Effect of change in posture and exercise on repolarization in patients with long QT syndrome with HERG channel mutations.

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.