Etiology

The etiologies of syncope are myriad and can be classified in various ways, including cardiac, noncardiac, and unknown causes.[3] There may be a degree of overlap between cardiac and non-cardiac causes; the cause of syncope may not be determined (idiopathic etiology) in up to one third of cases.[4]

Syncope is caused by the transient reduction in cerebral blood flow which results in hypoperfusion of both cerebral hemispheres simultaneously or sections of the brainstem thought to be responsible for the conscious state (the reticular activating system).

The role of patient age in the diagnostic evaluation of syncope is not clearly defined. Although some studies suggest the importance of age as a predictor of poorer outcome in patients with syncope of any cause, others have demonstrated that age is not an independent predictor of adverse outcome in syncope.[5][6][7]

While a single pathologic process often causes syncope in younger patients, in older patients it is often multifactorial. Older patients are especially prone to syncope as a consequence of a combination of age-related alterations in the cardiovascular system, multiple comorbidities, and the use of numerous medications.[8]

Cardiac syncope

Defined as syncope caused by bradycardia, tachycardia, or hypotension due to low cardiac index, blood flow obstruction, vasodilatation, or acute vascular dissection.[9]

Dysrhythmias

Produce syncope by decreasing ventricular filling and stroke volume, resulting in hypotension and diminished cerebral blood flow. Examples include:

  • Ventricular arrhythmias

  • Sinus node dysfunction: including bradycardia/tachycardia syndrome

  • Atrioventricular conduction system blocks

  • Paroxysmal supraventricular tachycardia

  • Inherited syndromes: long QT syndromes, Brugada syndrome

  • Implanted device malfunction: pacemaker or implantable cardioverter defibrillator; pacemaker malfunction may produce syncope as a result of bradydysrhythmias or pacemaker-induced tachycardia

  • Drug-induced proarrhythmias: sotalol, flecainide, quinidine, procainamide, disopyramide.

Structural cardiac and cardiopulmonary disease

  • Cardiac valvular diseases

    • aortic or mitral stenosis: severe mitral stenosis is most commonly associated with syncope during periods of atrial fibrillation; exertional syncope may be due to aortic stenosis[10]

    • acute aortic, mitral, or tricuspid insufficiency

    • prosthetic valve dysfunction

  • Hypertrophic obstructive cardiomyopathy: exertional syncope may be due to hypertrophic cardiomyopathy

  • Acute myocardial ischemia/infarction: syncope is a relatively rare initial presentation of acute myocardial infarction and is related to dysrhythmia or pump failure

  • Atrial myxoma

  • Acute aortic dissection

  • Pulmonary embolism and pulmonary hypertension: acute pulmonary hypertension can cause a functional obstruction to pulmonary flow, abruptly decreasing left ventricular preload and thus cardiac output. This is most likely the mechanism of syncope associated with massive pulmonary embolism. In patients with chronic pulmonary hypertension, activities that acutely raise intrathoracic pressure, such as coughing or Valsalva during defecation, can produce the same phenomenon

  • Cardiac tamponade: increased pericardial pressure causes compression of the heart chambers and subsequently decreases cardiac output.

Noncardiac syncope

Reflex (neurally mediated)

This is syncope due to a reflex that causes vasodilation, bradycardia, or both. It has several subtypes.

  • Vasovagal syndrome: the most common type of syncope in children and adults.[11][12]

  • Carotid sinus syndrome

  • Situational syncope.

Orthostatic

  • Dysautonomia:

    • Catecholamine disorders: baroreflex failure, dopamine-beta-hydroxylase deficiency, pheochromocytoma, neuroblastoma, familial paraganglioma syndrome, tetrahydrobiopterin deficiency

    • Central autonomic disorders: multiple system atrophy (Shy-Drager syndrome), Parkinson disease with autonomic failure

    • Orthostatic intolerance syndrome: postural tachycardia syndrome, mitral valve prolapse, idiopathic hypovolemia

    • Paroxysmal autonomic syncopes: neurocardiogenic syncope

    • Peripheral autonomic disorders: acute idiopathic polyneuropathy (Guillain-Barre syndrome), Chagas disease, diabetic autonomic failure, familial dysautonomia, pure autonomic failure (Bradbury-Eggleston syndrome).

  • Hypovolemia

    • Diarrhea

    • Hemorrhage (may be occult): gastrointestinal bleeding, tissue trauma, ruptured aortic aneurysm, ruptured ovarian cyst, ruptured ectopic pregnancy, retroperitoneal hemorrhage, ruptured spleen

    • Addison disease

  • Postexercise

  • Postprandial

  • Drug-induced (most common cause of orthostatic hypotension): for example, with diuretics, alpha-adrenergic blocking agents such as prazosin, ACE inhibitors, alcohol, clonidine, tricyclic antidepressants, phenothiazines, antihistamines, L-dopa, monoamine oxidase inhibitors. The effects of drugs and their interactions are exacerbated in older people because of the dysautonomia that occurs with aging.

Anatomic

  • Subclavian steal syndrome.

Neurologic

  • Subarachnoid hemorrhage: unusual cause of syncope, presumably related to a sudden increase in intracranial pressure

  • Traumatic brain injury: transient reversible hypoperfusion in the brain may be caused by a sudden increase in intracranial pressure from trauma or other brain injuries that limit cerebral blood flow[13]

  • Migraine is uncommonly associated with syncope (may be vasovagal or due to orthostatic intolerance).

Toxic or metabolic

  • Drug toxicities (such as antiarrhythmic agents causing proarrhythmic effects)

  • Antihypertensive agents (causing orthostatic hypotension)

  • Hypoglycemia

  • Hypoxia

  • Hyperventilation with hypocapnia.

Psychiatric

There is no true impairment of consciousness in these disorders.[14][15]

  • Anxiety

  • Cataplexy

  • Conversion disorders can sometimes present as syncope.

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