SYNCOPE

• ACRONYMS AND DEFINITIONS

• AHA - American Heart Association
• DBP - Diastolic blood pressure
• ECG - Electrocardiogram
• EFAS - European Federation of Autonomic Societies
• ESC - European Society of Cardiology
• LOC - Loss of consciousness
• OH - Orthostatic hypotension
• POTS - Postural orthostatic tachycardia syndrome
• SBP - Systolic blood pressure

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• PREVALENCE

• Syncope is a common occurrence. In a random sample of 1925 adults with an average age of 62 years, the reported lifetime prevalence of ≥ 1 syncopal episode was 19%. Females are affected more than males, and peak incidences occur around the ages of 20, 60, and 80 years. In the U.S., syncope accounts for 3.5% of all ER visits and 1 - 6% of all hospital admissions.
• The cause of syncope can be difficult to discern since some of the more common etiologies do not have a definitive objective finding and their mechanisms are poorly understood. The table below gives the reported frequencies of different types of syncope from studies. [2,5]

• References [3]

Causes of Syncope
Causes	% of cases
Neurocardiogenic	21%
Cardiac	9%
Orthostatic hypotension	9%
Unknown	37%

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• TYPES OF SYNCOPE

• Overview
• Syncope is defined as a total loss of consciousness secondary to generalized cerebral hypoperfusion. Consciousness may also be altered by other conditions, and it is important to consider these syndromes when evaluating someone for syncope (see differential below).
• The 3 main types of syncope are neurocardiogenic (also called reflex), cardiac, and orthostatic hypotension. Each type is discussed below.

• Neurocardiogenic (reflex / vasovagal) syncope
• NOTE: Neurocardiogenic syncope is also referred to as reflex syncope and vasovagal syncope
• Epidemiology: Neurocardiogenic syncope is the most common cause of syncope. It accounts for 21% of syncopal cases, and most likely, it is the cause in a large number of unknown cases.
• Pathology: The exact mechanism of neurocardiogenic syncope is not completely understood, but it is believed to affect people who have a predisposition for excessive peripheral venous blood pooling. The excessive pooling causes a sudden drop in venous return that induces cardiac hypercontractility. The hypercontractility inappropriately activates cardiac mechanoreceptors that are normally stimulated by cardiac wall distension. The mechanoreceptors send signals to the brain that cause an increase in vagal tone. Increased vagal tone leads to bradycardia, hypotension, and syncope. Mechanoreceptors are also found in other parts of the body including the bladder, rectum, esophagus, and lungs. Syncope related to urination or defecation is thought to occur from overstimulation of these receptors.
• Risk factors
• Prolonged standing
• Vigorous exercise in a warm environment
• Fear
• Emotional distress
• Severe pain
• Symptoms: Presyncopal symptoms may occur seconds to minutes before an episode and include weakness, lightheadedness, diaphoresis, blurred vision, headache, nausea, cold or hot feeling, and facial pallor. Loss of consciousness is usually brief, lasting seconds to minutes, and confusion after the event is typically mild. [1,3,4]

• Orthostatic hypotension
• Epidemiology: Orthostatic hypotension accounts for about 9% of syncope cases
• Pathology: When a person rises from a lying or sitting position to standing, large amounts of blood (500 - 1000 ml) shift from the upper to lower body. In order to compensate for this shift, the body must increase cardiac output and raise blood pressure so that normal peripheral perfusion is maintained. If the body's ability to compensate is impaired in some way, brain perfusion may be reduced and syncope can occur. Orthostatic hypotension may result from one or a combination of the following: (1) drugs that inhibit changes in blood pressure (e.g. hypertension medications), (2) drugs that inhibit cardiac output (e.g. beta blockers), (3) volume depletion (e.g. dehydration), (4) disorders of the autonomic nervous system (e.g. Parkinson's disease, diabetic neuropathy). [6]
• Risk factors
• Blood pressure medications (most common cause)
• Dehydration
• Central neurologic diseases (e.g. Parkinson's, Lewy body dementia)
• Peripheral neurologic diseases (e.g. diabetic neuropathy, amyloidosis)
• Spinal cord injuries
• Symptoms: The main feature of orthostatic hypotension is that symptoms occur when a person transitions from a sitting or lying position to standing. Factors such as eating a large meal or standing after exerting oneself may exacerbate orthostatic hypotension. [1,3,4]

• Cardiac syncope
• Epidemiology: Cardiac syncope accounts for about 9% of syncope cases
• Pathology: Cardiac syncope is caused by heart and lung conditions that impair cardiac output and reduce blood flow to the brain. Reduced cardiac output may occur from structural diseases (e.g. aortic stenosis), electrical abnormalities (e.g. arrhythmias), or pulmonary conditions (e.g. pulmonary embolism).
• Risk factors
• Older age (> 60 years)
• Male sex
• Heart failure
• Coronary artery disease
• Structural heart disease
• History of arrhythmia
• Family history of premature sudden cardiac death (< 50 years)
• Symptoms: In contrast to neurocardiogenic syncope, cardiac syncope is more likely to present either without or with very brief prodromal symptoms. Presyncopal symptoms like nausea and diaphoresis are uncommon, but the patient may remember palpitations just prior to the event. Syncope with exertion or when lying down or sitting should also raise the suspicion for cardiac syncope. [1,3,4]

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• EVALUATION

• Overview
• Even though syncope is a common occurrence, it can be difficult to evaluate. Causes of syncope range from benign disorders to life-threatening cardiac conditions, and the challenge lies in determining which patients warrant an extensive workup. It is also important to assess for other causes of LOC when evaluating syncope (see differential), because a serious condition may be missed if only syncope is considered. In most cases, the patient history will provide the most important clues in determining a cause. The ESC and AHA have published guidelines on evaluating syncope, and important parts of those guidelines are reviewed below.

• History
• In many cases, syncope has no obvious cause, and even with serious etiologies, objective findings may not be present when the patient presents for evaluation (e.g. intermittent arrhythmias). The history surrounding the event is therefore very important in helping to determine possible causes. The table below lists features that are consistent with different types of syncope.

• References [1,3]

Neurocardiogenic features
Long history of syncopal episodes, particularly if they started before the age of 40 years Syncope related to pain, fear, or an unpleasant sight, sound, or smell Syncope occurring during prolonged standing or during a meal Syncope related to a crowd and/or hot place Presyncopal symptoms are present (e.g. sweating, pallor, hot/cold sensation, nausea, vomiting) Syncope related to urination, defecation, swallowing, coughing, laughing, or sneezing Syncope after exercise Syncope related to carotid sinus pressure (e.g. head turning, tight collars, shaving) Younger patients and absence of heart disease
Orthostatic hypotension features
Syncope that occurs upon rising to a standing position or after prolonged standing Syncope that occurs upon standing after exertion Treatment with antihypertensives, particularly if they were recently started or doses were recently increased Patients with neurologic conditions (e.g. Parkinson's, diabetic neuropathy) Syncope that occurs after eating Patients who are dehydrated
Cardiac features
Older age (> 60 years) and male sex Syncope during exercise or when lying down New-onset syncope at an older age (> 40 years) Sudden onset of palpitations immediately before syncope Absence of prodromal symptoms (e.g. sweating, pallor, nausea, vomiting) Unrelated to fear or other trigger Family history of unexplained sudden death at a young age (< 50 years) History of structural heart disease History of coronary artery disease and/or CHF History of previous arrhythmia

• Physical exam
• In patients who present with syncope, the physical exam should focus on vital signs, orthostatic testing (see orthostatic testing below), and the heart (e.g. abnormal rhythms, murmurs, etc.). Patients who are short of breath and/or have decreased oxygenation should be evaluated for pulmonary embolism. A neurologic exam should be performed to look for other causes of LOC (see differential below). If neurocardiogenic syncope is suspected, a carotid sinus massage test may be appropriate, particularly in older patients.

• Orthostatic tests
• All patients who present with syncope should have orthostatic testing done. The easiest and most common method of orthostatic testing is the active stand test. The procedure for performing the test is outlined in the table below along with diagnostic criteria for different orthostatic syndromes. If the active stand test criteria are met and the patient experiences their syncopal symptoms during testing, OH is the most likely cause of syncope.

• Active stand testing procedure
• When performing the active stand test, manual blood pressure measurements with a sphygmomanometer are preferred
• Have patient lie on exam table (supine) for at least 5 minutes before recording blood pressure and pulse
• Have patient stand up and record blood pressure and pulse upon standing, at 1 minute, 2 minutes, and 3 minutes
• If orthostatic criteria are not met after 3 minutes, continued measurements may be performed to look for delayed orthostatic hypotension

• References [1,8]

Orthostatic hypotension (OH) testing criteria
Immediate (initial) OH criteria Any one of the following within 15 seconds of standing: Fall in SBP ≥ 20 mmHg (some guidelines use > 40 mmHg✝) Fall in DBP ≥ 10 mmHg (some guidelines use > 20 mmHg✝) Decrease in SBP to < 90 mmHg ✝The EFAS/AAS/EAN guidelines use the higher cutoff
Classic OH criteria Any one of the following within 3 minutes of standing: Fall in SBP ≥ 20 mmHg (if patient has supine hypertension, fall of ≥ 30 mmHg is required) Fall in DBP ≥ 10 mmHg Decrease in SBP to < 90 mmHg NOTE: Fall in BP must be sustained, meaning it lasts for minutes
Delayed OH criteria Any one of the following that develops after 3 minutes of standing: Fall in SBP ≥ 20 mmHg Fall in DBP ≥ 10 mmHg Decrease in SBP to < 90 mmHg Other In delayed OH, blood pressure usually decreases gradually Fall in BP must be sustained, meaning it lasts for minutes
Postural orthostatic tachycardia syndrome (POTS) criteria Both of the following within 10 minutes of standing: Increase in heart rate of ≥ 30 bpm (≥ 40 bpm in patients 12 - 19 years old) or heart rate > 120 bpm Does not meet blood pressure criteria for OH Other POTS is defined as an inappropriate heart rate increase with standing that does not meet the criteria of OH POTS rarely causes syncope, but presyncopal symptoms (e.g. lightheadedness, palpitations, weakness, blurred vision) are often present The mechanism behind POTS is not completely understood but may include severe deconditioning, immune-mediated processes, excessive venous pooling, and hyperadrenergic state. See POTS treatment for more.

• Carotid sinus massage
• The carotid sinus is located at the bifurcation of the common carotid artery. It can be palpated just medial to the sternocleidomastoid muscle at the level of the upper thyroid cartilage. The carotid sinus has baroreceptors that sense changes in arterial blood pressure. When the baroreceptors sense high blood pressure, they inhibit sympathetic tone and increase parasympathetic tone; this results in a decrease in blood pressure and heart rate.
• Carotid sinus hypersensitivity is a rare disorder that primarily affects elderly patients and is uncommon before the age of 50. It is believed to be caused by hypersensitive carotid sinus baroreceptors that respond inappropriately to external stimuli, and in turn, cause a drop in blood pressure that can lead to syncope. Activities that may elicit symptoms include head turning with a tight collar on, shaving, and chiropractic maneuvers, to name a few.
• To test for carotid hypersensitivity, a procedure called a carotid sinus massage can be performed. The technique for performing the procedure is described below along with criteria for a positive test. See carotid sinus hypersensitivity treatment for more.
• Carotid sinus massage procedure
• Patient lies supine on bed with continuous heart rate and ECG monitor attached
• Provider locates one of the carotid sinuses and applies 5 - 10 seconds of continuous pressure. A mark is made on the ECG when pressure is first applied.
• If the first side does not elicit a response, the procedure should be repeated on the other side.
• If supine testing is negative, the test may be repeated in the upright or sitting position
• Criteria for a positive test
• A ventricular pause on ECG that lasts ≥ 3 seconds and/or a fall in SBP of ≥ 50 mmHg
• Some guidelines state that in order to diagnose carotid sinus hypersensitivity, the patient must experience their symptoms during the test and have a history that is consistent with neurocardiogenic syncope [1,3,7]

• ECG
• All patients with syncope should have a 12-lead ECG. The ECG findings listed below are divided into two groups based on whether they are more likely to be associated with cardiac syncope (major findings) or not (minor findings). Minor findings are only considered relevant if the patient history is consistent with arrhythmic syncope. Some major findings make arrhythmic syncope highly probable and are noted as such below.


• Major findings on ECG
• Findings that make arrhythmic syncope highly probable
• Persistent sinus bradycardia (< 40 bpm) or repetitive sinoatrial block or sinus pauses > 3 seconds in awake state and in absence of physical training
• Mobitz II second-degree AV block
• Third-degree AV block
• Alternating left and right bundle branch block
• Sustained or non-sustained ventricular tachycardia
• Rapid paroxysmal supraventricular tachycardia
• Non-sustained episodes of polymorphic VT and long or short QT interval
• Dysfunction of pacemaker or implantable cardioverter defibrillator
• Other major findings
• Any changes consistent with ongoing cardiac ischemia (e.g. ST segment depression or elevation, Q waves)
• Atrial fibrillation with bradycardia of < 40 bpm
• Right or left bundle branch block
• Intraventricular conduction disturbance (e.g. fascicular blocks)
• Signs of cardiac hypertrophy or cardiomyopathy (e.g. large QRS complex amplitude)
• Brugada pattern (ST-segment elevation in V1 - V3)
• Prolonged QT interval


• Minor findings on ECG (only relevant if history indicates arrhythmic syncope)
• Mobitz I second-degree AV block (Wenckebach)
• First degree AV block with markedly prolonged PR interval
• Atrial fibrillation with bradycardia of 40 - 50 bpm
• Sinus bradycardia of 40 - 50 bpm in someone who is not well conditioned (e.g. runner)
• Paroxysmal SVT or atrial fibrillation
• Pre-excited QRS complex
• Atypical brugada patterns
• Negative T waves in right precordial leads
• Epsilon waves suggestive of arrhythmogenic right ventricular cardiomyopathy [1]

• Laboratories
• Professional guidelines do not recommend any type of routine lab testing in syncope. Instead, they endorse a targeted approach based on the history and physical exam. In practice, most patients who present to the ER with syncope have basic labs done (e.g. CBC, CMP), and older patients often have more extensive testing (e.g. cardiac enzymes, natriuretic peptide, d-dimer).

• Hospital admission
• One of the main issues in evaluating syncope is deciding who should be admitted to the hospital and who can be safely discharged home. Approximately 50% of patients who present to the ER with syncope are admitted, and 10% will have a serious outcome within 10 - 30 days of their ER visit. A number of risk stratification tools have been developed that are supposed to help identify high-risk patients (see risk prediction tools below). In studies, these tools perform no better than good clinical judgement. Guidelines from professional organizations have limited utility since they recommend hospital admission or some type of "syncope observational unit," which are not widely available, in the majority of cases. The ESC guidelines give low-risk features that support discharge from the ER if all criteria are met. Those features are listed below. It is recommended that presyncopal symptoms without actual syncope be managed the same as syncope. [1,3]

• Reference [1]

Low-risk syncope features that support discharge from the ER
Syncopal event features Prodromal symptoms consistent with reflex syncope (e.g. lightheadedness, sweating, nausea, cold/hot sensation) Syncope related to pain, fear, or an unpleasant sight, sound, or smell Syncope with prolonged standing or in crowded, hot places Syncope during a meal or postprandial Syncope triggered by cough, defecation, or urination Syncope related to head rotation or pressure on the carotid sinus (e.g. tight collars, shaving) Syncope related to standing
Past medical history Long history (years) of recurrent syncope with low-risk features including the current episode Absence of structural heart disease
Physical exam Normal exam
ECG Normal ECG
Other In young patients with unexplained syncope and no history of cardiac disease, no family history of sudden death, no supine syncope or syncope during sleep or exercise, no unusual triggers, and a normal ECG, the chance of cardiac syncope is very low.

• Tilt table testing
• Tilt table testing is a procedure that can help distinguish between neurocardiogenic syncope, orthostatic hypotension, and psychogenic pseudosyncope. It is basically a longer, more controlled version of the active stand test (see orthostatic tests above). Tilt table testing may be helpful in diagnostically challenging cases, but in practice, it is not widely performed.
• During a tilt table test, the patient is strapped to a bed, and continuous blood pressure, pulse, and ECG monitoring are set up. After lying supine for 5 - 10 minutes, the table is tilted to 60 - 80 degrees. Depending on the protocol and findings, the patient may be left in the tilted position for up to 45 minutes. If some type of provoking event is thought to contribute to the patient's syncope (e.g. blood draw, coughing, carotid pressure, postexercise, postprandial), it can be performed before or during the test. In some cases, pharmacological provocation with sublingual nitroglycerin or intravenous isoproterenol may be used, but these medications raise the likelihood of false-positive results. [8]

• Other testing
• Other testing in syncope should be individualized and primarily involves more extensive cardiac testing. If arrhythmic syncope is suspected, prolonged electrocardiographic monitoring (e.g. Holter, loop recorder) may be performed. Structural heart disease can be found with an echocardiography. Electrophysiological studies can unmask difficult to find conduction abnormalities, and exercise stress testing may be helpful in syncope related to exertion.

• Risk prediction tools
• Ten percent of patients who present to the ER with syncope will have a serious outcome within 30 days. Because of this, a number of risk prediction tools have been developed to try and help determine which patients should be admitted and/or receive a more extensive workup. In trials, these tools have performed no better than good clinical judgement. Links to some of the more popular tools are provided below.


• Canadian Syncope Risk Score - estimates 30-day probability of a serious adverse event based on ECG findings, troponin level, blood pressure, and patient history
• San Francisco Syncope Rule - If any of the following are present (SBP < 90 mmHg, shortness of breath, history of congestive heart failure, abnormal ECG, hematocrit < 30%), patient is considered high risk for serious outcome within 7 days
• EGSYS Score for Syncope - predicts likelihood syncope is from cardiac cause

• Differential
• When evaluating syncope, it is important to consider other causes of LOC. The table below provides a list of conditions that can present with features that are similar to syncope.

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• TREATMENT

• Neurocardiogenic (reflex/vasovagal)
• Education and lifestyle modifications - the following educational/lifestyle measures may be helpful in neurocardiogenic syncope: (1) discussing the benign nature of the condition, (2) awareness and avoidance (if possible) of potential triggers, (3) sitting or lying down at the first sign of prodromal symptoms, (4) increased intake of fluids


• Discontinuation or reduction of medications that can cause hypotension - discontinuation or reduction of medications that contribute to hypotension may be beneficial. Examples include hypertension medications, alpha blockers, antipsychotics, diuretics, nitrates, and antidepressants.


• Counter-pressure maneuvers - counter-pressure maneuvers are exercises that can be performed when prodromal symptoms occur. They involve a series of muscle contractions that increase cardiac output and blood pressure. A pdf that describes how to perform the maneuvers is available here - counter-pressure maneuvers pdf


• Fludrocortisone - fludrocortisone is a mineralocorticoid that promotes volume expansion by enhancing sodium reabsorption in the kidneys. It has been studied as a treatment for neurocardiogenic syncope in several small studies. In one study (N=210), doses of 0.05 - 0.2 mg once daily had a modest effect on syncope in adults. [PMID 27364043] The ESC guidelines state that fludrocortisone may be effective in reducing syncopal recurrences in young patients with low-normal blood pressure and no comorbidities.


• Midodrine - midodrine is an alpha agonist that increases blood pressure. It is FDA-approved for the treatment of orthostatic hypotension. A small study (N=133) in young people (median age 32 years) found that midodrine 5 - 10 mg three times a day reduced the absolute risk of vasovagal syncope by 19% compared to placebo. [PMID 34339231] [Midodrine PI]


• Pacemaker - in older patients (> 40 years) with severe neurocardiogenic syncope where asystole is a predominant feature, implantation of a pacemaker may be considered [1,3]


• Cardioneuroablation - cardioneuroablation, a procedure where vagal inputs in the left and right atria are ablated with radiofrequency, has been performed in some patients. A small 2-year trial (N=48) found that it was superior to no ablation for preventing syncope in patients with cardioinhibitory vasovagal syncope. [PMID 36114133]

• Orthostatic hypotension
• Education and lifestyle modifications - the following educational/lifestyle measures may be helpful in orthostatic hypotension: (1) slowing the process of going from sitting/lying to standing, (2) awareness and avoidance (if possible) of potential triggers (e.g. eating a large meal), (3) sitting down at the first sign of prodromal symptoms, (4) rapid ingestion of water if symptoms occur


• Adequate fluid and salt intake - in patients without contraindications (e.g. heart failure, hypertension, kidney disease), ensuring adequate fluid and salt intake may improve symptoms. Water intake of 2 - 3 liters per day and salt intake of 10 grams of sodium chloride per day may be considered.


• Discontinuation or reduction of medications that can cause hypotension - discontinuation or reduction of medications that contribute to hypotension may be beneficial. Examples include hypertension medications, alpha blockers, antipsychotics, diuretics, nitrates, and antidepressants. For antihypertensives, ACE inhibitors, ARBs, and calcium channel blockers may be associated with a lower risk of OH when compared to other classes of drugs.


• Counter-pressure maneuvers - counter-pressure maneuvers are exercises that can be performed when prodromal symptoms occur. They involve a series of muscle contractions that increase cardiac output and blood pressure. A pdf that describes how to perform the maneuvers is available here - counter-pressure maneuvers pdf


• Head-up tilt sleeping - sleeping with the head of the bed elevated (> 10 degrees) helps to prevent nocturnal polyuria and can increase body fluid volume


• Compression garments - compression stockings and/or abdominal binders may improve symptoms by reducing venous pooling


• Midodrine - midodrine is an alpha agonist that increases blood pressure. It is FDA-approved for the treatment of orthostatic hypotension. Recommended dosing is 10 mg three times a day with doses given upon waking, at midday, and late afternoon (no later than 6PM). Patients must be monitored closely for the development of supine hypertension, and the drug may worsen urinary retention. In a study of 171 patients, midodrine was more effective than placebo in relieving symptoms of OH. [PMID 9091692] [Midodrine PI]


• Droxidopa (Northera®) - Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine, a vasoconstrictor. It is FDA-approved for the treatment of neurogenic orthostatic hypotension. Recommended dosing is 100 - 600 mg three times a day with doses given upon waking, at midday, and late afternoon (at least 3 hours prior to bedtime). Patients must be monitored closely for the development of supine hypertension. The effects of droxidopa on blood pressure wane after a short period, and it has not been proven to be effective beyond 2 weeks of treatment. [Droxidopa PI]


• Fludrocortisone - fludrocortisone is a mineralocorticoid that promotes volume expansion by enhancing sodium reabsorption in the kidneys. Fludrocortisone (0.1 - 0.3 mg once daily) combined with head-up tilt sleeping has been shown to be beneficial in some very small trials. [1,3]

• Cardiac syncope
• The treatment of cardiac syncope is focused on addressing the underlying cause and may include the following: implantation of a pacemaker for conduction abnormalities, heart valve replacement (e.g. aortic stenosis), cardiac resynchronization therapy (e.g. heart failure), catheter ablation (e.g. SVT, A fib), and implantable defibrillator (e.g. prolonged QT interval, Brugada syndrome). [1,3]

• Carotid sinus hypersensitivity
• The primary treatment of carotid sinus hypersensitivity is avoidance of external carotid sinus pressure (e.g. tight collars, shaving). If these modalities are unsuccessful, cardiac pacing may be appropriate. [1,3]

• Postural orthostatic tachycardia syndrome (POTS)
• Treating POTS can be difficult, and no single therapy is uniformly successful. In addition, there is little data from randomized controlled trials to help guide treatment decisions. The recommendations below are from the Heart Rhythm Society 2015 guidelines; none of them are considered strong and/or based on good clinical evidence.
• Treatment recommendations for POTS:
• A regular, structured, and progressive exercise program for patients with POTS can be effective
• It is reasonable to treat patients with POTS who have short-term clinical decompensations with an acute intravenous infusion of up to 2 L of saline
• The consumption of up to 2 - 3 L of water and 10 - 12 g of NaCl daily by patients with POTS may be considered
• It seems reasonable to treat patients with POTS with fludrocortisone or pyridostigmine
• Treatment of patients with POTS with midodrine or low-dose propranolol may be considered
• It seems reasonable to treat patients with POTS who have prominent hyperadrenergic features with clonidine or alpha-methyldopa
• Drugs that block the norepinephrine reuptake transporter (e.g. SNRI antidepressants) can worsen symptoms in patients with POTS and should not be administered [9]

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• BIBLIOGRAPHY

• 1 - PMID 29562304 - 2018 ESC Guidelines for the diagnosis and management of syncope, European Heart Journal (2018)
• 2 - PMID 12239256 - Incidence and prognosis of syncope, NEJM (2002)
• 3 - PMID 28280232 - 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: Executive Summary, Circulation (2017)
• 4 - PMID 21916389 - Evaluation of Syncope, American Family Physician (2011)
• 5 - PMID 15758011 - Neurocardiogenic Syncope, NEJM (2005)
• 6 - PMID 27428203 - Effect of postural changes on cardiovascular parameters across gender, Medicine, (2016)
• 7 - PMID 29020587 - Carotid Sinus Massage NEJM (2017)
• 8 - PMID 33752997 - Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness, Clinical Autonomic Research (2021)
• 9 - PMID 25980576 - 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm (2015)