INTRODUCTION — The upright tilt table test is sometimes performed as part of the evaluation of a patient with suspected vasovagal or orthostatic syncope. Tilt table testing may be helpful in patients in whom the diagnosis of vasovagal syncope is suspected but not certain [1-3]. It is particularly useful if the faint is induced and for patients to be able to confirm verbally that this is what they experience during spontaneous spells. The latter not only helps to confirm the diagnosis but also gives patients the confidence that the clinician has witnessed a true symptom spell and thereby knows what to recommend in regard to next steps. The test may also help identify patients with psychogenic pseudosyncope/pseudoseizures, especially if an electroencephalogram recording is obtained during the procedure. Additionally, in older persons, in whom the recollection of events may be poor, the tilt table test may help to assess susceptibility to orthostatic and vasovagal syncope [1,4]. Finally, tilt table testing is a useful part of overall evaluation of interactions between the autonomic nervous system and the cardiovascular system. The "active standing" test may also be used as part of the autonomic system evaluation, but does not replace the head-up tilt test; these tests supplement each other, but active standing is less thoroughly studied.

The indications for tilt table testing, along with a description of the procedures and discussion of the results, will be reviewed here. The general evaluation of the patient with transient loss of consciousness (TLOC) and suspected syncope, as well as a detailed discussion of reflex syncope, are discussed separately. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)

DEFINITION AND CAUSES OF SYNCOPE — Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a period of inadequate cerebral nutrient flow (usually diminished blood flow but on rare occasion severe hypoxemia), most often the result of an abrupt drop of systemic blood pressure. Typically, the inadequate cerebral nutrient flow is of relatively brief duration (8 to 10 seconds) and, in syncope, is by definition spontaneously self-limited.

Loss of postural tone is inevitable with loss of consciousness, and consequently syncope usually is associated with collapse, which may trigger injury due to a fall (such as may occur if the person is standing) or other type of accident (eg, if syncope occurs while driving). Recovery from true syncope is usually complete and rapid, with episodes rarely lasting more than a minute or two. Longer periods of real or apparent loss of consciousness suggest that the event is not syncope.

Syncope is but one form of TLOC. The possible causes of TLOC resulting in true syncope are generally grouped into four major categories:

●Reflex syncope (also termed neurally-mediated reflex syncope)

●Orthostatic syncope

●Cardiac arrhythmias

●Structural cardiopulmonary disease

In addition to the causes of true syncope, in the evaluation of a patient with TLOC in whom syncope is suspected, the clinician must also consider and exclude conditions that mimic syncope but are not true syncope. The most common of these conditions are seizures, sleep disturbances, accidental falls, and some psychiatric conditions (eg, pseudosyncope and pseudoseizures). The major causes of syncope are discussed in greater detail separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies".)

INDICATIONS — In general, our approach to tilt table testing is consistent with the published recommendations of various professional societies [2,3,5]. With the understanding that tilt table testing is an imperfect diagnostic test, we recommend tilt table testing for patients in the following instances (see 'Test performance' below):

●Patients with recurrent episodes of syncope of unknown cause in the absence of structural heart disease, or in the presence of structural heart disease after cardiac causes of syncope (ie, arrhythmias) have been excluded.

●Patients with suspected vasovagal syncope who lack a confident diagnosis after the initial assessment or who do not have clear diagnostic features.

●Patients with a single unexplained syncopal episode in high-risk settings (eg, occurrence or potential risk for physical injury or occupational hazard).

●Patients for whom there is clinical value of demonstrating susceptibility to reflex or orthostatic syncope. Most importantly, this may help to reassure the patient that a diagnosis has been established. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Upright tilt table test'.)

●To discriminate between suspected reflex syncope and orthostatic hypotension syncope. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)

●As part of the overall evaluation of interactions between the autonomic nervous system and the cardiovascular system. The "active standing" test and other tests of autonomic nervous system function may also be used as part of the evaluation procedure.

●Patients being assessed for postural tachycardia syndrome (POTS), although the diagnostic utility of tilt testing is not well established. (See "Postural tachycardia syndrome", section on 'Diagnostic approach'.)

●To differentiate between convulsive syncope and epilepsy, or to establish a diagnosis of pseudosyncope or pseudoseizures (sometimes also known as psychogenic nonepileptic seizures). (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".)

●To identify patients in whom bradyarrhythmia has been documented during reflex syncope in order to determine whether a vasodepressor response is present, in which case the individual would be less likely to respond to permanent cardiac pacing. (See "Reflex syncope in adults and adolescents: Treatment", section on 'Pacemaker therapy'.)

Tilt table testing is generally not helpful to identify patients with situational vagal syncope (ie, syncope due to situations associated with enhanced vagal tone such as micturition, defecation, cough, or vomiting) [6]. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Upright tilt table test'.)

CONTRAINDICATIONS — Tilt table testing should not be performed in patients who have severe coronary or cerebrovascular disease in whom hypotension may cause myocardial or cerebral ischemia. Similarly, tilt tests are discouraged in pregnant women as hypotension may potentially be harmful to the fetus.

In addition, although a controlled infusion of isoproterenol is safe in patients without heart disease, it must be used cautiously in patients with coronary artery disease since angina and serious arrhythmia can be provoked [7,8]. In many locations, isoproterenol has become very expensive, and consequently, nitroglycerin provocation (the so-called Italian protocol) has become increasingly preferable. In any case, drug provocation is only used after a baseline drug-free test has been nondiagnostic. (See 'Isoproterenol' below.)

TILT TABLE TESTING PROCEDURE — Upright tilt table testing is typically performed in an electrophysiology laboratory or dedicated procedure room using a special motorized tilt table that raises to 70 degrees above supine. The drug-free test duration is approximately 20 minutes in most laboratories. Thereafter, if the initial drug-free portion of the test is negative, isoproterenol or nitroglycerin may be given as provocative diagnostic agents, and the test is typically carried out for an additional 10 minutes [9]. In patients exhibiting marked orthostatic hypotension, testing may be repeated after hydration with intravenous saline.

Patient preparation and necessary equipment — Patient preparation, along with the facilities and equipment necessary for performing a tilt table test, is straightforward.

●The patient should fast at least three to four hours before the test.

●Depending upon the clinical circumstances, patients may be asked to take their usual meds or alternatively hold their usual drugs.

●The test should be performed in a quiet room with a comfortable temperature and minimal distractions for the patient.

●The patient should have an intravenous catheter placed prior to the procedure, allowing for administration of fluids and/or medications (ie, isoproterenol or nitroglycerin) if needed. This is best done more than 30 minutes prior to the test.

●The patient is placed on a motorized tilt-table with a foot board and safety restraints. The bed should be capable of smoothly and rapidly moving the patient passively from a supine position to a head-up position between 60 to 80 degrees and quickly (in <10 seconds) returning the patient to a supine position to avoid the consequences of prolonged hypotension.

●Continuous electrocardiogram (ECG) and beat-to-beat blood pressure monitoring are employed throughout the test. Careful monitoring is required because many patients have a pronounced cardioinhibitory response characterized by symptomatic hypotension, bradycardia, or both.

•There is no defined consensus regarding ECG monitoring, but most tests are performed using either three or six ECG leads. Conventional limb leads are commonly used as they are convenient and offer more than adequate monitoring to assess for changes in heart rate and rhythm.

•Blood pressure recording should be beat-to-beat and is typically noninvasive. Invasive arterial monitoring is rarely used with current tilt table tests, but it is acceptable as long as the line is placed at least an hour before the procedure to allow autonomic tone to return to baseline. Intermittent blood pressure measurement via sphygmomanometer is not adequate as the number of data points precludes identifying developing problems and even more importantly the cuff disturbance may alter patient autonomics and may thereby undermine the objective of the study.

•Other autonomic testing may be carried out during the same test procedure, but sufficient time is needed between steps to allow the patient to return to basal state. These additional tests could include "active standing," Valsalva maneuver, carotid massage, respiratory sinus arrhythmia, and sweat testing.

•Electroencephalogram monitoring may be warranted in certain cases, especially if pseudosyncope/pseudoseizure or ictal asystole are suspected.

Tilt protocol — A variety of protocols have been described for the test that vary in the angle of tilt (60 to 70 degrees above supine), duration of tilt (10 to 60 minutes), and the administration of isoproterenol or nitroglycerin. The most commonly used protocol is described. (See 'Patient preparation and necessary equipment' above.)

Starting the test — To begin the test, the patient is monitored in the supine position for 5 to 10 minutes to obtain baseline heart rate and blood pressure measurements. If venous or arterial cannulation other than a routine intravenous line is performed just prior to the test, a longer supine time period of at least 20 minutes is recommended in order to allow any stimulated circulating catecholamines to return to baseline. The patient should be instructed to remain as calm and relaxed as possible and to report any symptoms that may develop.

Passive phase — A passive phase (upright with no isoproterenol or nitroglycerin infusion) of usually 20 minutes is performed first, with the patient positioned in a head-up tilt position at a tilt angle between 60 and 70 degrees. Heart rate and symptoms are recorded every three to five minutes, and the ECG is recorded continuously. The blood pressure should be monitored noninvasively by beat-to-beat finger arterial monitoring. As noted above, an arm cuff is discouraged, as it interferes with the patient and inevitably alters autonomic tone.

Possible outcomes resulting from the passive phase include a positive response for reflex syncope, a positive response for orthostatic hypotension, a positive response for psychogenic pseudosyncope, and a nondiagnostic response. If no symptoms or ECG abnormalities consistent with the patient's history have developed after a period of 20 minutes, the patient is returned to the supine position, and the passive test is considered nondiagnostic.

In the case of reflex syncope evaluation, the decision to proceed with a drug provocation phase is up to the discretion of the clinician and is generally determined by the perceived necessity of inducing a response suggestive of reflex syncope. (See 'Test interpretation' below.)

It may be possible to reduce the time necessary for the tilt table test and avoid the need for isoproterenol infusion based upon the heart rate response early in the passive phase. In a study of 109 patients, a heart rate change ≤18 beats per minute during the first six minutes of the test prospectively predicted a negative tilt table test with a 96 percent specificity, 98 percent positive predictive accuracy, and 87 percent sensitivity, even with the subsequent use of isoproterenol [10]. However, this shortened procedure is not widely used and is not our recommended approach.

Drug provocation phase — If the patient has remained asymptomatic during the passive phase of tilt table testing, a second tilt table test is often performed after a vasoactive medication (usually either isoproterenol or nitroglycerin) is administered [9]. Either drug can be used for the drug provocation phase, with the choice of isoproterenol or nitroglycerin usually directed by local practice and clinician expertise.

Isoproterenol — If the passive phase is negative and isoproterenol infusion is chosen, the infusion is administered with the patient in the supine position, although some advocate for the infusion to be initiated with the patient already in the 60 to 70 degree head-up tilt position [3]. Isoproterenol is usually titrated from 1 to 3 mcg/minute to increase the heart rate by 20 to 25 percent above baseline. Once the desired heart rate has been achieved, the patient is placed in the 60 to 70 degree head-up tilt position for an additional 15 to 20 minutes. Generally, loss of consciousness during isoproterenol infusion is required to consider the test positive, although the 2018 European Society of Cardiology (ESC) guidelines include no separate diagnostic criteria for tilt table testing following isoproterenol infusion [3]. A modest decrease in blood pressure with symptoms is common with isoproterenol and is nonspecific.

The fact that isoproterenol may trigger vasovagal syncope may seem somewhat paradoxical. The mechanism is thought to be due to activation of central circulation mechanoreceptors, but the exact basis for the effect is not absolutely known. The potential efficacy of isoproterenol infusion was illustrated in a study in which a single-stage isoproterenol tilt table test more frequently induced syncope than a standard passive tilt table test (56 versus 32 percent) and reduced the time necessary for the procedure [11]. There was, however, a lower specificity (83 versus 91 percent for standard tilt table testing). (See 'Test performance' below.)

Nitroglycerin — If the passive phase is negative and nitroglycerin is required, we administer a fixed dose of 300 to 400 mcg of sublingual nitroglycerin in the 60 to 70 degree upright position [3]. The use of intravenously administered nitroglycerin has been described but is rarely used. Generally, loss of consciousness following nitroglycerin administration is required to consider the test positive [3]. A modest decrease in blood pressure with symptoms is common with nitroglycerin and is nonspecific.

Nitroglycerin likely increases susceptibility to vasovagal syncope by reducing venous return to the heart and thereby enhancing cardiac activity and activating the reflex via central cardiac mechanoreceptors [12-14]. Nitroglycerin causes venodilation with consequent reduction in venous return and stroke volume, without impeding the sympathetic responses of increased heart rate and arterial vasoconstriction [15]. The addition of nitroglycerin to tilt table testing increases the frequency of hemodynamic changes and reproduction of symptoms and may shorten test duration but also increases the rate of false positive tests. In a study of 232 patients, including 149 with unexplained syncope and 83 asymptomatic controls, participants were randomly assigned to receive nitroglycerin (800 mcg metered spray) and a 20-minute tilt table test or no nitroglycerin and a standard 40-minute tilt table test [16]. Nitroglycerin increased the frequency of a positive tilt table test from 11 to 36 percent in all patients, although the results are nonspecific as the rate of positive tests increased in both patients with prior syncope and control patients.

Comparison of isoproterenol and nitroglycerin — Isoproterenol and nitroglycerin have been compared as adjuncts to tilt table testing [17,18]:

●In one study of 71 patients with unexplained syncope and 30 controls who underwent tilt table testing twice on separate days, with all patients receiving isoproterenol and nitroglycerin on separate days, rates of test positivity were similar in patients receiving nitroglycerin and isoproterenol (49 and 41 percent, respectively) [17]. However, sublingual nitroglycerin was simpler to use and better tolerated than isoproterenol.

●In a study of 96 patients with unexplained syncope who underwent three separate tilt table tests on the same day (passive, once with isoproterenol, once with nitroglycerin), sublingual nitroglycerin with tilt table testing led to a higher number of positive responses than isoproterenol (55 versus 42 percent), especially among patients with a positive tilt table test without pharmacologic agents (94 versus 67 percent) [18].

TILT TABLE TEST RESULTS — A positive test for vasovagal syncope is characterized by the development of syncope in association with a cardioinhibitory and/or a vasodepressor response causing symptomatic hypotension (figure 1). The vasovagal reflex seen on a tilt table test may reflect a given patient's predisposition to vasovagal syncope; however, the actual physiologic response on the tilt table test may differ from episodes experienced clinically. The tilt table test findings should always be interpreted in the context of the patient's history and spontaneous symptoms. It is prudent to inquire after a positive test if the patient thinks that the test resulted in symptoms identical to those experienced during spontaneous events. (See 'Passive phase' above.)

Test interpretation — The clinical significance of abnormal responses other than induction of syncope is not clear [2,3]. Although isoproterenol and nitroglycerin increase the sensitivity of the test, these two interventions also decrease the specificity (ie, more false positives). A positive test does not necessarily indicate that syncope is due to a vasovagal cause. Interpretation of the results and their relation to a cause for syncope must be made in light of all clinical data, particularly the patient's description of spontaneous events.

Interpretation of response to tilt table test varies depending upon the clinical setting (see 'Passive phase' above):

●In patients without structural heart disease:

•If the patient experiences a significant fall in blood pressure or heart rate with loss of consciousness or the inability to maintain posture, he or she is returned to a supine position, and the test is considered positive for reflex syncope.

•If the patient experiences a significant fall in blood pressure or heart rate with symptoms suggestive of presyncope but without loss of consciousness, he or she is returned to a supine position, and the test is considered suggestive of reflex syncope. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Upright tilt table test'.)

•If the patient experiences progressive orthostatic hypotension (slow progressive decrease in systolic blood pressure) with or without symptoms, the test is diagnostic for orthostatic hypotension syncope, not reflex syncope. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".)

•If the patient appears to lose consciousness or is unable to maintain posture in association without a significant fall in blood pressure or heart rate, he or she is returned to a supine position, and the test is considered positive for psychogenic pseudosyncope. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".)

•If the test is being done to assess orthostatic hypotension, a posture-triggered fall of blood pressure is usually accompanied by an increase in heart rate. However, in some older patients or individuals with autonomic failure, the heart rate increment may be missing.

•If the tilt table test is being done to evaluate for postural tachycardia syndrome, the test would be considered diagnostic if there is a sustained heart rate increase of greater than 30 beats per minute or an increase to 120 beats per minute or greater within the first 10 minutes of the passive phase. However, other factors (eg, dehydration, concomitant inflammatory conditions, anemia, hyperthyroidism, etc) must be excluded before testing. (See "Postural tachycardia syndrome", section on 'Diagnostic approach'.)

●In patients with structural heart disease, the same diagnostic criteria apply. However, arrhythmias and other cardiac causes of syncope should be excluded before considering a positive tilt table test as diagnostic of reflex syncope.

Test performance — Although the tilt table test is frequently positive in patients with vasovagal syncope, it is not the gold standard for the diagnosis of vasovagal syncope, as it has limited sensitivity, specificity, and reproducibility. The medical history is key, and the response to tilt table testing can be highly variable. Even the severity of cardioinhibitory versus vasodepressor components may differ from one test to another. Additionally, factors such as prior history of syncope, age, and the use of medications during the protocol all seem to have an effect on the likelihood of a positive test. Ultimately, in all patients with syncope, obtaining a thorough history as part of the initial evaluation is the most important thing clinicians can do to make the appropriate diagnosis and direct further diagnostic testing. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on 'Initial evaluation'.)

The sensitivity of tilt table testing is as high as 80 percent, depending upon the protocol and patient selection, but this high sensitivity is at the expense of a lowered specificity (ie, more false positive tests). Among individuals who undergo a tilt table test with isoproterenol, a positive response is seen in as many as 45 percent or more of those who do not have a history of syncope (ie, induction of syncope in normal volunteers) [19]. The reported false negative rate is as high as 14 to 30 percent but can be higher depending upon the protocol and patient age. However, the true false negative rate is difficult to determine since there is no gold standard for comparison. Thus, vasovagal syncope cannot be excluded by a negative tilt table test. The interpretation of a test outcome requires clinician experience, in particular consideration of whether the findings are consistent with the patient's spontaneous symptoms.

The characteristics of induced syncope during tilt table testing appears to be different in normals exhibiting false positive results, and patients with a history of vasovagal syncope (ie, true positives).

●In a study that compared eight normals with a positive tilt table test, eight normals with a negative tilt table test, and 15 patients with vasovagal syncope, patients with vasovagal syncope had a shorter time to syncope (9.5 versus 17 minutes), an immediate and persistent drop in mean blood pressure, more rapid peripheral pooling of blood, and higher peak serum epinephrine levels [20].

●In one study of 145 patients with a history of presyncope or syncope, patients with a history of recurrent syncope were significantly more likely to have a positive test compared with those with a single episode or with recurrent presyncope [21]. Additionally, patients with structural heart disease or with a noncardiovascular cause for syncope were significantly less likely to have a positive test (16 versus 42 percent) (figure 2).

The response to tilt table testing appears to vary with the patient age. Younger subjects are more likely to have a bradycardic response, whereas older subjects are more likely to have a vasodepression response [22-24].

COMPLICATIONS — Complications are rare with tilt table testing, but prolonged asystole or hypotension occasionally occurs. If either occurs and is associated with syncope, the patient should be placed in a supine position immediately until recovery.

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".)

SUMMARY AND RECOMMENDATIONS

●With the understanding that tilt table testing is an imperfect test, we recommend tilt table testing for patients in the following instances (see 'Indications' above):

•Patients with recurrent episodes of syncope of an unknown cause in the absence of structural heart disease, or in the presence of structural heart disease after cardiac causes of syncope (ie, arrhythmias) have been excluded.

•Patients with suspected vasovagal syncope who lack a confident diagnosis after the initial assessment or who do not have clear diagnostic features.

•Patients with a single unexplained syncopal episode in high-risk settings (eg, occurrence or potential risk for physical injury or occupational hazard).

•Patients for whom there is clinical value of demonstrating susceptibility to reflex syncope. Most importantly, this may help to reassure the patient that a diagnosis has been established. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Upright tilt table test'.)

•Tilt table testing may also be used to discriminate between suspected reflex syncope and orthostatic hypotension syncope, to evaluate for postural tachycardia syndrome, to differentiate between convulsive syncope and epilepsy, or to establish a diagnosis of psychogenic nonepileptic seizures (formerly called pseudosyncope). However, a non-positive test should not be used to absolutely "exclude" a diagnosis. On any given day, the test may be nondiagnostic.

●Tilt table testing should not be performed in patients who have severe coronary or cerebrovascular disease in whom hypotension may cause myocardial or cerebral ischemia. Similarly, tilt tests are discouraged in pregnant women as hypotension may potentially be harmful to the fetus. (See 'Contraindications' above.)

●Upright tilt table testing is typically performed in an electrophysiology laboratory or dedicated procedure room using a special motorized tilt table that raises to 70 degrees above supine. The drug-free test duration is approximately 20 minutes in most laboratories. Thereafter, if the initial drug-free portion of the test is negative, isoproterenol or nitroglycerin may be given as provocative diagnostic agents, and the test is carried out for an additional 10 minutes. (See 'Tilt protocol' above.)

●Interpretation of response to tilt table testing varies depending upon the clinical setting and requires both clinician experience as well as careful consideration of the relation of the test outcome to the patient's spontaneous symptoms (see 'Test interpretation' above). The following are representative of possible test outcomes:

•If the patient experiences a significant fall in blood pressure or heart rate with loss of consciousness or the inability to maintain posture, he or she is returned to a supine position, and the test is considered positive for reflex syncope.

•If the patient experiences a significant fall in blood pressure or heart rate with symptoms suggestive of presyncope but without loss of consciousness, he or she is returned to a supine position, and the test is considered suggestive of reflex syncope. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation", section on 'Upright tilt table test'.)

•If the patient experiences progressive orthostatic hypotension (slow progressive decrease in systolic blood pressure) with or without symptoms, the test is diagnostic for orthostatic hypotension syncope, not reflex syncope. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".)

•If the patient appears to lose consciousness or is unable to maintain posture without a significant fall in blood pressure or heart rate, he or she is returned to a supine position, and the test is considered positive for psychogenic pseudosyncope. Additional supportive observations include eyes tightly closed and prolonged period of apparent loss of consciousness (typically >2 to 3 minutes even after return to supine posture). (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".)

•If the tilt table test is being done to evaluate for postural tachycardia syndrome, the test would be considered diagnostic if there is a sustained heart rate increase of greater than 30 beats per minute or an increase to 120 beats per minute or greater within the first 10 minutes of the passive phase. However, multiple caveats apply. (See "Postural tachycardia syndrome", section on 'Diagnostic approach'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Brian Olshansky, MD, who contributed to an earlier version of this topic review.