What are the potential causes of syncope in a patient?

Etiology of Syncope

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

Major Categories and Their Mechanisms

Neurally-Mediated (Reflex) Syncope

This is the most common form of syncope overall, characterized by inappropriate vasodilation and bradycardia leading to systemic hypotension and cerebral hypoperfusion. 1, 2

Vasovagal syncope is triggered by:

• Emotional stress, fear, or pain 1
• Blood phobia 1
• Prolonged standing 1
• Typically preceded by prodromal symptoms: lightheadedness, dizziness, nausea, diaphoresis, and pallor 2

Carotid sinus syncope occurs when mechanical manipulation of the carotid sinuses triggers the vasovagal reflex, predominantly affecting older adults. 1, 2

Situational syncope is associated with specific triggers:

• Cough or sneeze 1
• Gastrointestinal stimulation 1
• Micturition 1
• Post-exercise 1
• Post-prandial 1

Orthostatic Hypotension

Defined as sustained reduction of systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg within 3 minutes of standing. 1, 2

Primary autonomic failure syndromes:

• Pure autonomic failure 1
• Multiple system atrophy 1
• Parkinson's disease with autonomic failure 1

Secondary causes:

• Drug-induced (tricyclic antidepressants, nitrates, antiparkinsonian medications) 1
• Volume depletion 2
• Alcohol-induced 2

Variants to recognize:

• Initial (immediate) orthostatic hypotension: transient BP decrease within 15 seconds after standing 2
• Delayed orthostatic hypotension: sustained reduction taking >3 minutes of upright posture 2

Cardiac Syncope

This category carries the highest mortality risk and demands urgent evaluation. 1

Arrhythmic causes (most common cardiac etiology):

• Sinus node dysfunction 1, 3
• Atrioventricular conduction system disease 1, 3
• Paroxysmal supraventricular and ventricular tachycardias 2, 3
• Inherited syndromes: long QT syndrome, Brugada syndrome 4
• Both bradyarrhythmias and tachyarrhythmias can cause sudden decrease in cardiac output 3

Structural cardiac/cardiopulmonary disease:

• Cardiac valvular disease 1
• Obstructive cardiomyopathy 1
• Acute myocardial infarction/ischemia 2
• Pulmonary embolus/pulmonary hypertension 2
• Atrial myxoma 4
• Acute aortic dissection 4
• Pericardial disease/tamponade 4

Age-Related Patterns

Pediatric and young patients most commonly experience:

• Neurocardiogenic syncope 2
• Primary arrhythmic causes (long QT syndrome, Wolff-Parkinson-White syndrome) 2
• Conversion reactions 2

Middle-aged patients experience:

• Neurocardiogenic syncope 2
• Situational syncope 2
• Orthostasis 2
• Panic disorders 2

Elderly patients have higher frequency of:

• Cardiac causes (obstructions to cardiac output, arrhythmias from underlying heart disease) 1, 2
• Orthostatic hypotension (6-33% of cases) 1
• Carotid sinus hypersensitivity (30% of unexplained syncope) 1

Prognostic Implications

Cardiac syncope carries significantly higher mortality:

• Annual mortality: 18-33% 1
• 24% one-year mortality rate 4

Non-cardiac causes:

• Annual mortality: 0-12% 1, 5
• Generally benign course with main risks being accidents and injury 6

Key predictor: The presence of suspected or certain heart disease after initial evaluation is the strongest predictor of cardiac syncope (95% sensitivity), while absence of heart disease excludes cardiac syncope in 97% of patients. 2

Neurological Causes

Neurological causes such as cerebrovascular disease and seizure disorders are rare and should only be pursued if suggested by history or physical examination. 1

Critical Pitfalls to Avoid

Do not pursue unnecessary neurological testing in the absence of head trauma or evident neurological signs—these have low diagnostic yield. 1, 7

Recognize that cardiac causes can mimic seizures: Cardiac syncope from global cerebral hypoperfusion can be accompanied by upward gaze deviation, asynchronous myoclonic jerks, and brief automatisms—these are not indications for neurological evaluation. 1

Avoid wasteful testing: Short-term ambulatory ECG recordings (Holter monitors) and neurologic tests (EEG, head MRI/CT) are rarely positive without specific clinical indications. 7

Multiple mechanisms may coexist: Patients with structural heart disease may have syncope from multiple contributing mechanisms. 4