Effects of β-blockers on ventricular repolarization documented by 24-hour electrocardiography in long QT syndrome type 2

Funding Information: Funding Sources: Dr Koponen was supported by a research grant from the Aarne Koskelo Foundation. Publisher Copyright: © 2022 Heart Rhythm Society Background: Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are prolonged repolarization, increased dispersion of repolarization, and early afterdepolarizations, which are clinically estimated as QT interval, T-wave peak to T-wave end (TPE) interval, and T2/T1-wave amplitude ratio, respectively. In experimental LQTS type 2 (LQT2) models, β-blockers decrease dispersion of repolarization and prevent early afterdepolarizations. In clinical studies in patients with LQT2, β-blockers are more effective against exercise-induced than arousal-induced cardiac events. Objectives: The aim of the study was to investigate the effects of β-blocker therapy on repolarization properties in LQT2. Methods: QT and TPE intervals and maximal T2/T1-wave amplitude ratios recorded by 24-hour electrocardiograms before and during β-blocker therapy were evaluated in 25 patients with LQT2. Results: β-Blocker therapy decreased the maximal T2/T1-wave amplitude ratio from 2.9 ± 1.1 to 1.8 ± 0.7 (P < .001), but did not change the pause-induced T2/T1-wave amplitude ratio. Under medication, abrupt maximal TPE intervals were shorter at heart rates of ≥75 beats/min and maximal QT intervals were shorter at a heart rate of 100 beats/min. Conclusion: β-Blockers stabilize ventricular repolarization in LQT2 by reducing electrocardiographic early afterdepolarizations and by reducing abrupt prolongation of electrocardiographic dispersion of repolarization and ventricular repolarization duration at elevated heart rates. The effect of β-blockers on pause-induced electrocardiographic early afterdepolarizations is weak. The findings provide electrocardiographic explanation for the protective effects of β-blockers against exercise-induced cardiac events in LQT2.