Electrocardiographic interventricular dispersion of repolarization during autonomic adaptation in LQT1 subtype of long QT syndrome.

OBJECTIVES: In LQT1 subtype of inherited long QT syndrome, repolarization abnormalities originating from defective I(Ks) render patients vulnerable to ventricular arrhythmia during sudden sympathetic activation. Experimental studies show lower I(Ks) density and longer action potential duration in left (LV) than in right (RV) ventricle. We studied interventricular dispersion of repolarization in patients with I(Ks) defect during autonomic tests. DESIGN: We measured interventricular (difference of QT intervals between LV and RV type leads) and transmural electrocardiographic dispersion of repolarization from 25-lead electrocardiograms in nine asymptomatic KCNQ1 mutation carriers (LQT1) and eight controls during rest, Valsalva maneuver, mental stress, sustained handgrip and supine exercise. RESULTS: LQT1 carriers showed increased interventricular dispersion of repolarization (13+/-9 ms vs. 4+/-4 ms, p=0.03) during all tests. Valsalva strain increased the difference between the study groups. In LQT1 carriers, interventricular dispersion of repolarization correlated weakly with electrocardiographic transmural dispersion of repolarization. CONCLUSIONS: Asymptomatic KCNQ1 mutation carriers exhibit increased and by abrupt sympathetic activation augmented interventricular difference in electrocardiographic repolarization times. Interventricular and transmural repolarization dispersion behave similarly in patients with I(Ks) defect.

Ventricular repolarization and heart rate responses during cardiovascular autonomic function testing in LQT1 subtype of long QT syndrome.

BACKGROUND: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients. METHODS: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat-to-beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise. RESULTS: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals--a QT overshoot--during the recovery phases. The number of tests with a QT overshoot was 2.4 +/- 1.7 in LQT1 patients and 0.8 +/- 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups. CONCLUSIONS: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.