Lown-Ganong-Levine syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Usman Ali Akbar, M.B.B.S.[3]

Synonyms and keywords: Lown-Ganong-Levine Syndrome, LGL syndrome, Pre-excitation syndromes, Short PR Normal QRS Complex Syndrome, Clerc-Lévy-Cristesco syndrome, Coronary nodal rhythm syndrome, Short PQ interval syndrome, Short P-R syndrome.

Overview

Lown-Ganong-Levine syndrome (LGL) is one of the pre-excitation syndromes that present with EKG findings of the short PR interval, narrow/normal QRS complex, and normal P wave. The presence of accessory bundles fibers such as James fiber leads to the development of abnormal conduction pathways. The LGL pattern was described in 1952 by Bernard Lown, William Francis Ganong, and Samual Levine. Patients present with a history of palpitations, lightheadedness, shortness of breath, and sometimes chest pain. There is an increased risk of tachyarrhythmias and syncope. EKG is the principal modality of investigation for establishing a diagnosis. Usually, antiarrhythmics are given to prevent the development of tachyarrhythmias but recently radiofrequency ablation of the accessory pathway has been the main stray of treatment with a good prognosis.

Historical Perspective

Following is timeline of of LGL syndrome with its discovery and developments of its bypass tracts.

Historical timeline of LGL Syndrome

Year	Description
1938	Clerc, Levy and Critesco in 1938 first reported cases in which there was occurence of frequent paroxysms of tachycardia. The EKG of such patients consist of a short PR interval and normal QRS interval
1946	Burch and Kimball hinted on existence of the atrio-Hisian pathway
1952	The Lown-Ganong-Levine (LGL) pattern was described in 1952 by Bernard Lown, William Francis Ganong, and Samual Levine.
1961,1974	In 1961 and subsequently in 1974 anatomic pathway was identified and reported by James and Brechemacher respectively.

Classification

• LGL syndrome can be classified based on the accessory pathways into the following categories.

Accessory Pathway	Description
James Fibers	They can be present as a normal part of AV node but these fibers have been established as an anatomic reason for LGL syndrome
Brechmacher fibers	These atrio-Hisian tracts are reported to have a frequency of 0.03 % and can be theoratically a cause of LGL syndrome
Intra-nodal bypass tracts	Intra-nodal bypass tracts would allow the conduction of rapid action potential through AV node bypassing the other slow pathways.

Pathophysiology

• The pathophysiology of LGL syndrome is not yet completely understood.
• Multiple theories have been proposed to suggest the mechanism of LGL.
• The current theory supporting the mechanism of LGL is that it may result from numerous underlying causes that involve junctional pathways that partially or wholly bypass the AV node with subsequent normal conduction down the bundle of His.
• The three accessory pathways as discussed in classification has been proposed to be the main triggering factors for the development of LGL.
• Lown-Ganong-Levine pattern may occur include Brechenmacher fibers or intranodal bypass tracts and James Fibers. Brenchmacher fibers account for 0.03% of the patients presenting with LGL.
• The intra-nodal bypass tracts allow the conduction of rapid action potential through AV-node bypassing the other slow pathways.

Differentiating Lown-Ganong-Levine Syndrome from other Diseases

The differential diagnosis for Lown-Ganong-Levine includes

• Supraventricular tachycardia
• Atrial fibrillation or flutter with a rapid ventricular response
• AV nodal reentry tachycardia
• Wolf-Parkinson-White Syndrome

Arrhythmia	Rhythm	Rate	P wave	PR Interval	QRS Complex	Response to Maneuvers	Epidemiology	Co-existing Conditions
Atrial fibrillation (AFib)	Irregularly irregular	On a 10-second 12-lead EKG strip, multiply number of QRS complexes by 6	Absent Fibrillatory waves	Absent	Less than 0.12 seconds, consistent, and normal in morphology in the absence of aberrant conduction	Does not break with adenosine or vagal maneuvers	2.7–6.1 million people in the United States have AFib 2% of people younger than age 65 have AFib, while about 9% of people aged 65 years or older have AFib	Elderly Following bypass surgery Mitral valve disease Hyperthyroidism Diabetes Heart failure Ischemic heart disease Chronic kidney disease Heavy alcohol use Left chamber enlargement
Atrial flutter	Regular or Irregular	75 (4:1 block), 100 (3:1 block) and 150 (2:1 block) beats per minute (bpm), but 150 is more common	Sawtooth pattern of P waves at 250 to 350 bpm Biphasic deflection in V1	Varies depending upon the magnitude of the block, but is short	Less than 0.12 seconds, consistent, and normal in morphology	Conduction may vary in response to drugs and maneuvers dropping the rate from 150 to 100 or to 75 bpm	Incidence: 88 per 100,000 individuals	Elderly Alcohol
Atrioventricular nodal reentry tachycardia (AVNRT)	Regular	140-280 bpm	Slow-Fast AVNRT: Pseudo-S wave in leads II, III, and AVF Pseudo-R' in lead V1. Fast-Slow AVNRT P waves between the QRS and T waves (QRS-P-T complexes) Slow-Slow AVNRT Late P waves after a QRS Often appears as atrial tachycardia. Inverted, superimposed on or buried within the QRS complex (pseudo R prime in V1/pseudo S wave in inferior leads)	Absent (P wave can appear after the QRS complex and before the T wave, and in atypical AVNRT, the P wave can appear just before the QRS complex)	Less than 0.12 seconds, consistent, and normal in morphology in the absence of aberrant conduction QRS alternans may be present	May break with adenosine or vagal maneuvers	60%-70% of all supraventricular tachycardias	Structural heart disease Atrial tachyarrhythmias
Multifocal atrial tachycardia	Irregular	Atrial rate is > 100 beats per minute	Varying morphology from at least three different foci Absence of one dominant atrial pacemaker, can be mistaken for atrial fibrillation if the P waves are of low amplitude	Variable PR intervals, RR intervals, and PP intervals	Less than 0.12 seconds, consistent, and normal in morphology	Does not terminate with adenosine or vagal maneuvers	0.05% to 0.32% of electrocardiograms in general hospital admissions	Elderly Chronic obstructive pulmonary disease (COPD)
Paroxysmal supraventricular tachycardia	Regular	150 and 240 bpm	Absent Hidden in QRS	Absent	Narrow complexes (< 0.12 s)	Breaks with vagal maneuvers, adenosine, diving reflex, oculocardiac reflex	Prevalence: 0.023 per 100,000	Alcohol Caffeine Nicotine Psychological stress Wolff-Parkinson-White syndrome
Premature atrial contractrions (PAC)	Regular except when disturbed by premature beat(s)	80-120 bpm	Upright	> 0.12 seconds May be shorter than that in normal sinus rhythm (NSR) if the origin of PAC is located closer to the AV node Ashman’s Phenomenon: PAC displaying a right bundle branch block pattern	Usually narrow (< 0.12 s)	Breaks with vagal maneuvers, adenosine, diving reflex, oculocardiac reflex		Infants Cardiomyopathy Myocarditis Elderly Coronary artery disease Stroke Increased atrial natriuretic peptide (ANP) Hypercholesterolemia
Wolff-Parkinson-White Syndrome	Regular	Atrial rate is nearly 300 bpm and ventricular rate is at 150 bpm	With orthodromic conduction due to a bypass tract, the P wave generally follows the QRS complex, whereas in AVNRT, the P wave is generally buried in the QRS complex.	Less than 0.12 seconds	A delta wave and evidence of ventricular pre-excitation if there is conduction to the ventricle via ante-grade conduction down an accessory pathway A delta wave and pre-excitation may not be present because bypass tracts do not conduct ante-grade.	May break in response to procainamide, adenosine, vagal maneuvers	Worldwide prevalence of WPW syndrome is 100 - 300 per 100,000	Ebstein's anomaly Mitral valve prolapse: This cardiac disorder, if present, is associated with left-sided accessory pathways. Hypertrophic cardiomyopathy: This disorder is associated with familial/inherited form of WPW syndrome. Hypokalemic periodic paralysis Pompe disease Tuberous sclerosis
Ventricular fibrillation (VF)	Irregular	150 to 500 bpm	Absent	Absent	Absent (R on T phenomenon in the setting of ischemia)	Does not break in response to procainamide, adenosine, vagal maneuvers	3-12% cases of acute myocardial infarction (AMI) Out of 356,500 out of hospital cardiac arrests, 23% have VF as initial rhythm	Myocardial ischemia / infarction Cardiomyopathy Channelopathies e.g. Long QT (acquired / congenital) Electrolyte abnormalities (hypokalemia/hyperkalemia, hypomagnesemia) Aortic stenosis Aortic dissection Myocarditis Cardiac tamponade Blunt trauma (Commotio Cordis) Sepsis Hypothermia Pneumothorax Seizures Stroke
Ventricular tachycardia	Regular	> 100 bpm (150-200 bpm common)	Absent	Absent Initial R wave in V1, initial r > 40 ms in V1/V2, notched S in V1, initial R in aVR, lead II R wave peak time ≥50 ms, no RS in V1-V6, and atrioventricular dissociation	Wide complex, QRS duration > 120 milliseconds	Does not break in response to procainamide, adenosine, vagal maneuvers	5-10% of patients presenting with AMI	Coronary artery disease Aortic stenosis Cardiomyopathy Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia) Inherited channelopathies (e.g., long-QT syndrome) Catecholaminergic polymorphic ventricular tachycardia Arrhythmogenic right ventricular dysplasia Myocardial infarction Torsades de pointes is a form of polymorphic VT that is often associated with a prolonged QT interval

Epidemiology and Demographics

• The Lown-Ganong-Levine pattern does not show an increased incidence in one particular sex or ethnic background.
• In a retrospective study conducted by Bernard Lown, William Francis Ganong, and Samual Levine 200 electrocardiograms (EKG) of 13500 patients showed EKG findings with the prevalence of just over 1%.

Age

• There is currently insufficient data regarding age predilection of LGL syndrome.

Gender

• There is currently insufficient data regarding gender predilection of LGL syndrome. However, Lown in 1952 reported 70.9% of the 34 cases in women.

Race

• There is currently insufficient data regarding race predilection of LGL syndrome.

Risk Factors

• The data regarding the risk factors predisposing to LGL syndrome is insufficient. However, the following conditions or factors may lead to various pre-excitation syndromes.
  • Presence of accessory bypass tracts
  • High risk population for sudden cardiac death in Pre-excitation syndromes include
    • Policemen
    • Athletes
    • Firemen
    • Pilots
    • Steelworkers

Natural History, Complications and Prognosis

Natural History

• LGL syndrome can be asymptomatic or can present with palpitations, lightheadedness, shortness of breath, and syncope. In the case of congenital heart disease or genetic anomaly, it can also present as paroxysms of tachycardia or chest pain.

Complications

• There is an increased risk of developing tachyarrhythmias.

• Certain medications such as sympathomimetics should be used with caution in the patients of LGL syndrome. Digitalis does not have any effect in LGL syndrome but it can slow conduction via the AV-node. This can prevent AVRT in these patients.
• Beta-blockers do not affect the accessory pathway directly but can slow conduction through the AV node similar to digitalis.

Prognosis

There is an overall good prognosis in patients with LGL syndrome. Patients are usually asymptomatic but some can develop certain clinical features such as palpitations, shortness of breath, and occasional episodes of atrial fibrillation, atrial flutter, AVRT, and other tachyarrhythmias. They can also lead to the development of ventricular arrhythmias in rare cases.

Diagnosis

Diagnostic Criteria

• Characteristic ECG findings of LGL syndrome are
  • Short PR interval (<120ms)
  • Normal P wave axis
  • Normal/narrow QRS morphology in the presence of paroxysmal tachyarrhythmia.

Lown-Ganong-Levine syndrome ECG features. [1]

History and Symptoms

• LGL syndrome is usually asymptomatic.
• Symptoms of LGL syndrome overlap with the pre-excitation syndrome and may include the following:

• Palpitations
• Dizziness
• Lightheadedness
• Shortness of breath
• Racing heart
• Syncope
• Chest pain or tachycardia {in case of an underlying cardiac structural defect)

Physical Examination

• Patients with LGL syndrome usually appear normal.
• Physical examination findings are limited in LGL syndrome.
• During cardiac auscultation or palpation of peripheral pulses, there can be irregular rhythm.

Laboratory Findings

• There are no specific laboratory findings associated with LGL syndrome.

Imaging Findings

ECG

• The diagnosis of LGL syndrome can be made by the use of resting EKG. EKG findings usually show:
  • Short PR interval (<120ms)
  • Normal P wave axis
  • Normal/narrow QRS morphology in the presence of paroxysmal tachyarrhythmia.

ECG showing LGL syndrome with short PR interval, narrow QRS complex, and normal P waves. Source: LITFL

Other Diagnostic Studies

• Holter monitors or implantable loop recorders may provide insight to the underlying conductions abnormalities.

Treatment

Medical Therapy

• The mainstay of therapy for LGL syndrome is the use of antiarrhythmic medications to prevent tachyarrhythmias.
• Medications such as digitalis, beta-blockers, calcium channel blockers and Class I and III antiarrhythmic drugs have been used to slow down AV conduction and prevent AVRT and other arrhythmias.
• Drugs like sotalol and amiodarone are under investigations and have promising effect in LGL syndrome but needs further studies.

Surgery

Patients refractory to medical management can be managed by the use of radiofrequency catheter ablation as it has become primary treatment in various pre-excitation syndromes. This can be further implicated by the implantation of a permanent pacemaker.

Prevention

• There are no primary preventive measures available for LGL syndrome.