Sinus Node Dysfunction and Atrioventricular Conduction Disease

SINUS NODE DYSFUNCTION AND

ATRIOVENTRICULAR CONDUCTION DISEASE

ACCSAP

Copyright © 2020 American College of Cardiology 0

Sinus Node Dysfunction and Atrioventricular Conduction Disease

Table of Contents
Sinus Node Dysfunction and Atrioventricular Conduction Disease ...............................................................1
Sinus Node Dysfunction and Atrioventricular Conduction Disease ................................................................... 2
Introduction ....................................................................................................................................................... 3
Sinus Node Dysfunction ..................................................................................................................................... 4
Diagnosis and Treatment of Sinus and AV Conduction Disease ...................................................................... 17
Indications for Pacing ....................................................................................................................................... 19
Future Directions ............................................................................................................................................. 21
References ....................................................................................................................................................... 22
Sinus Node Dysfunction and Atrioventricular Conduction Disease

Sinus Node Dysfunction and Atrioventricular

Conduction Disease

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 Sinus Node Dysfunction and Atrioventricular Conduction Disease

Sinus Node Dysfunction and Atrioventricular

Conduction Disease

Sinus Node Dysfunction and Atrioventricular Conduction Disease

Author
Nazem Akoum, MD, MS, FACC
Disclosures
This author has nothing to disclose.
Learner Objectives
Upon completion of this module, the reader will be able to:
1. Classify causes of bradycardia as impulse generation in sinus node dysfunction (SND) or impulse
propagation in atrioventricular (AV) conduction disease.
2. Recognize that, in AV conduction disease, the site of block can be in the AV node or further
downstream in the His-Purkinje system.
3. Distinguish AV dissociation, in which the ventricular rate is faster than the atrial rate, from AV block,
in which the atrial rate is faster than the ventricular rate.
4. Match the appropriate workup, including exercise testing, ambulatory monitoring, and invasive
electrophysiology testing, with the suspected cause of bradycardia.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Introduction

Introduction

The cardiac electrical system consists of

tissue capable of spontaneous electrical Key Point
depolarization and impulse propagation.
• The sinus node is located at the junction of the
Under normal conditions, the sinoatrial superior vena cava and lateral right atrium. A
(SA) node, located at the junction of the spontaneously depolarizing current, known as If or
superior vena cava and the right atrium, the “funny current,” drives spontaneous sinus
has the fastest rate of spontaneous node activity.
depolarization due to the presence of a
depolarizing current, called the “funny
current.” An impulse generated from the SA node propagates to the atria, resulting in atrial depolarization,
which manifests with the P wave on the surface electrocardiogram (ECG). Following atrial depolarization,
the electrical wave traverses through the AV node, the bundle of His followed by the Purkinje system, and
ends in the ventricular myocardium. Ventricular depolarization manifests with the QRS complex on ECG.
Depolarization of the AV node, His bundle, and Purkinje fibers are not detected on the surface ECG.

Under normal physiologic function, SA node depolarization propagates to the ventricles with high fidelity so
that the sinus rate is the same as the ventricular rate, ranging from 60-100 bpm at rest. Electromechanical
coupling allows for sequential AV contraction, which ensures normal blood flow between the cardiac
chambers and out to the great vessels.

Normal physiologic function also includes input from the autonomic nervous system, which influences the
heart rate and AV conduction by exerting its effects on the SA and AV nodes. Nervous system input is
delivered through the vagus nerves, which provide the parasympathetic arm, and postganglionic
sympathetic nerves originating in the sympathetic trunk. Variations in the heart rate and AV conduction are
therefore expected, with shifts in the autonomic balance. The sinus rate is expected to increase with stress
or activity (vagal withdrawal and sympathetic stimulation) and to decrease with rest (increased vagal tone
and sympathetic withdrawal). The vagal tone is normally higher than the sympathetic tone. When both are
withdrawn (e.g., pharmacologically using simultaneous atropine and beta-blockers or in a denervated
transplanted heart), the intrinsic sinus rate is about 100 bpm.

In the remainder of this module, abnormalities in the sinus node function and AV electrical conduction will
be discussed, including their clinical presentations, workup, and treatment interventions.

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 Sinus Node Dysfunction and Atrioventricular Conduction Disease

Sinus Node Dysfunction

Sinus Node Dysfunction

Sinus Node Dysfunction

The term “sinus node dysfunction,” or
“sick sinus syndrome,” encompasses
several ECG and clinical findings that
suggest abnormal impulse generation
from the SA node. These ECG findings
include sinus pause (Figure 1), sinus
bradycardia (<60 bpm), SA exit block,
and failure of the SA node to increase its
firing rate relative to the physiologic
body demand (also known as
“chronotropic incompetence”).
Key Points
• Sinus node dysfunction comprises a number of
different manifestations including symptomatic
bradycardia, sinus pauses due to sinus arrest or
sinoatrial exit block, and chronotropic
incompetence.
• Sinus node dysfunction (SND) is a common and
often age-related cause of bradycardia, although
extrinsic causes such as drug therapy also may
cause apparent SND.

The etiology of SND is not clear and is
likely multifactorial. Fibrotic infiltration
of the sinus node region has been
reported and may slow the rate of
spontaneous depolarization. Advanced
age, atrial fibrillation (AF), hypertension,
valvular heart disease, ischemic heart
disease, and other conditions are
associated with SND. Aside from these
intrinsic problems with the sinus node,
SND can be extrinsic and caused by drugs, carotid sinus hypersensitivity or hypervagotonia, or metabolic
derangements (Table 1) .
• Age-related sinus node dysfunction also may be
associated with atrial fibrillation (AF), the so-called
tachy-brady syndrome. This may be associated
with prolonged pauses, which can be symptomatic
after termination of AF. A common scenario would
be an elderly patient with persistent AF who
develops a prolonged pause on termination of AF.
This can be exacerbated by drugs, especially those
that block sodium channels such as flecainide.

In patients with AF or other tachyarrhythmias, sinus node disease manifests with the so-called tachy-brady
syndrome. The overdrive of atrial tachyarrhythmias suppresses SA nodal depolarization. Upon termination
of a tachyarrhythmia episode, a diseased SA node takes a long time to recover and initiate spontaneous
depolarization. The resulting pause and bradycardia may cause symptoms of lightheadedness, presyncope,
or syncope. Often, patients are treated with sodium channel blockers, beta-blockers, or calcium channel
blockers to suppress atrial tachyarrhythmias. These drugs exacerbate SND with more severe bradycardia and
prolonged pauses. Figure 2 shows an example of AF terminating with a prolonged pause and ensuing sinus
bradycardia.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Figure 1

Figure 1

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 Sinus Node Dysfunction and Atrioventricular Conduction Disease

Table 1

Table 1

AV = atroventricular.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Figure 2

Figure 2

Disorders of AV Conduction

Disorders of AV Conduction

Key Point

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 Sinus Node Dysfunction and Atrioventricular Conduction Disease

Whereas SA node disease is a problem

of impulse generation, AV conduction
disease is one of impulse propagation.
Electrocardiographically, AV conduction
disease manifests with conduction delay
or conduction block and results in
bradycardia and pauses. Etiologies of AV
conduction disease are included in Table
1 and encompass a variety of reversible
and irreversible conditions, including
iatrogenic following valve surgery or
catheter-based procedures such as
transcatheter aortic valve replacement
and catheter ablation, ischemic heart
disease, age-related degeneration, infective endocarditis, Lyme disease, or drug effect/toxicity (beta-
blockers, calcium channel blockers, or digoxin).
• Atrioventricular (AV) block occurs due to a
failure of impulse propagation through the cardiac
conduction system. Several types of AV block are
recognized, most commonly first-, second-, and
third-degree block. Prognosis of AV block is related
to the severity of block. AV block may be due to
failure of impulse propagation in the AV nodal
tissues (narrow QRS complex) or within the His-
Purkinje system (intra- or infra-Hisian block).
Failure of impulse propagation due to infra-Hisian
block may be associated with a wide QRS complex
with bundle branch or fascicular block.

Recognizable ECG patterns of abnormal AV conduction include five different types of block: 1) first-degree
AV block; 2) Mobitz type I second-degree or Wenckebach block; 3) Mobitz type II second-degree block; 4)
third-degree AV block; and 5) advanced second-degree AV block.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Table 1

AV = atroventricular

First-Degree AV Block

First-Degree AV Block
In this pattern, the timing between the onset of the P wave and the onset of the QRS complex is longer than
the upper limit of normal conduction time of 200 msec. This is not truly a block in the conduction, as all
atrial depolarization waves traverse to the ventricles. First-degree AV block is commonly seen during periods
of high vagal tone (e.g., during sleep or treatment with beta-blockers or calcium channel blockers).

Mobitz Type I Second-Degree or Wenckebach Block

Mobitz Type I Second-Degree or Wenckebach Block

This pattern is characterized by progressive prolongation of the P-R interval leading up to a nonconducted P
wave; the cycle then repeats itself with a shorter P-R interval and so on (Figure 3). The site of block in Mobitz

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 Sinus Node Dysfunction and Atrioventricular Conduction Disease

type I second-degree AV block is usually in the AV node. Like first-degree AV block, this pattern is seen
frequently during sleep or periods of high vagal tone and with drug treatment.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Figure 3

Figure 3

AV = atrioventricular.

Mobitz Type II Second-Degree Block

Mobitz Type II Second-Degree Block

Key Point

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 Sinus Node Dysfunction and Atrioventricular Conduction Disease
Mobitz type II block is characterized by
an abrupt loss of AV conduction for one
beat. This pattern is usually repetitive
without any apparent P-R interval
prolongation (Figure 4). The site of block
for Mobitz type II is more commonly
distal to the AV node (intra- or infra-
Hisian). Patients with this pattern often
show other signs of conduction system
disease such as bundle branch block or
fascicular block.
Copyright © 2020 American College of Cardiology
• Atrioventricular (AV) block occurs due to a
failure of impulse propagation through the cardiac
conduction system. Several types of AV block are
recognized, most commonly first-, second-, and
third-degree block. Prognosis of AV block is related
to the severity of block. AV block may be due to
failure of impulse propagation in the AV nodal
tissues (narrow QRS complex) or within the His-
Purkinje system (intra- or infra-Hisian block).
Failure of impulse propagation due to infra-Hisian
block may be associated with a wide QRS complex
with bundle branch or fascicular block.
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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Figure 4

Figure 4

AV = atrioventricular.

Third-Degree AV Block

Third-Degree AV Block
In third-degree or complete heart block,
the electrical depolarizations of the Key Point
atrium are completely blocked from
• Atrioventricular (AV) block should be
conducting to the ventricles. Ventricular distinguished from AV dissociation, in which the
depolarization is provided through ventricular rate is faster than the atrial rate. In AV
backup or escape pacemakers found in block, the atrial rate is faster than the ventricular
the AV junction (junctional escape rate.
rhythm) or lower in the conduction
system or myocardial cells (ventricular
escape rhythm). The rate of the escape rhythm is slower than the sinus node and its morphology suggests its

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site of origin (Figure 5). This form of AV dissociation observed in complete heart block is to be distinguished
from that present in ventricular tachycardia, in which the ventricular rate is faster than the atrial rate.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Figure 5

Figure 5

Note the presence of AV dissociation with no conduction from the atrium to the ventricle.

AV = atrioventricular.

Advanced Second-Degree AV Block

Advanced Second-Degree AV Block

This type of AV block is more severe than second-degree block, but not quite complete AV block. In high-
degree AV block, some P waves do conduct and AV dissociation is not present (Figure 6). In advanced-degree
AV block, two or more consecutive P waves are blocked; whereas, in second-degree block, one P wave is
blocked at a time.

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Figure 6

Figure 6

Note that AV conduction is present for the first two beats, followed by loss of conduction for the following
two consecutive p waves, followed by resumption of conduction.

AV = atrioventricular.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease
Diagnosis and Treatment of Sinus and AV Conduction
Disease
Diagnosis and Treatment of Sinus and AV Conduction Disease
The workup of suspected bradycardia
includes a detailed history for the
description of symptoms and correlating
ECG findings with the patient’s account.
Ambulatory Monitoring
When patients present with symptoms
of bradycardia or pauses such as
syncope, lightheadedness, fatigue, loss
of energy, or stamina, and when the 12-
lead ECG is not diagnostic, ambulatory
monitoring is often undertaken to
document SND, pauses, AV conduction
disease, or tachy-brady episodes, and to
correlate these with symptoms. Several
types of ambulatory ECG monitors are
available, offering a wide range of
monitoring periods. Holter monitors are
used with daily symptoms. Automatic
trigger or patient-activated monitors
can be used for weeks at a time when
symptoms are less frequent. For even
more rare symptoms, especially with
syncope, implanted loop recorders are
sometimes used, and these extend the
monitoring period for up to 3 years.
Exercise testing can sometimes be used
to distinguish AV nodal block from intra-
or infra-Hisian block. The former is
expected to improve with exercise,
whereas the latter is expected to
worsen. Exercise testing also can be
used to workup patients with
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Key Points
• The diagnosis and treatment of sinus node
dysfunction and atrioventricular block include a
thorough history and symptom evaluation, as well
as examination of the electrocardiographic
evidence correlating these symptoms with
electrical abnormalities.
• When evaluating patients with lesser degrees of
bradycardia, symptom–rhythm correlation is
important. This can be achieved with ambulatory
monitoring (Holter or similar). More prolonged
monitoring with an implantable subcutaneous
monitor may be needed in some cases.
• In patients with block at the atrioventricular (AV)
node level, only block will improve with exercise;
with infra-Hisian block (i.e., below the AV node),
block will get worse with exercise. An exercise test
should be recommended if there is a question
regarding whether the bradycardia is intrinsic
(heart rate will not improve or may even worsen
with exercise). In contrast, in patients in whom
bradycardia is due to high vagal tone (e.g.,
athletes), there will be a normal and appropriate
increase in heart rate with exercise.
• In patients suspected of chronotropic
incompetence (failure to achieve expected heart
rate with exercise), a treadmill exercise test can
also be recommended.
• Much less commonly, an electrophysiologic
study can be performed to assess atrioventricular
nodal and His-Purkinje function, although, in most
cases, this invasive approach is reserved for
patients with worrisome syncope.
 Sinus Node Dysfunction and Atrioventricular Conduction Disease

chronotropic incompetence, in which they typically fail to achieve the expected heart rate with exercise.

Invasive Electrophysiology Testing

When presyncope or syncope occurs without documented bradycardia or heart block on ambulatory
monitoring, yet suspicion for SND or AV conduction disease remains high, invasive electrophysiologic testing
is performed. SA node function is studied by measuring the sinoatrial node recovery time (SNRT), corrected
to different pacing rates. Corrected SNRT >525 msec is considered abnormal.

Intracardiac His bundle recording is occasionally used for assessing AV conduction disease. Findings such as a
split His bundle recording or eliciting infra-Hisian conduction block through rapid pacing or programmed
stimulation constitute evidence of a diseased AV conduction system. This invasive approach is reserved for
patients with unexplained and worrisome syncope.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease
Indications for Pacing
Indications for Pacing
The treatment of sinus bradycardia and
pauses starts with investigating for any
reversible causes, most commonly
drugs. Permanent pacemakers are
commonly implanted in symptomatic
patients with SND without a reversible
cause. It is not uncommon for
pacemakers to be recommended for
tachy-brady syndrome or for patients
who need beta-blocker therapy
necessary for coronary artery disease or
congestive heart failure, when
treatment with such drugs results in
bradycardia.
The prognosis of AV block is related to
the anatomic site (i.e., AV node, intra-
or infra-Hisian disease) and degree of
block (i.e., first-, second-, advanced
second-, and third-degree block).
Patients demonstrating evidence of
significant AV conduction disease are
indicated for permanent pacing ,
sometimes without a documented
correlation with symptoms. The
rationale for these indications is based
on the higher risk of cardiovascular
events. The indications for permanent
pacing for AV conduction disease are
summarized in Table 2.1
When patients present with
symptomatic bradycardia, temporary pacing is indicated for hemodynamic instability. This is usually
encountered in third-degree AV block with escape rates <40 bpm, in patients unresponsive to medical
therapy, or in the setting of an acute myocardial infarction or brady-dependent torsade de pointes.
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Key Points
• Age-related sinus node dysfunction also may be
associated with atrial fibrillation (AF), the so-called
tachy-brady syndrome. This may be associated
with prolonged pauses, which can be symptomatic
after termination of AF. A common scenario would
be an elderly patient with persistent AF who
develops a prolonged pause on termination of AF.
This can be exacerbated by drugs, especially those
that block sodium channels such as flecainide.
• Implantation of a permanent pacemaker is
indicated for patients with irreversible
symptomatic bradycardia due to sinus node
dysfunction or atrioventricular block.
• Atrioventricular (AV) block occurs due to a
failure of impulse propagation through the cardiac
conduction system. Several types of AV block are
recognized, most commonly first-, second-, and
third-degree block. Prognosis of AV block is related
to the severity of block. AV block may be due to
failure of impulse propagation in the AV nodal
tissues (narrow QRS complex) or within the His-
Purkinje system (intra- or infra-Hisian block).
Failure of impulse propagation due to infra-Hisian
block may be associated with a wide QRS complex
with bundle branch or fascicular block.
• Patients with symptomatic irreversible
bradycardia due to sinus node dysfunction or
atrioventricular block require permanent
pacemaker implantation.
 Sinus Node Dysfunction and Atrioventricular Conduction Disease

Recommendations for pacing following myocardial infarction should include an assessment of the extent of
myocardial damage as well as the location of the obstruction and territory affected.

Table 2

AV = atrioventricular; CHB = complete heart block; ASDB = advanced second-degree block; HR = heart rate;
bpm = beats per minute; EPS = electrophysiology study; LV = left ventricular; SND = sinus node dysfunction.

References
1. Epstein AE, DiMarco JP, Ellenbogen KA, et al.; American College of Cardiology Foundation, American Heart
Association Task Force on Practice Guidelines, Heart Rhythm Society. 2012 ACCF/AHA/HRS focused update
incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm
abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013;61:e6-75.
2. Park DS, Fishman GI. The cardiac conduction system. Circulation 2011;123:904-15.

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Sinus Node Dysfunction and Atrioventricular Conduction Disease

Future Directions

Future Directions

Certain genetic mutations have been linked to sinus node and conduction system disease. Sodium voltage-
gated channel alpha subunit 5 (SCN5A), hyperpolarization activated cyclic nucleotide gated potassium
channel 4 (HCN4), ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2), and ankyrin-B mutations are
associated with SND, whereas mutations of SCN5A, sodium voltage-gated channel beta subunit 1 (SCN1B),
potassium inwardly rectifying channel subfamily J member 2 (KCNJ2), T-box transcription factor 5 (TBX5),
and NK2 homeobox 5 (NKX2-5) are associated with conduction system disease. Neuromuscular genetic
disorders including emerin, lamin A/C, and myotonic dystrophy type 1 are also associated with AV
conduction disease.2 Gene- and stem cell–based therapies are currently being investigated as therapeutic
options for patients with either genetic or degenerative abnormalities of the cardiac electrical conduction
system.

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References

References

1. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS guideline on the evaluation and
management of patients with bradycardia and cardiac conduction delay: a report of the American
College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the
Heart Rhythm Society. J Am Coll Cardiol 2019;74:e51-e156.
2. Park DS, Fishman GI. Development and function of the cardiac conduction system in health and
disease. J Cardiovasc Dev Dis 2017;4:7.

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