CHAPTER 16: THE BRADYARRHYTHMIAS: DISORDERS OF THE ATRIOVENTRICULAR NODE

Impulses generated in the sinoatrial (SA) node or in ectopic atrial loci are conducted to the ventricles through the electrically and anatomically complex atrioventricular (AV) node. As described in Chap. 15, the electrophysiologic properties of nodal tissue are distinct from atrial and ventricular myocardium. Cells located in the AV node sit at a relatively higher resting membrane potential than surrounding atrial and ventricular myocytes, exhibit spontaneous depolarization during phase 4 of the action potential, and have slower phase 0 depolarization (mediated by calcium influx in nodal tissue) than that seen in ventricular tissue (mediated by sodium influx).

Bradycardia may occur when conduction across the AV node is compromised, resulting in ineffective ventricular rates, with the possibility of attendant symptoms, including fatigue, syncope, and (if subsidiary pacemaker activity is insufficient) even death. It is important to recognize that in the setting of disturbed AV conduction, SA activation and atrial systole may occur at normal or even accelerated rates, while ventricular activation is either slowed or nonexistent. Transient AV conduction block is common in the young and is most likely the result of high vagal tone found in up to 10% of young adults. Acquired and persistent failure of AV conduction is decidedly rare in healthy adult populations, with an estimated incidence of 200 per million population per year. In the setting of myocardial ischemia, aging and fibrosis, or cardiac infiltrative diseases, however, persistent AV block is much more common.

As with symptomatic bradycardia arising from SA node dysfunction, permanent pacing is the only reliable therapy for symptoms arising from AV conduction block. Approximately 50% of the 150,000 permanent pacemakers implanted in the United States and 70–80% of those in Europe are implanted for disorders of AV conduction.

The AV conduction axis is structurally complex, involving the atria and ventricles as well as the AV node. Unlike the SA node, the AV node is a subendocardial structure originating in the transitional zone, which is composed of aggregates of cells in the posterior-inferior right atrium. Superior, medial, and posterior transitional atrionodal bundles converge on the compact AV node. The compact AV node (~1 × 3 × 5 mm) is situated at the apex of the triangle of Koch, which is defined by the coronary sinus ostium posteriorly, the septal tricuspid valve annulus anteriorly, and the tendon of Todaro superiorly. The compact AV node continues as the penetrating AV bundle where it immediately traverses the central fibrous body and is in close proximity to the aortic, mitral, and tricuspid valve annuli; thus, it is subject to injury in the setting of valvular heart disease or its surgical treatment. The penetrating AV bundle continues through the annulus fibrosis and emerges along the ventricular septum adjacent to the membranous septum as the bundle of His. The right bundle branch (RBB) emerges from the distal AV bundle in a band that traverses the right ventricle (moderator band). In contrast, the left bundle branch (LBB) is a broad subendocardial sheet of tissue on the septal left ventricle. The Purkinje fiber network emerges from the RBB and LBB and extensively ramifies on the endocardial surfaces of the right and left ventricles, respectively.

The blood supply to the penetrating AV bundle is from the AV nodal artery and first septal perforator of the left anterior descending coronary artery. The bundle branches also have a dual blood supply from the septal perforators of the left anterior descending coronary artery and branches of the posterior descending coronary artery. The AV node is highly innervated with postganglionic sympathetic and parasympathetic nerves. The bundle of His and distal conducting system are minimally influenced by autonomic tone.

The cells that constitute the AV node complex are heterogeneous with a range of action potential profiles. In the transitional zones, the cells have an electrical phenotype between those of atrial myocytes and cells of the compact node (see Fig. 15-1). Atrionodal transitional connections may exhibit decremental conduction, defined as slowing of conduction with increasingly rapid rates of stimulation. Fast and slow AV nodal pathways have been described, but it is controversial whether these two types of pathway are anatomically distinct or represent functional heterogeneities in different regions of the AV nodal complex. Myocytes that constitute the compact node are depolarized (resting membrane potential ~–60 mV) and exhibit action potentials with low amplitudes, slow upstrokes of phase 0 (<10 V/s), and phase 4 diastolic depolarization; high-input resistance; and relative insensitivity to external [K⁺]. The action potential phenotype is explained by the complement of ionic currents expressed. AV nodal cells lack a robust inward rectifier potassium current (I_K1) and fast sodium current (I_Na); L-type calcium current (I_Ca-L) is responsible for phase 0; and phase 4 depolarization reflects the composite activity of the depolarizing currents—funny current (I_f), I_Ca-L, T-type calcium current (I_Ca-T), and sodium calcium exchanger current (I_NCX)—and the repolarizing currents—delayed rectifier (I_Kr) and acetylcholine-gated (I_KACh) potassium currents. Electrical coupling between cells in the AV node is tenuous due to the relatively sparse expression of gap junction channels (predominantly connexin-40) and increased extracellular volume.

The His bundle and the bundle branches are insulated from ventricular myocardium. The most rapid conduction in the heart is observed in these tissues. The action potentials exhibit very rapid upstrokes (phase 0), prolonged plateaus (phase 2), and modest automaticity (phase 4 depolarization). Gap junctions, composed largely of connexin-40, are abundant, but bundles are poorly connected transversely to ventricular myocardium.

Conduction block from the atrium to the ventricle can occur for a variety of reasons in a number of clinical situations, and AV conduction block may be classified in a number of ways. The etiologies may be functional or structural, in part analogous to extrinsic and intrinsic causes of SA nodal dysfunction. The block may be classified by its severity from first to third degree or complete AV block or by the location of block within the AV conduction system. Table 16-1 summarizes the etiologies of AV conduction block. Those that are functional (autonomic, metabolic/endocrine, and drug-related) tend to be reversible. Most other etiologies produce structural changes, typically fibrosis, in segments of the AV conduction axis that are generally permanent. Heightened vagal tone during sleep or in well-conditioned individuals can be associated with all grades of AV block. Carotid sinus hypersensitivity, vasovagal syncope, and cough and micturition syncope may be associated with SA node slowing and AV conduction block. Transient metabolic and endocrinologic disturbances as well as a number of pharmacologic agents also may produce reversible AV conduction block.

Several infectious diseases have a predilection for the conducting system. Lyme disease may involve the heart in up to 50% of cases; 10% of patients with Lyme carditis develop AV conduction block, which is generally reversible but may require temporary pacing support. Chagas’ disease, which is common in Latin America, and syphilis may produce more persistent AV conduction disturbances. Some autoimmune and infiltrative diseases may produce AV conduction block, including systemic lupus erythematosus (SLE), rheumatoid arthritis, mixed connective tissue disease, scleroderma, amyloidosis (primary and secondary), sarcoidosis, and hemochromatosis; rare malignancies also may impair AV conduction.

Idiopathic progressive fibrosis of the conduction system is one of the more common and degenerative causes of AV conduction block. Aging is associated with degenerative changes in the summit of the ventricular septum, central fibrous body, and aortic and mitral annuli and has been described as “sclerosis of the left cardiac skeleton.” The process typically begins in the fourth decade of life and may be accelerated by atherosclerosis, hypertension, and diabetes mellitus. Accelerated forms of progressive familial heart block have been identified in families with mutations in the cardiac sodium channel gene (SCN5A) and other loci that have been mapped to chromosomes 1 and 19.

AV conduction block has been associated with heritable neuromuscular diseases, including the nucleotide repeat disease myotonic dystrophy, the mitochondrial myopathy Kearns-Sayre syndrome, and several of the monogenic muscular dystrophies. Congenital AV block may be observed in complex congenital cardiac anomalies (Chap. 22), such as transposition of the great arteries, ostium primum atrial septal defects (ASDs), ventricular septal defects (VSDs), endocardial cushion defects, and some single-ventricle defects. Congenital AV block in the setting of a structurally normal heart has been seen in children born to mothers with SLE. Iatrogenic AV block may occur during mitral or aortic valve surgery, rarely in the setting of thoracic radiation, and as a consequence of catheter ablation. AV block is a decidedly rare complication of the surgical repair of VSDs or ASDs but may complicate repairs of transposition of the great arteries.

Coronary artery disease may produce transient or persistent AV block. In the setting of coronary spasm, ischemia, particularly in the right coronary artery distribution, may produce transient AV block. In acute myocardial infarction (MI), AV block transiently develops in 10–25% of patients; most commonly, this is first-or second-degree AV block, but complete heart block (CHB) may also occur. Second-degree and higher-grade AV block tends to occur more often in inferior than in anterior acute MI; however, the level of block in inferior MI tends to be in the AV node with more stable, narrow escape rhythms. In contrast, acute anterior MI is associated with block in the distal AV nodal complex, His bundle, or bundle branches and results in wide complex, unstable escape rhythms and a worse prognosis with high mortality rates.

AV conduction block typically is diagnosed electrocardiographically, which characterizes the severity of the conduction disturbance and allows one to draw inferences about the location of the block. AV conduction block manifests as slow conduction in its mildest forms and failure to conduct, either intermittent or persistently, in more severe varieties. First-degree AV block (PR interval >200 ms) is a slowing of conduction through the AV junction (Fig. 16-1). The site of delay is typically in the AV node but may be in the atria, bundle of His, or His-Purkinje system. A wide QRS is suggestive of delay in the distal conduction system, whereas a narrow QRS suggests delay in the AV node proper or, less commonly, in the bundle of His. In second-degree AV block there is an intermittent failure of electrical impulse conduction from atrium to ventricle. Second-degree AV block is subclassified as Mobitz type I (Wenckebach) or Mobitz type II. The periodic failure of conduction in Mobitz type I block is characterized by a progressively lengthening PR interval, shortening of the RR interval, and a pause that is less than two times the immediately preceding RR interval on the electrocardiogram (ECG). The ECG complex after the pause exhibits a shorter PR interval than that immediately preceding the pause (Fig. 16-2). This ECG pattern most often arises because of decremental conduction of electrical impulses in the AV node.

It is important to distinguish type I from type II second-degree AV nodal block because the latter has more serious prognostic implications. Type II second-degree AV block is characterized by intermittent failure of conduction of the P wave without changes in the preceding PR or RR intervals. When AV block is 2:1, it may be difficult to distinguish type I from type II block. Type II second-degree AV block typically occurs in the distal or infra-His conduction system, is often associated with intraventricular conduction delays (e.g., bundle branch block), and is more likely to proceed to higher grades of AV block than is type I second-degree AV block. Second-degree AV block (particularly type II) may be associated with a series of nonconducted P waves, referred to as paroxysmal AV block (Fig. 16-3), and implies significant conduction system disease and is an indication for permanent pacing. Complete failure of conduction from atrium to ventricle is referred to as complete or third-degree AV block. AV block that is intermediate between second degree and third degree is referred to as high-grade AV block and, as with CHB, implies advanced AV conduction system disease. In both cases, the block is most often distal to the AV node, and the duration of the QRS complex can be helpful in determining the level of the block. In the absence of a preexisting bundle branch block, a wide QRS escape rhythm (Fig. 16-4B) implies a block in the distal His or bundle branches; in contrast, a narrow QRS rhythm implies a block in the AV node or proximal His and an escape rhythm originating in the AV junction (Fig. 16-4A). Narrow QRS escape rhythms are typically faster and more stable than wide QRS escape rhythms and originate more proximally in the AV conduction system.

Diagnostic testing in the evaluation of AV block is aimed at determining the level of conduction block, particularly in asymptomatic patients, since the prognosis and therapy depend on whether the block is in or below the AV node. Vagal maneuvers, carotid sinus massage, exercise, and administration of drugs such as atropine and isoproterenol may be diagnostically informative. Owing to the differences in the innervation of the AV node and infranodal conduction system, vagal stimulation and carotid sinus massage slow conduction in the AV node but have less of an effect on infranodal tissue and may even improve conduction due to a reduced rate of activation of distal tissues. Conversely, atropine, isoproterenol, and exercise improve conduction through the AV node and impair infranodal conduction. In patients with congenital CHB and a narrow QRS complex, exercise typically increases heart rate; by contrast, those with acquired CHB, particularly with wide QRS, do not respond to exercise with an increase in heart rate.

Additional diagnostic evaluation, including electrophysiologic testing, may be indicated in patients with syncope and suspected high-grade AV block. This is particularly relevant if noninvasive testing does not reveal the cause of syncope or if the patient has structural heart disease with ventricular tachyarrhythmias as a cause of symptoms. Electrophysiologic testing provides more precise information regarding the location of AV conduction block and permits studies of AV conduction under conditions of pharmacologic stress and exercise. Recording of the His bundle electrogram by a catheter positioned at the superior margin of the tricuspid valve annulus provides information about conduction at all levels of the AV conduction axis. A properly recorded His bundle electrogram reveals local atrial activity, the His electrogram, and local ventricular activation; when it is monitored simultaneously with recorded body surface electrocardiographic traces, intraatrial, AV nodal, and infranodal conduction times can be assessed (Fig. 16-1). The time from the most rapid deflection of the atrial electrogram in the His bundle recording to the His electrogram (AH interval) represents conduction through the AV node and is normally <130 ms. The time from the His electrogram to the earliest onset of the QRS on the surface ECG (HV interval) represents the conduction time through the His-Purkinje system and is normally ≤55 ms.

Rate stress produced by pacing can unveil abnormal AV conduction. Mobitz I second-degree AV block at short atrial paced cycle lengths is a normal response. However, when it occurs at atrial cycle lengths >500 ms (<120 beats/min) in the absence of high vagal tone, it is abnormal. Typically, type I second-degree AV block is associated with prolongation of the AH interval, representing conduction slowing and block in the AV node. AH prolongation occasionally is due to the effect of drugs (beta blockers, calcium channel blockers, digitalis) or increased vagal tone. Atropine can be used to reverse high vagal tone; however, if AH prolongation and AV block at long pacing cycle lengths persists, intrinsic AV node disease is likely. Type II second-degree block is typically infranodal, often in the His-Purkinje system. Block below the node with prolongation of the HV interval or a His bundle electrogram with no ventricular activation (Fig. 16-5) is abnormal unless it is elicited at fast pacing rates or short coupling intervals with extra stimulation. It is often difficult to determine the type of second-degree AV block when 2:1 conduction is present; however, the finding of a His bundle electrogram after every atrial electrogram indicates that block is occurring in the distal conduction system.

Intracardiac recording at electrophysiologic study that reveals prolongation of conduction through the His-Purkinje system (i.e., long HV interval) is associated with an increased risk of progression to higher grades of block and is generally an indication for pacing. In the setting of bundle branch block, the HV interval may reveal the condition of the unblocked bundle and the prognosis for developing more advanced AV conduction block. Prolongation of the HV interval in patients with asymptomatic bundle branch block is associated with an increased risk of developing higher-grade AV block. The risk increases with greater prolongation of the HV interval such that in patients with an HV interval >100 ms, the annual incidence of complete AV block approaches 10%, indicating a need for pacing. In patients with acquired CHB, even if intermittent, there is little role for electrophysiologic testing, and pacemaker implantation is almost always indicated.