Q J Med 2003; 96: 133-142
© 2003 Association of Physicians
The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome
From the Departments of Internal Medicine A and 1 Rheumatology, Bnai Zion Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Received 28 May 2002 and in revised form 2 December 2002
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Summary |
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Background: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a ‘haemodynamic instability score’ (HIS).
Aim: To assess HIS sensitivity and specificity in the diagnosis of CFS.
Design: Prospective controlled study.
Methods: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT.
Results: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%.
Discussion: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.
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Introduction |
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Clinically evaluated, medically unexplained fatigue of at least 6 months duration, that is of new onset, is not a result of ongoing exertion, not substantially alleviated by rest, and that substantially reduces previous levels of activity, is called chronic fatigue syndrome (CFS).1 Other prominent features of the syndrome are chronic and recurrent low-grade fever, pharyngitis, lymphadenopathy, arthralgia and neuropsychological symptoms. The prevalence of CFS is 0.07–0.2% of the population.2 The aetiology and pathogenesis of CFS are poorly understood.
Previous studies have documented a close connection between impairment of autonomic functions, i.e. dysautonomia, and CFS.2–7 Abnormalities of central nervous system on magnetic resonance imaging9 and single-photon emission tomography,10 as well as disruption of the hypothalamic-pituitary-adrenal axis and serotoninergic and noradrenergic pathways have been demonstrated,11,12 and a ‘distal dysautonomia’ has been described in CFS patients.13
As the fast response of the blood pressure (BP) and heart rate (HR) to acute stimuli is under autonomic nervous control, BP and HR measurements during orthostatic challenge can be used as one measure of cardiovascular autonomic activity. For this purpose, the head-up tilt test (HUTT) is used. Classical pathological reactions to the HUTT are: vasodepressor reaction, cardioinhibitory reaction, orthostatic hypotension and postural tachycardia syndrome. In studies using these outcome measures, evidence for abnormal cardiovascular reactivity was found in one half of CFS patients. The latter measures are non-specific, however, and also occur in a variety of disorders unrelated to CFS.3–8 HR variability during the HUTT is another measure of cardiovascular reactivity in CFS.14,15 As with the classical outcomes of the HUTT, abnormalities of HR variability in CFS are not specific for this disorder.16,17 A third method, recently proposed for the study of the cardiovascular reactivity of CFS patients involves computing BP and HR changes during the course of a HUTT, followed by processing the data by image analysis methods. These data receive numerical expression as the ‘haemodynamic instability score’ (HIS). In our previous study,18,19 the best cut-off differentiating CFS from healthy patients was HIS -0.98. HIS values above -0.98 were associated with CFS (sensitivity 97%, specificity 96.6%). In a second study, we applied the proposed HIS threshold of -0.98 to study populations which served as ‘test groups’.19 In the ‘test groups’, similarly to the earlier ‘training groups’, the HIS threshold of -0.98 differentiated between CFS patients (HIS=+2.02, SD 4.07) and healthy subjects (HIS=-2.48, SD 4.07).19 HIS values higher than -0.98 were usually associated with CFS.18–20
The diagnosis of CFS rests largely on patient history. In any illness defined by a group of symptoms, two questions arise: do the patients in fact report the symptoms that investigators say they should, and do those symptoms distinguish patients with CFS from other fatiguing illnesses?2 Two studies have validated the CFS questionnaires: the symptoms of CFS, but not the control symptoms, are much more frequently reported by patients with CFS than by patients with other diseases which produce fatigue.21,22 However, the differentiation of CFS from the other functional somatic syndromes, fibromyalgia and myofascial pain syndrome, may be difficult, because features of these three disorders can overlap.23 No physical finding or laboratory test is generally accepted or in common use to strengthen the diagnosis of CFS.3,4 Two developments might advance the diagnosis of CFS. The first is based on a recent study showing that 72% of subjects in a group of patients with CFS had increased plasma levels of an abnormal 37 kDa protein.24 The possible application of this finding for diagnostic purposes has not been appraised. The second development is evaluation of dysautonomia as a possible marker of CFS. A diagnostic role for the HUTT classical endpoints, as well as for spectral analysis of HR and BP variability in patients with CFS, has not been defined,2,8,16,17 although we have previously suggested that the HIS may be useful in confirming the diagnosis of CFS.18–20 In the present study, we reassessed the sensitivity of HIS >-0.98 for the diagnosis of CFS in a new group of CFS patients. The reproducibility of the HIS on repeated examinations was evaluated. Specificity for the diagnosis of CFS was evaluated in comparison with controls, some exhibiting shared clinical features with CFS (patients with non-CFS chronic fatigue, fibromyalgia, generalized anxiety disorder, neurally mediated syncope) and others not suffering from fatigue (patients with Familial Mediterranean Fever, essential hypertension, healthy subjects).
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Methods |
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All participants gave informed consent, and our institution's committee for human research approved the study. All patients were fully ambulatory at the time of the study. The patients were not taking medications for at least 2 weeks before the study. Technicians carrying out the HUTT were informed as to the patients' diagnosis, but did not know of the intention to compare between the groups. Data of earlier studies, which used somewhat different equations and were based upon slightly different dependent measures18,20,25 were revised, expanded and processed according to the latest equation.18
Patients
CFS patients (n=40) were consecutive subjects referred from a CFS clinic for evaluation with the HUTT. All patients met the Centers of Disease Control and Prevention definition1 of CFS, had no other diagnosable medical or psychiatric illness to explain their symptoms, and did not have fibromyalgia (FM), based on a specific tender points count <11/18.26 The subjects' median age was 27 years (range 20–71 years) and the M:F ratio was 12:28. The median duration of illness was 16.7 months (range 7 months to 4 years). All patients had moderate fatigue at rest and severe fatigue with exertion. The patients' mean fatigue impact score27 was 69.1 (SD 12.8). The fatigue impact score examines the patients' perception of the functional limitations that fatigue has caused over several months. Subjects are asked to rate the extent to which fatigue has caused problems for them in relation to exemplar statements, and each item is quantified on a scale of 0-3: 0, no problem to 3, extreme problem. The fatigue impact score includes three subscales to assess perceived fatigue impact on cognitive functioning (10 items), physical functioning (10 items), and psychosocial functioning (20 items). The maximum score is 120. Healthy persons score <20.
Patients with non-CFS chronic fatigue (n=73) were consecutive subjects referred from a CFS clinic. Similarly to the CFS patients, they complained of fatigue of new onset,28 not a result of ongoing exertion, not substantially alleviated by rest, associated with substantial reduction in previous levels of activity, and lasting 3 months or more, but they did not otherwise meet the definition criteria of CFS. The subjects' median age was 38 years (range 19–65 years) and the M:F ratio was 24:49. Median duration of illness was 7 months (range 3–13 months). The patients' mean fatigue impact score was 69.3 (SD 10.2).
Syncope patients (n=58) were consecutive subjects referred for HUTT for evaluation of syncope of unknown cause. All subjects had two or more syncopal or presyncopal spells during the previous 3 months. Patients with co-morbidities, inclusive CFS were excluded. Fifteen subjects reported chronic fatigue. The subjects' median age was 24 years (range 18–48 years) and the M:F ratio was 18:40. The diagnosis of neurally mediated syncope29 was eventually established.
Fibromyalgia (FM) patients (n=41) were referred from a rheumatology clinic. The diagnosis of FM was based on criteria of the American College of Rheumatology for FM.26 Sixteen subjects who also reported fatigue but did not meet the diagnosis of CFS were included. The patients' median age was 30 years (range 22–67) and the M:F ratio was 13:28.
Generalized anxiety disorder patients (30) (n=28) were referred from a psychiatry clinic. They had a history of palpitation and atypical chest pain, but no symptoms consistent with CFS, FM or other co-morbidities. The patients' mean age was 31.4 years (SD 8.8) and 75% patients were women.
Familial Mediterranean Fever (FMF) patients (n=50) were referred from an adult rheumatology clinic. The patients had recovered from the last attack of FMF31 at least 14 days before the HUTT. Patients with co-morbidities were excluded. The patients' median age was 30 years (range 21–60 years) and the M:F ratio was 25:25.
Essential hypertension (HT) patients (n=28) included subjects with mild to moderate systolic and diastolic hypertension (HT) according to criteria of the Sixth Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure.32 Patients had normal chest X-rays and electrocardiograms. Their median age was 29 years (range 18–49 years) and the M:F ratio was 9:19.
Healthy control subjects (n=59) were physicians and paramedics working on the medical ward, who volunteered to participate in the study. Subjects were eligible if they did not report persistent fatigue or syncope during the preceding 12 months, and had normal findings on physical examination, routine laboratory tests, chest X-rays, and electrocardiogram. Their median age was 27 years (range 23–54 years) and the M:F ratio was 31:28.
The patient age was significantly higher in the non-CFS group compared to all other groups (p<0.01). Male predominance in the group of healthy subjects was statistically significant only in comparison to the CFS patients group (p<0.05).
Computation of the haemodynamic instability score (HIS)
The protocol of the HUTT was based on the 10-min supine/30-min head-up tilt test as previously described.18 Testing was conducted from 0800 h to 1100 h, in a quiet environment, and at constant room temperature of 22–25 °C. The patients maintained a regular meal schedule, but were restricted from smoking and caffeine ingestion for 6 h prior to the examination. Intake of food products and medications with sympathomimetic activity prior to the study was prohibited.
Manual BP readings were taken by a physician certified in the BP measurement technique according to American Heart Association recommendations.33 We favoured the mercury column sphygmomanometer (Baumanometer, standby model 0661–0250), since this is the standard non-invasive method for BP measurement, and is the most accurate for evaluation of BP at rest34 and during HUTT.35 The HR measurements were recorded on an electrocardiographic monitor. The patient lay in a supine position on the tilt table, secured to the table at the chest, hips and knees with adhesive girdles. The cuff of the BP recording device was attached to the left arm, which was supported at heart level at all times during the study. Three measurements in the supine position were recorded at 5-min intervals. The table was then gently tilted head-up to an angle of 70 °C. The duration of the tilt was 30 min. During the initial 5 min of tilt, measurements were obtained at 1-min intervals, followed by readings every 5 min. When dizziness or faintness occurred, repeated measurements were taken at 30-s intervals. In the event of a loss of consciousness, the test was discontinued. Measures to avoid inaccuracies in processing the HIS were strictly followed (Appendix).
The HIS was computed based on BP and HR-differences along the HUTT.18 The ‘BP differences' and ‘HR differences' were computed (Figure 1
). Systolic and diastolic BP-differences were defined as the differences between individual BP values measured during HUTT and the last recumbent BP value, and divided by the last recumbent BP value. The result is BP difference, expressed as a relative value by comparison to the last supine measurement, and calculated according to the following equation:
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The means and SDs of the current values of the systolic and diastolic BP differences were calculated for each subject. The BP differences were also represented graphically in time-curves. These figures were constructed in a fixed template on Microsoft Excel graphics. The frame measured two standard rectangles on the horizontal axis (72 pixels width each) and 12 rectangles on the vertical axis (21 pixels height each). The x-axis was calibrated from 1 to 13, representing the sequentially fixed measurements. The y-axis was calibrated from 0 to 0.6, representing the amplitude of the BP change. The default of the time-curves was set so that BP differences <0.02 were represented as =0.02, and BP differences >0.6 as =0.6. The time-curves were depicted as continuous, thin, black lines on white background. Subsequently, MS Paint was used to invert the original colours to white line on black background. The images were then saved as 320x320-pixel 24-bit bitmap images and loaded into the computerized image analyser Benoit Version 1.3 (Trusoft). The time-curve's fractal dimension (FD) was automatically assessed by using the box counting method. FD represents a ‘self-similarity’ in dynamic behaviour over multiple scales of time. FD is calculated as FD=log(number of self-similar pieces)/log(magnification factor). The side length of the largest box of the grid was 80 pixels. The coefficient of box size decrease was 1.3. The number of box sizes used was 17. The increment of grid rotation was 15°.
Absolute systolic and diastolic BP-differences were computed by transforming positive and negative BP changes into positive values. The relative values of BP differences were calculated as above. HR differences were defined as the difference between successive HR values and the last recumbent HR value, and divided by the last recumbent HR value. The HR differences mean, SD and FD were calculated. Absolute HR differences were derived from the transformation of positive and negative HR differences into positive numbers, and were processed as for natural HR differences. On multivariate analysis, the independent predictors of CFS vs. healthy controls were: SYS-DIFF-a-FD, the fractal dimension of absolute values of the systolic BP differences; SYS-DIFF-c-SD, the standard deviation of the current values of the systolic BP differences; and HR-DIFF-c-SD, the standard deviation of the current values of the HR differences. Based on these three variables, the HIS was calculated:
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According to the results of our previous study,18 the best cut-off differentiating CFS from healthy is HIS -0.98. In that study, HIS values >-0.98 were associated with CFS (sensitivity 97% and specificity 97%).
Statistical analysis
A non-parametric comparison between CFS patients and each other patient group was performed with the Mann-Whitney U test. Multivariate analysis using the logistic regression model was used to test the groups' adjustment for age and gender. Sensitivity and specificity of the HIS cut-off >-0.98 for the diagnosis of CFS versus other disorders were computed. Two-tailed p values of 0.05 or less were considered to be statistically significant.
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Results |
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The HUTT was prematurely terminated because of presyncope or syncope in nine patients with CFS (22.5%), in 17 patients with non-CFS fatigue (23.3%), three patients with fibromyalgia (7.3%), 19 patients evaluated for recurrent faints (32.7%), and eight patients with generalized anxiety disorder (28.6%). None of the healthy controls, patients with FMF or arterial hypertension patients developed orthostatic symptoms. HIS could be calculated only in the subjects who completed the HUTT.
The HIS values in different patient groups are shown in Table 1 and Figure 2. HIS values in CFS were significantly different to those in the other groups (p<0.0001), except for the group of patients with generalized anxiety disorder, where differences were not significant. These results were not affected by age and gender differences between the groups, according to multivariate analysis of the covariates.
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The sensitivity of the HIS >-0.98 cut-off for CFS was 90.3%. The overall specificity of HIS >-0.98 cut-off for CFS vs. all control groups was 84.5%. The specificity of HIS >-0.98 for CFS vs. non-CFS fatigue was 78.4%, vs. fibromyalgia 86.8%, vs. generalized anxiety disorder 55%, vs. neurally mediated syncope 82.1%, vs. healthy subjects 88.1%, vs. FMF 92%, and vs. essential hypertension 96.4%.
The reproducibility of the HIS was assessed with reference to the -0.98 cutoff in 14 patients who agreed to undergo repeated HUTT (Figure 3). These included six patients with CFS, who had HIS >-0.98 on initial examination as well as three patients with non-CFS fatigue and six healthy subjects, all having HIS <-0.98 on initial examination. Two to five HUTT examinations were performed in each subject at one- to two-week intervals, totalling 35 examinations performed in the 14 patients. The HIS was correctly classified with reference to the proposed cut-off in all instances. Subjects with HIS >-0.98 on initial examination also had HIS >-0.98 on re-testing and subjects with HIS <-0.98 on initial examination had similar values on repeated HUTT.
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Discussion |
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The HUTT used in this study has been previously applied to the investigation of dysautonomia in CFS patients.4–8,15,17 but its use as a diagnostic tool in CFS was not possible until the HIS was introduced.18,19 The HIS cut-off >-0.98 usually distinguished CFS patients from other patient populations. In the present study, 91.4% of our CFS patients exhibited HIS values >-0.98.
The HIS differs from methods that assess cardiovascular reactivity by analysing absolute BP and HR values36,37 rather than their changes. In our study, the ‘BP differences' indicated BP instability and ‘HR differences’, HR instability. Since the BP differences were corrected with respect to BP at baseline, a direct comparison of values between hypertensives and normotensives was possible. Similarly, the correction of HR change with respect to baseline HR values enabled comparison of subjects with initial bradycardia or tachycardia. We used computer-assisted image analysis to calculate the FD of the time curves. Fractal measurements differ from measurements used in regular Euclidean geometry.38,39 The FD represents a ‘self-similarity’ in dynamic behaviour over multiple scales of time, and can be seen as the minimum number of underlying variables that are required to explain the signal's shape.
The HIS was characteristic of the diagnosis of dysautonomia in CFS, and distinguished CFS from several disorders that either display clinical similarity with CFS or in which dysautonomia is known to be present. The 90.3% sensitivity and 84.5% overall specificity of HIS for CFS contrasts with the merely moderate sensitivity and poor specificity of classical autonomic testing for CFS.3–8,15–17 Though direct intraneural measurement of the efferent sympathetic nerve traffic to blood vessels, combined with spectral analysis of cardiovascular reactivity during rest and postural challenge, has advanced our understanding of the pathophysiology of dysautonomia,40 these data are not specific for CFS and have no application in the diagnosis of CFS.41,42
To further support this observation, the ‘Fractal and Recurrence Analysis Score’ was recently proposed.43 A 10-min supine phase of the HUTT was followed by recording 600 cardiac cycles on tilt, i.e. 5–10 min. Beat-to-beat HR and pulse transit time were acquired. Data were processed by recurrence plot and fractal analysis. Fifty-two variables were calculated in each subject. On multivariate analysis, the best predictors of CFS were determined and based on these predictors, the ‘Fractal and Recurrence Analysis-based Score’ (FRAS) was calculated. The best cut-off differentiating CFS from the control population was FRAS=+0.22. FRAS >+0.22 was associated with CFS with 88% specificity and 70% sensitivity, which is comparable with the figures for the HIS. The difficulty in evaluating cardiovascular reactivity by classical methods derives from the high degree of non-linearity between external stimuli and cardiovascular response that characterizes the autonomic cardiovascular modulation. The proposed solution to this problem uses joint quantification of BP and HR fluctuations, and non-Euclidian mathematical analysis: these methods were used in computing the HIS and FRAS.
Classification of fatigue syndromes by HIS values could be important in differentiating CFS from other fatigue syndromes as well as in the application of therapies directed at the autonomic nervous system in patients who present with dysautonomia. Since dysautonomia is almost always present in CFS patients, it has been proposed that therapies which may counter the haemodynamic disturbance in CFS could improve some of their symptoms. Midodrine HCl, a potent 
-1-adrenergic agonist, is efficient in the treatment of haemodynamic disturbances such as symptomatic orthostatic hypotension, vasovagal syncope and postural tachycardia syndrome.44 Ten patients with CFS and five controls with non-CFS fatigue were studied. In CFS patients receiving long-term treatment with midodrine, a decrease in the HIS from +4.8 (range +2.28 to +7.03) to -1.51 (range -0.87 to -4.2) was paralleled by patients' ability to return to activities and subsequent remission of fatigue. Patients with fatigue other than CFS did not change on midodrine treatment (Naschitz et al, personal communication).
Dysautonomia is often perceived as a ‘black box of nebulous disorders' compounded by poor demarcation from variants of normality, spontaneous fluctuations in disease severity, and heterogeneity of clinical manifestations.45 It has been suggested that patients with altered cardiovascular regulation may be all part of a single continuum of autonomic disturbances. Although there is considerable overlap of symptoms, and a possible common autonomic substrate linking patients with disorders such as CFS, the postural hypotension syndrome, neurally mediated syncope, and fibromyalgia, there are considerable differences between these disorders in terms of predominant clinical symptoms, haemodynamic profiles, and therapeutic response to volume expansion or augmenting peripheral vasoconstriction with midodrine.45 The possibility of using the HIS and FRAS to distinguish the cardiovascular reactivity of CFS from that of other functional somatic syndromes, such as fibromyalgia20 and neurally-mediated syncope, suggests that a CFS-characteristic dysautonomia may exist. The presence of this distinctive dysautonomia in CFS, which is not usually observed in other fatigue syndromes, lends support to the concept that CFS is a separate entity among illnesses characterized by fatigue. The observation that 45% of patients with generalized anxiety disorder were found to have comparable HIS values to CFS patients lends support to the recognized association between generalized anxiety disorder and CFS.2 Our study did not approach the mechanisms of dysautonomia in the different groups of patients. The idea that cardiovascular reactivity is the outcome of arterial baroreflexes is simplistic, and no longer tenable. Serotonin, adenosine and opioids are additional triggers of the Betzold-Jarisch reflex, peripheral sympathetic afferents are directly activated by circulating mediators, and higher nervous centres modulate the cardiovascular reflexes.46,47 Investigation of the elaborate mechanisms involved in particular phenotypes of cardiovascular reactivity was beyond the aims of our study.
In clinical practice, the HIS can reinforce the diagnosis of CFS by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred. Thus, a HIS >-0.98 may support the diagnosis of CFS, providing certain confounding conditions are excluded. As a general rule, patients with other active medical or psychiatric conditions should not be diagnosed with CFS.1,2 From the clinical point of view, differentiation of these disorders from CFS is usually simple. Pathologically elevated HIS may be expected to occur in cardiovascular deconditioning following prolonged bed rest or under zero-gravity,48 in autonomic dysfunction associated with neurological or chronic inflammatory disorders49,50 or as result of drug effects on the autonomic nervous system, though no systematic studies have appraised the effects of any of these conditions on the HIS. The HIS does not, unfortunately, assist in the challenging differential diagnosis between CFS and generalized anxiety disorder.
There are limitations to our study. First, the HIS was established and tested in patients with mild to moderate forms of CFS, but not in subjects who were debilitated or bedridden. Second, the HIS could only be processed in patients who were able to complete 30 min of tilt. When orthostatic symptoms occurred and precluded termination of the tilt, the score became unsuitable. The lack of blinding of the technicians who performed the HUTT to the patients' diagnoses might have potentially increased their inclination to interrupt the tilt if symptoms occurred in CFS patients. However, dropout rates in patient groups with CFS, non-CFS fatigue, syncope and anxiety disorder were similar, thus this form of bias is unlikely. As calculation of the HIS depends on completion of the HUTT, it cannot be ascertained or assumed that those with syncope would have had a HIS >-0.98. Only the use of other methodologies, not dependant on completion of the HUTT, could tell us whether cardiovascular reactivity differs between CFS patients with syncope and those without. Third, the difference between diagnosing CFS by CDC criteria alone1 or based on combined, CDC and HIS criteria is unclear. No available test can definitely establish the diagnosis of CFS and serve as gold standard to assess a hierarchy among surrogate measures such as HIS and the 37 kDa protein.22 The possibility of targeting treatment of CFS at normalizing autonomic nervous function and using the HIS as a measure of the response to treatment, supports the role of HIS in clinical practice. Prospective studies may answer this question.
As a practical tool, the HUTT is easily administered, its use is not restricted by cultural constraints, and it is applicable to a wide range of populations. While performing a HUTT is time-consuming, the calculation of HIS is speedy. There are many accessible and reasonably priced computer programs that can perform a fractal analysis. A dedicated software package for calculation of the HIS is being developed at our institution, and will be made available through the Internet.
Elaboration of the FRAS, which recognized the specific cardiovascular reactivity in CFS by using a short and well-tolerated tilt phase, may increase the applicability of this method. Future investigations may show whether application of the FRAS to the study of cardiovascular reactivity in CFS reveals similar reactivity in CFS patients who can and those who cannot complete a 30-min tilt.
In conclusion, there exists a particular dysautonomia in CFS that differs from dysautonomia in several other disorders. This distinct abnormality is described by HIS >-0.98. Therefore, HIS may be used in the appropriate clinical context to support the diagnosis of CFS, which until now, could only be subjectively inferred.
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Appendix: Sources of error and measures to avoid inaccuracies in processing the HIS |
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Mental or physical stress, caffeine, smoking, medications
No medications for at least two weeks before the HUTT
Restriction from smoking and caffeine ingestion for 6 h
Testing from 0800 to 1100 h
Laboratory and equipment shown to patient prior to the start of the test
Quiet environment and constant room temperature of 22–25 °C
No conversation during the HUTT
Calm and attentive examiners
BP measurement with the mercury sphygmomanometer
Automatic BP measurement devices not used for assessment of the HIS, due to inaccuracies
Physician certified in the BP measurement technique according to American Heart Association recommendations
‘Last supine BP’ is the median of three consecutive measurements before tilt
Measurements may be inaccurate in the presence of arrhythmia
Calibration of the computer programs SNN1 and Benoit 1.3
Construct 0–change BP and HR data (place identical BP values throughout the HUTT).
The FDSL (fractal dimension of a straight line) should measure 1.077
If different FDSL values are obtained, reinstall the program
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Notes |
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Address correspondence to Dr J.E. Naschitz, Department of Internal Medicine A, Bnai Zion Medical Center, Haifa 31048, PO Box 4940, Israel. e-mail: Naschitz{at}tx.technion.ac.il
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References |
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