What is the differential diagnosis and inpatient workup for syncope?

Differential Diagnosis and Inpatient Workup for Syncope

Differential Diagnosis by Mechanism

The differential diagnosis for syncope should be organized into four primary categories: reflex-mediated (neurally-mediated), cardiac, orthostatic hypotension, and cerebrovascular causes, with cardiac syncope representing the highest-risk category requiring immediate exclusion. 1, 2, 3

Cardiac Syncope (Highest Risk - 20-30% one-year mortality)

Arrhythmic causes:

• Bradyarrhythmias: Sinus bradycardia (<50 bpm), sinoatrial block, sinus pause ≥3 seconds, Mobitz I or II second-degree AV block, complete heart block 1
• Tachyarrhythmias: Ventricular tachycardia, supraventricular tachycardia, atrial fibrillation with rapid ventricular response 4
• Inherited arrhythmia syndromes: Long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, Wolff-Parkinson-White syndrome 5

Structural heart disease:

• Severe aortic stenosis, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, anomalous coronary artery origin, acute myocardial infarction, cardiac tamponade, pulmonary embolism 1, 5

Reflex-Mediated (Neurally-Mediated) Syncope

• Vasovagal syncope: Most common type overall, triggered by prolonged standing, crowded/hot places, unpleasant sights/sounds/smells, pain, emotional stress 1
• Situational syncope: Cough syncope, micturition syncope, defecation syncope, post-exercise syncope, post-prandial syncope 1, 5
• Carotid sinus hypersensitivity: Triggered by head rotation, pressure on carotid sinus, tight collars, shaving 1

Orthostatic Hypotension

• Medication-induced: Antihypertensives, diuretics, vasodilators, antidepressants, QT-prolonging agents 1, 5
• Volume depletion: Hemorrhage, dehydration, anemia 2
• Autonomic failure: Primary autonomic failure, Parkinsonism, diabetic neuropathy 1

Cerebrovascular (Rare - <1% of cases)

• Subclavian steal syndrome (syncope with arm exercise and blood pressure differences between arms) 1

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Initial Inpatient Evaluation - The Essential Triad

Every patient admitted for syncope must receive three mandatory initial assessments: detailed history, physical examination with orthostatic vital signs, and 12-lead ECG - this triad establishes the diagnosis in 23-50% of cases. 6, 5

Detailed History - Critical Elements to Document

Circumstances before the attack:

• Position during event (supine suggests cardiac; standing suggests reflex/orthostatic) 1, 2
• Activity (exertional syncope is high-risk and suggests cardiac etiology) 1
• Precipitating factors (warm crowded places, prolonged standing, emotional triggers) 1
• Medications (antihypertensives, diuretics, QT-prolonging agents) 1

Prodromal symptoms:

• Presence of warning symptoms (nausea, diaphoresis, blurred vision suggests vasovagal) 1, 2
• Palpitations before syncope (suggests arrhythmic cause) 1
• Brief or absent prodrome (high-risk feature suggesting cardiac cause) 2, 5

Eyewitness account:

• Duration of unconsciousness (>1 minute suggests seizure) 5
• Skin color (pallor suggests vasovagal; cyanosis suggests cardiac) 1
• Movements (tonic-clonic suggests seizure; brief myoclonic jerks can occur in syncope) 1
• Tongue biting (lateral tongue biting strongly suggests epilepsy) 5

Recovery phase:

• Rapid, complete recovery without confusion confirms syncope 2
• Prolonged confusion suggests seizure or metabolic cause 1

Background information:

• Family history of sudden cardiac death or inherited arrhythmia syndromes 1, 5
• Known structural heart disease or heart failure (95% sensitivity for cardiac syncope) 2, 5
• Previous cardiac disease, neurological history (Parkinsonism, epilepsy) 1

Physical Examination - Key Components

Cardiovascular examination:

• Heart rate and rhythm (bradycardia <50 bpm, irregular rhythm) 1
• Murmurs (severe aortic stenosis, hypertrophic cardiomyopathy) 1
• Gallops or rubs (heart failure, pericarditis) 2
• Blood pressure (systolic BP <90 mmHg is high-risk feature) 1, 2

Orthostatic vital signs (mandatory):

• Measure blood pressure and heart rate supine, then at 1 and 3 minutes after standing 6, 5
• Orthostatic hypotension defined as systolic BP drop ≥20 mmHg or to <90 mmHg 6, 5

Carotid sinus massage (in patients >40 years without history of TIA/stroke):

• Positive test: asystole >3 seconds or systolic BP drop >50 mmHg 1, 5
• Do not perform if history of TIA or carotid stenosis 5

Neurological examination:

• Focal neurological signs suggest neurological cause requiring brain imaging 2, 6

12-Lead ECG - Critical Findings

ECG abnormalities suggesting arrhythmic syncope requiring urgent evaluation:

• Conduction abnormalities: Bifascicular block, QRS duration ≥0.12 seconds, Mobitz I second-degree AV block 1
• Bradycardia: Sinus bradycardia <50 bpm, sinoatrial block, sinus pause ≥3 seconds 1
• QT prolongation: Suggests Long QT syndrome 1
• Brugada pattern: Right bundle branch block with ST-elevation in V1-V3 1
• Pre-excitation: Delta waves suggesting Wolff-Parkinson-White syndrome 1
• Arrhythmogenic right ventricular cardiomyopathy: Negative T waves in right precordial leads, epsilon waves 1
• Q waves: Suggesting prior myocardial infarction 1

Any abnormality on baseline ECG is an independent predictor of cardiac syncope and increased mortality, requiring cardiac evaluation. 1

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Risk Stratification and Admission Criteria

High-risk features requiring hospital admission and cardiac evaluation:

• Age >60 years 2, 5
• Known structural heart disease or heart failure 1, 2, 5
• Abnormal ECG (any of the findings listed above) 1, 2
• Syncope during exertion or while supine 1, 2
• Brief or absent prodrome 2, 5
• Palpitations associated with syncope 1
• Family history of sudden cardiac death or inherited cardiac conditions 1, 2
• Systolic blood pressure <90 mmHg 1, 2
• Abnormal cardiac examination (murmur, irregular rhythm, gallop) 2, 5

Low-risk features suggesting outpatient management:

• Age <45 years 5
• No known cardiac disease 1, 2
• Normal ECG 1
• Syncope only when standing 1, 2
• Clear prodromal symptoms (nausea, diaphoresis, blurred vision) 1, 2
• Specific situational triggers (prolonged standing, warm crowded places) 1

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Targeted Inpatient Diagnostic Testing

The choice of additional testing must be guided by the initial evaluation findings - avoid comprehensive testing without specific clinical indication. 2, 6

Cardiac Evaluation (for high-risk patients or suspected cardiac syncope)

Continuous cardiac telemetry monitoring:

• Mandatory for all admitted patients with syncope and abnormal ECG or suspected arrhythmic cause 5
• Monitor for bradyarrhythmias, tachyarrhythmias, conduction abnormalities 4

Transthoracic echocardiography:

• Indicated when structural heart disease is suspected based on abnormal cardiac examination, abnormal ECG, syncope during exertion, or family history of sudden cardiac death 2, 6, 5
• Assess for valvular disease (aortic stenosis), cardiomyopathy (hypertrophic, arrhythmogenic right ventricular), left ventricular function 1, 6

Exercise stress testing:

• Mandatory if syncope occurred during or immediately after physical exertion 2, 6, 5
• Screens for hypertrophic cardiomyopathy, anomalous coronary arteries, exercise-induced arrhythmias 5

Prolonged ECG monitoring (Holter, external loop recorder, implantable loop recorder):

• Selection based on frequency and nature of syncope events 2, 6
• Holter monitor (24-48 hours) for frequent symptoms 5
• External loop recorder for symptoms occurring every few weeks 5
• Implantable loop recorder for infrequent symptoms or recurrent unexplained syncope after full evaluation 1, 6

Electrophysiological study:

• Indicated in patients with structural heart disease when non-invasive testing is non-diagnostic 1, 4
• Identifies potential arrhythmic cause in up to two-thirds of patients with structural heart disease 4

Laboratory Testing (Targeted, Not Routine)

Basic laboratory tests only indicated if specific clinical suspicion:

• Complete blood count/hematocrit: If syncope may be due to blood loss or anemia (hematocrit <30% is risk factor) 2
• Electrolytes, BUN, creatinine: If dehydration or renal dysfunction suspected 2, 6
• Glucose: If metabolic cause suspected 2, 6
• Cardiac biomarkers (troponin, BNP): If cardiac cause suspected, though usefulness is uncertain 2

Routine comprehensive laboratory testing is not useful and should be avoided. 2, 6

Neurological Testing (Rarely Indicated)

Brain imaging (CT/MRI) is NOT recommended routinely:

• Diagnostic yield only 0.24% for MRI and 1% for CT 2
• Only indicated if focal neurological findings or head injury present 2, 6

EEG is NOT recommended routinely:

• Diagnostic yield only 0.7% 2
• Only indicated if seizure suspected based on prolonged unconsciousness, lateral tongue biting, or post-ictal confusion 5

Carotid artery imaging is NOT recommended routinely:

• Diagnostic yield only 0.5% 2
• Only indicated if focal neurological findings suggest cerebrovascular cause 2

Testing for Reflex-Mediated Syncope

Tilt-table testing:

• Indicated for recurrent unexplained syncope in young patients without heart disease when reflex mechanism suspected 2, 6, 5
• Can confirm vasovagal syncope when history is suggestive but not diagnostic 2
• Should not be used as first-line test due to high false-positive and false-negative rates 5

Carotid sinus massage:

• Indicated in older patients (>40 years) with recurrent syncope 1, 2
• Contraindicated if history of TIA, stroke, or known carotid stenosis 5

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Management of Unexplained Syncope After Initial Workup

If no diagnosis is established after initial evaluation and targeted testing, reappraisal is mandatory:

• Obtain additional history details from patient and witnesses 1, 2
• Re-examine the patient for subtle findings 1, 2
• Review all test results for overlooked abnormalities 1, 2
• Consider specialty consultation (cardiology, neurology, electrophysiology) if unexplored clues to cardiac or neurological disease are present 2, 6
• Consider implantable loop recorder for recurrent unexplained syncope with injury or high clinical suspicion for arrhythmic cause 1, 6

The majority of patients with unexplained syncope after initial evaluation likely have neurally-mediated syncope, and tests for confirmation (tilt-table testing) are usually not necessary for single or rare episodes. 1

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Critical Pitfalls to Avoid

• Do not dismiss cardiac causes based on age alone - inherited arrhythmia syndromes can present in adolescence 5
• Do not order comprehensive laboratory panels without specific clinical indication - this is low-yield and not recommended 2, 6
• Do not order brain imaging (CT/MRI) or EEG routinely - only indicated with focal neurological findings 2, 6
• Do not overlook medication effects - antihypertensives, diuretics, and QT-prolonging drugs are common contributors 1, 2
• Do not perform carotid sinus massage in patients with history of TIA or carotid stenosis 5
• Do not assume vasovagal syncope based on situational trigger alone in elderly patients with cardiac comorbidities - age and comorbidities demand thorough cardiac evaluation 5
• Do not fail to distinguish true syncope from seizure, stroke, or metabolic causes - verify rapid, complete recovery without post-event confusion 1, 6