7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation : Munther K Homoud, MD : Samuel L vy, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 30, 2022. INTRODUCTION Sinus node dysfunction (SND), also historically referred to as sick sinus syndrome (SSS) is characterized by dysfunction of the sinoatrial (SA) node that is often secondary to senescence of the SA node and surrounding atrial myocardium. Patients with SND are typically symptomatic with fatigue, lightheadedness, palpitations, presyncope, and/or syncope, although the occasional patient may be identified during electrocardiography (ECG) or ambulatory ECG monitoring performed for another indication. The clinical manifestations, evaluation, and approach to diagnosis of SND will be reviewed here. The causes, natural history, and management of SND, along with the appropriate timing of referral to a specialist, are discussed in detail separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinus node dysfunction: Treatment" and "Arrhythmia management for the primary care clinician", section on 'Referral to a specialist'.) DEFINITION SND is a clinical syndrome characterized by chronic sinoatrial (SA) node dysfunction, a sluggish or absent SA nodal pacemaker after electrical cardioversion, and/or depressed escape pacemakers in the presence or absence of atrioventricular (AV) nodal conduction disturbances [1-3]. SND may also manifest as chronotropic incompetence with inappropriate heart rate responses to physiological demands during activity. SND can also be accompanied by AV nodal https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 1/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate conduction disturbances and by atrial tachyarrhythmias as part of the tachycardia-bradycardia syndrome. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Definition'.) CLINICAL PRESENTATION SND is defined by electrocardiogram (ECG) abnormalities (eg, bradycardia, sinus pauses, sinus arrest) that occur in association with clinical signs and symptoms. Most patients with SND present with one or more of the following nonspecific symptoms: fatigue, lightheadedness, palpitations, presyncope, syncope, dyspnea on exertion, or chest discomfort. Symptoms are frequently intermittent with gradual progression in frequency and severity, although some patients may present with profound, persistent symptoms at the initial visit. Rarely, SND may be asymptomatic and identified on routine ECG or ambulatory ECG monitoring. Symptoms Patients with symptomatic SND are primarily older and frequently have comorbid diseases. Patients with SND often seek medical attention with symptoms of lightheadedness, presyncope, syncope, and, in patients with alternating periods of bradycardia and tachycardia, palpitations and/or other symptoms associated with a rapid heart rate. Patients with coexisting cardiac pathology may notice increasing dyspnea on exertion or worsening chest discomfort related to lower heart rate and the resulting reduction in cardiac output. Because symptoms may be variable in nature, nonspecific, and frequently transient, it may be challenging at times to establish this symptom-rhythm relationship. Prior to any testing beyond an ECG, a thorough evaluation should be performed for potentially reversible causes, which include medication use (eg, beta blockers, calcium channel blockers, digoxin, antiarrhythmics), myocardial ischemia, systemic illness (eg, hypothyroidism), and autonomic imbalance. (See 'Approach to the diagnosis' below.) SND is defined by ECG abnormalities (eg, bradycardia, sinus pauses, sinus arrest) that occur in association with clinical signs and symptoms. Of note, ECG abnormalities alone, in particular sinus bradycardia, do not always denote the presence of SND. As an example, highly conditioned athletes often have a pronounced increase in vagal tone at rest with heart rates well below 60 beats per minute in the absence of symptoms. ECG findings The diagnosis of SND in persons with suggestive symptoms is often made from the surface ECG. ECG manifestations can include: Periods of inappropriate, and often severe (less than 50 beats per minutes), bradycardia [1,3]. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 2/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Sinus pauses, arrest, and sinoatrial (SA) exit block with, and often without, appropriate atrial and junctional escape rhythms. The failure of escape pacemakers may lead to symptoms including syncope [1,3]. (See "Sinoatrial nodal pause, arrest, and exit block".) Alternating bradycardia and atrial tachyarrhythmias in over 50 percent of cases [1,4-9]. Atrial fibrillation is most common, but atrial flutter and paroxysmal supraventricular tachycardias (ie, due to atrial tachycardia) may also occur. Atrial arrhythmias seem to develop slowly over time, possibly the result of a progressive pathological process that affects the SA node and the atrium [10-12]. Various examples of the ECG findings that may be seen are shown in the accompanying figures ( waveform 1 and waveform 2 and waveform 3). APPROACH TO THE DIAGNOSIS There are no standardized criteria for establishing a diagnosis of SND, and the initial clues to the diagnosis of SND are most often gleaned from the patient s history. However, the symptoms of SND are nonspecific and the electrocardiogram (ECG) findings may not be diagnostic. Hence, the key to making a diagnosis of SND is to establish a correlation between the patient's symptoms and the underlying rhythm at the time of the symptoms. Patients may present with symptoms of fatigue, lightheadedness, presyncope, syncope, dyspnea on exertion, chest discomfort, and/or palpitations. A routine ECG and/or ambulatory ECG monitoring may confirm the diagnosis if typical ECG findings (eg, one or more of sinus bradycardia; sinus pauses, arrest, and sinoatrial [SA] exit block; or alternating bradycardia and atrial tachyarrhythmias) can be correlated with symptoms. In some patients, however, additional diagnostic testing may be required, and SND should not be diagnosed until any potentially reversible causes have been identified and treated. Our approach is as follows ( algorithm 1): Comprehensive history and physical examination, resting 12-lead ECG, review of prior records and ECG tracings, and exercise stress testing The key to making a diagnosis of SND is establishing a symptom-rhythm correlation. Hence, a good history and ECG findings during symptoms are often sufficient to diagnose SND. Careful review of prior records, in particular previous ECG tracings, can provide subtle clues to changes in the ECG over time. For patients with clinically suspected SND in whom the diagnosis remains uncertain following the initial ECG, we perform exercise stress testing. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 3/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Exercise stress testing can aid in identifying abnormal sinus node function, excluding myocardial ischemia, and can help guide device programming for patients who ultimately receive a permanent pacemaker (eg, rate responsiveness). A subnormal increase in heart rate after exercise (ie, chronotropic incompetence) can help identify individuals with abnormal sinus node function who may benefit from a pacemaker implantation [13,14]. While there are various definitions on what is considered subnormal, most clinicians diagnose chronotropic incompetence as the inability of achieving at least 80 percent of the maximum predicted heart rate with exercise testing [15]. The sensitivity and specificity of this latter approach, however, are uncertain, and the results obtained may not be reproducible [16]. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".) Careful review for potentially reversible causes and medication use should be performed to exclude remediable causes for apparent SND [15]. In patients with medication use (eg, beta blockers, calcium channel blockers, digoxin, antiarrhythmics, and acetylcholine esterase inhibitors) suspected to result in symptomatic bradycardia, the patient should remain on an ECG monitor while the medications are withdrawn. If symptoms and ECG abnormalities persist following the withdrawal of the medications (ie, after three to five half-lives), then SND can be diagnosed. Similarly, patients with symptomatic bradycardia suspected to be due to myocardial ischemia, hypothyroidism, or another condition should receive treatment directed at that condition while ECG monitoring continues. If SND cannot be definitively diagnosed following history, physical, and initial 12-lead ECG, ambulatory ECG monitoring (with a continuous monitor [Holter] for 1 to 14 days and/or event monitor for up to four weeks) should be performed to identify symptomatic episodes of arrhythmias and average heart rates over extended periods of surveillance [15]. (See "Ambulatory ECG monitoring".) In patients with suspected SND but without a confirmed diagnosis following ambulatory ECG monitoring, additional testing may include: Extended ambulatory ECG monitoring with an insertable cardiac monitor (also sometimes called an implantable cardiac monitor or an implantable loop recorder). (See 'Ambulatory ECG monitoring and event recording' below.) Electrophysiology studies (EPS) have historically been used, but the very limited sensitivity of EPS in detecting evidence of SND has limited the usefulness of EPS. In symptomatic patients with suspected SND but no ECG documentation, EPS may be considered. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 4/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Referral to a cardiac electrophysiologist should be considered at any point in the diagnostic approach, but is most helpful if SND is suspected but not confirmed following the initial period of ambulatory ECG monitoring (up to four weeks). Once SND is confirmed, treatment typically involves referral for implantation of a pacemaker. Management of SND is discussed in detail separately. (See "Sinus node dysfunction: Treatment".) DIAGNOSTIC TESTING For patients in whom SND is clinically suspected but not confirmed by electrocardiogram (ECG) and/or exercise stress test findings, a number of different modalities may be helpful. In most patients, ambulatory ECG monitoring for an extended period of time (typically two to four weeks but potentially longer) has the greatest yield and allows for correlation with symptoms. In select patients where the diagnosis remains uncertain, other diagnostic testing options include adenosine administration, carotid sinus massage, and invasive electrophysiology studies. Ambulatory ECG monitoring and event recording For patients with clinically suspected SND in whom the initial ECG and monitoring are non-diagnostic, we perform additional ambulatory ECG monitoring [15]. We most frequently use an ambulatory event monitor for two to four weeks to try to capture the ECG during a symptomatic episode. Rare patients with frequent symptoms may be successfully diagnosed with an ambulatory Holter monitor worn for 24 to 48 hours, while patients with less frequent symptoms may require extended monitoring for months to years with an implantable cardiac monitor. The introduction of the insertable cardiac monitor into the diagnostic armamentarium has enhanced the diagnostic yield of the clinical evaluation [17]. The challenge of evaluating patients with SND remains the nonspecificity of symptoms, apart from syncope, and the inconsistency of electrocardiographic clues. Management requires correlation between symptoms and electrocardiographic findings. The insertable cardiac monitor is uniquely suited to achieve this goal and is becoming more frequently and earlier in the cascade of diagnostic tools. (See "Ambulatory ECG monitoring".) Ambulatory ECG monitoring with a 24-hour Holter monitor may provide important clues in 50 to 70 percent of patients with suspected SND [18-20]. However, the sensitivity and specificity of a 24-hour continuous monitor is relatively low due to the variable nature of symptoms and short duration of monitoring [21]. The use of cardiac event monitors, ambulatory ECG monitors which are typically worn for two to four weeks, has been shown to be more effective than 24-hour continuous monitors in establishing a diagnosis [22,23]. In some instances where the symptoms are very infrequent, the use of implantable event monitors have been used that allow for monitoring periods of greater than one year [24]. Variable patient compliance and sensitivity to https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 5/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate the adhesive electrode patches further limits the utility of two- to four-week week monitoring. The enhanced diagnostic utility of insertable cardiac monitoring has significantly reduced the role of pharmacological challenge, determining the intrinsic heart rate and invasive electrophysiological studies. The latter tests are of limited diagnostic yield lacking both sensitivity and specificity. Pharmacologic challenge A number of drugs have been used in aiding the diagnosis of SND, but none are used in routine clinical practice. Atropine and isoproterenol Atropine (1 or 2 mg) and isoproterenol (2 to 3 mcg/minute) may be useful, since both agents normally increase the sinus rate [25,26]. A suggested abnormal response is an increase in the sinus rate of less than 25 percent, or to a rate below 90 beats per minute. Since in most cases the diagnosis of SND can be achieved by establishing a symptom-rhythm correlation with the use of ambulatory monitor and a comprehensive history and physical exam, testing with these agents is rarely necessary. Adenosine Adenosine has been proposed as an alternative to invasive electrophysiology studies, but its routine use is not yet established [27-29]. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Electrocardiographic and electrophysiologic recordings'.) Calculating the intrinsic heart rate The intrinsic heart rate (IHR) is the heart rate in the presence of complete pharmacological denervation of the sinus node [30]. This is achieved with the simultaneous use of beta blockers and atropine. The calculation of the IHR following simultaneous administration of beta blockers and atropine is largely of historical interest and is rarely performed in the modern evaluation of patients with suspected SND. Electrophysiologic testing Invasive electrophysiologic studies (EPS) are rarely used for the evaluation of SND (eg, symptomatic patient who has no electrocardiographic findings suggestive of SND but no other evident cause for the symptoms) because of their limited sensitivity in eliciting bradyarrhythmic abnormalities as well as the widespread availability of diagnostic options for long-term monitoring. However, EPS may be helpful in patients with suspected SND who also describe sustained episodes of tachyarrhythmias in an effort to identify a tachycardia (eg, atrial tachycardia) that would be potentially curable with ablation [15]. The 2018 ACC/AHA/HRS guidelines do not support performing invasive EP studies for the sole purpose of establishing a diagnosis of SND [15]. The function of the sinus node can be evaluated invasively (ie, EP studies) within the context of evaluating a patient with other conditions such as a life-threatening arrhythmia that may warrant an implantable cardioverter defibrillator. Establishing a diagnosis of SND under such circumstances may lead the operator to consider https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 6/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate implanting an ICD with atrial pacing capabilities. These guidelines have conferred a Class IIb indication for invasive EP studies for establishing the diagnosis of SND. The salient aspects of electrophysiology studies that aid in eliciting a bradyarrhythmic abnormality include assessment of the SA node recovery time, SA conduction time, and the sinus node and atrial tissue refractory periods. A more detailed discuss of invasive EPS is presented separately. (See "Invasive diagnostic cardiac electrophysiology studies".) DIFFERENTIAL DIAGNOSIS While SND is common, other conditions should also be considered in the differential diagnosis, including carotid sinus hypersensitivity, neurocardiogenic syncope with a predominant cardioinhibitory component, and physiologically normal bradycardia especially among highly conditioned athletes. Carotid sinus massage is typically not employed in diagnosing SND but is often used to establish the presence of carotid sinus hypersensitivity that may elucidate a cause for syncope. Some have advocated for its use in the assessment of SND due to previous reports describing an association between carotid sinus hypersensitivity and SND [31]. With carotid sinus massage, a pause longer than three seconds and/or a symptomatic drop in blood pressure are indicative of carotid sinus hypersensitivity. This study has limited specificity in establishing a diagnosis of carotid sinus hypersensitivity as the reason for syncope. Occasionally, otherwise asymptomatic older adult individuals may exhibit sinus pauses greater than three seconds in duration. Hence, interpretation of the results of carotid sinus massage must be made in the proper clinical context. The technique for performing this test and contraindications are discussed in detail elsewhere. (See "Vagal maneuvers", section on 'Carotid sinus massage'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Syncope" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 7/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Sinus node dysfunction (The Basics)") SUMMARY AND RECOMMENDATIONS Definition Sinus node dysfunction (SND) is characterized by dysfunction of the sinoatrial (SA) node that is often secondary to senescence of the SA node and surrounding atrial myocardium. SND is characterized by chronic sinoatrial (SA) node dysfunction, a sluggish or absent SA nodal pacemaker after electrical cardioversion, and/or depressed escape pacemakers in the presence or absence of atrioventricular (AV) nodal conduction disturbances. SND may also manifest as chronotropic incompetence with inappropriate heart rate responses to physiological demands during activity. (See 'Definition' above.) Clinical presentation SND is defined by ECG abnormalities that occur in association with clinical signs and symptoms. Most patients with SND with present with one or more of the following nonspecific symptoms: fatigue, lightheadedness, palpitations, presyncope, syncope, dyspnea on exertion, or angina. Symptoms are frequently intermittent with gradual progression in frequency and severity. (See 'Clinical presentation' above.) ECG findings Typical ECG findings in patients with SND include one or more of sinus bradycardia; sinus pauses, arrest, and SA exit block; and alternating bradycardia and atrial tachyarrhythmias ( waveform 1 and waveform 2 and waveform 3). (See 'ECG findings' above.) Diagnosis There are no standardized criteria for making a diagnosis of SND, and the key is to establish a symptom-rhythm correlation. The initial clues to the diagnosis of SND are most often gleaned from the patient s history. However, the symptoms of SND are https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 8/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate nonspecific and the ECG findings may not be diagnostic. Hence, the key to making a diagnosis of SND is to establish a correlation between the patient's symptoms and the underlying rhythm at the time of the symptoms. Our approach to the diagnosis of SND is summarized in the text ( algorithm 1). (See 'Approach to the diagnosis' above.) Role of ambulatory monitoring Patients with clinically suspected SND in whom the initial ECG and monitoring are non-diagnostic should undergo ambulatory ECG monitoring. We most frequently use an ambulatory event monitor for two to four weeks to try to capture the ECG during a symptomatic episode. (See 'Ambulatory ECG monitoring and event recording' above.) Role of additional evaluation For patients in whom the diagnosis remains uncertain following ambulatory ECG monitoring, additional diagnostic options include the insertion of an insertable cardiac monitor that may last as long as three years. Pharmacologic challenge and invasive electrophysiology testing are rarely employed. Referral to a cardiac electrophysiologist should be considered. (See 'Diagnostic testing' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Alan Cheng, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Ferrer MI. The sick sinus syndrome in atrial disease. JAMA 1968; 206:645. 2. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967; 29:469. 3. Ferrer MI. The Sick Sinus Syndrome, Futura Press, New York 1974. 4. SHORT DS. The syndrome of alternating bradycardia and tachycardia. Br Heart J 1954; 16:208. 5. BIRCHFIELD RI, MENEFEE EE, BRYANT GD. Disease of the sinoatrial node associated with bradycardia, asystole, syncope, and paroxysmal atrial fibrillation. Circulation 1957; 16:20. 6. Rubenstein JJ, Schulman CL, Yurchak PM, DeSanctis RW. Clinical spectrum of the sick sinus syndrome. Circulation 1972; 46:5. 7. Kaplan BM, Langendorf R, Lev M, Pick A. Tachycardia-bradycardia syndrome (so-called "sick sinus syndrome"). Pathology, mechanisms and treatment. Am J Cardiol 1973; 31:497. https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 9/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate 8. Gomes JA, Kang PS, Matheson M, et al. Coexistence of sick sinus rhythm and atrial flutter- fibrillation. Circulation 1981; 63:80. 9. Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus- node dysfunction. N Engl J Med 2002; 346:1854. 10. Ferrer MI. The etiology and natural history of sinus node disorders. Arch Intern Med 1982; 142:371. 11. Simonsen E, Nielsen JS, Nielsen BL. Sinus node dysfunction in 128 patients. A retrospective study with follow-up. Acta Med Scand 1980; 208:343. 12. Thery C, Gosselin B, Lekieffre J, Warembourg H. Pathology of sinoatrial node. Correlations with electrocardiographic findings in 111 patients. Am Heart J 1977; 93:735. 13. Eraut D, Shaw DB. Sinus bradycardia. Br Heart J 1971; 33:742. 14. Kay GN. Quantitation of chronotropic response: comparison of methods for rate- modulating permanent pacemakers. J Am Coll Cardiol 1992; 20:1533. 15. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 16. Josephson, ME. Sinus Node Function. In: Clinical Cardiac Electrophysiology: Techniques and I nterpretations, 4th, Lippincott, Williams, & Wilkins, Philadelphia 2008. p.69-92. 17. Furukawa T, Maggi R, Bertolone C, et al. Additional diagnostic value of very prolonged observation by implantable loop recorder in patients with unexplained syncope. J Cardiovasc Electrophysiol 2012; 23:67. 18. Lipski J, Cohen L, Espinoza J, et al. Value of Holter monitoring in assessing cardiac arrhythmias in symptomatic patients. Am J Cardiol 1976; 37:102. 19. Reiffel JA, Bigger JT Jr, Cramer M, Reid DS. Ability of Holter electrocardiographic recording and atrial stimulation to detect sinus nodal dysfunction in symptomatic and asymptomatic patients with sinus bradycardia. Am J Cardiol 1977; 40:189. 20. Gibson TC, Heitzman MR. Diagnostic efficacy of 24-hour electrocardiographic monitoring for syncope. Am J Cardiol 1984; 53:1013. 21. Kerr CR, Strauss HC. The measurement of sinus node refractoriness in man. Circulation 1983; 68:1231. 22. Kinlay S, Leitch JW, Neil A, et al. Cardiac event recorders yield more diagnoses and are more cost-effective than 48-hour Holter monitoring in patients with palpitations. A controlled https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 10/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate clinical trial. Ann Intern Med 1996; 124:16. 23. Zimetbaum PJ, Josephson ME. The evolving role of ambulatory arrhythmia monitoring in general clinical practice. Ann Intern Med 1999; 130:848. 24. Vavetsi S, Nikolaou N, Tsarouhas K, et al. Consecutive administration of atropine and isoproterenol for the evaluation of asymptomatic sinus bradycardia. Europace 2008; 10:1176. 25. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al. Electrophysiologic effects of atropine on sinus node and atrium in patients with sinus nodal dysfunction. Am J Cardiol 1976; 38:848. 26. Talano JV, Euler D, Randall WC, et al. Sinus node dysfunction. An overview with emphasis on autonomic and pharmacologic consideration. Am J Med 1978; 64:773. 27. Burnett D, Abi-Samra F, Vacek JL. Use of intravenous adenosine as a noninvasive diagnostic test for sick sinus syndrome. Am Heart J 1999; 137:435. 28. Fragakis N, Iliadis I, Sidopoulos E, et al. The value of adenosine test in the diagnosis of sick sinus syndrome: susceptibility of sinus and atrioventricular node to adenosine in patients with sick sinus syndrome and unexplained syncope. Europace 2007; 9:559. 29. Viskin S, Justo D, Halkin A. Should the 'adenosine-challenge test' be part of the routine work- up for syncope? Europace 2007; 9:557. 30. Opthof T. The normal range and determinants of the intrinsic heart rate in man. Cardiovasc Res 2000; 45:177. 31. Thormann J, Schwarz F, Ensslen R, Sesto M. Vagal tone, significance of electrophysiologic findings and clinical course in symptomatic sinus node dysfunction. Am Heart J 1978; 95:725. Topic 896 Version 35.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 11/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate GRAPHICS Single lead electrocardiogram (ECG) showing sick sinus syndrome and atrial fibrillation Rhythm strip showing sick sinus syndrome. The initial part (left) of the tracing reveals coarse atrial fibrillation with irregular ventricular response in the absence of drugs that slow AV nodal conduction. The atrial fibrillation terminates and is followed by a sinus beat with a prolonged sinus node recovery time of nearly four seconds. Courtesy of Ary Goldberger, MD. Graphic 51193 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 12/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram (ECG) showing manifestations of sick sinus syndrome (SSS) with sinus arrest Example of sick sinus syndrome (SSS). In this example, sinus arrest is seen with a junctional escape beat, a premature atrial complex, and eventual resumption of sinus activity. Courtesy of Alan Cheng, MD, FACC, FAHA, FHRS. Graphic 91605 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 13/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Single lead electrocardiogram (ECG) showing sick sinus syndrome (SSS) with ectopic atrial and junctional beats Example of sick sinus syndrome (SSS). In this example, sinus rhythm abruptly pauses, followed by two ectopic atrial beats, a junctional escape beat, and resumption of sinus activity. Courtesy of Alan Cheng, MD, FACC, FAHA, FHRS. Graphic 91606 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 14/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Algorithm for evaluation of the patient with suspected sick sinus syndrome (SSS) H&P: history and physical; ECG: electrocardiogram; ETT: exercise treadmill test; PPM: permanent pacemaker; SSS: sick sinus syndrome. Graphic 103295 Version 1.0 https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 15/16 7/6/23, 11:21 AM Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sinus-node-dysfunction-clinical-manifestations-diagnosis-and-evaluation/print 16/16