Search Results (41)

Background/Objectives: Catheter ablation has become the standard of care for patients with symptomatic and drug-refractory atrial fibrillation (AF). Both Class IC and Class III antiarrhythmic drugs (AADs) are effective in preventing early recurrences of AF, but not late recurrences, compared with the usual care. We aimed to compare the effects of two months of Class IC versus Class III AADs following AF catheter ablation on clinical outcomes, including arrhythmia recurrence and safety endpoints. Methods: All patients undergoing AF catheter ablation between January 2015 and November 2024 were screened, and cases meeting the inclusion criteria were included. Primary outcome was defined as atrial tachycardia recurrence-free survival. Results: A total of 98 patients (mean age 54.2 ± 14.0 years; 55.1% male) were enrolled, with 66.3% presenting with paroxysmal atrial fibrillation (AF). The mean left atrial diameter was 38.7 ± 5.1 mm, and 78.6% underwent cryoballoon ablation. Class IC AADs were administered to 62 cases, while the remaining 36 patients received amiodarone following catheter ablation. The rate of atrial tachycardia (ATa) recurrence was comparable between the patients treated with Class IC and Class III AADs (9.7% vs. 19.4%; p = 0.169). Predictors of ATa recurrence were identified as history of direct current cardioversion—DCCV (HR: 5.86; 95%CI: 1.44–23.82)—and LA diameter (HR: 1.17; 95%CI: 1.04–1.31). The most frequent AAD-related adverse event was symptomatic bradycardia (6.1%), which resolved in all cases following dose reduction. Conclusions: Class IC and Class III antiarrhythmics show comparable efficacy in terms of preventing ATa recurrence following AF catheter ablation. AAD-related adverse event rates are negligible for short-term use. Full article

Enterovirus (EV) infections in neonates can be transmitted vertically or horizontally, with symptoms ranging from mild to severe, including myocarditis, meningoencephalitis, and hepatitis. Neonates with EV-induced myocarditis may present severe cardiovascular disease with sudden onset of arrhythmia. Neonatal arrhythmias, particularly in low birth weight or critically ill infants, can impair cardiac function and worsen outcomes. EV targets cardiomyocyte receptors, inducing apoptosis pathways and triggering cardiac conduction disturbances. We present an extremely low-birth-weight preterm infant (GW 27 + 6) who developed EV-induced myocarditis, complicated with a sudden onset of supraventricular tachycardia (SVT), pericardial effusion and bi-atrial enlargement. Despite multi-agent regimen, including propranolol, flecainide, and amiodarone, the infant showed persistent junctional rhythm until seven months of age, later transitioning to atrial rhythm with stable cardiac function. A review of previously published rhythm disturbances due to EV-induced myocarditis is presented. Newborns with EV-induced arrhythmia may require a multi-modal treatment such as a multi-agent medical regimen or, in severe non-responsive cases, an electrophysiological approach. EV infections may cause long-term cardiovascular comorbidities (such as left ventricular dysfunction or mitral valve regurgitation), necessitating continuous monitoring through echocardiography and ECG. Collaboration between neonatologists and pediatric cardiologists is crucial for effective treatment and follow-up. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. External direct current cardioversion (DCCV) is a cornerstone intervention for rhythm control in AF; however, its success is influenced by various patient-specific and procedural factors. This review examines the predictors of DCCV success and AF recurrence with specific focus upon demographics, biochemical, cardiovascular imaging, and P-wave parameters and their likely ability to predict procedural outcomes. Demographic factors such as age, sex, and comorbidities influence DCCV outcomes, with prolonged AF duration, obesity, and heart failure being associated with higher failure rates. Elevated biochemical markers of inflammation and fibrosis, including C-reactive protein, galectin-3, and Type III procollagen-N-peptide, were predictive of poor outcomes. Imaging parameters, particularly left atrial (LA) volume and strain, emerged as critical indicators of atrial remodelling and DCCV failure. Increased P-wave duration and dispersion on electrocardiography were associated with an increased risk of recurrence. Biphasic waveforms and antiarrhythmic drugs, such as amiodarone and flecainide, improved cardioversion success. The predictors of DCCV success and recurrence reflect the interplay of structural, biochemical, and electrical remodelling in AF. Integrating these parameters into clinical practice can guide individualised patient management and improve outcomes. Further research is needed to validate these predictors and enhance precision medicine approaches in DCCV. Full article

Background and Objective: Implantable Cardioverter Defibrillators (ICDs) are crucial in treating ventricular tachyarrhythmias (VTs) and preventing sudden cardiac death. However, ICD shocks are linked to higher mortality and a lower quality of life. Many patients suffer from recurrent VTs despite concomitant antiarrhythmic drug (AAD) therapy with amiodarone, and it is unclear if changing the AAD while on chronic amiodarone therapy is beneficial. Hence, we investigated the impact of changing the AAD on the incidence of appropriate ICD shocks in patients on chronic amiodarone, impaired LV function, and at least one previous VT ablation. Methods and Results: We retrospectively analyzed 131 ICD patients (LVEF < 40%) from a single-center registry. All were on chronic amiodarone and had undergone VT ablation. The mean age was 66.0 ± 12.8 years; 82.4% were male; and the follow-up period averaged 5.8 ± 0.6 years. Ischemic cardiomyopathy was present in 52.7% of patients. AAD therapy was changed in 49 patients (37.4%), primarily due to inefficacy (40.8%), intolerance (16.3%), or other reasons (42.9%). Of those, 8 received flecainide (≥200 mg) and 41 sotalol (≥240 mg); 82 (62.6%) continued amiodarone. VT re-ablation was performed in 23.7%. During follow-up, 11 patients (8.4%) died and 18 (13.7%) received appropriate ICD shocks—17 with changed AAD vs. 1 with continued amiodarone (p ≤ 0.01). A multivariate regression showed that switching from amiodarone to flecainide or sotalol was significantly associated with increased ICD shock risk (OR 34.9; 95% CI 4.3–283.8; p < 0.01). Conclusions: In patients on chronic amiodarone with severely impaired LV function and at least one previous VT ablation, changing AAD therapy to flecainide or sotalol is associated with an increased incidence of appropriate ICD shocks. Full article

Background/Objectives: Persistent high Premature Ventricular Contraction (PVC) burden (>10%) may result in PVC-induced cardiomyopathy. Current guidelines, supported by limited evidence, recommend flecainide for PVCs originating from the ventricular outflow tract (Class IIa). UNIFLECA is a prospective cohort study, aiming to assess the efficacy and safety of flecainide in PVC burden reduction in adults, irrespective of PVC origin, focusing secondarily on symptom relief and improvement of left ventricular ejection fraction (LVEF) in patients suffering from PVC-induced cardiomyopathy. Methods: Participants were adults with frequent PVCs, defined as PVC burden > 5%, confirmed by two 24 h Holter recordings taken at least one month apart, who denied catheter ablation treatment. Patients who were deemed ineligible for catheter ablation were also included. A total of 50 patients were screened and 35 were administered Flecainide, with dosage adjustment based on follow-up Holter results and QRS increases. Changes in PVC burden, LVEF, symptomatic status, along with treatment adherence, were evaluated. Results: In adults with frequent PVCs, flecainide led to a significant reduction in PVC burden, with a mean decrease of 76.2% in the first month, and 63.1% of patients achieving a PVC burden reduction greater than 80%. Conclusions: UNIFLECA contributes to the understanding of how personalized, non-interventional therapeutic modalities can be employed to manage PVCs, especially for patients unwilling to have or ineligible for ablation procedures. Full article

Voltage-gated sodium channels (Navs) are critical for membrane potential depolarisation in cells, with especially important roles in neuronal and cardiomyocyte membranes. Their malfunction results in a range of disorders, and they are the target of many widely used drugs. A rapid yet accurate functional assay is therefore desirable both to probe for novel active compounds and to better understand the many different Nav isoforms. Here, we use fluorescence to monitor Nav function: cells expressing either the cardiac Nav 1.5 or pain-associated Nav 1.7 were loaded with fluorescent membrane potential sensitive dye and then stimulated with veratridine. Cells expressing Nav 1.5 show a concentration-dependent slow rise and then a plateau in fluorescence. In contrast, cells expressing Nav 1.7 show a more rapid rise and then unexpected oscillatory behavior. Inhibition by flecainide and mexiletine demonstrates that these oscillations are Nav-dependent. Thus, we show that this fluorescent membrane potential dye can provide useful functional data and that we can readily distinguish between these two Nav isoforms because of the behavior of cells expressing them when activated by veratridine. We consider these distinct behaviors may be due to different interactions of veratridine with the different Nav isoforms, although more studies are needed to understand the mechanism underlying the oscillations. Full article

Multifocal ectopic Purkinje-related premature contractions (MEPPC) syndrome is a recently recognized rare form of arrhythmia involving the entire His–Purkinje system and often coinciding with dilated cardiomyopathy (DCM). Certain variants in the SCN5A gene may be linked to MEPPC syndrome. We present a case of a 32-year-old Caucasian female who exhibited a high burden of premature ventricular contractions (PVCs) and non-sustained episodes of ventricular tachycardia (NSVT) with an alternating QRS pattern, and who was resistant to traditional medical therapy and radiofrequency catheter ablation (RFCA), necessitating implantation of a cardioverter-defibrillator (ICD). A positive family history (father’s death at the age of 40 years) and the rapid deterioration of left ventricular function parameters echocardiographically during recurrent arrhythmic episodes raised concern about a potentially complex disease scenario. Genetic testing revealed a heterozygous variant of the SCN5A gene, c.2440C>T, p.(Arg814Trp), confirming the diagnosis of MEPPC syndrome. Treatment with a combination of class I antiarrhythmic drugs, flecainide and mexiletine, concomitant with beta blockers, led to symptomatic improvement, a reduction of PVCs (from 66 491 (44%) to 858 (1%)), and the restoration of left ventricular function (LV EF from 44% to 53%). A lack of defined diagnostic criteria hampers timely diagnosis, leading to ineffective interventions and delayed initiation of treatment with antiarrhythmic drugs. MEPPC patients remain at significant risk for severe heart failure and sudden cardiac death. Our clinical case report underscores the importance of accurate and timely diagnosis, which allows effective treatment with a combination of antiarrhythmic drugs and mitigates the risk associated with MEPPC syndrome. Full article

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly arrhythmogenic syndrome triggered by stress, primarily linked to gain-of-function point mutations in the cardiac ryanodine receptor (RyR2). Flecainide, as an effective therapy for CPVT, is a known blocker of the surface-membrane Na⁺ channel, also affecting the intracellular RyR2 channel. The therapeutic relevance of the flecainide-RyR2 interaction remains controversial, as flecainide blocks only the RyR2 current flowing in the opposite direction to the physiological Ca²⁺ release from the sarcoplasmic reticulum (SR). However, it has been proposed that charge-compensating countercurrent from the cytosol to SR lumen plays a critical role, and its reduction may indeed suppress excessive diastolic SR Ca²⁺ release through RyR2 channels in CPVT. Monitoring single-channel properties, we examined whether flecainide can target intracellular pathways for charge-balancing currents carried by RyR2 and SR Cl⁻ channels under cell-like conditions. Particularly, the Tris⁺ countercurrent flowed through the RyR2 channel simultaneously with a dominant reverse Ca²⁺/Ba²⁺ current. We demonstrate that flecainide blocked the RyR2-mediated countercurrent without affecting channel activity. In contrast, the SR Cl⁻ channel was completely resistant to flecainide. Based on these findings, it is reasonable to propose that the primary intracellular target of flecainide in vivo is the RyR2-mediated countercurrent. Full article

Background: The aim of this study was to evaluate the performance of the diagnostic pathway proposed by the European Society of Cardiology (ESC) guidelines for identifying the underlying aetiology of sudden cardiac death (SCD) through the screening of first-degree family members of patients with SCD who either had a negative autopsy or no autopsy performed. Methods: To be eligible for enrolment, patients had to meet the following inclusion criteria: a family history of SCD in a first-degree relative under the age of 50 years; the SCD decedents must not have undergone an autopsy, or if an autopsy was performed, non-cardiac and structural cardiac causes must have been excluded. Patients underwent a comprehensive assessment, including the evaluation of family and medical history, electrocardiography (ECG) and ECG with high precordial leads, Holter ECG monitoring, echocardiography, cardiac magnetic resonance imaging, and exercise stress testing. A sodium channel blocker test (i.e., flecainide test) was performed when other clinical investigations were negative and the suspicion of Brugada syndrome was high. Results: Forty-one patients from 25 different families fulfilled the inclusion criteria and represented the final study cohort. After the comprehensive diagnostic work-up, a total of seven patients from five different families (5/25, 20%) were diagnosed with an inherited cardiac condition: two families with arrhythmogenic right ventricular cardiomyopathy, one with dilated cardiomyopathy, one with non-dilated left ventricular cardiomyopathy, and one with long QT syndrome. Conclusions: The comprehensive cardiologic work-up of relatives of mainly young SCD victims results in the diagnosis of inherited cardiac conditions in one-fifth of cases. Full article

Background: Intravenous (IV) flecainide is recommended for the pharmacological cardioversion of recent-onset atrial fibrillation (AF). The aim of this study was to study the efficacy and safety of IV flecainide, co-administered with oral b-blockers, for the cardioversion of paroxysmal AF. Methods: Single-center registry, initiated in the “Skylitseion” General Hospital of Chios in January 2020. The main inclusion criterion was IV flecainide administration plus oral b-blocker for recent-onset AF (≤48 h). The primary outcome was conversion to sinus rhythm at 2 h. Results: A total of 121 (73 males and 48 females, with mean age 61.4 years) consecutive, unselected patients who complied with the study protocol were included. A successful conversion to sinus rhythm at 2 h was achieved in 99 patients (success rate: 81.8%). The median conversion time was 11.7 min (varied from 3 to 23 min). Duration of hospitalization was significantly shorter in patients who were successfully cardioverted with IV flecainide (10.9 vs. 30.7 h, p < 0.001). No serious adverse events were recorded. Conclusion: This is one of the largest registries worldwide, evaluating the effectiveness and safety of IV flecainide co-administered with a b-blocker in the acute management of recent-onset AF. The successful conversion rate at 2 h is very high and quick with no serious adverse events. Full article

Atrial fibrillation has progressively become a more common reason for emergency department visits, representing 0.5% of presenting reasons. Registry data have indicated that about 60% of atrial fibrillation patients who present to the emergency department are admitted, emphasizing the need for more efficient management of atrial fibrillation in the acute phase. Management of atrial fibrillation in the setting of the emergency department varies between countries and healthcare systems. The most plausible reason to justify a conservative rather than an aggressive strategy in the management of atrial fibrillation is the absence of specific guidelines from diverse societies. Several trials of atrial fibrillation treatment strategies, including cardioversion, have demonstrated that atrial fibrillation in the emergency department can be treated safely and effectively, avoiding admission. In the present study, we present the epidemiology and characteristics of atrial fibrillation patients presenting to the emergency department, as well as the impact of diverse management strategies on atrial-fibrillation-related hospital admissions. Lastly, the design and initial data of the HEROMEDICUS protocol will be presented, which constitutes an electrophysiology-based aggressive rhythm control strategy in patients with atrial fibrillation in the emergency department setting. Full article

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe hereditary arrhythmia syndrome predominantly affecting children and young adults. It manifests through bidirectional or polymorphic ventricular arrhythmia, often culminating in syncope triggered by physical exertion or emotional stress which can lead to sudden cardiac death. Most cases stem from mutations in the gene responsible for encoding the cardiac ryanodine receptor (RyR2), or in the Calsequestrin 2 gene (CASQ2), disrupting the handling of calcium ions within the cardiac myocyte sarcoplasmic reticulum. Diagnosing CPVT typically involves unmasking the arrhythmia through exercise stress testing. This diagnosis emerges in the absence of structural heart disease by cardiac imaging and with a normal baseline electrocardiogram. Traditional first-line treatment primarily involves β-blocker therapy, significantly reducing CPVT-associated mortality. Adjunctive therapies such as moderate exercise training, flecainide, left cardiac sympathetic denervation and implantable cardioverter-defibrillators have been utilized with reasonable success. However, the spectrum of options for managing CPVT has expanded over time, demonstrating decreased rates of arrhythmic events. Furthermore, ongoing research into potential new therapies including gene therapies has the potential to further enhance treatment paradigms. This review aims to succinctly encapsulate the contemporary understanding of the clinical characteristics, diagnostic approach, established therapeutic interventions and the promising future directions in managing CPVT. Full article

Background and aim: The GORE^® CARDIOFORM (GCO) septal occluder is an atrial septal defect/patent foramen ovale closure device with theoretical advantages over other commercialized devices thanks to its softness and anatomical compliance. Our aim was to evaluate the short- and medium-term electrocardiographic changes after percutaneous ASD closure with GCO in a pediatric population. Methods: We enrolled 39 patients with isolated ASD submitted to trans-catheter closure from January 2020 to June 2021. ECG was performed before, at 24 h and 6 months after the procedure. P wave dispersion, QTc and QTc dispersion were calculated. ECG Holter was recorded at 6 months after implantation. Results: Patients’ age and body surface area (BSA) were 8.2 ± 4.2 years and 1.0 ± 0.3 m² respectively. At the baseline, mean P wave dispersion was 40 ± 15 msec and decreased at 24 h (p < 0.002), without any further change at 6 months. At 24 h, PR conduction and QTc dispersion significantly improved (p = 0.018 and p < 0.02 respectively), while the absolute QTc value considerably improved after 6 months. During mid-term follow-up, QTc dispersion remained stable without a significant change in PR conduction. The baseline cardiac frequency was 88.6 ± 12.6 bpm, followed by a slight reduction at 24 h, with a further amelioration at 6 months after the procedure (87.3 ± 14.2, p = 0.9 and 81.0 ± 12.7, p = 0.009, respectively). After device deployment, two patients developed transient, self-limited junctional rhythm. One of them needed a short course of Flecainide for atrial ectopic tachycardia. No tachy/brady-arrhythmias were recorded at the 6-month follow-up. ASD closure resulted in a marked decrease in right heart volumes and diameters at 6 months after percutaneous closure. Conclusions: Percutaneous ASD closure with the GCO device results in significant, sudden improvement of intra-atrial, atrio-ventricular and intraventricular electrical homogeneity. This benefit persists unaltered over a medium-term follow-up. These electrical changes are associated with a documented positive right heart volumetric remodeling at mid-term follow-up. Full article

Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder that may lead patients to sudden cell death through the occurrence of ventricular arrhythmias. ACM is characterised by the progressive substitution of cardiomyocytes with fibrofatty scar tissue that predisposes the heart to life-threatening arrhythmic events. Cardiac mesenchymal stromal cells (C-MSCs) contribute to the ACM by differentiating into fibroblasts and adipocytes, thereby supporting aberrant remodelling of the cardiac structure. Flecainide is an I_c antiarrhythmic drug that can be administered in combination with β-adrenergic blockers to treat ACM due to its ability to target both Na_v1.5 and type 2 ryanodine receptors (RyR2). However, a recent study showed that flecainide may also prevent fibro-adipogenic differentiation by inhibiting store-operated Ca²⁺ entry (SOCE) and thereby suppressing spontaneous Ca²⁺ oscillations in C-MSCs isolated from human ACM patients (ACM C-hMSCs). Herein, we briefly survey ACM pathogenesis and therapies and then recapitulate the main molecular mechanisms targeted by flecainide to mitigate arrhythmic events, including Na_v1.5 and RyR2. Subsequently, we describe the role of spontaneous Ca²⁺ oscillations in determining MSC fate. Next, we discuss recent work showing that spontaneous Ca²⁺ oscillations in ACM C-hMSCs are accelerated to stimulate their fibro-adipogenic differentiation. Finally, we describe the evidence that flecainide suppresses spontaneous Ca²⁺ oscillations and fibro-adipogenic differentiation in ACM C-hMSCs by inhibiting constitutive SOCE. Full article

Pharmacologic cardioversion is a well-established alternative to electric cardioversion for hemodynamically stable patients, as it skips the risks associated with anesthesia. A recent network meta-analysis identifies the most effective antiarrhythmics for pharmacologic cardioversion with flecainide exhibiting a more efficacious and safer profile towards faster cardioversion. Moreover, the meta-analysis of class Ic antiarrhythmics revealed an absence of adverse events when used for pharmacologic cardioversion of AF in the ED, including patients with structural heart disease. The primary goals of this clinical trial are to prove the superiority of flecainide over amiodarone in the successful cardioversion of paroxysmal atrial fibrillation in the Emergency Department and to prove that the safety of flecainide is non-inferior to amiodarone in patients with coronary artery disease without residual ischemia, and an ejection fraction over 35%. The secondary goals of this study are to prove the superiority of flecainide over amiodarone in the reduction in hospitalizations from the Emergency Department due to atrial fibrillation in the time taken to achieve cardioversion, and in the reduction in the need to conduct electrical cardioversion. Full article