DEFINITION

Syncope is an abrupt loss of consciousness with a concomitant loss of postural tone. Presyncope, also called near syncope, is the prodrome of syncope, but without loss of consciousness. Syncope is part of a broader clinical network of symptoms that is best described as postural intolerance, which is a constellation of symptoms that occur in the upright posture including dizziness, lightheadedness, tremulousness, sweating, nausea, and palpitations. These symptoms improve with the assumption of a recumbent posture.

PREVALENCE AND INCIDENCE

Syncope accounts for 3% of emergency room visits and 1% to 6% of hospital admissions.¹ It happens to men and women of all ages, but it increases in prevalence with age. In our syncope clinic from 1997 to 2007, we treated more women than men; it is unclear if this was due to a higher prevalence in women or to a higher tendency for women to seek medical assistance for this condition. Figure 1 shows the number of tests we performed, broken down by gender.

Figure 1 Number of tilt tests from the syncope clinic, 1997-2007, shown according to gender.

PATHOPHYSIOLOGY AND NATURAL HISTORY

The autonomic nervous system is vital for maintaining internal homeostasis, including regulation of blood pressure (BP), heart rate, fluid and electrolyte balance, and body temperature.

The hemodynamic response to standing exemplifies the interaction between the circulatory and autonomic nervous systems. When standing, initially the force of gravity pools blood in the distensible veins below heart level. Increased capillary pressure follows, and plasma is lost to interstitial fluid due to ultrafiltration. 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 fall of arterial pressure.

Normally the physiologic response to standing is gravitational blood pooling in the lower extremities, leading to reduced venous return to the heart. The mean arterial BP and stroke volume decrease, which deactivates strategically located mechanoreceptors that will initiate neural reflexes. These reflexes increase sympathetic outflow, decrease parasympathetic responses, and lead to tachycardia and vasoconstriction. In addition, unloading of the low pressure cardiopulmonary receptors play a role in regulating the release of arginine vasopressin (AVP). The reduction in effective plasma volume and renal blood flow stimulate the postural responses of the renin-angiotensin-aldosterone (RAA) system. Compensatory mechanisms include: increased sympathetic outflow leading to arteriolar vasoconstriction, venoconstriction, and increase in heart rate; increased catecholamine concentration in the plasma and urine; and rise in plasma epinephrine originating from the adrenal medulla.

The autonomic supply to the cardiovascular system is coordinated at the central autonomic network (CAN) in the brainstem. The autonomic nervous system counterbalances postural stressors to maintain mean arterial pressure. During orthostasis, the initial reduction of cardiac filling and stroke volume is sensed by pressure receptors in the heart, carotid sinuses, and aortic arch, which send impulses to the CAN. This initiates sympathetic vasomotor outflow to vascular beds in the skeletal muscles and cutaneous vasculature. Norepinephrine is released, causing vasoconstriction, venoconstriction, and increased heart rate and contractility.

Decreased atrial stretch during postural stress causes increased secretion of AVP and decreased secretion of A-type atrial natriuretic peptide (ANP). This antinatriuresis helps increase extra cellular fluid (ECF) volume and compensates for cardiac filling.

Orthostasis leads to a reflexive decrease of renal blood flow followed by decreased glomerular filtration of sodium. Decreases in renal blood flow and renal perfusion pressure stimulate the RAA system to enhance vasoconstriction.

Sympathetic stimulation plays a major role in the immediate response to upright posture. It maintains mean arterial pressure via constriction of several vascular beds. Venoconstriction causes correction of orthostasis by increasing cardiac filling for a given amount of gravitational pooling of blood. Increased cardiac inotropic function augments stroke volume for cardiac filling. Increased heart rate augments cardiac output for stroke volume. Leg pumping of skeletal muscles enhances venous return to the heart. The venoarterial reflex augments arterial vasoconstriction in response to venous distention.

On the other hand, the RAA system plays a minor role in the immediate constrictive response to orthostasis, and its effects are relatively late. In the absence of sympathetic postganglionic outflow, like that seen in cases of spinal cord injury and quadriplegia, orthostatic hypotension occurs despite marked stimulation of the RAA system.

Not every fall in BP leads to brain hypoxia. Syncope or presyncope occurs as a result of brain hypoxia, which is usually secondary to a reduction of cerebral perfusion pressure. This is because the cerebral circulation is autoregulated so brain perfusion is maintained in the face of significant changes in BP. Cerebral autoregulation allows regional cerebral blood flow to remain constant over a range of perfusion pressure (50-140 mm Hg).

ETIOLOGY

In stratifying the etiology of syncope, prospective studies have found that neurally mediated causes account for the largest percentage of events (38%-56%). Cardiovascular causes, separated into cardiac causes (11%-23%) and postural hypotension (2%-24%), account for a smaller percentage of cases. Undetermined causes occur in 14% to 18% of events.

Poor prognosis was reported in syncope patients with underlying heart disease. The etiologies of syncope can be subdivided into those occurring in patients with or without structural heart disease. Hospital admission criteria following emergency department evaluation for a syncope event have been extensively discussed, and decision making about prevention of serious outcomes is critical.^2,³

Presence of Structural Heart Disease

In patients with structural heart disease, syncope can occur secondary to bradyarrhythmias, tachyarrhythmias, or arrhythmias secondary to medication and electrolyte abnormalities. Cardiac left ventricular outflow obstruction (including aortic stenosis or hypertrophic cardiomyopathy) or right ventricular obstruction (including pulmonary embolus or pulmonary hypertension) can cause syncope. Other cardiac structural abnormalities, such as mitral stenosis, atrial myxoma, or dissecting aortic aneurysm, can also lead to syncope. Finally, the syndromes that accompany cardiac events including myocardial ischemia or infarction, cardiac tamponade, or subclavian steal syndrome can include syncope.

Absence of Structural Heart Disease

In the absence of structural heart disease, neurally mediated mechanisms, postural hypotension, postural orthostatic tachycardia syndrome (POTS), metabolic or neurologic abnormalities, and psychogenic causes should be considered as a possible etiology of a syncopal event. For practical purposes, syncope in the absence of heart disease may be grouped into events where the BP declines steadily, those where BP drops only at the endpoint, and those where BP response to upright posture remains normal.

Neurally Mediated Mechanisms

Neurocardiogenic Syncope

Also known as vasovagal syncope and vasodepressor syncope, neurocardiogenic syncope is commonly described using the Bezold-Jarisch reflex model.² 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. The central nervous system responds with reflex sympathetic withdrawal and increased parasympathetic output. These signals cause vasodilation, hypotension, and bradycardia in the vasovagal type, but only vasodilation occurs in the vasodepressor type.

Other potential mechanisms include involvement of central serotoninergic pathways and release of endogenous opioids or catecholamines. Of importance is the report of a monitored vasovagal event in a heart transplant patient.⁴

Autonomic dysfunction (Box 1) is a disorder of postganglionic noradrenergic transmission. The central nervous system does not appropriately activate efferent sympathetic fibers. Mechanisms of dysfunction include subnormal norepinephrine release, impaired vasoconstriction, and reduced vascular volume from urinary sodium wasting. Autonomic dysfunction is classified as primary or secondary.

Postural Orthostatic Tachycardia Syndrome

POTS ^10,¹¹ is defined by excessive heart rate increments upon upright posture. A person with POTS experiences heart rates that increase 30 beats or more per minute—and that can increase to 120 beats or more per minute—upon standing. These heart rate increases usually occur within 10 minutes of rising. We have described early versus late POTS (accentuated postural tachycardia).¹¹

A variety of circulatory and autonomic neural abnormalities occur in association with POTS and can cause accentuated postural tachycardia including hypovolemia, augmentation of postural venous pooling, β-adrenergic hypersensitivity, hyperbradykininemia, and autonomic imbalance. In a substantial number of patients, no definite cause is found. The literature describes this condition as associated with mitral valve prolapse, basilar migraine, chronic fatigue syndrome, and neurocardiogenic (vasovagal) syncope.