Pre-Excitation Syndrome

I. What every physician needs to know.

Ventricular pre-excitation is a condition in which some or all of the ventricular muscle of the heart undergoes electrical activation (or depolarization) earlier in relation to atrial events than would be expected had the electrical impulses travelled normally by way of the atrioventricular (AV) conduction system.

Pre-excitation exists when there is an accessory pathway (AP) for electrical conduction between the atria and ventricles. The pathophysiology of pre-excitation occurs when impulses are transmitted across an AP from the atria to the ventricles thus bypassing the AV nodal pathway. The AP consists of normal myocardium and can permit either anterograde or retrograde conduction of electrical activity between the chambers of the heart. The pathway is thought to develop due to incomplete separation of the atria and ventricles during embryogenesis.

There are three types of APs based upon their conduction properties: manifest, concealed, and latent.

Continue Reading

1. Manifest APs conduct more rapidly in antegrade fashion than that of the AV node. This type of conduction causes a delta wave to manifest on the electrocardiogram (ECG).

2. Concealed APs conduct in retrograde fashion only; thus, the pathway is concealed and there is no delta wave present on ECG.

3. Latent APs can conduct antegrade but typically are located quite laterally in the heart making conduction through the AV node more likely given the shorter distance an impulse has to travel to the AV node rather than the longer distance to the AP.

Pre-excitation is also known as ventricular pre-excitation or accessory pathway. Pre-excitation describes the electrical phenomena occurring in the heart and seen on ECG in some cases due to the presence of an AP. When there is an associated tachyarrhythmia due to the presence of an AP or in patients who experience symptoms due to the AP, this disorder is termed pre-excitation syndrome (PES). PES may also be called ventricular PES or AP syndrome. Syndromes of pre-excitation include Wolff-Parkinson-White (WPW) syndrome, concealed WPW syndrome, Lown-Ganong-Levine syndrome, and Mahaim type of pre-excitation.

WPW, in which pre-excitation is associated with supraventricular tachycardia, is the most common and prototypical syndrome of the pre-excitation syndromes and from here on WPW syndrome and PES will be synonymous unless stated otherwise.

II. Diagnostic Confirmation: Are you sure your patient has Pre-Excitation Syndrome?

Pre-excitation demonstrated on ECG in a patient with an associated tachyarrhythmia due to the presence of an AP. The presence of an AP or pre-excitation may need advanced testing, including electrophysiologic (EP) studies.

A. History Part I: Pattern Recognition:

Patients with pre-excitation may be asymptomatic, particularly if only ECG findings of pre-excitation are present. Male gender or young age may predispose to the development of symptoms or sudden cardiac death (SCD). In patients with an associated tachyarrhythmia and PES, common signs and symptoms include: palpitations, heart fluttering, racing heartbeat, dizziness, lightheadedness, presyncope/syncope, anxiety, pounding sensation in the neck/chest, chest discomfort or pain, and shortness of breath. These symptoms typically are paroxysmal but may be persistent in some cases.

Tachyarrhythmias in patients with PES may be episodic, follow a circadian rhythm, or occur more often at certain times of day. Some patients may recognize precipitating factors associated with arrhythmias including: drugs/chemicals, toxins, physical/emotional stress, sudden body movements, hypovolemia/dehydration, endocrine abnormalities, pregnancy or menstrual cycle-related, infection/fever, lung disease or hypoxia, and swallowing/coughing/choking. Sudden death or cardiac arrest is a major concern in patients with PES. Patients with PES may have a family history of sudden death or heart arrhythmias, particularly presenting at a young age.

B. History Part 2: Prevalence:

The exact prevalence of pre-excitation is unknown. WPW is the most common pattern and syndrome of pre-excitation. The prevalence of WPW pattern on ECG is about 0.2%. The actual syndrome which includes the WPW pattern on ECG and an associated tachyarrhythmia is unknown.

Most cases of PES occur in young patients without a previous history of heart disease, including ischemic heart disease, structural/valvular heart disease, cardiomyopathy, or heart failure. There are several medical conditions, mostly congenital heart disease, that are associated with PES including: Ebstein’s anomaly, ventricular septal defect, mitral valve prolapse, hypertrophic obstructive cardiomyopathy, atrial septal defect, anomalous pulmonary venous return, corrected transposition of the great arteries, aortic insufficiency, Tetralogy of Fallot, tricuspid atresia, rhabdomyosarcoma, polycystic kidney disease, rheumatic heart disease, and other genetic abnormalities such as mutations in the PRKAG2 gene.

C. History Part 3: Competing diagnoses that can mimic Pre-Excitation Syndrome.

The differential diagnoses for pre-excitation syndromes include other tachycardias not necessarily involving accessory pathways as the pathophysiologic cause such as the following: sinus tachycardia, atrial fibrillation, atrial flutter, focal atrial tachycardia, multifocal atrial tachycardia, macroreentrant atrial tachycardia, atrioventricular nodal reciprocating tachycardia, atrioventricular reciprocating tachycardia (AVRT), permanent junctional reciprocating tachycardia, focal junctional tachycardia, atriofascicular tachycardia, nodofascicular tachycardia, supraventricular tachycardia with aberrancy, and ventricular tachycardia.

D. Physical Examination Findings.

Physical examination findings are nonspecific for PES, particularly if the patient is not experiencing a tachyarrhythmia. Common findings that may be present in a patient experiencing an acute tachyarrhythmia include: tachycardia, rapid regular or irregular heartbeat/pulse, diaphoresis, prominent neck pulsations, elevated jugular venous pressure, signs of heart failure, hypotension or signs of shock (in cases of unstable tachycardia), and altered mental status or loss of consciousness (in cases of unstable tachycardia with decreased cerebral perfusion).

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no specific laboratory findings for pre-excitation syndrome. Electrolyte abnormalities are commonly monitored and corrected in order to prevent or decrease the chance for arrhythmias. Similarly, patients are usually screened with thyroid function tests which could indicate a potential treatable trigger for tachycardia.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Electrocardiogram

Wolff-Parkinson-White syndrome

  • Short PR interval (less than 0.12 seconds).
  • Delta wave (slurred upstroke in the QRS complex due to fusion of early ventricular activation from pre-excitation via the accessory pathway with normal ventricular activation via the AV nodal pathway).
  • Wide QRS interval (typically greater than 0.10 seconds).
  • Secondary ST-T wave changes due to pre-excitation and/or tachyarrhythmia.
  • Presence or prior documentation of a tachyarrhythmia commonly seen in pre-excitation such as AVRT or atrial fibrillation with rapid ventricular rate (RVR).
  • ECG findings with AVRT vary depending on whether the re-entrant circuit is orthodromic or antidromic (orthodromic AVRT has narrow QRS complexes versus antidromic AVRT which may have wide QRS complexes due to antegrade conduction occurring via the accessory pathway with retrograde conduction occurring via the AV node and His-Purkinje system).
  • Atrial fibrillation with RVR can be diagnosed in a patient with WPW by comparing pre-excited QRS complexes on baseline ECG while in sinus rhythm versus those seen during the irregular tachycardia.
  • It should be noted that although the wide and aberrated QRS complexes seen in patients with PES and atrial fibrillation may be similar or identical to those seen when in sinus rhythm, the width of the QRS complexes may vary and at times be normal due to a rate-related phenomenon.
  • Atrial fibrillation may degenerate into ventricular fibrillation.

Long-Ganong-Levine syndrome

  • Short PR interval
  • No Delta wave present; QRS interval may appear normal
  • Associated tachyarrhythmia

Mahaim-type tachycardia

  • Normal PR interval
  • No Delta wave present; QRS interval may appear normal or sometimes a left bundle-branch block pattern may be present
  • Associated tachyarrhythmia

AVRT is a reentrant tachycardia commonly seen in PES. There are two types of AVRT based on the direction of the reentrant rhythm: orthodromic and antidromic. Orthodromic AVRT involves antegrade conduction down the AV node and His-Purkinje system (normal conduction system) whereas retrograde conduction occurs via the AP. Antidromic AVRT involves antegrade conduction down the AP and retrograde conduction via the normal conduction system. It is important to note that pre-excitation is seen on ECG with antidromic AVRT; whereas orthodromic AVRT usually has normal QRS complexes seen on ECG. Orthodromic AVRT occurs much more often than antidromic AVRT.

Orthodromic AVRT in PES typically appears as a regular narrow complex tachycardia.

Antidromic AVRT in PES typically appears as a regular wide complex tachycardia, which is due to the pre-excitation manifesting on ECG.

Atrial fibrillation with RVR in patients with PES typically appears as an irregular wide complex tachycardia (but may be narrow complex or with varying narrow/wide complexes). Diagnosis is made by comparing the QRS complexes showing pre-excitation seen during atrial fibrillation to those seen on baseline ECG while a patient is in sinus rhythm.

Numerous ECG algorithms exist which can aid in localizing the AP. These are usually guided by the polarity of the Delta wave and the R- to S-wave relationship in the anterior or precordial leads of the ECG. Consultation with either a cardiologist or cardiac electrophysiologist is recommended in order identify the location of an AP and also diagnose PES.

In controlled settings, adenosine adminstration is sometimes used as a diagnostic tool in order to unmask accessory pathways if there is no apparent retrograde conduction on ECG or if the pathway is concealed. Procainamide or amjaline can be used as a challenge test to assess the refractoriness of antegrade conduction down the AP. There is a risk of AV block with the use of these drugs. Treadmill exercise testing can also be used to assess the risk for potential conduction down the AP or dangerous tachyarrhythmias.

Electophysiologic studies may be used to both identify asymptomatic patients at risk for malignant tachyarrhythmias associated with the presence of an AP as well as confirm the presence of APs in patients with suspected PES.

Holter or event monitors are sometimes employed to record or document tachyarrhythmias in patients in whom there is a suspicion for both arrhythmias and pre-excitation.

Echocardiography is often used to exclude structural heart disease, valvular/anatomic abnormalities, or depressed left ventricular ejection fraction (LVEF) in patients with pre-excitation and/or tachyarrhythmias.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Other cardiac testing may be indicated based on the above results or findings, but the tests mentioned above are the recommended initial tests to be considered in the diagnosis and management of patients with PES.

III. Default Management.

Immediate management steps in patients with PES include prompt diagnosis and rapid treatment of any life-threatening arrhythmias. Long-term management of patients with PES include reduction or prevention of recurrent tachyarrhythmias with medications and/or ablation of the accessory pathway for potential cure.

A. Immediate management.

The first step in the immediate management of patients with PES and an associated tachyarrhythmia is determining whether or not the patient is considered to be stable. Advanced cardiac life support guidelines exist for management of both stable and unstable tachycardia. The following will discuss management tips specific to inpatients with PES who develop stable tachycardia.

Patients experiencing an acute tachyarrhythmia should be placed on telemetry with serial vital sign measurements. Supplemental oxygen should also be considered in certain patients. An ECG should be completed to help determine what type of arrhythmia the patient is experiencing. Continuous ECG monitoring or rhythm strips may be needed to assess the immediate effect of certain treatments. In some cases, stable patients should be connected to a defibrillator with defibrillator pads in the event they become unstable or if cardioversion is needed.

Patients should have a functioning intravenous (IV) catheter in place in order to effectively administer drugs as needed. If available, electrolytes and thyroid function should be reviewed or sent for analysis in order to correct any abnormalities which may have triggered or contributed to the arrhythmia. Likewise, any other possible triggers of tachyarrhythmia (e.g., infection) should also be addressed in the ongoing management of patients with PES.

Treatment is also different depending on the type of tachyarrhythmia present. Unstable tachycardia should be treated with emergent electrical cardioversion. For stable tachycardia, vagal maneuvers or pharmacologic treatment may achieve the desired goals in management. There is recent evidence to suggest that postural modification to the Valsalva maneuver may be more effective than the standard Valsalva maneuver alone for the emergency treatment of supraventricular tachycardia. In cases of stable tachycardia not responding to treatment with pharmacologic or noninvasive means, cardioversion may have to be considered. In patients who are stable and in whom cardioversion is being used, sedatives and anesthetic agents should be administered prior to cardioversion if possible.

Pharmacologic treatment has two purposes in the treatment of patients with PES and an associated tachyarrhythmia. First, some medications can reduce certain factors that may induce tachycardia in these patients. Second, some medications target the weaker limb of the reentrant circuit (either the AV node or the AP), which generally has a longer refractory period and is less conductive.

In orthodromic AVRT, the AV node is targeted as the weaker limb in conduction. Thus, in orthodromic AVRT without pre-excitation on baseline ECG (concealed accessory pathway), or with pre-excitation pattern if other antiarrhythmics have failed, maneuvers and drugs that block the AV node by either increasing its refractory period or decreasing conduction along the tract are recommended. These include vagal maneuvers, carotid massage, IV adenosine, beta blockers, and calcium-channel blockers. IV digoxin is not typically used in the immediate management of this arrhythmia given its delayed onset of action and risk of ventricular fibrillation. AV nodal agents in general carry an inherent risk of increased conduction via the accessory pathway if the rhythm spontaneously degenerates to atrial fibrillation.

IV procainamide is another option to use as it prolongs refractoriness and decreases conduction in most all cardiac tissues. Thus, procainamide can also block conduction down the AP. Procainamide is typically used for this reason in the acute treatment of patients with known AP or in those whom the diagnosis is unclear and the fear of AV nodal blockade leading to dangerous conduction down the AP exists (e.g., those patients presenting with irregular wide complex tachycardia or patients with atrial fibrillation and a known AP).

In antidromic AVRT, the weaker limb of the reentrant circuit is retrograde conduction through the AV node. AV nodal blockade should be avoided though, as the RVR seen in the setting of atrial fibrillation (in cases of degeneration to atrial fibrillation or misdiagnosis) can be transmitted via the AP, therefore increasing the risk of life-threatening ventricular fibrillation. Thus, AV nodal blockers such as beta blockers, calcium-channel blockers, adenosine, and digoxin should not be used to treat new antidromic AVRT as it may lead to accelerated tachycardia, degeneration into atrial fibrillation, or even ventricular fibrillation.

It should also be entertained that some patients may have multiple APs and retrograde conduction may actually be occurring via another AP and not the AV node. As mentioned above, conduction in antidromic AVRT occurs antegrade down the AP and in most cases retrograde via the normal conduction system (unless multiple APs exists). This type of conduction causes wide QRS complexes to appear on ECG. In cases where antidromic AVRT has previously been documented or known to exist in a patient with pre-excitation, the arrhythmia should be treated as ventricular tachycardia or an unknown wide complex tachycardia.

Wide complex tachycardia is treated with synchronized cardioversion in unstable patients and sometimes in stable patients if control cannot be achieved with antiarrhythmic drugs. Medications recommended for the treatment of wide complex tachycardia include IV procainamide, sotalol, amiodarone, or lidocaine in patients with a structurally normal heart. Amiodarone or lidocaine can be used in patients with structurally abnormal hearts or known decreased LVEF. If a patient with antidromic AVRT is known to have PES or an AP, procainamide should be considered first-line treatment. The wide complex tachycardia in antidromic AVRT is typically monomorphic. Treatment of stable polymorphic wide complex tachycardia varies based on whether a patient’s baseline QT interval is normal or prolonged (e.g., Torsade de pointes; see ACLS guidelines).

Atrial fibrillation with RVR in patients with PES can be diagnosed by comparing the irregular, rapid QRS complexes showing pre-excitation with those seen on baseline ECG while a patient is in sinus rhythm. It should be noted that although the QRS complexes are usually wide and aberrated compared to those seen when the patient is in sinus rhythm, the width of the QRS complexes may vary and at times be normal due to a rate-related phenomenon.

In patients with known pre-excitation or PES, or in those where it is unknown or if there is no baseline ECG showing pre-excitation while in sinus rhythm but the suspicion is high, a rhythm control strategy is recommended for atrial fibrillation. There is no single clear first-line agent, but options include the class III antiarrhythmic ibutilide or the class IA antiarrhythmic procainamide, both of which are available IV. Procainamide is recommended if ibutilide is not available or if there is significant concern for prolonged QT interval (which may occur with ibutilide).

Amiodarone is another IV antiarrhythmic that may come to mind because it is safe in patients with heart failure and decreased LVEF. It should be noted, however, that amiodarone is not approved for the acute control of atrial fibrillation in patients with PES, and, notably, has beta blocking effects and may increase ventricular response. Amiodarone therefore should not be used IV for acute control of pre-excited atrial fibrillation. In addition to amiodarone, AV nodal blocking agents such as IV beta blockers, calcium-channel blockers, digoxin, and adenosine are also contraindicated in patients with PES and atrial fibrillation. Any of these medications may accelerate the ventricular rate and cause ventricular fibrillation. It should also be noted that patients who have been in atrial fibrillation for greater than 48 hours or of unknown duration should be anticoagulated if able before undergoing rhythm control or cardioversion. Use of antiarrhythmic agents which may convert patients in atrial fibrillation to sinus rhythm (e.g., amiodarone) should be used with extreme caution in patients not receiving adequate anticoagulation as there is an increased risk for stroke or embolic complications in these patients.

B. Physical Examination Tips to Guide Management.

The physical exam is extremely important in helping determine which patients are considered to have stable versus unstable tachycardia and thus what acute treatment algorithm should be used. Patients who are hemodynamically unstable, especially if they have signs or symptoms of hypoperfusion, should be treated following ACLS protocol and typically undergoing immediate electrical cardioversion.

C. Laboratory Tests to Monitor Response to, and Adjustments in, Management.

Repeat ECG as needed with close monitoring for bradycardia, AV block, and QT prolongation.

Telemetry monitoring for recurrent arrhythmias and also heart rate.

Serum chemistry panel with BUN/Creatinine, electrolytes, and liver function tests at least daily (if not more often if abnormalities are found) with drug dosage adjustment depending on the pharmacologic agent used and its mode of elimination from the body.

D. Long-term management.

For all patients with PES, identification and then elimination of possible triggers of tachyarrhythmias is advised.

For asymptomatic patients with PES, the overall low risk of sudden cardiac death and supraventricular tachycardia argue against routine invasive management. Noninvasive exercise testing or procainamide challenge may be used to help risk-stratify patients and can be done in a step-wise fashion prior to invasive testing. Noninvasive testing is especially useful for identifying low-risk patients. For patients deemed at risk, electrophysiologic (EP) testing may then help further stratify individual patients’ risk of both developing symptoms and suffering SCD. A high-risk patient identified by EP study may then undergo catheter ablation.

For patients who have symptomatic PES, EP study with catheter-based ablation is recommended. It is a class I recommendation by the American College of Cardiology/American Heart Association/Heart Rhythm Society in patients with PES who are resuscitated after experiencing sudden cardiac arrest due to atrial fibrillation and rapid conduction across the AP degenerating into ventricular fibrillation. Ablation of the AP should be considered in other patients with pre-excitation, particularly if they are at high risk for developing malignant tachyarrhythmias. This also should be considered in patients who have high risk professions, are athletes, or have a family history of sudden cardiac death.

Patients should be referred to experienced interventional cardiologists/cardiac electrophysiologists and arrhythmia centers. Invasive testing and treatment with EP and catheter-based ablation is usually considered to have a low risk for complications, especially at experienced treatment centers. Regardless, complications do occur and each patient should be evaluated individually on the appropriateness for testing and treatment based on their history and goals of care.

The type of approach and ablation strategy varies depending on the location of the accessory pathway, the number of pathways present, and also the preferred mode of treatment by the electrophysiologist. Typically, EP studies with ablation occur using a catheter with sheath and endovascular approach. Epicardial pathways do exist which may require a percutaneous or surgical approach. In rare cases, a surgical approach for ablation may be needed in certain patients who fail other approaches or treatment.

Strategies for termination of tachyarrhythmias vary based on the frequency of the episodes and the degree of the patient’s symptoms. Some patients who have infrequent episodes of tachycardia and/or who are not very symptomatic may do better with an as needed drug therapy or the “pill-in-the-pocket” approach. These medications are usually given as a single, higher-dose administration than that used for chronic maintenance therapy to prevent arrhythmias. This strategy in suitable patients decreases the long-term side effects and toxicities associated with chronic medication use and may in some cases decrease the medical costs for the patient.

Whether used as chronic maintenance therapy or pill-in-the-pocket, first-line medications include oral class IC antiarrhythmic drugs such as flecainide or propafenone. Second-line medications include class III agents dofetilide or sotalol. Class IA drugs such as quinidine, procainamide, and disopyramide may also be useful. Other drugs used in the chronic prevention of orthodromic AVRT in patients with PES include oral beta blockers (second-line in low-risk patients), non-dihydropyridine calcium-channel blockers, amiodarone (if refractory to other agents), and digoxin (not recommended as monotherapy).

Long-term management of antidromic AVRT in patients with PES should focus on ablation, reserving medical management for patients who refuse, are unable to undergo, or are refractory to ablation. Therapies include class IC medications as first-line such as oral flecainide or propafenone. Second-line medications include class IA drugs such as quinidine, procainamide, and disopyramide. Amiodarone is another second-line therapy for the treatment of antidromic AVRT in patients with PES but should be used with caution due to its AV nodal blocking properties. AV nodal blockers, such as oral beta blockers, calcium-channel blockers, and digoxin are contraindicated in the chronic prevention or antidromic AVRT in patients with PES.

Long-term treatment of atrial fibrillation in patients with PES includes class IC medications (flecainide or propafenone), class IA medications (quinidine, procainamide, and disopyramide), and amiodarone. AV nodal blockers such as oral beta blockers, calcium-channel blockers, and dignoxin are contraindicated in the chronic prevention of atrial fibrillation in patients with PES. Ablation of the AP is the preferred treatment in PES patients with history of atrial fibrillation. If this procedure cannot be done or if it is unsuccessful, long-term anticoagulation or antiplatelet agents should be considered in appropriate patients with atrial fibrillation based on current guidelines which take stroke risk into consideration.

Patients with PES who are symptomatic typically undergo catheter-based ablation. This is especially true if a patient shows a poor response to medical therapy. The success of ablation is highly dependent on the ability of the operator to localize the accessory pathway(s). The location of the pathway(s) also determines the type of approach used, the vessel cannulated, and the type of ablation used. The success rate of ablation is around 95%, with a recurrence rate of 5% and a 1/1000 chance of mortality associated with the procedure.

Possible complications of EP study with catheter-based ablation of the AP include:

  • Local bleeding/hematoma/infection at site of catheter/sheath insertion
  • Vascular damage/aneurysm/pseudoaneurysm/dissection
  • Side effects from local anesthesia and mild sedation used during the procedure
  • Autonomic dysfunction
  • Inappropriate sinus tachycardia
  • Heart block (AV or bundle branch block)
  • Induced arrhythmia potentially leading to cardiac arrest
  • Perforation of the heart wall potentially leading to cardiac tamponade
  • Stroke
  • Air embolism during catheter exchange
  • Radiation exposure from fluoroscopy
  • Complication leading to cardiac surgery

Caution should always be used with the administration of both IV and PO nodal agents with PES, as PES may spontaneously degenerate into atrial fibrillation, in which case nodal agents may increase ventricular response predisposing to malignant ventricular arrhythmias.

Please review medication dosing, adverse effects, and contraindications prior to administering any of the below medications. Guidelines for administration and dosing of medications may vary by hospital or institution. Suggestions for dosing of medications for patients with PES and important adverse effects for IV drugs and some oral drugs are included below.

Procainamide

15 mg/kg IV load over 30 minutes or 3-6 mg/kg up to 100 mg IV every 5-10 minutes then 20-80 mcg/kg/min IV drip (gtt) if needed.

Adverse effects include hypotension, prolonged QT interval, ventricular fibrillation, asystole, thrombocytopenia, hemolytic anemia, agranulocytosis, and lupus-like syndrome.

Lidocaine

1-1.5 mg/kg IV once then 0.5-0.75 mg/kg IV up to 3 times as needed. Can give as 1-1.5 mg/kg IV every 3-5 minutes followed by 1-4 mg/min) IV gtt if needed. Adverse effects include seizures, coma, bronchospasm, respiratory depression, and heart block.

Lidocaine is recommended in the treatment of unknown wide complex tachycardia but should be avoided in patients with known PES, particularly those experiencing antidromic AVRT in the setting of an AP. In this setting, IV procainamide is the recommended treatment in patients with wide complex tachycardia (WCT) due to known AP and PES.

Beta blockers

Contraindications to beta blockers include active wheezing, decompensated heart failure, and cardiogenic shock.

Metroprolol 5 mg IV every 5 minutes up to a total dose of 15 mg.

Esmolol 500 mcg/kg IV bolus followed by 50-200 mcg/kg/min IV gtt.

Calcium-channel blockers

Contraindications to calcium-channel blockers include ventricular tachycardia, advanced AV block without pacemaker, severe hypotension, cardiogenic shock, and concurrent administration of beta blockers.

Verapamil 5 mg IV given every 2-3 minutes up to a total dose of 15 mg; continuous IV gtt may be needed.

Monitor closely for hypotension.

Diltiazem 5-20 mg/hr IV; continuous IV gtt may be needed.

Monitor closely for hypotension.

Other medications

Amiodarone 150 mg initial IV bolus over 10 minutes followed by 1 mg/min IV gtt for 6 hours then 0.5 mg/min IV gtt for 18 hours before starting oral (PO) maintenance therapy (amiodarone can be loaded orally in stable patients as well).

Most side effects with amiodarone are long-term but bradycardia, hypotension, and AV block are potential immediate adverse effects in patients undergoing IV bolus and gtt administration. Amiodarone can be used in patients with structural heart disease or decreased LVEF.

Digoxin 0.5 mg IV once then 0.25 mg IV every 6 hours x2 followed by maintenance dose at 0.125-0.25 mg IV daily (or PO).

Caution should be taken with administering this medication in patients with renal failure or electrolyte abnormalities.

Beta blockers

(See above for contraindications)

Metroprolol tartrate 25 mg PO two or three times daily with dose increases as needed up to a total maximum daily dose of 450 mg.

Propranolol 10-40 mg PO Q6-8 hours

Calcium channel blockers

(See above for contraindications)

Diltiazem 240-320 mg PO daily.

Verapamil 160 mg PO daily.

Oral medications in patients with no known structural heart disease and normal LVEF: Generally, these antiarrhythmic drugs are contraindicated in patients with recent myocardial infarction, QT interval prolongation, heart failure, cardiogenic shock, heart block, and drug class hypersensitivity.

Flecainide should be started at 50 mg PO every 8-12 hours with dose increases as needed up to a total daily dose of 300 mg. The dose must be adjusted in patients with renal insufficiency; however, the drug must be avoided in patients with hepatic impairment.

Flecainide is also proarrhythmic and may cause bradycardia as well. Hospitalization for initiation of this drug is recommended for at least 3 days with continuous cardiac monitoring for arrhythmias and serial ECGs for QT prolongation.

Flecainide should not be used in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent (<2 years) myocardial infarction.

Serious adverse effects include arrhythmias, prolonged QT interval, hepatic failure, cytopenias, blood dyscrasias, and pneumonitis.

Propafenone should be started with a one-time dose of 450 mg PO then 150 mg PO every 8 hours with dose increases as needed up to a total daily dose of 900 mg. The dose must be adjusted in patients with hepatic impairment.

Propafenone should not be used in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent (<2 years) myocardial infarction.

Propafenone can cause bradycardia and hospitalization at initiation of this drug is recommended to monitor for adverse effects before the patient is considered safe to take this therapy as a pill-in-the-pocket approach.

Disopyramide should be started with a one-time dose of 300 mg PO then 200 mg PO every 4-6 hours up to a total daily dose of 1600 mg. Extended release dosing is 400-750 mg/day PO at every 12-hour dosing; the dose must be adjusted in patients with renal insufficiency and hepatic impairment.

Disopyramide should not be used in patients with asymptomatic, non-life-threatening ventricular arrhythmias and recent (<2 years) myocardial infarction.

Contraindications include drug hypersensitivity, heart failure, prolonged QT interval, cardiogenic shock, and AV block.

Adverse effects include hypotension, prolonged QT interval, arrhythmias, drug hypersensitivity, thrombocytopenia, agranulocytosis, and gastrointestinal disturbances.

Quinidine should be started with a one-time dose of 600 mg PO then 200-300 mg PO every 4-6 hours. The extended-release form is dosed 300-600 mg PO every 8-12 hours. The dose must be adjusted in patients with renal insufficiency and hepatic impairment.

Adverse effects include gastrointestinal disturbances, drug hypersensitivity, and cinchonism.

Quinidine increases the risk of torsade de pointes particularly in patients with electrolyte disturbances or concomitant use with other QT-prolonging drugs or digoxin.

Other serious adverse effects include arrhythmias, cytopenias, and hepatic impairment.

Procainamide should be started with a one-time dose of 1500 mg PO then 250-500 mg 4 times a day. The dose must be adjusted in patients with renal insufficiency or hepatic impairment.

Adverse effects include hypotension, prolonged QT interval, ventricular fibrillation, asystole, thrombocytopenia, hemolytic anemia, agranulocytosis, drug hypersensitivity, and lupus-like syndrome.

Sotalol should be started at 80 mg PO every 12 hours with total daily dosing up to 320 mg/day. The dose must be adjusted in patients with renal impairment.

Sotalol is also proarrhythmic. Hospitalization for initiation of this drug is recommended for at least 3 days with continuous cardiac monitoring and serial ECGs for QT prolongation. Outpatient initiation may be performed cautiously in patients with no heart disease if they have no QT prolongation at baseline, normal electrolytes, and no known proarrhythmia risk factors.

Adverse effects include arrhythmias, bradycardia, heart block, and bronchospasm.

Oral medications in patients with known structural heart disease and decreased LVEF:

Amiodarone has a usual maintenance dose of 200 mg PO daily but sometimes higher doses up to 400 mg PO twice a day may be required at the time treatment is initiated.

Long-term adverse effects include hepatic, ophthalmic, thyroid, and pulmonary side effects.

Digoxin usually ranges from 0.125-0.25 mg PO daily.

Caution should be taken with administering this medication in patients with renal failure or electrolyte abnormalities.

IV. Management with Co-Morbidities.

N/A

A. Renal Insufficiency.

Certain medications used to treat PES may need dosage adjustment or may be contraindicated in patients with renal insufficiency.

B. Liver Insufficiency.

Certain medications used to treat PES may need dosage adjustment or may be contraindicated in patients with liver disease.

C. Systolic and Diastolic Heart Failure.

Certain medications used to treat PES may be contraindicated in patients with structural heart disease, cardiomyopathy, or decreased LVEF. Please see above.

D. Coronary Artery Disease or Peripheral Vascular Disease.

Certain medications used to treat PES may be contraindicated in patients with coronary artery or peripheral vascular disease. Please see above.

E. Diabetes or other Endocrine issues.

Patients who are diabetic and undergoing EP study which requires NPO (nothing by mouth) status will need more frequent blood glucose testing, hypoglycemia protocol, and adjustments made to their insulin, oral pharmacologic, and/or injectable pharmacologic regimen for diabetes depending on the patient and type of insulin or drug.

F. Malignancy.

No change in standard management but goals of care and management strategy should be carefully addressed in patients with advanced or terminal cancer and/or poor long-term prognosis.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management but medication interactions should be checked for in patients requiring long-term immunosuppressive or antimicrobial drugs.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management except beta blockers should be used carefully or perhaps avoided in patients with severe reactive airway disease. Amiodarone should be avoided in patients with already existing pulmonary fibrosis or advanced lung disease.

I. Gastrointestinal or Nutrition Issues.

No change in standard management but considerations should be made for routes of administration for medications in selected patients and also those with disorders affecting drug absorption.

J. Hematologic or Coagulation Issues.

Anticoagulation and risk of peri-procedural complications needs careful consideration in patients with hematologic conditions or coagulopathies who are undergoing EP study and/or procedures. These patients may need more frequent monitoring of either their blood counts or coagulation profile while undergoing treatment with supportive transfusions or reversal of coagulopathy as needed.

These patients may require longer lengths of stay for either bridging/reversal therapies or observation peri-procedure. Additionally, some medications used to treat PES may cause cytopenias and blood dyscrasias. These medications should be avoided or used cautiously in patients with already underlying cytopenias or blood dyscrasias with frequent complete blood counts checked as indicated.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management but goals of care and management strategy should be carefully addressed in patients with advanced dementia and in those with debilitating mental illness which may affect medication adherence or preferences.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Reminder to avoid AV nodal blocking agents in the treatment of tachyarrhythmias in most patients with PES, especially if atrial fibrillation or wide complex tachycardia develops.

Telemetry and/or heart rate check in appropriate patients with specific recommendations for how to manage both tachyarrhythmias and bradyarrhythmias in certain patients depending upon the characteristics of their underlying PES.

Check ECG if needed and consider checking electrolytes and correcting any disturbances that my trigger or exacerbate arrhythmias.

Examine the groin area for bleeding/hematoma/bruit/pulse as well as distal extremity and pulse check in patients who are status post EP study with catheterization requiring vascular insertion/access.

Most institutions have guidelines regarding post-procedure monitoring, moderate sedation, and vascular sheath care/removal that should by adhered to in patients undergoing EP study.

Consider consulting with an on-call cardiologist or cardiac electrophysiologist should patients develop any complications related to their PES and/or treatment of PES.

B. Anticipated Length of Stay.

The length of stay (LOS) for patients with PES may vary based on their reason for presentation or admission to the hospital. Patients presenting status post-resuscitative measures following cardiac arrest due to PES and malignant tachyarrhythmia should remain hospitalized until a preventative treatment has been initiated or perhaps even after undergoing definitive treatment with EP study and catheter-based ablation of the AP.

Patients who are being initiated on certain antiarrhythmic drugs may require at least 3 days of hospitalization with monitoring on telemetry and serial ECGs. LOS may be different in individual patients due to how quickly they become both symptom- and arrhythmia-free. Patients undergoing elective EP study and catheter-based ablation are typically monitored overnight or for less than 24 hours’ observation so post cardiac catheterization care can be performed and to make sure there are no arrhythmias or immediate complications.

C. When is the Patient Ready for Discharge?

Discharge criteria for patients with PES are based on two major factors. First, the patient should be both symptom- and arrhythmia-free. Second, a treatment and follow-up plan should be initiated and in place prior to discharge.

For patients with a history of atrial fibrillation who are appropriate for anticoagulation, discharge typically does not occur until the patient has achieved therapeutic anticoagulation depending on a patient’s risk factors for stroke. Most patients with PES and atrial fibrillation are treated with some sort of rhythm control or ablative strategy. For those instances where rate control is the treatment of choice, a patient’s heart rate should be less than 100 beats per minute for at least 24 hours. Those patients should also be able to ambulate and exert themselves on the wards without feeling symptomatic or developing inappropriate tachycardia.

D. Arranging for Clinic Follow-up.

Follow-up for patients with PES may involve three different clinics: cardiology/cardiac electrophysiology, primary care, and anticoagulation (in those patients for whom anticoagulation is indicated).

1. When should clinic follow up be arranged and with whom.

Timing depends on treatment plan with perhaps patients needing evaluation for definitive treatment of their PES or with new changes in the treatment plan being more urgent and occurring sooner than those patients with stable PES on chronic maintenance therapy.

Patients with PES should be given routine follow-up with their primary care provider. It is important for the primary care provider to be notified of the patient’s treatment and follow-up plan at time of discharge.

Patients who will be on anticoagulation should have follow-up with their anticoagulation clinic. Timing of this appointment varies depending on any dosage changes made to a patient’s anticoagulation and also the stability of a patient’s coagulation profile. Follow-up within a week is usually recommended for most patients unless there have been no issues or changes regarding their anticoagulation, in which case those patients can resume their routine anticoagulation monitoring.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Depending on the treatment and follow-up plan in place, patients with PES may need additional testing done prior to their arranged follow-up. For undiagnosed patients or those without evidence of an associated tachyarrhythmia but with pre-excitation on ECG, Holter or event monitoring may be recommended to be completed prior to follow-up with cardiology.

Depending on the medication started, repeat complete blood count and serum chemistry with BUN/Creatinine, electrolytes, and liver function tests may need to be checked prior to follow-up.

Patients on amiodarone typically have their thyroid function tests monitored.

Patients started on digoxin also require monitoring of their renal function and digoxin levels. Likewise, a repeat ECG is typically checked in most patients who have been treated or are undergoing treatment for an arrhythmia at the time of their next follow-up appointment.

Patients who will be on anticoagulation will need a repeat coagulation profile prior to their next outpatient visit with either their primary care provider or anticoagulation clinic.

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

The prevalence of pre-excitation on ECG is about 0.2%.

The actual prevalence of pre-excitation syndrome (pre-excitation with an associated tachyarrhythmia) is unknown but is much less than the prevalence for pre-excitation alone.

The risk of death due to arrhythmia in asymptomatic patients with pre-excitation is extremely low.

The lifetime risk of sudden death in patients with PES is less than 5%.

Up to 9% of patients with PES who do not undergo ablation may develop atrial fibrillation, and up to 2.5% ventricular fibrillation.

EP study with catheter-based ablation has around a 95% success rate in the treatment of PES, but this can approach 100%; the recurrence rate for tachyarrhythmias is at most 5%.

EP study with catheter-based ablation is a very safe procedure with a procedure-related mortality rate of 1/1000.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

Class I recommendations which should be documented in the management or plan of care for patients with PES:

  • Catheter-based ablation of AP in symptomatic patients with PES, especially those with a history of syncope or resuscitation from sudden cardiac arrest.
  • Catheter-based ablation of AP in patients with pre-excitation and atrial fibrillation or flutter.

If a patient with PES is unable to undergo catheter-based ablation of the AP or fails catheter-based ablation, it should be documented with the reasons why and also alternate plans depending on the patient’s characteristics and preferences (e.g., medical management, surgical ablation, or observation).

The role for ablation of the AP in asymptomatic patients with pre-excitation is somewhat unclear, but recommendations are in place for identifying higher-risk populations who should be considered for EP study and possible catheter-based ablation. It should be noted whether an asymptomatic patient with pre-excitation has a higher-risk for poor outcome based on patient characteristics or noninvasive testing. Higher-risk patient characteristics include any profession or personal activity that increases the likelihood for arrhythmia or poor outcome in the patient (or perhaps others) if a malignant tachyarrhythmia were to later develop. This assessment should be documented and these patients should always be referred for EP study to help risk-stratify the properties of the AP and for possible ablation.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

  • Place patient on telemetry.
  • No venous thromboembolism prophylaxis necessary in certain patients who are adequately anticoagulated for atrial fibrillation or other conditions requiring chronic anticoagulation.

Discharge instructions

  • Ensure patient has all medications and has undergone medication reconciliation/teaching prior to discharge, especially for those patients opting for the pill-in-the-pocket strategy.
  • Counsel patients regarding medication adherence as well as avoidance of potential triggers for their disease.
  • Counsel patient on any warning signs or symptoms that should prompt medical evaluation.
  • Provide post-catheterization or EP study instructions to appropriate patients, including that patients should wait at least 24 hours before removing the bandage from their groin or before showering/bathing, patients should avoid strenuous activity or heavy lifting (more than 10 lbs) for a period of 1 week, and what patients should do should they develop bleeding/bruising/redness/swelling at the site of groin insertion.
  • Ensure patient has appropriate follow-up appointments prior to discharge.

VII. What’s the evidence?

Al-Khatib, SM, Arshad, A, Balk, EM. “Risk Stratification for Arrhythmic Events in Patients with Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society”. Circulation. 2015 Sep 16.

Anderson, RH, Becker, AE, Brechenmacher, C. “Ventricular preexcitation: a proposed nomenclature for its substrates”. Eur J Cardiol. vol. 3. 1975. pp. 27-36.

Appelboam, A, Reuben, A, Mann, C. “Postural modification to the standard Valsalva manoeuvre for the emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial”. Lancet. vol. 386. 2015. pp. 1747-53.

Arruda, MS, McClelland, JH, Wang, X. “Development and validation of an ECG algorithm for identifying accessory pathway ablation site in Wolff-Parkinson-White syndrome”. J Cardiovasc Electrophysiol. vol. 9. 1998. pp. 2-12.

Atié, J, Brugada, P, Brugada, J. “Clinical and electrophysiologic characteristics of patients with antidromic circus movement tachycardia in the Wolff-Parkinson-White syndrome”. Am J Cardiol. vol. 66. 1990. pp. 1082-91.

Boahene, KA, Klein, GJ, Yee, R. “Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: importance of atrial fibrillatory cycle length”. J Am Coll Cardiol. vol. 16. 1990. pp. 1408-14.

Calkins, H, Sousa, J, El-Atassi, R. “Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test”. N Engl J Med. vol. 324. 1991. pp. 1612-8.

Chen, SA, Chiang, CE, Tai, CT. “Complications of diagnostic electrophysiologic studies and radiofrequency catheter ablation in patients with tachyarrhythmias: an eight-year survey of 3,966 consecutive procedures in a tertiary referral center”. Am J Cardiol. vol. 77. 1996. pp. 41-6.

Chevalier, P, Cadi, F, Scridon, A. “Prophylactic radiofrequency ablation in asymptomatic patients with Wolff-Parkinson-White is not yet a good strategy: a decision analysis”. Circa Arrhythmia Electrophysiol. vol. 6. 2013. pp. 185-90.

Crozier, I. “Flecainide in the Wolff-Parkinson-White syndrome”. Am J Cardiol. vol. 70. 1992. pp. 26A-32A.

De Chillou, C, Rodriguez, LM, Schläpfer, J. “Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location”. J Am Coll Cardiol. vol. 20. 1992. pp. 666-71.

Dreifus, LS, Haiat, R, Watanabe, Y. “Ventricular fibrillation”. A possible mechanism of sudden death in patients and Wolff-Parkinson-White syndrome. Circ. vol. 43. 1971. pp. 520-7.

Dunnigan, A, Benditt, DG, Benson, BW. “Developmental aspects and natural history of preexcitation syndromes”. 1986. pp. 21-9.

Feld, GK, Nademanee, K, Stevenson, W. “Clinical and electrophysiologic effects of amiodarone in patients with atrial fibrillation complicating the Wolff-Parkinson-White syndrome”. Am Heart J. vol. 115. 1988. pp. 102-7.

Fitzsimmons, PJ, McWhirter, PD, Peterson, DW, Kruyer, WB. “The natural history of Wolff-Parkinson-White syndrome in 228 military aviators: a long-term follow-up of 22 years”. Am Heart J. vol. 142. 2001. pp. 530-6.

Flensted-Jensen, E. “Wolff-Parkinson-White syndrome. A long-term follow-up of 47 cases”. Acta Med Scand. vol. 186. 1969. pp. 65-74.

Gallagher, JJ, Pritchett, ELC, Sealy, WC. “The preexcitation syndromes”. Prog Cardiovasc Dis. vol. 20. 1978. pp. 285-327.

Gallagher, JJ, Gilbert, M, Svenson, RH. “Wolff-Parkinson-White syndrome: the problem, evaluation, and surgical correction”. Circ. vol. 51. 1975. pp. 767-85.

Gulamhusein, S, Ko, P, Carruthers, G. “Acceleration of the ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome after verapamil”. Circ. vol. 65. 1982. pp. 348-54.

Jackman, WM, Friday, KJ, Fitzgerald, DM. “Use of intracardiac recordings to determine the site of drug action in paroxysmal supraventricular tachycardia”. Am J Cardiol. vol. 62. 1988. pp. 8L-19L.

Jackman, WM, Wang, XZ, Friday, KJ. “Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current”. N Engl J Med. vol. 324. 1991. pp. 1605-11.

January, CT, Wann, LS, Alpert, JS. “2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society”. Circulation. vol. 130. 2014. pp. e199-267.

Kerr, CR, Prystowsky, EN, Smith, WM. “Electrophysiologic effects of disopyramide phosphate in patients with Wolff-Parkinson-White syndrome”. Circ. vol. 65. 1982. pp. 869-78.

Lee, KW, Badhwar, N, Scheinman, MM. “Supraventricular Tachycardia – Part I”. Curr Probl Cardiol. vol. 33. 2008. pp. 467-546.

Leitch, JW, Klein, GJ, Yee, R. “Prognostic value of electrophysiology testing in asymptomatic patients with Wolff-Parkinson-White pattern”. Circ. vol. 82. 1990. pp. 1718-23.

Ludmer, PL, McGowan, NE, Antman, EM. “Efficacy of propafenone in Wolff-Parkinson-white syndrome: electrophysiologic findings and long-term follow-up”. J Am Coll Cardiol. vol. 9. 1987. pp. 1357-63.

Madrid, AH, Moro, C, Marin Huerta, E. “Atrial fibrillation in Wolff-Parkinson-White syndrome: reversal of isoproterenol effects by sotalol”. Pacing Clinical Electrophysiol. vol. 15. 1992. pp. 2111-5.

McGovern, B, Garan, H, Ruskin, JN. “Precipitation of cardiac arrest by Verapamil in patients with Wolff-Parkinson-White syndrome”. Ann Intern Med. vol. 104. 1986. pp. 791-4.

Morady, F. “Catheter ablation of supraventricular arrhythmias: state of the art”. Pacing Clin Electrophysiol. vol. 27. 2004. pp. 125-42.

Munger, TM, Packer, DL, Hammill, SC. “A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989”. Circ. vol. 87. 1993. pp. 866-73.

Obeyesekere, MN, Leong-Sit, P, Massel, D. “Risk of arrhythmia and sudden death in patients with asymptomatic pre-excitation: a meta-analysis”. Circulation. vol. 125. 2012. pp. 2308-15.

Page, RL, Joglar, JA, Caldwell, MA. “2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society”. Circulation. 2015 Sep 23.

Pappone, C, Santinelli, V, Manguso, F. “A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome”. N Engl J Med. vol. 349. 2003. pp. 1803-11.

Pappone, C, Vicedomini, G, Manguso, F. “Wolff-Parkinson-White syndrome in the era of catheter ablation: insights from a registry study of 2169 patients”. Circulation. vol. 130. 2014. pp. 811-9.

Petri, H, Kafka, W, Rudolph, W. “Discrepant effects of oral and intravenous verapamil on A-V conduction in patients with ventricular preexcitation and atrial fibrillation”. Herz.. vol. 8. 1983. pp. 144-52.

Prystowsky, EN, Benson, DW, Fuster, V. “Management of patients with atrial fibrillation. A statement for healthcare professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association”. Circulation. vol. 93. 1996. pp. 1262-77.

Prystowsky, EN, Greer, S, Packer, DL. “Beta-blocker therapy for the Wolff-Parkinson-White syndrome”. Am J Cardiol. vol. 60. 1987. pp. 46D-50D.

Prystowsky, EN, Katz, AM. “Textbook of Cardiovascular Medicine”. Atrial fibrillation. vol. 1998. pp. 1661

Saksena, S, Epstein, AE, Lazzara, R. “Clinical investigation of antiarrhythmic devices: a statement for healthcare professionals from a joint task force of the American Heart Association, the North American Society of Pacing and Electrophysiology, the American College of Cardiology, and the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology”. Circ. vol. 91. 1995. pp. 2097-109.

Segers, PM, Lequime, J, Denolin, H. “L’activation ventriculaire précoce de certains coeurs hyperexcitables: Étude de l’onde delta de l’électrocardiogramme”. Cardiologia. vol. 8. 1944. pp. 113-67.

Scheinman, MM. “History of Wolff-Parkinson-White syndrome”. Pacing Clin Electrophysiol. vol. 28. 2005. pp. 152-6.

Sellers, TD, Bashore, TM, Gallagher, JJ. “Digitalis in the pre-excitation syndrome: analysis during atrial fibrillation”. Circulation. vol. 56. 1977. pp. 260-7.

Sellers, TD, Campbell, RWF, Bashore, TM. “Effects of procainamide and quinidine sulfate in the Wolff-Parkinson-White syndrome”. Circ. vol. 55. 1977. pp. 15-22.

Soria, R, Guize, L, Chretien, JM. “The natural history of 270 cases of Wolff-Parkinson-White syndrome in a survey of the general population (Article in French)”. Arch Mal Coeur Vaiss. vol. 82. 1989. pp. 331-6.

Steinbeck, G. “Should radiofrequency current ablation be performed in asymptomatic patients with the Wolff-Parkinson-White syndrome”. Pacing Clinical Electrophysiol. vol. 16. 1993. pp. 649-52.

Wellens, HJJ, Durrer, D. “The role of an accessory atrioventricular pathway in reciprocal tachycardia: observations in patients with and without the Wolff-Parkinson-White syndrome”. Circ. vol. 52. 1975. pp. 58-72.

Wolff, L, Parkinson, J, White, PD. “Bundle-branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia”. Am Heart J. vol. 5. 1930. pp. 685-704.

Zardini, M, Yee, R, Thakur, RK. “Risk of sudden arrhythmic death in the Wolff-Parkinson-White syndrome: current perspectives”. Pacing Clin Electrophysiol. vol. 17. 1994. pp. 966-75.

Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.

No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.

Jump to Section