Novel gravity exercise improves orthostatic symptoms in PoTS

1
A feasibility study to ascertain the impact of a novel
gravity induced exercise interventionfor individuals
with Postural Tachycardia Syndrome and establish
where the intervention mayfit in the multifaceted
management of the condition.
Student: Robert Andrew Ballantine
Student Number: 120007600
Supervisors: Professor Julia Newton and Victoria Strassheim
Degree Programme: MSc Medical Sciences
Academic Year: 2015-2016
Word Count: 6835

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1 Abstract:
Background:
Postural Tachycardia Syndrome (PoTS) is commonly underpinned by a dysfunctional
Autonomic Nervous System (ANS). A reduction in gravitational exposure in this population
has been shown to both instigate and perpetuate the condition. By conducting 8 exercises in
the presence of gravity, this novel intervention aimed to alleviate the debilitating orthostatic
symptoms that characterise the condition.
Methods:
7 patients with PoTS completed this novel exercise intervention run once a month over a 5
month period. The first patient was part of a pilot study and completed the intervention
individually, whereas it was delivered in a class format for the remaining 6. Patients attempted
to complete as many asymptomatic repetitions as possible of 8 progressively more difficult
exercises that aimed to directly challenge and therefore improve their dysfunctional ANS, the
root of their orthostatic symptoms. Objective and subjective measures were used to assess
progression throughout the intervention.
Results:
The intervention had a high rate of compliance, with no drop outs over its duration. In 3 out
of the 7 patients, there was an improvement in cumulative monthly repetitions completed,
combined orthostatic symptoms, fatigue impact score and measures of general health. For the
other 4 patients, results often fluctuated on a month per month basis. Even for these patients
though, the intervention did reinforce pacing. Functional activity levels were shown to
increase in two cases by 13% and 37%.
Conclusion:
Overall, this novel intervention had a variable effect on the 7 patients involved, however for
those that did improve, the impact it had was momentous. The patients’ background medical
and behavioural stability were determined to be key components in their progress. Further
studies should focus on ascertaining the most efficacious target group for the application of
this intervention.
2 Acknowledgements:
I would like to thank my two supervisors Professor Julia Newton and Victoria Strassheim for
their kind and unending support and guidance throughout this project. In addition to this,
they have allowed me to take on other ventures alongside my dissertation and gain both
extremely valuable and rewarding clinical experience with patients. I thank them for
entrusting me with this responsibility. I would also like to thank all of the individuals who
have participated in the exercise intervention. Their willingness and commitment to it whilst
still juggling all of their other responsibilities is incredibly motivating. Finally, I would like to
thank the members of staff at the CRESTA clinic, where the intervention took place, for their
tireless hard work.

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3 Contents:
1 Abstract:.............................................................................................................................. 2
2 Acknowledgements:............................................................................................................2
3 Contents:............................................................................................................................. 3
4 List of Figures:..................................................................................................................... 5
5 List of Tables: ...................................................................................................................... 5
6 List of Abbreviations: ..........................................................................................................5
7 Introduction:....................................................................................................................... 7
7.1 The Physiological Response to Standing:.....................................................................8
7.2 Postural Tachycardia Syndrome (PoTS):......................................................................9
7.2.1 Subtypes of PoTS:....................................................................................................10
7.2.2 Current Management and Treatment of PoTS:....................................................... 11
7.3 Exercise as an Intervention for Individuals with PoTS:............................................... 11
7.3.1 Rationale and Development of the Novel Gravity Induced Exercise Intervention: .12
7.4 Outline of this study:..................................................................................................13
8 Hypothesis and Aims:.........................................................................................................13
9 Materials and Methods:......................................................................................................13
9.1 CRESTA fatigue clinic:................................................................................................13
9.2 Inclusion Criteria for the Intervention:.......................................................................14
9.3 Tests and Questionnaires used:..................................................................................14
9.4 Delivery and Tailoring of the Exercise Intervention: ..................................................15
9.5 Wider Purpose of the Study:.......................................................................................17
10 Results:...............................................................................................................................17
10.1 Patient Characteristics:...............................................................................................17
10.2 Cumulative Monthly Repetitions:...............................................................................19
10.3 Compliance with the Intervention:............................................................................20
10.4 Effect of the Intervention on Orthostatic Symptoms:.................................................21
10.5 : Effect of the intervention on General Health Measures:.......................................... 22
10.5.1 Fatigue Impact Scale (FIS) Score: ....................................................................... 22
10.5.2 Combined Health Today and Likert Scale Scores:.............................................. 23
10.5.3 Functional Activity Levels: ................................................................................. 25
11 Discussion:........................................................................................................................ 28
11.1 Why did some patients improve with the intervention?............................................28
11.2 Why did other patients not improve with the intervention?.....................................29

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11.3 What is the future for the intervention and where may it fit in the multifaceted
management of the condition?............................................................................................. 30
11.4 How did this intervention meet the aims of this study?............................................ 32
12 Advantages and Limitations:............................................................................................. 33
13 Conclusions and Further Work:........................................................................................ 33
14 References:........................................................................................................................ 34
15 Appendices:....................................................................................................................... 37
15.1 Appendix 1:................................................................................................................. 37
15.2 Appendix 2:................................................................................................................ 39

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4 List of Figures:
Figure 1 – Role of the Sympathetic and Parasympathetic branches of the ANS.
Figure 2 – Cardiac parameter changes upon standing.
Figure 3 – Criteria needed for PoTS diagnosis.
Figure 4 – Subtypes of PoTS.
Figure 5 – PoTS Treatment and Management Options.
Figure 6 – Hydrostatic Column and Pooling Areas Location.
Figure 7 – Specialist gym facility at the CRESTA clinic.
Figure 8 - Exercise 1 of the intervention.
Figure 10 – Exercise 3 of the intervention.
Figure 15 – Monthly cumulative repetitions graph.
Figure 16 – Monthly combined orthostatic symptoms graph.
Figure 17 – Fatigue Impact Scale progression graph.
Figure 18 – Combined monthly Health Today and Likert Scale graph.
Figure 19 – Activity Logs Patient 1.
Figure 20 – Activity Logs Patient 6.
Figure 21 – Exercise Adaptation Curve.
Figure 22 – Overtraining Curve.
Figure 23 – N=1 Study
Figure 24 – RCT Study.
Figure 25 - Foci of Modifications for PoTS patients.
5 List of Tables:
Table 1 – Questionnaires used in this study.
Table 2 - Patient characteristics.
Table 3 – Monthly cumulative repetitions.
Table 4 – Monthly intervention attendance.
Table 5 - Monthly Orthostatic Symptoms.
Table 6 – Monthly Fatigue Impact Scale score.
Table 7 – Monthly combined Health Today and Likert Scale scores.
Table 8 – Overall changes in Objective and Subjective measures.
6 List of Abbreviations:
OI – Orthostatic Intolerance
ANS – Autonomic Nervous System
SV – Stroke Volume
BP – Blood Pressure
CO – Cardiac Output

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TPR- Total Peripheral Resistance
HR – Heart Rate
SNS – Sympathetic Nervous System
BPM – Beats Per Minute
PoTS – Postural Tachycardia Syndrome
CFS/ME – Chronic Fatigue Syndrome/Myalgic Encephalitis
CRESTA – Clinics for Research and Themed Assessment
OGS – Orthostatic Grading Scale
OH A/S – Orthostatic Hypotension Activity/Symptom
FIS – Fatigue Impact Scale
DNA – Did Not Attend
RCT – Randomised Control Trial

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7 Introduction:
According to the World Health Organisation, chronic diseases will underpin the most
significant cause of disability by 2020. Accompanying symptoms faced by the individuals
affected, such as fatigue and stress, will be the greatest challenge to future healthcare
provision (1). Symptoms of Orthostatic Intolerance (OI) have been found in up to 9 out of 10
people with chronic illnesses (2).
Individuals with OI experience symptoms when they stand up such as light headedness,
palpitations and dizziness that are alleviated when they lie down (3). These symptoms are
collectively referred to as orthostatic symptoms and they are often a by-product of a
dysfunctional Autonomic Nervous System (ANS) (4). The ANS is integral to involuntary
responses in the human body and is technically subdivided into sympathetic, parasympathetic
and enteric branches. The sympathetic and parasympathetic branches effectively antagonise
each other, with the sympathetic branch modulating the ‘fight or flight’ response and the
parasympathetic branch coordinating the ‘rest and digest’ response, as shown in figure 1. The
ANS in its entirety underpins the regulation of homeostatic processes and key bodily functions
such as heart rate and blood pressure, digestion and the stress response (5).
Figure 1: Comparing the effect of the sympathetic and parasympathetic branches of
the Autonomic Nervous System on the human body.

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7.1 The Physiological Response to Standing:
The physical act of standing is a stress on the human body. When an individual stands, 500ml
– 1000ml of blood accumulates in their lower abdomen, buttocks and legs as a result of gravity.
Most of the blood shift occurs in the veins due to their high compliance. This redistribution of
blood leads to a reduction of intrathoracic blood volume to the heart. As a result of the Frank -
Starling mechanism, Stroke Volume (SV) can decline by approximately 30-40% (6). Intricate
compensatory mechanisms maintain blood pressure at a fairly constant level despite this drop
in SV. The interrelationships of key cardiovascular parameters is detailed below.
Blood Pressure (BP) = Cardiac Output (CO) x Total Peripheral Resistance (TPR)
CO = Heart Rate (HR) x SV
Therefore: BP = HR x SV x TPR
As there is a fall in SV upon standing, HR and TPR increase to counteract this and help to
maintain BP. Mechanisms in place include a surge in Sympathetic Nervous System (SNS)
stimulation of the heart, increasing its rate by 15-20 beats per minute (bpm), and augmented
peripheral SNS stimulation, leading to arteriolar vasoconstriction and increased TPR (6).
These changing cardiovascular parameters are shown graphically in figure 2.
Additionally, the medulla oblongata in the brain incites vasoconstriction of smooth muscles
within arterioles, in particular those in the brain, to increase blood pressure against the force
of gravity. This aims to alleviate symptoms associated with cerebral hypoperfusion such as
dizziness, lightheadedness and fainting (7). Orthostatic stabilisation is maintained within <1
minute in a healthy person (8).
Figure 2: – Changes in various
cardiovascular parameters from
supine (lying flat) to standing.
Figure adapted from Smith J et al
(9).

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7.2 Postural Tachycardia Syndrome (PoTS):
Postural Tachycardia Syndrome (PoTS) is an example of an orthostatic condition that is
commonly underpinned by a dysfunctional ANS. It is five times more common in women than
men (10) and can present in all age groups. Its current prevalence in the UK is unknown. PoTS
is a group of heterogeneousdisorders that manifest themselves in a similar way clinically (11).
Individuals with PoTS often have a low blood volume (12) and their dysfunctional ANS can
lead to impaired peripheral vasoconstriction. Upon standing these two factors combine to
produce a significantly reduced venous return to the heart, leading to excessive tachycardia to
counteract this.
Obtaining a diagnosis of PoTS is often a fairly protracted process, due to both the lack of
awareness of the disorder and the battery of tests needed to rule out other conditions affecting
the ANS (13). The criteria for acquiring a diagnosis of PoTS are displayed in figure 3.
Figure 3: Criteria needed
for PoTS diagnosis.
Figure adapted from Raj
S (14).
Other orthostatic symptoms such as dizziness, headaches and syncope present in this
population, as well as customary symptoms of visual problems, gut problems and high levels
of fatigue (15). The nature and often multiple combinations of these symptoms can be
extremely debilitating, with approximately 25% of those with PoTS unable to work (16).
Certain triggers have been reported to accentuate these symptoms, such as excess heat,
dehydration and overly strenuous exercise (17).

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7.2.1 Subtypesof PoTS:
The modified blood flow physiology in those with PoTS has led to the subtyping of patients
depending on their altered blood flow and level of arterial resistance (18), as outlined below:
 High Blood Flow PoTS - This group has a high level of blood flow with decreased
resting peripheral resistance. This is due to deficient ANS modulated noradrenaline
release in their lower limbs and therefore attenuated postural vasoconstriction. They
have normal limb capacitance.
 Low Blood Flow PoTS - This group has a low level of blood flow as a result of high
arterial resistance, high venous pressure and low limb capacitance. A dysfunctional
ANS modulated response is reported to be present in the internal organs and lower
limbs of these patients.
 Normal Blood Flow PoTS - This group has normal blood flow with normal arterial
resistance and normal venous pressure. Evidence suggests increased pooling in their
internal organs and pelvic regional circulations.
PoTS can also be dichotomised into primary or secondary forms (19).Primary PoTS is
idiopathic and is not associated with other diseases. It can either be acquired developmentally,
follow a febrile illness, pregnancy or surgery, or be considered hyperadrenergic,which is of
genetic origin with a slower onset period. Secondary forms of PoTS occur in association with a
known disease or disorder, for example Joint Hypermobility Syndrome, Primary Sjorgens
Syndrome or Diabetes Mellitus. Finally, the deconditioning process following prolonged bed
rest can both lead to PoTS and perpetuate the condition further, as explained later on. The
various subtypes of PoTS are shown in figure 4.
Figure 4: Subtypes
of PoTS.
Figure adapted
from Conner et al
(20).

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7.2.2 CurrentManagementand Treatment of PoTS:
Due to the complexity of the condition, management and treatment of PoTS is often
multifaceted and bespoke to each patient. It may be dictated to an extent by their specific
PoTS subtype, or for those with secondary forms, their underlying condition. Figure 5 shows
the different treatment and management strategies avaliable for PoTS.
Figure 5: Flowchart displaying the plethora of treatment and management options available
for individuals with PoTS. Figure adapted from an article by Grubb (21).
7.3 Exercise as an Intervention for Individuals with PoTS:
In figure 5, exercise is listed as a physiological therapy for PoTS. This is evidenced by research
showing the beneficial role of exercise as a symptomatic management strategy for PoTS (22-
24). Current exercise interventions used for those with PoTS normally fall under the umbrella
of Graded Exercise Therapy, with certain types aiming to improve aerobic capacity, and
others, such as resistance training, improving the skeletal pump mechanism (25). A
consideration of these current interventions is that they may work by improving the
compensatory mechanisms in place for a dysfunctional ANS rather than targeting the
defective ANS itself. The exercise intervention used in this study specifically targets areas of
ANS regulation, as explained in the following section.

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7.3.1 RationaleandDevelopmentof theNovel GravityInduced Exercise
Intervention:
Individuals with PoTS understandably avoid the stimulus of gravity, as it is their exposure to it
that causes their orthostatic symptoms. However, a prolonged period of time in a low gravity
or microgravity environment can have a detrimental effect on the human body, as
demonstrated in studies conducted on astronauts (26-28). This detrimental effect is partly
attributable to a reduction in the functional capacity of certain bodily systems that have
evolved to operate in spite of gravity. The conjunctive action of the ANS and Cardiovascular
System upon standing, as explained in section 7.1, is an example of this. The decline in
functional capacity of these systems is due to their reduced challenge of gravity; they
effectively ‘decondition’ against it in the same way that unchallenged muscles degrade (29).
This attenuates the compensatory mechanisms in place to deal with further prospective
gravitational exposure, leading to greater orthostatic symptoms and a continuation of this
vicious cycle.
This intervention aimed to stop this vicious cycle by specifically challenging the cause of the
debilitating orthostatic symptoms seen in those with PoTS, their dysfunctional ANS. The
relationship between the ANS and CV system was specifically targeted, as improving their
association, by challenging them in the presence of gravity, would help deliver blood to the
correct areas, especially the brain, leading to a consequential decline in symptoms and
enhancement of function. Firstly, the ANS modulated hydrostatic column, which maintains
adequate blood flow between the heart and the brain, was challenged by exercises that
involved relocating the head in relation to the heart. Secondly, pooling areas were addressed
by exercises that involved moving the head and heart in relation to the ground. Figure 6
highlights the key targets of the intervention. Research by Antonutto and Di Prampero (30)
underpinned these concepts.
Figure 6 – The location of
the Hydrostatic Column
and Pooling Areas, both
key targets of the
intervention.

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7.4 Outline of this study:
Seven individuals with PoTS undertook this intervention. One was a pilot patient who
completed the intervention individually. This allowed for a refinement of the protocol in place
and to ensure that patients would be able to participate. Subsequently, a further six completed
the intervention in a specifically run group exercise class. The intervention took place once a
month and was run over a 5 month period.
8 Hypothesis and Aims:
The hypothesis for this study was that a novel gravity induced exercise intervention conducted
once a month over a 5 month period will have a positive impact on the symptoms of a small
group of individuals with PoTS.
There were four main aims of this study:
 To determine whether a group of patients would comply with the intervention, as
demonstrated by their attendance throughout its duration.
 To determine the efficacy of the intervention on the improvement of orthostatic
symptoms, its intended target.
 To determine whether there was an improvement in measures of general health as a
result of the intervention.
 To determine the future direction of this intervention and its potential role as a
management strategy of PoTS.
9 Materials andMethods:
9.1 CRESTA fatigue clinic:
The intervention occurred in the specialist gym facility (see figure 7) at the Clinics for
Research and Themed Assessment (CRESTA) fatigue clinic in Newcastle upon Tyne (31).
Figure 7 – A photograph showing
the specialist gym facility at the
CRESTA clinic, the location of the
intervention.

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Table 1 - Plethora of questionnaires completed by the study participants.
9.2 Inclusion Criteria for the Intervention:
All patients must have been diagnosed with PoTS, as determined by the diagnostic criteria
evident in figure 3. Due to the timing of the intervention, a Monday morning at 10am, the
patients involved were often those who were able to offset external factors such as childcare
and work commitments.
9.3 Tests and Questionnaires used:
Upon arrival at the clinic, all individuals complete an active stand test. An active stand test
can diagnose PoTS and give a general indication of the functioning of the ANS and CV system.
For those who participated in the intervention, a battery of questionnaires was completed
every month, evaluating different aspects of their condition, as shown in table 1.
To ascertain whether there were changes in activity levels within the 5 month duration of the
intervention, patients were asked to fill out an activity log at the start, middle and its
conclusion. A selection of the questionnaires used and an example of an activity log is shown
in Appendix 1.
Questionnaire Name Function Directionality Validated in
this
population?
Orthostatic Grading Scale
(OGS)
Symptoms of OI. Lower Score =
Improved
Yes
Orthostatic Hypotension
Activity/Symptom
assessment (OH A/S)
Severity of OI symptoms and how
these symptoms affect activity.
Lower Score =
Improved
No
EQ-5D-5L Simple, standardised and generic
measure of healthstatusforclinical
and economic appraisal.
Lower Score =
Improved
Yes
Health Today Value of 0 -100 to evaluate
patient’s health today.
Higher Score =
Improved
Yes
Fatigue Impact Scale (FIS) Impact fatigue has on patient’s
everyday life.
Lower Score =
Improved
Yes
Likert Function Assessmentof patient’s perspective
on their condition.
Higher Score =
Improved
No
Intervention Feedback Individualised feedback of the
exercise intervention.
N/A No

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9.4 Delivery and Tailoring of the Exercise Intervention:
An active stand test was completed by every patient before the commencement of the
intervention, at its midpoint and at its conclusion. The 1 hour intervention periodically began
with the completion of the aforementioned questionnaires and an unstructured discussion
between the specialist physiotherapist who ran the intervention and the patients about their
health over the previous weeks. Following this, the PoTS patients completed as many
asymptomatic repetitions as possible of each exercise. Depending on the severity of their
symptoms, patients often only accomplished very low repetitions or even missed out certain
exercises. Adequate rest periods were ensured by consistent dialogue between the patients
and specialist physiotherapist, in addition to those in the group exercise class always
completing each exercise in the same consecutive order.
The 8 exercises conducted in the intervention, shown below in figures 8-14, were designed to
become progressively more challenging throughout. Exercise 8 does not have a figure as it
entails getting up from the floor in any fashion possible, an individualised process.
Following the 8 exercises, the PoTS patients all completed 10 minutes of meditation to
conclude the intervention. They were then given a copy of how many repetitions they had
completed, feedback questionnaires and on specific occasions a weekly activity log to fill in.
A monthly interval was chosen between each juncture of the intervention to allow for
adequate recovery, as directly challenging the multifaceted ANS can have profound effects on
the rest of the body and its homeostatic processes (32).
Figure 8 – Exercise 1 of the intervention: Modified
sit up.
Figure 9 – Exercise 2 of the intervention: Movement
of head to the ground.

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Figure 12 – Exercise 5 of the intervention: Sit to
stand from a chair.
Figure 10 – Exercise 3 of the intervention: Full
upper body raise from a position of hands and
knees.
Figure 11 – Exercise 4 of the intervention:
Sitting arms raise.
Figure 13 – Exercise 6 of the intervention: Standing
arms raise.
Figure 14 – Exercise 7 of the intervention:
Standing incremental roll down, taking arms down
to the floor.

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9.5 Wider Purpose of the Study:
This study was run as a service development, aiming to enhance the current clinical service
delivered at the CRESTA clinic. The use of quality and service improvement tools are
frequently applied in health care settings to improve the quality, efficiency and productivity of
the patient care provided (33).
By gaining clinical observer status, I was able to observe the intervention taking place at the
CRESTA clinic and interact with a wide range of patients and their families.
10 Results:
10.1 Patient Characteristics:
A broad demographic of patients participated in the intervention. This is attributed to the
heterogeneous nature of the condition in its aetiology, affliction and presentation. Table 2
briefly describes the characteristics of each patient. The relative stability of the patient’s home
and work background can hugely impact on their symptoms and progression, hence the
reason for it being displayed in table 2. Patient 1 is the pilot patient who conducted the
intervention individually, whereas patients 2 – 7 participated in the exercise class.

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Patient ID Age Gender Condition (s) Home
Background
Work
Background
1 44 Female PoTS,Chronic
Fatigue
Syndrome/Myalgic
Encephalitis
(CFS/ME)
Livesat home
withparents.
Bedboundfor
10-15 years.
Stable.
Unable to work
due to severity
of symptoms.
2 40 Male PoTS,Psoriatic
Arthritis
2 young
children,wifeis
pregnantwith
anotherchild.
Unstable.
Workedas
joiner.Unable
to currently
workdue to
fatigue.
3 27 Female PoTS Liveswith
Partner.Stable.
Completing
PhD,extremely
demanding.
Fluctuating
stability.
4 29 Male PoTS Liveswith
parents.Stable
Works full time,
manageswork
well.Stable.
5 27 Female PoTS,Joint
Hypermobility
Sydrome,Irritable
Bowel Syndrome.
Veryprevalent
tachycardia.
Liveswith
partner.Stable.
Works full time,
unsympathetic
employer.1
hour commute.
Unstable.
6 35 Female PoTS,CFS/ME.
VitaminD
deficiency.
Liveswith
parents.Stable.
Fatigue too
severe to
accommodate
employment.
7 54 Female PoTS,Arrhythmia,
Fibromyalgia,
Connective Tissue
disorder.
Underactive
Thyroid.Recovered
frombreastcancer.
Liveswith
partnerand
twogrown up
sons.Fairly
stable.
Retirednurse.
Fatigue too
severe to
accommodate
employment.
Table 2 – Patient characteristics.

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0
10
20
30
40
50
60
70
1 2 3 4 5 6 7
CumulativeRepetions
Patient ID
Monthly Cumulative Repetitions completed
Month 1 Month 2 Month 3
Month 4 Month 5
10.2 Cumulative Monthly Repetitions:
The objective measure of the number of completed repetitions of each exercise every month
was important to assess as it was indicative of progress throughout the intervention. A
cumulative value of completed repetitions for all 8 exercises each month was calculated for
each patient. This is shown both in table 3 and graphically in figure 15. For reference,DNA =
Did Not Attend.
Cumulative Repetitions per Month
Month 1 Month 2 Month 3 Month 4 Month 5
PatientID
1 30 56 60 40 40
2 27 23 11 DNA 13
3 26 DNA 8 23 16
4 DNA 32 35 37 DNA
5 20 22 26 29 4
6 21 23 28 28 0
7 18 DNA 23 9 16
Table 3 – Monthly cumulative repetitions of all 8 exercises completed by the patients.
Figure 15 – A graph to show the monthly cumulative repetitions of all 8 exercises
completed by the patients.

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There were some months where patients could not participate in the intervention, however
for all individuals there was data from at least three months to assess. There was an increase in
the number of completed cumulative repetitions from the first month to the end of the study
in patients 1, 4 and 6. According to the specialist physiotherapist who ran the intervention,
patient 1 initially pushed herself too hard each month, hence the high number of repetitions.
She subsequently reduced her repetitions, helping her symptoms stabilise and functional
activity increase. Patients 4 and 6 started with lower repetitions and made fairly steady
progress in the number of repetitions that they completed over the 5 months. This was also
the case for patient 5 except for her final month. The cumulative repetitions for patients 2, 3
and 7 fluctuated fairly prominently over the 5 months and a general improvement was not
seen.
10.3 Compliance with the Intervention:
The level of patient compliance towards an intervention was indicative of their feelings
towards it. The completion rate of exercise interventions in studies concerning PoTS is often
fairly low as the intervention can precipitate detrimental symptoms for the patient. Table 4
documents the monthly attendance of all the patients completing the intervention.
Intervention Compliance per Month
PatientID
1     
2    DNA 
3  DNA   
4 DNA    DNA
5     
6     
7  DNA   
No one dropped out of the study over its 5-month duration. This high level of compliance
indicates that the patients felt the intervention aided them in some way, notwithstanding the
symptoms it may have provoked. The DNA rate was 14%, with mitigating circumstances for a
lack of attendance on occasion, such as holidays, work or family commitments.
Table 4 – Monthly attendance for all patients.

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0
20
40
60
80
100
120
1 2 3 4 5 6 7
CombinedOrthostaticSymptoms
Patient ID
CombinedMonthly Orthostatic SymptomTrends
Month 4 Month 5
10.4 Effect of the Interventionon Orthostatic Symptoms:
The intended target of this intervention was to alleviate the debilitating orthostatic symptoms
that characterise PoTS. If successful, this intervention would indicate that specifically
challenging the ANS is a potential treatment and management strategy for the condition. The
monthly results of the OGS and OH A/S questionnaires, described in section 9.3, have been
combined to produce one single integer to determine the patients’ orthostatic symptoms.
This is shown both in table 5 and graphically in figure 16.
Combined Orthostatic Symptoms
PatientID
1 50 53 52 50 35
2 79 79 80 DNA 91
3 71 98 72 78 75
4 DNA 60 51 43 DNA
5 73 77 71 75 75
6 48 47 47 47 DNA
7 80 64 83 78 94
Table 5 – Monthly combined orthostatic symptoms of the patients.
Figure 16 – A graphical representation of the patients’ monthly combined orthostatic
symptoms.

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There are contrasting results evident from both table 5 and figure 16. The orthostatic
symptoms of patients 1, 4 and 6 decrease from the initial measurement in month 1, albeit in a
different manner. Patient 1’s orthostatic symptoms show an initial increase before a fairly steep
decline at the end of the intervention; patient 4’s shows a steady decline throughout; patient
6’s stay very steady, with just a slight decline measured. The orthostatic symptoms of patients
2, 3, 5 and 7 increase from the initial measurement in month 1, again though in different
fashions. There is little perturbation in the orthostatic symptoms of patients 2,3 and 5
throughout the intervention except for one noteworthy fluctuation seen in patient 2 and 3,
occurring in different months. Patient 7 had fairly fluctuating orthostatic symptoms
throughout the intervention.
To conclude, an overall improvement in combined orthostatic symptoms was seen in 3 out of
7 of the patients, 43%.
10.5 : Effect of the intervention on General Health Measures:
Another way to evaluate the impact of the intervention was to determine whether there was
any progression in measures of general health during its 5 month duration. If shown to have a
positive impact on general health, then this would provide added weight for its use as an
interventional strategy for PoTS.
10.5.1FatigueImpactScale (FIS) Score:
Firstly, the influence of the intervention on the 7 patients’ level of fatigue was evaluated. A
decline in their fatigue as a result of the intervention would be a definite positive as this
symptom can be extremely debilitating for those with PoTS and the root of a plethora of
issues. The patients’ level of fatigue was assessed by their monthly FIS scores, as shown in
table 6 and graphically in figure 17.
FIS score
PatientID
1 79 70 71 65 60
2 117 109 114 DNA 126
3 91 118 103 114 102
4 DNA 75 66 60 DNA
5 115 128 120 132 132
6 107 108 107 104 DNA
7 129 111 113 122 141
Table 6 – Monthly FIS scores.

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0
20
40
60
80
100
120
140
160
1 2 3 4 5 6 7
FISScore
Patient ID
FIS score progression
Month 4 Month 5
Similar to the orthostatic symptoms discussed in section 10.4, there was a variable effect of the
intervention on the patients’ level of fatigue. An improvement in the measure was seen in
patients 1, 4 and 6, meaning that fatigue had less of an impact on them as the intervention
went on. For patients 2,3,5 and 7, FIS increased over the duration of the intervention. Patients
3 and 7 had larger fluctuations in their FIS than patients 2 and 5.
10.5.2 Combined HealthTodayandLikertScaleScores:
Secondly, the impact of the intervention on both the patients’ evaluation of their current
health and also their perspective of their condition was assessed by combining the monthly
results of their Health Today and Likert Scale questionnaires. A positive change in these
parameters, even without changes in symptoms, would be a reflection of the effect of the
intervention on the mental state of the individual, which can play a significant role in their
ability to adapt and recover from the condition. This is shown in table 7 and graphically in
figure 18. The Likert Scale was not used as an outcome measure in the pilot study, therefore
there are no results for patient 1.
Figure 17 – A graphical representation of patients’ FIS score progression.

24
Table 7 – Monthly combined Health Today and Likert Scale results for all patients who
competed this intervention other than Patient 1.
An improvement in the combined Health Today and Likert Scale results was seen in patients
2, 3 and 4 from their first month to the conclusion of the study. These values did often
fluctuate, understandably though as the nature of the condition dictates that people have
good days and bad days. The greatest change was seen in patient 4, whose final combined
score was 11% higher than his initial score.
For patients 5, 6 and 7 there was an overall decline in combined Health Today and Likert Scale
results from their first month to the conclusion of the study. The trends followed similar
patterns to what has been seen previously for these patients, with patient 6 showing little
perturbation in these values apart from a slight dip in her final month of attendance and
patient 7 having substantial fluctuation throughout. Patient 5 showed the greatest decline in
combined score, 29%. However, it is important to note that following quite a steep decline
from month 1 and 2, patient 5’s score did stabilise and was on a slight upward trend at the
commencement of the study.
0
50
100
150
200
250
1 2 3 4 5 6 7
CombinedHealthTodayandLikertScores
Primary ID
CombinedMonthly HealthToday and Likert
Scale Score Trends
Month 1 Month 2
Month 3 Month 4
Month 5
Combined Monthly Health Today and Likert Scale scores
PatientID
1 N/A N/A N/A N/A N/A
2 109.1 126.8 124.6 DNA 126.9
3 186.1 161 170.3 228.6 196.9
4 DNA 175.6 135.1 196.9 DNA
5 105.1 63.7 77 74.2 75.1
6 128.5 129.9 132.7 117.4 DNA
7 75.9 150.9 100.3 85.6 46
Figure 18 – A
graphical
representation of
patients’
Monthly
combined Health
Today and Likert
Scale scores.

25
Figure 19 – A representation of the activity levels of patient 1 at baseline and at the end of
the intervention.
10.5.3 FunctionalActivityLevels:
The final measure of general health assessed was the activity diaries filled in by the patients.
Not all of the patients filled them in and for the results to be worthwhile presenting at least
two were needed so that a ‘before’ and ‘after’ can be established. In the activity diaries
presented below, time asleep is coloured in red, sedentary activity (e.g. time on the sofa) is in
yellow and functional activity (e.g. exercise, cooking) is in green.
Patient 1’s activity diaries are shown below in figure 19. On the left hand side is her baseline
activity levels, whereas the right hand side depicts her activity levels at the end of the
intervention.
A cumulative increase in patient 1’s functional activity and also an extended duration of this
functional activity is evident. At baseline, she spent 41 hours of her week completing
functional activity as opposed to 47 hours at the end of the intervention. The nature of what
she could now do also changed. By the end of the intervention patient 1 had begun driving
lessons for the first time, a fairly energy intensive process. Moreover, when she visited the
clinic for a follow up appointment three months after she had finished the intervention, she
declared that she had passed her driving test, a fantastic achievement and indicative of a much
greater ability to complete functional activities.

26
Figure 20 – A representation of the activity levels of patient 6 at baseline and at the end
of the intervention.
It is also of interest to look at the activity diaries of patient 6, who has CFS/ME and is unable
to work due to her fatigue, similar to patient 1. Patient 6’s activity diaries are displayed below
in figure 20, in an identical format as before.
From these activity logs it is clear that patient 6’s baseline functional activity levels were low
but did increase by the commencement of the intervention. At baseline she spent 31 hours of
her week completing functional activity whereas at the end of the intervention she spent 49
hours of her week completing functional activity, a 37% increase. For an individual who has
had CFS/ME and PoTS for 20 years, this is momentous.
The EQ-5D-5L scores were not analysed in the results section as this generic measure is
similar to that of the Health Today questionnaire. These results can be found in Appendix 2 if
required.
An overall round up of the objective and subjective measures evaluated in section 10.5 for each
patient are displayed in table 8.

27
ID Behaviour
Stability
Medical
Stability
Cumulative
Monthly Reps
Combined
Orthostatic
Symptoms
Combined
Health Today
and Likert
Score
FIS score Activity
Levels
1 Good
understandingof
conditions.Stable
Stable Initial increase,
thendecline.
Initial
increase
before steep
decline.
N/A Steady
decline.
Increased
levelsof
functional
activity.
2 Pushesthrough
relentlessly.
‘Boomand Bust’
mentality.
Unstable.
Low Bloodcell
counts.
Comorbidities.
Unstable
Fluctuating–
exerciseshelp
reinforce
pacing.
Increased
frominitial
measure,
little
fluctuation.
Small
improvement,
remained
steady
throughout.
Declined. Didnot
complete.
3 ‘Boomand Bust’
Highwork
pressures.Not
fullystable but
improving.
Fairlystable. Repsstabilising.
More withless
recoveryperiod.
Increased
frominitial
measure,
little
fluctuation.
Improvement
frominitial
measure.
Fluctuate
s slightly,
higher
than
initial
score.
Relatively
high
levelsof
functional
activity.
4 Stable behaviour
traits.Manages
routine well.
Stable. Constant
increase inreps.
Steady
decline
throughout
intervention.
Improvement
frominitial
measure.
Declined
incremen
tally
monthby
month.
High
levelsof
functional
activity.
5 Unstable
behaviouroften
downto work
pressures.
Lots of
comorbidities,
unstable.
Incremental
improvement
until final
month.
Verysteady
overall,
slightly
higherat end
than initial
measure.
Declinedthen
stabilised,at
lowerlevel
than initial
score.
Increased
from
initial
value,
remains
high.
Didnot
complete.
6 Stable behaviour,
managesand
understands
conditionwell.
Stable,fairly
relianton
Midodrine.
Incremental
increase month
on month.
Stay very
steady,slight
decline at
endof the
intervention.
Incremental
improvement
before dropin
lastmonth.
Remained
highbut
has been
stable.
37%
increase
in
functional
activity.
7 Fairlystable,
understands
conditionwell.
Lots of
comorbidities,
unstable.
Fluctuating,
dependson
otherillnesses.
Fluctuated
throughout.
Fluctuating
levels,
droppedto
lowerthan
initial value.
Fluctuatin
g,
remains
high.
Manages
activity
fairly
well.
Table 8 – Individualised overall changes in objective and subjective measures over the course of
the intervention.

28
Figure 21 – Exercise Adaptation Curve displaying the Supercompensation process.
11 Discussion:
It is evident from the results section that this intervention had a variable impact on the group
of individuals with PoTS regarding improvements in their symptoms and general measures of
health. This section will portray possible reasons for this and describe the broader trends
generated from this study.
11.1 Why didsome patients improve with the intervention?
Patients 1, 4 and 6 showed a general improvement in the majority of objective and subjective
measures assessed, such as FIS score and combined orthostatic symptoms following the 5
month intervention. A potential reason for this improvement was their relative behavioural
and medical stability, as is evident in table 8. Following each monthly juncture of the
extremely demanding intervention, this relative stability enabled the patients’ bodies to rest
and put in place the correct infrastructure to effectively recuperate. Examples of important
processes occurring in this rest period include an increase in neutrophils, lymphocytes and
white blood cells to mediate waste products, cellular damage and inflammation respectively
(34). With an adequate and fairly undisrupted rest period following a specific challenge such
as this one, the respective patients’ fitness levels increased to surpass their baseline level in
anticipation of their next challenge; a process known as supercompensation (35).
The supercompensation process is displayed in an Exercise Adaptation Curve shown in figure
21. It must be noted that there is not a ‘one size fits all’ curve due to the many components of
the biological regeneration process (35).

29
11.2 Why didother patients not improve with the intervention?
Conversely, patients 2,3,5 and 7 did not show general improvements in the majority of
objective and subjective measures assessed. All of these individuals displayed instability either
behaviourally or medically to differing degrees. An example of a trait of unstable behaviour
present in this group of patients was for them to relentlessly push themselves through their
symptoms and then crash severely afterwards, the so called ‘Boom and Bust’ phenotype.
Achieving behavioural stability can be extremely challenging as there are often factors to
consider beyond a patient’s control, such as the flexibility of their employer or family
responsibilities. However, without this stability, patients are constantly challenging
themselves without the space or time to fully rest and recuperate. Consequently, their fitness
levels never quite reach their baseline or surpass it before being challenged again, creating a
negative trend and leading to the phenomenon of overtraining. Figure 22 documents an
example of an overtraining curve.
Figure 22 – Overtraining Curve

30
A second possible reason for the indifferent impact of this intervention for these patients
could be their medical instability. None of the patients in the study had their PoTS subtyped
so the pathology of their condition was unknown, however patients 2,5 and 7 displayed high
levels of comorbidities to which their PoTS may be secondary. It is essential that an
individual’s underlying condition is managed in conjunction with their PoTS. Evidence from
this study would suggest that stabilising comorbities is essential before pursuing this
demanding intervention if it is to have a positive impact.
Despite a lack of broad improvements in the objective and subjective measures assessed,
evidence would suggest that this intervention helped individuals understand and reinforce
pacing. Pacing is an important management tool in all conditions with fatigue as a prominent
symptom (36). For example this was evident with patient 3, who pushed herself far beyond her
asymptomatic range in her first month and required 11 days to get back to normal afterwards.
Subsequently, she reduced her repetitions, leading to small corresponding improvements
towards the end of the intervention in measures such as her level of functional activity and
combined Health Today and Likert Scale scores. Additionally, patient 5 had seen an
incremental improvement in her cumulative monthly repetitions (see figure 15) until the last
month of the intervention. During the two weeks prior to the final class, her employment
workload had increased. Consequently she stopped her exercises very early on in this class to
manage her symptoms and activity levels, another example of pacing.
11.3 What is the future for the intervention and where may it fit in the
multifaceted management of the condition?
As this was a novel intervention, it is important to look at ways it could be developed to have a
greater impact on patients. The reinforcement of pacing and peer support it provided
demonstrated the positives of running interventions such as this one in a group environment.
Although the greatest overall positive change in many of the outcome measures was made by
patient 1, the pilot patient who completed the intervention individually, it is probably the high
level of background stability that she had both medically and behaviourally that enabled her
to make this progress. In addition to this, it is more cost effective to treat six patients in an
hour rather than one.
The necessity of medical and behavioural stability for a patient to make progress as a result of
this intervention is the significant communication from this study and would help to shape
further research.
A series of ‘N=1 studies’ of stable PoTS patients could be conducted to ensure that it was
definitely this intervention that was having an effect (37). An N=1 study involves deriving
many preliminary outcome measures over a period of time before adding an intervention
whilst changing nothing else, to indicate the actual role of the intervention. This is depicted in
figure 23.
A Randomised Controlled Trial (RCT) is known to be the most rigorous method to determine
whether there is a relationship between the outcome and the intervention (38). Subjects are
randomly assigned to one group receiving the intervention and anotherreceiving an
alternative or control treatment and are followed up over time. Based on the results from this
intervention, there is too much variability in patient response to the outcome and disparity in

31
Figure 23 – Graphic to depict N=1
Study.
the patient group to elicit the use of an RCT. There may be scope for an RCT following other
studies, such as those previously described. A depiction of an RCT is displayed in figure 24.
It would also be of interest to subtype participating patients in future studies more stringently
either into Primary or Secondary PoTS or by their altered blood flow physiology, as described
in section 7.2.2, to determine whether this affected the efficacy of the intervention in any way.
Figure 24 – Graphic to depict an RCT.
Figure adapted from Kendall, J (38)
In reality, it was impossible to fully establish from one 5 month long study involving 7 patients
where this intervention may fit in the complex management of PoTS. Nonetheless, the results
from this study have provided an indication of this.
Patients with a relatively stable medical and behavioural background and who have the
resources available to rest and recover adequately may choose to incorporate the exercises
conducted in this intervention into the treatment and management of their condition. For
example they may complete the exercises at the start of the week and complete light lower
body resistance exercises at the end of the week to improve their skeletal pump mechanism.
For the PoTS patients that have a background of behavioural and/or medical instability, an
intervention that modifies their environment to accommodate their functional limitations, as
discussed by Utsun et al (39), may be more applicable. This would help them to reach a stable
baseline from which to progress. As prolonged gravitational exposure is the main stimulus of
PoTS patients, this is challenging; however adjustments can be made, typically at home. This
could include using a perching stool when washing up, resting for 10 minutes every houror
incorporating meditation into their everyday routines to reduce their SNS activity. Figure 25
depicts where possible modifications can be made for PoTS patients, with relevant examples.

32
A major advantage of patient treatment occurring at the CRESTA clinic is that its
interdisciplinary nature allows for the use of a holistic approach such as this to improve an
individual’s circumstances.
11.4 How didthis intervention meet the aims of this study?
The first aim of this study was to determine whether PoTS patients would comply with this
demanding intervention run over a 5 month period. The compliance rate was high, with no
patients dropping out and a DNA rate of only 14%. This indicated that the intervention was
generally well received and that interventions conducted only once a month can retain
patients if delivered correctly.
The second aim of this study was to evaluate the efficacy of the intervention on patients’
orthostatic symptoms. The subjective measurements of orthostatic symptoms were combined
into one value, with improvements seen in three out of the seven patients (43%) following the
intervention. For the other four patients, these values fluctuated quite broadly. A possible
reason for this fairly low efficacy is that it may take a longer a period of time than 5 months for
changes in orthostatic symptoms to come to the fore and be recognised by the patient.
The third aim of the study was to ascertain whether participation in the intervention led to an
improvement in measures of patients’ general health. FIS improved in 43% of patients,
combined Health Today and Likert Scale results improved in 50% of the patients assessed and
for two of the patients, functional activity levels increased 13% and 37%. These improvements
indicate the benefits an intervention such as this one can have over a short period of time and
why it is necessary to keep pursuing research in this area.
Figure 25 – Foci of Modifications
for PoTS patients

33
Finally, the fourth aim of this study was to look at the potential future role of the intervention
and its applicability in the treatment and management of the condition. This study displayed
promising results for 3 out of the 7 patients who had a relatively high background behavioural
and medical stability. This would indicate that the intervention should be targeted to this
subgroup of the patient population, who may choose to incorporate the specific exercises
involved into the management of their condition alongside other physiological or
pharmacological therapies such as those displayed in figure 5.
12 Advantages and Limitations:
The first advantage of this intervention was its high compliance rate, with no patients
dropping out. This is notable as other studies documenting exercise interventions for PoTS
have had high dropout rates (22, 40). Secondly, the intervention was fairly simple in its
delivery, requiring only a mat and a chair to perform the exercises. An adjunct to this however
is the need for a physiotherapist to run the intervention with the requisite specialist
knowledge and patient trust. A final advantage is that meaningful improvements were made,
especially in terms of functional activity levels, for 3 out of the 7 patients.
This study and the nature of the intervention does have some limitations. Firstly, there was
difficulty in ascertaining all of the subjective measures from each individual every month.
Reducing the amount of paperwork involved or making it electronic would help. Secondly,the
OH A/S questionnaires and Likert Scale questionnaires were not validated in this population,
so the results may not be fully applicable. Thirdly, the information derived fromthe active
stand tests could not be accessed properly and therefore it was impossible to determine
whether there were any changes in measures of ANS function such as maximum HR upon
standing and Baroreceptor Efficiency Index. A furtherlimitation of this study is the lack of
follow up results. Finally, as touched upon throughout, the high level of variability between
each patient in terms of their background both medically, behaviourally, at work and at home
meant that many factors were uncontrolled during the study. This variability will always be a
factor in studies involving patients, however stricter inclusion criteria would alleviate it
somewhat.
13 Conclusions andFurther Work:
This study documents the impact of a novel gravity induced exercise intervention delivered
over a 5 month period for 7 patients with PoTS. The intervention was generally positively
received, as documented by individual feedback and high compliance levels. Broadly speaking,
orthostatic symptoms and measures of general health improved in 3 out of the 7 patients.
Further studies using a greater selection of objective measures, stricter inclusion criteria,
follow up data and lasting for a longer duration would be useful. Finally, greater
comprehension of microgravity physiology in those with PoTS would help to develop the
intervention itself, improving its impact.

34
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37
15 Appendices:
15.1 Appendix 1:
Appendix 1 shows a photographic image of a selection of the questionnaires used as part of the
intervention, in addition to the activity log used.
1) OH Activity Scale 2) OH Symptom Assessment
3) EQ-5D-5L Questionnaire 4) Health Today Questionnaire

38
5) Part of the Fatigue Impact
Scale Questionnaire
6) Likert Scale Questionnaire
7) Intervention Feedback
Questionnaire
8) Example of a completed
Activity Diary

39
15.2 Appendix 2:
Below is a table of the monthly EQ-5D-5L scores for each individual who completed the
intervention.
EQ-5D-5L
PatientID
1 11 12 10 10 10
2 17 11 12 DNA 12
3 4 6 7 5 5
4 DNA 3 2 4 DNA
5 6 12 13 10 12
6 5 5 5 6 DNA
7 10 7 10 9 12

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