Navigational error in the heart leads to premature ventricular excitation

Abstract

In the normal heart, an insulating barrier separates the atria and ventricles. The only way in which electrical impulses can cross this barrier is via the atrioventricular (AV) node, which delays impulse conduction to ensure the forward flow of the blood. However, in some individuals, additional muscular bundles (accessory pathways) allow rapid conduction of electrical impulses from the atria to the ventricles, resulting in premature ventricular excitation and contraction. In this issue of the JCI, two independent research groups demonstrate that erroneous development of the embryonic AV canal, which performs a similar function to that of the adult AV node, is a novel mechanism by which accessory pathways can form.

Figure 1. Cardiac conduction in normal, Notch-inhibited, Notch1-activated, and Tbx2-deficient mice.

(A) In normal hearts, the electric impulses initiated by pacemaker cells in the sinoatrial (SA) node propagate through the atrial myocardium and trigger its contraction. At the AV node, the impulses are delayed for a period to facilitate alternating contraction of the atrial and ventricular myocardium. After the AV delay, the electrical impulses rapidly travel to the ventricular myocardium via the His-Purkinje system and stimulate the ventricular myocardium. (B) In Notch-inhibited hearts, the AV node is hypoplastic, and the PR interval on the ECG is shortened due to disruption of the AV nodal delay. (C) In Notch1-activated and (D) Tbx2-deficient hearts, accessory pathways are formed as a result of malformation of the AV canal myocardium. The accessory pathways are commonly right-sided in Notch1-activated mice and left-sided in Tbx2-deficient mice. Because of faster conduction through the accessory pathways than through the AV node, the ventricular myocardium is prematurely stimulated (preexcitation). The ECG shows a short PR interval, a slurred upstroke (“delta wave”) of the QRS complex, and a widened QRS complex.