Outcomes of catheter ablation in high-risk patients with Brugada syndrome refusing an implantable cardioverter defibrillator implantation.

AIMS: The aim of this study was to investigate the outcomes of catheter ablation (CA) in preventing arrhythmic events among patients with symptomatic Brugada syndrome (BrS) who declined implantable cardioverter defibrillator (ICD) implantation. METHODS AND RESULTS: A total of 40 patients with symptomatic BrS were included in the study, of which 18 refused ICD implantation and underwent CA, while 22 patients received ICD implantation. The study employed substrate modification (including endocardial and epicardial approaches) and ventricular fibrillation (VF)-triggering pre-mature ventricular contraction (PVC) ablation strategies. The primary outcomes were a composite endpoint consisting of episodes of VF and sudden cardiac death during the follow-up period. The study population had a mean age of 43.8 ± 9.6 years, with 36 (90.0%) of them being male. All patients exhibited the typical Type 1 BrS electrocardiogram pattern, and 16 (40.0%) were carriers of an SCN5A mutation. The Shanghai risk scores were comparable between the CA and the ICD groups (7.05 ± 0.80 vs. 6.71 ± 0.86, P = 0.351). Ventricular fibrillation-triggering PVCs were ablated in 3 patients (16.7%), while VF substrates were ablated in 15 patients (83.3%). Epicardial ablation was performed in 12 patients (66.7%). During a median follow-up of 46.2 (17.5-73.7) months, the primary outcomes occurred more frequently in the ICD group than in the CA group (5.6 vs. 54.5%, Log-rank P = 0.012). CONCLUSION: Catheter ablation is an effective alternative therapy for improving arrhythmic outcomes in patients with symptomatic BrS who decline ICD implantation. Our findings support the consideration of CA as an alternative treatment option in this population.

Long-Term Outcomes of Brugada Substrate Ablation: A Report from BRAVO (Brugada Ablation of VF Substrate Ongoing Multicenter Registry).

BACKGROUND: Treatment options for high-risk Brugada syndrome (BrS) with recurrent ventricular fibrillation (VF) are limited. Catheter ablation is increasingly performed but a large study with long-term outcome data is lacking. We report the results of the multicenter, international BRAVO (Brugada Ablation of VF Substrate Ongoing Registry) for treatment of high-risk symptomatic BrS. METHODS: We enrolled 159 patients (median age 42 years; 156 male) with BrS and spontaneous VF in BRAVO; 43 (27%) of them had BrS and early repolarization pattern. All but 5 had an implantable cardioverter-defibrillator for cardiac arrest (n=125) or syncope (n=34). A total of 140 (88%) had experienced numerous implantable cardioverter-defibrillator shocks for spontaneous VF before ablation. All patients underwent a percutaneous epicardial substrate ablation with electroanatomical mapping except for 8 who underwent open-thoracotomy ablation. RESULTS: In all patients, VF/BrS substrates were recorded in the epicardial surface of the right ventricular outflow tract; 45 (29%) patients also had an arrhythmic substrate in the inferior right ventricular epicardium and 3 in the posterior left ventricular epicardium. After a single ablation procedure, 128 of 159 (81%) patients remained free of VF recurrence; this number increased to 153 (96%) after a repeated procedure (mean 1.2±0.5 procedures; median=1), with a mean follow-up period of 48±29 months from the last ablation. VF burden and frequency of shocks decreased significantly from 1.1±2.1 per month before ablation to 0.003±0.14 per month after the last ablation (P<0.0001). The Kaplan-Meier VF-free survival beyond 5 years after the last ablation was 95%. The only variable associated with a VF-free outcome in multivariable analysis was normalization of the type 1 Brugada ECG, both with and without sodium-channel blockade, after the ablation (hazard ratio, 0.078 [95% CI, 0.008 to 0.753]; P=0.0274). There were no arrhythmic or cardiac deaths. Complications included hemopericardium in 4 (2.5%) patients. CONCLUSIONS: Ablation treatment is safe and highly effective in preventing VF recurrence in high-risk BrS. Prospective studies are needed to determine whether it can be an alternative treatment to implantable cardioverter-defibrillator implantation for selected patients with BrS. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04420078.

Efficacy and safety of catheter ablation for Brugada syndrome: an updated systematic review.

BACKGROUND: Patients with Brugada syndrome (BrS) may experience recurrent ventricular arrhythmias (VAs). Catheter ablation is becoming an emerging paradigm for treatment of BrS. OBJECTIVE: To assess the efficacy and safety of catheter ablation in BrS in an updated systematic review. METHODS: We comprehensively searched the databases of Pubmed/Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to 11th of August 2021. RESULTS: Fifty-six studies involving 388 patients were included. A substrate-based strategy was used in 338 cases (87%), and a strategy of targeting premature ventricular complex (PVCs)/ventricular tachycardias (VTs) that triggered ventricular fibrillation (VF) in 47 cases (12%), with combined abnormal electrogram and PVC/VT ablation in 3 cases (1%). Sodium channel blocker was frequently used to augment the arrhythmogenic substrate in 309/388 cases (80%), which included a variety of agents, of which ajmaline was most commonly used. After ablation procedure, the pooled incidence of non-inducibility of VA was 87.1% (95% confidence interval [CI], 73.4-94.3; I2 = 51%), and acute resolution of type I ECG was seen in 74.5% (95% CI [52.3-88.6]; I2 = 75%). Over a weighted mean follow up of 28 months, 7.6% (95% CI [2.1-24]; I2 = 67%) had recurrence of type I ECG either spontaneously or with drug challenge and 17.6% (95% CI [10.2-28.6]; I2 = 60%) had recurrence of VA. CONCLUSION: Catheter ablation appears to be an efficacious strategy for elimination of arrhythmias or substrate associated with BrS. Further study is needed to identify which patients stand to benefit, and optimal provocation protocol for identifying ablation targets.

High-risk Brugada syndrome: factors associated with arrhythmia recurrence and benefits of epicardial ablation in addition to implantable cardioverter defibrillator implantation.

AIMS: This study aims to evaluate the prognostic impact of the arrhythmogenic substrate size in symptomatic Brugada syndrome (BrS) as well as to validate the long-term safety and effectiveness of epicardial radiofrequency ablation (RFA) compared with no-RFA group. METHODS AND RESULTS: In this prospective investigational long-term registry study, 257 selected symptomatic BrS patients with implantable cardioverter defibrillator (ICD) implantation were included. Among them, 206 patients underwent epicardial RFA and were monitored for over 5 years post-ablation (RFA group), while 51 patients received only ICD implantation declining RFA. Primary endpoints included risk factors for ventricular fibrillation (VF) events pre-ablation and freedom from VF events post-ablation. In the RFA group, BrS substrates were identified in the epicardial surface of the right ventricle. During the pre-RFA follow-up period (median 27 months), VF episodes and VF storms were experienced by 53 patients. Independent risk factors included substrate size [hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.08-1.18; P < 0.001], aborted cardiac arrest (HR, 2.98; 95% CI, 1.68-5.28; P < 0.001), and SCN5A variants (HR, 2.22; 95% CI, 1.15-4.27; P = 0.017). In the post-RFA follow-up (median 40 months), the RFA group demonstrated superior outcomes compared with no-RFA (P < 0.001) without major procedure-related complications. CONCLUSION: Our study underscores the role of BrS substrate extent as a crucial prognostic factor for recurrent VF and validates the safety and efficacy of RFA when compared with a no-RFA group. Our findings highlight the importance of ajmaline in guiding epicardial mapping/ablation in symptomatic BrS patients, laying the groundwork for further exploration of non-invasive methods to guide informed clinical decision-making.

Advances in Ventricular Arrhythmia Ablation for Brugada Syndrome.

Three decades have passed since the Brugada syndrome (BrS) clinical entity was introduced in the early 1990s. During the first 2 decades, treatment of patients with BrS was challenging because there were limited treatment options, and an implantable cardioverter-defibrillator was the only choice for high-risk patients with BrS, that is, those who had aborted sudden cardiac death or had previous ventricular fibrillation episodes. In this article, the authors focus on these advances and how to treat patients with BrS with catheter ablation.

Long-Term Outcomes of Pulmonary Vein Isolation in Patients With Brugada Syndrome and Paroxysmal Atrial Fibrillation.

Background Pharmacological treatment of atrial fibrillation (AF) in the setting of Brugada syndrome (BrS) is challenging. In addition, patients with BrS with an implantable cardioverter-defibrillator (ICD) might experience inappropriate shocks for fast AF. Long-term outcome of pulmonary vein isolation in BrS has not been well established yet, and it is still unclear whether pulmonary vein triggers are the only pathophysiological mechanism of AF in BrS. The aim of the study is to assess the long-term outcomes in patients with BrS undergoing pulmonary vein isolation for paroxysmal AF compared with a matched cohort of patients without BrS. Methods and Results Sixty patients with BrS undergoing pulmonary vein isolation with cryoballoon catheter ablation for paroxysmal AF were matched with 60 patients without BrS, who underwent the same procedure. After a mean follow-up of 58.2±31.7 months, freedom from atrial tachyarrhythmias was achieved in 61.7% in the BrS group and in 78.3% in the non-BrS group (log-rank P=0.047). In particular, freedom from AF was 76.7% in the first group and in 83.3% in the second (P=0.27), while freedom from atrial tachycardia/atrial flutter was 85% and 95% (P=0.057). In the BrS group, 29 patients (48.3%) had an ICD and 8 (27.6%) had a previous ICD-inappropriate shock for fast AF. In the BrS cohort, ICD-inappropriate interventions for AF were significantly reduced after ablation (3.4% versus 27.6%; P=0.01). Conclusions Pulmonary vein isolation in patients with BrS was associated with higher rate of arrhythmic recurrence. Despite this, catheter ablation significantly reduced inappropriate ICD interventions in BrS patients and can be considered a therapeutic strategy to prevent inappropriate device therapies.

Cardiac surgery and Brugada syndrome: operative considerations.

Brugada syndrome is an uncommon arrhythmic disease due to abnormality in myocardial transmembrane sodium channels and is associated with sudden death due to ventricular arrhythmias. We report our strategy and highlight precautions to reduce the risk of perioperative arrhythmias in a patient with Brugada pattern who underwent successful coronary artery bypass grafting.

Role of endocardial ablation in eliminating an epicardial arrhythmogenic substrate in patients with Brugada syndrome.

BACKGROUND: Epicardial ablation is occasionally limited by coronary artery (CA) injuries or epicardial fat (EF). OBJECTIVE: The purpose of this study was to evaluate the anatomic obstacles that prevent ablation of epicardial abnormal potentials (EAPs) in patients with Brugada syndrome (BrS) and to investigate the feasibility of EAP elimination by endocardial right ventricular (RV) ablation. METHODS: This study included 16 BrS patients with previous ventricular fibrillation (VF), including 10 with an electrical storm. Data from multidetector computed tomography were assessed, and the proximity of the CA and EF was correlated with EAPs. RESULTS: EAPs were present in the epicardial RV outflow tract and RV inferior wall in all patients and 12 patients (75%), respectively. These EAPs were present within 5 mm of the main body and branches of the right CA in 14 patients (87.5%). However, only 1.4% ± 2.9% of the EAP area was covered with thick EF (≥8 mm). Partial EAP elimination by endocardial RV ablation was feasible in all 10 patients, with 53.3% successful endocardial RV radiofrequency applications for eliminating EAPs. After the procedure, VF remained inducible in 37.5% of the patients. During the 25.1 ± 29.1 months of follow-up, no patients experienced an electrical storm, and VF burden significantly decreased (median VF episodes before and after ablation: 7 and 0, respectively). CONCLUSION: EAPs are near the CA in most BrS patients, thereby requiring caution during epicardial ablation, whereas EF is less of an issue. Endocardial ablation is feasible to eliminate some EAPs and may be combined with epicardial ablation.

Propofol for Induction and Maintenance of Anesthesia in Patients With Brugada Syndrome: A Single-Center, 25-Year, Retrospective Cohort Analysis.

BACKGROUND: Propofol administration in patients with Brugada syndrome (BrS) is still a matter of debate. Despite lacking evidence for its feared arrhythmogenicity, up to date, expert cardiologists recommend avoiding propofol. The main aim of this study is to assess the occurrence of malignant arrhythmias or defibrillations in patients with BrS, during and 30 days after propofol administration. The secondary aim is to investigate the occurrence of adverse events during propofol administration and hospitalization, as the 30-day readmission and 30-day mortality rate. METHODS: We performed a retrospective cohort study on patients with BrS who received propofol anytime from January 1, 1996 to September 30, 2020. Anesthesia was induced by propofol in both groups. In the total intravenous anesthesia (TIVA) group, anesthesia was maintained by propofol, while in the BOLUS group, volatile anesthesia was provided. The individual anesthetic charts and the full electronic medical records up to 30 postprocedural days were scrutinized. RESULTS: One hundred thirty-five BrS patients who underwent a total of 304 procedures were analyzed. The TIVA group included 27 patients for 33 procedures, and the BOLUS group included 108 patients for 271 procedures. In the TIVA group, the median time of propofol infusion was 60 minutes (interquartile range [IQR] = 30-180). The estimated plasma or effect-site concentration ranged between 1.0 and 6.0 µg·mL-1 for target-controlled infusion (TCI). The infusion rate for manually driven TIVA varied between 0.8 and 10.0 mg·kg-1·h-1. In the BOLUS group, the mean propofol dose per kilogram total body weight was 2.4 ± 0.9 mg·kg-1. No malignant arrhythmias or defibrillations were registered in both groups. The estimated 95% confidence interval (CI) of the risk for malignant arrhythmias in the BOLUS and TIVA groups was 0-0.011 and 0-0.091, respectively. CONCLUSIONS: The analysis of 304 anesthetic procedures in BrS patients, who received propofol, either as a TIVA or as a bolus during induction of volatile-based anesthesia, revealed no evidence of malignant arrhythmias or defibrillations. The present data do not support an increased risk with propofol-based TIVA compared to propofol-induced volatile anesthesia. Prospective studies are needed to investigate the electrophysiologic effects of propofol in BrS patents.

Role of Catheter Ablation for Ventricular Arrhythmias in Brugada Syndrome.

PURPOSE OF REVIEW: To discuss the role of catheter ablation in treating life-threatening ventricular arrhythmias associated with Brugada syndrome (BrS), by presenting recent findings of BrS arrhythmogenic substrate, mechanisms underlying ventricular arrhythmias, and how they can be treated with catheter ablation. RECENT FINDINGS: Almost three decades ago when the clinical entity of Brugada syndrome (BrS) was described in patients who had abnormal coved-type ST elevation in the right precordial EKG leads in patients who had no apparent structural heart disease but died suddenly from ventricular fibrillation. Since its description, the syndrome has galvanized explosive research in this field over the past decades, driving major progress toward better understanding of BrS, gaining knowledge of the genetic pathophysiology and risk stratification of BrS, and creating significant advances in therapeutic modalities. One of such advances is the ability for electrophysiologists to map and identify the arrhythmogenic substrate sites of BrS, which serve as good target sites for catheter ablation. Subsequently, several studies have shown that catheter ablation of these substrates normalizes the Brugada ECG pattern and is very effective in eliminating these substrates and preventing recurrent VF episodes. Catheter ablation has become an important addition for treatment of symptomatic BrS patients with recurrent VT/VF episodes.

Dynamic Changes in Electrocardiogram Parameters After Epicardial Substrate Catheter Ablation of Brugada Syndrome.

BACKGROUND: Catheter ablation (CA) is effective for recurrent episodes of ventricular fibrillation (VF) in Brugada syndrome (BrS). VF development in BrS is associated with several electrocardiogram (ECG) abnormalities. This study investigated changes in ECG parameters in high-risk BrS patients who underwent epicardial CA.Methods and Results:In all, 27 BrS patients were implanted with an implantable cardioverter-defibrillator (ICD). Patients were divided into 2 groups: (1) an ablation group (n=11) that underwent epicardial CA because of VF recurrence; and (2) a primary prevention (PP) group (n=16) with ICD implantation only. ECG parameters were evaluated before and 12 months after CA and compared with ECG parameters in the PP group. The T wave peak-to-end interval was significantly longer and the number of abnormal spikes in leads V1-V3 at the second, third, and fourth intercostal spaces was greater in the ablation than PP group. After ablation, ST levels and the sum of abnormal spikes in leads V1-V3 were significantly decreased. The mean (±SD) number of ICD shocks decreased markedly during a mean follow-up period of 42.0 months (from 3.8±3.7 to 0.2±0.4/year). Four patients had an ICD shock following the ablation procedure. Greater reductions in ST-segment elevation and abnormal spikes were observed in the group without than with VF recurrence. CONCLUSIONS: Improvements in surface ECG parameters appear to be associated with successful ablation in high-risk BrS patients.

Dormant conduction in the right ventricular outflow tract unmasked by adenosine in a patient with Brugada syndrome.

Recent data of electrophysiological mapping in patients with Brugada syndrome (BrS) suggest that the presence of an abnormal arrhythmogenic substrate in the epicardial right ventricular outflow tract is responsible for ST-segment elevation and ventricular fibrillation (VF). Complete elimination of the epicardial abnormal potentials normalizes Brugada-pattern electrocardiogram and suppresses VF recurrence. We herein report the first case of BrS in which an injection of adenosine unmasked dormant conduction in the epicardial RVOT after the disappearance of the epicardial potentials.

Síndrome de brugada en el paciente quirúrgico de urgencia. Reporte de caso / Brugada syndrome in the emergency surgical patient. Case report.

Introducción: El síndrome de Brugada es una condición genética rara, el diagnóstico se establece por un patrón electrocardiográfico en particular que se asocia a un riesgo de fibrilación ventricular y muerte súbita; Objetivo: Presentar un caso interesante de un paciente joven quién ingreso a quirófano con la impresión clínica de apendicitis aguda para realizar apendicetomía video laparoscópica. Durante el procedimiento presento múltiples episodios de taquiarritmias; desencadenando Fibrilación Ventricular de difícil manejo trans y post operatorio, debido a los medicamentos peri-operatorios, agresión quirúrgica y fiebre. Material y Métodos: Se documento y presentó un caso interesante; Presentación de Caso: Paciente masculino de 26ª, sin antecedentes médicos, con impresión clínica de apendicitis aguda ingresa a quirófano, durante el acto quirúrgico presenta arritmias, documentándose Fibrilación Ventricular con inestabilidad hemodinámica que amerito desfibrilación externa, revirtió a ritmo sinusal. Al concluir el acto quirúrgico, se realiza EKG, evidenciando supradesnivel del segmento ST en V1 y V2 e inversión de la onda T por lo que pasa a unidad de cuidados intensivos, sin reversión anestésica y con tubo orotraqueal. Paciente se monitoriza en UTI, se realiza EKG evidencia ritmo nodal. Se extuba a las 12h post operatorias y se traslada a cardiología en 48h donde establecen que paciente cursa con patrón de Brugada. Conclusiones: Con el creciente número de pacientes con trastornos de conducción heredadas que se presentan para cirugía no cardiaca que están en riesgo de muerte súbita; el éxito en el manejo peri, trans y post operatorio depende de un conocimiento detallado de estas condiciones. (AU)

Introduction: Brugada syndrome is a rare genetic condition, the diagnosis is established by a particular electrocardiographic pattern and is associated with a risk of ventricular fibrillation and sudden death; Objective: To present an interesting case of a young patient who enters the operating room with the clinical impression of acute appendicitis to perform laparoscopic appendectomy and that during the procedure present multiple episodes of tachyarrhythmias; triggering Ventricular Fibrillation, what causes him difficult trans and postoperative management, due to peri-operative medications, surgical aggression and fever. Material and Methods: An interesting case was documented and presented; Case Presentation: Male patient of 26 years old, without medical history, with clinical impression of acute appendicitis was admitted to the operating room, during the surgical act it presents arrhythmias, showing Ventricular Fibrillation with hemodynamic instability that warrants external defibrillation, reversed at sinus pace, EKG is performed showing elevation gain of the ST segment in V1 and V2 and inversion of the T wave at the end of the surgical act, so it goes to intensive care unit, without anesthetic reversal and with orotracheal tube. Patient is monitored in ICU, EKG shows nodal rhythm, extubates at 12h post op and at 48h was transferred to cardiology where they establish that patient studies suggest Brugada pattern; Conclusions: With the increasing number of patients with inherited driving disorders who present the thee for non-cardiac surgery who are at risk of sudden death; success in peri, trans and postoperative management depends on a detailed knowledge of these conditions. (AU)

Epicardial Ablation in Brugada Syndrome.

Brugada syndrome is an inherited cardiac condition characterized by a typical electrocardiogram signature of coved-type ST-segment elevation in the right precordial leads and ventricular arrhythmias leading to sudden cardiac death, in the absence of unequivocal structural heart disease. Brugada syndrome specifically affects the right ventricle, which predisposes to cardiac arrest. Besides medical management with quinidine, emerging data indicate that catheter ablation can help reduce the ventricular arrhythmia burden in these patients. This review explores the mechanisms of ventricular arrhythmia, current approaches and evidence for ablating the epicardial arrhythmogenic substrate in this condition.

Refractoriness to subcutaneous implantable cardioverter defibrillator after frequent therapies for ventricular fibrillation storms in a Brugada syndrome case.

BACKGROUND: The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to the transvenous implantable cardioverter defibrillator for the prevention of sudden cardiac death. Here, we report a rare case of refractoriness to an S-ICD after frequent therapies for ventricular fibrillation (VF) storms. CASE PRESENTATION: A 24-year-old man underwent a bout of syncope with vomiting and incontinence at home. He was brought to the emergency room and was witnessed to spontaneously go into VF successfully converted by external defibrillation. Previously, he was diagnosed with a type I Brugada electrocardiogram pattern by a pilsicainide administration test in another hospital. Although he had a family history of sudden cardiac death in 3 relatives, including his brother, he was followed closely without any therapies because he had never had an episode of syncope. He was implanted with an S-ICD without any trouble. Seven months later, frequent S-ICD shocks for VF storms occurred. His VF was controlled by using intravenous amiodarone, which was converted to an oral preparation. However, his VF recurred after another 2 months. The analysis of his S-ICD data revealed that 4 consecutive shock deliveries could not terminate his VF and the final shock delivered could fortunately terminate it because of a high defibrillation threshold test (DFT) due to an increasing shock impedance (64 to 90 Ω). First, we performed an epicardial Brugada syndrome ablation and subsequently replaced and repositioned the S-ICD lead from a left to a right parasternal site. After the re-implantation of the S-ICD, the DFT test improved to within normal range. According to the pathological analysis, infiltration of inflammatory cells and extensive fibrosis were confirmed in the subcutaneous tissue around the shock lead and S-ICD body. CONCLUSION: Frequent S-ICD shocks for VF storms might cause various pathological changes around the device and lead to a high DFT.

Ablation for the treatment of Brugada syndrome: current status and future prospects.

Introduction: Brugada syndrome (BrS) is an inherited disease characterized by an increased risk of sudden cardiac death (SCD). Therapeutic options in symptomatic patients are limited to implantable cardioverter defibrillator (ICD) and quinidine, but catheter ablation of the right ventricular outflow tract (RVOT) offers a potential cure. Different ablation strategies have been used to treat patients with symptomatic Brugada syndrome. Epicardial radiofrequency substrate ablation of the RVOT/right ventricle (RV) has emerged as a promising tool for the management of the disease.Areas covered: The historical management of BrS, endocardial and epicardial ablation techniques, the use of sodium channel blockers (SCB) and complications are summarized here.Expert opinion: Ventricular fibrillation (VF)-triggering premature ventricular contractions (PVCs) in patients with BrS are unpredictable, spontaneous ones are rarely present to be mapped, making this approach impractical. Furthermore, endocardial mapping for BrS substrates does not seem effective due to the epicardial pathological substrate localization. The size variation of the BrS substrate areas during SCB infusion suggests a dynamic process as arrhythmogenic basis and SCB infusion should guide BrS epicardial ablation of all abnormal potentials areas. If BrS epicardial ablation can truly provide long-term prevention of ventricular arrhythmias it may potentially become an alternative to ICD therapy.