Prognostic Significance of the Sodium Channel Blocker Test in Patients With Brugada Syndrome

Abstract

BackgroundA drug provocation test using a sodium channel blocker (SCB) can unmask a type 1 ECG pattern in patients with Brugada syndrome. However, the prognostic value of the results of an SCB challenge is limited in patients with non–type 1 ECG. We investigated the associations of future risk for ventricular fibrillation with SCB‐induced ECG changes and ventricular tachyarrhythmias (VTAs).Methods and ResultsWe administered intravenous pilsicainide to 245 consecutive patients with Brugada syndrome (181 patients with spontaneous type 1 ECG, 64 patients with non–type 1 ECG). ECG parameters before and after the test and occurrence of drug‐induced VTAs were evaluated. During a mean follow‐up period of 113±57 months, fatal VTA events occurred in 31 patients (sudden death: n=3, ventricular tachycardia/ventricular fibrillation: n=28). Symptomatic patients and spontaneous type 1 ECG were associated with future fatal arrhythmic events. Univariable analysis of ECG parameters after the test showed that long PQ and QRS intervals, high ST level, and SCB‐induced VTAs were associated with later VTA events during follow‐up. Multivariable analysis showed that symptomatic patients, high ST level (V1) ≥0.3 mV after the test, and SCB‐induced VTAs were independent predictors for future fatal arrhythmic events (hazard ratios: 3.28, 2.80, and 3.62, 95% confidence intervals: 1.54–7.47, 1.32–6.35, and 1.64–7.75, respectively; P<0.05).Conclusions SCB‐induced VTAs and ST‐segment augmentation are associated with an increased risk of the development of ventricular tachycardia/ventricular fibrillation events during follow‐up in patients with Brugada syndrome.

Type‐I Paradox of Brugada Syndrome

“…The study by Ueoka et al6 provides limited insight into this intriguing second possibility. There were 105 patients with a nondiagnostic ECG at the time of the SCB test.…”

“…The patients were typical of Brugada syndrome: their mean age was 46 years, all but 2% were male, and the majority (62%) were asymptomatic at presentation 6. Importantly, 74% of patients had previous documentation of spontaneous type‐I, or had a spontaneous type‐I at the onset of the test but nevertheless underwent a SCB test to assess its prognostic (rather than diagnostic) value.…”

“…Here, Ueoka et al speculated that ECG changes of greater magnitude would identify patients at higher risk of spontaneous arrhythmias, and the infusion was continued irrespective of the ST‐segment elevation height. In fact, 106 (43%) patients undergoing the test already had ≥2‐mm ST‐segment elevation before the SCB infusion, and a stunning 6‐mm ST‐segment elevation in response to the drug challenge was the rule 6. With this audacious protocol, ≈10% of all patients developed ventricular arrhythmias during the test 6.…”

“…In fact, 106 (43%) patients undergoing the test already had ≥2‐mm ST‐segment elevation before the SCB infusion, and a stunning 6‐mm ST‐segment elevation in response to the drug challenge was the rule 6. With this audacious protocol, ≈10% of all patients developed ventricular arrhythmias during the test 6. During 9 years of follow‐up, 31 (13%) of the patients developed spontaneous ventricular fibrillation (VF) 6.…”

“…As in previous studies,5 cardiac arrest at presentation inferred a 3‐fold higher risk of VF during follow‐up. The new finding was that the development of ≥3‐mm ST‐segment elevation, or the appearance of ventricular arrhythmias in response to the SCB test, were also independent predictors of VF during follow‐up, with hazard ratios of 2.8 and 3.6, respectively 6. Risk stratification is of paramount importance for asymptomatic patients 5.…”