Epicardial ablation in high-risk Brugada syndrome to prevent ventricular fibrillation: results from a randomized clinical trial

Abstract

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.

Keywords: Arrhythmogenic substrate; Brugada syndrome; Cardiac arrest; Epicardium; ICD; Ventricular fibrillation.

Graphical Abstract

Figure 1

This flowchart outlines the study design, participant randomization, and clinical outcomes of all enrolled patients.

Figure 2

Exemplary case of a Brugada syndrome (BrS) patient displaying a spontaneous type 1 pattern and having a history of ICD discharges, as shown in the bottom panel, who underwent epicardial ablation. Top Panel: On the top left, the ECG exhibits the spontaneous type 1 BrS pattern. To the right, the electroanatomic map illustrates the cardiac substrate, with colour-coded regions indicating areas of electrical activity. The purple regions denote areas with abnormal electrograms, characterized by fragmented signals and prolonged durations (>160 ms). The red regions indicate areas with normal electrogram (EGM) signals of short duration (<110 ms). Middle Panel: The middle-left panel shows the ECG tracings post-ablation, revealing a normalized ECG pattern, which suggests a successful alteration of the arrhythmic substrate. The corresponding electroanatomic map on the right no longer shows the purple regions, indicating the removal of the previously identified abnormal substrate. The post-ablation signals are of normal duration and devoid of late activity, further confirming the effective ablation of the arrhythmic substrate. Bottom Panel: The bottom panel displays the ECG recording of an ICD discharge, demonstrating the last clinical arrhythmic event before randomization assignment to catheter ablation.

Figure 3

Exemplary case of a Brugada syndrome (BrS) patient presenting a spontaneous type 1 ECG pattern in the right precordial leads positioned from the second to the fourth intercostal space, and a late depolarization pattern in the lateral leads (indicated by red arrows; top left panel). This patient had a history of multiple ICD discharges, with the most recent event depicted in the bottom left panel. Epicardial mapping reveals diffuse electrical activity concentrated in the anterior wall of the RV, extending from the right ventricular outflow tract (RVOT) to the inferior aspect (top right panel), as well as in the lateral (middle right panel) and inferior walls (bottom right panel) of the left ventricle. Following extensive substrate homogenization, there was normalization of the ECG pattern which persisted in the follow-up (see Supplementary material online, Figure S1), and the patient experienced no VF recurrences during the follow-up period.

Figure 4

The left panel displays the cumulative failure function of arrhythmic episodes during the 6 months preceding randomization. The right panel illustrates freedom from VF recurrence after randomization in the ablation group (green line) and the control group (red line). In both plots, Time 0 represents the date of randomization.

Figure 5

This violin plot compares the burden of VF episode rate per year before and after randomization in the study population: the ablation group (green) and the control group (red). After treatment, the ablation group experienced a significant decrease in VF episodes. Following randomization, the rate of VF events per year was significantly lower in the ablation arm compared with the control group. Abbreviations: *** and ** marks indicate P-value <0.001 and <0.002, respectively; ‘ns’, not statistically significant.

Figure 6

Quality of life measures by the means of the EQ-5D-5L score questionnaire, indicating better performance in the ablation group compared with the control group. Abbreviations: *** and * marks indicate P-value <0.001 and <0.033, respectively; ‘ns’, not statistically significant.