Congenital long-QT syndromes: a clinical and genetic update from infancy through adulthood

Abstract

Long-QT syndromes (LQTSs) have been described in all ages and are a significant cause of cardiovascular mortality, especially in structurally normal hearts. Abnormalities in transmembrane ion conduction channels and structural proteins produce these clinical syndromes, labeled LQT1-LQT12; however, genotype-positive patients still represent only about 70% of LQTSs. Future research will determine the etiology of the remaining cases, further risk-stratify the known genetic defects, improve current treatment options for these syndromes, and uncover novel therapies.

Figure 1

Surface ECG showing a prolonged QTc of 687. Measurement of the QTc is calculated as the duration of the QT interval, divided by the square root of the preceding RR interval.

Figure 2

Surface ECG rhythm strip showing a QTc of 675 and 2:1 atrioventricular block.

Figure 3

Cartoon diagram of the 12 known LQTS genes and the LQT syndromes associated with mutations in each gene (LQT1-LQT12). The 3 most common (LQT1-3) are in bold. Eggs are color-coded by the functionality of each gene and its respective protein: pink, potassium channel; blue, sodium channel; green, calcium channel; ivory, structural protein.

Figure 4

(A) ICD ventricular intracardiac electrogram and a marker channel. The electrogram begins with sinus rhythm at a ventricular rate of 100 beats per minute with sudden initiation of a polymorphic ventricular rhythm at a rate of approximately 215 beats per minute. The marker channel assigns the electrical deflections as ventricular sensing (VS) and ventricular fibrillation detection (FS). (B) Ventricular intracardiac electrogram recording demonstrating successful ICD shock. The electrogram shows polymorphic ventricular tachycardia with a rate of 300 beats per minute. The marker channel assigns the electrical deflections as ventricular sensing (VS) and refractory (VR). The device discharges (CD) and the rhythm returns to a ventricular rate of approximately 110 beats per minute.