The Efficacy of Delayed Enhancement MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation of Atrial Fibrillation randomized trial showed no difference in atrial fibrillation (AF) recurrence with additional delayed enhancement magnetic resonance imaging (DE-MRI) fibrosis-targeted ablation to pulmonary vein isolation (PVI) in persistent AF.

We evaluated the effect of lesion delivery on ablation-induced scarring and AF recurrence.

Lesions delivered, targeting fibrotic and nonfibrotic areas identified from preablation DE-MRI, were studied in relation to ablation-induced scarring on 3-month DE-MRI, including their association with arrhythmia recurrence.

A total of 593 patients treated with radiofrequency were analyzed: 293 (49.4%) underwent PVI and 300 (50.6%) underwent additional fibrosis-guided ablation. Lesion analysis showed that 80.9% in the MRI fibrosis-guided group vs 16.5% in the PVI group (P < .001) had ≥40% of baseline fibrosis targeted. MRI assessment of ablation-induced scar showed that 44.8% of fibrosis-guided ablation and 15.5% of PVI had ≥40% of their fibrosis covered by scar (P < .001), demonstrating significant attenuation from lesions delivered to scar formed. In the overall population, fibrosis coverage with scar was not associated with recurrence (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.80-1.01; P = .08 per 20% increase). In patients with baseline fibrosis < 20%, fibrosis coverage with scar was associated with lower recurrence than PVI (HR 0.85; 95% CI 0.73-0.97; P = .03), whereas the association was not significant when baseline fibrosis ≥ 20% (HR 0.97; 95% CI 0.80-1.17; P = .77). Significant center variation was observed in fibrosis targeting and coverage with scarring.

Radiofrequency ablation lesions do not uniformly result in scar formation. A post hoc analysis suggests reduced arrhythmia recurrence when ablation-induced scarring covers fibrotic regions in patients with low baseline fibrosis.

Sepsis-induced atrial fibrillation (AF) is driven by systemic inflammation and macrophage-mediated atrial remodeling, with proinflammatory M1 macrophages playing a key role. This study investigates whether GTS-21, an α7nAChR agonist, can reduce AF susceptibility by promoting macrophage polarization towards the anti-inflammatory M2 phenotype.

A mouse model of lipopolysaccharide (LPS) (10 mg/kg)-induced sepsis was used to explore the relationship between atrial inflammation and AF. GTS-21 (20 mg/kg) was administered to assess its impact on 48-h survival and AF incidence. Cardiac function was evaluated using echocardiography. Markers of myocardial injury, including CK-MB, LDH, and cTnI, were measured. Macrophage polarization and atrial inflammation were assessed using immunofluorescence, flow cytometry, RT-qPCR, and western blotting. Oxidative stress and mitochondrial function were evaluated using reactive oxygen species (ROS) measurements, electron microscopy, and mitochondrial protein expression analysis. Calcium dynamics were studied using western blotting and confocal microscopy.

In LPS-induced septic mice, GTS-21 improved 48-h survival rates and reduced the induction rate and duration of AF (P < 0.05). Echocardiography showed a preserved left ventricular ejection fraction and enhanced diastolic function. Mechanistically, it promoted M2 macrophage polarization, inhibited the NF-κB P65/NLRP3/C-caspase 1 pathway to reduce IL-1β release, and alleviated oxidative stress. Additionally, mitochondrial structure was restored by reversing fission and promoting fusion, while calcium-handling proteins (NCX-1, RYR2, and SERCA2a) were regulated to prevent intracellular calcium overload, reducing AF susceptibility.

GTS-21 mitigated atrial inflammation and reduced the incidence of AF in mice with sepsis by regulating macrophage polarization, reducing oxidative stress, and preserving mitochondrial and calcium dynamics in cardiomyocytes. These findings highlight the therapeutic potential of GTS-21 in treating sepsis-induced AF.

Atrial fibrillation (AF) is a common arrhythmia with irregular atrial electrical activity. Circular RNAs (circRNAs) are key regulators in tissue homeostasis, yet their role in AF remains unclear. Here, we investigated the expression and function of circNAB1 in AF using high-throughput sequencing and functional assays in circNAB1 transgenic mice. We identified circNAB1 as a significantly downregulated circRNA in AF patient specimens. Silencing circNAB1 promoted collagen deposition and inflammation, whereas overexpression reduces atrial fibrosis and AF susceptibility in mice, consistent with results observed in human atrial tissues. Mechanistically, circNAB1 translates into a novel protein, NAB1-356, which is highly expressed in human cardiac hypertrophy. NAB1-356 interacts with EGR1 as NAB1 does, decreasing fibrosis and inflammation in the atrium. Furthermore, NAB1-356 also regulates transcription factor Runx1 and Gadd45b transcription, exerting regulatory effects on cytokine expression and fibrosis. Targeting EGR1, Gadd45b, and Runx1 by circNAB1 or siRNAs attenuate AF incidence and cardiac remodeling, suggesting potential therapeutic strategies for AF management. Delivery of circNAB1 improves AF conditions in LKB1 knockout mice, further highlighting its anti-arrhythmic potential. Our findings elucidate the mechanistic role of circNAB1 in AF pathogenesis and suggest its therapeutic implications for cardiac remodeling-associated disorders.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and many ultimately to advanced heart failure. The mechanisms by which this progression occurs are poorly understood. In this exploratory study, we sought to provide insight into the physiologic changes associated with the development of early CCC.

We used RNA sequencing to analyse the gene expression changes in the peripheral blood of six patients with Chagas disease with early structural heart disease, four patients with Chagas disease without any signs or symptoms of disease, thirteen patients without Chagas disease with early structural heart disease, and ten patients without Chagas disease or signs of heart disease. Pathway analyses and immune cell deconvolution were employed to further elucidate the biological processes underlying early CCC development.

Our analysis suggests that early CCC is associated with a downregulation of various peripheral immune response genes, including changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes appear to be distinct from those of non-Chagas cardiomyopathies.

This work highlights the potential importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease and how it may differ from other cardiomyopathies. The changes we have identified may serve as biomarkers of early CCC and could inform future longitudinal cohort studies of markers of disease progression and strategies for the treatment of CCC in its early stages.

NIH, FONDECYT, IDSA, NSF.

Atrial fibrillation (AF) recurrence after catheter ablation poses a persistent clinical challenge. This study investigates the predictive value of left atrial posterior (LA-P) volume and the posterior-anterior volume ratio (PAVR) using computed tomography angiography (CTA).

This study aimed to assess the predictive significance of LA-P volume and PAVR for AF recurrence using CTA in patients undergoing catheter ablation.

A retrospective cohort of 365 patients who underwent AF ablation was analyzed. CTA assessed LA-P volume, left atrial anterior volume, left atrial appendage volume, and PAVR. AF recurrence was the primary outcome. Kaplan-Meier survival analysis, multivariate Cox proportional hazards regression, and restricted cubic spline analyses evaluated associations between volumetric indices and AF recurrence.

LA-P volume was positively associated with AF recurrence in a linear pattern (P < .001). Patients in the highest LA-P volume quartile had significantly higher recurrence rates (log-rank P < .001), with a multivariate adjusted hazard ratio (aHR) of 2.90 (95% confidence interval [CI] 1.49-5.66; P for trend = .005) compared with the lowest quartile. Per standard deviation increment, LA-P volume was associated with a 42% increased recurrence risk (aHR 1.42; 95% CI 1.16-1.72). PAVR was independently linked to recurrence (aHR per standard deviation increment 1.35; 95% CI 1.15-1.58; P < .001).

LA-P volume and PAVR are significant predictors of AF recurrence, underscoring the importance of regional atrial volumetric assessments to refine risk stratification and inform personalized treatment strategies for patients undergoing AF ablation.

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.

To investigate the relationship between left atrium (LA) and epicardial adipose tissue (EAT) parameters and different disease severities (paroxysmal and persistent) in patients with atrial fibrillation (AF). A total of 115 patients with AF (58 paroxysmal and 57 persistent) who underwent cardiac computed tomography angiography (CTA) at our institution between October 2021 and May 2022 were included. The left atrium volume index (LAVI) and left atrium fractal dimension (LAFD) were measured for each patient. EAT volumes and attenuation values for total heart and LA in early and delayed enhancement phases were calculated using semi-automated software. LA and EAT parameters were compared with patients with paroxysmal and persistent AF. Compared with paroxysmal AF, persistent AF had significantly greater LAVI (33.60 ml/m2 vs. 26.65 ml/m2, P < 0.001) and LAFD (1.31 vs. 1.22, P = 0.001). At both early and late enhancement, the total EAT volume (136.29 cm3 vs. 88.68 cm3, 152.30 cm3 vs. 88.96 cm3; all P < 0.001) and attenuation values (-84.00 HU vs. -87.50 HU, -83.00 HU vs. -86.00 HU; all P < 0.05) were significantly higher in persistent AF than in paroxysmal AF. Additionally, LA EAT volumes (15.53 cm3 vs. 8.19 cm3, 18.57 cm3 vs. 9.26 cm3; all P < 0.001) and attenuation values (-74.00 HU vs. -77.00 HU, -75.00 HU vs. -77.00 HU; all P < 0.05) were significantly larger in persistent AF compared with paroxysmal AF, in both early and late enhancement phases. Correlation analysis showed that both LA (r = 0.381, 0.310; P < 0.05) and EAT parameters (r = 0.524, 0.334, 0.665, 0.208, 0.537, 0.223, 0.606, 0.276; P < 0.05) were positively associated with AF severity. Both EAT (volume and attenuation values) and parameters for assessing LA size and morphology, including LAVI and LAFD, were related to the severity of AF.

Postoperative atrial fibrillation (POAF) is a common complication after off-pump coronary artery bypass grafting (OPCABG), associated with increased morbidity and healthcare costs. Existing POAF prediction models, developed mainly for Western populations, may not account for genetic, lifestyle, and healthcare disparities in Chinese patients. This study aimed to develop and validate a Chinese-specific nomogram for POAF risk stratification in OPCABG patients.

A retrospective cohort study was conducted at a single Chinese center, including 456 consecutive OPCABG patients (2018-2022). Patients were divided into a training set (2018-2021, n = 319) and validation set (2022, n = 137). Multivariable logistic regression with LASSO regularization identified predictors of POAF (occurrence within 7 postoperative days). Model performance was evaluated using C-index, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC).

The final nomogram included five independent predictors: age (OR, 1.03), diabetes (OR, 1.85), hypertension (OR, 1.90), previous PCI (OR, 2.51) and last intraoperative blood potassium concentration (OR, 0.30). The model demonstrated excellent discrimination (C-index: 0.809 in training, 0.886 in validation) and good calibration. DCA and CIC showed superior clinical utility compared with existing scores (C2HEST, CHADS2, CHA2DS2-VASc).

This OPCABG-specific nomogram outperforms conventional risk scores in predicting POAF in Chinese patients, enabling personalized prophylaxis and resource allocation. External validation in diverse populations is needed to confirm generalizability.

Neutrophils, the most abundant leukocytes in human blood, have long been recognized as critical first responders in the innate immune system's defense against pathogens. Some of the more notable innate antimicrobial properties of neutrophils include generation of superoxide free radicals like myeloperoxidase, production of proteases that reshape the extracellular matrix allowing for easier access to infected tissues, and release of neutrophil extracellular traps, extruded pieces of DNA that ensnare bacterial and fungi. These mechanisms developed to provide neutrophils with a vast array of specialized functions to provide the host defense against infection in an acute setting. However, emerging evidence over the past few decades has revealed a far more complex and nuanced role for these neutrophil-driven processes in various chronic conditions, particularly in cardiovascular diseases. The pathophysiology of cardiac diseases involves a complex interplay of hemodynamic, neurohumoral, and inflammatory factors. Neutrophils, as key mediators of inflammation, contribute significantly to this intricate network. Their involvement extends far beyond their classical role in pathogen clearance, encompassing diverse functions that can both exacerbate tissue damage and contribute to repair processes. Here, we consider the contributions of neutrophils to myocardial infarction, heart failure, cardiac arrhythmias, and nonischemic cardiomyopathies. Understanding these complex interactions is crucial for developing novel therapeutic strategies aimed at modulating neutrophil functions in these highly morbid cardiac diseases.

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world and can cause serious complications such as stroke or heart failure. Paroxysmal atrial fibrillation (PAF), a subtype of AF, accounts for approximately 25% of AF cases and is estimated to affect approximately 30 million people worldwide. Despite extensive genetic research on AF, the genetic factors involved in PAF in East Asian (EAS) populations remain unidentified. The aim of our study was to identify genetic factors associated with PAF in the Japanese population, contributing to our understanding of the genetic architecture of AF in Japanese populations. We conducted whole-exome sequencing on a cohort of 1176 PAF individuals and 1172 non-PAF control subjects in a Japanese population. We processed the sequencing data in accordance with the best practices outlined in the Genome Analysis Toolkit (GATK) and conducted gene-based association tests under three variant grouping strategies (masks) using the burden test, SKAT, and SKAT-O. We then performed a meta-analysis of the resulting P-values, which revealed that four genes-ZNF785, SMPD3, GFRA4, and LGALS1-were significantly associated with PAF, representing novel findings. These findings provide new insights into PAF pathogenesis and suggest potential biomarkers for early detection.

Cardiac arrhythmias pose a major public health problem, and pharmacologic intervention remains key to their therapy. The 1970 landmark Vaughan Williams (VW) classification utilizing known actions of then available antiarrhythmic drugs (AADs) became and remains central to management, but it requires revision in response to extensive subsequent advances. Our modernized AAD classification reflected and sought to facilitate such fundamental physiological and clinical development. Here we respond to requests for an adaptation of our scheme specifically focused on clinical practice. (1) This adaptation improves the accessibility of our original scheme to clinical practice, focusing on key AADs in clinical use rather than investigational new drugs (INDs) while conserving and encompassing the classic VW scheme. (2) We preserve a rational conceptual framework based on current understanding of the relevant electrophysiological events, their underlying cellular or molecular cardiomyocyte targets, and the functional mechanisms they mediate. (3) The adopted subclasses within each AAD class parallel clinical practice by including only subclasses containing established AADs, or approved potential off-label drugs, as opposed to those only including INDs. (4) The simplified scheme remains flexible, permitting drugs to be placed in multiple classes where required, and the addition of classes and subclasses in light of future investigations and clinical approvals. Thus, we derive from our comprehensive modernized AAD classification a more focused and simpler scheme for clinical use. This both modernizes yet preserves the classic VW classification and remains flexible, thus accommodating future developments.

Atrial inflammatory and metabolic derangements have been reported in patients with atrial fibrillation (AF).

We sought to evaluate the association of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) in the left and right atria and AF.

We conducted a systematic review and meta-analysis, using the PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of studies involving patients undergoing FDG-PET scans with reported atrial or ventricular uptake and outcomes of AF. Data were pooled and analyzed, and FDG uptake in AF and non-AF patients was compared using odds ratios (ORs).

Six studies (4 retrospective, 1 prospective, and 1 case-control) were included in the meta-analysis of studies on patients not meeting diagnostic criteria for cardiac sarcoidosis (CS): 832 patients with a mean age of 67 years, 62% male, and 53% with hypertension. AF patients demonstrated higher odds of FDG uptake in the left atrium (pooled OR 14.50, 95% confidence interval 6.78-31.02; P < .0001, I 2 = 0) and right atrium (pooled OR 51.98, 95% confidence interval 22.77-118.63, P < .0001, I 2 = 0). Two studies on patients met diagnostic criteria for CS: one did not report atrial uptake and the other did not demonstrate a statistically significant association between right or left atrial uptake in AF patients.

In patients undergoing FDG-PET without meeting CS diagnostic criteria, FDG uptake in the atria was strongly associated with AF, suggesting altered metabolism or inflammation in AF pathophysiology and risk assessment.

Obesity is a significant risk factor for atrial fibrillation (AF), but the mechanisms by which obesity contributes to AF are not fully understood. Recent studies have indicated that the Stimulator of Interferon Genes (STING) signalling, mediated by mitochondrial damage, plays a crucial role in cardiac remodelling in various metabolic and cardiovascular diseases. This study aims to explore the role of STING in obesity-mediated AF and its potential mechanisms.

In this study, rats were divided into four groups: two groups received tail vein injections of AAV9-cTnT-STING siRNA and were fed either a normal diet or a high-fat diet (HFD) for 12 weeks; the other two groups received injections of AAV9-cTnT-NC siRNA and were similarly fed either a normal diet or a HFD. The atrial STING signalling, AF vulnerability, electrical remodelling, and substrate remodelling were assessed in all groups. Results showed that the induction of AF was increased in obese rats, accompanied by severe mitochondrial damage and upregulation of the STING inflammatory signalling cascade. STING activation was associated with atrial fibrosis, cardiomyocyte apoptosis, and substrate remodelling, including alterations in the gap junction protein CX40 and ion channels. Additionally, STING was linked to excessive calcium transfer from the endoplasmic reticulum to the mitochondria. Knockdown of STING prevented AF vulnerability and both electrical and substrate remodelling in obese rats.

Mitochondrial damage-mediated activation of the STING signalling pathway promotes obesity-induced atrial remodelling and the occurrence of AF.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. New treatments are needed to cardiovert recent-onset paroxysmal AF quickly and safely. RESTORE-1 was a multicentre, randomized, double-blind, placebo-controlled trial of a 120 mg orally inhaled solution of flecainide acetate (FlecIH-103) for cardioversion of symptomatic, recent-onset (≤48 h) paroxysmal AF. The study aim was to evaluate the efficacy and safety of FlecIH-103 administered via oral inhalation.

Patients experiencing a recent-onset paroxysmal AF episode were randomized to receive a single dose of FlecIH-103 or placebo delivered over two 3.5 min inhalation periods, while patients were monitored using 12-lead electrocardiograms and Holter. The trial was stopped prematurely after treating 55 patients, due to lower-than-expected conversion rates and plasma levels. Mean age was 59.6 years, 31.5% of patients were female, and 59.2% were having their first AF episode. Conversion rate was 30.8% (95% confidence interval: 14.7-43.8) for the active group (n = 39) and 0.0% for the placebo group (n = 12) (P = 0.04). Median time to conversion was 12.8 min (IQR: 17.2). In the active group, the mean flecainide plasma level was 198 ng/mL (SD: 156), which is ∼50% lower than in the previous studies. The most common adverse events (AEs) were dysgeusia, dyspnoea, and cough. All AEs were short-lasting and of mild or moderate intensity.

Despite early termination of the trial, FlecIH-103 was significantly more effective than placebo in cardioverting AF. Safety data did not show any serious AEs. Further studies of FlecIH-103 are needed to optimize the combination of drug formulation and inhalation delivery platform.

URL: https://clinicaltrials.gov, unique identifier: NCT05039359.

Atrial fibrillation (AF) is the most common arrhythmia in humans, affecting more than 40 million people worldwide. Radiofrequency catheter ablation (RFCA) was first introduced as a treatment for AF by Haïssaguerre M in the late 1990s. This procedure quickly became the treatment of choice, especially for symptomatic patients with AF refractory to medication. However, up to 45% of patients may experience AF recurrence within 12 months after RFCA. In this setting, AF recurrence is likely multifactorial, including atrial remodeling, local fibrosis or incomplete ablation due to failure in locating the trigger. Additionally, patients with obesity, sleep apnea, hypertension, or diabetes are at an increased risk of AF recurrence after RFCA. Inflammation is increasingly recognized as a potential key factor in AF recurrence and may arise both from the healing response of heart tissue post-ablation or from chronic low-grade inflammation, as observed in many risk factors. Here, we present an original study by Wang et al, which investigated the combination of the systemic immune-inflammation index-a marker developed to assess overall inflammatory status-and the APPLE score, designed to predict AF recurrence following RFCA. The study found that using both indicators together improved the accuracy of AF recurrence prediction. These findings underscore the significant role of inflammation in cardiovascular disease and demonstrated its impact on AF recurrence after RFCA. Further research is warranted to validate the combined use of these two scores in clinical settings for predicting AF recurrence following catheter ablation.

Atrial fibrillation (AF), the most prevalent tachyarrhythmia worldwide, is a complex condition influenced by genetic, structural, and environmental factors. While AF in the elderly is often associated with underlying cardiac disease, early-onset or "lone" AF (LAF) exhibits a stronger genetic predisposition. Studies have identified both monogenic and polygenic contributors to AF risk. Monogenic mutations, inherited in Mendelian patterns, often affect ion channels and regulatory proteins, while polygenic variants modulate susceptibility and interact with environmental factors. Genome-wide association studies (GWAS) and exosome-wide association studies (ExWAS) have expanded our understanding of AF genetics, identifying numerous susceptibility loci, though challenges remain in linking these variants to specific molecular mechanisms. Pathophysiologically, AF results from a balance of triggers, drivers, and substrates. Triggers, such as ectopic foci in the pulmonary veins, initiate AF episodes, while structural and electrical remodeling perpetuates the arrhythmia. Fibrosis, atrial dilation, and tachycardia-induced remodeling promote reentry circuits and irregular conduction, increasing AF vulnerability. The interplay between genetic predisposition and remodeling processes underscores the complexity of AF maintenance, particularly in persistent AF forms. Emerging insights into AF genetics and pathophysiology highlight the need for personalized approaches to its prevention and management. Understanding genetic risk, combined with targeted therapies addressing structural and electrical remodeling, holds promise for improved patient outcomes. Future research into AF's molecular and genetic mechanisms will be key to advancing precision medicine in this field.

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.

This review comprehensively examines the diverse roles of noncoding RNAs (ncRNAs) in the pathogenesis and treatment of cardiovascular disease (CVD), focusing on microRNA (miRNA), long noncoding RNA (lncRNA), piwi-interacting RNA (piRNA), small-interfering RNA (siRNA), circular RNA (circRNA), and vesicle-associated RNAs. These ncRNAs are integral regulators of key cellular processes, including gene expression, inflammation, and fibrosis, and they hold great potential as both diagnostic biomarkers and therapeutic targets. The review highlights novel insights into how these RNA species, particularly miRNAs, lncRNAs, and piRNAs, contribute to various CVDs such as hypertension, atherosclerosis, and myocardial infarction. In addition, it explores the emerging role of extracellular vesicles (EVs) in intercellular communication and their therapeutic potential in cardiovascular health. The review underscores the need for continued research into ncRNAs and RNA-based therapies, with a focus on advancing delivery systems and expanding personalized medicine approaches to improve cardiovascular outcomes.

Negative emotions can have a significant impact on individuals, which then influences their cardiovascular system. However, the underlying pathophysiological mechanisms and clinical implications of this association remain inadequately defined. A narrative review of pertinent literature was conducted to examine the pathophysiology, clinical manifestations, and treatment related to the interplay between emotions and conditions such as takotsubo cardiomyopathy, atherosclerosis, acute plaque rupture, and cardiac arrhythmias. Negative emotions can instigate a chronic stress response, which in turn heightens sympathetic nervous system activity and increases vulnerability to cardiovascular diseases. This intricate relationship between emotional states and cardiovascular health underscores the necessity for targeted lifestyle interventions and clinical strategies aimed at mitigating the adverse effects of negative emotions.

Atrial arrhythmia is the most common complication in the adult congenital heart disease population, and with an aging population, atrial fibrillation is rapidly increasing in prevalence-particularly in those with concomitant heart failure. There is much to be determined regarding the pathophysiology of atrial fibrillation in the adult congenital heart disease population, but it is likely linked to the congenital heart defects, shunts, surgical patches, and coexisting hemodynamic lesions associated with the congenital heart disease process and physiology. This review focuses on the management of atrial fibrillation and heart failure in patients with adult congenital heart disease.

Atrial fibrillation (AF) is the most common arrhythmia in the United States and the most common cause of embolic cerebrovascular events, with the majority of these thrombi originating in the left atrial appendage. The left atrial appendage (LAA) has separate developmental, ultrastructural, and physiological characteristics from the left atrium. Although LAA anatomy is highly variable, it can be categorized into 4 types: cactus, cauliflower, chicken wing, and windsock. The cauliflower type is associated with higher stroke risk in patients with nonvalvular AF. Although the cornerstone of therapy to prevent embolic strokes from AF has been anticoagulation with thrombin inhibitors, a large group of patients are unable to tolerate anticoagulation due to bleeding. This has led to the development and advancement of multiple surgical and percutaneous LAA closure devices to prevent embolic cerebrovascular accidents without the need for anticoagulation. In this article, we discuss the outcomes of major studies that utilized surgical LAA occlusion and its effectiveness. Furthermore, we summarize nonsurgical methods of LAA closure and future directions regarding LAA closure.

Atrial fibrillation and heart failure are common cardiovascular conditions that are intricately linked to each other, with a significant impact on morbidity, mortality, and quality of life. These two conditions can create a vicious pathophysiologic milieu associated with neurohormonal changes, elevated cardiac filling pressure, myocardial remodeling, systemic and regional inflammation, fibrosis, and diminished myocardial contractility. It is well known that cardiomyopathy can cause atrial fibrillation and vice-versa, but often it is difficult to sort which came first. Unfortunately, the disease burden will only continue to rise with an aging population, and understanding the epidemiology of the disease and the interplay of these two conditions is vital to improved patient care.

Dyslipidemia is a metabolic disorder characterized by quantitative and/or qualitative abnormalities in serum lipid levels. Elevated serum cholesterol levels can modify the turnover and recruitment of ionic channels in myocytes and cellular homeostasis, including those of inflammatory cells. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling, which is the substrate of atrial fibrillation (AF). Data about the association between increased lipid serum levels and AF are few and contrasting. Lipoprotein (a), adiposity, and inflammation seem to be the main drivers of AF; in contrast, low-density lipoproteins, high-density lipoproteins and triglycerides are not directly involved in AF onset. The present review aimed to describe the pathophysiological link between dyslipidemia and AF, the efficacy of lipid-lowering therapies in atherosclerotic cardiovascular disease (ASCVD) patients with and without AF, and the impact of lipid-lowering therapies on AF incidence.

Fibrillatory wave amplitude (fWA) on 12-lead ECG predicts the outcome of ablation in atrial fibrillation (AF). We hypothesized that changes in fWA following wide circumferential isolation of pulmonary veins (WPVI) in persistent AF (peAF) is a better predictor of ablation outcome compared to baseline fWA.

Eighty-nine patients (sustained peAF 7 ± 7 months) underwent a first-time WPVI. Sixty-second ECG signals devoid of QRST waves were recorded at baseline and at the end of the WPVI (endWPVI). fWA for each ECG lead and mean fWA (meanfWA) across the 12-lead ECG were computed. Patients with recurrence after the index WPVI underwent a redo to ensure complete PVI. The primary endpoint was long-term AF freedom OFF antiarrhythmics drugs (AADs) after one or two WPVI (SUCCESS group). The FAILURE group was defined as AF recurrence post-redo.

Over a mean follow-up of 35 ± 10 months, freedom from AF OFF AADs was achieved in 61% (SUCCESS group), while 29% had AF recurrence after redo WPVI (FAILURE group). The SUCCESS group showed significantly higher fWA values in ECG leads V1, V4, and V5 at baseline (p < 0.05), as well as in leads III, aVL, aVF, and V4, and in meanfWA at endWPVI (p < 0.05) compared to the FAILURE group. A baseline mean fWA ≥ 0.044 mV or a decrease in mean fWA ≤ 11% following WPVI predicted long-term sinus rhythm restoration with a sensitivity of 81% and a specificity of 69% (p < 0.05).

Low fWA values and a significant reduction in fWA following WPVI are associated with a high risk of AF recurrence in patients with peAF.

Over the past fifty years, the incidence of atrial fibrillation (AF) has tripled. Traditionally, the main treatment for this condition has been pulmonary vein isolation (PVI) performed using radiofrequency catheter ablation (RFCA). However, another technique known as cryoballoon ablation (CBA) has been developed as another option for managing this heart rhythm disorder. This study evaluated the efficacy and safety of CBA and RFCA for the treatment of AF.

This study compared the safety and effectiveness of CBA and RFCA for the treatment of AF using a thorough review of randomized controlled trials up until June 1, 2023.

The results revealed that CBA and RFCA had similar effectiveness and safety profiles in achieving freedom from AF (RR: 1.00; 95% CI: 0.93 to 1.07, p = 0.99) and paroxysmal atrial fibrillation (PAF) (RR: 0.99; 95% CI: 0.89 to 1.10, p = 0.79). CBA was faster (MD =  - 23.99; 95% CI: - 32.98 to - 15.00; p < 0.00001) with a higher risk of phrenic nerve palsy (RR = 6.88; 95% CI: 3.26 to 14.50, p < 0.00001). Acute PVI rate (RR = 1.0; 95% CI: 0.99 to 1.01, p = 0.95), overall complications (RR = 1.37; 95% CI: 0.93 to 2.01, p = 0.11), pericardial effusion (RR = 0.59; 95% CI: 0.25 to 1.41, p = 0.24), and fluoroscopy time (MD = 1.63; 95% CI: - 2.06 5.32; p = 0.39) did not significantly differ between the two procedures.

CBA and RFCA offer similar outcomes for patients with AF and PAF, with CBA being quicker but carrying a slightly higher risk of phrenic nerve palsy.

Pulmonary vein isolation (PVI) is effective in treating atrial fibrillation (AF), but outcomes are worse for persistent AF (persAF) patients than paroxysmal AF (PAF) patients. The study aimed to identify differences in left atrial (LA) and left atrial appendage (LAA) anatomy in different AF types.

In a single-center observational study, a blinded retrospective analysis of preprocedural cardiac computed tomography angiography (CCTA) images was performed. The study evaluated the dimensions of the LA and pulmonary veins (PV), as well as the size and morphology of the LAA using a 3D electroanatomical mapping system.

Between 2012 and 2016, a total of 1103 patients underwent second-generation cryoballoon PVI. Of these, 725 patients (65.7%) had CCTA available, and 473 of these (65.2%) had sufficient quality for measurements. The mean age of the patients was 66.3 ± 9.5 years, and PAF was present in 277 (58.6%) participants. The study found that in persAF patients, LA dimensions such as LA volume [mL] (108; 125; p < .001) or PV ostial dimensions were significantly larger than in those with PAF. LAA volume [mL] (8.3; 9.2; p = .005) and LAA ostial area [mm2] (325; 353; p = .01) were enlarged in persAF. There were no significant differences regarding LAA morphology, with the overall distribution being "windsock" (51%), "chicken-wing" (20%), "cauliflower" (15%), and "cactus" (13%).

Compared to PAF, persAF patients had significantly larger LA as well as LAA dimensions. LAA morphological types were distributed equally in both groups suggesting that LAA morphology may not be associated with the underlying AF type.

We present a case series of patients with granulomatous myocarditis presenting as atrial arrhythmias accompanied by lymphadenopathy.

Atrial myocarditis (AM) may be the cause of atrial fibrillation (AF) in patients without risk factors.

Patients with atrial fibrillation without risk factors underwent 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET). We performed biopsy of lymph nodes or myocardium in patients with atrial uptake of 18F-FDG-PET.

AM was observed in 15 patients. The median age of the patients was 42 years and left ventricular ejection fraction (LVEF) at presentation was 45%. All patients had AF, atrial flutter was noted in 4 patients (26.7%) and 2 patients (13.3%) had atrioventricular nodal reentrant tachycardia (AVNRT). 18F-FDG-PET uptake was noted in the atria in all patients and in the ventricles in 3 patients (20%). Cardiac sarcoidosis was the diagnosis in 12 patients (80%) while 3 patients (20%) had tuberculosis. The median CHA2DS2 VASc score was 1. Four patients (26.7%) presented with ischemic stroke. All patients were treated with disease-specific therapy in addition to antiarrhythmic medications. Over a median follow up of 26 months, a significant improvement in clinical status commensurate with a decline in atrial uptake was noted. A non-significant improvement in LVEF to 56% with disease-specific therapy was observed. (p = 0.09).

Atrial fibrillation with granulomatous lymphadenopathy may be a presenting feature of AM. The risk of stroke is high in these individuals. AM should be suspected in young individuals presenting with atrial fibrillation and stroke without conventional risk factors.

Atrial flutter (AFL) and atrial fibrillation (AF) are the most commonly detected supraventricular arrhythmias and share similar pathophysiological mechanisms. After the successful ablation of AFL, AF frequently occurs in the long-term follow-up. As emphasized in some studies, certain mechanisms seem to predispose to the development of AF in AFL patients, and approximately 20% of these patients have accompanying AFL.

We aimed to analyze independent risk factors that predict the development of AF in patients who underwent typical AFL ablation.

This was a multicenter, cross-sectional, and retrospective study. A total of 442 patients who underwent typical AFL ablation at three different centers between January 1, 2018 and January 1, 2022 were included retrospectively. After the ablation procedure the patients were divided into those who developed AF and those who did not. The patients were followed up for an average of 12 (4-20) months. In the post-procedural period, atrial arrhythmias were investigated with 24‑h Holter and ECG at 1 month, 6 months, and 12 months and then at 6‑month intervals thereafter.

Overall, AF developed in 206 (46.6%) patients in the long-term follow-up. Age, hypertension (HT), obstructive sleep apnea syndrome (OSAS), previous cerebrovascular accident (CVA), left atrium anteroposterior diameter, severe mitral regurgitation, hemoglobin, blood glucose, and HbA1c values were found to be significant in univariable analysis. According to multivariable analysis, HT (p = 0.014; HR: 1.483 [1.084-2.030]), OSAS (p = 0.008; HR: 1.520 [1.117-2.068]) and previous CVA (p = 0.038; HR: 1.749 [1.031-2.968]) were independently associated with the development of AF in AFL patients who underwent ablation procedure.

In the present study, we found that HT, OSAS, and previous CVA were independently correlated with the development of AF in the long-term follow-up of patients who underwent typical AFL ablation. We consider that AFL patients with such risk factors should be followed up closely following cavotricuspid isthmus ablation for the development of AF.

Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation.

We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure.

Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups (P<0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality (P<0.01) and showed a trend toward an association with a lower incidence of stroke (P=0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year.

Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke.

URL: https://www.crd.york.ac.uk/prospero/display_record.php?; Unique identifier: CRD42024525542.

Left atrial (LA) remodeling plays a significant role in the progression of atrial fibrillation (AF). Although LA wall thickness (LAWT) has emerged as an indicator of structural remodeling, its impact on AF outcomes remains unclear. We aimed to determine the association between LAWT and AF recurrence after pulmonary vein isolation (PVI), as well as to evaluate the relationship between LAWT and LA fibrosis.

Single-center registry of patients enrolled for radiofrequency PVI from 2016 to 2018. In all cases, a pre-ablation CT was performed within less than 48 h. Mean LAWT was retrospectively measured by a semi-automated machine learning method (ADAS 3D). A subgroup of patients also underwent pre-ablation cardiac MRI. The primary endpoint was time to AF recurrence after a 3-month blanking period.

A total of 439 patients (mean age 61 ± 12 years, 62% male, 78% with paroxysmal AF) were included. The mean LAWT was 1.4 ± 0.2 mm (0.9-1.9 mm). During a median follow-up of 5.8 (IQR: 4.9-6.6) years, 238 patients (54%) had an AF relapse. After adjusting for 8 clinical and imaging potential confounders, LAWT remained an independent predictor of time-to-recurrence (aHR: 4.25 [95% CI: 1.65-10.95], p = 0.003). AF recurrence rates were 11%, 15%, and 21%/year across terciles of increasing LAWT (log-rank p < 0.001). Additionally, the AF recurrence rate increased across the spectrum of LA structural remodeling, ranging from 8% (normal LAWT and LAVI) to 30%/year (LAWT and LAVI both increased). In the 62 patients who also underwent pre-ablation MRI, a moderate relationship between LAWT and fibrosis (assessed by late-gadolinium enhancement) was found (Spearman R 0.468; p < 0.001).

Mean LAWT, easily assessed by commercially available machine learning software, is an independent predictor of time to AF recurrence after PVI in the long term. Whether patients with increased LAWT should receive tailored therapy deserves further investigation.

Causal machine learning (ML) provides an efficient way of identifying heterogeneous treatment effect groups from hundreds of possible combinations, especially for randomized trial data.

The aim of this paper is to illustrate the potential of applying causal ML on the DECAAF II trial data. We proposed a causal ML model to predict the treatment response heterogeneity.

We applied causal tree learning to the DECAAF II trial data as an example of real applications, identifying subgroups that may be superior when subject to one of the treatments over the other through an easily interpretable process. For each subgroup identified, the characteristics were summarized, and the relationship between treatment arms and risk for recurrence of atrial tachyarrhythmia (aTA) among subjects was assessed.

Causal tree learning demonstrated that, among all the preablation predictors, dividing subgroups according to age, with a cutoff of 58 years, provides the most heterogeneous subgroups in response to fibrosis-guided ablation in addition to pulmonary vein isolation (PVI) compared with PVI alone. The difference in the risk of recurrence of aTA between 2 treatments was nonsignificant in older patients (hazard ratio [HR] 1.06; 95% confidence interval [CI] 0.77-1.47; P = .72). However, among the younger patients, the risk of aTA recurrence was significantly lower in the fibrosis-guided ablation group compared with PVI-only (HR 0.50; 95% CI 0.28-0.90); P = .02).

Applying causal ML on random controlled trial datasets helped us identify groups of patients that profited from the treatment of interest in an efficient and unbiased manner.

This study aimed to evaluate the predictive ability of two widely used early warning scoring systems, the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), for predicting stroke occurrence in hospitalized patients.

The study enrolled 5,474 patients admitted to the intensive care unit from the general ward using data from the Smart Clinical Data Warehouse (CDW). MEWS and NEWS were calculated based on vital signs and clinical parameters within four hours of stroke onset. Stroke occurrence was categorized as ischemic or hemorrhagic. Logistic regression and receiver operating characteristic curve analyses were performed to assess the predictive abilities of the scoring systems.

Of the enrolled patients, 33.9% (n = 1853) experienced stroke, comprising 783 cases of ischemic stroke and 1,070 cases of hemorrhagic stroke. Both the MEWS and the NEWS were found to significantly predict overall stroke occurrence with a cutoff value of 4 (MEWS>4; OR [95% CI]: 13.90 [11.51-16.79], p<0.001; NEWS>4; OR [95% CI]: 6.71 [5.75-7.83], p<0.001). Parameters, such as prior malignancy, atrial fibrillation, AVPU response, heart rate, respiratory rate, and oxygen saturation, are also associated with stroke occurrence. The predictive ability of MEWS and NEWS was good for overall stroke occurrence. (AUC of MEWS: 0.92, 95% CI [0.91-0.93], p<0.001; AUC of NEWS: 0.85, 95% CI [0.84-0.86], p<0.001). The predictive ability was considered fair for ischemic stroke but good for hemorrhagic stroke.

MEWS and NEWS demonstrated significant predictive abilities for overall stroke occurrence among hospitalized patients, with MEWS slightly outperforming NEWS.