Syncope¶

Chapter 23 | Part 2: Cardinal Manifestations and Presentation of Diseases | Section 3: Nervous System Dysfunction

KEY CLINICAL POINTS¶

Syncope is transient, self-limited loss of consciousness due to acute global impairment of cerebral blood flow with rapid onset, brief duration, and spontaneous complete recovery
Three major categories: neurally mediated (reflex/vasovagal) syncope, orthostatic hypotension, and cardiac syncope - each with distinct pathophysiology and prognosis
Cardiac syncope carries increased risk of sudden cardiac death and mortality; neurally mediated syncope in young patients has excellent prognosis
Cessation of cerebral blood flow for 6-8 seconds or fall in systolic BP to ~50 mmHg results in loss of consciousness
Initial evaluation includes detailed history, eyewitness accounts, orthostatic vital signs, ECG, and risk stratification for hospitalization

1. DEFINITION & OVERVIEW¶

Syncope is a transient, self-limited loss of consciousness due to acute global impairment of cerebral blood flow. The onset is rapid, duration brief, and recovery spontaneous and complete. Syncope represents a failure of cerebral blood flow autoregulatory mechanisms and is a form of transient loss of consciousness (TLOC) that is a consequence of global cerebral hypoperfusion.

1.1 Key Characteristics¶

Rapid onset of unconsciousness
Brief duration
Spontaneous and complete recovery
Due to acute global impairment of cerebral blood flow
Syncopal prodrome (presyncope) is common, although loss of consciousness may occur without warning

1.2 Presyncopal Symptoms¶

Typical presyncopal symptoms include: - Lightheadedness or faintness - Dizziness - Weakness - Fatigue - Visual disturbances - Auditory disturbances

1.3 Conditions to Differentiate from Syncope¶

Other causes of transient loss of consciousness that must be distinguished from syncope include: - Seizures (generalized and partial) - Vertebrobasilar ischemia - Hypoxemia - Hypoglycemia - Cataplexy - Psychogenic episodes

2. EPIDEMIOLOGY¶

Syncope is a common presenting problem with significant healthcare utilization and costs. Understanding the epidemiologic patterns helps guide diagnostic evaluation and prognostication.

2.1 Incidence and Prevalence¶

Accounts for ~3% of all emergency department visits
Accounts for 1% of all hospital admissions
Annual cost for syncope-related hospitalization in the United States is ~$2.4 billion
Lifetime cumulative incidence of up to 40% in the general population

2.2 Age Distribution¶

Bimodal age distribution: - Peak in young: ages 10-30 years with median peak around 15 years - Neurally mediated syncope is the etiology in the vast majority of these cases - Peak in elderly: sharp rise in incidence after 70 years of age

2.3 Demographics by Etiology¶

Neurally mediated syncope: most common cause in population-based studies; incidence higher in women than men; often family history in first-degree relatives
Cardiovascular disease (structural or arrhythmias): next most common, particularly in ED settings and older patients
Orthostatic hypotension: increases in prevalence with age due to reduced baroreflex responsiveness, decreased cardiac compliance, and attenuation of vestibulosympathetic reflex
In elderly: orthostatic hypotension more common in institutionalized than community-dwelling individuals

2.4 Prognosis by Etiology¶

Noncardiac and unexplained syncope in younger individuals: excellent prognosis; life expectancy unaffected
Cardiac syncope (structural heart disease or primary arrhythmic disorder): increased risk of sudden cardiac death and mortality from other causes
Orthostatic hypotension: increased mortality rate related to age and associated comorbid conditions
Hospitalization likelihood and mortality risk are higher in older adults

3. ETIOLOGY & PATHOPHYSIOLOGY¶

The pathophysiology of syncope involves failure of mechanisms that maintain adequate cerebral blood flow. The upright posture imposes unique physiologic stress, and most syncopal episodes occur from a standing position.

3.1 Physiologic Response to Standing¶

Standing results in: - Pooling of 500-1000 mL of blood in lower extremities, buttocks, and splanchnic circulation - Decreased venous return to heart and reduced ventricular filling - Diminished cardiac output and blood pressure Compensatory reflex response: - Initiated by baroreceptors in carotid sinus and aortic arch - Increased sympathetic outflow - Decreased vagal nerve activity - Results in increased peripheral resistance, venous return, cardiac output - Limits fall in blood pressure If this response fails (chronically in orthostatic hypotension, transiently in neurally mediated syncope), hypotension and cerebral hypoperfusion occur.

3.2 Cerebral Blood Flow Autoregulation¶

Myogenic factors, local metabolites, and autonomic neurovascular control are responsible for autoregulation
Latency of autoregulatory response: 5-10 seconds
Normal cerebral blood flow: 50-60 mL/min per 100 g brain tissue
Remains relatively constant over perfusion pressures 50-150 mmHg
Cessation of blood flow for 6-8 seconds → loss of consciousness
Blood flow decrease to 25 mL/min per 100 g brain tissue → impairment of consciousness
Fall in systemic systolic BP to ~50 mmHg or lower → usually results in syncope

3.3 Determinants of Syncope¶

Syncope results from decrease in cardiac output and/or systemic vascular resistance (the determinants of blood pressure). Causes of impaired cardiac output: - Decreased effective circulating blood volume - Increased thoracic pressure - Massive pulmonary embolus - Cardiac bradyarrhythmias and tachyarrhythmias - Valvular heart disease - Myocardial dysfunction Causes of decreased systemic vascular resistance: - Central and peripheral autonomic nervous system diseases - Sympatholytic medications - Transient autonomic changes during neurally mediated syncope Increased cerebral vascular resistance (most frequently due to hypocarbia from hyperventilation) may also contribute.

3.4 EEG Patterns During Syncope¶

Two patterns of electroencephalographic changes occur: 1. "Slow-flat-slow" pattern: - Normal background activity replaced with high-amplitude slow delta waves - Followed by sudden flattening of EEG (cessation/attenuation of cortical activity) - Followed by return of slow waves, then normal activity - EEG flattening is marker of more severe cerebral hypoperfusion 2. "Slow pattern": - Characterized by increasing and decreasing slow wave activity only Important: Despite myoclonic movements during some syncopal events, EEG seizure discharges are NOT detected.

4. CLASSIFICATION & CAUSES¶

Syncope can be divided into three general categories based on underlying mechanism: neurally mediated syncope, orthostatic hypotension, and cardiac syncope.

Causes of Syncope¶

Category	Subcategory	Specific Causes
A. Neurally Mediated Syncope	Vasovagal syncope	Fear, pain, anxiety, intense emotion, sight of blood, unpleasant sights/odors, orthostatic stress
	Situational - Pulmonary	Cough syncope, wind instrument player's syncope, weightlifter's syncope, 'mess trick', 'fainting lark', sneeze syncope, airway instrumentation
	Situational - Urogenital	Postmicturition syncope, urogenital tract instrumentation, prostatic massage
	Situational - Gastrointestinal	Swallow syncope, glossopharyngeal neuralgia, esophageal stimulation, GI tract instrumentation, rectal examination, defecation syncope
	Situational - Cardiac	Bezold-Jarisch reflex, cardiac outflow obstruction
	Carotid sinus	Carotid sinus sensitivity, carotid sinus massage
	Ocular	Ocular pressure, examination, surgery
B. Orthostatic Hypotension	Primary autonomic failure (Synucleinopathies)	Parkinson's disease, Lewy body dementia, Pure autonomic failure, Multiple system atrophy (Shy-Drager syndrome)
	Secondary autonomic failure	Diabetes, Hereditary amyloidosis (FAP), Primary amyloidosis (AL), HSAN (especially type III), Autoimmune autonomic ganglionopathy, Sjögren's syndrome, Paraneoplastic neuropathy, HIV neuropathy
	Other causes	Postprandial hypotension, Iatrogenic (drug-induced), Volume depletion
C. Cardiac Syncope	Arrhythmias	Sinus node dysfunction, AV dysfunction, SVT, VT, Inherited channelopathies

Category	Subcategory	Specific Causes
	Structural disease	Valvular disease, Myocardial ischemia, Cardiomyopathies, Atrial myxoma, Pericardial effusions/tamponade

4.1 Neurally Mediated Syncope¶

Neurally mediated (reflex; vasovagal) syncope is the final pathway of a complex central and peripheral nervous system reflex arc. Characterized by: - Transient change in autonomic efferent activity - Increased parasympathetic outflow plus sympathoinhibition - Results in bradycardia, vasodilation, and/or reduced vasoconstrictor tone (vasodepressor response) - Reduced cardiac output - Fall in systemic blood pressure reducing cerebral blood flow below autoregulatory limits Key distinction: Requires a functioning autonomic nervous system (in contrast to syncope from autonomic failure).

4.2 Classification by Efferent Pathway¶

Vasodepressor syncope: predominantly due to efferent sympathetic vasoconstrictor failure
Cardioinhibitory syncope: predominantly associated with bradycardia or asystole due to increased vagal outflow
Mixed response syncope: both vagal and sympathetic reflex changes present

4.3 Orthostatic Hypotension¶

Defined as reduction in systolic BP ≥ 20 mmHg OR diastolic BP ≥ 10 mmHg after 3 minutes of standing or head-up tilt. Variants: - Delayed orthostatic hypotension: occurs beyond 3 minutes of standing; may reflect mild or early sympathetic adrenergic dysfunction - Initial orthostatic hypotension: occurs within 15 seconds of standing with full resolution within 45 seconds; reflects transient mismatch between cardiac output and peripheral vascular resistance (does NOT represent autonomic failure)

4.4 Cardiac Syncope¶

Caused by arrhythmias and structural heart disease. These may occur in combination because structural disease renders the heart more vulnerable to abnormal electrical activity. Arrhythmias: - Bradyarrhythmias: severe sinus node dysfunction (sinus arrest, sinoatrial block), AV block (Mobitz type II, high-grade, complete) - Tachycardia-bradycardia syndrome: sinus node dysfunction with atrial tachyarrhythmia; prolonged pause after tachycardia termination - Ventricular tachyarrhythmias: likelihood depends on rate (<200 bpm less likely to cause syncope) and ventricular function - Inherited channelopathies: long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia Structural disease: - Valvular disease (especially aortic stenosis) - Myocardial ischemia - Hypertrophic and other cardiomyopathies - Cardiac masses (atrial myxoma) - Pericardial effusions and tamponade

5. CLINICAL FEATURES¶

The clinical features of syncope vary based on the underlying etiology and can help guide diagnosis and management.

5.1 Features of Neurally Mediated Syncope¶

Premonitory symptoms of autonomic activation: - Diaphoresis - Pallor - Palpitations - Nausea - Hyperventilation - Yawning During syncopal event: - Proximal and distal myoclonus (typically arrhythmic and multifocal) - Eyes typically remain open and usually deviate upward - Pupils usually dilated - Roving eye movements may occur - Grunting, moaning, snorting, stertorous breathing may be present - Urinary incontinence may occur - Fecal incontinence is very rare - Postictal confusion is rare - Visual and auditory hallucinations, near-death and out-of-body experiences sometimes reported

5.2 Predisposing Factors and Triggers¶

Well-established predisposing factors: - Motionless upright posture - Warm ambient temperature - Intravascular volume depletion - Alcohol ingestion - Hypoxemia - Anemia - Pain - Sight of blood - Venipuncture - Intense emotion Genetic basis: Increased incidence of syncope in first-degree relatives of fainters; some candidate genes identified with sex-specific associations (not reproduced in other cohorts). Environmental, social, and cultural factors likely play a large role.

5.3 Features of Orthostatic Hypotension¶

Characteristic symptoms: - Lightheadedness, dizziness, presyncope occurring with postural change Nonspecific symptoms (may be only manifestation): - Generalized weakness - Fatigue - Cognitive slowing - Leg buckling - Headache - Visual blurring (retinal or occipital lobe ischemia) - 'Coat-hanger headache': neck pain in suboccipital, posterior cervical, and shoulder region (due to neck muscle ischemia) - Orthostatic dyspnea (ventilation-perfusion mismatch) - Angina (impaired myocardial perfusion) Exacerbating factors: - Exertion - Prolonged standing - Increased ambient temperature - Meals Syncope characteristics: Usually preceded by warning symptoms, but may occur suddenly. Some patients have profound BP decreases without symptoms but at risk for falls.

5.4 Supine Hypertension¶

Common in patients with orthostatic hypotension due to autonomic failure (>50% in some series)
Orthostatic hypotension may present after initiation of hypertension therapy
Supine hypertension may follow treatment of orthostatic hypotension
May be explained by baroreflex dysfunction in presence of residual sympathetic outflow, particularly in central autonomic degeneration

5.5 Features of Cardiac Syncope¶

Bradyarrhythmias: - Syncope due to bradycardia or asystole = Stokes-Adams attack - May be associated with tachycardia-bradycardia syndrome Ventricular tachyarrhythmias: - Likelihood of syncope depends on rate (<200 bpm less likely) and ventricular function (poor function → more likely) - Compromised hemodynamics from: ineffective ventricular contraction, reduced diastolic filling, loss of AV synchrony, concurrent myocardial ischemia

6. DIFFERENTIAL DIAGNOSIS¶

Several disorders with real or apparent transient loss of consciousness may create diagnostic confusion with syncope.

6.1 Seizures vs Syncope¶

Differentiating features: Movements: - Seizures: tonic-clonic movements are hallmark of generalized seizure - Syncope: myoclonic jerks may occur in up to 90% of episodes; typically multifocal or generalized, arrhythmic, and short duration (<30 s); mild flexor and extensor posturing may occur Aura: - Partial/partial-complex seizures with secondary generalization: usually preceded by aura (unpleasant smell, fear, anxiety, abdominal discomfort, visceral sensations) - These should be differentiated from premonitory features of syncope Duration and recovery: - Seizure: loss of consciousness usually >5 min with prolonged postictal drowsiness and disorientation - Syncope: reorientation occurs almost immediately Other features: - Muscle aches: occur after both, but longer and more severe after seizures - Seizures rarely provoked by emotions or pain (unlike syncope) - Urinary incontinence: occurs with both - Fecal incontinence: only very rarely with syncope

6.2 Autonomic Epilepsy¶

Autonomic seizures provide a more difficult diagnostic challenge: - Cardiovascular, GI, pulmonary, urogenital, pupillary, and cutaneous manifestations similar to premonitory features of syncope - Cardiovascular manifestations include clinically significant tachycardias and bradycardias that may cause loss of consciousness - Presence of accompanying non-autonomic auras may help differentiate from syncope

6.3 Hypoglycemia¶

May cause transient loss of consciousness, typically in diabetes patients treated with insulin. Clinical features of impending/actual hypoglycemia (due to autonomic activation): - Tremor - Palpitations - Anxiety - Diaphoresis - Hunger (NOT typical of syncope prodrome) - Paresthesias Neuronal dysfunction symptoms: - Fatigue, weakness, dizziness - Cognitive and behavioral symptoms Diagnostic difficulty: Patients in strict glycemic control may have impaired counterregulatory response and loss of characteristic warning symptoms.

6.4 Cataplexy¶

Abrupt partial or complete loss of muscular tone triggered by strong emotions (typically anger or laughter)
CONSCIOUSNESS IS MAINTAINED throughout (unlike syncope)
Duration: 30 s to 2 min
No premonitory symptoms
Occurs in 60-75% of patients with narcolepsy

6.5 Falls and Gait Disorders¶

Clinical interview and eyewitness interrogation usually allow differentiation of syncope from falls due to: - Vestibular dysfunction - Cerebellar disease - Extrapyramidal system dysfunction - Other gait disorders Diagnostic challenge in dementia patients with repeated falls and inability to provide clear history. Head trauma with postconcussive syndrome, amnesia, and/or loss/alteration of consciousness may also contribute to difficulty.

6.6 Psychogenic Episodes¶

Apparent loss of consciousness may manifest in: - Generalized anxiety - Panic disorders - Major depression - Somatization disorder Features suggesting psychogenic cause: - Frequent fainting without prodromal symptoms - Rarely injured despite numerous falls - No clinically significant hemodynamic changes concurrent with episodes Distinction: Vasovagal syncope precipitated by fear, stress, anxiety, emotional distress IS accompanied by hypotension and sometimes bradycardia.

7. INVESTIGATIONS & DIAGNOSIS¶

The goals of initial evaluation are to determine whether transient loss of consciousness was due to syncope, identify the cause, and assess risk for future episodes and serious harm.

High-Risk Features Indicating Hospitalization or Intensive Evaluation of Syncope¶

Category	Feature
Symptoms/History	Chest pain suggesting coronary ischemia
	Features of congestive heart failure
	Palpitations at time of syncope
	Syncope at rest or during exercise
	History of ventricular arrhythmias
	Family history of sudden death
Structural Disease	Moderate or severe valvular disease
	Moderate or severe structural cardiac disease
ECG Findings	Features of ischemia
	Prolonged QT interval (>500 ms)
	Repetitive sinoatrial block or sinus pauses
	Persistent sinus bradycardia
	Bi- or trifascicular block or intraventricular conduction delay with QRS ‡120 ms
	Atrial fibrillation
	Nonsustained ventricular tachycardia

Category	Feature
	Preexcitation syndromes
	Brugada pattern on ECG

7.1 Initial Evaluation¶

Components: - Detailed history - Thorough questioning of eyewitnesses - Ancillary cellphone video of the spell (when available) - Complete physical examination - Complete neurologic examination - Orthostatic vital signs: BP and HR in supine position and after 3 minutes of standing This initial assessment identifies cause of syncope in ~50% of patients and allows risk stratification.

7.2 High-Risk Features on History¶

New onset of chest discomfort
Abdominal pain
Shortness of breath
Headache
Syncope during exertion
Syncope while supine
Sudden onset of palpitations followed by syncope
Severe coronary artery or structural heart disease

7.3 High-Risk Features on Examination¶

Unexplained systolic BP <90 mmHg
Suggestion of gastrointestinal hemorrhage
Persistent bradycardia (<40 beats/min)
Undiagnosed systolic murmur

7.4 Electrocardiogram¶

ECG should be performed if there is suspicion of syncope due to arrhythmia or underlying cardiac disease. Relevant ECG abnormalities: - Bradyarrhythmias or tachyarrhythmias - AV block - Acute myocardial ischemia - Old myocardial infarction - Long QT interval - Bundle branch block

7.5 Laboratory Tests¶

Baseline laboratory blood tests are RARELY helpful in identifying the cause of syncope. Indications for blood tests: - Suspected myocardial infarction - Suspected anemia - Suspected secondary autonomic failure

7.6 Autonomic Nervous System Testing¶

Performed in specialized centers. Helpful to: - Uncover objective evidence of autonomic failure - Demonstrate predisposition to neurally mediated syncope Components: - Parasympathetic function: heart rate variability to deep respiration and Valsalva maneuver - Sympathetic cholinergic function: thermoregulatory sweat response, quantitative sudomotor axon reflex test - Sympathetic adrenergic function: BP response to Valsalva maneuver, tilt-table test with beat-to-beat BP measurement Tilt-table test utility: - Distinguishes orthostatic hypotension (autonomic failure) from hypotensive-bradycardic response of neurally mediated syncope - Identifies patients with immediate or delayed orthostatic hypotension - May reproduce symptoms in patients with suspected psychogenic syncope

7.7 Carotid Sinus Massage¶

Consider in: - Patients with symptoms suggestive of carotid sinus syncope - Patients >40 years with recurrent syncope of unknown etiology Perform under: - Continuous ECG monitoring - Continuous blood pressure monitoring Avoid in patients with: - Carotid bruits - Possible or known plaques - Carotid stenosis

7.8 Cardiac Evaluation¶

ECG Monitoring: - Indicated for patients with high pretest probability of arrhythmia causing syncope - Hospital monitoring if high likelihood of life-threatening arrhythmia - Continuous ambulatory (Holter) monitoring for frequent syncopal episodes (daily or almost daily) - Loop recorders for suspected arrhythmias with low risk of sudden cardiac death: - External: episodes >1 per month - Implantable: episodes less frequent - Monitoring duration should be at least twice the interspell duration Echocardiography: - Perform in patients with history of cardiac disease or abnormalities on exam/ECG - Diagnoses: aortic stenosis, hypertrophic cardiomyopathy, cardiac tumors, aortic dissection, pericardial tamponade - Role in risk stratification for sudden cardiac death based on LVEF Exercise Testing: - Perform in patients with syncope during or shortly after exercise - Helps identify exercise-induced arrhythmias (e.g., tachycardia-related AV block) and exercise-induced exaggerated vasodilation Electrophysiologic Studies: - Indicated in patients with structural heart disease and ECG abnormalities when noninvasive investigations fail - Low sensitivity and specificity - Only perform when high pretest probability exists - Rarely performed currently to evaluate syncope

7.9 Psychiatric Evaluation¶

Screening may be appropriate in patients with recurrent unexplained syncope episodes
Tilt-table testing with demonstration of symptoms in absence of hemodynamic change may be useful in suspected psychogenic syncope

8. MANAGEMENT & TREATMENT¶

Treatment approach varies based on the underlying etiology of syncope.

8.1 Treatment of Neurally Mediated Syncope¶

Cornerstones of management: - Reassurance - Education - Avoidance of provocative stimuli - Plasma volume expansion with fluid and salt Isometric counterpressure maneuvers: - Tensing of abdominal and leg muscles (MOST EFFECTIVE) - Handgrip and arm tensing - Leg crossing - Mechanism: raises BP by increasing central blood volume and cardiac output - Maintains pressure in autoregulatory zone - Particularly helpful in patients with long prodrome - Avoids or delays onset of syncope - Supported by randomized controlled trial

8.2 Pharmacologic Therapy for Neurally Mediated Syncope¶

Widely used for refractory patients: - Fludrocortisone - Vasoconstricting agents - β -adrenoreceptor antagonists Evidence: Only MIDODRINE has been shown effective in international, multicenter randomized controlled trials

8.3 Cardiac Pacing for Neurally Mediated Syncope¶

General principle: Because vasodilation, decreased central blood volume, decreased stroke volume, and cardiac output are the dominant pathophysiologic mechanisms in most patients, use of cardiac pacemaker is RARELY beneficial. Indications for pacing: - Cardioinhibitory syncope response during tilt-table testing - Recent sham-controlled RCT data show dual-chamber pacemaker with closed-loop stimulation algorithm can decrease syncope recurrence Patient selection (based on RCT enrollment criteria): - Age >40 years - Frequent recurrence of syncope - Cardioinhibitory response on tilt-table test Note: This continues to be an area of uncertainty.

8.4 Treatment of Orthostatic Hypotension¶

Step 1: Remove reversible causes - Usually vasoactive medications Step 2: Nonpharmacologic interventions - Patient education regarding staged moves from supine to upright - Warnings about hypotensive effects of large meals - Isometric counterpressure maneuvers - Raising head of bed to reduce supine hypertension and nocturnal diuresis - Increase dietary fluid and salt - Rapid ingestion of 500 mL plain water (may effect short-term pressor response) Step 3: Pharmacologic intervention (if nonpharmacologic measures fail) - Fludrocortisone acetate - Vasoconstricting agents: midodrine or L-dihydroxyphenylserine (droxidopa) Supplementary agents for intractable symptoms: - Pyridostigmine - Atomoxetine - Yohimbine - Octreotide - Desmopressin acetate (DDAVP) - Erythropoietin

8.5 Treatment of Cardiac Syncope¶

Treatment depends on underlying disorder. Bradycardia (sinus node disease, AV block): - Cardiac pacing Atrial and ventricular tachyarrhythmias: - Ablation - Antiarrhythmic drugs - Cardioverter-defibrillators Note: These disorders are best managed by physicians with specialized skills in this area.

9. CAUSES OF NEUROGENIC ORTHOSTATIC HYPOTENSION¶

Neurogenic orthostatic hypotension results from central and peripheral autonomic nervous system dysfunction. Autonomic dysfunction of other organ systems frequently accompanies orthostatic hypotension.

9.1 Primary Autonomic Degenerative Disorders (Synucleinopathies)¶

Characterized by presence of α -synuclein, a protein that aggregates in different locations: Lewy body disorders ( α -synuclein in cytoplasm of neurons): - Parkinson's disease - Dementia with Lewy bodies - Pure autonomic failure Multiple system atrophy ( α -synuclein in glia): - Shy-Drager syndrome

9.2 Secondary Autonomic Failure (Peripheral Neuropathies)¶

Associated with small-fiber peripheral neuropathies: - Diabetes mellitus - Acquired and hereditary amyloidosis - Immune-mediated neuropathies - Hereditary sensory and autonomic neuropathies (HSAN) - particularly HSAN type III (familial dysautonomia) Less frequent associations: - Vitamin B12 deficiency - Neurotoxin exposure - HIV and other infections - Porphyria

9.3 Postprandial Hypotension¶

Patients with autonomic failure and elderly are susceptible to BP falls associated with meals
Mechanism not fully elucidated Exacerbating factors:
Large meals
Meals high in carbohydrate
Alcohol intake

9.4 Iatrogenic (Drug-Induced)¶

Drugs that may lower peripheral resistance: α -adrenoreceptor antagonists (for hypertension and prostatic hypertrophy) - Diuretics - Nitrates and other venodilators/vasodilators - Other antihypertensive agents - Tricyclic agents - Phenothiazines

9.5 Volume Depletion¶

Iatrogenic: - Diuresis Medical causes: - Hemorrhage - Vomiting - Diarrhea - Decreased fluid intake

10. INHERITED CHANNELOPATHIES¶

Several disorders associated with cardiac electrophysiologic instability and arrhythmogenesis are due to mutations in ion channel subunit genes.

10.1 Long QT Syndrome¶

Genetically heterogeneous disorder
Associated with prolonged cardiac repolarization and predisposition to ventricular arrhythmias
Syncope and sudden death result from torsades des pointes (unique polymorphic VT) that may degenerate into ventricular fibrillation Genetic links:
K+ channel α -subunits
K+ channel β -subunits
Voltage-gated Na+ channel
Scaffolding protein ankyrin B (ANK2) Acquired QT prolongation:
Most commonly due to drugs
May also result in ventricular arrhythmias and syncope

10.2 Brugada Syndrome¶

Characterized by: - Syncope - Polymorphic ventricular tachycardia - Idiopathic ventricular fibrillation - Right ventricular ECG abnormalities - Without structural heart disease Genetics: - Genetically heterogeneous - Most frequently linked to mutations in Na+ channel α -subunit, SCN5A

10.3 Catecholaminergic Polymorphic Ventricular Tachycardia¶

Inherited, genetically heterogeneous disorder
Often involves cardiac calcium handling
Associated with exercise- or stress-induced ventricular arrhythmias, syncope, or sudden death

11. KEY POINTS & CLINICAL PEARLS¶

Essential clinical pearls for the diagnosis and management of syncope.

11.1 Diagnostic Pearls¶

Initial assessment identifies cause of syncope in ~50% of patients
Most syncopal episodes occur from a standing position
Cessation of blood flow for 6-8 seconds results in loss of consciousness
Fall in systolic BP to ~50 mmHg usually results in syncope
Myoclonic movements occur in up to 90% of syncopal episodes - do not assume seizure
EEG does NOT show seizure discharges during syncopal myoclonus
Hunger as a premonitory symptom suggests hypoglycemia, NOT syncope
Fecal incontinence is very rare in syncope (suggests seizure)
Prolonged postictal confusion suggests seizure rather than syncope

11.2 Prognostic Pearls¶

Noncardiac syncope in young individuals: excellent prognosis
Cardiac syncope: increased risk of sudden cardiac death
Orthostatic hypotension: mortality related to comorbidities
Bimodal age distribution: young (peak ~15 years) and elderly (rise after 70 years)
Neurally mediated syncope is most common in young; cardiac causes more common in elderly

11.3 Management Pearls¶

First step in orthostatic hypotension: remove vasoactive medications
Isometric counterpressure maneuvers: abdominal and leg muscle tensing is MOST effective
Only midodrine has RCT evidence for neurally mediated syncope
Cardiac pacing rarely beneficial in neurally mediated syncope (vasodilation is dominant mechanism)
500 mL water bolus can provide short-term pressor response in orthostatic hypotension
'Coat-hanger headache' may be only symptom of orthostatic hypotension
Supine hypertension affects >50% of patients with orthostatic hypotension due to autonomic failure

11.4 Red Flags Requiring Hospitalization¶

Syncope during exertion or while supine
Chest pain suggesting coronary ischemia
Features of congestive heart failure
Moderate or severe structural cardiac disease
Prolonged QT interval (>500 ms)
History of ventricular arrhythmias
Family history of sudden death
Brugada pattern on ECG
Palpitations at time of syncope