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.

Human model simulating right ventricular outflow tract tachycardia by high-frequency stimulation in the left pulmonary artery: autonomics and idiopathic ventricular arrhythmias.

INTRODUCTION: Frequent monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia (VT) in patients with structurally normal heart usually arise from the right ventricular outflow tract (RVOT). An animal model simulating RVOT tachycardia by high-frequency stimulation (HFS) of the sympathetic input to the proximal pulmonary artery (PA) has been previously described. The aim of this study was to similarly induce RVOT tachycardia in humans. METHODS: In 9 patients with no history of ventricular arrhythmias, a circumferential catheter was placed in the left, main, and proximal PA to contact the endovascular circumference of the PA. A 50-ms train of HFS (200 Hz/0.3 ms pulse duration), coupled to atrial pacing, was applied at each bipolar pair of the circumferential catheter. The coupling interval was adjusted so that the 50-ms train occurred during the ventricular refractory period. RESULTS: In 6 out of 9 patients, HFS in the left PA during dobutamine infusion induced monomorphic PVCs and/or VT with left bundle branch block (LBBB) morphology and inferior axis at an average stimulation level of 12.5 +/- 2.7 V. HFS in the main PA and in the proximal PA did not induce any ventricular arrhythmias with the highest energy of 15 V in baseline state and during dobutamine infusion. HFS in the left PA was associated with hiccough in all patients. CONCLUSION: Stimulation of the sympathetic input to the left PA during dobutamine infusion induces PVCs and/or VT exhibiting LBBB-morphology and inferior axis, closely simulating clinical RVOT tachycardia in humans.