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Diagnosis and Treatment of Sick Sinus Syndrome VICTOR ADÁN, M.D., Angel Medical Center, Franklin, North Carolina LOREN A. CROWN, M.D., University of Tennessee Health Sciences Center, Covington, Tennessee

Sick sinus syndrome comprises a variety of conditions involving sinus node dys- function and commonly affects elderly persons. While the syndrome can have many O A patient informa- causes, it usually is idiopathic. Patients may experience , pre-syncope, pal- tion handout on sick pitations, or ; however, they often are asymptomatic or have subtle or sinus syndrome, writ- ten by the authors of nonspecific symptoms. Sick sinus syndrome has multiple manifestations on electro- this article, is provided cardiogram, including sinus , sinus arrest, , and alternat- on page 1738. ing patterns of bradycardia and (bradycardia-tachycardia syndrome). Diagnosis of sick sinus syndrome can be difficult because of its nonspecific symp- toms and elusive findings on electrocardiogram or . The mainstay of treatment is atrial or dual-chamber pacemaker placement, which generally provides effective relief of symptoms and lowers the incidence of atrial , throm- boembolic events, failure, and mortality, compared with ventricular pace- makers. (Am Fam Physician 2003;67:1725-32,1738. Copyright©2003 American Acad- emy of Family Physicians)

ick sinus syndrome is a generalized abnormality of cardiac impulse Etiology formation that may be caused by Most cases of sick sinus syndrome are idio- an intrinsic disease of the sinus pathic, and the cause can be multifactorial node that makes it unable to per- (Table 1).3 Degenerative of nodal tis- Sform its pacemaking function, or by extrinsic sue is the most common cause of intrinsic causes.1 Abnormalities encompassed in this changes in the that lead to sick syndrome include , sinus sinus syndrome. Certain conditions can cause arrest or exit block, combinations of sino- these intrinsic changes.3,5,6 There also are atrial and atrioventricular nodal conduction extrinsic causes of and disturbances, and atrial tachyarrhythmias. conditions that can cause this problem in chil- Sick sinus syndrome is not a disease with a dren (Table 1).3 single etiology and pathogenesis but, rather, a Coronary disease may coexist with collection of conditions in which the electro- sick sinus syndrome in a significant number of cardiogram (ECG) indicates sinus node dys- patients, although it is not considered a major function.2 cause of the syndrome. It is unclear whether Sick sinus syndrome is characterized by , sinus node , or local sinus node dysfunction with an atrial rate autonomic neural effects lead to the develop- inappropriate for physiologic requirements. ment of sick sinus syndrome in patients with Although the condition is most common in . Sinus node dysfunction the elderly, it can occur in persons of all ages, usually is temporary when it follows an acute including neonates.3 The mean age of pa- myocardial infarction. Uncommonly, chronic tients with this condition is 68 years, and ischemia may cause fibrosis and lead to symp- both sexes are affected approximately equally.4 toms of sick sinus syndrome for months to The syndrome occurs in one of every 600 car- years after myocardial infarction. diac patients older than 65 years and may account for 50 percent or more of perma- Clinical Manifestations nent pacemaker placements in the United Patients with sick sinus syndrome often States.5 are asymptomatic or have symptoms that are

APRIL 15, 2003 / VOLUME 67, NUMBER 8 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1725 mild and nonspecific7 (Table 2).3 Symptoms TABLE 1 are related to the decreased Causes of Sick Sinus Syndrome that occurs with the bradyarrhythmias or tachyarrhythmias.3 Most of the symptoms Intrinsic causes Extrinsic causes are caused by decreased cerebral perfusion, Cholinesterase deficiency (suggested) and 50 percent of patients have syncope or Arteritis pre-syncope.5 Symptoms, which may have been present Chagas’ disease Pharmacologic agents for months or years, can include syncope, , and dizziness, as well as symp- Calcium channel blockers Familial sinoatrial node disorders Beta blockers toms caused by the worsening of conditions Fatty replacement Sympatholytic agents such as congestive , pec- 8 Friedreich’s Antiarrhythmics toris, and cerebral vascular accident. Periph- Hemochromatosis Toxins eral thromboembolism and , which Idiopathic degenerative fibrotic Pediatric causes can occur in the presence of bradycardia- infiltration* Congenital abnormalities tachycardia syndrome (alternating brady- Ischemia/infarction Sinoatrial nodal artery deficiency and tachyarrhythmias), may be Leukemia related to dysrhythmia-induced emboli.3 A Metastatic disease slow in the presence of , left Muscular dystrophy ventricular failure, or pulmonary may 2,9 be suggestive of sick sinus syndrome. Asso- Rheumatic heart disease ciated tachycardia may cause of the face, pounding of the heart, and retrosternal Surgical injury pressure.10 Other symptoms include irritabil- ity, nocturnal wakefulness, memory loss, *—Most common intrinsic cause. errors in judgment, lethargy, lightheaded- 2,11 3 Adapted with permission from Wahls SA. Sick sinus syndrome. Am Fam Physician ness, and fatigue (Table 2). More subtle 1985;31:118. symptoms include mild digestive distur- bances, periodic oliguria or edema, and mild intermittent dyspnea.2

ECG Manifestations Sick sinus syndrome can produce a variety TABLE 2 of ECG manifestations consisting of atrial Symptoms of Sick Sinus Syndrome bradyarrhythmias, atrial tachyarrhythmias, and alternating bradyarrhythmias and Central nervous system Cardiovascular system Other tachyarrhythmias7 (Table 3).3 Supraventric- Angina pectoris Digestive disturbances ular bradyarrhythmias may include sinus Irritability Arterial thromboemboli Dizziness bradycardia, sinus arrest with or without Lethargy Cerebrovascular Errors in judgment junctional escape, sinoatrial exit block, accident Facial flushing Memory loss Congestive heart failure Fatigue ectopic atrial bradycardia, and atrial fibrilla- Nocturnal wakefulness Palpitations Oliguria tion with slow ventricular response. The Syncope or pre-syncope sinus bradycardia that occurs in patients with sick sinus syndrome is inappropriate Adapted with permission from Wahls SA. Sick sinus syndrome. Am Fam Physician and not caused by medications.2,5 The sino- 1985;31:123. atrial exit block that occurs in patients with sick sinus syndrome may demonstrate a

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TABLE 3 The treatment of choice for symptomatic bradyarrhythmias Arrhythmias Associated in patients with sick sinus syndrome is the placement of a with Sick Sinus Syndrome pacemaker.

Atrial bradyarrhythmias Sinus bradycardia Sinus arrest (with or without junctional escape) Mobitz type I block (Wenckebach block) Sinoatrial exit block and a Mobitz type II block.2 The ECG may Mobitz type I block (Wenckebach block) reveal a long pause following Mobitz type II block of atrial tachyarrhythmias, and a greater- Ectopic atrial bradycardia with slow ventricular response than three-second pause following carotid 5 Greater-than 3-second pause following carotid massage. Sixty percent of patients have massage tachyarrhythmias.8 Long pause following cardioversion of atrial Supraventricular tachyarrhythmias that tachyarrhythmias occur in patients with sick sinus syndrome Atrial tachyarrhythmias include paroxysmal supraventricular tachy- Atrial fibrillation cardia, , atrial fibrillation, and Atrial flutter .2,3 Atrial fibrillation is the Atrial tachycardia most common tachydysrhythmia in these pa- Paroxysmal supraventricular tachycardia tients.12 Rarely, a ventricular escape tachy- Ventricular (escape) tachyarrhythmia may be seen on ECG.8 Sinus node Alternating and re-entrant rhythm is another ECG manifesta- Bradycardia-tachycardia syndrome tion.5 Bradycardia-tachycardia syndrome may be seen on ECG or cardiac rhythm strip Adapted with permission from Wahls SA. Sick sinus (Figure 1); this syndrome is more common in syndrome. Am Fam Physician 1985;31:120. older patients with advanced sick sinus syndrome.3

FIGURE 1. Electrocardiogram exhibiting alternating patterns of bradycardia and tachycardia as seen in patients with sick sinus syndrome.

APRIL 15, 2003 / VOLUME 67, NUMBER 8 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1727 TABLE 4 Indications for Permanent Pacemaker Implantation in Sick Sinus Syndrome

Class I* 1. SSS with documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms. In some patients, bradycardia is iatrogenic and will occur as a consequence of essential long-term drug therapy of a type and dosage for which there are no acceptable alternatives. with ECG changes.2 If the patient is asympto- 2. Symptomatic chronotropic incompetence matic when ECG or ambulatory is Class IIa performed, the dysrhythmias of the syndrome 1. SSS occurring spontaneously or as a result of necessary drug therapy, with are often not present.5 Furthermore, there is heart rate less than 40 bpm when a clear association between significant no definitive way to distinguish patients with symptoms consistent with bradycardia and the actual presence of bradycardia has not been documented. atrial fibrillation associated with sick sinus Class IIb syndrome from patients with atrial fibrillation 1. In minimally symptomatic patients, chronic heart rate less than 30 bpm and normal sinus function; this distinction is while awake clinically important because treating atrial fib- Class III rillation with cardioversion or medications can 1. SSS in asymptomatic patients, including those in whom substantial sinus have catastrophic consequences if the sinus bradycardia (heart rate less than 40 bpm) is a consequence of long-term node is inadequate. drug treatment 2. SSS in patients with symptoms suggestive of bradycardia that are clearly One manifestation of serious sinus node documented as not associated with a slow heart rate dysfunction in patients with atrial fibrillation 3. SSS with symptomatic bradycardia caused by nonessential drug therapy is a slow ventricular rate in the absence of medications such as (Inderal) or 2 SSS = sick sinus syndrome; bpm = beats per minute. digitalis. Bradycardia may be misattributed *—Class I represents conditions for which there is evidence and/or general to treatment in a patient with conges- agreement that a given procedure or treatment is beneficial, useful, and effec- tive heart failure. Cardioactive drugs, such as tive. Class II represents conditions for which there is conflicting evidence and/or digoxin, (Quinaglute), and pro- a divergence of opinion about the usefulness/efficacy of a procedure or treat- cainamide (Pronestyl), as well as hyper- ment. Class IIa represents conditions in which the weight of evidence/opinion is kalemia, can cause periodic sinus arrest or in favor of usefulness/efficacy. Class IIb represents conditions in which the use- fulness/efficacy is less well established by evidence/opinion. Class III represents sinoatrial exit block. conditions for which there is evidence and/or general agreement that a proce- Functional sinus bradycardia, enhanced dure/treatment is not useful/effective and in some cases may be harmful. vagal drive, gastrointestinal and neurologic Information from Gregoratos G, Cheitlin MD, Conill A, Epstein AE, Fellows C, Fer- conditions, and other causes of syncope can guson TB Jr, et al. ACC/AHA guidelines for implantation of cardiac pacemakers produce symptoms similar to those of sick and antiarrhythmia devices: a report of the American College of / sinus syndrome and must be included in the American Heart Association Task Force on Practice Guidelines (Committee on of the syndrome. Sinus Pacemaker Implantation). J Am Coll Cardiol 1998;31:1178,1182. node dysfunction can occur perioperatively because of increased caused by anes- thesia or surgical intervention.13 All of these Diagnosis possibilities must be excluded before the diag- The diagnosis of sick sinus syndrome may nosis of sick sinus syndrome can be made.9 be difficult because of the slow and erratic The diagnosis requires not only documen- course of the syndrome. The condition often tation of sinus node dysfunction but also cor- goes undetected in the early stages because relation with the associated symptoms of sick only sinus bradycardia may be present at its sinus syndrome. The most common method origin.9 Some symptoms of patients with sick of diagnosis is Holter monitoring. During sinus syndrome (e.g., fatigue, irritability, monitoring, patients must keep a precise diary memory loss, lightheadedness, palpitations, of their activities and symptoms, so that these cognitive defects) are present in several other factors can be correlated with the ECG disorders that occur in elderly patients and changes.3 may be misdiagnosed as those of senile If two 24-hour periods of Holter monitor- dementia.5 ing fail to reveal the dysrhythmias of sick sinus Symptoms of sick sinus syndrome may be syndrome, but the symptoms are severe and variable, intermittent, and difficult to associate intermittent, it is likely that the sinus node

1728 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 67, NUMBER 8 / APRIL 15, 2003 Symptoms associated with sick sinus syndrome may be wors- ened in patients who are receiving digitalis, , beta blockers, sympatholytic agents such as and methyl- dopa, and antiarrhythmic agents.

dysfunction is severe but intermittent. In these to document symptoms concurrent with the cases, patients can carry a pocket-sized device dysrhythmia when evaluating whether pace- for transmitting ECG readings via telephone maker placement will be beneficial. when they are having symptoms. For this pro- The treatment of choice for symptomatic cedure to be successful, the arrhythmia must bradyarrhythmias in patients with sick sinus last for at least one minute. Another approach syndrome is the placement of a pacemaker.1,3 is to have patients activate a recording device Artificial pacemakers are well tolerated in to monitor the events of cardiac dysrhythmias elderly patients.2 In all patients with this syn- when they are having symptoms.2 drome, except those with chronic atrial fibril- There are several other methods of diag- lation, atrial-based pacemakers are recom- nosing sick sinus syndrome. Isometric hand- mended1,16 (Figure 2).16 grip or Valsalva’s maneuvers nor- mally increase the heart rate, but this effect may be minimal or absent in patients with Optimal Pacemaker Mode Recommendations this syndrome. If carotid massage produces in Sick Sinus Syndrome abrupt sinus arrest of three seconds’ dura- tion, sinus node dysfunction may be sus- pected.8 These measures and monitoring car- diac response to such agents as and isoproterenol (Isuprel) should only be attempted while a patient is undergoing care- The rightsholder did not ful ECG monitoring.3 grant rights to reproduce testing may be useful in determin- this item in electronic ing the response of the sinus node to physio- media. For the missing logic demands. At an equal level of oxygen consumption, some patients with sick sinus item, see the original print syndrome have a decreased heart rate re- version of this publication. sponse to exercise compared with healthy pa- tients.5 Intracardiac electrophysiologic tests (atrial overdrive pacing and premature atrial stimulation) can be used to elicit intrinsic sinus node disease or to document the effects of cardioactive drugs2,3;however,electrophysi- ologic testing is no longer routinely recom- mended for diagnostic purposes because of its poor sensitivity and specificity.14 The risks and benefits of these diagnostic modalities must be considered and discussed with the patient before they are used.

Treatment Pacemaker therapy is warranted in many patients with sick sinus syndrome. Table 415 lists practice guidelines from the American College FIGURE 2. of Cardiology/American Heart Association task force on permanent pacemaker placement in patients with this condition.15 It is essential

APRIL 15, 2003 / VOLUME 67, NUMBER 8 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1729 When tachyarrhythmias are a problem in Patients with sick sinus syndrome who have bradycardia- a patient with sick sinus syndrome, a pace- tachycardia syndrome or chronic atrial fibrillation are at risk maker may decrease the risk of complete or associated with phar- for embolic stroke. macotherapy.3 Digitalis can cause brady- arrhythmias in patients with sick sinus syndrome and should only be used in con- Table 514,17 lists the international codes junction with a pacemaker in the manage- describing pacemakers and implanted devices. ment of supraventricular tachyarrhythmias.5 Patients who have sick sinus syndrome with Severe sinus bradycardia, , or right have an increased sinoatrial exit block occasionally occurs with risk of developing symptomatic high-degree the use of beta-blocker medications in and should be treated patients with this condition.2 with a dual-chamber pacemaker. Patients with Symptoms associated with this syndrome no signs of atrioventricular conduction may be worsened in patients who are receiving abnormalities should be treated with an atrial- digitalis, verapamil (Calan), beta blockers, based pacemaker.18 Pacing with a dual-cham- sympatholytic agents such as clonidine (- ber demand pacemaker with automatic apres) and (Aldomet), and mode-switching function is appropriate in antiarrhythmic agents.3,5 Therefore, the use of patients with sick sinus syndrome who have negative chronotropic drugs should be cau- intermittent tachyarrhythmic components. tiously considered.7 The effects of pro- Pacing with a rate-responsive single-chamber cainamide and quinidine are unpredictable. In ventricular demand pacemaker should be certain patients with sick sinus syndrome and used in patients with the syndrome and episodes of heart failure, oral chronic atrial fibrillation.7 therapy and dual-chamber pacemakers have Complications, including myocardial per- been shown to reduce the occurrence of heart foration, , wound , failure.20 In the absence of pacing, cardiover- venous , pacemaker lead failure, sion may be dangerous because of the likeli- and , can occur with permanent hood of prolonged sinus arrest.3 endocardial pacemaker therapy, but they are Patients with sick sinus syndrome who have uncommon.19 bradycardia-tachycardia syndrome or chronic atrial fibrillation (especially in association with congestive heart failure, large left atria, or disease) are at risk for embolic The Authors stroke. Although the risk-to-benefit ratio for VICTOR ADÁN, M.D., is an attending physician in and medical director of the Depart- anticoagulation is not well defined in these ment of Emergency Medicine at Angel Medical Center, Franklin, N.C. He received his patients, (Coumadin) has been medical degree from the Medical College of Georgia, Augusta, and completed a fam- shown to decrease the number of and ily medicine residency at the Medical Center in Columbus, Ga. He also completed a fellowship in rural emergency medicine at the University of Tennessee Health Sciences embolic events in patients with sick sinus syn- Center Department of Family Medicine in Covington, Tenn. drome who have paroxysmal and chronic 5,11 LOREN A. CROWN, M.D., is the Emergency Medicine Fellowship Director for the atrial fibrillation. Department of Family Medicine at the University of Tennessee Health Sciences Center in Covington. He received his medical degree from Washington University, St. Louis. Prognosis He completed a family medicine residency at MacNeal Memorial Hospital, Berwyn, Ill., 4,21 and is a fellow of the American Board of Family Practice. Randomized controlled trials have examined morbidity and mortality in Address correspondence to Loren A. Crown, M.D., Department of Family Medicine, University of Tennessee Health Sciences Center, 1999 Highway 51 South, Covington, patients with sick sinus syndrome using vari- TN 38019 (e-mail: [email protected]). Reprints are not available from the author. ous pacing modes. Compared with ventricu-

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lar pacing, atrial pacing is associated with a lower incidence of thromboembolic compli- Compared with ventricular pacing, atrial pacing is associated cations, atrial fibrillation, heart failure, car- with a lower incidence of thromboembolic complications, diovascular mortality, and total morbidity.1,18 atrial fibrillation, heart failure, cardiovascular mortality, and In a retrospective study,22 patients with sick sinus syndrome who had pacemaker therapy total morbidity. were followed for 12 years; at eight years, mortality among those with ventricular pac- ing was 59 percent compared with 29 percent a high prevalence of in among those with atrial pacing. This discrep- patients with sick sinus syndrome who die ancy may well be a result of the physiologic or within the first few years of pacemaker anatomic disorder (e.g., fibrosis of conductive implantation.2 tissue) leading to the requirement for the par- Recent improvements in rate-responsive ticular pacemaker rather than the type of pacemaker engineering have led to im- pacemaker used. provements in maximum heart rate, exercise Patients who have sick sinus syndrome tolerance, functional status, suppression of with only sinus bradycardia have a better dysrhythmias, and sense of well-being in pa- prognosis. One study3 indicated that mortal- tients.16 The achievement of near-physiologic ity rates in these patients may not be different rate responsiveness and atrioventricular syn- from mortality rates in the normal popula- chrony, as well as decreased mortality and tion. Researchers conducting one literature morbidity, has led to a better prognosis in review22 concluded that patients with this patients with sick sinus syndrome.19 syndrome who require atrial or dual-cham- ber pacing have a mortality rate of 3.6 percent The authors indicate that they do not have any con- (plus or minus 1.8 percent) per year. There is flicts of interest. Sources of funding: none reported.

TABLE 5 International Codes Describing Pacemakers and Implanted Devices

The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication.

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REFERENCES 14. The Merck manual of diagnosis and therapy. 17th ed. Whitehouse Station, N.J.: Merck, 1999:1719. 1. Mangrum JM, DiMarco JP. The evaluation and 15. Gregoratos G, Cheitlin MD, Conill A, Epstein AE, management of bradycardia. N Engl J Med 2000; Fellows C, Ferguson TB Jr, et al. ACC/AHA guide- 342:703-9. lines for implantation of cardiac pacemakers and 2. Bigger JT Jr, Reiffel JA. Sick sinus syndrome. Annu antiarrhythmia devices: a report of the American Rev Med 1979;30:91-118. College of Cardiology/American Heart Association 3. Wahls SA. Sick sinus syndrome. Am Fam Physician Task Force on Practice Guidelines (Committee on 1985;31:117-24. Pacemaker Implantation). J Am Coll Cardiol 1998; 4. Lamas GA, Lee K, Sweeney M, Leon A, Yee R, Ellen- 31:1175-209. bogen K, et al. The mode selection trial (MOST) in 16. Alagona P Jr. Advances in pacing for the patient sinus node dysfunction: design, rationale, and base- with sick sinus syndrome. Curr Opin Cardiol 1997; line characteristics of the first 1000 patients. Am 12:3-11. Heart J 2000;140:541-51. 17. Bernstein AD, Camm AJ, Fletcher RD, Gold RD, 5. Rodriguez RD, Schocken DD. Update on sick sinus Rickards AF, Smyth NP, et al. The NASPE/BPEG syndrome, a cardiac disorder of aging. Geriatrics generic pacemaker code for antibradyarrhythmia 1990;45:26-30. and adaptive-rate pacing and antitachyarrhyth- 6. Tierney LM, McPhee SJ, Papadakis MA. Heart con- mia devices. Pacing Clin Electrophysiol 1987;10: duction disturbances: sick sinus syndrome. In: 794-9. Papadakis MA, Tierney LM, McPhee SJ. Current 18. Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, & treatment, 2000. 39th ed. Mortensen PT, Vesterlund T, et al. Long-term fol- New York, N.Y.: Lange Medical Books/McGraw- low-up of patients from a randomised trial of atrial Hill, 2000:412. versus ventricular pacing for sick-sinus syndrome. 7. Fuster V, Alexander RW, O’Rourke RA, eds. Hurst’s Lancet 1997;350:1210-6. The heart. 10th ed. New York, N.Y.: McGraw-Hill 19. Kiviniemi MS, Pirnes MA, Eranen HJ, Kettunen RV, Medical Publishing Division, 2001. Hartikainen JE. Complications related to perma- 8. Bower PJ. Sick sinus syndrome. Arch Intern Med nent pacemaker therapy. Pacing Clin Electrophysiol 1978;138:133-7. 1999;22:711-20. 9. Ferrer MI. The sick sinus syndrome. Hosp Pract 20. Alboni P, Menozzi C, Brignole M, Paparella N, Gag- 1980;15:79-89. gioli G, Lolli G, et al. Effects of permanent pace- 10. Kaplan BM. The tachycardia-bradycardia syn- maker and oral theophylline in sick sinus syn- drome. Med Clin North Am 1976;60:81-99. drome. The THEOPACE study: a randomized 11. Colquhoun M. When should you suspect sick sinus controlled trial. Circulation 1997;96:260-6. syndrome? Practitioner 1999;243:422-5. 21. Tang CY, Kerr CR, Connolly SJ. Clinical trials of 12. Atlee JL. Perioperative cardiac dysrhythmias: diag- pacing mode selection. Cardiol Clin 2000;18:1- nosis and management. Anesthesiology 1997;86: 23. 1397-424. 22. McComb JM, Gribbin GM. Effect of pacing mode 13. Hollenberg SM, Dellinger RP. Noncardiac surgery: on morbidity and mortality: update of clinical pac- postoperative arrhythmias. Crit Care Med 2000; ing trials. Am J Cardiol 1999;83(5B):211-3D. 28(10 suppl):N145-50.

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