Syncope is an episode of sudden loss of consciousness associated with loss of postural tone followed by spontaneous recovery. It is a common reason for emergency room evaluations and accounts for 740,000 emergency room visits per year in the United States.¹ Syncope can result from a variety of different mechanisms including neurologic, cardiovascular, orthostatic, and metabolic etiologies. Historical details regarding the episodes and thorough knowledge regarding a patient’s concomitant medical problems and medications are essential in determining the cause for a particular patient.

Incidence and Age of Onset

Although syncope may occur in all age groups, the incidence varies greatly by age. The lifetime cumulative incidence of syncope has been reported to be 35%, with a high incidence in the pediatric population, in whom neurocardiogenic syncope is the most common etiology.² Of note, 37% of patients in this study never sought medical attention for syncope, suggesting that both emergency room data and studies relying on medical reports of syncope likely underestimate the true incidence of syncope. The incidence of syncope in children and adolescents seeking medical attention has been reported to be between 71.9 and 125.8 per 100,000 over a 5-year period.³ Individual studies have generally evaluated specific age groups, rather than a broad pediatric-to-elderly range. However, these data suggest that there may be two peaks in incidence rates, one occurring between the ages of 15 and 19 years,^2,3 and another occurring in advanced age. The incidence rate in adulthood has been reported to be 6.2 per 1000 person-years, with a greater incidence rate seen in those older than 70.⁴ For the institutionalized elderly, the annual incidence rate has been reported to be as high as 6%.⁵

For all age groups, neurocardiogenic syncope appears to be the most common etiology. In a group of 822 adult patients (mean age 65.8 years) with syncope, 21.2% had neurocardiogenic syncope, 9.5% had cardiac syncope, 9.4 % had orthostatic syncope, and 36.6% had syncope of undetermined etiology.⁴

Gender Distribution

In most series, women are reported to experience syncope more commonly than men.^2,3,6,7 This gender difference is reported in both younger and older populations. The reason for this difference is not clear. Although neurocardiogenic syncope is reported to be the most common cause of syncope in both the elderly and young populations in both sexes, men are more likely than women to be diagnosed with a cardiac etiology for syncope and to experience a subsequent cardiac event, such as myocardial infarction, recurrent cardiac syncope, or sudden death.^7,8

Associated Medical Syndromes and Natural History

Syncope can be classified into four different categories: cardiovascular, neurally mediated, orthostatic, and metabolic. Such a classification is important not only mechanistically but also prognostically, as cardiovascular syncope carries a 1-year mortality approaching 30%, whereas neurally mediated syncope is typically benign (Figure 23-1).^4,9 Those with vasovagal episodes have a similar overall survival as those without syncope, and those without a clear etiology have an intermediate survival.

Cardiovascular etiologies of syncope include both mechanical and electrical causes. Mechanical causes reduce cardiac output and cerebral blood flow by outflow obstruction or loss of effective pump function. Etiologies of right ventricular outflow obstruction include pulmonary embolus, severe pulmonary hypertension, and, rarely, pulmonic stenosis. Syncope as a manifestation of a pulmonary embolus suggests a large (e.g., saddle-type) embolus. Etiologies of left ventricular outflow obstruction include aortic stenosis and hypertrophic obstructive cardiomyopathy. Aortic stenosis can be congenital (e.g., bicuspid aortic valve) or acquired (idiopathic calcific) and results in a systolic pressure gradient between the left ventricle and aorta causing pressure overload to the left ventricle. The classic triad of symptoms of severe aortic stenosis is angina, syncope, and heart failure. Physical examination findings include a harsh systolic (crescendo-decrescendo) murmur best heard at the second right intercostal space and a delayed upstroke with diminished amplitude of the carotid pulse (pulsus parvus et tardus). The best noninvasive method to evaluate aortic valve area and degree of stenosis is echocardiography. The average survival of patients with nonsurgically treated aortic stenosis after onset of syncope is 3 years.¹⁰

Another form of left ventricular outflow tract obstruction is hypertrophic obstructive cardiomyopathy, which is often an inherited autosomal dominant disorder of sarcomeric proteins that causes abnormal hypertrophy of the ventricles, particularly the interventricular septum. Although left ventricular outflow tract obstruction in aortic stenosis is fixed, it is dynamic in hypertrophic obstructive cardiomyopathy as a result of septal hypertrophy and systolic anterior motion of the mitral valve. Increased myocardial contractility (e.g., exercise) and decreased ventricular volume (e.g., standing) worsen the gradient and systolic murmur. The natural history of hypertrophic cardiomyopathy is variable, but syncope is an alarming sign. Echocardiography remains a valuable tool for diagnosis. Etiologies of loss of pump function include myocardial infarction and cardiac tamponade, both of which reduce cardiac output.

Electrical causes of syncope include brady- and tachyarrhythmias. Bradyarrhythmic syncope can result from both sinus node dysfunction (e.g., sinus arrest) and atrioventricular (AV) block, typically in older patients with sclerodegenerative changes of the conduction system. The presence of bifasicular block (left bundle branch block alone or right bundle branch block with left hemiblock) should raise the suspicion of AV block as the cause of syncope (Figure 23-2). Syncope in patients with remote myocardial infarction and/or left ventricular dysfunction should be considered to have ventricular tachycardia until proven otherwise.

Neurally mediated (or reflexogenic) etiologies of syncope include vasovagal, viscerovagal (situational), and carotid sinus hypersensitivity. Neurally mediated syncope results from an exaggerated reflex that activates the vagus nerve, causing asystole (cardioinhibitory response), reduces sympathetic outflow, causing vasodilation and hypotension (vasodepressor response), or both (mixed response). A pure vasodepressor response causing syncope without bradycardia can occur but is rare. The classic vasovagal episode occurs in a young individual after triggers such as prolonged standing, emotional stress (e.g., blood draws), or pain (Video 23-1). Prodromal symptoms include warmth, diaphoresis, yawning, and nausea. Though frequently recurrent, vasovagal syncope tends to have a benign prognosis.⁴ Vasovagal reflexes can also be triggered by visceral stretch or baroreceptors that are activated during specific situations: defecation, micturition, laughing, or coughing (Video 23-2). Carotid sinus hypersensitivity is a specific vagally mediated cause of syncope that occurs in older patients, often with carotid artery disease or prior neck surgery.^11,12 Syncope occurs during neck manipulation (e.g., shaving or neck turning). Gentle pressure on the carotid bulb elicits one of three hypersensitivity responses: cardioinhibitory (asystole >3 s), vasodepressor (>50 mm Hg drop in blood pressure), or mixed (combination of both types).¹³

Orthostatic syncope is due to an abrupt drop in blood pressure when assuming an upright posture and can be due to loss of circulating blood volume (e.g., hemorrhage) or failure of vasoconstrictor mechanisms that normally maintain blood pressure. Autonomic dysfunction, loss of baroreceptor responses, and medication usage (e.g., antihypertensive drugs) can cause failure of vasoconstrictor responses.

Primary central or peripheral autonomic nervous system dysfunction may result in syncope. Peripheral neuropathies with prominent autonomic nerve involvement can cause syncope due to orthostatic hypotension. Diabetic neuropathy, familial amyloid neuropathy, acute intermittent porphyria, and paraneoplastic syndromes are often associated with prominent autonomic dysfunction. Associated symptoms in these neuropathies may include other signs of autonomic dysfunction, such as impaired sweating, gastrointestinal tract dysmobility, and genitourinary dysfunction, as well as numbness and pain. The prognosis is directly related to the underlying etiology for the neuropathy but is often poor, as these etiologies often result in some degree of permanent nerve dysfunction. Lifelong symptomatic treatment is generally needed in these cases.

Several central neurodegenerative disorders may cause syncope via prominent autonomic nervous system dysfunction. Multiple system atrophy, dementia with Lewy bodies, and progressive supranuclear palsy are some of the central neurodegenerative disorders that may have associated prominent autonomic dysfunction. Additionally, spinal cord dysfunction, such as that due to trauma, demyelinating disorders, and syringomyelia, may cause prominent orthostatic hypotension.^14,15

Motor neuron disease has also been associated with autonomic failure and orthostatic hypotension.¹⁶ In amyotrophic lateral sclerosis (ALS), symptoms of motor neuron disease generally precede symptoms of autonomic dysfunction, but autonomic failure preceding typical ALS symptoms has also been reported.¹⁷

Autonomic dysfunction may occur without a sensory or motor neuropathy or evidence of central nervous system disease and is termed pure autonomic failure.

In this condition, symptoms usually first begin gradually between the ages of 50 and 70 years¹⁸ with presyncope and syncope symptoms. There may also be posturally associated headache or neck pain, convulsive syncope, visual loss, or even anginal symptoms.

Rarely, there is a primary vascular etiology for syncope, such as vertebrobasilar disease, resulting in cerebral ischemia and syncope. In the case of posterior circulation focal ischemia, there are generally other focal neurologic signs and symptoms present, particularly brainstem findings, such as diplopia, nausea, ataxia, hemiparesis, and focal sensory loss.

Metabolic etiologies of syncope are rare and include high-altitude sickness (low partial pressure of oxygen [pO₂]), acute hyperventilation (low pCO₂, which causes cerebral vasoconstriction), and hypoglycemia. Insulinomas are a rare cause of recurrent hypoglycemia, which may mimic seizure symptoms.¹⁹ These may cause recurrent episodes of alteration in level of consciousness and headache, which are often associated with more typical hypoglycemia symptoms, such as diaphoresis and palpitations.