Pre-excitation syndrome

Pre-excitation syndrome Microchapters
Overview
Historical Perspective
Classification
Pathophysiology
Differentiating Pre-excitation Syndrome from other Diseases
Epidemiology and Demographics
Risk Factors
Natural History, Complications, and Prognosis
Diagnosis
Treatment
Prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor-In-Chief: Shivam Singla, M.D.[2]

Overview

Pre-excitation syndrome is a condition where ventricles of the heart depolarize earlier than the normal leading to premature contraction. Normally the atria and the ventricles are isolated electrically and only electrical passage existing in between atria and ventricles is at Atrioventricular Node. In all pre-excitation syndromes, there is also present an additional conducting pathway beside the AV junction. So the electrical impulses pass to the ventricles even before the normal wave of depolarization that is about to conduct through the AV node. This mechanism of depolarization of ventricles through an additional bypass pathway ( Bundle of Kent) much earlier than the usual depolarization pathway (through AV node) is referred to as "Pre- Excitation". The secondary conduction pathways are generally named as Bundle of His.

The typical ECG findings are shortened PR interval and widened QRS interval with a slight slurring in the upstroke region. The clinical syndrome of the above clinical finding of ECG and history of SVT is referred to as Wolff-Parkinson-White syndrome. pre-excitation syndromes are getting more common in the pediatric population as well. The main component is the presence of an additional accessory bypass pathway in the heart through which the impulse conducts faster than than the physiological conduction through AV node, resulting in quick depolarization ofventricles and leads to dangerous arrhythmias. The most common subtype is Wolf-Parkinson -White syndrome. The severe consequences range from arrhythmias, SVT, and sudden cardiac death. The main therapeutic measures for managing the patients are pharmacotherapy and ablation therapy.

Historical Perspective

• WPW syndrome was described in 1930 and named for the John Parkinson, Paul Dudley White, and Louis Wolff.
• They successfully interpreted a series of 11 healthy young patients who had repeated attacks of tachycardia's in the presence os short PR interval and bundle branch block pattern on the ECG findings.

• British physiologist "Albert Frank Stanley Kent" (1863 - 1958), first described the lateral branches of AV grove of the monkey heart, which was later named accessory bundle of Kent.

• In 1915, Frank Norman Wilson became the first to describe the condition which would later be referred to as Wolff–Parkinson–White syndrome.

• In 1930, it was first described by Louis Wolff, John Parkinson, and Paul Dudley White.
• They also found the association of WPW with increasing the risk of sudden cardiac death.

Classification

• Pre-excitation syndrome may be classified into sub-types

Type	Conduction pathway	QRS interval	PR interval	Delta wave
Wolff-Parkinson-White syndrome	Bundle of Kent	Wide/long	Usually short	yes
Lown-Ganong-Levine syndrome	"James bundle" (atria to bundle of His)	Normal/Unaffected	Short	no
Mahaim-type	Mahaim fibers	long	normal

• Based on their conduction properties, there types of Accessory pathways are there:
  1. Manifest Accessory Pathways: Conducts more rapidly as compared to AV nodal conduction. Delta waves will commonly be seen on ECG.
  2. Concealed Accessory Pathways: Conducts in the retrograde direction. As it's name represents, the changes on ECG will be concealed. No delta waves will be seen.
  3. Latent Accessory Pathways: These are located in the lateral part of heart as compared to AV node. So the impulses will be delayed in travelling to ventricles through the AV node which is at a much shorter distance as compared to latent fibers that are at the far other end.
     

Pathophysiology

Basics of Pre excitation sydrome

Basic concept of Pathophysiology in pre excitation syndrome lies in the concept of by passing the AV node conduction and letting the impulse conduct faster through atria to ventricles via accessory pathways.

WPW- ECG findings

These accessory pathways usually [ Usually called Bundle of Kent in WPW syndrome, James fiber in LGL syndrome and Mahaim fibers in Mahaim type pre excitation syndrome} conducts impulses in forward (not common), backward ( around 15-20%) and in both directions ( Most common type) as well.

The accessory pathways mediates the occurence of tachyarrhythmia's by forming a re-entry circuit and commonly known as AVRT. The direct conduction of impulses from atria to ventricles can also result in development of tachyarrhythmia's under the condition of A. Fib with RVR

WPW Syndrome

• WPW syndrome is a combination of WPW pattern on ECG + Paroxysmal arrhythmias. The accessory pathways are usually named as Bundle of Kent or AV bypass tracts.

• ECG features of WPW syndrome are
  • Short PR interval <120 ms ( < .12 seconds) with Normal P wave morphology.
  • Widened QRS complex ( >.12 seconds)
  • Delta wave - slurring upstroke of the initial QRS complex due to the early and rapid depolarization of ventricles, most important criteria for the diagnosis of WPW syndrome.
  • Deflection of T waves opposite to the direction of QRS complexes / Secondary changes in ST segment and T wave.
  • 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 anterograde conduction occurring via the accessory pathway with retrograde conduction occurring via the AV node and His-Purkinje system).
  • Mainly categorized into 2 subtypes
    • Type A - Positive delta wave
    • Type B - Negative delta wave

Lown-Ganong-Levine(LGL) Syndrome

• The accessory pathways here are named as James fibers, also known as atrionodal fibers connecting the atrium to the distal AV node. These usually conduct the impulses from atria to the initial portion of the AV node.

• ECG features:
  • PR interval is less than 120ms or .12 seconds with usual normal P wave morphology
  • Normal QRS complex
  • Absence of delta waves
  • Episodic paroxysmal SVT

Mahaim-Type Pre-excitation

• The accessory pathways named as mahaim fibers connect the Atrium, AV node, or bundle of His to the Purkinje fibers or ventricular myocardium.

• ECG findings are usually normal

Differentiating Pre-excitation Syndrome from other Diseases

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 second Maybe 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 the 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

• Incidence 0.1 – 3.0 per 1000
• LGL syndrome is a rare Man > woman.
• prognosis is good with SCD is noted in only 0.1% (rare)
  

Risk Factors

High risk population for sudden cardiac death in Wolff-Parkinson-White syndrome include:

• Policemen
• Athletes
• Firemen
• Pilots
• Steelworkers

Risk factors for the development of atrial fibrillation in WPW syndrome include:

• Male gender
• Age (peak ages for the development of atrial fibrillation include 30 years and 50 years)
• Past history of syncope

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Atrioventricular Reentry Tachycardia's (AVRT)

AVRT ( Orthodromic and Antidromic)

AVRT is a form of PSVT. Reentry circuit results from the combination of signal transduction from normal conduction system and accessory pathway.( See: Diagram)

• During tachyarrythmias, the accessory pathway forms part of the reentry circuit that results in the disappearance of features of tachyarrhythmias.
• AVRT are further divided into
  • Orthodromic or Antidromic conduction based on ECG morphology and direction of formation of re-entry circuit.

History and Symptoms

People with Pre- Excitation syndromes may be asymptomatic, however, the individual may experience following symptoms

• Palpitations
• Dizziness or lightheadedness.
• Shortness of breath.
• Chest pain
• Fatigue.
• Anxiety.
• Fainting
• Difficulty breathing

1) AVRT with Orthodromic Conduction

In this, the anterograde conduction occurs via the AV node and retrograde conduction occurs via an accessory pathway.

ECG features of AVRT with orthodromic conduction

• Rate usually 200 – 300 bpm

• P waves may be buried in QRS complex or retrograde
• QRS Complex usually <120 ms unless pre-existing bundle branch block, or rate-related aberrant conduction
• QRS Alternans – phasic variation in QRS amplitude associated with AVNRT and AVRT, distinguished from electrical altrens by a normal QRS amplitude
• T wave inversion common
• ST segment depression

2) AVRT with Antidromic Conduction

In this, the anterograde conduction occurs via the accessory pathway and retrograde conduction via the AV node. Occurring only in-app. 5% of patients with WPW.

ECG features are:

• Rate usually 200 – 300 bpm.
• Wide QRS complexes due to abnormal accessory pathway ventricular depolarisation.
• Due to wide complex, Commonly mistaken for Ventricular Tachycardia.

3) Atrial Fib/Atrial Flutter in WPW

• In 20% of the patients WPW Atrial fibrillation can occur and in approx 7% of patients with WPW atrial flutter can occur. Accessory pathways plays major role by allowing the rapid conduction of impulses directly to the ventricles without involving AV node, in extreme cases may lead to VT or VF.

ECG features are:

• Rate > 200 bpm
• Irregular rhythm
• Wide QRS complexes due to abnormal ventricular depolarisation via an accessory pathway
• QRS Complexes change in shape and morphology
• Axis remains stable unlike Polymorphic VT
• Atrial Flutter presents with same features as atrial fibrillation in WPW except rhythm is regular and commonly mistaken for VT

Treatment

Medical Treatment

Orthodromic AVRT

• Hemodynamically Unstable patients (Low BP, Altered mental state, pulmonary edema)- Synchronized DC Cardioversion.
• Hemodynamically stable- Vagal maneuvers, Adenosine, CCB, and DC cardioversion as a last resort only if the patient not responding to medical therapy.

Antidromic AVRT

• Hemodynamically unstable patients:- Urgent synchronized DC cardioversion.
• Hemodynamically stable patients:- Amiodarone, procainamide, or ibutilide.

AF with WPW

• Hemodynamically unstable patients: Urgent synchronized DC cardioversion
• Hemodynamically stable patients:- Procainamide or ibutilide.
• Caution: Adenosine, CCB, Beta blockers enhances conduction via accessory pathway resulting in worsening & possible degeneration into VT or VF

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

For preventing the recurrence of episodes major options available are

• Radio frequency ablation
  • Ablation of accessory pathway tracts
  • cures 95% of the time
• Surgery.
  • Success rate for surgical ablation is around 100 percent along with lower complication rates. Radiofrequency ablation is a less invasive option and preferred over surgery.
  • Surgery can be considered if a patient is undergoing cardiac surgery for other reasons such as CABG or other heart valve surgery.
• Medications
  • Although Medications can prevent recurrent episodes of tachycardia they are only used on patients who are not the candidates for ablation or surgery.
  • These patients must be taught to perform Valsalva maneuvers that can relieve tachycardia during the episodes.