Vasovagal syncope accounts for the largest percentage of cases. Although it is the most common cause of syncope in otherwise healthy young persons, it occurs in all age groups. Its hallmarks are inappropriate bradycardia and vasodilation due to an increase in vagal tone and interruption of normal sympathetic responses. The resultant bradycardia and vasodilation cause systemic blood pressure to plummet, compromising cerebral perfusion and leading to loss of consciousness.

Purported triggers of the heightened vagal activity include psychological distress, excess venous pooling, hypersensitivity of organ mechanoreceptors (in the heart, esophagus, bladder, and respiratory tract), and the Bezold-Jarisch reflex (an extra-strong cardiac contraction in reaction to decreased preload). The latter is a brainstem-mediated autonomic reflex that increases vagal tone, inhibits sympathetic activity, and results in reduced cardiac contractility, bradycardia, and peripheral vasodilation. Central nervous system modulators (e.g., serotonin, adenosine, opioids, and beta-endorphins) may also play a role in this reflex, perhaps mediating the vasovagal response to emotional distress and other cortical stimuli. The myocardium and conduction system are normal in such persons, accounting for the excellent prognosis. The seemingly paradoxical use of beta-blockers in treatment of this condition aims to inhibit the Bezold-Jarisch reflex by blunting the initial myocardial response.

A less-appreciated form of vagally mediated syncope is use of cholinesterase inhibitors (e.g., donepezil, galantamine, rivastigmine), which are commonly prescribed for patients with dementia (see Chapter 173). The augmented vagal tone puts the patient at risk for significant bradycardia that can lead to syncope. Users of these medications have increased rates of hospital admissions for syncope, pacemaker insertion, and fallrelated injuries.

The clinical presentations of vasovagal syncope can be quite variable, but in most instances, the episodes occur in the upright or standing position or during exercise. Although some patients (particularly the elderly) may report no premonitory symptoms, most experience prodromal autonomic symptoms of sweating (often a warm “flush” initially), epigastric queasiness or nausea, light-headedness, dizziness, blurred or dimmed vision, weakness or extreme fatigue, and occasionally a feeling of depersonalization. Patients feel restless and unable to concentrate. Yawning, sighing, or hyperventilation may be noted. The onset of premonitory symptoms may help to prevent a drop attack and resultant injury. The unconscious patient appears ashen or pale, cold, and diaphoretic with dilated pupils. At the outset, the heart rate may be rapid, but it slows markedly as the process unfolds. The presence of pallor and diaphoresis is paradoxical, but both may be prominent and reflect the high circulating levels of epinephrine found in this state of otherwise marked sympathetic inhibition. Such features make for a very distressing clinical presentation, mimicking serious cardiovascular disease. After several minutes, full consciousness is regained, although weakness, sweatiness, and nausea may persist. In the elderly, there may be some retrograde amnesia, but control of bladder and bowels is never lost, helping to differentiate the episode from a seizure. Tilt-table study can reproduce the symptoms in susceptible persons, with many
reporting a prodrome of blurred vision, vertigo, tinnitus, and nausea when tested (see later discussion).

Sometimes, the hypotension and hypoperfusion that occur are so profound that transient cerebral hypoxia and a brief period of seizure activity (convulsive syncope) ensue. This convulsive syncope is distinct from loss of consciousness that accompanies a generalized seizure disorder and does not respond to antiseizure medication.

Situational syncopes can be considered variants of vasovagally mediated disease, precipitated by factors that reduce venous return. The inciting event may be a coughing spell, voiding, straining at stool, pain, or emotional stress. Posttussive syncope is characterized by loss of consciousness following a prolonged bout of forceful coughing. Men with chronic bronchitis are most often affected. The precipitant of the vasovagal response is believed to involve decreased cardiac output due to decreased venous return. In addition, there may be increased cerebral vascular resistance secondary to hypocapnia and compression of cerebral vessels by an increase in cerebrospinal fluid pressure. Prolonged Valsalva maneuvers have a similar effect—the increase in intrathoracic pressure impedes venous return. Postmicturition syncope takes place in the context of emptying a distended bladder. The typical setting involves a man who has gotten up at night to urinate after consuming considerable amounts of alcohol. Consciousness is lost without much warning. Drainage of ascitic fluid or a distended bladder may produce a similar effect. Valsalva plays an important role in postdefecation syncope, in which straining decreases venous return and sets in motion the vasovagal reflex response. Pain and acute psychological distress can trigger a similar vasovagal response.

Psychiatric disease as a trigger of syncope probably represents a class of vasovagal variants mediated by central factors. The precise pathophysiology is incompletely understood, but underlying psychopathology is becoming increasingly appreciated as an important etiologic factor, especially in investigations of syncope of unknown origin. Generalized anxiety disorder, panic disorder, and depression are frequently found in populations of such patients who have no evidence of heart disease. Their fainting spells often resolve with treatment of the underlying psychopathology. Prevalence is greatest in younger persons with frequent syncopal episodes, in those who never sustain injury from their loss of consciousness, and in patients who present with multiple somatic and psychiatric symptoms, such as fear, anxiousness, nausea, light-headedness, and numbness. Reproduction of symptoms by 2 to 3 minutes of open-mouth hyperventilation is characteristic. Hysteria may result in apparent loss of consciousness; the spell is a conversion reaction characterized by graceful fainting to the floor or couch; frequent presence of an audience; normal pulse, skin color, and blood pressure; and an emotionally detached description of the episode.

A failure to mount a normal baroreflex response to standing represents the dysautonomic common denominator for a spectrum of conditions that produce postural (orthostatic) hypotension—defined as greater than 20 mm Hg decrease in systolic pressure and greater than 10 mm Hg decrease in diastolic pressure within the first 3 minutes of standing up. Both central and peripheral disorders of the autonomic nervous system can cause the problem (see Differential Diagnosis). Patients characteristically develop symptoms on standing because the normal responses of vasoconstriction and increase in heart rate fail to occur and reduced cerebral perfusion ensues. Episodes are especially common in the setting of reduced effective intravascular volume (e.g., dehydration, vasodilating drugs, acute blood loss, prolonged standing), which can cause postural hypotension even in the absence of autonomic insufficiency. Unlike the vasovagal etiologies, there is no slowing of heart rate, but heart rate typically remains inappropriately slow for the degree of reduction in blood pressure. Hypotension progresses over seconds to minutes, capable of producing transient ischemia for a number of organ systems (e.g., visual, muscular, pulmonary, cardiac) and culminating in loss of consciousness.

Carotid sinus hypersensitivity represents a form of neurocardiogenic syncope that occurs most commonly in elderly persons with underlying atherosclerotic disease. Massage of the carotid sinus can trigger long asystolic pauses. Digitalis administration seems to aggravate the condition. Carotid sinus hypersensitivity may also cause a vasodepressor form of syncope in which heart rate remains unchanged but there is vasodilation and hypotension. Actions that lead to compression of the carotid sinus (wearing a tight collar, turning
the head, or shaving) characteristically cause symptoms, which include light-headedness, sweating, pallor, and nausea, followed by fainting. When the predominant mechanism is asystole, the loss of consciousness can be precipitous.

Aortic stenosis and hypertrophic cardiomyopathy can result in syncope when they cause hemodynamically significant obstruction of the left ventricular outflow tract (see Chapter 33). The characteristic clinical picture is one of effort syncope, with loss of consciousness in the context of vigorous exercise and sweating. The latter contributes to hemodynamic compromise by causing vasodilation and a drop in venous return. A vicious cycle of inability to raise cardiac output and falling venous return can lead to hypotension, loss of consciousness, and even sudden death. Syncope in the setting of known aortic stenosis carries a very poor prognosis (see Chapter 33). Total blockade of the mitral orifice from an atrial myxoma and massive pulmonary embolization leading to acute pulmonary hypertension can have similar consequences. Loss of consciousness comes with little warning. Anomalous origin of a coronary artery from the coronary sinus places a patient at risk for kinking or twisting of the artery, especially during vigorous exercise, and can cause syncope or even sudden death. Premonitory symptoms may be absent, but sometimes there is a history of exercise-induced chest pain or syncope. Constrictive pericarditis can lead to orthostatic hypotension by limiting both venous return and cardiac output.

Cardiac dysrhythmias may precipitate sudden loss of consciousness with none of the premonitory manifestations of neurocardiogenic syncope. At times, palpitations are reported to precede the syncopal event. Once effective systoles have ceased, less than 5 seconds of consciousness remain. Palpitations are sometimes reported, and loss of consciousness can occur while the patient is supine. Important dysrhythmias associated with syncope include complete heart block (Stokes-Adams attacks) and ventricular tachycardia (VT) (see Chapter 29). Most persons with VT have evidence of underlying heart disease (ischemia, cardiomyopathy, QT prolongation), but in others, the heart may appear normal (see Chapter 29). Important clinical clues of a serious arrhythmic etiology in those without overt heart disease include a history of palpitations (particularly exercise induced) and a family history of syncope or sudden death. The clinical picture of those with VT may include exercise-induced palpitations and dyspnea in addition to syncope. Beta-blockade lowers VT risk but does not change the QT interval.

The long QT syndrome represents a potentially tragic, genetic form of cardiac syncope, occurring in young people and associated with high risk of cardiac sudden death. The condition results from mutations (designated LQT1,2,3) affecting myocardial ion channel proteins and putting the patient at risk for ventricular fibrillation as a consequence of polymorphic VTs (torsade de pointes). QT-interval prolongation (>460 msec for women and >440 msec in men) is the hallmark on the condition; prolongation increases with exercise. Patients may report palpitations, presyncope, or syncopal episodes, which may be triggered by exercise or other forms of exertion. Family history is usually notable not only for sudden death in a young family member but also for atypical presentations such as drowning, sudden infant death, and death while driving. Risk is proportional to the extent of QT-interval prolongation and especially high (upward of 70%) as the interval exceeds 500 msec.

Occasionally, a supraventricular tachycardia (e.g., paroxysmal supraventricular tachycardia or, less commonly, atrial fibrillation or flutter) with a very rapid ventricular response rate will sufficiently compromise cardiac output to result in near or complete syncope (see Chapter 29). Common precipitants of supraventricular tachyarrhythmias include ischemia, sick sinus syndrome, digitalis toxicity, and the preexcitation syndromes. Patients with chronic bifascicular and trifascicular block are more likely to have syncopal attacks, but those with syncope have not been found to have an increased risk of sudden death.

Seizures differ from causes of syncope in that the loss of consciousness derives from an electrical disturbance rather than inadequate cerebral perfusion. The typical clinical presentation is unique, with aura, postictal symptoms, incontinence, and tonic-clonic movements often dominating the clinical picture. However, akinetic petit mal attacks have few of these features, although normal blood pressure and pulse help to distinguish them from seizures having cardiovascular causes (see Chapter 170). As noted previously, convulsions may occur in the setting of vagally mediated cerebral hypoperfusion in the absence of an underlying seizure disorder.

Metabolic factors (e.g., hypoxia, hypocarbia, hypoglycemia) are more likely to alter consciousness than to cause actual syncope. Restlessness, confusion, and anxiety are prominent and precede
loss of consciousness. When hyperventilation is responsible, the patient first complains of a smothering or suffocating feeling in conjunction with paresthesias in the limbs and circumorally (see Chapter 226). Syncope may take place while the patient is sitting or lying down. Hypoglycemia rarely causes loss of consciousness but always needs to be considered, especially in diabetics taking insulin or sulfonylureas (see Chapter 97). Severe hypoglycemia may precipitate a generalized seizure.