Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome

Electrophysiological and Clinical Effects of Subtrate-directed Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome: a Randomized, Sham-controlled, Masked Clinical Trial

This randomized, sham-controlled, and blinded clinical trial aims to evaluate the effects of radiofrequency catheter ablation on the phenotypic expression of patients with Brugada syndrome. The main questions it seeks to address are:

• What are the immediate effects of radiofrequency catheter ablation on cardiac electrophysiology?
• Is substrate-directed radiofrequency catheter ablation safe for patients with Brugada syndrome?
• Is substrate-directed epicardial radiofrequency catheter ablation effective in normalizing the electrocardiographic pattern and preventing life-threatening arrhythmic events?

Researchers will compare the ablation group with the control group to determine if there are differences in clinical and invasive markers of the disease after one year of follow-up.

Study Overview

• Status: Completed
• Conditions: Brugada Syndrome
• Intervention / Treatment: Device: Radiofrequency catheter ablation; Device: Sham procedure

Detailed Description

Brugada syndrome (BS) is a cardiac disorder characterized by a specific electrocardiographic pattern and an increased risk of cardiac arrhythmias and sudden death. Most arrhythmic events occur during periods of rest, fever, or situations of heightened vagal activity. Over the past decade, catheter ablation has emerged as a valuable and potentially curative treatment for patients with BS. However, there is limited knowledge of its mechanisms or of its long-term effects on clinical and invasive markers.

This single-center, randomized, sham-controlled, and masked pilot study aims to investigate the impact of catheter ablation in 20 patients with Brugada syndrome. Participants will be randomly assigned to either the ablation or control group in a 1:1 allocation ratio and will be clinically monitored for at least 12 months following the intervention.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-000
      • Instituto do Coração - InCor - HC/FMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a type 1 Brugada ECG pattern, as characterized by ST-segment elevation (≥2mm) with upward concavity associated with T-wave inversion, in at least one of the right precordial leads, positioned at the second, third or fourth intercostal space, either spontaneously or induced by a provocative test with Class I anti-arrhythmic drugs according to Vaughan Williams
• Patients clinically stable for at least six months before the enrollment
• Able to cope with follow-up visits up to one year after the intervention
• Patients who have signed the written informed consent

Exclusion Criteria:

• Pregnant women
• Patients with structural heart disease
• Patients with a known cardiac or systemic autonomic disorder
• Patients with a history of previous right ventricular outflow tract ablation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ablation; Radiofrequency catheter ablation of the abnormal - prolonged and fragmented - electrophysiologic substrate of Brugada syndrome	Device: Radiofrequency catheter ablation; Radiofrequency application via catheter to burn the electroanatomic substrate implicated in Brugada syndrome
Sham Comparator: Control; Femoral venous punctions, catheter insertion, programmed electrical stimulation and electroanatomic mapping, with a similar duration to the ablation procedure	Device: Sham procedure; Venous and epicardial punctions, catheter insertions, programmed electrical stimulation and electroanatomical mapping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activation recovery interval (ARI)	The activation recovery interval, which serves as a surrogate marker for the duration of the action potential, will be measured on both the epicardial and endocardial surfaces of the right ventricular outflow tract. This measurement will be taken from the onset of the minimum of the derivative of ventricular activation (dVdT) to the end of ventricular repolarization, following the classic methodology	First 30 minutes after the intervention
Area of abnormal electrical potentials measured in square centimeters (cm²)	Abnormal electrical potentials were defined as low-frequency electrograms (up to 100 Hz) with prolonged duration (>200 ms), fragmented patterns (more than three deflections), and late components extending beyond the QRS complex	First 30 minutes after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local activation time	Measured by unipolar catheters placed in the epicardial and endocardial ventricular surfaces	First 30 minutes after the intervention
Maximum potential duration	Maximum length of ventricular signs on bipolar electrogram	First 30 minutes after the intervention
Induction of sustained ventricular arrhythmias by programmed electrical stimulation	Programmed electrical stimulation will be performed at two locations: the right ventricular apex and the right ventricular outflow tract, unless the patient experiences inducible ventricular tachycardia at the first site. The stimulation will use energy that is twice the diastolic threshold. Two drive cycles will be implemented: S1 at 600 ms and S1 at 430 ms. Up to two additional stimuli (S2 and S3) will be applied, with a minimum coupling time of 200 ms. A positive result from the programmed ventricular stimulation is identified if sustained ventricular fibrillation or polymorphic ventricular tachycardia is induced.	Immediately (first 30 minutes) after the intervention and again 12 months after
Acute post-procedure complications	Acute post-procedure complications were monitored over a three-day hospital stay, focusing on major events such as sustained ventricular arrhythmias, cardiac arrest, death, thromboembolic events, subxiphoid puncture accidents (significant bleeding (≥ 500 ml), or pericardial tamponade necessitating surgical intervention), and pericarditis. Diagnosis of pericarditis was based on characteristic pain, pericardial effusion, electrocardiographic findings (PR segment depression and diffuse ST-segment elevation), and elevated serum inflammatory markers.	During the first 72 hours following the intervention
Spontaneous type 1 Brugada electrocardiographic pattern in standard12 lead and superior leads electrocardiogram	Upward ST segment elevation ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces.	Up to one year after the procedure
Spontaneous type 1 Brugada electrocardiographic pattern during treadmill test	Upward ST segment elevation ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces, during treadmill test.	Up to one year after the procedure
Spontaneous type 1 Brugada electrocardiographic pattern in 12 lead 24 hour Holter monitoring	Upward ST segment elevation ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces during 12 lead 24h Holter ECG Monitoring	Up to one year after the procedure
Brugada type 1 electrocardiographic pattern induced by sodium channel blocker challenge	Upward ST-segment elevation ≥2 mm followed by a negative T wave (type 1 Brugada electrocardiographic pattern) in one or more right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal spaces after an ajmaline challenge after an ajmaline challenge	During the electrophysiological study, conducted 12 months after the intervention
Occurrence of life threatening arrhythmic events	Occurrence of at least one of the following: arrhythmic syncope, documented sustained ventricular tachycardia or ventricular fibrillation, sudden cardiac death or appropriate implantable cardiac defibrillator therapy	At least one year after the intervention
Combined efficacy endpoint	Induced sustained ventricular arrhythmias during programmed ventricular stimulation one year after the intervention or any life-threatening events (such as arrhythmic syncope, spontaneous sustained ventricular arrhythmias, appropriate ICD therapy, or sudden arrhythmic death) throughout at least 12 months of follow-up.	At least one year after the intervention

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Biosense Webster, Inc.

Publications and helpful links

General Publications

• Pappone C, Brugada J, Vicedomini G, Ciconte G, Manguso F, Saviano M, Vitale R, Cuko A, Giannelli L, Calovic Z, Conti M, Pozzi P, Natalizia A, Crisa S, Borrelli V, Brugada R, Sarquella-Brugada G, Guazzi M, Frigiola A, Menicanti L, Santinelli V. Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome. Circ Arrhythm Electrophysiol. 2017 May;10(5):e005053. doi: 10.1161/CIRCEP.117.005053.
• Patocskai B, Yoon N, Antzelevitch C. Mechanisms Underlying Epicardial Radiofrequency Ablation to Suppress Arrhythmogenesis in Experimental Models of Brugada Syndrome. JACC Clin Electrophysiol. 2017 Apr;3(4):353-363. doi: 10.1016/j.jacep.2016.10.011. Epub 2016 Dec 21.
• Kotake Y, Barua S, Kazi S, Virk S, Bhaskaran A, Campbell T, Bennett RG, Kumar S. Efficacy and safety of catheter ablation for Brugada syndrome: an updated systematic review. Clin Res Cardiol. 2023 Dec;112(12):1715-1726. doi: 10.1007/s00392-022-02020-3. Epub 2022 Apr 22.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2020
• Primary Completion (Actual): April 7, 2026
• Study Completion (Actual): April 7, 2026

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Actual): January 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radiofrequency catheter ablation; Brugada syndrome; Electroanatomic mapping; Invasive electrophysiological study
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Arrhythmias, Cardiac; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brugada Syndrome; Therapeutics; Surgical Procedures, Operative; Ablation Techniques; Radiofrequency Ablation; Radiofrequency Therapy; Catheter Ablation
• Other Study ID Numbers: IIS-470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing will be provided under proper request to the principal investigator
• IPD Sharing Time Frame: After the article's publication
• IPD Sharing Access Criteria: Under request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes