7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation : David Benditt, MD : Peter Kowey, MD, FACC, FAHA, FHRS : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 18, 2022. INTRODUCTION Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of an abrupt drop of systemic blood pressure. Unfortunately, the term "syncope" is often misapplied by clinicians to encompass any form of abrupt collapse that may or may not be accompanied by TLOC, including seizures and concussions; this latter broad and less-specific usage should be avoided. Reflex syncope (previously termed neurally-mediated syncope) is TLOC due to a reflex response that encompasses vasodilatation and/or bradycardia, leading to systemic hypotension and cerebral hypoperfusion [1,2]. Types of reflex syncope include vasovagal syncope, situational reflex syncope (eg, micturition syncope), carotid sinus syncope, and some cases without apparent triggers ( table 1). In these cases, the syncope is due to hypotension, which may be caused by severe bradycardia, vascular dilation (vasodepressor effect), or both. Vasovagal syncope is the most common cause of syncope in patients of all ages [3,4], and its diagnosis may usually be made by taking a careful history detailing the features of symptomatic events and identifying well-known triggers; however, a classic history is not always present, especially in older individuals. Acute vasovagal reactions leading to syncope or presyncope are also common in a number of potentially stressful settings, such as blood donation or emotional upset. Even among patients with structural heart disease, if electrophysiology testing is nondiagnostic, approximately 60 percent of syncope recurrences are reflex in origin [5]. The https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 1/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate diagnosis can also be suggested by exclusion of other causes of syncope and by a characteristic response to upright tilt table testing, during which the patient may become syncopal. (See "Blood donor screening: Overview of recipient and donor protections", section on 'Vasovagal and hypovolemic reactions'.) The clinical presentation and diagnostic evaluation of patients with vasovagal syncope and situational reflex syncope will be reviewed here. Discussions of the treatment of patients with reflex syncope, as well as the pathogenesis, etiology, evaluation and management of syncope in general, are discussed separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Syncope in adults: Management and prognosis" and "Reflex syncope in adults and adolescents: Treatment".) PATHOGENESIS OF REFLEX SYNCOPE Understanding the pathophysiology involved in reflex syncope is essential to understanding its clinical manifestations and prevention strategies. Both neural (arterial and cardiac baroreceptor, including carotid sinus reflexes) and endogenous chemical pathways are thought to be involved ( figure 1) [6]. The potential neurohumoral events that participate in vasovagal reactions are complex but remain poorly understood; better understanding may be expected to lead to more specific therapeutic strategies in the future [7]. The most frequent mechanism for reflex syncope is a mixed hemodynamic response combining cardioinhibitory (ie, heart slowing, usually to <30 beats per minute and/or pauses >5 sec) and vasodepressor features (ie, a drop of systemic blood pressure independent of change of heart rate). An individual patient may have syncopal events caused by varying mechanisms, with vasodepressor, cardioinhibitory, or mixed responses at different times. Infrequently, an individual patient may have syncopal events characterized entirely by vasodepressor or cardioinhibitory responses. Cardioinhibitory and vasodepressor responses Alterations in autonomic activation are responsible for reflex syncope. Vasovagal syncope may be caused by autonomic cardioinhibitory and/or vasodilator responses. Three types of responses are seen [8]: Cardioinhibitory response The cardioinhibitory response (ie, marked sinus bradycardia or pauses) results principally from increased parasympathetic activation and may be manifested by any or all of the following: sinus bradycardia, PR interval prolongation, advanced atrioventricular (AV) block, or asystole. The simultaneous presence of sinus bradycardia and AV block on a heart rhythm tracing strongly favors a reflex mechanism. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 2/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Vasodepressor response The vasodepressor response is principally due to inhibition of (decreased) peripheral sympathetic activity and can lead to symptomatic hypotension even in the absence of severe bradycardia. In one report, for example, the final trigger for symptomatic hypotension appeared to be the abrupt disappearance of muscle sympathetic nerve activity, but this has not been a consistent observation [9]. Reduced cardiopulmonary baroreceptor sensitivity may be a contributing factor [10]. Paradoxically, circulating epinephrine may be quite high [11]. Mixed response The mixed response contains components of both the cardioinhibitory response and the vasodepressor response. In one cohort of 111 patients with presumed vasovagal syncope who received an insertable cardiac monitor (sometimes referred to as an implantable loop recorder) and were followed for 3 to 15 months, 34 percent experienced recurrent syncope [12]. A correlation between syncope and electrocardiographic changes was found in 84 percent, with the most frequent abnormality (seen in 50 percent) being one or more prolonged asystolic pauses, primarily due to sinus arrest. Bradycardia (<40 beats per minute) without pauses was seen in 9 percent, while the remaining patients had normal sinus rhythm or sinus tachycardia and probably had a vasodepressor response. Although wearable ambulatory electrocardiogram (ECG) recorders and insertable cardiac monitors have proved valuable in improving understanding of bradycardias as potential contributors to syncope/collapse, they do not offer insight into possible concomitant vasodepressor activity. Merely observing a slow heart rate is insufficient to conclude that the faint was solely cardioinhibitory in nature. Autonomic dysfunction Underlying autonomic dysfunction only infrequently contributes to reflex syncope, but may be relevant in those whose presentation does not include the usual premonitory symptoms (ie, feeling hot or cold, nausea, sweating, etc); the latter are often associated with cardiovascular or neurologic disorders, which may include orthostatic or postprandial hypotension [1,2]. Reflexes initiated in various arterial and cardiac baroreceptors and carotid sinus reflexes may be involved (in the past, the term Bezold-Jarisch reflex has been used, but it is now best abandoned as it does not fully express the complex pathophysiology) [6]. Patients may have increased muscle sympathetic nerve activity at rest and a blunted response to orthostatic stress [13]. Baroreceptor reflexes Receptors in the atria, great veins, aorta, and left ventricle exist whose activation results in reflex bradycardia and vasodilation. Activation of these mechanoreceptors (including those in the left ventricle and stretch receptors in the great https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 3/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate vessels) with pressure or volume changes (as may occur with sympathetic stimulation) activate afferent C fibers to the midbrain; such stimulation may result in activation of vagal afferents and then vagal efferents. However, the neural pathways are not well established. In particular, the role of epicardial atrial cardiac ganglia as a trigger site is of increased interest, as cardioneuroablation has been proposed as a means to diminish susceptibility to vasovagal reflex events [14]. Carotid sinus reflex Blood pressure and heart rate are normally controlled in part by input from baroreceptors located within the carotid sinus and aortic arch. An increase in blood pressure or pressure applied to the carotid sinus enhances the baroreceptor firing rate and activates vagal activity, thereby slowing the heart rate and reducing the blood pressure. Central serotonergic pathways It has been argued that central serotonergic pathways may participate in the pathogenesis of vasovagal syncope, but the evidence is weak, and serotonin re-uptake inhibition is not routinely very helpful for prevention of attacks. Adenosine Adenosine has a variety of actions, including negative chronotropic and inotropic activity and vasodepression [15]. Adenosine release, perhaps mediated by mechanoreceptors in the heart, may be involved in the triggering mechanism of syncope, at least during tilt testing. The observation that adenosine administration can provoke reflex syncope raises the possibility that endogenous adenosine plays a role in the pathogenesis of vasovagal syncope. Recently, a low-adenosine phenotype has been described with low expression of A2A receptors. These individuals are thought to be particularly susceptible to endogenous adenosine and manifest reflex syncope with sinus arrest and/or paroxysmal AV block [16]. This topic remains to be more fully explored. TYPES OF REFLEX SYNCOPE Vasovagal syncope Vasovagal syncope (also known as the "common faint") refers to a variety of clinical scenarios in which a neural reflex results in usually self-limited systemic hypotension characterized by bradycardia and/or peripheral vasodilation/venodilation. It is the most common cause of syncope (approximately 35 to 70 percent of cases depending on the age group being evaluated), particularly in patients without apparent cardiovascular or neurologic disease [4,17- 23]. However, vasovagal syncope remains the most common cause of syncope even among patients with heart disease and should be considered as a potential cause in such patients after more worrisome causes ( table 2) have been excluded [5,20]. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 4/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Vasovagal syncope is a common cause of syncope in athletes. However, other potential causes of syncope should be considered, particularly if the syncope occurs during exertion (ie, during "full flight" not during the post exercise cooling down period). Athletes with syncope during physical activity should be evaluated for underlying structural heart disease, which, if present, increases potential risk of sudden death. (See "Athletes with arrhythmias: Clinical manifestations and diagnostic evaluation".) Situational syncope Situational syncope refers to syncope associated with specific scenarios. Some situations (eg, micturition, defecation, posttussive, etc) appear to trigger a neural reflex; others (eg, straining, squatting) may cause syncope via additional mechanisms unrelated to neural reflexes. Avoidance of trigger situations is the first step in prevention of recurrences. Glossopharyngeal neuralgia (GN) is an uncommon cause of reflex syncope. Episodes of GN pain are frequently triggered by activities such as swallowing, coughing, or yawning. Episodes of GN pain are rarely associated with syncope. (See "Glossopharyngeal neuralgia", section on 'Clinical features'.) CLINICAL PRESENTATION The clinical features associated with a syncopal event may be diagnostic ( table 1) [1,2,24,25]. Patients with vasovagal syncope are often young and otherwise healthy. In younger persons, vasovagal syncope is usually associated with a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. Typical triggers and premonitory symptoms are strongly suggestive of vasovagal syncope, although these may be absent or difficult to correlate to the syncopal episode in some individuals, particularly in older adults. However, as noted earlier, vasovagal syncope is the most common form of syncope in all age groups and, consequently, should not be overlooked as a possibility in older individuals. The history may not be classical in older patients. Symptoms The classic prodromal symptoms associated with imminent syncope and presyncope, particularly in the case of the vasovagal form of reflex syncope, include: Lightheadedness A feeling of being warm or cold Sweating Palpitations Nausea or non-specific abdominal discomfort Visual "blurring" occasionally proceeding to temporary darkening or "white-out" of vision https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 5/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Diminution of hearing and/or occurrence of unusual sounds (particularly a "whooshing" noise) Pallor reported by onlookers Fatigue after recovery Vasovagal syncope typically occurs in the sitting or standing position, as the supine position helps to maintain adequate blood flow to the brain. Typically, reflex syncope is short in duration (one to two minutes), but full recovery may be delayed as the patient may feel fatigued for an extended period following the event. This course may help distinguish vasovagal syncope from syncope associated with arrhythmia, which is typically of abrupt onset and of short duration but without autonomic-mediated prodrome or post-episode fatigue. Loss of consciousness may be prolonged with some other causes of TLOC, such as seizures, but rarely with vasovagal syncope. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation".) Older patients, unlike younger patients, may not only experience vasovagal syncope, but also be at increased risk of carotid sinus hypersensitivity and/or orthostatic hypotension [26,27]. They are also more likely to have coexisting cardiovascular disease and to be taking hypotension- provoking medications. Consequently, in older patients, patients with syncope during exertion, and other patients who may have structural heart disease, potential causes of syncope other than reflex syncope must be considered. (See 'Medical history' below and "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Approach to initial evaluation' and "Carotid sinus hypersensitivity and carotid sinus syndrome".) Triggers Women and patients younger than 40 years are more likely to have typical symptoms and triggers for vasovagal syncope [28]. However, older patients may also be diagnosed with vasovagal syncope but, as emphasized earlier, may not have typical premonitory symptoms [29]. The "classical" of "typical" presentation of vasovagal syncope refers to syncope triggered by emotional or orthostatic stress, painful or noxious stimuli, fear of bodily injury, prolonged standing, heat exposure, or after physical exertion. The "atypical" (also referred to as "nonclassical") presentation of vasovagal syncope occurs in some patients, especially those who are older, who have recurrent episodes of syncope without an identifiable cause or trigger. Situation syncope may be triggered by a variety of scenarios, including micturition, coughing, defecating, swallowing, etc. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 6/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Recurrence Reflex syncope can be a recurrent problem, depending on the particular individual and triggers. However, a significant proportion of patients will do well without any further episodes. A study of self-reported symptom burden in 418 patients diagnosed with vasovagal syncope indicated that 35 percent were symptom free at median five-year follow-up, regardless of presenting symptom or treatment received [30]. Evaluation of vasovagal syncope recurrence has demonstrated the randomness of recurrence, but events often occur in clusters [31]. Consequently, evaluating treatment efficacy is complex both for individual patients and in the setting of clinical trials. INITIAL EVALUATION The initial evaluation of suspected reflex syncope should include obtaining a comprehensive history detailing the nature of and circumstances surrounding spontaneous events, performance of a physical examination (which may include careful carotid sinus massage in patients over age 55 years), and review of resting and ambulatory ECG recordings. Additional diagnostic evaluation, if indicated, should be individualized based upon the suspected etiology of syncope, but is rarely needed in patients with suspected reflex syncope in whom the story and associated symptoms are often adequate to establish the diagnosis. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Approach to initial evaluation'.) Medical history Obtaining a detailed medical history is the first step in determining whether syncope is reflex syncope or due to some other cause. If the history obtained is thorough, the story provided by the patient (and witnesses, if any) will often reveal that the collapse was due to syncope of reflex origin and will provide a means of guiding subsequent testing and treatment. However, history taking is highly dependent upon the experience of the clinician, and in addition depends on the whether the patient and witnesses can give an accurate account of events (which may be limited in patients who are very young, very elderly, uncomfortable [eg, experiencing pain], intoxicated, or in whom a language barrier exists). Key points from the medical history include (see "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Clinical features'): Number, frequency, and duration of episodes (true syncope is usually brief unless complicated by head injury due to a fall) Associated symptoms preceding syncope (ie, prodromal symptoms) Patient position at the time of syncope Triggers or provocative factors https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 7/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Associated symptoms following syncope Witnessed signs Preexisting medical conditions, medications, and family history Symptoms after recovery Syncope precipitated by emotional distress or orthostatic stress and associated with typical prodrome is suggestive but not diagnostic of vasovagal syncope. Further evaluation with tilt table test is not usually indicated if diagnostic vasovagal features are identified and further testing will not alter treatment. However, reproduction of symptoms during tilt table testing may help reassure patients that the clinician has observed a spell and therefore is better positioned to care for the patient. Recent history may be more helpful than lifetime history in predicting vasovagal syncope recurrence. In a study of 208 subjects with a positive tilt test and 3 lifetime syncope spells, the number of vasovagal syncope spells in the preceding year better predicted syncope recurrence than total number of historical spells (likelihood ratio statistic 28.4 versus 20.4) [32]. However, as noted earlier, randomness is also a feature of vasovagal recurrences. Physical examination A number of findings on physical examination can aid in the identification of some of the common causes of syncope, including abnormalities in the vital signs, cardiovascular abnormalities, and less frequently neurological signs. Typically, patients with reflex syncope will have a normal physical examination, or non-specific findings on physical examination which do not relate to the syncopal episode. Electrocardiogram An ECG should be obtained in all patients with syncope, including patients with suspected reflex syncope. The 12-lead ECG is usually normal or nonspecific in patients with vasovagal and most other forms of reflex syncope. Certain ECG findings (eg, conduction system abnormalities, prolonged QT interval, Brugada pattern) may suggest underlying cardiac disease that would potentially require additional evaluation and monitoring. Risk stratification As part of the initial syncope evaluation, clinicians must determine whether the affected individual needs in-hospital care for further evaluation and/or initiation of treatment. The primary factor determining whether the patient with presumed syncope should be hospitalized is the individual's immediate mortality, falls/injury risk, and, to a lesser extent, the issue of whether the patient has adequate home care and whether certain treatments require hospital monitoring for safe initiation. The risk stratification of patients with syncope is discussed in detail separately. In most cases, when the collapse is thought to be reflex syncope, patients are considered to be at low risk of near-term mortality or recurrent syncope resulting in injury. Patients with reflex https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 8/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate syncope most often have no evidence of structural heart disease and have a normal baseline ECG, although patients with these conditions can also experience reflex syncope. Reflex syncope is considered relatively benign with regard to the risk of early mortality, but not necessarily with regard to recurrent syncope with risk of falls resulting in injury. Most patients can be treated and discharged home for further outpatient evaluation as needed if their home care situation is appropriate to prevent injury should there be a recurrence. SELECTED ADDITIONAL TESTING Patients with a certain diagnosis of reflex syncope (ie, a classic history) generally do not require further diagnostic evaluation, although on occasion a confirmatory test may be warranted [1,2]. For patients with an uncertain diagnosis after the initial evaluation, particularly for patients with an atypical presentation, specific confirmatory testing utilizing upright tilt table testing or ambulatory ECG monitoring is warranted in order to solidify or refute the diagnosis of reflex syncope. Such testing may help reassure the patient that the correct diagnosis has been established and that the physician has now witnessed the patient's symptom event. Upright tilt table test Tilt-table testing is an example of a "confirmatory" test, which can be used when the diagnosis of a reflex vasovagal syncope is suspected, but the presentation is not classical [33,34]. However, the tilt table test has limited specificity. The test result must be interpreted by an experienced clinician in light of other history and physical finding data. A detailed discussion of the tilt table test is found elsewhere. (See "Upright tilt table testing in the evaluation of syncope".) We proceed with tilt table testing in the following situations: Patients with unexplained single syncopal episodes in high-risk settings (eg, collapse while driving, using machinery, or working in an occupation that may result in injury). Patients with recurrent syncopal episodes in the absence of organic heart disease, or in the presence of organic heart disease after cardiac causes have been excluded. Patients in whom it is of clinical value to demonstrate susceptibility to reflex syncope. Patients in whom both reflex syncope and orthostatic hypotension syncope are being considered. Patients who express skepticism regarding the proposed diagnosis or in whom job requirements necessitate such testing to confirm the proposed diagnosis. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 9/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Electrocardiographic monitoring Ambulatory ECG monitoring is most commonly used when there is suspicion that a cardiac arrhythmia may be the cause of syncope, but may also be used in patients with suspected reflex syncope in an attempt to document the heart rhythm during an event and to exclude primary cardiac causes (eg, high grade atrioventricular block, ventricular tachycardia, etc). In patients with more frequent reflex syncope, relatively short-term (one month) non-invasive electrocardiographic monitoring (eg, an event [loop] recorder) may suffice (bearing in mind the limitations of such testing due to the randomness and clustering of recurrences discussed earlier). Since syncopal episodes often occur less frequently (eg, less than once per month), longer-term monitoring options may be required and can significantly improve the diagnostic yield over shorter-term monitoring [35]. The insertable cardiac monitor (ICM) is a subcutaneous monitoring device for the detection of cardiac arrhythmias [35,36]. ICMs are most commonly utilized in the evaluation of palpitations or syncope of undetermined etiology, particularly when symptoms are infrequent (eg, less than once per month) and/or other ambulatory monitoring has been unrevealing or inconclusive ( table 3). The use of ICMs and other electrocardiographic monitoring in the diagnosis of otherwise unexplained syncope is discussed separately. (See "Ambulatory ECG monitoring".) DIAGNOSIS The diagnosis of reflex syncope is made primarily based on the clinical features of the event ( table 4). Laboratory testing is used mainly to support a clinical suspicion. There are no testing procedures that are sensitive or specific enough to definitively establish a diagnosis on their own; laboratory findings must be compatible with the history in order to be diagnostically useful. Diagnostic criteria have been proposed, but these are primarily based on the clinical features of the event. Patients with vasovagal syncope usually experience a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. Typical triggers and premonitory symptoms are strongly suggestive of vasovagal syncope. Situational syncope is usually diagnosed with the same prodromal symptoms as are seen in vasovagal syncope based on the setting of a specific scenario or trigger, such as micturition, coughing, defecating, or swallowing. Situational faints often do not have prodromal symptoms. DIFFERENTIAL DIAGNOSIS https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 10/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate The differential diagnosis of vasovagal syncope includes other causes of syncope ( table 1), as well as non-syncopal conditions that produce apparent or real transient loss of consciousness (eg, falls, transient ischemic attacks, seizures) ( table 5). The major causes of syncope are discussed in greater detail separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".) Vasovagal syncope may be considered in some cases a cause of acute postural hypotension. Other causes of postural hypotension are discussed separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Postural tachycardia syndrome".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definitions Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow, most often the result of https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 11/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate an abrupt drop of systemic blood pressure. Reflex syncope (previously termed neurally- mediated syncope) is TLOC due to a reflex response that encompasses vasodilatation and/or bradycardia (rarely tachycardia), leading to systemic hypotension and cerebral hypoperfusion. Types of reflex syncope include vasovagal syncope, situational syncope, carotid sinus syncope, and some cases without apparent triggers ( table 1). (See 'Introduction' above and "Carotid sinus hypersensitivity and carotid sinus syndrome".) Pathogenesis The most frequent mechanism for reflex syncope is a mixed cardioinhibitory and vasodepressor hemodynamic response. An individual patient may have syncopal events caused by varying mechanisms, with vasodepressor, cardioinhibitory, or mixed responses at different times. Cardioinhibitory response This response results primarily from increased parasympathetic activation and may be manifested by sinus bradycardia, PR interval prolongation, advanced atrioventricular block, and/or asystole. Vasodepressor response This response is due to decreased sympathetic activity and can lead to symptomatic hypotension even in the absence of severe bradycardia. Mixed response This response contains components of both the cardioinhibitory and vasodepressor responses. (See 'Pathogenesis of reflex syncope' above.) Clinical presentation The clinical features associated with a syncopal event may be diagnostic ( table 4). In younger individuals, vasovagal syncope is usually associated with a prodrome of nausea, pallor, and diaphoresis, consistent with increased vagal tone. These symptoms may be absent or difficult to correlate to the syncopal episode in some individuals, particularly in older adults. (See 'Clinical presentation' above.) Initial evaluation The initial evaluation of patients with suspected TLOC due to reflex syncope serves both diagnostic and prognostic purposes. For nearly all patients, the initial evaluation of suspected reflex syncope should include obtaining a comprehensive history, performance of a physical examination (which may include careful carotid sinus massage in older patients), and review of an electrocardiogram (ECG). Additional diagnostic evaluation is rarely needed in patients with suspected reflex syncope. (See 'Initial evaluation' above.) Risk stratification The initial syncope evaluation includes a determination of whether the affected individual requires hospitalization. In most cases of suspected reflex syncope, patients are considered to be at low risk of near-term mortality, but not necessarily with regard to recurrent syncope with risk of falls resulting in injury. Most patients can be https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 12/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate treated and discharged home for further outpatient evaluation as needed. (See 'Risk stratification' above.) Additional testing Patients with a certain diagnosis of reflex syncope generally do not require further diagnostic evaluation, although on occasion a confirmatory test may be warranted. Such a test may reassure the patient that the physician has witnessed the patient's symptoms. For patients with an uncertain diagnosis after the initial evaluation, particularly for patients with an atypical presentation, specific confirmatory testing utilizing upright tilt table testing or ambulatory ECG monitoring is warranted in order to solidify or exclude the diagnosis of reflex syncope. (See 'Selected additional testing' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Brian Olshansky, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: 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. 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Chen-Scarabelli C, Scarabelli TM. Neurocardiogenic syncope. BMJ 2004; 329:336. 4. Parry SW, Tan MP. An approach to the evaluation and management of syncope in adults. BMJ 2010; 340:c880. 5. Shenthar J, Prabhu MA, Banavalikar B, et al. Etiology and Outcomes of Syncope in Patients With Structural Heart Disease and Negative Electrophysiology Study. JACC Clin Electrophysiol 2019; 5:608. 6. Mosqueda-Garcia R, Furlan R, Tank J, Fernandez-Violante R. The elusive pathophysiology of neurally mediated syncope. Circulation 2000; 102:2898. 7. Benditt DG, van Dijk JG, Krishnappa D, et al. Neurohormones in the Pathophysiology of Vasovagal Syncope in Adults. Front Cardiovasc Med 2020; 7:76. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 13/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate 8. Chen MY, Goldenberg IF, Milstein S, et al. Cardiac electrophysiologic and hemodynamic correlates of neurally mediated syncope. Am J Cardiol 1989; 63:66. 9. Morillo CA, Eckberg DL, Ellenbogen KA, et al. Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation 1997; 96:2509. 10. Thomson HL, Wright K, Frenneaux M. Baroreflex sensitivity in patients with vasovagal syncope. Circulation 1997; 95:395. 11. Kohno R, Detloff BLS, Chen LY, et al. Greater early epinephrine rise with head-up posture: A marker of increased syncope susceptibility in vasovagal fainters. J Cardiovasc Electrophysiol 2019; 30:289. 12. Moya A, Brignole M, Menozzi C, et al. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Circulation 2001; 104:1261. 13. B chir M, Binggeli C, Corti R, et al. Dysfunctional baroreflex regulation of sympathetic nerve activity in patients with vasovagal syncope. Circulation 2003; 107:1620. 14. Yao Y, Shi R, Wong T, et al. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol 2012; 5:279. 15. Saadjian AY, L vy S, Franceschi F, et al. Role of endogenous adenosine as a modulator of syncope induced during tilt testing. Circulation 2002; 106:569. 16. Brignole M, Groppelli A, Brambilla R, et al. Plasma adenosine and neurally mediated syncope: ready for clinical use. Europace 2020; 22:847. 17. WAYNE HH. Syncope. Physiological considerations and an analysis of the clinical characteristics in 510 patients. Am J Med 1961; 30:418. 18. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet 2001; 357:348. 19. Engelstein, ED, Hutchins, et al. Normal cardiac sympathetic innervation in patients with neurocardiac syncope (abstract). J Am Coll Cardiol 1998; 31:165A. 20. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with or without heart disease. J Am Coll Cardiol 2001; 37:1921. 21. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878. 22. Colivicchi F, Ammirati F, Biffi A, et al. Exercise-related syncope in young competitive athletes without evidence of structural heart disease. Clinical presentation and long-term outcome. Eur Heart J 2002; 23:1125. https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 14/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate 23. Sakaguchi S, Shultz JJ, Remole SC, et al. Syncope associated with exercise, a manifestation of neurally mediated syncope. Am J Cardiol 1995; 75:476. 24. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997; 126:989. 25. Calkins H, Shyr Y, Frumin H, et al. The value of the clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope. Am J Med 1995; 98:365. 26. McIntosh S, Da Costa D, Kenny RA. Outcome of an integrated approach to the investigation of dizziness, falls and syncope in elderly patients referred to a 'syncope' clinic. Age Ageing 1993; 22:53. 27. Alboni P, Brignole M, Menozzi C, et al. Clinical spectrum of neurally mediated reflex syncopes. Europace 2004; 6:55.