median follow-up time was 5.3(1.6-5.5) years. Among the 123 AF patients, 69 experienced adverse outcomes. Multivariable logistic regression analysis showed that RACI and left atrial ejection fraction (LAEF) were the independent predictors of adverse events (95% CI, 0.643-0.806; P < 0.0001 and 95% CI, 0.628-0.795; P < 0.0001; respectively). The optimal cutoff values of RACI and LAEF were 70.97% and 35%, respectively. Spearman's correlation analysis showed that RACI was negatively correlated with RA reservoir strain and RA boost strain (r=-0.583, P < 0.001; r=-0.572, P < 0.001, respectively), and LAEF was positively correlated with LA reservoir strain and LA boost strain (r = 0.859, P < 0.001; r = 0.765, P < 0.001, respectively). Increased RACI and impaired LAEF are strongly associated with long-term outcomes, with RACI showing better independent predictive value.

Reducing AF-related symptoms and improving health-related quality of life (HRQoL) are important drivers in the decision for pulmonary vein isolation (PVI) in treating symptomatic atrial fibrillation (AF). We assessed the association between various patient characteristics, intervention, and outcome variables, and HRQoL both prior to and one year after PVI, with specific attention to groups that did not improve or were still impaired in HRQoL post PVI. Observational, retrospective multicenter cohort study within 8hospitals participating in the Netherlands Heart Registration (NHR). Patients who underwent PVI between 2016 and 2019 and completed the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire both prior to and one year after were included. Accepted cut-off values for impaired HRQoL and clinically important difference (CID) were used. Mean AFEQT score (n = 2,534) was 55.6 ± 19.7 prior to intervention and 79.8 ± 20.2 after. Post-PVI, 39.5% of the population was still impaired in HRQoL (< 80points), and 19.2% failed to achieve CID (delta ≥ 5points). Lower baseline AFEQT-score (odds ratio [OR], 0.96 [per 1‑point increase]; 95% CI, 0.96-0.97; p < 0.001) and female sex (odds ratio [OR], 1.42; 95% CI, 1.16-1.75; p < 0.001) were the most prominent related factors with impaired HRQoL post-PVI. Higher baseline AFEQT-score (odds ratio [OR], 1.04 [per 1‑point increase]; 95% CI, 1.04-1.05; p < 0.001) was strongly associated with failure to achieve CID. Despite amajor increase in HRQoL across the population, over one-third of patients were still impaired in HRQoL post-PVI. Multiple factors were identified that may guide counselling of AF patients about treatment choice.

Arrhythmogenic fibrotic substrates facilitate reentrant activity in the atria, contributing to the perpetuation of atrial fibrillation (AF). Catheter ablation may disrupt existing reentrant pathways but can also create new ones. This longitudinal study aimed to assess whether post-ablation AF recurrence is associated with incomplete elimination of native arrhythmogenic substrates or emergence of new arrhythmogenic substrates created by ablation lesions, addressing important questions in current AF management: why some patients experience recurrence post-ablation while others do not, and whether ablation lesions themselves contribute to post-ablation arrhythmogenesis. Biatrial digital twins (DTs) derived from pre- and post-ablation contrast-enhanced MRI were used to evaluate the arrhythmogenic propensity of the fibrotic substrate - quantified by potential reentry-sites (PRs) and a vulnerability index (VI) reflecting reentry inducibility. Pre- and post-ablation DT pairs were generated for 11 patients who experienced AF recurrence (R-DTs) and 11 who did not (N-DTs). In total, 58 pre-ablation PRs and 32 post-ablation PRs were detected, with a nearly even distribution of PRs between the LA and RA both pre- and post-ablation. Pre-ablation VI was similar between N-DTs and R-DTs; however, post-ablation VI was significantly higher in R-DTs (P = 0.015). N-DTs exhibited a marked reduction in PRs following ablation, whereas R-DTs did not (P = 0.017). Both groups had few residual PRs from pre- to post-ablation, but R-DTs had many newly emergent PRs. In R-DTs, emergent PRs in the RA were accompanied by a post-ablation increase in RA fibrotic burden. In the LA, where lesions were delivered, all post-ablation reentries anchored around ablation-induced scar (ScAReentries). ScAReentries were significantly more inducible than those occurring within fibrotic substrate and were nearly three times more prevalent in R-DTs, accounting for the elevated post-ablation VI. In DTs, emergent PRs in both atria underlie AF recurrence post-ablation, with ablation itself creating some PRs of high arrhythmogenic propensity.