Physiology & Behavior 147 (2015) 227–232
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A prospective 1-year study of postural tachycardia and the relationship to non-postural versus orthostatic symptoms Jacquie Baker a, Kurt Kimpinski a,b,⁎ a b
Department of Clinical Neurological Sciences, University Hospital, London Health Sciences Centre, London, Ontario, Canada Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
H I G H L I G H T S • • • •
Asymptomatic orthostatic tachycardia in young population Head-up tilt and symptom assessments for orthostatic tachycardia No non-postural or orthostatic symptoms present despite tachycardia on HUT Need for re-evaluation of heart rate criteria for POTS in young population
a r t i c l e
i n f o
Article history: Received 21 October 2014 Received in revised form 23 March 2015 Accepted 27 April 2015 Available online 1 May 2015 Keywords: Orthostatic tachycardia Postural Tachycardia Syndrome Orthostasis SF-36 Multidimensional Fatigue Inventory Body Vigilance Questionnaire
a b s t r a c t Purpose: Healthy subjects with asymptomatic postural tachycardia at baseline were evaluated over a one year period to determine whether they developed non-postural versus orthostatic symptoms that could predispose them to develop Postural Tachycardia Syndrome (POTS). Methods: Participants (n = 30) were recruited for a 1-year follow-up (FUP) study if at baseline they demonstrated a heart rate increment of ≥ 30 bpm on head-up tilt (HUT). At FUP, HUT was repeated and four self-report questionnaires were used to assess symptoms. Results: Heart rate (HR) increment was reduced in 19 subjects (−11.8 ± 7.4 bpm) and increased in 11 subjects (8.3 ± 6.1 bpm) at FUP versus baseline. Heart rate increment at FUP demonstrated no correlation to general fatigue (r = 0.006), body vigilance (r = 0.195), or the component scores for physical (r = −0.087) and mental (r = − 0.137) health of the SF-36. Similarly, there was no correlation between HR increment at FUP and orthostatic scores (r = 0.04). However, orthostatic scores did show a significant positive correlation with general fatigue and body vigilance scores (r = 0.374, r = 0.392, respectively; p b 0.05). Conclusions: Despite meeting the heart rate criteria for POTS, these findings further support that the majority of young individuals express benign orthostatic tachycardia. In addition, after one year this patient population showed no predisposition to develop non-postural or postural symptoms that could lead to the full syndrome of POTS. These data further argue for the re-evaluation of the heart rate criteria for diagnosing POTS in young populations. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Postural Tachycardia Syndrome (POTS) is characterized by symptoms of lightheadedness, dizziness and palpitations in the standing or upright position [11]. The physiological criteria for POTS is defined as a heart rate increment greater than 30 bpm on head-up tilt (HUT) [11]. In younger populations, orthostatic disorders, including POTS, have been shown to have significant morbidity and impaired social development [1,11,19]. ⁎ Corresponding author at: Rm. C7-131, University Hospital, London Health Sciences Centre, 339 Windermere Road, London, Ontario N6A 5A5, Canada. E-mail address: [email protected] (K. Kimpinski).
http://dx.doi.org/10.1016/j.physbeh.2015.04.049 0031-9384/© 2015 Elsevier Inc. All rights reserved.
The degree of postural tachycardia that is considered abnormal or likely to be associated with orthostatic symptoms has come into question in younger individuals [8,23]. There are a large proportion of asymptomatic adolescents and young adults who naturally express excessive heart rate increments on HUT [8,9,23]. These selected populations could be considered as having an orthostatic tachycardia without symptoms. These issues have raised questions regarding the diagnostic criteria for POTS and whether revision is needed in younger patient populations. Some have proposed increasing the HR criteria for POTS to 40 bpm, but little study has primarily focused on this crucial question [5]. Furthermore, our lab previously undertook a prospective one year study of persons with asymptomatic orthostatic tachycardia that showed that individuals were not predisposed to developing orthostasis
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[4]. These findings argue that orthostatic tachycardia is a benign finding in the young and not associated with a significant predisposition to develop orthostasis or POTS. There is evidence to support the lack of significant mental illness in POTS including the argument that anxiety is not a significant contributor to the postural tachycardia [20]. However, it is very likely that poor adaptation strategies to psychosocial/environmental stressors may contribute to the disability experienced by POTS patients [2,3]. Therefore, we questioned whether those individuals with asymptomatic orthostatic tachycardia may become symptomatic with respect to their potential orthostatic disorder based on poor coping strategies to psychosocial stressors. We undertook a follow-up study of persons with asymptomatic postural tachycardia (≥ 30 bpm) at baseline to determine whether these individuals were predisposed to the development of constitutional symptoms including hyper-vigilance, fatigue, and changes in their physical/mental health that in turn, could result in the full syndrome of POTS. We evaluated participants at one year using the Body Vigilance Questionnaire (BVQ), Multidimensional Fatigue Inventory (MFI) and the 36-item Short-Form health survey (SF-36). Our objectives were to determine whether these symptoms correlated to changes in postural heart rate and/or orthostatic symptoms (as defined by the Orthostatic Hypotension Questionnaire).
2. Methods and materials 2.1. Subjects Participants between the ages of 13 and 80 were recruited as part of a normative database being compiled by our lab. Participants with a heart rate increment of ≥30 bpm on head-up tilt were asked to return 1-year later at a similar time of day for a follow-up (FUP) visit. The following steps were taken to rule out other possible explanations for the excessive tachycardia, in addition to determining the general health of our studied population: 1) Participants were examined by a neurologist (KK) prior to testing to exclude any neurological conditions, including chronic pain disorders, and to verify that they did not have a history of orthostatic and/or autonomic dysfunction. 2) A list of medications was provided from each participant from which, there were no medications that would indicate the presence of chronic pain or anxiety disorders. 3) Following testing the results of the Body Vigilance Questionnaire, which has been significantly correlated to both panic and generalized anxiety disorders [7,12], revealed values within the normal range for a control population [22]. 4) Despite no reported findings of anxiety disorders, anxiety was not found to be a significant contributing factor to postural tachycardia [20].Therefore, we would argue that the presence of excessive tachycardia was not a result of co-existing/alternative morbidities, including chronic pain, anxiety and panic disorders. Additional exclusion criteria to verify that our studied population was of good general health included at least one of the following: i) pregnant or lactating females, ii) the presence of another cause of autonomic failure, iii) clinically significant coronary artery disease, iv) concomitant therapy with anticholinergic, alpha- and beta-adrenergic antagonists or other medication which could interfere with testing of autonomic function, and v) failure of other organ systems or systemic illness that could affect autonomic function or the subject's ability to cooperate. This included: dementia, pheochromocytoma, heart failure, hypertension, renal or hepatic disease, severe anemia, alcoholism, malignant neoplasms, hypothyroidism, sympathectomy, diabetes, amyloidosis or cerebrovascular accidents. A total of 30 participants were included in this study. Ethical approval was obtained from the Health Science Research Ethics Board at Western University and written consent was obtained from each participant prior to study commencement.
2.2. Head-up tilt Subjects were placed in the supine position for a minimum of 15 min prior to testing. The subject's beat-to-beat blood pressure and heart rate were measured using a BMEYE Nexfin device (Amsterdam, The Netherlands) and an electrocardiography (ECG) device (Model 3000 Cardiac Trigger Monitor, IVY Biomedical Systems, Inc., Branford, CT) with ECG electrodes (Ambu® Blue Sensor SP, Glen Burnie, MD), respectively. All recordings were made using WR TestWorks™ software (WR Medical Electronics Co., Stillwater, MN). Baseline recordings were obtained for 1 min. The subject was then passively tilted to 70° upward from horizontal for a period of 5 min followed by an additional 5 min recovery period in the supine position. A change in HR (ΔHR) was calculated by obtaining the average HR during the 1-minute baseline and subtracting it from the maximal HR achieved between the second and fifth minutes of tilt (maximal HR-average baseline HR). 2.3. Questionnaires 2.3.1. The 36-item Short-Form health survey (SF36) The SF36 is a self-report questionnaire used to assess quality of life in clinical and non-clinical populations [2,18,27]. The questionnaire contains 36 items to yield scores in 8 domains: physical functioning, role limitations caused by physical problems, bodily pain, general health, vitality, role limitations caused by emotional problems, social functioning, and mental health. The 8 domains can be further aggregated into physical and mental summary scores. Each domain was scored using a norm-based approach which can be compared to general populations with a mean of 50 and standard deviation of 10, with higher scores indicating better health. 2.3.2. Multidimensional Fatigue Inventory (MFI) The MFI is a self-report instrument used to assess fatigue as experienced by patients [24]. The MFI-20 contains 20 items organized into 5 sub-scales: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Each item was scored between 1 and 5, with higher scores indicating more fatigue. Summation of each item per scale yielded a total score ranging from 4 to 20. 2.3.3. Body Vigilance Questionnaire (BVQ) The BVQ is a 4 item self-report questionnaire used to assess the degree to which a subject focuses on internal bodily sensations [22]. Items 1–3 assess the degree of focus to bodily sensations, perceived sensitivity to bodily changes, and the average amount of time spent attending to bodily sensations. The fourth item gathers ratings for attention to 15 sensations that include all of the physical symptoms described for panic attacks in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Ratings for the 15 sensations were averaged to yield one overall score for item 4. A total score was calculated by finding the sum of items 1–4, with higher scores indicating greater focus on bodily sensations, which has been correlated to anxiety and panic disorders. 2.3.4. Orthostatic Hypotension Questionnaire (OHQ) The OHQ is divided into two parts. Part I: the orthostatic hypotension symptoms assessment (OHSA), consists of six questions to measure the presence and severity of orthostatic symptoms, and Part II: the orthostatic hypotension daily activity scale (OHDAS), consists of four questions to assess the impact of orthostatic symptoms on daily activities [14]. Each item was scored on an 11-point scale from 0–10, with 0 indicating no symptoms/no interference and 10 indicating the worst symptoms/complete interference. Included was the option of selecting “cannot do for other reasons”. The total OHQ score was calculated by averaging the OHSA and OHDAS scores.
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2.4. Statistical analysis Descriptive statistics are presented as mean ± standard deviations. We grouped participants according to their heart rate change between visits, and compared questionnaire scores between the two groups using an independent t-test with an alpha level of 0.05 used to denote significance. All statistical analyses were performed using SPSS® statistical software version 21 for Windows (SPSS, Inc., Chicago, IL). 3. Results Participants (n = 30; Table 1) who met the standard HR criteria (≥30 bpm) for Postural Tachycardia Syndrome (POTS) on initial headup tilt (HUT) returned for a follow-up (FUP) visit 1-year later. Participants repeated HUT in addition to completing four pen and paper questionnaires (MFI, BVQ, SF36, and OHQ) to evaluate non-postural constitutional and orthostatic symptoms. Our results demonstrate a significant correlation of both physical and mental fatigue with general fatigue (r = 0.67 at p b 0.01; r = 0.43 at p b 0.05. respectively; Table 1 and Fig. 3a).
Fig. 1. Mean scores of all participants (n = 30) for all 5 sub-scales of the multidimensional fatigue inventory (MFI).
3.1. Constitutional and orthostatic symptom scores 3.3. Norm-based scores of 36-item Short-Form health survey In response to HUT, 19 participants demonstrated an improved HR response at FUP compared to their initial visit; 11 demonstrated an elevated HR response to HUT at FUP. Two groups were formed based on HR change. Table 1 presents mean scores on all four questionnaires for both subject groups, which showed no significant differences.
Fig. 2 presents mean norm-based SF36 domain scores (n = 30). Despite meeting the HR criteria for POTS, participants reported above average scores, indicative of better health, across multiple domains of functioning. These data would further argue that our studied population was of good mental and physical health.
3.2. Multidimensional Fatigue Inventory scores Fig. 1 shows the mean scores for all participants (n = 30) in each MFI sub-scale. We compared the results of our population to those of a validation study collected from a healthy control population (n = 157)[17]. As a result, our studied population revealed lower scores in all 5 domains of fatigue. Furthermore, there were no significant differences between each sub-set domain of fatigue. These results would further support the lack of co-morbidities including chronic fatigue syndrome, and would further argue that these results are in fact taken from a relatively healthy population.
3.4. Correlation between heart rate increments and constitutional symptoms Fig. 3a–d demonstrates that the heart rate increment (Δ heart rate) to HUT during FUP did not correlate with a) general fatigue (MFI-GF; r = 0.006; p = 0.97), b) body vigilance (BVQ; r = 0.195; p = 0.31), c) the physical component summary (PCS; r = −0.087; p = 0.66), or d) the mental component summary scores (MCS; r = − 0.137; p = 0.48) (n = 30). Furthermore, Δ heart rate at FUP did not correlate with the total OHQ score (r = 0.04; p = 0.84).
Table 1 Participant characteristics (n = 30) and questionnaire data stratified by postural heart rate increment change. Age (year) Sex Height (cm) Weight (kg) BMI (kg/m2)
Average age (years) Median age (years) Heart rate (bpm) MFIa BVQ SF36 PCS MCS OHQ Symptoms Impact Total
26 ± 6 M = 14; F = 16 173 ± 8.1 72.3 ± 13.2 24.00 ± 3.08 Decrease ΔHR (N = 19)
Increase ΔHR (N = 11)
p-Value
27 ± 7 26 −11.8 ± 7.4 8.68 ± 2.93 16.88 ± 7.58
24 ± 5 24 8.3 ± 6.1 9.09 ± 3.36 18.57 ± 5.80
0.12
0.731 0.529
55.09 ± 3.65 53.81 ± 7.38
54.87 ± 2.58 52.92 ± 6.99
0.864 0.749
2.42 ± 3.75 0.05 ± 0.23 1.24 ± 1.87
2.09 ± 4.59 0.00 ± 0.00 1.05 ± 2.30
0.832 0.456 0.805
Values are expressed as mean ± SD. Participant characteristics (n = 30) and comparison of Multidimensional Fatigue Inventory (MFI), Body Vigilance Questionnaire (BVQ), physical and mental component summaries (PCS and MCS, respectively) and Orthostatic Hypotension Questionnaire (OHQ) scores stratified by heart rate improvement (decrease) or further impairment (increase) in response to HUT at 1-year. a General fatigue score of the MFI.
Fig. 2. Norm-based scores for each 36-item Short Form (SF36) category for participants (n = 30) who met the standard heart rate criteria for Postural Tachycardia Syndrome (POTS). Horizontal line represents general population mean score (50). PF, physical functioning; RP, role limitations — physical; BP, bodily pain; GH, general health; VT, vitality; RE, role limitations — emotional; SF, social functioning; and MH, mental health.
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Fig. 3. Heart rate increment (Δ heart rate) on head-up tilt did not correlate with a) general fatigue (MFI-GF), b) body vigilance (BVQ), c) physical component summary (PCS), or d) mental component summary scores at the follow-up (FUP) visit (a: r = 0.006, p = 0.97; b: r = 0.195, p = 0.31; c: r = −0.087, p = 0.66; d: r = −0.137, p = 0.48; n = 30).
3.5. Correlation between orthostatic and constitutional symptoms Lastly, total OHQ score showed a significant positive correlation with both the MFI (general fatigue) and BVQ scores (r = 0.374, r = 0.392, respectively; p b 0.05). Total OHQ neared a significant correlation with the PCS score (r = −0.342, p = 0.065). Contrary to the other scores, total OHQ scores showed no correlation with the MCS (r = 0.035, p = 0.854; Fig. 4a–d).
4. Discussion Our results reveal three major findings. First, there was no correlation between postural heart rate and non-postural constitutional symptoms in our patient group at the 1-year follow-up assessment. Second, there was no correlation between postural heart rate increment on HUT and total OHQ score. However, total OHQ was significantly correlated with both the general fatigue and body vigilance scores at one year. Third, non-postural constitutional symptoms did not differ when subjects were divided into separate groups based on an improved versus worsened heart rate increment on head-up tilt at the 1-year follow-up period. These findings further support that the majority of young individuals express elevated but benign heart rate increments
on HUT. In addition, after one year this patient population shows no predisposition to develop non-postural constitutional or orthostatic symptoms that could lead to symptomatic orthostasis or the full syndrome of POTS. The ability of a patient to manage or interpret orthostatic symptoms may be an important factor in developing POTS. There has been interest in the psychological aspects of POTS based strongly on routine clinical experience and the large number of patients who manifest poor coping strategies. While definable mental illnesses in POTS are no more prevalent than that of the general public, poor adaptation and coping strategies do result in greater patient difficulties [2,3,20]. Therefore, this is an important but complicating factor in being diagnosed with POTS. It is reasonable to question whether younger patients with syndromes characterized by multiple constitutional symptoms (i.e. chronic fatigue syndrome (CFS), fibromyalgia) such as fatigue, dizziness, and lightheadedness, may be over-diagnosed with POTS. There has been much work on the coexistence of CFS and POTS, and it appears that younger age groups are more likely to co-express both disorders [6,16, 21]. There has been interesting work looking at patients with common underlying pathophysiological mechanisms where POTS and CFS coexist. Previous work has shown impaired vagal components of the vagal baroreflex with a potential increase in sympathetic activity leading to greater vasomotor tone [25]. However, other authors have
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Fig. 4. Total Orthostatic Hypotension Questionnaire (OHQ) score correlated with the general fatigue score (GF) of the Multidimensional Fatigue Inventory (MFI), Body Vigilance Questionnaire (BVQ) score, and the physical and mental component summaries (PCS and MCS, respectively) scores of the SF36. OHQ had a significant positive correlation with the GF score of the MFI (r = 0.374, p b 0.05), and the BVQ score (r = 0.392, p b 0.05). The PCS score neared significance with a negative correlation (r = −0.342, p = 0.065), while the MCS score showed no correlation to the total OHQ score (r = 0.035, p = 0.854).
questioned whether physical deconditioning in such constitutional disorders may lead to the development of orthostatic tachycardia and potentially POTS [13]. There are likely subsets of patients with unique overlapping pathophysiology between POTS and CFS (and other similar disorders). However, there are some important questions that need to be raised. The first is the matter of deconditioning. Deconditioning can result in similar heart rate responses as that seen in POTS [13]. The second is the question of symptom interpretation. If you take non-positional symptoms that occur in constitutional disorders such as fatigue, dizziness, and lightheadedness, but then measure these symptoms by the current scales of orthostatic intolerance, you are likely to obtain significant results as there are no specific measures that distinguish between postural (orthostatic) and non-postural symptoms (with the potential exception of clinical evaluation). Therefore we would argue that in young patient populations the combination of pre-existing orthostatic tachycardia, misinterpretation of postural versus non-postural symptoms and the likely contribution of deconditioning results in the overestimation of POTS in various constitutional disorders. But why should clinicians care? There is an argument that conservative measures (fluid hydration, exercise,
compression garments etc.) focused toward improving orthostatic symptoms are non-invasive and potentially helpful. We would agree with this assertion to a point. It is also important to stress that interventions focused on psychological factors are equally as important, and the potential for such interventions to be minimized by the patient who is diagnosed with a “physical” illness is common in our clinical experience. This is supported by prospective studies that show that POTS patients can have improved hemodynamic measures but continue to experience symptoms [15]. It is our experience that such patients tend to be refractory to treatment and incur the greatest morbidity. Our study has four major limitations. The first is how to define an appropriate control group. As we have previously stated in prior studies there is a strong correlation with heart rate increment and age in that younger individuals while not meeting our present heart rate criteria usually have heart rates close to the N30 bpm criteria [8,10]. This makes it difficult to define any meaningful age/gender matched control group. We have used an arbitrary heart rate criteria based on an improved or worsened heart rate response on HUT in comparing subjects with respect to non-postural constitutional and orthostatic symptoms. Given that there were no significant differences between groups, we would argue that such limitations of being able to define an appropriate
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control group at baseline are less likely to be a confounding factor of this study. The second limitation is the lack of knowledge of the natural history of POTS [15,26]. We do not know the incidence of POTS and therefore it is difficult to determine how such a study should be powered and what the appropriate follow-up period should be. We are currently undertaking long term prospective studies to address these study limitations. The third limitation is the lack of a specific scale capable of distinguishing between postural (orthostatic) versus non-postural symptoms. We are currently working to address this study limitation. However, there is evidence to argue that non-postural constitutional symptoms are not seen to any significant extent in individuals with asymptomatic orthostatic tachycardia. The final study limitation is the lack of baseline values pertaining to questionnaire scores. The purpose of this study was to evaluate asymptomatic individuals with excessive postural tachycardia and to determine if this was a predisposing factor that would precipitate the development of constitutional symptoms, which in turn could develop into the full syndrome of POTS. Therefore, the sole defining determinant in bringing an individual back for a follow-up visit was the presence of excessive postural tachycardia. Given that we are interested in factors predisposing individuals to the development of POTS these studies continue to be ongoing. However we would argue that this study provides important initial data comparing orthostatic and constitutional (nonpostural) symptoms. 5. Conclusions There continues to be ongoing questions surrounding the heart rate criteria for POTS in younger persons, and the current study adds to these concerns. Our study demonstrates the lack of constitutional symptoms associated with asymptomatic orthostatic tachycardia. In addition, orthostatic symptoms correlated significantly with both general fatigue and body vigilance scores. Therefore these results suggest that changes in constitutional symptoms may contribute to greater orthostatic difficulties in these individuals, which could lead to the full syndrome of POTS. However, these findings require further elucidation with regard to postural versus non-postural symptoms. Long term prospective follow-up studies are required to answer these complex questions. Conflict of interest The authors have no conflicts of interest to declare. Summary of author contributions KK and JB each contributed to experimental design, data analysis and manuscript preparation. Acknowledgments This work was supported by unrestricted grant funds from the Department of Clinical Neurological Sciences Internal Research Fund. References [1] R.M. Antiel, J.M. Risma, R.M. Grothe, C.K. Brands, P.R. Fischer, Orthostatic intolerance and gastrointestinal motility in adolescents with nausea and abdominal pain, J. Pediatr. Gastroenterol. Nutr. 46 (2008) 285–288. [2] L.M. Benrud-Larson, M.S. Dewar, P. Sandroni, T.A. Rummans, J.A. Haythornthwaite, P.A. Low, Quality of life in patients with postural tachycardia syndrome, Mayo Clin. Proc. 77 (2002) 531–537.
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Physiology & Behavior journal homepage: www.elsevier.com/locate/phb
A prospective 1-year study of postural tachycardia and the relationship to non-postural versus orthostatic symptoms Jacquie Baker a, Kurt Kimpinski a,b,⁎ a b
Department of Clinical Neurological Sciences, University Hospital, London Health Sciences Centre, London, Ontario, Canada Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
H I G H L I G H T S • • • •
Asymptomatic orthostatic tachycardia in young population Head-up tilt and symptom assessments for orthostatic tachycardia No non-postural or orthostatic symptoms present despite tachycardia on HUT Need for re-evaluation of heart rate criteria for POTS in young population
a r t i c l e
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Article history: Received 21 October 2014 Received in revised form 23 March 2015 Accepted 27 April 2015 Available online 1 May 2015 Keywords: Orthostatic tachycardia Postural Tachycardia Syndrome Orthostasis SF-36 Multidimensional Fatigue Inventory Body Vigilance Questionnaire
a b s t r a c t Purpose: Healthy subjects with asymptomatic postural tachycardia at baseline were evaluated over a one year period to determine whether they developed non-postural versus orthostatic symptoms that could predispose them to develop Postural Tachycardia Syndrome (POTS). Methods: Participants (n = 30) were recruited for a 1-year follow-up (FUP) study if at baseline they demonstrated a heart rate increment of ≥ 30 bpm on head-up tilt (HUT). At FUP, HUT was repeated and four self-report questionnaires were used to assess symptoms. Results: Heart rate (HR) increment was reduced in 19 subjects (−11.8 ± 7.4 bpm) and increased in 11 subjects (8.3 ± 6.1 bpm) at FUP versus baseline. Heart rate increment at FUP demonstrated no correlation to general fatigue (r = 0.006), body vigilance (r = 0.195), or the component scores for physical (r = −0.087) and mental (r = − 0.137) health of the SF-36. Similarly, there was no correlation between HR increment at FUP and orthostatic scores (r = 0.04). However, orthostatic scores did show a significant positive correlation with general fatigue and body vigilance scores (r = 0.374, r = 0.392, respectively; p b 0.05). Conclusions: Despite meeting the heart rate criteria for POTS, these findings further support that the majority of young individuals express benign orthostatic tachycardia. In addition, after one year this patient population showed no predisposition to develop non-postural or postural symptoms that could lead to the full syndrome of POTS. These data further argue for the re-evaluation of the heart rate criteria for diagnosing POTS in young populations. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Postural Tachycardia Syndrome (POTS) is characterized by symptoms of lightheadedness, dizziness and palpitations in the standing or upright position [11]. The physiological criteria for POTS is defined as a heart rate increment greater than 30 bpm on head-up tilt (HUT) [11]. In younger populations, orthostatic disorders, including POTS, have been shown to have significant morbidity and impaired social development [1,11,19]. ⁎ Corresponding author at: Rm. C7-131, University Hospital, London Health Sciences Centre, 339 Windermere Road, London, Ontario N6A 5A5, Canada. E-mail address: [email protected] (K. Kimpinski).
http://dx.doi.org/10.1016/j.physbeh.2015.04.049 0031-9384/© 2015 Elsevier Inc. All rights reserved.
The degree of postural tachycardia that is considered abnormal or likely to be associated with orthostatic symptoms has come into question in younger individuals [8,23]. There are a large proportion of asymptomatic adolescents and young adults who naturally express excessive heart rate increments on HUT [8,9,23]. These selected populations could be considered as having an orthostatic tachycardia without symptoms. These issues have raised questions regarding the diagnostic criteria for POTS and whether revision is needed in younger patient populations. Some have proposed increasing the HR criteria for POTS to 40 bpm, but little study has primarily focused on this crucial question [5]. Furthermore, our lab previously undertook a prospective one year study of persons with asymptomatic orthostatic tachycardia that showed that individuals were not predisposed to developing orthostasis
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[4]. These findings argue that orthostatic tachycardia is a benign finding in the young and not associated with a significant predisposition to develop orthostasis or POTS. There is evidence to support the lack of significant mental illness in POTS including the argument that anxiety is not a significant contributor to the postural tachycardia [20]. However, it is very likely that poor adaptation strategies to psychosocial/environmental stressors may contribute to the disability experienced by POTS patients [2,3]. Therefore, we questioned whether those individuals with asymptomatic orthostatic tachycardia may become symptomatic with respect to their potential orthostatic disorder based on poor coping strategies to psychosocial stressors. We undertook a follow-up study of persons with asymptomatic postural tachycardia (≥ 30 bpm) at baseline to determine whether these individuals were predisposed to the development of constitutional symptoms including hyper-vigilance, fatigue, and changes in their physical/mental health that in turn, could result in the full syndrome of POTS. We evaluated participants at one year using the Body Vigilance Questionnaire (BVQ), Multidimensional Fatigue Inventory (MFI) and the 36-item Short-Form health survey (SF-36). Our objectives were to determine whether these symptoms correlated to changes in postural heart rate and/or orthostatic symptoms (as defined by the Orthostatic Hypotension Questionnaire).
2. Methods and materials 2.1. Subjects Participants between the ages of 13 and 80 were recruited as part of a normative database being compiled by our lab. Participants with a heart rate increment of ≥30 bpm on head-up tilt were asked to return 1-year later at a similar time of day for a follow-up (FUP) visit. The following steps were taken to rule out other possible explanations for the excessive tachycardia, in addition to determining the general health of our studied population: 1) Participants were examined by a neurologist (KK) prior to testing to exclude any neurological conditions, including chronic pain disorders, and to verify that they did not have a history of orthostatic and/or autonomic dysfunction. 2) A list of medications was provided from each participant from which, there were no medications that would indicate the presence of chronic pain or anxiety disorders. 3) Following testing the results of the Body Vigilance Questionnaire, which has been significantly correlated to both panic and generalized anxiety disorders [7,12], revealed values within the normal range for a control population [22]. 4) Despite no reported findings of anxiety disorders, anxiety was not found to be a significant contributing factor to postural tachycardia [20].Therefore, we would argue that the presence of excessive tachycardia was not a result of co-existing/alternative morbidities, including chronic pain, anxiety and panic disorders. Additional exclusion criteria to verify that our studied population was of good general health included at least one of the following: i) pregnant or lactating females, ii) the presence of another cause of autonomic failure, iii) clinically significant coronary artery disease, iv) concomitant therapy with anticholinergic, alpha- and beta-adrenergic antagonists or other medication which could interfere with testing of autonomic function, and v) failure of other organ systems or systemic illness that could affect autonomic function or the subject's ability to cooperate. This included: dementia, pheochromocytoma, heart failure, hypertension, renal or hepatic disease, severe anemia, alcoholism, malignant neoplasms, hypothyroidism, sympathectomy, diabetes, amyloidosis or cerebrovascular accidents. A total of 30 participants were included in this study. Ethical approval was obtained from the Health Science Research Ethics Board at Western University and written consent was obtained from each participant prior to study commencement.
2.2. Head-up tilt Subjects were placed in the supine position for a minimum of 15 min prior to testing. The subject's beat-to-beat blood pressure and heart rate were measured using a BMEYE Nexfin device (Amsterdam, The Netherlands) and an electrocardiography (ECG) device (Model 3000 Cardiac Trigger Monitor, IVY Biomedical Systems, Inc., Branford, CT) with ECG electrodes (Ambu® Blue Sensor SP, Glen Burnie, MD), respectively. All recordings were made using WR TestWorks™ software (WR Medical Electronics Co., Stillwater, MN). Baseline recordings were obtained for 1 min. The subject was then passively tilted to 70° upward from horizontal for a period of 5 min followed by an additional 5 min recovery period in the supine position. A change in HR (ΔHR) was calculated by obtaining the average HR during the 1-minute baseline and subtracting it from the maximal HR achieved between the second and fifth minutes of tilt (maximal HR-average baseline HR). 2.3. Questionnaires 2.3.1. The 36-item Short-Form health survey (SF36) The SF36 is a self-report questionnaire used to assess quality of life in clinical and non-clinical populations [2,18,27]. The questionnaire contains 36 items to yield scores in 8 domains: physical functioning, role limitations caused by physical problems, bodily pain, general health, vitality, role limitations caused by emotional problems, social functioning, and mental health. The 8 domains can be further aggregated into physical and mental summary scores. Each domain was scored using a norm-based approach which can be compared to general populations with a mean of 50 and standard deviation of 10, with higher scores indicating better health. 2.3.2. Multidimensional Fatigue Inventory (MFI) The MFI is a self-report instrument used to assess fatigue as experienced by patients [24]. The MFI-20 contains 20 items organized into 5 sub-scales: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Each item was scored between 1 and 5, with higher scores indicating more fatigue. Summation of each item per scale yielded a total score ranging from 4 to 20. 2.3.3. Body Vigilance Questionnaire (BVQ) The BVQ is a 4 item self-report questionnaire used to assess the degree to which a subject focuses on internal bodily sensations [22]. Items 1–3 assess the degree of focus to bodily sensations, perceived sensitivity to bodily changes, and the average amount of time spent attending to bodily sensations. The fourth item gathers ratings for attention to 15 sensations that include all of the physical symptoms described for panic attacks in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Ratings for the 15 sensations were averaged to yield one overall score for item 4. A total score was calculated by finding the sum of items 1–4, with higher scores indicating greater focus on bodily sensations, which has been correlated to anxiety and panic disorders. 2.3.4. Orthostatic Hypotension Questionnaire (OHQ) The OHQ is divided into two parts. Part I: the orthostatic hypotension symptoms assessment (OHSA), consists of six questions to measure the presence and severity of orthostatic symptoms, and Part II: the orthostatic hypotension daily activity scale (OHDAS), consists of four questions to assess the impact of orthostatic symptoms on daily activities [14]. Each item was scored on an 11-point scale from 0–10, with 0 indicating no symptoms/no interference and 10 indicating the worst symptoms/complete interference. Included was the option of selecting “cannot do for other reasons”. The total OHQ score was calculated by averaging the OHSA and OHDAS scores.
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2.4. Statistical analysis Descriptive statistics are presented as mean ± standard deviations. We grouped participants according to their heart rate change between visits, and compared questionnaire scores between the two groups using an independent t-test with an alpha level of 0.05 used to denote significance. All statistical analyses were performed using SPSS® statistical software version 21 for Windows (SPSS, Inc., Chicago, IL). 3. Results Participants (n = 30; Table 1) who met the standard HR criteria (≥30 bpm) for Postural Tachycardia Syndrome (POTS) on initial headup tilt (HUT) returned for a follow-up (FUP) visit 1-year later. Participants repeated HUT in addition to completing four pen and paper questionnaires (MFI, BVQ, SF36, and OHQ) to evaluate non-postural constitutional and orthostatic symptoms. Our results demonstrate a significant correlation of both physical and mental fatigue with general fatigue (r = 0.67 at p b 0.01; r = 0.43 at p b 0.05. respectively; Table 1 and Fig. 3a).
Fig. 1. Mean scores of all participants (n = 30) for all 5 sub-scales of the multidimensional fatigue inventory (MFI).
3.1. Constitutional and orthostatic symptom scores 3.3. Norm-based scores of 36-item Short-Form health survey In response to HUT, 19 participants demonstrated an improved HR response at FUP compared to their initial visit; 11 demonstrated an elevated HR response to HUT at FUP. Two groups were formed based on HR change. Table 1 presents mean scores on all four questionnaires for both subject groups, which showed no significant differences.
Fig. 2 presents mean norm-based SF36 domain scores (n = 30). Despite meeting the HR criteria for POTS, participants reported above average scores, indicative of better health, across multiple domains of functioning. These data would further argue that our studied population was of good mental and physical health.
3.2. Multidimensional Fatigue Inventory scores Fig. 1 shows the mean scores for all participants (n = 30) in each MFI sub-scale. We compared the results of our population to those of a validation study collected from a healthy control population (n = 157)[17]. As a result, our studied population revealed lower scores in all 5 domains of fatigue. Furthermore, there were no significant differences between each sub-set domain of fatigue. These results would further support the lack of co-morbidities including chronic fatigue syndrome, and would further argue that these results are in fact taken from a relatively healthy population.
3.4. Correlation between heart rate increments and constitutional symptoms Fig. 3a–d demonstrates that the heart rate increment (Δ heart rate) to HUT during FUP did not correlate with a) general fatigue (MFI-GF; r = 0.006; p = 0.97), b) body vigilance (BVQ; r = 0.195; p = 0.31), c) the physical component summary (PCS; r = −0.087; p = 0.66), or d) the mental component summary scores (MCS; r = − 0.137; p = 0.48) (n = 30). Furthermore, Δ heart rate at FUP did not correlate with the total OHQ score (r = 0.04; p = 0.84).
Table 1 Participant characteristics (n = 30) and questionnaire data stratified by postural heart rate increment change. Age (year) Sex Height (cm) Weight (kg) BMI (kg/m2)
Average age (years) Median age (years) Heart rate (bpm) MFIa BVQ SF36 PCS MCS OHQ Symptoms Impact Total
26 ± 6 M = 14; F = 16 173 ± 8.1 72.3 ± 13.2 24.00 ± 3.08 Decrease ΔHR (N = 19)
Increase ΔHR (N = 11)
p-Value
27 ± 7 26 −11.8 ± 7.4 8.68 ± 2.93 16.88 ± 7.58
24 ± 5 24 8.3 ± 6.1 9.09 ± 3.36 18.57 ± 5.80
0.12
0.731 0.529
55.09 ± 3.65 53.81 ± 7.38
54.87 ± 2.58 52.92 ± 6.99
0.864 0.749
2.42 ± 3.75 0.05 ± 0.23 1.24 ± 1.87
2.09 ± 4.59 0.00 ± 0.00 1.05 ± 2.30
0.832 0.456 0.805
Values are expressed as mean ± SD. Participant characteristics (n = 30) and comparison of Multidimensional Fatigue Inventory (MFI), Body Vigilance Questionnaire (BVQ), physical and mental component summaries (PCS and MCS, respectively) and Orthostatic Hypotension Questionnaire (OHQ) scores stratified by heart rate improvement (decrease) or further impairment (increase) in response to HUT at 1-year. a General fatigue score of the MFI.
Fig. 2. Norm-based scores for each 36-item Short Form (SF36) category for participants (n = 30) who met the standard heart rate criteria for Postural Tachycardia Syndrome (POTS). Horizontal line represents general population mean score (50). PF, physical functioning; RP, role limitations — physical; BP, bodily pain; GH, general health; VT, vitality; RE, role limitations — emotional; SF, social functioning; and MH, mental health.
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Fig. 3. Heart rate increment (Δ heart rate) on head-up tilt did not correlate with a) general fatigue (MFI-GF), b) body vigilance (BVQ), c) physical component summary (PCS), or d) mental component summary scores at the follow-up (FUP) visit (a: r = 0.006, p = 0.97; b: r = 0.195, p = 0.31; c: r = −0.087, p = 0.66; d: r = −0.137, p = 0.48; n = 30).
3.5. Correlation between orthostatic and constitutional symptoms Lastly, total OHQ score showed a significant positive correlation with both the MFI (general fatigue) and BVQ scores (r = 0.374, r = 0.392, respectively; p b 0.05). Total OHQ neared a significant correlation with the PCS score (r = −0.342, p = 0.065). Contrary to the other scores, total OHQ scores showed no correlation with the MCS (r = 0.035, p = 0.854; Fig. 4a–d).
4. Discussion Our results reveal three major findings. First, there was no correlation between postural heart rate and non-postural constitutional symptoms in our patient group at the 1-year follow-up assessment. Second, there was no correlation between postural heart rate increment on HUT and total OHQ score. However, total OHQ was significantly correlated with both the general fatigue and body vigilance scores at one year. Third, non-postural constitutional symptoms did not differ when subjects were divided into separate groups based on an improved versus worsened heart rate increment on head-up tilt at the 1-year follow-up period. These findings further support that the majority of young individuals express elevated but benign heart rate increments
on HUT. In addition, after one year this patient population shows no predisposition to develop non-postural constitutional or orthostatic symptoms that could lead to symptomatic orthostasis or the full syndrome of POTS. The ability of a patient to manage or interpret orthostatic symptoms may be an important factor in developing POTS. There has been interest in the psychological aspects of POTS based strongly on routine clinical experience and the large number of patients who manifest poor coping strategies. While definable mental illnesses in POTS are no more prevalent than that of the general public, poor adaptation and coping strategies do result in greater patient difficulties [2,3,20]. Therefore, this is an important but complicating factor in being diagnosed with POTS. It is reasonable to question whether younger patients with syndromes characterized by multiple constitutional symptoms (i.e. chronic fatigue syndrome (CFS), fibromyalgia) such as fatigue, dizziness, and lightheadedness, may be over-diagnosed with POTS. There has been much work on the coexistence of CFS and POTS, and it appears that younger age groups are more likely to co-express both disorders [6,16, 21]. There has been interesting work looking at patients with common underlying pathophysiological mechanisms where POTS and CFS coexist. Previous work has shown impaired vagal components of the vagal baroreflex with a potential increase in sympathetic activity leading to greater vasomotor tone [25]. However, other authors have
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Fig. 4. Total Orthostatic Hypotension Questionnaire (OHQ) score correlated with the general fatigue score (GF) of the Multidimensional Fatigue Inventory (MFI), Body Vigilance Questionnaire (BVQ) score, and the physical and mental component summaries (PCS and MCS, respectively) scores of the SF36. OHQ had a significant positive correlation with the GF score of the MFI (r = 0.374, p b 0.05), and the BVQ score (r = 0.392, p b 0.05). The PCS score neared significance with a negative correlation (r = −0.342, p = 0.065), while the MCS score showed no correlation to the total OHQ score (r = 0.035, p = 0.854).
questioned whether physical deconditioning in such constitutional disorders may lead to the development of orthostatic tachycardia and potentially POTS [13]. There are likely subsets of patients with unique overlapping pathophysiology between POTS and CFS (and other similar disorders). However, there are some important questions that need to be raised. The first is the matter of deconditioning. Deconditioning can result in similar heart rate responses as that seen in POTS [13]. The second is the question of symptom interpretation. If you take non-positional symptoms that occur in constitutional disorders such as fatigue, dizziness, and lightheadedness, but then measure these symptoms by the current scales of orthostatic intolerance, you are likely to obtain significant results as there are no specific measures that distinguish between postural (orthostatic) and non-postural symptoms (with the potential exception of clinical evaluation). Therefore we would argue that in young patient populations the combination of pre-existing orthostatic tachycardia, misinterpretation of postural versus non-postural symptoms and the likely contribution of deconditioning results in the overestimation of POTS in various constitutional disorders. But why should clinicians care? There is an argument that conservative measures (fluid hydration, exercise,
compression garments etc.) focused toward improving orthostatic symptoms are non-invasive and potentially helpful. We would agree with this assertion to a point. It is also important to stress that interventions focused on psychological factors are equally as important, and the potential for such interventions to be minimized by the patient who is diagnosed with a “physical” illness is common in our clinical experience. This is supported by prospective studies that show that POTS patients can have improved hemodynamic measures but continue to experience symptoms [15]. It is our experience that such patients tend to be refractory to treatment and incur the greatest morbidity. Our study has four major limitations. The first is how to define an appropriate control group. As we have previously stated in prior studies there is a strong correlation with heart rate increment and age in that younger individuals while not meeting our present heart rate criteria usually have heart rates close to the N30 bpm criteria [8,10]. This makes it difficult to define any meaningful age/gender matched control group. We have used an arbitrary heart rate criteria based on an improved or worsened heart rate response on HUT in comparing subjects with respect to non-postural constitutional and orthostatic symptoms. Given that there were no significant differences between groups, we would argue that such limitations of being able to define an appropriate
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control group at baseline are less likely to be a confounding factor of this study. The second limitation is the lack of knowledge of the natural history of POTS [15,26]. We do not know the incidence of POTS and therefore it is difficult to determine how such a study should be powered and what the appropriate follow-up period should be. We are currently undertaking long term prospective studies to address these study limitations. The third limitation is the lack of a specific scale capable of distinguishing between postural (orthostatic) versus non-postural symptoms. We are currently working to address this study limitation. However, there is evidence to argue that non-postural constitutional symptoms are not seen to any significant extent in individuals with asymptomatic orthostatic tachycardia. The final study limitation is the lack of baseline values pertaining to questionnaire scores. The purpose of this study was to evaluate asymptomatic individuals with excessive postural tachycardia and to determine if this was a predisposing factor that would precipitate the development of constitutional symptoms, which in turn could develop into the full syndrome of POTS. Therefore, the sole defining determinant in bringing an individual back for a follow-up visit was the presence of excessive postural tachycardia. Given that we are interested in factors predisposing individuals to the development of POTS these studies continue to be ongoing. However we would argue that this study provides important initial data comparing orthostatic and constitutional (nonpostural) symptoms. 5. Conclusions There continues to be ongoing questions surrounding the heart rate criteria for POTS in younger persons, and the current study adds to these concerns. Our study demonstrates the lack of constitutional symptoms associated with asymptomatic orthostatic tachycardia. In addition, orthostatic symptoms correlated significantly with both general fatigue and body vigilance scores. Therefore these results suggest that changes in constitutional symptoms may contribute to greater orthostatic difficulties in these individuals, which could lead to the full syndrome of POTS. However, these findings require further elucidation with regard to postural versus non-postural symptoms. Long term prospective follow-up studies are required to answer these complex questions. Conflict of interest The authors have no conflicts of interest to declare. Summary of author contributions KK and JB each contributed to experimental design, data analysis and manuscript preparation. Acknowledgments This work was supported by unrestricted grant funds from the Department of Clinical Neurological Sciences Internal Research Fund. References [1] R.M. Antiel, J.M. Risma, R.M. Grothe, C.K. Brands, P.R. Fischer, Orthostatic intolerance and gastrointestinal motility in adolescents with nausea and abdominal pain, J. Pediatr. Gastroenterol. Nutr. 46 (2008) 285–288. [2] L.M. Benrud-Larson, M.S. Dewar, P. Sandroni, T.A. Rummans, J.A. Haythornthwaite, P.A. Low, Quality of life in patients with postural tachycardia syndrome, Mayo Clin. Proc. 77 (2002) 531–537.
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