Torsades de pointes during complete atrioventricular block: Genetic factors and electrocardiogram correlates

Atrioventricular (AV) block is infrequently associated with QT prolongation and torsades de pointes (TdP). It was hypothesized that patients with AV block-mediated QT-related arrhythmia may have latent congenital long QT syndrome or a vulnerable genetic polymorphism.

Eleven patients with complete AV block and TdP were prospectively identified. Patients underwent assessment, resting electrocardiography and telemetry at baseline, during AV block and pre-TdP. Genetic testing of KCNH2, KCNQ1, KCNE1, KCNE2 and SCN5A was performed. Thirty-three patients with AV block without TdP were included for comparison.

Genetic variants were identified in 36% of patients with AV block and TdP. Patients with AV block who developed TdP had significantly longer mean (+/- SD) corrected QT intervals (440+/-93 ms versus 376+/-40 ms, P=0.048) and Tpeak to Tend (Tp-Te) intervals (147+/-25 ms versus 94+/-25 ms, P=0.0001) than patients with AV block alone. In patients with a genetic variant, there was a significant increase in Tp-Te intervals at baseline, in AV block and pre-TdP compared with those who were genotype negative. A personal or family history of syncope or sudden death was more likely observed in patients with a genetic variant.

TdP in the setting of AV block may be a marker of an underlying genetic predisposition to reduced repolarization reserve. The Tp-Te interval at baseline, in AV block and pre-TdP may predict a genetic mutation or polymorphism compromising repolarization reserve. Patients with TdP in the setting of AV block represent a phenotypic manifestation of latent congenital long QT syndrome.