Short QT syndrome. Genotype-phenotype correlations

Abstract

The short QT syndrome is a new congenital entity associated with familial atrial fibrillation and/or sudden death or syncope. Three different gain-of-function mutations in genes encoding for cardiac potassium channels (KCNH2, KCNQ1, and KCNJ2) have been identified up to now to cause short QT syndrome. The syndrome is characterized electrocardiographically by a shortened QTc interval less than 300 to 320 milliseconds and a lack of adaptation during increasing heart rates. During programmed electrical stimulation, atrial and ventricular effective refractory periods are shortened, and in a high percentage, ventricular tachyarrhythmias are inducible. Sudden cardiac death occurs in all age groups and even in newborns. Therapy for choice seems to be the implantable cardioverter-defibrillator because of the high incidence of sudden death. However, ICD therapy may be associated with an increased risk of inappropriate therapies for T wave oversensing, which, however, can be resolved by reprogramming ICD detection algorithms. The impact of sotalol, ibutilide, flecainide, and quinidine on QT prolongation has been evaluated. But only quinidine effectively suppressed gain-of-function in IKr, along with prolongation of the QT interval. Furthermore, in patients with a mutation in HERG (SQT1), quinidine rendered ventricular tachyarrhythmias noninducible and restored the QT interval/heart rate relationship toward a reference range. It may serve as an adjunct to ICD therapy or as possible alternative treatment especially for children and newborns.

Fig. 1

This tracing depicts the induction of ventricular fibrillation during invasive electrophysiological stimulation. Three premature stimuli induce ventricular fibrillation (HRA 1/2, HRA 3/4 bipolar electrogram from right atrial electrode, RVA 1/2 and RVA 3/4 bipolar electrogram at right ventricle).

Fig. 2

This tracing depicts the induction of ventricular fibrillation during programed stimulation during the prehospital discharge test after ICD implantation. Ventricular fibrillation could be reproducibly induced by 3 premature stimuli (upper line, ventricular shock electrogram; lower electrogram strip, rate electrogram; ICD markers: S, sensing event; STIM, stimulated complex; F, fibrillation sensing; HV, high-voltage capacitor discharge).

Fig. 3

Stored endocardial electrogram derived from the ICD memory showing an episode of primary ventricular fibrillation in short QT syndrome. The ventricular tachyarrhythmia was initiated by a short coupled premature ventricular beat (VS encircled; coupling interval, 180 milliseconds) (upper electrogram strip, shock electrogram; lower electrogram strip, rate electrogram; ICD markers: FS, fibrillation sensing; FD, fibrillation detection; VS, ventricular sensing).