Wolff-Parkinson-White syndrome medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Sara Zand, M.D.[2] Cafer Zorkun, M.D., Ph.D. [3]; Rim Halaby, M.D. [4]

Overview

Wolff-Parkinson-White syndrome patients who are hemodynamically unstable, as reflected by the presence of hypotension, cold extremities, mottling or peripheral cyanosis, or those who present with ischemic chest pain or decompensated heart failure should urgently undergo direct current cardioversion. The medical therapy of hemodynamically stable patients with WPW syndrome depends on the type of the tachycardia. When the ECG findings suggest orthodromic AVRT, the patient should be managed similarly to patients with supreventricular tachycardia followed by the sequential administration of adenosine, verapamil and procainamide in case of failure to improve. Among patients with antidromic AVRT, AV nodal blocking agents should be avoided and patients should be treated with either procainamide, ibutilide or flecainide. The long term treatment of patients with WPW syndrome depends on the presence or absence of symptoms and their severity. Patients who have poorly tolerated symptomatic WPW syndrome should undergo [[catheter ablation.

Acute Treatment

Atrioventricular Reentrant Tachycardia (AVRT)

• AVRT is one of the type of tachycardia that can occur in patients with WPW pattern.
• AVRT can be either orthodromic or antidromic and the treatment of them is different.

Hemodynamically Unstable Patients

• WPW syndrome patients with AVRT who are hemodynamically unstable,should urgently undergo direct current cardioversion
• The signs of instability of hemodynamic include the following:

• hypotension,
• cold extremities
• mottling
• peripheral cyanosis
• chest pain
• decompensated heart failure
  • The shocks should be delivered as follows:
  • Narrow regular rhythm: synchronized electrical cardioversion, 50-100 Joules
  • Narrow irregular rhythm: synchronized electrical cardioversion, 120-200 Joules biphasic or 200 Joules monophasic
  • Wide regular rhythm: synchronized electrical cardioversion, 100 Joules
  • Wide irregular rhythm: unsynchronized electrical cardioversion, 200-360 Joules monophasic, or 100-200 Joules biphasic

Orthodromic AVRT in Hemodynamically Stable Patients

• The management of WPW syndrome patients who are hemodynamically stable depends on the type of AVRT.
• When the ECG findings suggest orthodromic AVRT and QRS complex is narrow, the patient should be managed similarly to patients with supreventricular tachycardia.
• The management should begin with vagal maneuvers such as carotid sinus massage and valsalva maneuver.
• If the patient's tachycardia does not resolve, the patient should be administered IV adenosine.
• In case of failure to improve, administration of ibutilide may be considered followed by procainamide

The sequence of therapeutic decisions is summarized below.

Recommendations for acute treatment of orthodromic AVRT

Vagal maneuver (Class I, Level of Evidence B):

❑ Carotid sinus massage for 5-10 seconds in the absence of bruit ❑ Valsalva maneuver for 10-30 seconds by bearing down against closed glottis, a more successful technique ❑ Applying ice-cold wet towel to the face

Adenosin(Class I, Level of Evidence B) :

❑ Effective in conversion of AVRT in 90-95% patients ❑ Episode of AVRT may be induced again by PAC or PVC after termination of tachyarrhythmia by adenosin ❑ AF may be induced by adenosin, rapidly passing through accessory pathway Contraindications: asthma, second degree AV block or third degree AV block unless a pacemaker is present

Synchronized cardioversion : (Class I, Level of Evidence B)

❑ Highly effective in termination of AVRT ❑ In unstable hemodynamic or stable hemodynamic and ineffectiveness of vagal maneuver or adenosine is recommended ❑ Avoidance of complications associated antiarrhythmic drugs ❑ In the presence of PVC or PAC just after cardioversion, antiarrhythmic drugs is recommended for prevention of restarting AVRT ❑ In the presence of hemodynamically unstable and pre excited AF, synchronized cardioversion is recommended

Ibutilide or intravenous procainamide:(Class I, Level of Evidence C)

❑ effective in hemodynamic stable and preexcited AF by slowing conduction over the accessory pathway Contraindications: Compromised left ventricular function

Intravenous diltiazem,verapamil ,beta blockers : (Class 2a, Level of Evidence B-C)

❑ Effective for acute treatment of orthodromic AVRT without pre-excitation on resting ECG during sinus rhythm(LOR=B) ❑ Intravenous diltiazem or verapamil effectively terminate 90% to 95% of AVRT without pre-excitation on their resting sinus-rhythm ECG ❑ Hypotension may occur in 3% patients receiving Intravenous diltiazem or verapamil ❑ Intravenous beta blocker are effective for terminating AVRT with low risk of associated complications(LOR=C)

Intravenous betablockers,diltiazem,verapamil (Class 2b, Level of Evidence B):

❑ Acute termination of orthodromic AVRT with pre-excitation on resting ECG without response to other treatment ❑ The complication is enhancing conduction over the accessory pathway if the AVRT converts to AF during the administration of the medication

Intravenous digoxin,intravenous amiodarone,intravenous or oral beta blockers,diltiazem,verapamil : (Class 3, Harm, Level of Evidence B)

❑ Harmful in acute termination of peexcitated AF due to increased risk of ventricular fibrillation by these mechanisms: ❑ Increased conduction over the accessory pathway and slowing or blocking conduction over AV node ❑ Deceased refractory period of accessory pathway by digoxin ❑ Increased cathecolamin due to drug induced hypotension such as amiodarone, beta blocker, verapamil, diltiazem

Antidromic AVRT in Hemodynamically Stable Patients

• In antidromic AVRT, the antegrade conduction of the electrical signals occurs through the accessory pathway, while the retrograde conduction occurs through either the AV node or a second accessory pathway.
• In antidromic AVRT, AV nodal blocking agents should be avoided.
• Digoxin, calcium channel blockers, beta blockers and adenosine should be avoided.
• Adenosine may lead to atrial fibrillation with rapid ventricular response.
• Procainamide or ibutilide are recommended .

Treatment of Antidromic AVRT in Hemodynamically Stable Patients
Medication	Dosage	Notes
Procainamide	100 mg infusion diluted to 100mg/ml at a rate of 25-50 mg/min every 5 minutes	❑ Give until the arrhythmia is suppressed or until 500 mg has been administered ❑ Wait 10 minutes or longer to administer new dosage Contraindications: third degree AV block, lupus erythematosus, idiosyncratic hypersensitivity, torsades de pointes
Ibutilide	1 mg IV infusion over 10 minutes	❑ Repeat the dosage if the tachycardia continues Contraindications: hypersensitivity to ibutilide or any component of the formulation, QTc >440 msec

Atrial Fibrillation

• WPW syndrome with atrial fibrillation should be suspected whenever the ECG reveals an irregular rhythm with absent P wave in the presence of a heart rate more than 240 beats per minute.

Hemodynamically Unstable Patients

In hemodynamically unstable patients, urgent direct current cardioversion should be performed.

Long Term Treatment

Management of patients with AVRT includes the following:

Recommendations for longterm treatment of orthodromic AVRT

Catheter ablation (Class I, Level of Evidence B):

❑ Successful rate of ablation for AF+ AVRT is 93-95% ❑ In young patients, the risk of recurrent AF after ablation of the accessory pathway is low ❑ Recurrence of AF in older patients after ablation may be related to other causes ❑ Successful rate of ablation for mahain accessory pathway is 70-100%

Oral beta blockers, diltiazem, verapamil (Class I, Level of Evidence C):

❑ Effective in patients without preexcitation in resting ECG ❑ Prevention of AVRT recurrence in 50% patients

Oral flecainide or propafenone (Class 2a, Level of Evidence B):

❑ For patients with AVRT and/or pre-excited AF that are not candidates or do not prefer catheter ablation ❑ Mechanism of action is slowing or blocking conduction over the accessory pathway ❑ Contraindications are ischemic or structural heart disease due to increased risk of VT

Oral dofetilide or sotalol (Class 2b, Level of Evidence C):

❑ For patients with AVRT and/or pre-excited AF that are not candidated or do not prefer catheter ablation ❑ Be useful in patients with structural heart disease or coronary artery disease ❑ Side effect is QT prolongation and torsades de poites

Oral amiodarone (Class 2b, Level of Evidence C ):

❑ For patients with AVRT and/or pre-excited AF that are not candidated or do not prefer catheter ablation ❑ For patients that using betablocker, diltiazem or verapamil and flecainide are contraindicated or ineffective

Oral beta blockers, diltiazem, verapamil (Class 2b, Level of Evidence C):

❑For patients with AVRT and/or pre-excited AF that are not candidates or do not prefer catheter ablation ❑ Due to the risk of developing rapid AF in AVRT, these drugs should be used with causion ❑ Only one RCT supported the use of verapamil for the prevention of orthodromic AVRT in patients with pre-excitation on resting ECG

Oral digoxin (Class 2b, Level of Evidence C):

❑ In AVRT without pre-excited AF that are not candidates or do not prefer catheter ablation ❑ Because of low efficacy, in case of failure other antiarrhythmic agents, are recommended

Oral digoxin (Class 3,Harm, Level of Evidence C):

❑ Harmful in AVRT or AF and preexcitation on resting ECG due to decreased refractory period of accessory pathway and increased risk of VF

Recommendations for the management of patients with asymptomatic pre-excitation

(Class I, Level of Evidence B):
❑Performance of an electrophysiologic study, with the use of isoprenaline, is recommended to risk stratify individuals with asymptomatic pre-excitation who have high-risk occupations/hobbies, or are competitive athletics ❑Catheter ablation is recommended in asymptomatic patients who are high risk in electrophysiology testing with the use of isoprenaline, such as the shortest pre-excited RR interval during atrial fibrillation≤ 250 ms, accessory pathway effective refractory period ≤250 ms, multiple accessory pathways, and an inducible accessory pathway-mediated tachycardia
(Class I, Level of Evidence C):
❑ Catheter ablation is recommended in high-risk patients with asymptomatic pre-excitation after discussing the risks, especially of heart block associated with ablation of anteroseptal or mis-septal accessory pathway, and benefits of the procedure
(Class 2a, Level of Evidence C):
❑ Patient should be clinically followed in the presence of asymptomatic pre-excitation and a low-risk accessory pathway at invasive risk stratification ❑Catheter ablation should be considered in patients with asymptomatic pre-excitation and left ventricular dysfunction due to electrical dyssynchrony
(Class 2b, Level of Evidence C):
❑ Catheter ablation may be considered in a patient with asymptomatic pre-excitation, and a low-risk accessory pathway at invasive or non-invasive risk stratification ❑ Catheter ablation may be considered in patients with low-risk asymptomatic pre-excitation in experienced centres according to patient preferences

The above table adopted from 2019 ESC Guideline