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

Abstract

V entricular arrhythmias have been reported in the setting of complete atrioventricular (AV) block since 1918 (1). In 1966, Dessertenne (2) described such an arrhythmia as torsades de pointes (TdP), a polymorphic ventricular tachycardia preceded by QT interval prolongation, now known to be caused by congenital or acquired long QT syndrome (LQTS) (3).Bradyarrhythmias caused by high-grade AV block are common. It is, however, infrequent that bradyarrhythmias are associated with QT interval prolongation and TdP phenomena (4-6). In patients with bradycardia-induced TdP, a number of electrocardiogram (ECG) parameters during bradycardia correlate with increased risk of TdP, including the QT interval (4-6), T wave morphology and T peak to T end (T p -T e ) (6). Although ECG parameters can be reasonable predictors of TdP in bradyarrhythmias (4-6), there are limited data on cellular or genetic mechanisms of bradycardia-induced TdP (7,8).We hypothesized that patients with bradycardia-mediated QT arrhythmia may have latent congenital LQTS or a vulnerable genetic polymorphism. In the setting of AV block, reduced repolarization reserve may be 'unmasked' in patients, manifesting as QT interval prolongation and TdP. Such an occult form of LQTS has previously been reported among patients with undiagnosed congenital LQTS who develop marked QT interval prolongation and TdP when exposed to QT-prolonging drugs (9,10). Moreover, the development of TdP in the setting of AV block may identify ion channel mutations that have a propensity to cause TdP and sudden cardiac death. INtRodUCtIoN: 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. Methods: 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. ResULts: 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 T peak to T end (T p -T e ) 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 T p -T e 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. CoNCLUsIoNs: TdP in the setting of AV block may be a marker of an underlying genetic predisposition to reduced repolarization reserve. The T p -T e interval at baseline, in AV block and pre-TdP may predict a genetic mutation ...

Bradycardia alters Ca2+dynamics enhancing dispersion of repolarization and arrhythmia risk

“…Bradycardia-dependent TdP is more prevalent in women (ϳ75%) than men (54,57), which parallels the well-established finding for drug-induced LQT type 2 (LQT2). On the other hand, most episodes of TdP in humans are not preceded by profound bradycardia, and more than one factor is often identified (29,32 (21) and the late Na ϩ current (I Na,L ) (24).…”

“…Slow ventricular rate is an established proarrhythmic factor known to increase the propensity to TdP, an arrhythmia associated with delayed repolarization (40,54). Abnormal Ca 2ϩ handling and spontaneous SR Ca 2ϩ release has been suggested as the mechanism of EADs, the form of triggered activity which underlies TdP.…”

Acquired Long QT Interval: A Case Series of Multifactorial QT Prolongation

“…25 Torsades de pointes is a known complication of AV block, and it is thought that TdP in the setting of AV block may be a marker of an underlying predisposition to reduced repolarization reserve and that this may represent a phenotypic manifestation of latent congenital long QT syndrome. 26 Finally, one of the patients in this series had a history of dilated cardiomyopathy on a background of muscular dystrophy, and, given the known increased risk of LQT in the setting of dilated cardiomyopathy, 17 it is likely that the medications and electrolyte disturbances present in this patient had an additive effect in contributing to generating LQT.…”

Unveiling Specific Triggers and Precipitating Factors for Fatal Cardiac Events in Inherited Arrhythmia Syndromes

“…38 KCNQ1, KCNH2, KCNE2 and SCN5A mutations have been reported in approximately 17-28% patients with bradycardiainduced LQTS (Table 3). [49][50][51] Of note, the KCNH2 mutation has been the most common, but KCNQ mutation is quite rare compared with cLQTS. Only a single KCNQ1 mutation, G272V, had been reported to date.…”