Atrial Fibrillation Progression Research Articles

Left atrial wall thickness measured by a machine learning method predicts AF recurrence after pulmonary vein isolation

Abstract Background 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). Methods Single-center registry of patients enrolled for radiofrequency PVI from 2016 to 2018. In all cases, a pre-ablation CT scan was performed within less than 48 hours. Mean LAWT was retrospectively determined by a semi-automated machine learning method with minimal human intervention (ADAS 3D®). Additionally, regional tissue thickness was assessed in four locations: roof and inferior, posterior, and anterior walls. In a subgroup of patients, a pre-ablation cardiac magnetic resonance (CMR) was also performed within the same week. LA functional parameters and fibrosis, using 3D delayed gadolinium enhancement, were analyzed. The primary endpoint was AF recurrence after a 3-month blanking period. Results A total of 439 patients (mean age 61±12years, 62% male, 78% with paroxysmal AF) were included. The mean LAWT was 1.4±0.2mm (ranging from 0.9 to 1.9mm). Software processing duration was 8.2±0.4 min, and the mean human input time was 1.3±0.1 min. There was no correlation between LAWT and CT-derived LA-indexed volume (Spearman –0.01, p=0.845). During a median follow-up of 5.8 (IQR 4.9–6.6) years, 238 patients (54%) had an AF relapse. LAWT was an independent predictor of recurrence, after adjusting for known confounders including age, non-paroxysmal AF, LA-indexed volume, and chronic kidney disease (adjusted HR 6.49 [95% CI 2.70-15.49], p<0.001). AF recurrence rates were 11%, 15%, and 21%/year across terciles of increasing LAWT (log-rank p<0.001) – Figure. The posterior LAWT revealed the strongest association with the study endpoint (HR 1.93 [95% CI 1.24-3.02], p=0.004). In the cohort of 62 patients with both CT and CMR, LAWT showed weak correlations with LA ejection fraction and LA coupling index (Spearman <0.25; p=0.054 and p=0.093, respectively), and a moderate correlation with LA fibrosis (Spearman 0.468; p<0.001). Conclusions Mean LAWT, easily assessed by commercially available machine learning software, is an independent predictor of AF recurrence after PVI in the long-term follow-up. This association is mainly driven by the posterior LAWT. Whether patients with increased LAWT should receive tailored therapy deserves further investigation.Figure

Application value of real-time 3D speckle tracking imaging in left atrial function evaluation of patients with paroxysmal atrial fibrillation.

To evaluate left atrial volume and function in patients with paroxysmal atrial fibrillation (AF) combined with left atrial appendage thrombosis and patients with paroxysmal AF without left atrial appendage thrombosis by 3-dimensional speckle tracking imaging (3D-STI), and to explore the application value of this set of parameters in the evaluation of left atrial function in patients with paroxysmal AF. A total of 40 patients with paroxysmal AF admitted from December 2018 to December 2020 were selected as the observation group. All patients with paroxysmal AF in the observation group underwent transesophageal echocardiography. According to the presence of left atrial appendage thrombosis, the patients were divided into the AF without thrombosis group (24 cases) and the AF with thrombosis group (16 cases). Thirty normal people were selected as control group who were chosen as having no heart-related disease. The left atrial volume parameters (Left atrial maximum volume LAVmax, Left atrial minimum volume LAVmin, Left atrial volume before atrial contraction LAVpre-A, Left atrial stroke volume LAEV), left atrial ejection fraction (LAEF) and left atrial strain parameters (Left atrial reservoir longitudinal strain LASr, Left atrial conduit longitudinal strain LAScd, Left atrial contraction longitudinal strain LASct, Left atrial reservoir circumferential strain LASr-c, Left atrial conduit circumferential strain LAScd-c, Left atrial contraction circumferential strain LASct-c) of the 3 groups were measured by 3D-STI. With the progression of paroxysmal AF, the left atrial volume increased, and the reservoir, conduit and contractile function were damaged. The left atrial volume continued to increase, and the reservoir, conduit and contractile function further decreased significantly in patients with AF combined with left atrial appendage thrombosis. LAEF was positively correlated with LASr and LASr_c. Real-time 3-dimensional spot tracking imaging (3D-STI) can evaluate the changes in left atrial volume and function in patients with paroxysmal AF, and has a certain reference value for clinical judgment of disease progression and prognosis.

Sex differences at diagnosis and in one-year outcomes in patients with early atrial fibrillation

Abstract Background Little is known about differences in clinical phenotype between men and women with atrial fibrillation (AF). Our aim was to explore phenotypical sex differences at diagnosis and at one-year follow-up, in patients with early AF. Methods We used data from 5,469 participants of the DUTCH-AF registry; a nationwide prospective registry of patients with early AF or atrial flutter (diagnosis ≤ 6 months before inclusion) in the Netherlands, aged ≥ 18 years. We describe sex differences in clinical phenotype at diagnosis and at one-year follow-up, including the following outcomes: i) ischemic and bleeding events, ii) all-cause mortality, iii) AF-related hospital admissions, including ablation and cardioversion, and iv) AF progression patterns. Results At inclusion, women were older than men (median 73 vs. 69 years, p<0.001), had more often paroxysmal AF (66% vs. 55%, p<0.001), and less often persistent AF (27% vs. 37%, p<0.001). They also had hypertension more often (59% vs. 53%, p<0.001), and less often vascular disease (12% vs. 21%, p<0.001, and reported more often symptoms at inclusion and in the month before follow-up; 56% vs. 46%, p<0.001, and 31% vs. 23%, p<0.001, respectively. Women underwent cardioversion and ablation procedures less often than men (14% vs. 21% p<0.001 and 3% vs. 5%, p<0.001, respectively). Moreover, for the combined rhythm control intervention cardioversion and ablation, women also underwent this rhythm control outcome less often than men (unadjusted odds ratio was 0.63 95% CI (0.55-0.73)), regardless of age, and the type of AF (i.e., paroxysmal or persistent AF) at inclusion (adjusted odds ratio 0.77 95% CI (0.62-0.92)). No differences were observed for ischemic and bleeding events, all-cause mortality, or AF progression patterns, but the number of these events was small. Conclusion Men and women with early AF differ in age, comorbidities, symptoms, and management. These findings are building blocks for individualized sex-specific AF care and research.

Association of Gut Dysbiosis with Potential Mechanisms Leading to Atrial Fibrillation: A Narrative Review

Atrial fibrillation stands as one of the deadliest forms of arrhythmia known to mankind due to its severe complication and co-morbidities. Its association with gut dysbiosis is profound. The gut microbiota hosts a diverse variety of microbes crucial for immune function and protection against cardiovascular and metabolic diseases. Poor lifestyle habits such as diet, decreased physical activity, and drug disrupt this gut homeostasis. Multiple studies have provided compelling evidence linking alterations in gut microbiota to the risk and progression of atrial fibrillation. Some proposed mechanisms involve key metabolites such as trimethylamine N-oxide (TMAO), lipopolysaccharides, short-chain fatty acids (SCFAs), bile acids, and tryptophan. These mechanisms encompass inflammation, oxidative stress, autonomic dysfunction, atrial remodeling, altered electrical activity, and calcium homeostasis. This review meticulously examines gut dysbiosis and its pivotal role in the progression of atrial fibrillation through diverse potential mechanisms, emphasizing the significance of dietary factors and potential interventions.

ECG-based estimation of respiration-induced autonomic modulation of AV nodal conduction during atrial fibrillation.

Introduction: Information about autonomic nervous system (ANS) activity may offer insights about atrial fibrillation (AF) progression and support personalized AF treatment but is not easily accessible from the ECG. In this study, we propose a new approach for ECG-based assessment of respiratory modulation in atrioventricular (AV) nodal refractory period and conduction delay. Methods: A 1-dimensional convolutional neural network (1D-CNN) was trained to estimate respiratory modulation of AV nodal conduction properties from 1-minute segments of RR series, respiration signals, and atrial fibrillatory rates (AFR) using synthetic data that replicates clinical ECG-derived data. The synthetic data were generated using a network model of the AV node and 4 million unique model parameter sets. The 1D-CNN was then used to analyze respiratory modulation in clinical deep breathing test data of 28 patients in AF, where an ECG-derived respiration signal was extracted using a novel approach based on periodic component analysis. Results: We demonstrated using synthetic data that the 1D-CNN can estimate the respiratory modulation from RR series alone with a Pearson sample correlation of r = 0.805 and that the addition of either respiration signal (r = 0.830), AFR (r = 0.837), or both (r = 0.855) improves the estimation. Discussion: Initial results from analysis of ECG data suggest that our proposed estimate of respiration-induced autonomic modulation, a resp, is reproducible and sufficiently sensitive to monitor changes and detect individual differences. However, further studies are needed to verify the reproducibility, sensitivity, and clinical significance of a resp.

Single-cell sequencing of immune cells from the coronary sinus reveals immune mechanisms of the progression of persistent atrial fibrillation

Single-cell sequencing of immune cells from the coronary sinus reveals immune mechanisms of the progression of persistent atrial fibrillation

Structural, Functional, and Electrical Remodeling of the Atria With Reduced Cardiorespiratory Fitness: Implications for AF

BackgroundReduced cardiorespiratory fitness (CRF) is an independent risk factor for the progression of atrial fibrillation (AF). We hypothesized that reduced CRF is associated with structural, functional, and electrical remodeling of the left atrium. ObjectivesThis study sought to correlate objectively assessed CRF with functional and electrical left atrial (LA) parameters using invasive and noninvasive assessments. MethodsConsecutive patients with symptomatic AF undergoing catheter ablation were recruited. CRF was objectively quantified pre-ablation by using cardiopulmonary exercise testing. Using peak oxygen consumption, participants were classified as preserved CRF (>20 mL/kg/min) or reduced CRF (<20 mL/kg/min). LA stiffness was assessed invasively with hemodynamic monitoring and imaging during high-volume LA saline infusion. LA stiffness was calculated as ΔLA diameter/ΔLA pressure over the course of the infusion. LA function was assessed with echocardiographic measures of LA emptying fraction and LA strain. Electrical remodeling was assessed by using high-density electroanatomical maps for LA voltage and conduction. ResultsIn total, 100 participants were recruited; 43 had reduced CRF and 57 had preserved CRF. Patients with reduced CRF displayed elevated LA stiffness (P = 0.004), reduced LA emptying fraction (P = 0.006), and reduced LA reservoir strain (P < 0.001). Reduced CRF was also associated with reduced LA voltage (P = 0.039) with greater heterogeneity (P = 0.027) and conduction slowing (P = 0.04) with greater conduction heterogeneity (P = 0.02). On multivariable analysis, peak oxygen consumption was independently associated with LA stiffness (P = 0.003) and LA conduction velocities (P = 0.04). ConclusionsReduced CRF in patients with AF is independently associated with worse LA disease involving functional and electrical changes. Improving CRF may be a target for restoring LA function in AF.

Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions.

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression of atrial fibrillation, the potential impact of environmental determinants on this prevalent condition has received comparatively less attention. This review aims to provide a comprehensive overview of the current evidence on environmental determinants of atrial fibrillation, encompassing factors such as air pollution, temperature, humidity, and other meteorologic conditions, noise pollution, greenspace, and the social environment. We discuss the existing evidence from epidemiological and mechanistic studies, critically evaluating the strengths and limitations of these investigations and the potential underlying biological mechanisms through which environmental exposures may affect atrial fibrillation risk. Furthermore, we address the potential implications of these findings for public health and clinical practice and identify knowledge gaps and future research directions in this emerging field.

Flecainide sebagai Antiaritmia untuk Fibrilasi Atrium dan Aritmia Lainnya

Atrial fibrillation (AF) is one of the most common arrhythmias globally, and its prevalence is projected to increase, including in Indonesia. AF progression is related to lower quality of life and less responsive to therapy or even becomes irreversible. The progression of AF is significantly slower with the rhythm control strategy than with the rate control strategy alone. The options for therapy in Indonesia are limited to amiodarone and propafenone. Amiodarone is one of the most common drugs prescribed for AF rhythm control, but associated with multiple organ toxicities, thus increasing the risk of multiple side effects, especially on long-term usage, potentially leading to drug discontinuation. Flecainide is an antiarrhythmia with a favourable effectiveness and safety profile, especially for AF management, used for acute cardioversion, long-term rhythm control, and as a therapeutic modality for AF with preexcitation syndrome. Flecainide is a potential drug to address the unmet needs of amiodarone as a long-term management for AF.

Usformer: A small network for left atrium segmentation of 3D LGE MRI

Left atrial (LA) fibrosis plays a vital role as a mediator in the progression of atrial fibrillation. 3D late gadolinium-enhancement (LGE) MRI has been proven effective in identifying LA fibrosis. Image analysis of 3D LA LGE involves manual segmentation of the LA wall, which is both lengthy and challenging. Automated segmentation poses challenges owing to the diverse intensities in data from various vendors, the limited contrast between LA and surrounding tissues, and the intricate anatomical structures of the LA. Current approaches relying on 3D networks are computationally intensive since 3D LGE MRIs and the networks are large. Regarding this issue, most researchers came up with two-stage methods: initially identifying the LA center using a scaled-down version of the MRIs and subsequently cropping the full-resolution MRIs around the LA center for final segmentation. We propose a lightweight transformer-based 3D architecture, Usformer, designed to precisely segment LA volume in a single stage, eliminating error propagation associated with suboptimal two-stage training. The transposed attention facilitates capturing the global context in large 3D volumes without significant computation requirements. Usformer outperforms the state-of-the-art supervised learning methods in terms of accuracy and speed. First, with the smallest Hausdorff Distance (HD) and Average Symmetric Surface Distance (ASSD), it achieved a dice score of 93.1% and 92.0% in the 2018 Atrial Segmentation Challenge and our local institutional dataset, respectively. Second, the number of parameters and computation complexity are largely reduced by 2.8x and 3.8x, respectively. Moreover, Usformer does not require a large dataset. When only 16 labeled MRI scans are used for training, Usformer achieves a 92.1% dice score in the challenge dataset. The proposed Usformer delineates the boundaries of the LA wall relatively accurately, which may assist in the clinical translation of LA LGE for planning catheter ablation of atrial fibrillation.

Clinical Predictors of Device-Detected Atrial Fibrillation During 2.5 Years After Cardiac Surgery: Prospective RACE V Cohort

BackgroundPostoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery that is associated with late atrial fibrillation (AF) recurrences (late-POAF) and increased morbidity and long-term mortality. ObjectivesThis study sought to determine device-detected POAF incidence and to identify clinical variables associated with POAF, both in patients with and without preoperative AF history. MethodsA total of 133 consecutive patients undergoing cardiac surgery were prospectively enrolled and continuously monitored with an implantable loop recorder for 2.5 years after surgery. Preoperative transthoracic echocardiography, 12-lead electrocardiogram, blood biomarkers, and clinical data were analyzed to develop prediction models for early- and late-POAF. ResultsIn patients without preoperative AF history, early-POAF within the first 90 postoperative days occurred in 41 (47.1%) of 87 patients. Late-POAF after the first 90 postoperative days occurred in 22 (25%) of 87 patients, and 20 of these patients also had early-POAF during the first 90 days (20 of 22 [91%]). Increased right atrial minimum volume indexed for body surface area (RAVImin) and early-POAF were independently associated with late-POAF. A prediction model for late-POAF, which included RAVImin >11 mL/m2, age >65 years, and early-POAF, achieved an area under the curve of 0.82 (95% CI: 0.72-0.92). For patients with preoperative AF-history, late-POAF recurrences were frequent (22 of 33 [67%]). Increased RAVImin was independently associated with a higher incidence of late-POAF. ConclusionsIn patients with and without AF history, late-POAF recurrences are frequent, including in patients undergoing surgical AF ablation. In patients with no history of AF, late-POAF might be predicted with excellent accuracy by using a combination of preoperative variables. In patients with a history of AF, signs of advanced AF substrate (eg, increased right atrial volumes) were associated with long-term AF recurrences. [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF; NCT03124576]

Conduction Velocity and Anisotropic Properties of Fibrillation Waves During Acutely Induced and Long-Standing Persistent AF.

Quantified features of local conduction heterogeneity due to pathological alterations of myocardial tissue could serve as a marker for the degree of electrical remodeling and hence be used to determine the stage of atrial fibrillation (AF). In this study, the authors investigated whether local directional heterogeneity (LDH) and anisotropy ratio, derived from estimated local conduction velocities (CVs) during AF, are suitable electrical parameters to stage AF. Epicardial mapping (244-electrode array, interelectrode distance 2.25mm) of the right atrium was performed during acute atrial fibrillation (AAF) (n = 25, 32 ± 11 years of age) and during long-standing persistent atrial fibrillation (LSPAF) (n=23, 64 ± 9 years of age). Episodes of 9 ± 4 seconds of AF were analyzed. Local CV vectors were constructed to assess the degree of anisotropy. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. Compared with the entire AAF group, LSPAF was characterized by slower conduction (71.5 ± 6.8cm/s vs 67.6 ± 5.6cm/s; P = 0.037) with a larger dispersion (1.59 ± 0.21 vs 1.95 ± 0.17; P< 0.001) and temporal variability (32.0 ± 4.7cm/s vs 38.5 ± 3.3cm/s; P< 0.001). Also, LSPAF was characterized by more LDH (19.6% ± 4.4% vs 26.0% ± 3.4%; P< 0.001) and a higher degree of anisotropy (1.38 ± 0.07 vs 1.51 ± 0.14; P< 0.001). Compared with the most complex type of AAF (type III), LSPAF was still associated with a larger CV dispersion, higher temporal variability of CV, and larger amount of LDH. Increasing AF complexity was associated with increased spatiotemporal variability of local CV vectors, local conduction heterogeneity, and anisotropy ratio. By using these novel parameters, LSPAF could potentially be discriminated from the most complex type of AAF. These observations may indicate pathological alterations of myocardial tissue underlying progression of AF.

Possible risk factors for atrial fibrillation in patients with heart failure with mildly reduced ejection fraction

Aim. To study possible risk factors (RFs) for the development of paroxysmal and persistent atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrHF).Material and methods. The study included 193 patients with chronic HFmrHF and non-valvular paroxysmal/persistent AF. Seventy-six comparable patients, but without AF, were studied as a control group. All patients underwent a detailed physical examination, including electrocardiography (ECG), echocardiography, ambulatory blood pressure monitoring, and Holter ECG monitoring. Levels of inflammatory markers, namely high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-a and fibrotic marker, transforming growth factor-b1 (TGF-b1) were measured using ELISA. The results obtained were analyzed using the method of binary logistic regression and odds ratio (OR), which allows us to assess the relationship of a specific outcome with possible risk factors and compare study groups according to the detection rate of risk factors.Results. A higher level of diastolic blood pressure (DBP) (OR=1,09, confidence interval (CI)=1,01-1,17, p=0,017) is a possible risk factor for paroxysmal AF in patients with CHF. Possible risk factors for paroxysmal and persistent AF in such patients are an increase in episodes of hypertensive crisis (OR=1,17, CI=1,071,43, p=0,001) and an increase in body mass index (BMI) (OR=1,13, CI=0,931,27, p=0,031). An increase in the OR index of left ventricular diastolic and systolic parameters was associated with significant atrial and ventricular remodeling, which contributes to AF progression from paroxysmal to persistent. Higher levels of inflammatory markers were observed in patients with AF compared with patients with HFmrHF without AF. The increase in the OR level of TGF-b1 (OR=3,84, CI=2,106,23, p=0,005) was significant in patients with persistent AF.Conclusion. Using the OR method, an increase in DBP, the prevalence of hypertensive crisis, BMI, left atrial and ventricular remodeling, an increase in markers of systemic inflammation and fibrosis are possible risk factors for AF in patients with HFmrHF.

Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-β/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.

Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation.

Transcriptomic analysis reveals the potential crosstalk genes and immune relationship between Crohn's disease and atrial fibrillation.

At present, there is a paucity of research on the link between Crohn's disease (CD) and atrial fibrillation (AF). Nevertheless, both ailments are thought to entail inflammatory and autoimmune processes, and emerging evidence indicates that individuals with CD may face an elevated risk of AF. To shed light on this issue, our study seeks to explore the possibility of shared genes, pathways, and immune cells between these two conditions. We retrieved the gene expression profiles of both CD and AF from the Gene Expression Omnibus (GEO) database and subjected them to analysis. Afterward, we utilized the weighted gene co-expression network analysis (WGCNA) to identify shared genes, which were then subjected to further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, we employed a rigorous analytical approach by screening hub genes through both least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM), and subsequently constructing a receiver operating characteristic (ROC) curve based on the screening outcomes. Finally, we utilized single-sample gene set enrichment analysis (ssGSEA) to comprehensively evaluate the levels of infiltration of 28 immune cells within the expression profile and their potential association with the shared hub genes. Using the WGCNA method, we identified 30 genes that appear to be involved in the pathological progression of both AF and CD. Through GO enrichment analysis on the key gene modules derived from WGCNA, we observed a significant enrichment of pathways related to major histocompatibility complex (MHC) and antigen processing. By leveraging the intersection of LASSO and SVM algorithms, we were able to pinpoint two overlapping genes, namely CXCL16 and HLA-DPB1. Additionally, we evaluated the infiltration of immune cells and observed the upregulation of CD4+ and CD8+ T cells, as well as dendritic cells in patients with AF and CD. By employing bioinformatics tools, we conducted an investigation with the objective of elucidating the genetic foundations that connect AF and CD. This study culminated in the identification of CXCL16 and HLA-DPB1 as the most substantial genes implicated in the development of both disorders. Our findings suggest that the immune responses mediated by CD4+ and CD8+ T cells, along with dendritic cells, may hold a crucial role in the intricate interplay between AF and CD.

Hybrid Endo-Epicardial Therapies for Advanced Atrial Fibrillation

Atrial fibrillation (AF) is a growing health problem that increases morbidity and mortality, and in most patients progresses to more advanced diseases over time. Recent research has examined the underlying mechanisms, risk factors, and progression of AF, leading to updated AF disease classification schemes. Although endocardial catheter ablation is effective for early-stage paroxysmal AF, it consistently achieves suboptimal outcomes in patients with advanced AF. Identification of the factors that lead to the increased risk of treatment failure in advanced AF has spurred the development and adoption of hybrid ablation therapies and collaborative heart care teams that result in higher long-term arrhythmia-free survival. Patients with non-paroxysmal AF, atrial remodeling, comorbidities, or AF otherwise deemed difficult to treat may find hybrid treatment to be the most effective option. Future research of hybrid therapies in advanced AF patient populations, including those with dual diagnoses, may provide further evidence establishing the safety and efficacy of hybrid endo-epicardial ablation as a first line treatment.

Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.

Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.

Predictive value of soluble suppression of tumorigenicity 2 in atrial fibrillation: a systematic review and meta-analysis.

Atrial fibrosis is the main pathological basis for the pathogenesis and progression of atrial fibrillation (AF). Soluble suppression of tumorigenicity 2 (sST2) is involved in fibrosis. Recent studies have explored its predictive value in AF outcomes. We performed this study to assess whether sST2 is an independent biomarker of AF outcomes and explore the potential mechanism. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched systematically from inception through July 1, 2023, to identify relevant studies. Outcomes of interest included occurrence, recurrence, and major adverse cardiac events (MACEs) of AF. This meta-analysis was reported following the criteria outlined in PRISMA 2020, and the protocol was registered in PROSPERO (number: CRD42023459789). All statistical analyses were performed using the STATA version 16. Twenty four studies with 14,755 patients were included in the meta-analysis. The meta-analyses found that sST2 was significantly associated with the risk of occurrence [HR:1.04, 95% CI: 1.02-1.07, P < 0.01; I2 = 67.8%], recurrence [HR:1.09, 95% CI: 1.02-1.16, P < 0.01; I2 = 89.5%], and MACEs (HR:1.60, 95% CI: 1.13-2.27, P < 0.01; I2 = 82.0%) of AF. Furthermore, patients with AF showed higher sST2 than controls without AF (SMD: 0.41, 95% CI: 0.27-0.54, P < 0.01; I2 = 0%), and AF patients with recurrence after catheter ablation (CA) showed significantly higher sST2 than those without recurrence (SMD: 0.81, 95% CI: 0.33-1.28, P < 0.01; I2 = 83.9%). Sensitivity analyses showed that the outcomes were stable. Higher sST2 was association with an increased risk of occurrence, recurrence, and MACEs of AF. Assessing sST2 can be used as a potential screening method to predict AF outcomes. PROSPERO (CRD42023459789).

A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.