High prevalence of concealed Brugada syndrome in patients with atrioventricular nodal reentrant tachycardia

BACKGROUND Atrioventricular nodal reentrant tachycardia (AVNRT) may coexist with Brugada syndrome (BrS). OBJECTIVES The present study was designed to determine the prevalence of drug-induced type 1 Brugada ECG pattern (concealed BrS) in patients presenting with clinical spontaneous AVNRT and to investigate their electrocardiographic, electrophysiological, and genetic characteristics. METHODS Ninety-six consecutive patients without any sign of BrS on baseline electrocardiogram undergoing electrophysiological study and ablation for symptomatic, drug-resistant AVNRT and 66 control subjects underwent an ajmaline challenge to unmask BrS. Genetic screening was performed in 17 patients displaying both AVNRT and BrS. RESULTS A concealed BrS electrocardiogram was uncovered in 26 of 96 patients with AVNRT (27.1%) and in 3 of 66 control subjects (4.5%) (P <= .001). Patients with concealed BrS were predominantly female patients (n = 23 [88.5%] vs n = 44 [62.9%], P = .015), had higher prevalence of chest pain (n = 10 [38.5%] vs n = 13 [18.6%], p = 0.042), migraine headaches (n = 10 [38.5%] vs n = 10 [14.2%], p = 0.008), and drug-induced initiation and/or worsening of duration and/or frequency of AVNRT (n = 4 [15.4%] vs n = 1 [1.4%], p = 0.006) as compared to patients with AVNRT without BrS. Genetic screening identified 19 mutations or rare variants in 13 genes in 13 of 17 patients with both AVNRT and BrS (yield = 76.5%). Ten of these 13 genotype-positive patients (76.9%) harbored genetic variants known or suspected to cause a loss of function of cardiac sodium channel current (SCN5A, SCN10A, SCN1B, GPD1L, PKP2, and HEY2). CONCLUSION Our results suggest that spontaneous AVNRT and concealed BrS co-occur, particularly in female patients, and that genetic variants that reduce sodium channel current may provide a mechanistic link between AVNRT and BrS and predispose to expression of both phenotypes.