Syncope: Etiology and diagnostic approach

ORTHOSTATIC HYPOTENSION

Orthostatic hypotension accounts for about 10% of cases of syncope.^1–3

Normally, after the first few minutes of standing, about 25% to 30% of the blood pools in the veins of the pelvis and the lower extremities, strikingly reducing venous return and stroke volume. Upon more prolonged standing, more blood leaves the vascular space and collects in the extravascular space, further reducing venous return. This normally leads to a reflex increase in sympathetic tone, peripheral and splanchnic vasoconstriction, and an increase in heart rate of 10 to 15 beats per minute. Overall, cardiac output is reduced and vascular resistance is increased while blood pressure is maintained, blood pressure being equal to cardiac output times vascular resistance.

Vasovagal syncope is initiated by anything that leads to strong contractions in an 'empty' heart

Orthostatic hypotension is characterized by autonomic failure, with a lack of compensatory increase in vascular resistance or heart rate upon orthostasis, or by significant hypovolemia that cannot be overcome by sympathetic mechanisms. It is defined as a drop in systolic blood pressure of 20 mm Hg or more or a drop in diastolic pressure of 10 mm Hg or more after 30 seconds to 5 minutes of upright posture. Blood pressure is checked immediately upon standing and at 3 and 5 minutes. This may be done at the bedside or during tilt-table testing.^2,4

Some patients have an immediate drop in blood pressure of more than 40 mm Hg upon standing, with a quick return to normal within 30 seconds. This "initial orthostatic hypotension" may be common in elderly patients taking antihypertensive drugs and may elude detection during standard blood pressure measurement.² Other patients with milder orthostatic hypotension may develop a more delayed hypotension 10 to 15 minutes later, as more blood pools in the periphery.¹⁶

Along with the drop in blood pressure, a failure of the heart rate to increase identifies autonomic dysfunction. On the other hand, an increase in the heart rate of more than 20 to 30 beats per minute may signify a hypovolemic state even if blood pressure is maintained, the lack of blood pressure drop being related to the excessive heart rate increase.

Orthostatic hypotension is the most common cause of syncope in the elderly and may be due to autonomic dysfunction (related to age, diabetes, uremia, or Parkinson disease), volume depletion, or drugs that block autonomic effects or cause hypovolemia, such as vasodilators, beta-blockers, diuretics, neuropsychiatric medications, and alcohol.

Since digestion leads to peripheral vasodilation and splanchnic blood pooling, syncope that occurs within 1 hour after eating has a mechanism similar to that of orthostatic syncope.

Supine hypertension with orthostatic hypotension. Some patients with severe autonomic dysfunction and the inability to regulate vascular tone have severe hypertension when supine and significant hypotension when upright.

Postural orthostatic tachycardia syndrome, another form of orthostatic failure, occurs most frequently in young women (under the age of 50). In this syndrome, autonomic dysfunction affects peripheral vascular resistance, which fails to increase in response to orthostatic stress. This autonomic dysfunction does not affect the heart, which manifests a striking compensatory increase in rate of more than 30 beats per minute within the first 10 minutes of orthostasis, or an absolute heart rate greater than 120 beats per minute. Unlike in orthostatic hypotension, blood pressure and cardiac output are maintained through this increase in heart rate, although the patient still develops symptoms of severe fatigue or near-syncope, possibly because of flow maldistribution and reduced cerebral flow.²

While postural orthostatic tachycardia syndrome per se does not induce syncope,² it may be associated with a vasovagal form of syncope that occurs beyond the first 10 minutes of orthostasis in up to 38% of these patients.¹⁷

In a less common, hyperadrenergic form of postural orthostatic tachycardia syndrome, there is no autonomic failure but the sympathetic system is overly activated, with orthostasis leading to excessive tachycardia.^10,18

CARDIAC SYNCOPE

Accounting for 10% to 20% of cases of syncope, a cardiac cause is the main concern in patients presenting with syncope, as cardiac syncope predicts an increased risk of death and may herald sudden cardiac death.^1,2,8,19,20 It often occurs suddenly without any warning signs, in which case it is called malignant syncope. Unlike what occurs in neurally mediated syncope, the postrecovery period is not usually marked by lingering malaise.

There are three forms of cardiac syncope:

Syncope due to structural heart disease with cardiac obstruction

In cases of aortic stenosis, hypertrophic obstructive cardiomyopathy, or severe pulmonary arterial hypertension, peripheral vasodilation occurs during exercise, but cardiac output cannot increase because of the fixed or dynamic obstruction to the ventricular outflow. Since blood pressure is equal to cardiac output times peripheral vascular resistance, pressure drops with the reduction in peripheral vascular resistance. Exertional ventricular arrhythmias may also occur in these patients. Conversely, postexertional syncope is usually benign.

Syncope due to ventricular tachycardia

Ventricular tachycardia can be secondary to underlying structural heart disease, with or without reduced ejection fraction, such as coronary arterial disease, hypertrophic cardiomyopathy, hypertensive cardiomyopathy, or valvular disease. It can also be secondary to primary electrical disease (eg, long QT syndrome, Wolff-Parkinson-White syndrome, Brugada syndrome, arrhythmogenic right ventricular dysplasia, sarcoidosis).

Occasionally, fast supraventricular tachycardia causes syncope at its onset, before vascular compensation develops. This occurs in patients with underlying heart disease.^2,8,19

Syncope from bradyarrhythmias

Bradyarrhythmias can occur with or without underlying structural heart disease. They are most often related to degeneration of the conduction system or to medications rather than to cardiomyopathy.

Caveats

When a patient with a history of heart failure presents with syncope, the top considerations are ventricular tachycardia and bradyarrhythmia. Nevertheless, about half of cases of syncope in patients with cardiac disease have a noncardiac cause,¹⁹ including the hypotensive or bradycardiac side effect of drugs.

As noted above, most cases of syncope are neurally mediated. However, long asystolic pauses due to sinus or atrioventricular nodal block are the most frequent mechanism of unexplained syncope and are seen in more than 50% of syncope cases on prolonged rhythm monitoring.^1,21 These pauses may be related to intrinsic sinus or atrioventricular nodal disease or, more commonly, to extrinsic effects such as the vasovagal mechanism. Some experts favor classifying and treating syncope on the basis of the final mechanism rather than the initiating process, but this is not universally accepted.^1,22

OTHER CAUSES OF SYNCOPE

Acute medical or cardiovascular illnesses can cause syncope and are looked for in the appropriate clinical context: severe hypovolemia or gastrointestinal bleeding, large pulmonary embolus with hemodynamic compromise, tamponade, aortic dissection, or hypoglycemia.

Bilateral critical carotid disease or severe vertebrobasilar disease very rarely cause syncope, and, when they do, they are associated with focal neurologic deficits.² Vertebrobasilar disease may cause "drop attacks," ie, a loss of muscular tone with falling but without loss of consciousness.²³

Severe proximal subclavian disease leads to reversal of the flow in the ipsilateral vertebral artery as blood is shunted toward the upper extremity. It manifests as dizziness and syncope during the ipsilateral upper extremity activity, usually with focal neurologic signs (subclavian steal syndrome).²

Psychogenic pseudosyncope is characterized by frequent attacks that typically last longer than true syncope and occur multiple times per day or week, sometimes with a loss of motor tone.² It occurs in patients with anxiety or somatization disorders.