Upright tilt table testing in children and adolescents: An aid to the clinical diagnosis of postural orthostatic tachycardia syndrome

Abstract

The use of upright tilt table testing (TTT) in adults was first described over 40 years ago. Initially used to assess orthostatic hypotension, it also tested an individual's sensitivity to the Bezold-Jarisch (BZ) reflex, thought to play a dominant role in many cases of neurocardiogenic syncope (‘fainting’).¹

Assuming the upright posture, and then standing still, reduces venous return to the heart, thereby reducing its stroke volume and initiating reflex sympathetic stimulation. These changes create a ‘dry pump’ situation, stimulating cardiac stretch receptors. Cardiac distress from the receptors is then transmitted to the vasomotor centre via vagal afferents and activation of the 5HT1A serotonin brain receptors. In susceptible individuals the BZ reflex may be initiated, shutting down the circulation with vasodilatation from sympathetic withdrawal and vagally mediated bradycardia. There may be other internal and external triggers that contribute to a vasovagal outcome, so that in most cases fainting involves multiple coincident triggers including activation of the BZ reflex.²

TTT mimics physical conditions that may initiate the BZ reflex. Patients are brought to the erect posture from a supine position and remain there without movement for varying periods. The ‘dry pump’ phenomenon occurs and can be enhanced by the administration of nitrates (to further reduce venous return), or isoprenaline (to further increase cardiac rate and contractility) as a form of pharmacological challenge.³ The BZ reflex may be universal in humans but susceptibility varies widely even within an individual over time. TTT protocols vary, with differences in tilt angle, duration of tilting and whether a pharmacological challenge is initiated and the dosages administered.⁴ The sensitivity and specificity of protocols varies according to their design. Unsurprisingly, the common use of low stress protocols sacrifices sensitivity to avoid false positive outcomes that would reflect poor specificity and poor diagnostic usefulness.

The lead author has been using the same TTT protocol over many years, utilising a 10 min, 70° tilt, followed by another 10 min of tilting with a nitrate or high-dose isoprenaline infusion (Fig. 1). Generally our protocol complies with recent guidelines,⁵ although a hesitancy in them to recommend Isoprenaline use is unexplained. In our practice isoprenaline is preferred in younger patients, rather than nitrates, as it reflects the higher sympathetic activity of the young that may be present at times of symptomatic events.⁶ In contrast, provocation by isoprenaline of an arrhythmia (e.g. atrial fibrillation) or symptoms from coronary artery disease in the elderly may demand the use of a nitrate instead. The specificity of our high-stress protocol using isoprenaline is ensured by patient validation immediately after the test, in that any symptomatic outcome closely matches their previous clinical experience. Furthermore, a targeted patient questionnaire is performed by the physician before each test, determining the pretest likelihood of a relevant outcome. That further enhances the validity of the test result providing our protocol with a high diagnostic accuracy.

In the last 25 years or so, TTT has also been used to assess other forms of orthostatic blood pressure intolerance, particularly postural orthostatic tachycardia syndrome (POTS). In this situation, a passive TTT can detect the well described signature hemodynamics of POTS: excessive age-indexed heart rate increases with tilting without a substantial (<20 mmHg) fall in blood pressure, which may or may not be associated with reproduction of tachycardia-related symptoms.^{3, 6} Further testing with a pharmacological challenge often reveals the mechanism for hypotensive events that frequently occur in POTS, being either vasodepressor (hypotension with extreme sinus tachycardia), or vasovagal events. Critics maintain that the finding of POTS hemodynamics in the absence of symptoms is not diagnostic of the condition. This concern ignores the clinical reality that long-term ECG monitoring of patients with POTS has revealed that many show periods of excessive sinus tachycardia (and relative lack of sinus bradycardia) on a long-term basis, but may only be symptomatic on occasion. Furthermore, a sustained hemodynamic pattern appears to be unique to this condition and therefore should be diagnostic as such. If no symptoms occur despite the POTS hemodynamics during passive tilting, symptoms may be easily provoked with tilting with an isoprenaline infusion which exacerbates the degree of tachycardia, again emphasising the role of TTT with pharmacological challenge in patients with POTS.

Although there has been extensive experience with TTT in adults and adolescents, its use in children and young adolescents has been limited. Nonetheless the literature has shown a role for TTT to investigate syncope and other forms of orthostatic blood pressure intolerance (including POTS) in children, some less than 5 years of age.⁷ We recently described the role of TTT to assess POTS in this age group⁶ where it is surprisingly common.⁸ In our experience, symptoms from POTS in young patients usually begin with the hormonal changes of puberty, combined with the increased stresses of education, social interaction and sporting activities. Protocols used have been similar to those in adults, including the use of pharmacological challenge with equivalent tolerance and safety.

The lead author has been performing outpatient TTT with the availability of full resuscitative facilities, on adolescents using pharmacological challenge with isoprenaline for many years, without any safety concerns. This is ensured by an intravenous infusion of a weight-based dose (70 ng/kg/min), resulting in a predictable heart rate response without arrhythmia. When ceased, the infusion has a short half-time, and any effect on heart rate disappears in 2–5 min. In contrast, the tolerance to nitrates in some children is poor.

Older clinical guidelines related to POTS and vasovagal syncope in paediatric patients suggested that TTT is usually not needed and has imperfect sensitivity and specificity.⁹ They previously suggested that it be used in highly selected patients with vasovagal syncope but not POTS. We are not aware of more recent opinions.

Compared to the experience in adults, performing TTT in young children may have limitations. The ability of the child to articulate their experiences during a pre-test interview outlining their previous symptoms, triggers and other observations at the time of symptoms may limit the ability of the physician to recognise the characteristic pattern of neurocardiogenic syncope or POTS prior to a referral for a TTT, thereby affecting the ability to gauge the pre-test likelihood of a positive outcome. Similarly, validation by the child of the outcome of the TTT may be difficult. Here the observations of close family members (in particular the parents or other eye witnesses) become invaluable. Their presence during the test allows them to compare the previous events to what is observed during the test. Similarly, they may be helpful in assisting the child in tolerating parts of the test, especially if a pharmacological challenge is deemed necessary. Parents witnessing the validation of the diagnosis by TTT is likely to foster their willingness to accept the diagnosis and assist their child in carrying out preventive measures such as first aid, avoidance of triggers and simple interventions such as maintenance of hydration and salt loading for blood pressure support, as well as the supervision of medication if indicated.⁶

Although the authors believe that a comprehensive TTT is a gold standard for the assessment of hypotensive syncope, POTS and other related issues, the reality is that TTT has limited availability in some communities. We believe the value of TTT in children is currently under-appreciated, perhaps due to a lack of knowledge of its potential, not helped by lukewarm recommendations from Clinical Guidelines over the years despite advances in technique improving its sensitivity and specificity. Other non-invasive cardiac tests, aimed at rhythm analysis and/or ruling out cardiac disease have a role but have a limited diagnostic ability to capture symptomatic events. We strongly support the value of a comprehensive, targeted history, as both POTS and neurocardiogenic syncope have a recognisable pattern of illness with some common features for an experienced physician. This has led to our development of a questionnaire derived from noting similar symptoms and signs described by a large number of patients with these conditions. It is administered in clinic or immediately prior to the TTT. Positive responses from the patient strengthens the pre-test likelihood of a positive, reliable diagnosis. Furthermore, in some patients with a diagnostic history from the questionnaire but without significant hypotensive features may not then warrant a TTT. Others, including those with ambiguous and/or significant hypotensive events may still require the test.

TTT is under-utilized in children and adolescents for the assessment of hypotensive symptoms that commonly occur in POTS as well as validation of their tachycardic symptoms. TTT protocols, usually including pharmacological challenges, can be redesigned to produce a high diagnostic accuracy. The availability and use of TTT for children should be encouraged.