CHAPTER 86: BRADYARRHYTHMIAS

Bradyarrhythmias are most commonly caused by failure of impulse formation (sinus node dysfunction) or by failure of impulse conduction over the atrioventricular (AV) node/His-Purkinje system. Bradyarrhythmias may be caused by disease processes that directly alter the structural and functional integrity of the sinus node, atria, AV node, and His-Purkinje system or by extrinsic factors (autonomic disturbances, drugs, etc) without causing structural abnormalities (Table 86–1).

Sinoatrial Node

Normal electrical activation of the heart arises from the principal pacemaker cells that spontaneously depolarize, located laterally in the epicardial groove of the sulcus terminalis,¹ near the junction of the right atrium and the superior vena cava (Fig. 86–1). The sinus node in adults measures approximately 1 to 2 cm long and 0.5 mm wide. The central zone of the sinus node containing the principal central pacemaker cells is small and located within a fibrous tissue matrix. In the periphery of the node along the crista terminalis, transitional cells with pacemaker function are also present. In essence, the sinoatrial (SA) node has a complex three-dimensional tissue architecture with central and peripheral components made up of distinct ion channel and gap junction expression profiles. This heterogeneity is necessary to maintain normal automaticity and impulse conduction. The principal pacemaker site within this region may migrate, resulting in subtle alterations in P-wave morphology. Once the impulse exits the sinus node and the perinodal tissues, it traverses the atrium to the AV node. The conduction of impulses from right to left atrium has been postulated to occur preferentially via Bachmann’s bundle, and secondarily across the musculature of the coronary sinus.

Atrioventricular Node

Once the sinus node impulse activates the atrium, electrical activation continues through the AV node, with a conduction delay ensuring complete atrial contraction before initiation of ventricular conduction. The AV nodal complex is considered to have three related regions: (1) the transitional cell zone, (2) the compact AV node, and (3) the penetrating AV bundle.² The transitional zone consists of the main atrial approaches to the compact AV node. The compact AV node is shaped like a half oval and is located beneath the right atrial (RA) endocardium at the apex of the triangle of Koch. The triangle of Koch is formed by the base of the septal leaflet of the tricuspid valve and the tendon of Todaro (formed by the extension of the eustachian valve into the central fibrous body). The coronary sinus ostium is located at the base of this triangle. The distal end of the compact AV node enters the central fibrous body to become the penetrating bundle and continues in the membranous septum as the bundle of His. The speed of conduction through the AV nodal complex is 0.03 m/s, whereas the His-Purkinje fibers conduct at 2.4 m/s.

His-Purkinje System

The penetrating part of the AV bundle continues through the annulus fibrosis into the membranous septum, along the crest of the left side of the interventricular septum for 1 to 2 cm, and then divides into the right and left bundle branches. The right bundle branch continues intramyocardially along the right side of the interventricular septum and emerges subendocardially beneath the anterior papillary muscle of the right ventricle. The left bundle begins as a sheet of fascicles and runs along the left side of the interventricular septum and soon separates into anterior and posterior sheets (most anatomists agree it is a trifascicular system with a substantial septal branch) corresponding to the anterior and posterior papillary muscles. In many hearts, the left bundle may appear more as a network rather than a well-defined bifascicular system. The terminal Purkinje fibers arising from the bundle branches form interweaving networks on the endocardial surface of both the right and left ventricles. The rapid conduction of electrical impulses across this network results in near simultaneous activation of both right and left ventricles.

The anatomy of the main His bundle has practical implications for permanent His bundle pacing. While early reports on permanent His bundle pacing demonstrated its feasibility, it had been technically challenging.³ Recent studies have shown that routine permanent His bundle pacing is possible both in patients with AV nodal and proximal His bundle disease.⁴ Understanding the anatomy of the His bundle is critical in achieving procedural success. The proximal part of the His bundle rests on the RA-left ventricular (LV) part of the membranous septum, and the more distal part travels along the right ventricular (RV)-LV part of the membranous septum, immediately below the aortic root (Fig. 86–2). Kawashima and Sasaki⁵ reported anatomical variations of the AV bundle from their macroscopic anatomical investigation of 105 elderly human hearts. They reported three distinct variations of the His bundle relative to the membranous part of the ventricular septum. The His bundle consistently coursed along the lower border of the membranous part of the interventricular septum (Fig. 86–3), but was covered with a thin layer of myocardial fibers spanning from the muscular part of the septum (type I, 46.7% of 105 cases). The His bundle was apart from the lower border of the membranous part of the interventricular septum and ran within the interventricular muscle (type II, 32.4%). The His bundle was immediately beneath the endocardium and coursed onto the membranous part of the interventricular septum (naked atrioventricular bundle, type III, 21%). These anatomical variations of the His bundle may have clinical implications for permanent His bundle pacing and to avoid His bundle injury during surgical reconstruction of membranous part of the ventricular septal defect.

Blood Supply

The sinus node receives its blood supply from the SA nodal artery arising from the right coronary artery in 59% of patients, from the left circumflex artery in 38%, and from both arteries with a dual blood supply in 3%. The AV node is supplied by the AV nodal artery arising from the right coronary artery in 90% of patients, whereas the left circumflex artery provides it in the remaining 10% of patients. Both the AV nodal artery and branches of the left anterior descending artery supply the bundle of His. The left bundle has a rich blood supply from the AV nodal artery, posterior descending artery, and branches of the left anterior descending artery.

Innervation

The conduction system of the heart is significantly influenced by both the parasympathetic and sympathetic nervous systems. The sinus node is richly innervated with postganglionic adrenergic and cholinergic nerve terminals. Vagal stimulation slows the sinus node discharge rate and increases the intranodal conduction time, occasionally to the point of sinus node exit block. Adrenergic stimulation increases the sinus node discharge rate. Parasympathetic tone predominates at rest in healthy individuals, and parasympathetic withdrawal occurs with increased sympathetic discharge during exercise and emotion. The effects of sympathetic and parasympathetic stimulation on the AV node are more pronounced than they are on the His-Purkinje system. Although sympathetic stimulation shortens AV-nodal conduction time and refractoriness, vagal stimulation prolongs AV-nodal conduction time and refractoriness. Both sympathetic and vagal stimulation have minimal effect on normal conduction in the His bundle.

Sinus node dysfunction is a common clinical syndrome, comprising a wide range of electrophysiologic abnormalities, including failure of impulse generation, failure of impulse transmission to the atria, inadequate subsidiary pacemaker activity, and increased susceptibility to atrial tachyarrhythmias.⁶ This disorder has also been variably termed the sick sinus syndrome, tachycardia-bradycardia syndrome, SA disease, and SA dysfunction.

Sinus Node Electrical Activity

Normal myocardium has a stable hyperpolarized (negative) resting potential during phase 4 of the action potential. The SA node, in contrast, displays phase 4 diastolic depolarization (Fig. 86–4). The cell membrane potential becomes gradually more positive until an action potential is triggered at the threshold potential. Alteration of this phase 4 slope changes the heart rate.⁷ The current paradigm of SA node automaticity is modeled as mutual entrainment of two molecular clocks, the “membrane voltage clock” and the “Ca²⁺ clock.”⁸ The membrane clock is produced by the net disequilibrium between the hyperpolarizing outward potassium current (I_k) and the depolarizing inward current (principally the I_f). The pacemaker, or funny current, I_f, is generated by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel.⁹ The I_f is activated at hyperpolarized membrane potentials (between –65 and –40 mV) and this current contributes to diastolic depolarization. The subsarcolemmal Ca²⁺ clock contributes significantly to late diastolic depolarization of SA node through the spontaneous rhythmic release of Ca²⁺ from the sarcoplasmic reticulum (SR) via the ryanodine type 2 receptor (RYR2).¹⁰ The elevation of the local intracellular Ca²⁺ drives the Na⁺-Ca²⁺ exchange current (I_NCX) to substitute one intracellular Ca²⁺ for three extracelluar Na⁺, leading to net gain in positive charge and resulting in membrane depolarization. Both the membrane and Ca²⁺ clocks are modulated by cyclic adenosine monophosphate (cAMP) and hence sensitive to adrenergic stimulation (Fig. 86–5). Human mutations affecting the membrane clock (SCN5A and HCN4), Ca²⁺ clock (RYR2 and CASQ2), or both mechanisms (ANKB) have been identified to negatively affect sinus node function.¹¹

Pathophysiology

Disorders of sinus node dysfunction may be caused by intrinsic factors (processes that directly affect the anatomy and physiology of the sinus node and/or the surrounding atrial tissue) or extrinsic factors (processes that affect sinus node function in the absence of structural abnormalities) (Table 86–2). However, in some patients, a combination of intrinsic and extrinsic factors may be responsible for sinus node dysfunction. In patients with sinus node dysfunction, histopathologic evaluation has revealed the following patterns¹²: significant loss of nodal cells with replacement fibrosis, amyloid deposition in the nodal region, hypoplastic or atrophic sinus node, and no detectable morphologic abnormality.

Aging is associated with alterations in sinus node function, causing a decrease in the intrinsic heart rate, an increase in sinoatrial conduction time (SACT), and conduction slowing and voltage loss around the region of crista terminalis. In the presence of clinically detectable sinus node dysfunction there is caudal shift of the leading pacemaker site within the SA node pacemaker complex. Decreased expression of Cx43 in the vicinity of the SA node may lead to increase in SACT and the SA exit block seen with aging.¹³ While structural changes such as fibrosis and degeneration had been implicated in sinus node dysfunction, there is also evidence for reverse remodeling of the SA node. Electrical remodeling of the sinus node pacemaker complex and molecular remodeling of key ion channels and regulatory elements has been demonstrated in response to variety of conditions known to lead to sinus node dysfunction.¹⁴

Sinus node dysfunction is a well-known association with recurrent atrial arrhythmia (atrial fibrillation, atrial flutter). Chronic overdrive of the SA node by a primary atrial arrhythmia leads to electrical remodeling and sinus node dysfunction. Rapid atrial pacing induces abnormalities of both membrane clock (reduction in HCN4 and HCN2 expression with reduction in I_f and I_k,s currents) and Ca²⁺ clock (altered Ca²⁺ cycling and RYR expression).¹⁵ Reverse remodeling of sinus node dysfunction can be demonstrated after restoration of sinus rhythm following catheter ablation of atrial fibrillation.

Although an idiopathic degenerative disorder of the sinus node is the most common cause for intrinsic sinus node dysfunction, ischemic heart disease is responsible in a significant number of patients. Chronic ischemia from sinus node artery disease or acute myocardial infarction (MI), especially inferior wall MI, may result in sinus bradycardia, sinus arrest, and atrial tachyarrhythmias. Transient sinus bradycardia and sinus arrest seen in acute MI may in part be related to altered neurologic influences on the heart. Other potential causes include long-standing hypertension, cardiomyopathy (especially infiltrative disorders such as amyloidosis and sarcoidosis), inflammation, collagen vascular disease, and inherited neuromuscular disorders.

In some cases, the condition appears to be familial in origin.¹⁶ Sinus node dysfunction can occur in children and young adults without structural heart disease. In addition to autosomal inheritance, polygenetic susceptibility to sinus node dysfunction has been described. HCN4 mutations result in a lack of channel responsiveness to cAMP or reduction in I_f, leading to sinus bradycardia, chronotropic incompetence, and atrial fibrillation.¹⁷ Mutations in Ca²⁺ channels and Ca²⁺ handling proteins (RYR or calsequestrin 2[CASQ2]) are also associated with sinus node dysfunction.¹⁸ Mutations in the cardiac Na⁺ channel gene, SCN5A, have been reported in families to result in primary cardiac conduction disease. The mutations that are associated with conduction system disease result in reduced Na⁺ current. The spectrum of these conduction diseases varies widely, but includes sinus node dysfunction, atrial standstill, AV block, and progressive cardiac conduction disease (PCCD). An inherited form of Lev-Lenégre disease is associated with loss of function mutations in SCN5A and can exist alone or as overlap syndromes with Brugada or long QT syndrome. Mutations in ankyrin-B (ANKB) are associated with long QT type 4 and familial sinus node dysfunction by disrupting the membrane and Ca²⁺ clocks.^19,20

Rare cases of sinus node dysfunction requiring pacemaker therapy have been reported with Lyme disease (Borrelia burgdorferi infection).²¹ In children and young adults, damage to the sinus node during atrial surgery (closure of atrial septal defects of the sinus-venosus type, Mustard procedure for transposition of great arteries) has been commonly associated with sinus node dysfunction. Sinus node dysfunction is also not uncommon in the donor hearts of patients with orthotopic cardiac transplantation.

The most important causes of sinus node dysfunction in patients without structural abnormalities are drugs and autonomic nervous system influences (see Table 86–2). Drugs may alter sinus node function by direct pharmacologic effects on nodal tissue or indirectly by neurally mediated effects. Antiarrhythmic drugs used to maintain sinus rhythm in patients with atrial fibrillation may cause significant sinus node dysfunction, especially in patients with underlying sinus node dysfunction. Other causes for sinus node dysfunction include electrolyte abnormalities, such as hyperkalemia, hypothermia, intracranial hypertension, hypoxia, hypercapnia, and hypothyroidism.

Electrocardiographic Manifestations

A variety of electrocardiographic abnormalities have been described in patients with sinus node dysfunction. Many of the electrocardiographic abnormalities that define sinus node dysfunction may be asymptomatic, and these abnormalities by themselves do not warrant therapy.

Sinus Bradycardia

Sinus bradycardia is defined as a sinus rate < 60 bpm. In most instances sinus bradycardia is a benign arrhythmia. In healthy young adults and trained athletes, resting sinus bradycardia may be a normal phenomenon caused by increased vagal tone. Sinus bradycardia during sleep in elderly individuals is common. Inability to increase sinus rates adequately during exercise is considered abnormal (see below). Sinus bradycardia < 40 bpm (not associated with sleep or physical conditioning) is generally considered abnormal. Correlation of symptoms with sinus bradycardia is critical in the evaluation of these patients.

Sinus Pause and Sinus Arrest

Sinus pause or arrest means failure of sinus node discharge with lack of atrial activation of sinus origin. This results in absence of P waves and periods of ventricular asystole if lower pacemakers (junctional or ventricular) do not initiate escape beats (Fig. 86–6). The resulting pause in sinus activity should not be in multiples of preceding sinus cycle length (P-P interval), which would indicate that SA exit block is present (see below). Asymptomatic sinus pauses of up to 3 seconds in duration are not uncommon in trained athletes.²² Pauses longer than 3 seconds need careful clinical correlation with symptoms and warrant further evaluation.

Sinoatrial Exit Block

In SA exit block, as the name implies, the impulse is formed in the sinus node, but fails to conduct to the atria, unlike sinus arrest. This particular arrhythmia is recognized on an electrocardiogram (ECG) by pauses resulting from the absence of normal P waves and the duration of the pause, measuring an exact multiple of the preceding P-P interval (Fig. 86–7). SA block can also be described in the same way as AV block. In first-degree SA block, there is significant prolongation of the time for the sinus impulse to exit into the atria (SA conduction time). This cannot be identified clinically or electrocardiographically. Similar to AV block, second-degree SA block can be type I (Wenckebach) or type II. In type I there is progressive prolongation of SA conduction, manifested on surface ECG as progressive shortening of P-P interval, before the pause created by loss of a P wave. In type II SA exit block, the P-P intervals remain constant before the pause. Third-degree or complete SA block will manifest as absence of P waves, with long pauses resulting in lower pacemaker escape rhythm; it is impossible to diagnose with certainty without invasive sinus node recordings.

Tachycardia-Bradycardia Syndrome

Sinus bradycardia interspersed with periods of atrial tachyarrhythmias is a common manifestation of sinus node dysfunction. The atrial tachyarrhythmias usually range from paroxysmal atrial tachycardia to atrial flutter and atrial fibrillation. Apart from underlying sinus bradycardia of varying severity, these patients often experience prolonged sinus arrest and asystole upon termination of the atrial tachyarrhythmias, resulting from suppression of sinus node and secondary pacemakers (Fig. 86–8). Long sinus pauses that occur after electrical cardioversion of atrial fibrillation are another manifestation of sinus node dysfunction. Therapeutic strategies to control tachyarrhythmias often result in the need for pacemaker therapy. These patients are at increased risk for thromboembolism,²³ and the issue of long-term anticoagulation should be addressed to prevent strokes.

Chronic atrial fibrillation with a slow ventricular response in the absence of AV nodal-blocking drugs may also be a manifestation of sinus node dysfunction. These patients may demonstrate very slow ventricular rates at rest or during sleep and occasionally have long pauses. They may also conduct rapidly and develop symptoms caused by tachycardia during exercise. Occasionally they may develop complete AV block with junctional or ventricular escape rhythms.

Persistent Atrial Standstill

Atrial standstill is a rare clinical syndrome in which there is no spontaneous atrial activity and the atria cannot be electrically stimulated.²⁴ The surface ECG usually reveals junctional bradycardia without atrial activity (Fig. 86–9). This must be differentiated from fine atrial fibrillation with complete heart block. Intracardiac electrograms fail to show any atrial activity. Atria are generally fibrotic and without any functional myocardium. Myocarditis, amyloidosis, and familial etiology have been recognized as causes in some cases. Lack of mechanical atrial contraction poses a high risk for thromboembolism in these patients.

Chronotropic Incompetence

Chronotropic incompetence is most commonly defined as the inability of the sinus node to achieve at least 85%, 80%, or less commonly 70% of the age-predicted maximal heart rate (APMHR, 220 –age) obtained during an incremental dynamic exercise test. Chronotropic incompetence has also been determined from change in heart rate from rest to peak exercise during an exercise test, commonly referred to as the heart rate reserve. Adjusted (percent) heart rate reserve is determined from the change in heart rate from rest to peak exercise divided by the difference of the resting heart rate and the APMHR. The majority of studies in the literature have used failure to attain > 80% of the heart rate reserve, measured during a graded exercise test, as the primary criterion for chronotropic incompetence.²⁵ It is present in approximately 20% to 60% of patients with sinus node dysfunction. Although the resting heart rates may be normal, these patients may have either the inability to increase their heart rate during exercise or have unpredictable fluctuations in heart rate during activity. Some patients may initially experience a normal increase in heart rate with exercise, which then plateaus or decreases inappropriately. Chronotropic incompetence may be secondary to intrinsic sinus node dysfunction or secondary to drugs with negative chronotropic effects. Chronotropic incompetence is also common in patients with heart failure.²⁶

Clinical Presentation

Even though sinus node dysfunction may occur in any age group, more than half of the patients affected are older than 50 years of age at the time of diagnosis. The incidence of sinus node dysfunction is approximately equal in both men and women. Patients with sinus node dysfunction commonly present with symptoms of syncope, near syncope, or dizzy spells, predominantly related to prolonged sinus pauses. Patients with sinus bradycardia or chronotropic incompetence, however, may present with relatively nonspecifc symptoms, such as decreased exercise capacity, recurrent falls, or fatigue. Patients with atrial fibrillation may also present with palpitations or congestive heart failure. Elderly individuals may have unexplained confusion or memory loss. Occasionally, stroke may be the first manifestation of sinus node dysfunction in patients presenting with paroxysmal atrial fibrillation and thromboembolism.

Diagnostic Evaluation

The diagnosis of sinus node dysfunction in patients who present with typical symptoms and ECG findings is straightforward. However, because of the intermittent nature of the symptoms and rhythm manifestations, the diagnosis can be time-consuming and frustrating. A number of noninvasive and invasive tests are available to assist in the evaluation.

Electrocardiographic Recordings

Documentation of the various arrhythmias associated with sinus node dysfunction can be obtained with routine telemetric monitoring during hospitalization or with outpatient ambulatory 24- to 48-hour Holter recordings. If the symptoms are infrequent in nature, event recorders capable of intermittent or continuous monitoring can be used. Newer monitoring systems use remote real-time monitoring of patients’ rhythm using wireless cellular technology as well as physician-defined triggers. If other noninvasive and invasive tests are inconclusive, patients may benefit from an implantable loop recorder (ILR), which has the ability to record both patient-triggered and automatic device-triggered events over a period of 18 to 36 months. Recently a miniaturized implantable monitor (Reveal LINQ, Medtronic, Minneapolis, MN) with wireless capability has become commercially available (Fig. 86–10). The implantation can easily be performed under local anesthesia in a subcutaneous location to the left of patient’s fourth intercostal space.²⁷ The device transmits data to Medtronic’s CareLink network automatically on a daily basis. Alerts are sent from CareLink to physicians when one of the following conditions is detected: patient-activated episodes, including episodes that occur within 20 minutes of a device-detected episode; device-detected tachycardia, asystole, bradycardia, and atrial fibrillation; atrial fibrillation burden above a threshold determined by the clinician; or ventricular rates (with or without ventricular fibrillation) above a threshold set by the clinician (Fig. 86–11). The storage capacity of the device allows for up to 59 minutes of ECG recordings from patient-activated episodes and automatically detected arrhythmias. Exercise testing to assess chronotropic incompetence can be valuable in select patients. Many patients with sinus node dysfunction may achieve peak heart rates similar to matched controls during specific exercise protocols; however, the time course of heart rate acceleration during activity and deceleration after activity may be markedly abnormal.

Autonomic Testing

Abnormalities of autonomic control of sinus node alone or in association with intrinsic sinus node disease can result in clinical symptoms and electrocardiographic findings of sinus node dysfunction. This can be assessed by observing the response of heart rate and rhythm with carotid sinus massage, head-up tilt testing, and Valsalva maneuver. Pharmacologic evaluation of the sinus node can be performed with atropine, isoproterenol, and propranolol. After injection of atropine 0.04 mg/kg intravenously, the heart rate increases by 15% and to more than 90 bpm. Isoproterenol infusion at 1 to 3 μg/min increases heart rate by 25%. Not all normal patients will respond as described. Patients with sinus node dysfunction show blunted heart rate responses to the preceding infusions. Another method to assess sinus node function is to measure the intrinsic heart rate (IHR) of the sinus node when the autonomic influence is negated by both atropine (0.04 mg/kg) and propranolol (0.2 mg/kg), using the following equation²⁸:

Patients with sinus node dysfunction often demonstrate a decreased IHR.

Electrophysiology Study

Invasive electrophysiology study, in addition to assessing sinus node function, offers insight into other potential etiologies for symptoms of syncope and palpitations (AV block, supraventricular tachycardia, ventricular tachycardia [VT]) (see Chap. 82). The sinus node recovery time is a measure of sinus node automaticity and is measured as the longest pause after atrial overdrive pacing. SA conduction time is a measure of the interval from sinus node depolarization to activation of atrial muscle. With improved modalities for monitoring, it is less common to require electrophysiology studies to make this diagnosis.

Management

Pharmacologic Treatment

Theophylline and β-adrenergic agonists have been used to treat symptomatic bradycardia. Although they have been shown to increase the heart rate and reduce the duration of sinus pauses, they do not prevent recurrent syncope.²⁹ In patients with extrinsic causes for sinus node dysfunction, treatment should be directed toward the underlying etiology. Drugs known to depress sinus node function can be switched to other agents that lack effects on the cardiac conduction system. This is not possible, however, in many patients. Patients with paroxysmal atrial tachyarrhythmias either require drugs to maintain sinus rhythm or agents to control ventricular rate, both of which may have significant sinus node depressant effects. In many of these patients, pacemaker therapy becomes essential. At the time of diagnosis of sinus node dysfunction, the incidence of atrial fibrillation is reported to be approximately 8%, and the likelihood of developing new atrial fibrillation in this group of patients is approximately 5% per year.³⁰ The prevalence of thromboembolism was reported to be 15.2% in this group. This underscores the importance of monitoring for atrial fibrillation and the need for oral anticoagulation in intermediate- to high-risk patients.

Pacing Therapy in Sinus Node Dysfunction

The current indications for pacing in the setting of sinus node dysfunction are shown in Table 86–3. In this and subsequent tables, the format used for American Heart Association (AHA)/American College of Cardiology (ACC) guidelines is used, with class I to III indications denoting the degree of agreement for a given procedure or treatment that is useful and effective.³¹

Sinus node dysfunction is the most common indication for permanent pacemaker implantation in North America, accounting for more than 42% to 60% of new pacemaker implants. The optimal pacemaker choice is influenced by a number of factors. At the time of diagnosis of sinus node dysfunction, 17% of patients have been reported to have AV conduction abnormalities in the form of a PR interval > 240 ms, bundle branch block, His to ventricular (HV) interval prolongation, AV Wenckebach rates < 120 bpm, and second- or third-degree AV block. The incidence of new AV block developing over time was reported to be < 2.7% per year.³² Generally, if the patient has persistent atrial fibrillation, a single-chamber ventricular pacemaker (VVIR) is recommended. In all other situations, a rate-responsive dual-chamber pacemaker (DDDR) is used, whereas a single-chamber atrial pacemaker (AAIR) can be implanted if no evidence of AV conduction disease is present.

Clinical Trials and Pacing Mode

Many nonprospective, nonrandomized studies have suggested significant survival benefits with physiologic pacing compared with ventricular demand pacing (VVI mode) in patients with sinus node dysfunction. This led to randomized, large-scale prospective trials, the results of which are summarized in Table 86–4. The first randomized trial comparing atrial with ventricular pacing in 225 patients with sick sinus syndrome demonstrated significant reduction in the incidence of atrial fibrillation, thromboembolism, and cardiovascular mortality in the atrial pacing group.³³ Subsequent large-scale trials have not confirmed these mortality or stroke prevention benefits. The Canadian Trial of Physiologic Pacing (CTOPP)³⁴ randomized patients with symptomatic bradycardia without chronic atrial fibrillation to receive either a physiologic (atrial or dual-chamber) pacemaker or a ventricular pacemaker, and showed no difference in stroke or cardiovascular mortality, but a decreased annual rate of atrial fibrillation in the physiologic pacing group (5.3%) compared with the ventricular pacing group (6.6%). Another large randomized trial of dual-chamber pacing versus ventricular pacing was Mode Selection Trial in Sinus Node Dysfunction (MOST),³⁵ which also confirmed the benefit of dual-chamber pacing to reduce the risk for atrial fibrillation. The United Kingdom Pacing and Cardiovascular Events (UKPACE) trial compared dual-chamber pacing with single-chamber ventricular pacing in patients older than 70 years of age with high-grade AV block.³⁶ Over a mean follow-up period of 4.6 years, there was no difference in annual mortality, atrial fibrillation, or heart failure between the groups. The DANPACE trial randomized 1415 patients with sinus node dysfunction to AAIR mode or DDDR mode and followed them for a mean of 5.4 ± 2.6 years.³⁷ There was no difference in the primary outcome of all-cause mortality (29.6% vs 27.3%, P = .53). There was no difference in the secondary outcome of chronic atrial fibrillation, stroke, and heart failure. The incidence of paroxysmal atrial fibrillation (28.4% vs 23%, P = .024) and the need for pacemaker reoperation (22.1% vs 11.9%, P < .001) were higher in the AAIR group compared to the DDDR group. In a meta-analysis of randomized pacing modes, atrial-based pacing was associated with a significant reduction in atrial fibrillation of approximately 20% (95% confidence interval [CI], 0.77-0.89; P = .00003) and a borderline significant reduction in the risk of stroke of 19% (95% CI, 0.67-0.99; P = .035). The use of atrial-based pacing did not reduce mortality or the incidence of congestive heart failure.³⁸

The failure to easily demonstrate clinical benefits of dual-chamber pacing has forced a rethinking of physiologic pacing. It is now well accepted that long-term RV pacing causes a deterioration of LV function through complex effects on regional ventricular wall strain and loading conditions. This deterioration is thought to result from intraventricular dyssynchrony between different regions of the left ventricle induced by RV apical pacing. Sweeney and coworkers demonstrated, by careful review of data from MOST, that an increase in the frequency of ventricular pacing in patients with sick sinus syndrome who had a narrow native QRS complex was associated with an increased incidence of atrial fibrillation and congestive heart failure.³⁹ These observations were confirmed by Wilkoff and colleagues in the Dual Chamber and VVI Implantable Defibrillator (DAVID) study, in which backup ventricular pacing and dual-chamber pacing were prospectively compared in patients with dual-chamber defibrillators.⁴⁰ The primary end point was a composite of congestive heart failure, hospitalization, and death, which was increased by a factor of 1.6 in patients with an increased frequency of ventricular pacing. Thus, RV pacing is a double-edged sword, conferring atrioventricular synchrony but at the same time possibly negating its benefit by inducing ventricular dysfunction. Sweeney and associates⁴¹ randomized 1065 patients with sinus node dysfunction and intact ventricular conduction to receive conventional dual-chamber pacing or dual-chamber minimal ventricular pacing with the use of new pacemaker features designed to promote atrioventricular conduction and prevent ventricular desynchronization. The hazard ratio for development of persistent atrial fibrillation in patients with dual-chamber minimal ventricular pacing as compared with those with conventional dual-chamber pacing was 0.60 (95% confidence interval [CI], 0.41-0.88; P = .009), indicating a 42% reduction in relative risk. We recommend that patients with sinus node dysfunction have the pacemaker programmed to either AAI(R) or DDD(R) with an algorithm that minimizes unnecessary ventricular pacing.

The pathophysiology, diagnosis, and specific management of these disorders are discussed separately elsewhere in this textbook (see Chap. 90). A hypersensitive response to carotid sinus stimulation of 5 to 10 seconds is defined as asystole caused by sinus arrest or AV block of more than 3 seconds (cardio inhibitory), a substantial symptomatic decrease in systolic blood pressure of 50 mm Hg or more (vasodepressor), or both (mixed). The pathophysiology of carotid sinus syncope is complex and poorly understood and is hypothesized to result from abnormalities of neuromuscular structures surrounding the carotid sinus mechanoreceptors, a central defect of the autonomic nervous system, and association with atherosclerotic disease. Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome as measured using iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning.⁴² Carotid sinus syncope predominantly occurs in elderly males with associated coronary artery disease. Although carotid sinus hypersensitivity is common, carotid sinus syncope is relatively rare, accounting for 11% to 19% of patients with syncope of undetermined cause. For patients with recurrent or severe carotid sinus syncope of the cardioinhibitory type, permanent pacemaker implantation is the accepted and proven modality of treatment as evidenced by many small randomized trials.⁴³ DDI or DDD pacemakers are generally the accepted mode of pacing for patients with carotid sinus syncope, whereas AAI pacing is contraindicated because many patients may demonstrate associated AV block. The current indications for pacing in hypersensitive carotid sinus syndrome and neurocardiogenic syncope are shown in Table 86–5.

Vasovagal syncope is a common condition caused by inappropriate reflex vasodilation and bradycardia and occasionally even asystole. Dual-chamber pacemakers with rate-drop response or rate hysteresis features are currently a treatment option in a select group of patients with recurrent syncope and refractory to conventional medical therapy. Three randomized, but non–placebo-controlled, trials have assessed the role of permanent pacemakers in patients with vasovagal syncope and cardioinhibitory response during tilt-table testing (Table 86–6).^44,45 The results of these trials are somewhat contradictory, and subsequent randomized, controlled trials^46,47 did not show a significant reduction in recurrent syncope. The Third International Study on Syncope of Uncertain Etiology (ISSUE-3) was a double-blind, placebo-controlled randomized study in patients > 40 years of age, three or more epiosdes of syncope in the previous 2 years, and ILR-documented asystole of ≥ 3 seconds with syncope or ≥ 6 seconds without syncope. Of 89 patients, 77 were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. There was a 32% absolute and 57% relative reduction of occurrence of syncope in patients with dual-chamber pacing compared to no pacing.⁴⁸ Cardiac pacing was effective in neurally mediated syncope patients with documented asystolic episodes in whom tilt table test was negative.⁴⁹ As a result, we recommend pacing therapy as a last resort for patients who are severely symptomatic and refractory to medical therapy.

AV block occurs when atrial conduction to the ventricle is blocked at a time when the AV junction is not physiologically refractory. This can be caused by conduction block in the atrium, AV node, and/or His-Purkinje system. Using His-bundle electrogram recordings, three anatomic sites of AV block can be identified: AV nodal, intra-Hisian, or infra-Hisian. Block at the AV nodal level implies a favorable prognosis, whereas block at or below the His-bundle level implies an unfavorable prognosis. Surface ECGs often provide adequate information to make a diagnosis regarding the site of the block, whereas intracardiac recordings are often necessary to define the level of the block at or below the His.

Pathophysiology of Atrioventricular Block

Transient or persistent AV block of varying degrees can occur in a variety of clinical situations (Table 86–7). Heightened vagal tone in athletes or during sleep may be associated with first-degree or type I second-degree AV block and occasionally even complete heart block. The AV block in these situations is usually preceded by slowing of the heart rate. Increased vagal tone during sleep is often associated with obstructive sleep apnea and may lead to high grade AV block and long pauses (Fig. 86–12). This is a common occurrence and pacemaker therapy is rarely indicated in this situation. Vagally mediated AV block may occur in response to various stimuli, such as carotid sinus hypersensitivity, coughing, swallowing, or micturition. Varying degrees of heart block have been described in a large variety of infectious diseases. Heart block associated with endocarditis may be transient or permanent. In patients with endocarditis and ring abscess, heart block may not resolve and pacing may be required. With Lyme disease, cardiac involvement may occur in 8% to 10% of patients. More than 50% of patients with cardiac involvement may develop advanced heart block requiring temporary pacing.²¹ Even complete AV block generally resolves in 1 to 2 weeks, and permanent pacing is seldom necessary.²¹ Chagas cardiomyopathy may be associated with persistent AV block.

Mutations in the cardiac-specific Na⁺ channel gene (SCN5A) have been associated with PCCD, also referred to as Lev or Lenegre disease.⁵⁰ It is a relatively common cardiac conduction disorder characterized by age-dependent progressive delay in the propagation of cardiac impulse through the His-Purkinje system with right bundle branch block (RBBB) or left bundle branch block (LBBB), eventually resulting in complete AV block. Patients with classic Lev disease demonstrate fibrosis within the proximal His bundle, whereas those diagnosed with Lenegre disease often demonstrate fibrosis within the more distal bundle branches and Purkinje fibers. SCN5A mutations can produce a variety of other phenotypes, including Brugada syndrome, congenital type 3 long QT syndrome, idiopathic ventricular fibrillation, congenital sick sinus syndrome, atrial fibrillation, and dilated cardiomyopathy. Dominantly inherited mutations in the transient receptor potential melastatin 4 (TRPM4) gene are associated with isolated cardiac conduction disease (ICCD), giving rise to AV conduction block.⁵¹ The TRPM4 channel mediates a Ca²⁺-activated nonelective cationic current (I_NSCca) involved in cardiac conduction, pacemaking, and action-potential repolarization. Andersen-Tawil syndrome (LQT7) is caused by mutations in the KCNJ2 gene encoding an inward rectifier potassium channel, Kir2.1. Patients may present with conduction abnormalities, such as AV block, bundle branch block, or intraventricular conduction delay. This syndrome is characterized by potassium-sensitive periodic paralysis, ventricular arrhythmias, and dysmorphic features.⁵² A variety of inherited heart disease has been recently reported to be associated with dilated cardiomyopathy and conduction system disease, including disorders of the nuclear envelope proteins lamin A and C.³⁵ Lamin A/C is necessary for the structural integrity of the nucleus; in the presence of LMNA mutation, myocardial cells exposed to mechanical stress undergo cell damage. LMNA mutations also are associated with dilated cardiomyopathy, with AV conduction defects referred to as “laminopathy.”⁵³

Acute Myocardial Infarction

AV block occurs in 12% to 25% of all patients with acute MI; first-degree AV block occurs in 2% to 12%, second-degree AV block in 3% to 10%, and third-degree AV block in 3% to 7%.⁵⁴ Ischemic injury can produce conduction block at any level of the AV or intraventricular conduction system. Second-degree type I AV block occurs more commonly in inferior than anterior MIs. Inferior infarctions are often associated early on with increased vagal tone causing sinus bradycardia and AV block. Most patients are asymptomatic, and rarely type I AV block may progress to complete AV block. Second-degree type II AV block occurs in 1% of patients with acute MI and predominantly occurs in patients with anterior infarctions. The risk of progression to complete AV block is high in these patients. Complete AV block can occur in both inferior and anterior infarction. In inferior MI, the block is typically at the level of the AV node and the escape rhythm generally arises from the AV junction, with a narrow QRS and an escape rate of 40 to 60 beats/min. The prognosis in these patients is generally good, as the AV block resolves in almost all patients within a few days and almost always by 1 week. Complete AV block resulting from anterior infarction is usually at the His or infra-Hisian level, and the escape rhythm is from the distal Purkinje fibers or the ventricle, with a wide QRS interval and a rate of 20 to 40 bpm. Because of the coexisting extensive infarction and pump failure, AV block resulting from anterior infarctions are associated with high mortality. In patients with acute MI, temporary pacing is generally indicated in patients with complete AV block at any level, type II second-degree AV block, and in patients with type I second-degree AV block if associated with symptomatic bradycardia. Although the incidence of complete AV block in acute MIs has decreased after thrombolytic therapy, the mortality still remains high. In the current era of percutaneous coronary intervention for acute ST-segment elevation MI, the incidence of second or third-degree AV block is significantly lower (3.2% in a retrospective study of 2073 patients).⁵⁵ In a recent study using the 2003 to 2012 National Inpatient Sample databases, the incidence of complete heart block complicating acute ST-segment elevation MI was 2.2% and the in-hospital mortality was higher in patients with complete heart block compared to those without complete heart block (20.4% vs 8.7%).⁵⁶ The indications for permanent pacing in patients with acute MI are listed in Table 86–8. Patients with coronary artery disease and ischemic cardiomyopathy may develop persistent AV block. AV nodal block can occur transiently during episodes of ischemia, especially with Prinzmetal angina.

A variety of uncommon autoimmune, oncologic, infectious, and iatrogenic disorders can also lead to heart block and are listed in Table 86–7. Certain neuromuscular disorders (myotonic dystrophy, Kearns-Sayre syndrome, peroneal muscular atrophy, Erb limb-girdle dystrophy, Emory-Dreifuss muscular dystrophy, and X-linked muscular dystrophies) may give rise to progressive and insidiously developing conduction disorders of the His-Purkinje system. Myotonic dystrophy and Kearns-Sayre syndrome are associated with high incidence of unpredictable and rapidly progressive conduction system disease.⁵⁷ Complete heart block may occur after aortic or mitral valve replacement surgery and, rarely, after coronary artery bypass surgery. Preoperative RBBB and multivalve surgery involving the tricuspid valve were shown to be strong independent predictors of postoperative heart block requiring permanent pacemaker implantation. Complete AV block is more common after surgical procedures to correct ventricular septal defects, tetralogy of Fallot, AV canal defects, or myectomy for hypertrophic obstructive cardiomyopathy. Transcatheter aortic valve replacement (TAVR) is a rapidly evolving technology for severe, calcific aortic stenosis. The incidence of complete heart block requiring permanent pacemaker following TAVR is significantly higher than the approximate 5% following surgical aortic valve replacement.^58,59 A recent meta-analysis of 41 studies including 11,210 patients undergoing TAVR showed that 17% required permanent pacemaker implantation (Fig. 86–13).⁶⁰ Two TAVR devices are most currently in clinical use in North America: the Edwards SAPIEN valve (ESV, Edwards Lifesciences Corp., Irvine, CA) and the CoreValve Revalving system (CV, Medtronics, Minneapolis, MN). The rate of permanent pacemaker implantation ranged from 2% to 51% in individual studies (with a median of 28% for the CV and 6% for the ESV). The rate of permanent pacemaker requirement is lower for the ESV compared to CV. The higher rate with CV may be a result of the design (self-expanding as compared to balloon expanding) and lower position in the LV outflow tract.⁶¹ Recent changes to the ESV (S3) were noted to be associated with a higher pacemaker implantation rate attributable to lower positioning of the valve in the LV outflow tract.⁶¹ Male sex, preexisting conduction abnormalities (first-degree AV block, RBBB, left anterior hemiblock,) and intraprocedural AV block are predictors of need for permanent pacer post-TAVR.⁶² Recent meta-analysis also suggests that new-onset LBBB post-TAVR is a marker of an increased risk of cardiac death and need for a permanent pacemaker at 1-year follow-up.⁶³

Complete AV block can also occur in 0.5% to 2% of patients as a complication during radiofrequency catheter ablation of supraventricular arrhythmias, primarily AV node reentrant tachycardias and septal accessory pathways. Radiofrequency catheter ablation is also used to create permanent complete AV block in patients with paroxysmal and chronic atrial tachyarrhythmias (most frequently AF). This treatment option is reserved for the small group of patients in whom AV node–blocking drugs cannot control the heart rate or who are intolerant, unwilling, or unable to take drugs to maintain sinus rhythm or control the ventricular response during AF.

Congenital heart diseases such as corrected transposition of great arteries, ostium primum atrial septal defects, and ventricular septal defects may be associated with complete heart block. Congenital complete AV block is a rare anomaly that results from abnormal embryonic development of the AV node and is not associated with structural heart disease in 50% of cases. Congenital complete heart block is also associated with maternal lupus erythematosus. When congenital complete heart block is detected in utero in a child with a structurally normal heart, the condition is frequently associated with intrauterine exposure to maternal autoantibodies to Ro and La (ie, neonatal lupus); this situation has a better prognosis than when congenital heart disease is present.⁶⁴ Most children with isolated congenital complete AV block have a stable escape rhythm with a narrow complex. Pacing is generally indicated in children with complete heart block if the heart rate in the awake child is < 50 bpm or if associated with LV systolic dysfunction or ventricular arrhythmias. The indications for pacing in children, adolescents, and patients with congenital heart disease are outlined in Table 86–9.

Anti-Ro/SSA-associated AV block has been described in adults. Currently available data suggest two possible forms of anti-Ro/SSA-associated AV block in adults: (1) an acquired form and (2) a late progressive congenital form.⁶⁵ The acquired form is characterized by the presence of anti-Ro/SSA antibody in the affected subject. In these patients immunosuppressive therapy (methylprednisolone plus azathioprine) may normalize rhythm disturbances. By contrast, in the late progressive congenital form, anti-Ro/SSA antibodies are not detectable in the subjects while their mothers are seropositive. Immunosuppressive therapy has no clinical value in these patients. It is estimated that these two forms may represent at least 20% of all cases of isolated complete heart block of unknown origin in adults (10% of each form).

Cardiac sarcoidosis should be considered in the differential diagnosis in a young patient (20-40 years old) presenting with complete heart block.⁶⁶ Cardiac manifestations of sarcoidosis are present in at least 25% of patients with systemic sarcoidosis and can include Mobitz II, second-degree AV block, LBBB, RBBB, complete heart block (~30%), ventricular tachyarrhythmias, intracardiac masses, ventricular aneurysms, and dilated cardiomyopathy. Current expert consensus statement on arrhythmias associated with cardiac sarcoidosis recommends that in patients aged < 60 years presenting with unexplained Mobitz II second-degree AV block or complete heart block, further evaluation with high-resolution chest computed tomography and/or cardiac magnetic resonance imaging may be necessary to diagnose cardiac sarcoidosis.⁶⁷ Patients with conduction system disease and evidence of cardiac or sarcoidosis in other organs should undergo implantation of either a dual-chamber pacemaker or defibrillator.

Drug-induced bradycardia is a common and important clinical problem.⁶⁸ Many common drugs, including β-adrenergic blockers, calcium channel antagonists, digoxin, class I and III antiarrhythmic drugs, tricyclic antidepressants, phenothiazines, lithium, and donepezil (a cholinesterase inhibitor used to treat Alzheimer disease), can cause AV conduction disturbances. If the AV block is caused by drug toxicity, is expected to resolve, and is unlikely to recur, pacemaker implantation is generally considered unnecessary, according to current guidelines. However, if AV block occurs in the setting of drug use or toxicity, and the block is expected to recur even after the drug is withdrawn, pacemaker implantation may be considered (class IIb indication). In the majority of patients presenting with presumed drug-induced AV block, discontinuation of the offending medications does not obviate the need for pacemaker implantation.⁶⁹

Paroxysmal AV block is defined as the sudden occurrence, during a period of 1:1 AV conduction, of a block of sequential atrial impulses resulting in a transient total interruption of AV conduction.^70,71 It is thus the onset of a paroxysm of high-grade AV block associated with a period of ventricular asystole before conduction returns or a subsidiary pacemaker escapes. It may occur in variety of clinical conditions associated with vagal stimulation (eg, coughing, swallowing, vomiting, micturition, during abdominal pain) or in the setting of His-Purkinje conduction system disease. Idiopathic paroxysmal AV block is a distinct form of syncope characterized by a long history of recurrent syncope as a result of idiopathic paroxysmal AV block with long pauses, absence of cardiac and ECG abnormalities, absence of progression to persistent forms of AV block, and efficacy of cardiac pacing therapy.⁷² These patients show an increased susceptibility to exogenous adenosine. Permanent pacemakers are effective in these patients to prevent symptoms such as syncope.

Electrocardiographic Manifestations

First-Degree Atrioventricular Block

Prolongation of the PR interval to > 200 ms constitutes first-degree AV block. It is most commonly caused by conduction delay within the AV node and occasionally caused by intra-atrial or infra-Hisian conduction delay. If the QRS duration is normal, the site of conduction delay is almost always within the AV node. If first-degree AV block occurs in the presence of bundle branch block, the conduction delay can be in the AV node (60% of cases), His-Purkinje system, or both. Patients with first-degree AV block have an excellent prognosis even when associated with chronic bifascicular block, as the rate of progression to third-degree AV block is low, and no specific therapy is indicated (Fig. 86–14).

Second-Degree Atrioventricular Block

Second-degree AV block is characterized by intermittent failure of conduction from the atria to the ventricles. If the AV block occurs with the atrial rate in the physiologic range, it is considered a primary arrhythmia. AV block in the setting of atrial tachyarrhythmias is generally a normal response. Based on the electrocardiographic patterns, second-degree AV block is classified into Mobitz types I and II.

Second-Degree Atrioventricular Block of the Wenckebach Type (Mobitz Type I)

Second-degree AV block of the Wenckebach type (Mobitz type I) is characterized by the following features: (1) progressive prolongation of the PR interval before a nonconducted P wave, (2) PR interval prolongation at progressively decreasing increments, (3) progressive shortening of R-R intervals, (4) pause encompassing the blocked P wave shorter than the sum of two P-P cycles, and (5) the last conducted PR interval before the blocked P wave longer than the next conducted PR interval (Fig. 86–15). Type I second-degree AV block often occurs with regularity leading to patterns of group beating. When type I second-degree AV block occurs in association with a normal QRS interval, block is almost always in the AV node. In the presence of a prolonged QRS interval, block may be in the AV node, His-Purkinje (rare), or both. Very long PR intervals are usually caused by a block in the AV node. Type I second-degree AV block occurs in a small percentage of normal people and, not uncommonly, in well-trained athletes. Most patients are asymptomatic, whereas some develop symptomatic bradycardia, near syncope, or occasionally syncope caused by progression to complete AV block.

Mobitz Type II Second-Degree Atrioventricular Block

Mobitz type II second-degree AV block is characterized by (1) constant P-P intervals and R-R intervals, (2) constant PR intervals before a nonconducted P wave, and (3) pause encompassing the nonconducted P wave equal to two P-P cycles. Type II AV block usually occurs in the presence of bundle-branch block and is almost always caused by a block in the His-Purkinje system (Fig. 86–16). Type II AV block rarely occurs in patients with normal QRS duration. Type II AV block frequently progresses to a complete AV block and may result in syncopal attacks.

2:1 Atrioventricular Block

In this form of second-degree AV block, every other P wave is not conducted, making it difficult to diagnose the level of AV block (Fig. 86–17). A 2:1 AV block pattern with normal QRS duration or with a very long PR interval generally suggests block in the AV node. A 2:1 AV block pattern in the presence of bundle branch block especially in the setting of normal PR interval favors block below the AV node, but is not diagnostic (Fig. 86–18). A prolonged electrocardiographic recording may sometimes reveal a transition to varying degrees of AV block (3:2 or 4:3), with type I or type II features that aid in the diagnosis. Rarely, Wenckebach conduction may be noted in the His-Purkinje system. Intracardiac recordings with a His-bundle catheter are sometimes necessary to determine the site of the block (Fig. 86–19). In patients with a 2:1 AV block, vagal maneuvers are helpful in diagnosing the level of AV block. Carotid sinus stimulation may worsen the degree of block if it is in the AV node, whereas slowing of the sinus rate may paradoxically improve the ratio of AV conduction and increase ventricular rate if the block is located in the His-Purkinje system. Similarly, atropine improves AV nodal conduction, but the increased sinus rate may worsen the ratio of AV conduction in patients with His-Purkinje block, resulting in worsened bradycardia. Hence atropine should be used with caution in patients with a 2:1 AV block and bundle branch block where His-Purkinje disease is strongly suspected.

High-Grade Atrioventricular Block

When two or more consecutive atrial impulses do not conduct to the ventricle, it is defined as high-grade AV block. It may be associated with a junctional or ventricular escape rhythm. Occasionally, runs of consecutive atrial impulses may fail to conduct to the ventricles for up to 10 to 20 s with or without an escape rhythm, resulting in ventricular asystole and syncope. The block is usually initiated by a conducted or blocked atrial or ventricular premature beat. The block persists until terminated by an escape beat. Unless a clearly defined reversible etiology is identified, permanent pacing is indicated.

Third-Degree Atrioventricular Block

Complete or third-degree AV block is characterized by failure of all P waves to conduct to the ventricle. This results in complete dissociation of P waves and QRS complexes. Complete AV block may occur as a result of block in the AV node or at the His-Purkinje level. In patients with block at the AV node level, the escape rhythm is usually junctional, with a narrow QRS complex (unless associated with preexisting bundle branch block), at rates of 40 to 60 bpm (Fig. 86–20). In complete heart block resulting from His-Purkinje disease, the escape rhythm is ventricular in origin, with a wide QRS interval and at rates of 20 to 40 bpm (Fig. 86–21).

Atrioventricular Dissociation

This rhythm is characterized by atrial and ventricular activity independent of each other. AV dissociation may be secondary to AV block (complete heart block) or physiologic refractoriness. AV dissociation can occur when the sinus rate is slower than the secondary junctional or ventricular pacemaker as in patients with sinus bradycardia. In contrast, AV dissociation can also occur in the presence of normal sinus rhythm and accelerated junctional (junctional tachycardia) or ventricular (VT) rhythm with retrograde conduction block. In patients with complete heart block, the atrial rate is faster than the ventricular rate, whereas in AV dissociation, the ventricular rate is faster than the atrial rate. Although AV dissociation is present in complete heart block, it is not synonymous. AV dissociation is usually a manifestation of another rhythm abnormality, such as complete heart block, sinus bradycardia, or VT. Treatment is usually directed toward the underlying cause.

Clinical Presentation

Symptoms in patients with AV conduction abnormalities are generally caused by bradycardia and loss of AV synchrony. Patients with significantly prolonged PR intervals may behave in a similar fashion to patients with pacemaker syndrome because of loss of AV synchrony. In patients with structural heart disease and LV dysfunction, this may result in worsening of heart failure. Symptoms caused by more advanced AV block may range from exercise intolerance, easy fatigability, dyspnea on exertion, dizzy spells, and near syncope to frank syncope. In patients with paroxysmal or intermittent complete heart block, these symptoms are episodic, and routine ECGs may not be diagnostic. Children and adolescents with isolated complete heart block may be generally asymptomatic, whereas some may develop symptoms later as adults because of chronotropic incompetence. Other late signs and symptoms include the development of congestive heart failure and nonsustained VT. Children with complete heart block associated with structural heart disease are symptomatic very early on and have an increased risk for sudden death.

Diagnostic Evaluation

The prognosis and treatment of AV block depends on its association with symptoms and the level of AV block. Routine 12-lead surface ECGs adequately establish the diagnosis of varying degrees of AV block in many patients. Analyzing the PR interval, QRS duration, Wenckebach phenomenon, and ventricular rates on the surface ECG provides important clues to the level of AV block. In certain situations such as 2:1 AV block, additional maneuvers may be necessary to establish the level of AV block. Responses to carotid sinus massage, atropine, and exercise are often very helpful.

In patients with complete heart block at the level of the AV node, the resultant junctional escape rhythm usually accelerates with exercise in contrast to the ventricular escape rhythm with infranodal block, which usually remains unchanged. Early studies using His bundle recordings have suggested that intra-His block contributes only 15% to 20% of patients with infranodal AV block.^73,74 However, recent observations suggest that in the majority of patients with infranodal AV block, the conduction disease is in the main His bundle, suggesting intra-His block.^4,75 In a consecutive series of 100 patients, AV nodal block was noted in 46% of the patients and infranodal (HV) block was observed in 54% of the patients.⁴ Presence of split His potentials, narrow QRS in the setting of HV block, identification of distal His potential, and correction of His-Purkinje conduction by permanent His bundle pacing were used to identify a high (76%) percentage of patients with intra-His block (Fig. 86–22).

In patients with paroxysmal symptoms of near syncope or syncope and no significant conduction abnormalities on the surface ECG, prolonged electrocardiographic monitoring with 24- to 48-hour Holter recordings or 30-day event monitors may be helpful. Newer event monitors with automatic detection algorithms and cellular technology have increased the yield of these monitors. An ILR may be necessary to establish the diagnosis, particularly in patients with infrequent symptoms. Electrophysiology study is indicated in patients with syncope or near syncope in whom high-grade AV block is suspected as the cause. In patients with structural heart disease, in addition to AV conduction disease, VT can also be a major etiology for syncope, and electrophysiology study can be very useful in establishing the diagnosis.

Management

Identifying transient or reversible causes for AV conduction disturbances is the first step in management. Withdrawal of any offending drugs, correction of any electrolyte abnormalities, or treatment of any infectious processes should be considered before permanent pacing therapy. If the drugs causing AV block are essential for treatment of other medical conditions, permanent pacing may be considered. However, it has become increasingly realized that many patients with AV block believed to be precipitated by drugs may develop recurrent heart block in follow-up even after discontinuation of the offending agent(s).⁶⁸ In patients with advanced AV block and hemodynamic decompensation unresponsive to drug therapy such as atropine or isoprenaline, as in digitalis toxicity, hyperkalemia, acute anterior MI, or Lyme myocarditis, temporary pacing should be instituted until AV block resolves or permanent pacing can be initiated. Temporary pacing can be accomplished by transcutaneous pacing systems in those patients at low-to-moderate risk for developing complete heart block or in patients with complete heart block and hemodynamically stable escape rhythms. Transcutaneous pacing for prolonged periods is very uncomfortable and transvenous pacing should be performed in patients with need for continuous active pacing.

Permanent pacemaker implantation is indicated in most patients with advanced heart block associated with symptoms. Permanent pacemakers are also indicated in asymptomatic patients with complete heart block and infra-Hisian second-degree AV block. Permanent pacing has clearly been shown to decrease mortality in patients with advanced heart block and syncope.⁷⁶ The indications for pacing in children with AV block and in adults with acquired heart block are described in Table 86–9 and Table 86–10, respectively.

Most patients with AV block require dual-chamber pacemakers, because this mode of pacing maintains AV synchrony and prevents development of pacemaker syndrome. In patients with associated sinus node dysfunction, dual-chamber pacemakers with a rate-responsive function (DDDR) are the preferred mode of choice. In patients with normal sinus node function and AV block, VDD pacing using a single lead with a series of electrodes for atrial sensing and ventricular pacing and sensing is an ideal mode of pacing, because it provides AV synchrony and rate responsiveness and is superior to single-chamber VVI pacing. In patients with chronic atrial fibrillation and bradycardia, rate-responsive single-chamber ventricular pacing (VVIR) is adequate. Early studies of comparison of pacing modes in a small number of patients with AV block had shown that physiologic pacing (DDD or VDD) enhanced survival compared with VVI pacing.^75,77 However, prospective, randomized, large-scale trials showed that dual-chamber pacing provided little benefit over ventricular pacing for the prevention of death (see Table 86–4). The incidence of pacemaker syndrome was as high as 26% in patients with ventricular pacing, necessitating cross-over to dual-chamber pacing in the pacemaker selection in the elderly trial.³⁵

Growing recognition of the long-term adverse effects of RV apex pacing has stimulated interest in strategies to promote physiologic pacing and to minimize or eliminate the deleterious effects.^78,79 There is controversy, however, regarding the optimal ventricular pacing sites and approach in patients undergoing permanent pacemaker implantation for AV block in whom ventricular pacing cannot be avoided.⁸⁰ Some investigators advocate LV or biventricular pacing, whereas others suggest a role for selective-site RV pacing. Alternative RV pacing sites (ie, non-RV apex), including the His bundle, RV septum, RV outflow tract, and dual-site right ventricle, have been investigated, but the benefits of alternative-site pacing remain unresolved.^81,82 In a recently published protect-pace study that randomized 240 patients with high-grade AV block to high septal or RV apical pacing (> 90% RV pacing), there was no significant difference in intrapatient change in LV ejection fraction (LVEF) between the two groups.⁸³

Current guidelines indicate that cardiac resynchronization therapy can be useful for patients with symptomatic heart failure and LVEF ≤ 35% who are expected to require frequent ventricular pacing (> 40%) after device implantation. However, the role of biventricular pacing in patients with AV block and a normal LVEF or only modest depression of LV function remains unsettled. The Biventricular Versus RV Pacing in Heart Failure Patients With Atrioventricular Block (BLOCK HF) study was a prospective trial that randomized 691 patients with mild-to-moderate heart failure (NYHA Class I, II, or III), LV dysfunction (LVEF ≤ 0.50), and AV block to RV pacing versus biventricular pacing with an average follow-up of 37 months.⁸⁴ Patients randomly assigned to biventricular pacing had a significantly lower incidence of the primary outcome (time to death from any cause, an urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the LV end-systolic volume index) over time than did those assigned to RV pacing (hazard ratio, 0.74; 95% credible interval, 0.60 to 0.90). The Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) trial⁸⁵ randomized 1810 patients with AV block (mean age 73.5 years) to either RV pacing (n = 908) or biventricular pacing (n = 902) and after a mean follow-up of 5.6 years, the groups had a similar rate of the composite end point that included time-to-death or first hospitalization as a result of heart failure, with a nonsignificant trend in favor of biventricular (hazard ratio 0.87; P = .08). It is unclear which patients, if any, would benefit from biventricular pacing in the setting of normal LV function.

The His bundle is an ideal RV stimulation site from a hemodynamic standpoint. However, the technical challenge of long-term implementation of permanent His bundle pacing (HBP) had thus far been a major obstacle to its reliable application in routine clinical practice. By preserving normal electrical activation of the ventricles, HBP prevents ventricular dyssynchrony and its long-term consequences (Fig. 86–23). Recent studies have shown that permanent HBP is technically feasible and may be safe in routine clinical practice.^86,87 Preliminary data suggest that permanent HBP is associated with an improvement in exercise capacity, myocardial perfusion, ventricular synchrony, and LVEF compared to RV pacing.^88,89

Bundle Branch Block

Conduction disturbances that occur at various levels of the branches of the His-Purkinje system are described as bundle branch block or intraventricular conduction defects. In patients with isolated chronic RBBB or LBBB, the progression to advanced AV block is rare. Patients with bifascicular block (RBBB and left anterior or posterior fascicular block) or LBBB and left axis deviation have a 6% annual incidence of progression to complete heart block.⁹⁰ In patients with acute MI, the development of new bifascicular block and first-degree AV block is associated with a very high risk (42%) for progression to high-grade AV block. These patients are generally recommended to undergo prophylactic temporary pacing. Alternating bundle branch block, even in asymptomatic patients, is a sign of advanced conduction disturbance in the His-Purkinje system and is considered a class I indication for permanent pacing. In patients with bundle branch block, His-bundle recordings can occasionally be helpful in identifying patients at high risk for progression to high-grade AV block. The incidental findings of markedly prolonged HV interval (> 100 ms) or atrial-pacing–induced infra-Hisian block⁹¹ that is not physiologic during an electrophysiology study are considered to indicate high risk for progression to advanced AV block, and prophylactic permanent pacing is recommended (Table 86–11). Intraventricular conduction disturbances are usually associated with significant structural heart disease, especially dilated (ischemic or idiopathic) cardiomyopathies, and are a marker of poor prognosis both in terms of advanced heart failure and increased mortality in these patients. LBBB in patients with cardiomyopathy is associated with significant ventricular dyssynchrony, worsening heart failure, and increased mortality. Biventricular pacing in these patients has been shown to improve heart failure and decrease mortality.^92,93 In a subgroup of patients with nonischemic cardiomyopathy, biventricular pacing can normalize LV function (hyperresponders), raising the possibility of LBBB-induced cardiomyopathy.⁹⁴ Recent evidence also suggests that bundle branch block is often caused by to disease in the proximal His bundle and may be amenable to correction by permanent HBP.^95,96