Syncope
Authors: Benjamin Rhee, MD, Fellow, Division of Cardiology, Division of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and Brian Olshansky, MD, Director, Cardiac Electrophysiology, Professor of Medicine, Division of Cardiology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Editor’s Note—Syncope is a symptom defined as a transient loss of consciousness associated with loss of postural tone and spontaneous recovery. The onset of syncope may be relatively rapid and may be accompanied by certain premonitory symptoms. Recovery is usually spontaneous and complete.
Syncope is a common condition, estimated to occur in 3%1 to 37%2 of the general population, and to have a 6% annual incidence among elderly residents of a long-term care institution.3 It accounts for 3% of emergency department visits and 6% of hospital admissions.4 These numbers underestimate the true prevalence that are due primarily to syncope but present with other problems, such as trauma, hip fracture, motor vehicle accidents, or burns. Injuries occur in as many as 35% of patients and may be more common when a serious underlying condition is diagnosed. The cost to treat and evaluate syncope and related conditions is in the billions of dollars.
Clinicians face a difficult challenge when evaluating patients with syncope. The condition’s prognosis ranges from benign, self-limited outcomes, to a mortality rate as high as 33% at 1 year in patients with a cardiac origin.4 Diagnosis of the etiology of syncope is made difficult by the intermittent nature of the symptoms, the large number of potential causes, and the lack of a criterion for clinical investigation.
The differential diagnoses are listed in Table 1. Estimates are varied depending on research methods and are based on population studies.5
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Patients with syncope frequently undergo extensive investigations that consume significant health care resources. Patients often see primary care physicians and specialists. The average number of doctors exceeds 3 and the average number of visits can exceed 10 per year. The cost of evaluation for syncope has been estimated to range from $2800 to $6560, depending on the evaluation planned. Most often, the evaluation is not useful. The cause may not be diagnosed in as many as 50% of the patients.6 Even so, the cornerstone of the initial evaluation of a patient with syncope must be the clinical history, physical examination, and electrocardiography.4
History
History taking should focus on: 1) characteristic and length of the episode; 2) patient and witnessed accounts; 3) patient age; 4) concomitant (especially cardiac) disease, including family history of sudden death (long QT syndrome, HCM, Brugada syndrome); 5) associated temporally related symptoms (eg, neurological symptoms, angina, palpitations, and heart failure); 6) premonitory (prodromal) symptoms; 7) symptoms on awakening (postsyncope symptoms); 8) the circumstances and situations surrounding the episode; 9) exercise, body position, posture, and emotional state; 10) number, frequency, and timing of previous syncopal episodes; 11) medications; and 12) family history. Medications, such as antihypertensive agents and antidepressants, may not only cause orthostatic hypotension, particularly in the elderly, but also favor neurocardiogenic syncope.
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Physical Examination
After obtaining a careful history, evaluation should continue with a physical examination including the determination of orthostatic vital signs. This should include: supine, sitting, and standing measurements. In patients with idiopathic orthostatic hypotension, diabetes, amyloidosis, and autonomic insufficiency, the blood pressure can drop over several minutes in the standing position and the heart rate may not change.
Carotid sinus massage can give insight into carotid sinus hypersensitivity. There are no firm standards for performing a carotid sinus massage, and the results can be highly variable. Even if positive, other causes of syncope should be explored.
Particular attention should be given to determining the patient’s level of hydration and detecting the presence of significant neurologic abnormalities suggestive of a dysautonomia or a cerebrovascular accident. Evaluation of pulses can provide insight into the presence of a dissecting aneurysm or subclavian steal. The cardiovascular examination is critical.
Murmurs consistent with hypertrophic cardiomyopathy, aortic stenosis, mitral valve prolapse, tricuspid regurgitation, or mitral stenosis may be discovered. The presence of S4 and S3 gallops may suggest the presence of cardiac disease or heart failure.
Evidence of prosthetic valve dysfunction, tumor plop, or presence of permanent pacemaker or implantable defibrillator may provide further clues for the diagnosis of syncope.
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Testing after History and Physical
After history and physical are completed, an electrocardiogram should be obtained. The basis for the electrocardiogram will be discussed shortly. Nonetheless, the electrocardiogram may help in determining whether hospitalization is necessary. Reasons for hospitalization include: 1) to monitor the patient suspected of having a serious, poorly tolerated arrhythmia; 2) to perform tests not readily performed as an outpatient; 3) to formulate and undertake specific treatment plans not possible as an outpatient; 4) medical-legal purposes; 5) when the patient is having multiple, closely spaced episodes; 6) when there is a new neurological abnormality or a suspected neurological cause, new seizure disorder, transient ischemic attack, or stroke; 7) when the patient is elderly, has been injured, or is at risk for serious injury; 8) when there is a severe abnormality on physical examination; 9) when any cardiovascular cause is suspected due to an arrhythmia or hemodynamic problem; 10) when there is symptomatic orthostatic hypotension; and 11) for patients with suspected malignant vasovagal syncope or vasovagal syncope that is difficult to control and causes severe symptoms. The goals of hospitalization must be clear before admission because nondirected admissions for syncope are generally nonproductive. The prognosis and recurrence rate of syncope may not change with hospitalization.
European Society of Cardiology Guidelines
Throughout this paper, the guidelines of the European Society of Cardiology will be presented. These guidelines were created and reviewed by panels of experts over the course of 2 years. The experts were charged with the task of reviewing the literature and developing a consensus opinion regarding specific diagnoses and treatment. These guidelines were developed using expert opinion, randomized controlled studies when available, and finally retrospective analyses, case series, and cohort studies.
The strength of the recommendations have been ranked as follows:
• Class I, when there is evidence and/or general agreement that the procedure or treatment is useful.
• Class II, when usefulness of the procedure or treatment is less well established or divergence of opinion exists among the members of the Task Force.
• Class III, when the procedure or treatment is not useful and in some cases may be harmful.
Pretest probability will aid the clinician in determining the most efficient evaluation. Basic laboratory testing rarely yield useful diagnostic information. In most cases, blood tests will serve only to confirm a clinical suspicion. Pregnancy testing should be considered for women of childbearing age, particularly if tilt-table or electrophysiology testing is being considered.
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Electrocardiography
Electrocardiography identifies a direct cause of syncope in only 5% of patients.7 However, more than 50% of patients evaluated with syncope will have an abnormal ECG. The ECG may provide information that leads to the cause of the syncope. Some findings including bundle branch block, first-degree heart block, or sinus bradycardia suggest a bradyarrhythmic cause of syncope. QRS duration > 110 ms in leads V1-3, RBBB, and precordial T wave inversion may suggest arrhythmogenic right ventricular dysplasia. It is therefore recommended to obtain an ECG in all patients with syncope, with the possible exception of young healthy patients with an obvious situational or vasovagal cause.
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Echocardiography
The role of echocardiography has yet to be defined in a rigorous scientific manner. The recommendations to use echocardiography are largely based on epidemiologic studies and expert opinion. Echocardiograms are useful when there is evidence of structural heart disease, suspected arrhythmic syncope, or an abnormal electrocardiogram. One retrospective study of 128 patients admitted for syncope found that 64% underwent echocardiography. The results were negative or provided no additional diagnostic information among the 46% of patients who had no clinical evidence of heart disease by history, physical examination, or ECG. Among the patients in whom cardiac disease was suspected, the echocardiogram confirmed the suspected diagnosis in 48% and ruled out the diagnosis in 52%.8 This study suggests echocardiography may be best used in patients in whom cardiac disease is suspected and to quantify the degree of disease. Further investigation will be needed to confirm these results.
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Electrocardiographic Monitoring
Electrocardiographic monitoring is indicated in the evaluation of syncopal patients when an arrhythmic source is suspected. Prolonged monitoring is frequently necessary due to the transient nature of symptoms. Inpatient telemetry and Holter monitors have been used, but in the outpatient setting, event recorders are more likely to yield results. The American College of Physicians position paper summarized the results of Holter monitoring. In 4% of cases, a correlation was found between patients’ symptoms and a diagnostic arrhythmia. In 15% of cases, symptoms were noted without arrhythmia. This may possibly exclude an arrhythmic cause of syncope in these patients, and increases the diagnostic yield of Holter monitoring to 19%. Another 14% of these patients had an arrhythmia on monitoring. Some of these arrhythmias, such as complete heart block and sustained ventricular tachycardia, led to treatment. It is felt that the external loop recorders with extended monitoring may increase the diagnostic yield.
Implantable Loop Recorders
The implantable loop recorder is a new device that can be used to record electrocardiograms. Once activated by the patient in response to a syncopal event, it can retain electrocardiograms several minutes before activation and a few minutes afterward. This device is implanted in the left pectoral region with local anesthetic. The recorder can be explanted after a diagnosis is made or at battery depletion (2 years). In one study, implantable loop recorder monitoring in 85 patients enabled symptomatic correlation in 68% of patients and an arrhythmia was documented in 25%. The overall yield of the device was 59% including a positive yield (arrhythmia or neurocardiogenic syncope) of 27% and a negative yield (symptoms without arrhythmia) of 32%.9
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Exercise Testing
Exercise testing in syncope has not been well studied. The direct yield of identifying a cause of syncope is probably less than 1%.4 It may play a greater role in patients with exertion-related syncope or exercise-induced arrhythmias.
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Electrophysiology Studies
Electrophysiology studies are invasive tests that use programmed electrical stimulation and monitoring with intracardiac and surface ECGs. The propensity to develop tachycardia can be assessed with these relatively safe but expensive tests. Criteria for a positive test include inducible, sustained monomorphic ventricular tachycardia, prolonged sinus node recovery time, prolonged His-ventricular interval, spontaneous infra-His block, and supraventricular tachycardia with hypotension. The American College of Physicians position paper on syncope summarized the body of evidence that shows a clear link between positive electrophysiology studies and the presence of organic heart disease. Among patients with organic heart disease, an estimated 21% of patients have inducible ventricular tachycardia during electrophysiology studies, and 34% have evidence of conduction disease. In contrast, in patients without organic heart disease, less than 1% have inducible ventricular tachycardia and approximately 10% have bradycardia.
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Neurologic Testing
The role of neurologic testing has remained in question as well. Recent consensus opinion has been that in the absence of suggestive signs and symptoms, neurologic studies have been shown to be low yield in patients with syncope.
Electroencephalography was widely used in the 1980s. Studies show it is of little use in unselected patients without seizure activity. The yield may be as low as 1 to 2%.10 Head computed tomography is another test that is currently recommended in patients with focal neurologic symptoms and signs or seizure activity or to rule out hemorrhage. This test has a low yield in patients with syncope as well, estimated as low as 4%.11
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Tilt-Table Testing
Tilt-table testing has evolved into the procedure of choice for the evaluation of syncope of unknown origin, especially in patients with structurally normal hearts. The tilt-table has been used extensively in the diagnosis of neurocardiogenic syncope, both drug-free and with pharmacologic interventions. Unfortunately, the studies have used different protocols making it difficult to compare the data accumulated. However, patients with a known vasovagal cause of syncope have positive tilt-table sensitivity of 71-87%.12 Specificity of the tests have been close to 90%.12
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Diagnosis of Syncope
The diagnosis of syncope is based on separating patients into diagnostic, suggestive, and unexplained categories. The patients with unexplained syncope are further divided into groups based on the presence of organic heart disease. Echocardiography and/or exercise treadmill tests are used to evaluate and quantify the degree of heart disease. Holter monitor and EP studies are reserved for patients with confirmed heart disease. Tilt testing, psychiatric evaluation, and loop recorders are reserved for patients with unexplained syncope and no suspected heart disease. Several algorithms have been created to guide the clinician. These are based on the frequency of syncope.
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Neurocardiogenic Syncope
Neurocardiogenic syncope may require treatment for severe cases. Most patients will have a benign and self-limited course, and of those requiring pharmacologic treatment, most will become asymptomatic on a single agent. The initial therapy, however, is aimed at increasing dietary salt and fluid intake. Increase in the blood volume may reduce the development of orthostatic hypotension. Patients should be educated to avoid situations known to provoke syncope such as extreme heat, dehydration, postexertional standing, alcohol, and certain medications. Elastic support hose (Jobst stockings, up to and including the thigh) may be used to treat this condition as well.
In younger patients who do not respond to nonpharmacologic therapy, the mineralocorticoid fludrocortisone is the next step. Grubb and colleagues evaluated 21 patients, and 20 experienced no further syncope on therapy. Ten of the 21 converted from a positive tilt-table test to a negative study.13 Fludrocortisone has a large amount of safety data and is relatively affordable to use. It has been used extensively in the treatment of orthostatic hypotension.
The most widely used pharmacologic agents for the treatment of neurocardiogenic syncope in older patients are beta-blockers. Mahanonda et al published a randomized placebo-controlled study comparing beta-blocker with placebo. Forty-two patients with a positive tilt-table test and history of syncope were randomized. After 1 month of treatment, 1 of 21 control patients and 13 of 21 atenolol patients had a negative tilt test. Patients on atenolol also reported decreased symptoms.14
Several other drugs have been investigated as well. These include midodrine, 2.5-10 mg t.i.d. phenylephrine, 60 mg every 6-12 hours, and fluoxetine, 10-20 mg q.d. (requires several weeks of therapy) have all been tried with some success.
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Cardiac Syncope
Detailed discussion of cardiac syncope is beyond the scope of this discussion. However, clinicians are reminded to be vigilant in evaluating the patient’s ECG for signs of arrhythmia, infarction, or congenital and/or structural heart disease that may be a cause of syncope. Recall that cardiac causes of syncope carry a significantly higher mortality rate than noncardiac causes. This however, may be related to the severity of the underlying illness rather than the syncope itself. Treatment of syncope associated with obstructive cardiac disease, such as hypertrophic cardiomyopathy and aortic stenosis, should focus first on relieving the obstruction.
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Restrictions
The management of syncope includes such everyday items as restrictions on driving. The decision to continue driving should be based on an individual assessment of potential future risk and applicable laws in each state. The AHA/NASPE position paper makes the following recommendations regarding neurally mediated syncope:
• Mild vasovagal episode (presyncope only, with warning, only with standing, clear precipitating causes, infrequent): no restrictions on private driving.
• Severe vasovagal syncope (true loss of consciousness, without warning, in any position, without clear precipitating causes, or frequent): private driving permitted once syncope treated and with documented control for 3 months.
• Severe untreated vasovagal syncope: driving completely prohibited.
Conclusion
In summary, syncope is a common condition that presents an interesting challenge to physicians. It is a manifestation of many different disease processes, whose prognoses range from benign to life-threatening. Difficulty in accurately diagnosing the etiology of the syncope further vexes physicians. Despite a wide array of expensive and sophisticated tests that can aid in diagnosing the root cause of syncope, extensive testing and repeated investigations frequently do not provide a definitive diagnosis and have a low yield. The key to the initial work-up remains a detailed history and physical examination that allows judicious use of diagnostic tools. Clinicians are reminded to stratify the patients with evidence of heart disease and a positive family history of sudden cardiac death or syncope into a particularly high risk for death group. No series of tests is universally applicable, and extensive undirected testing and repeat hospitalizations are frequently unrewarding and expensive. Fortunately, many of the patients without structural heart disease will not require specific pharmacologic therapy, and many will not have recurrence of their symptom. The astute clinician will discover clues from the history and physical that will guide the initial management of the patient.
References
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2. Dermaksian G, Lamb LE. Syncope in a population of healthy young adults. JAMA. 1958;168:1200-1207.
3. Lipsitz LA, et al. Syncope in an elderly, institutionalized population: Prevalence, incidence, and associated risk. Q J Med. 1985; 55:45-54.
4. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore). 1990;69:160-175.
5. Schnipper JL, Kappor WN. Diagnostic evaluation and management of patients with syncope. Med Clin North Am. 2001;85: 423-456.
6. Krahn AD, et al. The high cost of syncope: Cost implications of a new insert able loop recorder in the investigation of recurrent syncope. Am Heart J. 1999;137:870-877.
7. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope: Part 1. Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med. 1997;126:989-996.
8. Recchia D, Barzilai B. Echocardiography in the evaluation of patients with syncope. J Gen Intern Med. 1995;10(12):649-655.
9. Krahn AD, et al. Use of an extended monitoring strategy in patients with problematic syncope. Circulation. 1999;99: 406-410.
10. Davis TL, Freemon FR. Electroencephalography should not be routine in the evaluation of syncope in adults. Arch Intern Med. 1990;150:2027-2029.
11. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope: Part 2. Unexplained syncope. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med. 1997;127:76-87.
12. Kapoor WN, et al. Upright tilt testing in evaluating syncope: A comprehensive literature review. Am J Med. 1994;97:78-88.
13. Grubb BP, et al. The use of head-upright tilt testing in the evaluation and management of syncope in children and adolescents. Pacing Clin Electrophysiol. 1992;15:742-748.
14. Mahanonda N, et al. Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results. Am Heart J. 1995; 130:1250-1253.
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