Beta blockers normalize QT hysteresis in long QT syndrome.
OBJECTIVE
This study was performed to evaluate the impact of beta blockers on QT adaptation to heart rate during the exercise and recovery phases of exercise testing in long QT syndrome.


BACKGROUND
Long QT syndrome is characterized by familial syncope and sudden death in the context of sudden heart rate changes. QT hysteresis has been proposed as a phenotypic marker of long QT syndrome, suggesting altered QT adaptation to changes in heart rate.


METHODS
Fourteen patients with long QT syndrome (aged 26 +/- 16 years, 6 male) and 10 healthy volunteers (aged 37 +/- 11 years, 9 male) underwent graded exercise testing with continuous lead II electrocardiographic monitoring. Long QT patients underwent repeat assessment after 1 month of beta blockade. QT intervals at matching heart rates were compared during exercise and recovery to determine the effect of beta blockade on QT hysteresis, defined as the recovery QT peak interval subtracted from the exercise QT peak interval.


RESULTS
In the 14 long QT syndrome patients, beta blockers slowed the resting heart rate without affecting the corrected QT interval (502 +/- 52 ms baseline vs 481 +/- 40 ms beta blocker, P =.17). The increase in heart rate with exercise was similar in the 3 groups (P =.73). Exaggerated hysteresis of the QT interval was seen in the patients with long QT syndrome at baseline compared with controls (46 +/-19 ms vs 19 +/- 11 ms 1 minute into recovery, P =.006). Beta blockers had minimal effect on the QT interval but markedly reduced hysteresis with minimal separation of the exercise and recovery QT/RR curves (25 +/- 35 ms 1 minute into recovery, P =.027). The combined curve separation at all 6 time points analyzed was 165 +/- 95 ms in patients with long QT syndrome at baseline, 40 +/- 131 ms after beta blockade, and 29 +/- 30 ms in control subjects (P =.002). Comparison of the beta blocker effect on hysteresis in the 2 genotypes suggested a greater reduction in hysteresis in the 3 patients with long QT syndrome 1 compared with the 11 patients with long QT syndrome 2.


CONCLUSIONS
Beta blockers reduce QT hysteresis in patients with long QT syndrome to values seen in normal patients. This improved QT adaptation to changes in heart rate may explain the clinical benefit of beta blockers in long QT syndrome.
Krahn
Andrew D
AD
Division of Cardiology, University of Western Ontario, London, Ontario, Canada. akrahn@julian.uwo.ca.
Yee
Raymond
R
Chauhan
Vijay
V
Skanes
Allan C
AC
Wang
Jian
J
Hegele
Robert A
RA
Klein
George J
GJ
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001262:Atenolol / Q000627:therapeutic use; D016022:Case-Control Studies; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009248:Nadolol / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D009248:Nadolol; D001262:Atenolol