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Definition

Syncope is an abrupt, transient loss of consciousness due to transient global cerebral hypoperfusion with a concomitant loss of postural tone and rapid, spontaneous recovery.¹ Syncope is distinct other causes of transient loss of consciousness such seizures, hypoglycemia, stroke, trauma.² Recovery from syncope is characterized by immediate restoration in orientation and normal behavior, although it may be accompanied by fatigue.²

Syncope is part of a broader clinical network of symptoms that is best described as orthostatic intolerance, which is a constellation of symptoms that occur in the upright posture and include: dizziness, lightheadedness, tremulousness, sweating, nausea and palpitations. These symptoms improve with the assumption of a recumbent posture. Presyncope, also called near-syncope, is the prodrome of syncope, but without loss of consciousness. It is characterized by diaphoresis, warmth, nausea and pallor.¹

There are 3 main types of syncope. Reflex syncope (neurocardiogenic syncope) is the most common cause of syncope in any setting, followed by syncope secondary to cardiovascular disease. In the elderly, orthostatic hypotension (OH) is a very frequent cause of syncope.²

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Prevalence and Incidence

The prevalence of syncope differs based on the clinical setting and the age of the patient. It is estimated that 3% of men and 3.5% of women experience syncope during their lifetime.³ Syncope has been estimated to account for 1% to 3% of emergency department visits and 1% to 6% of hospital admissions.⁴ The prevalence of syncope increases with age and is estimated to be 0.7% in patients age 35 to 44 compared with 4% to 6% in patients 75 and older. In the Framingham study, the incidence of syncope increased after the age of 70, from 5.7 per 1,000 events person-years in men aged 60 to 69 to 11.1 per 1,000 events person-years in men 70 to 79.^2,3

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Prognosis

The overall prognosis of syncope depends on the underlying cause. Patients with syncope with structural heart disease and primary electrical disease are at high risk of overall mortality and sudden cardiac death. Young patients with reflex syncope have an excellent prognosis.²

Morbidity in patients with syncope is associated with recurrence of episodes and physical injury. In population studies, approximately a third of patients have recurrence of syncope in 3 years of follow up, and the rate of recurrence seems to be dependent on the number of previous episodes, but independent of gender, tilt test results, severity and presence of heart disease. The predicted recurrence in 1 to 2 years for patients with 1 or 2 syncope episodes is 15% to 20% whereas for patients with 3 syncope episodes it is 36% to 45%. Young patients with psychiatric disease have high rates of recurrence of pseudosyncope.²

In patients with syncope presenting to the emergency department, 29.1% have minor trauma, 4.7% have major trauma, and in older patients with carotid disease, 43% have major trauma. Morbidity is particularly high in the elderly, and is associated with loss of confidence, fear of falling, depression, fractures, and institutionalization.²

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Physiology and Pathophysiology

The pathophysiology of syncope involves the interaction between the circulatory system and the autonomic nervous system. The autonomic nervous system is vital for the maintenance of internal homeostasis including regulation of blood pressure, heart rate, fluid and electrolyte balance, and body temperature. If one considers orthostatic intolerance, postural hypotension, and syncope/presyncope as a continuum, it becomes possible to link them all to a disturbance of homeostasis.

When standing, initially the force of gravity pools 500 to 800 mL of blood in the distensible veins below heart level.¹ This increases capillary pressure and plasma is lost to interstitial fluid due to ultrafiltration in the kidney. It is estimated that plasma volume decreases by 15% within 20 minutes of standing. Pooling of blood in the veins decreases venous return to the heart with subsequent reduction of cardiac output, which in turn, triggers compensatory mechanisms to prevent the reduction of arterial pressure. Compensatory mechanisms include: sympathetic outflow upregulation mediated by the central autonomic network (CAN); and the venoarterial reflex, leg pumping of skeletal muscles, the cerebral autoregulatory mechanism, and to a lesser extent, the renin angiotensin aldosterone system (RAAS).

The autonomic supply to the cardiovascular system is coordinated at the CAN located in the brain stem. The sympathetic nervous system acts as the main effector in the hemodynamic response to postural stressors. Upon standing, there is an initial reduction of cardiac filling and thus, of stroke volume. Pressure receptors in the heart, carotids, and aortic arch sense the perturbation and send impulses to the CAN. This initiates sympathetic vasomotor outflow and norepinephrine is released to vascular beds in the skeletal muscles and cutaneous vasculature; causing vasoconstriction, venoconstriction, as well as increased heart rate and contractility. Venoconstriction causes a correction of orthostasis by increasing cardiac filling for a given amount of gravitational pooling of blood. At the same time, leg pumping of skeletal muscles enhances venous return to the heart and the venoarterial reflex augments arterial vasoconstriction in response to venous distention.

In the nephron, orthostasis causes a decrease in renal blood flow, which leads to a decrease in glomerular sodium filtration and excretion. Norepinephrine release by the sympathetic response results in reabsorption of filtered sodium and increase in extracellular fluid (ECF) volume. At the same time, the RAAS is activated and promotes sodium and water conservation, but the magnitude of this response is less when compared to that caused by norepinephrine in the immediate setting. This was observed in cases of spinal cord injury and quadriplegia, where OH occurs despite marked stimulation of the RAAS but in the absence of sympathetic postganglionic outflow.

Postural stress in the atrium is sensed by mechanoreceptors as a decreased in atrial stretch. This causes increase of arginine vasopressin (AVP) and decrease in A-type atrial natriuretic peptide (ANP) secretion. This results in “anti-natriuresis” that leads to an increase of ECF volume and cardiac filling.

Syncope or presyncope occurs as a result of brain hypoxia, which is usually secondary to a reduction of cerebral perfusion pressure. However, not every reduction in blood pressure leads to brain hypoxia. This is because the cerebral circulation is autoregulated so that brain perfusion is maintained in the face of significant changes in mean blood pressure. This homeostatic mechanism allows regional cerebral blood flow to remain constant over a range of cerebral perfusion pressure (CPP) of 50 to 150 mm Hg or mean arterial pressure (MAP) of 60 to 160 mm Hg. So, as MAP or CPP increases, resistance in small cerebral arteries increases via vasoconstriction and vice versa.⁵ Blood pressure above the upper level of autoregulation can cause cerebral edema, like that seen in hypertensive encephalopathy and blood pressure below the lower level result in syncope secondary to brain hypoxia.

The pathophysiology of syncope is summarized as a reduction in systemic blood pressure that causes a decrease in the global cerebral blood flow, which results in loss of consciousness. A sudden cessation of cerebral blood flow for 6 to 8 seconds has been shown to cause loss of consciousness.²

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Etiology

The Task Force for the Diagnostic Management Syncope of the European Society of Cardiology (Task Force of the ESC) has classified syncope into 3 main categories: reflex syncope, syncope due to OH, and cardiac syncope.² Prospective studies have found that neurally mediated causes of syncope account for the largest percentage of events (38% to 56%). Cardiovascular causes, separated into syncope due to OH (2% to 24%) and structural heart disease (11% to 23%) account for smaller percentages of cases. The cause of syncope is undetermined in 14% to 18% of events.^6,7

Reflex syncope (neurally-mediated)

Reflex syncope includes vasovagal syncope, situational syncope, carotid sinus syncope, and atypical forms, which are a result of an inappropriate cardiovascular reflex in response to a trigger. Reflex syncope can be classified based in the type of efferent response:

• vasodepressor if hypotension due to loss of upright vasoconstriction tone predominate
• cardioinhibitory if bradycardia or asystole predominate.²

Vasovagal syncope

Vasovagal syncope, also known as neurocardiogenic syncope, is commonly described using the Bezold-Jarisch reflex model, where a reduction in ventricular preload stimulates mechanoreceptors in the inferoposterior part of the left ventricle leading to a vigorous contraction. This causes an increased afferent discharge of the unmyelinated C fibers from the ventricular mechanoreceptors and the central nervous system responds with reflex sympathetic withdrawal and increased parasympathetic output. These signals cause vasodilation, hypotension and bradycardia.⁶ This ineffective reflex response causes venous pooling in the periphery or splanchnic regions or both with paradoxical vasodilation leading to further hypotension and loss of consciousness.¹

Other potential mechanisms include involvement of central serotonergic pathways and release of endogenous opioids or catecholamines.⁶ Vaddadi et al⁸ described 2 phenotypes in patients with recurrent vasovagal syncope, both associated with reduced norepinephrine availability: 1 phenotype with low pressure (systolic blood pressure less than 100 mm Hg) and low tyrosine hydroxylase levels; and 1 phenotype with normal pressure (systolic blood pressure greater than 100 mm Hg) and increased norepinephrine reuptake.

Vasovagal syncope usually occurs with an upright posture held for more than 30 seconds (postural challenge) or with exposure to emotional stress, pain or a medical setting. It is characterized by prodromal features of presyncope, diaphoresis, a sense of warmth, flushing, nausea, abdominal discomfort, blurry vision, and vision loss. While unconscious, the patient is usually motionless.¹

Situational syncope

Situational syncope includes syncope due to cough, laughing, deglutition, micturition, and defecation. The underlying mechanism of these events is similar to that of vasovagal syncope. Some other situational events may be related to human fear circuitry and sociogenic pseudoneurologic symptoms.^9-11

Carotid sinus syncope

Carotid sinus syncope is due to hypersensitivity of carotid sinus baroreceptors leading to vagal overstimulation and syncope. It is usually triggered by mechanical manipulation of the carotid sinuses as with wearing a tight shirt collar, shaving, neck movements or carotid massage.¹²

Atypical forms

Atypical forms of reflex syncope include those situations in which reflex syncope occurs with uncertain or absent triggers. As such, it is a diagnosis of exclusion and usually needs to be confirmed by tilt testing.²

Syncope due to orthostatic hypotension (OH)

Postural or OH is defined as reduction in systolic blood pressure of at least 20 mm Hg accompanied by a diastolic blood pressure decrease of at least 10 mm Hg with upright posture.² OH syncope includes syncope due to various types of primary and secondary autonomic dysfunction (Table 1). The autonomic nervous system is the main effector in the hemodynamic response to standing and any deviation from the normal response to a postural stressor will lead to postural hypotension. OH can also result from use of alcohol or medications such as tricyclic antidepressants, diuretics, and vasodilators. Intravascular volume depletion due to vomiting, diarrhea, or hemorrhage can result in OH.

Syndromes of orthostatic intolerance, which may cause syncope, include classic OH, initial OH, delayed or progressive OH, and postural tachycardia syndrome (POTS).¹

Classic OH

Classic OH typically presents 30 seconds to 3 minutes after standing and is caused by impaired increase in systemic vascular resistance due to autonomic dysfunction or severe volume depletion over-riding reflex adjustments.² Classic OH is more common in the elderly, associated with diuretic use, and frequently preceded by presyncope.¹

Initial OH

Initial OH is characterized by a blood pressure reduction of greater than 40 mm Hg immediately on standing and lasting less than 30 seconds.² The underlying pathophysiology is a mismatch between cardiac output and systemic vascular resistances. It presents in young asthenic subjects and old individuals using alpha-blockers. Symptoms are lightheadedness and visual disturbances that present immediately after standing and are short-lived.¹

Delayed OH

Delayed/progressive OH is characterized by a slow progressive decrease in blood pressure that presents 3 to 45 minutes after assuming the erect posture.¹³

It may be attributed to age-related impairment of compensatory reflexes and stiffer hearts in the elderly sensitive to a decrease in preload. The absence of bradycardic reflex can help differentiate it from vasovagal syncope. It can present with a prolonged prodrome characterized by dizziness, fatigue, weakness, palpitations, hearing and vision disturbances, hyperhidrosis, low back pain, neck or precordial pain; followed by rapid syncope.¹

Postural (orthostatic) tachycardia syndrome (POTS)

POTS is characterized by an excessive heart rate after standing. As defined by the Heart Rhythm Society, POTS is a clinical syndrome characterized by frequent symptoms that occur with standing (ie, lightheadedness, palpitations, tremor, blurred vision, weakness, fatigue), an increase in heart rate of greater than 30 beats per minute, or a standing heart rate greater than 120 beats per minute.¹ It has been divided in early versus late POTS if the rise in heart rate is before or after 10 minutes of tilt.¹⁴ A number of mechanisms have been proposed including autonomic denervation, hypovolemia, hyperadrenergic hypersensitivity, deconditioning, excessive blood venous pooling, and hypervigilance.¹³

Cardiac syncope

Cardiac syncope include syncope due to arrhythmia and structural heart disease.

Arrhythmias

Arrhythmias are the most common causes of cardiac syncope. They lead to hemodynamic impairment by decreasing the cardiac output.¹ These include bradyarrhythmias, tachyarrhythmias and arrhythmias secondary to medications and electrolyte abnormalities. Significant bradycardia (such as from sinus node dysfunction or atrioventricular (AV) nodal conduction disease) and significant tachycardia (from either a supraventricular or ventricular origin) can both result in syncope. In intrinsic sick sinus syndrome, syncope typically occurs secondary to long pauses caused by sinus arrest or sinoatrial block.¹

In the setting of tachyarrhythmia, syncope or near-syncope occurs at the onset of paroxysmal tachycardia, before vascular compensation develops. Consciousness is, in general, restored before tachycardia terminates, unless hemodynamics remain inadequate. In this case, unconsciousness will be maintained and spontaneous recovery will be absent, which no longer fulfills the definition of syncope and constitutes cardiac arrest.¹

Arrhythmias induced by drugs and electrolyte disturbances can be both brady or tachyarrthythmias. Bradycardia can result as a consequence of the medication effect on the sinus node or AV conduction while tachyarrhythmias, for example, can be induced in patients affected by long QT syndrome taking medications which further prolong the QT interval, and initiates torsade de pointes.¹ Regardless of such contributing effects, when the arrhythmia is the primary cause of syncope, it should be treated.¹

Structural heart disease

Structural heart disease can also cause syncope when circulatory demands greater than the heart’s ability to increase its output. Syncope in this setting is of great concern when it is associated with fixed or dynamic obstruction to the left ventricular outflow, like that seen in hypertrophic obstructive cardiomyopathy, aortic stenosis, and cardiac tamponade.¹ In the setting of valvular aortic stenosis, syncope is not solely the result of restricted cardiac output, but may be due to inappropriate reflex vasodilation or primary cardiac arrhythmia or both.¹ Right ventricular obstruction like that seen in pulmonary embolus or pulmonary hypertension can also cause syncope. Other causes of cardiac syncope include mitral stenosis, atrial myxoma, dissecting aortic aneurysm, subclavian steal syndrome, and ischemic cardiomyopathy.

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Diagnosis

The diagnosis of syncope is based on the clinical history and physical examination.¹ A thorough history from patients and witnesses and a comprehensive physical examination will identify the cause of syncope in up to 50% of cases.¹

History

Table 2 lists some of the most important questions to be answered during the clinical history. Complete loss of consciousness, rapid onset, loss of postural tone, short duration, and complete and spontaneous recovery all suggest syncope as the cause of loss of consciousness. The prodromal symptoms of syncope can further help elucidate the etiology. Symptoms of orthostatic intolerance include lightheadedness, dizziness, imbalance, tunnel vision, blurriness, spotted visual field, and headache. Patients may find it is possible to abort these symptoms by assuming a sitting or supine posture. The quantitative drop of blood pressure does not only determine the severity and occurrence of these symptoms but also by the rapidity in which blood pressure declines. While unconscious, the patient is usually motionless, however fine and coarse myoclonic movements have been observed in approximately 10% of cases, which can result in the condition being erroneously diagnosed as epilepsy.¹

Alarming features indicating a high-risk scenario include syncope during exertion, syncope while lying down, family history of sudden cardiac death, or slow recovery from syncope.

Physical exam

A careful and comprehensive physical examination is essential. Blood pressure should to be checked in both arms, and in the supine and standing positions. Signs to look for in the physical exam are dehydration, flushing, carotid bruits, cardiac murmurs, abdominal masses, varicose veins, and signs of endocrine disorders in skin, eyes and thyroid. Table 3 lists clinical features suggesting specific etiologies.²

Diagnostic workup

After a thorough history and physical exam, an electrocardiogram (ECG) should be obtained. Blood work should be obtained when metabolic diseases or anemia are suspected. Although the ECG is often normal on presentation, it is an essential part of the initial evaluation of syncope. Only 5% of initial ECGs are diagnostic and 5% suggest an underlying etiology.¹⁵ The Task Force of the ESC establishes that arrhythmia related syncope can be diagnosed by ECG (class I recommendation, level evidence C) with the presence of: persistent sinus bradycardia (< 40 bpm) or recurrent sinoatrial block or pause (≥3 seconds), high degree AV block (Mobitz II or third degree), alternating left and right bundle branch block (BBB), ventricular tachycardia (VT) or paroxysmal rapid supraventricular tachycardia (SVT), non-sustained polymorphic VT, long or short QT interval, or pacemaker/implantable cardioverter defibrillator malfunction with cardiac pauses.²

In many situations, the mechanism of syncope is not evident after initial evaluation. In this setting, the next step is to assess the risk of major cardiovascular events or sudden cardiac death that prompt hospitalization or intensive evaluation (Table 4).²

Proper additional evaluations include: carotid sinus massage, echocardiogram, ECG monitoring (Holter, external or internal loop recorder), orthostatic challenge (tilt test), electrophysiological testing, stress testing, and cardiac catheterization.²

Carotid sinus massage

Carotid sinus massage (CSM) is indicated in patients older than 40 years with syncope of unknown etiology after initial evaluation. Carotid sinus hypersensitivity (CSH) is defined by CSM causing a ventricular pause longer than 3 second or a drop in systolic blood pressure of at least 50 mm Hg. When associated with spontaneous syncope, CSH defines carotid sinus syndrome.² The massage should be performed at the point of maximum pulsation over the carotid artery, between the angle of the mandible and the thyroid cartilage, applying firm longitudinal pressure. It should be performed for 10 seconds in each side, ideally in the dominant side first, in both supine and upright positions, and with the patient on telemetry and periodic blood pressure monitoring. It is contraindicated in the setting of myocardial infarction, stroke, or transient ischemic attack in the preceding 3 months, history of significant carotid stenosis, carotid bruit (except if Doppler excludes significant carotid stenosis), or clinical suspicion of carotid stenosis.¹⁶

ECG monitoring

ECG monitoring is indicated in patients who have clinical or ECG findings suggestive of arrhythmic syncope and is diagnostic when a correlation between syncope and an arrhythmia is detected. In the absence of such correlation, it is diagnostic when periods of or a high degree atrioventricular block, prolonged ventricular pauses, or rapid prolonged paroxysmal SVT or VT are detected.² Several ECG ambulatory monitoring methods are available: conventional ambulatory Holter monitoring, in-hospital monitoring, event recorders, external or implantable loop recorders (ILRs), and remote (at home) telemetry.²

Holter monitoring is indicated in patients who have very frequent syncope or pre-syncope, defined as 1 or more episodes per week. In most patients, symptoms do not recur during the monitoring period so the true yield of Holter in syncope may be as low as 1% to 2%, but increases when used in high-risk patients.^2,18,19 In-hospital monitoring is warranted only when the patient is at high risk for a life-threatening arrhythmia. In such circumstances, the diagnostic yield of ECG monitoring may be only as high as 16%, but it is justified by the need to avoid immediate risk to the patient.²

ILRs are indicated in the early phase of evaluation of patients with recurrent syncope of uncertain origin without high-risk criteria and high likelihood of recurrence within the device’s battery life (up to 36 months); or in high-risk patient in whom a comprehensive evaluation did not reveal the cause of syncope. These devices have a solid-state loop memory that stores retrospective ECG recordings, when activated either by the patient or a bystander, usually after a syncopal episode, or automatically activated in the case of occurrence of predefined arrhythmias.² Numerous observational studies have shown that ILRs can deliver diagnoses for approximately 35% of patients during the devices’ lifetime. However, randomized controlled trials have shown that in older patients with unexplained syncope, early use of ILRs provide more diagnoses and are cost effective. This patient population also benefits from pacemaker implantation when the device documents asystole.¹ External loop recorders should be considered in patients with inter-symptom interval of 4 weeks or less. Their usefulness in the evaluation of syncope has been controversial.²

Remote telemetry consists of external or internal device systems that provide continuous ECG recording or 24-hour loop memory, with wireless real time transmission to a service center, where they are continuously read. Initial data showed that a mobile cardiac outpatient telemetry system had a higher diagnostic yield than a patient-activated external looping event monitor in patients with syncope or pre-syncope,²⁰ but the potential role of these systems in the diagnostic work-up of patients with syncope needs further evaluation.²

Orthostatic challenge

The tilt table test is a simple test that moves a patient from a supine to an upright position using a tilt table. It is used to examine autonomic neural regulation of cardiovascular orthostatic responses.²⁰ During the tilt table procedure, the patient is monitored with continuous ECG recording, and an automatic sphygmomanometer or beat-to-beat finger arterial pressure recording. The patient is tilted from the supine position to 60 to 80 degrees over a period of 30 to 45 minutes. A normal response to the test is a 10-15 beat/min increase in heart rate or a 10% to 15% rise from baseline, a 0 to 10 mm Hg decrease in systolic blood pressure and a 5 to 10 mm Hg increase in diastolic blood pressure. Abnormal responses may be seen in susceptible individuals who experience vigorous cardiac contractions in the setting of relative central hypovolemia due to peripheral blood pooling.²¹ This leads to secondary reflex sympathetic withdrawal and increase in vagal output, resulting in bradycardia or hypotension with symptoms or both.²⁰ End points of the test include induction of syncope or presyncope in association with hypotension or bradycardia, change in blood pressure, heart rate and symptoms, or completion of planned tilt duration. Table 5 lists the possible abnormal hemodynamic patterns induced during tilt testing.

Tilt testing is indicated in cases of unexplained single syncopal episode in a high-risk patient; in recurrent syncopal episodes in the absence of organic heart disease; or in the presence of organic heart disease after a cardiac cause of syncope has been ruled out. It is also indicated when it is of clinical value to demonstrate susceptibility of reflex syncope to the patient. It may be considered to differentiate seizures and pseudosyncope (in psychiatric patients) from true syncope, to evaluate patients with recurrent unexplained falls, and to discriminate between reflex syncope and syncope due to OH.²

Additional testing may be planned according to the tilt response pattern, such as hemodynamic evaluation, blood volume studies, and autonomic reflex testing. The role of blood volume determination was enhanced by research findings.²² Pharmacophysiologic interventions help differentiation of preganglionic from postganglionic lesions.²³ If the tilt test is negative, and the patient’s history is suggestive of reflex syncope, the patient is subjected to the isoproterenol tilt test. The addition of isoproterenol increases the sensitivity of the tilt test for the diagnosis of vasovagal syncope at the expense of a reduction in the specificity of the test for the same diagnosis.²⁴

Relative contraindications to the tilt test include severe left ventricular outflow tract obstruction, critical mitral stenosis, critical proximal coronary artery stenosis, or active angina and critical cerebrovascular stenosis. The isoproterenol tilt testing is contraindicated in patients with ischemic heart disease.² Limitations to the head-up tilt test include: inability to stand (leg weakness or pain, severe back pain), unstable medical conditions, inability to obtain blood pressure (incompressible arm arteries, bilateral arm AV fistula, bilateral subclavian artery stenosis), and inability to secure an intravenous access. In patients with a high pretest probability for vasovagal syncope, tilt test approaches a sensitivity of 78% to 92% and a specificity of 90% when following recommended protocols.¹

Active standing is another method to evaluate the patient’s orthostatic response. It is indicated as initial evaluation when OH is suspected. It is done with intermittent measurement of blood pressure using a manual sphygmomanometer in a supine position and 3 minutes after active standing. The test is diagnostic when it documents a symptomatic or asymptomatic drop in systolic blood pressure of 20 mm Hg or greater or drop in diastolic blood pressure of 10 mm Hg or greater or a decrease in systolic blood pressure to less than 90 mm Hg. Continuous beat-to-beat noninvasive pressure measurement may be helpful in cases of doubt or when more frequent blood pressure values are required, as sphygmomanometer cannot be used more than 4 times per minute without causing venous obstruction of the arm.²

Echocardiogram

Evaluation with echocardiography is a class IIa recommendation from the American College of Cardiology/American Heart Association if there is clinical suspicion of structural heart disease and it is of no benefit unless cardiac etiology is suspected.¹ Echocardiography alone is diagnostic of the cause of syncope in severe aortic stenosis, obstructive cardiac tumor or thrombi, pericardial tamponade, aortic dissection, and congenital anomalies of coronary artery.²

Electrophysiology testing

Electrophysiology testing has a low yield in patients with normal ECG, no evidence of structural heart disease, and ejection fraction > 40%. Predictors of positive findings include ejection fraction < 40%, male sex, BBB, history of myocardial infarction injury, and non-sustained VT. Overall diagnostic yield is 50% in patients with organic heart disease and 10% in patients without structural heart disease.¹ Electrophysiological study is a class I recommendation by the Task Force of the ESC in patients with ischemic heart disease when initial evaluation suggests an arrhythmic cause of syncope unless there is an already established indication for an implantable cardioverter defibrillator.² It may be considered in patients with BBB or syncope preceded by palpitations when non-invasive studies have failed to identify the diagnosis. It is not recommended in patients without heart disease, normal ECG, and no palpitations associated with syncope. Electrophysiology testing results diagnostic for syncope are listed in Table 6.²

Stress testing

Exercise induced syncope is infrequent but exercise testing should be performed in patients who experience syncope during or shortly after exertion.² Stress testing should be avoided in patients with severe, symptomatic aortic stenosis or hypertrophic cardiomyopathy and severe outflow tract obstruction. It is considered diagnostic when syncope is reproduced during or immediately after exercise in the presence of ECG abnormalities or severe hypotension and if Mobitz II second-degree or third-degree AV block develops, even in the absence of syncope.²

Additional testing

Additional more specialized syncope evaluations include an assessment of global autonomic function. This entails a number of maneuvers, pressor testing, Valsalva maneuver, phenylephrine test, amyl nitrite inhalation. These are performed while heart rate variability and blood pressure are monitored.

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Treatment

The treatment for syncope varies based on the cause of syncope (Table 7). While some causes are relatively benign, patients with frequent episodes of syncope occasionally need treatment. There are 2 main treatment strategies: conservative/nonpharmacologic therapy and medical treatment. The management of syncope during acute episodes is the same for both treatment strategies.¹

Managing acute episodes

Patients with syncope and those around them should be informed about how to recognize early symptoms of an impending episode. Pallor, sweating, lack of concentration, disorientation, and nausea are features suggestive of postural hypotension and brain hypoperfusion. Convulsions may suggest prolonged or severe brain hypoperfusion; shakiness may accompany hyperadrenergic activity. Assisting the patient to sit or lay down quickly and raising the legs above heart level aid recovery in patients with a typical reflex postural hypotension event.

Physicians should check the pulse for amplitude and rhythm. When a patient recovers from the acute event, re-ambulation should be done with care because recurrence of hypotension may occur due to circulatory instability. In patients no known previous history of heart disease, oral hydration with salty fluids usually is helpful in the early recovery phase. Serious arrhythmogenic events, coronary insufficiency syndromes, pulmonary embolism, strokes or transient ischemic attacks, and blood loss require immediate medical care. Evaluation for and treatment of any injuries sustained during a sudden fall require immediate attention.

Admission to a hospital is necessary for syncope that may be secondary to coronary events, pulmonary embolization, stroke, unstable arrhythmias, and syncope-related injuries. Hospital admission is necessary for status epilepticus, need for detoxication, severe dehydration, or hypertensive crises, which may be part of the autonomic failure syndromes or a complication of the treatment given for syncope.

Conservative/Nonpharmacologic therapy

Conservative therapy includes lifestyle modifications like avoidance of provocative triggers such as heat, prolonged standing, decongestants, excess caffeine, large meals, and alcohol; increased salt and fluid intake; reduction or withdrawal of antihypertensive medications, and physical counterpressure maneuvers.¹ Physical counter maneuvers and simple postural maneuvers like leg crossing, leg raising, genuflexion, toe-raising to contract calf/gastrocnemius muscle, squatting, and isotonic contraction of the thighs/quadriceps muscle are easy to teach to patients and may be useful in mild orthostatic symptoms, at the very onset of orthostatic symptoms. During these maneuvers patient should avoid Valsalva straining. Compression support stockings are also effective (at various amount of compression and various heights according to patient tolerance) in patients with postural hypotension and those with accentuated postural venous pooling. An abdominal binder and small frequent meals are advised in patients with post-prandial hypotension. In patients with supine hypertension and postural hypotension, elevation of the head-of-bed by 6 to 8 inches may also be helpful.

Pharmacologic treatment

Medical treatment should be used in patients experiencing recurrent episodes despite adequate conservative therapy.¹ Many drugs have been tested in the treatment of reflex syncope, most with disappointing results.² This list includes beta blockers, fludrohydrocortisone, midodrine, calcium channel blockers, anticholinergic agents, and serotonin transporter inhibitors.¹

Beta Blockers

Beta blockers have been presumed to lessen the degree of ventricular mechanoreceptor activation owing to their negative inotropic effect in reflex syncope.² However, adequately designed and controlled randomized studies have found that beta blockers are not effective for treating vasovagal syncope. A possible exception to this may be in patients older than 40 in whom there was evidence of benefit in a metaanalysis of a prespecified, prestratified substudy of POST 1 and in a large earlier observational study.^1,25 This finding is yet to be confirmed prospectively by the ongoing POST5 randomized clinical trial,²⁶ but currently the ACC/AHA/HRS Expert Consensus Statement recommends the use of metoprolol in patients older than 40 with frequent vasovagal syncope.¹

Fludrocortisone

Fludrocortisone is a synthetic selective mineralocorticoid when used in small doses; it retains salt and water and promotes plasma volume expansion. It has only shown benefits in the pediatric population with vasovagal syncope whose severity merits it and is considered reasonable for patients with frequent episodes and lack of contraindications.¹ The therapeutic effect of fludrocortisone occurs after about 5 days of treatment. It has been used in the treatment of hypovolemia as well as autonomic insufficiency. It is contraindicated in patients with heart failure. Blood pressure, body weight and serum potassium need to be monitored during treatment.

Midodrine

Midodrine is an alpha-adrenergic agonist used for the treatment of autonomic insufficiency and neurocardiogenic syncope. It has shown a risk reduction in episodes of 70% but none of the trials provided high level evidence for adults.¹ For this reason, the Heart Rhythm Society Expert Consensus Statement considers the use of midodrine reasonable for frequent vasovagal syncope in patients without hypertension or urinary retention.¹ On the other hand, the Task Force of the ESC recommends the use of midodrine in patients with vasovagal syncope refractory to lifestyle modifications.² Due to its effect of increasing afterload, it is not advised in hypertension, heart failure, active coronary artery disease and peripheral vascular disease.

Other agents

Anticholinergic agents like hyoscyamine; ephedrine, dihydroergotamine, caffeine, ocreotide, vasopressin and calcium channel blockers like verapamil have been used in the past but current evidence do not support their use.

Follow-up

Patients with syncope of unknown etiology and without underlying structural heart disease have a favorable outcome compared with those having organic heart disease. Response to treatment can be assessed by noting a patient’s overall improvement of symptoms, standing time, number of syncopal episodes per a defined period of time, extent of drop of blood pressure during standing, and time to drop of standing blood pressure. Patients with syncope and underlying structural heart disease need regular and close follow-up. Attention should be paid to potential side effects of therapy, such as supine hypertension in susceptible individuals taking midodrine and hypokalemia in patients taking fludrocortisone. Patients with a pacemaker or implantable cardiac defibrillator should have routine device analysis.

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Prevention and Screening

Recurrence of syncopal episodes may be prevented by patient education and treatment. Patients need to be aware of triggers that may predispose to or precipitate syncopal spells and orthostatic intolerance. There is no definite procedure for screening individuals for syncope.

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Summary

• Syncope is an abrupt, transient loss of consciousness due to transient global cerebral hypoperfusion with a concomitant loss of postural tone and rapid, spontaneous recovery.
• Syncope is a part of a broader network of symptoms that is best described as postural intolerance.
• The interaction between the circulatory system and the autonomic nervous system is crucial to understanding the pathophysiology of syncope.
• Etiologically, syncope is classified into reflex syncope, syncope due to orthostatic hypotension, and cardiac syncope; with reflex syncope being the most common and cardiac syncope having the worst prognosis.
• The diagnosis of syncope is clinical but electrocardiogram, carotid sinus massage, orthostatic challenge testing, and more specialized workup may aid in establishing the cause of syncope.

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