Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
Status:
Completed
Trial end date:
2008-12-01
Target enrollment:
Participant gender:
Summary
Background. In congenital long QT syndrome type 1 (LQT1), episodes of ventricular tachycardia
are usually triggered by exercise and can be prevented in most patients by beta-blocker
therapy. In addition, LQT1 associated with a normal resting QT interval can be unmasked by
the abnormal QT response to exercise testing (failure of the QT interval to shorten
normally). Preliminary data from our laboratory show that the exercise QT intervals of
patients with LQT1 are partially normalized by beta-blocker therapy. It is still currently
not known if beta-blockers modify the QT/heart rate relationship (a primary effect on
repolarization) or if the "normalizing" effect is due to the inability of subjects on
beta-blockers to attain sufficiently high workloads (due to reduced heart rate) for
prolongation to occur. Moreover, the physiologic response of the exercise QT interval to
beta-blockers in healthy control subjects is not known.
Objective. The objective of this study is to define the impact of beta-blocker therapy on the
QT response to exercise and recovery in normal subjects.
Methods. Approximately 36 healthy adult subjects age-matched to previously studied LQT1
subjects will undergo 1) screening history, 2) two weeks of beta-blocker therapy ending in an
exercise test, and 3) two weeks of placebo therapy ending in an exercise test. Beta blocker
and placebo will be given in random order in a double-blind fashion. The QT response to
exercise and recovery will be compared between drug-free and beta-blocker-treated states.
These data will be compared to those previously collected for LQT1 subjects.
Implications. These results will provide new information about the effect of beta-blocker
therapy on repolarization parameters in normal subjects, and will provide a context in which
to interpret the previous findings that beta-blocker administration modifies the QT response
to exercise in LQT1 subjects.