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 (i) the last 2 mins of the supine period; (ii) the 15 secs of tilting movement (TM); and (iii) 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: (i) PD (n = 19), MSA (n = 14), and uncertain (n = 14). The performance of the patients with PD was compared with that of the MSA patients on 5 autonomic tests: (i) R-R interval variations during deep breathing, (ii) heart rate changes with the Valsalva maneuvre, (iii) tilt table testing, (iv) the sudomotor axon reflex test, and (v) 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: (i) deep breathing, (ii) Valsalva maneuvre, (iii) tilt-table testing, (iv) sympathetic skin response, (v) 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 (i) autonomic function tests (HUT test), (ii) oscillations at respiratory and non-respiratory frequencies (0.01 to 0.09 Hz) in R-R interval and BP (Wigner distribution), and (iii) deterministic component (re-scaled range analysis). The 4 clinical and laboratory indices that independently supported the diagnosis of POTS are as follows: (i) orthostatic HR during the 1st minute of the HUT test, (ii) autonomic deficit (adrenergic autonomic score), (iii) loss of spectral powers in R-R interval during the HUT test at the 5th minute, and (iv) 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: (i) normal TT, (ii) OH, (iii) POTS, and (iv) 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.