You are on page 1of 16


Sinus node dysfunction (SND) refers to abnormalities in SN impulse formation and propagation and
includes sinus bradycardia, sinus pause/arrest, chronotropic incompetence, and sinoatrial exit block. (See
Workup.)[1, 2, 3]

SND is frequently associated with conduction system disease in the heart and various supraventricular
tachyarrhythmias, such as atrial fibrillation[3, 4] and atrial flutter. When associated with supraventricular
tachyarrhythmias, SND is often termed tachy-brady syndrome. (See Pathophysiology and Etiology.) [2, 3]

SND is referred to as sick sinus syndrome when it is accompanied by symptoms such as dizziness or
syncope. (See Etiology and Presentation.)

Although SND may occur at any age, it is primarily a disease of the elderly and, presumably, is related to
the senescence of the SN, which is often accompanied with the senescence of the atrium and the
conduction system in the heart.[3, 5]When SND occurs earlier in life, it is often secondary to other cardiac
disease processes.[6] It constitutes an important cause of morbidity in patients who have undergone surgery
for congenital heart disease (CHD). (See Etiology, Prognosis, and Epidemiology.)

The natural history of SND may be highly variable, although it tends to be progressive in nature. The only
effective treatment for patients with chronic symptomatic SND is pacemaker therapy. Asymptomatic
patients do not require therapy. (See Pathophysiology, Prognosis, Treatment, and Medication.)

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, on the other hand, 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.

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

Heart failure symptoms and palpitations
Although the exact etiology of SND is usually not identified, most cases are believed to be attributable to a
combination of various intrinsic and extrinsic factors. The most common intrinsic causes are cardiac age-
related SN changes and coronary artery disease. The most common extrinsic causes are medications and
autonomic hyperactivity.

The acquired form of SND may also occur after damage to the SN artery during cardiac surgery or may be
due to occlusion, such as after myocardial infarction. In the pediatric population, SND and atrioventricular
(AV) block have been found to occur more frequently in patients with Kawasaki disease with moderate to
severe coronary artery disease than in the general population. This is believed to be secondary to
myocarditis or abnormal microcirculation in the SN artery and the AV-node artery.[7]

The idiopathic form of SND is degenerative, with fibrosis and fatty infiltration of the SN and consequent
decrease of functional nodal cells.

Intrinsic SND
Age-related changes

Age-related changes are believed to be the most common cause of SND and are related to fibrosis in the
SN. These fibrotic changes also occur in the atrium and the conduction system of the heart and are
believed to contribute to the association among SND, tachy-brady syndrome, conductive system disease,
and an inappropriately slow escape rhythm.

The pacemaker activity in the SN has been found to be related to voltage and calcium clocks. [8] Age-related
down-regulation of calcium channel expression in the SN has been suggested as a potential cause of SND
with aging.[9]

Coronary artery disease

Coronary artery disease is believed to be a common contributory cause of SND, probably through
atherosclerotic changes in the SN artery.

Genetic causes

SND may be familial; an autosomal dominant pattern of inheritance has been described. Several molecular
defects in human hearts (defects in the sodium channel, calcium channel, hyperpolarization-activated cyclic
nucleotide-gated cation (HCN) channel, ankyrin-B, and connexin 40) have been associated with familial
sick sinus syndromes.[6]

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.

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

Mechanisms in tachy-brady syndrome

Tachycardia-mediated remodeling of the SN is present in patients with atrial fibrillation/flutter and it may
contribute to SND in these patients. In patients with tachy-brady syndrome, atrial fibrillation ablation can
reverse SND, as evidenced by a reduction in SN recovery time, an increase in mean and maximal heart
rates, and a lack of symptoms related to sinus bradycardia or pause. [10] The mechanism of SND in tachy-
brady syndrome may involve the abnormal function of voltage and calcium clocks in the SN. [11, 12]

Other heart diseases

Other structural heart diseases are uncommon causes of SND. These include, but are not limited to, the

Various cardiomyopathies
Infiltrative heart diseases - Amyloidosis, hemochromatosis, neoplasm
Collagen vascular diseases - Systemic lupus, scleroderma
Neuromuscular diseases - Myotonic dystrophy, Friedreich ataxia
Extrinsic SND
Beta blockers, calcium channel blockers, digoxin, and various anti-arrhythmic drugs suppress SN function.
Antiarrhythmic drugs that can lead to SND include the following:

Digitalis - Because of SN exit block

Autonomic dysfunction

SND can be secondary to autonomic nervous system dysfunction in patients with neurocardiogenic
syncope, and carotid sinus hypersensitivity. Conditions associated with marked hypervagotonia, as in well-
trained athletes, can also result in SND. However, evidence suggests that there may be some intrinsic
factor as well in well-trained athletes who develop SND.[13]

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 withtransposition 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, 2.6-11 years earlier.[14]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 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.
Rheumatic fever is another cause of SND. Such dysfunction may also result from CNS disease, which is
usually secondary to increased intracranial pressure with 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 of 202 subjects indicated that in patients with persistent atrial fibrillation, those with
low-amplitude fibrillatory waves and a large left atrial volume index are at increased risk for the appearance
of concealed SND after catheter ablation has restored sinus rhythm. [15]

Occurrence in the United States
The exact incidence of SN dysfunction is unknown. The syndrome occurs in approximately 1 in 600 cardiac
patients older than 65 years.[16]

International occurrence
Due to its relationship with advanced age, SND is more prevalent in countries where citizens have a longer
life expectancy.

Age-related demographics
SND may develop at any age but it is primarily a disease of the elderly, with the average age of occurrence
being about 68 years.[17] SND in young patients is often related to underlying heart disease.

The incidence of sudden cardiac death in patients with SND is very low.[18]Mortality in patients with SND is
primarily determined by underlying heart disease. Pacemaker therapy does not appear to affect survival in
patients with SND[19, 20, 21] and is, therefore, used primarily for the alleviation of symptoms. Symptomatic
patients with normal systemic ventricular function and SND have an overall good prognosis with atrial (rate-
responsive) pacing.

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).

A study has shown that 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.[22]

Morbidity and mortality

The complications of SND include the following:

Sudden cardiac death (rare)

Thromboembolic events, including stroke - Especially in patients with tachy-brady syndrome
Exercise intolerance
Cardiac dysfunction due to bradycardia and loss of AV synchrony
Atrial tachyarrhythmias - Such as atrial flutter or fibrillation
Symptoms of SN dysfunction almost invariably progress over time. The most dramatic symptom in patients
with SND is syncope.

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.[18]

The treatment of symptoms is achieved with the implant of an atrial pacemaker to provide atrial rate
support. This prevents symptoms related to bradycardia from occurring. In patients with atrial
tachyarrhythmias, it is a useful adjunct to antiarrhythmic therapy.

Patient Education
Educate patients to recognize symptoms of SND. Family members should learn cardiopulmonary
resuscitation (CPR).

Because most pediatric patients with SND have already received surgery for CHD (eg, Mustard procedure,
Fontan procedure), their education is focused on recognizing symptoms of CHF and tachyarrhythmias,
such as atrial flutter/fibrillation, which are usually poorly tolerated.

Patients who are on antiarrhythmic medication for atrial flutter or fibrillation should be instructed to take
their medication regularly and to visit the cardiologist as scheduled. They should also be cognizant of the
adverse effects and toxicity of the medication.

In patents who have already received a Mustard or Fontan procedure, undergoing yearly echocardiography
to monitor cardiac function is advisable. If cardiac function is decreased, anti-CHF management should be
started and close follow-ups with the cardiologist are advisable.

Patients who have a pacemaker should be instructed on the means of obtaining regular checks. Such
checks are usually achieved from home with a transtelephonic monitor that transmits to a central
monitoring station, which, in turn, contacts the cardiologist in case a problem is detected (eg, device
malfunction, arrhythmia).

Patients who have an intracardiac defibrillator (ICD) device should receive the same instructions that
patients who have pacemakers receive. Because patients with ICDs often are placed on antiarrhythmic
medication, they also should receive instruction regarding medication schedules and information about
adverse effects and toxicity.

In addition, in patients with frequent atrial flutter or fibrillation episodes, which are followed by a shock from
the ICD, patients are instructed to avoid activities that may pose a risk to themselves and/or other people
(eg, driving). They also receive instruction on when to go to the cardiologist or the emergency department.

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

With mild sinus node dysfunction (SND), patients are usually asymptomatic. As SND progresses, patients
often develop symptoms due to pulse irregularity and organ hypoperfusion. The severity of organ
hypoperfusion symptoms depends on the severity of the SND and on the functional reserve state of an

Specific symptoms of SND include the following:

Cerebral symptoms - Irritability, labile mood swings, forgetfulness, dizziness, slurred speech,
blanking periods, falls, and syncope
Cardiac symptoms - Palpitations, angina, CHF symptoms, and sudden cardiac death (rare)
Vague gastrointestinal symptoms and oliguria
Patients with tachy-brady syndrome may have symptoms of stroke or transient ischemia attack
Exercise intolerance
Shortness of breath with or without palpitations

Infants may present with poor feeding or easy fatigability, which may also be evident in toddlers and older

Physical Examination
Patients may demonstrate an inappropriately slow heart rate. Carotid sinus massage may reveal sinus
pause of more than 3 seconds and/or hypotension symptoms in patients with carotid sinus hypersensitivity.

Patients with SND and no structural congenital heart defects may be asymptomatic in general, despite
being bradycardic for their age. Conversely, they may present with signs and symptoms of CHF, especially
those who have undergone a Mustard operation for transposition of the great arteries or a Fontan operation
for a single ventricle.

Infants with CHF secondary to SND may be tachypneic and may have signs of pulmonary congestion on
auscultation (ie, wheezing and rales), as well as hepatomegaly. In addition, they may show evidence
of failure to thrive, with weight below the fifth percentile.

Diagnostic Considerations
Because sinus node dysfunction (SND) in the pediatric population mainly affects patients who have
undergone a Mustard or intracardiac Fontan operation for CHD, failure to recognize or treat SND may lead
to CHF, as a result of bradycardia and/or atrial tachyarrhythmias. Both of these complications may cause
sudden cardiac death, resulting from cardiac arrest in the case of bradycardia or from rapid ventricular
response with development of ventricular fibrillation in the case of tachyarrhythmias.

Conditions to consider in the differential diagnosis of SND include the following:

Premature ventricular beats in bigeminy - May cause apparent slow pulse rate in the physical
Recording equipment problems - Ie, intermittent recording of monitor leads
Blocked premature atrial contractions (PACs) that are concealed in the preceding T wave
Concealed premature junctional extrasystoles
First-degree AV block in which a prolonged conduction is present from the SN through the atrial
tissue but the electrical impulse is not blocked - Usually a benign and asymptomatic condition
Vasovagal syncope

Causes of syncope in children aside from SND include the following:

Breath-holding spells
Hypoxic spells
Aortic stenosis
Cerebral and spinal cord disorders - Eg, trauma, polyneuropathies, migraine, inner ear/vestibular
dysfunction, and micturition syncope
Subclavian artery steal
Hysterical reactions

Drugs such as beta blockers and calcium channel blockers can suppress SN function, causing marked SN
bradycardia, as well as prolonged SN recovery time (SNRT) and sinoatrial conduction time (SACT).

Vasovagal syncope

Patients with SND should be differentiated from patients with normal SN and vasovagal syncope who have
an increased parasympathetic tone with periods of marked bradycardia and even asystole that lasts
several seconds. In the latter group, the high parasympathetic tone is accompanied by marked
vasodilatation with consequent hypotension, which causes the syncopal event. SACT and SNRT are
usually within the reference range, as opposed to what is observed in patients with SND.

Treatment for this condition consists of hydration and increasing the amount of salt in the diet; treatment for
refractory cases may include fludrocortisone acetate (Florinef), beta blockers, alpha agonists, or selective
serotonin reuptake inhibitors.

Differential Diagnoses
Atrial Fibrillation

Atrial Flutter

Atrioventricular Block

Approach Considerations
The current recommendation is that the diagnosis of sinus node dysfunction (SND) should rely on
noninvasive methods rather than on measuring SN recovery time (SNRT) or sinoatrial conduction time
(SACT) in the electrophysiology laboratory, because results can be normal despite the patient having
symptoms of SND or vice versa. The most reliable noninvasive methods for diagnosing SND are 24-hour
Holter monitoring (which may show 1 or more of the ECG criteria for SND) and exercise testing (which may
reveal chronotropic incompetence).

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.


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.

In addition, this study is suitable for the evaluation of ventricular function and is also useful in patients with
coexistent CHD for the assessment of associated anatomic and hemodynamic abnormalities.

Transesophageal atrial pacing

Esophageal EP study constitutes a relatively safe and inexpensive method to detect SND by determining
SN recovery time in patients who present with dizziness or syncope and palpitations.

Electrocardiographic criteria for SND include the presence of 1 or more of the following (see the images

Sinus bradycardia below the heart rate expected for age - Ie, under 100 beats per minute (bpm) in
an infant, under 80 bpm in a preschool child, under 60 bpm in a school child, and under 50 bpm in an
Sinus pause or absence of an expected P wave for more than 3 seconds - May be due to sinus
arrest (failure of the SN pacemaker cells to depolarize) or be the result of sinoatrial exit block
(depolarization of the SN but failure to conduct to the atria)
Slow escape rhythms that originate within the atria, His bundle, or ventricles
Marked sinus arrhythmia with constant variation in the P-P interval, which is likely to be
accompanied by sinus bradycardia
Presence of both bradyarrhythmias and tachyarrhythmias - Ie, SN reentry tachycardia, atrial
tachycardias from an ectopic focus, atrial flutter, and atrial fibrillation
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.
Inappropriate sinus bradycardia

The arbitrary cutoff for a low sinus rate in a person who is at rest but awake is usually defined as under 55-
60 bpm. However, a study in 500 healthy subjects suggested that the low afternoon sinus rate for men and
women should be around 46 and 51 bpm, respectively.[23] Pacemaker therapy is a class IIb indication for
patients with minimal symptoms and a chronic heart rate of less than 40 bpm while awake, according to the
2008 guidelines from the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart
Rhythm Society (HRS).[2] A focused update of these guidelines was published in 2013. [3]

Sinus pause or arrest

Sinus pause or arrest is defined as absence of sinus P waves on the electrocardiogram (ECG) for more
than 2 seconds due to a lack of sinus nodal pacemaker activity. The duration of the pauses should have no
arithmetical relationship to the baseline sinus rate (ie, the P-P interval should not be an interval of the
pause); otherwise, the diagnosis of sinoatrial exit block should be considered. Symptomatic long sinus
pauses or arrests in patients with SND often occur after the termination of atrial fibrillation or atrial flutter.

A sinus pause of 2 seconds is not unusual in a healthy person. However, a sinus pause of more than 3
seconds is very uncommon except under certain conditions, such as sleep apnea, hypervagotonia state, or
seizure activity.[24]

Sinoatrial exit block

First degree

First-degree sinoatrial (SA) exit block reflects a conduction delay between the SN and the atrium that
cannot be recognized on regular electrocardiographic recordings.

Second degree

Second-degree SA exit block reflects intermittent conduction block between the SN and the atrium. It has 2
classic types and likely some atypical types. Only the classic types can be recognized on regular
electrocardiographic recordings. They are as follows:

Type I (Wenckebach type) - Manifested as group beating, which is progressive shortening of the P-
P intervals, and then a pause that is less than twice the shortest P-P interval
Type II - Manifested as a pause that is a multiple of the baseline sinus P-P interval

Type I SA exit block occurs when prolonged conduction of the SN impulse through the atrial tissue is
present without actual block in the AV node (all QRS complexes are preceded by P waves). The P-P
intervals shorten until block occurs (ie, while the SN-to-SN interval is constant, the SNtohigh right atrium
[HRA] interval lengthens until an SN impulse is not followed by a P wave). The surface ECG shows
progressively shortening P-P intervals until the SN impulse is dropped; it also shows P-P intervals that are
less than twice the preceding (normal) P-P intervals.

Long pauses follow PACs. Sinoatrial conduction time can be directly measured with electrophysiologic (EP)
testing when PACs are present. In SND, the prolonged P-P interval is not a multiple of the sinus (normal) P-
P interval. Pauses in SND occur at the end of lengthening P-P intervals rather than at the end of shortening
P-P intervals (which is observed in type 1 SA exit block).

Third degree
Third-degree SA exit block reflects complete conduction block from the SN to the atrium. It cannot be
definitely distinguished from sinus arrest on regular electrocardiographic recordings. An atrial, junctional, or
ventricular escape rhythm is present.

Escape rhythms

Escape rhythms occur at slow rates occurs after prolonged sinus arrest. The escape rhythm may originate
in the atria, such as an ectopic right or left atrial rhythm, or it may originate from multiple foci in the atria, as
is observed in wandering atrial pacemaker (in which the P-wave axis changes on the same
electrocardiographic recording).

An escape rhythm may also originate below the atria at the His-Purkinje junction (ie, junctional escape
rhythm, with a rate of 60-80 min in infants and 50-70 min in children) or lower if originating in the ventricles
(ie, ventricular escape rhythm). The further below the atria the escape rhythm originates, the slower the

Escape rhythms, which are those that occur by default, should be distinguished from usurpation rhythms,
which are those that occur because of increased automaticity from pacemakers that fire at a faster rate
than the SN.

Chronotropic incompetence

Because the SN usually responds to autonomic nervous system input, exercise increases the heart rate in
response to increased sympathetic tone. Patients with SND usually have a blunted response. Therefore, an
exercise stress test can determine whether chronotropic incompetence is present.

Chronotropic incompetence is defined as failure to achieve 70-80% of maximal predicted heart rate
(maximal predicted heart rate = 220 - age) at peak exercise. The clinical value of this definition, however,
has not been well validated.[25] The peak exercise heart rate can be influenced by multiple factors.

Tachy-brady syndrome

Bradyarrhythmias-tachyarrhythmias occur when bradycardia and tachycardia alternate. The bradycardia

may originate in the sinus, atria, AV junction, or ventricle; the tachycardia is usually caused by atrial flutter
or fibrillation, although it can also be caused, albeit less commonly, by reentrant supraventricular
tachycardia in the SN or atrial muscle.

Holter Monitoring
Recording the ECG for 24-48 hours is useful in the assessment of SND related to the previously explained
ECG findings that may be present.

The specificity of a direct observation of spontaneous (ie, not provoked by 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

Due to their moderate sensitivity and specificity for SND diagnosis, intrinsic heart rate and atropine
stimulation tests are occasionally used as accessory tests in selected patients (such as those with
suspected hypervagotonia). The value of isoproterenol, propranolol, and adenosine stimulation tests in
SND diagnosis is more controversial.

Intrinsic heart rate

Atropine (0.04 mg/kg) and propranolol (0.2 mg/kg) have been used to pharmacologically denervate the SN,
which is then followed 5-20 minutes later by an evaluation of its intrinsic heart rate (IHR). The IHR in a
healthy person is approximately equal to 117.2 (0.53 x Age).

Intrinsic SND is presumed to be present if the sinus rate after medications is below the calculated IHR.
Patients with mild SND may have a normal or exacerbated response. This test is probably helpful in
patients with sinus bradycardia due to suspected hypervagotonia, [26] in whom the IHR is expected to be

Atropine test

Atropine alone (up to 0.04 mg/kg) may provide as much information as the combination of atropine (0.04
mg/kg) and propranolol (0.2 mg/kg).[27] Atropine (1-3 mg) is the most commonly used agent to assess the
parasympathetic tone. A normal response is an increase in the sinus rate above 90 bpm or an increase of
more than 25% above the baseline sinus rate.[25] Patients with symptomatic SND usually demonstrate a
decrease in IHR. However, patients with only mild SND may have a normal or exacerbated response to

Electrophysiologic Studies
EP studies are indicated in patients with signs of bradyarrhythmias (mainly syncope) in whom bradycardia
could not be documented during Holter monitoring. Classic EP criteria for SND include the presence of 1 or
more of the following:

Corrected SN recovery time (CSNRT) greater than 275 milliseconds

SA conduction time greater than 200 milliseconds
SA node arrest
SA exit block
SN reentry tachycardia

SN recovery time

EP studies can document SND when studying SN automaticity by directly recording electrical activity. One
EP catheter, which has 2 proximal electrodes that record the HRA electrogram and 2 distal electrodes to
pace the HRA near the SN, is positioned in the RA.

A second EP catheter, which is used to record low RA (LRA) electrical activity, is positioned across the
tricuspid valve.

Measurement of SNRT is achieved by pacing the atrium. Pacing should be performed in the 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

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 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 x 100) is more than 160%.

Sinoatrial conduction time

SACT is another parameter to use in assessing SN function. It is the time interval in milliseconds for an
impulse that originates in the SN to conduct through the perinodal tissue to the adjacent right atrial tissue.
(The tissue that surrounds the SN or perinodal tissue has characteristics that are similar to those of the AV

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 markedly prolonged SA conduction and/or increased refractory period of
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, P-wave axis and morphology are the same as those in the sinus rhythm). It is
usually indicative of SND.


Complications from a diagnostic EP study are rare but may include the following:

Hematoma at the puncture site in the groin and or neck

Infection caused by manipulation of catheters inside the heart (theoretical risk)
Perforation upon catheter manipulation inside the heart of small patients (most commonly involving
the right atrial appendage and the right ventricular (RV) outflow tract)

Approach Considerations
The only effective medical care in patients with sinus node dysfunction (SND) is correction of extrinsic

No treatment is required for asymptomatic patients, even if they have abnormal SNRTs or SACTs. If the
patient is receiving medications that can provoke sinus bradyarrhythmias (eg, beta-blockers, angiotensin-
converting enzyme [ACE] inhibitors), the medications should be stopped if possible.

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

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, CHF); if this is the case, permanent pacemaker therapy is also required.

Inpatient care

Admit patients for testing and pacemaker placement when indicated.


Patients with vasovagal syncope may require increased dietary salt intake.


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


These include cardiac electrophysiology consultation.


Transfer patients for complicated dysrhythmias and pacemaker implant.

Pacemaker Therapy
Pacemaker therapy is the only effective surgical care for patients with chronic, symptomatic SND.

Because the incidence of sudden death in patients with SND is extremely low and pacemaker therapy does
not appear to affect survival, the major goal of pacemaker therapy in patients with SND is to relieve
Pacemaker indications

According to the 2008 ACC/AHA/HRS guidelines (updated in 2013), pacemaker therapy has the following
indications[2, 3] :

Class I indication - For patients with documented symptomatic sinus bradycardia, sinus pause, and
chronotropic incompetence; this includes patients who have iatrogenic SND secondary to essential
medications for which no acceptable alternatives exist
Class IIa indication - For patients with SND and a sinus rate below 40 bpm when a clear
association between symptoms (ie, symptoms consistent with bradycardia) and bradycardia has not been
Class IIa indication - For patients with syncope of unexplained origin when clinically significant
abnormalities of SN are discovered or provoked in EP studies
Class IIb indication - For patients with minimal symptoms and a chronic heart rate of less than 40
bpm while awake
Class III indication - Pacemaker therapy is contraindicated in patients with asymptomatic SND or
symptomatic bradycardia due to medications that are not essential.

In 2013, the European Society of Cardiology (ESC) published clinical practice guidelines on cardiac pacing
and cardiac resynchronization therapy.[28]

Single- versus dual-chamber pacemakers

In patients with SND, the annual incidence of complete heart block is about 0.6%. [29] 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 (AAIR) required upgrade to a dual-chamber pacemaker (DDDR) over 5.4
years follow-up due to new development of significant AV conduction abnormalities. This was necessary
despite the fact that these patients had no significant intraventricular conduction abnormality, PR intervals
below 260ms, and no Wenckebach AV block with atrial pacing at 100 bpm at baseline. [30]

In addition, patients in AAIR mode had more atrial fibrillation than did patients in DDDR mode. Importantly,
however, no significant mortality difference between AAIR and DDDR mode was noted.

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).

Pacemaker programming features

Chronic right ventricular pacing has been shown to be associated with an increased incidence of atrial
fibrillation, stroke, heart failure, and probably death.[18, 31, 32] A study suggested that RV pacing is detrimental
to left ventricular (LV) function even in patients with a normal LV ejection fraction (LVEF). [33] 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). [30] Theoretically,
a very long PR interval may result in pacemaker syndrome during sinus tachycardia or fast atrial pacing

In the DANPACE trial, about 65% of patients with a moderate AV delay setting in DDDR mode with mean
RV pacing had less atrial fibrillation and no increased rate of heart failure, as compared with patients in
AAIR mode. Clearly, the optimal AV delay settings in patients with SND are still 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 fibrillation events. Because more than 50%
of patients with SND may over time develop tachy-brady syndrome, [18] it is very important to identify these
patients through pacemaker monitoring and anticoagulate them to reduce their risk of stroke. However, the
most appropriate anticoagulant therapy is still uncertain for patients in whom atrial fibrillation is detected
only as an incidental finding on pacemaker or ICD diagnostics.

Pacemakers with a rate drop response program may benefit some patients with neurocardiogenic syncope.
Studies have suggested that closed-loop stimulation technique in the Biotronik pacemaker may be quite
helpful in reducing syncope in patients with neurocardiogenic syncope. [34, 35]

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. [36]

Long-Term Monitoring
Asymptomatic patients with 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, such as pacemaker-mediated tachycardia
Ensure minimal RV pacing.
Monitor for atrial fibrillation and atrial flutter events

Medication Summary
Currently, no medications are routinely used to treat symptomatic sinus node dysfunction (SND). However,
acute treatment with the anticholinergic agent atropine and/or the adrenergic agonist isoproterenol may be
warranted. Pharmacotherapy may also be used as an adjunct to implanted pacing devices.

Patients with tachyarrhythmias may require treatment with antiarrhythmic agents, such as digoxin,
quinidine, or propranolol. In addition, individuals with increased parasympathetic tone may experience
vasovagal syncope, requiring pharmacologic intervention.

Anticholinergic Agents
Class Summary
Atropine depresses the vagus, thereby increasing the heart rate. This agent is used in various disorders or
circumstances in which bradyarrhythmias occur and is frequently used in sudden-onset bradyarrhythmias.
Although it may also be used for the initial treatment of chronic arrhythmias, cardiac pacing is preferred for
long-term control.

View full drug information

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.

View full drug information

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

Cardiovascular, Other
Class Summary
These agents alter the EP mechanisms responsible for arrhythmia. In SND, they may be used when
tachyarrhythmias occur. Patients must be carefully monitored to ascertain if bradyarrhythmia is

View full drug information

Digoxin (Lanoxin)
Digoxin is a cardiac glycoside with direct inotropic effects, as well as indirect effects, on the cardiovascular
system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Digoxin's indirect
actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given
increase in mean arterial pressure.

View full drug information

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.

View full drug information

Propranolol (Inderal LA, InnoPran XL)
Propranolol is a class II antiarrhythmic, nonselective beta-adrenergic receptor blocker; it has membrane-
stabilizing activity that decreases the automaticity of contractions.

Class Summary
These agents are used to treat syncopal episodes caused by fluid or electrolyte imbalances. They restore
fluid and electrolyte balance by enhancing sodium reabsorption in the kidney, which results in expanded
extracellular fluid volume. Mineralocorticoids also increase renal excretion of potassium and hydrogen ions.

View full drug information

Fludrocortisone is a potent mineralocorticoid that is used to raise standing blood pressure. It acts to
increase sodium retention and expand plasma volume.