Tilt Table Testing

Number: 0299

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses tilt table testing.

1. Medical Necessity

   Aetna considers tilt table testing, alone or in combination with administration of provocative agents (e.g., isoproterenol), medically necessary for the following indications when criteria are met:

   1. For the evaluation of members with recurrent unexplained syncope who have an inconclusive history and physical examination, as well as negative non-invasive tests of cardiac structure and function;
   2. As part of a diagnostic workup for individual with suspected postural orthostatic tachycardia syndrome (POTS).

2. Experimental and Investigational

   The use of tilt table testing is considered experimental and investigational for all other indications, including any of the following (not an all-inclusive list) because there is little support in the peer-reviewed medical literature for tilt table testing for these indications:

   1. Determining the effectiveness of medications in treating recurrent unexplained syncope; or
   2. Diagnosing joint hypermobility syndrome; or
   3. Differential diagnosis of parkinsonian syndromes (e.g., Parkinson's disease, multiple system atrophy and progressive supranuclear palsy); or
   4. Evaluating autonomic dysfunction in childhood hypersomnia disorders; or
   5. Evaluating dizziness and vertigo; or
   6. Evaluating post-concussion syndrome; or
   7. Guiding surgical decision-making as well as predicting the clinical response to surgical decompression of Chiari type I-malformation (Chiari drop attacks); or
   8. Identifying members with chronic fatigue syndrome and/or evaluating treatment effectiveness of this condition.

3. Related Policies

   • CPB 0369 - Chronic Fatigue Syndrome

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
93660	Evaluation of cardiovascular function with tilt table evaluation, with continuous ECG monitoring and intermittent blood pressure monitoring, with or without pharmacological intervention
HCPCS codes covered if selection criteria are met:
J7657	Isoproterenol hcl, inhalation solution, compounded product, administered through dme, concentrated form, per milligram
J7658	Isoproterenol hcl, inhalation solution, fda-approved final product, non-compounded, administered through dme, concentrated form, per milligram
J7659	Isoproterenol hcl, inhalation solution, fda-approved final product, non-compounded, administered through dme, unit dose form, per milligram
J7660	Isoproterenol hcl, inhalation solution, compounded product, administered through dme, unit dose form, per milligram
ICD-10 codes covered if selection criteria are met:
I49.5	Sick sinus syndrome
I49.8	Other specified cardiac arrhythmias [postural orthostatic tachycardia syndrome]
R00.0	Tachycardia, unspecified [postural orthostatic tachycardia syndrome]
R55	Syncope and collapse
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
F07.81	Postconcussional syndrome
G20	Parkinson's disease
G21.11 - G21.9	Secondary parkinsonism
G47.10 – G47.19	Hypersomnia [including childhood hypersomnia disorders]
G60.8	Other hereditary and idiopathic neuropathies [supranuclear palsy]
G93.5	Compression of the brain [Chiari type I-malformation (Chiari drop attacks)]
G96.810, G96.811, G96.819, G96.89	Other specified disorders of central nervous system [multiple system atrophy]
G98.8	Other disorders of nervous system
M35.7	Hypermobility syndrome
R42	Dizziness and giddiness
R53.0 - R83.83	Malaise and fatigue
Z79.890 - Z79.899	Other long term (current) drug therapy [Determining the effectiveness of medications in treating recurrent unexplained syncope]

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Background

There is sufficient evidence that tilt table testing, with or without isoproterenol, is safe and effective as a diagnostic tool for the evaluation of patients with recurrent unexplained syncope.  The reported sensitivity, specificity, and reproducibility of tilt table testing ranged from 65 to 87 %, 55 to 96 %, and 71 to 88 %, respectively.  This procedure helps to identify a largely benign disorder and, indirectly, exclude other possibly life-threatening conditions.  Tilt table testing performed early in the evaluation may obviate extensive and expensive tests such as intra-cardiac electrophysiological studies, CAT scan, and MRI of the brain.  In contrast, there is insufficient evidence that tilt table testing following intravenous infusion of metoprolol can accurately predict the effectiveness of oral metoprolol therapy in treating patients with recurrent unexplained syncope.  This procedure has not been shown to provide any additional information than would have been obtained from a trial of oral therapy.

There is inadequate evidence of the effectiveness of tilt-table testing for identifying chronic fatigue syndrome (CFS) patients who would respond to medications to increase their blood pressure.  Several case series have shown that patients with known CFS frequently have abnormal responses to tilt-table testing, and CFS patients in these series also frequently appear to respond to anti-hypotensive medications commonly used in patients with neurally mediated hypotension.  These case studies fail to demonstrate, however, any value of tilt-table testing in distinguishing CFS patients that would respond to these medications from those who would not.

Straus and colleagues (2009) stated that Chiari I malformation (CM1) is characterized by impaired cerebrospinal fluid flow through the foramen magnum.  Dysfunctional autonomic cardiovascular regulation may result in syncope, which may be the primary presenting symptom of CM1 (a syndrome termed Chiari drop attack).  It has been postulated that Chiari drop attack is secondary to dysautonomia caused by hind-brain compression.  These researchers studied patients with Chiari drop attacks who had negative work-ups for cardiac syncope, followed by tilt table testing and subsequent surgical decompression.  They reported test results and clinical outcomes following CM1 decompression.  A total of 10 patients met the inclusion criteria: 5 patients had positive and 5 negative tilt table tests.  Following decompression, 7 had symptomatic improvement or resolution and 3 failed to improve.  The sensitivity and specificity of the tilt table test for detecting clinical improvement with surgical decompression was 43 % and 33 %, respectively.  Tilt table testing had 40 % accuracy in predicting clinical response to decompression.  The authors concluded that in this short series, surgical decompression of CM1 has a high success rate (70 %) for patients with Chiari drop attacks.  Moreover, tilt table testing has poor predictive value in judging the clinical response to surgical decompression and is not a useful test to guide surgical decision-making.

Uno and colleagues (2009) noted that although it is well known that autonomic dysfunction in obstructive sleep apnea syndrome (OSAS) is associated with hypertension, its relationship to hypotension and orthostatic dysregulation is still unclear.  These investigators examined the response of blood pressure (BP) and cardiovascular autonomic function to head-up tilt (HUT) test in patients with OSAS.  In this study, a total of 14 patients (mean age of 65 +/- 2 years old, male/female: 11/3) with diagnosed OSAS by over-night polysomnography and 84 healthy subjects (mean age of 62 +/- 1 years old, male/female: 46/38) underwent HUT test (from 5 to 10 mins at 45 degrees).  Autonomic functions were evaluated by spectrum analysis of BP and heart rate variability.  In healthy subjects, systolic BP was unchanged by HUT test due to the enhancement of sympathetic nerve activity and the inhibition of parasympathetic nerve activity.  In contrast, autonomic responses were unchanged and systolic BP tended to be decreased by HUT test in OSAS patients.  The authors concluded that the findings of this study suggested that baroreflex function is impaired in patients with OSAS.  Furthermore, HUT test with spectrum analysis may be useful to evaluate autonomic functions in OSAS patients.

Oliveira et al (2009) stated that the autonomic nervous system (ANS) is known to be an important modulator in the pathogenesis of paroxysmal atrial fibrillation (PAF).  Changes in ANS control of heart rate variability (HRV) occur during orthostatism to maintain cardiovascular homeostasis.  Wavelet transform has emerged as a useful tool that provides time-frequency decomposition of the signal under investigation, enabling intermittent components of transient phenomena to be analyzed.  These investigators studied HRV during HUT with wavelet transform analysis in PAF patients and healthy individuals (normals).  A total of 21 patients with PAF (8 men; age of 58 +/- 14 yrs) were examined and compared with 21 normals (7 men, age of 48 +/- 12 yrs).  After a supine resting period, all subjects underwent passive HUT (60 degrees) while in sinus rhythm.  Continuous monitoring of electroencephalography and BP was carried out.  Acute changes in RR-intervals were assessed by wavelet analysis and low-frequency power (LF: 0.04 to 0.15 Hz), high-frequency power (HF: 0.15 to 0.60 Hz) and LF/HF (sympatho-vagal) were calculated for

1. the last 2 mins of the supine period;
2. the 15 secs of tilting movement (TM); and
3. the 1st (TT1) and 2nd (TT2) min of HUT. 

Data were expressed as means +/- SEM.  Baseline and HUT RR-intervals were similar for the 2 groups.  Supine basal BP was also similar for the 2 groups, with a sustained increase in PAF patients, and a decrease followed by an increase and then recovery in normals.  Basal LF, HF and LF/ HF values in PAF patients were 632 +/- 162 ms2, 534 +/- 231 ms2 and 1.95 +/- 0.39, respectively, and 1,058 +/- 223 ms2, 789 +/- 244 ms2 and 2.4 +/- 0.36, respectively, in normals (p = NS).  During TM, LF, HF and LF/HF values for PAF patients were 747 +/- 277 ms2, 387 +/- 94 ms2 and 2.9 +/- 0.6, respectively, and 1316 +/- 315 ms2, 698 +/- 148 ms2 and 2.8 +/- 0.6, respectively, in normals (p < 0.05 for LF and HF).  During TF1, LF, HF and LF/ HF values for PAF patients were 1,243 +/- 432 ms2, 302 +/- 88 ms2 and 7.7 +/- 2.4, respectively, and 1,992 +/- 398 ms2, 333 +/- 76 ms2 and 7.8 +/- 0.98, respectively, for normals (p < 0.05 for LF).  During TF2, LF, HF and LF/HF values for PAF patients were 871 +/- 256 ms2, 242 +/- 51 ms2 and 4.7 +/- 0.9, respectively, and 1263 +/- 335 ms2, 317 +/- 108 ms2 and 8.6 +/- 0.68, respectively, for normals (p < 0.05 for LF/HF).  The dynamic profile of HRV showed that LF and HF values in PAF patients did not change significantly during TM or TT2, and LF/HF did not change during TM but increased in TT1 and TT2.  The authors concluded that patients with PAF present alterations in HRV during orthostatism, with decreased LF and HF power during TM, without significant variations during the first minutes of HUT.  These findings suggested that wavelet transform analysis may provide new insights when assessing autonomic heart regulation and highlight the presence of ANS disturbances in PAF.  The findings of these small preliminary studies need to be validated by well-designed studies.

Riley and Chelimsky (2003) stated that formal laboratory testing of autonomic function is reported to distinguish between patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA), but such studies segregated patients according to clinical criteria that select those with autonomic dysfunction for the MSA category.  These researchers attempted to characterize the profiles of autonomic disturbances in patients in whom the diagnosis of PD or MSA used criteria other than autonomic dysfunction.  A total of 47 patients with parkinsonism and autonomic symptoms who had undergone autonomic laboratory testing were identified and their case records reviewed for non-autonomic features.  They were classified clinically into 3 diagnostic groups:

1. PD (n = 19),
2. MSA (n = 14),and
3. uncertain (n = 14). 

The performance of the patients with PD was compared with that of the MSA patients on 5 autonomic tests:

1. R-R interval variations during deep breathing,
2. heart rate changes with the Valsalva maneuvre,
3. tilt table testing,
4. the sudomotor axon reflex test, and
5. thermoregulatory sweat testing. 

None of the tests distinguished one group from the other with any statistical significance, alone or in combination.  Parkinson's disease and MSA patients showed similar patterns of autonomic dysfunction on formal testing of cardiac sympathetic and parasympathetic, vasomotor, and central and peripheral sudomotor functions.  The authors concluded that these findings supported the clinical observation that PD is often indistinguishable from MSA when it involves the autonomic nervous system.  The clinical combination of parkinsonism and dysautonomia is as likely to be caused by PD as by MSA.  Current clinical criteria for PD and MSA that direct patients with dysautonomia into the MSA group may be inappropriate.

Reimann et al (2010) stated that differential diagnosis of parkinsonian syndromes is a major challenge in movement disorders.  Dysautonomia is a common feature but may vary in clinical severity and onset.  These investigators attempted to find a pattern of autonomic abnormalities discriminative for patients with different parkinsonian syndromes.  The cross-sectional study included 38 patients with MSA, 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic PD (IPD), and 27 age-matched healthy controls.  Autonomic symptoms were evaluated by a standardized questionnaire.  The performance of patients and controls was compared on 5 autonomic function tests:

1. deep breathing,
2. Valsalva maneuvre,
3. tilt-table testing,
4. sympathetic skin response,
5. pupillography, as well as 24-hr ambulatory BP monitoring (ABPM). 

Disease severity was significantly lower in IPD than PSP and MSA.  Except for pupillography, none of the laboratory autonomic tests distinguished one patient group from the other alone or in combination.  The same was observed on the questionnaire.  Receiver operating characteristic curve revealed discriminating performance of pupil diameter in darkness and nocturnal BP change.  The composite score of urogenital and vasomotor domains significantly distinguished MSA from IPD patients but not from PSP.  These findings supported the observation that even mild IPD is frequently indistinguishable from more severe MSA and PSP.  Thus, clinical combination of motor and non-motor symptoms does not exclusively point at MSA.  Pupillography, ABPM and the questionnaire may assist in delineating the 3 syndromes when applied in combination.

Postural orthostatic tachycardia syndrome (POTS), also known as postural tachycardia syndrome, is a type of orthostatic intolerance that is characterized by excessive tachycardia and decreased cerebral blood flow in the upright position.  This can result in significant symptoms of dizziness and light-headedness that can eventually lead to syncope.  Symptoms of POTS include light-headedness, visual blurring, palpitations and weakness on assuming an upright posture; these symptoms are relieved by resuming a supine posture.  Tilt table testing has been used to aid in the diagnosis of POTS. 

An UpToDate review on “Postural tachycardia syndrome” (Freeman and Kaufmann, 2012) states that: “The diagnosis of POTS is established from the history and head-up tilt testing which demonstrates a heart rate increase of >30 bpm over baseline or to >120 bpm.  Dehydration, prolonged bedrest, medications, and other dysautonomias should be excluded as etiologies”.

Grubb et al (1997) stated that HUT testing has emerged as an accepted modality for identifying an individual's predisposition to episodes of autonomically mediated hypotension and bradycardia that are sufficiently profound so that transient loss of consciousness ensues (neuro-cardiogenic syncope [NCS]).  However it has also become apparent that less dramatic falls in BP, while not sufficient to cause full syncope, may produce symptoms such as near syncope, vertigo, dizziness, and transient ischemia attack-like episodes.  These investigators have identified a subgroup of individuals with a mild form of autonomic dysfunction with symptoms of postural tachycardia and lightheadedness, disabling fatigue, exercise intolerance, dizziness, and near syncope.  During baseline tilt table testing these patients demonstrated a HR increase of greater than or equal to 30 beats per min [bpm] (or a maximum HR of 120 bpm) within the first 10 mins upright (unassociated with profound hypotension), which reproduced their symptom complex.  In addition these patients exhibited an exaggerated response to isoproterenol infusions.  Similar observations have been made by others who have dubbed this entity the POTS.  The authors concluded that POTS represents a mild (and potentially treatable) from of autonomic dysfunction that can be readily diagnosed during HUT testing.

Novak et al (1998) identified clinical and laboratory indices that improve the diagnosis of the POTS.  These investigators assessed associations of orthostatic intolerance (OI) by using multi-variate regression analysis.  They evaluated autonomic symptoms and autonomic function in 30 patients with POTS, 30 patients with mild OI, and 19 age- and gender-matched control subjects.  Indices of para-sympathetic and sympathetic functions were analyzed on the basis of

1. autonomic function tests (HUT test),
2. oscillations at respiratory and non-respiratory frequencies (0.01 to 0.09 Hz) in R-R interval and BP (Wigner distribution), and
3. deterministic component (re-scaled range analysis). 

The 4 clinical and laboratory indices that independently supported the diagnosis of POTS are as follows:

1. orthostatic HR during the 1st minute of the HUT test,
2. autonomic deficit (adrenergic autonomic score),
3. loss of spectral powers in R-R interval during the HUT test at the 5th minute, and
4. severity of orthostatic dizziness, fatigue, palpitations, and shortness of breath. 

The authors concluded that enhancing the sensitivity and specificity of the diagnosis of POTS should be possible by using these 4 indices.

Lamarre-Cliche and Cusson (2001) stated that the HUT test is used primarily for the investigation of orthostatic symptoms.  Although this test is frequently the gold standard for the evaluation of NCS, dysautonomia and POTS, there is a debate over its diagnostic value and method.  The authors reviewed the physiologic basis of the HUT test, the method, patterns of response, indications and contraindications, and diagnostic validity.  They concluded that despite its limitations, the HUT test is useful in patients with a variety of clinical manifestations induced by orthostatism.  It is most useful in documenting objective measures of orthostatic hypertension (OH) that cannot be obtained in a clinical setting.

In a prospective study, Singer et al (2002) examined if an intrinsic sinus node abnormality is involved in the pathophysiology of POTS.  These researchers compared the relationship between P-wave axis (PWA) and HR in 11 healthy controls and 14 patients with POTS by obtaining 12-lead electrocardiographic recordings during supine rest and during gradual HUT test.  The HR of controls was titrated with isoproterenol infusion to match the HR of patients.  The PWA was compared at different HR levels, and the relationship between HR and PWA was assessed for patients and controls.  Primary end points were the PWA-HR relationship in healthy controls, comparison of these data with data from patients with POTS as a group, and identification of a possible subgroup of patients with POTS with irregular PWA-HR relationship.  The PWA increased with increasing HR following a similar logarithmic trend-line in both groups.  The PWA of patients was significantly lower at the lowest comparable HR level, but not different at faster HR levels.  Three patients (21 %) had a clearly abnormal HR-PWA relationship with substantial shift toward lower PWA.  The authors concluded that these findings supported the hypothesis of a primary sinus node abnormality in a subset of patients with POTS.

Winker et al (2005) evaluated the role of the Schellong test (ST) in forms of orthostatic dysregulation in comparison with the tilt-table test (TT).  A total of 67 young males (mean age of 22 +/- 4 years) from the military service, representing 2 different cohorts, were examined by ST and TT, which served as gold standard.  Overall, 32 of the 67 subjects were asymptomatic while 35 had sought medical advice because of orthostatic complaints.  The subjects subsequently were classified into 4 categories according to the TT:

1. normal TT,
2. OH,
3. POTS, and
4. NCS. 

Chi-square test was used to calculate the sensitivity and specificity of ST in detecting forms of orthostatic dysregulation (OH, POTS and NCS).  In total, TT detected 23 recruits with POTS, 16 with NCS and 2 with OH.  Out of the 32 asymptomatic subjects only 1 was diagnosed having POTS by TT and ST, the rest had a normal ST and TT.  For detecting POTS, ST sensitivity was 61 % and specificity was 100 % compared with TT.  For detecting NCS, ST sensitivity was 31 % and specificity 100 % compared with the reference test, the TT.  The data concerning OH could not be analyzed because of the small number of cases.  The authors concluded that these findings indicated that ST can be used in first line in the diagnosis of patients with orthostatic symptoms by the medical practitioner.  If the ST is normal, further examination by TT is indispensable, because sensitivity of ST concerning POTS and NCS is relatively low.

Qingyou et al (2008) stated that OI is a common clinical manifestation in clinical pediatrics.  The HUT test is considered the standard of orthostatic assessment, but the physiologic neuro-circulatory profile during HUT has not been fully realized in children with OI.  The present study, therefore, was designed to investigate the physiologic patterns that occur during HUT in children with OI.  A total 90 children (56 girls; mean age of 11.6 +/- 2.3 years) with OI underwent HUT test under quiet circumstances; BP and HR were monitored simultaneously.  A total of 49 children with OI (54.4 %) had vaso-vagal response with HUT testing; 33 (36.7 %), vasodepressor response; 6 (6.7 %), cardio-inhibitory response; and 10 (11.1 %), mixed response.  Twenty-eight children (31.1 %) had POTS; 1 (1.1 %), OH; and 12 (13.3 %), normal physiologic response.  Patterns of cerebral syncope response and chronotropic incompetence were not observed.  The authors concluded that classical vaso-vagal response was the major physiologic pattern seen in children with OI during HUT testing, and POTS response ranked second.

In a case-control study, Carew and colleagues (2009) defined the optimal duration of TT for the assessment of patients with suspected POTS.  Cases were identified retrospectively from a database of patients referred with OI.  All met the diagnostic criteria for POTS.  Controls were enrolled prospectively.  All subjects underwent tilting to 70 degrees for 40 mins if tolerated.  Continuous monitoring was provided by a Finometer.  Analysis of responses to TT was performed on 28 cases and 28 controls.  The mean age in the case group was 23.6 years and in the control group was 26.2 years.  The majority was female in both groups (cases = 4 females and 3 males, controls = 2 females and 1 male).  All cases met the criteria for POTS within 7 mins of orthostasis.  No controls demonstrated a sustained tachycardia.  The prevalence of vaso-vagal syncope (VVS) was 36 % in cases versus 7 % in controls (p = 0.02) and 25 % in the remaining patients (n = 233) on the OI database (p = 0.259).  The authors concluded that a 10-min TT will diagnose POTS in the majority of patients.  It will not, however, be sufficient to identify the overlap that exists between POTS and VVS.  The optimal duration of TT in patients suspected of POTS is 40 mins.

Singer et al (2012) examined if the use of adult HR criteria is appropriate for diagnosing OI POTS in children and adolescents, and established normative data and diagnostic criteria for pediatric OI and POTS.  A total of 106 normal controls aged 8 to 19 years (mean age of 14.5 +/- 3.3 years) underwent standardized autonomic testing, including 5 mins of 70-degree HUT testing.  The orthostatic HR increment and absolute orthostatic HR were assessed and retrospectively compared with values in 654 pediatric patients of similar age (mean age of 15.5 +/- 2.3 years) who were referred to our Clinical Autonomic Laboratory with symptoms of OI.  The HR increment was mildly higher in patients referred for OI/POTS, but there was considerable overlap between the patient and control groups.  Some 42 % of the normal controls had an HR increment of greater than or equal to 30 bpm.  The 95th percentile for the orthostatic HR increment in the normal controls was 42.9 bpm.  There was a greater and more consistent difference in absolute orthostatic HR between the 2 groups, although there was still considerable overlap.  The authors concluded that the diagnostic criteria for OI and POTS in adults are unsuitable for children and adolescents.  Based on the normative data from this study, the authors proposed new criteria for the diagnosis of OI and POTS in children and adolescents.

UpToDate reviews on “Evaluation of dizziness in children and adolescents” (Walls and Teach, 2013) and “Approach to the patient with vertigo” (Furman and Barton, 2013) do not mention the use of tilt table testing as a management tool.

Post-Concussion Syndrome

Heyer et al (2016) examined HUT signs of autonomic dysfunction in a cohort of youth with persistent post-concussion symptoms (PCSs) that include light-headedness and to correlate repeat tilt table results with symptom improvements for those patients found to have POTS on initial testing.  A total of 34 patients (13 to 18 years of age) with persistent PCSs participated in this study.  All patients underwent at least 1 tilt table test.  The PCS Interview (PCS-I) and patient ratings of light-headedness and vertigo were used to measure symptom burden.  Patients found to have POTS were asked to repeat tilt table testing when PCSs improved or 3 to 6 months after the initial test if symptoms persisted.  Overall, 24 of the 34 (70.6 %) patients had abnormal tilt table results with patients categorized as normal (n = 10), isolated syncope (n = 10), and POTS (n = 14).  Patients with POTS had higher PCS-I scores than normal patients (p < 0.001) and higher ratings of light-headedness than both normal patients (p = 0.015) and syncope patients (p = 0.04); 12 POTS patients underwent repeat tilt table testing, and 9 of 12 (75 %) no longer met POTS diagnostic criteria.  All patients with resolution of POTS had corresponding improvements in PCSs, including light-headedness and vertigo.  The authors concluded that the findings of this study demonstrated a high rate of tilt table abnormalities among youth with persistent PCSs.  Several patients with POTS had normalization of tilt table testing when PCSs improved.  They stated that these findings warrant further research of autonomic dysfunction related to concussion.

Furthermore, an UpToDate review on “Postconcussion syndrome’ (Evans, 2016) does not mention tilt table testing as a management tool.

Guidance of Pacing Therapy for Reflex Syncope

Furukawa (2017) stated that the tilt table test (TTT) is a method used for the management of reflex syncope.  However, the TTT is incomplete and has several problems.  The TTT is unsuitable for all syncopal patients.  Several questions on this technology remain unclear: When should the TTT be used; for which types of patients TTT should be performed; and does the TTT provide useful information to guide indication for pacing therapy for reflex syncope.  The answers to these questions appear in recent reports from 2 guidelines published by the European Society of Cardiology and the Japan Circulation Society.  The indications for TTT do not apply to all syncopal patients, but selected patients.  For patients with low risks and rare syncopal events, the TTT is not necessary, even when diagnoses are unconfirmed.  The TTT is used not only for diagnosis of reflex syncope, but also for many clinical management of several conditions (i.e., exclusion of cardiac syncope).  The author stated that positive TTT results cannot predict the effects of pacing therapy for reflex syncope; pacing therapy should be administered based on documented electrocardiograms, TTT results (negative or positive), and other findings.

Abbreviated Tilt Table Testing for Diagnosing Postural Tachycardia Syndrome in Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

van Campen and colleagues (2018) noted that orthostatic intolerance is common among individuals with myalgic encephalomyelitis (ME) / CFS.  In some ME/CFS case definitions, orthostatic intolerance is considered a core feature of the disorder.  Some studies have employed tilt table tests lasting 2 to 5 mins to diagnose one common form of orthostatic intolerance, POTS.  These investigators examined the diagnostic yield of abbreviated durations of tilt table testing in adults meeting criteria for ME/CFS, and identified the proportion with POTS misdiagnosed using testing of less than 10 mins.  Eligible participants were consecutive individuals satisfying study criteria for ME/CFS and POTS evaluated at the Stichting CardioZorg (SCZ, Hoofddorp, NL) between November 2012 and August 2018.  Individuals being treated with medications commonly used to manage orthostatic intolerance were excluded.  Head-up tilt table testing involved 15 mins of supine posture then 20 mins at 70 degrees upright.  Only the data from the first 10-min upright were used.  POTS was defined as an increase in HR during a maximum of 10 mins of upright tilt of at least 30 beats/min (bpm), in the absence of either classical or delayed orthostatic hypotension.  These investigators measured the time until HR criteria for POTS were reached using survival curves, and compared survival curves between subgroups divided by age, sex, disease duration, and degree of hypocapnia during the test.  Of 627 individuals with ME/CFS evaluated during the study period, 155 met criteria for POTS.  The median time to reaching HR criteria for POTS was 3 mins.  A 2-minute tilt table test would miss 55 % (95 % confidence interval [CI]: 48 to 63 %) of those meeting POTS criteria over the course of 10-min upright.  The median time to reaching HR criteria for POTS did not differ by sex, age, duration of ME/CFS, or hypocapnia during tilt.  The authors concluded that abbreviated tilt table testing missed a substantial proportion of those ultimately diagnosed with POTS during a 10-min tilt table test, and should be abandoned for the clinical diagnosis and in epidemiologic studies designed to estimate the prevalence of POTS among those with ME/CFS.

Nelson and colleagues (2019) noted that ME/CFS is a complex condition with no reliable diagnostic biomarkers.  Studies have shown evidence of autonomic dysfunction in patients with ME/CFS, but results have been equivocal.  Heart rate parameters can reflect changes in autonomic function in healthy individuals; however, this has not been thoroughly evaluated in ME/CFS.  These researchers carried out a systematic database search for case-control literature.  Meta-analysis was conducted to determine differences in HR parameters between ME/CFS patients and controls.  A total of 64 articles were included in the systematic review.  HR parameters assessed in ME/CFS patients and controls were grouped into 10 categories: resting HR (RHR), maximal HR (HRmax), HR during submaximal exercise, HR response to head-up tilt testing (HRtilt), resting HR variability (HRVrest), HR variability during head-up tilt testing (HRVtilt), orthostatic HR response (HROR), HR during mental task(s) (HRmentaltask), daily average HR (HRdailyaverage), and HR recovery (HRR).  Meta-analysis revealed RHR (MD ± 95 % CI: 4.14 ± 1.38, p < 0.001), HRtilt (SMD ± 95 % CI :  0.92 ± 0.24, p < 0.001), HROR (0.50 ± 0.27, p < 0.001), and the ratio of low-frequency power to high-frequency power of HRVrest (0.39 ± 0.22, p < 0.001) were higher in ME/CFS patients compared to controls, while HRmax (MD ± 95 % CI: -13.81 ± 4.15, p < 0.001), HR at anaerobic threshold (SMD ± 95 % CI: -0.44 ± 0.30, p = 0.005) and the high-frequency portion of HRVrest (-0.34 ± 0.22, p = 0.002) were lower in ME/CFS patients.  The authors concluded that numerous HR parameters have been reported on in ME/CFS patients, with wide variations in study design and data acquisition methods, including body position and the duration/intensity of interventions (HUTT, exercise etc.).  Meta-analysis revealed significant differences between patients and controls in a number of parameters, including patients having: higher RHR, HRtilt, orthostatic HR response, and LF/HF ratio; and lower HRmax, HRthreshold, HFP and RMSSD.  These differences suggested an altered regulation of HR in ME/CFS patients that is suggestive of reduced vagal and increased sympathetic modulation of heart rate.  However, it does not appear that any of the currently used HR parameters have the sensitivity to detect the presence of ME/CFS on their own, as demonstrated by the presence of high levels of statistical heterogeneity and methodological issues that limit the usefulness of these parameters.  The findings of this review suggested that there are quantifiable differences in autonomic HR regulation in ME/CFS patients, and future research in ME/CFS populations should therefore focus on determining if there are additional HR parameters that have diagnostic utility in this group.

van Campen and colleagues (2020) noted that in a study of 429 adults with ME/CFS, these researchers showed that 86 % had symptoms of OI in daily life.  By means of extra-cranial Doppler measurements of the internal carotid and vertebral arteries during a 30-min head-up tilt to 70 degrees, 90 % had an abnormal reduction in cerebral blood flow (CBF).  A standard head-up tilt test of this duration might not be tolerated by the most severely affected bed-ridden ME/CFS patients.  These investigators examined if a shorter 15-min test at a lower 20-degree tilt angle would be sufficient to provoke reductions in CBF in severe ME/CFS patients.  A total of 19 severe ME/CFS patients with OI complaints in daily life were studied: 18 women.  The mean (SD) age was 35 (14) years, body surface area (BSA) was 1.8(0.2) m² and body mass index (BMI) was 24.0(5.4) kg/m².  The median disease duration was 14 (inter-quartile range [IQR] 5 to 18) years.  Heart rate increased, and stroke volume index and end-tidal CO² decreased significantly during the test (p ranging from < 0.001 to < 0.0001).  The cardiac index decreased by 26(7) %: p < 0.0001.  CBF decreased from 617 (72) to 452 (63) ml/min, a 27 (5) % decline.  All 19 severely affected ME/CFS patients met the criteria for an abnormal CBF reduction.  The authors concluded that using a less demanding 20-degree tilt test for 15 mins in severe ME/CFS patients resulted in a mean CBF decline of 27 %.  This was comparable to the mean 26 % decline previously noted in less severely affected patients studied during a 30-min, 70-degree head-up tilt.  These observations have implications for the evaluation and treatment of severely affected individuals with ME/CFS.

The authors stated that this study had several drawbacks.  It only included ME/CFS patients who were bed-bound, and these researchers cautioned that the 20-degree head-up tilt angle needs further study before it can replace longer 70-degree tilt angles for evaluating less severely impaired ME/CFS patients.  Comparisons of the hemodynamic and CBF abnormalities of 20 and 70 degrees of tilting are needed.  In addition, these researchers did not include healthy controls for comparison.  It was possible that healthy controls would have little or no perturbation in response to a 20-degree head-up angle, which would have the effect of widening the physiologic differences between ME/CFS patients and controls.  Whether disease severity differences led to differences in CBF reduction needs to be examined future trials.  Finally, while it was reasonable to expect that the 20-degree abbreviated tilt test would be less taxing than a longer 70-degree tilt test; thus, less likely to provoke post-exertional malaise, this hypothesis remains to be tested.

Tilt Table Testing for Diagnosing Joint Hypermobility Syndrome

Joint hypermobility syndrome (JHS) is a chronic disorder that presents with arthralgia, myalgia and is periodically associated with visceral manifestations and POTS.  Patients with JHS are more likely to be diagnosed with CFS or fibromyalgia compared to the general population (Mandel et al, 2017).

In a prospective study, Adamec and colleagues (2018) examined the association of ANS abnormalities on head-up tilt table test (HUTT) with generalized joint hypermobility, expressed by Beighton score (BS).  This trial enrolled 115 consecutive patients (91 women; mean age of 34.35 ± 14.11 years) referred either for the HUTT or testing of the cardiovascular autonomic reflexes together with HUTT.  Generalized joint hypermobility was evaluated according to the BS system after which HUTT was performed.  Clinically significance was considered if BS was greater than or equal to 4.  A total of 15 patients (15.1 %) had BS greater than or equal to 4.  Results of the HUTT were normal in 58 (50.4 %) patients and in 57 (49.6 %) patient HUTT was abnormal; 15 (13.0 %) patients fulfilled criteria for orthostatic hypotension, 30 (26.1 %) for reflex syncope and 21 (18.3 %) for POTS.  Patients with pathological findings on HUTT had significantly higher BS compared to patients with normal HUTT (median of 1 versus 0, p = 0.001).  There was a significant association between participants with BS greater than or equal to 4 and pathological HUTT (χ[1] = 6.392, p = 0.011).  Results of the multi-variate regression analysis revealed that increase in the BS was associated with the increased likelihood of HUTT pathology (Exp[B] 1.44, 95 % confidence interval [CI]: 1.084 to 1.922, p = 0.012), while increase in age was associated with lower risk of HUTT pathology (Exp[B] 0.968, 95 % CI: 0.939 to 0.998, p = 0.036).  The authors concluded that there was an association between ANS abnormalities on HUTT test and generalized joint hypermobility.  The clinical significance of this association needs to be further investigated.

The British Society for Paediatric and Adolescent Rheumatology’s guidelines for “Management of Joint Hypermobility Syndrome in Children and Young People” (BSPAR, 2012) stated that “Diagnosis of POTS is not easy and though it is often done by performing a tilt table test (or standing and lying heart rate if tilt table unavailable) this not validated in children and adolescents so the results of the tilt table test have to be interpreted carefully”.

Furthermore, an UpToDate review on “Joint hypermobility syndrome” (Grahame and Hakim, 2019) does not mention tilt table testing as a management tool.

Tilt Table Test for Evaluation of Autonomic Dysfunction in Childhood Hypersomnia Disorders

Jagadish and colleagues (2021) noted that OI is a common manifestation of autonomic dysfunction.  It is characterized by light-headedness and palpitations in the upright position, with relief when supine.  It can affect the quality of life (QOL).  Other symptoms that may accompany OI include headache, fatigue, nausea, palpitations and abdominal pain.  The prevalence and characteristics of autonomic symptoms in childhood hypersomnia disorders of childhood has not been examined, and hence were studied.  The medical records of children and adolescents with hypersomnia disorders were reviewed.  Subjects had been diagnosed with narcolepsy types 1 or 2 (NT1 or NT2), idiopathic hypersomnia (IH) or the KLS, or hypersomnia related to medical conditions, were under 18 years of age at sleep diagnosis, and had been evaluated at the authors’ sleep center between 2000 and 2018.  Those with co-morbidities such as obstructive sleep apnea (OSA) and major depression were excluded.  The medical records were reviewed for symptoms at initial presentation suggestive of autonomic dysfunction, such as OI, headache, fatigue, nausea, palpitations and abdominal pain.  If these symptoms had been recorded, the chart was examined further to determine if an autonomic reflex screen (ARS) battery had been conducted.  The ARS battery examines both sympathetic and parasympathetic function.  It is composed of a tilt table test, heart rate and BP responses to the Valsalva maneuver and deep breathing, a quantitative sudomotor axon reflex test and beat-to-beat BP measurements during the Valsalva maneuver.  Results of the ARS battery were interpreted by an autonomic neurology specialist (WS), who was not otherwise involved in the care of the patients.  Medications taken at the time of autonomic testing were recorded.  There were 89 patients with hypersomnia disorders; 46 had NT1, 17 had NT2, 18 had IH, 1 with KLS, and 7 had hypersomnia associated with medical disorders; 33 89 subjects (37 %) had the symptom of OI at initial presentation, hence had undergone autonomic reflex screen testing.  The median age at diagnosis of hypersomnia in the 33 subjects with the OI symptom was 14.5 years (IQR 12 to 16) and similar (14.5 years, IQR 11.5 to 16) in the 56 subjects without OI.  In the group with OI, 25/33 had not received medications for treating hypersomnia at the time of autonomic testing.  OI was not related to the degree of sleepiness -- the mean sleep latency in the subjects with OI was 5.3 ± 2.9 mins while in those without OI it was 4.5 ± 3.8 mins.  The symptom of OI was not more likely to occur in any specific type of hypersomnia.  OI however tended to occur predominantly in females -- the female: male ratio in the OI subgroup was 2:1 (n = 33) while in the subgroup without OI, it was 1: 2.1 (n = 56; p = 0.0015).  Additional symptoms recorded in the OI subgroup included lightheadedness in 25/33, palpitations in 6/33, nausea and vomiting in 4/33, fatigue in 25/33, headache in 15/33 and constipation in 3/33.  The symptoms of OI were reproduced during the tilt table test in 17/33 subjects; 5 of these patients had a rise in heart rate consistent with POTS.  The authors concluded that in this retrospective study, 1/3 of children with hypersomnia disorders exhibited the symptom of OI at initial presentation, with female predominance.  A smaller subgroup met criteria for POTS.

Furthermore, an UpToDate review on “Idiopathic hypersomnia” (Chervin, 2021) does not mention tilt table testing as a management tool.

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References