Syncope

Definition

• Harrison's Principles of Internal Medicine 22E, p. 199
• Fuster and Hurst's The Heart, 15th Ed, p. 1250

Epidemiology

• Accounts for ~3% of all emergency department visits and 1-6% of hospital admissions
• Lifetime prevalence: ~40% of the general population; recurrence rate ~14%
• Annual cost of syncope hospitalizations in the US: $1.7 billion ($26,000/hospitalization)
• In adolescents, 15-25% experience at least one episode; ~80% of pediatric fainting is vasovagal
• Prevalence exceeds 20% in adults aged ≥75 years; 2-year mortality rate 25-30% in patients over 75

Classification and Causes

1. Neurally Mediated (Reflex) Syncope - Most Common

• Vasovagal (common faint): triggered by emotional stress, pain, sight of blood, venipuncture, warm environments, prolonged standing
• Situational: micturition syncope, defecation, cough, swallow, post-exercise, Valsalva
• Carotid sinus syncope: carotid sinus hypersensitivity (common in elderly)
• Glossopharyngeal neuralgia syncope

• Vasodepressor: predominantly sympathetic vasoconstrictor failure (hypotension)
• Cardioinhibitory: predominantly vagal bradycardia/asystole
• Mixed: both vagal and sympathetic changes

2. Orthostatic Hypotension

• Parkinson's disease / Lewy body dementia
• Pure autonomic failure
• Multiple system atrophy (Shy-Drager syndrome)

• Diabetes mellitus (most common secondary cause)
• Hereditary amyloidosis, primary amyloidosis
• Hereditary sensory and autonomic neuropathies
• Autoimmune autonomic ganglionopathy, Sjogren's syndrome
• Paraneoplastic, HIV neuropathy

• Drug-induced (antihypertensives, diuretics, alpha-blockers, tricyclics)
• Volume depletion (hemorrhage, dehydration)
• POTS (Postural Orthostatic Tachycardia Syndrome)

3. Cardiac Syncope

• Sinus node dysfunction (sick sinus syndrome)
• AV conduction abnormalities (high-degree heart block)
• Supraventricular tachycardia
• Ventricular tachycardia / fibrillation
• Inherited channelopathies: Long QT syndrome, Brugada syndrome, CPVT

• Valvular disease - especially aortic stenosis (classic triad: angina, dyspnea, syncope)
• Myocardial ischemia / acute MI
• Hypertrophic obstructive cardiomyopathy (HOCM) - exertional syncope
• Cardiac tamponade
• Atrial myxoma
• Pulmonary embolism / pulmonary hypertension

Pathophysiology

• Neurally mediated: paradoxical reflex arc - venous pooling or vigorous stimuli reduce venous return, activating mechanoreceptors, triggering efferent vagal (bradycardia) and sympathoinhibitory (vasodilation) responses
• Orthostatic: upright posture causes venous pooling in the lower extremities; impaired baroreflexes fail to maintain BP
• Cardiac: reduced cardiac output from structural obstruction or arrhythmia drops systemic BP below cerebral autoregulatory threshold
• CO = SV × HR - any cause that dramatically reduces either heart rate or stroke volume can precipitate syncope

Clinical Features

Prodrome (Presyncope)

• Lightheadedness, dizziness (not true vertigo), weakness, fatigue
• Visual disturbances (tunneling, graying of vision)
• Auditory disturbances, tinnitus
• Diaphoresis, pallor, nausea, yawning, palpitations

During the Syncopal Episode

• Loss of consciousness + loss of postural tone
• Eyes typically open, deviated upward; pupils dilated
• Brief myoclonic jerks (arrhythmic, multifocal, <30 s) - seen in up to 90% - can mimic seizure
• Urinary incontinence possible; fecal incontinence very rare

Recovery

• Rapid return to normal mentation (key distinguishing feature from seizure)
• Pallor, nausea, and fatigue may persist for hours (particularly after vasovagal)
• No significant postictal confusion

Differential Diagnosis: Syncope vs. Seizure

Evaluation

History (cornerstone)

• Circumstances: position, activity (exertion suggests cardiac/HOCM), environment
• Prodrome: its character distinguishes vasovagal from cardiac
• Palpitations before syncope: strongly suggest dysrhythmia
• Medication review (especially antihypertensives, QT-prolonging drugs)
• Family history: sudden cardiac death, arrhythmias, cardiomyopathy
• Eyewitness account; smartphone video is invaluable

Physical Examination

• Orthostatic vital signs (supine, sitting, and standing BP/HR)
• Cardiac auscultation: murmurs (AS, HOCM)
• Neurologic exam

Investigations

• 12-lead ECG (mandatory) - look for: long QT, Brugada pattern, delta wave (WPW), LBBB, AV block, ischemic changes, LVH

• Echocardiogram: if structural disease suspected
• Holter monitor / prolonged ECG monitoring: arrhythmic cause suspected
• Implantable loop recorder: high diagnostic yield for recurrent unexplained syncope
• Tilt-table test: suspected neurally mediated or orthostatic syncope (modest sensitivity/specificity)
• Carotid sinus massage: if CSH suspected (especially elderly)
• Lab work (CBC, glucose, electrolytes): targeted, not routine
• Electrophysiology study: selected high-risk cardiac patients

• Brain CT, MRI, EEG (unless focal neurologic signs present - to rule out seizure)
• Carotid Doppler (unilateral carotid stenosis does NOT cause syncope)
• Cardiac stress testing: only in highly selected patients

Risk Stratification

• Syncope during exertion
• Preceded by palpitations or chest pain
• Structural heart disease or known arrhythmia
• Abnormal ECG (new changes)
• Family history of sudden cardiac death
• No prodrome; syncope while supine
• Injury during syncope
• Age >65 with cardiac cause suspected (almost 50% have serious etiology)

Management

Neurally Mediated Syncope

• Reassurance and education - cornerstone; explain benign nature
• Avoidance of triggers: prolonged standing, dehydration, warm environments, alcohol
• Plasma volume expansion: increased fluid/salt intake; compression stockings; head-up tilt sleeping
• Physical counterpressure maneuvers: leg crossing, abdominal tensing, handgrip and arm tensing (supported by RCT) - most effective for patients with a prodrome
• Pharmacotherapy (refractory cases):
  • Midodrine (alpha-1 agonist vasoconstrictor): only agent shown effective in international multicenter RCTs
  • Fludrocortisone (mineralocorticoid; volume expansion): widely used
  • Beta-blockers: used but not proven effective in RCTs
• Pacemaker: indicated for documented cardioinhibitory syncope with prolonged asystole

Orthostatic Hypotension

• Non-pharmacologic: head-up tilt sleep, abdominal binders, compression stockings, slow positional changes, increased fluid/salt, avoid large meals and alcohol
• Pharmacologic: fludrocortisone, midodrine, droxidopa (for neurogenic OH)
• Treat underlying cause where possible

Cardiac Arrhythmic Syncope

• Pacemaker implantation: for bradyarrhythmias (sinus node dysfunction, AV block)
• ICD implantation: for ventricular tachyarrhythmias
• Catheter ablation: for SVT, some VT
• Antiarrhythmic drugs: selected cases

Structural Cardiac Syncope

• Treat the underlying lesion: aortic valve replacement for severe AS, septal reduction for HOCM, pericardiocentesis for tamponade

Special Populations

Elderly

• Syncope is often multifactorial in the elderly (interplay of age-related CV changes, multimorbidity, polypharmacy)
• Vasovagal syncope in the elderly less likely to have a prodrome
• Most common causes: neurally mediated > orthostatic hypotension > cardiac
• Carotid sinus hypersensitivity more prevalent
• 2-year mortality 25-30% in patients >75 years
• Amnesia for syncope is common - syncope may be the cause of unexplained falls
• Braunwald's Heart Disease

Children/Adolescents

• ~80% is neurocardiogenic/vasovagal
• Neurologic causes (~10%): mostly seizures
• Cardiac causes: only 2-3%, but include inherited channelopathies (long QT, Brugada, CPVT)
• Any child with a pacemaker who develops syncope should be presumed to have pacemaker malfunction until proven otherwise
• Tintinalli's Emergency Medicine

Exertional Syncope

• Always requires thorough cardiac evaluation
• Key differentials: HOCM, aortic stenosis, pulmonary hypertension, anomalous coronary artery, WPW, channelopathies
• Higher risk of sudden cardiac death

Prognosis

• Neurally mediated syncope: benign course; recurrence possible but mortality not increased
• Orthostatic syncope: depends on underlying cause; risk of falls and injury
• Cardiac syncope: significantly increased risk of sudden cardiac death if untreated
• Unknown etiology after full evaluation: ~40% of cases; prognosis generally similar to vasovagal

• Harrison's Principles of Internal Medicine, 22nd ed. (2025), Chapter 23 (Syncope) and Chapter 436 (Seizures/Syncope differentiation)
• Fuster and Hurst's The Heart, 15th ed., Chapter 39
• Braunwald's Heart Disease, 2-Vol Set, Chapter 71 (Syncope in the Elderly)
• Tintinalli's Emergency Medicine, Comprehensive Study, Chapter 130 (Pediatric Syncope)