Sunday, August 31, 2008


Ann Maguire - Kochar's Clinical Medicine for Students, 5th Edition. Lippincott Williams & Wilkins. 2008

Syncope is a sudden and brief loss of consciousness associated with a loss of postural tone. Recovery is usually spontaneous. Syncope is not a disease, but rather a symptom with causes ranging from benign to life-threatening. It is a common reason for emergency department evaluation and hospitalization; however, the etiology is often difficult to identify. The cause of syncope may be “unknown” in more than one third of cases. Because of the potential seriousness of this diagnosis and the high frequency of unknown etiology, it is helpful to approach the evaluation of patients with syncope in an organized fashion. The goal in evaluation of patients with syncope is to distinguish between benign and life-threatening causes of syncope so that hospitalization and invasive testing can be appropriately used in the care of those most at risk for adverse outcomes.

Differential Diagnosis
The causes of syncope can be broadly organized according to six major categories: neurally mediated syncope, cardiac syncope, orthostatic hypotension, neurologic disease, medications, and psychiatric disorders (Table 1).

Neurally Mediated Syncope
Neurally mediated syncope, also known as neurocardiogenic or reflex-mediated syncope, is the most common cause of syncope, particularly in younger patients without a history of organic heart disease. It includes three subtypes: vasovagal attacks or vasodepressor syncope, situational syncope, and carotid-sinus syncope or carotid sinus hypersensitivity. Individuals with neurally mediated syncope appear to be particularly susceptible to activities or exposures that stimulate the Bezold-Jarisch reflex. This reflex is activated via intracardiac vagal mechanoreceptors. Valsalva maneuver or prolonged standing may cause decreased cardiac venous return or venous pooling which leads to a drop in blood pressure and subsequent release of catecholamines. The catecholamine release triggers the Bezold-Jarisch reflex and results in a further increase in vagal tone causing simultaneous bradycardia and peripheral vasodilation. Hypotension and loss of consciousness may follow. This pathway explains vasovagal attacks and situational syncope quite well. In carotid sinus syncope, direct stimulation of the carotid artery can cause a cardioinhibitory (bradycardic) or vasodepressor response regardless of posture or adequacy of cardiac venous return.
Individuals with neurally mediated syncope often report a symptomatic prodrome that includes nausea, feelings of warmth, diaphoresis, and blurring or darkening of vision followed immediately by a brief loss of consciousness. Vasovagal attacks may occur after prolonged standing or intense emotional experiences such as unexpected pain, fear, or unpleasant sights, sounds, and smells. Patients may report syncope associated with throat or facial pain. Common causes of situational syncope include cough, defecation, micturition, or swallowing. Those with carotid-sinus syncope may experience syncope with head rotation or with pressure applied to the carotid sinus caused by shaving, tight collars, or tumors (Table 2).

Table 1 Causes of syncope


Mean prevalence (range)a

Neurally mediated syncope

Vasovagal attack

18 (8-37)

Situational syncope

5 (1-8)

Carotid-sinus syncope

1 (0-4)

Psychiatric disorders

2 (1-7)

Orthostatic hypotension

8 (4-10)


3 (1-7)

Neurologic disease

10 (3-32)

Cardiac syncope

Organic heart diseaseb

4 (1-8)


14 (4-38)


34 (13-41)

aPercent of patients with syncope.
bStructural heart disease that causes syncope such as aortic stenosis, pulmonary hypertension, pulmonary embolism, or myocardial infarction.
Adapted from Figure 36.1 in Kochar 4th edition, p. 211 and Kapoor WN. Syncope. N Engl J Med 2000;343:1856-1862, with permission.

Cardiac Syncope
Cardiac causes of syncope can be categorized according to the presence or absence of organic heart disease and arrhythmia. Organic heart disease includes structural heart disease due to aortic stenosis, mitral stenosis, hypertrophic cardiomyopathy, and ischemic heart disease as well as vascular causes such as pulmonary embolus and pulmonary hypertension. Syncope in the setting of exertion is characteristic of patients who have severe aortic stenosis, hypertrophic cardiomyopathy, or ischemic heart disease. Syncope due to a sudden drop in cardiac output may also be a presenting symptom of life-threatening diseases such as aortic dissection and pericardial tamponade. Pulmonary embolism and pulmonary hypertension are uncommon vascular causes of syncope. Syncope in the setting of pulmonary embolism is caused by a massive thrombus formation leading to right ventricular failure, diminished right ventricular output, and consequent decreased left ventricular cardiac output.
Arrhythmias, either bradycardic or tachycardic, are more common cardiac causes of syncope. Bradyarrhythmias include sinus node disease, second- and third-degree heart block, and bradycardia associated with pacemaker malfunction. Medications causing bradycardia and syncope will be discussed separately. Tachyarrhythmias include ventricular tachycardia, torsades de pointes, ventricular fibrillation, and supraventricular tachycardia. A known history of ischemic heart disease or a dilated or hypertrophic cardiomyopathy makes arrhythmia more likely to be the cause of syncope. A family history of sudden cardiac death raises the possibility of ventricular fibrillation due to long QT syndrome or Brugada syndrome (pseudo right bundle branch block and persistent ST segment elevation in V1 to V3). Patients with bradycardia often experience sudden loss of consciousness without warning, whereas those with tachyarrhythmias are more likely to describe palpitations.

Orthostatic Hypotension
Syncope associated with changes in position is often due to orthostatic hypotension. When an individual assumes an upright posture, normal homeostatic mechanisms (arteriolar and venous constriction, enhanced heart rate, and increased lower-extremity muscle tone) prevent a significant decrease in systolic blood pressure. Patients with orthostatic hypotension may have inadequate responses or impaired reflexes that cause postural symptoms. Symptomatic orthostatic hypotension may be related to inadequate volume due to dehydration or autonomic impairment caused by a primary autonomic neuropathy secondary to diabetes or other disorders. Medications known to cause orthostatic hypotension will be discussed separately. The hallmark of syncope due to orthostatic hypotension is that it usually occurs immediately upon standing. Vital signs demonstrate an increase in heart rate and a simultaneous drop in blood pressure with position changes from lying to sitting or standing.

Table 2 Clinical features, electrocardiogram, and other key diagnostic testing related to common causes of syncope


Clinical features

Physical findings




Occurs after prolonged standing, associated nausea, diaphoresis, darkened vision



History may be diagnostic, tilt table testing


Occurs with cough, defecation, micturition, or swallowing



History may be diagnostic

Carotid sinus

Occurs with head rotation or carotid pressure

Sometimes carotid bruits


Carotid massage

Organic heart disease

Occurs with exertion, associated dyspnea

Normal exam, murmur

Evidence of ischemia or cardiomyopathy

Stress testing indicated


Palpitations prior to syncope

Normal exam or arrhythmia

Prolonged QT or other arrhythmia

Telemetry or Holter monitor

Orthostatic hypotension

Occurs upon standing

Characteristic rise in pulse and fall in blood pressure


Tilt table testing


Sudden onset, prolonged period of confusion or lethargy

Witnessed seizures, incontinence




Multiple drugs, older age

Hypotension, bradycardia

Normal or prolonged QT

History may be diagnostic


Frequent occurrence, young age, no injuries



History may be diagnostic

Neurologic Disease
Neurologic disorders are an uncommon cause of syncope. Potential causes include migraine, transient ischemic attack (TIA), seizure, and subclavian steal syndrome. Seizures including unwitnessed grand mal seizures and temporal lobe epilepsy are by far the most common neurologic causes of syncope. TIA involving the vertebrobasilar artery can impair cerebellar circulation and lead to syncope. Basilar artery migraines are another reported cause of syncope. Symptoms that suggest a neurologic cause of syncope include witnessed seizure activity, headache, diplopia, and hemiparesis. Syncope due to cardiac and other causes may also result in brief spells of tonic-clonic activity or irregular muscle twitching making it difficult to distinguish these individuals from those with seizure as the underlying cause of syncope. The presence of incontinence or prolonged postictal lethargy and confusion make seizure activity more likely to be the primary cause.

Medications can lead to syncope by a variety of different mechanisms. Antihypertensives and antidepressant agents are the drug classes most likely to cause syncope. Diuretics are known to cause orthostatic hypotension. Vasodilating antihypertensives can increase the risk of vasovagal attacks and orthostatic hypotension. Beta blockers, clonidine, and cardioselective calcium channel blockers can lead to bradyarrhythmia and syncope. Tricyclic antidepressants and other drugs that cause QT prolongation can lead to ventricular fibrillation and syncope. Opiates, alcohol, and cocaine have been reported to cause syncope and seizures. Elderly patients in particular are at highest risk for medication-related syncope due to the increased prevalence of polypharmacy in this population, the increased risk for organic heart disease, and the greater prevalence of underlying autonomic impairment.

Psychiatric Disorders
A large proportion of patients with otherwise unexplained syncope have been diagnosed with a psychiatric disorder. Generalized anxiety disorder, panic disorder, major depression, and conversion disorders have all been reported to have an increased prevalence among patients who present with syncope. Psychiatric disorders should be considered as potential causes of syncope in young patients who faint frequently, those in whom syncope does not cause any injury, and in those who report many symptoms associated with their syncopal events.

The most common causes of syncope are vasovagal attacks, organic heart disease, arrhythmias, orthostatic hypotension, and seizures. In many cases, it is possible to identify a potential cause of syncope using history and physical examination alone. Family members and other witnesses can be very helpful historians because they are in some cases better able to describe the events leading up to and following loss of consciousness. History taking should focus on postural symptoms (orthostatic or vasovagal syncope), exertional symptoms or a positive family history of syncope (cardiac syncope,
prolonged QT syndromes), palpitations (tachyarrhythmias), postictal symptoms (neurologic syncope), situational symptoms (such as defecation and urination), use of medications, and history of organic heart disease (predisposing to arrhythmias or ischemia). Careful evaluation for the presence of physical findings including murmurs, carotid bruits, asymmetric pulses, and muffled heart sounds is important. Assessment of pulse and blood pressure while lying, sitting, and standing should be performed on all patients presenting with syncope during the initial examination. Every patient should also undergo electrocardiogram (ECG) testing to screen further for evidence of organic heart disease including ischemia, prolonged QT, and arrhythmia (Fig. 1).
Situations in which the history, physical examination, and ECG are often diagnostic in patients with syncope include vasovagal attacks, situational syncope, orthostatic hypotension, and polypharmacy. In other cases, the history, physical examination, and ECG may be highly suggestive. Examples include aortic stenosis, pulmonary embolism, seizure, and individuals in whom there is a strong family history of sudden cardiac death. These individuals should undergo further evaluation with specific testing that is dictated by the clinical scenario. Examples of appropriate testing include echocardiography to confirm valvular heart disease and cardiomyopathy, cardiac catheterization to look for evidence of acute coronary syndromes, ventilation-perfusion scanning or computed tomographic angiography to diagnose pulmonary embolism, electroencephalography to assess for seizures, or computed tomography scan of the brain to identify a focal neurologic lesion. Carotid or transcranial Doppler ultrasonography may be performed in the presence of bruits or when symptoms are suggestive of a neurovascular cause of syncope. Holter monitoring, Loop recorders, and electrophysiologic testing may be indicated when arrhythmia is suspected in individuals with a family history of sudden cardiac death. Routine use of basic laboratory tests is not recommended because of evidence that they rarely yield diagnostically useful information; however, these tests may be performed when they are indicated by the results of the history or physical examination.

Evaluation of Unexplained Syncope
After applying the algorithm (Fig. 1), a potential cause of syncope can be identified in nearly half of all patients. Before proceeding further, remaining patients with unexplained syncope should be stratified according to age and the likelihood that organic heart disease is present. In this way, it is possible to divide unexplained syncope into three branches.

Branch 1: High Likelihood of Underlying Organic Heart Disease
Patients likely to have organic heart disease are characterized by abnormal ECG, exertional symptoms, and sudden syncope without warning symptoms. All patients in this group should undergo echocardiography and cardiac stress testing. When these studies are abnormal, the next step is Holter monitoring or inpatient telemetry to identify arrhythmias. Those with evidence of ischemia will require appropriate revascularization procedures. Symptoms that increase the likelihood that syncope is related to an arrhythmia include: clustering of “spells”, palpitations, sudden loss of consciousness, and use of certain medications. In appropriate cases, patients may require invasive electrophysiologic testing to make a diagnosis of tachyarrhythmia or bradyarrhythmia. If these studies fail to yield a diagnosis, tilt table testing and ultimately psychiatric evaluation is in order.
Branch 2: Age >60 Years, Without Likely Organic Heart Disease
Older individuals are at increased risk for carotid sinus syncope; therefore, this should be evaluated early. After examining the patient to verify the absence of carotid bruits, a carotid massage is diagnostically positive when more than 3 seconds of pressure results in asystole, hypertension, or both. Carotid massage can be performed at the bedside while the patient is monitored or during a tilt test. Following carotid massage, older patients should undergo echocardiography and cardiac stress testing. If there is evidence of organic heart disease, patients should undergo further evaluation as outlined in Branch 1. In the absence of organic heart disease, arrhythmia must be excluded. This can be investigated using Holter or telemetry monitoring and ultimately electrophysiologic testing. In appropriate situations, evaluation for neurally mediated syncope as outlined in Branch 3 is indicated.

Figure 1 Algorithm for diagnosing syncope. CT, computed tomography; ECG, electrocardiogram; EEG, electroencephalogram; EPS, electrophysiology study; OHD, organic heart disease. Adapted from Linzer M, Yang EH, Estes NA, et al. Diagnosing syncope, Part 1: value of history, physical examination, and electrocardiography. Ann Intern Med 1997;126:989-996.)

Branch 3: No Suspected Organic Heart Disease, Age <60>
In this subgroup, the frequency of syncope is most helpful in predicting the need for further testing. Individuals for whom syncope is a frequent occurrence require immediate evaluation with Holter monitoring, Loop recording, and/or tilt table testing. Loop recording is a type of event monitor that is useful in patients with relatively frequent syncopal events that vary from once per week to once every 2 to 3 months. The device can be worn for 30 days or more and patients can make recordings whenever they are symptomatic. Patients who have unexplained recurrent syncope and no evidence of organic heart disease should undergo tilt table testing to confirm the diagnosis of neurally mediated syncope. Most protocols begin with a passive phase where patients are tilted head up for 15 minutes at 60 degrees followed by an isoproterenol infusion that is slowly titrated up to increase the sensitivity of the test as the patient is retilted. If both arrhythmia and neurally mediated syncope are excluded, psychiatric evaluation should be considered. Those with a single episode of syncope can usually be observed without immediate evaluation.