Normal versus abnormal: What normative data tells us about the utility of heart rate in postural tachycardia, 2019, Baker and Kimpinski

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https://www.autonomicneuroscience.com/article/S1566-0702(18)30298-4/abstract
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Short Communication - Autonomic Neuroscience


The autonomic reflex screen (ARS) has been established as an important clinical tool in the evaluation and diagnosis of autonomic disorders ( Low, 2003 ). Specifically, passive Head-up Tilt (HUT) to a minimum 60° angle from the horizontal provides an orthostatic challenge that is sensitive in diagnosing disorders of orthostatic intolerance, including but not limited to, neurogenic orthostatic hypotension, autonomic failure, postural orthostatic tachycardia syndrome, syncope, etc. ( Low and Benarroch, 2008 ).

While various pathologies can adversely affect normal autonomic functioning, age also plays a significant role in the responsiveness and integrity of the autonomic nervous system. Therefore, from a clinical perspective it is important to acquire and maintain normative data across various age groups to more clearly pars out the effects of normal aging versus a pathological state. For example, the current clinical definition of postural orthostatic tachycardia syndrome (POTS) is a heart rate (HR) increment ≥30 bpm on HUT or active standing and the absence of orthostatic hypotension (Low et al., 2008 ). However, in children and adolescents, previous reports demonstrate considerable overlap between patients and controls with 42% of the controls meeting or exceeding the HR criteria for POTS ( Singer et al., 2012 ). Moreover, in 2015 the Heart Rhythm Society released an expert consensus statement observing a HR increment ≥40 bpm should be considered in individuals aged 12–19 years ( Sheldon et al., 2015 ). However, a growing source of literature has begun to accumulate to suggest that these findings have expanded such that even young adults frequently manifest benign postural tachycardia at levels ≥30 bpm on HUT without any associated orthostatic symptoms ( Baker and Kimpinski, 2015 ).

To better understand ‘normal’ values, and to accurately assess the presence or absence of disease, clinicians require the most up-to-date and representative sample that can be acquired. As such, it is important for individual clinics to generate their own normative dataset to account for differences between different geographical regions, populations and laboratories ( Low and Benarroch, 2008 ). Therefore, the objective of the current report was to provide normative hemodynamic values with a specific focus on heart rate and blood pressure changes during Head-up Tilt that is representative of young, middle aged and older individuals from Ontario, Canada.
 
Thanks to @MECFS Skeptic for posting about this paper on another thread.
The authors did 5 minute tilt table testing in a sample of the general population and found that POT was quite common. The median heart rate increase in young people (18-29 years) was 33 the 95% was 50.9. That indicates that this is very common in healthy people.

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The authors write:

"[given...] the lack of any clinically significant orthostatic symptomatology, we would argue that the current hemodynamic values represent normal orthostatic responses, despite meeting the physiological criterion for POTS. [...] We would argue this point further to suggest that even among young healthy adults the current HR increment of 30 bpm is a normal response, warranting reconsideration in age groups beyond pediatric patient populations. Our young adult population (18–29 years) attained an average HR response of 33.7 bpm on HUT, with ΔHR's > 40 bpm for individuals in the 95th percentile. So why is this important? The age range for most POTS patients is 15–40 years (Low et al., 2008). Given the high propensity for young healthy adults to express higher HR increments on orthostatic challenges, it is reasonable to question whether younger individuals who present with, arguably a normal HR response, along with some constitutional symptoms such as generalized lightheadedness, dizziness, fatigue, etc. that aren't appropriately interpreted, may be over diagnosed with POTS."
 
These authors have been involved in other relevant studies.

A prospective 1-year study of postural tachycardia and the relationship to non-postural versus orthostatic symptoms.
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 < 0.05)....
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.


The Orthostatic Discriminant and Severity Scale (ODSS): an assessment of orthostatic intolerance.

Higher postural heart rate increments on head-up tilt correlate with younger age but not orthostatic symptoms.
 
There were 252 participants in this study of which 123 in the age group of 18-29 (where POTS diagnosis is common).

They only did 5 instead of 10 minute testing but don't think that would impact the conclusion (one would expect the HR increase to be even higher with 10 minute testing).

Half of the 123 healthy young people had an HR increase of 33 or higher. 5% had an increase of 50.9 of higher.
 
The original criterion in the 1993 Schondorf-Low paper was 2SD above the mean for a sex-matched control population which excluded children and adolescents. I'm not sure who originally proposed the 30bpm value but in the 2011 consensus statement the definition is characterized by a sustained heart rate increment of 30 beats/minute within 10 min of standing or head-up tilt. . . For individuals aged 12–19 years the required increment is at least 40 beats/minute.

I don't have the energy to check right now but the history is fairly well-documented in the Gall et al. "Postural Tachycardia Syndrome" book.
 
This paper (link) may also be of interest:
However, while the 10-minute tilt correctly identified 93% of the POTS patients, it also identified 60% of the normal control subjects as having orthostatic tachycardia (false positives). This suggests that at 10 min for tilt, the 30 bpm criterion is highly sensitive, but has poor specificity. By increasing the HR cutoff to 37 bpm, the test was made much more specific (40% to 73%) while maintaining good sensitivity

Also, of some potential interest given the use of POTS criteria in paediatric populations - from a paediatric study (link):
Adult diagnostic criteria for OI and POTS have been adopted in studies on OI in the pediatric population, although little is known about the normal range of orthostatic HR and HR increment in children and adolescents.[6–9] We and others have observed higher, asymptomatic orthostatic increases in HR in normal adolescents, an observation that was further underlined in a recently reported study among high-school students in the community of Rochester, MN, which reports the HR increment with active standing in normal high-school students to be as high as 48bpm.

And an older study in adolescents:
Orthostatic measurements in a normal adolescent population may result in a heart rate increase of 40 to 50 beats per minute and a systolic blood pressure decrease of 15 mm Hg.
 
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Thanks for the useful references @Nightsong

Found some other ones too:

Orthostatic heart rate does not predict symptomatic burden in pediatric patients with chronic orthostatic intolerance - PubMed (nih.gov)
Patients were divided into two groups: those with HR increase of 30–39 bpm, and those with HR increase of ≥40 bpm or upright HR of >120 bpm. A total of 28 symptoms described prior to diagnosis were evaluated using chi-square testing to assess for signifcant diferences. Results Only insomnia was found to be signifcantly diferent between the two groups. The other 27 symptoms showed no signifcant diference as a function of HR.

Orthostatic intolerance without postural tachycardia: how much dysautonomia? - PubMed (nih.gov)
Eighty-four POTS and 100 OI fulfilled inclusion criteria, 89 % were females. The mean age was 25 and 32 years, respectively. Clinical presentation, autonomic parameters, laboratory findings, and degree of deconditioning were overall similar between the two groups,

Higher heart rate increments on head-up tilt in control subjects are not associated with autonomic dysfunction - PubMed (nih.gov)
Heart rate increment on HUT did not show a correlation with Composite Autonomic Severity Score (CASS) and the individual CASS scores were low (score 0/10, n = 103; score 1/10, n = 27; score 2/ 10, n = 1; score 3/10, n = 2) [...] These findings argue that the development of Postural Tachycardia Syndrome involves mechanisms that potentially occur independently of heart rate increment.
 
I think that patients who have no previous experience with this test will have raised heart beats simply because it is a new procedure to them and do not fully understand everything that will happen . results would be skewed by this.
I actually haven't come across a paper that tries to assess pre-test apprehension in head-up tilt, although while searching yesterday I found a Roma et al. paper that briefly considered the potential effects while performing passive-standing tests in POTS patients:
Our data show that the supine HR before a 10-minute standing test was significantly higher than the post-test supine HR. In the full sample, an additional 14% more adolescents and young adults were categorized as having POTS when the definition of their lowest supine HR included a brief 2-minute post-test measurement along with the conventional pre-test measure.
those who met criteria for POTS based on their post-test supine HR values alone had significantly elevated pre-test supine HRs, suggesting that uncertainty or apprehension about what was about to occur during an unfamiliar test was associated with atypical pre-test cardiac acceleration above their usual supine baseline values
 
I actually haven't come across a paper that tries to assess pre-test apprehension in head-up tilt, although while searching yesterday I found a Roma et al. paper that briefly considered the potential effects while performing passive-standing tests in POTS patients:
This abstract from a German study did 10 repeated tests and found that it did not lead to stable results.
Intra- and interindividual reproducibility of heart rate variations in the tilt-table test - PubMed (nih.gov)
The tilt-table test was repeated 10 times in all 40 subjects under standardised conditions, and heart rate and blood pressure response were presented in a diagram. Reproducible courses of initial heart rate response were not seen, neither on intra- nor on interindividual comparison. After an initial rise, most subjects showed a rather horizontal course of heart rate, whereas others presented a heart rate response similar to that in the Ewing test, with an initial rise of heart rate around the 15th beat, followed by a decrease, and a maximum around the 30th beat. However, all subjects showed considerable variations in heart rate response within the 10 tilting manoeuvres. A reliable quotient comparable with the 30/15 ratio (Ewing's ratio) in active orthostasis was not seen. Based on these results, we conclude that the initial heart rate response in the tilt-table test is not suitable for routine diagnosis of autonomic regulation disorders, since it is not sufficiently reproducible in healthy individuals.
 
Also, of some potential interest given the use of POTS criteria in paediatric populations - from a paediatric study (link):
I suspect that study forms the justification for the > 40 bpm threshold for children, even though it showed that 5% of healthy controls had a HR increase higher than 42 bpm.

The study not included healthy controls but also more than 600 children who were referred with diagnoses of orthostatic intolerance, lightheadedness, orthostatic tachycardia, and postural tachycardia. Then they compared to two and the difference was minimal. At the 10 minute point the 22 healthy controls even had a higher HR increase than the patients with orthostatic symptoms.

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The authors write:
we included all patients in whom OI was clinically suspected and found that although a significantly higher orthostatic HR rise was seen, that difference was less than 5 bpm on average. This overlap is intriguing and raises the question whether HR increment alone can be relied upon when diagnosing OI in a pediatric setting. Considering that the absolute orthostatic HR showed a greater and more consistent difference between patients and controls, one could argue that the absolute orthostatic HR may be more important for the development of orthostatic symptoms and should be emphasized more in diagnosis of pediatric OI. One could ask the question whether OI at this age may not depend as much on HR as it does in adults or even whether the use of HR criteria in general may not be appropriate.

Source: https://www.sciencedirect.com/science/article/abs/pii/S0022347611008845
 
This paper (link) may also be of interest:
Same finding here: 9 of the 15 controls (60%) had an HR increase that was higher than 30 bpm after 10 minute passive tilt table testing. With a 10 minute standing test, 5 (33%) met the POT criterium.
Using only the current 30 bpm criterion, 80% of control subjects would have been diagnosed with orthostatic tachycardia (false positive rate) using a 30 minute tilt table test, compared to only 47% with a 30 minute stand. The false positive rate for a 10 minute tilt was 60%, compared to 33% during a 10 minute stand.

They proposed to increase the HR cutoff to 37 bpm which resulted in a sensitivity of 40% and a specificity of 73%. That means that 60% of the POTS patients would no longer meet that threshold, while 27% of the healthy controls would still do.

Instead of requiring a new threshold those numbers show that orthostatic tachycardia testing cannot reliable discriminate between those with orthostatic symptoms and healthy controls.
 
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I've found an earlier reference than the 2011 consensus statement for the use of a 30 bpm threshold: this 1999 follow-up paper by Low et al.
Inclusion criteria were (1) baseline sinus rhythm with no evidence of arrhythmia or cardiac disease; (2) sustained heart rate increment of 30 beats/min or greater in response to 10 minutes of tilt-up for 60% or more of the recording after head-up tilt; and (3) 3 or more clinical symptoms that de- velop on standing up or after head-up tilt and resolve with recumbency.

ETA: I'm not sure that that paediatric study could have formed the basis for the 40 bpm recommendation in the consensus statement since it was published on October 13 2011 and the consensus statement was published on March 24 2011.
 
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