Despite significant advancements in prevention and treatment over the past decades, cardiovascular diseases (CVDs) remain the leading cause of death worldwide. CVDs involve multifactorial inheritance, but our understanding of the genetic impact on these diseases is still incomplete. Sorbin and SH3 domain-containing protein 2 (Sorbs2) is ubiquitously expressed in various tissues, including the cardiovascular system. Increasing evidence suggests that Sorbs2 malfunction contributes to CVDs. This manuscript will review our current understanding of the potential mechanisms underlying Sorbs2 dysregulation in the development of CVDs.

The international Working Group of the Signal Summit is a consortium of experts in the field of cardiac electrophysiology dedicated to advancing knowledge on understanding and clinical application of signal recording and processing techniques. In 2023, the working group met in Reykjavik, Iceland, and laid the foundation for this manuscript. Atrial fibrillation (AF) is the most common arrhythmia in adults, with a rapidly increasing prevalence worldwide. Despite substantial research efforts, advancements in elucidating the underlying mechanisms of AF have been relatively modest. Since the discovery of pulmonary veins as a frequent trigger region for AF initiation more than 2½ decades ago, advancements in patient care have primarily focused on technologic innovations to improve the safety and efficacy of pulmonary vein isolation (PVI). Several factors may explain the limited scientific progress made. First, whereas AF initiation usually begins with an ectopic beat, the mechanisms of initiation, maintenance, and electrical propagation have not been fully elucidated in humans, largely owing to suboptimal spatiotemporal mapping. Second, underlying structural changes have not been clarified and may involve different types of reentry. Third, inconsistent definitions and terminology regarding fibrillatory characteristics contribute to the challenges of comparing results between studies. Fourth, a growing appreciation for phenotypical differences probably explains the wide range of clinical outcomes to catheter ablation in patients with seemingly similar AF types. Last, restoring sinus rhythm in advanced phenotypic forms of AF is often not feasible or may require extensive ablation with minimal or no positive impact on quality of life. The aims of this international position paper are to provide practical definitions as a foundation for discussing potential mechanisms and mapping results and to propose pathways toward meaningful advancements in AF research, ultimately leading to improved therapies for AF.

Levosimendan has demonstrated beneficial effects in the treatment of acute decompensated heart failure (ADHF). However, it is also associated with proarrhythmic effects owing to its influence on cardiac electrophysiology. We aimed to analyze the clinical features of atrial fibrillation (AF) after levosimendan treatment in patients with ADHF and to identify the predictors of AF after levosimendan treatment. The data of patients with ADHF treated with levosimendan were propensity score-matched and retrospectively analyzed. This study retrospectively collected patients admitted to the emergency department between 2021 and 2024 with a diagnosis of acute decompensated heart failure who received levosimendan therapy. Overall, 38 patients (16.8%) developed AF after levosimendan treatment. Levosimendan therapy was an independent predictor of AF (odds ratio 1.442, 95% confidence interval 1.005-2.067; P = .014). Patients who developed AF were older (P < .001) and more likely to have comorbid left atrial enlargement (P < .001) and previous AF/atrial flutter (P = .004). Patients with AF after levosimendan treatment had a longer median in-hospital stay than those without AF. Age (P = .005), left atrial enlargement (P = .032), and history of atrial flutter/AF (P = .002) were significant predictors of AF after levosimendan treatment. The area under the receiver operating characteristic curve values for age, left atrial enlargement, and history of atrial flutter/AF for predicting AF after treatment with levosimendan were 0.679 (P < .001), 0.687 (P < .001), and 0.603 (P = .012), respectively. Age, left atrial enlargement, and previous atrial flutter/AF were independent predictors of AF after levosimendan treatment. Levosimendan-associated AF increased the length of in-hospital stay, but had no effect on in-hospital mortality. Although this was a retrospective study, the study was registered as a clinical study, and the registration numbers will be uploaded later.

Atrial fibrillation (AF) is common in patients with chronic heart failure (HF). Nevertheless, some patients with HF remain in sinus rhythm (SR) even with marked left atrial (LA) dilatation and fibrosis. The underlying mechanisms for the differences in atrial arrhythmogenicity are poorly uncovered. Recent findings indicate that distinct microRNAs (miRNA) might induce LA structural and molecular alterations. However, the impact of miRNA dysregulation on AF development in the context of HF has not been studied independently of LA remodeling.

This study aimed to evaluate the differences in LA miRNA expressions in HF patients with AF or SR.

LA myocardial samples were obtained from advanced HF patients with AF (n=12; paroxysmal n=4, chronic as persistent/permanent n=8) or SR (n=12) undergoing heart transplantation. The extent of LA interstitial fibrosis was evaluated using picrosirius red-staining. The LA load was estimated by measuring LA mRNA expression of the NPPA gene encoding atrial natriuretic peptide with qRT-PCR and circulating N-terminal proatrial natriuretic peptide (NT-proANP) by ELISA. The LA miRNA screening was performed using the NanoString technology.

LA dilatation, fibrosis, NPPA gene expression, as well as circulating NT-proANP levels were similar between the AF and SR groups, suggesting a comparable extent of atrial remodeling and load among the study groups. The miRNA analysis revealed no differences in atrial miRNA expression between the groups, even after AF subgroup analysis.

The LA miRNA expression profile shows no distinction between AF and SR in advanced HF patients with similar levels of pathological atrial remodeling.

The efficacy of radiofrequency catheter ablation (RFCA) alone for nonparoxysmal atrial fibrillation (NPAF) is unsatisfactory. This study investigated the effect of sacubitril/valsartan, a type of angiotensin receptor neprilysin inhibitor (ARNI), on NPAF patients with hypertension who underwent RFCA and analysed the possible influencing factors.

In this prospective, randomized clinical trial, 240 NPAF patients were randomly divided into a control group (n = 121) and an ARNI group (n = 119). The primary outcome was freedom from atrial fibrillation (AF) and atrial tachycardia/atrial flutter (AT/AFL) for ≥ 30 s without antiarrhythmic medications at 15 months after the 3-month blanking period. The secondary outcomes included recurrence types, blood pressure, echocardiographic parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

At 15 months, a higher maintenance rate of sinus rhythm was achieved in the ARNI group compared to the control group (79.8% vs. 69.4%, hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.36-0.98; P = 0.04). Moreover, a smaller left atrial diameter (adjusted mean difference -1.9 mm [95% CI -3.2 to -0.5], P = 0.02) and lower NT-proBNP level (adjusted median difference -34 pg/ml [95% CI -62 to -6], P = 0.03) were observed in the ARNI group than in the control group at 15 months. Among the patients who recurred, a lower incidence of AF (50.0% vs. 62.2%, P = 0.01) was found in the ARNI group, but presented a significantly higher incidence of AT/AFL. In the subgroup analysis, compared with those in the control group, more patients in the ARNI group achieved success in patients with EF < 50% (93.6% vs. 61.1%, P = 0.01) or low-voltage areas (LVAs) (80.0% vs. 61.3%, P = 0.02). Multivariate Cox regression analysis revealed that ARNI was an independent protective factor against AF or AT/AFL recurrence in patients with EF < 50% or LVAs at 15 months.

ARNI is effective in NPAF patients with hypertension after RFCA, especially those with EF < 50% or LVAs, which can significantly improve their prognosis.

The level of atrial remodeling is closely related to the recurrence of atrial fibrillation (AF). Although structural remodeling has been extensively evaluated, methods for assessing atrial electrical remodeling have not been established. The purpose of our study is to investigate the relationship between atrial conduction velocity and the recurrence of atrial fibrillation (AF) following radiofrequency ablation with pulmonary vein isolation.

We prospectively enrolled 155 patients with paroxysmal atrial fibrillation who underwent their first AF ablation at our center. High-density bipolar voltage mapping was conducted during sinus rhythm in all patients. A coherent mapping was constructed to accurately evaluate the total conduction time, distance, and left atrial conduction velocity (LACV) on the anterior, posterior, and septal routes between the earliest and latest activation sites during sinus rhythm. Out of the patients, 24 experienced a recurrence of AF. The LACV was significantly lower in the patients with AF recurrence compared to those without (anterior, 0.81 ± 0.03 vs. 1.07 ± 0.02 m/s, p < 0.01; posterior, 1.06 ± 0.05 vs. 1.32 ± 0.03 m/s, p < 0.01; septal, 0.91 ± 0.05 vs. 1.13 ± 0.02 m/s, p < 0.01). A multivariate logistic analysis, which included age, left atrial diameter (LAD), LA low-voltage area, P-wave duration, and LA conduction velocity, demonstrated that a slow anterior left atrial conduction velocity (LACV) was an independent predictor of AF recurrence with an adjusted odds ratio of 1.64 (95% confidence interval [CI]: 1.24-3.78, p < 0.01). ROC curve analysis confirmed that the anterior LACV was the most accurate predictor of AF recurrence after pulmonary vein isolation (PVI) with a cut-off value of 0.83 m/s, a sensitivity of 93.9%, and a specificity of 70.8%. Anterior LACV was lower in patients with low-voltage areas than in those without low-voltage areas (0.81 ± 0.03 vs. 1.09 ± 0.02 cm/s, p < 0.01).

An anterior LACV < 0.83 m/s was identified as a strong independent predictor of AF recurrence after PVI in patients with paroxysmal AF.

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.

The efficacy of catheter ablation in reducing major adverse events in atrial fibrillation (AF) is still inconclusive, warranting identification of clinical markers.

The purpose of this study was to explore whether the benefits of catheter ablation varied across different extents of atrial remodeling in the CABANA (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial.

The CABANA trial randomized 2204 participants with AF to catheter ablation or drug therapy. Patients who underwent echocardiographic measurement for left atrial diameter (LAD) at baseline constituted the study population of this present analysis. The primary outcome was composite of death, disabling stroke, serious bleeding, or cardiac arrest.

Of the 1130 patients with documented LAD at baseline (median LAD 44 mm), 570 (50.4%) were randomized to ablation and 560 (49.6%) to drug therapy. The estimated benefits of ablation vs drug therapy on the primary outcome (a composite of death, disabling stroke, serious bleeding, or cardiac arrest) and total mortality were greatest in the lowest end of the LAD spectrum and declined substantially as LAD increased. For the primary outcome, the adjusted hazard ratios were 0.30 (95% confidence interval [CI] 0.11-0.78) in patients without enlarged LAD (LAD ≤ 40 mm) and 0.92 (95% CI 0.55-1.54) in those with enlarged LAD (LAD > 40 mm) (interaction P = .035). The corresponding adjusted hazard ratios for total mortality were 0.09 (95% CI 0.01-0.58) and 0.76 (95% CI 0.40-1.41) in patients without and with enlarged LAD (interaction P = .045).

In CABANA patients without enlarged LAD, catheter ablation significantly reduced major cardiovascular events while the prognostic benefits of ablation diminished with atrial remodeling aggravation. Ablation at the initial stage of atrial remodeling provided an effective early rhythm control strategy to reduce cardiovascular risk in AF.

Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms.

Single-cell RNA sequencing and multicolour flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (P < 0.0001) and the left atria (P < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, P < 0.05) and postprocedural recurrence (hazard ratio = 22.955, P < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping.

An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.

Rheumatic heart disease (RHD) and its complications are major health problems worldwide, especially in developing countries, owing to their high prevalence. Mitral stenosis (MS) is one of the most common lesions in RHD, either isolated or in combination with mitral regurgitation, and eventually leads to atrial fibrillation (AF), congestive heart failure, pulmonary hypertension (PH), and other complications, including ischemic stroke or limb ischemia, if not promptly diagnosed and treated. Recent studies have suggested that MS affects the cardiovascular system beyond mere obstructions. The presence of MS in RHD causes significant changes in the cardiovascular system, both upstream and downstream, affecting both the left and right ventricles. Rheumatic MS causes significant structural changes through inflammatory pathways and hemodynamic changes, owing to its obstructive effects. This review aims to discuss the vast changes in the cardiovascular system caused by rheumatic MS.

The left atrioventricular coupling index (LACI) has emerged as a novel and transformative biomarker in cardiovascular research, addressing long-standing limitations in traditional cardiac function assessments. By quantifying the ratio of left atrial to left ventricular end-diastolic volumes, LACI offers unprecedented prognostic insights into a wide range of cardiovascular diseases, including atrial fibrillation, heart failure, and myocardial infarction, as well as other conditions such as hypertension and cardiomyopathies. Recent evidence highlights its unique ability to integrate atrial and ventricular dynamics, offering a more comprehensive perspective on cardiac health and disease progression. This review synthesizes the latest advancements in LACI research, elucidates its underlying pathophysiological mechanisms, and explores its expanding clinical applications as a pivotal tool for risk stratification, precision diagnostics, and personalized therapy in cardiovascular medicine.

Rodents are increasingly used in atrial electrophysiology research, yet such studies are often performed under anesthesia owing to technical challenges. Here we developed an implantable device for comprehensive atrial studies in ambulatory rats and investigated the effects of commonly used anesthetics on supraventricular electrophysiology and arrhythmic substrate, comparing them with the unanesthetized state (UAS). Adult rats were evaluated 4 weeks after implantation. Studies were conducted in the UAS under 2% isoflurane (ISO) and under 40 mg/kg pentobarbital (PEN). Pacing protocols determined various parameters, including sinoatrial node recovery time, atrioventricular node effective refractory period and atrial effective refractory period. Arrhythmic substrate was assessed after 20 triggering bursts per condition, and arrhythmic tendency was analyzed manually and through the complexity ratio, an unbiased measure recently developed by our group. PEN mildly increased heart rate in both sexes, while ISO did not affect heart rate but prolonged the corrected sinus node recovery time in males. PEN increased atrioventricular node effective refractory period in both sexes, while ISO affected males only. Both ISO and PEN prolonged atrial effective refractory period compared with UAS in both sexes. Arrhythmic measures were higher in males and were attenuated by ISO and, to a lesser extent, by PEN in males only. The dominant frequency of arrhythmic events was reduced by both anesthetics in both sexes. These findings demonstrate a significant impact of commonly used anesthetics on rat supraventricular electrophysiology, with sex-based differences, highlighting the importance of methodologies that enable cardiac electrophysiology studies in unanesthetized rodents.

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.

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.

Multimorbidity is common among patients with atrial fibrillation (AF) and is associated with worse outcomes. We aimed to investigate the association between multimorbidity, AF progression and AF symptom severity in patients with paroxysmal AF.

The RACE V (Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilization in the Progression of AF) study included patients with paroxysmal AF and continuous rhythm monitoring. Multimorbidity was defined as ≥2 comorbidities (heart failure, hypertension, diabetes, coronary heart disease, kidney dysfunction, moderate or severe mitral valve regurgitation, or obesity). AF symptom severity was assessed via the University of Toronto AF Severity Scale questionnaire. The associations between multimorbidity, AF progression, and AF symptom severity were determined using logistic regression analyses. Median age was 65 (58-71) years and 179 of 417 patients (43%) were women, with a median of 1 (1-2) comorbidities. Median follow-up was 2.2 (1.6-2.8) years. Multimorbidity was associated with AF progression (odds ratio [OR], 2.02 [95% CI, 1.10-3.72], P=0.024) and increased AF symptom severity (OR, 2.67 [95% CI, 1.79-3.99], P<0.001). There was a positive dose-response relation between the number of comorbidities and AF progression (OR, 1.40 [95% CI, 1.09-1.79], P=0.008), as well as AF symptom severity (OR, 1.64 [95% CI, 1.35-1.99], P<0.001). These results remained significant after adjusting for age.

In patients with paroxysmal AF, multimorbidity was associated with AF progression and AF symptom severity. The risk of AF progression and AF symptom severity increased with every additional comorbidity.

URL: clinicaltrials.gov. Unique Identifier: NCT02726698.

Structural, architectural, contractile, or electrophysiological alterations may occur in the left atrium (LA). The concept of LA cardiopathy is supported by accumulating scientific evidence demonstrating that LA remodelling has become a cornerstone diagnostic and prognostic marker. The structure and the function of the LA and left atrial appendage (LAA), which is an integral part of the LA, are key elements for a better understanding of multiple clinical conditions, most notably atrial fibrillation, cardioembolism, heart failure, and mitral valve diseases. Rational use of various imaging modalities is key to obtain the relevant clinical information. Accordingly, this clinical consensus document from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists and cardiac imagers for the best practice of imaging LA and LAA for the diagnosis, management, and prognostication of the patients.

There is no clear consensus regarding the discontinuation of oral anticoagulants (OACs) after catheter ablation (CA) for atrial fibrillation (AF).

To evaluate thromboembolic and major bleeding events and all-cause death following OAC discontinuation and characteristics associated with patient prognoses after successful CA.

This retrospective cohort study included patients without AF recurrence or adverse events 12 months after CA among those undergoing their first CA between January 1, 2006, and December 31, 2021. The study population was divided into groups according to the continuation and discontinuation of OACs at the landmark period of 12 months after CA. Follow-up data were acquired until December 31, 2023, and the study analysis was conducted from January to April 2024.

OAC discontinuation.

Primary outcomes were thromboembolic and major bleeding events and all-cause death after 12 months. Inverse probability of treatment weighting (IPTW) and propensity score-matched analyses were used to adjust baseline characteristics.

This study included 1821 patients (mean [SD] age, 63.6 [11.7] years; 1339 men [73.5%]). Overall, 922 patients (50.6%) continued OAC for 12 months, whereas 899 (49.4%) discontinued OAC. During a mean (SD) follow-up of 4.8 (4.0) years, thromboembolic events, major bleeding events, and death occurred in 43 (2.4%), 41 (2.3%), and 71 (3.9%) patients, respectively. After IPTW adjustment, the OAC discontinuation group demonstrated a significantly higher incidence of thromboembolism (incidence rate, 0.86 [95% CI, 0.45-1.35] vs 0.37 [95% CI, 0.22-0.54] per 100 person-years; log-rank P = .04) and a lower incidence of major bleeding (incidence rate, 0.10 [95% CI, 0.02-0.19] vs 0.65 [95% CI, 0.43-0.90] per 100 person-years; log-rank P < .001) than in the continuation group. In a subgroup analysis, OAC discontinuation was associated with a higher risk of thromboembolism in patients with asymptomatic AF, left ventricular ejection fraction of less than 60%, and left atrial diameter of 45 mm or greater. In contrast, OAC discontinuation was beneficial for reducing major bleeding risks in patients with a HAS-BLED score of 2 or greater. These outcomes were similar in the propensity score-matched analysis using 1100 paired matched patients, except for insignificant differences in thromboembolic events. Differences in mortality between the 2 groups were not statistically significant.

In this retrospective cohort study, discontinuation of OACs after successful CA was associated with increased thromboembolic events and decreased bleeding events. The benefits of discontinuing OACs were stratified according to specific characteristics, pending a future prospective randomized study.

Atrial fibrillation (AF) is the most common arrhythmia, which is tightly associated with the abnormal expression and function of ion channels in the atrial cardiomyocytes. N6-methyladenosine (m6A), a widespread chemical modification in eukaryotic mRNA, is known to play a significant regulatory role in the pathogenesis of heart disease. However, the significance of m6A regulatory proteins in the onset of AF remains unclear. Here, we demonstrate that the m6A reader protein YTHDF2 regulates atrial electrical remodeling and AF onset by modulating the Cav1.2 expression. Firstly, YTHDF2 expression was selectively upregulated in rat atrial cardiomyocytes with AF. Secondly, YTHDF2 knockout reduced AF susceptibility in mice. Thirdly, the knockout of YTHDF2 increased Cav1.2 protein levels in an m6A-in-dependent manner, ultimately prolonging the atrial myocardial refractory period, a critical electrophysiological substrate for the onset of AF. Fourthly, the N-terminal domain of YTHDF2 was identified as critical for Cacna1c mRNA translation regulation. Overall, our findings unveil that YTHDF2 can alter Cav1.2 protein expression in an m6A-independent manner, thereby facilitating the onset of AF. Our study suggests that YTHDF2 may be a potential intervention target for AF.

Cilia are highly specialized cellular projections emanating from the cell surface, whose defects contribute to a spectrum of diseases collectively known as ciliopathies. Intraflagellar transport protein 88 (IFT88) is a crucial component of the intraflagellar transport-B (IFT-B) subcomplex, a protein complex integral to ciliary transport. The absence of IFT88 disrupts the formation of ciliary structures; thus, animal models with IFT88 mutations, including the oak ridge polycystic kidney (ORPK) mouse model and IFT88 conditional allelic mouse model, are frequently employed in molecular and clinical studies of ciliary functions and ciliopathies. IFT88 plays a pivotal role in a variety of cilium-related processes, including organ fibrosis and cyst formation, metabolic regulation, chondrocyte development, and neurological functions. Moreover, IFT88 also exhibits cilium-independent functions, such as spindle orientation, planar cell polarity establishment, and actin organization. A deeper understanding of the biological events and molecular mechanisms mediated by IFT88 is anticipated to advance the development of diagnostic and therapeutic strategies for related diseases.

Left atrial (LA) and ventricular (LV) functional impairment often co-exist in patients with heart failure (HF). However, some patients with HF have a disproportionate LA or LV dysfunction. We aimed to characterize patients with predominant LA and LV myopathy in a cohort of patients with chronic HF across the spectrum of LV ejection fraction (LVEF).

From a nationwide, prospective, multi-center, observational HF cohort, transthoracic echocardiographic examination was performed on each patient. LA reservoir strain and LV global longitudinal strain (LVGLS) were measured using dedicated software of the two-dimensional speckle tracking analysis to evaluate LA and LV function and to define the myopathy.

A total of 374 patients with chronic HF (mean age 58.9±11.5 years, 20% female, mean LVEF 39±17%) were included. By calculating the residuals from the linear regression between LA reservoir and LVGLS, we identified 47 patients with predominant LA myopathy, 271 patients with balanced LA/LV and 56 patients with predominant LV myopathy. Patients with predominant LA myopathy were older, had a higher prevalence of atrial fibrillation (AF), diabetes, higher plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), Growth differential factor 15(GDF15), high sensitivity Troponin T (hs-TNT) as well as more dilated left and right atria, and worse right atrial function compared to other groups (all p-values < 0.05). Using multivariable logistic regression adjusted for LVEF and LA size, independent predictors of predominant LA myopathy were the presence of AF, diabetes, and higher GDF15, whereas absence of diabetes independently predicted predominant LV myopathy. Patients with predominant LA myopathy group had a lower probability of survival than the other groups (Log rank p-value = 0.01).

While most patients with HF have balanced LA/LV myopathy, those with predominant LA myopathy are characterized by older age, more AF, more diabetes, higher circulating biomarkers of cardiac stress and injury, and worse outcomes.

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.

Atrial remodeling is a major pathophysiological mechanism of atrial fibrillation (AF). Atrial remodeling progresses with aging and background diseases, including hypertension, heart failure, and AF itself. However, its mechanism of action and reversibility have not been completely elucidated. In this study, we investigated the involvement of DNA methylation in atrial remodeling. Mice underwent transverse aortic constriction (TAC) to generate a pressure overload model. After 14 days, the TAC-operated mice showed a significant increase in the atrium/body weight ratio and deposition of collagen fibers in the atria. A comprehensive analysis using RNA-sequencing (RNA-Seq) and methyl-CpG-binding domain sequencing (MBD-Seq) in the left atrial tissue identified Hif3a and Ifltd1 as showing increased DNA methylation in their promoter regions and decreased RNA expression. In addition, we created a transient pressure overload model by removing the aortic constriction 3 or 7 days after the initial TAC procedure (R3 or R7 groups). A reduction in RNA expression was achieved at R3 for Hif3a and at R7 for Ifltd1. Heterozygous Dnmt1 gene-targeting mice (Dnmt1mut) showed disappearance of the reduction in RNA expression and an increase in the atrium/body weight ratio. Altogether, DNA methylation contributed to at least part of atrial remodeling in the pressure overload mouse model.

Many engineering and healthcare systems are featured with spatiotemporal dynamic processes. The optimal control of such systems often involves sequential decision making. However, traditional sequential decision-making methods are not applicable to optimize dynamic systems that involves complex 3D geometries. Simulation modeling offers an unprecedented opportunity to evaluate alternative decision options and search for the optimal plan. In this paper, we develop a novel simulation optimization framework for sequential optimization of 3D dynamic systems. We first propose to measure the similarity between functional simulation outputs using coherence to assess the effectiveness of decision actions. Second, we develop a novel Gaussian Process (GP) model by constructing a valid kernel based on Hausdorff distance to estimate the coherence for different decision paths. Finally, we devise a new Monte Carlo Tree Search (MCTS) algorithm, i.e., Normal-Gamma GP MCTS (NG-GP-MCTS), to sequentially optimize the spatiotemporal dynamics. We implement the NG-GP-MCTS algorithm to design an optimal ablation path for restoring normal sinus rhythm (NSR) from atrial fibrillation (AF). We evaluate the performance of NG-GP-MCTS with spatiotemporal cardiac simulation in a 3D atrial geometry. Computer experiments show that our algorithm is highly promising for designing effective sequential procedures to optimize spatiotemporal dynamics in complex geometries.

Catheter ablation for atrial fibrillation (AF) reduces heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). However, the long-term outcomes and subclinical HF after nonparoxysmal AF ablation in HFpEF patients have not been fully evaluated.

One-hundred-ninety nonparoxysmal AF patients with left ventricular ejection fraction ≥50% who underwent first-time AF ablation were studied. HFpEF was diagnosed from a history of congestive HF and/or combined criteria of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and transthoracic echocardiogram parameters, including average septal-lateral E/e' and tricuspid regurgitation peak velocity. Ninety-five patients with HFpEF (HFpEF group) were compared with 95 patients without HF (CNT group). Low voltage area (LVA) was defined as an area with a bipolar electrogram of <0.5 mV covering >5% of the total left atrial surface. The primary endpoint was a composite of death from any cause or hospitalization for worsening HF. The secondary endpoint was subclinical HFpEF defined from NT-proBNP concentration and average septal-lateral E/e' or tricuspid regurgitation peak velocity at 6-12 months after the procedure irrespective of the rhythm. Kaplan-Meier curves showed that the primary composite endpoint did not differ between the two groups (mean follow-up period 707 ± 75 days, log-rank p = 0.5330). However, significantly more patients in the HFpEF group reached the secondary endpoint (42 [44%] vs. 13 [14%], p < 0.0001). Multivariate analysis revealed that a high preablation NT-proBNP (odds ratio [OR] 1.001, 95% confidence interval [CI] 1.001-1.002, p = 0.0040) and the existence of LVA (OR 5.983, 95% CI 1.463-31.768, p = 0.0194) independently predicted the secondary endpoint in HFpEF patients.

After nonparoxysmal AF ablation, mortality of HFpEF patients was not inferior compared to patients without coexisting HF. However, subclinical HF occasionally persisted especially in HFpEF patients with a high preprocedure NT-proBNP concentration and LVA.

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

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

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

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

Cyclophosphamide is a widely used immunosuppressant for inducing remission in various immune-mediated conditions. However, its potential for cardiotoxicity is well documented. One of the earliest possible manifestations of this cardiotoxicity following cyclophosphamide infusion is atrial fibrillation (AF), which typically presents within 48 h of the infusion.

The authors present a case of a 58-year-old male with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis who presented to the emergency department with clinical features of acute kidney injury. Following subsequent assessment and evaluation, the patient was managed in the intensive care unit with hemodialysis and intravenous corticosteroids. He was aimed at inducing remission with cyclophosphamide infusion. However, a few hours following induction with cyclophosphamide infusion, the patient developed palpitation, sweating, and tachycardia with a heart rate of 140-180/min. The electrocardiogram showed an irregular QRS complex with an absent p-wave. AF was diagnosed and managed with amiodarone infusion for 24 h followed by oral maintenance dosing. No further episode of AF occurred following cessation of cyclophosphamide and switching to rituximab for the treatment of ANCA-associated vasculitis.

Cyclophosphamide, even at lower dosages, can cause cardiotoxicity in patients with renal impairment due to the delayed elimination of its toxic metabolites. In addition, patients who receive CYP 450 inducers, such as prednisone, may experience the accelerated build-up of its toxic metabolites, thereby raising the risk for cardiotoxicity.

The cardiotoxic manifestation of cyclophosphamide can arise from its use in several immune-mediated conditions. Given its potential for cardiotoxicity, careful cardiac monitoring during and after cyclophosphamide infusion is essential to ensure timely intervention, if needed.

Reduced left atrial (LA) mechanical function associates with atrial myopathy and adverse clinical endpoints in atrial fibrillation (AF) patients; however, conventional 2D imaging modalities are limited by atrial foreshortening and sub-optimally capture 3D LA motion.

We set out to test the hypothesis that 3D LA motion features from 4D (3D + time) retrospective gated computed tomography (RGCT) associate with AF phenotypes and predict AF recurrence in patients undergoing catheter ablation.

Sixty-nine AF patients (60.8 ± 12.2 years, 39% female, 30% non-paroxysmal AF) who were indicated for CT coronary angiography including a RGCT protocol in sinus rhythm prior to ablation were included. We measured 3D LA endocardial motion by optimized 3D feature tracking and calculated 3D global and regional phasic strain and peak strain rates (SRs). AF recurrence was observed in 18 patients (26%) at 1-year. Global reservoir strain (P < 0.05) and contractile strain and SR (both P < 0.01) were reduced in patients with vs. those without recurrent AF. Global and anterior wall contractile SR were more predictive of recurrent AF than LA volume index (area under the curve, AUC: 0.74, 0.77, and 0.68, respectively). Reduced global conduit SR and septal reservoir strain were more strongly associated with non-paroxysmal AF than CHADS2-VASc (AUCs: 0.74, 0.75, and 0.59, respectively).

Reduced passive and active 3D LA motion from 4D RGCT associates with more advanced AF and AF recurrence post-ablation, respectively. Future work should extend this approach to larger populations, with new low-radiation CT technologies to widen its applicability.

Interest in advanced echocardiographic imaging methods is growing. Left atrial strain (LAS) is among recently developed echocardiographic parameters. LAS represents an index of tissue deformation of the left atrium (LA). This parameter is an expression of LA function. Several arrhythmias are caused by impaired LA function. LAS can be assessed with a resting echocardiogram. The evaluation of LAS during stress echocardiography represents another model for assessing LA function. The development of altered LAS during physical or pharmacological stress is a predictor of early LA disease. Our review aims to evaluate the relationship between alterations in LAS and the development of atrial fibrillation (AF), and the diagnostic and prognostic roles of the stress echocardiogram in clinical practice.

Asthma is a known risk factor for atrial fibrillation (AF), the most common sustained arrhythmia. Whereas radiofrequency catheter ablation is effective in treating AF, the impact of asthma and its severity on ablation outcomes has not been previously explored.

The purpose of this study was to evaluate the impact of asthma and its severity on AF recurrence after ablation.

In this single-center retrospective case-control study, 63 case patients with AF and asthma who underwent ablation were matched with 126 controls with AF but without asthma who underwent ablation. Case patients were also compared with a nonablated cohort of patients with asthma. AF recurrence was compared between groups. Univariate and multivariate analyses were conducted to determine associations with recurrence.

Compared with controls who underwent ablation, patients with asthma, particularly those with severe asthma, had a higher likelihood of AF recurrence after catheter ablation (odds ratio, 3.76 [P = .047] and 5.06 [P = .041], respectively). However, case patients were not more likely to experience adverse outcomes. Multivariate analysis revealed that persistent AF and use of a beta blocker were associated with recurrence. Patients with moderate or severe persistent asthma were more likely than patients with intermittent or mild persistent asthma to have left atrial enlargement (odds ratio, 2.53; P = .009).

Patients with AF and asthma, particularly those with severe asthma, were more likely than patients with AF but without asthma to have AF recurrence after ablation. Patients with AF and severe asthma were also more likely to have severe left atrial enlargement, a known predictor of recurrence after ablation.

Atrial fibrillation (AF), the most common sustained arrhythmia, increases stroke and heart failure risks. Here we review genes linked to AF and mechanisms by which they alter AF risk. We highlight gene expression differences between atrial and ventricular cardiomyocytes, regulatory mechanisms responsible for these differences, and their potential contribution to AF. Understanding AF mechanisms through the lens of atrial gene regulation is crucial to improving AF treatment.

Atrial fibrillation (AF) inducibility with burst pacing (BP) after radiofrequency ablation (RFA) has been reported to be associated with AF recurrence. In contrast, the relevance of inducibility and recurrence after cryoablation (CRA) is unclear.

We investigated 367 patients undergoing initial ablation for paroxysmal AF (RFA: 174, CRA: 193). Propensity score matching was conducted, retaining 134 patients in each group. Following pulmonary vein isolation (PVI), the inducibility by BP was tested. Inductions at 250 ppm were defined as low-frequency burst pacing (LFBP) positive, and those at 300 ppm were classified as medium-frequency burst pacing (MFBP) positive. They were followed for 600 days.

Forty-eight patients (18%) had AF recurrence. There was no significant difference in the recurrence rate between RFA and CRA (17% vs. 19%, Log-rank p = 0.79). In RFA, significant differences were observed for both LFBP (Log-rank p < 0.001) and MFBP (Log-rank p < 0.001). In contrast, in CRA, there were no significant differences for either LFBP (Log-rank p = 0.39) or MFBP (Log-rank p = 0.19). Multivariable analysis revealed that LFBP-positive (hazards ratio [HR] = 5.75, 95% confidence interval [CI] 2.41-13.7, p < 0.001) was an independent predictor for recurrence with RFA. Acute reconnection (HR = 2.73, 95% CI 1.13-6.56, p = 0.025) was an independent predictor for recurrence with CRA.

The inducibility by BP after RFA predicted recurrence at both low and medium frequencies. LFBP-positive was an independent predictor of recurrence in multivariable analysis. In contrast, the inducibility by BP after CRA was not a predictor of recurrence.

This study did not require clinical trial registration.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society.