Search Results (1,044)

Background/Objectives: Atrial fibrillation (AF) is a prevalent arrhythmia associated with severe clinical complications. This exploratory study aimed to evaluate the prognostic value of clinical characteristics, echocardiographic parameters, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting new-onset AF among patients previously diagnosed with non-AF arrhythmias. Methods: A prospective cohort study was conducted involving 232 patients who were followed for a median period of 12 months. Data collection included baseline NT-proBNP levels, demographic characteristics, medical history, presenting clinical symptoms, and various paraclinical indices, including echocardiographic measurements. Results: The most frequent presenting symptoms in the study population were syncope (59.9%) and dizziness (55.6%). Statistical analysis indicated that initial NT-proBNP levels were not a significant predictor for the development of new-onset AF (HR = 0.9995; p = 0.717). Conversely, left atrial (LA) size, a history of diabetes mellitus, and a history of stroke were identified as preliminary risk factors requiring confirmation. Specifically, a history of stroke was associated with a nearly 5-fold increase in AF risk (HR = 4.65), while diabetes mellitus increased the risk nearly 4-fold (HR = 3.84). Furthermore, each one-millimeter increase in LA size was associated with a 21% increase in the risk of developing AF (HR = 1.21). Conclusions: The findings suggest that NT-proBNP is not an effective prognostic marker for new-onset AF in patients with non-AF arrhythmias. Instead, left atrial enlargement and clinical comorbidities, such as diabetes and a history of stroke, emerged as suggestive, hypothesis-generating predictors for clinical screening and risk management in this patient population. Full article

Atrial fibrillation (AF) is a major cardiac arrhythmia characterized by impaired hemodynamics caused by irregular ventricular activation and loss of coordinated atrial contraction. However, the coupled effects of rhythm irregularity and progressive atrial remodeling on cardiovascular hemodynamics have not been sufficiently quantified. In this study, a closed-loop lumped-parameter cardiovascular framework was developed to investigate hemodynamic alterations under normal sinus rhythm (NSR) and AF conditions. Time-varying elastance functions were used to represent cardiac chamber mechanics, while stochastic RR interval sequences reproduced the irregular ventricular response characteristic of AF. Progressive atrial remodeling was represented through systematic increases in atrial elastance to simulate increasing chamber stiffness. The results demonstrated that AF produced irregular left atrial pressure fluctuations and pronounced beat-to-beat variability in ventricular pressure and volume. Ventricular stroke volume decreased from 70–75 mL under NSR to 55–65 mL under AF conditions. With progressive remodeling, left atrial volume decreased by 36.4%, while ventricular end-diastolic volume increased from 130 to 134 mL, indicating compensatory ventricular adaptation. These findings suggested that atrial stiffening impaired atrial compliance and reservoir function, whereas ventricular adaptation partially compensated for the impairment in atrial mechanical function. Full article

Background/Objectives: Atrial fibrillation (AF) is a complex polygenic disorder; its genetic architecture remains challenging to fully elucidate. Methods: In this study, we leveraged the extensive genetic overlap between AF and a spectrum of cardiometabolic and behavioral factors—collectively defined by Life’s Essential 8 (LE8)—to advance our understanding of its etiology. Results: We first estimated significant genetic correlations between AF and all LE8 components (r_g: −0.11 to 0.19) using LD score regression. We then applied conditional false discovery rate analysis and detected 970 pleiotropic loci associated with AF and at least one LE8 trait. Subsequent colocalization analysis identified 179 loci harboring shared causal variants between AF and one or more LE8 components, which were further refined into 137 distinct colocalized regions. Through region-based annotation and functional predictors, we finally prioritized 164 candidate genes from these colocalized loci, including 40 novel genes. These candidate genes were enriched in pathways related to heart development and regulation of cardiac contraction, and were also enriched among molecular targets of otological agents. Among all LE8 components, blood pressure demonstrated the most extensive shared genetic architecture with AF, supported by the strongest genetic correlation, highest pleiotropic enrichment, and the greatest number of colocalized loci with AF. Polygenic risk scores constructed from these colocalized loci demonstrated significant associations not only for AF but also for arrhythmia and heart failure. Conclusions: Our findings establish a genetic pleiotropy-informed framework that enhances the discovery of novel risk loci of AF and advances our understanding of the shared genetic architecture and potential biological mechanisms between AF and LE8 components. Full article

Background and Objectives: Elective electrical cardioversion (eECV) in patients with atrial fibrillation (AF) or atrial flutter is associated with a low risk of thromboembolic events (TEs) when adequate anticoagulation is provided. However, the role of routine transesophageal echocardiography (TEE) prior to eECV remains uncertain. This study aimed to assess thromboembolic outcomes in patients undergoing eECV with or without TEE guidance in a real-world clinical setting. Methods: A single-center, combined retrospective–prospective observational study including 296 adequately anticoagulated patients with AF or atrial flutter scheduled for eECV was conducted. The retrospective cohort (n = 220) underwent eECV without routine TEE, while the prospective cohort (n = 85) underwent TEE prior to eECV. The primary outcome was the occurrence of thromboembolic events (ischemic stroke or systemic embolism) within 30 days after eECV. Arrhythmia recurrence at 30 days was assessed as a secondary, exploratory outcome. Results: Among patients undergoing eECV, thromboembolic events were rare. In the retrospective cohort, 3/220 patients (1.36%) experienced a TE, whereas no events were observed in the prospective cohort (0/76). Due to the low number of events, the study was underpowered to detect meaningful differences between strategies (RR 2.44; 95% CI 0.13–46.7; p = 0.55). TEE identified left atrial appendage thrombus in 9/85 screened patients (10.6%), who were subsequently excluded from cardioversion. Arrhythmia recurrence at one month was more frequent in the prospective cohort (19.7% vs. 7.3%), likely reflecting differences in baseline clinical characteristics. Conclusions: Thromboembolic events after eECV in adequately anticoagulated patients were infrequent in this real-world cohort. While the study design limits direct comparison between strategies, the results indicate that a conventional anticoagulation-based approach without routine TEE is associated with a low risk of thromboembolic events in most patients. At the same time, the detection of left atrial appendage thrombus in a subset of patients underscores the importance of individualized risk assessment and supports the selective use of TEE in higher-risk clinical settings. Full article

Background: Brugada Syndrome (BrS) is a cardiac arrhythmia associated with an increased risk of ventricular arrhythmias and sudden cardiac arrest. Although the arrhythmic substrate is traditionally localized to the ventricles, atrial fibrillation (AF) is frequently observed, suggesting a shared molecular substrate between atrial and ventricular arrhythmias. C-type natriuretic peptide (CNP) and related microRNAs (miRNAs) modulate atrial and ventricular physiology, but their roles in exosomes in BrS have not been investigated. Objectives: To investigate alterations in CNP mRNA expression and changes in the expression of selected CNP-associated miRNAs implicated in AF, both analyzed in exosomes isolated from individuals with BrS and from healthy controls. Methods: Exosomes were isolated from the plasma of BrS patients without a history of overt AF and from healthy controls. In silico analyses identified CNP-targeting miRNAs implicated in AF. Exosomal CNP and CNP-related miRNAs were analyzed using Droplet Digital PCR. Results: BrS patients exhibited a significant increase in exosomal CNP mRNA expression levels compared with controls. MiR-138-5p was selectively downregulated, whereas other AF-related CNP-targeting miRNAs (miR-4443, miR-206, miR-142-5p, miR-223-5p) showed comparable levels between groups. A positive correlation between exosomal CNP and miR-223-5p and miR-4443 suggests shared regulatory pathways. Conclusions: these findings indicate that exosomal profiling may provide a more sensitive approach than conventional circulating measurements to detect molecular remodeling in BrS. The observed alterations highlight a potential shared molecular substrate between atrial and ventricular arrhythmias and may inform future studies aimed at refining diagnostics and developing targeted therapeutic strategies. Full article

Wearable sensors enable continuous recording of electrocardiographic, photoplethysmographic, and inertial signals and have accelerated the development of digital biomarkers in cardiovascular medicine. Transthyretin amyloidosis (ATTR) is a progressive multisystem disease characterized by arrhythmia, conduction disturbances, hemodynamic impairment, autonomic dysfunction, and gait abnormalities, making it theoretically suitable for multimodal wearable monitoring. This review summarizes current knowledge on wearable applications in amyloidosis with ATTR serving as an illustrative case, evaluates the plausibility of extrapolating signal-based biomarkers from related cardiovascular and neurological cohorts, and outlines methodological and implementation challenges. ATTR-specific data remain limited to small observational studies, mainly on long-term rhythm monitoring and supervised functional assessment. More comprehensive findings support the extraction of metrics such as atrial fibrillation burden, activity patterns, gait variability, and heart rate variability. However, ATTR-related structural remodeling and high arrhythmia burden may distort conventional digital biomarkers, necessitating disease-specific preprocessing and prospective validation. Wearable monitoring in ATTR is technically feasible and biologically plausible but remains investigational. Before routine integration into care pathways can be recommended, standardized, phenotype-stratified studies are needed that link wearable-derived characteristics to assessed clinical outcomes. Full article

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) yields variable positivity rates. Identifying clinical predictors of positive genetic tests could improve pre-test counseling and refine expectations about diagnostic yield. Methods: We analyzed consecutive genotyped HCM probands from a contemporary multicenter cohort across four Italian tertiary centers. Genotype positivity was defined as the presence of ≥1 pathogenic or likely pathogenic variant (ACMG classes 4–5). Multivariable logistic regression identified predictors of genotype positivity. Sensitivity analyses assessed the incremental value of left atrial volume index (LAVI) ≥ 34 mL/m² and the mode of first clinical presentation. Results: Among 274 genotyped probands (median age at diagnosis 54 years; 62% male), 86 (31%) were genotype-positive (38% MYBPC3, 29% MYH7). Age at diagnosis <40 years (OR 2.38, 95%CI 1.26–4.51, p = 0.008), family history of sudden cardiac death/major ventricular arrhythmias (OR 2.34, 95%CI 1.16–4.84, p = 0.019) and family history of non-ischemic cardiomyopathy (OR 1.92, 95%CI 1.04–3.54, p = 0.038), were independently associated with genotype positivity whereas arterial hypertension was inversely associated (OR 0.42, 95%CI 0.23–0.77). Maximal left ventricular wall thickness > 20 mm and gender were not predictive of genotype positivity. Inclusion of LAVI modestly improved the model performance (AUC 0.769, p = 0.016, ΔAUC +0.024; DeLong p = 0.016) but without leading to meaningful patient reclassification. Conclusions: Genotype positivity in HCM links to earlier onset and family history; traditional severity markers and initial presentation may not independently suggest genetic causality. These findings may help shape a personalized approach to genetic counseling in HCM. Full article

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with an elevated risk of severe complications, including stroke and heart failure. Due to its paroxysmal nature and the inherent complexity of electrocardiogram (ECG) signals, developing highly accurate and robust automated detection methods remains a critical challenge. To address the limitations of existing models in simultaneously capturing local morphological anomalies and long-range temporal dependencies, we proposed RT-AFNet, a novel hybrid ResNet-Transformer architecture. Specifically, RT-AFNet integrated the robust local feature extraction capabilities of a Residual Neural Network (ResNet) backbone with the global temporal modeling power of a lightweight self-attention mechanism. Furthermore, a multi-scale feature fusion strategy was introduced to optimize feature representation. The proposed RT-AFNet model was evaluated on three public AF databases: the China Physiological Signal Challenge 2018 (CPSC2018), the PhysioNet/Computing in Cardiology Challenge 2017 (CinC2017), and the MIT-BIH Atrial Fibrillation Database (MIT-BIH AF). The proposed model achieved F1 scores of 99.76%, 97.47%, and 96.20%, along with area under the curve (AUC) values of 99.97%, 98.98%, and 98.28% on the three datasets, respectively. These results demonstrate that the proposed architecture exhibits excellent generalization ability and stability across different databases, providing a robust and reliable deep learning solution for automated AF screening. Full article

Atrial fibrillation (AF) is a highly prevalent arrhythmia associated with stroke, heart failure and excess mortality. Yet, “silent” AF episodes remain undetected, leading to underestimation of disease burden. Additionally, paroxysms occur in an “unpredictable” way, and available clinical scores only stratify long-term AF risk with moderate discrimination, lacking the ability to evaluate near-term events. Artificial intelligence (AI) applied to sinus rhythm from short or continuous electrocardiogram (ECG) recordings shows that such predictive information is hidden in “plain sight.” This complementary approach seeks to uncover latent AF substrate and forecast imminent AF episodes. Deep-learning models trained on 10-s, 12-lead ECGs can identify individuals with prevalent or long- or near-term AF with areas under the curve (AUCs) up to 0.90, outperforming established clinical scores. Image-based AI-ECG models extend these capabilities to paper or scanned ECGs. Furthermore, AI algorithms applied to 24-h Holter and multi-day patch recordings achieve AUCs ≥0.80 for detecting occult AF or predicting it within 14 days, consistently surpassing risk scores like C₂HEST and HATCH. Short-term models utilizing heart-rate variability features further demonstrate that AF can be anticipated minutes to hours before onset, with accuracies around 90% in curated datasets. However, most AI-AF studies remain retrospective, single-system and focused on diagnostic yield rather than clinical outcomes like stroke or mortality. Moreover, few pragmatic trials have evaluated AI-guided AF screening and its translation into clinical benefit. Robust prospective trials and standardized evaluation frameworks are needed before AI-guided AF prediction can be routinely integrated into clinical decision-making. Full article

Background: Flecainide has remained largely excluded from use in structural heart disease for more than three decades, mainly because of the Cardiac Arrhythmia Suppression Trial, which showed excess mortality in post-myocardial infarction patients treated for ventricular ectopy. However, the influence of this trial has extended well beyond the population actually studied, fostering a broad safety paradigm that may not fully reflect contemporary clinical practice. Aim: This review aims to re-examine the role of flecainide in structural heart disease by examining the historical basis for its restriction and contrasting it with emerging contemporary evidence across specific structural substrates. Discussion: Flecainide remains one of the most effective antiarrhythmic drugs for rhythm control in atrial fibrillation and for the suppression of selected ventricular arrhythmias in patients without overt structural abnormalities. Emerging observational and early prospective data suggest that, in carefully selected patients with stable coronary artery disease without active ischemia, preserved left ventricular function, arrhythmogenic right ventricular cardiomyopathy, and premature ventricular complex-induced cardiomyopathy, flecainide may provide meaningful antiarrhythmic benefit without a clear signal of excess proarrhythmia or mortality. Advances in cardiac imaging, ischemia assessment, and phenotypic risk stratification further support a more individualized approach to candidate selection. Conclusions: Flecainide should not be considered uniformly contraindicated across all forms of structural heart disease. Rather than supporting indiscriminate use, the available evidence supports a mechanistically informed and phenotype-specific reassessment of its role in selected patients. Prospective studies are needed to determine whether current guideline restrictions remain justified in the modern era. Full article

Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia, present in up to 14–20% of patients undergoing cardiac surgery, with the number of patients expected to double within the next decade. Despite a Class I recommendation for concomitant surgical ablation and a Class I-B recommendation for left atrial appendage (LAA) occlusion in patients with AF undergoing cardiac surgery (Class IIa for endoscopic or hybrid AF ablation), both procedures remain substantially underutilized in clinical practice. The design of the Mapping atrial fibrillation after Epicardial Surgical Ablation plus AtriClip to Guide Endocardial ablation (MESAGE) prospective study is presented. Materials and Methods: A narrative literature review was conducted using PubMed through March 2025. Randomized controlled trials, multicenter registries, meta-analyses and current clinical guidelines were prioritized. The MESAGE study protocol is presented in accordance with the SPIRIT recommendations. Results: Randomized evidence demonstrates that hybrid ablation achieves 32–48% greater arrhythmia freedom than catheter ablation (CA) alone in persistent and long-standing persistent AF, with comparable safety and significantly fewer interventions at two-year follow-up. Epicardial LAA occlusion with the AtriClip device achieves complete occlusion in all patients with an 87.5% relative reduction in ischemic stroke risk in anticoagulation-free follow-up. Continuous implantable loop recorder (ILR)-based monitoring reveals AF recurrence in substantially more patients than conventional monitoring, with AF burden emerging as a more meaningful endpoint than arrhythmia freedom. The MESAGE study enrolls 40 patients undergoing cardiac surgery who have pre-existing AF, pre-randomized 1:1 to pulmonary vein isolation (PVI) alone versus PVI-BOX, with mandatory pre-operative ILR implantation, intra-operative AtriClip LAA exclusion, and systematic Day-60 endocardial mapping and supplementary ablation using the Affera dual-energy system. Conclusions: Hybrid epicardial–endocardial ablation combined with LAA exclusion and continuous ILR monitoring represents a comprehensive, mechanistically rational and evidence-informed approach to AF management in patients undergoing cardiac surgery, although current evidence remains heterogeneous, and the benefits depend on the AF phenotype and monitoring strategy. The MESAGE pilot study will generate hypothesis-generating prospective comparative data on epicardial PVI versus PVI-BOX in the concomitant surgical setting, assessed through systematic post-surgical endocardial mapping and continuous rhythm monitoring. Full article

Background: Atrial fibrillation (AF) is a common clinical arrhythmia associated with mitochondrial dysfunction, oxidative stress, and atrial fibrosis. Mitochondrial-derived peptides (MDPs), including humanin (HN) and MOTS-c, exhibit cytoprotective properties, but their role in AF remains largely unknown. Objective: This study aimed to investigate the expression of HN and MOTS-c in AF patients and to evaluate their therapeutic potential and underlying mechanisms in an AngII-induced mouse model and primary cardiac cells. Methods: HN and MOTS-c expression in human atrial tissues was analyzed using public GEO data, immunohistochemistry, and immunofluorescence. Plasma levels were measured in a matched cohort (39 AF patients, 39 sinus rhythm controls). Murine AF models (male C57BL/6J mice, n = 36) and primary rat cardiomyocytes and fibroblasts were exposed to angiotensin II (AngII) with or without treatment with HNG (an HN analogue) or MOTS-c. Results: HN and MOTS-c were significantly downregulated in human AF atrial tissue, and their levels inversely correlated with fibrosis extent. Plasma MOTS-c was decreased in AF patients and inversely correlated with NT-proBNP. In vivo, HNG or MOTS-c treatment reduced AF inducibility and attenuated AngII-induced atrial fibrosis and hypertrophy. Peptide treatment was associated with improved mitochondrial ultrastructure, reduced mitochondrial fission proteins (Drp1, Fis1), and lower pro-inflammatory cytokines (IL-1β, IL-6) in mouse atria. In primary cardiomyocytes, both peptides mitigated AngII-induced oxidative stress. In fibroblasts, they directly inhibited AngII-induced activation, proliferation, and migration. Exploratory RNA-seq suggested that HNG predominantly affects cell adhesion pathways, while MOTS-c acts on metabolic processes. Conclusions: Downregulation of HN and MOTS-c in human AF is associated with disease severity. In murine models, HNG or MOTS-c administration attenuates atrial fibrosis and mitochondrial dysfunction and reduces AF inducibility. These findings suggest that MDPs may represent a novel therapeutic avenue for AF, although further validation with larger cohorts and mechanistic studies are required. Full article

Background: Short QT syndrome (SQTS) is a rare inherited cardiac channelopathy associated with high risk of atrial and ventricular arrhythmias and sudden cardiac death (SCD). Data on its natural history, genotype–phenotype correlations, and risk stratification remain limited. We aimed to evaluate all families with a confirmed diagnosis of SQTS identified at our National Referral Center through a descriptive case series, thereby contributing additional real-world data on this rare condition. Methods: A retrospective review was conducted of all families evaluated for suspected SQTS between 2011 and 2025 at the Inherited Cardiac Diseases Unit. Diagnosis was based on 2022 ESC guidelines (QTc ≤320 ms or ≤360 ms plus supportive features), clinical evaluation, and genetic testing. Families meeting diagnostic criteria were included for detailed phenotypic and genotypic characterization and longitudinal follow-up. Results: Among all patients assessed, two families met the criteria for SQTS. One family with three phenotype-positive individuals was gene-elusive. This family had a history of SCD and the proband presented atrial fibrillation. The second family carried a pathogenic KCNJ2 variant (p.Asp172Asn). However, only the proband fulfilled ECG criteria for SQTS (phenotype-positive) and there was no family history of SCD. No patients were treated with pharmacological therapy for QT prolongation. All affected individuals showed stable QT intervals (none <320 ms) and there were no malignant arrhythmic events during follow-up. Conclusions: These two families illustrate the wide phenotypic spectrum of SQTS and underscore the difficulty of risk stratification in asymptomatic individuals. The rarity of the disease, variable penetrance, and absence of robust prospective data hinder evidence-based management. Systematic registry participation and longitudinal studies are essential to refine risk prediction and therapeutic strategies. Full article

Background and Objectives: Diazepam, a GABA_A receptor agonist with sympatholytic properties, is sometimes co-administered with antiarrhythmic agents in the emergency management of atrial fibrillation (AF), yet evidence supporting this practice is remarkably limited. Given the established role of sympathetic activation in the initiation and maintenance of AF, we investigated whether adjunctive diazepam influences treatment outcomes. Materials and Methods: This single-centre retrospective cohort study included 72 hemodynamically stable patients presenting with AF to the emergency department of University Hospital Centre Split, Croatia. Patients were stratified by treatment strategy into a rhythm control group (n = 33, receiving any Class IC/III antiarrhythmic) and a rate control only group (n = 39, beta-blockers and/or digoxin). Diazepam was administered orally at the physician’s discretion (median dose 5 mg). Primary outcomes were rhythm conversion and achievement of a heart rate < 110 bpm. Secondary outcomes included changes in heart rate, blood pressure, and time to therapeutic goal. Results: Diazepam was administered to 32 patients (44.4%). In the rate control stratum, spontaneous rhythm conversion was significantly higher with diazepam (40.0% vs. 9.5%; OR 6.33, 95% CI 1.06–37.78, p = 0.046), corresponding to a model-predicted increase in conversion probability from 8% to 33%. This effect was absent in the rhythm control group (64.3% vs. 64.7%; OR 0.98, p = 1.000). Diazepam increased the odds of achieving HR < 110 bpm by 3.46-fold (95% CrI 0.63–23.1, posterior probability of benefit 92%) in the rate control group. Diazepam-treated patients in the rate control group had longer median time to therapeutic goal (4.2 vs. 2.8 h, p = 0.005). In the rhythm control group, diazepam was associated with reduced variability in diastolic blood pressure response (p = 0.006). Conclusions: Adjunctive diazepam was associated with a significantly higher rate of spontaneous rhythm conversion in AF patients receiving rate control therapy only, consistent with sympatholysis removing a key factor sustaining the arrhythmia. This effect was not observed when Class IC/III antiarrhythmics were co-administered, suggesting that diazepam’s benefit is context-dependent. These hypothesis-generating findings warrant prospective validation, with attention to thromboembolic risk in patients who convert unexpectedly. Full article

Fatty acids serve dual roles in cardiac physiology: as energy substrates and as precursors of bioactive lipid mediators (prostaglandins, leukotrienes, oxylipins) from n-3/n-6 PUFAs that regulate inflammation, thrombosis, and remodeling. Saturated, monounsaturated, and trans fatty acids modulate metabolism and membrane function, thereby shaping these pathways. Clinically, n-3 long-chain PUFAs (EPA and DHA) reduce cardiovascular mortality and aid postischemic remodeling; however, high doses increase the risk of atrial fibrillation. By contrast, trans and saturated fatty acids promote dyslipidemia, dysfunction, and higher rates of coronary artery disease and heart failure. Mechanistically, fatty acid uptake via FABPpm, CD36 (FAT), and FATPs, along with β-oxidation and PPAR signaling, regulates metabolism, while COX/LOX/CYP pathways generate eicosanoids and resolvins that influence inflammation and repair. This review synthesizes evidence on the roles of fatty acids and oxylipins in lipotoxicity, heart failure, ischemia–reperfusion, and arrhythmias, and evaluates dietary and supplemental interventions to optimize cardiac lipid metabolism, aligning with fatty acid signaling. Full article