- Author: Daniel M Beyerbach, MD, PhD; Chief Editor: Jeffrey N Rottman, MD more...
The Lown-Ganong-Levine syndrome (LGL) is a clinical syndrome consisting of paroxysms of tachycardia and electrocardiogram (ECG) findings of a short PR interval and normal QRS duration. LGL is usually categorized in a class of preexcitation syndromes that includes the Wolff-Parkinson-White syndrome (WPW), LGL, and Mahaim-type preexcitation. Investigations into WPW have revealed that an accessory pathway for conduction, called a bundle of Kent, from the atria to the ventricles underlies the preexcitation observed in patients with WPW. Less is known regarding the structural anomalies underlying LGL. Theories proposed to explain LGL have centered around the possible existence of intranodal or paranodal fibers that bypass all or part of the atrioventricular (AV) node.
Historically, some authors have referred to patients with a short PR interval and normal QRS duration as having LGL. However, this practice has been largely abandoned as more evidence has accumulated demonstrating that such patients without a history of tachycardia likely fall into a class of normal variants. Patients with an isolated finding of short PR interval may be characterized as having accelerated AV nodal conduction.
In 1938, Clerc, Levy, and Critesco first described the occurrence of frequent paroxysms of tachycardia in patients with a short PR interval and normal QRS duration. This syndrome was again described in 1952 by Lown, Ganong, and Levine, whose names form the eponym now used to describe it. In 1946, Burch and Kimball proposed that an atrio-Hisian (AH) pathway might explain the findings of the syndrome, although no such pathway had yet been identified anatomically. In 1961, James described fibers that originate in the low atrium and terminate low in the AV node. Brechenmacher et al reported anatomic findings of an AH bundle in 1974. Subsequent investigations into the origin of LGL have largely involved invasive electrophysiologic studies that have sought to identify structural and functional anomalies that might explain the findings of LGL.[7, 8]
Criteria for LGL include a PR interval less than or equal to 0.12 second (120 ms), normal QRS complex duration of less than 120 ms, and occurrence of a clinical tachycardia.[3, 9, 10]
The term enhanced atrioventricular nodal conduction (EAVNC) refers to a set of functional criteria that includes an AH interval less than or equal to 60 ms, 1-to-1 AV nodal conduction at rates as high as 200 beats per minute, and an abnormally small increase in AH interval as atrial pacing rate is increased.
EAVNC represents a functional characterization of the AV node, whereas LGL refers to a syndrome of supraventricular tachycardia in association with a short PR interval. The short PR interval in LGL may be related to the presence of EAVNC. LGL and EAVNC may coexist, or either may exist alone in a given patient.
No environmental factors that contribute to occurrence of LGL have been identified. Some evidence suggests that both WPW and LGL may be hereditary in certain families.
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. 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,[12, 13, 14] 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.[15, 16]
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,[17, 18] including the presence of James fibers, Mahaim fibers, Brechenmacher-type fibers, and an anatomically underdeveloped (hypoplastic) or small AV node.[15, 22]
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. 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. 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.
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. 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.
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.[23, 26]
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. 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.
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.
United States and International data
Lown and associates described tachyarrhythmias in 17% of patients with a short PR interval. Some 2-4% of the adult population has a PR interval less than or equal to 0.12 second. Taken together, these data provide an estimate of the frequency of LGL as 0.5% of the adult population.
The international frequency mirrors that in the United States.
Sex- and age-related demographics
In their 1952 manuscript, Lown, Ganong, and Levine reported 70.9% of their 34 cases to have occurred in women.
The average age of onset of tachycardia in LGL is 33.5 years.
Regarding prognosis, no studies have shown an increased risk of sudden death or decreased survival for patients meeting criteria for diagnosis of LGL.
Complications vary by the underlying condition.
Paroxysms of tachycardia represent the primary morbidity of LGL. Few data are available regarding the frequency of these paroxysms. Data regarding mortality from LGL are scant. In their original report, Lown, Ganong, and Levine reported 6 patients with paroxysmal atrial fibrillation, 2 of whom suffered sudden cardiac death. Numbers in published studies are too small to estimate mortality rate with significant accuracy or confidence. In the absence of significant structural heart disease, the mortality rate appears to be very low.
LGL is an outdated clinical diagnosis with no known unique underlying anatomic correlate. No specific risks are conferred with the diagnosis.
Advise patients who have experienced syncope to not drive or operate vehicles of public transport for 6 months after the occurrence of the most recent episode of syncope, or until the cause of syncope has been identified and adequately treated. Within the United States, laws regarding restrictions on driving and operating vehicles of public transport after an episode of syncope vary by state.
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