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Effect of change in posture and exercise on repolarization in patients with long QT syndrome with HERG channel
Bruce D Walker1, Andrew D Krahn, George J Klein
1Division of Cardiology and the Blackburn Genetics Laboratory, Roberts Research Institute, University of Western Ontario, London.
Introduction:
Congenital long QT syndrome (LQTS) is characterized by syncope and cardiac arrest, often in association with exercise or sudden arousal. It was hypothesized that patients with LQTS with human ether-a-go-go-related gene (HERG) mutations (LQT2) have an abnormal QT adaptation to changes in heart rate induced by exercise and that such abnormalities may be ameliorated by treatment with beta-adrenoreceptor blockers.
Methods And Results:
Sixteen LQT2 patients (26+/-15 years of age, 10 female) and 27 healthy volunteers (34+/-16 years of age, 17 female) had 12-lead electrocardiograms recorded while supine, immediately on standing and continuously during treadmill exercise testing. Changing from supine to standing alone caused a significant increase in QTc in the LQT2 group compared with in control subjects (change in QTc of 48+/-38 ms versus 21+/-29 ms, respectively, P=0.02). While QT and QTc remained longer in LQT2 patients at peak exercise, QT shortening (QT peak minus QT supine) was greater in LQT2 patients than in control subjects (-158+/-32 ms versus -117+/-32 ms, P<0.001). Beta-blocker treatment had no effect on the resting QTc, but it normalized the increase in QTc on standing (45+/-29 ms before beta-blocker versus 23+/-32 ms after beta-blocker, P=0.03). During exercise, QT shortening and peak QTc were not affected by beta-blocker treatment.
Conclusions:
Abnormal repolarization in LQT2 is accentuated by a change in posture and exercise. Beta-blockers normalize the QTc prolongation elicited by such manoeuvres.
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