AIMS:Obesity adversely affects atrial fibrillation (AF) outcomes and is associated with higher recurrence after catheter ablation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) promote weight loss and improve metabolic inflammation, but their role as adjuncts to ablation has not been completely defined. This study investigated the impact of semaglutide on post-ablation rhythm outcomes in obese patients with AF. METHODS AND RESULTS:This single-centre, propensity-matched study included obese patients [body mass index (BMI) ≥ 30 kg/m²] undergoing first-time catheter ablation for paroxysmal AF (2019-2024). Patients who initiated semaglutide within 3 months before or 1 month after ablation were compared with matched controls who did not receive GLP-1RA therapy. All patients underwent continuous rhythm monitoring using implantable cardiac monitors. The primary endpoint was any atrial tachyarrhythmia recurrence beyond a 2-month blanking period. The final cohort included 181 semaglutide-treated patients and 181 controls with matched clinical and procedural characteristics. At 18-month follow-up, freedom from recurrence was 80.2% vs. 65.2%; semaglutide was associated with a significantly lower risk of recurrence (hazard ratio 0.52; 95% confidence interval 0.34-0.78; P = 0.002). Weight and BMI decreased significantly in the semaglutide group (-11.8 ± 3.8 kg; -4.0 ± 1.4 kg/m²) compared with controls (-1.9 ± 1.2 kg; -0.3 ± 0.8 kg/m²; both P < 0.001). A substantial proportion of treated patients achieved ≥10% weight reduction. CONCLUSION:Glucagon-like peptide-1 receptor agonist therapy using semaglutide is associated with a reduced risk of AF recurrence in obese patients undergoing AF catheter ablation, indicating its potential as an adjunctive treatment. Further studies are needed to confirm these findings and elucidate the effects of GLP-1RA on AF recurrence.

Transcatheter ablation for atrial fibrillation (AF) prevents recurrences, reduces AF burden, and improves quality of life. Robust evidence supports its use as a first-line therapy for rhythm control, demonstrating a comparable risk of adverse events to antiarrhythmic drug (AAD) therapy. Anatomically guided third-generation laser balloon ablation provides a safe and effective option, offering excellent long-term outcomes in both paroxysmal and persistent AF cases. This study presents the first prospective multicentre assessment of third-generation laser balloon ablation as an initial therapy for paroxysmal and persistent AF, conducted without acute confirmation of pulmonary vein isolation We conducted a multicentre study in Italy involving patients with either paroxysmal or persistent AF, who had not previously undergone rhythm control therapy. Participants were treated with third-generation laser balloon ablation targeting pulmonary vein isolation. The primary endpoint was freedom from any atrial tachyarrhythmia (ATa) recurrence following a 3-month blanking period (BP), monitored using implantable cardiac monitors (ICM). Among the 113 patients (71% male; mean age 60.2 ± 10.9 years) who underwent ablation, 76% had paroxysmal AF. The mean left atrial volume/body surface area was 33.9 ± 7.0 mL/m², with 7% of patients (n=8) presenting moderate left atrial dilation. No significant periprocedural or follow-up complications occurred. At an average follow-up of 35.7 ± 9.6 months, freedom from ATa recurrence was achieved in 77% of patients with paroxysmal AF and 59% with persistent AF. Recurrences during the BP [hazard ratio (HR) = 2.334, P = 0.030] and left atrial dilation (HR = 2.843, P = 0.035) were independent predictors of recurrence. Anatomically guided third-generation laser balloon ablation is a safe and effective first-line therapy for paroxysmal and persistent AF, providing strong clinical outcomes with nearly three years of ICM-based follow-up.

AIMS:Epicardial ablation for Brugada syndrome (BrS) has shown promise in reducing ventricular fibrillation (VF), but its role remains controversial due to the lack of randomized trials. This study evaluates the efficacy of catheter ablation in high-risk BrS patients. METHODS AND RESULTS:This prospective, single-centre, randomized (2:1) study enrolled BrS patients with cardiac arrest (CA) or appropriate ICD therapies. All patients had an ICD and were randomized to undergo epicardial ablation (ablation group) or no ablation (control group). Enrolment began in September 2017 and prematurely terminated in February 2024. The primary endpoint was freedom from VF recurrences. Secondary endpoints included procedure safety, ICD-related complications, and quality-of-life assessment. Forty patients (83% male, mean age 43.7 ± 12.1) were randomized: 26 in the ablation group and 14 in the control group. Thirty-six patients received appropriate ICD therapies before enrolment: 24 (92%) in the ablation group and 12 (86%) in the control group. One patient in the ablation group experienced a post-procedural pericardial effusion requiring pericardiocentesis. Thirteen patients (33%) had major ICD-related complications. After a mean follow-up of 4.0 ± 1.7 years, freedom from VF recurrence was 96% (25/26) in the ablation group and 50% (7/14) in the control group (P < 0.001). No unexplained or arrhythmic deaths occurred during follow-up. CONCLUSION:Epicardial catheter ablation was associated with a reduction in VF recurrence compared with ICD therapy alone. These findings support the use of epicardial ablation in high-risk BrS patients. CLINICALTRIALS.GOV:ID NCT03294278.

Aims The third-generation laser balloon (LB3) is an established ablation device for pulmonary vein isolation (PVI) that allows direct visualization of the anatomical target. Equipped with an automatic circumferential laser delivery modality, it aims at continuous circumferential PVI, improving both acute and clinical outcomes. We sought to evaluate the clinical efficacy of LB3 ablation using an anatomical-based approach without verifying electrical isolation. Methods and results Among 257 paroxysmal AF patients undergoing LB3 ablation across four Italian centres, 204 (72% male, mean age 60.4 +/- 11.1 years) were included. The primary endpoint was freedom from any atrial tachyarrhythmia (ATa) recurrence after the blanking period (BP), assessed with implantable cardiac monitors (ICMs). All pulmonary veins (PVs) were targeted using the LB3, with the RAPID mode used on an average of 96 +/- 8, 86 +/- 19, 98 +/- 11, and 84 +/- 15% for the left superior, left inferior, right superior, right inferior PV, and left common ostium, respectively. Freedom from arrhythmia recurrences was 84.8% at 1, 80.4% at 2, and 76.0% at 3 years. An ATa burden >= 5% was documented in 2.5, 4.4, and 5.4% at 1, 2, and 3 years, respectively. Relapses during the BP [hazard ratio (HR) = 2.182, P = 0.032] and left atrial dilation (HR = 1.964, P = 0.048) were independent predictors of recurrences. Conclusion Anatomical-guided LB3 ablation for paroxysmal AF is a safe and effective approach, providing excellent clinical outcomes as assessed by ICM over nearly 3 years of follow-up.

Ablation of para-hisian accessory pathways (APs) is challenging because of their proximity to the conduction system. A high incidence of atrio-ventricular (AV) conduction injury (up to 50%) was observed for the ablation of true para-hisian APs.

Atrial fibrillation (AF) is the most common arrhythmia encountered with hypertrophic cardiomyopathy (HCM) and is associated with adverse cardiovascular outcomes. The outcomes of ablate-and-pace strategy for the management of refractory AF in HCM patients are unclear.

Symptomatic Brugada Syndrome (BrS) patients face a significant risk of life-threatening recurrent ventricular arrhythmias (VT/VF). Radiofrequency catheter ablation (RFCA) of the arrhythmogenic substrate can mitigate the incidence of such events.

Abstract Short-coupled idiopathic ventricular fibrillation (SC-IVF) is a rare, life-threatening arrhythmia, accountable for 5–10% of out-of-hospital cardiac arrests (OHCA). Catheter ablation of the short-coupled premature ventricular contraction (PVC) that triggers VF has been shown to prevent VF recurrences in outdated case series. Aim To evaluate the clinical outcome and summarize the recent experience of 3D electrophysiological mapping and radiofrequency catheter ablation (RFCA) of SC-IVFs in a tertiary high-volume referral centre. Methods from January 2016, we enrolled all consecutive patients diagnosed with SC-IVF and treated by RFCA. Structural heart disease was excluded in all patients by means of echocardiography, cardiac magnetic resonance, coronary angiography, and exercise test. Brugada syndrome and long QT syndrome were excluded by Ajmaline and Epinephrine tests, respectively. The CARTO system was used to construct detailed 3D electroanatomic maps of the right and left ventricle. Mapping and ablation were performed with a standard 3.5- irrigated tip catheter. The PVCs were localized by mapping the earliest bipolar electrogram relative to the onset of the ectopic surface QRS (confirmed by QS complex in the unipolar configuration). Pace mapping was used in patients with infrequent PVCs. The origin of PVCs from fascicles/Purkinje network was indicated by initial sharp potentials preceding the ectopic QRS complex. The procedural end point was the abolition of all clinical PVCs. Outcome (freedom from SC-PVCs and VF episodes) was assessed by Holter monitoring and defibrillator memory interrogation. Results eleven consecutive patients [8 men, 3 women; median age 41 (± 5 years)] were enrolled. 10/11 patients (91%) were asymptomatic prior the index VF event, while 1 patient (9%) experienced recurrent syncope. An aborted OHCA was the index event in all patients. Arrhythmic storm was observed at the index presentation in 2 patients (18%). No patient had family history of sudden cardiac death. All patients were implanted with an ICD after the index event. The delay in SC-IVF diagnosis was 3 (± 2 years) from the index event. 2 patients (18%) had ≥ 2 SC-PVC morphologies. The mean coupling interval (CI) of the SC-PVCs ranged from 230 to 330 msec (mean 303 ± 26 msec). The CI/QT ratio ranged from 0.6 to 1 (mean 0.81 ± 0.15). 10 patients underwent RFCA for recurrent VF/ICD shocks and 1 patient for refractory electrical storm. RFCA was based on activation mapping, pace-mapping, and both in 1 (9%), 1 (9%), and 9 (82%) patients, respectively. The sites of ablation were LV Purkinje, RV Purkinje, RV non-Purkinje (RV outflow tract and tricuspid annulus), and LV non-Purkinje (LV Summit) in 3 (27%), 4 (36%), 3 (27%), and 1 (9%) patient, respectively. The first ablation was acutely successful in all patients. 1 patient experienced recurrence of SC-PVCs and VF episodes after 5 days from the first ablation and underwent a second RFCA. There were no peri-procedural complications. After a median follow-up of 22 months (ranging from 6 to 39 months) all patients were free from sustained ventricular arrhythmia recurrences: 10 patients (91%) were free from VF and PVCs; 1 patient (9%) had recurrent SC-PVCs without VF episodes. Conclusions this retrospective study explored the effectiveness of RFCA combined with the advanced electroanatomic mapping in a current cohort of patients with history of OHCA diagnosed with SC-IVF. RFCA of SC-PVCs was safe and highly effective in abolishing VF episodes in all patients.

Key Teaching Points•Antiepileptic drugs may interfere with cardiac electrophysiology and expose vulnerable patients to potentially fatal arrhythmias.•Syncope with tonic-clonic movements may be confused with epilepsy. A thorough cardiac evaluation is important before starting antiepileptic drugs.•Suspicious symptoms, a family history of sudden death, and equivocal dubious electrocardiogram abnormalities are warning signs of an underlying arrhythmic disorder.IntroductionBrugada syndrome (BrS) is an inherited disorder characterized by coved-type ST-segment elevation in the right precordial leads and increased risk of sudden cardiac death (SCD) in ostensibly normal heart.1Antzelevitch C. Yan G.X. J-wave syndromes: Brugada and early repolarization syndromes.Heart Rhythm. 2015; 12: 1852-1866Google Scholar The electrocardiogram (ECG) manifestations may occur spontaneously or after the exposure to sodium channel blocking agents.2Brugada R. Brugada J. Antzelevitch C. et al.Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts.Circulation. 2000; 101: 510-515Google Scholar The main clinical manifestations (syncope and SCD) are caused by malignant ventricular tachycardia / ventricular fibrillation, which are related to an arrhythmogenic epicardial substrate located in the anterior aspect of the right ventricular outflow tract.3Pappone C. Brugada J. Vicedomini G. et al.Electrical substrate elimination in 135 consecutive patients with brugada syndrome.Circ Arrhythm Electrophysiol. 2017; 10e005053Google Scholar,4Brugada J. Pappone C. Berruezo A. et al.Brugada syndrome phenotype elimination by epicardial substrate ablation.Circ Arrhythm Electrophysiol. 2015; 8: 1373-1381Google ScholarIdiopathic epilepsy and BrS share the pathophysiology of altered transmembrane ion current caused by mutations of ion channel subunit genes. Sodium channel dysfunction represents a common pathogenetic pathway for these 2 clinical entities that may be involved as a mechanism of sudden death. In addition, mutations of ion channel or arrhythmia-related genes are the most common defects found in patients experiencing sudden death in epilepsy.5Chahal C.A.A. Salloum M.N. Alahdab F. et al.Systematic review of the genetics of sudden unexpected death in epilepsy: potential overlap with sudden cardiac death and arrhythmia-related genes.J Am Heart Assoc. 2020; 9e012264Google ScholarCoexistence of epilepsy and BrS in a family with SCN5A mutation has been reported, suggesting that sodium channel mutation may be responsible for cardiac and cerebral manifestations, probably at different ages in the same individual and/or in the same family.6Parisi P. Oliva A. Coll Vidal M. et al.Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation.Epilepsy Res. 2013; 105: 415-418Google Scholar The latter underlines the importance of careful assessment of symptoms, detailed family history, and a thorough ECG analysis when evaluating patients with seizure-like symptoms.Antiepileptic drugs (AEDs) are useful in controlling malignant neurologic manifestations, and their adjunctive use in refractory epilepsy reduces mortality 7-fold.7Ryvlin P. Cucherat M. Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials.Lancet Neurol. 2011; 10: 961-968Google Scholar On the other hand, a community-based study found an increased risk of SCD in patients with epilepsy treated with AEDs, and this risk was specifically associated with the use of sodium channel blockers.8Bardai A. Lamberts R.J. Blom M.T. et al.Epilepsy is a risk factor for sudden cardiac arrest in the general population.PLoS One. 2012; 7e42749Google ScholarAmong sodium channel blockers used as AEDs, phenytoin (which belongs to the IB class of antiarrhythmic drugs) has been described to induce a type 1 ECG Brugada pattern at supratherapeutic doses.9Swe T. Bhattarai B. Dufresne A. Type 1 Brugada pattern ECG due to supra-therapeutic phenytoin level.BMJ Case Rep. 2016; 2016Google Scholar However, its direct role as a trigger of a fatal ventricular arrhythmia in a patient with BrS has never been described.Case reportThe proband is a 36-year-old man of Italian origin with a family history of sudden death (father and paternal grandfather). He came to our clinic because of a previous episode of syncope without prodromes, showing a suspicious Brugada pattern on ECG. A transthoracic echocardiogram excluded structural abnormalities. The patient underwent an ajmaline challenge, which was stopped at 35 mg (ie, 50% of the full dose for the patient’s weight) owing to the appearance of a typical type 1 Brugada pattern (Figure 1). Ventricular programmed stimulation was performed from the right ventricle apex, which was negative for ventricular tachycardia / ventricular fibrillation inducibility. However, owing to the symptoms and family history, he was implanted with an implantable cardioverter-defibrillator in primary prevention.The proband’s family history, summarized by his mother, revealed that his paternal grandfather suffered from epileptic seizures, and he died suddenly at the age of 70. In addition, the proband’s father died at the age of 65 years. He suffered from arterial hypertension and dyslipidemia, well controlled with adequate medical therapy. More recently before the fatal event, while still 65 years of age, this subject developed high fever (40°C) due to SARS-CoV-2 infection and asked his family doctor for intervention at home; the doctor diagnosed pneumonia and prescribed clarithromycin (1000 mg daily for 10 days). After 2 days, this patient experienced a syncope episode (associated with tonic-clonic movements and sphincter release), resulting in a sudden fall, which caused cranial trauma and a nasal bone fracture. He was admitted to the Emergency Department of the local hospital with high fever (40 C°) and an unstable state of consciousness despite a good cardiac and respiratory function. A nasal swab confirmed SARS-CoV-2 infection. A cranial computed tomography scan excluded intracranial lesions and hemorrhage and reported the nasal bone fracture. Cerebrospinal fluid exam resulted negative for meningitis and other common infectious diseases affecting the central nervous system.Of note, the 12-lead ECG during hospitalization (before the treatment with AEDs) clearly showed spontaneous type 1 Brugada pattern (Figure 2), in the absence of any electrolyte imbalance or metabolic disorders at serial blood tests. Supportive measures and intensive care were provided, leading to progressive clinical improvement and complete neurological recovery.Figure 2Proband’s father’s electrocardiogram (ECG) with spontaneous type 1 Brugada ECG pattern with ST-segment elevation in the inferior leads and T-wave abnormalities from V4 to V6.View Large Image Figure ViewerDownload Hi-res image Download (PPT)According to the clinical presentation and family history, a diagnosis of epilepsy was made, and AEDs were prescribed. Phenytoin was administered at a dosage of 100 mg daily and the patient was instructed to undergo monthly neurological examination with serial checks of phenytoin blood levels. The first 2 consecutive controls were normal, and so the patient was advised to continue the established treatment.The last crisis of syncope occurred at home, in the early morning, and was characterized by trismus, diaphoresis, and muscle rigidity. After this crisis, the proband’s father was again taken to the emergency room of the local hospital. His ECG on admission is shown in Figure 3. He was diagnosed with ventricular tachycardia at 150 beats per minute, originating from the right ventricular outflow tract, causing hemodynamic instability, which was successfully treated by external DC shock.Figure 3Proband’s father’s electrocardiogram showing ventricular tachycardia.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Phenytoin blood levels were above the upper therapeutic window threshold, and recurrent ventricular arrhythmias were reported on the continuous ECG monitoring, requiring multiple external DC shocks. The patient was sedated, intubated, and admitted to the intensive care unit. On the same day an arrhythmic storm, relapsing despite multiple external DC shocks, resulted in hemodynamic decompensation and, eventually, the patient’s death.DiscussionTo our knowledge, this is the first report of arrhythmic death due to an overdosage of an antiepileptic drug (phenytoin) in a patient with misdiagnosed BrS. An atypical clinical manifestation (seizure-like syncope), drug interference (phenytoin), and a wide arrhythmogenic substrate (spontaneous type 1 ECG Brugada pattern) resulted in a perfect storm leading to a tragic outcome.BrS is recognized as a relevant cause of life-threatening ventricular arrhythmias and SCD among individuals with structurally normal hearts. Epilepsy can be associated with both cardiac arrhythmias and an increased risk of SCD. Uncontrolled epilepsy results in alterations of cardiac electrophysiology, potentially leading to arrhythmias owing to ictal discharges in brain regions controlling sympathetic and parasympathetic tone or life-threatening abnormalities of cardiac repolarization.10van der Lende M. Surges R. Sander J.W. Thijs R.D. Cardiac arrhythmias during or after epileptic seizures.J Neurol Neurosurg Psychiatry. 2016; 87: 69-74Google Scholar Non-seizure-related arrhythmias have also been observed in patients with epilepsy, which can be life-threatening and manifest as sudden cardiac death.11Lamberts R.J. Blom M.T. Wassenaar M. et al.Sudden cardiac arrest in people with epilepsy in the community: circumstances and risk factors.Neurology. 2015; 85: 212-218Google Scholar The role of AED in these circumstances is controversial and debated. In a community-based study, AED use was associated with an increased risk of SCD, and specifically with the use of sodium channel blocker agents.11Lamberts R.J. Blom M.T. Wassenaar M. et al.Sudden cardiac arrest in people with epilepsy in the community: circumstances and risk factors.Neurology. 2015; 85: 212-218Google ScholarThe susceptibility to SCD in epilepsy might be the consequence of a shared genetic cause with arrhythmogenic syndromes. Indeed, both BrS and idiopathic epilepsy are associated with heterozygous mutations in ion channel genes. The role of channel dysfunction in the pathogenesis of cardiac arrhythmias and epilepsy is well known, as variants of the cardiac sodium channel (ie, SCN4A, SCN5A, SCN10A, and SCN11A), gated potassium channel (ie, HCN1), and calcium channel (ie, EFHC1 and CACNA1A) are frequently documented.12Lerche H. Shah M. Beck H. Noebels J. Johnston D. Vincent A. Ion channels in genetic and acquired forms of epilepsy.J Physiol. 2013; 591: 753-764Google Scholar,13Blandin C.E. Gravez B.J. Hatem S.N. Balse E. Remodeling of ion channel trafficking and cardiac arrhythmias.Cells. 2021; : 10Google Scholar The most clinically relevant mutations are those affecting the voltage-gated sodium channel, which are expressed in various tissues and are involved in various clinical manifestations: brain (epilepsy), heart (cardiac arrhythmias), skeletal muscle (myotonia and periodic paralysis), peripheral nervous system (pain disorders).14Brunklaus A. Ellis R. Reavey E. Semsarian C. Zuberi S.M. Genotype phenotype associations across the voltage-gated sodium channel family.J Med Genet. 2014; 51: 650-658Google ScholarEpilepsy and cardiac arrhythmias can be confused in the early stages of the diagnostic process when a syncope occurs as the first clinical manifestation. Once considered specific to epileptic phenomena, generalized tonic-clonic movements during loss of consciousness are commonly reported in cardiac syncope as well. This overlap in clinical manifestations can lead to misdiagnosis of life-threatening cardiac conditions and, as occurred in this case, to prescription of potentially harmful drugs.Phenytoin can elicit type 1 Brugada ECG pattern at supratherapeutic blood levels,9Swe T. Bhattarai B. Dufresne A. Type 1 Brugada pattern ECG due to supra-therapeutic phenytoin level.BMJ Case Rep. 2016; 2016Google Scholar but its proarrhythmic effect has never been documented. Phenytoin is a first-generation antiepileptic and a class IB antiarrhythmic drug used for the treatment of epilepsy. It acts by blocking the voltage-dependent sodium channels and, because of this particular activity, may exacerbate the voltage gradient between endocardium and epicardium, which could be lethal in BrS patients. Sodium channel blockade in a patient with BrS can lead to spontaneous, sustained ventricular arrhythmias, refractory to external cardioversion, resulting in cardiocirculatory collapse, as also reported by our group.15Conte G. Sieira J. Sarkozy A. et al.Life-threatening ventricular arrhythmias during ajmaline challenge in patients with Brugada syndrome: incidence, clinical features, and prognosis.Heart Rhythm. 2013; 10: 1869-1874Google Scholar,16Ciconte G. Monasky M.M. Vicedomini G. Borrelli V. Giannelli L. Pappone C. Unusual response to ajmaline test in Brugada syndrome patient leads to extracorporeal membrane oxygenator support.Europace. 2019; 21: 1574Google ScholarConclusionThis case report demonstrates the deleterious effect of phenytoin administration in a patient with BrS, whose predisposing condition was initially overlooked. Patients with seizure-like events should always be carefully evaluated by a cardiologist to rule out an underlying condition, especially if a neurologic etiology is not clearly established. In cases of suspicious symptoms, a family history of sudden death, and/or equivocal dubious ECG abnormalities, a sodium channel blocker test should be performed before initiating a specific drug treatment. Key Teaching Points•Antiepileptic drugs may interfere with cardiac electrophysiology and expose vulnerable patients to potentially fatal arrhythmias.•Syncope with tonic-clonic movements may be confused with epilepsy. A thorough cardiac evaluation is important before starting antiepileptic drugs.•Suspicious symptoms, a family history of sudden death, and equivocal dubious electrocardiogram abnormalities are warning signs of an underlying arrhythmic disorder. •Antiepileptic drugs may interfere with cardiac electrophysiology and expose vulnerable patients to potentially fatal arrhythmias.•Syncope with tonic-clonic movements may be confused with epilepsy. A thorough cardiac evaluation is important before starting antiepileptic drugs.•Suspicious symptoms, a family history of sudden death, and equivocal dubious electrocardiogram abnormalities are warning signs of an underlying arrhythmic disorder. •Antiepileptic drugs may interfere with cardiac electrophysiology and expose vulnerable patients to potentially fatal arrhythmias.•Syncope with tonic-clonic movements may be confused with epilepsy. A thorough cardiac evaluation is important before starting antiepileptic drugs.•Suspicious symptoms, a family history of sudden death, and equivocal dubious electrocardiogram abnormalities are warning signs of an underlying arrhythmic disorder. IntroductionBrugada syndrome (BrS) is an inherited disorder characterized by coved-type ST-segment elevation in the right precordial leads and increased risk of sudden cardiac death (SCD) in ostensibly normal heart.1Antzelevitch C. Yan G.X. J-wave syndromes: Brugada and early repolarization syndromes.Heart Rhythm. 2015; 12: 1852-1866Google Scholar The electrocardiogram (ECG) manifestations may occur spontaneously or after the exposure to sodium channel blocking agents.2Brugada R. Brugada J. Antzelevitch C. et al.Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts.Circulation. 2000; 101: 510-515Google Scholar The main clinical manifestations (syncope and SCD) are caused by malignant ventricular tachycardia / ventricular fibrillation, which are related to an arrhythmogenic epicardial substrate located in the anterior aspect of the right ventricular outflow tract.3Pappone C. Brugada J. Vicedomini G. et al.Electrical substrate elimination in 135 consecutive patients with brugada syndrome.Circ Arrhythm Electrophysiol. 2017; 10e005053Google Scholar,4Brugada J. Pappone C. Berruezo A. et al.Brugada syndrome phenotype elimination by epicardial substrate ablation.Circ Arrhythm Electrophysiol. 2015; 8: 1373-1381Google ScholarIdiopathic epilepsy and BrS share the pathophysiology of altered transmembrane ion current caused by mutations of ion channel subunit genes. Sodium channel dysfunction represents a common pathogenetic pathway for these 2 clinical entities that may be involved as a mechanism of sudden death. In addition, mutations of ion channel or arrhythmia-related genes are the most common defects found in patients experiencing sudden death in epilepsy.5Chahal C.A.A. Salloum M.N. Alahdab F. et al.Systematic review of the genetics of sudden unexpected death in epilepsy: potential overlap with sudden cardiac death and arrhythmia-related genes.J Am Heart Assoc. 2020; 9e012264Google ScholarCoexistence of epilepsy and BrS in a family with SCN5A mutation has been reported, suggesting that sodium channel mutation may be responsible for cardiac and cerebral manifestations, probably at different ages in the same individual and/or in the same family.6Parisi P. Oliva A. Coll Vidal M. et al.Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation.Epilepsy Res. 2013; 105: 415-418Google Scholar The latter underlines the importance of careful assessment of symptoms, detailed family history, and a thorough ECG analysis when evaluating patients with seizure-like symptoms.Antiepileptic drugs (AEDs) are useful in controlling malignant neurologic manifestations, and their adjunctive use in refractory epilepsy reduces mortality 7-fold.7Ryvlin P. Cucherat M. Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials.Lancet Neurol. 2011; 10: 961-968Google Scholar On the other hand, a community-based study found an increased risk of SCD in patients with epilepsy treated with AEDs, and this risk was specifically associated with the use of sodium channel blockers.8Bardai A. Lamberts R.J. Blom M.T. et al.Epilepsy is a risk factor for sudden cardiac arrest in the general population.PLoS One. 2012; 7e42749Google ScholarAmong sodium channel blockers used as AEDs, phenytoin (which belongs to the IB class of antiarrhythmic drugs) has been described to induce a type 1 ECG Brugada pattern at supratherapeutic doses.9Swe T. Bhattarai B. Dufresne A. Type 1 Brugada pattern ECG due to supra-therapeutic phenytoin level.BMJ Case Rep. 2016; 2016Google Scholar However, its direct role as a trigger of a fatal ventricular arrhythmia in a patient with BrS has never been described.

AIMS Balloon-based technologies have been developed to simplify catheter ablation of atrial fibrillation (AF), to improve the clinical outcome of the procedure and to achieve durable pulmonary vein isolation (PVI). The objective of this study is to evaluate the safety and efficacy of second-generation laser balloon (LB2) ablation in the treatment of AF using a continuous cardiac rhythm monitoring strategy. Atrial tachyarrhythmias (ATas) recurrences were assessed with implantable cardiac monitors (ICMs) or devices. METHODS AND RESULTS All patients underwent LB2 ablation procedure. The primary endpoint was the first recurrence of any, >5.5 and >24 h duration ATas after the blanking period (90 days). In-hospital visits were performed at 3, 6, and 12 months. Seventy-three patients (68% male, mean age 59.8 ± 11.3) were included in the study. The average procedure, fluoroscopy, and laser ablation times were 81.5 ± 30.1, 21.5 ± 12.4, and 33.8 ± 9.7, respectively. All PVs were isolated using the LB2 with no need of touch-up using focal catheters. No major complications occurred during or after the procedures. The one-year freedom from recurrences was 66.9% (95% CI: 57.0-76.7%), 81.0% (69.5-88.5%), and 86.8% (76.1-92.9%) considering any, 5.5-h and 24-h cut-off duration, respectively. At 3, 6, and 12 months, any ATas was recorded in 22%, 32%, and 25% of patients, with a ≥5% arrhythmic burden documented in 4%, 5%, and 3%, respectively. Few patients reported AF-related symptoms (7%, 8%, and 5%). CONCLUSION LB2 ablation is a safe and effective procedure, showing a high freedom from recurrences and low arrhythmic burden as documented by a continuous rhythm monitoring strategy.

Aims Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype-phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype-phenotype correlation in BrS. Methods and results Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 +/- 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. Conclusion In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

Dataset from the article Bernardini A, Ciconte G, Negro G, Rondine R, Mecarocci V, Viva T, Santini F, de Innocentiis C, Giannelli L, Witkowska E, Locati ET, Castelvecchio S, Marrocco-Trischitta MM, Vicedomini G, Menicanti L, Pappone C. Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen. Int J Cardiol. 2021 Feb 1;324:242-248. doi: 10.1016/j.ijcard.2020.09.038. Epub 2020 Sep 19. PMID: 32956782; PMCID: PMC7501148. Abstract Background: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. Method: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). Results: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. Conclusions: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.