Recommendations for tilt table testing and other provocative cardiovascular autonomic tests in conditions that may cause transient loss of consciousness

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Abstract

An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO₂ or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.

Keywords: Transient loss of consciousness, Syncope, Tilt table testing, Vasovagal, Reflex syncope, Orthostatic hypotension, Psychogenic pseudosyncope

Introduction

Tilt table testing (TTT), while initially developed to study physiological compensatory responses to orthostatic stress, proved useful as a diagnostic test for vasovagal syncope (VVS) in 1986 [1]. TTT is now widely used in clinical practice with a variety of protocols, variants and extensions. On 6 July 2018, the European Federation of Autonomic Societies (EFAS) organised a round table discussion to obtain consensus on the use of TTT in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. The 2018 guidelines of the European Society of Cardiology [2] and the 2011 EFAS/American Autonomic Society (AAS) Consensus paper [3] were used as starting points. Definitions of various conditions and tests are used as presented in these sources, where necessary preference was given to the more recent ESC guidelines. Two authors (RDT and JGvD) searched PubMed for additional articles from 2014, with the keywords ‘tilt table’ AND ‘syncope’ OR ‘orthostatic intolerance’ (449 hits). We also cite occasional earlier articles and reviews, when these are relevant. The resulting consensus statement was reviewed by all participants, discussed at a second session on 30 June 2019, a third session on 27 January 2020, and sent for endorsement to the autonomic nervous system (ANS) panel of the European Academy of Neurology (EAN). This consensus statement reflects the opinion of experts in the field, but is not a formal evidence-based clinical guideline.

Indications

TTT and other provocative cardiovascular autonomic tests primarily aim to obtain a pathophysiological correlate for orthostatic intolerance and TLOC. The fundamental tool for the differential diagnosis is history taking of patients and eyewitnesses [2, 4]. TTT may provide an important addition to history taking if the initial evaluation does not yield a definite or highly likely diagnosis. TTT should neither be used as a substitute for history taking nor isolated from history taking. Figure 1 shows a pragmatic approach, beginning with the initial evaluation of TLOC including history taking, ECG and bedside orthostatic blood pressure measurements. Figure 2 provides a flow chart for the work-up of patients with orthostatic intolerance.

Flow chart of the diagnostic work-up following the initial evaluation of transient loss of consciousness (TLOC), i.e. history taking, ECG and bedside supine and standing blood pressure measurements. AST active standing test with continuous blood pressure measurements, BP blood pressure, cOH classic orthostatic hypotension, CSM carotid sinus massage, TLOC transient loss of consciousness, TTT tilt table testing, VVS vasovagal syncope

Flow chart of the diagnostic work-up of orthostatic intolerance, i.e. history taking and supine and standing blood pressure measurements. AST active standing test with continuous blood pressure measurements, classic OH classical orthostatic hypotension, POTS postural orthostatic tachycardia syndrome, TTT tilt table testing

To obtain a pathophysiological correlate for orthostatic intolerance and TLOC

The primary aim of TTT is to provoke an event with complaint recognition and to demonstrate the pathophysiological correlate [2, 5]. These aspects are both crucial: recognition may concern subjective sensations reported by patients as well as visible aspects, such as changes in facial colour or movements, recognised by eyewitnesses as similar to spontaneous ones. Together with demonstration of pathophysiological measurements, a clinical-pathophysiological correlate is obtained, thereby proving the cause of TLOC. For most indications, TTT relies on prolonged orthostatic stress in the near-vertical position (‘head-up tilt’). TTT is not useful for all TLOC forms, as epileptic seizures and cardiac syncope are not commonly provoked by the upright posture. In contrast, TTT is useful for diagnosing syncope forms with an orthostatic component, i.e. reflex syncope and syncope due to orthostatic hypotension. TTT is also useful to provoke psychogenic TLOC, i.e. short-lasting apparent unconsciousness due to conversion. TTT can provide a definite diagnosis of psychogenic TLOC by excluding epilepsy or syncope. In the elderly it may be difficult to distinguish between falls with and without loss of consciousness. Hence, TTT may be used to investigate unexplained falls in the elderly, as these may be due to syncope [6, 7].

The role of TTT in diagnosing vasovagal syncope (VVS) has been debated [8–11]. The yield of a certain or highly likely diagnosis with history taking following an initial evaluation by hospital physicians and long-term follow-up as a reference may amount to 60%, with an accuracy of about 90% [12]. The diagnostic yield can increase to as much as 85% with additional history taking by an expert in syncope [13]. In view of these findings, TTT is not needed in the majority of cases presenting with syncope. Another concern is the specificity of TTT. Syncope during TTT reflects a tendency towards hypotension due to low preload in the upright position, rather than a specific diagnosis [14]. TTT modulates the occurrence not only of orthostatic VVS, but also of other forms of syncope such as cardiac syncope [14]. TTT should therefore only be performed after a careful and detailed medical history and examination. The results of the test should be interpreted in the context of that history and examination. Estimates of sensitivity (overall 59%; 95% CI 53–64%; range 21–72%) and specificity (overall 91%; 95% CI 87–93%) of TTT in diagnosing VVS differ [15]. Important factors contributing to the variability relate to the specific test protocol (e.g. the use of pharmacological provocation, tilt angle, duration of TTT, etc.), interpretation of the results, meaning whether complaint recognition or pathophysiological measurements are used as the standard to judge abnormality, and the lack of an agreed reference standard other than long-term follow-up [2, 5, 15, 16]. The most marked contrasts are seen between 'passive' TTT, i.e. upright tilt without pharmacological provocation [sensitivity 37%; (95% CI 29–46%); specificity 99% (95% CI 97–99%)], and ‘active’ protocols [e.g. nitroglycerin provocation sensitivity 66% (95% CI 60–72%); specificity 89% (95% CI 84–92%) [15]. As TTT relies predominantly on the orthostatic, literally meaning ‘upright’, position, TTT indications comprise the conditions bundled under ‘orthostatic intolerance’ [2, 5, 16]. Orthostatic intolerance includes all three forms of OH (i.e. initial, classic and delayed OH), delayed orthostatic BP recovery, orthostatic VVS and postural orthostatic tachycardia syndrome (POTS). Although some forms of reflex syncope, e.g. emotional VVS and cough syncope, primarily rely on other triggers, subjects with these forms are often also susceptible to orthostatic VVS [17, 18]. TTT may therefore still help to provoke syncope in these cases. In other cases, specific additional provocations may be needed to provoke TLOC.

The role of TTT and other provocative cardiovascular autonomic tests is similar for the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed, in that a definite diagnosis can be made when complaint recognition coincides with the type of BP decrease that is specific for each form (Table ​ (Table1). 1 ). The three forms may, however, require specific test protocols: (1) initial OH is commonly not provoked by passive tilt, but requires an active standing test with continuous BP measurements [19, 20]; (2) classic OH is most commonly screened at bedside with intermittent BP measurements, but can also be assessed with TTT or an active standing test [21]; delayed OH may require prolongation of the test protocol to allow a blood pressure decrease to occur [21–23]. Note that classic OH and presumably delayed OH often fluctuate in severity, so the absence of complaints and a blood pressure decrease during the test do not exclude OH (Table ​ (Table2) 2 ) [2, 21]. Conversely, the finding of classic OH does not automatically provide an explanation for orthostatic intolerance or TLOC, as it is a common finding affecting up to one in five community-dwelling elderly [2, 24]. When there is such a discrepancy between measurement results and complaints, the question of whether the measured OH represents a clinically relevant finding critically depends on the clinical presentation. When doubt remains, home measurements during complaints may settle the issue.

Table 1

Haemodynamic criteria for conditions causing orthostatic intolerance [3, 41]

AST active standing test, classic OH classical orthostatic hypotension, DBP diastolic blood pressure, delayed OH delayed orthostatic hypotension, HR heart rate, initial OH initial orthostatic hypotension, POTS postural orthostatic tachycardia syndrome, SBP systolic blood pressure, TTT tilt table test

a BP fall should be sustained to avoid confusion with transient BP falls seen in initial OH or VVS

d POTS is a clinical diagnosis and requires symptoms of orthostatic intolerance and the documentation of an exaggerated postural tachycardia using TTT or an active standing test

e For individuals aged 12–19 years, the required increment is > 40 bpm

f For patients with supine hypertension, a reduction in SBP ≥ 30 mmHg is required, as the magnitude of the orthostatic BP fall is dependent on the baseline BP

g No formal criteria to differentiate between vasovagal (pre)syncope and other causes of presyncope. The haemodynamic patterns associated with vasovagal (pre)syncope are heterogeneous [30] and may or may not be accompanied by HR slowing. Various criteria have been proposed to differentiate between subtypes

Table 2

Association of orthostatic intolerance and orthostatic hypotension [2]

Reproduced with permission from the 2018 ESC Guidelines for the diagnosis and management of syncope

BP blood pressure, OH orthostatic hypotension

A diagnosis of psychogenic TLOC preferably requires documentation of an event, for which video or video-EEG recordings provide the most convincing evidence. History taking often raises a strong suspicion of psychogenic TLOC, but may not always be reliable enough to rule out other causes of TLOC [25]. The use of video-EEG is particularly important to exclude epilepsy when the clinical event is accompanied by positive motor phenomena [25]. Note that a normal EEG during a provoked event excludes syncope with certainty, but need not exclude all possible forms of epilepsy. It does, however, exclude those forms of epilepsy that present with TLOC, i.e. tonic, clonic and tonic–clonic seizures [26]. A diagnosis of psychogenic TLOC can also be established on clinical grounds if a clinician witnesses the event and observes features favouring psychogenic TLOC (e.g. eye closure, resisted eye-opening, partial responsiveness during the event, etc.) [25].

To classify classic OH

Treatment

TTT is not completely restricted to diagnosis. Patients may exhibit a decrease in syncope frequency after TTT, which may be due to patients having learned to recognise early signs of syncope, allowing them to take measures to prevent it [32]. TTT may easily be expanded with a biofeedback session to teach the ‘counter manoeuvres’ [33, 34]. This session can be performed when subjects are still symptomatic after syncope, thus allowing strong feedback regarding the effectiveness of these interventions. The session is also extremely important for patients’ education, as patients can see their own blood pressure fluctuate and discover which manoeuvres decrease (e.g., squat-to-stand) and which manoeuvres increase (e.g., leg crossing) their blood pressure. Applying these measures using biofeedback reduces the recurrence risk in patients with reflex syncope by 39% compared to conventional treatment only, i.e. explanation and life-style advice [33]. Patients with definite VVS and no need for additional testing could be referred to an animated video on physical counter manoeuvres [35]. TTT also allows the study of the temporal relation between onset of asystole and TLOC in those with asystolic VVS and helps to guide pacemaker recommendations. In one-third of cases of tilt-induced asystolic reflex syncope, asystole occurred too late to have been the primary cause of TLOC, thus making pacemaker implantation likely ineffective [36].