Brugada Syndrome
Conditions
Keywords
Brugada syndrome, Radiofrequency catheter ablation, Electroanatomic mapping, Invasive electrophysiological study
Brief summary
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.
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.
Interventions
DEVICERadiofrequency catheter ablation
Radiofrequency application via catheter to burn the electroanatomic substrate implicated in Brugada syndrome
DEVICESham procedure
Venous and epicardial punctions, catheter insertions, programmed electrical stimulation and electroanatomical mapping
Sponsors
University of Sao Paulo General Hospital
Biosense Webster, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Randomization will occur during the electrophysiology procedure, and the automated process will ensure allocation concealment. Patients randomized to the treatment group will undergo radiofrequency catheter ablation. Participants randomized to the control group will undergo a sham procedure consisting of femoral venous punctions, catheter insertion, programmed electrical stimulation, and electroanatomic mapping, with a similar duration to the ablation procedure. Medical follow-up will be standardized with the same protocol for both treatment groups. All medical documents will be anonymized before evaluation. The study protocol, for apparent reasons, precludes masking the principal investigator (electrophysiology specialist). Patients, care providers, outcome raters, and statisticians will be blinded.
Intervention model description
Single-centre, randomized, sham-controlled, and masked pilot study with two parallel arms, with a 1:1 allocation ratio to ablation or control group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Activation recovery interval (ARI) | First 30 minutes after the intervention | 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 |
| Area of abnormal electrical potentials measured in square centimeters (cm²) | First 30 minutes after the intervention | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local activation time | First 30 minutes after the intervention | Measured by unipolar catheters placed in the epicardial and endocardial ventricular surfaces |
| Maximum potential duration | First 30 minutes after the intervention | Maximum length of ventricular signs on bipolar electrogram |
| Induction of sustained ventricular arrhythmias by programmed electrical stimulation | Immediately (first 30 minutes) after the intervention and again 12 months after | 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. |
| Acute post-procedure complications | During the first 72 hours following the intervention | 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. |
| Spontaneous type 1 Brugada electrocardiographic pattern in standard12 lead and superior leads electrocardiogram | Up to one year after the procedure | 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. |
| Spontaneous type 1 Brugada electrocardiographic pattern during treadmill test | Up to one year after the procedure | 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. |
| Spontaneous type 1 Brugada electrocardiographic pattern in 12 lead 24 hour Holter monitoring | Up to one year after the procedure | 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 |
| Brugada type 1 electrocardiographic pattern induced by sodium channel blocker challenge | During the electrophysiological study, conducted 12 months after the intervention | 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 |
| Occurrence of life threatening arrhythmic events | At least one year after the intervention | 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 |
| Combined efficacy endpoint | At least one year after the intervention | 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. |
Countries
Brazil
Outcome results
None listed