The Lown‐Ganong‐Levine Syndrome

Overexpression of SCN5A in mouse heart mimics human syndrome of enhanced atrioventricular nodal conduction

“…In a study of a group of patients with LGL syndrome, the distinctive electrophysiological features of enhanced fast A-H pathway conduction were described as (1) a short A-H interval during sinus rhythm and during atrial pacing, (2) a reduced A-H increment in response to increasing the rate of atrial pacing, (3) a short Wenckebach CL, and (4) a short A-H functional refractory period. 10 It was also reported that the calcium channel-blocking agent verapamil had no effect on tachycardia in LGL syndrome. 9 Because these features are all found in mice overexpressing SCN5A, we speculate that the A-V nodal conduction path in patients with EAVNC or LGL may be sodium channel dependent .…”

“…In EAVNC, the P-R interval is shortened and A-V conduction time is decreased. [2][3][4][5][6] Several mechanisms have been proposed to explain short P-R intervals in EAVNC, including a partial bypass of the A-V node, an underdeveloped or anatomically small A-V node, and an anatomically normal A-V node that has rapid conduction properties either intrinsically or as a result of alterations in autonomic tone, [6][7][8][9][10][11][12] but the subject has not been resolved. A transgenic (TG) mouse with cardiacspecific overexpression of SCN5A (which encodes the cardiac sodium channel Na V 1.5) was recently developed and studied by Zhang et al 13 In this mouse model, prominent functional manifestations of overexpression of SCN5A included shortening of the P wave and the P-R interval on the surface electrocardiogram (ECG).…”

Characteristics of Ventriculoatrial Conduction in Patients with Enhanced Atrioventricular Nodal Conduction

“…Discontinuous ventriculoatrial curves were observed in 5 triculoatrial conduction during either incremental ventricular pacing or extrastimulus testing, compared to 1/16 (6%, p = NS) Group II patients. As demonstrated in Figure 2, Group I patients numbered 8, 10, and 18 have discontinuous curves during incremental ventricular pacing.…”

“…Multipolar pacing catheters were then advanced with fluoroscopic guidance to the high lateral right atrium, across the tricuspid valve in the region of the His bundle and to either the right ventricular apex or outflow tract. A multipolar coronary sinus catheter was also used in six subjects (5 Group I, 1 Group II) to determine the sequence of retrograde atrial activation. Intracardiac electrograms were filtered at 30-500 Hz.…”