Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

Atrioventricular block may be classified anatomically by the site of block, usually divided into atrioventricular nodal, intra-Hisian (within the His bundle itself), and infra-Hisian (below the His bundle). Paroxysmal AV block is defined as a delayed escape rhythm which repetitively blocks conduction from the atria to the ventricles, thereby causing syncope, conduction defects such as asystole and sudden cardiac death. It may or may not be associated with Phase 3 or Phase 4 conduction defects. It may be due to an increased vagal tone, innately low adenosine levels or an intrinsic conduction defect, all of which lead to different ECG presentations. Insufficient data is available regarding the exact etiology, diagnostic study of choice and treatment of paroxysmal AV blocks. It can be thought of more as a disease of exclusion. However,efforts must be made to have a standardized approach to such patients. The site of block may be clinically important and can be determined by invasive EPS when not apparent from the ECG and clinical circumstances. In general, atrioventricular block at the atrioventricular nodal level is associated with slower progression, a faster and more reliable atrioventricular junctional escape mechanism, and greater responsiveness to autonomic manipulation such as atropine, isoproterenol, and epinephrine administration. In contrast, atrioventricular block within or below the His bundle may progress rapidly and unexpectedly, is associated with a slower and more unpredictable ventricular escape mechanism, will not respond to atropine but will sometimes improve with catecholamines.

One of the first reported cases of paroxysmal AV block was secondary to mitral valvulitis, indicating an intrinsic conduction defect. A similar block was later seen in the Bundle of His, wherein during a hypothesized zone of opportunity, a spontaneous depolarization of conducting fibres was seen. Idiopathic paroxysmal AV block may be diagnosed by a positive response to adenosine triphosphate.

Based on the cause, paroxysmal AV block maybe classified into Intrinsic paroxysmal AV Block, Extrinsic Vagal paroxysmal AV block and Extrinsic Idiopathic paroxysmal AV Block.

Intrinsic paroxysmal AV block (I-AVB) is an AV block secondary to an innate anatomical defect. Given the presence of such a defect it’s prognosis, compared to extrinsic paroxysmal vagal AV block and extrinsic paroxysmal idiopathic AV block is poor. It may have a bradycardia or tachycardia component associated with it and is characterized by atrial/ventricular premature beats prior to the period of asystole. Extrinsic vagal paroxysmal AV Block occurs secondary to an increase in vagal tone. ECG findings reflecting this include sinus rate slowing and increasing PP interval/ PR interval prior to the period of asystole. Individuals with low levels of adenosine are susceptible to sudden surges in adenosine levels which act on the AV node and cause episodes of presyncope or syncope. This would be seen on an ECG as a sudden increase in sinus rate with narrow QRS complexes just prior to the period of asystole.

Intrinsic conduction/ structural defects particularly those located in this intra His Bundle (intrinsic paroxysmal AV block), low adenosine levels (idiopathic paroxysmal AV block) and increase vagal tone/vagal surge (extrinsic vagal paroxysmal AV block) are the major causes of paroxysmal AV block. However, several reversible causes need to be ruled out before coming to a diagnosis.

Considering that a number of conditions may present with a history of syncope and presyncope, paroxysmal AV block must treated as a diagnosis of exclusion. Vasaovagal syncope, situational syncope, carotid sinus hypersensitivity, seizures, structural heart defects such as aortic stenosis, hypertrophic cardiomyopathy and conduction defects such as atrial fibrillation, atrial flutter are a few conditions that need to be ruled out initially.

Exact data reflecting the epidemiology of paroxysmal AV block is unavailable. However certain studies have shown an increased incidence in the elderly, no gender predisposition and an association with bundle branch blocks.

There are no established risk factors for paroxysmal AV Block.

There is insufficient evidence to recommend routine screening for paroxysmal AV Block.

Natural history most commonly includes recurrent unexplained syncope and presyncope. Complications such as sudden cardian death or indefinite periods of asystole may arise. Prognosis of intrinsic paroxysmal AV block is more dire than extrinsic idiopathic paroxysmal AV block or extrinsic vagal paroxysmal AV block.

An initial evaluation strategy of taking a detailed history, physical examination, risk stratification, ECG recording and BP measurement should help decide what investigations should be ordered (based on whether the syncope is cardiac related, reflex/neutrally mediated, secondary to cerebrovascular disease or due to orthostatic hypotension). The majority of patients with paroxysmal AV Block present with presyncope, syncope, with or without a prodrome or are asymptomatic.

Adenosine Plasma levels, adenosine triphosphate stimulation tests and lab values related to potential reversible causes of AV block such as a thyroid profile, electrolyte values,etc are important laboratory investigations.

Electrocardiography is an important initial diagnostic test in diagnosing paroxysmal AV Block. Excercise ECG testing and ambulatory ECG monitoring may be employed.Intrinsic paroxysmal AV block is characterized by atrial premature beats/ventricular premature beats prior to and during the period of asystole. Extrinsic vagal paroxysmal AV block is characterized by sinus rate slowing, increasing PP interval/PR interval prior to the period or asystole. Extrinsic idiopathic paroxysmal AV block is characterized by narrowing of QRS complexes and sinus rate increase prior to the period of asystole.

There are no x-ray findings associated with paroxysmal AV block.

MRI can be helpful in diagnosing infiltrative processes, including sarcoidosis, hemochromatosis, and amyloidosis.

CT offers superior information regarding calcification of cardiac structures and has some advantages in evaluating coronary artery anatomy when epicardial coronary atherosclerotic disease is suspected.

Echocardiography has a highler yield where diagnosing syncope and presyncope is concerned, in patients with structural heart disease.

Cardiac nuclear imaging techniques can be useful to detect and/or discriminate amongst infiltrative cardiomyopathies.

An Implantable Cardiac Monitor is almost exclusively used in the diagnosis of bradycardia related disorders such as high-grade atrioventricular block, sinus node dysfunction and neurocardiogenic syncope (with predominant cardio-inhibitory component). This prolonged monitoring (up to 3 years) can help correlate bradycardia conduction disorders with symptoms. An EPS is an invasive catheter based procedure that is employed to detect and anatomically locate conduction disorders. An increased HH interval is seen in intrinsic paroxysmal AV Block. Certain maneuvers cause an increase in vagal surge and may precipitate symptoms in extrinsic vagal paroxysmal AV block. These include carotid sinus massage and tilt table testing.

In patients with acute onset AV block,reversible causes such as drug toxicity,thyroid dysfunction, Lyme disease, etc should be taken into consideration. A decision should then be made regarding usage of [medical]] therapy or other treatment modalities such as temporary pacing. Theophylline is an adenosine antagonist that may be used in the diagnosis of extrinsic vagal paroxysmal AV Block.

Several studies have demonstrated the efficacy of cardiac pacing in paroxysmal AV block. Temporary pacing should be used for the minimum duration necessary to prevent hemodynamic compromise and asystole. The presence or absence of symptoms and the correlation of those symptoms with a conduction defect is an important determinant of cardiac pacing. An improvement in conduction suggests that the level of the block is at the level of the AV node. Counterpressure maneuvers may be helpful in preventing vagally mediated syncope.

Surgical intervention is not recommended for the management of paroxysmal AV Block.

There are no established measures for the primary prevention of paroxysmal AV Block.

There are no established measures for the secondary prevention of paroxysmal AV Block.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

One of the first reported cases of paroxysmal AV block was secondary to mitral valvulitis, indicating an intrinsic conduction defect. A similar block was later seen in the Bundle of His, wherein during a hypothesized zone of opportunity, a spontaneous depolarization of conducting fibres was seen. Idiopathic paroxysmal AV block may be diagnosed by a positive response to adenosine triphosphate.

• In 1931, Adolph Sachs et al reported one of the first cases on paroxysmal AV block. The patient had presented with multiple spells of palpitations, hot flashes, dizziness, ringing in the ears, weakness and diaphoresis accompanied by convulsions. During an acute episode, he noticed an irregular ventricular rhythm, irregular complexes and given a time interval of 30 seconds, the ventricle would beat once in the first 15 second window and 4-5 times in the succeeding window. It was noticed that the duration of the block progressively increased until it was present all the time. Mitral valvulitis was put down as the cause of the attack and the fact that a response to atropine does not rule out an intrinsic conduction defect was emphasized. “Paroxysmal complete auriculo-ventricular heart-block: A case report – ScienceDirect”.
• In 1972, Philippe Coumel et al hypothesized that the cause of bradycardia/pause dependent AV block was the spontaneous depolarization of specialized conducting fibers in the late stages of diastole. It was during this ‘zone of opportunity’ that they noticed this ‘AV dissociation’. In this case, they found that the block occurred to be proximal to the division of the His bundle. ^[1]
• In 1997. Brignole et al first described EI AVB in a group of 15 syncope patients with an initial negative work up. They fortuitously stumbled upon ECG findings indicating a paroxysmal AV block and reconfirmed this by performing an adenosine triphosphate test in each patient. ^[2]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

Based on the cause, paroxysmal AV block maybe classified into Intrinsic paroxysmal AV Block, Extrinsic Vagal paroxysmal AV block and Extrinsic Idiopathic paroxysmal AV Block.

• Paroxysmal AV Block may be classified according to the cause into three types :

1. Intrinsic AV Block (I-AVB)
2. Extrinsic Vagal AV Block (EV- AVB)
3. Extrinsic Idiopathic AV Block (EI- AVB) “Syncope and paroxysmal atrioventricular block – Aste – 2017 – Journal of Arrhythmia – Wiley Online Library”.

Paroxysmal AV Block classification based on cause

Intrinsic AV Block (I-AVB): Due to innate structural/ conduction defect

Extrinsic Vagal AV Block (EV- AVB): Due to vagal surge/reflex

Extrinsic Idiopathic AV Block (EI- AVB) : Due to innately low adenosine plasma levels

Tachycardia Dependent AV Block (TD- AVB)

Bradcardia/Pause Dependent AV Block (BD- AVB/PD-AVB)

^[1]

Template:WH Template:WS

Intrinsic paroxysmal AV block (I-AVB) is an AV block secondary to an innate anatomical defect. Given the presence of such a defect it’s prognosis, compared to extrinsic paroxysmal vagal AV block and extrinsic paroxysmal idiopathic AV block is poor. It may have a bradycardia or tachycardia component associated with it and is characterized by atrial/ventricular premature beats prior to the period of asystole. Extrinsic vagal paroxysmal AV Block occurs secondary to an increase in vagal tone. ECG findings reflecting this include sinus rate slowing and increasing PP interval/ PR interval prior to the period of asystole. Individuals with low levels of adenosine are susceptible to sudden surges in adenosine levels which act on the AV node and cause episodes of presyncope or syncope. This would be seen on an ECG as a sudden increase in sinus rate with narrow QRS complexes just prior to the period of asystole.

• Intrinsic AV block (I-AVB) is an AV block secondary to an innate anatomical defect.
• It is hugely recognized on an ECG as an atrial premature beat (APB) or ventricular premature beat (VPB) before and after a variable period of complete AV block/asystole.
  • Sinus rate increase/ decrease prior to the VPB/APB or during the period of asystole further divides it into Tachycardia Dependent AV block (TD-AVB) and Pause/Bradycardia dependent AV block (PD- AVB).

• Normal cardiac myocytes are associated with a more negative resting membrane potential, an increased amplitude of action potential and a fast depolarizing sodium current.
• An exact opposite is seen in diseased myocytes responsible for TD- PAVB. An imbalance between inward depolarizing sodium and calcium currents and outward repolarizing potassium currents causes an increase in recovery time and leads to a phenomenon called ‘post-repolarization refractoriness’.
• Despite repolarization being complete, a stimulus would not be able to induce an action potential. ^[1]
• A hypothetical line of thinking that could be attributed to both PD-AVB and TD-AVB is a ‘concealed conduction’ in the intra His Bundle which serves as a source of a delayed escape rhythm, thereby disrupting the refractoriness and recovery time of the surrounding myocytes. This predisposes the patient to fatal complications such as syncope, presyncope, sudden cardiac death and atrial fibrillation with a rapid ventricular response rate.
• Certain studies hypothesize that ventricular or supraventricular impulses reach this ‘concealed conduction’ at a time when there is a local phase 4 block (when sodium channels are inactive.) This subsequent long pause is reflected by the increased H-H interval in EPS studies and confirms an intra His Bundle block (an entity commonly missed and mislabeled as an infra-His Bundle block or AV block on electrophysiological studies) ^[2]
• Much debate surrounds this as it has also been documented that TD- AV/ PD-AV blocks are not related to phase 3 or phase 4 conduction defects, as previously hypothesized. It is related to myocardial ischemia, Mobitz type II block, RBBB and Intra His bundle conduction defects, retrograde ventricular premature beats and anterograde atrial premature beats; all factors that are independent of local phase 4 blocks.

• An extrinsic vagally mediated AV block (EV-AVB) may occur due to a vagal surge or a condition causing an increase in vagal tone such as during tilt table testing, carotid sinus massage, coughing, micturition, defecation, swallowing, myocardial infarction, injection of dypramidole and cardiac transplant rejection.
• It causes SA and AV node slowing and is therefore reflected on the ECG as sinus rate slowing, increasing/irregular PP and PR intervals prior to a period of compete AV block. A heterogenous presentation in terms of Mobitz type I or II and complete heart block may also be noted. This is followed by a period of sinus acceleration.
• Electrophysiological studies indicate a normal H-H interval and therefore it can be assumed that it does not have any effect on conduction in the bundle of His and is not associated with any anatomic involvement, as seen in intrinsic AV Block. ^[3]
• The pathophysiology of EV-AVB may even be related to the autonomic control of the sinus and AV nodes. A parasympathetic predominance over the SA node and sympathetic predominance over the AV node is exerted in a normal autonomic nervous system.
  • A disruption in this regulation may cause parasympathetic bursts and therefore, an AV block. ^[4]
• The effect of vagal stimulation depends on the method and intensity of stimulation and the resting sympathetic activity.
• Vasalva maneuver, carotid sinus massage, water face immersion, tilt table testing may or may not induce an EV- AVB and in some cases a reversal may be seen on atropine administration. “Paroxysmal vagally mediated av block with recurrent syncope – Talwar – 1985 – Clinical Cardiology – Wiley Online Library”.

• The pathogenesis of extrinsic idiopathic paroxysmal AV block (EI-AVB) can be correlated to adenosine plasma levels (APL) and increased affinity of adenosine A1 receptors.
• There is a recurrent history of unexplained syncope, absence of ECG and cardiac abnormalities and a good prognosis.
• Due to innately low APL values seen in these patients, there is an upregulation of A1 receptors, such that even during a mild transient surge in endogenous adenosine levels, AV block occurs.
• A1 receptors, which are present more in the AV node than the SA node, impose an antiadrenergic action by antagonizing β1 receptors, the sympathetic nervous system, hyperpolarizing the SA and AV nodes through potassium channels and lowering intracellular cAMP levels. ^[5]
• Therefore, in such patients an injection of adenosine or adenosine triphosphate (ATP) may reproduce the attack and adenosine antagonists such as theophylline may be an efficacious treatment option.
• On an ECG, there is an absence of signs of vagal stimulation, atrial/ventricular premature beats and there may be a presence of narrow QRS complexes prior to the period of complete AV Block/ asystole
• Certain studies have also noticed genetic polymorphisms in A2A receptors in a population of people experiencing recurrent unexplained syncope. .^[6]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

Intrinsic conduction/ structural defects particularly those located in this intra His Bundle (intrinsic paroxysmal AV block), low adenosine levels (idiopathic paroxysmal AV block) and increase vagal tone/vagal surge (extrinsic vagal paroxysmal AV block) are the major causes of paroxysmal AV block. However, several reversible causes need to be ruled out before coming to a diagnosis.

• Intrinsic conduction/ structural defects particularly those located in this intra His Bundle (intrinsic paroxysmal AV block), low adenosine levels (idiopathic paroxysmal AV block) and increase vagal tone/vagal surge (extrinsic paroxysmal AV block) are the major causes of paroxysmal AV block.
• However, some studies have shown an association of AV nodal blocking agents (beta blockers, calcium channel blockers), degenerative valvular heart disease, degeneration of the conduction system (the His bundle in particular), acute coronary syndromes (inferior /anterior wall myocardial infarction in particular) and paroxysmal AV block.
• Less common causes that have been cited are Lev- Lenegre disease, aneurysmal membranous septum, rheumatic heart disease, mitral valvulitis, sarcoidosis, h/o surgery and infective endocarditis with abscess formation.^[1]
• A study of 20 patients conducted by Zabarski et al found that ischemic heart disease, dilated cardiomyopathy, carotid sinus hypersensitivity, chronic AV blocker consumption and aortic valve replacement were associated paroxysmal AV block.^[2]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

Considering that a number of conditions may present with a history of syncope and presyncope, paroxysmal AV block must treated as a diagnosis of exclusion. Vasaovagal syncope, situational syncope, carotid sinus hypersensitivity, seizures, structural heart defects such as aortic stenosis, hypertrophic cardiomyopathy and conduction defects such as atrial fibrillation, atrial flutter are a few conditions that need to be ruled out initially.

Disease	Findings
Vasaovagal Syncope	Occurs secondary to emotional distress, prolonged standing, painful stimuli. Seen more in women and may be diagnosed by tilt table testing. Not associated with periods of asystole.
Situational Syncope	Due to cardioinhibitory and vasopressor mechanisms. Syncope may be associated with cough, micturition and defecation. Not associated with periods of asystole.
Carotid Sinus hypersensitivity	Common causes of unexplained syncope in individuals more than 40 years of age. Syncope may be associated with wearing shirts with tight collars. Not associated with periods of asystole.
Aortic Stenosis	Presents with syncope, angina and dyspnea on exertion. Not associated with periods of asystole but may show features of left ventricular hypertrophy. On Physical examination,pulsus parvus et tardus may be noted and a systolic click followed by a crescendo decrescendo murmur may be heard over the aortic area.
Hypertrophic Cardiomyopathy	Common cause of sudden cardiac death in adolescents during physical activity. Family history is often present. Not associated with periods of asystole.
1st Degree AV Block	P waves associated with 1:1 atrioventricular conduction and a PR interval >200 ms (this is more accurately defined as atrioventricular delay because no P waves are blocked) [1]
2nd Degree AV Block	P waves with a constant rate (<100 bpm) where atrioventricular conduction is present but not 1:1. Mobitz Type 1: P waves with a constant rate (<100 bpm) with a periodic single nonconducted P wave associated with P waves before and after the nonconducted P wave with inconstant PR intervals. Mobitz Type 2 : P waves with a constant rate (< 100 bpm) with a periodic single nonconducted P wave associated with other P waves before and after the nonconducted P wave with constant PR intervals (excluding 2:1 atrioventricular block) [1]
3rd Degree AV Block	No evidence of atrioventricular conduction. [1]
Atrial Fibrillation	May present with syncope, presyncope, lightheadedness or palpitations. Associated with irregular RR intervals and absence of clearly defined P waves.
Congenital long QT syndrome/ Torsade de pointes	Associated with electrolyte abnormalities such as hypokalemia, hypomagnesemia, hypocalcemia or congenital conditions such as Jervell- Lange- Nielsen Syndrome and Romano Ward Syndrome which may degenerate into a life threatening polymorphic ventricular tachycardia.
Seizures	May be associated with generalized tonic clonic movements, tongue bite, bowel or bladder incontinence, a post ictal state and Todd’s paralysis. Following a loss of consciousness, there is a delayed recovery time.
Others	Atrial Flutter,Subclavian Steal syndrome, Vertebrobasilar Transient Ischemic Attacks, Sick Sinus Syndrome, Psychogenic Pseudosyncope, Psychogenic Non epileptic Seizures.

“ESC Guidelines on Syncope (Diagnosis and Management of)”.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

Exact data reflecting the epidemiology of paroxysmal AV block is unavailable. However certain studies have shown an increased incidence in the elderly, no gender predisposition and an association with bundle branch blocks.

• Given the difficulty in diagnosis, sporadic presentation and sparse literature available, the exact incidence and prevalence of paroxysmal AV block is unknown.

• An unpublished study done at Beth Israel Deaconess Medical Centre in collaboration with a cardiology department in the Netherlands found that paroxysmal AV block was most associated with RBBBs followed by LBBBs, intraventricular conduction delays and normal QRS complexes.
  • An age presentation of 26-99 years of age, an equal incidence in both men and women and an increased prevalence in older individuals were also seen.
  • However, the association between paroxysmal AV block and RBBB is a matter of much debate, as it is not sure whether RBBB causes a direct effect or is a sign seen in an aging population.^[1]

• The ISSUE 2 study was characterised by a population of individuals with a high mean age, a history of recurrent syncope beginning in middle or older ages, and frequent injuries probably due to presentation without warning.^[2]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

There are no established risk factors for paroxysmal AV Block.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

There is insufficient evidence to recommend routine screening for paroxysmal AV Block.

There is insufficient evidence to recommend routine screening for paroxysmal AV Block.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]

Natural history most commonly includes recurrent unexplained syncope and presyncope. Complications such as sudden cardian death or indefinite periods of asystole may arise. Prognosis of intrinsic paroxysmal AV block is more dire than extrinsic idiopathic paroxysmal AV block or extrinsic vagal paroxysmal AV block.

• Paroxysmal AV Block is a poorly defined entity.
• The symptoms of paroxysmal AV block can develop at any age (with some studies suggesting a predominance in older individuals) and presents with symptoms such as recurrent unexplained syncope and presyncope, which further manifests on an ECG as intermittent and progressively increasing periods of asystole.

• Common complications of paroxysmal AV Block include asystole, complete AV Block and sudden cardiac death.
• Complications that can develop as a result of theophylline therapy are nausea, vomiting, abdominal pain, irritability, hallucinations, arrhythmias, acute lung injury and seizures.^[1]
• Complications that can develop as a result of cardiac pacing are procedural, component or biophysical interface related. These include hemothroax, pneumothorax,acute thromboembolism, arrhythmia, pericarditis, device battery failure, pulse generator circuit failure, wound dehiscence, erosion, pain and infection.^[2]

• Given the presence of an innate structural defect, there is an increase risk of progression to complete AV Block in patients with intrinsic AV block. Sparse literature suggest some correlation between length of asystole and increased severity.^[3]
• Given that extrinsic vagally mediated AV block is not associated with an innate conduction defect (seen in intrinsic paroxysmal AV block) and is at the level of the AV node, it is considered benign. ^[4]
• Given the absence of structural heart disease, the paroxysmal nature of the episodes and the low probability of progression into more severe forms of AV block, extrinsic idiopathic paroxysmal AV block has a good prognosis. ^[5]

Template:WH Template:WS