AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The term sick sinus syndrome first appeared in the literature in 1967 to describe a rapid atrial rhythm interspersed with varying periods of bradycardia that followed cardioversion. Today, the term is applied to a broad range of electrophysiological abnormalities, including inappropriate sinus bradycardia, sinus arrest, sinus node exit block, chronic atrial fibrillation, and bradycardia-tachycardia syndrome. Although the term remains popular, the more comprehensive title sinus nodal dysfunction (SND) is gaining favor.

The disease commonly is observed in older patients with a history of concomitant heart disease. Its natural history is largely unknown, but it frequently runs an erratic and progressively malignant course. For this reason, cardiac pacing has become the cornerstone of therapy for symptomatic patients.

Pathophysiology

SND is characterized by delayed or failed conduction between the sinus node and the atria, either due to inadequate sinus node pacemaking or because of intrinsic or extrinsic conduction disturbance. If the degree of dysfunction is minimal, the patient usually is asymptomatic. Advanced SND is unpredictably malignant, however, and it often is characterized by significant cardiovascular impairment. Clinical manifestations are due to hypoperfusion of the vital organs, specifically the brain and heart, usually as a result of an inadequate ventricular rate. Patients commonly present with complaints related to cerebral or cardiac dysfunction.

Frequency

United States

The exact incidence rate of SND is unknown because it never has been evaluated adequately in asymptomatic patients. One study estimates the incidence to be about 3 cases in 5000 patients older than 50 years.

International

SND is more prevalent in countries where citizens have a longer life expectancy, indicating that the disease is more common in elderly people.

Mortality/Morbidity

Duration from the onset of symptoms to death is not well defined. Untreated patients may live a couple of weeks to more than 10 years. SND almost always is progressive, and patients usually become increasingly symptomatic if they remain untreated. Survival appears to depend primarily on the severity of the underlying cardiac disease. Thromboembolic complications are a frequent cause of morbidity and mortality. Chronic atrial fibrillation and tachycardia-bradycardia syndrome are the variants with the most significant stroke risk. Sudden cardiac death is possible at any point during the disease

Race

No racial preponderance exists.

Sex

Men and women are affected in equal numbers.

Age

• SND tends to be a disease of elderly people, with a peak incidence in the sixth and seventh decades of life.
• The disease may be observed in any age group, including adolescents and children.
• Pediatric patients are most susceptible during the postoperative period of major cardiac surgery, especially transposition of the great vessels.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Because SND is a heterogenous condition, its clinical manifestations may vary widely. In the early stages of SND, most patients are asymptomatic. As the disease advances, however, patients often seek medical attention for bradycardia-related symptoms. Syncope, near-syncope, and dizziness are the most frequently reported complaints, followed by palpitations, angina, or shortness of breath. Because these symptoms are relatively nonspecific, a high index of suspicion is necessary to make the correct diagnosis.

• Cerebral symptoms
• • Patients with mild symptoms present with vague complaints of fatigue, irritability, labile mood swings, or forgetfulness.
  • As the disease progresses and blood flow is further compromised, the cerebral manifestations become more profound. They can include lightheadedness, slurred speech, near-syncope, and, finally, syncope. Syncope almost always implies marked bradycardia. It is believed to occur in most patients with SND.
• Cardiac symptoms
• • Early in the course of the disease, patients may note an abnormally slow or irregular pulse.
  • As the disease progresses, the 3 most common cardiac manifestations are palpitations, angina, and shortness of breath, which is due to congestive heart failure (CHF).
  • Palpitations may be attributed to runs of supraventricular tachycardia (SVT) or to a mixture of tachycardia and bradycardia.
  • Angina and CHF symptoms usually are due to cardiac hypoperfusion. Cases of flash pulmonary edema have been reported.
  • In late stages, the incidence of ventricular tachycardia or fibrillation increases, thereby augmenting the risk for sudden cardiac death.
• Other symptoms
• • Other symptoms include hypoperfusion of the kidney with resultant oliguria.
  • Some patients have a history of vague gastrointestinal complaints, probably also related to inadequate oxygenation.

Physical

Certain physical findings are suggestive, but the results of the physical examination alone never are diagnostic. The most persistent finding is long periods of bradycardia, appearing in as many as 75% of patients. Any person with unexplained, marked bradycardia probably requires further workup. Occasionally, arrhythmia may be detected with careful assessment of the pulse. Several basic maneuvers can help establish the diagnosis.

• Valsalva maneuver
• • In a healthy individual, the Valsalva maneuver will increase heart rate.
  • A patient with SND, however, usually will not respond appropriately (heart rate will not change).
• Carotid sinus massage: Carotid sinus massage may be helpful. If carotid massage provokes a sinus pause of longer than 3 seconds, SND must be considered carefully.

Causes

Although the exact etiology usually is not identified, most cases are believed to be attributable to a combination of intrinsic and extrinsic influences. The most common intrinsic causes are idiopathic degenerative disease and coronary artery disease. The most common extrinsic causes are medications and autonomic hyperactivity. Remember that SND is always an acquired condition.

• Intrinsic sinus nodal dysfunction
• • Idiopathic degenerative disease is the most common intrinsic cause. With aging, the myocardium surrounding the sinus node gradually becomes replaced by fibrous stroma. As this fibrosis progresses, automaticity and sinoatrial conduction can become impaired. In a patient with SND, fibrosis of the sinus node is virtually complete. Why certain patients with diffuse fibrosis develop SND while others do not remains unclear.
  • Coronary artery disease may cause SND either by chronic hypoperfusion or as a complication of an acute ischemic event. An acute inferior or lateral myocardial infarction sometimes is complicated by significant bradycardia or sinus arrest; these arrhythmias are due to local neural effects and usually are transient. Temporary SND has been reported in 5-10% of acute myocardial infarctions.
  • The following also may cause intrinsic SND:
  • • Infiltrative diseases (amyloid, hemochromatosis, neoplasms)
    • Cardiomyopathy
    • Hypertension
    • Collagen vascular diseases (systemic lupus erythematosus [SLE], scleroderma)
    • Congenital heart disease
    • Surgical trauma/heart transplant
    • Musculoskeletal disorders (myotonic dystrophy, Friedreich ataxia)
    • Myocarditis/pericarditis
• Extrinsic sinus nodal dysfunction
• • Medications that depress sinus nodal function often are implicated as the cause of SND. Common offending agents include the following:
  • • Beta-blockers
    • Nondihydropyridine calcium channel blockers (diltiazem, verapamil)
    • Cardiac glycosides (digoxin)
    • Sympatholytic antihypertensives (clonidine, methyldopa, and reserpine)
    • Membrane-active antiarrhythmics (amiodarone, sotalol, bretylium)
    • Less commonly, phenytoin, amitriptyline, lithium, and phenothiazine
  • Autonomic dysfunction may be caused by vagal stimulation slowing the sinus rate and lengthening the refractory period of the sinus node. Conditions associated with marked hypervagotonia can result in SND. Symptomatic bradycardias secondary to excess vagal tone have been observed in well-trained athletes. Vasovagal syncope, specifically in elderly people, can present with SND. Finally, carotid sinus syndrome has been associated with increased vagal tone that infrequently leads to symptomatic bradyarrhythmias.
  • The following also can cause extrinsic SND: electrolyte imbalance (eg, hypokalemia or hypocarbia), hypothyroidism or hyperthyroidism, hypothermia, and sepsis.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Laboratory blood tests rarely are helpful in the workup of SND.
• Because hypokalemia, hyponatremia, and hypocarbia sometimes can aggravate underlying susceptibility for SND, a renal panel should be ordered routinely.
• Thyroid dysfunction also has been reported to cause SND, so ordering a thyroid screening test should be considered in appropriate patients.

Imaging Studies

• No specific imaging studies are required in the initial workup of SND.
• An echocardiogram should be considered because it can document the presence of underlying valvular or ischemic heart disease.

Other Tests

• Electrocardiogram: The best diagnostic test for SND is electrocardiographic documentation during a symptomatic episode. Therefore, a 12-lead ECG should be obtained in any patient presenting with symptoms suggestive of SND. The ECG rarely is helpful in milder cases, but it can be diagnostic in more severe disease. SND may manifest as any of the following:
• • Inappropriate sinus bradycardia: Refractory sinus bradycardia, defined as bradycardia that does not increase with exertion, usually is the earliest manifestation of SND. Therefore, the diagnosis should be considered strongly in any patient with unexplained chronic bradycardia.
  • Sinus arrest/sinus pause: A sinus arrest will occur whenever the sinus node becomes so diseased that it ceases to fire impulses appropriately. A pause greater than 3 seconds is strongly suggestive for SND. A well-trained athlete occasionally can produce a pause greater than 2 seconds, but a 3-second pause is very unusual in a healthy individual.
  • Sinoatrial exit block: Sinoatrial exit block occurs whenever a conduction barrier within the sinoatrial node blocks exiting impulses directed to the atria. Because the atria are not depolarized, the asystolic pause will not be terminated by a P wave, but instead by a sinus beat. A way to distinguish sinoatrial block from sinus arrest is to examine the period of asystole. The pause that occurs in sinoatrial block typically is an exact multiple of the preceding P-P interval, whereas the pause observed in sinus arrest usually is not.
  • Chronic atrial fibrillation: Chronic atrial fibrillation with slow ventricular response often implies SND. Attempts at cardioversion typically produce a long sinus pause, followed by a slow unstable rhythm.
  • Tachycardia-bradycardia syndrome: This syndrome affects about 50% of the patients with SND. The term refers to alternating periods of sinus bradycardia and SVT. A long pause often follows spontaneous termination of the tachycardia. During this pause, patients frequently experience lightheadedness or syncope.
• Holter monitoring: A 24- to 48-hour Holter monitor may be useful in patients who report frequent symptoms. Most often, its true benefit is to exclude SND as the cause of symptoms. If only normal sinus rhythm is documented, SND is unlikely to be the diagnosis.
• Event recorder: A loop monitor is a helpful tool for those patients with infrequent complaints. It can be triggered to record an ECG with the onset of symptoms. This test requires a certain degree of patient compliance; they must tolerate carrying the device, and they must remember to turn on the recorder at the appropriate moment.
• Electrophysiological study
• • Although electrophysiological studies are performed frequently on patients with suspected SND, their usefulness remains controversial.
  • Most commonly, the test is used to measure sinus nodal recovery time via overdrive suppression of the sinus node. Patients are diagnosed with SND if they have a longer sinus node recovery time than healthy individuals. The primary criticism of the test is that the laboratory method usually employed yields an indirect measurement of sinus nodal recovery time. Even under the best circumstances, the sensitivity of this test for SND is only about 70%.
  • The second commonly used electrophysiological test measures sinoatrial conduction time using premature atrial stimuli. Once again, the results often are not conclusive because the measurements are obtained indirectly. Because of these limitations, most experts agree that an invasive electrophysiological study should be reserved only for those patients who have a history consistent with SND but who have failed to have the disease documented via noninvasive means.
• Exercise testing: Exercise testing has limited value in the diagnosis of SND. It can be helpful in differentiating patients with resting sinus bradycardia with normal exercise response from those patients with chronotropic incompetence.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Once the diagnosis of SND has been established, the treatment plan should be individualized to address the specific arrhythmias and symptoms of each patient.

• Asymptomatic SND requires no treatment. Individuals with asymptomatic bradycardia or sinus pauses simply can be observed.
• Medications that depress the sinus node should be discontinued whenever possible in patients with symptomatic bradycardia.
• Patients with chronic atrial fibrillation have a significant risk for thromboembolic complications. They should undergo prophylactic anticoagulation with warfarin. If strong contraindications exist for the use of warfarin or if a patient has lone atrial fibrillation, then an aspirin a day will suffice.
• Tachycardia-bradycardia syndrome usually needs a treatment plan for both components. The tachycardia typically is treated with medications that control ventricular rate. Unfortunately, these drugs may exacerbate bradycardia by further depressing sinus nodal function. In these instances, pacemaker insertion is indicated to prevent the recurrence of symptoms related to bradycardia or sinus arrest.

Surgical Care

Pacemaker placement is the cornerstone of treatment for symptomatic SND. Various studies estimate that 25-50% of all pacemaker implantations in Western countries are performed for some form of SND.

• Most often, pacing is recommended only for those patients who experience symptomatic bradycardia. According to recent American College of Cardiology guidelines, a pacemaker is not indicated for individuals with asymptomatic bradycardia or sinus pauses.
• Mounting evidence suggests that atrial-based pacing is the preferred pacing mode for SND in the absence of atrioventricular conduction disease. Although dual-chamber and ventricular-based pacing are used more commonly, several recent retrospective studies suggest that single-chamber atrial pacing incurs a lower risk of atrial fibrillation, thromboembolic events, CHF, and mortality. In one trial, these benefits were maintained over an 8-year follow-up period. A frequent criticism of atrial pacing has been the possibility that a pacemaker revision might become necessary if atrioventricular block develops later in the course of the disease. Any such risk is minimal, however, and does not warrant routine dual-chamber pacemaker placement, especially when cost is factored into the equation.
• Ventricular pacing remains an appropriate choice for chronic atrial fibrillation with slow ventricular response.
• Dual-chamber pacing theoretically provides hemodynamic advantages by synchronizing atrial and ventricular contraction. Consistent atrial contribution could improve stroke volume, raise systolic blood pressure, and reduce right atrial and pulmonary-capillary wedge pressure. Randomized controlled trials comparing single-chamber versus dual-chamber (physiological) pacing modes in patients with SND have noted an improvement in quality of life, and a reduction in risk of atrial fibrillation and symptomatic heart failure for those patients randomized to dual-chamber pacing therapy. However, no significant difference in total mortality, mortality from cardiovascular causes, or stroke has been observed.
  
  Further, the widespread use of physiological pacemakers is not an economically attractive strategy. Atrial based ("AAI") pacing has been used more in Europe with good success and with probable long-term benefits versus ventricular-based ("VVI") pacing. This may not be as acceptable in the United States as there is no back-up ventricular pacing should AV block occur. Compared with ventricular pacing, atrial pacing is associated with a lower incidence of thromboembolic complications, atrial fibrillation, heart failure, cardiovascular mortality, and total morbidity.
• Dual-chamber pacing is clearly the preferred method of pacing when comparisons of different pacing modes within individual patients have been obtained. One randomized crossover study studied the effects of different pacing modes on symptoms, functional class, and perceived health status. Dual-chamber pacing was the preferred mode for 86% of patients. Only 5% chose single-chamber ventricular pacing, while 9% had no preference. Many electrophysiologists preferentially place dual-chamber devices due to perceived improvement in quality of life.
• Indications for permanent pacemaker implantation in sinus node dysfunction

  Class I - Represents conditions for which evidence and/or general agreement exist that a given procedure or treatment is beneficial, useful, and effective

  • SND with documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms (In some patients, bradycardia is iatrogenic and occurs as a consequence of essential long-term drug therapy of a type and dosage for which no acceptable alternatives are available.)
  • Symptomatic chronotropic incompetence

  Class IIa - Represents conditions for which conflicting evidence and/or a divergence of opinion exist about the usefulness and efficacy of a procedure or treatment

  • SND occurring spontaneously or as a result of necessary drug therapy; heart rate less than 40 beats per minute and a clear association between significant symptoms consistent with bradycardia and the actual presence of bradycardia has not been documented

  Class IIb - Represents conditions in which the usefulness and efficacy is less well established by evidence and opinion

  • Chronic heart rate in minimally symptomatic patients is less than 30 beats per minute while awake

  Class III - Represents conditions for which evidence and/or general agreement exist that a procedure or treatment is not useful or effective and in some cases may be harmful

• • SND in asymptomatic patients, including those in whom substantial sinus bradycardia (heart rate less than 40 beats per minute) is a consequence of long-term drug treatment
  • SND in patients with symptoms suggestive of bradycardia that are clearly documented as not associated with a slow heart rate
  • SND with symptomatic bradycardia caused by nonessential drug therapy

Consultations

• Cardiology consultation
• Cardiothoracic surgery consultation

Diet

No specific dietary recommendations exist.

Activity

Patients diagnosed with SND should titrate their level of exertion to minimize symptoms.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

As discussed above, pacemakers are the primary treatment modality for patients with symptomatic SND and usually obviate the need for drug therapy. Individuals who experience SVT or chronic atrial fibrillation as a component of their disease frequently need medicines for ventricular rate control. Those drugs are discussed in detail in Atrial Fibrillation. Chronic atrial fibrillation is an indication for anticoagulation with warfarin (unless no coexistent heart or lung disease is present). Finally, one study has demonstrated that oral theophylline reduces the recurrence of heart failure by enhancing sinus node automaticity and atrioventricular conduction.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients for testing and pacemaker placement when indicated.

Further Outpatient Care

• Monitor medications and potential side effects.
• Those patients on warfarin will need regularly scheduled blood draws to monitor the international normalized ratio (INR).
• Routine pacemaker interrogations are necessary.

Transfer

• Transfer patients for complicated dysrhythmias or pacemaker placement.

Deterrence/Prevention

• Limit activity to minimize symptoms.

Complications

• Thromboembolic events (stroke)
• Angina
• Congestive heart failure
• Arrhythmia
• Sudden cardiac death
• Syncope

Prognosis

• The prognosis is uncertain. Mortality usually is not related to SND directly but rather to associated conditions such as CHF, thromboembolic events, and myocardial ischemia.
• The most important prognostic indicators are age, the type of arrhythmia, and the severity of concomitant heart disease.
• Patients whose SND manifests as sinus bradycardia have a better prognosis than those with chronic atrial fibrillation or tachycardia-bradycardia syndrome.

Patient Education

• Family members should learn cardiopulmonary resuscitation (CPR).
• Pacemaker education is necessary.
• Educate patients to recognize symptoms.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize SND as a cause of symptoms related to cardiac or cerebral dysfunction
• Inappropriate pacemaker implantation

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Aggarwal RK, Ray SG, Connelly DT, et al. Trends in pacemaker mode prescription 1984-1994: a single centre study of 3710 patients. Heart. May 1996;75(5):518-21. [Medline].
• Alboni P, Menozzi C, Brignole M, et al. Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial. Circulation. Jul 1 1997;96(1):260-6. [Medline].
• Andersen HR, Thuesen L, Bagger JP, et al. Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet. Dec 3 1994;344(8936):1523-8. [Medline].
• Andersen HR, Nielsen JC, Thomsen PE, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet. Oct 25 1997;350(9086):1210-6. [Medline].
• Andersen HR, Nielsen JC, Thomsen PE, et al. Arterial thromboembolism in patients with sick sinus syndrome: prediction from pacing mode, atrial fibrillation, and echocardiographic findings. Heart. Apr 1999;81(4):412-8. [Medline].
• Bernstein SB, Van Natta BE, Ellestad MH. Experiences with atrial pacing. Am J Cardiol. Jan 1 1988;61(1):113-6. [Medline].
• Gregoratos G, Abrams J, Epstein AE. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee t. J Cardiovasc Electrophysiol. Nov 2002;13(11):1183-99.
• Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. Jun 13 2002;346(24):1854-62.
• Lamas GA, Orav EJ, Stambler BS, et al. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators. N Engl J Med. Apr 16 1998;338(16):1097-104. [Medline].
• Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J. Jul 1967;29(4):469-89. [Medline].
• Menozzi C, Brignole M, Alboni P, et al. The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome. Am J Cardiol. Nov 15 1998;82(10):1205-9. [Medline].
• Ozcan C, Jahangir A, Friedman PA, et al. Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation. N Engl J Med. Apr 5 2001;344(14):1043-51.
• Topol EJ. Textbook of Cardiovascular Medicine. Philadelphia, Pa:. Lippincott Williams & Wilkins;1998:1637-45.
• Zipes D. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, Pa:. W.B. Saunders;1995:1215-40.

Article Last Updated: Jun 27, 2006