Cardiac arrhythmias, including atrial fibrillation and ventricular arrhythmias, remain leading causes of morbidity and mortality worldwide. While structural, electrical, and metabolic remodeling have long been recognized as drivers of arrhythmogenesis, emerging evidence identifies inflammation—particularly inflammasome signaling—as a central orchestrator of this pathological triad. Among the various inflammasome complexes, the NLRP3 inflammasome has garnered particular attention due to its activation in cardiomyocytes, fibroblasts, and immune cells in diverse clinical contexts. NLRP3 activation precipitates a cascade of downstream events, including interleukin-1β and -18 maturation, oxidative stress amplification, calcium mishandling, and extracellular matrix remodeling, thereby fostering a proarrhythmic substrate. This review synthesizes mechanistic and translational data implicating inflammasome signaling in both atrial and ventricular arrhythmias, with a focus on cellular specificity and electrophysiological sequelae. We explore upstream triggers, such as metabolic stress, gut dysbiosis, and epicardial adipose inflammation, and delineate the downstream impact on cardiac conduction and structural integrity. Emerging therapeutic strategies—including NLRP3 inhibitors, IL-1 antagonists, colchicine, and SGLT2 inhibitors—are critically appraised for their anti-inflammatory and antifibrotic potential. By bridging molecular insights with clinical application, this review underscores the inflammasome as a unifying mechanistic hub in arrhythmia pathogenesis and a promising target for precision-guided therapy.

Aims: Asymptomatic atrial fibrillation (AF) is frequent and associated with disease progression. This meta-analysis aimed to estimate the prevalence of asymptomatic AF and identify risk factors associated with asymptomatic status. Methods and results: MEDLINE (PubMed), Scopus, Cochrane, and ClinicalTrials.gov were searched until 8 January 2025. Double-independent study selection, data extraction, and quality assessments were performed. Random-effects meta-analysis was used. Estimates are presented with the asymptomatic individuals in the nominator and the symptomatic patients in the denominator. The assessment of the prevalence of asymptomatic AF and the identification of risk factors associated with the asymptomatic status comprised the main endpoints. Thirty-seven studies (224 273 participants) were included. The prevalence of asymptomatic AF was 27% [95% confidence interval (CI) = (22%, 33%); I2 = 100%]. Risk factors positively associated with the asymptomatic status were male sex [odds ratio (OR)=1.67, 95% CI = (1.48, 1.89), P < 0.001, I2 = 85%), diabetes mellitus [OR = 1.19, 95% CI = (1.07, 1.33), P = 0.002, I2 = 87%], chronic kidney disease [OR = 1.21, 95% CI = (1.08, 1.36), P < 0.001, I2 = 80%] and stroke/transient ischemic attack [OR = 1.43, 95% CI = (1.18, 1.73), P < 0.001, I2 = 95%], while heart failure was negatively associated with asymptomatic AF [OR = 0.71, 95% CI = (0.54, 0.94), P = 0.017, I2 = 97%]. Asymptomatic status was also positively associated with permanent AF [OR = 2.13, 95% CI = (1.28, 3.55); P = 0.004; I2 = 98%] and negatively associated with catheter ablation [OR = 0.63, 95% CI = (0.44, 0.91); P = 0.012; I2 = 95%], beta-blockers [OR = 0.90, 95% CI = (0.82, 0.98); P = 0.018; I2 = 68%] and antiarrhythmics [OR = 0.53, 95% CI = (0.35, 0.79); P = 0.002; I2 = 95%]. Conclusion: Asymptomatic AF was estimated at around 27%, with large variability depending on the prevalence of risk factors associated with asymptomatic status. Asymptomatic individuals had distinct characteristics compared with symptomatic patients, regardless of symptoms’ assessment methods and rhythm/rate control interventions. Our results could inform AF screening practices to target asymptomatic individuals. Registration: PROSPERO: CRD42024578738.

Atrial fibrillation (AF) is the most common sustained arrhythmia and a major contributor to stroke and cardiovascular morbidity. However, current approaches to rhythm control and stroke prevention are often limited by variable treatment responses and population-based risk stratification tools that fail to capture individual disease mechanisms. Digital twin technology—computational models built using patient-specific anatomical and physiological data—has emerged as a promising approach to address these limitations. In the context of AF, left atrial (LA) digital twins integrate structural, electrophysiological, and hemodynamic information to simulate arrhythmia behavior, therapeutic response, and thromboembolic risk with high mechanistic fidelity. Recent applications include stroke risk prediction using computational fluid dynamics, in silico testing of antiarrhythmic drugs, and virtual planning of catheter ablation strategies. These models have shown potential to enhance the personalization of care, offering a more nuanced and predictive framework than conventional scoring systems or imaging alone. Despite promising progress, challenges related to model personalization, computational scalability, and clinical validation remain. Nevertheless, LA digital twins are poised to advance the precision management of AF by bridging in silico modeling with real-world decision-making. This review summarizes the current state and future directions of left atrial digital twin models in AF, focusing on their application in stroke risk prediction, pharmacologic decision-making, and ablation strategy optimization.

Aims: Catheter ablation is a well-established treatment for symptomatic paroxysmal atrial fibrillation (PAF) or persistent atrial fibrillation (PsAF) refractory to antiarrhythmic agents, and current guidelines have also upgraded its role as a first-line option for recurrent PAF. However, the optimal timing to maximize rhythm outcomes remains uncertain. To address this gap, the present study sought to investigate the association between diagnosis-to-ablation time (DAT) and age-stratified atrial fibrillation (AF) recurrence and clinical outcomes. Methods and results: Medline, the Cochrane Library, and Scopus were searched through 18 February 2025. Triple-independent selection, extraction, and quality assessment were conducted, with evidence pooled via random-effects meta-analyses. Among the 28 studies (41 431 participants) with a median 24-month follow-up, early ablation (DAT ≤ 1 year) significantly reduced AF recurrence compared to delayed ablation [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.59–0.73]. The benefit of early ablation was consistent for both PAF (HR 0.72, 95% CI 0.67–0.77) and PsAF (HR 0.70, 95% CI 0.61–0.81). Age-stratified analysis revealed that this effect was significant regardless of age, with the greatest risk reduction observed in individuals ≤ 55 years (HR 0.49, 95% CI 0.34–0.71). Early ablation was also associated with a reduced risk of repeat ablation, new cardioversion, and cardiovascular hospitalization compared to delayed ablation. Higher CHA₂DS₂-VASc scores, heart failure prevalence, and lower mean left ventricular ejection fraction were associated with greater benefits from early ablation. Conclusion: Early catheter ablation within 1 year of AF diagnosis is associated with a lower risk of recurrence in both PAF and PsAF, with the strongest association observed in patients ≤ 55 years.

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs—has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways—ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing—are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance.

In the context of multi-organ involvement in sepsis, cardiac toxicity is manifested as sepsis-induced cardiomyopathy (SICM). To date, no unified SICM definition exists, though a left ventricular ejection fraction ≤ 50% and/or an absolute drop ≥ 10% from baseline are the most widely accepted components. Several molecular pathways have been associated with SICM, including (i) pro-inflammatory mediator-induced cardiac depression; (ii) sarcolemmal membrane dysfunction; (iii) autonomic nervous system (ANS) imbalance; (iv) blunted cardiovascular response to catecholamines; (v) dysfunctional intracellular calcium handling; (vi) mitochondrial dysfunction; (vii) metabolic reprogramming; and (viii) disturbed endothelial and microcirculatory function. Atrial and ventricular arrhythmias—particularly atrial fibrillation—commonly complicate disease management and are associated with adverse outcomes. Key mechanisms outlining sepsis-induced arrhythmogenesis are (i) inflammation; (ii) electrolyte imbalances; (iii) myocardial ischemia; (iv) QT prolongation/dispersion; (v) adrenergic overactivation; (vi) calcium mishandling; and (vii) fever-induced arrhythmogenesis in Brugada. Established therapeutic approaches include prompt treatment with antibiotics, hemodynamic optimization, and/or selective use of beta-blockers. Furthermore, several molecules are currently being investigated targeting numerous pathways activated in sepsis. Vitamin C, ginsenoside Rc, Schistosoma Japonicum cystatin, and gasmerdin-D inhibitor Y2 exert anti-inflammatory actions, while melatonin and α-ketoglutarate regulate mitochondrial homeostasis. Triiodothyronine targets microcirculatory optimization and regulates protective pathways against stress-related cell death. Engineered exosomes may facilitate targeted drug delivery, inflammatory response modulation, and activation of pathways related to cell survival, while sodium octanoate exhibits anti-inflammatory actions coupled with improved energy metabolism. Finally, gene-regulating therapies aiming at inflammatory response optimization have also been proposed and are currently under development. Future research should aim to standardize the SICM definition, translate emerging therapeutics into clinical practice, identify novel molecular targets, and implement personalized treatment strategies for SICM.