Sudden sympathetic activation and electrocardiographic interventricular dispersion of repolarization in type 1 long QT syndrome

Abstract

Patients with type 1 inherited long QT syndrome (LQT1) experience ventricular arrhythmias during sudden sympathetic activation. Experimental studies show smaller IKs density and consequently longer action potential duration in left (LV) than in right (RV) ventricle creating interventricular dispersion of repolarization (IDR). Increased IDR predisposes LV to initiate torsade de pointes. We hypothesized that sudden sympathetic activation may increase electrocardiographic (ECG) IDR in LQT1 patients. We studied 9 asymptomatic carriers of the same C-terminal KCNQ1 mutation (age 41±12) and 8 healthy controls (44±10) by measuring QT intervals from 25 simultaneous ECG leads over anterior thorax at rest and during mental stress, sustained handgrip and Valsalva maneuver. IDR was defined as difference of QT peak intervals between LV and RV type leads, identified according to QRS morphology. LQT1 carriers showed greater IDR than control subjects (13±9 ms vs. 4±4 ms, P=0.03) at baseline. Mental stress and handgrip did not change IDR in the study groups, whereas Valsalva strain augmented IDR in LQT1 carriers but reduced it in controls (Figure). Asymptomatic KCNQ1 mutation carriers exhibit increased IDR. Abrupt autonomic sympathetic activation augments IDR in LQT1 patients whereas during static sympathetic activity IDR remains stable. By abrupt sympathetic activation increased IDR may predispose patients with IKs defect to torsade de pointes.