Diurnal variation of ventricular repolarization in a large family with LQT3-Brugada syndrome characterized by nocturnal sudden death

Abstract

Background: In patients with long-QT syndrome type 3 (LQT3), symptoms occur particularly at rest or during sleep. As to the underlying mechanism, excessive prolongation of the QT interval at slow heart rates probably plays a role.

Objectives: The purpose of the present study was to investigate QT interval prolongation unrelated to heart rate comparing nighttime and daytime in a family with features of both LQT3 and Brugada syndrome.

Methods: The study group consisted of 38 carriers of the mutant gene (SCN5A, 1795insD) and 30 noncarrier family members, who served as controls. Holter monitoring was performed with beat-to-beat QT interval measurement. In addition, in a subset of subjects, an exercise test and a pacing test (carriers only) with measurement of the RT interval were performed.

Results: In carriers, the slope between heart rate and QT interval was significantly steeper during nighttime (0:00 a.m. to 6:00 a.m.) than during daytime (8:00 a.m. to 22:00 p.m.) (regression coefficient -6.18 and -2.80, respectively), (p=0.03),no such effect being observed in the noncarriers. Further, the RT interval was markedly shorter during recovery than during exercise in carriers but not in noncarriers. In contrast, during AAI pacing in the carriers, RT interval shortening along with increasing heart rate was followed by a comparable prolongation of the RT interval along with subsequent decreasing heart rate.

Conclusions: In this large LQT3-Brugada syndrome family, carriers of the mutant gene (SCN5A, 1795insD) are characterized by diurnal variation of ventricular repolarization by exhibiting QT interval prolongation, which is more pronounced during nighttime compared with daytime, even when taking into account differences in heart rate. The autonomic nervous system appears to play a role in mediating this effect. This observation may be of relevance for explaining the high incidence of nocturnal sudden death in this family, but this remains to be proven. In addition, whether our findings also apply to other families with LQT3 is uncertain.