β-blockers protect against dispersion of repolarization during exercise in congenital long-QT syndrome type 1

Abstract

Introduction: β-Blocker therapy reduces syncope and sudden death in long-QT syndrome type 1 (LQT1), but the mechanism of protection is incompletely understood. This study tested the hypothesis that β-blockade reduces QT prolongation and dispersion of repolarization, measured as the T peak-to-end interval (T(pe) ), during exercise and recovery in LQT1 patients.

Methods and results: QT and T(pe) were measured in 10 LQT1 patients (33 ± 13 years) and 35 normal subjects (32 ± 12 years) during exercise tests on and off β-blockade. In LQT1 patients, β-blockade reduced QT (391 ± 25 milliseconds vs 375 ± 26 milliseconds, P = 0.04 during exercise; 419 ± 41 milliseconds vs 391 ± 39 milliseconds, P = 0.02 during recovery) and markedly reduced T(pe) (91 ± 26 milliseconds vs 67 ± 19 milliseconds, P = 0.03 during exercise; 103 ± 26 milliseconds vs 78 ± 11 milliseconds, P = 0.02 during recovery). In contrast, in normal subjects, β-blockade had no effect on QT (320 ± 17 milliseconds vs 317 ± 16 milliseconds, P = 0.29 during exercise; 317 ± 13 milliseconds vs 315 ± 14 milliseconds, P = 0.15 during recovery) and mildly reduced T(pe) (69 ± 13 milliseconds vs 61 ± 11 milliseconds, P = 0.01 during exercise; 77 ± 19 milliseconds vs. 68 ± 14 milliseconds, P < 0.001 during recovery).

Conclusion: In LQT1 patients, β-blockers reduced QT and T(pe) during exercise and recovery, supporting the theory that β-blocker therapy protects LQT1 patients by reducing dispersion of repolarization during exercise and recovery.

Figure 1

Example of T_pe measurement, in which a best-fit tangent line was drawn to the isoelectric line, and T_pe interval was defined by drawing a vertical line from the T_peak to the isoelectric line.

Figure 2

QT at matched HR (106 ± 3 bpm) during exercise in normal subjects = 320 ± 17 msec before BB and 317 ± 16 msec after BB; p = 0.29. QT at matched HR (106 ± 4 bpm) in LQT1 subjects = 391 ± 25 msec before BB and 375 ± 26 msec after BB; p = 0.04.

Figure 3

QT at matched HR (105 ± 2 bpm) during recovery in normal subjects = 317 ± 13 msec before BB and 315 ± 14 msec after BB; p = 0.15. QT at matched HR (106 ± 5 bpm) = 419 ± 41 msec before BB and 391 ± 39 msec after BB; p = 0.02.

Figure 4

QT at matched HR during exercise and recovery before and after BB. Solid dots represent individual LQT1 subjects and open dots represent mean values for 35 normal subjects.

Figure 5

T_pe at rest, peak exercise, and 1 minute into recovery in normal subjects and LQT1 subjects on and off BB. *p < 0.05 for comparison of off vs. on BB between paired samples of normal or LQT1 subjects.