Syncope: Step-by-Step Through the Workup

ABSTRACT: Syncope is often benign and self-limited; however, it may sometimes indicate a life-threatening condition. Advanced age, heart disease, and abnormal ECG findings are associated with potentially adverse outcomes. The initial evaluation, which consists of a careful history taking, physical examination, and ECG, often suffices to make the diagnosis. Neurally mediated disorders, the most common cause of syncope, are usually benign. Cardiac syncope, which usually requires admission and further assessment, may result from rhythm disturbances or from outflow obstruction attributable to structural or pathophysiologic mechanisms. Patients with cardiac syncope may be evaluated with echocardiography, Holter monitoring, stress testing, loop event recorders, or electrophysiologic studies. Other causes of syncope include orthostatic hypotension, use of certain medications, a primary neurologic disorder, and psychiatric disturbance. A significant number of patients have unexplained syncope. Key words: syncope, diagnosis, neurocardiogenic ______________________________________________________________________________________________________________ Syncope is a transient loss of consciousness and postural tone caused by an abrupt decrease in cerebral blood flow and followed by a spontaneous, complete recovery.1 The reticular activating system, a part of the hindbrain that is intricately tied to consciousness and is particularly vulnerable to alterations in homeostasis, appears to be implicated.2 Once the patient is recumbent, blood flow to the brain is restored. Syncopal episodes occur in persons of any age, ethnicity, or health status. They account for 1% to 3% of all emergency department (ED) visits and approximately 5% of hospital admissions through the ED.3 Syncope is a manifestation of underlying pathology. Although it is often benign and self-limited, it may indicate a serious chronic disease or potentially fatal disorder. Of the cases of syncope in which a cause is identified, approximately 25% to 30% of these causes are potentially serious. Among other variables, advanced age, heart disease, and abnormal ECG findings are associated with potentially adverse outcomes. In patients with significant heart disease, a syncopal episode may presage sudden cardiac death. The challenge for the clinician is to establish the cause of the syncopal episode and assess the patient’s prognosis. Risk stratification depends on the patient’s age and comorbidities, as well as on features of the syncopal episode itself. Characteristics of an episode—such as the duration of unconsciousness, type of activity in which the patient was engaged at onset, and the presence of premonitory or concomitant symptoms—may point to a specific cause. Guidelines for evaluation and risk stratification have been developed in recent years.4-10  Although these guidelines have yet to be validated prospectively, they offer a  framework for diagnosis and management. In this article, I review the diagnostic approach to the patient with syncope. WHEN IS IT SYNCOPE? The initial step in the evaluation is to determine whether the syncopal event represents true syncope or an alternative condition.11  Some patients who say they “passed out” or “fell out” may have actually had a seizure or a drop attack. Seizures are typically associated with a premonitory aura, tonic-clonic movements during unconsciousness, and a postictal period associated with prolonged decreased alertness and confusion once the patient regains consciousness. Drop attacks involve a loss of postural tone without alteration of consciousness. Table 1 lists some of the features that help differentiate syncope from seizures and drop attacks. IMPLICATIONS OF AGE Most young, healthy adults who have a single syncopal episode and a normal initial evaluation require no further workup. In these patients, the cause of syncope is generally neurocardiogenic, psychiatric, or situational. Similarly, syncope in children is usually benign (Box). In contrast, elderly patients with significant comorbidities may require hospital admission and immediate intervention. The incidence of syncope increases with age, with a sharp rise at age 70 years.12  In elderly persons, syncope is associated with increased morbidity.1-3  As patients age, they may have significant comorbidities, such as aortic stenosis, myocardial infarction (MI), transient ischemic attack (TIA), and carotid sinus syndrome, which can all cause syncope. Medication use, another risk factor for syncope, may preferentially affect elderly persons. Not only are they more susceptible to the effects of medication, but they are also more likely to be taking multiple medications that may adversely interact with each other and precipitate a syncopal episode. CAUSES The principal causes of syncope are summarized in Table 2.  Neurally mediated causes.  In population studies, neurally mediated disorders are the most common cause of syncope in cases in which a cause is identified.2,3,12  Neurocardiogenic syncope (NCS) (vasovagal syncope) encompasses situational syncope (such as that associated with coughing, swallowing, micturition, or defecation) and carotid sinus syndrome/ hypersensitivity. Vasovagal spells typically occur while the patient is in an upright position and may be preceded by dizziness, warmth, and diaphoresis. Some episodes are associated with exposure to a noxious stimulus. NCS is usually benign, and once a neurally mediated cause is established, further acute intervention is rarely necessary. Cardiac causes. In contrast, cardiac syncope, the second most common type of syncope, may be associated with increased morbidity and mortality and often portends a poor prognosis. Cardiac syncope may result from rhythmic disturbances (both bradyarrhythmic and tachyarrhythmic) or from outflow obstruction attributable to structural or pathophysiologic mechanisms. Patients with heart disease are more likely to have cardiogenic syncope, and in these patients, the incidence of negative outcomes, including death, tends to be higher.1,8,9,11 Evidence suggests that the prognosis for these patients depends more on the underlying heart disease than on the syncope, regardless of the cause of the syncope.11 However, syncope may be the presenting symptom of a diseased heart. Patients with low-flow states attributable to heart failure or poor left ventricular function, as well as those with outflow obstruction caused by structural heart disease or valve dysfunction, may present with syncope. A related subset of patients may have syncope in the setting of functional outflow impairment, as is sometimes seen in pulmonary embolus or pulmonary hypertension. Other causes. Orthostatic hypotension is a common cause of syncope, especially if symptoms can be reproduced or elicited when the patient moves from a recumbent to an upright position. When patients are placed in an upright position, an evident drop of more than 20 mm Hg in the systolic blood pressure that coincides with presyncopal symptoms suggests orthostatic hypotension. If no symptoms are elicited during the postural change, another cause may be involved.8  However, even when orthostatic hypotension is identified, this may not be the cause of syncope, and more serious causes should be excluded if possible. Orthostasis in syncope has equivocal sensitivity and specificity, and thus, its predictive value is questionable.2 Medication use is another frequent cause of syncope, particularly in elderly persons.13  Agents commonly implicated include antihypertensives and antidepressants. Patients who take antiarrhythmic medications require careful evaluation, because many of these agents have arrhythmogenic properties. Syncope attributable to a primary neurologic disorder is less common; it may occur as a result of a TIA or migraine.1,9  Seizures can often be clinically differentiated from syncope, especially if the episode is witnessed. A psychogenic mechanism has been identified in a growing number of patients with syncope.2,9  This mechanism is more prevalent than previously recognized, and the recent decrease in cases of “unexplained” syncope is attributable in part to greater awareness of a psychiatric mechanism. Psychogenic syncope remains a diagnosis of exclusion. EVALUATION Because of the significant number of possible causes of syncope, a rational management strategy is best directed at identifying patients at risk for adverse outcomes.3,8,9  Standardized stepped approaches may help guide the evaluation (Algorithm). It is not known, however, whether adherence to these guidelines improves patient outcomes. The core of the workup includes a thorough history taking, a focused physical examination, and electrocardiography.8  The cumulative diagnostic yield of these procedures is more than 50%, with 5% being contributed by electrocardiography.2,8,9  Despite a low diagnostic yield, the utility of electrocardiography is demonstrated by the fact that up to 50% of patients with unexplained syncope have ECG abnormalities that predict a poor prognosis.5,7 History. Inquire about the patient’s activity just before the syncopal episode. Determine whether he or she was standing, sitting, or lying down, or if the syncope followed exertion.8,9,11  Ask about prodromal symptoms, such as light-headedness, diaphoresis, and blurred vision; these often precede NCS. A severe headache may precede neurogenic syncope. Palpitations, chest pain, or shortness of breath are often associated with cardiac syncope, as is the absence of a prodrome.1-3  Tongue-biting or urinary incontinence may suggest a seizure. Review the patient’s medications and note any recent additions or dosage changes. Inquire about the use of alcohol and illicit drugs. An evaluation of the family history—including a history of sudden cardiac death—is required. Obtain a witness account, if possible, to determine whether the patient exhibited seizure activity or postictal confusion. Physical examination. The cardiovascular and neurologic systems are the focus of the physical examination. Findings such as jugular venous distention, pulmonary rales, or a cardiac gallop consistent with congestive heart failure may suggest a cardiac cause.8,13  Evaluate patients with orthostasis for signs of hypovolemia and internal bleeding. Palpate extremity pulses, and investigate unequal pulses or blood pressures. Some experts advocate carotid massage as part of the evaluation, particularly in elderly patients, in whom carotid sinus syndrome may be a fairly common cause of syncope.8,9  Exercise caution when performing this test, because in elderly persons carotid massage may trigger an exaggerated vagal response or carotid plaque dislodgement, which may result in an embolic event. Contraindications to carotid massage include audible bruit, history of recent stroke or MI, ventricular tachycardia, and evidence of a new neurologic deficit.9  Massage is performed on the carotid arteries sequentially, never simultaneously. However, because of the high prevalence of syncope in elderly persons, the syncopal episode in question may not have been the result of carotid sinus hypersensitivity, even if carotid massage yields a positive response. A full neurologic examination is required to determine whether focal signs are present. Bear in mind that the patient may have suffered an injury during the episode as a result of a fall. Check for signs of trauma, and evaluate the cervical spine. Electrocardiography. Electrocardiography is recommended in virtually all patients with syncope.2,8 In addition to ongoing rhythm disturbances, it may show conduction abnormalities, such as bundlebranch block and atrioventricular block. Abnormal ECG findings may suggest a diagnosis: for example, a prolonged QT interval may point toward an arrhythmia, a right-sided heart-strain pattern might indicate pulmonary hypertension or embolus, and significant left ventricular hypertrophy may suggest outflow obstruction. Evidence of ongoing or previous ischemia, such as dynamic T-wave or ST-segment changes or significant Q waves, also suggests a cardiac cause. FURTHER DIAGNOSTIC TESTING A thorough history, physical examination, and electrocardiography will lead to a diagnosis in up to 50% of patients with syncope; in the remaining patients, other tests may be required. In patients with suspected cardiac syncope, further testing may be warranted to help identify the cause and direct treatment. In contrast, no further workup is needed in patients in whom a benign cause is strongly suspected (ie, young, healthy persons who have normal physical and ECG findings and whose syncope is thought to be vasovagal). The goal of additional testing is to find treatable causes, and any information gleaned should be weighed in terms of its effect on prognosis. In cases of suspected cardiac syncope, echocardiography ins the usual next step in the diagnostic workup. An echocardiogram may identify congenital or acquired structural heart disease as well as cardiac dysfunction.2  In patients with suspected cardiac syncope, stress testing is performed as well, usually after an echocardiogram has shown no significant outflow barriers.9,13  Stress testing is used to evaluate for ischemia or exercise-induced arrhythmias, but its diagnostic yield is unknown. In patients with suspected arrhythmic syncope (including those who report prodromal palpitations or no prodrome, or who have abnormal ECG findings), 24-hour Holter monitoring is commonly performed. In high-risk patients admitted for syncope, inpatient telemetry monitoring may replace or precede Holter monitoring. The inherent limitation of this modality is its duration: syncope, even if recurrent, tends to occur sporadically, and a 24-hour monitoring period is usually insufficient. Holter monitoring is indicated in patients with suspected arrhythmic syncope and in those with suspected organic heart disease (including coronary artery disease, congestive heart failure, valvular disease, and cardiomyopathy) or abnormal ECG findings. Loop event recorders are external (or implantable) recording devices that store in their memory the previous 2 to 5 minutes and subsequent 60 seconds of a patient’s cardiac rhythm. These devices are typically worn for a month at a time, although the newer implantable recorders may be left in place for up to 18 months. If the patient experiences a syncopal episode while wearing the loop recorder, the information stored in the recorder can be transmitted via telephone line so that any rhythm abnormalities can be identified. The limitations of this test include compliance (the patient must be wearing the recorder at the time of the episode, and he must phone in the information), and the duration of monitoring (syncope may not recur during the time the patient is being monitored). Loop recorders are indicated in patients without known or suspected heart disease who have recurrent syncope.9 Electrophysiologic study (EPS) uses electric stimulation and monitoring to identify inducible arrhythmias, particularly unifocal ventricular tachycardia. The principal limitations of the test are its invasive nature and its cost. After echocardiography, EPS is the preferred testing modality for elderly patients with presumed arrhythmic syncope and for all patients with organic heart disease. In patients with documented heart disease, the diagnostic yield may be as high as 50%.9  EPS rarely provides useful diagnostic information in patients with normal hearts. During tilt-table testing the patient is initially monitored in a supine position and then quickly shifted to a semi-upright position for 45 minutes; changes in vital signs and symptoms are recorded. Although tilt testing may unmask autonomic instability, the test has limited utility because of its poor sensitivity and specificity. Protocols that enhance the predictive value of tilt testing include the addition of agents such as nitrates and isoproterenol.1,3  Tilt testing may help confirm the diagnosis in patients with recurrent syncope in whom a cardiac cause has been excluded and whose syncope is thought to be attributable to neurocardiogenic mechanisms. Additional diagnostic tests are rarely indicated in the initial workup.8 Electroencephalographic monitoring is now typically performed on an outpatient basis only in those patients whose history suggests a seizure. Head CT is indicated only if focal neurologic signs are found on examination, if there is evidence of significant head trauma, or if a headache preceded or followed the episode. Routine blood tests have a low yeild, especially in the absence of other clinical evidence that points to a specific diagnosis.3  However, management guidelines for syncope often include determination of serum glucose levels and hematocrit.4,7,14  In addition, all women of childbearing age should have a urine pregnancy test.2  Although the literature on syncope in pregnancy is limited,8  an ectopic pregnancy may present as syncope, even in the absence of abdominal pain or vaginal bleeding. In late pregnancy, the gravid uterus may cause aortocaval compression that results in syncope. Once other medical causes of syncope have been reasonably excluded, a thorough psychiatric evaluation should be performed. The usual patient with psychogenic syncope is a young person who experiences frequent syncopal episodes without sustaining mechanical injuries. The evaluation includes the hyperventilation maneuver, during which the patient is directed to breathe deeply at 20 to 30 breaths per minute with his mouth open. In many persons with psychogenic syncope, this test reproduces syncopal or presyncopal symptoms.9 Unexplained syncope. A significant number of patients have syncope for which the cause cannot be determined despite comprehensive diagnostic evaluation, including the tests described above. More than one third of patients enrolled in studies in the 1980s had unexplained syncope.12 A specific cause for the spells was not identified after a thorough initial evaluation and additional testing. In contrast, a European study found a reduction in unexplained syncope from 54% to 17.5% once a specific diagnostic algorithm was applied.4 WHEN TO ADMIT Patients at high risk for a poor outcome based on the initial history, physical examination, and ECG may need to undergo further diagnostic and therapeutic interventions. These include pacemaker placement in patients with malignant arrhythmias, cardiac catheterization in patients with significant ischemia possibly related to exercise-induced syncope, and anticoagulation in those with pulmonary embolus. Conversely, patients with a benign condition, such as vasovagal syncope, have a good prognosis and usually do not require admission. In fact, if the episode is isolated and apparently attributable to a benign cause, no further workup is indicated. Recent research has attempted to define low-risk criteria, including a lack of cardiopulmonary or focal neurologic symptoms or signs, normal vital signs, and normal ECG findings.14  The low recurrence rate in patients with a negative diagnostic evaluation suggests that they do not require an aggressive workup.15 Because there is no gold standard for the evaluation of syncope, determining which patients must be admitted and which may be safely discharged requires a systematic approach.14,16  The rationale for admission should be related to the perceived risk of adverse outcome, particularly if a cardiac cause is suspected.6  Compared with healthy counterparts, patients with heart disease are 4 times as likely to have cardiogenic syncope and 50% less likely to have vasovagal syncope.12  In a recent study, 11.5% of unselected syncope patients had a “serious outcome” by day 7 after presentation.7 Patients at risk were older and had cardiac disease and/or abnormal ECG results. These findings support the practice of admitting patients in whom syncope is thought to be a symptom of heart disease. REFERENCES: 1. Kapoor WN. Syncope. N Engl J Med. 2000;343: 1856-1862. 2. Blok BK, Newman TM. Syncope. In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergency Medicine: A Comprehensive Study Guide. 6th ed. New York: McGraw-Hill; 2004:359-364. 3. Sun BC, Emond JA, Camargo CA Jr. Characteristics and admission patterns of patients presenting with syncope to US emergency departments, 1992-2000. Acad Emerg Med. 2004;11:1029-1034. 4. Ammirati F, Colivicchi F, Santini M. Diagnosing syncope in clinical practice. Implementation of a simplified diagnostic algorithm in a multicentre prospective trial—the OESIL 2 study (Osservatorio Epidemiologico della Sincope nel Lazio). Eur Heart J. 2000;21:935-940. 5. Sarasin FP, Hanusa BH, Perneger T, et al. A risk score to predict arrhythmias in patients with unexplained syncope. Acad Emerg Med. 2003;10: 1312-1317. 6. Shen WK, Decker WW, Smars PA, et al. Syncope Evaluation in the Emergency Department Study (SEEDS): a multidisciplinary approach to syncope management. Circulation. 2004;110:3636-3645. 7. Quinn JV, Stiell IG, McDermott DA, et al. Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes. Ann Emerg Med. 2004;43:224-232. 8. 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. 9. 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;127:76-86. 10. Kapoor WN. A standardized sequential clinical examination identified probable causes of syncope in 69% of patients. ACP J Club. 2002;136:77. 11. Kapoor WN. Current evaluation and management of syncope. Circulation. 2002;106:1606-1609. 12. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347:878-885. 13. Arthur W, Kaye GC. Important points in the clinical evaluation of patients with syncope. Postgrad Med J. 2001;77:99-102. 14. Morag RM, Murdock LF, Khan ZA, et al. Do patients with a negative emergency department evaluation for syncope require hospital admission? J Emerg Med. 2004;27:339-343. 15. Olshansky B. Syncope evaluation at a crossroad: for which patients? Circulation. 2001;104:7-8. 16. Oh JH, Hanusa BH, Kapoor WN. Do symptoms predict cardiac arrhythmias and mortality in patients with syncope? Arch Intern Med. 1999;159: 375-380. 17. Massin MM, Bourguignont A, Coremans C, et al. Syncope in pediatric patients presenting to an emergency department. J Pediatr. 2004;145:223-228. 18. Driscoll DJ, Jacobsen SJ, Porter CJ, Wollan PC. Syncope in children and adolescents. J Am Coll Cardiol. 1997;29:1039-1045.