topics

11/6/25

1874 PART 6 Disorders of the Cardiovascular System

+30 mV

–60 mV

–30 mV

0 mV

Threshold

Phase 4

Phase 0 Phase 3

Sinus Node Pacemaker Cells

Phase 4

Ca-T

Ca-L

K i

FIGURE 244-1 Cellular ion currents involved in depolarization and automaticity of SA nodal pacemaker cells. Phase 4 spontaneous depolarization results from if

(funny)

current, along with T- and L-type calcium channels. Phase 0 is the depolarization phase of the action potential. This is followed by phase 3 repolarization, which results from

the outward directed hyperpolarizing K+ currents. if

, funny current; iCa-T, T-type calcium current; iCa-L, L-type calcium current; iK

, potassium current.

400 ms

4 Sinus (55 bpm), pause (3.4 seconds)

08/18/20 12:22:10pm Associated with patient triggered event

FIGURE 244-2 Sinoatrial exit block. A pause in the heart rhythm is seen that results from a sinus pause. On the second line of the tracing there is a pause that results from

the absence of a sinus beat (absent P wave) and no subsequent QRS. This is followed by a junctional escape beat and eventually recovery of the presence of sinus rhythm

P waves.

■ DIAGNOSIS OF SA NODAL DISEASE

Intrinsic sinus node disease is sometimes referred to as sick sinus syndrome or sinus node dysfunction (SND) and can manifest as fatigue,

exercise intolerance, or syncope resulting from either reduced heart

rate or pauses. Electrocardiographic recording plays a central role in

the diagnosis and management of SA node dysfunction. The correlation between symptoms and slow heart rate or pauses is essential in

determining whether bradycardia may be considered pathologic and

necessitating intervention. Baseline ECG can detect baseline sinus

bradycardia but may not indicate symptom correlation in certain

settings. To address the limitations of the resting ECG, longer-term

recording employing mobile telemetry devices such as Holter monitors

or mobile cardiac telemetry can also be helpful in correlating symptoms with rate abnormalities (Fig. 244-2).

The Bradyarrhythmias: Disorders of the Sinoatrial Node

1875CHAPTER 244

TABLE 244-1 Reversible Causes of Sinus Node Dysfunction

Medical Conditions Associated with Sinus Bradycardia

• Hypothyroidism

• Sleep apnea

• Hypoxia

• Hypothermia

• Increased intracranial pressure

• Lyme disease

• Myocarditis

• COVID-19

• Vagal reflex (cough, pain, etc.)

Medications Associated with Sinus Node Dysfunction

Antihypertensive Medications

• Beta-adrenergic receptor blockers

• Clonidine

• Methyldopa

• Nondihydropyridine calcium channel blockers

Antiarrhythmic Medications

• Amiodarone

• Dronedarone

• Flecainide

• Procainamide

• Propafenone

• Quinidine

• Sotalol

• Ivabradine

Psychiatric Medications

• Donepezil

• Lithium

• Opioid analgesics

• Phenothiazine antiemetics and antipsychotics

• Phenytoin

• Selective serotonin reuptake inhibitors

• Tricyclic antidepressants

Other

• Anesthetic drugs (propofol)

• Cannabis

• Digoxin

• Muscle relaxants

In addition, commercially available wearable devices, such as

watches with electrocardiographic recording capabilities, can also have

excellent fidelity electrograms that may also be utilized. Contemporary

event monitors may be automatically triggered to record the ECG

when certain programmed heart rate criteria are met and implantable

monitors permit very long-term recording (years) in particularly

challenging patients. Treadmill testing can be utilized to assess for

maximum heart rate. It is worth noting, however, that standard Bruce

protocol treadmill testing may be helpful in detecting abnormalities in

maximum heart rate, but more insidious chronotropic incompetence

that manifests as abnormalities of rate increase during submaximal

exercise may be more evident with treadmill protocols that have more

gradual effort increases.

Once there is evidence of sinus node dysfunction, it is important to

rule out reversible causes of resting sinus bradycardia or chronotropic

incompetence. Table 244-1 lists the potentially reversible causes of

sinus node disease and includes hypothyroidism and rate-slowing

medications. Many patients with sleep apnea will have high vagal tone

during sleep and especially during apneic events. Sinus bradycardia

and sinus pauses frequently are seen if a patient is being monitored

during this period. Sleep apnea, a common reversible cause, should be

suspected if marked sinus bradycardia and prolonged sinus pauses are

observed in a telemetry monitoring period during sleep.

If structural heart disease is suspected, transthoracic echocardiography should be used to detect potential cardiac abnormalities associated

with sinus node dysfunction (Fig. 244-3). Advanced cardiac imaging

is indicated for evaluation of possible myocardial diseases such as

amyloidosis, infiltrative cardiomyopathy, or myocarditis. Invasive

electrophysiology testing solely to assess sinus node function is rarely

utilized beyond the noninvasive techniques mentioned. In patients

who are also undergoing electrophysiology studies (EPS) for other

indications, evaluation of sinus node function as part of the EPS may

be considered. In symptomatic patients with suspected SND, EPS may

rarely be considered when the diagnosis remains uncertain and after

initial noninvasive evaluation is inconclusive. Investigation of the sinus

node during EPS can consist of determination of sinus node recovery

time (SNRT) and sinoatrial conduction time (SACT). In addition, the

intrinsic heart rate [118.1 – (0.57 × age)] can be assessed via pharmacologic blockade of autonomic tone with intravenous propranolol and

atropine. EPS is not widely used, however, as there is no evidence that

abnormal SNRT or SACT alone can be used as an indication for permanent pacing (PPM). There is no indication for EPS in asymptomatic

patients with sinus bradycardia.

■ SA NODAL DYSFUNCTION SUBTYPES

SND can be categorized into problems with impulse formation and

problems with impulse conduction. The term sick sinus syndrome may

be used interchangeably with SND and refers to a group of related conditions comprising problems of both impulse formation and impulse

conduction.

Sinus Node Exit Block (See Fig. 244-4) “Sinus arrest” results

from failure of impulse formation within the sinus node. Sinoatrial

exit block results from failure of sinus node activity to propagate to the

atrium. Sinoatrial exit block can have similar pattern characteristics of

types of AV node block. It can manifest as complete SA block. Type I

SA block involves fixed delay out of the sinus node. Type II SA block

can occur with either progressive delay and then intermittent failure to

propagate to the atrium (Mobitz I type) or fixed delay with intermittent

failure to conduct (Mobitz II). The mass of the sinus node is not large

enough to have an appearance on the ECG. Instead, the P waves that

result from atrial depolarization can provide information that reflects

the health of the sinus node. Type II second-degree SA block can be

inferred on the ECG if the sinus rate abruptly transitions to a sinus

rate that is half the previous rate (every other sinus depolarization is

blocked from exiting to the atrium). Sinoatrial Wenckebach can be

inferred from the ECG in the setting of progressive shortening of the

P-P interval leading up to a sinus pause. This is due to progressive

prolongation of sinoatrial conduction, but to a lesser extent with each

successive prolongation. This is similar to the typical progressive shortening of the R-R interval that is observed with AV nodal Wenckebach.

Other types of SA block require invasive EPS to decipher. The exercise

of determining the type of SA block with invasive electrophysiology

testing is typically not necessary because it does not alter management.

Tachy-Brady Syndrome Tachycardia-bradycardia (tachy-brady)

syndrome is a subset of sick sinus syndrome/sinus node disease that

consists of high heart rates (most commonly atrial fibrillation) with

alternating symptomatic bradycardia or offset pauses (Fig. 244-5).

Commonly, medications that are needed for rate control of tachycardia

exacerbate bradycardia episodes, and thus the presence of tachy-brady

syndrome is often a reason to consider pacemaker implantation.

Chronotropic Incompetence Chronotropic incompetence (CI)

is broadly defined as the inability of the heart to increase its rate to

meet activity or demand. Compared to an increase stroke volume, the

increase in heart rate is a stronger contributor to the increase in oxygen

uptake (VO2

) during aerobic exercise. Therefore, CI can be associated

with severe exercise intolerance and increased cardiovascular events

and overall morality. CI can take many forms including failure to

achieve a maximum heart rate [208 – (0.7 × age)], heart rate instability

with exercise, or failure to achieve submaximal heart rate. Due to this

1876 PART 6 Disorders of the Cardiovascular System

Evidence for sinus

node dysfunction

Reversible or

physiologic cause

Treat underlying cause as

needed, e.g., sleep apnea

(Class I)

Transthoracic

echocardiography

(Class IIa)

Suspicion

for infiltrative CM,

endocarditis,

ACHD

Treatment

effective or

unnecessary

Yes No

Yes

Observe

Yes

Observe

Symptoms

Exercise

Advanced imaging

(Class IIa)

Treat identified

abnormalities

Yes

Diagnostic

Sinus node dysfunction

treatment algorithm

If not already performed:

Ambulatory ECG monitoring

(Class I)

Electrophysiology study

(if performed for other reasons)

(Class IIb)

Suspicion for

structural heart

disease

If not already performed:

Exercise ECG testing

(Class IIa)

FIGURE 244-3 Evaluation of bradycardia and conduction disease. In patients with sinus node dysfunction, reversible causes should be identified and eliminated when

possible. If no reversible cause can be identified, structural heart disease should be considered and evaluated for, if appropriate. If no symptoms are present, an observation

strategy is appropriate. In patients who are symptomatic, further evaluation with ambulatory monitoring or exercise testing to identify symptom-rhythm correlation should

be considered. (Reproduced with permission from FM Kusumoto et al: 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and

cardiac conduction delay. Heart Rhythm 16:e128, 2019.)

The Bradyarrhythmias: Disorders of the Sinoatrial Node

1877CHAPTER 244

latter category, standard exercise testing can, at times, fail to recognize

a patient with CI as some patients can achieve an appropriate maximum heart rate but may exhibit heart rate instability. Ambulatory heart

rate monitoring along with a diary can be helpful to correlate symptoms with abnormally slow heart rates. Because CI can be insidious and

multiple definitions exist, it can be easily overlooked.

Sinus Node Fibrosis Clinical SND is most common in older

adults. This is due to normally occurring age-associated increase in

fibrotic tissue in the SA node, which can exacerbate any degree of SND.

A loss of pacemaker cells in the sinus node is also seen with age. It is

worth noting, however, that while increased fibrosis in the SA node

and decreased numbers of pacemaker myocytes are part of a normal

process of aging, SND is pathologic and there are many elderly patients

with extensive fibrosis and normal heart rate.

SA Nodal Ischemia and Infarction Sinus bradycardia is common in patients with acute inferior or posterior MI and can be

exacerbated by increased vagal tone (Bezold-Jarisch reflex) or with

the use of drugs such as morphine and beta blockers. Ischemia of the

SA nodal artery probably occurs in acute coronary syndromes more

typically with involvement with the right coronary artery, and even

with infarction, the effect on SA node function most often is transient.

However, there are rare cases where sinoatrial infarction can affect

sinus node function. One potential complication of atrial fibrillation

ablation is the inadvertent injury to the SA nodal artery that may be

coursing over a targeted ablation region in the right and left atrium.

SND and arrest have been described following ablation of atrial fibrillation and flutter.

Carotid Sinus Hypersensitivity and Neurally Mediated

Bradycardia Sinus bradycardia is a prominent feature of carotid

sinus hypersensitivity and neurally mediated bradycardia associated

with the cardioinhibitory variant of vasovagal syncope. Carotid hypersensitivity with recurrent syncope or presyncope associated with a

III

SAN EG

FIGURE 244-4 A. Mobitz type I SA nodal exit block. A theoretical SA node electrogram (SAN EG) is shown. Note that there is grouped beating producing a regularly irregular

heart rhythm. The SA node EG rate is constant with progressive delay in exit from the node and activation of the atria, inscribing the P wave. This produces subtly decreasing

P-P intervals before the pause, and the pause is less than twice the cycle length of the last sinus interval. B. Mobitz type II SA nodal exit block. This panel shows sinus

rhythm in the first four beats followed by a sinus pause with the absence of a P wave. The interval comprising the absent P wave is exactly twice as long as the preceding

P-P interval consistent with type II sinoatrial exit block. SA, sinoatrial.

400 ms

Termination of Atrial Fibrillation (90-105 bpm), Pause (7.4 seconds)

09/04/20 06:22:16pm

10 mm/mV, 24 s

FIGURE 244-5 Offset pause and tachy-brady syndrome. An offset pause after termination of atrial fibrillation is seen and is consistent with tachy-brady syndrome.

1878 PART 6 Disorders of the Cardiovascular System

predominant cardioinhibitory component responds to pacemaker

implantation. The vasodepressor effect of the enhanced vagal tone is

unaffected by the pacing support, but the lack of bradycardia often

prevents injury with this subtype of vasovagal syncope. Several randomized trials have investigated the efficacy of permanent pacing in

patients with drug-refractory vasovagal syncope, with mixed results.

Although initial trials suggested that patients undergoing pacemaker

implantation have fewer recurrences and a longer time to recurrence

of symptoms, at least one follow-up study did not confirm these results.

TREATMENT

SA Nodal Disease

TEMPORARY PACING FOR TRANSIENT SUPPORT

In symptomatic patients presenting with sinus node disease, removing any possible reversible cause remains the initial strategy. Acute

myocardial infarction, electrolyte abnormalities, medications, and

hypothyroidism should all be considered as potentially reversible

causes. Unnecessary medications that may be causing bradycardia

should be eliminated. Beta blockers, calcium channel blockers, and

digoxin are some of the more common medications in use that may

case bradycardia. These drugs may have a wide range of indications

in patients after MI and with chronic systolic dysfunction. If stopping the medication or decreasing the dose is an option, this should

be tried first. If the medication is felt to be essential in patient management, a pacemaker may be indicated.

In patients with tachy-brady syndrome, alleviation of the

tachycardia, whether it is atrial fibrillation or other forms of

supraventricular tachyarrhythmias, can prevent bradycardia events.

Treatment of the tachycardia can sometimes be accomplished with

antiarrhythmic drug therapy or catheter ablation. If this cannot be

achieved, permanent pacing may be necessary.

Hypoxia from decrease in blood flow to the SA node, which can

occur with cardiac ischemia or MI, can lead to slowing of phase

4 depolarization and resultant bradycardia. Further ischemia and

necrosis of pacemaker cells can cause irreversible sinus node disease. On occasion, reversal of ischemia with revascularization can

alleviate bradycardia. Sinus pauses in the setting of tachy-brady

syndrome may be eliminated if atrial tachyarrhythmias can be successfully treated. It is also important to recognize when bradycardia

may be transient. Acute illness associated with episodes of extreme

vagal tone may lead to transient SA node abnormalities. Typically

this may be observed as sinus slowing, followed by transient sinus

arrest and/or AV block. Although a pacemaker may be needed in

extreme instances of prolonged arrest, recovery from the acute illness may make the pacemaker unnecessary in follow-up.

Sinus bradycardia is often observed after heart transplantation

and cardiac surgery. In the case of heart transplantation, this may

be because of accumulated amiodarone that affects the donor heart

or ischemic injury to the SA node upon transplantation. If the SA

nodal artery is injured at the time of right atriotomy during cardiac

surgery, sinus arrest with junctional rhythm may be observed. Temporary pacing or pharmacologic support with beta-1 adrenergic

agonists may be needed in these circumstances while awaiting SA

nodal recovery.

In addition, sinus bradycardia and sinus pauses are common

after spinal cord injury. The mechanism of bradycardia is enhanced

parasympathetic tone and autonomic dysreflexia. Common triggers can be tracheal suctioning and turning the patient. Atropine

and inotropes have shown mixed success. Adenosine blockade

with theophylline or aminophylline can sometimes be successful.

Temporary and sometimes permanent pacing may be necessary in

extreme circumstances.

PERMANENT PACEMAKER IMPLANTATION

Pacing in SA nodal disease is indicated to alleviate symptoms of

bradycardia. Consensus guidelines published by the American

Heart Association (AHA)/American College of Cardiology (ACC)/

Heart Rhythm Society (HRS) outline the indications for the use of

pacemakers and categorize them by class based on levels of evidence (Fig. 244-6). Since the first implementation of permanent

pacing in the 1950s, many advances in technology have resulted in

miniaturization, increased longevity of pulse generators, improvement in leads, and increased functionality. To better understand

pacemaker therapy for bradycardias, it is important to be familiar

with the fundamentals of pacemaker function.

There is no established heart rate below which pacemaker treatment is indicated (Table 244-2). Well-conditioned athletes can have

resting sinus rates well below 40 beats/min, and some individuals

can have similar levels of bradycardia during sleep. Permanent pacing is typically not indicated for sleep-related pauses felt secondary

to high vagal tone in the absence of other symptoms. Asymptomatic

sinus bradycardia has not been associated with adverse outcomes

and does not typically warrant permanent pacing. In situations

such as asymptomatic sinus bradycardia, sinus pauses secondary

to physiologically elevated parasympathetic tone, transient pauses

during sleep, or asymptomatic SND where symptoms have been

documented to occur in the absence of bradycardia, a pacemaker is

generally not indicated.

Medications to improve heart rate in order to avoid PPM are

very rarely utilized. Medications such as methylxanthines (e.g.,

theophylline) are sometimes utilized on a temporary basis when

a pacemaker may need to be delayed due to unique circumstances

such as active infection. In addition, oral theophylline may be considered to determine if an increase in heart rate is associated with

improvement in symptoms in a patient with sinus bradycardia to

suggest that a PPM may be beneficial. This latter strategy is rarely

utilized in more equivocal situations.

PPM is the principal treatment for sinus node dysfunction and

the decision to pursue this treatment is largely driven by a correlation between symptoms and bradycardia. The stronger the correlation between symptoms and bradycardia, the greater the likelihood

of improvement. PPM is most commonly achieved through transvenous implantation of one or more leads through the left or right

subclavian veins into the cardiac chambers. The leads are attached

to a pacemaker generator that is placed subcutaneously in the

pectoral chest region. Less commonly, pacing leads can be placed

in the epicardium via surgical approaches including sternotomy or

thoracotomy. This latter approach can be accomplished as a standalone procedure but is more commonly performed concomitantly

during another primary cardiac surgery. Leadless pacemakers that

are totally self-contained pacing devices can also be placed in the

right ventricle to provide ventricular-based pacing. Some leadless

pacemakers can also incorporate technology to sense atrial activity

to attempt to coordinate atrial sensing with ventricular pacing.

Currently, leadless pacemakers are only available for implant in the

right ventricle. Although these devices can sense atrial activity and

coordinate this with ventricular pacing (A-V synchrony), if atrial-based pacing is desired, a transvenous or epicardial atrial pacing

lead is required.

A standard nomenclature for pacing mode programming utilizes a four-letter code. The first letter indicates the chamber(s)

paced (O, none; A, atrium; V, ventricular; D, dual; S, single). The

second letter indicates the chamber(s) sensed. The third letter is

the response to a sensed event (O, none; I, inhibited; T, triggered;

D, inhibition and triggered). The fourth letter refers to whether rate

response (R) is turned on. Therefore a dual-chamber pacemaker

programmed in a DDDR mode provides atrial and ventricular

pacing, A and V sensing, can be inhibited or triggered by a sensed

beat, and is programmed to provide rate responsiveness to activity

via either a built-in accelerometer, minute ventilation sensor, or

both. Rate response is essential for the treatment of CI as it attempts

to mimic the natural physiologic increase in heart rate in response

to exertion.

A single-chamber atrial pacemaker can be a consideration in

patients with pure sinus node dysfunction who are felt to be at low

risk for developing AV nodal block. However, fibrosis of the sinus

The Bradyarrhythmias: Disorders of the Sinoatrial Node

1879CHAPTER 244

Sinus node dysfunction

Confirm symptoms

Rule out reversible

causes

Symptoms

correlate with

bradycardia

Due

to required GDMT

(no reasonable

alternative)

No (or asymptomatic)

Observation

Permanent pacing

(Class III: Harm)

Single chamber

ventricular pacing

(Class IIa)

Single chamber

atrial pacing

(Class I)

Dual chamber pacing

(Class I)

Normal

AV conduction

and reason to

avoid an RV

lead?

Willing to

have a PPM?

Response

suggests symptomatic

sinus node

dysfunction?

Program to minimize

ventricular pacing

(Class IIa)

Oral theophylline

(Class IIb)

Oral theophylline

(Class IIb)

Permanent pacing

(Class I)

Infrequent

pacing? Significant

comorbidities?

No No

Yes

Likely/uncertain

Yes

FIGURE 244-6 Management of sinus node dysfunction. Management of sinus node dysfunction begins with eliminating reversible causes and confirming whether

symptoms correlate with bradycardia. If symptoms are clearly correlated, permanent pacing should be offered. If it is unclear, a trial of oral theophylline can be considered

diagnostically. If there is no correlation between symptoms and bradycardia, then observation is appropriate. Class I recommendations should be performed or are

indicated. Class IIa recommendations are considered reasonable to perform. Class IIb recommendations may be considered. Class III recommendations are associated

with harm more than benefit. AV, atrioventricular; GDMT, guideline-directed management and therapy; PPM, permanent pacemaker; RV, right ventricular. (Reproduced with

permission from FM Kusumoto et al: 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay. Heart

Rhythm 16:e128, 2019.)

TABLE 244-2 Indications for Permanent Pacing in Sinus Node

Dysfunction (SND)

• Symptoms that are directly attributable to SND

• Symptomatic sinus bradycardia because of essential medication therapy for

which there is no alternative treatment

• Tachy-brady syndrome and symptoms attributable to bradycardia

• Symptomatic chronotropic incompetence

• In patients with symptoms that are possibly attributable to SND, a trial of

oral theophylline may be considered to increase heart rate and determine if

permanent pacing may be beneficial

Source: FM Kusumoto et al: Heart Rhythm 16:e128, 2019.

node is associated with fibrosis of the AV node on pathology series

in older patients and many patients with SND will develop AV node

disease. Therefore, although a single-chamber atrial pacemaker

can be a consideration in younger patients with pure sinus node

dysfunction, a majority of patients receiving a pacemaker for

sinus node disease (particularly older individuals) often receive

a dual-chamber pacemaker with backup ventricular pacing if

needed.

Class I indications for pacing in SA node dysfunction include

documented symptomatic bradycardia, SND-associated long-term

drug therapy for which there is no alternative, and symptomatic

CI. Class IIa indications include those outlined previously in which

SND is suspected but not documented and for syncope of unexplained origin in the presence of major abnormalities of SA node

dysfunction. Mildly symptomatic individuals with heart rates consistently <40 beats/min constitute a class IIb indication for pacing.

Pacing is not indicated in patients with SA node dysfunction who

do not have symptoms and in those in whom bradycardia is associated with the use of nonessential drugs.

1880 PART 6 Disorders of the Cardiovascular System

COMPLICATIONS RELATED TO PACEMAKER

IMPLANTATION

Although pacemakers are highly reliable, they are subject to a

number of complications related to implantation and electronic

function. In adults, permanent pacemakers are most commonly

implanted with access to the heart by way of the subclavian superior

vena cava venous system. Rare, but possible, acute complications of

transvenous pacemaker implantation include infection, hematoma,

pneumothorax, cardiac perforation, diaphragmatic/phrenic nerve

stimulation, and lead dislodgment. Limitations of chronic pacemaker therapy include infection, erosion, lead failure, and abnormalities resulting from inappropriate programming or interaction

with the patient’s native electrical cardiac function. Rotation of the

pacemaker pulse generator in its subcutaneous pocket, either intentionally or inadvertently, often referred to as “twiddler’s syndrome,”

can wrap the leads around the generator and produce dislodgment

with failure to sense or pace the heart. The small size and light weight

of contemporary pacemakers make this a rare complication. Transvenous leads are considered the least reliable component of permanent pacing systems. Enhancements in battery technology and

component design have produced a pacing system small enough to

be implanted in the heart without the need for a transvenous lead.

The first “leadless” pacemakers were only appropriate for patients

with indications for single-chamber ventricular (right ventricle)

pacing. More recently these devices have been modified to detect

mechanical atrial contraction, and thus can be programmed to preserve AV synchrony in patients with heart block but without SND.

Acknowledgment

David Spragg and Gordon Tomaselli contributed to this chapter in the

20th edition and some material from that chapter has been retained here.

■ FURTHER READING

Callans DJ: Josephson’s Clinical Cardiac Electrophysiology: Techniques

and Interpretations, 6th ed. Philadelphia, Wolters Kluwer, 2021.

Ellenbogen K et al (eds): Clinical Cardiac Pacing, Defibrillation, and

Resynchronization Therapy, 5th ed. Philadelphia, Elsevier, 2016.

Jalife J, Stevenson W (eds): Zipes and Jalife’s Cardiac Electrophysiology: From Cell to Bedside, 8th ed. Philadelphia, Elsevier, 2021.

Impulses generated in the sinoatrial (SA) node are conducted to the

ventricles through the electrically and anatomically complex atrioventricular (AV) node. The AV node is specialized for slow conduction

of the action potential to create a delay between atrial and ventricular

activation. There is a similar pattern of arrangement of gap junctions

and expression of connexins in the AV node as in the sinus node. This

allows for weak electrical coupling in the center of the node to slow

conduction and protect it from the periphery. This unique arrangement of gap junctions, along with extracellular matrix and fibroblasts,

and a lack of conductance in adjacent valvular tissue allow the AV

node to slow conduction and serve as the electrical “gatekeeper” to the

ventricle.

As described in previous chapters, cells located in the AV node sit at

a relatively higher resting membrane potential than surrounding atrial

245 The Bradyarrhythmias:

Disorders of the

Atrioventricular Node

William H. Sauer, Bruce A. Koplan

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 with a lack of the type of

fast sodium channels found in atrial and ventricular myocytes) compared to ventricular tissue (mediated by sodium influx). Although the

AV node has the potential for pacemaker activity, the normal automaticity rate is 20–60 beats/min, which is overridden by the higher intrinsic rate of the SA node (60–100 beats/min). Therefore, the AV node can

provide backup heart rate when the SA node fails to depolarize. There

is a progressive decrease in the frequency of spontaneous depolarization down the His and Purkinje fibers. This progressive decrease in rate

of depolarization allows for unidirectional flow of impulses through

the conduction system.

Bradycardia may occur when conduction across the AV node is

compromised, resulting in slow ventricular rates. The consequences

can be fatigue, syncope, and, if a reliable escape rhythm does not occur,

death. 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 rare in

healthy adult populations, with an estimated incidence of 1 per 5000

in the U.S. 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.

STRUCTURE AND PHYSIOLOGY OF THE AV

NODE

The normal AV junctional area can be divided into a transition cell

zone (which results from approaches from the atrium to the AV node),

the compact AV node, and the penetrating part of the His bundle.

Conduction from the SA node to the AV node occurs in a preferential

manner via intra-atrial pathways with higher conduction velocity than

the remainder of atrial tissue. The AV node itself is a small region (~1 ×

3 × 5 mm) that lies beneath the right atrial endocardium at the apex of

the triangle of Koch, a region defined by three landmarks: the coronary

sinus ostium posteriorly, the septal tricuspid valve annulus anteriorly,

and the tendon of Todaro superiorly. The AV node can be further

subdivided into the lower nodal bundle and compact node. A rightward inferior node extension spreads along the tricuspid valve toward

the coronary sinus, and the leftward nodal extension spreads from

the compact node along the tendon of Todaro. In some people, there

are two functional pathways in the AV node: a slow pathway located in

the inferior node extension and a fast pathway that is less well defined

but is superior to the slow pathway. The role of these pathways in

supraventricular tachycardia is described in another chapter.

The compact AV node continues anteriorly and superiorly as the

penetrating AV bundle where it traverses the central fibrous body in

close proximity to the aortic, mitral, and tricuspid valve annuli. The

penetrating AV bundle continues through the annulus fibrosis and

emerges as the His bundle along the ventricular septum. The right bundle branch (RBB) emerges from the distal AV bundle and terminates to

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 cells that constitute the AV node complex are heterogeneous

with a range of action potential profiles. The AV junction has distinct

regions including a transitional cell zone (atrionodal cells), the compact AV node, and the cells of the penetrating part of the His bundle.

In the transitional zones, the cells have an electrical phenotype between

those of atrial myocytes and cells of the compact node. Atrionodal

transitional connections exhibit decremental conduction, defined as

slowing of conduction with increasingly rapid rates of stimulation.

Myocytes that constitute the compact AV node are similar to sinus

node myocytes, having a resting membrane potential of ~–60 mV;

exhibit action potentials with low amplitudes, slow upstrokes of phase 0

The Bradyarrhythmias: Disorders of the Atrioventricular Node

1881C

odal recovery.