Etiology of Syncope
Syncope results from transient global cerebral hypoperfusion and can be categorized into three major groups: neurally-mediated (reflex) syncope, orthostatic hypotension, and cardiac syncope—with cardiac causes carrying the highest mortality risk and requiring urgent evaluation. 1
Major Categories of Syncope
Neurally-Mediated (Reflex) Syncope
Vasovagal syncope is the most common form, characterized by inappropriate vasodilation and bradycardia triggered by emotional stress, fear, pain, blood phobia, or prolonged standing. 2 Prodromal symptoms typically include lightheadedness, dizziness, nausea, diaphoresis, and pallor. 2
Carotid sinus syncope occurs when mechanical manipulation of the carotid sinuses triggers the vasovagal reflex, more commonly affecting older adults. 1, 2
Situational syncope is associated with specific triggers: 1
- Cough or sneeze
- Gastrointestinal stimulation (swallowing, defecation, visceral pain)
- Micturition (post-micturition)
- Post-exercise
- Post-prandial
- Other triggers (brass instrument playing, weightlifting)
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. 2
Primary autonomic failure syndromes include pure autonomic failure, multiple system atrophy, and Parkinson's disease with autonomic failure. 1
Secondary autonomic failure syndromes encompass diabetic neuropathy and amyloid neuropathy. 1
Drug-induced orthostatic hypotension can result from tricyclic antidepressants, nitrates, antiparkinsonian medications, diuretics, β-blockers, calcium antagonists, ACE inhibitors, antipsychotic agents, antihistamines, dopamine agonists/antagonists, and narcotics. 1
Volume depletion from any cause can precipitate orthostatic syncope. 1
Cardiac Syncope
Cardiac arrhythmias represent the most common cardiac cause: 1, 3
- Sinus node dysfunction (including bradycardia/tachycardia syndrome)
- Atrioventricular conduction system disease
- Paroxysmal supraventricular and ventricular tachycardias
- Inherited syndromes (long QT syndrome, Brugada syndrome)
- Implanted device malfunction (pacemaker, ICD)
- Drug-induced proarrhythmias
Structural cardiac or cardiopulmonary disease: 1
- Cardiac valvular disease (especially aortic stenosis)
- Acute myocardial infarction/ischemia
- Obstructive cardiomyopathy
- Atrial myxoma
- Acute aortic dissection
- Pericardial disease/tamponade
- Pulmonary embolus/pulmonary hypertension
Critical distinction: In valvular aortic stenosis or left ventricular outflow tract obstruction, syncope results not solely from restricted cardiac output but also from inappropriate neurally mediated reflex vasodilation and/or primary cardiac arrhythmias. 1
Neurological Causes (Rare)
Neurological causes should only be pursued if suggested by history or physical examination, as syncope is an unusual manifestation of neurological processes. 1
Cerebrovascular disease can cause syncope only in the presence of severe bilateral carotid or basilar artery disease, and rarely occurs without other focal neurological signs or symptoms. 1
Seizure disorders are the most common neurological cause of episodic unresponsiveness but are not true syncope. 1
Red flags for neurological etiology: 1
- Syncope in the supine position
- Preceded by an aura
- Followed by confusion or amnesia
- Focal neurological signs (diplopia, limb weakness, sensory deficits, speech difficulties)
Disorders increasing intracranial pressure (subarachnoid hemorrhage, brain tumors) can result in true syncope but are usually obvious with headache, meningismus, and/or focal neurological findings. 1
Age-Related Patterns
Pediatric and young patients most commonly experience neurocardiogenic syncope, conversion reactions, and primary arrhythmic causes such as long QT syndrome and Wolff-Parkinson-White syndrome. 2
Middle-aged patients experience neurocardiogenic syncope, situational syncope, orthostasis, and panic disorders. 2
Elderly patients have a higher frequency of cardiac causes, including obstructions to cardiac output and arrhythmias from underlying heart disease. 2 Orthostatic hypotension causes syncope in 6% to 33% of elderly patients. 1 Carotid sinus hypersensitivity accounts for 30% of unexplained syncope in the elderly. 1 Complete amnesia is present in up to 40% of elderly patients with syncope, and classic prodromal symptoms are often absent. 1
Prognostic Implications
Cardiac syncope carries significantly higher mortality risk, with annual mortality rates of 18-33% compared to 0-12% for non-cardiac causes. 4 The presence of suspected or certain heart disease after initial evaluation is the strongest predictor of cardiac syncope with 95% sensitivity. 2
Common Pitfalls
Avoid unnecessary neurological testing (EEG, head CT/MRI) in the absence of head trauma or evident neurological signs, as these have low diagnostic yield. 5, 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
In elderly patients, multiple origins of syncope frequently coexist, requiring particular emphasis on polypharmacy, orthostatic intolerance, autonomic dysfunction, and carotid sinus hypersensitivity. 1
Postprandial hypotension in the elderly is frequently confused with transient ischemic attacks or seizures. 1