Longer Outflow Tract Conduction Time by Magnetocardiography as a Novel Non-Invasive Maker for Predicting Lethal Events in Patients With Brugada Syndrome Without Ventricular Fibrillation

Introduction: Many of the Brugada syndrome (BrS) patients have no symptom or only syncope without ventricular fibrillation (VF)/sudden cardiac death (SCD), thus to whom we should recommend implantable cardioverter defibrillator (ICD) for primary prevention of SCD is still the biggest concern in the BrS. Here we investigated whether a high spatial resolution magnetocardiography (MCG) could predict lethal events of the BrS without history of VF/SCD. Methods: This study retrospectively enrolled 157 BrS patients without VF or cardiopulmonary arrest (CPA) (150 male, 42±13 years old, 118 spontaneous and 39 drug-induced type-1 ECG). Outflow tract conduction time (OT-CT) from 2-D current map of MCG was measured in all patients as well as the standard 12-lead ECG and signal-averaged ECG (SAECG). Programmed electrical stimulation (PES) for VF induction was performed in 47 patients. Results: Patients with spontaneous type-1 ECG had longer OT-CT compared with type-2 BrS patients. Na channel blocker, pilsicainide (25-50mg) unmasked type-1 ECG as well as increased OT-CT (54±18 to 127±62 ms; p<0.05), whereas additional isoproterenol (1ug/kg/min) reversed the pilsicainide-induced delayed OT-CT, thus normalized the ST elevation of ECG. During follow-up (mean 72 [6-147] months), 10 (6%) patients suffered VF/CPA, and those had a higher incidence of previous syncope (50% vs. 14.4%, p=0.01) and longer baseline OT-CT (83±31ms vs. 55±24ms, p=0.01) compared with event-free patients. Receiver operating curve (ROC) revealed OT-CT=65ms was a cut-off value of VF/CPA (AUC=0.78), whereas, spontaneous type-1 ECG, late potential of SAECG, family history, and VF inducibility by PES were not associated with VF/CPA events during follow-up. Multivariate Cox proportional analysis revealed that previous syncope (HR=1.70, 95%CI:1.01-3.05, p=0.04) and OT-CT≥65ms (HR=1.72, 95%CI=1.16-2.62) were the independent predictor for lethal events in the BrS without VF/CPA. Among asymptomatic BrS patients (n=131), OT-CT≥65ms was also an independent predictor for VF/CPA (HR=1.69, 95%CI=1.04-2.79, p=0.03). Conclusion: Longer OT-CT in the MCG may noninvasively demonstrate substrate of VF in BrS and stratify the risk of lethal events in patients with BrS without history of VF or CPA.