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Atrioventricular conduction abnormalities
Anatomy and physiology of the atrioventricular junction
Internodal and interatrial conduction
Evidence suggests the presence of preferential impulse propagation from the sinus node to the atrioventricular node (AVN)—that is, higher conduction velocity between the nodes in some parts of the atrium than in other parts. However, whether preferential internodal conduction is caused by fiber orientation, size, or geometry or by the presence of specialized preferentially conducting pathways located between the nodes has been controversial. It is believed by many that there are three preferential anatomic conduction pathways from the sinus node to the AVN: anterior, posterior, and middle. However, ultrastructural evidence for discrete bands of rapidly conducting myocytes is sparse, and it is more likely that preferential conduction occurs over muscle bundles and not discrete internodal tracts. These groups of internodal tissue are best referred to as internodal atrial myocardium , not tracts, because they do not appear to be histologically recognizable specialized tracts, only plain atrial myocardium arranged in bundles that promote rapid conduction. Also, detailed electroanatomical activation maps do not reveal more rapidly conducting tracts.
The anterior “internodal atrial myocardium” begins at the anterior margin of the sinus node and curves anteriorly around the superior vena cava to the interatrial septum and then splits into two bundles: one (Bachmann’s bundle) passes to the left atrium (LA), while the second bundle descends along the interatrial septum and connects to the superior margin of the AVN. Bachmann’s bundle is a large, flat muscle bundle that appears to conduct the cardiac impulse preferentially from the right atrium (RA) to the LA. It connects the anterosuperior RA and LA behind the ascending aorta, just beneath the epicardium, and is recognized as the preferential path of LA activation during sinus rhythm. Histologically, Bachmann’s bundle has characteristics of atrial myocardium and is considered the main, but not the exclusive, route of interatrial conduction. Three other interatrial conduction pathways have been described: muscular bundles on the inferior atrial surface near the coronary sinus (CS), transseptal fibers in the fossa ovalis, and posteriorly in the vicinity of the right pulmonary veins.
The middle “internodal atrial myocardium” begins at the superior and posterior margins of the sinus node, travels posteriorly behind the superior vena cava to the crest of the interatrial septum, and descends within the interatrial septum to the superior margin of the AVN. The posterior “internodal atrial myocardium” starts at the inferoposterior margin of the sinus node and travels inferiorly through the crista terminalis to the Eustachian ridge and then into the interatrial septum above the CS ostium, where it joins the posterior portion of the AVN. Some fibers from all three pathways bypass the crest of the AVN and enter its more distal segment.
Central fibrous body
The cardiac skeleton consists of four rings of dense connective tissue that surround the atrioventricular (AV) canals (mitral and tricuspid) and extends to the origins of the aorta and the pulmonary trunk. The aortic valve occupies the central position with the other valve rings attached to it. The triangular formation between the aortic valve and the medial parts of the tricuspid and mitral valves is the right fibrous trigone, which is a dense accretion of fibrous tissue and represents the largest thickening and strongest portion of the cardiac skeleton. The right fibrous trigone, together with the membranous septum, constitutes the central fibrous body.
The membranous septum is an inferior extension of the central fibrous body that attaches to the muscular interventricular septum. The membranous septum is formed between the commissure between the septal and anterior leaflets of the tricuspid valve (on the right side) and the commissure between the right and noncoronary cusps of the aortic valve (on the left side). The membranous septum is crossed on its right aspect by the attachment of the tricuspid valve, dividing the membranous septum into two components: a pretricuspid atrioventricular component (which separates the RA from the left ventricle [LV]) and a posttricuspid interventricular component (which separates the right ventricle [RV] from the LV). The latter component can be covered by valve tissues or there can be a gap in the leaflet ( Fig. 10.1 ). ,
Another junction between the mitral annulus and aortic valvular ring occurs at the left fibrous trigone, anchoring the anteromedial aspect of the mitral annulus to the base of the left coronary cusp. The left fibrous trigone is less substantial than the right fibrous trigone. Between the left and right fibrous trigones, a rigid and broad fibrous curtain (often referred to as the aortic curtain) extends across the anterior leaflet of the mitral valve and supports the aortic valve leaflets. The aortomitral continuity refers to a fibrous continuity of the medial part of the noncoronary and left coronary sinuses and the anterior mitral leaflet.
The tendon of Todaro is a fibrous band that connects to the central fibrous body as a fibrous extension of the membranous septum. It courses obliquely between the fossa ovalis and the CS ostium, crossing the Eustachian ridge in the floor of the RA, and connecting to the valve of the inferior vena cava (Eustachian valve).
The electrically inert central body and skeleton of the heart functions to electrically isolate the atria from the ventricles, except at the site of penetration of the AV conducting system.
Triangle of Koch
The triangle of Koch constitutes the endocardial surface of the region of the lower RA septum. It is bordered anteriorly by the insertion of the septal leaflet of the tricuspid valve and posteriorly by the fibrous tendon of Todaro. The apex of the triangle is formed by the junction of these two boundaries. The base of the triangle is formed by the anteromedial edge of the CS ostium and is continuous with the sub-Eustachian pouch ( Fig. 10.2 ).
Of note, the interatrial sulcus is displaced to the far left of the interventricular sulcus, and the AV valves are not isoplanar; the attachment of the septal leaflet of the tricuspid valve into the most anterior part of the central fibrous body is displaced a few millimeters apically relative to the attachment of the septal leaflet of the mitral valve. As a result, the true septal part of the AV junction (the RA-LV sulcus) actually separates the inferomedial RA from the posterior superior process of the LV (the right side is above the tricuspid valve while the left side is below the mitral valve). Hence, the triangle of Koch can be considered the RA side of the AV muscular septum.
Atrioventricular node
The AVN is an interatrial structure, measuring approximately 5 mm long, 5 mm wide, and 0.8 mm thick in adults. The AVN is located beneath the RA endocardium at the apex of the triangle of Koch, anterior to the CS ostium and directly above the insertion of the septal leaflet of the tricuspid valve, where the tendon of Todaro merges with the central fibrous body. Slightly more anteriorly and superiorly is where the His bundle (HB) penetrates the AV junction through the central fibrous body and the posterior aspect of the membranous AV septum. The compact AVN is adjacent to the central fibrous body on one side but is uninsulated by fibrous tissue on its other sides, thus allowing contiguity with the atrial myocardium. When traced inferiorly, toward the base of the triangle of Koch, the compact AVN area separates into two (rightward and leftward) posterior extensions, usually with the artery supplying the AVN running between them. These prongs bifurcate toward the tricuspid and mitral annuli, respectively. The rightward posterior extension has been implicated in the so-called slow pathway in the typical AVN reentrant tachycardia circuit.
The normal AV junctional area can be divided into distinct regions: the transitional cell zone (which represents the approaches from the working atrial myocardium to the AVN), the compact AVN, and the penetrating part of the HB. The AVN and perinodal area are composed of at least three electrophysiologically distinct cells: the atrionodal (AN), nodal (N), and nodal-His (NH) cells. The AN region corresponds to the cells in the transitional region that are activated shortly after the atrial cells. The N region corresponds to the region where the transitional cells merge with midnodal cells. The N cells represent the most typical of the nodal cells, which are smaller than atrial myocytes, are closely grouped, and frequently are arranged in an interweaving fashion. Sodium (Na + ) channel density is lower in the midnodal zone of the AVN than in the AN and NH cell zones, and the inward L-type calcium (Ca 2+ ) current is the basis of the upstroke of the N cell action potential. Therefore, conduction is slower through the N-region in the compact AVN than in the AN and NH cell zones. Additionally, the N cells exhibit diastolic depolarization and are capable of automatic impulse formation. The N cells in the compact AVN appear to be responsible for the major part of AV conduction delay and exhibit decremental properties in response to premature stimulation because of their slow-rising and longer action potentials. They are likely the site of Wenckebach block and the site at which calcium channel blockers delay AV conduction. Fast pathway conduction through the AVN apparently bypasses many of the N cells by transitional cells, whereas slow pathway conduction traverses the entire compact AVN. Importantly, the recovery of excitability after conduction of an impulse is faster for the slow pathway than for the fast pathway, for reasons that are unclear. The NH region corresponds to the lower nodal cells, typically distal to the site of Wenckebach block, connecting to the insulated penetrating portion of the HB. The action potentials of the NH cells are closer in appearance to the fast-rising and long action potentials of the HB.
The AVN is the only normal electrical connection between the atria and the ventricles; the fibrous skeleton acts as an insulator to prevent electrical impulses from entering the ventricles by any other route. The main function of the AVN is modulation of atrial impulse transmission to the ventricles; it introduces a delay between atrial and ventricular systole, thereby allowing atrial systole and ventricular filling to complete prior to initiation of ventricular systole. Another primary function of the AVN is to limit the number of impulses conducted from the atria to the ventricles. This function is particularly important during fast atrial rates (e.g., during atrial fibrillation [AF] or atrial flutter), in which only a portion of impulses are conducted to the ventricles, and the remaining impulses are blocked in the AVN. Additionally, fibers in the lower part of the AVN can exhibit automatic impulse formation, serving as a subsidiary pacemaker.
The AVN region is innervated by a rich supply of cholinergic and adrenergic fibers. Sympathetic stimulation shortens AVN conduction time and refractoriness, whereas vagal stimulation prolongs AVN conduction time and refractoriness. The negative dromotropic response of the AVN to vagal stimulation is mediated by activation of the inwardly rectifying potassium (K + ) current (I KACh ), which results in hyperpolarization and action potential shortening of AVN cells, increased threshold of excitation, depression of action potential amplitude, and prolonged conduction time. The positive dromotropic effect of sympathetic stimulation arises as a consequence of activation of the L-type Ca 2+ current.
The blood supply to the AVN predominantly comes via the AV nodal artery, a branch of the right coronary artery in about 90% of hearts and from the circumflex artery in 10%.
His bundle
The HB connects with the distal part of the compact AVN and penetrates the central fibrous body (where it is called the “nonbranching” or “penetrating” bundle) in a leftward direction (away from the RA endocardium and toward the crest of the muscular interventricular septum). The HB then emerges on the crest of the ventricular septum and continues sandwiched between the muscular and the membranous components of the septum for 1 to 2 cm before dividing into the right and left bundle branches.
Viewed from the aorta, the HB passes beneath the part of the membranous septum that adjoins the interleaflet fibrous triangle between the right and noncoronary sinuses. The HB is insulated from the atrial myocardium by the membranous septum and from the ventricular myocardium by connective tissue of the central fibrous body, thus preventing atrial impulses from bypassing the AVN. Proximal cells of the penetrating portion of the HB are heterogeneous and resemble those of the compact AVN; distal cells are larger, similar to cells in the proximal bundle branches and ventricular myocytes.
The HB is supplied by the AV nodal artery and the first septal branch of the left anterior descending artery. The dual blood supply makes the conduction system at this site less vulnerable to ischemic damage unless the ischemia is extensive.
The AVN and the HB region are innervated by a rich supply of cholinergic and adrenergic fibers, with a density exceeding that found in the ventricular myocardium. Although neither sympathetic stimulation nor vagal stimulation affects normal conduction in the HB, either can affect abnormal AV conduction.
Pathophysiology of atrioventricular block
Block or delay of a cardiac impulse can take place anywhere in the heart, or even within a single cell. AV block can be defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles caused by an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent ( Table 10.1 ).
TABLE 10.1
Causes of Atrioventricular Block
| Congenital |
| Associated with neonatal lupus |
| Associated congenital heart defects |
| Hereditary Progressive Cardiac Conduction Disease |
| Neuropathies |
| Becker muscular dystrophy |
| Peroneal muscular dystrophy |
| Kearns-Sayre syndrome |
| Erb dystrophy |
| Myotonic muscular dystrophy |
| Ischemic |
| Myocardial infarction |
| Myocardial ischemia |
| Degenerative |
| Lev disease |
| Lenègre disease |
| Calcification of the aortic mitral valve annulus |
| Autonomic (Vagal) |
| High-level athletic conditioning |
| Neurocardiogenic |
| Hypersensitive carotid sinus syndrome |
| Sleep |
| Obstructive sleep apnea |
| Infectious |
| Bacterial endocarditis with perivalvular abscess |
| Lyme disease |
| Chagas disease |
| Acute rheumatic fever |
| Tuberculosis |
| Measles |
| Mumps |
| Toxoplasmosis |
| Infiltrative |
| Cardiac sarcoidosis |
| Amyloidosis |
| Hemochromatosis |
| Cardiac tumors |
| Rheumatic Diseases |
| Rheumatoid arthritis |
| Scleroderma |
| Reiter syndrome |
| Systemic lupus erythematosus |
| Ankylosing spondylitis |
| Polymyositis |
| Polyarteritis nodosa |
| Wegener granulomatosis |
| Metabolic/Endocrine |
| Hyperthyroidism |
| Hypothyroidism |
| Pheochromocytoma |
| Adrenal insufficiency |
| Acid-base disorders |
| Hypermagnesemia |
| Hyperkalemia |
| Drugs |
| Beta-blockers |
| Calcium channel blockers (verapamil, diltiazem) |
| Digoxin |
| Antiarrhythmic drugs (class I and III) |
| Adenosine |
| Clonidine |
| Iatrogenic |
| Catheter ablation |
| Cardiac surgery |
| Transcatheter aortic valve replacement |
| Alcohol septal ablation |
| Poisoning |
| Carbon monoxide |
| Mercury |
| Cyanide |
Congenital and inherited atrioventricular block
Congenital atrioventricular block
Congenital complete AV block is thought to result from embryonic maldevelopment of the AVN (and, much less frequently, the His-Purkinje system [HPS]), resulting in a lack of connection between the atria and the peripheral conduction system, with fatty replacement of the AVN and nodal approaches. The incidence of congenital complete AV block varies from 1 in 15,000 to 1 in 22,000 live births. The defect usually occurs proximal to the HB and is associated with a stable escape rhythm (>60 beats/min) with a narrow QRS complex.
In 60% to 90% of cases, congenital AV block is associated with neonatal lupus caused by passively acquired autoimmune disease in which maternal autoantibodies to the intracellular ribonucleoproteins Ro (SS-A) and La (SS-B) cross the placenta and injure the previously normal fetal heart. These antibodies can be seen with subclinical or clinical maternal lupus erythematosus, maternal Sjögren syndrome, and other maternal autoimmune diseases. The exact mechanism by which these autoantibodies can cause AV block or other cardiac abnormalities remains uncertain. Involvement of the AV conduction system produces different degrees of AV block. While first-degree AV delay can be transient, complete AV block is irreversible. The risk of the fetus developing congenital AV block in a single anti-Ro– or anti-La–positive pregnancy is relatively low (1%–2%), but the risk in the same mother increases significantly (12%–20%) in subsequent pregnancies. Although the severity of AV block can vary, most cases diagnosed in utero present with second- or third-degree block.
Approximately one-third of patients with congenital AV block have concurrent congenital heart disease (e.g., congenitally corrected transposition of the great vessels, AV discordance, ventricular septal defects, AV canal defects, tricuspid atresia, anomalous left coronary artery arising from the pulmonary artery, or Ebstein anomaly of the tricuspid valve). The AV conduction system can be displaced if atrial and ventricular septa are malaligned, AV arrangements are discordant, or the heart is univentricular. Generally, if the AV conduction system is displaced, it will also tend to be more fragile and susceptible to degeneration, thus placing patients at greater risk for AV block.
Familial progressive cardiac conduction disease
The term progressive cardiac conduction disease encompasses disease forms with either hereditary or acquired nature, which can occur with or without concomitant structural heart disease. Progressive cardiac conduction disorder is often a primarily genetic disorder that usually presents as an isolated condition but can also overlap or coexist with other inherited heart diseases or manifest in the context of multisystem syndromes such as Andersen-Tawil syndrome (periodic paralysis), Holt-Oram syndrome (upper limb skeletal abnormalities), and Emery-Dreifuss muscular dystrophy (muscular dystrophy).
Familial progressive cardiac conduction disease (in the absence of systemic, structural, and congenital heart disease) usually results from mutations in genes encoding cardiac ion channels ( HCN4 , SCN5A , TRPM4 , SCN1B ), membrane adaptor proteins ( ANK2 ), transcription factors ( NKX2 -5, TBX5 , GATA4 ), components of the inner nuclear membrane ( LMNA , EMD ), and Cx40 ( GJA5 ), which all regulate action potential generation and propagation (see Chapter 3 ). On the other hand, progressive cardiac conduction disease in the context of structural heart disease is usually caused by mutations in genes encoding transcriptional factors, enzymes, or structural proteins. Disease can occur at any level of the cardiac conduction system and can manifest as sinoatrial exit block, AV block, or bundle branch block (BBB).
Loss-of-function mutations in the SCN5A gene (encoding the α-subunit of the cardiac Na + channel) cause the majority of familial forms of progressive cardiac conduction disease (referred to as hereditary Lenègre disease, primary cardiac conduction system disease, and familial AV block). This disease is characterized by slowing of electrical conduction through the atria, AVN, HB, Purkinje fibers, and ventricles, accompanied by an age-related degenerative process and fibrosis of the cardiac conduction system, in the absence of structural or systemic disease. It is often reflected by varying degrees of AV block and BBB. A single loss-of-function SCN5A mutation can cause isolated progressive cardiac conduction disease or can be combined with the Brugada syndrome (overlap syndrome). Furthermore, loss-of-function mutations in the SCN1B gene (encoding the β1 and β1b subunits of the Na + channel) have been identified in patients with progressive cardiac conduction disease who carried no mutation in SCN5A .
Mutations in the gene TRPM4 gene (encoding the calcium-activated nonselective cation channel of the transient receptor potential melastatin, which is highly expressed in cardiac Purkinje fibers) have been associated with isolated progressive cardiac conduction block. Another channelopathy that has been associated with conduction system disorders is the LQT7, or Andersen-Tawil syndrome, caused by mutations in the KCNJ2 gene (encoding the inward rectifier Kir2.1, a critical component of the cardiac inward K + rectifier current, IK1). Additionally, mutations in the PRKAG2 gene (encoding the γ2 regulatory subunit of adenosine monophosphate–activated protein kinase) have been described in patients with Wolff-Parkinson-White syndrome and AV conduction block. Furthermore, mutations in GJA5 gene (encoding for connexin-40 protein) have been linked to progressive familial heart block and malignant ventricular arrhythmias.
Neuromyopathies
Neuromuscular disorders represent a diverse collection of inherited diseases affecting skeletal muscle, frequently caused by mutations in genes encoding cytoskeletal, nuclear envelope (e.g., lamin A/C and emerin), or mitochondrial proteins. Cardiac involvement is common and usually manifests as dilated or hypertrophic cardiomyopathy, AV conduction abnormalities, and atrial and ventricular dysrhythmias. AV conduction disturbances are usually the major cardiac manifestation of Becker muscular dystrophy, peroneal muscular dystrophy, Kearns-Sayre syndrome, Erb dystrophy, and myotonic muscular dystrophy. Progression of AV block is unpredictable and can be an important cause of mortality in such cases.
Long QT syndrome
In long QT syndrome (LQTS) with a very long QT interval (e.g., in LQT2, LQT3, LQT8, and LQT9), functional block between the HB and ventricular muscle caused by prolonged ventricular refractoriness can lead to 2:1 AV block and severe bradycardia. Additionally, conduction abnormalities of the HPS, including PR prolongation and right BBB (RBBB) or left BBB (LBBB), can occur in some patients with LQTS.
Acquired atrioventricular block
Drugs
Various drugs can impair conduction and cause AV block. Digoxin and beta-blockers act primarily indirectly on the AVN through their effects on the autonomic nervous system. Calcium channel blockers and other antiarrhythmic drugs, such as amiodarone and dronedarone, act directly to slow conduction in the AVN. Class I and III antiarrhythmic drugs can also affect conduction in the HPS and cause infranodal block. These effects, however, typically occur in patients with preexisting conduction abnormalities. Patients with a normal conduction system function rarely develop complete heart block as a result of using antiarrhythmic agents. Other agents that can produce AV conduction disturbances include clonidine, lithium (in toxic concentrations), and fingolimod (usually transient).
Ischemic heart disease
AV block occurs in 12% to 25% of all patients with acute ST-elevation myocardial infarction (MI); first-degree AV delay occurs in 2% to 12%, second-degree AV block occurs in 3% to 10%, and third-degree AV block occurs in 3% to 7%.
First-degree AV delay and type 1 second-degree (Wenckebach) AV block occur more commonly in inferior MI, usually caused by increased vagal tone (Bezold-Jarisch reflex), rather than direct nodal ischemia, and generally associated with other signs of vagotonia, such as sinus bradycardia and responsiveness to atropine and catecholamine stimulation. Wenckebach AV block in the setting of acute inferior MI is usually transient (resolving within 48–72 hours of onset) and asymptomatic and rarely progresses to more advanced degrees of AV block. Wenckebach AV block occurring later in the course of acute inferior MI is less responsive to atropine and probably is associated with ischemia of the AVN.
Type 2 second-degree (Mobitz type II) AV block occurs in only 1% of patients with acute MI (more commonly in anterior than inferior MI) and has a worse prognosis than type 1 second-degree AV block. Type 2 second-degree AV block occurring during acute anterior MI is typically associated with HB or bundle branch ischemia or infarction and frequently progresses to complete heart block.
The incidence of new-onset, high-grade AV block in patients complicating ST elevation MI has decreased in the reperfusion era from 5% to 7% with thrombolytic therapy to 2.2% with primary percutaneous coronary intervention. The risk is even less in non-ST elevation MI. Predictors of AV block in acute MI patients include older age, female gender, inferior acute MI, prior MI, smoking, hypertension, and diabetes. Furthermore, the risk is two to four times higher in acute inferior MI as compared to anterior MI (9.4% versus 2.5% in the thrombolytic era). In patients undergoing primary percutaneous coronary intervention, the incidence of high-grade AV block is about 7% when the culprit lesion is in the right coronary artery, compared to 1% when the culprit lesion is in the left anterior descending artery.
High-degree AV block complicating acute MI is an ominous prognostic marker and is independently associated with three times higher in-hospital and 30-day mortality as compared to those with preserved AV conduction, irrespective of the site of the infarction or LV function. This markedly adverse prognostic impact of high-grade AV block has not been reduced by primary percutaneous coronary intervention as compared to thrombolytic therapy or even to prethrombolytic era. The negative prognostic impact of complete AV block is greater in patients with anterior than in patients with inferior ST elevation MI. The risk of death is higher in patients with occlusion of the left anterior descending artery as compared to those with right coronary artery occlusion (55% versus 36%). Importantly, AV block itself is not responsible for the increased mortality but rather is a marker for a more extensive infarct size. Similar to observations from the prethrombolytic era, the occurrence of high-degree AV block during acute MI has no impact on 1-year mortality among 30-day survivors. Of note, new-onset intraventricular conduction disturbances complicate 10% to 20% of anterior MI (with or without AV block) and are usually associated with high mortality due to the associated extensive myocardial necrosis (rather than the conduction disturbance).
High-grade AV block develops upon hospital admission in more than half of patients with this complication, and within 48 hours after admission in the majority of patients. The block is typically transient and most often resolves spontaneously within a few days or weeks, with only 9% of these patients requiring pacemaker implantation prior to hospital discharge.
Of note, in the thrombolytic era, thrombolytic therapy frequently precipitated transient AV block, likely due to enhanced vagal tone secondary to reperfusion. Whether this effect is different when reperfusion is achieved by intracoronary stenting is unknown.
Acute inferior myocardial infarction
In the setting of acute right coronary artery occlusion, AV block is almost always (90% of cases) located above the HB. The block often progresses gradually (from first-degree, to type 1 second-degree, to complete AV block) and is associated with a junctional escape rhythm with a narrow QRS complex (in 70% of cases) and a rate of 40 to 60 beats/min. Complete AV block occurring in the early phase of acute inferior MI (within 6 hours of onset of symptoms) is more likely related to enhanced vagal tone, tends to be reversed by vagolytic drugs or catecholamines, and usually resolves within several days. In contrast, AV block developing later in the course of acute inferior MI tends to be more persistent and is more likely related to ischemia of the AVN (hypoperfusion of the AVN artery). Small areas of focal necrosis can occur; however, complete infarction and necrosis of the AVN or occlusion of the AVN artery are rare.
Acute anterior myocardial infarction
Development of complete AV block in the setting of acute anterior MI is usually a marker of a large infarct area and, hence, is commonly associated with a higher risk of ventricular tachycardia (VT) and ventricular fibrillation, hypotension, pulmonary edema, and in-hospital mortality. Frequently, these patients have extensive infarction of the septum and anterior wall in the presence of severe multivessel disease involving both the left anterior descending artery and the right or a dominant left circumflex coronary artery.
In the setting of anterior MI, AV block is most often located below the AVN and is usually associated with ischemia or infarction of the HB or bundle branches (related to interruption of septal perfusion) and is less likely to be reversible. Complete AV block during acute anterior MI generally occurs abruptly during the first 24 hours after MI and often is preceded by the development of a new RBBB, fascicular block, or type 2 second-degree AV block. The escape rhythm usually originates from a bundle branch and more distal Purkinje system, with a rate of less than 40 beats/ min and a wide QRS complex, with higher risk of ventricular asystole in the event of failure of the escape pacemaker.
Chronic ischemic heart disease
Chronic ischemic heart disease, with or without infarction, can result in persistent AV block secondary to fibrotic changes in the bifurcating HB and bundle branches. Transient AV block can occasionally occur during angina pectoris whether due to atherosclerosis or spasm in relatively normal caliber vessels (Prinzmetal angina).
Degenerative diseases
Fibrosis and sclerosis of the conduction system are the most common causes of acquired conduction system disease. These disorders account for approximately half the cases of AV block in adults and can be induced by several different conditions, which often cannot be distinguished clinically.
Progressive cardiac conduction disease (including Lev disease or Lenègre disease) manifests as progressive slowing of electrical conduction through the atria, AVN, HB, Purkinje fibers, and ventricles, accompanied by an age-related degenerative process, in which fibrosis affects only the cardiac conduction system. Complete AV block can develop and cause syncope or sudden death. Lev’s disease is a result of proximal bundle branch calcification or fibrosis and is often described as senile degeneration of the conduction system. Its postulated cause is a hastening of the aging process by hypertension and arteriosclerosis of the blood vessels supplying the conduction system. Lenègre disease is a sclerodegenerative process that occurs in a younger population and involves the more distal portions of the bundle branches. As noted, an inherited form of progressive cardiac conduction disease has been identified, whereby conduction slowing may be attributed to loss-of-function mutations in the SCN5A gene. Whether the age-dependent fibrosis of the conduction system is a primary degenerative process in progressive cardiac conduction disease or a physiological process that is accelerated by I Na reduction remains to be investigated.
Calcification of the aortic or (less commonly) mitral valve annulus can extend to the nearby conduction system and produce AV block. As noted, the HB penetrates the central fibrous body adjacent to the fibrous continuity between the aortic and mitral valves that is the usual site of dystrophic calcification, and extension of calcification can directly involve the HB and the origin of the left bundle branch.
Rheumatic diseases
AV block can occur in association with collagen vascular diseases such as scleroderma, rheumatoid arthritis, Reiter syndrome, systemic lupus erythematosus, ankylosing spondylitis, and polymyositis. Polyarteritis nodosa and Wegener granulomatosis also can cause AV block.
Infectious diseases
Infective endocarditis (especially of the aortic valve) and myocarditis of various viral, bacterial, and parasitic causes (including Lyme disease, Chagas disease, rheumatic fever, tuberculosis, measles, and mumps) can cause varying degrees of AV block.
In the setting of infective endocarditis, AV block and BBB can develop due to perivalvular extension complicating aortic valve involvement and typically predict poor prognosis. Lyme disease involves the heart in 1% to 2% of cases. AV block (ranging from asymptomatic first-degree AV delay to complete AV block, typically intranodal) is the most common manifestation of Lyme carditis. The degree of AV block can fluctuate rapidly over minutes to hours and days. In the majority of patients, AV block is a transient phenomenon and almost always resolves completely within 1 to 6 weeks. Resolution of AV block is usually gradual, from complete heart block to Wenckebach AV block, to first-degree AV delay. Although temporary pacing can be required in approximately 40% of patients who are identified clinically, implantation of a permanent pacemaker is not recommended. Hence, Lyme disease should be excluded prior to considering permanent pacemaker implantation in young patients in endemic areas who present with complete AV block. In Chagas disease, conduction system abnormalities, most frequently RBBB or left anterior fascicular (LAF) block, and various degrees of AV block are observed in about 36% of patients. Complete AV block can develop in more than 8% and is correlated with increased mortality.
Infiltrative processes
Infiltrative cardiomyopathies such as amyloidosis, sarcoidosis, hemochromatosis, and tumors can be associated with AV block. Cardiac involvement occurs in more than 25% of the patients with pulmonary/systemic sarcoidosis but frequently remains asymptomatic. Symptomatic cardiac involvement occurs in about 5% of sarcoidosis patients. Various conduction abnormalities can develop as a result of granulomatous infiltration (with inflammation and subsequent scarring) of the basal interventricular septum and conduction system or involvement of the nodal artery causing ischemia in the conduction system. BBB (more commonly RBBB) has been observed in 12% to 32% of cases of cardiac sarcoidosis, and complete AV block in 23% to 30%. AV block can manifest early or late in the course of the disease and occasionally can be the first clinical manifestation of sarcoidosis involving any organ. In early stages, before scar formation, AV block can be reversible with immunosuppression therapy. However, permanent pacing is frequently required. In these patients, since AV block likely signifies extensive cardiac disease and portends a higher risk of future ventricular arrhythmias, implantation of an ICD (for the primary prevention of sudden cardiac death) instead of a pacemaker needs to be considered, regardless of LV ejection fraction or prior occurrence of ventricular arrhythmias. Cardiac sarcoidosis should be suspected in young patients (especially African Americans) who present with complete AV block, even in those who do not carry a previous diagnosis of extracardiac sarcoidosis.
Atrioventricular block in athletes
AV block occurs in highly conditioned athletes, probably an expression of hypervagotonia related to physical training, and is usually correlated to type and intensity of training. First-degree AV delay has been observed in up to 40% of athletes, and type 1 second-degree block in up to 22%. Other signs of hypervagotonia (e.g., sinus bradycardia, respiratory sinus arrhythmia, wandering pacemaker, and junctional bradycardia) are also more common in this population, but AV block can develop without significant sinus bradycardia because the relative effects of sympathetic and parasympathetic systems on the AVN and sinus node can differ. First-degree and Wenckebach AV block in athletes is usually benign and asymptomatic, resolves with aerobic exercise (as vagal tone is withdrawn), and frequently disappears or decreases after deconditioning. Therefore, further diagnostic evaluation is not required. In contrast, AV block that does not respond to exercise or atropine and type II second-degree and complete AV block are rare in athletes, and their presence should prompt careful evaluation and management.
Iatrogenic atrioventricular block
Cardiac catheterization
Intracardiac catheter manipulation can inadvertently produce varying degrees of heart block, which is usually temporary. Complete heart block can occur during right-sided heart catheterization in a patient with preexisting LBBB ( eFig. 10.1 ), or during LV catheterization (LV angiography or ablation procedures) in a patient with preexisting RBBB. Catheter trauma has been reported to cause AV nodal block as well as block in each of the fascicles of the conduction system; while most blocks are transient, catheter-induced LBBB may persist.
Catheter ablation
AV block can be a complication of catheter ablation of AVN reentrant tachycardia, bypass tracts, and atrial tachycardias in the AVN vicinity, as well as VTs originating in the interventricular septum adjacent to the HB. Rarely, ablation on the left side of the interatrial septum can damage AVN conduction.
Cardiac surgery
Cardiac surgery can be complicated by varying degrees of AV block caused by trauma and ischemic damage to the conduction system. Mechanical trauma to the conduction system is more common in valvular surgeries, septal myectomy for hypertrophic cardiomyopathy, or repair of basal ventricular septal defect. Ischemic injury can occur as a result of inadequate myocardial protection during surgery. Not infrequently, the block is temporary and is thought to be secondary to postoperative local inflammation. However, AV block can appear years later, usually in patients who had transient block just after the operation.
AV block occurs with an overall incidence of 1% to 3% after surgical procedures for congenital heart disease and 0.8% to 2.1% after noncongenital cardiac surgeries. Significant risk factors for high-degree AV block include older age, preoperative AV and intraventricular conduction abnormalities, AF, valvular surgery (except pulmonic), and cardiopulmonary bypass time. Congenital heart disease substrates associated with a relatively high prevalence of postoperative AV block include displaced AV conduction systems (congenitally corrected transposition of the great arteries, AV septal defects), ventricular septal defect, and subaortic stenosis. AV block resolves within 7 to 10 days in 50% of patients.
Complete or high-degree AV block requiring permanent pacing complicates approximately 0.6% of coronary bypass surgeries and 4.5% of cardiac transplant surgeries. In patients with obstructive hypertrophic cardiomyopathy, persistent AV block complicates 10% to 33% of septal alcohol ablation procedures and 2% to 4% of surgical myectomy. Of note, AV block can initially manifest more than 48 hours after alcohol septal ablation in up to 9% of patients. Late development of AV block after surgical myectomy has not been reported.
In patients undergoing cardiac valve surgery, the risk of complete or high-degree AV block requiring permanent pacing varies widely and depends on the type of valve surgery and concomitant procedures. The incidence of AV block following surgical aortic valve replacement is about 6% to 7%. The close anatomical proximity of the aortic valve annulus, AVN, and HB makes the AV conduction system especially vulnerable to injury during prosthetic aortic valve procedures. In contrast, the risk is significantly lower following surgical replacement of the mitral valve. The mitral valve lies in close proximity to the AVN artery, suggesting that damage to the artery may play a role in the development of AV block after mitral valve surgery, as opposed to injury to the HB during aortic valve surgery. This risk is even lower when mitral repair rather than replacement is performed; an incomplete annuloplasty band could avoid injury to the AVN artery.
The AVN is located between its anterior and septal leaflets of the tricuspid valve, rendering it particularly prone to injury with any tricuspid valve intervention. The risk of AVN trauma can be reduced with contemporary surgical techniques, such as the design of several incomplete tricuspid rings that have gaps between the anterior and septal leaflets and avoid suture placement in the area of the AVN. Nonetheless, the risk of AV block remains a significant following tricuspid valve surgery.
In a recent report, the 1-year pacemaker implantation rate (for AV block sinus node dysfunction indications) was 4.5% after mitral valve repair, 6.6% after aortic valve replacement, 9.3% after aortic valve replacement plus mitral valve repair, 10.5% after mitral valve replacement, and 13.3% after combined aortic and mitral valve replacement. Moreover, concomitant procedures including surgical AF ablation and tricuspid intervention significantly increased the risk for pacemaker implantation.
Transcatheter aortic valve replacement
The risk of high-grade AV block requiring pacemaker implantation post transcatheter aortic valve replacement (TAVR) is estimated at 4% to 20%. The deployed valve can cause direct damage to the AVN and/or HB and infra-Hisian conduction system, leading to transient or permanent AV and intraventricular conduction disturbances. Several clinical, anatomic, and procedure-related factors have been correlated with an increased risk of postprocedural conduction disturbances. The presence of preexisting RBBB has the strongest correlation for pacemaker after TAVR, likely due to the vulnerability of the left bundle (LB) to damage from the valve deployment due to its close proximity to the interleaflet triangle separating the noncoronary and right coronary cusps of the aortic valve. Preexisting LBBB has not been shown to consistently predict pacemaker implantation. Other predictors include preexisting LAF block, first-degree AV delay, increasing age, and male gender. Also, the development of intraprocedural AV block is an important predictor of high risk.
Although old data showed higher risk of pacemaker with self-expanding or mechanically expanding devices over balloon-expandable devices, recent evidence showed that pacemaker rates with newer generation valves are comparable. Nonetheless, a larger implanted valve size relative to LV outflow diameter can potentially lead to greater compression of the intrinsic conduction system, increasing the need for pacemaker requirement. Recently, the assessment of the length of the membranous septum (i.e., the distance between the aortic valve annular plane and the HB) on pre-TAVR computed tomography has been gaining interest. A shorter membranous septum length was associated with increased pacemaker rates after TAVR. Specifically, the most inferior portion of the membranous septum serves as the exit point for the HB, and compression of this area is associated with higher pacemaker implantation rates ( Fig. 10.1 ). Hence, in patients with considerable tapering of the LV outflow tract just below the aortic annulus, at risk of juxtaposing the entire membranous septum with valve deployment, and/or considerable calcium under the noncoronary cusp, a higher valve implantation depths should be considered.
Other causes of atrioventricular block
AV block can also occur in a variety of other disorders including hyperkalemia, hypermagnesemia, hyperthyroidism, myxedema, and Addison’s disease.
Paroxysmal atrioventricular block
Three forms of paroxysmal AV block have been described: vagally mediated AV block, intrinsic AV block, and idiopathic AV block.
Paroxysmal vagally mediated atrioventricular block
Vagally mediated AV block is a paroxysmal form of AV block induced by surges of vagal discharge. It occurs in patients with or without heart disease, most of them with no prior evidence of AV or intraventricular conduction abnormalities. AV block is localized within the AVN, is associated with a narrow QRS escape rhythm, and is generally benign.
The prevalence of vagally mediated AV block is unknown. Not infrequently, it is accidentally encountered as an asymptomatic event during cardiac monitoring, occurring more often during the night (commonly, but not always, precipitated by nocturnal apnea), and in most cases without ventricular asystole. However, prolonged ventricular pauses are common during syncope, typically preceded by identifiable triggering and predisposing factors suggesting a diagnosis of reflex syncope, such as vomiting, coughing, micturition, or phlebotomy, among others. Additionally, transient AV block (Wenckebach, 2:1, high grade, or complete AV block) can occur secondary to enhanced vagal tone caused by hypersensitive carotid sinus syndrome and neurocardiogenic syncope. However, the cause of the vagal surge may not be evident in some patients. Often, the episodes of syncope are preceded by a prodrome of symptoms of vagotonia (lightheadedness, diaphoresis, warm clammy feeling, and nausea). However, some patients experience no such warnings.
A classic vagal effect on the conduction system includes gradual slowing of the sinus rate (P-P interval) and AV conduction (first-degree or Wenckebach block), due to simultaneous vagal effect on both the sinus node and AVN, occasionally followed by sinus arrest or complete AV block. Not infrequently, a more prominent AV response with sudden AV block can occur with heightened vagal tone; nevertheless, slowing of the sinus rate and prolongation of PR interval in at least one beat typically precedes complete AV block. The sinus rate continues to slow down during ventricular asystole. This is followed by gradual resumption of AV conduction (with initial significant PR interval prolongation) and sinus acceleration.
Paroxysmal intrinsic atrioventricular block
Paroxysmal intrinsic AV block is characterized by pause-dependent, abrupt, and sustained AV block occurring in diseased HPS. The change from apparently normal 1:1 AV conduction to complete heart block is sudden and unexpected. The block is usually initiated by conducted or nonconducted premature atrial complex (PAC) or premature ventricular complex (PVC) or by a change of baseline heart rate, and it persists until another PAC or PVC or rate change terminates it ( Fig. 10.3 ). Episodes of AV block are commonly associated with prolonged periods of ventricular asystole (of unpredictable duration) precipitating presyncope or syncope and potentially sudden death. Long-term outcome is characterized by a rapid progression toward permanent AV block.
Paroxysmal AV block is a rare, unique disorder of the HPS, possibly caused by local phase 4 block in the HPS after a critical change in the H-H interval (see Chapter 11 ). Phase 4 or diastolic depolarization is a property of pacemaker cells of the heart; normal His-Purkinje fibers do not possess this property. On the other hand, diseased Purkinje cells can manifest phase 4 depolarization. During a long pause (prolonged diastolic period), the fibers of the often-diseased HPS spontaneously depolarize (membrane potential becomes less negative) and become less responsive to subsequent impulses due to Na + channel inactivation. The critical prolongation of the input stimulus is typically initiated by a compensatory pause after a PAC or PVC, spontaneous slowing of the sinus rate, or overdrive suppression of sinus rhythm on termination of a fast supraventricular rhythm. Once a critical diastolic membrane potential is reached (at which Na + channel inactivation occurs), subsequent conduction may not resume until a well-timed escape beat or premature beat (sinus or ectopic) resets the transmembrane potential to its excitable state. It is important to note that, in some cases, pause-dependent block may be caused by other mechanisms (e.g., source-to-sink mismatch) that may not be related to phase 4 depolarization.
No specific tests exist to diagnose paroxysmal AV block. Patients with paroxysmal intrinsic AV block may or may not have structural heart disease at baseline, conduction abnormalities may not be evident on resting ECGs, and when present, RBBB is the most common finding. The role of electrophysiological (EP) testing remains uncertain because there is no predictable marker for identifying patients at risk for paroxysmal AV block. Although paroxysmal AV block may be reproduced during EP testing via critically timed atrial or ventricular extrastimuli, a negative EP study result does not exclude the diagnosis of paroxysmal AV block.
Paroxysmal idiopathic atrioventricular block
Paroxysmal “idiopathic” AV block is a recently described distinct form of paroxysmal AV block in patients with recurrent syncope. This form of AV block is unexplainable in terms of currently known mechanisms and has clinical and EP features distinct from those of the two other known types of paroxysmal AV block: intrinsic AV block due to AV conduction disease and extrinsic vagal AV block.
Idiopathic paroxysmal AV block is characterized by sudden onset of complete AV block causing one or multiple consecutive asystolic pauses and recurrent syncope, absence of cardiac and resting ECG abnormalities, and absence of progression to persistent forms of AV block ( Fig. 10.4 ). AV block occurs without P-P cycle lengthening or PR interval prolongation (unlike paroxysmal vagal AV block) and is not triggered by PACs or PVCs or by variations in the baseline heart rate (unlike paroxysmal intrinsic AV block).
The mechanism of idiopathic AV block has not been elucidated yet. A possible role of adenosine has been suggested. Patients with this form of AV block have low baseline adenosine plasma level values as compared to controls or to patients with reflex (vagal) asystolic syncope. Furthermore, patients with idiopathic AV block frequently exhibit an increased susceptibility to exogenous adenosine; the rapid intravenous injection of 18 mg adenosine or 20 mg adenosine triphosphate (ATP) reproduced spontaneous AV block in the majority of patients. The adenosine response could be abolished by theophylline (an adenosine antagonist), but not by atropine (a vagal antagonist). However, the adenosine test does not appear to be specific, and its value in clinical practice requires further evaluation. Carotid sinus massage and tilt table testing did not reproduce AV block. Permanent pacing was successful in preventing syncopal recurrences during long-term follow-up in patients with idiopathic AV block.
Distinction between the three forms of paroxysmal AV block (vagally mediated, intrinsic, and idiopathic) has important prognostic and therapeutic implications. Table 10.2 lists features of each entity, although some of those characteristics can have limited sensitivity and/or specificity, as discussed previously.
TABLE 10.2
Differential Diagnosis of Paroxysmal Atrioventricular (AV) Block
| PAROXYSMAL VAGALLY MEDIATED AV BLOCK | PAROXYSMAL INTRINSIC AV BLOCK | PAROXYSMAL IDIOPATHIC AV BLOCK | |
|---|---|---|---|
| Triggers | Heightened vagal tone | PAC, PVC, change in heart rate | No identifiable triggers |
| Sinus rate before/during AV block | Slowing | Accelerating | Accelerating |
| First-degree and/or Wenckebach AV block before or after complete AV block | Common | Absent | Absent |
| Wide QRS | Uncommon | Common | Common |
| Level of block | AVN | HPS | HPS |
| Adenosine plasma level | High | Normal | Low |
| Sensitivity to Adenosine | Uncommon | Uncommon | Common |
| Response to pacing therapy | Modest | Good | Good |
Clinical presentation
Symptoms in patients with AV conduction abnormalities are generally caused by bradycardia and loss of AV synchrony. Symptoms caused by advanced AV block can range from exercise intolerance, easy fatigability, exertional dyspnea, angina, mental status changes, dizziness, and near syncope to frank syncope. In patients with paroxysmal or intermittent complete AV block, symptoms are episodic, and routine ECGs may not be diagnostic. Importantly, heart rate slowing accompanying acquired AV block can lead to prolongation of the QT interval and torsades de pointes, a potentially lethal complication.
Individuals with first-degree AV delay are usually asymptomatic; however, marked prolongation of the PR interval (longer than 300 milliseconds) can precipitate symptoms similar to those with pacemaker syndrome caused by loss of AV synchrony and atrial contraction against closed AV valves. Additionally, in patients with LV dysfunction, severe first-degree AV delay can lead to impaired hemodynamics, “diastolic” mitral regurgitation, and reduction in cardiac output, with consequent worsening of heart failure symptoms.
On physical examination, the “a” to “c” wave interval in the jugular venous pulse prolongs and intensity of the first heart sound diminishes as the PR interval lengthens. These changes can be constant in first-degree AV delay, or dynamic, mirroring the changes in PR interval in type I second-degree AV block. In the latter setting, the “a” wave is intermittently not followed by “v” wave, indicating failure of conduction of the P wave to the ventricles. Wenckebach used an analysis of the jugular venous pulse to first describe the phenomenon of type I second-degree AV block.
Congenital AV block can be apparent in utero or at birth; however, many individuals have few or no symptoms and reach their teens or young adulthood before the diagnosis is made. Because of the presence of reliable subsidiary HB pacemakers with adequate rates (especially in the presence of catecholamines), syncope is rare with congenital complete AVN block. Some patients become symptomatic only when aging produces chronotropic incompetence of the escape rhythm.
Natural history
The natural history of patients with AV block depends on the underlying cardiac condition. Additionally, the site of the block and the resulting rhythm disturbances themselves contribute to the prognosis. Healthy middle-aged subjects with first-degree AV delay have an excellent prognosis, even when associated with chronic bifascicular block, because the rate of progression to third-degree AV block is low. However, in older populations and in patients with underlying heart failure or coronary artery disease, prolongation of the PR interval was found to be an adverse prognostic marker and a predictor of higher risk of AF and heart failure.
Type 1 second-degree AV block is generally benign; however, when type 1 AV block occurs in association with bifascicular block, the risk of progression to complete heart block is significantly increased because of probable infranodal site of AV conduction delay. Type 2 second-degree AV block carries a high risk of progression to advanced or complete AV block, which can occur suddenly. The prognosis of 2:1 AV block depends on whether the site of block is within or below the AVN.
The prognosis for patients with symptomatic acquired complete heart block is poor in the absence of pacing, regardless of the extent of the underlying heart disease. Once appropriate pacing therapy has been established, however, the prognosis depends on the underlying disease process. As noted above, high-degree AV block complicating acute MI is associated with high in-hospital and 30-day mortality but has no impact on 1-year mortality among 30-day survivors. In contrast, complete AV block secondary to idiopathic fibrosis of the conduction system in the absence of additional cardiac disease carries a more benign prognosis. AV block after valve surgery can recover; however, if conduction has not recovered by 48 hours after surgery, permanent pacing will likely be necessary.
Congenital complete AV block diagnosed in utero or at birth is associated with an approximately 30% mortality rate in utero or in the early postnatal life. Mortality is much lower during childhood and adolescence and increases slowly later in life. The outlook for patients with congenital heart block depends largely on the presence or absence of underlying structural heart disease. Patients with concomitant structural heart disease, a wide QRS complex, or LQTS are more likely to develop symptoms early and are at an increased risk for sudden death. Of all cases that have been recognized with congenital heart block, approximately two-thirds will have a pacemaker placed before reaching adulthood.
Diagnostic evaluation
Diagnostic testing is aimed at determining the presence and degree of AV block, the level of block (intranodal versus infranodal), the relationship to symptoms, the underlying etiology of AV conduction disease, and the presence of other cardiac or noncardiac diseases that can affect long-term prognosis and management decisions regarding permanent pacing therapy. In most cases, this can be achieved noninvasively.
Electrocardiogram and ambulatory monitoring
The QRS duration, PR interval, and ventricular rate on the surface ECG can provide important clues for localizing the level of AV block (see later). Furthermore, cardiac ambulatory monitoring can be used to identify the presence of intermittent AV block when suspected based on clinical presentation. Additionally, in patients with first-degree AV delay or second-degree Wenckebach AV block, ambulatory monitoring can help investigate the relationship of cardiac rhythm to clinical symptoms and guide decisions regarding the need for permanent pacing. The type of monitor chosen will depend on the frequency of symptoms. In patients with frequent symptoms, 24- or 48-hour ambulatory Holter monitoring can be useful. Cardiac event monitoring or implantable loop recorders may be necessary in patients with less frequent symptoms.
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