Chapter 99. Syncope

1. What diagnostic testing should be considered for common causes of syncope?

2. When do clinicians need to rule out arrhythmias and how is this done?

3. What are the diagnostic criteria for neurocardiogenic syncope?

4. When do patients require hospital admission?

5. How do elderly patients differ from younger patients?

6. How should the history and physical examination be utilized to direct further testing or limit further testing in the evaluation of syncope?

7. What are the indications for advanced noninvasive or invasive tests in the evaluation of syncope?

Definition

Syncope is defined as a sudden, transient loss of consciousness and postural tone with rapid spontaneous recovery. Syncope results from cerebral hypoperfusion to the reticular activating system in the brain stem. Any condition that does not result from cerebral hypoperfusion should not be classified as syncope.

Epidemiology

Syncope has a 3% incidence in the general population and 6% incidence in persons over age 75 years. It is responsible for up to 5% of emergency department (ED) visits and up to 3% of hospital admissions. The median cost of hospitalization of patients with syncope is approximately $8500, and many (up to 50%) may be discharged from the hospital without a clear or specific diagnosis that caused the syncopal episode.

Syncope can present various diagnostic challenges, as many episodes of transient loss of consciousness may occur as unwitnessed events and with limited available history. Furthermore, while the vast majority of syncope etiology is benign, a sizable minority of patients have etiologies with high risk of mortality (ie, patients with cardiac causes). Many testing modalities are also available in the evaluation of syncope, and judicious selection as well as timing and order of the most appropriate modalities can be challenging. Finally, while many patients are admitted to the hospital, up to 40% of patients are discharged without a clear, well-delineated diagnosis following initial workup. However, following extended systematic evaluation (including outpatient evaluation when indicated), less than 20% of patients diagnosed with syncope will remain with a final diagnosis of unknown cause.

Estimates of syncope recurrence suggest that prior syncope, psychiatric illness, and age less than 45 years confer a higher risk of recurrent syncope. Surprisingly, severities of presentation, structural heart disease, and tilt test response have no predictive value on syncope recurrence. Carotid sinus syndrome (CSS), the association of a syncopal event or events with carotid sinus hypersensitivity, has the highest prevalence (43%) in a population of patients presenting with recurrent syncope to the ED. Approximately 12% of patients with recurrent syncope presenting to an ED have associated soft-tissue injury or fracture.

Transient hypoperfusion of the brainstem or both cerebral hemispheres can result from either decreased cardiac output or significant decrease in peripheral vascular resistance. These two mechanisms form the basis of the pathophysiology behind all syncopal events (Figure 99-2). Specific diagnoses (or etiologies of the syncopal episode) may then be derived based on symptoms, signs, and additional testing that lead to their likely pathophysiologic origin.

In patients with traumatic injury (eg, coup-contracoup or concusion injury), transient LOC is not associated with decreased blood flow. In nontraumatic transient LOC, clinicians should consider seizure and psychogenic etiologies. Rarer causes of transient LOC without syncope include tumor, metabolic etiologies, or intoxications. Several conditions may be incorrectly diagnosed as syncope, (ie, “nonsyncope”) (Table 99-1). Clinicians should consider anemia or pregnancy in the appropriate clinical setting.

Syncope etiologies (and relative frequencies) are broadly divided into four major categories (reflex syncope, orthostatic, cardiac, and neurologic) in addition to unknown etiology (Table 99-2). Reflex (most commonly vasovagal) syncope occurs most commonly, followed by cardiac etiologies. More than 70% of cardiac causes are due to arrhythmia, while the remainder is due to various types of structural heart disease.

Following identification of true syncope (ie, excluding nonsyncope based on history, physical exam, and initial testing), narrowing the differential diagnosis should be accomplished based on suggestive clinical features and appropriate diagnostic testing (Table 99-3). The relative yield and contribution of advanced diagnostic modalities in syncope should be considered when selecting modalities in the diagnosis of syncope patients.

History

The relevant aspects of the history include the patient's symptoms experienced prior to and following loss of consciousness, the setting in which syncope occurred, the patient's past medical and psychiatric history, medications, and social history. Prior episodes and frequency of syncope episodes may also potentially help guide diagnosis and/or testing.

Determination if the event is truly syncope, rather than nonsyncope, can help include or exclude items within the differential diagnosis (Table 99-1). This initial evaluation incorporates a careful history of events before and after the LOC, a thorough assessment of past medical history, a complete medication and allergy review, and assessment of family history (including sudden death) and social history (Table 99-4).

Did the patient actually experience a sudden, transient LOC? Was there spontaneous recovery without resuscitation?

Certain historical features may point toward a nonsyncopal event (Table 99-1). History should delineate if there was actual loss of consciousness. A mechanical fall or confusion (altered consciousness) would not be termed syncope or even LOC.

If the patient did actually lose consciousness, consideration of nonsyncopal etiologies of transient LOC including intoxications, hypoglycemia, hypoxia, or severe anemia may be appropriate even though these rarely lead to LOC. These patients may have more gradual development of symptoms prior to a syncopal episode and/or delayed recovery (many minutes to hours) compared with true syncope.

When LOC was witnessed, description of tonic-clonic activity obviously points toward seizure as a nonsyncopal etiology of transient LOC; however, lay person witnesses of seizure activity may not be reliable in description. When a seizure is not witnessed, historical features that may point toward seizure as an etiology include lateral tongue biting or laceration (reasonably specific for seizure), pre-LOC aura, and bowel or bladder incontinence (the latter, a nonspecific finding that may occur in syncope as well). Prolonged recovery (more than one or a few minutes) to normal mentation is another hallmark of seizure, and differs significantly compared to true syncope.

Importantly, many patients with syncope are misdiagnosed as seizure due to misperception of witnesses or misinterpretation of body movement descriptions from bystanders. Any syncopal episode can lead to brief myoclonic activity (occurs in up to 10% of patients with vasovagal syncope and other types of syncope), and up to 1% of syncope patients can have benign brief (lasting one or a few seconds) “full body stiffening” prior to awakening. Many may misinterpret this as seizure activity (which alternately should last minutes or longer rather than seconds).

Extended duration of actual LOC is referred to as coma rather than syncope (which is transient). LOC that required resuscitation or defibrillation to return a pulse and consciousness is referred to as sudden cardiac death and not syncope.

Cardiac Syncope (Inadequate Cardiac Output, Arrhythmias)

Historical features suggesting cardiac etiologies of syncope include chest pain prior to syncope, syncope during exertion, and syncope while supine. In ventricular tachycardia, patients may present with syncope that has no prodrome. Often those patients recall no specific symptoms prior to the syncopal episode, only recall awakening, and are often injured from a fall.

Pump failure:

Is this patient having an acute MI?

Up to 10% of patients with acute myocardial infarction (MI) present with syncope. Similarly, up to 7% of patients who present with syncope and no chest pain may have ischemia as the cause of their syncopal event. Please refer to Chapter 124 on acute coronary syndromes (ACS) for relevant aspects of history and examination presentation of patients with acute MI or unstable angina. Any patient who presents with syncope who also had chest pain either before or after the syncopal episode needs to be evaluated for possible ACS with cardiac enzymes, telemetry monitoring, serial ECGs, and stress testing if indicated. In patients who have syncopebut no chest pain, four factors are predictive of ACS as the etiology of the syncope: (1) arm, neck, shoulder, and throat pain, (2) history of stable angina (provoked by exercise), (3) the presence of rales on physical examination, and (4) electrocardiographic ischemic abnormalities.

Patients without ischemic abnormalities on ECG are not at risk for an acute ischemic event compared to those with ischemic abnormalities on ECG.

Obstruction:

Is there obstruction to flow resulting in inadequate cardiac output?

Patients may have valvular, subvalvular, or vascular obstruction leading to reduced or transiently blocked cardiac output and a syncopal event. Valvular causes include aortic stenosis (AS), mitral stenosis, pulmonic stenosis (PS), or prosthetic valve malfunction. Historical features may include exertional syncope.

Subvalvular cardiac causes include hypertrophic obstructive cardiomyopathy (HOCM) and atrial myxoma. Classic symptoms in HOCM include postexertional syncope. Vascular obstruction can occur due to pulmonary embolus (PE) or significant pulmonary hypertension. Of all patients admitted to the hospital with syncope, less than 1% are due to PE. However, despite occurring uncommonly clinicians should consider the diagnosis in patients with pleuritic chest pain, shortness of breath or symptoms to suggest lower-extremity venous thromboembolism.

Are ventricular arrhythmias suspected as the cause of syncope?

Risk factors include CAD, valvular AS, cardiomyopathy, congenital heart disease, prolonged QT interval on ECG, use of antiarrhythmic drugs especially in patients with reduced LV function, hypo- or hyperkalemia, and hypomagnesemia. History may include palpitations, chest pain, or syncope in association with exercise. However, classically patients with ventricular arrhythmia causing syncope present with no symptoms at all prior to the syncopal event, and injury can occur commonly. Syncope while supine is also concerning for possible ventricular arrhythmia. Finally, a variety of drugs may prolong the QT interval (www.qtdrugs.org), and place patients at risk for torsades de pointe.

Are supraventricular arrhythmias or bradyarrhythmias suspected as a cause of syncope?

While syncope occurs uncommonly in supraventricular tachyarrhythmias, risk factors may include prior history or risk of atrial fibrillation, atrial flutter, multifocal atrial tachycardia, and AV node reentrant tachycardia. Malignant bradyarrhythmias can lead to syncopal events, and may be due to conduction system disease, especially with AV nodal blocking agents, pacemaker malfunction, bundle branch blocks (BBB), or bifascicular block.

Reflex Syncope

Is the patient having a benign vasovagal episode?

Reflex syncope, also known as vasodepressor syncope, vasovagal syncope, neurocardiogenic syncope, or the “common faint,” is the most common cause of syncope. Reflex syncope is mediated by inappropriate vasodepressor (ie, loss of vasoconstriction during standing) or cardioinhibitory (ie, reflex reaction characterized by bradycardia and/or asystole) responses to orthostatic challenge or emotional stress. It may also be precipitated by Valsalva (eg, micturition, defecation, swallowing) or mobilization after prolonged bed rest.

Diagnosis is clinical by eliciting classic symptoms. The classic prodrome, exhibited by a sympathetic response—diaphoresis, palpitations/tachycardia, piloerection, anxiety, pallor—followed by a parasympathetic response—nausea and/or vomiting, warmth/venodilation, low heart rate—can help correctly diagnose the condition. Obviously, individual patients may exhibit only a portion of the classic symptoms.

In reflex syncope related to carotid sinus hypersensitivity, classically there is no mechanical trigger leading to syncope, and it should be diagnosed by provocation through carotid sinus massage. Occasionally, these patients may describe syncope after rapid head or neck movements.

Sometimes, reflex syncope can occur in response to serious vascular events, particularly subarachnoid hemorrhage or aortic dissection. In these cases, the syncope itself may be a benign reflex event, but the underlying precipitant is life threatening and must be identified through additional historical clues such as severe headache or intense chest and back pain.

Orthostatic Hypotension

Is orthostasis causing the patient's syncope?

Syncope due to orthostatic hypotension (OH) can occur with (1) inadequate venous return (low cardiac output), (2) structural damage to the autonomic nervous system (ANS), or (3) transient impairment of normal autonomic nervous system function. The latter may occur with medications that block the normal autonomic responses of the heart (eg, beta-blockers or nonselective calcium channel blockers [CCBs]), or with medications that block the normal autonomic responses of the vasculature (eg, peripherally-acting CCBs or alpha-blockers).

Inadequate venous return may be caused by volume depletion due to inadequate intake or excess losses through the gastrointestinal track, kidneys, or insensible losses (skin, lungs). Low venous return due to venous pooling can occur within the splanchnic system following a meal or in the peripheral venous system (eg, venous insufficiency).

Low peripheral resistance can result from primary or secondary autonomic nervous system (ANS) failure (Figure 99-2). With an intact ANS, drug-induced ANS failure or inappropriate vasodepression during a reflex response can cause syncope. These etiologies can be categorized as syncope due to orthostatic intolerance or orthostatic hypotension (OH). Vasovagal syncope occurs when the initial adaptation reflex is appropriate with orthostatic challenge, but eventually venous return falls and there is an inappropriate cardioinhibitory response, leading to bradycardia (and low cardiac output) while blood pressure (peripheral vascular resistance) is already low.

Finally, postural orthostatic tachycardia syndrome (POTS) is a poorly understood entity believed to occur due to autonomic dysfunction that can be exacerbated by deconditioning. It is manifested by a pathologic excess of venous pooling, early palpitations (in which HR increases by 30 bpm, or up to 120 bpm with standing) and BP instability in response to the venous pooling. It may be associated with chronic fatigue syndrome.

In the elderly, in addition to drug-induced OH, there are two predominant forms of OH: classical OH and delayed OH. In classical OH, chronic ANS failure impairs sympathetic vasoconstriction leading to low systemic vascular resistance in an orthostatic challenge. systemic vascular resistance (SVR) in an orthostatic challenge. In delayed OH, a decline in venous return is coupled with inappropriately low CO and impaired vasoconstriction, leading to syncope.

Physical Examination

Initial physical examination should focus on vital signs, including orthostatic assessment and thorough cardiac and neurologic evaluations. At least two retrospective studies (including more than 2700 patients) have shown that orthostatic evaluation is documented in less than 40% of patients admitted to the hospital with syncope. The orthostatic evaluation is a critical piece of information (irrespective of having received intravenous fluids in the emergency department), and should always include heart rate in addition to pulse. Supine parameters should be obtained after the patient has been resting quietly for a few minutes, followed by having the patient stand upright if possible. Obtain and record blood pressure immediately upon standing, then repeat the process in the next two to three minutes, with a pulse rate obtained at the end of the standing period. Cardiac examination should include inspection, evaluation of arterial and venous pulsations and bruits (especially carotid auscultation), and cardiac palpation and auscultation. Evaluation for rales, jugular venous distention, any displacement of the apical impulse, and S3 can aid in the diagnosis. A neurologic examination should include level of consciousness and orientation, cranial nerves, motor, sensory, cerebellar, and gait evaluations.

Key historical features and physical examination should guide appropriate diagnostic direction (Table 99-4). The history and physical examination aid with rapid recognition of life-threatening etiologies and are critical for clinicians to make appropriate decisions regarding discharge versus further triage and management.

Significance of the ECG

The ECG plays a critical role in the initial evaluation, risk stratification, and treatment course related to a syncopal event. An ECG should be obtained in all patients who present to the ED, clinic, or hospital following a syncopal episode. The ECG is abnormal in 50% of patients who present with syncope. However, the ECG is diagnostic in only approximately 5% of patients. An ECG can reveal ischemia, rhythm abnormalities, atrioventricular (AV) conduction abnormalities, preexcitation (Wolff-Parkinson-White, WPW), Brugada pattern (ST elevation in V1-V3 with right bundle branch pattern), long QT syndrome (LQTS), and arrhythmogenic right ventricular cardiomyopathy (V1-V2 negative T waves, epsilon waves, and delayed ventricular potential, ARVC). Please refer to the chapters on supraventricular tachyarrhythmias, Chapter 126, and ventricular arrhythmias, Chapter 128, for more information.

Findings considered diagnostic of syncope at the time of an event include high-grade AV block such as Mobitz type II second degree AV block or complete heart block, symptomatic sinus bradycardia (< 50 bpm), sinoatrial exit block, alternating RBBB and LBBB, rapid paroxysmal SVT or VT, sinus pause greater than three seconds, and pacemaker malfunction. ECG monitoring during inpatient telemetry is diagnostic when a syncopal event can be correlated to an ECG abnormality. However, inpatient telemetry is diagnostic for syncope etiology in only about 1% of inpatients admitted with a syncopal event.

Identification of Lower-Risk Patients Based on ECG

Relevant studies help clinicians utilize the ECG to identify patients at lower risk for ischemia or ventricular arrhythmias following a syncopal episode. The greatest predictors to identify patients with ischemia or ACS leading to syncope include ischemic abnormalities on ECG; history of arm, neck, or shoulder pain; rales on pulmonary exam; and history of stable angina.

Clinical predictors of ventricular arrhythmia or death within one year include abnormal ECG, history of ventricular arrhythmia, history of heart failure, and older age. Patients with none of these risk factors have <1% risk of death or ventricular arrhythmia at one year; compared to >10% risk in those with two or more of the risk factors present.

A reassuring ECG coupled with a history suggestive of a benign syncopal etiology can help to identify low-risk patients who may be safe to discharge from an ED or hospital early in the evaluation process.

Risk Stratification

When the etiology of syncope remains uncertain after initial evaluation (history, physical examination, and ECG), risk stratification helps determine who deserves further immediate inpatient evaluation, and who can be safely discharged home for either no further evaluation or outpatient evaluation. Several risk stratification algorithms or “rules” have undergone prospective validation and can be used to identify short-term or longer-term risk (Table 99-5). These tools can help clinicians stratify patients for possible early discharge from the ED or hospital versus continued evaluation based on estimated risk of adverse outcome.

Further Evaluation in the Hospitalized Patient

Reasons for hospital admission include suspicion of a neurologic or cardiac cause of syncope, frequent or recurrent symptoms, and/or documented injury or high estimated risk for injury. Clinicians should strongly consider hospital admission and evaluation of syncope patients with structural heart disease or coronary atherosclerotic heart disease, those with ECG or clinical findings suggestive of syncope due to arrhythmia or ischemia, and those with important comorbidities such as culprit electrolyte deficiencies (magnesium, potassium, calcium) or significant/symptomatic anemia.

Syncope guidelines suggest clinical criteria for admission of patients presenting with syncope (see Table 99-6).

Inpatient Admission versus 24-Hour Observation

Patients with syncope should be admitted under observation status unless there is a clear etiology identified or significant risk of bodily injury, recurrent syncope, or high mortality risk.

Figure 99-3 outlines a proposed algorithm for initial hospital evaluation of the patient and provides direction for further consultation and testing. In the patient without a clear cause of syncope, if historical features suggest a vasovagal cause or suspicion is low for cardiogenic syncope, the patient can be safely discharged with close follow-up.

Other Inpatient Testing

The following sections highlight key points of ancillary testing for inpatients and outpatients presenting with syncope (Table 99-7).

Telemetry Monitoring

Although telemetry—inpatient continuous electrocardiographic monitoring—has been shown to have a poor diagnostic yield (1%-16%) in the evaluation of syncope, it should be employed for patients with a high pretest probability of arrhythmia as the syncope etiology to avoid incurring further morbidity or short-term mortality. Telemetry monitoring during a hospitalization for syncope only occasionally identifies arrhythmia as syncope etiology, but also may help document absence of arrhythmia during a witnessed syncopal event, if that occurs during the monitoring.

Echocardiography and Cardiac Imaging

While seldom diagnostic of syncope in the absence of severe aortic stenosis, atrial myxoma, or tamponade, echocardiography is a valuable tool in assessing cardiac structure and function. The echocardiogram can rapidly identify structural abnormalities including left ventricular dysfunction, hypertrophic cardiomyopathy with or without outflow tract obstruction, right ventricular strain or dysfunction in the setting of PE or moderate to severe pulmonary hypertension, and pericardial effusions or thickening in the setting of constrictive cardiomyopathy or cardiac tamponade.

In a patient with unexplained syncope, abnormal ECG, or history of cardiac disease, an echocardiogram helps risk stratify patients by ejection fraction and can help identify a subset of patients who may benefit from implantable cardioverter-defibrillator (ICD) placement for the primary prevention of sudden cardiac death (SCD). However, one study showed that patients with an unremarkable cardiac history and normal ECG do not benefit from echocardiography in the evaluation of syncope.

The use of CT, MRI, and transesophageal echocardiography (TEE) are limited to more specific situations, such as in the evaluation of aortic dissection, cardiac masses seen on transthoracic echocardiography, pulmonary embolism, diseases of the pericardium/myocardium predisposing to restrictive/constrictive cardiomyopathy, and congenital coronary artery anomalies.

Cardiac Enzymes

Cardiac enzymes have relatively low yield if ordered in unselected patients presenting with syncope, and can lead to additional significant health care costs with the average cost effectiveness (ie, total screening cost of syncope patients per number of diagnoses yielded by screening) of indiscriminate screening equal to >$22,000 per diagnosis. However, at least one retrospective study suggested that up to 7% of patients with syncope and without chest pain had acute coronary syndrome as the etiology of the syncope. It is appropriate to order cardiac enzymes in syncope patients who present with signs or symptoms suggestive of cardiac-related syncope (eg, exertional syncope or syncope associated with chest pain, neck or arm pain, or shortness of breath), and in those with known or suspected coronary disease

Exercise Stress Testing

While exercise testing for syncope evaluation has very low diagnostic yield, such testing can provide value when ordered for specific indications (see Table 99-8). The 2006 ACC/AHA guidelines on syncope management recommend exercise testing in patients with history of coronary artery disease, after echocardiography has been completed to rule out outflow tract obstruction or other contraindication to exercise stress.

Syncope after exercise can be reflex-mediated, whereby tachycardia induces a high-grade AV block distal to the AV node; this finding is associated with underlying conduction disease and a risk for permanent AV block. Exercise stress testing is diagnostic when syncope and hemodynamic changes consistent with a syncopal state are reproduced and documented during exercise or when Mobitz II second degree or third degree AV block develop during exercise even without syncope.

Carotid Sinus Hypersensitivity/Syndrome (CSH/CSS) Testing

At the bifurcation of the common carotid artery lies the carotid body baroreceptor, compression of which can lead to a slowing of heart rate and fall in blood pressure. CSH is defined as: carotid sinus massage (CSM) leading to a ventricular pause of greater than three seconds and/or a drop in systolic BP of 50 mm Hg or more without symptoms (or a SBP drop of 30 mm Hg or more with symptoms). CSH that produces syncope is classified as CSS.

CSS occurs more frequently in patients above 40 years old, and much more so in elderly patients (>70 years). The majority of patients with CSH do not present with a classic history of neck rotation or neck constriction leading to syncope. In those patients over age 40 without clear etiology of syncope after initial thorough workup, CSH should be evaluated with carotid sinus massage (CSM).

CSM should be conducted in a structured manner (Figure 99-4). Neurologic complications estimated from a compilation of over 7000 patients in three studies indicates a complication rate of 0.29%, suggesting this is a safe procedure with appropriate patient selection. CSM is recommended for elderly patients with unclear etiology of syncope.

Neurologic Evaluation

Well-performed retrospective observational studies have demonstrated that indiscriminate ordering of neurologic testing (brain imaging, electroencephalogram [EEG], or carotid ultrasound) in patients with syncope has very low yield (1–2%) to find a neurologic cause of syncope, and is fraught with false-positive tests, particularly when carotid disease is identified, which is a common condition that almost never causes syncope absent a clinical stroke. Ordering neurological studies only when the history or physical examination suggests a neurologic etiology for syncope improves the yield of testing to 30–35%. Therefore, brain imaging, EEG, and carotid ultrasonography are not part of the routine evaluation of patients with syncope and should be reserved for patients with neurologic symptoms and/or signs.

Neurologic causes of syncope are rare and a more thorough evaluation should be pursued if the initial assessment is suggestive of such an etiology. Dysautonomia can lead to autonomic nervous system failure (ANF) in the elderly and should be evaluated as part of the orthostatic hypotension workup (Table 99-3).

Trauma and elevated intracranial pressure: While head trauma and conditions predisposing to increased intracranial pressure (eg subarachnoid hemorrhage and intracranial neoplasm) can cause transient loss of consciousness the patient's history and physical exam will generally identify neurologic findings such as headache, meningismus, pupil defect, and sensorimotor or cranial nerve defect. In these cases, it is appropriate to pursue further workup with head imaging such as computerized tomography or magnetic resonance imaging.

Cerebrovascular event: Cerebrovascular disorders can rarely lead to syncope. Subclavian “steal” phenomenon is seen when there is retrograde blood flow in a vertebral artery in the setting of a proximally stenosed left subclavian artery. Blood is, effectively, rerouted from the posterior cerebral circulation to supply the arm, and this may lead to syncope or other symptoms of posterior cerebral ischemia during asymmetric arm exercise.

A transient ischemia attack (TIA) or stroke of the carotid artery does not cause transient loss of consciousness, but global cerebral ischemia from chronic diffuse intracranial vascular disease can lead to syncope if the vertebrobasilar circulation is involved; however, focal neurologic deficit such as limb weakness, ataxia, or cranial nerve deficit would also be present.

The role of carotid ultrasound in the routine evaluation of syncope has not been established. However, carotid ultrasound in patients at high risk of carotid disease may be appropriate prior to carotid sinus massage (Figure 99-4). Finally, in the absence of focal neurologic deficit, the diagnostic yield of this test is demonstrably poor.

Seizure: Active seizures can predispose to transient loss of consciousness, and up to 5–10% of all events described as syncope may be due to seizures. Some cases of syncope are misdiagnosed as seizure because cerebral hypoxia from any cause can lead to myoclonic jerking motions or involuntary movement misrepresented by onlookers as a tonic-clonic or generalized seizure. The history is the most useful tool in distinguishing seizure from true syncope; seizure is more likely if an aura phenomenon is described preceding the event, classic automatisms (lip smacking, frothy oral secretions) are involved, postrecovery myalgia and fatigue are seen, or if recovery is prolonged more than seconds to a minute. Importantly, a postictal, prolonged (usually more than one minute) recovery state is suggestive of seizure rather than syncope.

If seizure is suspected as the most likely diagnosis or if there is a provoked attack resulting in a suspected case of psychogenic pseudosyncope or pseudoseizure, an electroencephalogram (EEG) is an important diagnostic tool. When syncope is the most likely cause, an EEG is usually inappropriate, because interictal EEGs often are usually normal and cannot rule out seizure, and because a small subset of patients without any clinical seizures have asymptomatic epileptiform spikes on EEG.

Additional Outpatient Testing for Syncope

Syncope that is recurrent or which is not considered life threatening after 24–48 hours of inpatient monitoring can be evaluated safely in an outpatient setting.

Electrophysiological Study

Electrophysiologic (EP) studies evaluate patients for an abnormal cardiac electrical system that might lead to tachyarrhythmias or bradyarrhythmias as a cause of syncope. EP studies can be used to identify intermittent significant AV nodal block that is not caught on ECG in patients at risk (eg, patients with bifascicular block on ECG). It can also be used to identify inducible ventricular arrhythmias in patients with structurally abnormal hearts or those with other symptoms, signs, or testing to suggest ventricular arrhythmia risk. EP studies may also identify supraventricular tachyarrhythmias (SVTs), but most SVTs do not require invasive diagnostic modalities. However, it is sometimes used for treatment (eg, catheter ablation) of SVTs that cause symptoms, including recurrent syncope.

Head Up Tilt Table Testing

Introduced in 1986, head-up tilt-table testing (HUTT) can be utilized to establish the diagnosis of reflex syncope when the diagnosis is not obvious or clear based on the patient's history, physical examination (including orthostatic vital sign measurements), or other basic testing. Its greatest utility is in patients with recurrent episodes in which reflex syncope is suspected. Unless there are occupational hazards or a high risk of injury associated with syncope, testing for a single or rare event is not indicated. Furthermore, tilt testing can be used to help distinguish syncope from epilepsy (when the patient presents with jerking movements and seizure disorder is in doubt) or to help identify the cause of syncope in the elderly with multiple falls. Some protocols with HUTT use provocative agents (eg, isoproterenol or sublingual nitroglycerin) to decrease vascular tone or increase heart rate. These agents, when used, increase the test's sensitivity, but reduce specificity and reproducibility (Table 99-9).

When the patient undergoes head-up tilt, venous pooling is the norm, but impaired cardiac output without an appropriate vasoconstriction response is seen in patients with reflex syncope. A positive response to tilt testing is documented when syncope occurs in the setting of hypotension preceding either a mixed cardioinhibitory/vasodepressor response (ie, HR falls to less than 40 bpm for 10 seconds or less), cardioinhibitory response (HR < 40 for > 10sec, with or without asystole), or vasodepressor response (HR does not fall more than 10% from its peak). Exceptions to the diagnosis of vasodepressor response include chronotropic incompetence, in which the HR does not rise more than 10% above baseline at any time, and POTS, in which an excessive HR rise (defined as HR >130 bpm) is seen at the onset of tilt and for the duration of the entire procedure.

Holter Monitoring, External Loop Recorders and Implantable Loop Recorders

Short-term or long-term electrocardiographic monitoring can help establish the diagnosis of arrhythmia as the cause of syncope or help in ruling out arrhythmia. In the patient whose syncope is not life threatening and in whom a definitive diagnosis has not been established, outpatient telemetry via Holter monitoring or loop recorders should be considered. In general, Holter recordings are most useful in patients with daily symptoms of lightheadedness or palpitations, whereas loop recorders are indicated for patients with less frequent symptoms.

Holter monitoring: Holter monitoring provides 24–72 hours (rarely a few days longer) of continuous ECG monitoring via surface electrodes and a portable battery pack/recording device at a cost of roughly $1000 per device and associated servicing costs. Patients who may benefit include those with a high suspicion of arrhythmia, structural heart disease, or an abnormal ECG without meeting inpatient criteria for syncope; or in the evaluation of the discharged patient without a definitive diagnosis. The yield for a diagnosis of syncope is from 1–4% and negative yield (ie, patients in whom an arrhythmia was not detected during a syncopal event, effectively ruling out arrhythmia) is near 15%. Holter monitoring carries a very high cost-per-diagnosis ratio due to the infrequency of arrhythmic events in most patients with syncope of unknown etiology.

External loop recorder: An external loop recorder, also a portable system with cutaneous electrodes, can be worn and used to retrieve data generated over 3-4 weeks and up to 2-3 months if there is a history of syncope or symptoms suspicious for arrhythmia. Indications are similar to those for Holter monitoring. The loop recorder continually stores and deletes ECG data. At the time of patient manual activation of the recorder, 5–15 minutes of preactivation ECG data is stored for analysis. From prospective studies, at best the positive yield to achieve diagnosis is approximately 15–25%, and the negative yield is approximately 20%, giving this modality also a high cost-per-diagnosis ratio. Patient compliance beyond three weeks is unusual and further limits the usefulness of this test.

Implantable loop recorders: Implantable loop recorders (ILRs) can provide ECG data up to 36 months and obtain higher diagnostic yield per device than other recording modalities such as the Holter monitor. In selected populations, ILRs yield a diagnosis in 50–90% of patients, but come with an initial high cost (˜$10,000 or more) and the requirement of implantation during a minor surgical procedure (similar to pacemaker placement).

The majority of patients evaluated in studies of ILR do not have an initial presentation consistent with reflex syncope or evidence of structural heart disease. Investigators in the International Study on Syncope of Unknown Etiology (ISSUE) group have proposed classification of ILR data into four broad groups: asystole, bradycardia, no/minimal rhythm disturbance, and tachycardia for standardization of patient data. ISSUE2 reported lower recurrent syncope rates in patients given therapy specific to their arrhythmia (ICD, pacemaker, catheter ablation, antiarrhythmic) in comparison to those who were given no specific therapy after patients in both treatment groups suffered from a vasovagal event. ISSUE3 will conduct a randomized placebo-controlled trial to test the efficacy of pacing for reflex syncope.

Syncope in the Patient with Psychiatric Illness

Antipsychotic medications and side effects from chronic use can lead to orthostatic hypotension or QT interval prolongation, either of which may result in syncope. Key medications to inquire about include benzodiazepines, SSRI or MAOI antidepressants, barbiturates, neuroleptics and tricyclic antidepressants, as well as drugs of abuse such as ethanol.

In the evaluation of transient loss of consciousness (T-LOC), an EEG can be valuable in diagnosing pseudoepilepsy (ie, nonepileptic seizures or nonepileptic attack disorder), in which gross limb movements accompany T-LOC but an EEG shows no epileptiform activity. Furthermore, if the patient should lose postural tone, suffer a T-LOC, but show no signs of limb movement or epileptiform attack, a negative EEG and normal BP/HR during a positive tilt-table test help to effectively diagnose a condition referred to as pseudosyncope. In pseudosyncope, the patient history does not usually identify a trigger to the event. Attacks occur frequently and can last for several minutes—in contrast to only several seconds of T-LOC seen in true syncope. While pseudosyncopal events are believed to be involuntary just as syncopal events, suggestion by the clinician can potentially trigger a syncopal event in this functional disorder.

Psychiatric testing can be valuable and indicated in patients with multiple or frequent episodes of syncope without injury, or in recurrent syncope when other exhaustive workup or evaluation has not yielded any certain diagnosis.

Special Case: Recurrent Syncope

Regardless of etiology, syncope recurs in approximately 30–40% of patients followed for three years after the diagnosis. In patients with vasovagal syncope, prognosis is generally excellent, but recurrence occurs in approximately 30% of patients followed from seven months up to five years. While age is not predictive of future risk of recurrence, shortened time to recurrence after diagnosis and number of previous syncopal episodes increase recurrence risk. While recurrent syncope does not confer a higher mortality risk than an isolated syncopal episode, the morbidity incurred via injury and trauma with recurrent episodes does impose restrictions on patient quality of life and well-being.

Special Case: Elderly Patients with Syncope

Elderly patients often have coexistence of many predisposing medical conditions that can lead to syncope. Common causes in the elderly population include orthostatic hypotension, reflex syncope, and arrhythmias. Syncope of cardiac origin carries a similar mortality risk in both young and old.

As in all patients, a detailed but focused history and physical examination can yield a diagnosis in the great majority of initial evaluations. A comprehensive medication history focusing on temporal relationships between the falls/syncope and initiation of new medications or dosing changes is critical, as is consideration of changing drug levels due to dynamic renal or hepatic function. Any associated comorbidities such as deconditioning, dependence for activities of daily living, cognitive impairment, and performance status can also increase risk. A focused neurologic examination should be complemented by assessment of gait instability, orthostatic challenge, and balance. Routine carotid sinus massage is recommended for elderly patients presenting with syncope (who do not have contraindications to the test) in addition to the thorough initial assessment as used for younger patients (see Figure 99-4).

Treatment Overview

Irrespective of establishing an etiology for syncope, the primary goals in the treatment of syncope are to reduce the risk of injury/trauma, improve survival, and evaluate and prevent recurrent syncopal events. At the time of initial evaluation, an etiology and mechanism of syncope is pursued. Treatment is aimed at an underlying cause if one can be identified (Figure 99-5).

Reflex Syncope, Autonomic Dysfunction, and Orthostatic Hypotension/Intolerance

In autonomic dysfunction and consequent orthostatic hypotension (OH) or reflex/vasovagal syncope, the aim is to prevent syncope recurrence and limit risk of bodily injury or harm to the patient. Treatment of reflex syncope includes patient education, reassurance, and avoidance of triggers. Recognition of triggers and recognition of a prodrome warning period, such as nausea, lightheadedness, and sense of impending fall or loss of balance can help abort a syncopal event.

Physical counter-pressure maneuvers (PCMS) to increase venous return can be instituted with success if done in a timely manner during prodrome or trigger recognition. These maneuvers involve causing a rapid increase in systolic and diastolic blood pressure through the timely initiation of either gluteal muscle tightening with concomitant leg crossing or arm tensing through interlocking handgrip and isometric contraction. In a multicenter, prospective trial, the burden of recurrent syncope enjoyed a relative risk reduction of near 40% when comparing patients who had received physical counter-pressure maneuver training with those who did not.

Pharmacologic therapy for prevention and treatment of reflex syncope address peripheral vasoconstriction, volume expansion, prevention of paradoxical bradycardia and excess vagal activity, and treatment of anxiety (Table 99-10). No randomized controlled trial evidence establishes benefit of these therapies. Acute reflex syncope during tilt testing is modestly improved with midodrine, but long-term studies are lacking. While a “pill-in-the-pocket” strategy for impending syncope along with counter-pressure maneuvers may benefit some patients taking midodrine, its frequent dosing and urinary retention limit its effectiveness. Randomized, placebo-controlled trials with beta-blockers to prevent reflex syncope show no long-term risk reduction from future syncopal events. A short-term follow-up study in a small number of patients showed modest benefit for paroxetine in preventing recurrent syncope in patients who did not tolerate beta-blockers, mineralocorticoids, and vagolytics. Fludrocortisone has not been proven effective in syncope prevention. None of the medications commonly used for reflex syncope has Food and Drug Administration approval for this indication.

Cardiac pacing and device therapy has shown no significant aggregate benefit in syncope based on meta-analysis of five large trials. The development of autonomic dysfunction and failure (ANF) is manifested by an inappropriate sympathetic nervous system response to orthostatic challenge and can be due to medications, underlying systemic illness, or primary systemic illness (Table 99-3). Volume depletion from dehydration and blood loss should be ruled out initially in the evaluation of these patients. A thorough medication history should rule out medication as the cause; common culprit medications include nitrates, alpha-blockers, calcium channel blockers, beta-blockers, anti-Parkinson medications, antipsychotics, and diuretics.

Treatment of orthostatic hypotension (OH) and intolerance should first seek to employ nonpharmacologic measures. Patients should change posture slowly, increase fluid and salt intake to 3 liters and up to 10 grams sodium per day if supine hypertension is not a comorbid illness, seek adjustment of antihypertensives with physician guidance, and avoid excessive durations of recumbency and sleep, while maintaining the head of the bed at 10–20 degrees. Avoiding the rapid ingestion of cold water, limiting the size of meals and carbohydrate intake, and avoidance of alcohol help reduce postprandial hypotension. The use of tight lower-extremity elastic stockings and occasionally abdominal binders can help maintain venous return while standing. Finally, as in reflex syncope, all patients should be counseled on anticipatory physical counter-pressure maneuvers (PCMs).

Pharmacologic measures for OH treatment are aimed at expanding central volume, improving vasoconstriction, and mitigating various factors such as anemia of chronic inflammation, nocturnal diuresis, and poor sympathetic tone. In those with insufficient plasma volume despite increased salt and water intake, fludrocortisone can be used to enhance distal tubular sodium absorption. Adverse effects include supine hypertension, hypokalemia, and headache. Midodrine, a direct alpha1-receptor agonist, is approved by the FDA for OH. Adverse effects include supine hypertension, bradycardia, and urinary retention. An adjunct therapy in select patients taking or having failed midodrine is the use of pseudoephedrine/ephedrine, direct and indirect alpha-receptor agonists. Adverse effects include tachycardia, central sympathomimesis, and worsening supine hypertension. Finally, adjunct therapies in special situations include desmopressin (DDAVP) to reduce nocturnal diuresis, erythropoietin to correct anemia of chronic inflammation or renal insufficiency, and pyridostigmine to enhance sympathetic nervous system transmission.

Arrhythmias

Specific to the nature of the arrhythmia, treatment of syncope due to arrhythmia varies from medication discontinuation to ICD placement and radiofrequency catheter ablation (RFCA). The choice of therapy is influenced by systolic function and the presence or absence of a vasodepressor component to syncope. See Chapter 126 for more detailed information about supraventricular tachycarrhythmias, Chapter 127 for bradyarrhythmias, and Chapter 128 for ventricular arrhythmias.

For sinus node dysfunction manifested primarily with bradycardia, if syncope is documented during a bradyarrhythmia, cardiac pacing has class I indications for the following situations, according to the European Society of Cardiology 2009 syncope guidelines: sinus arrest without a correctable cause, sinus node disease and evident abnormal corrected sinus node recovery time (CSNRT), and syncope with asymptomatic sinus pauses greater than three seconds. Presence of a vasodepressor component to sinus node dysfunction is an unfortunate cause of syncope recurrence in up to 20% of patients treated with pacing. Atrial tachyarrhythmias, especially as a manifestation of the sick sinus syndrome (SSS), can be effectively treated with RFCA.

For atrioventricular (AV) nodal conduction disease, there are only two class I indications for pacing: 1) syncope with second degree type II (Mobitz) block, complete AV block or advanced AV block; and 2) syncope with bundle branch block and inducible high-degree AV block on EPS.

For patients suffering from paroxysmal supraventricular tachyarrhythmias (pSVT) such as AV nodal reentrant tachycardia (AVNRT), AV reentrant tachycardia (AVRT), and typical atrial flutter (AFL), the availability, safety, and high efficacy of RFCA make this the preferred treatment of choice for syncopal episodes attributable to pSVTs. Syncope due to atrial fibrillation can be managed with RFCA or with pharmacologic therapy aimed at rate or rhythm control. In patients with refractory symptomatic atrial fibrillation producing rapid ventricular response and a predisposition to syncopal events, ablation of the bundle of His with subsequent pacemaker implantation can be considered a safe and effective therapy. Please see Chapter 126 on Supraventricular Tachyarrhythmias for further details about SVT management.

Rarely, ICD or pacemaker device malfunction can lead to syncope. Usually, this is manifested as retrograde conduction in a pacemaker. Device reprogramming or conversion of a single ventricular lead to dual chamber pacing can effectively resolve the problem. In battery/pulse generator failure or in lead fracture/dislodgement/conduction failure, device replacement is necessary and effective.

Structural Heart Disease Management

The primary aim in treating patients with syncope due to structural heart disease is to identify the causative factor contributing to syncope and treat the primary process. An important aim also is to prevent sudden cardiac death (SCD). Structural heart disease such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HoCM), inferior segment myocardial infarction, and cardiac tamponade can directly cause syncope, whereas conditions such as severely impaired systolic function from ischemic cardiomyopathy can lead to macro-reentrant ventricular tachycardia (VT), and predispose to syncope. Treatment is aimed at the underlying process believed to be causing syncope. Placement of an ICD has been established solely to improve mortality risk (not as a means to treat syncope) in patients with a) severe systolic heart failure (with an ejection fraction < 35%), b) HoCM with outflow tract obstruction, and c) patients with a specific predisposition to malignant ventricular arrhythmia (eg, arrhythmogenic right ventricular cardiomyopathy).

Hospitalists should rely on their consultant colleagues when there is a specific question or therapeutic aim to address by the approached specialty. A particularly useful result of the frugal use of consultation is deciding with the consultant whether the patient needs further inpatient testing or treatment and whether outpatient follow-up is sufficient for an otherwise stable condition.

Cardiology

In cases of syncope due to structural heart disease in which a link between the two conditions is relevant and clear, such as in moderate to severe aortic stenosis and exertional syncope, consultation with a cardiologist is valuable and necessary. When an outcome can be improved, such as in ICD placement for a syncopal patient presenting with VT and severely depressed ejection fraction, consultation for further treatment is also necessary and straightforward. Where outcome or causal relationship cannot be entirely established, as in a case of longstanding moderate to severe pulmonary hypertension with syncope, consultation can bring about a second opinion regarding advanced therapeutics.

Inpatient consultation for diagnostic or therapeutic catheterization, tilt-table carotid sinus massage (in elderly patients with recurrent symptomatic syncope of unclear origin), and EPS/pacemaker issues/ICD implantation are all appropriate. The presence of structural heart disease does not mean another noncardiac cause of syncope is less likely.

Neurology

It is rare for syncope to be due directly to neurologic causes. The routine use of brain computed tomography or carotid artery Doppler ultrasound in the initial evaluation of syncope does not have diagnostic value or cost effectiveness when active neurologic symptoms or findings are absent. Syncope can occur from vertebrobasilar insufficiency and associated “steal” syndrome, and a presentation that suggests vertebrobasilar insufficiency may be a rare instance in which neurology consultation is justified.

In the clarification of the patient's initial presentation with loss of consciousness, an EEG can be useful if the history and physical exam indicate seizure disorder or epilepsy in the differential diagnosis. Video-monitored 24-hour EEG can be undertaken if necessary with the help of a neurologic consultation.

Psychiatry

Consultation with a psychiatrist in the evaluation of syncope is done rarely. Indications include identification of psychosomatic conditions predisposing to syncope, such as conversion, somatoform, or factitious disorder. Establishing a psychiatric diagnosis may be useful in patients with recurrent symptomatic syncope who have undergone a thorough negative workup for cardiac, reflex, and orthostatic syncope as appropriate. These patients, prone to suggestion, can be diagnosed with the assistance of a psychiatric consultation as having psychogenic pseudosyncope. Outpatient treatment may include SSRIs, cognitive behavioral therapy, and psychiatric outpatient follow-up.

Prior to discharge, patients should be educated on measures to prevent recurrent reflex syncope, recognition of prodromal symptoms, and warning signs that warrant emergency care. Of particular concern to patients is the fear of syncope recurrence while driving. Driving following a syncopal episode is regulated by individual states, and clinicians should refer to their specific state laws when making recommendations. However, in general, private drivers have no restrictions on driving independent of those imposed by having an ICD according to current society guidelines. If, however, unexplained syncope occurs while driving and/or in the presence of structural heart disease, driving may be prohibited. For professional drivers, permanent restrictions are recommended if an ICD has been implanted, occasional syncope occurs during high-risk activity, syncope is recurrent and severe and treatment has not been established, and in unexplained syncope if treatment has not been established. Long-term accident and insurance data indicate, reassuringly, that rates of vehicular accidents are no higher than in the general population without syncope. Timely follow-up with appropriate outpatient physicians (primary care physicians, cardiologists, neurologists, as indicated) should occur within two to four weeks of hospital discharge.

One of the major areas of practice improvement related to syncope (ICD-9 780.2) is resource utilization. Patients with syncope require a multidisciplinary approach in some cases and in other instances can be discharged safely from the emergency department with close follow-up.

In the United States, up to 5% of all ED patients present with syncope. This equates to approximately 500,000 visits per year. In addition, 3% or approximately 150,000 of all inpatient admissions per year are for syncope. With the cost of each admission ranging from $8000 to $75,000, it comes as no surprise that our annual expenditure for syncope is approximately $2 billion.

Hospitalists are keenly positioned to appreciate costs associated with syncope admissions and the benefits reaped by thoughtful resource utilization. Patients should be risk stratified using well-validated criteria, and further testing carried out to assess posthospital risk or injury and mortality.

Testing should be limited to that necessary for immediate risk stratification and/or diagnosis confirmation or treatments of the syncopal event. In a retrospective analysis of costs associated with inpatient admission of syncope in elderly patients, researchers found that postural blood pressure recording (ie, orthostatics measurement) costs $17 per test affecting the diagnosis or management of a case of syncope. In contrast, the cost effectiveness of cardiac enzyme measurement was $22,397, head CT $24,881, ECG $1020, and telemetry $710 per clinically relevant finding affecting diagnosis or treatment.

Admission for the syncopal patient should not be unnecessarily prolonged. On the part of the hospitalist as coordinator of care, this may require earlier consultation with specialists to plan earlier testing, discharge, and follow-up. In prospective, randomized controlled trials incorporating strict adherence to syncope criteria for admission and utilization of Syncope Management Units (SMU) in the ED to triage syncope patients, there is a marked reduction of hospital length-of-stay, number of tests conducted per patient, and associated lower costs. SMUs involve staffing by ED physicians, cardiologists, and/or neurologists and ready access to echocardiogram, tilt testing, beat-to-beat blood pressure, and continuous telemetry monitoring for up to six hours with a decision reached to admit or discharge in that timeframe. Long-term follow-up to two years has shown no difference in morbidity and mortality in these patients. With careful selection, triage, and early discharge, hospitalists can make a lasting impact on the resources utilized in the management of syncope.

Syncope is characterized by sudden, transient, reversible loss of consciousness with prompt recovery. Recurrent syncope can be distressing to the patient, carries a serious risk of bodily injury and harm, and can lead to significant lifestyle changes including loss of gainful employment. Diagnosis should occur in a timely, cost-efficient manner. At the time of discharge, the goal is to provide the patient with a reasonably confident estimate of prognosis, risk of recurrence, and goals and timing of further diagnostic studies and therapy.

A high-yield approach at initial evaluation involves a thorough history; medication review; physical examination focused on postural blood pressure measurement, cardiac, and neurologic examinations; and electrocardiogram. In those with an unclear etiology, further testing should be done with a focus on efficiency and high-yield tools based on the thorough history and physical examination. Risk stratification should be carried out on initial evaluation in accordance with well-validated risk scoring tools. (see Table 99-5)

Specific causes of syncope such as arrhythmias and structural cardiopulmonary disease should be quickly identified and treated in consultation with a specialist to expedite care as well as to establish adequate, timely follow-up after hospital discharge.

Finally, an area of active research in syncope is the use of syncope management units (SMUs), primarily in emergency departments. Success in Europe is the basis for ongoing investment of this concept in the United States. SMUs can help identify patients who would otherwise be deemed low risk by standardized triage protocols and discharged from the emergency department for rapid follow-up (Table 99-11).