Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome

The purpose of this study was to test the hypothesis that differences in autonomic responses might modify clinical severity in long QT syndrome type 1 (LQT1) patients, those with KCNQ1 mutations and reduced I(Ks), in whom the main arrhythmia trigger is sympathetic activation.

Some long QT syndrome (LQTS) patients experience life-threatening cardiac arrhythmias, whereas others remain asymptomatic throughout life. This clinical heterogeneity is currently unexplained.

In a South African LQT1 founder population segregating KCNQ1-A341V, we correlated major cardiac events to resting heart rate (HR) and to baroreflex sensitivity (BRS) on and off beta-adrenergic blockers (BB).

In 56 mutation carriers (MCs), mean HR was lower among asymptomatic patients (p < 0.05). Among MCs with a QT interval corrected for heart rate

Lower resting HR and "relatively low" BRS are protective factors in KCNQ1-A341V carriers. A plausible underlying mechanism is that blunted autonomic responses prevent rapid HR changes, arrhythmogenic when I(Ks) is reduced. These findings help understanding phenotypic heterogeneity in LQTS and identify a physiological risk modifier, which is probably genetically determined.