Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2

Abstract

Background-Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and ␤-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2. Methods and Results-We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112Ϯ5 ms) than LQT1 (91Ϯ2 ms) or unaffected (86Ϯ3 ms) patients (PϽ0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs. Conclusions-TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP. Key Words: arrhythmia Ⅲ electrocardiography Ⅲ long-QT syndrome Ⅲ torsade de pointes T orsade de pointes is the arrhythmia producing syncope and risk of sudden death in patients with the congenital long-QT syndrome (LQTS). 1 Torsade de pointes tends to appear during exercise (especially swimming) or psychological stress in LQT1, during stress or startle (particularly auditory stimuli) in LQT2, and during rest in LQT3. 2 In experimental LQTS models, transmural dispersion of repolarization (TDR) has been linked to the genesis of torsade de pointes, 3 and LQT2 shows increased TDR, determined as the action potential duration difference between midmyocardial and epicardial cells, compared with LQT1 and normal hearts. 4 Conversely, ␤-adrenergic stimulation increases TDR in both LQTS models, transiently in LQT2 and persistently in LQT1. 4 In addition, the interval from QRS onset to the T-wave termination and T-wave apex correspond to action potential durations of midmyocardial and epicardial cells, respectively. 5 We hypothesized that the T-wave peak to T-wave end (TPE) interval would prolong preferentially with abrupt elevation of heart rates in LQT1 patients, whereas LQT2 patients would show prolonged TPE intervals at a wider range of heart rates. Although earlier studies have shown a weak correlation between the length of the QT interval and symptoms, 6,7 we hypothesized that the history of cardiac symptoms may be related to TPE interval rather than the length of the QT interval. Methods Study SubjectsWe reviewed Holter recordings in 90 individuals either ...

The Time Course of New T‐Wave ECG Descriptors Following Single‐ and Double‐Dose Administration of Sotalol in Healthy Subjects

“…13,14 Hence, both scalar measurements and principal component analysis (PCA) have been used to describe T-wave morphology and changes in T-wave morphology parameters have been associated with impaired repolarization and bad prognosis. [15][16][17][18][19][20] The relative time course of QT prolonging drugs effect on these new biomarkers has been so far poorly evaluated.…”

Assessment of repolarization abnormalities in baseline electrocardiograms of patients with myocarditis

“…Another well-investigated index of transmural dispersion of repolarization is TpTe, which was shown to be helpful for predicting the risk for lifethreatening ventricular arrhythmias (21). Furthermore, previous studies reported that prolonged TpTe was associated with ventricular arrhythmia and sudden cardiac death in patients with hypertrophic cardiomyopathy (22), end-stage renal failure (23), inducible ventricular tachycardia (24), recent MI (25), long-QT syndrome (26), operated tetralogy of Fallot (27), and Brugada syndrome (28). TpTe/QT and TpTe/QTC, relatively novel markers for repolarization abnormalities, are not affected by heart rate and body mass in contrast to TpTe (29).…”

Pharmacological Enhancement of Cardiac Gap Junction Coupling Prevents Arrhythmias in Canine LQT2 Model

“…Increased transmural dispersion of repolarization (TDR) is well acknowledged to underlie the genesis of TdP in LQTS (Shimizu et al 2000;Viitasalo et al 2002;Lankipalli et al 2005;Liu et al 2005). The present study showed that gap junction enhancer AAP10 is capable of preventing augmentation of TDR and suppressing TdP in a canine LQT2 model, possibly through preventing dephosphorylation of Cx43.…”

“…Previous studies have demonstrated that amplified transmural dispersion of repolarization (TDR) plays a critical role in the genesis and maintenance of TdP in LQTS (Shimizu et al 2000;Viitasalo et al 2002;Lankipalli et al 2005;Liu et al 2005). In vitro studies have revealed that TDR is a result of significant heterogeneity in the expression of ion channels among different cell types across the ventricular wall (Antzelevitch et al 1991(Antzelevitch et al , 1999.…”