What is the differential diagnosis and management approach for a patient presenting with syncope?

Syncope Differential Diagnosis and Management

Immediate Risk Stratification Framework

The differential diagnosis for syncope must be organized by mortality risk, with cardiac causes (18-33% one-year mortality) requiring immediate exclusion before considering benign etiologies like vasovagal syncope (0-12% mortality). 1, 2, 3

Three Mandatory Initial Assessments

Every patient presenting with syncope requires these three components, which establish the diagnosis in 23-50% of cases 1, 4:

• Detailed history focusing on position during event (supine suggests cardiac; standing suggests reflex/orthostatic), activity (exertional syncope mandates cardiac evaluation), triggers (warm crowded places/emotional stress suggest vasovagal; urination/defecation suggest situational), prodromal symptoms (nausea/diaphoresis favor vasovagal; palpitations suggest arrhythmia), and witness account of duration and recovery 5, 1, 4

• Physical examination including orthostatic vital signs in lying, sitting, and standing positions (orthostatic hypotension defined as systolic BP drop ≥20 mmHg or to <90 mmHg), cardiovascular examination for murmurs/gallops/rubs suggesting structural disease, and carotid sinus massage in patients >40 years (positive if asystole >3 seconds or systolic BP drop >50 mmHg) 5, 1

• 12-lead ECG looking for QT prolongation (Long QT syndrome), conduction abnormalities (bundle branch blocks, bifascicular block, Mobitz II or III AV block), pre-excitation (Wolff-Parkinson-White), Brugada pattern (ST-elevation in V1-V3 with RBBB), signs of ischemia or prior MI, and ventricular hypertrophy 5, 1

Differential Diagnosis by Mechanism

High-Risk Cardiac Causes (Require Immediate Hospital Admission)

Arrhythmic syncope 5, 6:

• Bradyarrhythmias: sinus bradycardia <50 bpm, sinoatrial blocks, Mobitz II or III AV block, asymptomatic sinus pause >3 seconds 5
• Tachyarrhythmias: ventricular tachycardia, supraventricular tachycardia, inherited channelopathies (Long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT) 5, 6

Structural heart disease 5, 6:

• Severe aortic stenosis, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy 5, 6
• Severe ostial left main stenosis, acute myocardial infarction 6
• Pulmonary embolism, cardiac tamponade, atrial myxoma 6

Reflex-Mediated (Neurally-Mediated) Syncope

Vasovagal syncope (most common overall cause) 5, 6, 3:

• Triggered by emotional stress, pain, fear, unpleasant sight/sound/smell, prolonged standing, warm crowded environments 5, 6
• Characterized by prodromal symptoms (nausea, vomiting, diaphoresis, blurred vision, dizziness) 5, 1
• Long history of recurrent syncope, absence of cardiac disease 5

Situational syncope 5, 6:

• Micturition, defecation, cough, swallowing, post-prandial, post-exercise 5, 6

Carotid sinus hypersensitivity 5, 6:

• Triggered by head rotation, pressure on carotid sinus (tumors, shaving, tight collars) 5
• More common in elderly patients 6

Orthostatic Hypotension

Medication-induced (most common cause) 6:

• Antihypertensives, diuretics, vasodilators, phenothiazines, tricyclic antidepressants, QT-prolonging agents 5, 6
• Temporal relationship with medication start or dose changes 5

Volume depletion 6:

• Hemorrhage, dehydration, anemia 6

Autonomic failure 5, 6:

• Primary: Parkinson disease, multiple system atrophy 5, 6
• Secondary: diabetic neuropathy, amyloidosis 6

Cerebrovascular (Rare)

• Subclavian steal syndrome (syncope with arm exercise, BP/pulse differences between arms) 5

High-Risk Features Requiring Hospital Admission

Admit immediately if any of the following are present 1, 4:

• Age >60-65 years 5, 1
• Known structural heart disease, heart failure, or coronary artery disease (95% sensitivity for cardiac syncope) 5, 1, 4
• Syncope during exertion or in supine position 5, 1
• Brief or absent prodrome 1
• Palpitations before syncope 1, 4
• Family history of sudden cardiac death or inherited arrhythmia syndromes 1
• Abnormal ECG findings (any abnormality is independent predictor of cardiac syncope) 5, 1
• Abnormal cardiac examination (murmurs, gallops, irregular rhythm) 1, 4
• Systolic BP <90 mmHg 1

Low-Risk Features Appropriate for Outpatient Management

Consider outpatient evaluation if all of the following 1, 6:

• Younger age (<45 years), no known cardiac disease 1, 6
• Normal ECG and normal cardiac examination 1, 6
• Syncope only when standing 1, 6
• Clear prodromal symptoms (nausea, diaphoresis, dizziness) 1, 6
• Specific situational triggers (micturition, defecation, cough) 1, 6
• Single or rare episodes in setting suggesting vasovagal mechanism 5

Directed Testing Algorithm

For Suspected Cardiac Syncope (High-Risk Patients)

Transthoracic echocardiography 5, 1, 4:

• Mandatory when structural heart disease suspected based on abnormal cardiac examination, abnormal ECG, or syncope during exertion 1, 4
• Evaluates for valvular disease, cardiomyopathy, ventricular function 1

Continuous cardiac telemetry monitoring 1, 4:

• Initiate immediately for patients with abnormal ECG, palpitations before syncope, or high-risk features 1
• Choice of device based on symptom frequency: Holter monitor for daily symptoms, external loop recorder for weekly symptoms, implantable loop recorder for monthly symptoms 5, 1

Exercise stress testing 5, 1, 4:

• Mandatory for syncope during or immediately after exertion 1, 4
• Screens for hypertrophic cardiomyopathy, anomalous coronary arteries, exercise-induced arrhythmias 1, 4

Electrophysiological study 5:

• For patients with structural heart disease and unexplained syncope after noninvasive testing 5
• Identifies potential cause in up to two-thirds of high-risk patients 2

For Suspected Reflex-Mediated Syncope (Low-Risk Patients)

Tilt-table testing 5, 1:

• For young patients without heart disease with recurrent unexplained syncope when reflex mechanism suspected 5, 1
• Can confirm vasovagal syncope when history suggestive but not diagnostic 1
• Caution: High false-positive and false-negative rates in adolescents 4

Carotid sinus massage 5:

• First evaluation step in older patients (>40 years) with recurrent syncope 5
• Contraindication: Do not perform in patients with history of TIA or stroke 4

For Suspected Orthostatic Hypotension

Orthostatic vital signs testing 1, 4:

• Measure BP and heart rate supine, then at 1 and 3 minutes after standing 4
• Positive if systolic BP drop ≥20 mmHg or to <90 mmHg 1, 4

Medication review 5, 1:

• Identify and reduce/withdraw hypotensive medications, especially in elderly patients 4
• Consider reducing diuretic dose first if orthostatic hypotension confirmed 4

Tests NOT Routinely Recommended

Avoid these tests without specific clinical indication 1, 6:

• Brain imaging (CT/MRI): diagnostic yield only 0.24-1%, not recommended without focal neurological findings or head injury 1, 6
• EEG: diagnostic yield only 0.7%, not recommended without features suggesting seizure 1, 6
• Carotid ultrasound: diagnostic yield only 0.5%, not recommended routinely 1, 6
• Comprehensive laboratory panels: not useful in routine evaluation; order targeted tests only when clinically indicated (CBC for suspected anemia, electrolytes for dehydration, BNP/troponin for suspected cardiac cause) 1, 4

Management of Unexplained Syncope

If no diagnosis after initial evaluation 5, 1:

• Reappraise entire workup for subtle findings or new historical information 5, 1
• Obtain additional history details and re-examine patient 1
• Consider specialty consultation if unexplored clues to cardiac or neurological disease 1
• Consider implantable loop recorder for recurrent episodes with high clinical suspicion for arrhythmic cause 5, 1, 4
• For single or rare episodes in young patients without cardiac disease, likely neurally-mediated and tests for confirmation usually unnecessary 5

Critical Pitfalls to Avoid

• Do not dismiss cardiac causes based on age alone—inherited arrhythmia syndromes can present in adolescence 4
• Do not overlook medication effects as contributors to syncope, especially polypharmacy in elderly 5, 1, 4
• Do not miss exertional syncope as high-risk—this mandates immediate cardiac evaluation 1, 4
• Do not use Holter monitoring for infrequent events—select monitoring device based on symptom frequency 5, 6
• Do not order brain imaging without focal neurological findings—extremely low yield 1, 6
• Do not fail to distinguish true syncope from seizure—duration >1 minute and lateral tongue biting suggest epilepsy 4
• Do not perform carotid sinus massage in patients with history of TIA or stroke 4