Congenital heart disease and familial disorders of sinus node function can occur in younger individuals including the newborn.3 Typically, corrective surgical procedures, such as the Mustard procedure performed for transposition of the great vessels and closure of atrial septal defects, contribute to SND.7,8 A genetic component also appears to play a role in the development of SND in children and young adults3,12 as does an autoimmune mechanism.13
Numerous factors can affect sinus node function without causing structural disturbances including medications, autonomic nervous system influences, and metabolic disturbances. Cardioactive drugs may initiate/aggravate sinus bradycardia or chronotropic incompetence.4 The medications most likely to affect sinus node function are beta-adrenergic blockers, calcium channel blockers, antiarrhythmic drugs (specifically Class IA, IC, and III), and cardiac glycosides.8,11 (See Classification of antiarrhythmic drugs.) Psychotropic medications may also contribute to sinus node depression.4,14
Influences from the autonomic nervous system can affect normal sinus node function. Parasympathetic stimulation slows the sinus discharge rate and increases the intranodal conduction time, resulting in sinus node exit block at times.4 Individuals with conditions such as vasovagal syncope and carotid sinus hypersensitivity frequently have associated bradycardia.4,8 Heightened vagal tone from excessive physical training may result in syncope related to bradycardia or atrioventricular (AV) conduction abnormalities in otherwise healthy individuals.7
Hyperthyroidism and hypothyroidism produce changes in the cardiovascular system. Thyroid hormone affects the action potential duration and repolarization currents in the cardiac myocytes, resulting in changes in HR and development of dysrhythmias;15 in hypothyroidism, this produces bradycardia. Electrolyte imbalances (particularly hyperkalemia) can result in bradycardia, sinus arrest, and SA exit block as well as AV block.5
The pathophysiologic mechanisms for SND include failure of impulse generation and failure of the impulse to spread throughout the atria.3 In addition, there may be failure of secondary pacemaker activity (AV junction and Bundle of His) manifested as failed escape rhythms and increased atrial vulnerability to fibrillation and other tachydysrhythmias.8 Atrial fibrillation results in sinus node remodeling on a cellular and molecular basis that may promote SND.16
The clinical manifestations of SND reflect the rhythm disturbances previously described. They are also related to a reduction in cerebral or peripheral perfusion and abrupt changes in HR. Symptoms are diverse and range from the following: nonspecific complaints of fatigue, palpitations, irritability, lassitude, lack of concentration, forgetfulness to the more dramatic symptoms of syncope, recurrent dizziness, and heart failure.14,17 In some cases, stroke may be the first indication of SND in patients with paroxysmal atrial fibrillation and thromboembolism.4 Furthermore, unrecognized SND may manifest as a perioperative complication that can cause various dysrhythmias—even cardiac arrest.18
Syncope in patients with SND is believed to be associated with dysrhythmias producing long periods of bradycardia (sinus pauses and SA block) occurring spontaneously or after termination of a tachydysrhythmia, resulting in inadequate cerebral blood flow.2,8 Sinus bradycardia, even if severe, is rarely a cause of syncope; however, presyncopal symptoms such as lightheadedness, dizziness, and other nonspecific complaints may be observed.8 The degree of bradycardia that may produce symptoms will vary based on the individual's physiologic condition, age, and functional ability.14
In some patients, the clinical manifestations may be more subtle and correspond to an inadequate HR response to daily activities. Most patients with chronotropic incompetence will exhibit symptoms of fatigue or shortness of breath with exertion.14 A number of these complaints (especially fatigue, dizziness, and lightheadedness) are relatively common in many patients (older adults) who represent a large proportion of the SND population.8
Abnormalities related to impulse formation within the sinus node and conduction through surrounding atrial tissue produce a variety of electrocardiographic manifestations. These include persistent sinus bradycardia, sinus arrest, sinoatrial exit block, chronotropic incompetence, and atrial or junctional tachydysrhythmias alternating between periods of bradycardia and asystole.14
Persistent sinus bradycardia is the most frequent ECG manifestation in SND.17 This sinus bradycardia is persistent (not caused by drugs) and is inappropriate for the physiologic circumstances.7 In chronotropic incompetence, the sinus rate does not adequately increase in response to physical stress or exertion.10 Chronotropic incompetence is present in 20% to 60% of individuals with SND.4 In SA block, the SA node discharges at regular intervals, but some impulses are blocked from reaching the atria, and it is recognized by the dropping of sinus beats in a regular pattern. Sinus arrest is due to a failure of impulse formation in the sinus node itself. Sinus arrest is distinguished from SA block by the absence of sinus P waves that occur without any discernible pattern.14 Bradycardia–tachycardia syndrome manifests as alternating periods of sinus bradycardia and tachycardia—most commonly atrial fibrillation or flutter.7,14 Conversion from the tachycardia may be manifested by bradycardia or periods of sinus arrest,11 which is referred to as postconversion pause or asystole.
More than one of these ECG manifestations may be recorded in the same individual at different times and may be associated with abnormal AV conduction as well.7 This can be represented by atrial fibrillation—a common expression of SND—accompanied by a slow ventricular response in the absence of medication that depress AV conduction.14
If the patient presents with typical symptoms, and the ECG findings are straightforward, the diagnosis may be simple. In many cases, however, the diagnosis of SND can be difficult. Many of the symptoms are nonspecific and are present in other disorders, especially among older adults; symptoms may be variable and intermittent. If the patient is asymptomatic at the time of evaluation, no ECG manifestations may be apparent. The history surrounding symptoms warrants a thorough investigation. Physical exam may reveal concomitant medical problems, evidence of structural heart disease, or extrinsic causes of SND. Carotid sinus massage (CSM), which is usually performed during autonomic testing with continuous ECG and BP monitoring, may reveal sinus pause of more than 3 seconds and/or hypotension in patients with carotid sinus hypersensitivity. Making the diagnosis of SND requires correlation of the symptoms with bradydysrhythmias,14 which may be accomplished through ambulatory ECG monitoring. The ambulatory electrocardiography device is a continuous ECG recorder that records and stores data on two to three channels for 24- or 48-hour periods.19 During monitoring, the patient maintains a diary of activities and symptoms, marking the events by pressing a button, so they can be correlated with ECG changes.20 When symptoms are transient or infrequent, the brief snapshot of ECG activity (provided by the ambulatory electrocardiography device) is often inadequate in documenting an ECG-related cause, making long-term monitoring necessary.
Intermittent patient or event-activated recorders (also referred to as event monitors) allow for extended monitoring. Event monitors are typically worn for 30 days, and devices vary from those that save data only when activated by the patient to those with automatic triggers that transmit data transtelephonically to a central monitoring station for analysis.20 These devices are highly effective in documenting infrequent events, although the quality of recording is not as consistent as that of the ambulatory electrocardiography device.19 This type of event monitoring requires more effort on the part of the patient and some technical skill to transmit the data.
Real-time continuous monitoring systems automatically record and transmit event data from ambulatory patients to an attended monitoring station. Data can also be recorded through patient-triggered activation;20 this type of device may be useful for patients unable to manage the technical requirements of the standard type of event monitor.
For patients with infrequent syncopal or presyncopal events suspicious for a dysrhythmic origin, an implantable loop recorder may be indicated.20 The small, leadless device is implanted under the skin at about the second rib on the left front of the chest.19 The device can be triggered by the patient when they place a special magnet over it or automatically, saving the data for retrieval at a later time.20
Invasive electrophysiologic testing
When noninvasive methods fail to provide an explanation for symptoms like syncope or presyncope that are suggestive of bradycardia or asystole, invasive electrophysiologic (EP) testing should be considered.19 Sinus node recovery time (SNRT) and SACT are two tests that may be used as adjuncts in the evaluation of sinus node function.21 SNRT is a measure of sinus node automaticity4 and is the time required for sinus rhythm to resume once multiple stimuli of overdrive atrial pacing is terminated.10 Since the spontaneous sinus rate influences the SNRT, a corrected sinus node recovery time (CSNRT) is calculated by subtracting the sinus node cycle length from the SNRT value;21 a prolonged CSNRT has been found in patients suspected of having SND.19 SACT is the time from sinus activation to local atrial activation in the region surrounding the sinus node.21
The primary limitations of EP assessment in SND are the low sensitivity of the tests and the variable clinical significance of the abnormalities revealed.6 The sensitivity of the SNRT and SACT are about 50% alone and approximately 65% combined.6,19 The combined specificity is better at approximately 88%.19
If abnormalities are found, EP testing may support the diagnosis of SND but cannot be used to exclude sinus node disease in view of the limited sensitivity.6 The EP study may also offer insight into other dysrhythmias (supraventricular or ventricular tachycardia) that may be responsible for the symptoms.
Patients with sinus bradycardia and syncope (but no other symptoms attributable to SND) should undergo autonomic testing such as carotid massage and tilt table testing, as well as EP testing, to uncover the mechanism of syncope.17
Exercise stress testing
Patients with symptoms such as fatigue, shortness of breath with exercise, or daily activities may have chronotropic incompetence. This is defined as the inability of the sinus node to achieve at least 80% of the age-predicted HR.4 Exercise testing may be useful in determining the response of the sinus node to physiologic demands. If there is little or no increase in HR with exercise, the diagnosis of chronotropic incompetence is evident.14 In other cases, the diagnosis is not so clear. Definitions of chronotropic incompetence rely on the HR response to maximal exercise.22 Failure to achieve 80% of the maximum predicted HR (220 minus age) at peak exercise is considered evidence of a blunted HR response.2 However, many patients are unable to perform significant exercise on the treadmill—especially older adults. The Chronotropic Assessment Exercise Protocol (CAEP) is an easily performed treadmill test that utilizes gradual increases in both elevation and speed, allowing assessment of chronotropic response during submaximal exercise.22,23
Treatment of SND is directed toward alleviating symptoms, and management should begin with a search for reversible causes of sinus node depression; this includes consideration of medications, autonomic dysfunction, and ischemia. Antiarrhythmic agents (including beta-adrenergic blockers and calcium channel blockers) and other medications can suppress sinus node function.14 Whenever possible, an alternative medication that may be equally effective without slowing the HR should be selected. Although theophylline and beta-adrenergic agonists may still be used in isolated cases to treat symptomatic bradycardia, they do not prevent syncope4 and are not commonly employed in the treatment of SND.
Indications for pacemaker implantation
The only effective treatment for symptomatic bradycardia is permanent cardiac pacing.2 According to the most recent American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) device guidelines (see Recommendations for permanent pacing in SND), the Class I indications for permanent pacemaker implantation in SND include documented symptomatic bradycardia, symptomatic chronotropic incompetence, and symptomatic bradycardia that result from required drug therapy for medical conditions.2 Pacemaker placement is reasonable (Class IIa indication) for SND in individuals with an HR less than 40 bpm when a clear association between significant symptoms are consistent with bradycardia, but the actual presence of bradycardia has not been documented. Pacemaker placement is also reasonable for syncope of unexplained origin when clinically significant abnormalities of sinus node function are discovered or provoked during EP studies.2 Implantation may be considered in minimally symptomatic patients with chronic HR less than 40 bpm while awake (Class IIb indication).2 Permanent pacemaker implantation is not indicated for SND in asymptomatic patients, for those whom the symptoms suggestive of bradycardia have been clearly documented to occur in the absence of bradycardia, and when symptomatic bradycardia is due to nonessential drug therapy (Class III indication).2
Single vs. dual-chamber pacing
Cardiac pacemaker therapy has been found to be highly effective in SND when bradydysrhythmias account for the symptoms.8 Current practice has moved away from the use of single-chamber ventricular pacing (VVI and VVIR) in patients with SND unless permanent atrial fibrillation or other atrial disease prohibits the use of atrial pacing modes.8 In SND, dual chamber (AV pacing) (see Dual-chamber pacing leads) has been found to reduce the risk of atrial fibrillation, reduce signs and symptoms of heart failure, and slightly improve the quality of life compared to single-chamber ventricular pacing.24
Dual-chamber pacing is able to maintain AV synchrony, prevent syncope during AV block, and slightly reduce the risk of atrial fibrillation. However, it may result in a high percentage of right ventricular (RV) pacing, which causes ventricular dysynchrony and is linked to increased risk of atrial fibrillation in patients with sinus node disease.25 Pacing in the RV changes electrical activation and contraction of the ventricles resulting in ventricular remodeling, decreased LV EF, and left atrial dilatation.26 Ventricular dysynchrony caused by ventricular pacing (even when AV synchrony is preserved) has been found to increase the risk of heart failure and atrial fibrillation in patients with SND.27
Pacing the RV from sites such as the Bundle of His, para Hisian tissues, right ventricular outflow tract (RVOT), and the RV septum has been explored in an effort to find a more physiologic alternative to apical pacing.23,28 The sites most studied are the RVOT and septum, and to date, the results have failed to substantiate the perceived theoretical advantage.28,29 Since lead placement in the RV apex remains the standard, various pacing strategies are employed to reduce the percentage of RV pacing.
Pacing modalities in SND
Efforts to reduce frequent and unnecessary RV apical pacing may be accomplished through various pacing strategies. Most patients with SND have intrinsic AV and normal intraventricular conduction.30 Single-lead atrial pacing (AAIR) (see The pacemaker code) has been evaluated as an option to reduce unnecessary RV pacing. AAIR pacing requires intact conduction through the AV node and does not protect against bradycardia in the event AV block develops. When compared to dual-chamber (DDDR) pacing, AAIR pacing was associated with a higher incidence of paroxysmal atrial fibrillation, and a twofold increased risk of pacemaker reoperation. DDDR pacing, programmed with a moderately prolonged AV interval, was identified as a better choice for patients with SND.26 Pacemakers equipped with managed ventricular pacing mode, which automatically changes modes between AAI/R and DDD/R, can reduce unnecessary RV pacing as well.30
SND is associated with an inappropriate chronotropic response, the use of rate adaptive pacing, devices that incorporate one or more sensors to detect changes in activity, and is indicated to optimize tolerance with exertion.8,14 The CAEP treadmill test is also used to assess optimal rate response in pacemaker patients with any type sensor.23
Atrial fibrillation is present in around 8% of patients with SND at the time of diagnosis, and the possibility of developing atrial fibrillation is approximately 5% per year.4 Thromboembolic complications associated with atrial fibrillation contribute to the mortality and morbidity in patients with SND.8 Reducing the risk of stroke by monitoring for atrial fibrillation and treatment with appropriate anticoagulation is also an essential part of treatment.
Implications for practice
Sinus node dysfunction is commonly encountered in clinical practice. The clinical presentation can range from asymptomatic bradycardia to atrial standstill with a wide variety of symptoms (many of which are vague and intermittent). SND is commonly seen in older adults and is associated with a low incidence of sudden death. The survival of patients with SND appears to depend primarily on the severity of underlying cardiac disease and is not significantly changed by pacemaker therapy.31 Unrecognized SND can lead to perioperative complications. With the increasing numbers of older adult patients undergoing surgery, it is important to consider SND in any patient that may present with dizziness, forgetfulness, or decreased exercise tolerance. If SND is suspected, elimination of reversible causes should be undertaken with immediate attention to medications. The patient's physical/cognitive abilities and available support system should be considered when selecting an ambulatory monitoring system to ensure optimal data collection and transmission. Patients with physical limitations such as severe arthritis or cognitive impairments may require a monitoring system that involves minimal patient participation.
Referral to an appropriate specialist will be required if autonomic/invasive EP testing or implantation of a cardiac pacemaker is indicated. Once a pacemaker is implanted, patients must be aware of the importance for regular device follow-up. This will help to insure optimal device function and allow for detection of atrial fibrillation, which may require anticoagulation for stroke prevention.
A favorable outcome
After reviewing the stress test results with Mr. S and his daughter, he was referred to a cardiac electrophysiologist for further evaluation of chronotropic incompetence. A dual-chamber pacemaker was successfully implanted without complications and was programmed DDDR with a moderately prolonged AV interval to minimize unnecessary RV pacing. He returned to the clinic for a follow-up visit 3 months after pacemaker implantation. Mr. S was without complaints and reported he had resumed his daily walking routine. He denied any further fatigue, dizziness, or DOE. His physical exam revealed a well-healed left pectoral pacemaker site, a resting BP of 122/66, and HR of 60 bpm. His daughter expressed that although Mr. S continued to experience an occasional episode of “forgetfulness,” she was reassured by the improvement in his condition.
Recommendations for permanent pacing in SND.
Class I Pacemaer indicated
- – SND with documented symptomatic bradycardia.
- – SND as resulting from essential long-term drug therapy.
- – Symptomatic chronotropic incompetence.
Class IIa Pacemaker reasonable
- – SND with heart rate <40 bpm when a clear association between symptoms consistent with bradycardia and actual presence of bradycardia has not been documented.
- – Syncope of unexplained origin when clinically significant abnormalities of sinus node function are found during EP studies.
Class IIb Pacemaker considered
- – Minimally symptomatic with chronic heart rate <40 bpm while awake.
Class III Pacemaker not indicated
- – Asymptomatic patients.
- – Symptoms suggestive of bradycardia clearly documented to occur in the absence of bradycardia.
- – Symptomatic bradycardia due to non-essential drug therapy.
Adapted from ACC/AHA/HRS. 2008 Guideline for device-based therapy for cardiac rhythm abnormalities. Hert Rhythm. 2008;5:e1–e62.
1. Ferrer MI.The sick sinus syndrome
in atrial disease. JAMA. 1968;206(3):645–646.
2. Epstein AE, DiMarco JP, Ellenbogen KA, et al.ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities. Heart Rhythm. 2008;5(6):e1-e62.
3. Dobrzynski H, Boyett MR, Anderson RH.New insights into pacemaker activity: promoting understanding of sick sinus syndrome
. Circulation. 2007;115(14):1921–1932.
5. Adan V, Crown LA.Diagnosis and treatment of sick sinus syndrome
. Am Fam Physician. 2003;67(8):1725–1732.
6. Quinn F, McGavigan Rankin A.Sinus and atrial arrhythmias. In: Macfarlane J, Oosterom A, Pahlm O, Kligfield P, Janse M, Camm J, eds. Comprehensive Electrocardiology. London: Springer; 2011:1195–1212.
7. Olgin J, Zipes D.Specific arrhythmias: diagnosis and treatment. In: Bonow R, Mann D, Zipes D, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier; 2011:771–823.
8. Benditt D, Sutton R.Bradyarrhythmias and syncope. In: Grubb B, Olshansky B, eds. Syncope Mechanisms and Management. 2nd ed. Malden, MA: Blackwell Publishing; 2005:92–120.
9. Kodama I, Honjo H, Dobrynski H, Boyett M.Cellular mechanisms of sinoatrial activity. In: Zipes D, Jalife J. Cardiac Electrophysiology From Cell to Bedside. 4th ed. Philadelphia, PA: Saunders; 2004:192–201.
10. Civello K, Bhargava M, Burkhart D.Indications for permanent pacing and cardiac resynchronization therapy. In: Natale A, ed. Handbook of Cardiac Electrophysiology. London, UK: Informa Healthcare; 2007:61–68.
13. Lee HC, Huang KT, Wang XL, Shen WK.Autoantibodies and cardiac arrhythmias. Heart Rhythm. 2011;8(11):1788–1795.
14. Peters R, Vijayaraman P, Ellenbogen K.Indications for permanent and temporary cardiac pacing. In: Ellenbogen K, Wood M, eds. Cardiac Pacing and ICDs. 5th ed. Malden, MA: Blackwell Publishing; 2008:1–45.
15. Klein I, Danzi S.Cardiovascular involvement in general medical conditions. Circulation. 2007;116:1725–1735.
17. Alboni P, Gianfranchi L, Brignole M.Treatment of persistent sinus bradycardia with intermittent symptoms: are the guidelines clear. Europace. 2009;11(5):562–564.
18. Ishida R, Shido A, Kishimoto T, Sakura S, Saito Y.Prolonged cardiac arrest unveiled silent sick sinus syndrome
during general and epidural anesthesia. J Anesth. 2007;21(1):62–65.
19. Miller J, Zipes D.Diagnosis of cardiac arrhythmias. In: Bonow R, Mann D, Zipes D, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, PA: Elsevier; 2011:687–702.
20. Zimetbaum P, Goldman A.Ambulatory arrhythmia monitoring: choosing the right device. Circulation. 2010;122(16):1629–1636.
21. Lin D, Callans D.Sinus rhythm abnormalities. In: Zipes D, Jalife J. Cardiac Electrophysiology From Cell to Bedside. 4th ed. Philadelphia, PA: Saunders; 2004:479–484.
22. Katritsis D, Camm AJ.Chronotropic incompetence: a proposal for definition and diagnosis. Br Heart J. 1993;70(5):400–402.
23. Stamber B, Reynolds D.Hemodynamics of cardiac pacing and pacing mode selection. In: Ellenbogen K, Wood M, eds. Cardiac Pacing and ICDs. 5th ed. Malden, MA: Blackwell Publishing; 2008:116–174.
24. Lamas GA, Lee KL, Sweeney MO, et al.Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. 2002;346(24):1854–1862.
25. Sweeney MO, Bank AJ, Nsah E, et al.Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med. 2007;357(10):1000–1008.
26. Nielson JC, Thomsen PE, Hojberg S, et al.A comparision of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome
. Eur Heart J. 2011;32:687–696.
27. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al.Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction
. Circulation. 2003;107(23):2932–2937.
28. Hillock RJ, Mond HG.Pacing the right ventricular outflow tract septum: time to embrace the future. Europace. 2012;14(1):28–35. doi: 10.1093/europace/eur251.
29. Francis FJ, Jayesh B, Ashishkumar M, et al.Right ventricular septal pacing: has it come of age. Indian Pacing Electrophysiol J. 2010;10:69–72.
30. Gillis AM, Purefellner H, Israel CW, et al.Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Pacing Clin Electrophysiol. 2006;29:697–705.
31. 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. 1998;82(10):1205–1209.
Keywords:© 2012 Lippincott Williams & Wilkins, Inc.
cardiac pacemaker therapy; sick sinus syndrome; sinus node dysfunction