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Sinus Node Dysfunction

Updated: Nov 30, 2018
Author: Bharat K Kantharia, MD, FRCP, FAHA, FACC, FESC, FHRS; Chief Editor: Mikhael F El-Chami, MD

Overview

Practice Essentials
The sinoatrial (SA) node is innervated by the parasympathetic and the sympathetic nervous systems; the balance between these systems
controls the pacemaker rate. Parasympathetic input via the vagus nerves decreases the SA nodal pacemaker and is the dominant input at
rest, wheras sympathetic nerve input, as well as the adrenal medullary release of catecholamines, increases the sinus rate during
exercise and stress.

Sinus node dysfunction (SND) is often secondary to senescence of the SA node and surrounding atrial myocardium. Medications may
also contribute to, and can often unmask, subclinical SA dysfunction.

The epidemiology of SND is difficult to study, but patients with symptomatic SND are generally older (in the seventh or eighth decade of
life) with frequent comorbid diseases.SND occurs as a result of disorders in automaticity, conduction, or both. SN fibrosis is the most
common cause of SND.

The natural history of SND typically involves intermittent but progressive cardiac rhythm disorders, which have been associated with
higher rates of other cardiovascular events and higher mortality. There is a tendency for the rhythm disturbances associated with SND to
evolve over time, along with a higher likelihood of thromboembolic events and other cardiovascular events.

The treatment of sinus bradycardia and pauses starts with investigating/identifying any reversible causes, of which the most common are
medications. Permanent pacemakers are often implanted in symptomatic patients with SND.

Background
Sinus node dysfunction (SND) is characterized by dysfunction of the sinoatrial (SA) node that is often associated with senescence of the
node and surrounding atrial myocardium.[1, 2] Although the term "sick sinus syndrome" (SSS) was first used to describe the sluggish
return of SA nodal activity following electrical cardioversion, it is now commonly used to describe the inability of the SA node to generate a
heart rate commensurate with the physiologic needs of an individual.

A conglomeration of electrocardiogram (ECG) abnormalities represent manifestation of SND, including[1, 3, 4] :

Sinus bradycardia

Sinus pause

Sinus arrest

SA nodal exit block

Inadequate heart rate response to physiologic demands during activity (chronotropic incompetence)

Supraventricular tachycardia (eg, atrial fibrillation, atrial flutter, and atrial tachycardia as part of the tachycardia-bradycardia
syndrome)[1, 5]

When SND is associated with symptoms such as dizziness or syncope, SSS is a more clinically representative term. However, SND and
SSS are often used interchangeably.

Pathophysiology
The sinus node (SN) is a subepicardial structure normally located in the right atrial wall near the superior vena cava entrance on the
upper end of the sulcus terminalis. It is formed by a cluster of cells capable of spontaneous depolarization. Normally, these pacemaker
cells depolarize at faster rates than any other latent cardiac pacemaker cell inside the heart. Therefore, a healthy SN directs the rate at
which the heart beats. Electrical impulses generated in the SN must then be conducted outside the SN in order to depolarize the rest of
the heart.

SN activity is regulated by the autonomic nervous system. For example, parasympathetic stimulation causes sinus bradycardia, sinus
pauses, or sinoatrial exit block. These actions decrease SN automaticity, thereby decreasing the heart rate.

Sympathetic stimulation, however, increases the slope of phase 4 spontaneous depolarizations. This increases the automaticity of the SN,
thereby increasing the heart rate. Blood supply to the SN is provided by the right coronary artery in most cases.

Sinus node dysfunction (SND) involves abnormalities in SN impulse formation and propagation, which are often accompanied by similar
abnormalities in the atrium and in the conduction system of the heart. Together, these abnormalities may result in inappropriately slow
ventricular rates and long pauses at rest or during various stresses. When SND is mild, patients are usually asymptomatic. As SND
becomes more severe, patients may develop symptoms due to organ hypoperfusion and pulse irregularity. Such symptoms include the
following:

Fatigue

Dizziness

Confusion

Fall

Syncope

Angina

Heart failure symptoms and palpitations

Natural history of SND

The natural history of SND typically involves intermittent and/or progressive cardiac rhythm disorders, which have been associated with
higher rates of other cardiovascular events and higher mortality. There is a tendency for the rhythm disturbances associated with SND to
evolve over time, along with a higher likelihood of thromboembolic events and other cardiovascular events.

For many patients with SND, there are variable, and often long, periods of normal SN function. However, once present, in due course,
SND progresses in most patients, accompanied by a greater likelihood of developing atrial tachyarrhythmias. However, the time course of
disease progression is difficult to predict; hence, most patients with symptomatic SND are treated earlier in an attempt to alleviate
symptoms.

As noted, SND usually progresses over time. In a study of 52 patients with SND and sinus bradycardia associated with sinoatrial (SA)
block or sinus arrest, it took an average of 13 years (range, 7-29 years) for progression to total sinus arrest and an escape rhythm.[6]

The incidence of atrial arrhythmias and conduction disturbances occurs more frequently over time, which may be due in part to a
progressive pathologic process that affects the entire atrium and other parts of the heart. In a study comprising 213 patients with a history
of symptomatic SND who were treated with atrial pacing and followed for a median of 5 years, 7% developed atrial fibrillation and 8.5%
developed high-grade atrioventricular block.[7]

Patients with SND, especially those with tachycardia-bradycardia, are at higher risk for thromboembolic events—even after pacemaker
implantation. Asymptomatic episodes of atrial fibrillation resulting in thromboembolic events may contribute to cardiovascular events
following pacemaker implantation.

Etiology
Sinus node dysfunction (SND) occurs as a result of disorders in automaticity, conduction, or both of the sinoatrial (SA) node.[8] Local
cardiac pathology, systemic diseases that involve the heart, and medications or toxins can all be responsible for abnormal SA node
function and may result in SND.[8, 9, 10]

Abnormal automaticity (sinus arrest)

Abnormal automaticity, or sinus arrest, refers to a failure of sinus impulse generation. Abnormal conduction, or SA delay or block, is a
failure of impulse transmission. In such cases, the sinus impulse is generated normally, but it is abnormally conducted to the neighboring
atrial tissue. Both abnormal automaticity and abnormal conduction may result from one of several different mechanisms, including fibrosis,
atherosclerosis, and inflammatory or infiltrative myocardial processes.

Sinus node degeneration resulting in fibrosis, calcification, or amyloidosis

The most common cause of SND/sick sinus syndrome (SSS) is the replacement of sinus node (SN) tissue by fibrous tissue, which may
be accompanied by degeneration and fibrosis of other parts of the conduction system as well, including the atrioventricular (AV) node.
The transitional junction between the SN and atrial tissue may also be involved, and there may be degeneration of the nerve ganglia.
Medications and toxins

A number of medications and toxins can depress sinus node function, resulting in symptoms and electrocardiographic (ECG) changes
consistent with SND. The most commonly used prescription medications that alter myocardial conduction and may potentially result in
SND include:

Beta blockers

Non-dihydropyridine calcium channel blockers (eg, diltiazem, verapamil)

Digoxin

Antiarrhythmic medications

Ivabradine

Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine) used in the treatment of Alzheimer disease

Parasympathomimetic agents

Sympatholytic drugs (eg, methyldopa, clonidine)

Lithium

Poisoning by grayanotoxin, which is produced by some plants (eg, Rhododendron species) and found in certain varieties of honey,
has been associated with depressed SN function

Childhood and familial diseases

Although rare in children, when SND presents in this population, it is most often seen in those with congenital and acquired heart disease,
particularly after corrective cardiac surgery. Familial SSS is rare, with mutations in the cardiac sodium channel gene SCN5A[11, 12] and
the HCN4 gene[13] (thought to contribute to the SN pacemaker current) responsible for some familial cases.

In a series of 30 children and young adults (age range: 3 days to 25 years) with SND, 22 had significant cardiac disease, and 13
developed SND after cardiac surgery.[14] The causes of SND were inappropriate sinus bradycardia, sinus arrest, and SA exit block.[14]

In a study of 10 children from 7 families with familial SSS, in which genomic DNA encoding the alpha subunit of the cardiac sodium
channel was screened for mutations, compound heterozygous nucleotide changes were identified in 5 children from 3 families, but not in
any of over 75 control subjects.[11]

In a series of 38 patients with clinical evidence of Brugada syndrome, 4 had SCN5A mutations. Of these 4 patients, 3 had SND with
multiple affected family members. However, mutations in SCN5A are not pathognomonic for SND, as different SCN5A mutations are
associated with other cardiac abnormalities including Brugada syndrome, congenital long QT syndrome type 3, familial AV block, and
familial dilated cardiomyopathy with conduction defects and susceptibility to atrial fibrillation (AF).[12]

Infiltrative diseases

The SA node may be affected by infiltrative disease, such as amyloidosis, sarcoidosis, scleroderma, hemochromatosis, and rarely tumor.

Inflammatory diseases

Rheumatic fever, pericarditis, diphtheria, Chagas disease, and other disorders may depress SA nodal function.

SA nodal artery disease

The SN is perfused by branches of the right coronary artery in 55-60% of cases, and by the left circumflex artery in the remaining 40-45%.
Stenosis of the SA nodal artery may occur due to atherosclerosis or inflammatory processes, resulting in ischemia; the latter may also
occur with embolic events. Approximately 5% of patients with myocardial infarction (MI) (usually inferior wall MI) show SND that tends to
be reversible.[15]

Genetic mutations

Mutations in HCN4 can produce both symptomatic and asymptomatic SND, as illustrated by numerous reports of sinus bradycardia in
family members with such mutations.[16]

Trauma

Cardiac trauma may affect either the SA node directly or its blood supply.

Miscellaneous

Other disorders that can cause SND include hypothyroidism, hypothermia, hypoxia, and muscular dystrophies. Some infections (eg,
leptospirosis, trichinosis, Salmonella typhi infection) are associated with relative sinus bradycardia; however, these usually do not result in
permanent SND.[17]
In addition, SND is seen in children with congenital and acquired heart disease, particularly after corrective surgery. The cause of SND in
these children is likely related to the underlying structural heart disease and surgical trauma to the SN and/or SN artery.

Emery-Dreifuss muscular dystrophy is an X-linked muscle disorder associated with SND and AV conduction defects. If AV conduction
defects are present, sudden cardiac death may result unless the condition is treated with permanent pacing. Males and females may be
affected with equal frequency.

Sinus venosus atrial septal defect (ASD), Ebstein anomaly, and heterotaxy syndromes, particularly left atrial isomerism, can also lead to
SND.

Surgical causes, especially from operations involving the right atrium

Gradual loss of sinus rhythm occurs after the Mustard, Senning, and all varieties of the Fontan operation. This is thought to be secondary
to direct injury to the SN during surgery and also due to later, chronic hemodynamic abnormalities. Paroxysmal atrial tachycardias are
frequently associated with SND, and loss of sinus rhythm appears to increase the risk of sudden death. Patients with transposition of the
great arteries now undergo the arterial switch operation, which avoids the extensive atrial suture lines that lead to SN damage.

SND was described in 15% of patients who had undergone the Ross operation for aortic valve disease or complex left-sided heart
disease, 2.6 to 11 years earlier.[18] Other arrhythmias, such as complete AV block and ventricular tachycardia, were present as well after
the Ross operation.

When repairing ASDs, especially sinus venosus ASDs, SND frequently occurs because of the proximity of the defect with SN tissue.

Other surgically related causes of SND include the following:

Patients who have undergone surgery for endocardial cushion defects (ECDs) may later develop SND

SND may be caused by a Blalock-Hanlon atrial septectomy

SND may occur after repair of partial anomalous pulmonary venous return (PAPVR) or total anomalous pulmonary venous return
(TAPVR)

Cannulation of the superior vena cava (SVC), usually performed for cardiopulmonary bypass or extracorporeal membrane
oxygenation (ECMO), may damage SN tissue

Ischemic cardiac arrest may cause SND

Other

Rheumatic fever is another cause of SND. Such dysfunction may also result from central nervous system (CNS) disease, which is usually
secondary to increased intracranial pressure with a subsequent increase in the parasympathetic tone.

Endocrine-metabolic diseases (hypothyroidism and hypothermia) and electrolyte imbalances (hypokalemia and hypocalcemia) are other
conditions that can contribute to SND.

A study by Sunaga et al involving 202 subjects indicated that in patients with persistent AF, those with low-amplitude fibrillatory waves and
a large left atrial volume index are at an increased risk for the appearance of concealed SND after catheter ablation has restored sinus
rhythm.[19]

Epidemiology
The epidemiology of sinus node dysfunction (SND) is difficult to study, given its nature and varying manifestations, including nonspecific
symptoms and electrocardiographic (ECG) findings. It is estimated that the incidence of SND in the United States is approximately 1 in
600 cardiac patients older than 65 years.[20] Due to its relationship with advanced age, SND is more prevalent in countries where
citizens have a longer life expectancy.

Symptomatic patients are generally older, in seventh or eighth decade of life, with frequent comorbidities. Only a few epidemiologic
studies have been published.

A pooled analysis of 20,572 patients from 2 large epidemiology studies (the Atherosclerosis Risk in Communities [ARIC] and
Cardiovascular Health Study [CHS] trials) who were followed for an average of 17 years, 291 incident cases of sick sinus syndrome (SSS)
were noted, yielding an incidence rate of 0.8 cases per 1000 person-years.[2] Although several variables were associated with the
development of SSS (eg, higher body mass index, hypertension, prior cardiovascular event), advancing age was the most significant risk
factor for SSS (hazard ratio 1.73 for each additional 5 years of age (95% confidence interval: 1.47-2.05).[2]

In major trials of pacing in this disorder, the median or mean age of the patients with SND was 73 to 76 years. Men and women appear
equally affected and, although less common, SND/SSS can also occur in younger adults and children.[21, 22, 23]

Prognosis
The prognosis of patients with sinus node dysfunction (SND) is dependent on the underlying associated condition. The incidence of
sudden cardiac death in patients with SND is low.[21] Pacemaker therapy does not appear to affect survival in patients with SND.[24, 25,
26]

Patients with tachy-brady syndrome have a worse prognosis than do patients with isolated SND. The overall prognosis in patients with
SND and additional systemic ventricular dysfunction (eg, numerous postoperative Mustard and Fontan patients) depends on their
underlying ventricular dysfunction or degree of congestive heart failure (CHF).

In patients who have undergone a Fontan surgery and developed SND, endocardial atrial leads can be implanted relatively safely and
can permit low-energy thresholds for as long as 5 years after implantation.[27]

Morbidity and mortality

The relationship between SND and mortality is difficult to clearly understand, as many individuals with SND have preexisting comorbidities
(eg, hypertension, diabetes mellitus, atrial fibrillation) that are known to increase all-cause mortality.[28]

The complications of SND include the following:

Sudden cardiac death

Syncope

Thromboembolic events, including stroke

CHF

Atrial tachyarrhythmias

About 50% of patients with SND develop tachy-brady syndrome over a lifetime; such patients have a higher risk of stroke and death.
However, the incidence of sudden death owing directly to SND is extremely low.[21]

Patient Education
Given the complex nature of many underlying associated conditions with sinus node dysfunction (SND), especially in the pediatric
population, patients and family members need to be duly educated on the relevant issues, such as recognition of sudden cardiac death
(SCD) and learning cardiopulmonary resuscitation (CPR) techniques, scheduling and attending pacemaker and intracardiac defibrillator
(ICD) follow-ups, etc.

For patient education information, see the Heart Health Center, as well as Heart Rhythm Disorders.

Presentation

History and Physical Examination

History

Most patients with sinus node dysfunction (SND) present with one or more of the following nonspecific symptoms, primarily due to
bradycardia, sinus pause, and sinus arrest:

Fatigue

Lightheadedness

Palpitations

Presyncope/syncope

Dyspnea on exertion

Chest discomfort

Symptoms are frequently intermittent with gradual progression in frequency and severity, although some patients may present with
profound, persistent symptoms. Rarely, patients with SND may be asymptomatic and identified on routine electrocardiography (ECG) or
ambulatory ECG monitoring.

Patients with symptomatic SND are usually older with frequent comorbid diseases; they often seek medical attention owing to symptoms
of lightheadedness, presyncope, syncope and, in patients with alternating periods of bradycardia and tachycardia, palpitations and/or
other symptoms associated with a rapid heart rate.

Patients with coexisting cardiac pathologies such as valvular or ischemic heart disease may notice increasing dyspnea on exertion or
worsening chest discomfort related to a lower heart rate and the resulting reduction in cardiac output. Because symptoms may be variable
in nature, nonspecific and, frequently, transient, it may be challenging at times to establish this symptom-rhythm relationship. Atrial
arrhythmias appear to develop slowly over time, possibly the result of a progressive pathologic process that affects the sinoatrial (SA)
node and the atrium.[29]

Prior to any testing beyond an ECG, a thorough clinical evaluation should be performed for potentially reversible causes, which include
medication use (eg, beta blockers, calcium channel blockers, digoxin, antiarrhythmics), myocardial ischemia, systemic illness (eg,
hypothyroidism), and autonomic imbalance.

Physical examination

The physical examination essentially demonstrates findings of the underlying condition(s). The universal feature, however, is bradycardia.

DDx

Diagnostic Considerations
Conditions to consider in the differential diagnosis of sinus node dysfunction (SND) include the following:

Carotid sinus hypersensitivity

Neurocardiogenic syncope with a predominant cardioinhibitory component

Physiologic normal bradycardia, especially among highly conditioned athletes

Clinical approach to the diagnosis

There are no standardized criteria for establishing a diagnosis of SND, and the initial clues to the diagnosis are most often gleaned from
the patient’s history. However, the symptoms of SND are nonspecific and the electrocardiographic (ECG) findings may not be diagnostic.
Hence, the key to making a diagnosis of SND is to establish a correlation between the patient's symptoms and the underlying rhythm at
the time of the symptoms.

Patients may present with symptoms of fatigue, lightheadedness, presyncope, syncope, dyspnea on exertion, chest discomfort, and/or
palpitations. A routine ECG and/or ambulatory ECG monitoring may confirm the diagnosis if typical ECG findings (eg, one or more periods
of sinus bradycardia; sinus pause, arrest, and sinoatrial [SA] exit block; or alternating bradycardia and atrial tachyarrhythmias) can be
correlated with the symptoms. In some patients, however, additional diagnostic testing may be required, and SND should not be
diagnosed until any potentially reversible causes have been identified and treated.

Following a comprehensive history and physical examination, a resting 12-lead ECG, review of previous medical records and ECG
tracings, and exercise stress testing are the keys to making a diagnosis of SND and establishing a symptom-rhythm correlation. A
detailed history and ECG findings during symptoms are often sufficient to diagnose SND. Careful review of prior records, in particular
previous ECG tracings, can provide subtle clues to changes in the ECG over time. For patients with clinically suspected SND in whom the
diagnosis remains uncertain following the initial ECG, exercise stress testing is advised.

Carefully evaluate for potentially reversible causes and medication use to exclude remediable etiologies for apparent SND. In patients
with medication use (eg, beta blockers, calcium channel blockers, digoxin, antiarrhythmics, and acetylcholine esterase inhibitors)
suspected to result in symptomatic bradycardia, the patient should remain on an ECG monitor while the medications are withdrawn. If
symptoms and ECG abnormalities persist following the withdrawal of the medications (ie, after 3-5 half-lives), then SND/sick sinus
syndrome (SSS) may be diagnosed.

If the diagnosis of SND cannot be definitively diagnosed following a thorough history and physical examination, an initial 12-lead ECG,
and/or an ambulatory ECG monitoring [Holter] for 1 to 14 days, perform an event monitor for up to 4 weeks to identify symptomatic
episodes of arrhythmias and to monitor average heart rates over extended periods of surveillance.

Differential Diagnoses
Atrial Fibrillation

Atrial Flutter

Atrioventricular Block

Workup
Workup

Approach Considerations
See also the Guidelines section for recommendations from the American College of Cardiology, the American Heart Association, and the
Heart Rhythm Society for the evaluation and management of bradycardia and disorders of cardiac conduction delay.

For patients in whom sinus node dysfunction (SND) is clinically suspected but not confirmed by electrocardiography (ECG) and/or
exercise stress test findings, a number of different modalities may be helpful. In most patients, ambulatory ECG monitoring for an
extended period of time (typically 2-4 weeks but potentially longer) has the greatest yield and allows for correlation with symptoms. In
select patients in whom the diagnosis remains uncertain, other diagnostic testing options include adenosine administration, carotid sinus
massage, and invasive electrophysiologic (EP) studies.

The introduction of the implantable loop monitor has also enhanced the diagnostic yield of the clinical evaluation if symptoms are
intermittent, extending over weeks to months.

Laboratory studies

Because hypothyroidism and electrolyte imbalances can contribute to SND, thyroid function testing and serum electrolyte testing (Na+,
K+, Ca2+) can be useful. Infiltrative cardiomyopathies (eg, amyloid, sarcoid) can present with evidence of diffuse conduction system
disease, but screening is typically reserved for patients in whom specific clinical factors suggest the diagnosis.

Echocardiography

No specific imaging studies are required in the initial workup of SND. However, an echocardiogram should be considered because it can
document the presence of underlying valvular or ischemic heart disease and may suggest the diagnosis of amyloid when diffuse
conduction system findings are present.

Transesophageal atrial pacing

Transesophageal atrial pacing is reserved mainly for pediatric patients. It may be performed safely to determine sinus node recovery time
in children who present with dizziness, syncope, or palpitations.

Exercise stress testing

Exercise stress testing helps in identifying abnormal sinus node function. A subnormal increase in heart rate after exercise (ie,
chronotropic incompetence) can help identify individuals with SND who may benefit from a pacemaker implantation.

Electrocardiography
The diagnosis of sinus node dysfunction (SND) in patients with suggestive symptoms is often made on the basis of surface
electrocardiographic (ECG) features. Manifestations seen on ECG may include the following:

Periods of inappropriate and often severe bradycardia, with heart rate of below 50 beats per minute (bpm)

Sinus pauses, arrest, and sinoatrial (SA) exit block with, and often without, appropriate atrial and junctional escape rhythms

Alternating bradycardia and atrial tachyarrhythmias; atrial fibrillation is the most common arrhythmia, but atrial flutter and
paroxysmal supraventricular tachycardias (ie, due to atrial tachycardia) may also occur

See the images below.

This 12-lead electrocardiogram (ECG) is from an asymptomatic girl aged 10 years, which was brought to our attention because of the
irregularity of the P-P intervals. This ECG shows sinus arrhythmia at a rate of 65-75 beats per minute. The P waves all originate from
the sinus node (SN) because they have a positive axis (upright) in leads I, II, and aVF. The PR interval is 104ms, and the QRS is
narrow at 86ms, with a normal axis of 64°. The corrected QT (QTc) interval measures 402ms. Therefore, this is a normal ECG.

Below is an electrocardiogram (ECG) of a girl aged 2 years who was referred to the clinic by a pediatrician for evaluation of a heart
murmur. This ECG shows atrial rhythm originating most likely from the lower left atrium (P waves are inverted in lead I and are positive
in II and aVF, with a frontal axis of 124°). The PR interval measures 113 ms, and the QRS is narrow at 90 ms. Right ventricular (RV)
conduction delay is shown and is best seen in the precordial leads V1 and V2. The QRS frontal axis shows right axis deviation
(reference range for a child aged 2 years is 0-110°). The patient does not have RV hypertrophy by voltage criteria. The inverted T
waves in V1 are a normal finding at this age. An echocardiogram showed a moderately sized atrial septal defect. Nonsinus atrial
rhythm is not a synonym of sinus node dysfunction.

This is a 12-lead electrocardiogram (ECG) from a boy aged 12 years with a history of syncope. This patient was healthy until 1 month
earlier, when he started to experience episodes of lightheadedness. The ECG shows sinus arrhythmia (bradycardia) at a rate of 50-79
beats per minute, with a PR interval of 136 ms. Two junctional escape beats are present after a prolonged pause. The QRS is narrow
at 85 ms, with a normal frontal axis of 70°. The corrected QT interval (QTc) is 411 ms. A later electrophysiologic study showed
prolonged sinus node recovery time (SNRT) and sinoatrial conduction time (SACT). Because of the patient's symptoms and his sinus
node (SN) dysfunction, he received an atrial pacemaker. If this 12-lead ECG had been recorded from an asymptomatic patient, the
findings would be considered within normal limits and no further workup would be indicated. In this case, the lightheadedness and,
ultimately, the syncope defined sick sinus syndrome, with the patient requiring pacemaker therapy.

Ambulatory ECG (Holter) Monitoring and Event Recording

For patients with clinically suspected sinus node dysfunction (SND) in whom the initial electrocardiogram (ECG) and monitoring are not
diagnostic, ambulatory ECG monitoring or long-term event monitoring (eg, 7 or 30 days) is useful in the assessment of SND[30] and for
correlation with symptoms.

The specificity of a direct observation of spontaneous (ie, not provoked by an electrophysiologic [EP] study) SND is 100%, and an EP
study is not required. Therefore, cardiac monitoring, rather than EP study, is the method of choice to assess SND.

A 24-hour Holter study also has the advantage of revealing whether SND produces symptoms such as dizziness, presyncope, or
syncope; these cannot be determined during an EP study, because the patient is heavily sedated. Therefore, a 24-hour Holter study can
help decide if pacemaker therapy is required.

Pharmacologic Stimulation Tests

This section outlines steps to allow systematic evaluation of sinus node (SN) function.

Calculating the intrinsic heart rate (IHR)

The IHR is the heart rate in the presence of complete pharmacologic denervation of the SN. This is achieved with the simultaneous use of
beta blockers and atropine. The calculation of the IHR following simultaneous administration of beta blockers and atropine is largely of
historical interest and is rarely performed in the modern evaluation of patients with suspected SN dysfunction (SND). The IHR in a healthy
person is approximately equal to 117.2 – (0.53 × age in years).

Sinus node response to pharmacologic challenge

A number of drugs have been used in to aid in the diagnosis of SND. The pharmacologic protocols are briefly described below.

Atropine and isoproterenol

Atropine (1 or 2 mg) and isoproterenol (2-3 mcg/minute) may be useful, because both agents normally increase the sinus rate. A
suggested abnormal response is an increase in the sinus rate of less than 25% above the baseline, or to a sinus rate below 90 beats per
minute.[31] Due to fact that in most cases the diagnosis of SND can be achieved by establishing a symptom-rhythm correlation with the
use of ambulatory monitoring in conjunction with a comprehensive history and physical examination, testing with these agents is rarely
necessary.

Adenosine

Adenosine has been proposed as an alternative to invasive electrophysiology studies, but its routine use is not yet established.

Electrophysiologic Studies
Invasive electrophysiologic (EP) studies are rarely used for the evaluation of sinus node dysfunction (SND) because of their limited
sensitivity in eliciting bradyarrhythmias as well as due to the widespread availability of diagnostic options for long-term monitoring.
However, in patients with suspected SND who also describe sustained episodes of tachyarrhythmias, EP studies may be helpful in an
effort to identify a tachycardia (eg, atrial tachycardia) that would be potentially curable with ablation.[28] Nevertheless, invasive EP studies
may be performed in the following situations involving symptomatic patients[28] :

Those without ECG findings suggestive of SND and no other evident cause for their symptoms

Those in whom ECG events are compatible with SND but fail to correlate with symptoms

Those with SND who have sustained episodes of tachycardia that may be amenable to ablation

Those with syncope or near syncope who have bundle branch or bifascicular block; such patients may require invasive EP
evaluation of the sinoatrial (SA) node, the atrioventricular (AV) node, and the infranodal His-bundle-Purkinje system function. EP
testing that shows SA nodal dysfunction allows for the selection of appropriate therapy in up to 50% of these patients.

Those with syncope or near syncope who have ventricular arrhythmias may require EP study to assess for inducibility of
ventricular tachyarrhythmias

The salient aspects of EP studies that aid in eliciting a bradyarrhythmic abnormality include assessment of the SA node recovery time, SA
conduction time (SACT), and the SN and atrial tissue refractory periods.

Classic EP criteria for SND include the presence of 1 or more of the following:

Corrected SN recovery time (CSNRT) greater than 275 milliseconds (ms)

SA conduction time greater than 200 ms

SA node arrest

SA exit block

SN reentry tachycardia

SN recovery time (SNRT)

EP studies can document SND when studying SN automaticity by directly recording electrical activity.

Measurement of SNRT is achieved by pacing the atrium. Pacing should be performed from a catheter placed in the high right atrium
(HRA) near the SN at the junction of the superior vena cava (SVC) and the RA for 4-6 trials of 30 seconds each. Each trial should use
successively shorter pacing cycle lengths (eg, 600 ms, 550 ms, 500 ms), beginning with a cycle length just shorter than the resting sinus
cycle length. SNRT is the time interval between the last paced captured beat to the first spontaneous sinus beat.

Gradual return of the SN to its baseline rate occurs over 5-6 beats. Prolonged pauses (ie, secondary pauses) can occur after the initial
recovery interval in SND.

If the longest interval for the recovery interval or secondary pause exceeds 1500 ms, the SNRT is prolonged.

To adjust for heart rate and before each pacing increase, the resting sinus cycle length (SCL) is measured. When the resting SCL is
subtracted from the SNRT, the CSNRT is obtained. Its upper reference range limit is 525 ms; if the SNRT exceeds the SCL by more than
525 ms, the SNRT is abnormal. The same occurs if the ratio of SNRT to SCL (ie, SNRT/SCL × 100) is more than 160%.
Sinoatrial conduction time (SACT)

SACT is another parameter that can be used to assess SN function. It is defined as the time interval in milliseconds for an impulse that
originates in the SN to conduct through the perinodal tissue to the adjacent RA tissue. (The tissue that surrounds the SN or perinodal
tissue has characteristics that are similar to those of the AV node.)

Note the following:

Eight premature atrial contractions (PACs) are fired in the HRA at 5-10 bpm faster than the SN rate before they are stopped
abruptly.

SACT represents the time in milliseconds that it takes for the PAC fired in the HRA to enter and reset the SN. It also represents the
time for the new spontaneous SN impulse (ie, SCL) to reach the HRA. SACT is measured as the time in milliseconds from the last
PAC to the first spontaneous sinus beat.

When the time interval between the last spontaneous SN depolarization (ie, before the PAC) and the one that occurred after a PAC
is less than twice the value of the 2 previous spontaneous SN depolarizations, reset of the SN by the PAC has occurred.

SACT can be calculated as the interval from the PAC to the next spontaneous SN beat, which includes conduction through the
perinodal tissue into the SN, resetting the SN, and conduction through the same perinodal tissue back into the HRA (ie, [return
interval - SCL]/2). The reference range is 50-125 ms in children and 200-250 ms in adults.

If the SN cannot produce a spontaneous impulse following PACs (ie, these have not reset the SN and, therefore, SACT cannot be
calculated), SA entrance block is present. This block could be caused by a markedly prolonged SA conduction and/or an increased
refractory period of the peri-SN or SN fibers, both of which indicate SND. SN entrance block alternating with reset responses also
denotes SND.

SN reentry tachycardia occurs when activation of the atrium during the supraventricular tachycardia is the same as sinus beats (ie,
the P-wave axis and morphology are the same as those in the sinus rhythm). It is usually indicative of SND.

Treatment

Approach Considerations
See also the Guidelines section for recommendations from the American College of Cardiology, the American Heart Association, and the
Heart Rhythm Society for the evaluation and management of bradycardia and disorders of cardiac conduction delay.

The only effective medical care in patients with sinus node dysfunction (SND) is correction of extrinsic causes. Admit patients for testing
and pacemaker placement when indicated. Transfer patients for complicated dysrhythmias and pacemaker implantation.

No treatment is required for asymptomatic patients, even if they have abnormal SN recovery times (SNRTs) or sinoatrial conduction times
(SACTs). If the patient is receiving medications that can provoke sinus bradyarrhythmias (eg, beta blockers), the medications should be
stopped if possible.

Acute treatment consists of atropine (0.04 mg/kg intravenously [IV] every 2-4 h) and/or isoproterenol (0.05-0.5 mcg/kg/min intravenously
[IV]). A transvenous temporary pacemaker is sometimes required despite medical therapy.

In patients with bradyarrhythmias-tachyarrhythmias, the tachyarrhythmias may be controlled with digoxin, propranolol, or quinidine.
However, these patients should be monitored closely with frequent Holter monitoring to ensure that the bradyarrhythmias are not
exacerbated or causing symptoms (eg, dizziness, syncope, congestive heart failure); if exacerbation of arrhythmias or symptoms occur,
permanent pacemaker therapy is also required.

Activity

Patients with symptomatic SND who are not on pacemaker therapy should titrate their level of activity to minimize symptoms.

Consultations

These include cardiac electrophysiology consultation.

Pacemaker Therapy
Pacemaker therapy is the only effective surgical care for patients with chronic, symptomatic sinus node dysfunction (SND). The major
goal of pacemaker therapy in patients with SND is to relieve symptoms.

Recommendations for permanent pacing in SND

On the basis of the American College of Cardiology Foundation, American Heart Association, the Heart Rhythm Society
(ACCF/AHA/HRS), and the European Society of Cardiology (ESC), general recommendations for cardiac pacing therapy for SND are
outlined below.[1, 4, 32]

Class I recommendations (All level of evidence C)

Permanent pacemaker implantation is indicated for the following[1, 4, 32] :

SND with documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms

Symptomatic chronotropic incompetence

Symptomatic sinus bradycardia that results from required drug therapy for medical conditions

Class IIa recommendations (All level of evidence C)

Permanent pacemaker implantation is reasonable for the following[1, 4, 32] :

SND with a heart rate below 40 bpm, when a clear association between significant symptoms consistent with bradycardia and the
actual presence of bradycardia has not been documented

Syncope of unexplained origin, when clinically significant abnormalities of SN function are discovered or provoked in
electrophysiologic (EP) studies

Class IIb recommendation

Permanent pacemaker implantation may be considered in minimally symptomatic patients with a chronic heart rate below 40 bpm while
awake (level of evidence: C).[1, 4, 32]

Class III recommendations (All level of evidence C)

Permanent pacemaker implantation is not indicated for SND in the following individuals[1, 4, 32] :

Asymptomatic patients

Those for whom the symptoms suggestive of bradycardia have been clearly documented to occur in the absence of bradycardia

Those with symptomatic bradycardia due to nonessential drug therapy

Single- versus dual-chamber pacemakers

In patients with SND, the annual incidence of complete heart block is about 0.6%.[33] In the United States, the implantation of dual-
chamber pacemakers is preferred in practice because their use anticipates the possible subsequent development of conducting system
dysfunction.

This practice is supported by data from the Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual Chamber
Pacing in Sick Sinus Syndrome (DANPACE) trial, in which 9.3% of patients with single-lead atrial pacing (AAI) required upgrade to a dual-
chamber pacemaker (DDD) over 5.4 years of follow-up due to new development of significant atrioventricular (AV) conduction
abnormalities.[34] This was necessary despite the fact that these patients had no significant intraventricular conduction abnormality, had
PR intervals below 260 ms, and had no Wenckebach AV block with atrial pacing at 100 bpm at baseline. In addition, the incidence of atrial
fibrillation (AF) was higher in patients in AAI mode than those in DDD mode. However, no significant mortality difference was noted
between the groups in AAI and DDD modes.[34]

Arguably, a single-chamber atrial pacemaker with AAI mode is an acceptable alternative in patients with SND and normal AV and
intraventricular conduction because of the added expense of, and the potential for, more lead extraction with a dual-chamber pacemaker.

In patients with SND and known AV conduction abnormality (including bundle branch block and bifascicular block), a dual-chamber
pacemaker should be used due to the high risk of AV block (about 36% in a 5-year follow-up study).

In a collaborative pooled-analysis of 10 randomized trials (n = 6639) to evaluate the effect of existing pacing strategies on the risk of
postimplantation AF and heart failure events in SND patients, Chen et al stratified the pooled-analysis into two subsets—AAI versus DDD,
and minimal ventricular pacing (MinVP) versus DDD—and found that although composite AF and heart failure (HF) events were similar in
the AAI versus DDD subset, there was a substantially reduced risk of composite AF and HF in the MinVP group receiving pacemaker as
primary treatment.[35] Over the long term, however, the rate of AF and HF was similar in the MinVP versus DDD subset of patients who
were scheduled for device replacement. The investigators indicated their findings supported the use of MinVP over conventional DDD in
improving clinical outcomes for SND patients who received a pacemaker as primary treatment.[35]

Pacemaker programming features

Chronic right ventricular pacing has been shown to be associated with an increased incidence of AF, stroke, HF, and probably death.[21,
22, 36] A study suggested that right ventricular (RV) pacing is detrimental to left ventricular (LV) function even in patients with a normal LV
ejection fraction (LVEF).[37] Therefore, avoiding RV pacing is advantageous in patients with SND treated with pacemaker therapy.

However, using the intrinsic AV conduction in patients with a very long intrinsic PR interval may not be beneficial clinically, as suggested
by a trial in patients with an intracardiac defibrillator (ICD).[34] Theoretically, a very long PR interval may result in pacemaker syndrome
during sinus tachycardia or a fast atrial pacing rhythm.

As noted above, in the DANPACE trial, about 65% of patients with a moderate AV delay setting in DDD mode with mean RV pacing had a
lower incidence of AF and no increased rate of HF, as compared with patients in AAI mode.[34] The optimal AV delay settings in patients
with SND are remain unknown, although various programming algorithms from different pacemaker companies are very effective in
reducing RV pacing.

Mode switch is an important feature to monitor atrial flutter and AF events. Because more than 50% of patients with SND may develop
tachy-brady syndrome over time,[21] it is very important to identify these patients through pacemaker monitoring and to anticoagulate
them to reduce their risk of stroke. However, the most appropriate anticoagulant therapy is still uncertain for patients in whom AF is
detected only as an incidental finding on pacemaker or ICD diagnostics.

Rate response features have been used in patients with SND, especially in the presence of chronotropic incompetence. However, the
clinical benefits of this program feature are still controversial.[38]

Funny Current Blocker Ivabradine

Spontaneous depolarization of the sinus node involves "funny" (I(f)) current in sinoatrial (SA) node myocytes. This is an inward current
that is activated on hyperpolarization to the diastolic range of voltages, thereby generating repetitive activity and modulating spontaneous
rate. The degree of activation of the funny current determines the steepness of phase 4 depolarization and, hence, the frequency of action
potential firing.

I(f) is controlled by intracellular cyclic adenosine monophosphate (cAMP) and is thus activated and inhibited by beta-adrenergic and
muscarinic M2 receptor stimulation, respectively; it represents a basic physiologic mechanism for mediating autonomic regulation of the
heart rate. Typically, given their exclusive role, f-channels are ideal targets of drugs aiming for pharmacologic control of the cardiac rate.
Molecules able to bind specifically to and block f-channels can therefore be used as pharmacologic tools for heart rate control with little or
no adverse cardiovascular side effects.

In addition, several loss-of-function mutations of HCN4 (hyperpolarization-activated, cyclic-nucleotide gated 4), the major constitutive
subunit of f-channels in pacemaker cells, are known to cause rhythm disturbances (eg, inherited sinus bradycardia). Finally, gene- or cell-
based methods for in situ delivery of f-channels to silent or defective cardiac muscle represent novel approaches for the development of
biologic pacemakers that may eventually be able to replace electronic devices.

Current status of ivabradine

A selective f-channel inhibitor, ivabradine, is now commercially available and used in patients with heart failure (HF) and sinus
tachycardia.

The 2016 American College of Cardiology, American Heart Association, and the Heart Failure Society of America (ACC/AHA/HFSA)
guideline update on new pharmacologic therapy for HF gives a class IIa recommendation for the use of ivabradine to reduce HF
hospitalization in patients with symptomatic (New York Heart Association [NYHA] class II-III) stable chronic HF with reduced ejection
fraction (HFrEF) (left ventricular ejection fraction [LVEF] ≤35%) receiving guideline-directed evaluation and management, including a beta
blocker at the maximum tolerated dose, as well as who are in sinus rhythm with a resting heart rate of 70 bpm or more.[39] The guideline
indicates that, "given the well-proven mortality benefits of beta-blocker therapy, it is important to initiate and up titrate these agents to
target doses, as tolerated, before assessing the resting heart rate for consideration of ivabradine initiation."[39]

Ivabradine is contraindicated in patients with HF and SND without a permanent cardiac pacemaker.

Long-Term Monitoring
Asymptomatic patients with sinus node dysfunction (SND) should be observed for symptoms. In patients with a pacemaker, carry out the
following on routine pacemaker interrogations:

Monitor leads and battery status

Ensure adequate heart rate support at rest, during daily activities, and during exercise

Monitor for pacemaker malfunction

Ensure minimal right ventricular (RV) pacing.

Monitor for atrial fibrillation and atrial flutter events

Pregnancy

Patients with SND who become pregnant and take antiarrhythmic medications should have their medication levels measured because
these drug regimens frequently require adjustment. In addition, medication with teratogenic effects (eg, amiodarone, which is associated
with fetal thyroid dysfunction) should be avoided.
Patients with SND who become pregnant and have a pacemaker are advised to perform frequent pacemaker checks and make the
appropriate adjustments.

Patients with SND who become pregnant and have ventricular dysfunction due to cardiomyopathy or a Mustard or Fontan procedure
should have regular and close medical follow-ups with their obstetrician and cardiologist. This permits appropriate adjustment and
implementation of anti-congestive heart failure (CHF) medication. If the CHF progresses despite medical management and becomes
intractable, the mother and fetus are at risk and early delivery may be scheduled.

Future Directions
Certain genetic mutations have been linked to sinus node and conduction system disease. SCN5A, HCN4, RYR2, CASQ2, and ankyrin-B
(ANKB) mutations are associated with sinus node dysfunction, whereas mutations of SN5A, SCN1B, KCNJ2, TBX5, and NKX2-5 are
associated with conduction system disease. Neuromuscular genetic disorders including emerin (EMD), lamin A/C (LMNA), and myotonic
dystrophy type 1 (DM1) are also associated with AV conduction disease.[7] Gene- and stem cell-based therapies are currently being
investigated as therapeutic options for patients with genetic or degenerative abnormalities of the cardiac electrical conduction system.

Guidelines

Guidelines Summary
2018 ACC/AHA/HRS guidelines

The guideline on the evaluation and management of bradycardia and cardiac conduction delay was released in November 2018, by the
American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Rhythm Society (HRS).[40, 41]

The guideline’s top 10 key messages for assessing and treating patients with bradycardia or other disorders of cardiac conduction delay
are provided below.

Sinus node dysfunction is most often related to age-dependent progressive fibrosis of the sinus nodal tissue and surrounding atrial
myocardium leading to abnormalities of sinus node and atrial impulse formation and propagation and will therefore result in various
bradycardic or pause-related syndromes.

Sleep disorders of breathing and nocturnal bradycardias are relatively common. Treatment of sleep apnea reduces the frequency of these
arrhythmias and also may offer cardiovascular benefits. The presence of nocturnal bradycardias should prompt consideration for
screening for sleep apnea, beginning with solicitation of suspicious symptoms. However, nocturnal bradycardia is not in itself an indication
for permanent pacing.

The presence of left bundle branch block on electrocardiogram markedly increases the likelihood of underlying structural heart disease
and of diagnosing left ventricular (LV) systolic dysfunction. Echocardiography is usually the most appropriate initial screening test for
structural heart disease, including LV systolic dysfunction.

In sinus node dysfunction, there is no established minimum heart rate or pause duration where permanent pacing is recommended. It is
important to establish a temporal correlation between symptoms and bradycardia when determining whether permanent pacing is
needed.

In patients with acquired second-degree Mobitz type II atrioventricular (AV) block, high-grade AV block, or third-degree AV block not
caused by reversible or physiologic causes, permanent pacing is recommended regardless of symptoms. For all other types of AV block,
in the absence of conditions associated with progressive AV conduction abnormalities, permanent pacing should generally be considered
only in the presence of symptoms that correlate with AV block.

In patients with an LV ejection fraction between 36% and 50% and AV block, who have an indication for permanent pacing and are
expected to require ventricular pacing over 40% of the time, techniques that provide more physiologic ventricular activation (eg, cardiac
resynchronization therapy [CRT], His bundle pacing) are preferred to right ventricular pacing to prevent heart failure.

Because conduction system abnormalities are common after transcatheter aortic valve replacement (TAVR), recommendations on
postprocedure surveillance and pacemaker implantation are made in this guideline.

In patients with bradycardia who have indications for pacemaker implantation, shared decision-making and patient-centered care are
endorsed and emphasized in this guideline. Treatment decisions are based on the best available evidence and on the patient’s goals of
care and preferences.

Using the principles of shared decision-making and informed consent/refusal, patients with decision-making capacity or his/her legally
defined surrogate have/has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent,
which should be considered palliative, end-of-life care, and not physician-assisted suicide. However, any decision is complex, should
involve all stakeholders, and will always be patient specific.
Identifying patient populations that will benefit the most from emerging pacing technologies (eg, His bundle pacing, transcatheter leadless
pacing systems) will require further investigation as these modalities are incorporated into clinical practice.

Medication

Medication Summary
Currently, no medications are routinely used to treat symptomatic sinus node dysfunction (SND). Virtually most medications are ineffective
over the long term, and many demonstrate lack of efficacy from tachyphylaxis. Nonetheless, acute treatment with the anticholinergic
agent atropine and/or the adrenergic agonist isoproterenol may be warranted. Oral analogues of these drugs (eg, propantheline and
orciprenaline [metaproterenol], respectively) are not effective on a long-term basis.

Anticholinergic Agents

Class Summary
Atropine, by vagolytic effect, increases the heart rate. Although it may also be used for the initial treatment of chronic arrhythmias, cardiac
pacing is preferred for long-term control.

Atropine
Atropine increases the heart rate through vagolytic effects, causing an increase in cardiac output.

Beta1/Beta2 Adrenergic Agonists

Class Summary
When given systemically, isoproterenol stimulates beta receptors in the heart, which produces positive inotropic and chronotropic effects.
This results in increased cardiac output.

Isoproterenol (Isuprel)
Isoproterenol has sympathomimetic effects; specifically, beta1- and beta2-adrenergic receptor agonist activity.

Cardiovascular, Other

Class Summary
It may be necessary to use antiarrhythmic agents for concomitant tachyarrhythmia.

Quinidine
Quinidine maintains normal heart rhythm following cardioversion of atrial fibrillation or flutter. It depresses myocardial excitability and
conduction velocity. Control the ventricular rate and CHF (if present) with digoxin or calcium channel blockers before the administration of
quinidine.

Questions & Answers

Overview

What is sinus node dysfunction (SND)?

How is sinus node dysfunction (SND) characterized?

Which ECG abnormalities are characteristic of sinus node dysfunction (SND)?

What is the pathophysiology of sinus node dysfunction (SND)?

What are the signs and symptoms of sinus node dysfunction (SND)?

What is the natural history of sinus node dysfunction (SND)?

What is the role of genetics in the etiology of sinus node dysfunction (SND)?

What causes sinus node dysfunction (SND)?

What is the role of abnormal automaticity (sinus arrest) in the etiology of sinus node dysfunction (SND)?

What is the role of sinus node degeneration in the etiology of sinus node dysfunction (SND)?

What is the role of medications in the etiology of sinus node dysfunction (SND)?

Which childhood and familial diseases cause sinus node dysfunction (SND)?

Which infiltrative diseases cause sinus node dysfunction (SND)?

Which inflammatory diseases cause sinus node dysfunction (SND)?

What is the role of the SA artery in sinus node dysfunction?

What is the role of trauma in the etiology of sinus node dysfunction (SND)?

Which disorders are associated with sinus node dysfunction (SND)?

What are surgical causes of sinus node dysfunction (SND)?

What is the role of rheumatic fever in the etiology of sinus node dysfunction (SND)?

Which endocrine-metabolic disorders are associated with sinus node dysfunction (SND)?

Which factors increase the risk of sinus node dysfunction (SND) after catheter ablation to restore sinus rhythm?

What is the prevalence of sinus node dysfunction (SND)?

What is the prognosis of sinus node dysfunction (SND)?

What are the possible complications of sinus node dysfunction (SND)?

What is included in patient education about sinus node dysfunction (SND)?

Presentation

What are the signs and symptoms of sinus node dysfunction (SND)?

Which clinical history findings are characteristic of sinus node dysfunction (SND)?

Which physical findings are characteristic of sinus node dysfunction (SND)?

DDX

Which conditions are included in the differential diagnosis of sinus node dysfunction (SND)?

How is sinus node dysfunction (SND) diagnosed?

What are the differential diagnoses for Sinus Node Dysfunction?

Workup

Which tests are performed in the workup of sinus node dysfunction (SND)?

What is the role of lab testing in the workup of sinus node dysfunction (SND)?

What is the role of echocardiography in the workup of sinus node dysfunction (SND)?

What is the role of transesophageal atrial pacing in the workup of sinus node dysfunction (SND)?
What is the role of exercise stress testing in the workup of sinus node dysfunction (SND)?

What is the role of ECG in the workup of sinus node dysfunction (SND)?

What is the role of ambulatory ECG (Holter) monitoring in the workup of sinus node dysfunction (SND)?

What is the role of pharmacologic stimulation tests in the workup of sinus node dysfunction (SND)?

What is the role of electrophysiologic (EP) studies in the workup of sinus node dysfunction (SND)?

What are the electrophysiologic (EP) criteria for diagnosis of sinus node dysfunction (SND)?

How is sinus node recovery time (SNRT) determined?

How is sinoatrial conduction time (SACT) defined?

What is the role of sinoatrial conduction time (SACT) in the workup of sinus node dysfunction (SND)?

Treatment

How is sinus node dysfunction (SND) treated?

Which activity modifications are used in the treatment of sinus node dysfunction (SND)?

Which specialist consultations are beneficial to patients with sinus node dysfunction (SND)?

What is the role of pacemaker therapy in the treatment of sinus node dysfunction (SND)?

What are the guidelines for permanent pacing in sinus node dysfunction (SND)?

What is the comparison of single- and dual-chamber pacemakers for the treatment of sinus node dysfunction (SND)?

What are the pacemaker programming features used in the treatment of sinus node dysfunction (SND)?

What is the role of ivabradine in the treatment of sinus node dysfunction (SND)?

What is included in long-term monitoring of sinus node dysfunction (SND)?

How is sinus node dysfunction (SND) monitored during pregnancy?

What is the role of genetic therapies in the treatment of sinus node dysfunction (SND)?

Guidelines

What are the ACC/AHA/HRS treatment guidelines for sinus node dysfunction (SND)?

Medications

What is the role of medications in the treatment of sinus node dysfunction (SND)?

Which medications in the drug class Cardiovascular, Other are used in the treatment of Sinus Node Dysfunction?

Which medications in the drug class Beta1/Beta2 Adrenergic Agonists are used in the treatment of Sinus Node Dysfunction?

Which medications in the drug class Anticholinergic Agents are used in the treatment of Sinus Node Dysfunction?

Contributor Information and Disclosures

Author

Bharat K Kantharia, MD, FRCP, FAHA, FACC, FESC, FHRS Clinical Professor of Medicine, Icahn School of Medicine at Mount Sinai;
Cardiac Electrophysiologist, Mount Sinai Health System, New York-Presbyterian Healthcare System, Montefiore Medical Center, Lennox
Hill Hospital

Bharat K Kantharia, MD, FRCP, FAHA, FACC, FESC, FHRS is a member of the following medical societies: American College of
Cardiology, American Heart Association, Cardiac Electrophysiology Society, European Cardiac Arrhythmia Society, European Society of
Cardiology, Heart Rhythm Society, Medical Society of the State of New York, Royal College of Physicians of Edinburgh, Royal College of
Physicians of Ireland, Royal College of Physicians of London, Royal Society of Medicine, Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)
Arti N Shah, MD, MS, FACC, FACP, CEPS-AC, CEDS Assistant Professor of Medicine, Mount Sinai School of Medicine; Director of
Electrophysiology, Elmhurst Hospital Center and Queens Hospital Center

Arti N Shah, MD, MS, FACC, FACP, CEPS-AC, CEDS is a member of the following medical societies: American Association of
Cardiologists of Indian Origin, American College of Cardiology, American College of Physicians, American Heart Association, Cardiac
Electrophysiology Society, European Heart Rhythm Society, European Society of Cardiology, Heart Rhythm Society, New York Academy
of Medicine

Disclosure: Nothing to disclose.

Arun Chutani, MD Senior Registrar, Nair Hospital, Topiwala National Medical College, India

Disclosure: Nothing to disclose.

Surendra K Chutani, MD, DM, FACC, FHRS, CEPS-AC, CCDS Fellow, Department of Cardiology, Mount Sinai St Luke's Hospital Center

Surendra K Chutani, MD, DM, FACC, FHRS, CEPS-AC, CCDS is a member of the following medical societies: American College of
Cardiology, Asia Pacific Heart Rhythm Society, Association of Physicians of India, Cardiology Society of India, European Heart Rhythm
Society, Heart Rhythm Society, Heart Rhythm Society of India

Disclosure: Nothing to disclose.

Chief Editor

Mikhael F El-Chami, MD Associate Professor, Department of Medicine, Division of Cardiology, Section of Electrophysiology, Emory
University School of Medicine

Mikhael F El-Chami, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American
Heart Association, Heart Rhythm Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Medtronic; Boston Scientific,
Biotronik<br/>Received research grants (as part of Multicenter studies) from Medtronic and Boston Scientific.

Additional Contributors

Yasir Batres, MD Physician, Division of Cardiology, University of California, Davis, Medical Center

Yasir Batres, MD is a member of the following medical societies: American College of Cardiology

Disclosure: Nothing to disclose.

Acknowledgements

Stuart Berger, MD Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical
Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin

Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology,
American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Alan D Forker, MD Professor of Medicine, University of Missouri at Kansas City School of Medicine; Director, Outpatient Lipid Diabetes
Research, MidAmerica Heart Institute of St Luke's Hospital

Alan D Forker, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American
College of Physicians, American Heart Association, American Medical Association , American Society of Hypertension, and Phi Beta
Kappa

Disclosure: Nothing to disclose.

M Silvana Horenstein, MD Assistant Professor, Department of Pediatrics, University of Texas Medical School at Houston; Medical Doctor
Consultant, Legacy Department, Best Doctors, Inc

M Silvana Horenstein, MD is a member of the following medical societies: American Academy of Pediatrics, American College of
Cardiology, and American Medical Association

Disclosure: Nothing to disclose.

Peter P Karpawich, MD Professor of Pediatric Medicine, Department of Pediatrics (Cardiology), Wayne State University School of
Medicine; Director, Cardiac Electrophysiology and Pacemaker Services, Children's Hospital of Michigan

Peter P Karpawich, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology,
American Heart Association, Heart Rhythm Society, Michigan State Medical Society, and Pediatric Electrophysiology Society

Disclosure: Nothing to disclose.

Adrian W Messerli, MD Consulting Staff, Cardiology Associates of Kentucky

Disclosure: Nothing to disclose.

John W Moore, MD, MPH Professor of Clinical Pediatrics, Section of Pediatric Cardiology, Department of Pediatrics, University of
California San Diego School of Medicine; Director of Cardiology, Rady Children's Hospital

John W Moore, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of
Cardiology, and Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Brian Olshansky, MD Professor of Medicine, Department of Internal Medicine, University of Iowa College of Medicine

Brian Olshansky, MD is a member of the following medical societies: American Autonomic Society, American College of Cardiology,
American College of Chest Physicians, American College of Physicians, American College of Sports Medicine, American Federation for
Clinical Research, American Heart Association, Cardiac Electrophysiology Society, Heart Rhythm Society, and New York Academy of
Sciences

Disclosure: Guidant/Boston Scientific Honoraria Speaking and teaching; Medtronic Honoraria Speaking and teaching; Guidant/Boston
Scientific Consulting fee Consulting; Novartis Honoraria Speaking and teaching; Novartis Consulting fee Consulting

Justin D Pearlman, MD, PhD, ME, MA Director of Advanced Cardiovascular Imaging, Professor of Medicine, Professor of Radiology,
Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center

Justin D Pearlman, MD, PhD, ME, MA is a member of the following medical societies: American College of Cardiology, American College
of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological
Society of North America

Disclosure: Nothing to disclose.

Paul M Seib, MD Associate Professor of Pediatrics, University of Arkansas for Medical Sciences; Medical Director, Cardiac
Catheterization Laboratory, Co-Medical Director, Cardiovascular Intensive Care Unit, Arkansas Children's Hospital

Paul M Seib, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology,
American Heart Association, Arkansas Medical Society, International Society for Heart and Lung Transplantation, and Society for Cardiac
Angiography and Interventions

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-
Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief,
Medscape Drug Reference

Disclosure: Nothing to disclose.

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