Syncope: Evaluation and Differential Diagnosis LLOYD A

Syncope: Evaluation and Differential Diagnosis LLOYD A. RUNSER, MD, MPH; ROBERT L. GAUER, MD; and ALEX HOUSER, DO Womack Army Medical Center, Fort Bragg, North Carolina

Syncope is an abrupt and transient loss of consciousness caused by cerebral hypoperfusion. It accounts for 1% to 1.5% of emergency department visits, resulting in high hospital admission rates and significant medical costs. Syncope is classified as neurally mediated, cardiac, and orthostatic hypotension. Neurally mediated syncope is the most common type and has a benign course, whereas cardiac syncope is associated with increased morbidity and mortality. Patients with presyncope have similar prognoses to those with syncope and should undergo a similar evaluation. A standardized approach to syncope evaluation reduces hospital admissions and medical costs, and increases diagnostic accuracy. The initial assessment for all patients presenting with syncope includes a detailed history, physical examination, and electrocardiography. The initial evaluation may diagnose up to 50% of patients and allows immediate short-term risk stratification. Laboratory testing and neuroimaging have a low diagnostic yield and should be ordered only if clinically indicated. Several comparable clinical decision rules can be used to assess the short-term risk of death and the need for hospital admission. Low-risk patients with a single episode of syncope can often be reassured with no further investigation. High-risk patients with cardiovascular or structural heart disease, history concerning for arrhythmia, abnormal electrocardiographic findings, or severe comorbidities should be admitted to the hospital for further evaluation. In cases of unexplained syncope, provocative testing and prolonged electrocardiographic monitoring strategies can be diagnostic. The treatment of neurally mediated and orthostatic hypotension syncope is largely supportive, although severe cases may require pharmacotherapy. Cardiac syncope may require cardiac device placement or ablation. (Am Fam Physician. 2017;95(5):303-312. Copyright © 2017 American Academy of Family Physicians.)

More online yncope is a sudden, brief, and tran- within two years.8,9 Historically, neurally at http://www. sient loss of consciousness caused mediated and orthostatic hypotension syn- aafp.org/afp. by cerebral hypoperfusion.1 Other cope have not conferred an increased risk of CME This clinical content nontraumatic loss of consciousness death10; however, in a recent study, healthy conforms to AAFP criteria Ssyndromes include seizures, cataplexy, met- adults with a diagnosis of syncope had for continuing medical education (CME). See abolic disorders, acute intoxications, verte- higher rates of all-cause mortality, recur- CME Quiz Questions on brobasilar insufficiency, transient ischemic rent syncope, cardiovascular events, and page 288. attack, cerebrovascular accident, and psy- pacemaker or implantable cardioverter- Author disclosure: No rel- chogenic pseudosyncope.2,3 defibrillator placement compared with evant financial affiliations. Syncope accounts for 1% to 1.5% of matched controls. Patients 44 to 75 years of ▲ Patient information: all emergency department visits, 250,000 age had the highest risk.11,12 A handout on this topic is annual hospital admissions, and a median Management of syncope remains a chal- available at http://www. 4,5 aafp.org/afp/2017/0301/ hospital cost of $8,500. Approximately lenge, particularly in identifying patients p303-s1.html. 40% of the U.S. population will experience a with potentially life-threatening etiolo- syncopal episode in their lifetimes, and 30% gies. Lack of physician knowledge, a desire to 50% will be admitted to the hospital for to reassure the patient or clinician, and the further evaluation.6,7 The etiology is unex- fear of medicolegal ramifications result in plained in up to one-third of cases.8 overuse of diagnostic tests.13 A standardized Although syncope is associated with seri- approach for evaluating patients with syn- ous risks, short-term mortality is low (i.e., cope reduces admissions, hospital costs, and 0.7% at 10 days and 1.6% at 30 days). At number of tests performed, and increases one year, the mortality rate is 8.4%; one- accuracy of diagnosis.14 Only 10% to 15% third of these are attributed to cardiovascu- of patients will remain undiagnosed after lar causes. Approximately 25% of patients a comprehensive evaluation using current with syncope will experience another event guidelines.15,16

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Evidence Clinical recommendation rating References

Patients who present with presyncope should be evaluated similarly to those who present with syncope. C 20, 21 Patients with syncope and evidence of congestive heart failure or structural heart disease, abnormal C 1, 25, 27, 29 electrocardiographic findings, or a family history of sudden death should be admitted to the hospital for emergent evaluation. Patients presenting with syncope should have orthostatic blood pressure measurements and standard C 1, 2, 25, 27, 29 12-lead electrocardiography. Laboratory and imaging studies should be ordered for patients with syncope only if clinically indicated C 1, 27, 39, 40, 42, by the history and physical examination. 43, 50, 51 Implantable loop recorders increase diagnostic yield, reduce time to diagnosis, and are cost-effective for C 1, 39, 44-48 suspected cardiac syncope and unexplained syncope. Patients with syncope who are at low risk of adverse events (e.g., those with symptoms consistent with C 1, 25, 27, 29 vasovagal or orthostatic hypotension syncope, no history of heart disease, no family history of sudden cardiac death, and normal electrocardiographic findings) may be safely followed without further intervention or treatment.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

Classification and Etiology prevalent form of orthostatic intolerance, affecting Syncope is classified as cardiac, neurally mediated approximately 500,000 persons in the United States. (reflex), and orthostatic hypotension(Table 1).1,17 The dif- Younger adults, predominantly women who report ferential diagnosis should include nontraumatic causes symptoms of postural presyncope, are more likely to of transient loss of consciousness. Rare causes include have this condition.19 subclavian steal syndrome, pulmonary embolism, acute myocardial infarction, acute aortic dissection, leaking PRESYNCOPE aortic aneurysm, subarachnoid hemorrhage, and cardiac Presyncope is poorly studied, and the true incidence tamponade.2,3 is unknown. A study of 881 patients presenting to Neurally mediated syncope is the most common type, the emergency department with presyncope showed comprising approximately 45% of cases.6,10,18 It can be a 30-day risk of serious outcomes of 5% and a mortal- vasovagal, situational, or secondary to carotid sinus ity rate of 0.3%.20 Emergency physicians had difficulty hypersensitivity. The pathophysiology is complex, con- stratifying patients at increased risk of adverse outcomes, sisting of an interaction between autonomic systems regardless of presumed etiology. A prospective observa- paradoxically favoring parasympathetic or vagal tone, tional study (n = 244) compared adverse outcomes and which causes bradycardia and hypotension. Cardiac syncope occurs in approximately 20% of syncope presentations. It is most BEST PRACTICES IN NEUROLOGY: RECOMMENDATIONS often caused by an arrhythmia, and less FROM THE CHOOSING WISELY CAMPAIGN often by a structural cardiac abnormality. Sponsoring In a prospective cohort study, patients with Recommendation organization cardiac syncope had a twofold increase in mortality over 17 years.10 The presence of Avoid computed tomography of the head in American College cardiovascular disease predicts a cardiac eti- asymptomatic adult patients in the emergency of Emergency department with syncope, insignificant trauma, and Physicians ology of syncope with 85% to 94% sensitiv- a normal neurologic evaluation. 16 ity and 64% to 83% specificity. In the evaluation of simple syncope and a normal American College of Orthostatic hypotension syncope has neurologic evaluation, do not obtain brain imaging Physicians an incidence of approximately 10% and studies (computed tomography or magnetic resonance imaging). is typically characterized by posturally Do not perform imaging of the carotid arteries for American Academy induced hypotension, most often related simple syncope without other neurologic symptoms. of Neurology to impaired increase in systemic vascular resistance. Associated factors include Source: For more information on the Choosing Wisely Campaign, see http://www. medication effects, volume depletion, acute choosingwisely.org. For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see http://www.aafp.org/afp/recommenda hemorrhage, and autonomic dysfunction. tions/search.htm. Postural tachycardia syndrome is the most

304 American Family Physician www.aafp.org/afp Volume 95, Number 5 ◆ March 1, 2017 Syncope Table 1. Classification of Syncope

Syncope type Scenario Clinical features

Cardiac syncope Arrhythmia (e.g., bradyar- Generally abrupt and unprovoked; palpitations Abnormal electrocardiographic findings, family history rhythmias, ventricular may precede symptoms of sudden death, personal history of heart disease, tachyarrhythmias, sudden onset of palpitations, symptoms during or supraventricular tachyar- after exertion while in supine or prone position rhythmias), pacemaker dysfunction, channelopathies Obstructive cardiomyopathy Hypertrophic cardiomyopathy or exertional Often asymptomatic; may cause arrhythmias, chest syncope in persons with a family history of pain, shortness of breath, or syncope; dynamic sudden cardiac death systolic murmur that intensifies from squatting to standing or during Valsalva maneuver Structural cardiac disease Acute myocardial infarction or ischemia Diaphoresis, exertional chest pain, nausea, shortness of breath; rare cause of syncope Arrhythmogenic right ventricular Asymptomatic, atypical chest pain, dizziness, exertional cardiomyopathy syncope, family history of sudden cardiac death, palpitations, right ventricular structural abnormalities Infiltrative (e.g., amyloidosis, Arrhythmias, heart block, heart failure hemochromatosis, sarcoidosis) Valvular disease (e.g., aortic stenosis, mitral Symptoms dependent on severity; severe aortic stenosis, pulmonary stenosis) stenosis can manifest with congestive heart failure, exertional angina, or syncope Other structural disease Acute aortic dissection Hypotension or shock, severe sharp chest pain with or without radiation to the back, history of hypertension Cardiac masses (e.g., atrial myxoma, cardiac Arrhythmia via direct invasion, embolization, heart tumors) failure, systemic symptoms, valvular regurgitation Cardiac tamponade Elevated jugular venous pressure, hypotension, pulsus paradoxus, sinus tachycardia Pulmonary hypertension Often asymptomatic; may cause fatigue and shortness of breath Saddle pulmonary embolus Acute shortness of breath, chest pain, hypoxia, right heart strain, sinus tachycardia Neurally mediated (reflex) syncope Carotid sinus syndrome/ Head rotation or pressure on the carotid Ventricular pause or decreased systolic blood pressure hypersensitivity sinus (e.g., from shaving or tight collar) can after carotid sinus massage; may coincide with reproduce symptoms; consider in patients syncope with unexplained falls Situational Brought on by coughing, defecation, Absence of heart disease; history of similar syncope; gastrointestinal stimulation, or urination; prolonged standing, eating, or voiding may occur after exercise or meals Vasovagal Mediated by fear, heat exposure, noxious Prodromal symptoms (e.g., diaphoresis, dizziness, stimuli, pain, or stress nausea), precipitating factors Orthostatic hypotension syncope Drug induced Alcohol, antianginal agents, antidepressants, Initiation or change in dosage antidiabetic agents, antihypertensives, antiparkinsonian agents, diuretics, flibanserin (Addyi), insulin Postural tachycardia Young adults (predominantly female); Severe orthostatic intolerance with marked tachycardia syndrome associated with chronic fatigue syndrome and mitral valve prolapse Primary autonomic failure Multiple sclerosis, multiple system atrophy Orthostatic hypotension with postural change (e.g., Shy-Drager syndrome), Parkinson disease/ parkinsonism, Wernicke encephalopathy Secondary autonomic failure Amyloidosis, chronic inflammatory Orthostatic hypotension with postural change demyelinating polyneuropathy, connective tissue diseases, diabetes mellitus, Lewy body dementia, older age, spinal cord injury, uremia Volume depletion Acute blood loss (e.g., gastrointestinal Hypotension, tachycardia, history of volume/blood bleeding, ectopic pregnancy), diarrhea, loss, dehydration on examination inadequate fluid intake, vomiting

Information from references 1 and 17. Syncope

hospitalizations in patients who presented with presyn- elements: (1) Is the loss of consciousness attributable to cope and syncope.21 Adverse outcomes occurred in 49 of syncope? (2) Is there a history of cardiovascular disease? 244 patients (20%) with presyncope compared with 68 of (3) Are there clinical features to suggest a specific cause 293 patients (23%) with syncope. Admission rates were of syncope?30 Pertinent historical elements are listed 49% and 69%, respectively. Because rates of adverse out- in Table 3.18,30-33 Medication reconciliation is relevant comes are similar in patients with presyncope and syn- because medications are contributory in 5% to 15% of cope, both groups should receive a similar evaluation. syncope cases, typically causing orthostatic hypotension, sedation, symptomatic bradycardia, or QT interval Risk Stratification prolongation.34 The history should also assist in classify- The decision to perform an expedited and monitored ing patients as low or high risk. evaluation of patients presenting with syncope is based on the likelihood of short-term adverse outcomes. PHYSICAL EXAMINATION Unnecessary admissions for patients meeting low-risk Most patients with syncope will have normal physical criteria result in high medical costs without improve- examination findings, with the exception of any trauma ments in morbidity and mortality, patient safety, or incurred from the syncopal event. The examination quality of life.22 should focus on initial vital signs; orthostatic blood Several clinical decision rules have been developed pressure measurements35; and vascular (pulses and to risk stratify patients presenting to the emergency carotid bruits), cardiac, pulmonary (evidence of conges- department with syncope. Each has differing variables, tive heart failure), abdominal, rectal, and skin/nail (ane- and no single rule has proved significantly superior 23,24 mia) signs. Any new focal neurologic findings suggest a (eTable A). The San Francisco Syncope Rule, Evaluation primary central nervous system lesion. of Guidelines in Syncope Study, and Osser- vatorio Epidemiologico sulla Sincope nel Lazio are the only rules that have been exter- nally validated. High-risk patients should be Table 2. Risk Stratification in Patients with Syncope admitted for further evaluation (Table 2).1,25 High risk (hospital admission recommended)* Diagnostic Approach Clinical history suggestive of arrhythmic syncope (e.g., syncope during exercise, palpitations, or syncope without warning or prodrome) Guidelines from the Canadian Cardiovas- Comorbidities (e.g., severe anemia, electrolyte abnormalities) cular Society, European Society of Cardiol- Electrocardiographic history suggestive of arrhythmic syncope (e.g., bifascicular ogy, and the American College of Emergency block, sinus bradycardia < 40 beats per minute in absence of sinoatrial block Physicians recommend obtaining a detailed or medication use, QRS preexcitation, abnormal QT interval, ST segment elevation leads V through V [Brugada pattern], negative T wave in right history and performing a physical exami- 1 3 precordial leads and epsilon wave [arrhythmogenic right ventricular dysplasia/ nation, standard 12-lead electrocardiogra- cardiomyopathy]) phy (ECG), and orthostatic blood pressure Family history of sudden death measurement in patients presenting with Hypotension (systolic blood pressure < 90 mm Hg) 1,25-28 syncope. Additional testing should be Older age† individualized. Figure 1 provides a general Severe structural heart disease, congestive heart failure, or coronary framework, emphasizing classification and artery disease risk stratification to standardize the evalua- Low risk (outpatient evaluation recommended)‡ tion of syncope.2 High-risk patients should Age less than 50 years† be admitted for monitoring and further No history of cardiovascular disease workup. Low-risk patients with a first epi- Normal electrocardiographic findings sode of syncope may be reassured without Symptoms consistent with neurally mediated or orthostatic hypotension syncope further workup.1,25,27,29 Unremarkable cardiovascular findings

HISTORY *—Patient is at high risk if any of the criteria are met. †—Different age thresholds have been used in studies for decision making. Older age A detailed history will suggest a diagnosis in largely reflects the patient’s cardiovascular health. up to 50% of patients and is the most impor- ‡—Patient is at low risk only if all criteria are met. tant diagnostic tool in the evaluation of syn- Information from references 1 and 25. cope.1 The history should focus on three key

306 American Family Physician www.aafp.org/afp Volume 95, Number 5 ◆ March 1, 2017 Syncope Evaluation of Syncope

Transient loss of consciousness

Initial evaluation History and physical examination Orthostatic blood pressure measurements Nonsyncopal transient Electrocardiography loss of consciousness Laboratory testing as indicated

Treat based on etiology Suspected syncope Significant trauma*

Orthostatic Neurally mediated syncope A Cardiac syncope Unexplained syncope hypotension syncope Head-up tilt testing Carotid sinus massage Modify known risks Risk stratify (Table 2); use clinical decision rule (eTable A) Education Pharmacotherapy Diagnostic?

Yes No Low risk High risk†

Avoid precipitating Consider cardiac syncope or factors psychogenic pseudosyncope Frequent syncopal episodes: Electrocardiographic monitoring Education Holter or external loop Echocardiography as indicated recorder* Pharmacotherapy Carotid sinus massage as indicated Infrequent syncopal episodes: Electrophysiology as indicated implantable loop recorder Frequent syncopal episodes: Go to A Exercise stress testing as indicated psychiatry consultation, video Head-up tilt testing as indicated electroencephalography, Holter or external loop recorder Infrequent syncopal episodes: Diagnostic? external or implantable loop recorder‡

Yes No

Treat Implantable loop recorder

*—Consider admission for patients with significant trauma and those with frequent syncopal episodes. †—Admission is recommended for high-risk patients. ‡—In the absence of injuries, consider no further evaluation.

Figure 1. Algorithm for the evaluation of syncope. Information from reference 2.

DIAGNOSTIC TESTING formed initially on the right because the maneuver is Carotid sinus massage can be considered in patients more often positive on this side. If results are negative, it older than 40 years to confirm the diagnosis of carotid should be repeated with the patient upright at approxi- sinus hypersensitivity. The maneuver is positive when it mately 60 to 70 degrees.36 This maneuver should be produces an asystolic or ventricular pause longer than avoided in patients who have had a stroke or transient three seconds or a decrease in systolic blood pressure ischemic attack in the past three months and in patients of at least 50 mm Hg. The test is performed while the with carotid bruits. If a positive carotid hypersensitiv- patient is supine, with five to 10 seconds of massage ity test is associated with patient symptoms, then the consecutively to each carotid sinus. It should be per- patient has carotid sinus syndrome.

March 1, 2017 ◆ Volume 95, Number 5 www.aafp.org/afp American Family Physician 307 Syncope Table 3. Pertinent Historical Information in the Evaluation of Syncope

Features Possible diagnosis Routine laboratory studies have low Position before syncope diagnostic yield and should be ordered only Prolonged standing Neurally mediated syncope (vasovagal), orthostatic if clinically indicated. Laboratory tests can hypotension syncope distinguish syncope from other suspected Sudden change in posture* Orthostatic hypotension syncope nontraumatic etiologies of loss of con- Supine* Cardiac syncope (arrhythmia, structural heart sciousness. Elevated troponin and brain disease) natriuretic peptide levels have been shown Postsyncope to predict a higher likelihood of adverse Amnesia regarding loss of Seizure or neurally mediated syncope (vasovagal) outcomes but should be used only if cardio- consciousness in older patients 26,37,38 vascular disease is clinically suspected. Eyes closed during event* Pseudoseizure, psychogenic pseudosyncope ECG generally has a low diagnostic yield Eyes open during event Seizure or syncope (any cause) (approximately 3% to 5%) but is recom- Fatigue, nausea, vomiting* Neurally mediated syncope (vasovagal) mended for all patients with syncope.39,40 Focal neurologic deficit Neurogenic syncope (cerebrovascular accident or Although arrhythmias are unlikely to transient ischemic attack) be detected on a single ECG, ischemic, Immediate complete Cardiac syncope (arrhythmia), psychogenic structural, or conduction abnormalities recovery pseudosyncope Incontinence Seizure (uncommon in syncope; vasovagal syncope may be identified. Any ECG abnormality most likely) or change from baseline increases the risk Myoclonic, tonic-clonic Neurally mediated syncope (vasovagal), seizure of arrhythmia or death within one year of movement 41 the syncopal event. Prolonged confusion* Seizure Echocardiography is essential to evalu- Prolonged syncope Seizure, neurogenic, metabolic, infectious ate suspected structural abnormalities, but Slow pulse Cardiac syncope (bradyarrhythmia) it generally has low diagnostic yield. Two Tongue biting* Seizure studies (n = more than 310) found echocar- Transient disorientation Neurally mediated syncope (vasovagal) diography to be clinically useful in patients Precipitating factors with syncope if there is a history of cardiac Activities such as coughing, Neurally mediated syncope (situational) disease, abnormal ECG findings, or sus- defecation, eating, pected significant valvular disease.42,43 laughing, urination* Continuous cardiac monitoring is the Emotional distress, fear, Neurally mediated syncope (vasovagal) diagnostic standard to establish a corre- pain, prolonged standing, warm or crowded area* lation between symptoms and ECG find- Exertion* Cardiac syncope (arrhythmia, structural heart ings. Devices include Holter monitors disease) (generally up to 72 hours), external loop Hand or upper extremity Subclavian steal syndrome recorders (typically four to six weeks), and exercise implantable loop recorders (up to three Head movement, shaving, Neurally mediated syncope (carotid sinus) years). The diagnostic yield improves tight collar* with prolonged monitoring. Up to 50% Medication use of patients who present with syncope in Antiarrhythmics Cardiac syncope (arrhythmia, prolonged QT interval) the absence of heart disease will have an Antihypertensives Orthostatic hypotension syncope, cardiac syncope (prolonged QT interval) arrhythmia when an implantable loop Macrolides, antiemetics, Cardiac syncope (prolonged QT interval) 44 recorder is placed. These devices may antipsychotics, tricyclic increase diagnostic yield, decrease time to antidepressants diagnosis, and improve cost-effectiveness. Postexertion Neurally mediated syncope (vasovagal), cardiac Some guidelines recommend them early syncope (arrhythmia) in the diagnostic workup of unexplained Standing after prolonged Orthostatic hypotension syncope sitting syncope.45-48 Patients most likely to benefit Unexplained fall Neurally mediated syncope (carotid sinus), cardiac from these devices are those with cardio- syncope (arrhythmia, structural heart disease) vascular disease, abnormal baseline ECG continues findings, cardiac symptoms surrounding the syncopal event, and a family history *—Salient features from history for differentiation. of sudden cardiac death.39

308 American Family Physician www.aafp.org/afp Volume 95, Number 5 ◆ March 1, 2017 Syncope Table 3. Pertinent Historical Information in the Evaluation of Syncope (continued)

Features Possible diagnosis as prolonged ECG monitoring.1,7 Patients Preexisting disease who have an indication for implantable Alcoholism, diabetes Orthostatic hypotension syncope cardioverter-defibrillator placement do mellitus, Parkinson disease, not require electrophysiologic studies. renal replacement therapy Cranial or cardiac imaging, carotid Family history of sudden Cardiac syncope (long QT syndrome, Brugada cardiac death syndrome, arrhythmogenic right ventricular ultrasonography, electroencephalography, dysplasia/cardiomyopathy, structural heart disease) and cardiac enzyme testing are rarely help- Heart disease Cardiac syncope ful in determining the cause of syncope History of frequent and Psychogenic pseudosyncope, neurally mediated and should not be ordered routinely. These prolonged syncopal syncope (vasovagal) tests affect diagnosis and management events in less than 2% of older patients present- Older age with dementia Orthostatic hypotension syncope, cardiac syncope ing to the emergency department.40 For Psychiatric illness Psychogenic pseudosyncope most patients with tests results that were Prodrome significant and affected management, the Abdominal pain, Neurally mediated syncope (vasovagal) patient’s history indicated the diagno- diaphoresis, nausea* sis.50,51 Table 4 provides an overview of the Aura Seizure available testing modalities.1,11 Blurred vision, dizziness, Neurally mediated syncope (vasovagal), orthostatic lightheadedness, vertigo hypotension syncope Treatment Chest pain, dyspnea Cardiac syncope (structural heart disease, pulmonary embolus, acute myocardial infarction) The treatment of syncope is directed at Fluttering or palpitations* Cardiac syncope (arrhythmia) the underlying cause. Morbidity and Focal neurologic deficit Cerebrovascular accident, transient ischemic attack mortality are generally low except in car- Headache Subarachnoid hemorrhage diac syncope; therefore, patient reassur- Slow pulse Neurally mediated syncope (vasovagal), cardiac ance is an important part of treatment. syncope (bradyarrhythmia) Tonic-clonic movement or Seizure NEURALLY MEDIATED SYNCOPE posture Treatment of neurally mediated syncope None Vasovagal or cardiac syncope in older patients, includes reassurance, education, and cardiac syncope in younger patients physical therapy.1 In situational syncope, *—Salient features from history for differentiation. it is important to avoid potential trig- Adapted with permission from Parry SW, Tan MP. An approach to the evaluation and gers. Physical counterpressure maneu- management of syncope in adults. BMJ. 2010;340:c880, with additional information vers such as leg crossing, squatting, and from references 18, 30, 32 and 33. tensing the lower extremities are effective at the onset of prodromal symptoms.7 One randomized trial showed that Provocative testing strategies include head-up tilt test- these maneuvers reduce syncope by 39%.52 Tilt training ing, exercise testing, and electrophysiologic studies. The involves standing for prolonged periods, and compli- head-up tilt test is a safe procedure designed to precipitate ance is generally poor.7 hypotension and bradycardia and is used to confirm the Pharmacologic therapy with beta blockers, alpha ago- diagnosis of neurally mediated syncope in patients with nists, and fludrocortisone has shown no effectiveness an intermediate pretest probability.11 Persons in high- or conflicting results in reducing vasovagal syncope.1 risk settings with unexplained syncope should also be In one small randomized trial of patients with a his- considered for testing. Protocols using isoproterenol or tory of recurrent vasovagal syncope, paroxetine (Paxil) nitroglycerin have an overall sensitivity of 92% to 94%; prevented additional episodes in 82.4% compared with however, specificity is low.1,49 Exercise testing is useful in 47.1% in the placebo group over two years (P < .001), exertional syncope, ischemia, and arrhythmia evalua- although guidelines recommend its use only in patients tion. Less than 2% of patients referred to cardiologists for with concurrent psychiatric disease.53 In patients with evaluation of unexplained syncope undergo electrophysi- severe asystole from neurally mediated syncope, a ologic studies.1 These studies have poor sensitivity and double-blind, randomized, placebo-controlled trial specificity except in the setting of structural heart dis- showed that the use of permanent dual chamber pacing ease; they have been replaced by noninvasive tools such reduced the risk of recurrent syncope.54

March 1, 2017 ◆ Volume 95, Number 5 www.aafp.org/afp American Family Physician 309 Syncope Table 4. Diagnostic Evaluation of Syncope

Test Indication Comments

Basic laboratory As clinically indicated Rarely helpful; complete blood count, brain natriuretic peptide testing testing, fecal occult blood testing, human chorionic gonadotropin testing in women of childbearing age; troponin testing may be beneficial to identify cardiac etiology

Carotid sinus Syncope of unknown etiology in patients older Diagnostic if ventricular pause is more than three seconds or if systolic massage than 40 years1 blood pressure decreases by more than 50 mm Hg; contraindicated in patients with bruits or a history of transient ischemic attack/ cerebrovascular accident within the past three months

ECG All patients with syncope Diagnostic yield is 3% to 5%, but can aid in diagnosing arrhythmia, ischemia, pulmonary embolus (increased pulmonary pressures or right ventricular enlargement), hypertrophic cardiomyopathy, and Brugada syndrome; findings suggestive of arrhythmia include bundle branch block, intraventricular conduction delay, sinus bradycardia (less than 50 beats per minute), prolonged QT interval, QRS preexcitation, Q waves Recurrent syncope with unremarkable Holter monitoring for 24 to 48 hours, external loop recorders for initial evaluation; clinical or ECG features four to six weeks, implantable loop recorders for up to three suggestive of arrhythmic syncope; years; consider testing in patients with suspected epilepsy not unexplained falls responsive to therapy; implantable loop recorders have high diagnostic yield in recurrent unexplained syncope1

Echocardiography Suspected structural cardiac disease or when Diagnostic in aortic stenosis, pericardial tamponade, obstructive history, examination, and ECG are not cardiac tumors or thrombi, aortic dissection, hypertrophic diagnostic cardiomyopathy, congenital anomalies of the coronary arteries, acute right ventricular strain (in pulmonary embolism)

Electrophysiology Arrhythmogenic right ventricular Not recommended in patients without underlying heart disease; cardiomyopathy, Brugada syndrome, high- consider in high-risk patients with recurrent unexplained risk occupations, suspected intermittent syncope bradycardia, syncope in patients with bundle branch block,1 syncope preceded by palpitations suspicious for sinus tachycardia

Exercise testing Hemodynamic and ECG abnormalities with Inadequate blood pressure increase in younger patients suggests syncope during exercise, syncope reproduced hypertrophic cardiomyopathy or ischemia; similar findings in with exercise, polymorphic ventricular older persons may suggest autonomic dysfunction; may unmask tachycardia, prolonged QT interval, to ECG changes of channelopathies precipitate a Mobitz type 2 second- or third- degree block during exercise1

Head-up tilt test Neurally mediated syncope, recurrent Used in patients with negative initial findings, normal cardiac unexplained falls, frequent syncopal structure, and no evidence of ischemia; contraindicated in episodes, psychiatric disease, to distinguish patients with ischemic heart disease, uncontrolled hypertension, between neurally mediated and orthostatic left ventricular outflow tract obstruction, or aortic stenosis hypotension syncope, to differentiate syncope with jerking movements from seizure1

Neurologic Suspected seizures, cerebrovascular event, Seizure can be confirmed with electroencephalography; cranial testing* neurodegenerative disorder, increased imaging studies as clinically indicated; 20% to 30% of seizures intracranial pressure with transient loss of consciousness could be the result of syncope; tonic-clonic limb movements and muscle twitching may occur in cardiac and neurally mediated syncope

Orthostatic Neurally mediated syncope, postural Diagnostic if systolic blood pressure is less than 90 mm Hg blood pressure tachycardia syndrome, orthostatic or decreases by 20 mm Hg or more (10 mm Hg or more in measurement hypotension syncope1 symptomatic patients); increase of 30 beats per minute suggests postural tachycardia syndrome; up to 40% of asymptomatic adults older than 70 years and 23% of patients younger than 60 years will have positive orthostatic blood pressure measurements

Psychiatric Suspected psychogenic pseudosyncope1 Consider with concurrent electroencephalography and video evaluation monitoring

ECG = electrocardiography. *—Includes electroencephalography, computed tomography, magnetic resonance imaging, or carotid ultrasonography. Information from references 1 and 11. Syncope

ORTHOSTATIC HYPOTENSION 3. Puppala VK, Dickinson O, Benditt DG. Syncope: classification and risk stratification. J Cardiol. 2014;63(3): 171-177. Treatment of orthostatic hypotension includes education 4. Alshekhlee A, Shen WK, Mackall J, Chelimsky TC. Incidence and mor- and lifestyle modifications, such as slowly transitioning tality rates of syncope in the United States. Am J Med. 2009;122(2): from a supine or sitting position to standing and increas- 181-188. ing fluid and sodium intake.1 Contributing medications 5. Sun BC, Emond JA, Camargo CA Jr. Direct medical costs of syncope- related hospitalizations in the United States. Am J Cardiol. 2005;95(5): should be discontinued or decreased, if possible. Other 668-671. treatment modalities include elevating the head of the 6. Hatoum T, Sheldon R. A practical approach to investigation of syncope. bed by 10 degrees, compression stockings/abdominal Can J Cardiol. 2014;30(6):671-674 . binders, and counterpressure maneuvers.1 If these do not 7. Saklani P, Krahn A, Klein G. Syncope. Circulation. 2013;127(12): mitigate symptoms, midodrine and fludrocortisone are 1330-1339. 55 8. D’Ascenzo F, Biondi-Zoccai G, Reed MJ, et al. Incidence, etiology and effective treatments. predictors of adverse outcomes in 43,315 patients presenting to the emergency department with syncope: an international meta-analysis. CARDIAC SYNCOPE Int J Cardiol. 2013;167(1): 57-62 . Management of cardiac syncope is directed at the under- 9. Solbiati M, Casazza G, Dipaola F, et al. Syncope recurrence and mortality: a systematic review. Europace. 2015;17(2):300-308. lying etiology. Options include antiarrhythmic drugs, 10. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of cardiac pacing, catheter-directed ablation, and, rarely, syncope. N Engl J Med. 2002;347(12): 878-885 . implantable cardioverter-defibrillator placement.1 11. Ray JC, Kusumoto F, Goldschlager N. Syncope. J Intensive Care Med. 2016;31(2):79-93. This article updates previous articles on this topic by Gauer,56 and by 57 12. Ruwald MH, Hansen ML, Lamberts M, et al. Prognosis among healthy Miller and Kruse. individuals discharged with a primary diagnosis of syncope. J Am Coll Cardiol. 2013;61(3):325-332. Data Sources: We searched OvidSP, Essential Evidence Plus, the 13. Kachalia A, Berg A, Fagerlin A, et al. Overuse of testing in preoperative National Guideline Clearinghouse, Cochrane Library, and UpToDate evaluation and syncope: a survey of hospitalists. Ann Intern Med. 2015; using combinations of the following key words: syncope, transient loss 162(2):100-108 . of consciousness, presyncope, clinical decision rules, risk stratification, 14. Sun BC, McCreath H, Liang LJ, et al. Randomized clinical trial of an mortality, morbidity, etiology, incidence, electrocardiographic monitor- emergency department observation syncope protocol versus routine ing, electrophysiologic studies, diagnostic evaluation, hospitalization, inpatient admission. Ann Emerg Med. 2014;64(2):167-175 . brain natriuretic peptide, troponin, cardiac enzymes, implantable loop 15. Brignole M, Ungar A, Casagranda I, et al.; Syncope Unit Project (SUP) recorders, cost, quality of life, carotid sinus massage, head-up tilt table, investigators. Prospective multicentre systematic guideline-based man- implantable cardioverter defibrillator, guidelines, orthostatic hypoten- agement of patients referred to the syncope units of general hospitals. sion, diagnostic evaluation, medical cost, postural tachycardia syndrome. Europace. 2010;12(1): 109 -118. Search dates: June 22 to August 6, 2015, and October 15, 2016. 16. Mitro P, Kirsch P, Valocˇik G, Murín P. A prospective study of the stan- The opinions or assertions contained herein are the private views of the dardized diagnostic evaluation of syncope. Europace. 2011;13(4): authors and are not to be construed as official or as reflecting the views 566-571. of the Department of Defense. 17. Saal DP, van Dijk JG. Classifying syncope. Auton Neurosci. 2014;184: 3-9. 18. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol. The Authors 2001;37(7): 1921-1928. 19. Robertson D. The epidemic of orthostatic tachycardia and orthostatic LLOYD A. RUNSER, MD, MPH, FAAFP, is associate program director and intolerance. Am J Med Sci. 1999;317(2): 75-77. research coordinator at the Womack Army Medical Center Family Medi- cine Residency Program, Fort Bragg, N.C., and assistant professor in the 20. Thiruganasambandamoorthy V, Stiell IG, Wells GA, Vaidyanathan A, Mukarram M, Taljaard M. Outcomes in presyncope patients: a prospec- Department of Family Medicine at the Uniformed Services University of tive cohort study. Ann Emerg Med. 2015;65(3):268-276.e6. the Health Sciences, Bethesda, Md. 21. Grossman SA, Babineau M, Burke L, et al. Do outcomes of near syncope ROBERT L. GAUER, MD, is assistant professor of family medicine at the parallel syncope? Am J Emerg Med. 2012;30 (1):203-206 . Uniformed Services University of the Health Sciences and a hospitalist at 22. Sun BC, Costantino G, Barbic F, et al. Priorities for emergency depart- Womack Army Medical Center. ment syncope research. Ann Emerg Med. 2014;64(6):649-655 .e2. ALEX HOUSER, DO, is a second-year resident at the Womack Army Medi- 23. Ebell MH. Syncope: initial evaluation and prognosis. Am Fam Physician. 2006;74(8): 1367-1370. cal Center Family Medicine Residency Program. 24. Ebell MH. Risk stratification of patients presenting with syncope. Address correspondence to Lloyd A. Runser, MD, MPH, at lloyd.a.runser2. Am Fam Physician. 2012;85 (11):1047-1052. [email protected]. Reprints are not available from the authors. 25. Sheldon RS, Morillo CA, Krahn AD, et al. Standardized approaches to the investigation of syncope: Canadian Cardiovascular Society position paper. Can J Cardiol. 2011;27(2): 246-253. REFERENCES 26. Reed MJ, Newby DE, Coull AJ, Prescott RJ, Jacques KG, Gray AJ. The 1. The European Society of Cardiology guidelines for the diagnosis and ROSE (Risk Stratification of Syncope in the Emergency Department) management of syncope. Eur Heart J. 2009;30(21): 2539-2540. study. J Am Coll Cardiol. 2010;55(8): 713-721 . 2. Mereu R, Sau A, Lim PB. Diagnostic algorithm for syncope. Auton Neu- 27. Huff JS, Decker WW, Quinn JV, et al.; American College of Emergency rosci. 2014;184: 10-16. Physicians. Clinical policy: critical issues in the evaluation and manage-

March 1, 2017 ◆ Volume 95, Number 5 www.aafp.org/afp American Family Physician 311 Syncope

ment of adult patients presenting to the emergency department with Role of echocardiography in the evaluation of syncope: a prospective syncope. Ann Emerg Med. 2007;49(4):431-444 . study. Heart. 2002;88(4):363-367 . 28. van Dijk N, Boer KR, Colman N, et al. High diagnostic yield and accuracy 44. Ruwald MH, Zareba W. ECG monitoring in syncope. Prog Cardiovasc of history, physical examination, and ECG in patients with transient loss Dis. 2013;56(2):203-210. of consciousness in FAST: the Fainting Assessment study. J Cardiovasc 45. Davis S, Westby M, Pitcher D, Petkar S. Implantable loop recorders are Electrophysiol. 2008;19(1):48-55. cost-effective when used to investigate transient loss of consciousness 29. Strickberger SA, Benson DW, Biaggioni I, et al. AHA/ACCF scientific which is either suspected to be arrhythmic or remains unexplained. statement on the evaluation of syncope. J Am Coll Cardiol. 2006;47(2): Europace. 2012;14(3):402-409. 473-484. 46. Edvardsson N, Frykman V, van Mechelen R, et al.; PICTURE Study Inves- 30. Benditt DG, Adkisson WO. Approach to the patient with syncope: ven- tigators. Use of an implantable loop recorder to increase the diagnostic ues, presentations, diagnoses. Cardiol Clin. 2013;31(1):9-25 . yield in unexplained syncope: results from the PICTURE registry. Euro- 31. Parry SW, Tan MP. An approach to the evaluation and management of pace. 2011;13 (2):262-269. syncope in adults. BMJ. 2010;340:c880. 47. Edvardsson N, Wolff C, Tsintzos S, Rieger G, Linker NJ. Costs of unstruc- 32. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish tured investigation of unexplained syncope: insights from a micro- syncope from seizures. J Am Coll Cardiol. 2002;40(1): 142-148. costing analysis of the observational PICTURE registry. Europace. 2015; 17(7):1141-1148. 33. Moya A, Sutton R, Ammirati F, et al.; Task Force for the Diagnosis and 48. Krahn AD, Klein GJ, Yee R, Hoch JS, Skanes AC. Cost implications of Management of Syncope; European Society of Cardiology (ESC); Euro- testing strategy in patients with syncope: randomized assessment of pean Heart Rhythm Association (EHRA); Heart Failure Association (HFA); syncope trial. J Am Coll Cardiol. 2003;42(3):495-501 . Heart Rhythm Society (HRS). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30(21):2631-2671. 49. Forleo C, Guida P, Iacoviello M, et al. Head-up tilt testing for diagnosing vasovagal syncope: a meta-analysis. Int J Cardiol. 2013;168(1): 27-35. 34. Lemonick DM. Evaluation of syncope in the emergency department. Am J Clin Med. 2010;7(1): 11-19 . 50. Chiu DT, Shapiro NI, Sun BC, Mottley JL, Grossman SA. Are echocardiography, telemetry, ambulatory electrocardiography monitoring, and 35. Ooi WL, Hossain M, Lipsitz LA. The association between orthostatic cardiac enzymes in emergency department patients presenting with hypotension and recurrent falls in nursing home residents. Am J Med. syncope useful tests? A preliminary investigation. J Emerg Med. 2014; 2000;108(2): 106 -111. 47(1):113-118 . 36. Krediet CT, Parry SW, Jardine DL, Benditt DG, Brignole M, Wieling W. 51. Johnson PC, Ammar H, Zohdy W, Fouda R, Govindu R. Yield of diagnos- The history of diagnosing carotid sinus hypersensitivity: why are the tic tests and its impact on cost in adult patients with syncope presenting current criteria too sensitive? Europace. 2011;13 (1):14-22. to a community hospital. South Med J. 2014;107(11):707-714. 37. Costantino G, Furlan R. Syncope risk stratification in the emergency 52. van Dijk N, Quartieri F, Blanc JJ, et al.; P C-Trial Investigators. Effective- department. Cardiol Clin. 2013;31(1): 27-38 . ness of physical counterpressure maneuvers in preventing vasovagal 38. Reed MJ, Mills NL, Weir CJ. Sensitive troponin assay predicts outcome in syncope: the Physical Counterpressure Manoeuvres Trial (P C-Trial ). J Am syncope. Emerg Med J. 2012;29(12): 1001-1003. Coll Cardiol. 2006;48(8): 1652-1657. 39. Krahn AD, Andrade JG, Deyell MW. Selecting appropriate diagnostic 53. Di Girolamo E, Di Iorio C, Sabatini P, Leonzio L, Barbone C, Barsotti tools for evaluating the patient with syncope/collapse. Prog Cardiovasc A. Effects of paroxetine hydrochloride, a selective serotonin reuptake Dis. 2013;55(4):402-409. inhibitor, on refractory vasovagal syncope: a randomized, double-blind, 40. Mendu ML, McAvay G, Lampert R, Stoehr J, Tinetti ME. Yield of diag- placebo-controlled study. J Am Coll Cardiol. 1999;33(5): 1227-1230. nostic tests in evaluating syncopal episodes in older patients. Arch 54. Brignole M, Menozzi C, Moya A, et al. Pacemaker therapy in patients Intern Med. 2009;169(14):1299-1305 . with neurally mediated syncope and documented asystole: Third Inter- 41. Quinn JV, Stiell IG, McDermott DA, Sellers KL, Kohn MA, Wells GA. national Study on Syncope of Uncertain Etiology (ISSUE-3): a random- Derivation of the San Francisco Syncope Rule to predict patients with ized trial. Circulation. 2012;125(21): 2566-2571 . short-term serious outcomes. Ann Emerg Med. 2004;43(2):224-232 . 55. Benditt DG, Nguyen JT. Syncope: therapeutic approaches. J Am Coll 42. Anderson KL, Limkakeng A, Damuth E, Chandra A. Cardiac evaluation Cardiol. 2009;53(19):1741-1751 . for structural abnormalities may not be required in patients presenting 56. Gauer RL. Evaluation of syncope. Am Fam Physician. 2011;84(6): with syncope and a normal ECG result in an observation unit setting. 640-650. Ann Emerg Med. 2012;60(4):478-484.e1. 57. Miller TH, Kruse JE. Evaluation of syncope. Am Fam Physician. 2005; 43. Sarasin FP, Junod AF, Carballo D, Slama S, Unger PF, Louis-Simonet M. 72(8):1492-1500 .

312 American Family Physician www.aafp.org/afp Volume 95, Number 5 ◆ March 1, 2017 eTable A. Major Clinical Decision Rules for Syncope

Study Population Predictor variables Outcome measured Score results Validation Comments

Boston Syncope Derivation: a priori Signs of volume depletion Critical intervention or adverse outcome at Consider admission for Internal: 97% sensitivity, 25 variables in eight categories make it less Rule, 2007 Validation: 362 ED Persistent abnormal vital signs in the ED 30 days one or more variables 62% specificity practical (short-term risk) patients with syncope Signs and symptoms of acute coronary syndrome External: none Signs of conduction disease Worrisome cardiac history Family history of sudden death Primary central nervous system event Valvular heart disease (from history or physical examination)

Canadian Syncope Derivation: 4,030 ED Predisposition to vasovagal syncope (prodrome/trigger) Serious event at 30 days: death, arrhythmia, Estimated risk of serious Pending Largest prospective study, outcomes Risk Rule, 2016 patients with syncope History of heart disease MI, PE, aortic dissection, CVA, or procedural adverse event at 30 days consistent with guidelines, clarifies (short-term risk) Validation: pending Systolic blood pressure < 90 mm Hg or > 180 mm Hg intervention for syncope abnormal ECG findings, pending validation to support use of rule Elevated troponin level Abnormal QRS axis (< 30 or > 110 degrees) QRS duration > 130 milliseconds Corrected QT interval > 480 milliseconds ED diagnosis of vasovagal syncope ED diagnosis of cardiac syncope

EGSYS score, Derivation: 260 ED Palpitations preceding syncope (4 points) Probability of cardiogenic syncope at two years Consider admission for Internal: 92% sensitivity, Mortality at two years was 2% in patients 2008 (short- and patients with syncope Abnormal ECG findings* or history of heart disease (3 points) score of 3 or higher 69% specificity with scores < 3 and 21% for scores ≥ 3 long-term risk) Validation: 258 ED Syncope during effort (3 points) or when supine (2 points) External: 56% sensitivity, patients with syncope Autonomic prodromes (–1 point) 84% specificity Precipitating and/or predisposing factors (–1 point)

OESIL risk score, Derivation: 270 ED Abnormal ECG findings* Mortality at one year Consider admission for Internal: 100% sensitivity, Positive variables: 2003 (long-term patients with syncope Absence of prodromal syndrome one or more variables 22% specificity 0: 0% mortality risk) Validation: 328 ED Age > 65 years External: 95% sensitivity, 1: 0.6% mortality patients with syncope History of cardiac disease 31% specificity 2: 14% mortality 3: 29% mortality 4: 53% mortality

ROSE study, 2010 Derivation: 550 ED Anemia (hemoglobin ≤ 9 g per dL [90 g per L]) Serious events at one month: death, acute Consider admission for Internal: 87% sensitivity, Not useful for predicting outcomes at one (short-term risk) patients with syncope Bradycardia (< 50 beats per minute) MI, PE, CVA, arrhythmias, hemorrhage one or more variables 66% specificity year; first study to use a biomarker in risk Validation: 550 ED Brain natriuretic peptide ≥ 300 pg per mL (300 ng per L) requiring transfusion of two or more units, One-year outcomes: stratification subarachnoid hemorrhage, acute procedure, patients with syncope Chest pain with syncope 72% sensitivity, 71% need for pacemaker in first month specificity ECG showing Q waves (except in lead III) External: none Oxygen saturation < 94% on room air Rectal examination showing occult blood (if gastrointestinal bleeding suspected)

San Francisco Derivation: 684 ED Abnormal ECG findings* Serious events at seven days: acute MI, PE, CVA, Consider admission for Internal: 98% sensitivity, First tool for short-term events (seven days); Syncope Rule, patients with syncope Congestive heart failure arrhythmias, subarachnoid hemorrhage, return one or more variables 56% specificity inconsistencies in validation scores, but 2004 (short- or near syncope Hematocrit < 30% ED visit, readmission External: 87% sensitivity, the most studied decision tool term risk) Validation: 791 ED Shortness of breath 52% specificity patients with syncope Systolic blood pressure < 90 mm Hg or near syncope

Information from: Colivicchi F, Ammirati F, Melina D, Guido V, Imperoli G, Santini M; OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) Study Investigators. Develop- CVA = cerebrovascular accident; ECG = electrocardiography; ED = emergency department; EGSYS = Evaluation ment and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. Eur Heart J. 2003;24(9):811-819. of Guidelines in Syncope Study; MI = myocardial infarction; OESIL = Osservatorio Epidemiologico sulla Sincope Del Rosso A, Ungar A, Maggi R, et al. Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score. Heart. nel Lazio; PE = pulmonary embolism; ROSE = Risk Stratification of Syncope in the Emergency Department. 2008;94(12):1620-1626. *—Abnormal ECG definitions varied with each study. Ebell MH. Risk stratification of patients presenting with syncope. Am Fam Physician. 2012;85(11):1047-1052. Ebell MH. Syncope: initial evaluation and prognosis. Am Fam Physician. 2006;74(8):1367-1370. Grossman SA, Babineau M, Burke L, et al. Do outcomes of near syncope parallel syncope? Am J Emerg Med. 2012;30 (1):203-206. Sun BC, Costantino G, Barbic F, et al. Priorities for emergency department syncope research. Ann Emerg Med. 2014;64(6):649-655.e2. Thiruganasambandamoorthy V, Kwong K, Wells GA, et al. Development of the Canadian Syncope Risk Score to predict serious adverse events after emergency department assessment of syncope. CMAJ. 2016;188 (12):E289-E298.

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eTable A. Major Clinical Decision Rules for Syncope

Study Population Predictor variables Outcome measured Score results Validation Comments

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