Search Results (430)

Atrial fibrillation (AF) is the most common tachyarrhythmia worldwide. Accompanying the increasing age of the general population, as well as an increase in underlying cardiovascular disease in the United States, is an explosive rise in the incidence and prevalence of this condition. We reviewed observational cohort studies, systematic reviews, meta-analyses, and randomized controlled trials (RCTs) to determine both underlying risk factors and treatment of AF, with particular focus on comorbid conditions influencing treatment success. Numerous studies have demonstrated a reciprocal relationship between maladaptive cardiac remodeling and AF, with the suggestion that aggressive management of both AF itself and resultant cardiovascular disease can lead to reversal of both conditions. Ultimately, many modifiable risk factors for AF exist, with treatment delays associated with a shift towards these conditions becoming unmodifiable. While a large area of focus for AF research has been on determining the optimal pharmacological strategy (i.e., rate versus rhythm control), results have been mixed, with emerging guidelines now pointing towards a flexible treatment strategy that allows for consideration of patient comorbid conditions, medication ease and affordability, and patient preference. Treatment of AF also includes prevention of thromboembolic events. In recent years, novel strategies for surgical or physical occlusion of the left atrial appendage (LAA) with devices such as the Watchman have arisen. Multiple large RCTs have demonstrated the safety and efficacy of these devices, but consideration must be given towards the patient’s bleeding risk, as short-term courses of blood thinners are still considered the standard of care. Finally, emerging therapies for AF include novel drug combinations, neuromodulation devices, and potentially glucagon-like peptide receptor-1 (GLP-1) agonist medications for reduction in overall metabolic disease. Full article

Cardiac arrhythmias are increasingly recognized as dynamic clinical phenotypes arising from the interplay between myocardial substrate, systemic biology, and modifiable exposures rather than as isolated disorders of cardiac electrophysiology. Advances in the field have broadened the conceptual framework of arrhythmia medicine to include structural remodeling, inflammation, autonomic dysfunction, metabolic perturbation, endothelial injury, and aging-related vulnerability as central determinants of arrhythmic risk, progression, and treatment response. In parallel, diagnostic paradigms are evolving from rhythm classification alone toward multidimensional phenotyping that integrates clinical, physiological, and imaging-based markers to identify susceptibility earlier and with greater precision. These developments are also reshaping therapeutic strategy, supporting a shift from uniform treatment algorithms toward individualized care in which rhythm control, surveillance, risk-factor modification, anticoagulation, and antiarrhythmic drug selection are aligned with the underlying biological context. This more integrated view positions arrhythmias not simply as electrical events to be suppressed, but as manifestations of broader cardiovascular and systemic disease processes that require mechanistically informed and phenotype-directed management. Full article

Short QT syndrome (SQTS) is a rare, inherited cardiac channelopathy characterized by an abnormally shortened QT interval, accelerated ventricular repolarization, and an increased risk of atrial and ventricular tachyarrhythmias, including sudden cardiac death (SCD). We report the case of a 14-year-old girl diagnosed with SQTS presenting with persistent atrial fibrillation and a complex independent neurological background. The patient, with no significant family history of cardiac disease or SCD, was incidentally found to have atrial fibrillation and a markedly shortened QT interval during a routine medical evaluation. Although she remained entirely asymptomatic from a cardiovascular perspective, her medical history was notable for maternal Toxoplasma gondii infection during pregnancy, extreme prematurity, and delayed psychomotor development. Electrocardiographic (ECG) findings consistently demonstrated a short QT interval, and genetic testing revealed a likely pathogenic variant in the KCNJ2 gene, consistent with type 3 short QT syndrome (SQTS3). Despite the initiation of antiarrhythmic therapy, atrial fibrillation persisted and the QT interval remained significantly shortened throughout the 24-month follow-up. This case highlights the diagnostic and therapeutic challenges of managing short QT syndrome in pediatric patients, particularly in those who are asymptomatic yet exhibit sustained atrial arrhythmias. It also highlights the coexistence of cardiac channelopathy and neurological comorbidities, emphasizing the importance of a multidisciplinary approach for these distinct clinical entities. Full article

Our review focuses on methanesulfonamide-containing compounds, a well-characterized class of high-affinity blockers of the hERG potassium channel, which plays a critical role in cardiac repolarization by mediating the cardiac I_Kr. These compounds, which include notable class III antiarrhythmic drugs such as dofetilide and d-sotalol, block the hERG channel in its open state by binding within the inner vestibule. This interaction is particularly strong with some residues and the compounds form hydrogen bonds with others. This binding results in high-affinity inhibition with slow dissociation kinetics, frequently leading to drug trapping and prolonged action potential duration (APD). This can predispose patients to arrhythmias, including Torsades de Pointes. Beyond cardiac drugs, there are several non-cardiac methanesulfonamide drugs that also block the hERG channel. This causes pro-arrhythmic side effects despite their primary indications. The clinical significance of these effects, especially in patients with impaired drug elimination, is that accumulation increases the risk of arrhythmia. The objective of forthcoming research endeavors is to mitigate hERG affinity, with the aim of reducing pro-arrhythmic risks while maintaining therapeutic efficacy. This means structural modifications that seek to remove or modify the methanesulfonamide group. Machine learning also emerged as promising tool for exploring drug–protein interactions. It is evident that the methanesulfonamide moiety plays a pivotal role in the structural basis of hERG blockade. However, it should be noted that this moiety does not necessarily represent a universal pharmacophore. This observation underscores the necessity for a nuanced approach in drug development, aimed at achieving a balance between efficacy and safety. Full article

Dihydrosanguinarine (DHSA) is a naturally occurring benzo[c]phenanthridine alkaloid primarily isolated from plants of the Papaveraceae family. DHSA exhibits broad pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, neuroprotective, analgesic, anxiolytic, antiarrhythmic, and antimicrobial effects. Mechanistically, DHSA regulates multiple signaling pathways and molecular targets, including TMEM16A, p53, Ras/Raf/MEK/ERK, PI3K/AKT, NF-κB, PPARγ, GABA_A receptors, and voltage-gated sodium channels. Compared with its biosynthetic precursor sanguinarine (SA), DHSA exhibits a comparatively favorable safety profile while retaining considerable biological activity. Pharmacokinetic studies further suggest that DHSA possesses acceptable membrane permeability, gastrointestinal absorption potential, enterohepatic circulation characteristics, and sustained systemic exposure. In addition, structure–activity relationship (SAR) and electrostatic surface potential (ESP) analyses indicate that the chemically accessible C6 position may provide opportunities for rational structural optimization. Nevertheless, the clinical translation of DHSA still faces several challenges. Therefore, this review systematically summarizes the physicochemical properties, pharmacological activities, molecular mechanisms, SAR characteristics, ESP distribution, toxicity, pharmacokinetic behavior, and clinical prospects of DHSA, aiming to provide a theoretical basis for its future drug development and translational application. Full article

Background: Epicardial mapping and ablation of ventricular tachycardia (VT) are used in different clinical situations but pericardial adhesions following prior cardiac surgery or previous epicardial procedures may limit a percutaneous approach. The objective of this case series is to evaluate the safety and feasibility of a hybrid approach with surgical epicardial access as a valid alternative when pericardial space is not accessible percutaneously. Methods: After a complete preprocedural evaluation, four patients with prior cardiac surgery underwent hybrid VT ablation under general anesthesia. Surgical subxiphoid access was performed in three cases and one patient was subjected to median resternotomy for concomitant open-heart surgery. Epicardial electroanatomic voltage maps were acquired using the CARTO 3 system (Biosense Webster) or NavX (St. Jude Medical) and VT ablations with irrigated catheters were performed. The procedural endpoint was VT non-inducibility and/or LAVA/LP abolition. Results: No serious periprocedural complications occurred after hybrid VT ablation. Three patients had no complex ventricular arrhythmias after a median follow-up of 43 months. A symptomatic sustained VT relapsed in one patient, without requiring a redo ablation procedure but responded to escalation of antiarrhythmic therapy. Conclusions: A carefully planned hybrid VT ablation with surgical epicardial access is a safe and feasible procedure in patients with epicardial scar-related re-entry circuits and pericardial adhesions that limit a percutaneous approach. 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

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, making the search for new therapeutic strategies to prevent or mitigate cardiac damage mandatory. Essential oils, long used in traditional medicine, contain terpenoids as their most prominent constituents, and these molecules have emerged as promising cardioprotective agents. The review compiles 45 articles investigating the effects of plant-derived terpenoids on cardiovascular health. Evidence shows that their therapeutic properties rely on their antioxidant, anti-inflammatory, anti-apoptotic, anti-remodeling, antiarrhythmic, antihypertensive, anti-atherosclerotic, antidiabetic and antimicrobial actions. These effects result from the modulation of molecular pathways altered during cardiovascular diseases, resulting in oxidative stress, inflammation, cell death, fibrosis, ion channel dysregulation, alteration of lipid metabolism and glucose homeostasis. Key mechanisms of terpenes healing properties include activation of endogenous antioxidant defense—mainly via Nrf2-, inhibition of NLRP3 inflammosome-mediated pyroptosis and reduction in lipid oxidation involved in atherosclerotic plaque formation. Their therapeutic potential is reinforced by low toxicity profiles and broad botanical availability. However, challenges related to their translation to therapeutic practice remain unresolved, such as low bioavailability, limited yield and scarce results in human in vitro models. Future research should focus on nano- and micro-delivery systems, biotechnological production strategies and the use of human induced pluripotent stem cell-derived cardiomyocytes. Despite these limitations, terpenes represent valuable templates for developing more potent and clinically viable therapeutic agents. Further studies of this family are encouraged due to its promising ability to treat cardiovascular disorders. Full article

Background/Objectives: The management of ventricular arrhythmias (VAs) within cardiac intensive care units (CICUs) is undergoing a significant transformation. This review aims to analyze the historical transition from a narrow focus on arrhythmia-specific treatments toward on the multidisciplinary heart rhythm team. Methods: A narrative revies was conducted. Results: Effective management of electrical storm (ES) requires prompt attenuation of sympathetic hyperactivity, with a preference for non-selective beta-blockers and the implementation of deep sedation. The use of mechanical circulatory support (MCS) has emerged as a mechanical antiarrhythmic strategy by facilitating ventricular unloading and reducing myocardial wall stress. Furthermore, early catheter ablation, guided by 3D electroanatomical mapping and advanced imaging, has proven superior to salvage procedures for stabilizing the arrhythmic substrate. Finally, the integration of palliative care ensures ethical stewardship during refractory shock. Conclusions: Modern VAs management in the CICUs represents a convergence of technology, biology, and multidisciplinary coordination. 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

Background/Objectives: Persistent and long-standing persistent atrial fibrillation (AF) presents a therapeutic clinical challenge balancing complex rhythm management with a heightened stroke risk. The left atrial appendage (LAA) is the primary source of thromboembolisms in these patients. This study evaluated the safety and efficacy of combining LAA exclusion with Convergent Hybrid Ablation for stroke prevention and rhythm control in a refractory patient cohort. Methods: A single-center observational cohort study was conducted including 28 patients with symptomatic persistent or long-standing persistent AF. The cohort was highly refractory, with 82.1% having failed at least one endocardial catheter ablation. The hybrid procedure consisted of sub-xiphoid epicardial ablation, thoracoscopic LAA exclusion (AtriClip), and endocardial catheter ablation. Safety and efficacy were assessed at 3 months and 12 months. Results: LAA exclusion was successfully performed in 96.4% of patients. The peri-operative safety profile was acceptable, with zero procedure-related strokes or deaths. At the 12-month follow-up, the rate of stroke or any other major adverse events was at 0.0%. Freedom from AF was 75.0%, shown by a 12-lead electrocardiography (ECG). Freedom from any atrial arrhythmia off anti-arrhythmic drugs (AADs) was achieved in 50.0% of patients. A total of 32.1% of the cohort required catheter ablation within 12 months to maintain sinus rhythm as part of the hybrid treatment. Conclusions: Concomitant LAA exclusion during Convergent Hybrid Ablation is a safe procedure with a high clinical success rate in maintaining sinus rhythm in a highly complex AF patient group. While no thromboembolic events were observed at 12 months, larger studies with longer follow-up are needed to confirm the potential for long-term stroke risk reduction. The findings suggest that for many patients, the hybrid procedure should be viewed as part of a multi-step strategy often requiring endocardial “touch-up” ablation. Full article

The quantitative analysis of cardio selective beta-blockers, such as the antihypertensive and antiarrhythmic medication acebutolol (ABT), is critical for biomedical and environmental monitoring. This study describes the development of a high-performance electrochemical sensing platform for ABT based on a screen-printed carbon electrode (SPCE) modified with a silver nanoparticle/hexagonal boron nitride (Ag NPs/h-BN) nanocomposite. The morphological and structural properties of the synthesized materials were examined by using a microscopic and spectroscopic techniques. The Ag NPs/h-BN/SPCE demonstrated exceptional electrocatalytic activity toward ABT oxidation, characterized by a significant reduction in overpotential and a substantial enhancement in peak current relative to unmodified and mono-component electrodes. This superior performance is attributed to the synergistic integration of Ag NPs and h-BN, which provides a high density of active sites, an expanded electroactive surface area, and accelerated charge transfer kinetics. Under optimized experimental conditions, the sensor exhibited a broad linear dynamic range of 0.01–284 μM, a remarkably low limit of detection (LOD) of 0.0049 μM, and a high sensitivity of 0.873 µA µM⁻¹ cm⁻² for ABT detection. Furthermore, the platform displayed excellent selectivity in the presence of common interfering species and robust reproducibility (RSD of 4.8%). The practical utility of the Ag NPs/h-BN/SPCE was successfully validated through the precise quantification of ABT in complex biological and environmental matrices. This work provides a versatile strategy for the rational design of metal nanocatalysts confined within h-BN frameworks for the development of advanced electrochemical diagnostic tools. Full article

Introduction: Propofol is one of the most commonly used intravenous anesthetics worldwide and is considered safe for all age groups. However, there have been reports that propofol can induce severe atrioventricular block in humans, and several studies have shown that propofol hinders or prevents the inducibility of arrhythmias during electrophysiological studies (EPS) and radiofrequency (RF) ablation. Objectives: To compare arrhythmia inducibility during electrophysiological study and radiofrequency ablation in pediatric patients with Wolff–Parkinson–White syndrome undergoing propofol-based sedation versus sevoflurane-based general anesthesia. Methods: We conducted a retrospective observational cohort study including 45 pediatric patients aged 0–18 years. Patients were identified through a review and analysis of a database of individuals with Wolff–Parkinson–White syndrome who were referred for electrophysiological study and/or radiofrequency ablation at the Electrophysiology Laboratory of the Institute of Cardiology (IC/FUC) in Porto Alegre over the past five years (2019–2024). Patients with prior ablation, structural heart disease, or ongoing antiarrhythmic therapy were excluded. The patients were divided into two groups and designated as group S (who received sedation) or group G (who received general anesthesia). Sedation (group S) was performed with midazolam (0.08–0.2 mg/kg), fentanyl (0.1–0.2 μcg/kg), and propofol 50–60 µg/kg/min in continuous infusion. General anesthesia (group G), in turn, was performed with sevoflurane at an average dose of 2% (1 MAC according to age). Results: From 4874 invasive electrophysiology procedures performed during the study period, 45 involved pediatric patients with WPW. The sedation group (n = 29) had significantly older patients (14.6 ± 2.5 vs. 10.3 ± 2.8 years, p < 0.001) with higher weight (65.9 ± 16.3 vs. 41.2 ± 7.8 kg, p < 0.001) compared to the general anesthesia group (n = 16). Arrhythmia was successfully induced in 15/29 (51.7%) patients in the sedation group compared to 13/16 (81.2%) in the general anesthesia group (p = 0.062, Fisher’s exact test). Although this difference did not reach statistical significance, it represents a clinically relevant 29.5% lower induction rate in the sedation group. Post hoc power analysis revealed the study was underpowered (49.8%), suggesting a possible Type II error. Analysis of the “procedure room time” revealed a longer duration in the general anesthesia group (97.8 ± 36.7 vs. 67.8 ± 24.4 min), and this difference was statistically significant (p = 0.002). Conclusions: This study compared propofol-based sedation with sevoflurane-based general anesthesia in pediatric WPW patients. While sedation with propofol did not show a statistically significant reduction in arrhythmia inducibility, there was a concerning trend toward lower induction rates (29.5% difference) that may be clinically relevant. The study’s limited statistical power (49.8%) suggests these findings should be interpreted cautiously, and larger prospective studies are needed to definitively establish whether propofol affects arrhythmia inducibility in this population. Propofol remains a viable option for these procedures, but clinicians should be aware of the potential for reduced inducibility, particularly in cases where arrhythmia induction is critical for diagnosis and treatment. Full article

Background and Objectives: Idiopathic ventricular arrhythmias commonly occur in patients without structural heart disease and most often present as premature ventricular contractions (PVCs). Although generally considered benign, a high PVC burden may cause symptoms, reduce quality of life, and lead to reversible PVC-induced cardiomyopathy. This study aimed to evaluate long-term outcomes after radiofrequency catheter ablation of idiopathic outflow tract PVCs. Materials and Methods: This single-center retrospective study included 101 patients with idiopathic PVCs who underwent radiofrequency catheter ablation. PVC burden and clinical outcomes were assessed at baseline and during follow-up at 3 months, 12 months, and 5 years. Procedural success, predictors of success, and changes in antiarrhythmic drug therapy were analyzed. Results: During follow-up, a marked reduction in PVC burden was observed compared with baseline values. The median PVC burden decreased from 21.89% at baseline to 0.79% at 3 months, 0.23% at 12 months, and 0.09% at the 5-year follow-up after ablation. Acute procedural success was achieved in 88.1% of patients. Long-term success at 5 years was observed in 80.2% of patients. The use of antiarrhythmic drugs decreased during follow-up. Left ventricular ejection fraction remained stable, with no significant difference between baseline and 5-year values. Monomorphic PVC morphology and procedural success at 12 months were identified as independent predictors of long-term success. Conclusions: Radiofrequency catheter ablation provides effective and sustained reduction in PVC burden in patients with idiopathic outflow tract PVCs, with high acute success rates, durable long-term outcomes, and reduced reliance on antiarrhythmic drug therapy. Full article

Background and Clinical Significance: Patients with a left ventricular assist device (LVAD) are at risk of ventricular arrhythmias, which are generally hemodynamically tolerated if they occur. In such cases, patients may experience painful implantable cardioverter-defibrillator (ICD) shocks. Case Presentation: A 71-year-old patient with a history of dilated cardiomyopathy caused by a phospholamban (PLN) gain-of-function mutation, with a primary prevention ICD and an LVAD, presented with multiple ICD shocks which she experienced as painful and traumatic. She was found to have ongoing ventricular fibrillation with apparent hemodynamic stability. Conversion to sinus rhythm was achieved through intravenous administration of antiarrhythmic drugs followed by external defibrillation using stacked shocks. Due to the traumatic nature of the shocks, the shock function of the ICD was turned off. Nearly two months later, the patient presented for a second time and was again found to have ventricular fibrillation which had been present for at least six weeks. Conversion to sinus rhythm was unsuccessful and the patient was discharged to her home with an advanced care plan and her LVAD was deactivated. The patient died two months later. Conclusions: Patients with an LVAD can remain hemodynamically stable for prolonged periods of time during ventricular arrhythmias. ICD shocks are therefore mostly experienced as painful and even traumatic. Therefore, the routine use of ICD shock therapy in patients with an LVAD should be reconsidered. Adjustment of ICD programming to higher rates and longer detection may be warranted. Further investigation is warranted regarding a switch to devices with an alarm function rather than therapies for tachyarrhythmias. Full article