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. 28. Romme JJ, van Dijk N, Boer KR, et al. Influence of age and gender on the occurrence and presentation of reflex syncope. Clin Auton Res 2008; 18:127. 29. Tan MP, Parry SW. Vasovagal syncope in the older patient. J Am Coll Cardiol 2008; 51:599. 30. Ross R, Parry S, Norton M, Newton JL. Self-reported symptom burden; outcome in 418 patients from the Newcastle Vasovagal (Neurocardiogenic) cohort. QJM 2008; 101:127. 31. Sahota IS, Maxey C, Pournazari P, Sheldon RS. Clusters, Gaps, and Randomness: Vasovagal Syncope Recurrence Patterns. JACC Clin Electrophysiol 2017; 3:1046. 32. Sumner GL, Rose MS, Koshman ML, et al. Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden. J Cardiovasc Electrophysiol 2010; 21:1375. 33. Brignole M, Alboni P, Benditt D, et al. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001; 22:1256. 34. Oribe E, Caro S, Perera R, et al. Syncope: the diagnostic value of head-up tilt testing. Pacing Clin Electrophysiol 1997; 20:874. 35. Benditt DG, Adkisson WO, Sutton R, et al. Ambulatory diagnostic ECG monitoring for syncope and collapse: An assessment of clinical practice in the United States. Pacing Clin Electrophysiol 2018; 41:203. 36. Krahn AD, Klein GJ, Skanes AC, Yee R. Insertable loop recorder use for detection of intermittent arrhythmias. Pacing Clin Electrophysiol 2004; 27:657. Topic 1050 Version 40.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 15/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate GRAPHICS Major cardiovascular causes of syncope Reflex-mediated* Vasovagal Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm environment, etc Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc Unknown trigger Situational Micturition, defecation Swallowing Coughing/sneezing Carotid sinus syndrome Orthostatic hypotension* Medication-related Diuretics (eg, thiazide or loop diuretics) Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc) Antidepressants (eg, tricyclic drugs, SSRIs, etc) Volume depletion Hemorrhage Gastrointestinal losses (ie, vomiting or diarrhea) Diminished thirst drive (primarily in older patients) Autonomic failure Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body dementia Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy (eg, Guillain-Barr ), paraneoplastic neuropathy Cardiac Tachyarrhythmias Ventricular tachycardia Supraventricular tachycardias Bradyarrhythmias (with inadequate ventricular response) Sinus node dysfunction https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 16/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Atrioventricular block Structural disease Severe aortic stenosis Hypertrophic cardiomyopathy Cardiac tamponade Prosthetic valve dysfunction Congenital coronary anomalies Cardiac masses and tumors (eg, atrial myxoma) Cardiopulmonary/vascular Pulmonary embolus Severe pulmonary hypertension Aortic dissection SSRI: selective serotonin reuptake inhibitor. Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or are more severe, when other factors may also be contributing, such as medication(s) causing low blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply, alcohol use, and/or environmental factors (excessive heat or humidity). Adapted from: 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. Graphic 118175 Version 4.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 17/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Pathways in neurally mediated syncope Schematic representation of the specific syndromes, the suspected peripheral receptors (triggers), the afferent neural pathways, and the efferent pathways responsible for the clinical manifestations of bradycardia and hypotension in specific syncopal syndromes. GI: gastrointestinal; GU: genitourinary; NTS: nucleus tractus solitarius; V, VII, VIII, IX, and X: cranial nerves. Graphic 80233 Version 4.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 18/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Major life threatening causes of syncope Cardiovascular syncope Arrhythmia Ventricular tachycardia Long QT syndrome Brugada syndrome Bradycardia: Mobitz type II or 3rd degree heart block Significant sinus pause >3 seconds Ischemia Acute coronary syndrome, myocardial infarction Structural Abnormalities Valvular heart disease: aortic stenosis, mitral stenosis Cardiomyopathy (ischemic, dilated, hypertrophic) Atrial myxoma Cardiac tamponade Aortic dissection Significant hemorrhage Trauma with significant blood loss Gastrointestinal bleeding Tissue rupture: aortic aneurysm, spleen, ovarian cyst, ectopic pregnancy, retroperitoneal hemorrhage Pulmonary embolism Saddle embolus resulting in outflow tract obstruction or severe hypoxia Subarachnoid hemorrhage Graphic 81820 Version 1.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 19/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Electrocardiographic monitoring for syncope Recommendations Class* Level Indications ECG monitoring is indicated in patients who have clinical or ECG features I B suggesting arrhythmic syncope (listed in the "Risk stratification for syncope" table). The duration (and technology) of monitoring should be selected according to the risk and the predicted recurrence rate of syncope: Immediate in-hospital monitoring (in bed or telemetric) is indicated in high risk patients (as defined in the "Risk stratification for syncope" table) I C Holter monitoring is indicated in patients who have very frequent syncope or pre-syncope ( one per week) I B ILR is indicated in: An early phase of evaluation in patients with recurrent syncope of uncertain origin, absence of high risk criteria, and a high likelihood of recurrence within battery longevity of the device I B High risk patients (as defined in the "Risk stratification for syncope" table) in whom a comprehensive evaluation did not demonstrate a cause of syncope or lead to a specific treatment I B ILR should be considered to assess the contribution of bradycardia before embarking on cardiac pacing in patients with suspected or certain reflex IIa B syncope presenting with frequent or traumatic syncopal episodes External loop recorders should be considered in patients who have an inter-symptom interval four weeks IIa B Diagnostic criteria ECG monitoring is diagnostic when a correlation between syncope and an arrhythmia (brady- or tachyarrhythmia) is detected I B In the absence of such correlation, ECG monitoring is diagnostic when periods of Mobitz II or III degree AV block or a ventricular pause >3 s (with the possible exception of young trained persons, during sleep, medicated I C patients, or rate-controlled atrial fibrillation), or rapid prolonged paroxysmal SVT or VT are detected. The absence of arrhythmia during syncope excludes arrhythmic syncope. The ECG documentation of pre-syncope without any relevant arrhythmia is not an accurate surrogate for syncope III C Asymptomatic arrhythmias (other than those listed above) are not an accurate surrogate for syncope III C https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 20/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Sinus bradycardia (in the absence of syncope) is not an accurate surrogate for III C syncope AV: atrioventricular; ECG: electrocardiogram; ILR: implantable loop recorder; SVT: supraventricular tachyradia; VT: ventricular tachycardia. Class of recommendation. Level of evidence. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 57636 Version 11.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 21/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Clinical features of syncope that suggest a cause Neurally mediated syncope: Absence of heart disease Long history of recurrent syncope After sudden unexpected unpleasant sight, sound, smell, or pain Prolonged standing or crowded, hot places Nausea, vomiting associated with syncope During a meal or postprandial With head rotation or pressure on carotid sinus (as in tumors, shaving, tight collars) After exertion Syncope due to OH: After standing up Temporal relationship with start or changes of dose of vasodepressive drugs leading to hypotension Prolonged standing, especially in crowded, hot places Presence of autonomic neuropathy or Parkinsonism Standing after exertion Cardiovascular syncope: Presence of definite structural heart disease Family history of unexplained sudden death or channelopathy During exertion or supine Abnormal ECG Sudden onset palpitation immediately followed by syncope ECG findings suggesting arrhythmic syncope: Bifascicular block (defined as either LBBB or RBBB combined with left anterior or left posterior fascicular block) Other intraventricluar conduction abnormalities (QRS duration 0.12 s) Mobitz I second-degree AV block Asymptomatic inappropriate sinus bradycardia (<50 bpm), sinoatrial block or sinus pause 3 s in the absence of negatively chronotropic medications Nonsustained VT https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 22/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Preexcited QRS complexes Long or short QT intervals Early repolarization RBBB pattern with ST elevation in leads V1 to V3 (Brugada syndrome) Negative T waves in right precordial leads, epsilon waves and ventricular late potentials suggestive of ARVC Q waves suggesting myocardial infarction OH: orthostatic hypotension; ECG: electrocardiogram; LBBB: left bundle branch block; RBBB: right bundle branch block; AV: atrioventricular; bpm: beats per minute; VT: ventricular tachycardia; ARVC: arrhythmogenic right ventricular cardiomyopathy. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 66884 Version 10.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 23/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Conditions incorrectly diagnosed as syncope Disorders with partial or complete LOC but without global cerebral hypoperfusion Epilepsy Metabolic disorders including hypoglycaemia, hypoxia, hyperventilation with hypocapnia Intoxication Vertebrobasilar TIA Disorders without impairment of consciousness Cataplexy Drop attacks Falls Functional (psychogenic pseudosyncope) TIA or carotid origin LOC: loss of consciousness; TIA: transient ischaemic attack. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 76023 Version 6.0 https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 24/25 7/6/23, 2:38 PM Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation/print 25/25