Causes of Syncope
Overview by Major Categories
Syncope results from transient global cerebral hypoperfusion and falls into three major categories: neurally-mediated (reflex) syncope, orthostatic hypotension, and cardiac syncope—with cardiac causes carrying the highest mortality risk (18-33% annual mortality) and requiring urgent evaluation. 1
Neurally-Mediated (Reflex) Syncope
Vasovagal syncope is the most common form of syncope overall, characterized by inappropriate vasodilation and bradycardia triggered by emotional stress, fear, pain, blood phobia, or prolonged standing. 1, 2 Patients typically experience prodromal symptoms including lightheadedness, dizziness, nausea, diaphoresis, and pallor, followed by postepisode fatigue or weakness. 3, 2
Carotid sinus syncope occurs when mechanical manipulation of the carotid sinuses (such as neck turning) triggers the vasovagal reflex, more commonly affecting older adults. 1, 2 This can be assessed at bedside with carotid sinus massage in supine and/or upright positions, but should not be performed in patients with recent transient ischemic attack, stroke, or significant carotid artery stenosis. 3
Situational syncope is associated with specific triggers including:
- Cough or sneeze
- Gastrointestinal stimulation (deglutition, defecation)
- Micturition
- Post-exercise
- Post-prandial 1, 2
Orthostatic Hypotension
Classic orthostatic hypotension is defined as a sustained reduction of systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg within 3 minutes of standing. 1, 2 This accounts for 6-33% of syncope in elderly patients. 1
Primary autonomic failure syndromes include pure autonomic failure, multiple system atrophy, and Parkinson's disease with autonomic failure. 1
Drug-induced orthostatic hypotension can result from tricyclic antidepressants, phenothiazines, nitrates, antiparkinsonian medications, and antihypertensive agents. 3, 1 Fludrocortisone can cause hypertension, edema, and hypokalemic alkalosis when used to treat orthostatic hypotension. 4 Midodrine, an alpha-adrenergic agonist used for orthostatic hypotension, can cause supine hypertension and should be avoided 3-4 hours before bedtime. 5
Cardiac Syncope
Cardiac arrhythmias represent the most common cardiac cause of syncope and include:
- Sinus node dysfunction
- Atrioventricular conduction system disease
- Paroxysmal supraventricular and ventricular tachycardias
- Inherited syndromes (long QT syndrome, Brugada syndrome, Wolff-Parkinson-White syndrome) 1, 2
Structural cardiac or cardiopulmonary disease includes:
- Cardiac valvular disease (especially aortic stenosis)
- Acute myocardial infarction/ischemia
- Obstructive cardiomyopathy
- Pulmonary embolus/pulmonary hypertension
- Acute aortic dissection
- Pericardial disease/tamponade
- Atrial myxoma 1, 2
Cardiac syncope carries significantly higher mortality risk with annual mortality rates of 18-33% compared to 0-12% for non-cardiac causes. 1 The absence of a prodrome is consistent with cardiac arrhythmia. 3
Age-Related Patterns
Pediatric and young patients most commonly experience:
- Neurocardiogenic syncope
- Conversion reactions (psychiatric causes)
- Primary arrhythmic causes (long QT syndrome, Wolff-Parkinson-White syndrome) 3, 2
Middle-aged patients experience:
- Neurocardiogenic syncope (remains most frequent)
- Situational syncope (deglutition, micturition, defecation, cough)
- Orthostasis
- Panic disorders 3
Elderly patients have higher frequency of:
- Obstructions to cardiac output (aortic stenosis, pulmonary embolus)
- Arrhythmias resulting from underlying heart disease
- Carotid sinus hypersensitivity (accounts for 30% of unexplained syncope in elderly) 3, 1
Neurological Causes (Rare)
Cerebrovascular disease rarely causes syncope. Transient ischemic attacks rarely result in syncope, but patients with basilar artery or severe bilateral carotid artery disease may have syncope usually associated with focal neurological symptoms. 3
Seizure disorders should be considered when auras, premonitions, postictal confusion, and focal neurological signs are present. 3 However, tonic-clonic, seizure-like activity can be associated with both cardiac and neurological causes of syncope. 3
Critical Clinical Distinctions
High-risk features suggesting cardiac syncope include:
- Syncope in supine position or during exertion
- Palpitations preceding the event
- History of myocardial infarction with or without left ventricular dysfunction
- Repaired congenital heart disease
- Absence of prodrome
- Family history of unexpected sudden cardiac death 3, 1, 2
Medication-induced syncope should be considered with addition of new drugs, especially antiarrhythmic agents (Class IA and IC), antihypertensive agents, phenothiazines, and tricyclic drugs. 3
Common Pitfalls
Avoid unnecessary neurological testing in the absence of head trauma or evident neurological signs, as these have low diagnostic yield. 1, 6 Recognize that cardiac causes of syncope can be accompanied by upward gaze deviation, asynchronous myoclonic jerks, and brief automatisms from global cerebral hypoperfusion—these are not indications for neurological evaluation. 1
Do not overlook vascular causes including pulmonary embolism, aortic dissection, subclavian steal syndrome, and abdominal aortic aneurysm, which can result in significant morbidity and mortality. 7