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.

Differences in accessory pathway location by sex and race.

BACKGROUND: The etiology of accessory pathway (AP) formation is generally unknown. OBJECTIVE: The purpose of this study was to test the hypothesis that AP formation is genetically mediated by examining whether AP location differs by sex and/or race, using sex and race as proxies to distinguish genetically different individuals. METHODS: This was a single-center, retrospective cohort study of 282 consecutive patients undergoing their first electrophysiology study that revealed at least one AP between 2004 and 2008. Sex and race were compared with AP location determined by invasive electrophysiology study. RESULTS: Eighty-nine (52%) males and 40 (36%) females had a left posterior AP (P = .006). Sixty-four (57%) females had a right annular AP, compared with 55 (32%) males (P <.001). After adjusting for age and race, females had 2.8-fold greater odds of having a right annular AP compared with males (95% confidence interval [CI] 1.70-4.65 greater odds; P <.001). While right anterior (free-wall) pathways were rare in all other races (12%), a significantly larger proportion of Asians (n = 10, 26%) had a right anterior AP (P = .017). After adjusting for sex and age, Asians had 3.8-fold greater odds of having a right anterior AP compared with other races (95% CI 1.5-9.4 greater odds; P = .004). CONCLUSIONS: Females more commonly had right annular APs, and Asians had right anterior APs substantially more frequently than other races. These findings suggest that the pathogenesis of AP formation may have a genetic component.

Paroxysmal supraventricular tachycardia in identical twins with the same left lateral accessory pathways and innocent dual atrioventricular pathways.

We report on 16-year-old, female identical twins who both have atrioventricular reentrant tachycardia caused by the same left lateral atrioventricular accessory pathway. The Kent pathway in twin A was a unidirectional retrograde accessory pathway. A manifest Kent pathway was demonstrated in twin B. Both pathways were successfully ablated by radiofrequency (RF) energy and without recurrence. In addition, innocent dual AV nodal pathways were shown in both patients. These findings suggest that genetic factors may play a role in the pathogenesis of the formation of accessory atrioventricular pathways and dual AV nodal pathways.