You are in: eMedicine Specialties > Cardiology > Arrhythmias Lown-Ganong-Levine SyndromeArticle Last Updated: Sep 6, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Daniel M Beyerbach, MD, PhD, Consulting Staff, Florida Electrophysiology Associates Coauthor(s): Christopher Cadman, MD, Director of Arrhythmia Service, Assistant Professor, Department of Internal Medicine, Division of Cardiology, University of New Mexico Editors: Justin D Pearlman, MD, PhD, ME, MA, Director of Dartmouth Advanced Imaging Center, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Frank M Sheridan, MD, Cardiology, Providence Everett Medical Center; Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital; Leonard Ganz, MD, Associate Professor of Medicine, Temple University School of Medicine; Cardiac Electrophysiologist, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Cent, West Penn Hospital Author and Editor Disclosure Synonyms and related keywords: Lown-Gangong-Levine syndrome, LGL syndrome, enhanced atrioventricular nodal conduction, accelerated atrioventricular nodal conduction, short PR/normal QRS syndrome, short PR/narrow QRS syndrome INTRODUCTIONSection 2 of 11
  BackgroundThe Lown-Ganong-Levine syndrome (LGL) is usually considered 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. In 1938, Clerc et al 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-His (AH) bundle 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. Criteria for LGL include PR interval less than or equal to 0.12 second (120 ms), normal QRS complex duration, and occurrence of supraventricular tachycardia but not atrial fibrillation or atrial flutter. 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 atrioventricular nodal conduction. The term enhanced atrioventricular nodal conduction (EAVNC) refers to a set of functional criteria which 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. PathophysiologyNo single structural anomaly has been implicated directly as the cause of 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, including the presence of James fibers, Mahaim fibers, Brechenmacher-type fibers, and an anatomically underdeveloped (hypoplastic) or small AV node. James fibers run from the upper portion of the AV node and insert in the lower portion or in the bundle of His. Mahaim fibers may originate in the lower portion of the AV node, the bundle of His, or the bundle branches, and they terminate in the interventricular septum or in a bundle branch. Each of these fibers has been identified histologically. However, none of these anomalous communications has been linked causally to the presence of LGL. 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. In 1983, however, 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. The modern view of LGL is that no convincing evidence suggests that this is a syndrome separate from other known phenomena. LGL was identified as a syndrome prior to the advent of catheter-based electrophysiologic (EP) studies. EP studies have led to several realizations. The short PR interval of LGL likely represents one end of the spectrum of normal PR intervals. Most patients with putative LGL are found at EP study to have another basis for paroxysmal tachycardia. Most have AV nodal reentrant tachycardia. Others have concealed accessory pathways, usually near the septum. Thus, unless further studies demonstrate definitive structural or functional anomalies, the diagnosis of LGL remains a clinical diagnosis of the era before EP study. FrequencyUnited StatesLown 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. InternationalFrequency mirrors that in the United States. Mortality/MorbidityParoxysms 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. 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. CLINICALSection 3 of 11
HistorySymptoms of paroxysmal tachycardia may be elicited. The manifestations of these 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. PhysicalFindings are normal except during tachycardic episodes; cardiovascular examination may then reveal a rapid heart rate. However, absence of this finding does not exclude LGL as a possible diagnosis, as the tachycardia of LGL is paroxysmal. CausesNo 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. DIFFERENTIALSSection 4 of 11
Atrial Tachycardia Atrioventricular Nodal Reentry Tachycardia (AVNRT) Wolff-Parkinson-White Syndrome
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| Drug Name | Metoprolol (Lopressor, Toprol XL) |
|---|---|
| Description | Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG. |
| Adult Dose | 50 mg/d PO qd or divided bid/tid initially and increase at 1-wk intervals prn to total of 200 mg/d if necessary |
| Pediatric Dose | 1-5 mg/kg/24h PO divided bid |
| Contraindications | Documented hypersensitivity; uncompensated CHF; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities |
| Interactions | Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects Sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives may increase toxicity May increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Pregnancy category D in second or third trimester; beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG |
| Drug Name | Atenolol (Tenormin) |
|---|---|
| Description | Selectively blocks beta1-receptors with little or no effect on beta2 types. |
| Adult Dose | 50 mg PO qd; increase to 100 mg/d if necessary |
| Pediatric Dose | 1-2 mg/kg/dose PO qd |
| Contraindications | Documented hypersensitivity; CHF; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without pacemaker) |
| Interactions | Aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during IV, carefully monitor BP, heart rate, and ECG |
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.
| Drug Name | Verapamil (Calan, Covera, Isoptin) |
|---|---|
| Description | 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. |
| Adult Dose | 80-120 mg PO tid or 120-360 mg SR formulation; alternatively, 5-10 mg IV followed by second dose 15-30 min later if PSVT does not respond satisfactorily to initial dose |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic) |
| Interactions | May increase carbamazepine, digoxin, and cyclosporine levels; amiodarone can cause bradycardia and decrease in cardiac output; beta-blockers may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Hepatocellular injury may occur; transient elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have occurred (elevations have been transient and may disappear with continued treatment); monitor liver functions periodically |
| Drug Name | Diltiazem (Cardizem) |
|---|---|
| Description | During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. |
| Adult Dose | 30-90 mg PO tid, or 120-300 mg PO qd of CD formulation |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic) |
| Interactions | May increase carbamazepine, digoxin, cyclosporine, and theophylline levels; amiodarone may cause bradycardia and decrease in cardiac output; beta-blockers may increase cardiac depression; cimetidine may increase levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur |
Decrease AV nodal conduction, primarily by increasing vagal tone.
| Drug Name | Digoxin (Lanoxin) |
|---|---|
| Description | 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. |
| Adult Dose | 0.125-0.375 mg PO qd |
| Pediatric Dose | 5-10 years: 20-35 mcg/kg loading dose PO >10 years: 10-15 mcg/kg loading dose PO Maintenance dose: 25-35% of PO loading dose administered qd |
| Contraindications | Documented hypersensitivity; beriberi heart disease; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; carotid sinus syndrome |
| Interactions | Alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil may increase levels Aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid may decrease levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Hypokalemia may reduce positive inotropic effect; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients with incomplete AV block may progress to complete block when treated with digoxin; use caution in hypothyroidism, hypoxia, and acute myocarditis |
| Media file 1: ECG demonstrating short PR interval of approximately 100 ms. | |
 | View Full Size Image | Media type: ECG |
| Media file 2: 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. | |
 | View Full Size Image | Media type: ECG |
Lown-Ganong-Levine Syndrome excerpt
Article Last Updated: Sep 6, 2006
