Syncope is a transient, self-limited loss of consciousness due to acute global impairment of cerebral blood flow. The onset is rapid, duration brief, and recovery spontaneous and complete. Other causes of transient loss of consciousness need to be distinguished from syncope; these include seizures, vertebrobasilar ischemia, hypoxemia, and hypoglycemia. A syncopal prodrome (presyn-cope) is common, although loss of consciousness may occur without any warning symptoms. Typical presyncopal symptoms include dizziness, lightheadedness or faintness, weakness, fatigue, and visual and auditory disturbances. The causes of syncope can be divided into three general categories: (1) neurally mediated syncope (also called reflex syncope), (2) orthostatic hypotension, and (3) cardiac syncope.
Neurally mediated syncope comprises a heterogeneous group of functional disorders that are characterized by a transient change in the reflexes responsible for maintaining cardiovascular homeostasis. Episodic vaso-dilation and bradycardia occur in varying combinations, resulting in temporary failure of blood pressure control. In contrast, in patients with orthostatic hypotension due to autonomic failure, these cardiovascular homeostatic reflexes are chronically impaired. Cardiac syncope may be due to arrhythmias or structural cardiac diseases that cause a decrease in cardiac output. The clinical features, underlying pathophysiologic mechanisms, therapeutic interventions, and prognoses differ markedly among these three causes.
EPIDEMIOLOGY AND NATURAL HISTORY
Syncope is a common presenting problem, accounting for approximately 3% of all emergency room visits and 1% of all hospital admissions. The annual cost for syncope-related hospitalization in the United States is ~$2 billion. Syncope has a lifetime cumulative incidence of up to 35% in the general population. The peak incidence in the young occurs between ages 10 and 30 years, with a median peak around 15 years. Neurally mediated syncope is the etiology in the vast majority of these cases. In elderly adults, there is a sharp rise in the incidence of syncope after 70 years.
In population-based studies, neurally mediated syncope is the most common cause of syncope. The incidence is slightly higher in females than males. In young subjects there is often a family history in first-degree relatives. Cardiovascular disease due to structural disease or arrhythmias is the next most common cause in most series, particularly in emergency room settings and in older patients. Orthostatic hypotension also increases in prevalence with age because of the reduced baroreflex responsiveness, decreased cardiac compliance, and attenuation of the vestibulosympathetic reflex associated with aging. In the elderly, orthostatic hypotension is substantially more common in institutionalized (54–68%) than community dwelling (6%) individuals, an observation most likely explained by the greater prevalence of predisposing neurologic disorders, physiologic impairment, and vasoactive medication use among institutionalized patients.
The prognosis after a single syncopal event for all age groups is generally benign. In particular, syncope of noncardiac and unexplained origin in younger individuals has an excellent prognosis; life expectancy is unaffected. By contrast, syncope due to a cardiac cause, either structural heart disease or primary arrhythmic disease, is associated with an increased risk of sudden cardiac death and mortality from other causes. Similarly, mortality rate is increased in individuals with syncope due to orthostatic hypotension related to age and the associated comorbid conditions (Table 10-1).
HIGH-RISK FEATURES INDICATING HOSPITALIZATION OR INTENSIVE EVALUATION OF SYNCOPE
The upright posture imposes a unique physiologic stress upon humans; most, although not all, syncopal episodes occur from a standing position. Standing results in pooling of 500–1000 mL of blood in the lower extremities and splanchnic circulation. There is a decrease in venous return to the heart and reduced ventricular filling that result in diminished cardiac output and blood pressure. These hemodynamic changes provoke a compensatory reflex response, initiated by the baroreceptors in the carotid sinus and aortic arch, resulting in increased sympathetic outflow and decreased vagal nerve activity (Fig. 10-1). The reflex increases peripheral resistance, venous return to the heart, and cardiac output and thus limits the fall in blood pressure. If this response fails, as is the case chronically in orthostatic hypotension and transiently in neurally mediated syncope, cerebral hypoperfusion occurs.
The Baroreflex. A decrease in arterial pressure unloads the baroreceptors—the terminals of afferent fibers of the glossopharyngeal and vagus nerves—that are situated in the carotid sinus and aortic arch. This leads to a reduction in the afferent impulses that are relayed from these mechanoreceptors through the glossopharyngeal and vagus nerves to the nucleus of the tractus solitarius (NTS) in the dorsomedial medulla. The reduced baroreceptor afferent activity produces a decrease in vagal nerve input to the sinus node that is mediated by the neuroanatomical connections of the NTS to the nucleus ambiguus (NA). There is an increase in sympathetic efferent activity that is mediated by the NTS projections to the caudal ventrolateral medulla (CVLM) (an excitatory pathway) and from there to the rostral ventrolateral medulla (RVLM) (an inhibitory pathway). The activation of RVLM presympathetic neurons in response to hypotension is thus predominantly due to disinhibition. In response to a sustained fall in blood pressure, vasopressin release is mediated by projections from the A1 noradrenergic cell group in the ventrolateral medulla. This projection activates vasopressin-synthesizing neurons in the magnocellular portion of the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus. Blue denotes sympathetic neurons and green parasympathetic neurons. (From R Freeman: N Engl J Med 358:615, 2008.)
Syncope is a consequence of global cerebral hypoperfusion and thus represents a failure of cerebral blood flow autoregulatory mechanisms. Myogenic factors, local metabolites, and to a lesser extent autonomic neurovascular control are responsible for the autoregulation of cerebral blood flow (Chap. 28). Typically cerebral blood flow ranges from 50 to 60 mL/min per 100 g brain tissue and remains relatively constant over perfusion pressures ranging from 50 to 150 mmHg. Cessation of blood flow for 6–8 s will result in loss of consciousness, while impairment of consciousness ensues when blood flow decreases to 25 mL/min per 100 g brain tissue.
From the clinical standpoint, a fall in systemic systolic blood pressure to ~50 mmHg or lower will result in syncope. A decrease in cardiac output and/or systemic vascular resistance—the determinants of blood pressure—thus underlies the pathophysiology of syncope. Common causes of impaired cardiac output include decreased effective circulating blood volume; increased thoracic pressure; massive pulmonary embolus; cardiac brady- and tachyarrhythmias; valvular heart disease; and myocardial dysfunction. Systemic vascular resistance may be decreased by central and peripheral autonomic nervous system diseases, sympatholytic medications, and transiently during neurally mediated syncope. Increased cerebral vascular resistance, most frequently due to hypocarbia induced by hyperventilation, may also contribute to the pathophysiology of syncope.
The sequence of changes on the electroencephalogram of syncopal subjects during syncope comprises background slowing (often of high amplitude), followed by attenuation or cessation of cortical activity prior to return of slow waves, and then normal activity. Despite the presence of myoclonic movements and other motor activity, electroencephalographic seizure discharges are not present in syncopal subjects.
NEURALLY MEDIATED SYNCOPE
Neurally mediated syncope is the final pathway of a complex central and peripheral nervous system reflex arc. There is a sudden, transient change in autonomic efferent activity characterized by increased parasympathetic outflow causing bradycardia and sympathoinhibition causing vasodilation. The change in autonomic efferent activity leads to a decrease in blood pressure and a subsequent fall in cerebral blood flow to below the limits of autoregulation (Fig. 10-2). In order to elicit this reflex, a normal or functioning autonomic nervous system is necessary; this is in contrast to the situation in autonomic failure. The triggers of the afferent limb of the reflex arc vary and may be clearly defined, e.g., the carotid sinus, the gastrointestinal tract, or the bladder. In many cases, however, the afferent arc is less easily recognized and, under many circumstances, the cause is multifactorial. Under these circumstances it is likely that multiple afferent pathways converge on the central autonomic network within the medulla that integrates the neural impulses and mediates the vasodepressor-bradycardic response.
A. The paroxysmal hypotensive-bradycardic response that is characteristic of neurally mediated syncope. Noninvasive beat-to-beat blood pressure and heart rate are shown over 5 min (from 60 to 360 s) of an upright tilt on a tilt table. B. The same tracing expanded to show 80 s of the episode (from 80 to 200 s). BP, blood pressure; bpm, beats per minute; HR, heart rate.
Classification of neurally mediated syncope
Neurally mediated syncope may be subdivided based on the afferent pathway and provocative trigger. Vasovagal syncope (the common faint) is provoked by intense emotion, pain, and/or orthostatic stress, whereas the situational reflex syncopes have specific localized stimuli that provoke the reflex vasodilation and bradycardia that leads to syncope. The underlying mechanisms have been identified and pathophysiology delineated for most of these situational reflex syncopes. The afferent trigger may originate in the pulmonary system, gastrointestinal system, urogenital system, heart, and carotid artery (Table 10-2). Hyperventilation leading to hypocarbia and cerebral vasoconstriction, and raised intrathoracic pressure that impairs venous return to the heart, play a central role in many of the situational reflex syncopes. The afferent pathway of the reflex arc differs among these disorders, but the efferent response via the vagus and sympathetic pathways is similar.
CAUSES OF SYNCOPEA
Alternately, neurally mediated syncope may be subdivided based on the predominant efferent pathway. Vasodepressor syncope describes syncope predominantly due to efferent, sympathetic, vasoconstrictor failure; cardioinhibitory syncope describes syncope predominantly associated with bradycardia or asystole due to increased vagal outflow; while mixed syncope describes syncope in which there are both vagal and sympathetic reflex changes.
Features of neurally mediated syncope
In addition to symptoms of orthostatic intolerance such as dizziness, lightheadedness, and fatigue, premonitory features of autonomic activation may be present in patients with neurally mediated syncope. These include diaphoresis, pallor, palpitations, nausea, hyperventilation, and yawning. During the syncopal event, proximal and distal myoclonus (typically arrhythmic and multifocal) may occur, raising the possibility of epilepsy. The eyes typically remain open and usually deviate upward. Urinary but not fecal incontinence may occur. Postictal confusion is rare, although visual and auditory hallucinations are sometimes reported.
While some predisposing factors and provocative stimuli are well established (for example, motionless upright posture, warm ambient temperature, intravascular volume depletion, alcohol ingestion, hypoxemia, anemia, pain, the sight of blood, venipuncture, and intense emotion), the underlying basis for the widely different thresholds for syncope among individuals exposed to the same provocative stimulus is not known. A genetic basis for neurally mediated syncope may exist; several studies have reported an increased incidence of syncope in first-degree relatives of fainters, but no gene or genetic marker has been identified, and environmental, social, and cultural factors have not been excluded by these studies.
TREATMENT Neurally Mediated Syncope
Reassurance, avoidance of provocative stimuli, and plasma volume expansion with fluid and salt are the cornerstones of the management of neurally mediated syncope. Isometric counterpressure maneuvers of the limbs (leg crossing or handgrip and arm tensing) may raise blood pressure and, by maintaining pressure in the autoregulatory zone, avoid or delay the onset of syncope. Randomized controlled trials support this intervention.
Fludrocortisone, vasoconstricting agents, and beta-adrenoreceptor antagonists are widely used by experts to treat refractory patients, although there is no consistent evidence from randomized, controlled trials for any pharmacotherapy to treat neurally mediated syncope. Because vasodilation is the dominant pathophysiologic syncopal mechanism in most patients, use of a cardiac pacemaker is rarely beneficial. Possible exceptions are older patients in whom syncope is associated with asystole or severe bradycardia, and patients with prominent cardioinhibition due to carotid sinus syndrome. In these patients, dual-chamber pacing may be helpful.
Orthostatic hypotension, defined as a reduction in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 min of standing or head-up tilt on a tilt table, is a manifestation of sympathetic vasoconstrictor (autonomic) failure (Fig. 10-3). In many (but not all) cases, there is no compensatory increase in heart rate despite hypotension; with partial autonomic failure, heart rate may increase to some degree but is insufficient to maintain cardiac output. A variant of orthostatic hypotension is “delayed” orthostatic hypotension which occurs beyond 3 min of standing; this may reflect a mild or early form of sympathetic adrenergic dysfunction. In some cases, orthostatic hypotension occurs within 15 s of standing (so-called “initial” orthostatic hypotension), a finding that may represent a transient mismatch between cardiac output and peripheral vascular resistance and does not represent autonomic failure.
A. The gradual fall in blood pressure without a compensatory heart rate increase that is characteristic of orthostatic hypotension due to autonomic failure. Blood pressure and heart rate are shown over 5 min (from 60 to 360 s) of an upright tilt on a tilt table. B. The same tracing expanded to show 40 s of the episode (from 180 to 220 s). BP, blood pressure; bpm, beats per minute; HR, heart rate.
Characteristic symptoms of orthostatic hypotension include light-headedness, dizziness, and presyncope (near-faintness) occurring in response to sudden postural change. However, symptoms may be absent or nonspecific, such as generalized weakness, fatigue, cognitive slowing, leg buckling, or headache. Visual blurring may occur, likely due to retinal or occipital lobe ischemia. Neck pain—typically in the suboccipital, posterior cervical, and shoulder region (the “coat-hanger headache”)—most likely due to neck muscle ischemia, may be the only symptom. Patients may report orthostatic dyspnea (thought to reflect ventilation-perfusion mismatch due to inadequate perfusion of ventilated lung apices) or angina (attributed to impaired myocardial perfusion even with normal coronary arteries). Symptoms may be exacerbated by exertion, prolonged standing, increased ambient temperature, or meals. Syncope is usually preceded by warning symptoms, but may occur suddenly, suggesting the possibility of a seizure or cardiac cause.
Supine hypertension is common in patients with orthostatic hypotension due to autonomic failure, affecting over 50% of patients in some series. Ortho-static hypotension may present after initiation of therapy for hypertension, and supine hypertension may follow treatment of orthostatic hypotension. However, in other cases, the association of the two conditions is unrelated to therapy; it may in part be explained by baroreflex dysfunction in the presence of residual sympathetic outflow, particularly in patients with central autonomic degeneration.
Causes of neurogenic orthostatic hypotension
Causes of neurogenic orthostatic hypotension include central and peripheral autonomic nervous system dysfunction (Chap. 33). Autonomic dysfunction of other organ systems (including the bladder, bowels, sexual organs, and sudomotor system) of varying severity frequently accompanies orthostatic hypotension in these disorders (Table 10-2).
The primary autonomic degenerative disorders are multiple system atrophy (the Shy-Drager syndrome; Chap. 33), Parkinson’s disease (Chap. 30), dementia with Lewy bodies (Chap. 29), and pure autonomic failure (Chap. 33). These are often grouped together as “synucleinopathies” due to the presence of alpha-synuclein, a small protein that precipitates predominantly in the cytoplasm of neurons in the Lewy body disorders (Parkinson’s disease, dementia with Lewy bodies, and pure autonomic failure) and in the glia in multiple system atrophy.
Peripheral autonomic dysfunction may also accompany small fiber peripheral neuropathies such as those seen in diabetes, amyloid, immune-mediated neuropathies, hereditary sensory and autonomic neuropathies (HSAN; particularly HSAN type III; familial dysautonomia), and inflammatory neuropathies (Chaps. 46 and 47). Less frequently, orthostatic hypotension is associated with the peripheral neuropathies that accompany vitamin B12 deficiency, neurotoxic exposure, HIV and other infections, and porphyria.
Patients with autonomic failure and the elderly are susceptible to falls in blood pressure associated with meals. The magnitude of the blood pressure fall is exacerbated by large meals, meals high in carbohydrate, and alcohol intake. The mechanism of postprandial syncope is not fully elucidated.
Orthostatic hypotension is often iatrogenic. Drugs from several classes may lower peripheral resistance (e.g., alpha-adrenoreceptor antagonists used to treat hypertension and prostatic hypertrophy; antihypertensive agents of several classes; nitrates and other vasodilators; tricyclic agents and phenothiazines). Iatrogenic volume depletion due to diuresis and volume depletion due to medical causes (hemorrhage, vomiting, diarrhea, or decreased fluid intake) may also result in decreased effective circulatory volume, orthostatic hypotension, and syncope.
TREATMENT Orthostatic Hypotension
The first step is to remove reversible causes—usually vasoactive medications (Table 33-6). Next, nonpharmacologic interventions should be introduced. These interventions include patient education regarding staged moves from supine to upright; warnings about the hypotensive effects of meal ingestion; instructions about the isometric counterpressure maneuvers that increase intravascular pressure (see earlier in this chapter); and raising the head of the bed to reduce supine hypertension. Intravascular volume should be expanded by increasing dietary fluid and salt. If these nonpharmacologic measures fail, pharmacologic intervention with fludrocortisone acetate and vasoconstricting agents such as midodrine and pseudoephedrine should be introduced. Some patients with intractable symptoms require additional therapy with supplementary agents that include pyridostigmine, yohimbine, desmopressin acetate (DDAVP), and erythropoietin (Chap. 33).
Cardiac (or cardiovascular) syncope is caused by arrhythmias and structural heart disease. These may occur in combination because structural disease renders the heart more vulnerable to abnormal electrical activity.
Bradyarrhythmias that cause syncope include those due to severe sinus node dysfunction (e.g., sinus arrest or sinoatrial block) and atrioventricular block (e.g., Mobitz type II, high-grade, and complete AV block). The bradyarrhythmias due to sinus node dysfunction are often associated with an atrial tachyarrhythmia, a disorder known as the tachycardia-bradycardia syndrome. A prolonged pause following the termination of a tachycardic episode is a frequent cause of syncope in patients with the tachycardia-bradycardia syndrome. Medications of several classes may also cause bradyarrhythmias of sufficient severity to cause syncope. Syncope due to bradycardia or asystole is referred to as a Stokes-Adams attack.
Ventricular tachyarrhythmias frequently cause syncope. The likelihood of syncope with ventricular tachycardia is in part dependent on the ventricular rate; rates below 200 beats per min are less likely to cause syncope. The compromised hemodynamic function during ventricular tachycardia is caused by ineffective ventricular contraction, reduced diastolic filling due to abbreviated filling periods, loss of atrioventricular synchrony, and concurrent myocardial ischemia.
Several disorders associated with cardiac electro-physiologic instability and arrhythmogenesis are due to mutations in ion channel subunit genes. These include the long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. The long QT syndrome is a genetically heterogeneous disorder associated with prolonged cardiac repolarization and a predisposition to ventricular arrhythmias. Syncope and sudden death in patients with long QT syndrome result from a unique polymorphic ventricular tachycardia called torsades des pointes that degenerates into ventricular fibrillation. The long QT syndrome has been linked to genes encoding K+channel α-subunits, K+ channel β-subunits, voltage-gated Na+ channel, and a scaffolding protein, ankyrin B (ANK2). Brugada syndrome is characterized by idiopathic ventricular fibrillation in association with right ventricular electrocardiogram (ECG) abnormalities without structural heart disease. This disorder is also genetically heterogeneous, although it is most frequently linked to mutations in the Na+ channel α-subunit, SCN5A. Catecholaminergic polymorphic tachycardia is an inherited, genetically heterogeneous disorder associated with exercise-or stress-induced ventricular arrhythmias, syncope, or sudden death. Acquired QT interval prolongation, most commonly due to drugs, may also result in ventricular arrhythmias and syncope.
Structural heart disease, (e.g., valvular disease, myocar-dial ischemia, hypertrophic and other cardiomyopathies, cardiac masses such as atrial myxoma, and pericardial effusions) may lead to syncope by compromising cardiac output. Structural disease may also contribute to other pathophysiologic mechanisms of syncope. For example, cardiac structural disease may predispose to arrhythmogenesis; aggressive treatment of cardiac failure with diuretics and/or vasodilators may lead to orthostatic hypotension; and inappropriate reflex vasodilation may occur with structural disorders such as aortic stenosis and hypertrophic cardiomyopathy, possibly provoked by increased ventricular contractility.
TREATMENT Cardiac Syncope
Treatment of cardiac disease depends upon the underlying disorder. Therapies for arrhythmias include cardiac pacing for sinus node disease and AV block, and ablation, anti-arrhythmic drugs, and cardioverter-defibrillators for atrial and ventricular tachyarrhythmias. These disorders are best managed by physicians with specialized skills in this area.
APPROACH TO THE
DIFFERENTIAL DIAGNOSIS Syncope is easily diagnosed when the characteristic features are present; however, several disorders with transient real or apparent loss of consciousness may create diagnostic confusion.
Generalized and partial seizures may be confused with syncope; however, there are a number of differentiating features. Whereas tonic-clonic movements are the hallmark of a generalized seizure, myoclonic and other movements also may occur in up to 90% of syncopal episodes. Myoclonic jerks associated with syncope may be multifocal or generalized. They are typically arrhythmic and of short duration (<30 s). Mild flexor and extensor posturing also may occur. Partial- or partial-complex seizures with secondary generalization are usually preceded by an aura, commonly an unpleasant smell; fear anxiety; abdominal discomfort or other visceral sensations. These phenomena should be differentiated from the premonitory features of syncope.
Autonomic manifestations of seizures (autonomic epilepsy) may provide a more difficult diagnostic challenge. Autonomic seizures have cardiovascular, gastrointestinal, pulmonary, urogenital, pupillary, and cutaneous manifestations that are similar to the premonitory features of syncope. Furthermore, the cardiovascular manifestations of autonomic epilepsy include clinically significant tachycardias and bradycardias that may be of sufficient magnitude to cause loss of consciousness. The presence of accompanying nonautonomic auras may help differentiate these episodes from syncope.
Loss of consciousness associated with a seizure usually lasts longer than 5 min and is associated with prolonged postictal drowsiness and disorientation, whereas reorientation occurs almost immediately after a syncopal event. Muscle aches may occur after both syncope and seizures, although they tend to last longer following a seizure. Seizures, unlike syncope, are rarely provoked by emotions or pain. Incontinence of urine may occur with both seizures and syncope; however, fecal incontinence does not occur with syncope.
Hypoglycemia may cause transient loss of consciousness, typically in individuals with type 1 or type 2 diabetes treated with insulin. The clinical features associated with impending or actual hypoglycemia include tremor, palpitations, anxiety, diaphoresis, hunger, and paresthesias. These symptoms are due to autonomic activation to counter the falling blood glucose. Hunger, in particular, is not a typical premonitory feature of syncope. Hypoglycemia also impairs neuronal function, leading to fatigue, weakness, dizziness, and cognitive and behavioral symptoms. Diagnostic difficulties may occur in individuals in strict glycemic control; repeated hypoglycemia impairs the counterregulatory response and leads to a loss of the characteristic warning symptoms that are the hallmark of hypoglycemia.
Patients with cataplexy experience an abrupt partial or complete loss of muscular tone triggered by strong emotions, typically anger or laughter. Unlike syncope, consciousness is maintained throughout the attacks, which typically last between 30 s and 2 min. There are no premonitory symptoms. Cataplexy occurs in 60–75% of patients with narcolepsy.
The clinical interview and interrogation of eyewitnesses usually allow differentiation of syncope from falls due to vestibular dysfunction, cerebellar disease, extrapyramidal system dysfunction, and other gait disorders. If the fall is accompanied by head trauma, a postconcussive syndrome, amnesia for the precipitating events, and/or the presence of loss of consciousness may contribute to diagnostic difficulty.
Apparent loss of consciousness can be a manifestation of psychiatric disorders such as generalized anxiety, panic disorders, major depression, and somatization disorder. These possibilities should be considered in individuals who faint frequently without prodromal symptoms. Such patients are rarely injured despite numerous falls. There are no clinically significant hemodynamic changes concurrent with these episodes. In contrast, transient loss of consciousness due to vasovagal syncope precipitated by fear, stress, anxiety, and emotional distress is accompanied by hypotension, bradycardia, or both.
INITIAL EVALUATION The goals of the initial evaluation are to determine whether the transient loss of consciousness was due to syncope; to identify the cause; and to assess risk for future episodes and serious harm (Table 10-1). The initial evaluation should include a detailed history, thorough questioning of eyewitnesses, and a complete physical and neurologic examination. Blood pressure and heart rate should be measured in the supine position and after 3 min of standing to determine whether orthostatic hypotension is present. An ECG should be performed if there is suspicion of syncope due to an arrhythmia or underlying cardiac disease. Relevant electrocardiographic abnormalities include bradyarrhythmias or tachyarrhythmias, atrioventricular block, ischemia, old myocardial infarction, long QT syndrome, and bundle branch block. This initial assessment will lead to the identification of a cause of syncope in approximately 50% of patients and also allows stratification of patients at risk for cardiac mortality.
Laboratory Tests Baseline laboratory blood tests are rarely helpful in identifying the cause of syncope. Blood tests should be performed when specific disorders, e.g., myocardial infarction, anemia, and secondary autonomic failure, are suspected (Table 10-2).
Autonomic Nervous System Testing (Chap. 33) Autonomic testing including tilt table testing can be performed in specialized centers. Autonomic testing is helpful to uncover objective evidence of autonomic failure and also to demonstrate a predisposition to neurally mediated syncope. Autonomic testing includes assessments of parasympathetic autonomic nervous system function (e.g., heart rate variability to deep respiration and a Valsalva maneuver), sympathetic cholinergic function (e.g., thermoregulatory sweat response and quantitative sudomotor axon reflex test), and sympathetic adrenergic function (e.g., blood pressure response to a Valsalva maneuver and a tilt table test with beat-to-beat blood pressure measurement). The hemodynamic abnormalities demonstrated on tilt table test (Figs. 10-2 and 10-3) may be useful in distinguishing ortho-static hypotension due to autonomic failure from the hypotensive bradycardic response of neurally mediated syncope. Similarly, the tilt table test may help identify patients with syncope due to delayed or initial ortho-static hypotension.
Carotid sinus massage should be considered in patients with symptoms suggestive of carotid sinus syncope and in patients over age 50 years with recurrent syncope of unknown etiology. This test should only be carried out under continuous ECG and blood pressure monitoring and should be avoided in patients with carotid bruits, plaques, or stenosis.
Cardiac Evaluation ECG monitoring is indicated for patients with a high pretest probability of arrhythmia causing syncope. Patients should be monitored in hospital if the likelihood of a life-threatening arrhythmia is high, e.g., patients with severe structural or coronary artery disease, nonsustained ventricular tachycardia, trifascicular heart block, prolonged QT interval, Brugada’s syndrome ECG pattern, and family history of sudden cardiac death. Outpatient Holter monitoring is recommended for patients who experience frequent syncopal episodes (one or more per week), whereas loop recorders, which continually record and erase cardiac rhythm, are indicated for patients with suspected arrhythmias with low risk of sudden cardiac death. Loop recorders may be external (recommended for evaluation of episodes that occur at a frequency of greater than one per month) or implantable (if syncope occurs less frequently).
Echocardiography should be performed in patients with a history of cardiac disease or if abnormalities are found on physical examination or the electrocardiogram. Echocardiographic diagnoses that may be responsible for syncope include aortic stenosis, hyper-trophic cardiomyopathy, cardiac tumors, aortic dissection, and pericardial tamponade. Echocardiography also has a role in risk stratification based on the left ventricular ejection fraction.
Treadmill exercise testing with ECG and blood pressure monitoring should be performed in patients who have experienced syncope during or shortly after exercise. Treadmill testing may help identify exercise-induced arrhythmias (e.g., tachycardia-related AV block) and exercise-induced exaggerated vasodilation.
Electrophysiologic studies are indicated in patients with structural heart disease and ECG abnormalities in whom noninvasive investigations have failed to yield a diagnosis. Electrophysiologic studies have low sensitivity and specificity and should only be performed when a high pretest probability exists. Currently, this test is rarely performed to evaluate patients with syncope.
Psychiatric Evaluation Screening for psychiatric disorders may be appropriate in patients with recurrent unexplained syncope episodes. Tilt table testing, with demonstration of symptoms in the absence of hemodynamic change, may be useful in reproducing syncope in patients with suspected psychogenic syncope.