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

作者：Extramiana Fabrice^*; Dubois Remi; Vaglio Martino; Roussel Pierre; Dreyfus Gerard; Badilini Fabio; Leenhardt Antoine; Maison Blanche Pierre

来源：Annals of Noninvasive Electrocardiology, 2010, 15(1): 26-35.

DOI：10.1111/j.1542-474X.2009.00336.x

• ECG
• ventricular repolarization
• sotalol

Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation.
Methods: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 +/- 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave.
Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R(2) = 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms +/- 1.96*SD = 16 ms).
Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26-35

• 出版日期2010-1