The syndrome described by Lown, Ganong, and Levine in 1952 associated the occurrence of tachycardia with presence of a short PR interval and normal QRS. The pathophysiology underlying this syndrome remains unclear. [1] Subsequent investigations have failed to identify a unifying anatomic or functional basis that accounts for both occurrence of tachycardia and presence of a short PR interval. Rather, several mechanisms have been proposed for the coexistence of a short PR interval and normal QRS, [13, 14, 15] while the occurrence of tachycardias has separately been found to be largely based on previously identified conditions, such as AV nodal reentry tachycardia, atrial fibrillation, and ventricular tachycardia. [16, 17]
No single structural anomaly has been implicated directly as the cause of the short PR interval and normal QRS in LGL. Indeed, most authors believe that LGL does not exist as a phenomenon separate from other known conditions. Several structural anomalies have been proposed as the possible basis for LGL, [18, 19] including the presence of James fibers, [20] Mahaim fibers, [21] Brechenmacher-type fibers, [7] and an anatomically underdeveloped (hypoplastic) [22] or small AV node. [16, 23]
James fibers run from the upper portion of the AV node and insert into the lower portion of the AV node, or into the bundle of His. [6] Thus, conduction over James fibers bypasses some of the intrinsic AV nodal delay, which shortens the PR interval; the QRS configuration remains normal, as ventricular activation occurs normally via His-Purkinje system.
Mahaim fibers are muscular bridges, almost exclusively right-sided in occurrence, that may originate in the lower portion of the AV node, the upper portion of the bundle of His, or the bundle branches. Mahaim fibers terminate in the interventricular septum or in a bundle branch.
Brechenmacher described fibers that run from the atrium to the His bundle, bypassing the AV node altogether.
Each of these fibers has been identified histologically. However, none of these anomalous communications has been uniquely linked to the presence of LGL. Moreover, the histologic presence of fibers does not speak to whether these fibers are functional, with conductive properties.
EAVNC has been investigated as a possible functional basis for LGL. [24] The criteria for EAVNC were established arbitrarily on the basis of observations of some patients with what seemed to be abnormally rapid AV nodal conduction times. However, in 1980, Bauernfeind and colleagues described a unimodal distribution of PR intervals in a series of 65 patients with AV nodal reentrant tachycardia. [25]
Further, in 1983 Jackman et al provided convincing evidence that EAVNC does not exist as a phenomenon separate from normal AV nodal physiology, but that AV nodal conduction physiology comprises a spectrum of AH intervals. [12] In their series of 160 consecutive patients, they failed to identify a distinct group of patients with abnormally rapid AV nodal conduction. Rather, they found a broad spectrum of AH intervals in a unimodal, continuous distribution. Importantly, among patients with dual pathways, patients with shorter AH intervals do have a greater likelihood of developing AV nodal reentrant tachycardia. [26]
The modern view of LGL is that no convincing evidence suggests that this is a syndrome separate from other known and independently characterized electrophysiologic phenomena. LGL was identified as a clinical syndrome prior to the advent of catheter-based electrophysiologic (EP) studies. EP studies and histopathologic studies have identified several underlying mechanisms that can account for the presence of a short PR interval and normal QRS. These mechanisms include enhanced AV nodal conduction, several types of fibers that bypass all or part of the AV node, and an anatomically small AV node. Studies incorporating electrophysiologic data have separately identified several types tachycardias that occur in patients with LGL. The most common tachycardias include AV nodal reentry, accessory pathway mediated tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia. [24, 27]
To date, the underlying mechanisms that generate a short PR interval in LGL have not been found to be necessary for the development of the tachycardias identified in patients with LGL. In the case of enhanced AV nodal conduction, the short PR interval reflects anterograde conduction over the fast AV nodal pathway; however, during the most common form of AV nodal reentry, which is the most common tachycardia in patients with LGL, conduction occurs anterograde over the AV nodal slow pathway and retrograde up the AV nodal fast pathway.
Enhanced conduction over the fast pathway is not necessary for existence of the tachycardia (normal fast pathway conduction would suffice). Even the rate of the tachycardia is largely determined by slow pathway conduction, which is independent of the short PR interval mechanism. [25] Similarly, the presence of fibers that bypass all or part of the AV node is not necessary for the occurrence of atrial fibrillation or atrial flutter; functionally, these fibers may facilitate more rapid conduction of atrial arrhythmias to the ventricles.
Mutations in several ion channel genes have been linked to short-QT syndrome, the mechanisms of which are obscure. [28]
In summary, LGL is a clinical diagnosis born of the era before EP study. Many mechanisms have been identified to describe the coexistence of a short PR interval and normal QRS and many tachycardias have been identified in patients with LGL. However, none of the identified short PR interval mechanisms is necessary for the generation of LGL tachycardias.