Lown-Ganong-Levine Syndrome 

Updated: Jan 09, 2017
Author: Daniel M Beyerbach, MD, PhD; Chief Editor: Jeffrey N Rottman, MD 

Overview

Background

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.[1] 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.[2] This syndrome was again described in 1952 by Lown, Ganong, and Levine, whose names form the eponym now used to describe it.[3] 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.[4] In 1961, James described fibers that originate in the low atrium and terminate low in the AV node.[5] Brechenmacher et al reported anatomic findings of an AH bundle in 1974.[6] 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.[11]

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.

Pathophysiology

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,[19] Mahaim fibers,[20] Brechenmacher-type fibers,[6] and an anatomically underdeveloped (hypoplastic)[21] 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.[5] 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.[23] 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.[24]

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.[11] 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.[25]

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.[24] 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.[27]

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.

Epidemiology

United States and International data

Lown and associates described tachyarrhythmias in 17% of patients with a short PR interval.[3] Some 2-4% of the adult population has a PR interval less than or equal to 0.12 second.[23] 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.[3]

The average age of onset of tachycardia in LGL is 33.5 years.[3]

Prognosis

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.[3]  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.

Patient Education

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.

For patient education resources, visit see Heart Health Center as well as Supraventricular Tachycardia.

 

Presentation

History

Symptoms of paroxysmal tachycardia must be elicited. Manifestations of such paroxysms include palpitations, lightheadedness, and shortness of breath. In cases of underlying structural heart disease or coronary artery disease, episodes of tachycardia may induce cardiac stress and produce symptoms of chest pain or possibly of hypotension or other hemodynamic instability. At higher ventricular rates, syncope may occur, particularly if ventricular tachycardia or ventricular fibrillation are initiated.

Physical Examination

An accentuated first heart sound of mitral valve closure may be present in 87% of cases.[3]  During paroxysms of tachycardia, cardiovascular examination may reveal a rapid heart rate. Absence of a rapid heart rate does not exclude LGL as a possible diagnosis, as the tachycardia of LGL is paroxysmal.

 

DDx

Diagnostic Considerations

Other conditions to be considered in patients with suspected Lown-Ganong-Levine syndrome include the following:

  • Sinoatrial reentrant tachycardia

  • Mahaim-type preexcitation

  • Sinus tachycardia

  • Atypical AV nodal reentrant tachycardia

  • Persistent form of juvenile reentrant tachycardia

Differential Diagnoses

 

Workup

Laboratory Studies

Workup is directed at determining the cause of tachycardia. Lown-Ganong-Levine syndrome (LGL) is an outdated diagnosis, and as such no workup is directed at making this diagnosis. However, identification of a short PR interval during sinus rhythm in a patient with paroxysmal supraventricular tachycardia (PSVT) should raise suspicion of a possible underlying bypass tract (ie, Wolff-Parkinson-White syndrome [WPW]). In the case of isolated short PR interval with no history of tachycardia or symptoms suggestive of paroxysms of tachycardia, no further workup is indicated.

Patients may present in an acute episode of tachycardia or with a history of symptoms suggestive of paroxysms of tachycardia.

In the acute setting, institute a standard workup for tachycardia, including an ECG to document the rhythm, serum electrolytes, calcium, magnesium levels, and serum thyroid-stimulating hormone (TSH) levels.

For a history suggestive of recurrent paroxysms of tachycardia, a Holter monitor or event recorder may prove useful for documenting the rhythm during acute symptomatic episodes. Less commonly, particularly when paroxysms of tachycardia are more rare, an implantable loop recorder may prove helpful.

In the case of shortness of breath, posteroanterior and lateral chest films are indicated.

Other Tests

To meet criteria for LGL, the 12-lead ECG taken during a period of normal sinus rhythm must demonstrate a PR interval less than or equal to 0.12 second and a normal QRS upstroke and duration, as in the image below.

ECG demonstrating a short PR interval of approxima ECG demonstrating a short PR interval of approximately 100 ms and normal QRS.

One of the most useful diagnostic tools is a 12-lead ECG recorded during a paroxysm of tachycardia. Such documentation satisfies the LGL criterion of tachycardia.

A delta wave on the QRS complex precludes the diagnosis of LGL, because one of the criteria for LGL is a normal QRS complex. A delta wave suggests the presence of an accessory pathway; occurrence of supraventricular tachycardia in the presence of an accessory pathway suggests WPW, another preexcitation syndrome, as in the image below.

Noninvasive mapping of cardiac arrhythmias is also possible with a 252-lead ECG and computed-tomography scan–based three-dimensional electroimaging.[28]

ECG demonstrating ventricular preexcitation. A del ECG demonstrating ventricular preexcitation. A delta wave, which corresponds to initial myocardial depolarization via a bypass tract, appears at the beginning of each QRS complex.

 

Procedures

If tachycardia is present, diagnostic workup to determine the cause may include Valsalva maneuvers.

If the blood pressure is stable, the patient has no angina, is not presyncopal, and no carotid bruits are present, carotid massage may provide diagnostic information. Ideally, carotid massage should be performed during continuous 12-lead rhythm strip monitoring. The result of carotid massage may be termination of the tachycardia, or transient AV block that may provide a ventricular pause long enough to reveal an underlying atrial arrhythmia.

If these maneuvers fail to terminate the tachycardia, a trial of intravenous adenosine administration, again with simultaneous rhythm strip recording, may reveal the rhythm. Adenosine should not be administered if there is any indication of pre-excitation on the surface ECG.

In cases of recurrent tachycardia, an invasive electrophysiology study is warranted. This is particularly true when symptoms become intolerable, medical therapy is failing to prevent episodes of tachycardia, or when a ventricular arrhythmia is suspected.

 

Treatment

Medical Care

Because Lown-Ganong-Levine syndrome (LGL) is an outdated diagnosis, no specific therapy is indicated. In the acute setting of tachycardia, the goals of medical care include identifying the cause of tachycardia and, in symptomatic cases, controlling the ventricular rate.[29] Treatment should be based on the cause of tachycardia. As with any tachycardia, hospitalization is warranted in cases of hemodynamic instability.

To summarize:

  • Admit patients in unstable condition to telemetry
  • Institute pharmacologic therapy as dictated by symptoms and documented tachycardia
  • Obtain a cardiology consultation (see Consultations)
  • Consider exercise treadmill testing if tachycardia is induced by exercise

In the outpatient setting, empiric therapies for recurrent paroxysmal supraventricular tachycardia (PSVT) may be instituted. These therapies may include beta-blockers, calcium channel blockers, and digoxin. A full discussion of these therapies lies outside the scope of this article (see Paroxysmal Supraventricular Tachycardia).

Further outpatient care includes the following:

  • If no arrhythmia is documented on ECG or telemetry, and symptoms occur on a daily basis, consider Holter monitor with diary to document cardiac rhythm during symptomatic episodes.
  • If no arrhythmia is documented on ECG or telemetry, and symptoms occur less frequently than daily, consider an event recorder to document cardiac rhythm during symptomatic episodes.
  • If patient is in stable condition and does not require hospitalization, and if no tachyarrhythmia has been documented but symptoms are induced by exercise, consider outpatient exercise treadmill testing.
  • If symptoms persist, but no tachyarrhythmia can be documented by any of these methods, consider referral to an electrophysiologist for an outpatient EP study.

Surgical Care

Rare patients for whom the criteria of LGL are met may have no inducibility of tachyarrhythmias by EP study. Rarely, medical therapy fails in these patients, who continue to have recurrent, intolerable symptoms. In such extreme cases, pacemaker implantation, followed by radiofrequency (RF) ablation of the AV node or bundle of His may be considered.

Activity

Patients who have experienced an episode of syncope should be counseled to not drive or operate vehicles of public transport for 6 months from the time of the most recent episode of syncope, or until the cause of syncope has been identified and adequately treated.

Consultations

An immediate cardiology consultation is warranted if the patient has presyncope, syncope, hypotension with tachycardia, angina, or other evidence of instability at the time of evaluation.

Conditions appropriate for consideration of RF catheter ablation and referral to an electrophysiologist include the following:

  • Failure of pharmacologic therapy to control symptoms
  • Recurrence of any signs of hemodynamic instability or of intolerable symptoms under medical management
  • Patient's desire to avoid daily medication
  • Intolerable adverse effects of medication
 

Medication

Medication Summary

No medication therapy is specific to LGL. The goals of therapy are to identify the cause of tachycardia and to treat this cause appropriately.

Beta-blockers

Class Summary

Inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation and slow AV nodal conduction.

Metoprolol (Lopressor, Toprol XL)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG.

Atenolol (Tenormin)

Selectively blocks beta1-receptors with little or no effect on beta2 types.

Calcium channel blockers (nondihydropyridine)

Class Summary

In specialized conducting and automatic cells in the heart, calcium is involved in the generation of the action potential. Calcium channel blockers inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity.

Verapamil (Calan, Covera, Isoptin)

Can diminish PVCs associated with perfusion therapy and decrease risk of ventricular fibrillation and ventricular tachycardia. By interrupting reentry at AV node, can restore normal sinus rhythm in patients with PSVT.

Diltiazem (Cardizem)

During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.

Cardiac glycosides

Class Summary

Decrease AV nodal conduction, primarily by increasing vagal tone.

Digoxin (Lanoxin)

Cardiac glycoside with direct inotropic effects in addition to indirect effects on cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.