Syncope - Approach to the Patient Dynamed 2020

Overview and Recommendations

Background

• Syncope is a syndrome of transient loss of consciousness secondary to cerebral

hypoperfusion characterized by rapid onset, short duration, and complete spontaneous
recovery.
• Syncope may be classified into three types: neurally mediated, orthostatic, and cardiac
syncope. The most common cause is the neurally-mediated vasovagal syncope and
arrhythmias are the most common cause of cardiac syncope, accounting for 10% of all
syncopal events .
• The cause of syncope remains unexplained (cryptogenic syncope) in 17%-33% of cases in the
emergency department and may require inpatient cardiac workup.

Evaluation

• Obtain a history from the patient and/or witness, including a complete description of the setting
of the event, previous episodes, history of heart disease, and recent changes in medication
• Perform a complete physical exam for all patients with syncope, including
o heart rate measurement (Strong recommendation)..
o orthostatic blood pressure and heart rate measurements in all patients. Perform manual
intermittent blood pressure and heart rate measurement supine and during active
standing for 3 minutes (Strong recommendation).
• Obtain 12-lead electrocardiogram (ECG) for all patients with syncope to evaluate for
arrhythmic cause.
• Consider routine blood testing in patients with a high likelihood of other comorbidities such as
severe anemia or electrolyte abnormalities that could contribute to transient loss of
consciousness.
• Perform carotid sinus massage in patients > 40 years old with syncope of unknown origin
compatible with reflex mechanism after initial evaluation; perform with caution in patients with
previous transient ischemic attack, stroke, and known carotid stenosis > 70% (Strong
recommendation).
• Consider tilt testing for patients with suspected vasovagal syncope or orthostatic syncope
(Weak recommendation).
• Perform additional testing for patients with suspected cardiac syncope including:
o echocardiography in patients with suspected structural heart disease (Strong
recommendation)
o ECG monitoring using Holter monitor or loop recorder in patients suspected arrhythmic
syncope (Strong recommendation)
o electrophysiological studies for suspected tachycardia in patients with previous
myocardial infarction or other scar-related conditions if syncope remains unexplained
after noninvasive evaluation (Strong recommendation)
o exercise testing in patients who develop syncope during or soon after exertion (Strong
recommendation)
• Diagnose:
o Neurally mediated syncope in the absence of heart disease, a history of recurrent
syncope, and/or the presence of specific triggers prior to episode.
 ▪ Vasovagal syncope if triggered by pain, fear, or standing and associated with
typical progressive prodrome, such as nausea, diaphoresis, tunnel vision, or pale
appearance (Strong recommendation).
▪ Carotid sinus syncope if carotid sinus massage causes bradycardia suggesting
asystole and/or hypotension that reproduces spontaneous symptoms and history
features compatible with reflex mechanism of syncope
▪ Situational syncope if triggered by a specific event, such as defecation, urination,
or coughing (Strong recommendation).
o Orthostatic syncope if episode is related to assuming standing position and
documentation of orthostatic hypotension (Strong recommendation).
o Cardiac syncope
▪ When there is acute cardiac ischemia with or without myocardial infarction (MI)
secondary to ischemia (Strong recommendation).
▪ Consider a diagnosis of cardiac syncope with the presence of structural heart
disease, family history of unexplained sudden death, or when episodes occurred
in a supine position, during exercise, or associated with palpitations.

Management

Neurally mediated syncope

• Treatment of neurally mediated syncope based on risk of future syncope episodes and
identification of specific mechanism for syncope when possible
o if syncope predictable or occurs at low frequency, education, reassurance that syncope
benign, and avoidance of triggers usually sufficient
o if syncope unpredictable or occurs at high frequency, consider specific therapy or
delayed treatment (guided by electrocardiogram documentation)
• Explain diagnosis, assure patient that condition is benign, and explain risk of recurrence and
avoidance of triggers and situations (Strong recommendation).
• Consider modification or discontinuation of hypotensive drug regimen in patients with
vasodepressor syncope (neurally mediated reflex due to vasodepressor), if possible (Weak
recommendation).
• Additional treatment for Vasovagal syncope
o Consider nonpharmacologic treatments including physical counterpressure maneuvers
(isometric muscle contractions) for patients with prodrome and promotion of salt and
fluid intake, unless contraindicated (Weak recommendation).
o Consider one or more pharmacological approaches including midodrine or
fludrocortisone in patients with frequent vasovagal syncope (Weak recommendation).
o Consider cardiac pacing in patients > 40 years old with documented cardioinhibitory
response(reflex bradycardia) (Weak recommendation).
o See Vasovagal syncope for additional information.
• Additional treatment for Carotid sinus syncope
o Consider cardiac pacing in patients with carotid sinus syncope that is cardioinhibitory
(Weak recommendation).
o See Carotid sinus syncope for additional information.

Orthostatic syncope

• Consider nonpharmacologic treatment options for patients with orthostatic syncope including
avoiding carbohydrate-rich meals, limiting alcohol intake, ensuring adequate hydration, sodium
 supplementation and/or wearing lower extremity and abdominal binders - particularly in older
patients or patients with pooling issues.
• Consider pharmacological treatment with fludrocortisone, midodrine, droxidopa, or
pyridostigmine in patients that do not respond to nonpharmacological treatments.
• See Orthostatic hypotension and orthostatic syncope for additional information.

Cardiac syncope

• In patients with cardiac syncope due to an arrhythmia, treatment options include cardiac
pacing for bradyarrhythmias, and catheter ablation, antiarrhythmic medications, and/or
placement of an implantable cardioverter defibrillator (ICD) for tachyarrhythmias.
• For patients with syncope due to structural heart disease see Syncope secondary to structural
heart disease.
• See Treatment of cardiac syncope for additional information.

Related Summaries
• Carotid Sinus Syncope
• Orthostatic Hypotension and Orthostatic Syncope
• Vasovagal Syncope

General Information
Description

• syndrome of transient loss of consciousness secondary to cerebral hypoperfusion

characterized by rapid onset, short duration, and complete spontaneous recovery1,4

Also called

• fainting

Definitions

• presyncope may be used as noun or adjective1

o noun refers to state that resembles prodrome of syncope but that is not followed by loss
of consciousness
o adjective refers to symptoms or signs that occur before loss of consciousness
• transient loss of consciousness defined as state of real or apparent loss of consciousness with
loss of awareness characterized by amnesia for unconscious period, abnormal motor control,
loss of responsiveness, and short duration1
• true loss of consciousness refers to failure of both arousal and self-awareness2

Types

• neurally mediated (reflex syncope)1

o vasovagal syncope (most common)
o carotid sinus syncope
o situational syncope
o nonclassical syncope without prodrome, apparent triggers, or atypical presentation
 • orthostatic syncope, including autonomic dysfunction1
• cardiac syncope, including arrhythmia and structural disease causes1

Epidemiology
Incidence/Prevalence

• syncope reported to account for

o 0.8%-2.4% of emergency department visits4
o 1%-3% of hospital admissions (Mayo Clin Proc 2008 Nov;83(11):1280)
• risk of syncope 6.2 per 1,000 person-years
o based on mean 17-year follow-up of 7,814 men and women in Framingham Heart Study
(mean age 51 years)
o 822 reported syncope (mean age 66 years)
o Reference - N Engl J Med 2002 Sep 19;347(12):878, editorial can be found in N Engl J
Med 2002 Sep 19;347(12):931
• overall incidence of syncope
o lifetime prevalence ranges from 3% to 37%
o 6% annual incidence among institutionalized elderly
o 3% of emergency room visits
o 1% of hospital admissions
o Reference - Med Clin North Am 2001 Mar;85(2):423
• bimodal distribution of first faints1
o peak incidence between ages 10 and 30 years
o second peak may occur after age 65 years
o reported 10-year cumulative incidence of syncope (based on Framingham study data)
▪ 11% in both men and women aged 70-79 years
▪ 17% in men aged ≥ 80 years
▪ 19% in women aged ≥ 80 years

Prevalence of syncope types

• cause of syncope unexplained in 17%-33% of cases in emergency department1

• most frequently identified causes in 822 patients with syncope in Framingham Heart Study
o 36.6% unknown
o 21.2% vasovagal
o 9.5% cardiac
o 9.4% orthostatic
o 6.8% medication
o 7.5% other (including cough syncope, micturition syncope, situational syncope)
o 4.1% nonsyncope events (stroke or transient ischemic attack)
o Reference - N Engl J Med 2002 Sep 19;347(12):878full-text, editorial can be found in N
Engl J Med 2002 Sep 19;347(12):931
• distribution of causes of syncope in cohort of 341 patients referred to "syncope units" within 3
hospital cardiology departments
o neurally mediated in 57% (20% vasovagal, 25% situational, 47% carotid sinus)
o cardiac in 23% (15% bradyarrhythmia, 5% tachyarrhythmia, 3% mechanical or acute
ischemia)
o orthostatic in 2%
o unexplained in 18%
o nonsyncope events in 1% (neurologic or psychiatric)
 o Reference - J Am Coll Cardiol 2001 Jun 1;37(7):1921full-text
• distribution of causes of syncope in cohort of 195 patients aged 13-95 years (mean age 62.5
years) presenting to 9 emergency departments in Italy
o neurally mediated in 35% (30% vasovagal, 3.5% situational, 2% carotid sinus syncope)
o cardiac in 21% (11% bradyarrhythmia, 7% tachyarrhythmia, 3% hemodynamic)
o orthostatic in 6%
o undiagnosed in 17.5%
o nonsyncope events in 6.1% (5.6% psychiatric, 0.5% metabolic)
o Reference - Eur Heart J 2000 Jun;21(11):935full-text, editorial can be found in Eur
Heart J 2000 Jun;21(11):877
• distribution of causes of syncope in cohort of 242 older patients (aged > 65 years) referred for
evaluation of transient loss of consciousness
o neurally mediated syncope in 44.1%
o orthostatic in 22.5%
o cardiac syncope in 14.7%
o drug induced in 4.8%
o multifactorial in 3.5%
o unexplained in 10.4%
o nonsyncope events in 4.5% (2.5% seizure, 2% transient ischemic attack)
o Reference - J Am Geriatr Soc 2006 Oct;54(10):1531, commentary can be found in Am
Fam Physician 2007 Mar 15;75(6):915, J Am Geriatr Soc 2007 Apr;55(4):634
• neurally mediated syncope may be most common cause of syncope in children
o based on 2 chart reviews
o 226 children with 252 emergency department visits for syncope
▪ 181 (80%) had neurally mediated syncope
▪ 21 (9%) had nonsyncope events due to neurologic disorders (most commonly
seizure disorder)
▪ 5 (2%) had cardiac disorders
▪ other diagnoses included
▪ psychogenic problems
▪ breath-holding spells
▪ intoxication
▪ obstructive respiratory disease
▪ hypoglycemia
▪ aplastic crisis
▪ Reference - J Pediatr 2004 Aug;145(2):223
o 169 children aged 4-18 years evaluated for first episodes of syncope at tertiary care
center
▪ 24% did not have diagnosis established
▪ 116 (69% of cohort, 91% of diagnoses) had neurally mediated syncope
▪ diagnoses in 12 other patients included
▪ pseudoseizure
▪ anxiety disorder
▪ psychogenic syncope
▪ breath-holding spell
▪ long QT syndrome
▪ exertional ventricular tachycardia
▪ Reference - J Pediatr 2005 Mar;146(3):355
• psychiatric disorders may be common
o psychiatric disorders reported in 24%-31% patients with unexplained syncope in review
of several case series (Am J Med 1992 Jan 24;92(1A):18S)
 o 20% patients who did not have underlying medical explanation for syncopal episode
met diagnostic criteria for at least 1 of 4 major psychiatric disorders in series of 414
patients (Am J Med 1995 Nov;99(5):505)
• 18.4% of patients had multiple potential causes of syncope in retrospective cohort of 987
patients referred to electrophysiology service for syncope evaluation (Mayo Clin Proc 2003
Apr;78(4):414)
• pulmonary embolism pooled prevalence in systematic review of 12 observational studies
evaluating prevalence of pulmonary embolism in patients presenting to emergency department
with syncope or in hospitalized patients with syncope
o 0.8% (95% CI 0.5%-1.3%) in analysis of 9 studies with 6,608 patients presenting to
emergency department with syncope
o 1% (95% CI 0.5%-1.9%) in analysis of 3 studies with 975 hospitalized patients with
syncope
o Reference - Am J Emerg Med 2018 Apr;36(4):551

Risk factors

• risk factors for syncope (especially reflex syncope and orthostatic hypotension and syncope)
include1
o medications that lower blood pressure
o alcohol use
o volume depletion (may be due to hemorrhage, low fluid intake, diarrhea, or vomiting)
o pulmonary disease resulting in reduction in brain oxygen supply
o environmental factors (such as heat)
• structural heart disease is a risk factor for cardiac syncope2

Differential Diagnosis
Causes of neurally mediated syncope

• vasovagal syncope
o emotional stress1,2,4
o fear1,2
o blood phobia1,2
o instrumentation1,2
o pain (somatic or visceral)1,2,4
o venipuncture, other painful or medical procedures2
o standing1,4
o sitting (not common)1,4
• carotid sinus syncope1,2
• situational syncope
o coughing1,2,4
o sneezing1,2
o gastrointestinal stimulation
▪ swallowing1,2,4
▪ defecation1,2,4
▪ visceral pain 2
o micturition1,2,4
o post-exercise1,2
o post-prandial2
 o laughter1,2,4
o brass instrument playing 1,2
o weightlifting1,2
• atypical form can occur without apparent triggers1

Causes of orthostatic syncope

• displacement of blood from thorax to lower extremities when changing from supine to upright
posture resulting in decrease in venous return1
• most often from movement from prone to standing position2
o most likely to occur in elderly population
o minor symptoms may include greying out of vision or lightheaded sensation
• orthostatic hypotension may be exacerbated by venous pooling during exercise (exercise-
induced), after meals (post-prandial), and after prolonged bed rest (deconditioning)1
• primary autonomic failure
o multiple system atrophy1,2
o pure autonomic failure1,2
o autonomic failure associated with Parkinson disease1,2
o primary autonomic failure may be associated with autonomic failure in other organ
systems besides blood pressure control including2
▪ impotence
▪ disordered sweating (dry skin sometimes associated with patches
of hyperhidrosis)
o dementia with Lewy bodies1
• secondary autonomic failure due to other diseases including
o renal failure1,2
o liver failure2
o diabetes1,2
o amyloidosis2
o spinal cord injuries1
o alcoholism2
o autoimmune autonomic neuropathy1
o paraneoplastic autonomic neuropathy1
• volume depletion due to1,2
o hemorrhage
o diarrhea
o vomiting
• medication side effects usually related to control of blood pressure while standing
o beta adrenergic blockers2
o diuretics1,2
o vasodilators1,2
o other antihypertensive medications2
o nitroglycerin2
o antidepressants1,2
o phenothiazines1,2
o 3 cases of syncope and falls attributed to timolol eye drops can be found in BMJ 2006
Apr 22;332(7547):960full-text

Causes of cardiac syncope

• arrhythmias1
 o arrhythmias may be due to intrinsic disease, medications, or may be secondary to
structural cardiac, cardiopulmonary, or great vessel disease
o bradycardia due to
▪ sick sinus syndrome
▪ atrio-ventricular conduction disorders
▪ implanted device malfunction (such as pacemakers, implantable cardioverter
defibrillators (ICDs))
o tachycardia due to
▪ paroxysmal ventricular tachycardia
▪ paroxysmal supraventricular tachycardia (SVT)
▪ cardiac ischemia triggering ventricular tachyarrhythmia presenting as recurrent
syncope (diagnosed on loop recorder) in case report of 71 year old man (Lancet
2012 Mar 3;379(9818):866)
o medication induced bradycardia or tachyarrhythmias
o inherited syndromes
▪ long QT syndrome (Heart 2007 Jan;93(1):130)
▪ Brugada syndrome
▪ Brugada syndrome - inherited cardiac disease causing ventricular
tachyarrhythmias in structurally normal heart; electrocardiogram (ECG)
pattern includes right bundle branch block and ST elevation in V1-V3
(BMJ 2003 May 17;326(7398):1078full-text)
▪ case presentation of Brugada syndrome can be found in Lancet 2007 Jan
6;369(9555):78
• structural or ischemic heart disease1
o valvular disease
o acute coronary syndrome (such as myocardial infarction or ischemia)
o hypertrophic cardiomyopathy
o ischemic or dilated cardiomyopathy
o arrhythmogenic right ventricular cardiomyopathy (ARVC)
o cardiac masses (such as atrial myxoma and tumors)
o pericardial disease (such as tamponade)
o congenital anomalous coronary arteries
o prosthetic heart valve dysfunction
o anomalous origin of left coronary artery reported in 2 adolescent athletes with syncope
(BMJ 2006 May 13;332(7550):1139full-text)
• cardiopulmonary and great vessel disease1
o acute aortic dissection
o pulmonary hypertension
o pulmonary embolism (PE)
▪ prevalence of PE by International Classification of Diseases codes < 1% in
all patients with syncope and < 3% in patients hospitalized for syncope
▪ based on cross-sectional study
▪ 1,671,944 adults from Canada, Denmark, Italy, and United States
presenting to emergency department for syncope were evaluated for PE
using International Classification of Diseases codes
▪ prevalence of PE at first evaluation ranged from
▪ 0.06% to 0.55% in all patients
▪ 0.15% to 2.1% in patients hospitalized for syncope after first
evaluation
▪ prevalence of PE at 90-day follow-up ranged from
▪ 0.14% to 0.83% in all patients
 ▪ 0.35% to 2.63% in patients hospitalized for syncope after first
evaluation
▪ prevalence of venous thromboembolism (VTE) at 90-day follow-up ranged
from
▪ 0.3% to 1.37% in all patients
▪ 0.75% to 3.86% in patients hospitalized for syncope after first
evaluation
▪ Reference - JAMA Intern Med 2018 Mar 1;178(3):356
▪ DynaMed Commentary

The authors note that the higher rate of PE diagnosed in the PESIT study
may have been due to use of a structured algorithm to assess PE in all
patients, which may have increased false-positive test results as well as
detection of non-clinically relevant disease.
▪ pulmonary embolism diagnosed in 17% of patients hospitalized for first
episode of syncope, including in 13% of patients with clinically based
explanation for syncope other than PE
▪ based on cross-sectional study
▪ 560 adults (mean age 76 years, 60% women) hospitalized for first episode
of syncope were assessed for pulmonary embolism (PE) within 48 hours
of admission during syncope evaluation
▪ reasons for hospital admission after presentation at emergency
department were fall-related trauma, co-existing conditions, no
explanation of syncope identified, or high probability of cardiac
syncope based on Evaluation of Guidelines in Syncope Study score
▪ patients were excluded for previous syncope episodes,
anticoagulation therapy, or pregnancy
▪ diagnosis of PE determined by multi-stage assessment
(see Clinical prediction of pulmonary embolism)
▪ patients were assessed by Wells rule and D-dimer testing,
with PE ruled out if both Wells score ≤ 4 (low clinical risk)
and D-dimer negative
▪ if Wells score > 4 (high clinical risk) and/or positive D-dimer
assay, patients received computed tomographic (CT)
angiography or ventilation-perfusion lung scan (for contrast
allergy or severe renal impairment)
▪ PE confirmed if intraluminal filling defect on CT angiography
or perfusion defect of ≥ 75% of segment with normal
ventilation
▪ 63.4% had clinically based explanation for syncope other than PE
▪ 97 patients had confirmed PE, including
▪ 17.3% of entire cohort
▪ 42.2% of 230 patients with high clinical risk and/or positive D-dimer
assay
▪ 25.4% of 205 patients without clinically based explanation for
syncope
▪ 12.7% of 355 patients with clinically based explanation for syncope
▪ of patients with PE
▪ 24.7% had no clinical suspicion of PE such as tachypnea,
tachycardia, hypotension, or signs of deep vein thrombosis
 ▪ 62.9% had embolism location in main pulmonary or lobar artery or
perfusion defect > 25% of area of both lungs, which may account
for syncope
▪ clinical follow-up not reported
▪ Reference - PESIT trial (N Engl J Med 2016 Oct 20;375(16):1524)
▪ 1.4% prevalence of PE or DVT in patients hospitalized for first episode of
syncope
▪ based on cross-sectional study
▪ 1,305 patients (mean age 73 years) from 4 Canadian hospitals with first
episode of syncope were assessed for having evaluation for VTE
▪ exclusion criteria included use of anticoagulants and pregnancy (same
criteria as PESIT trial)
▪ 11.2% had evaluations for VTE including plasma D-dimer test,
compression ultrasound of limbs, computed tomographic pulmonary
angiography, and ventilation-perfusion scan
▪ 1.4% had VTE or PE
▪ Reference - JAMA Intern Med 2017 Jul 1;177(7):1046, full-text

Conditions that mimic syncope

Disorders with partial or complete loss of consciousness without global cerebral hypoperfusion

• seizures1
• metabolic disorders
o hypoxia
o hypoglycemia
o hyperventilation
o hypercapnia
• intoxicated state1
• cerebrovascular disorders1
o transient ischemic attack related to carotid artery
o vertebrobasilar transient ischemic attack
o history may include
▪ gait and limb ataxia
▪ limb weakness
▪ vertigo
▪ diplopia
▪ nystagmus
▪ dysarthria
▪ oropharyngeal dysfunction
o syncope during exercise of arms is consistent with cerebrovascular syncope due to
steal syndrome
• intracerebral hemorrhage or subarachnoid hemorrhage (history may include progressive
reduction in consciousness and abrupt, severe headache)1
• cardiac arrest (history may include no spontaneous recovery)1
• coma (history includes duration of loss of consciousness longer than in syncope)1

Disorders without impairment of consciousness

• cataplexy1
• drop attacks1
 • falls1
• transient ischemic attack (TIA) of carotid origin1
• sleep disturbances2
• vertigo2
• psychogenic pseudosyncope
o may have high event frequency (up to several times per day)1,2
o eyes usually closed during loss of consciousness1
o loss of consciousness usually short but may last 15-30 minutes1
o video-electroencephalogram (EEG) monitoring may be helpful1,2
▪ normal EEG, electrocardiogram (ECG) during "loss of consciousness"
▪ ability to carefully watch episode on video looking for other cues to psychiatric
etiology (such as thrashing, eye clenching)
o recommendations for diagnosis of psychogenic pseudosyncope1
▪ recording of spontaneous attacks with video by eyewitness should be considered
for diagnosis of psychogenic pseudosyncope (ESC Class IIa, Level C)
▪ tilt testing (preferably with concurrent EEG recording and video monitoring) may
be considered for diagnosis of psychogenic pseudosyncope (ESC Class IIb,
Level C)
• psychiatric conditions2
o anxiety attacks
o severe hyperventilation
o hysterical reactions
o history (eyewitness account) during episode may include
▪ eyes clenched tightly shut
▪ asymmetric, asynchronous movements

Differentiating seizure from syncope

Differentiating seizure from syncope

• history consistent with seizure

o history of epilepsy1
o prior to episode
▪ sleep deprivation2
▪ flashing light1,2
o onset of attack
▪ aura (such as unusually unpleasant smell)1
▪ burning smell2
▪ rising sensation in abdomen1,2
▪ focal motor movements2
o during episode (eyewitness account)
▪ falling over stiffly2
▪ associated movements2
▪ beginning before or after falling
▪ symmetric, synchronous
▪ unilateral distribution
▪ lasting minutes
▪ eyes open1,2
▪ automatisms (such as chewing, blinking, lip smacking)1,2
▪ biting side of tongue (bilateral rare)1
o episode may last minutes1
 o after episode2
▪ bitten tongue
▪ pallor, sweating, nausea
▪ incontinence
▪ prolonged confusion after regaining consciousness
▪ muscle soreness
• neurological evaluation indicated if transient loss of consciousness thought to be seizure
activity (ESC Class I, Level C)1
• symptom-based point score may differentiate seizure from syncope (level 2 [mid-level]
evidence)
o based on cohort study with multiple methodologic limitations
o 671 patients with loss of consciousness recruited from specialty clinics and hospital
cardiology wards completed 118-item questionnaire
o 539 patients (80%) had clear diagnosis
o 102 patients (19%) had seizures
▪ complex partial seizures in 50 patients
▪ primary generalized seizures in 52 patients
o 437 patients (81%) had syncope
▪ tilt table positive vasovagal syncope in 267
▪ ventricular tachycardia in 90
▪ other diagnoses included complete heart block and supraventricular tachycardia
in 80
o 538 patients with clear diagnosis of syncope or seizure were randomly divided into
▪ 270 in derivation cohort
▪ 268 in validation cohort
o methodologic limitations included
▪ no independent validation cohort
▪ exclusion of patients with uncertain diagnosis
▪ unclear if diagnosis (reference standard) and symptom collection were blinded to
each other
o point score (range -4 to +5) derived from
▪ waking with cut tongue (+2)
▪ abnormal behavior (witness of any amnesia for abnormal behavior,
unresponsiveness, unusual posturing, or abnormal limb jerking) (+1)
▪ loss of consciousness with emotional stress (+1)
▪ postictal confusion (+1)
▪ head turning to 1 side during loss of consciousness (+1)
▪ prodrome of deja vu or jamais vu (+1)
▪ any presyncope (-2)
▪ loss of consciousness with prolonged sitting or standing (-2)
▪ diaphoresis before spell (-2)
o total score +1 or more predicted seizure in validation cohort with
▪ sensitivity 94%
▪ specificity 94%
o among patients with 19% prevalence of syncope
▪ positive predictive value 79% (likelihood of seizure if score +1 or more)
▪ negative predictive value 98.5% (likelihood of syncope if score less than +1)
o Reference - J Am Coll Cardiol 2002 Jul 3;40(1):142

Evaluation
Algorithms

• American College of Cardiology/American Heart Association/Heart Rhythm Society

(ACC/AHA/HRS) algorithm for initial evaluation in patients with syncope4
o initial evaluation should include (ACC/AHA/HRS Class I, Level B-NR)
▪ detailed history and physical exam
▪ resting 12-lead electrocardiogram (ECG)
o if cause of syncope determined after initial evaluation, consider treatment and risk
assessment
o if cause of syncope unknown after initial evaluation, consider further evaluation and risk
assessment
• ACC/AHA/HRS algorithm for additional evaluation in patients with syncope4
o If clear diagnosis and normal initial evaluation without significant injury or cardiovascular
morbidities, no additional evaluation needed
o for patients with unclear initial evaluation
▪ targeted blood tests
▪ target blood tests reasonable based on clinical assessment and findings
on history and physical exam (ACC/AHA/HRS Class IIa, Level B-NR)
▪ usefulness of brain natriuretic peptide and high-sensitivity troponin
measurement uncertain in patients with suspected cardiac cause of
syncope (ACC/AHA/HRS Class IIb, Level C-LD)
▪ routine and comprehensive blood lab testing is not useful in evaluating
cause of syncope (ACC/AHA/HRS Class III, Level B-NR)
▪ if initial evaluation suggests neurogenic orthostatic hypotension, referral for
autonomic evaluation can be useful to improve diagnostic and prognostic
accuracy (ACC/AHA/HRS Class IIa, Level C-LD)
▪ tilt testing
▪ if initial evaluation suggests reflex mediated syncope, tilt testing can be
useful
▪ consider tilt testing in patients with suspected vasovagal syncope
(ACC/AHA/HRS Class IIa, Level B-R) or suspected delayed
orthostatic hypotension (ACC/AHA/HRS Class IIa, Level B-NR)
▪ tilt testing not recommended to predict response to medical therapy
in patients with vasovagal syncope (ACC/AHA/HRS Class III, Level
B-R)
▪ tilt testing reasonable to
▪ differentiate conclusive syncope from epilepsy in select patients
(ACC/AHA/HRS Class IIa, Level B-NR)
▪ establish diagnosis of pseudosyncope (ACC/AHA/HRS Class IIa,
Level B-NR)
o If initial evaluation suggests cardiovascular abnormalities
▪ cardiac telemetry monitoring
▪ continuous ECG monitoring useful for hospitalized patients with suspected
cardiac etiology (ACC/AHA/HRS Class I, Level B-NR)
▪ select cardiac monitoring device based on frequency and nature of
syncope episodes (ACC/AHA/HRS Class I, Level C-EO)
▪ options include external cardiac monitoring devices (ACC/AHA/HRS Class
IIa, Level B-NR) or implantable cardiac monitor (ACC/AHA/HRS Class IIa,
Level B-R)
▪ cardiac imaging
 ▪ transthoracic echocardiography can be useful in select patients with
suspected structural heart disease (ACC/AHA/HRS Class IIa, Level B-NR)
▪ computed tomography (CT) or magnetic resonance imaging (MRI) may be
useful in select patients with suspected cardiac etiology (ACC/AHA/HRS
Class IIb, Level B-NR)
▪ routine cardiac imaging is not useful unless cardiac etiology suspected
based on initial evaluation with history, physical exam, or
electrocardiogram (ECG) (ACC/AHA/HRS Class III, Level B-NR)
▪ exercise stress testing can be useful to determine cause of syncope in select
patients with syncope or presyncope during exertion (ACC/AHA/HRS Class IIa,
Level C-LD)
▪ electrophysiological studies (EPS)
▪ EPS can be useful in select patients with suspected arrhythmic cause of
syncope (ACC/AHA/HRS Class IIa, Level B-NR)
▪ EPS not recommended in patients with normal ECG and normal cardiac
structure and function unless suspect arrhythmic cause of syncope
(ACC/AHA/HRS Class III, Level B-NR)
• Diagnostic algorithms

IMAGE 1 OF 2

Syncope Additional Evaluation and Diagnosis

Algorithm for additional evaluation and diagnosis in patients with syncope. *Colors correspond to
class of recommendations in ACC/AHA/HRS Table 1. **Applies to patients after normal initial
evaluation without significant injury or cardiovascular morbidities; patients followed up by
primary care physical as needed. The algorithms do not represent a comprehensive list of
recommendations (see text for all recommendations). †In selected patients (see Section 1.4). CT
indicates computed tomography; CV cardiovascular; ECG, electrocardiogram; EPS
electrophysiological study; MRI, magnetic resonance imaging; OH, orthostatic hypotension; and
TT, transthoracic echocardiography.

IMAGE 2 OF 2

Diagnostic Algorithm for Syncope

Adapted from Strickberger SA, Benson DW, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, et al.;
American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing,
Cardiovascular Disease in the Young, and Stroke; Quality of Care and Outcomes Research
Interdisciplinary Working Group; American College of Cardiology Foundation; Heart Rhythm
Society; American Autonomic Society

History and Physical

History

General history

• obtain detailed history in all patients with syncope (ACC/AHA/HRS Class I, Level B-NR)4
 • detailed an accurate history and eyewitness account may help make diagnosis1,2
• history, including witness account2
o determine if event was true transient loss of consciousness
o ask if prior similar episodes
o patient may be unreliable historian
▪ patient may be unable to provide accurate details
▪ truth may result in patient losing driver's license, ability to perform hobby (such as
scuba diving or flying), or job and therefore may not be reliable
• also ask about2
o recent changes in medication
o history of heart disease
o family history of sudden death
o prior psychiatric history
• home recordings of spontaneous events1
o home video recordings of spontaneous events should be considered (ESC Class IIa,
Level C)
o encourage patients and their relatives to obtain home video recordings of spontaneous
events (ESC Class IIa, Level C)
o home video recording may help diagnose syncope-induced epileptic seizures

Suggested etiologies of transient loss of consciousness (TLOC) based on triggers

• supine position while awake before TLOC may suggest1

o vasovagal syncope with cardioinhibitory response
o cardiac syncope due to arrhythmia
o psychogenic pseudosyncope
o psychogenic non-epileptic seizures
• normal sleep during TLOC may suggest1
o cardiac syncope due to arrhythmia
o vasovagal syncope if prodrome causes awakening and syncope occurs while awake
o epilepsy
• sitting before TLOC may suggest1
o reflex syncope, including vasovagal syncope, situational syncope, and carotid sinus
syncope
o orthostatic syncope (classic type)
o cardiac syncope
• standing for period of time before TLOC may suggest1
o reflex syncope, including vasovagal syncope, situational syncope, and carotid sinus
syncope
o orthostatic syncope
o cardiac syncope
o TLOC only during standing may suggest orthostatic syncope or vasovagal syncope
• taking couple of steps after standing up or straightening up from bending or squatting position
before TLOC may suggest orthostatic syncope1
• micturition or defecation before TLOC may suggest1
o situational reflex syncope
o vasovagal syncope
• coughing before TLOC may suggest situational reflex syncope (coughing usually prolonged
and intense, especially in patients who smoke or have lung disease)1
• swallowing before TLOC may suggest situational reflex syncope1
• eating before or during TLOC may suggest1
 o reflex syncope, including vasovagal syncope, situational syncope, and carotid sinus
syncope
o orthostatic syncope
o cardiac syncope
o TLOC only during eating or < 15 minutes after eating may suggest postprandial
hypotension, especially in older patients with autonomic failure
o TLOC mostly during meals may suggest cardiac syncope due to arrhythmia or Brugada
syndrome
• head movements, pressure on neck, or shaving before TLOC may suggest spontaneous type
of carotid sinus syncope1
• fear, pain, or instrumentation before TLOC may suggest vasovagal syncope1
• physical exercise during TLOC may suggest1
o cardiac syncope due to structural heart disease
o cardiac syncope due to conduction disorders (such as atrioventricular (AV) conduction
disorders) or inherited arrhythmia syndromes (such as type 1 congenital long QT
syndrome, or catecholaminergic ventricular tachycardia)
• cessation of physical exercise just before TLOC may suggest1
o post-exercise hypotension in middle-aged and older persons (autonomic failure)
o vasovagal syncope in young persons, especially in trained athletes
• palpitations before TLOC may suggest1
o cardiac syncope due to arrhythmia
o postural tachycardia in vasovagal syncope or postural tachycardia syndrome
• strong emotions (other than fear) before TLOC (such as argument) may suggest1
o cardiac syncope due to catecholaminergic ventricular tachycardia (may also occur
during exercise in children and young adults)
o cataplexy
• being startled before TLOC (such as alarm clock) may suggest1
o cardiac syncope due to type 2 congenital long QT syndrome
o startle epilepsy
• fever during TLOC may suggest1
o vasovagal syncope (more common)
o cardiac syncope due to Brugada syndrome
• sleep deprivation before TLOC may suggest1
o vasovagal syncope
o epilepsy
• heat, warmth, or hot bath before TLOC may suggest1
o vasovagal syncope
o orthostatic syncope (classic type)
• flashing lights before TLOC may suggest epilepsy with photosensitivity
• arm exercise during TLOC may suggest steal syndrome (rare)1
• laughter before TLOC may suggest situational syncope (rare)1
• laughing out loud, telling jokes, or unexpectedly meeting acquaintances before TLOC may
suggest cataplexy (ask about excessive daytime sleepiness)1

Suggested etiologies of transient loss of consciousness (TLOC) based on onset of attack

• change in vision, such as seeing dark spots, loss of color vision (rare) at onset of TLOC may
suggest syncope (symptoms related to cerebral hypoperfusion and not cause of syncope)1
• change in hearing, such as sounds coming from a distance, buzzing, or ringing in ears at onset
of TLOC may suggest syncope (symptoms related to cerebral hypoperfusion and not cause of
syncope)1
 • nausea, sweating, or pallor at onset of TLOC may suggest reflex syncope (autonomic
activation)1
• pain in shoulders and neck (coat hanger pattern) at onset of TLOC may suggest orthostatic
syncope (classic type from ischemia of local muscles)1
• rising sensation from abdomen at onset of TLOC may suggest1
o epilepsy (epileptic aura)
o vasovagal syncope (uncommon)
• shout at onset of TLOC (ictal cry) may suggest epilepsy1
• rising sensation from abdomen, unpleasant smell or taste, or other phenomena specific to
subject but recurring in TLOC may suggest epilepsy (epileptic aura)1

Suggested etiologies of transient loss of consciousness (TLOC) based on witness account during event

• falling over stiff during TLOC may suggest1

o tonic phase epilepsy
o syncope (rare)
• flaccid collapse during TLOC may suggest1
o syncope (reflex syncope, including vasovagal syncope, situational syncope, and carotid
sinus syncope, orthostatic syncope, or cardiac syncope)
o atonic epilepsy (rare)
• presence of movement during TLOC may suggest1
o syncope
o epilepsy
• movements beginning before fall that are partial or one-sided may suggest epilepsy1
• movements beginning after fall may suggest1
o syncope
o epilepsy
• symmetrical, synchronous movements during TLOC may suggest epilepsy1
• asymmetrical, asynchronous movements during TLOC may suggest syncope1
• movements beginning at onset of TLOC may suggest1
o epilepsy
o syncope (usually seconds after TLOC)
• movements beginning after onset of TLOC may suggest syncope1
• duration of TLOC < 30 seconds may suggest syncope rather than epilepsy1
• duration of TLOC > 1 minute may suggest1
o epilepsy
o psychogenic non-epileptic seizures
• duration of TLOC > 5 minutes may suggest1
o psychogenic pseudosyncope
o psychogenic non-epileptic seizures
• few movement (about 10) during TLOC may suggest syncope rather epilepsy1
• many movements (> 100 or too many to count) during TLOC may suggest1
o epilepsy
o psychogenic non-epileptic seizures
• movement restricted to one limb or one side during TLOC may suggest1
o epilepsy
o syncope
• pelvic thrusting during TLOC may suggest1
o psychogenic non-epileptic seizures
o frontal lobe seizure (rare in temporal lobe seizures)
 • repeated waxing and waning in intensity and changes in movements during TLOC may
suggest psychogenic non-epileptic seizures1

Suggested etiology of transient loss of consciousness (TLOC) based on history after event

• nausea, sweating, or pallor after TLOC may suggest1

o reflex syncope (autonomic activation)
o stress response to TLOC of any cause
• clear-headed immediately after TLOC may suggest1
o syncope
o epilepsy (very rare)
• disoriented for 5-10 seconds after TLOC with memory restored once reoriented may suggest
syncope1
• confused with memory for many minutes after TLOC may suggest epilepsy1
• sleep after TLOC may suggest1
o epilepsy (initially stupor)
o reflex syncope (voluntary sleep, particularly in children)
• aching muscles not related to bruises after TLOC may suggest1
o epilepsy
o psychogenic non-epileptic seizures
• chest pain after TLOC may suggest cardiac syncope due to ischemia1

Suggested etiologies of transient loss of consciousness (TLOC) based on other features of history

• oral automatisms, such as chewing, smacking, and blinking during TLOC may suggest1
o epilepsy
o syncope (common but rarely noticed by patient)
• cyanotic face during TLOC may suggest1
o epilepsy
o cardiac syncope
• eyes open during TLOC may suggest1
o epilepsy
o syncope (eyes closed only in shallow and short-lasting syncope)
• eyes closed during TLOC may suggest1
o psychogenic pseudosyncope
o psychogenic non-epileptic seizures
o concussion
• tongue bitten during TLOC may suggest1
o epilepsy if later side of tongue (unilateral or bilateral)
o syncope if tip of tongue (rare)
o accidental falls if laceration of tongue
• urinary incontinence during TLOC may suggest1
o epilepsy
o syncope
• paresis, ataxia, and brain stem signs may suggest vertebrobasilar transient ischemic attack1
• stertorous (snoring) breathing may suggest1
o epilepsy
o syncope (only short [< 10 seconds] in deep hypoperfusion)
• head turning may suggest1
o epilepsy if prolong head turning
o syncope if < 30 seconds in deep hypoperfusion
 • sudden severe headache, later vomiting, and nuchal rigidity may suggest subarachnoid
hemorrhage1
• loss of consciousness lasting 10-30 minutes is not TLOC but instead true loss of
consciousness1
• eye fluttering during TLOC may suggest1
o psychogenic non-epileptic seizures (common)
o epilepsy (uncommon)
• bruises and other injuries may be present in all causes of TLOC1

Suggested etiologies of transient loss of consciousness (TLOC) based on past medical history

• history of heart disease may suggest cardiac syncope due to arrhythmia or structural heart
disease1
• history of hypertension may suggest orthostatic syncope due to medication or autonomic
failure1
• history of Parkinson disease may suggest orthostatic syncope due to autonomic failure1
• history of impotence and micturition for years may suggest autonomic failure if orthostatic
hypotension present1
• history of orthostatic intolerance may suggest1
o vasovagal syncope
o orthostatic syncope
o postural orthostatic tachycardia syndrome (POTS)
• history of epilepsy suggest epilepsy1
• history of structural brain damage may suggest epilepsy1
• possible history of early traumatizing events may suggest1
o psychogenic non-epileptic seizures
o psychogenic pseudosyncope
o other coincidental causes
• history of diabetes mellitus may suggest1
o cardiac syncope
o orthostatic syncope (secondary to autonomic failure)
o true loss of consciousness due to hypoglycemia if loss of consciousness for extended
duration
• history of vasovagal syncope before age 35 years may suggest vasovagal syncope (vasovagal
syncope not likely if no history of syncope before age 35 years)1
• history of similar vasovagal syncope episode in youth may suggest vasovagal syncope1

Suggested etiologies of transient loss of consciousness (TLOC) based on medication history

• recent change in medication or initiation of new medication may suggest1

o vasovagal syncope (due to volume depletion or antihypertensives)
o orthostatic syncope
• use of antidepressant or antipsychotic drugs may suggest orthostatic syncope1

Suggested etiologies of transient loss of consciousness (TLOC) based on family history

• family history of sudden death in relatives < 40 years old may suggest cardiac syncope due to1
o genetic arrhythmia
o cardiomyopathy
o thoracic aortic dissection
• family history of vasovagal syncope may suggest vasovagal syncope1
History consistent with neurally mediated syncope

• history consistent with neurally mediated syncope includes

o absence of heart disease1
o long history of recurrent syncope (usually occurring before age 40)1,2
o trigger prior to episode
▪ defecation, urination, or prolonged coughing2
▪ pain, fear, stress2
▪ heat exposure (especially in crowd)12
▪ prolonged standing1
▪ unpleasant sight, sound, or smell1
▪ during meal or post-prandial1
▪ head rotation or pressure on carotid sinus (such as shaving or tight collar)1
o onset of attack
▪ nausea1,2
▪ sweating1,2
▪ pale appearance1,2
▪ blurred or tunnel vision2
o during episode (eyewitness account)2
▪ falling over limply
▪ associated movements
▪ beginning after falling
▪ lasting < 15 seconds
▪ eyes open
o after episode2
▪ pallor, sweating, nausea
▪ prolonged fatigue
o situations where no additional testing needed for diagnosis of neurally mediated
syncope1
▪ vasovagal syncope highly probable if triggered by pain, fear, or standing and
associated with typical progressive prodrome, such as nausea, diaphoresis, or
pale appearance (ESC Class I, Level C) (see vasovagal syncope for information
on treatment)
▪ situational reflex syncope highly probable if syncope occurs during or
immediately after specific triggers, such as (ESC Class I, Level C)
▪ micturition
▪ gastrointestinal stimulation (swallowing or defecation)
▪ cough or sneeze
▪ post-exercise
▪ laughing
▪ brass instrument playing
o in absence of situations where additional testing not needed and no syncope while
standing with documented orthostatic hypotension, reflex syncope and orthostatic
syncope should be considered likely when features that suggest reflex syncope or
orthostatic syncope are present and features that suggest cardiac syncope are absent
(ESC Class IIa, Level C)1
o perform tilt testing if suspect reflex mechanism

History consistent with orthostatic syncope

• history consistent with orthostatic syncope

o presence of autonomic neuropathy or parkinsonism1
 o syncope associated with initiation or change of dosage of vasodepressive drugs or
diuretics leading to hypotension1
o possible triggers prior to episode
▪ standing quickly2
▪ prolonged standing (especially in crowded, hot places)1,2
▪ standing after exertion1,2
▪ eating1,2
▪ heat exposure2
▪ exercise2
o no additional testing needed for diagnosis of orthostatic syncope if episode related to
assuming standing position and documentation of orthostatic hypotension (ESC Class I,
Level C)1
o in absence of confirmed diagnosis of orthostatic syncope and no situations where
additional testing not needed for reflex syncope, reflex syncope and orthostatic syncope
should be considered likely when features that suggest reflex syncope or orthostatic
syncope are present and features that suggest cardiac syncope are absent (ESC Class
IIa, Level C)1
o see Orthostatic Hypotension and Orthostatic Syncope topic for additional information if
suspected

History consistent with cardiac syncope

• history consistent with cardiac syncope includes

o older age4
o male sex4
o presence of known conditions, including any
▪ structural heart disease1,4
▪ ischemic heart disease1,4
▪ arrhythmia4
▪ reduced ventricular function4
▪ congenital heart disease4
o family history of any
▪ premature sudden cardiac death (< 50 years old)1,4
▪ unexplained sudden death1
▪ channelopathy1
o lack of prodrome or brief prodrome (such as palpitations)4
o prior to episode
▪ during supine posture1,4
▪ during exercise1,2,4
▪ sudden onset of palpitations1,2
▪ startling (such as alarm clock, siren) - more likely prolonged QT syndrome
o low number of previous syncope episodes (such as 1-2)4
o abnormal cardiac exam4
o see cardiac syncope below for additional testing if suspect cardiac syncope
• cardiac syncope due to structural cardiopulmonary disorders highly probably when syncope
presents in patients with prolapsing atrial myxoma, left atrial thrombus, severe aortic stenosis,
pulmonary embolism, or acute aortic dissection (ESC Class I, Level C)1

History consistent with noncardiac cause of syncope

• history consistent with noncardiac cause of syncope4

 o younger age
o no known cardiac disease
o syncope occurring during
▪ standing position only
▪ position change from supine or sitting to standing
o syncope with trigger, including any
▪ dehydration
▪ pain
▪ distressful stimulus
▪ medical environment
▪ cough
▪ laugh
▪ micturition
▪ defecation
▪ deglutition
o prodrome symptoms, such as nausea, vomiting, or feeling warmth
o history of frequent syncope episodes with similar characteristics

Physical

• perform complete exam for all patients with syncope, including heart rate measurement
(ACC/AHA/HRS Class I, Level B-NR)4
• physical exam should include supine and standing blood pressure measurements (test of
active standing)1
• test of active standing1
o manual intermittent measurement with sphygmomanometer of blood pressure and heart
rate while supine and during active standing for 3 minutes indicated at initial syncope
evaluation (ESC Class I, Level C)
o continuous noninvasive beat-to-beat blood pressure and heart rate measurement may
be preferred when short-lived blood pressure variations suspected, such as in initial
orthostatic hypotension (ESC Class IIb, Level C)
o diagnostic criteria for orthostatic hypotension and orthostatic syncope
▪ test diagnostic for orthostatic hypotension and orthostatic syncope if symptomatic
fall in blood pressure with any of (ESC Class I, Level C)
▪ systolic blood pressure decreases by ≥ 20 mm Hg from baseline value
▪ diastolic blood pressure decreases by ≥ 10 mm Hg from baseline value
▪ systolic blood pressure < 90 mm Hg that reproduces spontaneous
symptoms
▪ test considered likely diagnostic for orthostatic hypotension and orthostatic
syncope if history consistent with orthostatic syncope and asymptomatic fall in
blood pressure with any of (ESC Class IIa, Level C)
▪ systolic blood pressure decreases by ≥ 20 mm Hg from baseline value
▪ diastolic blood pressure decreases by ≥ 10 mm Hg from baseline value
▪ systolic blood pressure < 90 mm Hg
▪ test considered likely diagnostic for orthostatic hypotension and orthostatic
syncope if not all features from history suggestive of orthostatic syncope and fall
in blood pressure with any (ESC Class IIa, Level C)
▪ systolic blood pressure decreases by ≥ 20 mm Hg from baseline value
▪ diastolic blood pressure decreases by ≥ 10 mm Hg from baseline value
▪ systolic blood pressure < 90 mm Hg
 ▪ test may be considered possibly diagnostic for orthostatic hypotension and
orthostatic syncope if features from history less consistent with orthostatic
syncope and fall in blood pressure with any (ESC Class IIb, Level C)
▪ systolic blood pressure decreases by ≥ 20 mm Hg from baseline value
▪ diastolic blood pressure decreases by ≥ 10 mm Hg from baseline value
▪ systolic blood pressure < 90 mm Hg
o test considered likely diagnostic for postural orthostatic tachycardia syndrome (POTS) if
orthostatic heart rate increase (> 30 beats/minute or to > 120 beats/minute within 10
minutes of active standing) in absence of orthostatic hypotension that reproduces
spontaneous symptoms (ESC Class IIa, Level C)
• carotid sinus massage indicated in patients < 40 years old with syncope of unknown origin
compatible with reflex mechanism (ESC Class I, Level B)1

Electrocardiogram (ECG)

• obtain resting 12-lead ECG for all patients with syncope (ACC/AHA/HRS Class I, Level B-NR)
to rule out arrhythmic cause1,4
• probability of cardiac syncope very low in young patients with normal ECG, unexplained
syncope, no history of cardiac disease, no family history of sudden cardiac death, no supine
syncope, no syncope during sleep or exercise, and no usual triggers (among persons < 35
years old, sudden cardiac death reported in 1-3 per 100,000 persons)1
• cardiac syncope due to arrhythmia highly probable if ECG findings include any (ESC Class I,
Level C)1
o persistent sinus bradycardia of < 40 beats/minute or sinoatrial pauses ≥ 3 seconds in
awake state and in absence of physical training
o Mobitz II second or third degree atrioventricular block
o alternating left and right bundle branch block
o ventricular tachycardia or rapid paroxysmal supraventricular tachycardia
o non-sustained episodes of polymorphic ventricular tachycardia and long or short QT
interval
o pacemaker or implantable cardioverter defibrillator malfunction with pauses
• cardiac syncope related to ischemia confirmed if syncope with ECG evidence of acute cardiac
ischemia with or without myocardial infarction (MI) (ESC Class I, Level C)1
• ECG findings suggestive of arrhythmic syncope1
o bifascicular block (left bundle-branch block or right bundle-branch block [RBBB] with left
anterior or left posterior fascicular block)
o intraventricular conduction abnormalities with QRS duration ≥ 120 milliseconds
o Mobitz type I second-degree atrioventricular (AV) block or first-degree AV block with
markedly prolonged PR interval
o asymptomatic mild inappropriate sinus bradycardia (heart rate 40-50 beats/minute) or
slow atrial fibrillation (40-50 beats/minute) in absence of negative chronotropic drugs
o sinoatrial block or sinus pause ≥ 3 seconds without negatively chronotropic medications
o non-sustained ventricular tachycardia
o pre-excited QRS complex
o prolonged or short QT interval
o early repolarization
o ST-elevation with type I pattern in leads V1-V3 (Brugada pattern)
o negative T waves in right precordial leads, epsilon waves suggestive of arrhythmogenic
right ventricular cardiomyopathy
o left ventricular hypertrophy suggesting hypertrophic cardiomyopathy
• see cardiac syncope below for
 o additional testing (such as ECG monitoring) for suspected arrhythmic syncope
o treatment of known cardiac syncope

Laboratory testing

• American College of Cardiology/American Heart Association/Heart Rhythm Society

(ACC/AHA/HRS) recommendations for targeted blood testing4
o targeted blood tests reasonable based on clinical assessment and findings on history
and physical exam (ACC/AHA/HRS Class IIa, Level B-NR)
o usefulness of brain natriuretic peptide and high-sensitivity troponin measurement
uncertain in patients with suspected cardiac cause of syncope (ACC/AHA/HRS Class
IIb, Level C-LD)
o routine and comprehensive blood lab testing is not useful in evaluating cause of
syncope (ACC/AHA/HRS Class III, Level B-NR)
• routine blood testing not generally indicated as part of initial testing unless there is high
suspicion of other conditions that can contribute to transient loss of consciousness, including
any
o severe anemia
o electrolyte abnormalities
o gastrointestinal hemorrhage
o hypoglycemia
o Reference - Am Fam Physician 2011 Sep 15;84(6):640EBSCOhost Full Text
• targeted blood tests to consider based on history and physical1
o hematocrit or hemoglobin if hemorrhage suspected
o oxygen saturation and blood gas analysis if hypoxia suspected
o troponin if cardiac ischemia suspected
o D-dimer when pulmonary embolism suspected
• targeted blood tests in patients with autonomic failure1
o screening for paraneoplastic antibodies and antiganglionic acetylcholine receptor
antibodies recommended if acute or subacute onset of multidomain autonomic failure
(ESC Class I, Level B) (if positive, consider additional evaluation for occult malignancy)
o in patients with autonomic failure and peripheral neuropathy, tests to consider include
▪ blood cell count
▪ fasting glucose
▪ Hb1AC
▪ anti- syndrome-associated antigen (anti-SS) A and anti-SS B antibodies
▪ neoplasm-associated antibodies (anti-Hu, anti-Purkinje cell cytoplasm antibody
type 2 [anti-PCA-2], anti-collapsin response mediator protein 5 [anti-CRMP-5])
▪ serum/urinary protein electrophoresis
▪ HIV

Clinical evaluation

• clinical exam plus electrocardiogram (ECG) may have moderate sensitivity and
specificity to identify cardiac syncope (level 2 [mid-level] evidence)
o based on systematic review of diagnostic cohort studies with unclear independence of
reference standard or exclusion of patients with unexplained syncope in some studies
o systematic review of 11 diagnostic studies evaluating performance of clinical
examination to identify cardiac syncope in 4,317 patients presenting to primary care,
emergency departments, or specialty clinics
 o studies with reference standards such as cardiology consultation, echocardiography,
Holter monitoring, loop monitoring, tilt table testing, carotid sinus massage, cardiac
catheterization, or electrophysiology were eligible for inclusion
o across studies, diagnosis of cardiac syncope ranged from 9% to 58% and no diagnosis
ranged from 3% to 37%
o Evaluation of Guidelines in Syncope Study (EGSYS) score
▪ palpitations = 4 points
▪ abnormal ECG or heart disease = 3 points
▪ effort syncope = 3 points
▪ syncope in supine position = 2 points
▪ neurovegetative prodromes = -1 point
▪ precipitating and predisposing factors = -1 point
o performance of factors for identifying cardiac syncope
Number of
Factor Patients Sensitivity Specificity
age ≥ 35 years at first syncope 323 91% 72%
range 89%- range 69%-
EGSYS score ≥ 3 points 456 91% 73%
Heart disease, abnormal ECG, or both 198 88% 61%
Cyanosis during episode 323 8% 99%
Atrial fibrillation or flutter 323 13% 98%
Prior feeling of cold 412 2% 89%
range 35%- range 84%-
Known severe structural heart disease 222 51% 93%
Mood change after syncope 323 3% 83%
Inability to remember behavior during
syncope 323 5% 82%
Prior headache 323 3% 80%
Prior mood change or prodromal
preoccupation with details 323 2% 76%
Abbreviations: ECG, electrocardiogram; EGSYS, Evaluation of Guidelines in Syncope Study.
o most useful symptoms during event to distinguish syncope from seizure
▪ head turning to identify seizure had
▪ sensitivity 43%
▪ specificity 97%
▪ likelihood ratio 14
▪ unusual positioning to identify seizure had
▪ sensitivity 35%
▪ specificity 97%
▪ likelihood ratio 13
o Reference - JAMA 2019 Jun 25;321(24):2448

Neurological evaluation

• guidelines agree that head imaging (computed tomography and magnetic resonance imaging),
carotid artery imaging, and electroencephalogram are generally not indicated during syncope
evaluation; there are specific recommendations for select situations when neurological
evaluation may be appropriate
o European Society of Cardiology (ESC) recommendation for neurological evaluation1
 ▪ neurological evaluation indicated if syncope due to autonomic failure to evaluate
underlying disease (ESC Class I, Level C)
▪ brain magnetic resonance imaging (MRI) recommended if neurological exam
indicates Parkinson disease, ataxia, or cognitive impairment (ESC Class I, Level
C)
▪ neurological tests not indicated include (ESC Class III, Level B)
▪ electroencephalogram
▪ ultrasound of neck and arteries
▪ neuroimaging (computed tomography [CT] or MRI)
o American College of Cardiology/American Heart Association/Hearth Rhythm Society
(ACC/AHA/HRS) recommendations for neurological evaluation4
▪ simultaneous monitoring of electroencephalogram and hemodynamic parameters
during tilt testing can be useful to differentiate syncope, pseudosyncope, and
epilepsy (ACC/AHA/HRS Class IIa, Level C-LD)
▪ neurological tests not recommended in routine evaluation include
(ACC/AHA/HRS Class III, Level B-NR)
▪ MRI and CT of head in absence of focal neurological findings or head
injury to support further evaluation
▪ carotid artery imaging in absence of focal neurological findings to support
further evaluation
▪ electroencephalogram in absence of specific neurological features
suggestive of seizure
o American College of Physicians recommends against obtaining brain imaging studies
(computed tomography [CT] or magnetic resonance imaging [MRI]) in the evaluation of
simple syncope and a normal neurological examination (Choosing Wisely 2012 Apr 4)
o American College of Emergency Physicians recommends avoiding CT of the head in
asymptomatic adult patients in the emergency department with syncope, insignificant
trauma and a normal neurological evaluation (Choosing Wisely 2014 Oct 27)
o American Academy of Neurology recommends against performing imaging of the
carotid arteries for simple syncope without other neurologic symptoms (Choosing
Wisely 2013 Feb 21)
o Canadian professional associations recommending against routinely obtaining neuro-
imaging studies (CT, MRI scans, or carotid doppler ultrasonography) in the evaluation of
simple syncope in patients with a normal neurological examination include
▪ Canadian Society of Hospital Medicine (Choosing Wisely Canada 2015 Jun 2)
▪ Canadian Society of Internal Medicine (Choosing Wisely Canada 2014 Apr 2)
▪ Canadian Association of Emergency Physicians (Choosing Wisely Canada 2016
Oct 3)
o Australian and New Zealand Association of Neurologists recommends against
performing imaging of carotid arteries for simple faints (Choosing Wisely Australia 2016
Oct 1 )
• EVIDENCE SYNOPSIS

Neurological testing (including head CT, EEG, and carotid artery imaging) performed as part of
a syncope workup is associated with a low diagnostic yield.

o head CT appears to have very low diagnostic yield for detecting intracranial
conditions in patients presenting to emergency department with syncope and in
patients hospitalized with syncope(level 2 [mid-level] evidence)
▪ based on systematic review of observational studies
 ▪ systematic review of 17 cohort studies (15 retrospective and 2 prospective) that
used head CT when evaluating cause of syncope in 3,361 adults with syncope
▪ 3 studies were not pooled for analysis due to heterogeneity in patient population
(2 studies with 214 patients used head CT in all patients and 1 study with 189
patients included patients aged ≥ 65 years)
▪ pooled diagnostic yield for detecting intracranial condition was low in all studies
▪ 3.8% (95% CI 3%-5%) in analysis of 8 studies with 1,669 patients
presenting to emergency department with syncope (pooled portion of
patients having head CT 54.4%, 95% CI 35%-73%)
▪ 1.2% (95% CI 0.5%-2%) in analysis of 6 studies with 1,289 patients
hospitalized with syncope (pooled portion of patients having head CT
45%, 95% CI 26%-64%)
▪ Reference - Acad Emerg Med 2019 Apr 22; early online
o neurologic tests may have low diagnostic yield
▪ based on retrospective cohort study
▪ 649 consecutive adult patients hospitalized with the principal diagnosis of
syncope, no control over what tests were ordered, not all patients had all tests
▪ postural blood pressure yielded diagnoses in 52 patients (30% of those tested)
▪ tilt table test yielded diagnoses in 32 patients (24% of those tested)
▪ electrophysiologic study yielded diagnoses in 5 patients (16% of those tested)
▪ brain computed tomography yielded diagnoses in 5 patients (2% of those tested),
all with history consistent with seizures or stroke
▪ EEG yielded diagnoses in 6 patients (2% of those tested), all with history
consistent with seizures or stroke
▪ carotid Doppler echocardiography in 185 patients did not yield any diagnoses
▪ Reference - Arch Intern Med 2001 Aug 13-27;161(15):1889EBSCOhost Full
Textfull-text
o many tests appear to have low diagnostic yield in syncope evaluation
▪ based on retrospective cohort study
▪ review of 2,106 admissions in 1,920 patients > 65 years old admitted following
syncopal episode
▪ test with highest (18%-26%) diagnostic yield was postural blood pressure
recording
▪ tests with < 5% diagnostic yield included
▪ cardiac enzymes
▪ CT scans
▪ echocardiography
▪ carotid ultrasound
▪ electroencephalography (EEG)
▪ Reference - Arch Intern Med 2009 Jul 27;169(14):1299EBSCOhost Full Textfull-
text, editorial can be found in Arch Intern Med 2009 Jul
27;169(14):1305EBSCOhost Full Text
• see also Epilepsy in Adults

Syncope of Unknown Cause (Cryptogenic Syncope) after Initial

Evaluation in Emergency Department
Risk Assessment

General information and recommendations from professional organizations

 • about 10% of patients presenting to emergency department with syncope reported to develop
serious outcomes within 7-10 days, of whom almost half experience event during stay in
emergency department1
• risk assessment goals1
o identify patients at high risk for developing serious outcomes to reducing mortality risk
o patients with high risk of sudden cardiac death require disease specific treatment to
reduce risk of death or life threatening events
o identify patients at low risk for developing serious outcomes who likely have reflex,
situational, or orthostatic syncope and can be safely discharged from emergency
department
• American College Cardiology/American Heart Association/Heart Rhythm Society
(ACC/AHA/HRS) recommendations4
o perform risk assessment for short- and long-term morbidity and mortality associated
with syncope (ACC/AHA/HRS Class I, Level B-NR)
o risk stratification scores may be reasonable in management of syncope (ACC/AHA/HRS
Class IIb, Level B-NR)
• European Society of Cardiology (ESC) recommendations1
o risk stratification scores may be considered for risk stratification in emergency
department (ESC Class IIb, Level B) but should be used in combination with clinical
judgement
o diagnostic radiology and laboratory tests (such as chest x-ray, brain computed
tomography, routine blood tests, biochemistry, D-dimer, and cardiac biomarkers should
not routinely be used unless specifically suggested by clinical evaluation due to low
diagnostic yield and low impact on risk stratification
• if cause of syncope unclear or unknown after initial evaluation, assess risk of short-term (1
week to 1 month) major cardiac events (such as sudden cardiac death)
o admit high risk patients to hospital for immediate evaluation and treatment
o consider placing intermediate risk patients in syncope observation unit if available
o refer low risk patients to outpatient care (preferably in syncope specialized clinic)
o Reference - J Cardiol 2014 Mar;63(3):171
• some patients at high risk of long-term (up to 1 year) major cardiac events may need
hospitalization for further evaluation (J Cardiol 2014 Mar;63(3):171)

Factors associated with short-term serious outcomes and longer hospitalization

• factors associated with increased likelihood of short-term (≤ 30 days) adverse outcomes and
usually resulting in hospitalization include4
o history
▪ older age
▪ male sex
▪ lack of prodrome
▪ palpitations before loss of consciousness
▪ exertional syncope
▪ medical conditions, including
▪ acute coronary syndrome (ACS) or symptoms suggestive of ACS
associated with syncope (J Cardiol 2014 Mar;63(3):171)
▪ heart failure
▪ structural heart disease
▪ cerebrovascular disease
▪ family history of sudden cardiac death
▪ trauma
o physical exam or lab test
 ▪ ECG abnormalities
▪ evidence of bleeding
▪ persistent abnormal vital signs
▪ positive troponin
• factors associated with increased risk of long-term (> 30 days) adverse outcomes4
o history
▪ male sex
▪ older age
▪ lack of prodrome
▪ medical conditions, including
▪ ventricular arrhythmias
▪ cancer
▪ structural heart disease
▪ heart failure
▪ cerebrovascular disease
▪ diabetes mellitus
▪ high CHADS-2 score
o physical exam or lab tests
▪ ECG abnormalities
▪ low glomerular filtration rate (GFR)
• age > 60 years associated with increased 14-day risk of serious clinical events after
syncope
o based on prospective cohort study
o 477 adults presenting to emergency department with syncope or near-syncope were
included
o 463 (97%) followed up at 14 days
o 47% were > 60 years old
o 17% had serious clinical events (such as death, arrhythmia, and stroke among others)
within 14 days
o compared to patients aged 18-39 years, risk for serious clinical events
▪ increased for patients aged 60-79 years (adjusted OR 3.8, 95% CI 1.3-12)
▪ increased for patients > 80 years old (adjusted OR 3.8, 95% CI 1.2-12)
▪ nonsignificantly increased for patients aged 40-59 years (adjusted odds ratio
[OR] 2.7, 95% CI 0.9-8.4)
o Reference - J Am Geriatr Soc 2007 Jun;55(6):907
• factors associated with decreased likelihood of short length of stay (≤ 1 day) in prospective
cohort study of adults hospitalized for syncope
o 350 adults (mean age 57 years, 60.4% women) hospitalized for syncope included
o length of stay was
▪ ≤ 1 day for 179 patients (mean age 66 years), of whom 27 were admitted to
syncope observation unit
▪ median 3 days (range 2-5 days) for 171 patients (mean age 72 years)
o clear vasovagal cause of syncope was associated with increased likelihood of length of
stay ≤ 1 day (adjusted odds ratio [OR] 1.92, 95% CI 1.09-3.38)
o factors associated with decreased likelihood of short length of stay (≤ 1 day) included
▪ dysrhythmia (adjusted OR 0.3, 0.14-0.67)
▪ coronary artery disease (adjusted OR 0.33, 95% CI 0.19-0.56)
▪ abnormal vital signs (adjusted OR 0.35, 95% CI 0.14-0.85)
▪ implantable cardioverter defibrillator/pacemaker device (adjusted OR 0.29, 95%
CI 0.1-0.85)
▪ anemia/gastrointestinal bleed (adjusted OR 0.34, 0.13-0.92)
▪ central nervous system abnormalities (adjusted OR 0.09, 95% CI 0.01-0.8)
 o Reference - Am J Emerg Med 2015 Nov;33(11):1684
• cardiac biomarkers (high-sensitivity cardiac troponin [hscTnT or hscTnI], B-type natriuretic
peptide [BNP], N-terminal proBNP [NT-proBNP])
O EVIDENCE SYNOPSIS

The use of cardiac biomarkers (including BNPs and troponins) to predict major adverse
cardiovascular events (MACE) in patients with syncope has been evaluated in multiple
cohort studies. Although these studies are promising, none have been validated.
▪ elevated natriuretic peptides (BNP and NT-proBNP) might have moderate
performance for predicting major adverse cardiac events (MACE) at 30
days and elevated high-sensitivity troponin may have fair performance in
patients presenting to emergency department or hospitalized with
syncope(level 2 [mid-level] evidence)
▪ based on systematic review of prognostic cohort studies without validation
and with clinical heterogeneity
▪ systematic review of 10 prognostic studies (7 prospective and 3
retrospective) evaluating cardiac biomarkers for predicting MACE at 30
days in 4,246 patients presenting to emergency department or
hospitalized with syncope
▪ 4 studies evaluated natriuretic peptides (BNP or NT-proBNP), 3 studies
evaluated high-sensitivity troponin I or T, and 4 studies evaluated troponin
I or T
▪ cardiac biomarker threshold used for predicting MACE varied across
studies
▪ pooled performance for predicting MACE at 30 days
▪ for natriuretic peptides in analysis of 4 studies with 1,353 patients
▪ pooled sensitivity 77% (95% CI 69%-85%)
▪ pooled specificity 73% (95% CI 70%-76%)
▪ for high-sensitivity troponin I or T in analysis of 3 studies with 819
patients
▪ pooled sensitivity 74% (95% CI 65%-83%)
▪ pooled specificity 65% (95% CI 62%-69%)
▪ for troponin I or T in analysis of 4 studies with 2,693 patients
▪ pooled sensitivity 29% (95% CI 24%-34)
▪ pooled specificity 88% (95% CI 86%-89%)
▪ Reference - Intern Emerg Med 2015 Dec;10(8):1003
▪ elevated cardiac biomarkers (hscTnT, hscTnI, BNP, and NT-proBNP) might
have moderate performance for predicting death and MACE at 30 days and
720 days in patients presenting to emergency department with
syncope (level 2 [mid-level] evidence)
▪ based on prognostic cohort study without validation
▪ 1,538 adults > 45 years old presenting to emergency department with
syncope had cardiac biomarkers measured (hscTnT, hscTnI, BNP, and
NT-proBNP) and were followed for 2 years
▪ primary outcome was death or major adverse cardiac events
(MACE) at 30 days and 720 days
▪ MACE were defined as death, cardiopulmonary resuscitation, life-
threatening arrhythmias, implantation of pacemaker or implantable
cardioverter defibrillator, acute myocardial infarction, pulmonary
embolism, stroke or transient ischemic attack, intracranial bleeding,
or valvular surgery
 ▪ follow-up was complete in 100% at 30 days, 99.7% at 360 days, and
83.2% at 720 days
▪ death occurred in 14.2% and ≥ 1 MACE event occurred in 28.8%
▪ elevated BNP and NT-proBNP levels were associated with significantly
increased risk of death and MACE
▪ for predicting death at 30 days and at 720 days, all cardiac biomarkers
had moderate performance (area under receiver operator curve 0.71-0.8)
▪ for predicting MACE at 30 days and 720 days, all cardiac biomarkers had
moderate performance (area under receiver operator curve 0.7-0.78)
▪ Reference - Circulation 2019 Feb 25 early online
▪ elevated hscTnT and elevated NT-proBNP each associated with increased
risk of all-cause mortality or serious cardiac events at 30 days in older
patients presenting to emergency department with syncope or presyncope
▪ based on prospective cohort study
▪ 3,392 older adults (≥ 60 years old) presenting to emergency department
with syncope or presyncope had hscTnT and NT-proBNP levels measured
and were followed for 30 days
▪ all patients had standard evaluation that included history, physical, and
12-lead electrocardiogram (ECG)
▪ primary outcome was composite outcome of all-cause mortality and
serious cardiac events at 30 days that were not identified during initial visit
▪ serious cardiac events were defined as sustained ventricular
arrhythmias (> 30 seconds), symptomatic ventricular tachycardia,
third-degree or Mobtiz type II atrioventricular block, symptomatic
ventricular tachycardia pacemaker/defibrillator malfunctions,
symptomatic bradycardia (heart rate ≤ 40 beats/minute), myocardial
infarction, new diagnosis of severe aortic stenosis (area ≤ 0.9 cm 2),
severe pulmonary hypertension, hypertrophic cardiomyopathy or
atrial mass causing outflow obstruction, aortic dissection, and
pulmonary embolism
▪ symptomatic was defined as simultaneous occurrence of dizziness,
lightheadedness, hypotension, or syncope with arrhythmia on ECG
monitoring
▪ 80% of patients were hospitalized and 10.8% of patients had primary
event
▪ elevated hscTnT and elevated NT-proBNP levels were associated with
increased risk of primary outcome
▪ adjusted absolute risk 29% (95% CI 26%-33%) for hscTnT > 50
ng/L
▪ adjusted absolute risk 29% (95% CI 25%-32%) for NT-proBNP >
2,000 ng/L
▪ Reference - Acad Emerg Med 2019 Feb 5; early online

European Society of Cardiology (ESC) proposed risk stratification based on initial syncope evaluation

• proposed risk stratification based on initial syncope evaluation with history, physical, and
electrocardiography (ECG)
Feature High-Risk Features Low-Risk Features
o Syncope associated with
o New-onset of chest discomfort, prodrome typical of reflex
Syncope event abdominal pain, or headache syncope (such as
 Feature High-Risk Features Low-Risk Features
o Syncope during exertion or in lightheadedness, feeling of
supine position warmth, sweating, nausea,
o Sudden onset palpitations vomiting)
immediately followed by syncope o Syncope after sudden
o No warning symptoms or short (< unexpected unpleasant sight,
10 seconds) prodrome in patients sound, smell, or pain
with structural heart disease or o Syncope after prolonged
abnormal ECG standing or crowded, hot
o Syncope when in sitting position places
in patients with structural heart o Syncope during a meal or post-
disease or abnormal ECG prandial
o Syncope triggered by cough,
defecation, or micturition
o Syncope with head rotation or
pressure on carotid sinus (such
as tumor, shaving, or tight
collars)
o Syncope after standing from
supine/sitting position
o Severe structural or coronary o Long history (years) of
artery disease, such as heart recurrent syncope with low-
failure, reduced LVEF, or previous risk features with same
myocardial infarction) characteristics of current
o Family history of SCD at young episode
Past medical age in patients with structural o Absence of structural heart
history heart disease or abnormal ECG disease
o Unexplained systolic blood
pressure < 90 mm Hg in
emergency department
o Suggestion of gastrointestinal
bleed on rectal exam
o Persistent bradycardia (< 40
beats/minute) in awake state and
in absence of physical training
Physical exam o Undiagnosed systolic murmur Normal physical exam
o ECG findings consistent with
ischemia
o Mobitz type II second-degree and
third-degree AV block
o Slow atrial fibrillation (< 40
beats/minute)
o Persistent sinus bradycardia (<
40 beats/minute) or repetitive
sinoatrial block or sinus pauses >
3 seconds in awake state and in
absence of physical training
o Bundle branch block,
intraventricular conduction
ECG disorders, ventricular Normal ECG
 Feature High-Risk Features Low-Risk Features
hypertrophy, or Q wave
consistent with ischemia or
cardiomyopathy
o Ventricular tachycardia
(sustained or unsustained)
o Pacemaker or ICD malfunction
o Type I Brugada pattern
o ST elevation with type I
morphology in leads V1-V3
(Brugada pattern)
o QTc > 460 milliseconds in
repeated 12-lead ECGs indicating
long QT syndrome
o Mobitz type I AV block and first-
degree AV block with markedly
prolonged PR interval
o Asymptomatic mild inappropriate
sinus bradycardia (40-50
beats/minute) or slow atrial
fibrillation (40-50 beats/minute)
o Paroxysmal SVT or atrial
fibrillation
o Pre-excited QRS complex
o Short QTc interval (≤ 340
milliseconds)
ECG in patients o Atypical Brugada pattern
with history o Negative T waves in right
consistent with precordial leads, epsilon waves
arrhythmic suggestive of arrhythmogenic
syncope right ventricular cardiomyopathy N/A
Abbreviations: AV, atrioventricular; ECG, electrocardiogram; ICD, implantable cardioverter
defibrillator; LVEF, left ventricular ejection fraction; N/A, not applicable; QTc, corrected QT; SCD,
sudden cardiac death; SVT, supraventricular tachycardia.
Table 1. European Society of Cardiology (ESC) Proposed High-Risk Features that Suggest Serious
Cause of Syncope and Low-Risk Features that Suggest Benign Cause of Syncope

San Francisco Syncope Rule

• San Francisco Syncope Rule uses CHESS mnemonic to identify 5 risk factors for developing
short-term serious outcomes (such as death, myocardial infarction, arrhythmia, pulmonary
embolism, and stroke among others)
o Congestive heart failure (history of or present at time of evaluation)
o Hematocrit < 30%
o Electrocardiogram (ECG) abnormalities (any nonsinus rhythm or any new changes)
o Shortness of breath
o Systolic blood pressure < 90 mm Hg
o Reference - J Cardiol 2014 Mar;63(3):171
• San Francisco Syncope Rule may rule out serious outcomes at 7 days in patients
presenting to emergency department with syncope or near-syncope (level 2 [mid-level]
evidence)
 o based on prognostic derivation cohort without external validation
o 684 patients (mean age 62 years, range 10-102 years) presenting to emergency
department with syncope or near-syncope were assessed
o serious outcomes were death, myocardial infarction (MI), arrhythmia, pulmonary
embolism, stroke, subarachnoid hemorrhage, significant hemorrhage, or any other
condition likely to result in return emergency department visit
o San Francisco Syncope Rule based on 5 risk factors significantly associated with
increased risk of serious outcomes (CHESS mnemonic)
o 79 patients (11.5%) had serious outcome at 7 days
o for predicting serious outcome, presence of at least 1 CHESS risk factor had
▪ sensitivity 96%
▪ specificity 62%
▪ positive predictive value 25%
▪ negative predictive value 99.2%
o Reference - Ann Emerg Med 2004 Feb;43(2):224, editorial can be found in Ann Emerg
Med 2004 Feb;43(2):233, commentary can be found in Ann Emerg Med 2004
Oct;44(4):422
• San Francisco Syncope Rule appears to have high sensitivity for predicting serious
adverse outcomes within 7 days in Asian patients with syncope (level 2 [mid-level]
evidence)
o based on validation cohort study with incomplete data
o 1,250 patients > 12 years old (mean age 47 years) presenting to emergency department
with syncope or near-syncope in Singapore (62% Chinese, 20% Malay, 10% Indian,
and 7.6% other races) were assessed
▪ 1,194 patients with complete data were included in primary analysis
▪ 55 patients who were lost to follow-up or had missing outcome or risk factor data
were included in sensitivity analysis
o serious outcomes were death, arrhythmia, myocardial infarction, acute pulmonary
edema, clinically significant heart disease, pulmonary embolism, major cardiac
procedure, stroke, subarachnoid hemorrhage, major bleeding, or anemia
o 138 patients (11.6%) had serious outcome within 7 days
o presence of ≥ 1 CHESS risk factor had sensitivity 94.2% and specificity 50.8% for
prediction of serious outcome at 7 days
o in sensitivity analysis with worst-case scenario assumptions for missing data, sensitivity
reduced to 82%
o Reference - Acad Emerg Med 2013 May;20(5):487, editorial can be found in Acad
Emerg Med 2013 May;20(5):503
• San Francisco Syncope Rule may have moderate sensitivity for identifying patients with
syncope who are at risk for serious outcome within 30 days (level 2 [mid-level]
evidence)
o based on systematic review limited by heterogeneity
o systematic review of 12 cohort studies evaluating accuracy of San Francisco Syncope
Rule for predicting serious outcome within 30 days in 5,684 patients presenting to the
emergency department with syncope
o time of outcome evaluation was 7 days in 5 studies, 10 days in 1 study, 30 days in 4
studies, 3 months in 1 study, and not reported in 1 study
o overall prevalence of serious outcome 11% (range 5%-26%)
o performance of San Francisco Syncope for prediction of serious outcome within 30 days
 Number of
Pooled Pooled Pooled Pooled Studies
Patients Sensitivity Specificity PPV NPV Analyzed
19% (95% 96% (95%
85% (95% CI 51% (95% CI CI 13%- CI 93%-
Presenting with syncope 76%-92%) 39%-64%) 26%) 98%) 9
For whom no cause of
syncope was identified 9% (95% 99% (95%
after emergency 88% (95% CI 54% (95% CI CI 6%- CI 98%-
department evaluation 70%-96%) 44%-63%) 13%) 99%) 5
Abbreviations: NPV, negative predictive value; PPV, positive predictive value.
Table 2. Results
o all analyses limited by heterogeneity
o Reference - CMAJ 2011 Oct 18;183(15):E1116EBSCOhost Full Textfull-text, editorial can
be found in CMAJ 2011 Oct 18;183(15):1694EBSCOhost Full Text
• San Francisco Syncope rule may help to predict mortality up to 1 year
o based on cohort of 1,418 patients with syncope presenting to emergency department
and followed for 1.5 years
o all-cause mortality was 4.3% at 6 months and 7.6% at 1 year
o San Francisco Syncope Rule positive if patient has ≥ 1 of these risk factors
▪ history heart failure
▪ hematocrit < 30%
▪ abnormal ECG (new changes or nonsinus rhythm)
▪ complaint of shortness of breath
▪ systolic blood pressure < 90 mm Hg at triage
o at 6 months San Francisco rule had
▪ 100% sensitivity and 52% specificity for predicting deaths possibly related to
syncope
▪ 89% sensitivity and 53% specificity for predicting all-cause mortality
o at 12 months San Francisco rule had
▪ 93% sensitivity and 53% specificity for predicting deaths possibly related to
syncope
▪ 83% sensitivity and 54% specificity for predicting all-cause mortality
o Reference - Ann Emerg Med 2008 May;51(5):585

Other risk models

• Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score predicts
mortality within 12 months of syncopal episode (level 1 [likely reliable] evidence)
o based on prognostic cohort study with independent derivation and validation cohorts
o derivation cohort included 270 consecutive patients (mean age 60 years) presenting to
emergency department with syncope
o validation cohort included 328 consecutive patients (mean age 58 years) with syncope
o 1 point assigned for each of 4 risk factors
▪ abnormal electrocardiogram (ECG)
▪ history of cardiovascular disease
▪ lack of prodrome
▪ age > 65 years
o death at 1 year increased in validation cohort with increasing score
▪ 1 point associated with 0.6% mortality
▪ 2 points associated with 14% mortality
 ▪ 3 points associated with 29% mortality
▪ 4 points associated with 52.9% mortality
o OESIL risk score had strong discrimination in derivation (c-statistic 0.9) and validation
(c-statistic 0.9) cohorts
o Reference - Eur Heart J 2003 May;24(9):811full-text
• Risk stratification of syncope in the emergency department (ROSE) rule may predict
serious outcomes within 1 month of syncope (level 2 [mid-level] evidence)
o based on prognostic derivation cohort study without external validation
o derivation cohort included 529 patients presenting to emergency department with
syncope
o serious outcome defined as any of the following within 1 month
▪ death
▪ acute MI
▪ life-threatening arrhythmia
▪ decision to implant pacemaker or cardiac defibrillator
▪ pulmonary embolism
▪ stroke
▪ intracranial hemorrhage
▪ subarachnoid hemorrhage
▪ hemorrhage requiring blood transfusion ≥ 2 units
▪ acute surgical procedure
▪ acute endoscopic intervention
o serious outcome in 7.6% in derivation cohort and 7.2% in validation cohort
o ROSE rule developed using 7 independent predictors of serious outcome (BBRACES
mnemonic)
▪ Brain natriuretic peptide (BNP) level ≥ 300 pg/mL
▪ Bradycardia ≤ 50 beats/minute
▪ Rectal exam showing fecal occult blood (if suspicion of gastrointestinal bleed)
▪ Anemia with hemoglobin ≤ 9 g/dL (90 g/L)
▪ Chest pain associated with syncope
▪ ECG showing Q wave (not in lead III)
▪ Saturation of oxygen ≤ 94% on room air
o internal validation cohort included 550 patients presenting to same emergency
department with syncope (538 with complete data included in analysis)
o ROSE rule predicted serious outcome in validation cohort with
▪ sensitivity 87.2%
▪ specificity 65.5%
▪ positive predictive value 16.5%
▪ negative predictive value 98.5%
▪ positive likelihood ratio 2.5
▪ negative likelihood ratio 0.2
o Reference - ROSE study (J Am Coll Cardiol 2010 Feb 23;55(8):713) full-text
o Rose rule may not predict serious outcomes within 1 year of syncope (Ann Emerg Med
2011 Sep;58(3):250)
• risk classification system may predict arrhythmia or mortality within 12 months in
patients presenting to emergency department with syncope (level 2 [mid-level]
evidence)
o based on prognostic derivation cohort without external validation
o derivation cohort included 252 patients with syncope presenting to emergency
department
o internal validation cohort included 374 patients with syncope were validation cohort
o increased risk for arrhythmias or death within first year associated with
 ▪ abnormal ECG (odds ratio [OR] 3.2, 95% CI 1.6-6.4)
▪ history of ventricular arrhythmia (OR 4.8, 95% CI 1.7-13.9)
▪ history of congestive heart failure (OR 3.1, 95% CI 1.3-7.4)
▪ age > 45 years (OR 3.2, 95% CI 1.3-8.1)
o comparing patients with 3-4 risk factors vs. patients without risk factors, arrhythmias or
death within 1 year occurred in
▪ 80.4% vs. 7.3% in derivation cohort (no p value reported)
▪ 57.6% vs. 4.4% in validation cohort (no p value reported)
o Reference - Ann Emerg Med 1997 Apr;29(4):459, editorial can be found in Ann Emerg
Med 1997 Apr;29(4):540

Treatment setting

Recommendations (including indications for hospitalization)

• American College of Cardiology/American Heart Association/Heart Rhythm Society

(ACC/AHA/HRS) recommendations for treatment setting based on initial evaluation4
o hospitalize patients for evaluation if any serious medical condition relevant to cause of
syncope is identified during initial evaluation (ACC/AHA/HRS Class I, Level B-NR)
o reasonable to manage presumptive neurally mediated syncope in outpatient setting
(ACC/AHA/HRS Class IIa, Level C-LD)
o in patients with unclear cause of syncope and intermediate risk, emergency department
syncope management unit can be effective for reducing hospital admission
(ACC/AHA/HRS Class IIa, Level B-R)
o consider managing select patients with suspected cardiac syncope in outpatient setting
if serious medical conditions absent (ACC/AHA/HRS Class IIb, Level C-LD)
o serious medical conditions relevant to cause of syncope include
▪ arrhythmias and conduction disorders
▪ sustained or symptomatic ventricular tachycardia
▪ symptomatic conduction disorder, such as Mobitz type II or third-degree
atrioventricular AV) block
▪ symptomatic bradycardia or sinus pauses not related to neutrally mediated
syncope
▪ symptomatic supraventricular tachycardia (SVT)
▪ malfunction of pacemaker or implantable cardioverter defibrillation (ICD)
▪ inheritable cardiovascular disease associated with arrhythmia
▪ cardiac or vascular conditions
▪ cardiac ischemia
▪ severe aortic stenosis
▪ cardiac tamponade
▪ hypertrophic cardiomyopathy
▪ severe prosthetic valve dysfunction
▪ pulmonary embolism
▪ aortic dissection
▪ acute heart failure
▪ moderate-to-severe left ventricular dysfunction
▪ noncardiac conditions
▪ severe anemia
▪ gastrointestinal bleeding
▪ major traumatic injury due to syncope
▪ persistent abnormal vital signs
 • European Society of Cardiology (ESC) recommendations for treatment setting based on risk
classification (high-risk or low-risk) from initial evaluation1
o in patients with low-risk features who are likely to have reflex, situational or orthostatic
syncope, discharge from emergency department recommended (ESC Class I, Level B)
o in patients with high-risk features
▪ recommended options include (ESC Class I, Level B)
▪ early intensive and prompt evaluation in syncope management unit or
emergency department (if available)
▪ hospital admission
▪ factors favoring syncope management unit or emergency department include
▪ stable, known structural heart disease
▪ severe chronic disease
▪ syncope during exertion
▪ syncope while supine or sitting
▪ palpitations at time of syncope
▪ inadequate sinus bradycardia or sinoatrial block
▪ suspected device malfunction or inappropriate intervention
▪ pre-excited QRS complex
▪ supraventricular tachycardia or paroxysmal atrial fibrillation
▪ electrocardiogram (ECG) suggesting inherited arrhythmia syndromes
▪ ECG suggest arrhythmogenic right ventricular cardiomyopathy
▪ factors favoring hospital admission include
▪ any potentially severe coexisting disease that requires admission
▪ injury caused by syncope
▪ need for further urgent evaluation or treatment if cannot be achieved in
another way (such as observation unit) (additional evaluation may include
ECG monitoring, echocardiography, stress test, electrophysiological
testing, angiography, or device malfunction)
▪ need for treatment of syncope
o in patients with neither low- or high-risk features, observation in emergency department
or syncope management unit recommended instead of hospital admission (ESC Class I,
Level B)
o in patients with implantable cardioverter defibrillator (ICD), prompt device interrogation
should be performed to reduce inappropriate hospital admissions

Syncope management unit

• syncope management units feature standardized approach to diagnosis and management of

transient loss of consciousness and related symptoms and have dedicated staff and access to
appropriate tests and therapies1
• syncope management unit goals include1
o assess symptoms using guideline directed methods to diagnose cause of syncope and
stratify patients based on risk of major cardiac events
o provide comprehensive management and follow-up
o reduce hospitalization
o set standards of care
• European Heart Rhythm Association (EHRA) position statement on syncope unit can be found
in Europace 2015 Sep;17(9):1325EBSCOhost Full Text
• evaluation in emergency department syncope unit may reduce hospital admission rate
in patients at intermediate risk of short-term adverse events (level 2 [mid-level]
evidence)
o based on 2 randomized trials with allocation concealment not stated
 o 103 patients (mean age 64 years) with syncope at intermediate risk of short-term
adverse events and hospital admission after initial emergency department evaluation
were randomized to syncope unit in emergency department vs. standard care
▪ comparing syncope unit vs. standard care
▪ initial diagnosis in 67% vs. 10% (p < 0.001)
▪ hospital admission required in 43% vs. 98% (p < 0.001)
▪ survival in 97% vs. 90% (not significant)
▪ Reference - Circulation 2004 Dec 14;110(24):3636full-text, editorial can be found
in Circulation 2004 Dec 14;110(24):3621
o 124 patients ≥ 50 years old with unexplained syncope or near syncope at intermediate
risk of short-term adverse events after initial emergency department (ED) evaluation
were randomized to ED observation syncope protocol for up to 24 hours vs. routine
inpatient admission and followed for 6 months
▪ ED observation syncope protocol associated with reduced hospital admission
(relative risk [RR] 0.16, 95% CI 0.09-0.29) and shorter hospital length of stay
(mean difference -18 hours, 95% CI -28 to -8)
▪ no significant difference in serious clinical outcomes during hospital stay (such as
mortality, arrhythmia, and pacemaker implantation)
▪ Reference - Ann Emerg Med 2014 Aug;64(2):167
• decision-making software based on European Society of Cardiology guidelines for diagnosing
syncope
o decision-making software based on European Society of Cardiology guidelines
for diagnosing syncope may reduce hospitalization rates and length of stay
compared to usual care (level 2 [mid-level] evidence)
▪ based on cohort study
▪ 1,674 adults attending to emergency department for suspected syncope included
▪ 745 were evaluated by trained physician using decision-making software
based on 2009 European Society of Cardiology guidelines for diagnosing
syncope (standard care)
▪ 929 were evaluated using usual procedures (usual care)
▪ comparing standard care vs. usual care
▪ hospital admission rate 39% vs. 47% (p = 0.001)
▪ hospital length of stay 7.2 vs. 8.1 days (p = 0.04)
▪ mean tests performed 2.6 vs. 3.4 (p = 0.001)
▪ diagnosis (p = 0.001 for all)
▪ neurally mediated syncope in 65% vs. 46%
▪ orthostatic syncope in 10% vs. 6%
▪ pseudo-syncope in 6% vs. 13%
▪ unexplained syncope in 5% vs. 20%
▪ Reference - Europace 2006 Aug;8(8):644EBSCOhost Full Textfull-text
o decision-making software based on European Society of Cardiology guidelines
for diagnosing syncope appears to diagnose 50% of patients admitted to
emergency services with suspected syncope
▪ based on cohort study
▪ 465 of 541 consecutive patients admitted to emergency services for syncope or
suspected syncope were evaluated using decision-making software based on
2009 European Society of Cardiology guidelines for diagnosing syncope
▪ 50% diagnosed from initial evaluation consisting of history, physical exam, and
standard electrocardiogram
▪ 182 of 193 patients diagnosed with additional testing
▪ Reference - Eur Heart J 2006 Jan;27(1):76full-text, editorial can be found in Eur
Heart J 2006 Jan;27(1):7
• standardized testing protocols may have > 70% diagnostic yield for syncope patients
o based on 3 cohort studies
o standardized clinical evaluation with additional targeted testing reported to have
76% diagnostic yield
▪ based on cohort study of 650 unselected patients presenting to emergency
department with syncope
▪ 492 patients (76%) diagnosed with initial evaluation and additional target testing
▪ 443 with initial evaluation
▪ 245 with history and clinical exam
▪ 156 with orthostatic blood pressure measurements
▪ 33 with 12-lead electrocardiogram (ECG)
▪ 4 with carotid sinus massage
▪ 5 with lab tests
▪ 49 of 67 patients with suspected causes confirmed with additional targeted
testing
▪ 122 of 155 patients with unknown cause of syncope after initial evaluation had
extensive cardiovascular testing, which led to diagnosis in only 30 patients (25%
of those tested)
▪ 11 with tilt testing
▪ 9 with Holter monitor
▪ 3 with ambulatory loop recorder
▪ 7 with electrophysiological studies
▪ Reference - Am J Med 2001 Aug 15;111(3):177, commentary can be found in J
Fam Pract 2001 Dec;50(12):1020EBSCOhost Full Text, ACP J Club 2002 Mar-
Apr;136(2):77EBSCOhost Full Text
o selective use of electrophysiologic study and tilt table testing reported to have
78% diagnostic yield
▪ based on cohort of 184 patients with syncope of unknown etiology after history,
physical exam, ECG, carotid sinus massage, orthostatic vital sign testing, and
24-hour Holter monitoring
▪ 72 patients with high risk for arrhythmic causes (structural heart disease, family
history of sudden death, abnormal ECG, significant abnormalities on Holter
monitoring, or paroxysmal palpitations) had electrophysiologic testing followed by
tilt table testing if electrophysiologic testing negative
▪ 112 low-risk patients had tilt table testing
▪ diagnosis achieved
▪ overall in 143 patients (78%)
▪ in 76% of high risk patients
▪ 44% with electrophysiologic testing
▪ 32% with tilt table testing
▪ in 80% of low risk patients
▪ Reference - J Am Coll Cardiol 2003 Mar 5;41(5):787, commentary can be found
in J Am Coll Cardiol 2003 Mar 5;41(5):791
o diagnostic algorithm reported to have 83% diagnostic yield
▪ based on cohort of 195 patients aged 13-95 years (mean age 62.5 years)
presenting with syncope to 9 emergency departments in Italy were evaluated
using a diagnostic algorithm
▪ initial evaluation included history, physical exam, 12-lead
electrocardiogram (ECG), and blood tests (hemoglobin count and glucose
test)
▪ if initial evaluation not diagnostic, additional testing based on initial
findings may have included echocardiogram, carotid sinus massage,
 head-up tilt testing, electroencephalogram, brain imaging, or carotid
Doppler ultrasound
▪ diagnosis achieved in 161 patients (83%)
▪ 27% with initial evaluation
▪ 73% with additional testing
▪ Reference - OESIL 2 trial Eur Heart J 2000 Jun;21(11):935full-text, editorial can
be found in Eur Heart J 2000 Jun;21(11):877

Additional Testing and Treatment for Neurally Mediated Syncope

Tilt testing

• also called tilt table testing1

• indications
o American College of Cardiology/American Heart Association/Heart Rhythm Society
(ACC/AHA/HRS) recommendations for tilt testing4
▪ consider tilt testing in patients with
▪ suspected vasovagal syncope (ACC/AHA/HRS Class IIa, Level B-R)
▪ suspected delayed orthostatic hypotension (ACC/AHA/HRS Class IIa,
Level B-NR)
▪ tilt testing not recommended to predict response to medical therapy in patients
with vasovagal syncope (ACC/AHA/HRS Class III, Level B-R)
▪ tilt testing reasonable to
▪ differentiate conclusive syncope from epilepsy in select patients
(ACC/AHA/HRS Class IIa, Level B-NR)
▪ establish diagnosis of pseudosyncope (ACC/AHA/HRS Class IIa, Level B-
NR)
o European Society of Cardiology (ESC) recommendations for tilt testing1
▪ tilt testing should be considered in patients with suspected (ESC Class IIa, Level
B)
▪ reflex syncope
▪ orthostatic hypotension and orthostatic syncope
▪ postural orthostatic tachycardia syndrome (POTS)
▪ psychogenic pseudosyncope
▪ tilt testing may be considered to educate patients to recognize symptoms and
learn physical maneuvers (ESC Class IIb, Level B)
▪ tilt testing may be helpful for distinguishing
▪ syncope with abnormal movements from epilepsy
▪ syncope from falls
▪ syncope from psychogenic pseudosyncope
▪ if suspect psychogenic pseudosyncope, tilt test should preferably
be performed with concomitant electroencephalogram (EEG)
monitoring (normal EEG confirms diagnosis)
▪ in absence of EEG, video recording will be helpful in confirming
diagnosis
▪ tilt testing should not be used to assess efficacy of drug treatment
▪ contraindications to administration of isoproterenol include
▪ ischemic heart disease (may result in life-threatening ventricular
arrhythmias)
▪ uncontrolled hypertension
▪ left ventricular outflow tract obstruction
 ▪ significant aortic stenosis
▪ isoproterenol should be used with caution in patients with known arrhythmias
▪ atrial fibrillation can be induced during or after positive tilt test and is usually self-
limited
▪ minor complications common and include palpitations with isoproterenol and
headache with nitroglycerin
• in reflex or neurally mediated syncope, tilt testing reproduces neurally mediated reflex due to
vasodepressor, cardioinhibitory, or mixed response1
o vasodepressor
▪ due to pooling of blood and decrease in venous return
▪ hypotension and heart rate slowing are response to impaired vasoconstriction
o cardioinhibitory
▪ due to bradycardia or asystole
▪ hypotension and heart rate slowing are response to sympathetic withdrawal and
vagal overactivity
• method of testing
o various protocols exist, including variations in initial stabilization phase, duration, tilt
angle, type of support, and pharmacologic provocation (Eur Heart J 2018 Jun
1;39(21):1883)
o agents used to provoke vasovagal response include
▪ low-dose IV isoproterenol
▪ sublingual nitroglycerine
▪ clomipramine (Heart Rhythm 2015 Jun;12(6):e41)
o more aggressive protocols associated with decreased specificity of test (Heart Rhythm
2015 Jun;12(6):e41)
o European Society of Cardiology (ESC) recommended method for testing
▪ patient should fast 2-4 hours before test
▪ supine pretilt phase should be ≥ 5 minutes when no IV line and ≥ 20 minutes
when IV line placed
▪ tilt angle between 60 and 70 degrees
▪ passive phase of tilt 20-45 minutes in duration
▪ use either sublingual nitroglycerin or IV isoproterenol for drug provocation if
passive phase negative (duration of drug challenge phase 15-20 minutes)
▪ if using sublingual nitroglycerin, fixed dose 300-400 mcg when patient
upright
▪ if using IV isoproterenol, incremental dose from 1 mcg/minute to 3
mcg/minute to increase average heart rate by 20%-25% over baseline
▪ continue test until complete loss of consciousness occurs or protocol completed
▪ tilt-down time should be short (< 15 seconds) as longer times increase duration
of precipitated asystole
▪ addition of video recording to tilt testing (camera is attached to tilt table to
visualize patient face and head)
▪ adding video recording to tilt testing may be considered to increase
reliability of clinical observation of induced events (ESC Class IIb, Level C)
▪ adding video recording to test allows objective and repeated review of
clinical signs in relation to blood pressure and heart rate and relative
contribution of bradycardia and hypotension to syncope, which may help
distinguish vasovagal syncope from psychogenic pseudosyncope
▪ Reference - Eur Heart J 2018 Jun 1;39(21):1883
• European Society of Cardiology (ESC) recommendations for tilt test interpretation and
circulatory patterns
o test interpretation
▪ reflex syncope, orthostatic hypotension and orthostatic syncope, POTS, and
psychogenic pseudosyncope should be considered likely if tilt testing reproduces
symptoms along with characteristic circulatory pattern of these conditions (ESC
Class IIa, Level B)
▪ classification of positive responses
▪ vasovagal response usually lasts ≤ 3 minutes before resulting in loss of
consciousness (LOC)
▪ decrease in systolic blood pressure to < 90 mm Hg is associated with
impending syncope and to < 60 mm Hg is associated with syncope
▪ prodromal symptoms exist is almost all cases of tilt-induced vasovagal
syncope, and syncope usually occurs 1 minute after onset of prodromal
symptoms
▪ during prodromal phase, blood pressure falls markedly and frequently
precedes decrease in heart rate, which may be absent at beginning of
prodromal phase
▪ reported temporal relationship between asystolic pause and LOC
▪ asystolic pause precedes LOC for 3-12 seconds in about 2/3 of
patients
▪ asystolic pause coincides with or follows LOC in about 1/3 of
patients
▪ negative tilt table test does not exclude diagnosis of reflex syncope
▪ positive cardioinhibitory response to tilt testing may suggest asystolic
spontaneous syncope, which has therapeutic implications when cardiac pacing is
considered, but presence of positive vasodepressor, mixed response, or negative
response does not exclude presence of asystole during spontaneous syncope
▪ tilt testing reported to have acceptable sensitivity and specificity in patients with
true vasovagal syncope or without history of syncope but has limited diagnostic
value in patients with unexplained syncope or cardiac arrhythmic syncope
▪ tilt testing in patients with syncope of uncertain origin or in patients with cardiac
syncope (hypotensive susceptibility)
▪ tilt testing suggests presence of hypotensive susceptibility, which may
exist not only in reflex syncope but also in other causes of syncope,
including cardiac syncope
▪ hypotensive susceptibility plays role in mechanism of syncope in patients
with cardiac syncope due to arrhythmia, aortic stenosis, hypertrophic
cardiomyopathy, and sick sinus syndrome
▪ presence of hypotensive susceptibility (not diagnosis of vasovagal
syncope) plays major role in guiding pacemaker therapy in patients
affected by reflex syncope and in management of hypotensive therapy,
which are frequently present in older persons with syncope
▪ blood pressure and heart rate patterns (circulatory patterns) of tilt table test
results
▪ normal tilt table test result pattern (negative test)
▪ no change in blood pressure or slight increase of ≤ 10%
▪ heart rate increased by ≤ 10% until patients tilted back again
▪ pattern of tilt-induced reflex syncope
▪ blood pressure start to decrease slowly and slightly for several
minutes at variable times after head-up tilt
▪ rate of blood pressure drop then increases to form convex curve
over time
▪ heart rate usually increases gradually and slightly before syncope
during tilt
 ▪ characteristics of heart rate decrease based on type of response
▪ in cardioinhibitory response
▪ heart rate decrease starts after blood pressure
decrease
▪ rate of heart rate decrease then increases
▪ in pure vasodepressive response, heart rate decreases
slightly
▪ heart rate and blood pressure increase quickly again after tilting
back
▪ core features differentiating reflex syncope from orthostatic
hypotension and orthostatic syncope include
▪ latency after head-up tilt
▪ convex blood pressure decrease
▪ decrease in heart rate
▪ patterns of tilt-induced orthostatic hypotension and orthostatic syncope
▪ classic orthostatic hypotension and orthostatic syncope
▪ blood pressure starts to decrease immediately after head-up
tilt with decreasing rate of drop resulting in concave curve
over time
▪ blood pressure may stabilize at lower level or may continue
to decrease during head-up tilt
▪ blood pressure may decrease considerably after 3 minutes
▪ if heart rate control functional, heart rate increases in attempt
to compensate for low blood pressure
▪ if heart rate control severely impaired, heart rate will not
increase or will increase only very little and will usually not
vary much between beats
▪ core feature of classic orthostatic hypotension include
▪ no blood pressure latency after head-up tilt
▪ upwards or concave shape of decrease in blood
pressure
▪ if heart rate changes, it increases
▪ delayed orthostatic hypotension and orthostatic syncope
▪ shape of decrease in heart rate and blood pressure more
variable than in classic type
▪ rate of decrease in heart rate and blood pressure may vary
▪ degree of heart rate compensation varies
▪ psychogenic pseudosyncope
▪ pseudosyncope occurs at variable intervals after head-up tilt,
but may occur within 1-2 minutes of head-up tilt
▪ blood pressure and heart rate do not decrease but instead
both usually increase several minutes before event and
reach peak values during event
▪ postural orthostatic tachycardia syndrome (POTS)
▪ heart rate increases after head-up tilt and decreases after
head-down tilt
▪ blood pressure increases slightly after head-up tilt and
decreases slightly after tilt-down
▪ can only be diagnosed in absence of orthostatic hypotension
o Reference - Eur Heart J 2018 Jun 1;39(21):1883

Carotid sinus massage

 • European Society of Cardiology (ESC) recommendations for carotid sinus massage1
o carotid sinus massage indicated in patients < 40 years old with syncope of unknown
origin compatible with reflex mechanism (ESC Class I, Level B)
o carotid sinus syncope confirmed if carotid sinus massage causes bradycardia
suggesting asystole and/or hypotension that reproduces spontaneous symptoms and
history features compatible with reflex mechanism of syncope (ESC Class I, Level B)
o positive carotid sinus massage defined as ventricular pause lasting > 3 seconds and/or
fall in blood pressure > 50 mm Hg
o positive carotid sinus massage without history of syncope defines carotid sinus
hypersensitivity, which may be nonspecific finding in patients with unexplained syncope
and is present in ≤ 40% of general population of older persons and should therefore be
used with caution for diagnosis of mechanism of syncope
o carotid sinus massage should be performed with patient in supine and upright positions
and with continuous beat-to-beat blood pressure monitoring (may be more readily
performed in tilt test lab)
o neurological complications very rare, but perform carotid sinus massage with caution in
patients with previous transient ischemic attack, stroke, or known carotid stenosis >
70%

Autonomic function tests

• autonomic function tests aim to characterize cardiovascular sympathetic and parasympathetic

autonomic function and may identify autonomic failure as cause of syncope1
• referral for autonomic evaluation can be useful to improve diagnostic and prognostic accuracy
in selected patients with syncope and known or suspected neurodegenerative disease
(ACC/AHA/HRS Class IIa, Level C-LD)4
• European Society of Cardiology (ESC) recommendation for Valsalva maneuver1
o Valsalva maneuver should be considered for assessment of autonomic function in
patients with suspected neurogenic orthostatic hypotension (ESC Class IIa, Level B)
o Valsalva maneuver may be considered for confirming hypotensive tendency induced by
some forms of situational syncope (such as coughing, brass instrument playing, singing,
and weightlifting) (ESC Class IIb, Level C) (if possible, reproduce trigger symptoms
during beat-to-beat noninvasive heart rate and blood pressure measurements)
o method
▪ ask patient to conduct maximally forced expiration against closed glottis (closed
nose and mouth or into closed loop system with resistance of 40 mm Hg) for 15
seconds
▪ monitor hemodynamic changes with beat-to-beat continuous noninvasive blood
pressure measurement and electrocardiogram (ECG)
o normal test results
▪ in phase I (2-3 seconds into test), blood pressure slightly increases due to
temporarily increased left ventricular filling
▪ in phase II (when intrathoracic pressure rises during forced expiration)
▪ blood pressure decreases due to strongly reduced venous return
▪ cardiac output declines and compensatory heart rate increases due to
baroreceptor reflex
▪ in response to hypotension, systemic vascular resistance (total peripheral
resistance) increases due to sympathetic outflow to vessels
▪ in phase III (when patient stops inflating lungs), blood pressure falls briefly
(mechanical effect and mirror of phase I)
▪ in phase IV (when patient releases air and starts breathing normally)
 ▪ intrathoracic pressure returns to negative and enhances venous return to
heart
▪ sympathetic vasoconstriction results in blood pressure overshoot
(confirms preserved autonomic control of cardiovascular system)
▪ heart rate decreases due to parasympathetic effect on heart and then
normalizes
o characteristics of autonomic failure test results (cardiovascular autonomic failure)
▪ absence of compensatory heart rate increase in phase II
▪ delayed blood pressure recovery in phase IV
o characteristic test result in situational syncope includes normal heart rate response
associated with pronounced hypotension and reproducible symptoms (such as
dizziness)

Treatment

• treatment for reflex syncope (all types)1

o treatment of reflex syncope based on risk of future syncope episodes and identification
of specific mechanism for syncope when possible
▪ if syncope predictable or occurs at low frequency, education, reassurance that
syncope benign, and avoidance of triggers usually sufficient
▪ if syncope unpredictable or occurs at high frequency, consider specific therapy or
delayed treatment (guided by electrocardiogram documentation)
o reduction in syncope burden is reasonable goal of therapy as no therapy can completely
prevent syncope recurrence
o explain diagnosis, assure patient that condition is benign, and explain risk of recurrence
and avoidance of triggers and situations (ESC Class I, Level B)
o modification or discontinuation of hypotensive drug regimen should be considered in
patients with vasodepressor syncope if possible (ESC Class IIa, Level B) (such as beta
blockers, diuretics, antihypertensive agents, nitrates, neuroleptic antidepressants, and
dopaminergic agents)
o activity
▪ isometric physical counter-pressure maneuvers should be considered in patients
< 60 years old with prodromes (ESC Class IIa, Level B)
▪ tilt training may be considered for education of young patients (ESC Class IIb,
Level B)
• additional treatment for vasovagal syncope
o treatment only warranted if syncopal event in previous year (Heart Rhythm 2015
Jun;12(6):e41)
o education about
▪ triggers to be aware of and avoid include
▪ hot, crowded environments
▪ volume depletion
▪ emotional stress, including fear
▪ pain (somatic or visceral)
▪ blood phobia
▪ blood pressure-lowering agents (such as diuretics, and alcohol)
o early recognition of prodromal symptoms, including nausea, pallor, and sweatiness
o encouraging increased salt and fluid intake may be reasonable in selected patients with
vasovagal syncope unless contraindicated (ACC/AHA/HRS Class IIb, Level C-LD; HRS
Class I, Level E)
o medications
▪ midodrine
 ▪ consider midodrine in patients with
▪ orthostatic form of vasovagal syncope (ESC Class IIb, Level B)
▪ frequent vasovagal syncope and no hypertension, urinary retention
(HRS Class IIb, Level B-R), or heart failure (ACC/AHA/HRS Class
IIa, Level B-R)
▪ midodrine may improve disease-related quality of life in adults and reduce
syncope recurrence in children and adults with recurrent reflex
syncope (level 2 [mid-level] evidence)
▪ fludrocortisone
▪ consider fludrocortisone in patients with
▪ orthostatic form of vasovagal syncope, low or normal arterial blood
pressure, and no contraindication to drug in patients who are young
(ESC Class IIb, Level B)
▪ recurrent vasovagal syncope and inadequate response to salt and
fluid intake if drug not contraindicated (ACC/AHA/HRS Class IIb,
Level B-R)
▪ frequent vasovagal syncope if no contraindications (HRS Class IIb,
Level E)
▪ fludrocortisone may not reduce recurrence of vasovagal syncope in
patients with > 2 syncopal events (level 2 [mid-level] evidence)
▪ selective serotonin reuptake inhibitors (SSRIs)
▪ SSRIs might be considered in patients with recurrent vasovagal syncope
(ACC/AHA/HRS Class IIb, Level C-LD)
▪ SSRIs may reduce recurrence of vasovagal syncope (level 2 [mid-level]
evidence)
▪ beta blockers
▪ guidelines disagree on use of beta blockers in patients with vasovagal
syncope
▪ European Society of Cardiology (ESC) guideline states that beta
adrenergic blocking medications are not indicated (ESC Class III,
Level A) based on lack of benefit in randomized trial enrolling
patients of all ages
▪ United States guidelines suggest a possible role for beta blockers
based on slight reduction in syncope recurrence in age stratified
analyses
▪ beta blockers might be reasonable in patients ≥ 42 years old
with recurrent vasovagal syncope (ACC/AHA/HRS Class IIb,
Level B-NR)
▪ beta blockers may be considered for patients ≥ 40 years old
with frequent vasovagal syncope (HRS Class IIb, Level B-R)
▪ beta blockers may reduce vasovagal syncope recurrence in patients ≥ 42
years old with positive tilt test (level 2 [mid-level] evidence)
o pacemaker therapy
▪ consider pacemaker therapy in patients with frequent vasovagal syncope and
documented cardioinhibitory response
▪ cardiac pacing should be considered to reduce syncope recurrences in
patients with reflex syncope who are > 40 years old who have
documented spontaneous symptomatic asystolic pauses > 3 seconds or
asymptomatic pauses > 6 seconds due to sinus arrest and/or
atrioventricular block (ESC Class IIa, Level B)
 ▪ dual-chamber pacing might be reasonable in select population of patients
≥ 40 years old with recurrent vasovagal syncope and prolonged
spontaneous pauses (ACC/AHA/HRS Class IIb, Level B-R)
▪ consider dual-chamber cardiac pacing in patients with recurrent and
unpredictable syncope who are > 40 years old and have documented
pause lasting ≥ 3 seconds during clinical syncope or asymptomatic pause
≥ 6 seconds (HRS Class IIa, Level B-NR)
▪ cardiac pacing may be considered to reduce syncope recurrences in
patients with tilt-induced asystolic response if aged > 40 years old and
recurrent frequent unpredictable syncope (ESC Class IIb, Level B)
▪ dual-chamber pacing with closed loop stimulation reduces syncope
recurrence in patients with cardioinhibitory vasovagal syncope (level 1
[likely reliable] evidence)
▪ active dual-chamber pacing with rate drop may reduce 2-year syncope
recurrence compared to inactive pacemaker in patients with recurrent
neurally-mediated syncope with documented asystole (level 2 [mid-level]
evidence)
▪ cardiac pacing may be considered to reduce syncope recurrences in patients
with clinical features of adenosine-sensitive syncope (ESC Class IIb, Level B)
▪ cardiac pacing is not indicated in patients without documented cardioinhibitory
reflex (ESC Class III, Level BC)
o see Vasovagal Syncope for additional details
• additional treatment for carotid sinus syncope
o triggers to be aware of and avoid include1
▪ turning of neck
▪ wearing a tight necktie or tight collar
▪ shaving the neck
▪ neck tumors
▪ pressure on neck
▪ mechanical manipulation of carotid sinus
o limited evidence for midodrine
o cardiac pacing
▪ presence of cardioinhibitory response to carotid sinus massage guides decision
for cardiac pacing
▪ cardiac pacing associated with reduced risk of syncope recurrence compared to
standard therapy in patients with hypersensitive carotid sinus syndrome (level 2
[mid-level] evidence)
▪ cardiac pacing reasonable in patients with carotid sinus syndrome that is
cardioinhibitory or mixed (ACC/AHA/HRS Class IIa, Level B-R)
▪ cardiac pacing should be considered to reduce syncope recurrences in patients
aged > 40 years old with
▪ spontaneous documented symptomatic asystolic pauses > 3 seconds or
asymptomatic pauses > 6 seconds due to sinus arrest and/or
atrioventricular bock (ESC Class IIa, Level B)
▪ cardioinhibitory carotid sinus syndrome and recurrent frequent
unpredictable syncope (ESC Class IIa, Level B)
▪ cardiac pacing may be considered to reduce syncope recurrences in patients
with
▪ tilt-induced asystolic response if aged > 40 years old and recurrent
frequent unpredictable syncope (ESC Class IIb, Level B)
▪ clinical features of adenosine-sensitive syncope (ESC Class IIb, Level B)
 ▪ dual-chamber cardiac pacing may be reasonable in patients with carotid sinus
syndrome who require cardiac pacing (ACC/AHA/HRS Class IIb, Level B-R)
▪ cardiac pacing is not indicated in patients without documented cardioinhibitory
reflex (ESC Class III, Level B)
o see Carotid Sinus Syncope for additional information
• additional treatment for situational syncope includes treatment of triggers if possible, such as1
o cough suppression in patients with syncope triggered by cough
o micturition in sitting position in patients with syncope triggered by micturition
• standardized diagnostic testing algorithm for dual-chamber pacemaker placement may
reduce total syncope recurrence compared to receiving implantable loop recorder
without diagnostic tests in patients with severe unpredictable recurrent reflex
syncope (level 2 [mid-level] evidence)
o based on prospective cohort study
o 253 patients > 40 years old (mean 70 years) with severe unpredictable recurrent
neurally mediated syncope were evaluated with standardized algorithm for dual-
chamber pacemaker and compared to 124 patients who received implantable loop
recorder without diagnostic tests
▪ standardized algorithm included receiving carotid sinus massage (CSM),
followed by tilt testing if CSM was negative, followed by implantation of
implantable loop recorder if tilt testing was negative
▪ patients received dual-chamber pacemaker if asystolic response to ≥ 1 test
o 89% without prodromes or with short prodromes
o 47% (120) received pacemakers
o 88% (106) followed for mean 13 months
o 9% syncope recurred (similar recurrence rate for CSM [11%], tilt testing [7%], and
implantable loop record [7%])
o comparing diagnostic testing vs. without testing for total syncope recurrence rate (p =
0.004)
▪ 9% vs. 22% at 1 year
▪ 15% vs. 37% at 2 years
o Reference - Eur Heart J 2015 Jun 21;36(24):1529full-text

Treatment for Orthostatic Syncope

• treatment goals for orthostatic intolerance to relieve syncope and presyncope symptoms
o explanation of diagnosis, provision of reassurance, and explanation of risk of recurrence
and avoidance of triggers and situation indicated in all patients (ESC Class I, Level C)
o triggers and situations to avoid and beware of include
▪ participating in activities or exposure to temperatures associated with increased
risk of dehydration
▪ standing for long periods (especially in crowded, hot places)
▪ rapidly rising from seated or supine position
o for symptoms that are unpredictable or occur frequently, consider specific therapy for
disease or condition causing symptoms
• for syncope caused by orthostatic hypotension due to dehydration and/or drugs
o fluid resuscitation via oral or IV bolus recommended in patients with syncope due to
acute dehydration (ACC/AHA/HRS Class I, Level C-LD)
o reasonable to encourage increased salt and fluid intake in selected patients with
syncope due to dehydration (ACC/AHA/HRS Class IIa, Level C-LD)
o reducing or withdrawing medications that may cause hypotension can be beneficial in
selected patients with syncope (ACC/AHA/HRS Class IIa, Level B-NR)
 • for syncope caused by neurogenic orthostatic hypotension
o increased water and salt intake
▪ acute water ingestion recommended in patients with syncope caused by
neurogenic orthostatic hypotension for occasional, temporary relief
(ACC/AHA/HRS Class I, Level B-R)
▪ encouraging increased salt and fluid intake may be reasonable in selected
patients with neurogenic orthostatic hypotension (ACC/AHA/HRS Class IIb, Level
C-LD)
o additional nonpharmacological therapy options for patients with persistent symptoms
▪ physical counterpressure maneuvers (PCMs)
▪ isometric PCMs should be considered (ESC Class IIa, Level C), especially
in patients with warning symptoms
▪ PCMs can be beneficial in patients with neurogenic orthostatic
hypotension and syncope (ACC/AHA/HRS Class IIa, Level C-LD)
▪ compression garments
▪ abdominal binders and/or support stockings to reduce venous pooling
should be considered (ESC Class IIa, Level B)
▪ compression garments can be beneficial in patients with syncope and
orthostatic hypotension (ACC/AHA/HRS Class IIa, Level C-LD)
▪ elastic leg and abdominal compression stockings may increase orthostatic
tolerance and reduce symptoms in patients with symptomatic progressive
orthostatic hypotension (level 2 [mid-level] evidence)
o consider medications in patients with persistent symptoms despite nonpharmacological
therapy
▪ midodrine (ESC Class IIa, Level B) or fludrocortisone (ESC Class IIa, Level C)
should be considered if symptoms persist
▪ midodrine (ACC/AHA/HRS Class IIa, Level B-R) or fludrocortisone
(ACC/AHA/HRS Class IIa, Level C-LD) can be beneficial in patients with syncope
due to neurogenic orthostatic hypotension
▪ midodrine may improve symptoms, but may increase risk of adverse events in
adults with symptomatic orthostatic hypotension (level 2 [mid-level] evidence)
▪ droxidopa can be beneficial in patients with syncope due to neurogenic
orthostatic hypotension (ACC/AHA/HRS Class IIa, Level B-R)
▪ pyridostigmine may be beneficial in patients with syncope due to neurogenic
orthostatic hypotension who are refractory to other treatments (ACC/AHA/HRS
Class IIb, Level C-LD)

Additional Testing and Treatment of Cardiac Syncope

Differentiating cardiac from non-cardiac syncope based on history and physical

• Evaluation of Guidelines in Syncope Study (EGSYS) score predicts likelihood of cardiac

cause of syncope using clinical history factors in emergency department (level 1 [likely
reliable] evidence)
o based on derivation and validation cohorts
o 516 consecutive adult patients ≥ 18 years old admitted to emergency department with
unexplained syncope were divided into derivation cohort (260 patients) and validation
cohort (256 patients)
o patients excluded for
▪ definite nonsyncopal cause of loss of consciousness
▪ referral ≥ 24 hours after syncope episode
 o cardiac syncope diagnosed in 16.9% of derivation cohort
▪ arrhythmic syncope diagnosed by ECG, ECG monitoring, 24-hour Holter
recording, or external loop recorder
▪ mechanical cardiac syncope diagnosed by angiography, echocardiography, or
chest computed tomography (CT)
o diagnostic score developed using clinical history factors to predict cardiac cause of
syncope
Risk Factor Points
Palpitations preceding syncope +4
Heart disease, abnormal ECG, or both +3
Syncope during effort +3
Syncope while supine +2
Precipitating or predisposing factors (warm crowded location, prolonged
orthostasis, fear, pain, emotion) -1
Autonomic prodromes (nausea, vomiting) -1
Abbreviation: ECG, electrocardiogram.
Table 3. Diagnostic Predictive Score
o risk of cardiac cause of syncope in validation cohort of 256 consecutive patients
▪ 2% for score < 3 points
▪ 13% for score = 3 points
▪ 33% for score = 4 points
▪ 77% for score > 4 points
o score ≥ 3 points had sensitivity 92% and specificity 69% in validation cohort
o mortality comparing score ≥ 3 points vs. score < 3 points at mean follow-up 614 days
▪ 17% vs. 3% in derivation cohort (p < 0.001)
▪ 21% vs. 2% in validation cohort (p < 0.001)
o Reference - Heart 2008 Dec;94(12):1620, commentary can be found in Evid Based Med
2009 Jun;14(3):91
• clinical history model helps distinguish cardiac syncope from other types of
syncope (level 1 [likely reliable] evidence)
o based on prognostic derivation cohort study with external validation cohort
o derivation cohort included 2,388 patients with syncope were evaluated for cardiac
syncope
o cardiac syncope in 20% of derivation cohort and in 11% of total validation cohorts
o Bernoulli model for distinguishing cardiac syncope from non-cardiac syncope developed
using 10 clinical history factors
▪ factors associated with cardiac syncope included
▪ age > 60 years
▪ male sex
▪ structural heart disease
▪ < 3 spells
▪ supine syncope
▪ syncope during effort
▪ factors associated with non-cardiac syncope included
▪ age < 40 years
▪ long prodrome
▪ nausea
▪ diaphoresis
▪ blurred vision
o external validation cohort included
▪ 670 patients (mean age 51 years) with ≥ 1 loss of consciousness in Calgary
 ▪503 patients (mean age 52 years) presenting with transient loss of
consciousness at emergency department in Amsterdam
▪ 689 patients (mean age 60 years) presenting with syncope at emergency
department in Milan
▪ 3,877 patients (mean age 57 years) evaluated for syncope in Rochester, United
States
o for distinguishing cardiac syncope from non-cardiac syncope, clinical history model had
▪ sensitivity 92% and specificity 68% for Calgary
▪ sensitivity 86% and specificity 67% for Amsterdam
▪ sensitivity 76% and specificity 59% for Milan
▪ sensitivity 73% and specificity 52% for Rochester
o Reference - PLoS One 2013;8(9):e75255EBSCOhost Full Textfull-text
• cardiac syncope appears unlikely if no suspected heart disease and no palpitations;
cardiac syncope likely if syncope in supine position (level 2 [mid-level] evidence)
o based on diagnostic cohort study with unclear reference standard
o 341 patients referred to syncope units within 3 hospital cardiology departments in Italy
were evaluated
o cardiac syncope diagnosed in 23%, neurally mediated syncope diagnosed in 58%
o among 146 patients without suspected or diagnosed heart disease
▪ only 4 (3%) had cardiac syncope
▪ only significant predictor of cardiac syncope was palpitations before loss of
consciousness (14% likelihood of cardiac syncope)
o among 191 patients with suspected or diagnosed heart disease
▪ syncope in supine position had 98% specificity for cardiac syncope (79%
likelihood of cardiac syncope)
▪ no other symptom had high specificity and remained statistically significant in
multivariate analysis
o Reference - J Am Coll Cardiol 2001 Jun 1;37(7):1921full-text
• symptoms and signs present before syncope may differentiate noncardiac from cardiac
syncope in older patients (level 2 [mid-level] evidence)
o based on cross-sectional observational study
o 242 patients (mean age 79 years) with syncope were assessed using European Society
of Cardiology syncope guidelines on symptoms and signs present before syncope
o 75.4% had noncardiac syncope and 14.7% had cardiac syncope
o 71.1% related symptoms before loss of consciousness
o prevalence of symptoms in noncardiac syncope 75.3% vs. cardiac syncope 24.7% (p <
0.01)
o symptoms with significant predictive value of noncardiac syncope
▪ nausea had 94.1% specificity and 94.9% likelihood of non-cardiac syncope
▪ blurred vision had 97.1% specificity and 97.8% likelihood of non-cardiac syncope
▪ sweating had 94.1% specificity and 96.2% likelihood of non-cardiac syncope
o in adjusted multivariate analysis only symptom predictive of cardiac syncope was
dyspnea (98.3% specificity, 50% likelihood of cardiac syncope)
o Reference - J Am Geriatr Soc 2009 Jan;57(1):18, commentary can be found in J Am
Geriatr Soc 2009 Aug;57(8):1504; author reply 1504

Additional testing

Testing overview

• additional testing should be based on initial findings of history, physical, and 12-lead ECG1
 • routine and comprehensive lab testing is not useful in evaluation of syncope (ACC/AHA/HRS
Class III No Benefit, Level B-NR)
• cardiac imaging
o echocardiography in patients with suspected structural heart disease (ESC Class I,
Level B; ACC/AHA/HRS Class IIa, Level B-NR)
o computed tomography or magnetic resonance imaging may be useful in select patients
with suspected cardiac etiology (ACC/AHA/HRS Class IIb, Level B-NR) when
echocardiography not diagnostic1,4
o indications for coronary angiography in patients with syncope should be considered
identical to those in patients without syncope (ESC Class IIa, Level C) (angiography
alone not diagnostic of cause of syncope)1
o routine cardiac imaging is not useful unless cardiac etiology suspected based on initial
evaluation with history, physical exam, or electrocardiogram (ECG) (ACC/AHA/HRS
Class III, Level B-NR)
• electrocardiography (ECG) monitoring only in patients with high pre-test probability of
identifying arrhythmia associated with syncope
• electrophysiological studies generally not useful in patients with syncope who have normal
ECG, no heart disease, and no palpitations
• exercise testing in patients who develop syncope during or soon after exertion (ESC Class I,
Level C)

Cardiac biomarkers

• guidelines agree that utility of cardiac biomarkers in syncope evaluation is uncertain

o American College of Cardiology/American Heart Association/Heart Rhythm Society
(ACC/AHA/HRS) - usefulness of brain natriuretic (BNP) and high-sensitivity troponin
measurement is uncertain in patients with suspected cardiac syncope (ACC/AHA/HRS
Class IIb, Level C-LD)
o European Society of Cardiology (ESC) makes no recommendations for cardiac
biomarkers in syncope evaluation due to lack of evidence and independent validation1
• cardiac biomarkers (high-sensitivity cardiac troponin [hscTnT or hscTnI], B-type natriuretic
peptide [BNP], N-terminal proBNP [NT-proBNP]) for diagnosing cardiac syncope
O EVIDENCE SYNOPSIS

Cardiac biomarkers have not been proven to be useful for diagnosing cardiac syncope
in patients presenting to the emergency department with syncope. Cohort studies
evaluating this have been inconsistent and none have been validated.
▪ cardiac biomarkers (hscTnT, hscTnI, BNP, and NT-proBNP) might have
moderate performance for diagnosing cardiac syncope in patients
presenting to emergency department with syncope with unequivocal
diagnosis, but have not been validated (level 2 [mid-level] evidence)
▪ based on diagnostic cohort study without validation
▪ 1,913 adults > 45 years old presenting to emergency department with
syncope had cardiac biomarkers measured (hscTnT, hscTnI, BNP, and
NT-proBNP) and were followed for 2 years
▪ reference standard for diagnosing cause of syncope was 2 physicians who
reviewed all available records and results
▪ 1,338 patients with definite diagnoses were included in analysis (patients
with possible cardiac syncope that could not be documented or ruled out
were excluded)
▪ 221 patients had cardiac syncope on reference standard
 ▪ cardiac biomarker levels were significantly elevated in patients with
cardiac syncope compared to patients with other causes of syncope
▪ diagnostic accuracy for diagnosing cardiac syncope
▪ all cardiac biomarkers had moderate performance (area under
receiver operator curve 0.77-0.78, 95% CI 0.74-0.81)
▪ all cardiac biomarkers had significantly better performance than
Evaluation of Guidelines in Syncope Study (EGSYS) score (area
under receiver operator curve 0.68, 95% CI 0.65-0.71)
▪ optimal cardiac biomarker cut-offs were derived using prespecified
specificity and sensitivity values
▪ cut-offs associated with specificity ≥ 95% included BNP 302 pg/mL,
NT-proBNP 1,966 pg/mL, hscTnT 42 ng/L, and hscTnI 31.1 ng/L
and in combination detected cardiac syncope in 9% of patients
▪ cut-offs associated with sensitivity ≥ 95% included BNP 14.9
pg/mL, NT-proBNP 69 pg/mL, hscTnT 5 ng/L, and hscTnI 2.2 ng/L
and in combination excluded cardiac syncope in 21%
▪ Reference - Circulation 2019 Feb 25; early online
▪ NT-proBNP > 156 pg/mL and hscTnT ≥ 0.014 mcg/L may not be useful for
diagnosing cardiac syncope in patients presenting to emergency
department or hospitalized with syncope (level 2 [mid-level] evidence)
▪ based on systematic review of diagnostic cohort studies without validation
▪ systematic review of 10 prognostic studies (7 prospective and 3
retrospective) evaluating cardiac biomarkers for predicting MACE at 30
days in 4,246 patients presenting to emergency department or
hospitalized with syncope
▪ secondary outcome was cardiac biomarkers for diagnosing cardiac
syncope at 30 days, and 2 studies evaluated cardiac biomarkers for this
outcome (1 study used NT-proBNP and 1 study used high-sensitivity
troponin T)
▪ performance for diagnostic cardiac syncope at 30 days
▪ NT-proBNP > 156 pg/mL had sensitivity 90% and specificity 52% in
analysis of 1 study with 161 patients
▪ high-sensitivity troponin T ≥ 0.014 mcg/L had sensitivity 74% and
specificity 68% in analysis of 1 study with 360 patients
▪ Reference - Intern Emerg Med 2015 Dec;10(8):1003
▪ BNP > 40 pg/mL may not be useful for diagnosing cardiac syncope in
patients hospitalized for syncope
▪ based on retrospective diagnostic cohort study without validation
▪ 148 adults hospitalized for syncope included
▪ 61 (41%) had cardiac syncope
▪ BNP > 40 pg/mL on morning after admission had sensitivity 82% and
specificity 92% for diagnosing cardiac syncope
▪ Reference - Am J Cardiol 2004 Jan 15;93(2):228

Echocardiography

• guidelines agree that echocardiography can be useful in patients with suspected structural
heart disease, but guidelines do not agree on strength of indication recommendations
o European Society of Cardiology (ESC) recommendations for echocardiography
indications1
▪ echocardiography indicated for diagnosis and risk determination of patients
thought to have structural heart disease (ESC Class I, Level B)
 ▪ two-dimensional and Doppler echocardiography during exercise in standing,
sitting, or semi-supine position indicated in patients with hypertrophic
cardiomyopathy, history of syncope, and resting or provoked peak instantaneous
left ventricular outflow tract (LVOT) gradient < 50 mm Hg to detect provocable
LVOT obstruction (ESC Class I, Level B)
▪ echocardiography not useful unless cardiac etiology suspected based on initial
evaluation with history, physical exam, or electrocardiogram
o American College of Cardiology/American Heart Association/Heart Rhythm Society
(ACC/AHA/HRS) recommendations for echocardiography indications4
▪ transthoracic echocardiography (TTE) can be useful in select patients with
suspected structural heart disease (ACC/AHA/HRS Class IIa, Level B-NR)
▪ select patients may include patients with suspected valvular heart disease (such
as aortic stenosis), hypertrophic cardiomyopathy, or left ventricular dysfunction
• ESC echocardiography diagnostic criteria1
o echocardiography can diagnose cardiac syncope with no further testing needed if
findings include (ESC Class I, Level C)
▪ aortic stenosis
▪ atrial myxoma and other obstructive cardiac tumors or thrombi
▪ pericardial tamponade
▪ aortic dissection
• findings associated with abnormal echocardiography in adults with syncope
o echocardiography screening may be useful if unexplained syncope and history of
cardiac disease or abnormal electrocardiogram (ECG)
▪ based on prospective cohort study
▪ 650 consecutive adults with syncope evaluated
▪ 155 patients with unexplained syncope and clinical suspicion of obstructive
valvular lesion had Doppler transthoracic echocardiography
▪ severe aortic stenosis confirmed in 8 of 20 patients (40%) with suspected aortic
stenosis (suspicious murmur with clinical syncope on exertion with or without
chest pain)
▪ 88 patients had history of cardiac disease or abnormal electrocardiogram (ECG)
▪ left ventricular ejection fraction (LVEF) ≤ 40% identified in 24 patients
(27%)
▪ abnormal but non-relevant echocardiography in 64 patients (73%)
▪ syncope due to arrhythmia diagnosed in 50% with reduced LVEF and 19%
with abnormal but non-relevant findings (p < 0.001)
▪ no significant abnormalities on echocardiography in 67 patients with negative
cardiac history and normal ECG
▪ Reference - Heart 2002 Oct;88(4):363full-text, commentary can be found in ACP
J Club 2003 May-Jun;138(3):83EBSCOhost Full Text
o history of heart failure, abnormal electrocardiogram (ECG), history of coronary
artery disease, N-terminal pro B-type natriuretic peptide (NT-proBNP), and high-
sensitivity cardiac troponin T (hscTnT) each associated with increased risk of
clinically important findings on TTE in older adults presenting to emergency
department with syncope or presyncope
▪ based on prospective cohort study
▪ 995 older adults (≥ 60 years old) presenting to emergency department with
syncope or presyncope had transthoracic echocardiography (TTE)
▪ all patients had standard general evaluation (history, physical exam, and
12-lead ECG), N-terminal pro B-type natriuretic peptide (NT-proBNP), and
high-sensitivity cardiac troponin T (hscTnT)
 ▪
clinically important findings on TTE were defined as severe aortic stenosis
(< 1 cm2), severe mitral stenosis, severe aortic/mitral regurgitation,
reduced ejection fraction (< 45% or severe left ventricular dysfunction),
hypertrophic cardiomyopathy with outflow tract obstruction, severe
pulmonary hypertension, right ventricular dysfunction/strain, large
pericardial effusion, atrial myxoma, or regional wall motion abnormalities
▪ 22% had clinically important findings on TTE
▪ factors associated with increased risk of clinically important findings on TTE
included
▪ history of heart failure (adjusted odds ratio [OR] 1.6, 95% CI 1.02-2.57)
▪ abnormal ECG (adjusted OR 1.53, 95% CI 1.18-2.48)
▪ history of coronary artery disease (adjusted OR 1.24, 95% CI 1-1.96)
▪ NT-proBNP > 125 pg/mL (adjusted OR 1.34, 95% CI 1-2.61)
▪ hscTnT > 14 pg/mL (adjusted OR 1.29, 95% CI 1-2.03)
▪ all 5 factors associated with increased risk of clinically important findings on TTE
were used to develop Risk Of Major Echocardiography findings in Older adults
with syncope (ROMEO) score
▪ for predicting risk of clinically important finding on TTE, ROMEO score = 0
(0 of 5 factors present) had sensitivity 99.5% and specificity 15.4%
▪ ROMEO score was not validated
▪ Reference - J Hosp Med 2018 Dec 1;13(12):823
• echocardiography screening not helpful for unselected children with syncope
o based on chart review
o retrospective record review of 480 patients ages 1.5-18 years with syncope
o final diagnoses were
▪ noncardiac causes in 458
▪ long QT syndrome in 14
▪ arrhythmias in 6
▪ cardiomyopathy in 2
o abnormal history, physical, or ECG identified 21 of 22 patients with a cardiac cause of
syncope
o of 322 echocardiograms performed, abnormalities were detected in 37 but only 2
cardiomyopathies were considered to be potential causes of syncope
o both cases of cardiomyopathy had markedly abnormal ECG
o Reference - Pediatrics 2000 May;105(5):e58full-text

Electrocardiography (ECG) monitoring

Indications and diagnostic criteria

• ECG monitoring is used to diagnose bradyarrhythmias and tachyarrhythmias during syncope

episode1
• ECG monitoring only indicated if high pre-test probability of identifying arrhythmia associated
with syncope, such as any1
o bifascicular block (left bundle-branch block or right bundle-branch block [RBBB] with left
anterior or left posterior fascicular block)
o intraventricular conduction abnormalities with QRS duration ≥ 120 milliseconds
o Mobitz type I second-degree atrioventricular (AV) block or first-degree AV block with
markedly prolonged PR interval
o asymptomatic mild inappropriate sinus bradycardia (heart rate 40-50 beats/minute) or
slow atrial fibrillation (40-50 beats/minute) in absence of negative chronotropic drugs
o sinoatrial block or sinus pause ≥ 3 seconds without negatively chronotropic medications
 o non-sustained ventricular tachycardia
o pre-excited QRS complex
o prolonged or short QT interval
o early repolarization
o ST-elevation with type I pattern in leads V1-V3 (Brugada pattern)
o negative T waves in right precordial leads, epsilon waves suggestive of arrhythmogenic
right ventricular cardiomyopathy
o left ventricular hypertrophy suggesting hypertrophic cardiomyopathy
• ECG monitoring not indicated in patients with clear indication for implantable cardioverter
defibrillator (ICD), pacemaker, or other treatments independent of definite diagnosis of cause
of syncope1
• European Society of Cardiology (ESC) recommendations for ECG monitoring1
o duration and type of monitoring should be selected based on risk and predicted
recurrence rate of syncope
o immediate in-hospital monitoring (in bed or with telemetry) indicated in high-risk patients
(ESC Class I, Level C)1
o Holter monitoring should be considered in patients with episodes of syncope or
presyncope at least weekly (ESC Class IIa, Level B)
o loop recorders
▪ external loop recorders should be considered early after index event in patients
with intervals between symptoms ≤ 4 weeks (ESC Class IIa, Level B)
▪ implantable loop recorder (ILR)
▪ ILR subcutaneously implanted under local anesthesia and has battery life
up to 36 months (Eur Heart J 2009 Nov;30(21):2631)
▪ ILR indicated in early phase of evaluation in patients with recurrent
syncope of uncertain origin (in absence of high-risk criteria) if high
likelihood of recurrent event during battery longevity (ESC Class I, Level
A)
▪ ILR indicated in high-risk patients when thorough evaluation did not find
cause of syncope or lead to a specific treatment and no conventional
indications for ICD for primary prevention of sudden cardiac death or
pacemaker indication (ESC Class I, Level A)
▪ ILR should be considered in patients with suspected or certain reflex
syncope presenting with frequent or severe syncopal episodes (ESC
Class IIa, Level B)
▪ ILR may be considered in patients in whom epilepsy was previously
suspected but treatment has proven ineffective (ESC Class IIb, Level B)
▪ ILR may be considered in patients with unexplained falls (ESC Class IIb,
Level B)
• American college of Cardiology/American Heart Association/Hearth Rhythm Society
(ACC/AHA/HRS) recommendations for cardiac telemetry monitoring4
o continuous ECG monitoring useful for hospitalized patients with suspected cardiac
etiology (ACC/AHA/HRS Class I, Level B-NR)
o select cardiac monitoring device based on frequency and nature of syncope episodes
(ACC/AHA/HRS Class I, Level C-EO)
o for ambulatory patients with suspected arrhythmic etiology
▪ useful external cardiac monitoring devices include (ACC/AHA/HRS Class IIa,
Level B-NR)
▪ Holter monitor
▪ transtelephonic monitor
▪ external loop recorder
▪ patch recorder
 ▪ mobile cardiac outpatient telemetry
▪ implantable cardiac monitor can be useful (ACC/AHA/HRS Class IIa, Level B-R)
• European Society of Cardiology diagnostic criteria1
o cardiac syncope due to arrhythmia confirmed if correlation found between syncope and
an arrhythmia (tachy- or bradyarrhythmia) (ESC Class I, Level B) (be prepared to wait
up to 4 years or more for correlation due to unpredictability of syncope recurrence)
o cardiac syncope due to arrhythmia should be considered likely if no correlation between
syncope and arrhythmia, but asymptomatic arrhythmias of (ESC Class IIa, Level C)
▪ periods of Mobitz type II second- or third-degree atrioventricular (AV) block
▪ ventricular pause > 3 seconds (possible exception in young trained athletes,
during sleep, or rate-controlled atrial fibrillation)
▪ rapid prolonged paroxysmal supraventricular tachycardia or ventricular
tachycardia
o presyncope cannot be considered surrogate for syncope in absence of documented
arrhythmia, but documentation of significant arrhythmia at time of presyncope can be
considered diagnostic of cardiac syncope due to arrhythmia
o exclude cardiac syncope due to arrhythmia in absence of arrhythmia during syncope
o documentation of bradycardia/asystole during syncope episode does not rule out
possibility of hidden hypotensive reflex as cause of syncope with bradycardia/asystole
as secondary late event due to inability to record blood pressure with ECG monitoring

In-hospital monitoring

• diagnostic yield of in-hospital ECG monitoring reported to vary 1.9%-17.6%, but monitoring
justified to avoid immediate risk to patient1
• immediate in-hospital monitoring (in bed or telemetry) indicated in high risk patients (ESC
Class I, Level C)1
• European Society of Cardiology (ESC) proposed high-risk features that suggest serious cause
of syncope1
ECG Features in
presence of History
Past Medical Consistent with
Syncope Event History Physical Exam Arrhythmic
Features Features Findings ECG Features Syncope
Severe
structural or
coronary
artery disease,
such as heart Mobitz type I AV
New-onset of chest failure, reducedUnexplained block and first-
discomfort, LVEF, or systolic blood degree AV block
breathlessness, previous pressure < 90 mm ECG findings with markedly
abdominal pain, or myocardial Hg in emergency consistent with prolonged PR
headache infarction) department ischemia interval
Asymptomatic mild
inappropriate sinus
bradycardia (40-50
Suggestion of beats/minute) or
Syncope during gastrointestinal Mobitz type II second- slow atrial
exertion or when in bleed on rectal degree and third- fibrillation (40-50
supine position N/A exam degree AV block beats/minute)
 ECG Features in
presence of History
Past Medical Consistent with
Syncope Event History Physical Exam Arrhythmic
Features Features Findings ECG Features Syncope
Persistent
Sudden onset bradycardia (< 40
palpitations beats/minute) in
immediately awake state and in
followed by absence of Slow atrial fibrillation Paroxysmal SVT or
syncope N/A physical training (< 40 beats/minute) atrial fibrillation
No warning Persistent sinus
symptoms or short bradycardia (< 40
(< 10 seconds) beats/minute) or
prodrome in repetitive sinoatrial
patients with block or sinus pauses
structural heart > 3 seconds in awake
disease or Undiagnosed state and in absence Pre-excited QRS
abnormal ECG N/A systolic murmur of physical training complex
Bundle branch block,
intraventricular
Family history of conduction disorders,
SCD at young age in ventricular
patients with hypertrophy, or Q
structural heart wave consistent with
disease or ischemia or Short QTc interval (≤
abnormal ECG N/A N/A cardiomyopathy 340 milliseconds)
Syncope when in
sitting position in
patients with Ventricular
structural heart tachycardia
disease or (sustained or Atypical Brugada
abnormal ECG N/A N/A unsustained) pattern
Negative T waves in
right precordial
leads, epsilon waves
suggestive of
arrhythmogenic
Pacemaker or ICD right ventricular
N/A N/A N/A malfunction cardiomyopathy
Type I Brugada
N/A N/A N/A pattern N/A
ST elevation with type
I morphology in leads
V1-V3 (Brugada
N/A N/A N/A pattern) N/A
QTc > 460
milliseconds in
N/A N/A N/A repeated 12-lead N/A
 ECG Features in
presence of History
Past Medical Consistent with
Syncope Event History Physical Exam Arrhythmic
Features Features Findings ECG Features Syncope
ECGs indicating long
QT syndrome
Abbreviations: AV, atrioventricular; ECG, electrocardiogram; ICD, implantable cardioverter
defibrillator; LVEF, left ventricular ejection fraction; N/A, not applicable; QTc, corrected QT; SCD,
sudden
cardiac death; SVT, supraventricular tachycardia.
Table 4. European Society of Cardiology (ESC) Proposed High-Risk Features that Suggest Serious
Cause of Syncope

Holter monitoring

• conventionally provides 24-48 hours of monitoring but can be extended to 7 days (Eur Heart J
2009 Nov;30(21):2631)
• may have low diagnostic yield (1%-2%) but can be useful for excluding cardiac syncope due to
arrhythmia1
• should be considered in patients with episodes of syncope or presyncope at least weekly (ESC
Class IIa, Level B)1
• duration of Holter monitoring affects diagnostic yield and 48 or 72 hours may be needed
if 24-hour recording normal
o based on cohort study
o 95 patients with unexplained syncope had 3 serial 24-hour (total 72 hours) Holter
recordings
o major abnormality detected in 26 patients (27%) during entire 72 hours of recording
▪ first 24-hour recording detected abnormality in 14 patients (15%)
▪ second 24-hour recording detected major abnormality in 9 additional patients
(11%,) overall detection yield 24% for 48 hours of Holter monitoring)
▪ third 24-hour recording detected major abnormality in 3 additional patients (4%,
overall detection yield 27% for 72 hours of Holter monitoring)
o none of the arrhythmias found after 24 hours were associated with symptoms
o Reference - Arch Intern Med 1990 May;150(5):1073
• Holter monitoring nondiagnostic in 78% cases of patients with symptoms of dizziness or
syncope in meta-analysis of 7 studies (Ann Intern Med 1990 Jul 1;113(1):53EBSCOhost Full
Text)

Loop recorders (implantable and external)

• external loop recorders

o provide up to 4 weeks monitoring3
o external loop recorders should be considered early after index event in patients with
intervals between symptoms ≤ 4 weeks (ESC Class IIa, Level B)1
o limitations include3
▪ improper device application and use by patient
▪ irritation from electrode adhesive
▪ poor contact during exercise
• implantable loop recorders (ILRs)
 o implanted under local anesthesia subcutaneously with battery life of about 36 months
(Eur Heart J 2009 Nov;30(21):2631)
o stores retrospective ECG recordings when activated by patient, bystander, or
automatically (Eur Heart J 2009 Nov;30(21):2631)
o ILR indicated in early phase of evaluation in patients with recurrent syncope of uncertain
origin (in absence of high-risk criteria) if high likelihood of recurrent event during battery
longevity (ESC Class I, Level A)1
o ILR indicated in high-risk patients when thorough evaluation did not find cause of
syncope or lead to a specific treatment and no conventional indications for ICD for
primary prevention of sudden cardiac death or pacemaker indication (ESC Class I,
Level A)1
o ILR should be considered in patients with suspected or certain reflex syncope
presenting with frequent or severe syncopal episodes (ESC Class IIa, Level B)1
o ILR may be considered in patients in whom epilepsy was previously suspected but
treatment has proven ineffective (ESC Class IIb, Level B)1
o ILR may be considered in patients with unexplained falls (ESC Class IIb, Level B)1
o advantages include3
▪ long recording times
▪ freedom from external electrodes
▪ does not require patient operation
o disadvantages include
▪ need for minor surgery
▪ sometimes difficult to distinguish between supraventricular and ventricular
arrhythmias
▪ Reference - Eur Heart J 2009 Nov;30(21):2631
o International Study on Syncope of Uncertain Etiology (ISSUE) classification of ECG
recordings obtained with implantable loop recorders
▪ Type 1, asystoles (R-R pause ≥ 3 seconds)
▪ sinus arrest (progressive sinus bradycardia or initial sinus tachycardia
followed by progressive sinus bradycardia until sinus arrest)
▪ sinus bradycardia plus atrioventricular (AV) block (progressive sinus
bradycardia followed by AV block and ventricular pauses with decrease in
sinus rate)
▪ Type 2, bradycardia (decrease in heart rate by > 30% or < 40 beats/minute for >
10 seconds)
▪ Type 3, no or slight variations of rhythms with
▪ variation in heart rate < 30%
▪ heart rate > 40 beats/minute
▪ Type 4, tachycardia (increase in heart rate > 30% or > 120 beats/minute
▪ progressive sinus tachycardia
▪ atrial fibrillation
▪ supraventricular tachycardia (except sinus)
▪ ventricular tachycardia
▪ Reference - Europace 2005 Jan;7(1):14EBSCOhost Full Textfull-text
• 4-week external loop recorder diagnostic yield 25% for patients with syncope with early
start of recording after event (≤ 15 days) and history of supraventricular arrhythmias
each associated with increased likelihood of diagnosis
o based on prospective cohort study
o 395 patients (mean age 57 years, 58% women) with syncope or palpitations (28.1% had
syncope and 71.9% had palpitations) were given external loop recorder for ECG
monitoring for 4 weeks
o diagnostic event defined as
 ▪ conclusive event with recurrence of syncope or palpitation with concomitant ECG
recording (with or without arrhythmias)
▪ asymptomatic predefined significant events, including sustained supraventricular
tachycardia or ventricular tachycardia, advanced atrioventricular block, sinus
bradycardia < 30 beats/minute, and pauses > 6 seconds
o diagnostic yield was 25% for patients with syncope and 72% for patients with
palpitations
o factors associated with higher likelihood of diagnosis of syncope included
▪ early start of recording (0-15 days after event) compared to later start of
recording (> 15 days after event) (odds ratio 6.2, 95% CI 1.3-29.6)
▪ history of supraventricular arrhythmias (odds ratio 3.6, 95% CI 1.4-9.7)
o Reference - Europace 2016 Aug;18(8):1265EBSCOhost Full Textfull-text
• implantable loop recorders may increase etiologic electrocardiogram diagnosis and
reduce second relapse but may not reduce mortality in patients with unexplained
recurrent syncope (level 2 [mid-level] evidence)
o based on Cochrane review of trials with methodologic limitations
o systematic review of 4 randomized trials comparing implantable loop recorders vs.
standard diagnostic assessment in 579 adults with unexplained recurrent syncope
o all trials had ≥ 1 limitation including
▪ unclear allocation concealment
▪ no blinding
o implantable loop recorders associated with
▪ decreased failure to achieve etiological electrocardiogram (ECG) diagnosis in
analysis of 4 trials with 579 patients
▪ risk ratio 0.61 (95% CI 0.54-0.68)
▪ NNT 3-4 with failure to achieve etiologic electrocardiogram diagnosis in
87% of standard diagnostic assessment group
▪ reduction in second syncope in 2 trials with 447 patients
▪ meta-analysis not performed due to difference in reported outcomes
▪ hazard ratio 0.38 (95% CI 0.17-0.86) in 1 trail with 246 patients
o no significant difference in mortality at 12-18 months in analysis of 2 trials with 255
patients
o no complications after implantable loop recorder implantation in 2 trials with 228
patients
o Reference - Cochrane Database Syst Rev 2016 Apr 19;(4):CD011637
o implantable loop recorder for recurrent unexplained syncope may be associated
with improved quality of life (level 2 [mid-level] evidence)
▪ based on randomized trial with unclear blinding
▪ 201 patients (median age 74 years) with recurrent unexplained syncope were
randomized to implantable loop recorder vs. conventional evaluation and
management
▪ median follow-up 17 months
▪ comparing implantable loop recorder vs. routine care
▪ recurrent syncope in 47% vs. 38% (no p value reported)
▪ diagnosis made in 42% vs. 7% (p < 0.001)
▪ mortality 8% vs. 9% (not significant)
▪ no differences in time to first syncope recurrence
▪ implantable loop recorder significantly increased time to second syncope (p =
0.04) and improved quality of life (p = 0.03)
▪ Reference - Eur Heart J 2006 Feb;27(3):351full-text
▪ DynaMed Commentary
 Some numbers in the full-text article (for example, mortality) did not agree with
those in the abstract.
• outpatient telemetry system may detect more arrhythmias than external loop recorders
in patients with syncope or presyncope (level 2 [mid-level] evidence)
o based on subgroup analysis of randomized trial
o 305 patients with syncope, presyncope, or severe palpitations were randomized to
outpatient telemetry system vs. external loop recorder
o arrhythmia detected with outpatient telemetry system in 89% and with external loop
record in 69% in subgroup analysis of patients with syncope or presyncope (p = 0.008)
o Reference - J Cardiovasc Electrophysiol 2007 Mar;18(3):241EBSCOhost Full Text,
editorial can be found in J Cardiovasc Electrophysiol 2007 Mar;18(3):248EBSCOhost Full
Text

Electrophysiological studies (EPS)

• role of EPS in syncope evaluation has decreased with higher diagnostic value of noninvasive
testing (such as electrocardiography [ECG] monitoring) but remains useful in some situations1
• EPS generally not useful in patients with syncope who have normal ECG, no heart disease,
and no palpitations1
• European Society of Cardiology (ESC) recommendations for electrophysiological studies
(EPS)1
o indications
▪ EPS indicated in patients with syncope and previous myocardial infarction (or
other scar-related conditions) when syncope remains unexplained after
noninvasive evaluation (ESC Class I, Level B) (suspected tachycardia)
▪ consider EPS in
▪ patients with syncope and bifascicular bundle branch block if noninvasive
testing has not resulted in diagnosis (ESC Class IIa, Level B) (due to
possibility of impending high-degree atrioventricular [AV] block)
▪ few instances in patients with syncope and asymptomatic sinus
bradycardia when noninvasive tests (such as ECG monitoring) have failed
to correlate bradycardia with syncope (ESC Class IIb, Level B) (due to
possibility of sinus arrest as cause of syncope)
▪ syncope preceded by sudden brief palpitations if noninvasive testing has
not resulted in diagnosis (ESC Class IIb, Level C) (suspected tachycardia)
o test interpretation and diagnostic criteria
▪ positive EPS study generally suggest arrhythmic syncope, but negative EPS
study does not exclude arrhythmic syncope
▪ asymptomatic bradycardia (suspected sinus arrest as cause of syncope)
▪ pre-test probability of bradycardia-related syncope relatively high if
asymptomatic bradycardia (< 50 beats/minute) or sinoatrial block on ECG
▪ abnormal or prolonged sinus node recovery time (SNRT) defined as > 2
seconds or ≥ 525 milliseconds for corrected SNRT
▪ bifascicular bundle branch block (possibility of impending high-degree AV block)
▪ prolonged HV interval (≥ 70 milliseconds) or induction of second- or third-
degree AV block with pacing or pharmacological stress (ajmaline,
procainamide, or disopyramide) suggests high risk of developing AV block
▪ EPS reported to have high positive predictive value (≥ 80%) but low
negative predictive value for predicting development of AV block
▪ suspected tachycardia as cause of syncope
 ▪ in patients with syncope preceded by sudden onset of brief palpitations,
EPS may identify mechanism of tachycardia, which may benefit from
curative catheter ablation
▪ in patients with previous myocardial infarction and preserved left
ventricular ejection fraction
▪ induction of sustained monomorphic ventricular tachycardia
strongly suggests tachycardia as cause of syncope
▪ induction of ventricular fibrillation considered nonspecific finding
▪ absence of induction of ventricular arrhythmias suggests low risk of
arrhythmic syncope
▪ in patients with ischemic cardiomyopathy or dilated cardiomyopathy, induction of
polymorphic ventricular tachycardia/fibrillation cannot be considered diagnostic
finding for cause of syncope
▪ in patients with syncope and suspected Brugada syndrome, role of EPS with
pharmacological challenge controversial as induction of ventricular
tachycardia/fibrillation plus other findings may suggest increased risk of
arrhythmic events while absence of induction may not help determine risk of
arrhythmic events
• American College of Cardiology/American Heart Association/Heart Rhythm Society
(ACC/AHA/HRS) recommendations for EPS4
o EPS can be useful in select patients with suspected arrhythmic cause of syncope
(ACC/AHA/HRS Class IIa, Level B-NR)
o EPS not recommended in patients with normal ECG and normal cardiac structure and
function unless suspect arrhythmic cause of syncope (ACC/AHA/HRS Class III, Level B-
NR)
• negative electrophysiologic testing may not rule out arrhythmia-related syncope in
syncopal patients with heart disease
o based on cohort study
o 35 patients with syncope and heart disease (previous MI or cardiomyopathy with
reduced ejection fraction or nonsustained ventricular tachycardia) and negative
electrophysiologic studies had implanted loop recorders for 3-15 months
o patients were instructed to activate devices after each syncopal or presyncopal episode
o 6 patients (17%) had syncope after mean 6 months (3 had bradycardia, 2 had atrial
fibrillation, and 1 had sinus tachycardia)
o 8 patients (23%) had presyncope
o Reference - Circulation 2002 Jun 11;105(23):2741full-text

Exercise testing

• European Society of Cardiology (ESC) recommendations for exercise stress testing1

o exercise testing indicated in patients who develop syncope during or soon after exertion
(ESC Class I, Level C)
o diagnostic criteria
▪ syncope due to second- or third-degree atrioventricular (AV) block confirmed if
AV block develops during exercise, even without syncope (ESC Class I, Level C)
▪ reflex syncope confirmed if syncope reproduced immediately after exercise in
presence of severe hypotension (ESC Class I, Level C)
▪ routine exercise testing not indicated in patients with syncope
• exercise stress testing can be useful to determine cause of syncope in select patients with
syncope or presyncope during exertion (ACC/AHA/HRS Class IIa, Level C-LD)4
Treatment of cardiac syncope

Syncope due to arrhythmias

• therapy goals include1

o prevention of symptom recurrence
o improvement of quality of life
o decrease risk of sudden cardiac death (SCD)
• European Society of Cardiology (ESC) treatment recommendations for syncope due to cardiac
arrhythmias1
o cardiac pacing
▪ cardiac pacing is indicated in patients with
▪ established relationship between syncope and symptomatic bradycardia
due to
▪ sick sinus syndrome (ESC Class I, Level B)
▪ intrinsic atrioventricular (AV) block (ESC Class I, Level B)
▪ syncope and intermittent/paroxysmal intrinsic third- or second-degree AV
block (including atrial fibrillation with slow ventricular conduction) even if
no documentation of relationship between symptoms and
electrocardiograms (ECGs) (ESC Class I, Level C)
▪ syncope, bundle branch block (BBB), and positive electrophysiological
studies or implantable loop recorder (ILR) documented AV block (ESC
Class I, Level B)
▪ unexplained syncope and bifascicular BBB in presence of baseline H-V
interval ≥ 70 milliseconds, second- or third-degree His-Purkinje block
during electrophysiological studies with incremental atrial pacing or with
pharmacological challenge (ESC Class I, Level B)
▪ cardiac pacing should be considered in patients with
▪ relationship between syncope and asymptomatic sinus node dysfunction
less established (ESC Class IIa, Level C)
▪ syncope and asymptomatic sinus bradycardia if prolonged correct sinus
node recovery time (SNRT) on electrophysiological studies (ESC Class
IIa, Level B) (prolonged SNRT defined as ≥ 525 milliseconds for corrected
SNRT)
▪ cardiac pacing may be considered in patients with unexplained syncope and
bifascicular BBB (ESC Class IIb, Level B)
▪ cardiac pacing is not indicated in patients with
▪ reversible causes of bradycardia (ESC Class III, Level C)
▪ unexplained syncope without evidence of any conduction abnormalities
▪ additional considerations for cardiac pacing
▪ factors reported to predict efficacy of cardiac pacing for preventing
syncope recurrent include established relationship between symptoms
and bradycardia and absence of associated hypotensive susceptibility
▪ when relationship between symptoms and bradycardia less established or
if hypotensive mechanism present, syncope can recur in minority of
patients
▪ in patients with bifascicular BBB, conduct useful investigations (carotid
sinus massage, electrophysiological studies, or implantable loop recorder)
to provoke/document mechanism of syncope before deciding to implant
cardiac pacemaker or select correct therapy as < 50% of these patients
have final diagnosis of cardiac syncope
 ▪ older patients with bifascicular BBB and unexplained syncope after
reasonable evaluation might benefit from empirical cardiac pacing,
especially if syncope unpredictable (with no or short prodromes) or if
syncope occurs in supine position or during effort
o catheter ablation is indicated in patients with syncope due to supraventricular
tachycardia or ventricular tachycardia to prevent syncope recurrence (ESC Class I,
Level B)
o antiarrhythmic drug therapy (including rate control drugs) should be considered in
patients with syncope due to supraventricular tachycardia or ventricular tachycardia
(ESC Class IIa, Level C)
o Implantable cardioverter defibrillator (ICD)
▪ ICD is indicated in patients with
▪ syncope due to ventricular tachycardia and left ventricular ejection fraction
(LVEF) ≤ 35% (ESC Class I, Level B)
▪ syncope, previous myocardial infarction, and ventricular tachycardia
induced during electrophysiological studies (ESC Class I, Level C)
▪ ICD should be considered in patients with LVEF > 35% and recurrent syncope
due to ventricular tachycardia if catheter ablation and pharmacological therapy
have failed or could not be performed (ESC Class IIa, Level C)
▪ when syncope due to ventricular tachycardia (including if diagnosis established
by induction of ventricular tachycardia during electrophysiological studies),
catheter ablation should always be attempted in addition to ICD when feasible as
ICD may be unable to prevent syncope due to recurrence of ventricular
tachycardia
o additional considerations for therapy guided by electrophysiological studies
▪ in patients with unexplained syncope and previous myocardial infarction (or other
scar-related conditions) in presence of induced sustained monomorphic
ventricular tachycardia, manage according to guidelines for management
of ventricular arrhythmias (ESC Class I, Level B)
▪ in patients without structural heart disease with syncope preceded by sudden
and brief palpitations, if rapid supraventricular tachycardia or ventricular
tachycardia induced during electrophysiological studies and result in reproduction
of hypotension or spontaneous symptoms, manage according to guidelines (ESC
Class I, Level C)

Syncope secondary to structural cardiac or cardiovascular disease

• therapy goals include1

o prevent syncope recurrence
o treat underlying disease
o decrease risk of sudden cardiac death
• treatment of syncope associated with structural heart disease varies with diagnosis
o in patients with syncope secondary to severe aortic stenosis or atrial myxoma, surgical
treatment of underlying disease is indicated
o in patients with syncope secondary to acute cardiovascular disease (pulmonary
embolism, myocardial infarction, or pericardial tamponade), treatment directed at
underlying process
o in patients with hypertrophic cardiomyopathy (with or without left ventricular outflow
obstruction)
▪ treatment is specific to arrhythmia
▪ implantable cardioverter defibrillator (ICD) should be implanted in most patients
to prevent sudden cardiac death
 o in patients with syncope associated with myocardial ischemia, therapy includes
medication or revascularization in most cases
o in patients with syncope caused by primary pulmonary hypertension or restrictive
cardiomyopathy, treatment of underlying condition often impossible
o Reference - Eur Heart J 2009 Nov;30(21):2631

Prognosis and Complications

Recurrence risk

• incidence of syncope recurrence

o pooled incidence of syncope recurrence in systematic review of 25 observational
studies evaluating prognosis in 11,158 patients presenting to emergency department
with syncope
▪ 0.3% (95% CI 0%-1.8%) at 30 days in analysis of 1 trial with 380 patients
▪ 5.2% (95% CI 3.3%-8.2%) at 6 months in analysis of 2 trials with 350 patients
▪ 9% (95% CI 7.2%-11.3%) at 1 year in analysis of 2 studies with 797 patients
▪ 16.1% (95% CI 14.2%-18.3%) at 1.5 years in analysis of 4 studies with 1,254
patients
▪ 22% (95% CI 16.3%-29.1%) at 2 years in analysis of 2 studies with 164 patients
▪ Reference - Europace 2015 Feb;17(2):300
o 30% men and 27% women who experienced syncope had > 1 episode based on cohort
of 5,209 adults with syncope in Framingham study (Stroke 1985 Jul-Aug;16(4):626)
o in patients with syncope and sinus node disease with less established relationship
between symptoms and electrocardiography, 15%-28% reported syncope recurrence at
5 years despite adequate pacing1
• in patients aged > 40 years with low risk of all-cause mortality, predictor of recurrent episodes
is number of prior episodes
o if previous 1-2 episodes, then reported recurrence rate
▪ 15% at 1 year
▪ 20% at 2 years
o if previous 3 episodes, then reported recurrence rate
▪ 36% at 1 year
▪ 42% at 2 years
o Reference - Eur Heart J 2009 Nov;30(21):2631
• relationship between recurrence risk and tilt test results in children has limited and
inconsistent evidence
o positive tilt test associated with increased risk of syncope recurrence in children
▪ based on retrospective study
▪ 45 children with syncope and normal electrocardiogram and echocardiogram had
tilt testing
▪ 20 children had negative tilt test and were counseled to increase fluid
intake
▪ 25 children had positive tilt test and were treated with fludrocortisone 0.3
mg/day for 1 week, then 0.1 mg/day after plus sodium chloride 1 g/day
▪ mean follow-up was 2.8 years in children with positive tilt test and 1.9 years in
children with negative tilt test
▪ 5 children with negative tilt test were lost to follow-up
▪ recurrent syncope occurred in 13 children with positive tilt test and 2 children with
negative tilt test (p = 0.02)
▪ Reference - Pediatrics 1998 Oct;102(4);924
 o syncope recurrence rate in children not associated with tilt test results
▪ based on prospective cohort study
▪ 101 children aged 7-18 years with syncope or presyncope and nondiagnostic
initial testing had tilt testing and followed for mean 46 months
▪ 67 children had positive tilt test (including 58 with vasovagal syncope and 9 with
psychogenic syncope), of whom 43 children were treated with beta blockers,
fludrocortisone, disopyramide, midodrine, or oral fluid therapy
▪ 4 children were lost to follow-up and excluded from analysis
▪ 31 children (32%) had recurrent syncope
▪ number of previous syncopal episodes was only factor significantly associated
with risk of recurrent syncope
▪ tilt test results and treatment were not associated with recurrence risk
▪ Reference - Eur Heart J 2001 Sep;22(17):1618full-text

Prognosis

• pooled incidence of mortality in systematic review of 25 observational studies evaluating

prognosis in 11,158 patients presenting to emergency department with syncope
o 0.7% (95% CI 0.4%-1.3%) at 10 days in analysis of 3 studies with 1,472 patients
o 1.6% (95% CI 1.2%-2.1%) at 30 days in analysis of 4 studies with 3,214 patients
o 3.7% (95% CI 2.5%-5.4%) at 6 months in analysis of 4 studies with 1,923 patients
o 8.4% (95% CI 6.7%-10.2%) at 1 year in analysis of 9 studies with 4,879 patients
o 8.9% (95% CI 7.4%-10.6%) at 1.5 years in analysis of 4 studies with 1,254 patients
o 11% (95% CI 7%-16.8%) at 2 years in analysis of 2 studies with 164 patients
o Reference - Europace 2015 Feb;17(2):300
• major risk factors for sudden cardiac death and overall mortality in patients with syncope
include1
o structural heart disease
o primary electrophysiological conditions
▪ congenital long QT syndrome
▪ short QT syndrome
▪ Wolff-Parkinson-White syndrome
▪ idiopathic ventricular fibrillation
▪ Brugada syndrome
▪ catecholaminergic polymorphic ventricular tachycardia (CPVT)
• prognosis by type of syncope1
o orthostatic syncope associated with 2-fold higher risk of mortality, coronary artery
disease, heart failure, and stroke compared to general population
o young patients with neurally mediated syncope without structural heart disease or
primary electrophysiological conditions have excellent prognosis
• risk of overall mortality and adverse cardiovascular outcomes appears increased
following hospitalization for syncope in patients with no previous comorbidity
o based on retrospective cohort study
o 37,017 patients discharged from hospital after first diagnosis of syncope and with no
previous comorbidity were compared to 185,085 age- and sex-matched patients without
syncope from general population in Denmark
o mean follow-up 4.5 years for patients with syncope
o comparing outcomes per 1,000 patient-years in patients with syncope vs. patients
without syncope
▪ overall mortality in 14.3 vs. 13.3 (hazard ratio [HR] 1.6, 95% CI 1.03-2.68)
▪ cardiovascular hospitalization in 26.5 vs. 15.3 (HR 1.74, 95% CI 1.68-1.8)
 ▪ stroke in 6.8 vs. 5 (HR 1.35, 95% CI 1.27-1.44)
▪ implantation of pacemaker or cardioverter-defibrillator in 4.2 vs. 0.8 (HR 5.52,
95% CI 4.67-5.73)
o Reference - J Am Coll Cardiol 2013 Jan 22;61(3):325full-text, editorial can be found in J
Am Coll Cardiol 2013 Jan 22;61(3):333
• morbidity and mortality differ according to underlying cause of syncope
o based on cohort study
o 7,814 patients followed for mean 17 years in Framingham Heart Study included
o 10.6% reported syncope
o cardiac syncope associated with increased risk for all-cause mortality and
cardiovascular events
o neurologic syncope or idiopathic syncope associated with increased risk for all-cause
mortality
o unknown syncope associated with increased risk for all-cause mortality
o vasovagal syncope not associated with increased risk for death or cardiovascular
events
o Reference - N Engl J Med 2002 Sep 19;347(12):878full-text, editorial can be found in N
Engl J Med 2002 Sep 19;347(12):931, summary can be found in Am Fam Physician
2003 Jan 15;67(2):414
• exercise-related syncope not associated with adverse outcomes over 3 years
o based on cohort study
o 33 athletes (mean age 21 years) with recurrent unexplained exercise-related syncope
had extensive evaluation and were followed for mean 33.5 months
o 11 (33%) had ≥ 1 recurrence of exercise-related syncope
o no other adverse events
o Reference - Eur Heart J 2002 Jul;23(14):1125, editorial can be found in Eur Heart J
2002 Jul;23(14):1080, commentary can be found in Eur Heart J 2003 Feb;24(3):289;
author reply 289
• isolated syncope not associated with increased morbidity or mortality
o based on cohort study
o 5,209 patients aged 30-62 years followed for mean 26 years in Framingham study
included
o 3.3% reported ≥ 1 syncope episode, 2.8% reported isolated syncope (defined as
transient loss of consciousness in the absence of prior or concurrent neurologic,
coronary, or other cardiovascular disease stigmata)
o isolated syncope was not associated with any excess risk for stroke, transient ischemic
attack, myocardial infarction (MI), all-cause mortality, cardiovascular mortality or sudden
death
o Reference - Stroke 1985 Jul-Aug;16(4):626full-text

Complications

• risk of injury in patients with recurrent syncope1

o fractures and soft tissue injuries reported in 12%
o major trauma reported in 4.7%
o minor trauma reported in 29%
• compromise in quality of life
o vocational implications1
o risk for depression, especially older persons1
o risk for disrupting participation in family and social activities1
o implications for driving
 ▪ European Society of Cardiology guideline on driving and heart disease can be
found in Eur Heart J 1998 Aug;19(8):1165
▪ driving restrictions rarely complied with based on anonymous survey of patients
with syncope (BMJ 2003 Jan 4;326(7379):21full-text), commentary can be found
in BMJ 2003 Mar 15;326(7389):601full-text

Quality Improvement
Choosing Wisely

• American College of Physicians recommends against obtaining brain imaging studies

(computed tomography [CT] or magnetic resonance imaging [MRI]) in the evaluation of simple
syncope and a normal neurological examination (Choosing Wisely 2012 Apr 4)
• American Academy of Neurology recommends against performing imaging of the carotid
arteries for simple syncope without other neurologic symptoms (Choosing Wisely 2013 Feb 21)
• American College of Emergency Physicians recommends avoiding CT of the head in
asymptomatic adult patients in the emergency department with syncope, insignificant trauma
and a normal neurological evaluation (Choosing Wisely 2014 Oct 27)

Choosing Wisely Australia

• Australian and New Zealand Association of Neurologists recommends against performing

imaging of carotid arteries for simple faints (Choosing Wisely Australia 2016 Oct 1 )
• Internal Medicine Society of Australia and New Zealand recommends against requesting
Holter monitoring, carotid duplex scans, echocardiography, electroencephalograms (EEGs) or
telemetry in patients with first presentation of uncomplicated syncope and no high risk
features. (Choosing Wisely Australia 2017 Oct 17)

Choosing Wisely Canada

• Canadian Society of Hospital Medicine recommends against routinely obtaining neuro-imaging

studies (CT, MRI scans, or carotid doppler ultrasonography) in the evaluation of simple
syncope in patients with a normal neurological examination (Choosing Wisely Canada 2015
Jun 2)
• Canadian Society of Internal Medicine recommends against routinely obtaining neuro-imaging
studies (CT, MRI scans, or carotid doppler ultrasonography) in the evaluation of simple
syncope in patients with a normal neurological examination (Choosing Wisely Canada 2014
Apr 2)
• Canadian Association of Emergency Physicians recommends against ordering CT head scans
in adults with simple syncope in absence of high-risk predictors
o high-risk predictors include (but are not limited to): trauma above clavicles, headache,
persistent neurologic deficit, > 65 years old, anticoagulants, and known malignancies
o in the absence of high-risk predictors, head CT unlikely to aid management of patients
with syncope
o CT scans expose patients to unnecessary ionizing radiation that may increase lifetime
risk of cancer
o Reference - Choosing Wisely Canada 2016 Oct 3

Choosing Wisely Italy

 • Italian Association for Cardiovascular Prevention, Rehabilitation, and Epidemiology (GICR-
IACPR) recommends against performing Holter electrocardiographic monitoring in patients
suffering from syncope, near-syncope, or dizziness, in whom a nonarrhythmic origin has been
documented. (Choosing Wisely Italy 2015 Sep PDF, Choosing Wisely Italy 2015 Sep
PDF [Italian])

Guidelines and Resources

Guidelines

United States guidelines

• American College of Cardiology/American Heart Association/Heart Rhythm Society

(ACC/AHA/HRS) guideline for the evaluation and management of patients with syncope can
be found in Circulation 2017 Aug 1;136(5):e25

• American Heart Association/American College of Cardiology Foundation (AHA/ACCF)

scientific statement on evaluation of syncope can be found in Circulation 2006 Jan
17;113(2):316full-text, correction can be found in Circulation. 2006 Apr 11;113(14):e697, or
in J Am Coll Cardiol 2006 Jan 17;47(2):473, summary can be found in Am Fam Physician
2006 Jul 1;74(1):179
• American College of Emergency Physicians (ACEP) clinical policy on critical issues in
evaluation and management of adult patients presenting to emergency department with
syncope can be found in Ann Emerg Med 2007 Apr;49(4):431
• Cincinnati Children's Hospital Medical Center Best evidence statement (BESt) on evaluation of
syncope can be found at 2010 Apr PDF
• American Heart Association/American College of Cardiology (AHA/ACC) scientific statement
on competitive athletes with cardiovascular abnormalities (Task Force 9): arrhythmias and
conduction defects can be found in Circulation 2015 Dec 1;132(22):e315 or in J Am Coll
Cardiol 2015 Dec 1;66(21):2412full-text
• American College of Cardiology/American Heart Association/American Society of
Echocardiography (ACC/AHA/ASE) guideline on clinical application of echocardiography can
be found in J Am Coll Cardiol 2003 Sep 3;42(5):954full-text, J Am Soc Echocardiogr 2003
Oct;16(10):1091, or in Circulation 2003 Sep 2;108(9):1146

United Kingdom guidelines

• National Institute for Health and Clinical Excellence (NICE) guideline on transient loss of
consciousness ('blackouts') management in adults and young people can be found at NICE
2010 Aug:CG109PDF (reaffirmed October 2014), summary can be found in BMJ 2010 Sep
2;341:c4457full-text, Br J Gen Pract 2011 Jan;61(582):40, or in Ann Intern Med 2011 Oct
18;155(8):543EBSCOhost Full Text

Canadian guidelines

• Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association (CCS/CPCA)

position statement on approach to syncope in pediatric patient can be found in Can J Cardiol
2017 Feb;33(2):189full-text
• Canadian Cardiovascular Society consensus conference on management of heart disease in
the elderly patient can be found in Can J Cardiol 2004 May;20 Suppl A:7A or at CCS 2002
PDF
European guidelines

• European Society of Cardiology (ESC) guideline on diagnosis and management of syncope

can be found in Eur Heart J 2018 Jun 1;39(21):1883

• European Heart Rate Association (EHRA) guideline on indications for use of diagnostic
implantable and external electrocardiogram (ECG) loop recorders can be found in Europace
2009 May;11(5):671EBSCOhost Full Textfull-text, correction can be found in Europace 2009
Jun;11(6):836, commentary can be found in Europace 2009 Nov;11(11):1566EBSCOhost Full
Textfull-text
• Haute Autorité de Santé (HAS) conseils sur pertes de connaissance brèves de l’adulte: prise
en charge diagnostique et thérapeutique des syncopes se trouvent sur le site Haute Autorité
de Santé 2008 May [French]

Review articles

• review can be found in Am Fam Physician 2011 Sep 15;84(6):640EBSCOhost Full Textfull-text,
commentary can be found in Am Fam Physician 2012 Sep 1;86(5):392, 394EBSCOhost Full
Text
• review of syncope evaluation and differential diagnosis can be found in Am Fam Physician
2017 Mar 1;95(5):303EBSCOhost Full Textfull-text
• review of clinical examination in the diagnosis of cardiac syncope can be found in Acad Emerg
Med 2019 Sep 30 early online
• review of evaluation and management of syncope in adults can be found in BMJ 2010 Feb
19;340:c880
• review of pediatric disorders of orthostatic intolerance can be found in Pediatrics 2018
Jan;141(1):e20171673full-text
• review of syncope in pregnancy, including case report can be found in Obstet Gynecol 2010
Feb;115(2 Pt 1):377
• reviews of syncope in older adults
o review of geriatric syncope and cardiovascular risk in emergency department can be
found in J Emerg Med 2017 Apr;52(4):438
o review of syncope evaluation in older adults can be found in Emerg Med Clin North Am
2016 Aug;34(3):601
• review of utility of orthostatic vital signs in evaluation of syncope can be found in J Emerg Med
2018 Dec;55(6):780
• review of vascular causes of syncope can be found in J Emerg Med 2017 Sep;53(3):322
• review of mimics of syncope can be found in J Emerg Med 2018 Jan;54(1):81

MEDLINE search

• to search MEDLINE for (Syncope) with targeted search (Clinical Queries),

click therapy, diagnosis, or prognosis

Patient Information
• handout from American Heart Association
• handout from Heart Rhythm Society
• handout from American Academy of Family Physicians or in Spanish
• handout from American Academy of Pediatrics
• handout from Patient UK PDF
 • handout from My Health Alberta

ICD Codes
ICD-10 codes

• R55 syncope and collapse

• T67.1 heat syncope

References
General references used

1. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and
management of syncope. Eur Heart J. 2018 Jun 1;39(21):1883-1948full-text
2. Jhanjee R, van Dijk JG, Sakaguchi S, Benditt DG. Syncope in adults: terminology,
classification, and diagnostic strategy. Pacing Clin Electrophysiol. 2006 Oct;29(10):1160-
9EBSCOhost Full Text
3. Saklani P, Krahn A, Klein G. Syncope. Circulation. 2013 Mar 26;127(12):1330-9full-text
4. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation
and Management of Patients With Syncope: Executive Summary: A Report of the American
College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines,
and the Heart Rhythm Society. J Am Coll Cardiol 2017 Aug 1;70(5):620full-text

Recommendation grading systems used

• American College of Cardiology/American Heart Association/Heart Rhythm Society

(ACC/AHA/HRS) grading system for recommendations
o classifications of recommendations
▪ Class I - procedure or treatment should be performed or administered
▪ Class IIa - reasonable to perform procedure or administer treatment, but
additional studies with focused objectives needed
▪ Class IIb - procedure or treatment may be considered; additional studies with
broad objectives needed, additional registry data would be useful
▪ Class III - procedure or treatment should not be performed or administered
because it is not helpful or may be harmful
▪ Class III ratings may be subclassified as Class III No Benefit or Class III
Harm
o levels of evidence
▪ Level A - high-quality evidence from > 1 randomized controlled trial or meta-
analysis of high-quality randomized controlled trials
▪ Level B-R - moderate-quality evidence from ≥ 1 randomized controlled trial or
meta-analysis of moderate-quality randomized controlled trials
▪ Level B-NR - moderate-quality evidence from ≥ 1 well-designed nonrandomized
trial, observational studies, or registry studies, or meta-analysis of such studies
▪ Level C-LD - randomized or nonrandomized studies with methodological
limitations or meta-analyses of such studies
▪ Level C-EO - consensus of expert opinion based on clinical experience
o Reference - ACC/AHA/HRS guideline on evaluation and management of patients with
syncope (J Am Coll Cardiol 2017 Aug 1;70(5):620full-text)
 • European Society of Cardiology (ESC) grading system for recommendations
o classes of recommendations
▪ Class I - evidence and/or general agreement that treatment or procedure is
beneficial, useful, effective
▪ Class II - conflicting evidence and/or divergence of opinion about
usefulness/efficacy of treatment or procedure
▪ Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
▪ Class IIb - weight of usefulness/efficacy less well established by
evidence/opinion
▪ Class III - evidence or general agreement that given treatment or procedure is
not useful/effective and may be harmful in some cases
o levels of evidence
▪ Level A - data from multiple randomized trials or meta-analyses
▪ Level B - data from single randomized trial or large nonrandomized studies
▪ Level C - expert consensus opinion and/or small studies, retrospective studies, or
registries
o Reference - ESC guideline on diagnosis and management of syncope (Eur Heart J
2018 Jun 1;39(21):1883full-text)

Synthesized Recommendation Grading System for DynaMed

• DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the

most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based
Methodology).
• Guideline recommendations summarized in the body of a DynaMed topic are provided with the
recommendation grading system used in the original guideline(s), and allow DynaMed users to
quickly see where guidelines agree and where guidelines differ from each other and from the
current evidence.
• In DynaMed (DM), we synthesize the current evidence, current guidelines from leading
authorities, and clinical expertise to provide recommendations to support clinical decision-
making in the Overview & Recommendations section.
• We use the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) to classify synthesized recommendations as Strong or Weak.
o Strong recommendations are used when, based on the available evidence, clinicians
(without conflicts of interest) consistently have a high degree of confidence that the
desirable consequences (health benefits, decreased costs and burdens) outweigh the
undesirable consequences (harms, costs, burdens).
o Weak recommendations are used when, based on the available evidence, clinicians
believe that desirable and undesirable consequences are finely balanced, or
appreciable uncertainty exists about the magnitude of expected consequences (benefits
and harms). Weak recommendations are used when clinicians disagree in judgments of
relative benefit and harm, or have limited confidence in their judgments. Weak
recommendations are also used when the range of patient values and preferences
suggests that informed patients are likely to make different choices.
• DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section)
are determined with a systematic methodology:
o Recommendations are initially drafted by clinical editors (including ≥ 1 with
methodological expertise and ≥ 1 with content domain expertise) aware of the best
current evidence for benefits and harms, and the recommendations from guidelines.
o Recommendations are phrased to match the strength of recommendation. Strong
recommendations use "should do" phrasing, or phrasing implying an expectation to
 perform the recommended action for most patients. Weak recommendations use
"consider" or "suggested" phrasing.
o Recommendations are explicitly labeled as Strong recommendations or Weak
recommendations when a qualified group has explicitly deliberated on making such a
recommendation. Group deliberation may occur during guideline development. When
group deliberation occurs through DynaMed-initiated groups:
▪ Clinical questions will be formulated using the PICO (Population, Intervention,
Comparison, Outcome) framework for all outcomes of interest specific to the
recommendation to be developed.
▪ Systematic searches will be conducted for any clinical questions where
systematic searches were not already completed through DynaMed content
development.
▪ Evidence will be summarized for recommendation panel review including for
each outcome, the relative importance of the outcome, the estimated effects
comparing intervention and comparison, the sample size, and the overall quality
rating for the body of evidence.
▪ Recommendation panel members will be selected to include at least 3 members
that together have sufficient clinical expertise for the subject(s) pertinent to the
recommendation, methodological expertise for the evidence being considered,
and experience with guideline development.
▪ All recommendation panel members must disclose any potential conflicts of
interest (professional, intellectual, and financial), and will not be included for the
specific panel if a significant conflict exists for the recommendation in question.
▪ Panel members will make Strong recommendations if and only if there is
consistent agreement in a high confidence in the likelihood that desirable
consequences outweigh undesirable consequences across the majority of
expected patient values and preferences. Panel members will make Weak
recommendations if there is limited confidence (or inconsistent assessment or
dissenting opinions) that desirable consequences outweigh undesirable
consequences across the majority of expected patient values and preferences.
No recommendation will be made if there is insufficient confidence to make a
recommendation.
▪ All steps in this process (including evidence summaries which were shared with
the panel, and identification of panel members) will be transparent and
accessible in support of the recommendation.
o Recommendations are verified by ≥ 1 editor with methodological expertise, not involved
in recommendation drafting or development, with explicit confirmation that Strong
recommendations are adequately supported.
o Recommendations are published only after consensus is established with agreement in
phrasing and strength of recommendation by all editors.
o If consensus cannot be reached then the recommendation can be published with a
notation of "dissenting commentary" and the dissenting commentary is included in the
topic details.
o If recommendations are questioned during peer review or post publication by a qualified
individual, or reevaluation is warranted based on new information detected through
systematic literature surveillance, the recommendation is subject to additional internal
review.

DynaMed Editorial Process

• DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
 • All editorial team members and reviewers have declared that they have no financial or other
competing interests related to this topic, unless otherwise indicated.
• DynaMed provides Practice-Changing DynaMed Updates, with support from our partners,
McMaster University and F1000.

Special acknowledgements

•
The American College of Physicians (Marjorie Lazoff, MD, FACP; ACP Deputy Editor, Clinical
Decision Resource) provided review in a collaborative effort to ensure DynaMed provides the
most valid and clinically relevant information in internal medicine.
• Choosing Wisely Canada acknowledges dissemination of their recommendations through
DynaMed Plus to reach the point of clinical decision-making.
• The Canadian Society of Hospital Medicine provides review for the incorporation of
Choosing Wisely Canada recommendations.
• The Canadian Society of Internal Medicine provides review for the incorporation of
Choosing Wisely Canada recommendations.
• DynaMed topics are written and edited through the collaborative efforts of the above
individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or
academic medical practice. Recommendations Editors are actively involved in development
and/or evaluation of guidelines.
• Editorial Team role definitions
Topic Editors define the scope and focus of each topic by formulating a set of clinical questions
and suggesting important guidelines, clinical trials, and other data to be addressed within each
topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the
writing and editing process, and review the final topic drafts prior to publication.
Section Editors have similar responsibilities to Topic Editors but have a broader role that includes
the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the
medical literature.
Recommendations Editors provide explicit review of DynaMed Overview and Recommendations
sections to ensure that all recommendations are sound, supported, and evidence-based. This
process is described in "Synthesized Recommendation Grading."
Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups.
Each is responsible for all content published within that group, including supervising topic
development at all stages of the writing and editing process, final review of all topics prior to
publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal

Editors):

• DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record

No. T116050, Syncope - Approach to the Patient; [updated 2018 Nov 30, cited place cited
date here]. Available from https://www.dynamed.com/topics/dmp~AN~T116050. Registration
and login required.