Author's Accepted Manuscript

The International POTS Registry: Evaluating the

Efficacy of an Exercise Training Intervention in a
Community Setting
Stephen A. George MD, PhD, Tiffany B. Bivens MS,
Erin J. Howden PhD, Yasir Saleem MD, M. Melyn
Galbreath PhD, Dianne Hendrickson MS, APRN,
FNP-C, Qi Fu MD, PhD, Benjamin D. Levine MD

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PII: S1547-5271(15)01527-1
DOI: http://dx.doi.org/10.1016/j.hrthm.2015.12.012
Reference: HRTHM6543

To appear in: Heart Rhythm

Cite this article as: Stephen A. George MD, PhD, Tiffany B. Bivens MS, Erin J. Howden
PhD, Yasir Saleem MD, M. Melyn Galbreath PhD, Dianne Hendrickson MS, APRN,
FNP-C, Qi Fu MD, PhD, Benjamin D. Levine MD, The International POTS Registry:
Evaluating the Efficacy of an Exercise Training Intervention in a Community Setting,
Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2015.12.012

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JHRM-D-15-01387 Revision 2 1

The International POTS Registry: Evaluating the Efficacy of an Exercise

Training Intervention in a Community Setting

Stephen A. George, MD, PhD1, Tiffany B. Bivens, MS2, Erin J. Howden, PhD 1,2,

Yasir Saleem, MD1, M. Melyn Galbreath, PhD2, Dianne Hendrickson, MS, APRN, FNP-C2,

Qi Fu, MD, PhD1,2, Benjamin D. Levine, MD1,2

1
Department of Internal Medicine, University of Texas Southwestern Medical Center
2
Institute of Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas,

Dallas, Texas, USA

Short Title: Exercise Training for POTS

Conflict of Interest Disclosure: None

Address for Correspondence:

Benjamin D. Levine, MD

Institute for Exercise and Environmental Medicine

Texas Health Presbyterian Hospital Dallas

7232 Greenville Ave., Dallas, Texas 75231

Email: BenjaminLevine@TexasHealth.org

Telephone (214) 345-4619

Fax (214) 345-4618

JHRM-D-15-01387 Revision 2 2

ABSTRACT

Background: The postural orthostatic tachycardia syndrome (POTS) affects primarily young

women and impairs quality of life. We found that in a research setting, exercise training along with

lifestyle intervention is effective as a non-drug therapy for POTS.

Objective: To evaluate the efficacy of our exercise training/lifestyle intervention in POTS patients

in a community environment.

Methods: We established a POTS registry and enrolled 251 patients (86% women, 26±11 [SD]

years) through their physicians. A 3-month program involving mild-to-moderate intensity

endurance training (progressing from semi-recumbent to upright, 3-5 times/wk, 30-45 min/session)

plus strength training was implemented along with increasing salt/water intake. The program was

delivered to the physicians, who oversaw training in their patients. A 10-min stand test was

performed at the physician’s office and patient quality of life was assessed using the 36-item Short-

Form Health Survey.

Results: 103 patients completed the program. Of those that completed, 71% no longer qualified

for POTS and were thus in remission. The increase in heart rate from supine to 10-min stand was

markedly lower (23±14 versus 46±17 beats/min before intervention; P<0.001), while patient quality

of life was improved dramatically after intervention (P<0.001). Of those who were followed for 6-

12 months (n=31), the effect was persistent.

Conclusions: A training/lifestyle intervention program can be implemented in a community setting

with physician supervision and is effective in the treatment of POTS. It remains to be determined
JHRM-D-15-01387 Revision 2 3

whether exercise can be an effective long-term treatment strategy for this condition, though patients

are encouraged to maintain an active lifestyle indefinitely.

KEY WORDS: Orthostatic intolerance; tachycardia; quality of life; exercise training; lifestyle

intervention

ABBREVIATIONS:

DBP = diastolic blood pressure

HR = heart rate

POTS = postural orthostatic tachycardia syndrome

RPE = rating of perceived exertion

SBP = systolic blood pressure

SF-36 = 36-item short-form health survey

JHRM-D-15-01387 Revision 2 4

INTRODUCTION

The postural orthostatic tachycardia syndrome (POTS) affects approximately 500,000

people, primarily premenopausal women, in the United States alone 1, 2. The clinical hallmark is the

inability to stand or remain upright for periods of time due to excessive heart rate increases,

intolerable palpitations, light-headedness, dizziness, fatigue, nausea, or near syncope 3, 4. Severely

affected patients are unable to work, go to school, or participate in recreational activities, resulting

in substantial morbidity and poor quality of life.

The underlying mechanisms are not well understood, but research from our group and others

suggests that physical deconditioning (i.e., cardiac atrophy and hypovolemia) and reduced standing

stroke volume may be important to the pathophysiology of POTS 5-10. This notion is supported by

studies showing that in a research setting, physical reconditioning with short-term exercise training

significantly increased peak oxygen uptake (an indicator of physical fitness), enlarged heart size and

mass, expanded blood and plasma volume, improved POTS or orthostatic intolerance symptoms,

and in most cases allowed these patients to be symptom free 5, 6, 10, 11. Furthermore, this unique

exercise training program improved the quality of life in virtually all patients as measured by a

reliable and valid questionnaire; the 36-item Short-Form (SF-36) Health Survey 5, 6. These results

demonstrate that this lifestyle intervention program is highly effective as a non-drug therapy for

patients with POTS. These findings are innovative because so far there are no effective

pharmacologic therapies for POTS and many patients have disabling side effects with standard drug

treatments. As such, the 2015 Heart Rhythm Society Scientific Statement on Dysautonomia has

advocated the use of an exercise training regimen in the management of POTS 12.

Translating research findings from the laboratory into a community environment or clinical

practice is essential to improve patient care in real life. To accomplish this objective, it is critical to

create a link among researchers, primary physicians, and patients. Indeed, the National Institutes of
JHRM-D-15-01387 Revision 2 5

Health have identified practice-based research networks as fundamentally necessary to support the

translation of research into clinical practice 13. To this end, we established a POTS registry that

connected us (researchers) with POTS patients through their primary physicians.

The main purpose of this study was to evaluate the efficacy of an intervention program

involving exercise training and lifestyle modification (primarily increasing intake of salt and water)

in the community setting outside the constraints of a controlled clinical trial. Specifically, we

determined whether the intervention program, if implemented and supervised by primary care

physicians, could eliminate or reduce orthostatic tachycardia and improve quality of life in POTS

patients.

METHODS

Study Population

We screened 304 patients and enrolled 251 of them (216 females, 35 males) in the POTS

registry between 2010 and 2012. Patients were from 36 different states in the United States and 7

different countries around the world, including North America, Europe and Australia. No direct

advertising of our registry or solicitation was used. The initial POTS exercise training studies 5, 6, 10

generated enough publicity that both patients and their physicians contacted our laboratory to

become enrolled in the registry. All patients enrolled in the registry met the inclusion criteria for

POTS including at least 6 months of orthostatic symptoms 14 and had a heart rate rise >30 beats/min

or a rate that exceeded 120 beats/min that occurred after 10 min of standing without any evidence of

orthostatic hypotension 15. Fifty-one percent of the patients enrolled met both criteria, 45% had an

orthostatic tachycardia >30 beats/min with a standing heart rate ≤120 beats/min, while 4% of the

patients were enrolled because of the 120 beats/min criteria without an orthostatic tachycardia >30

beats/min. Approximately 37% of them had mild POTS (i.e., an increase in heart rate ≤35
JHRM-D-15-01387 Revision 2 6

beats/min), whereas 63% had moderate-to-severe POTS (i.e., an increase in heart rate >35

beats/min). Most patients had been treated at some point with standard medications such as β-

blockers, volume expanders, and/or α1-adrenergic agonists.

All patients were informed of the purpose and procedures used in the study and gave their

written informed consent to a protocol approved by the Institutional Review Boards of the

University of Texas Southwestern Medical Center and Texas Health Presbyterian Hospital Dallas.

Table 1 depicts patients’ characteristics.

Study Design

Patients stopped taking medications that could affect the autonomic nervous system at least

24 h before screening and testing (both before and after training). After a qualifying stand test with

measurements of heart rate and blood pressure was received from a physician along with a

completed SF-36 questionnaire and signed informed consent, an introductory letter was sent to the

patient and the physician with recommendations for participation in our study. After that, we

distributed a packet directly to the overseeing physician. This packet included an introduction to

our study, global training guidelines, a month by month calendar of the exercise protocol, and heart

rate goals to help guide the exercise program. The direct communication with the physician

provided the initial level of oversight to ensure the diagnosis was secure, and that the patient was

medically appropriate to participate in the intervention.

To test the feasibility of administering our program in the community setting, it was stated

that we (the research team in Dallas) were not available to help in implementation of the program.

Regular appointments with the primary physician were recommended to follow the patient’s

progress and their response to the interventions. Decisions about medications, especially
JHRM-D-15-01387 Revision 2 7

psychiatric medications were left up to the patients and their physicians. If the primary physician

chose to maintain β-blockers during the training program, perceived exertion was used as a guide to

exercise intensity prescription.

Exercise Training and Lifestyle Intervention

The training program consisted of 3 months of daily schedules, outlined in Table 2. Based

on the predicted maximal heart rate and resting heart rate, 3 training zones were determined (i.e.,

recovery, base pace, and maximal steady state or “threshold” ) 16. Most of the training sessions,

particularly during the early stages, were prescribed as base training, with the target heart rate

equivalent to approximately 70-75% of maximal predicted heart rate, and the Rating of Perceived

Exertion of 13-15 corresponding to the words “somewhat hard” to “hard”. Initially, patients were

requested to train 3 to 4 times per week for 30 to 40 min per session by using rowing, swimming or

a recumbent bike. The use of semi-recumbent training is critical in the beginning, allowing patients

to exercise while avoiding upright posture and eliciting POTS symptoms. As patients became

increasingly fit, work out modalities, duration, intensity and frequency were increased. By the end

of the 2nd month or the beginning of the 3rd month, upright exercise, such as upright bicycle,

walking on a treadmill, or jogging was added. By the end of the third month, patients exercised 5-6

times per week.

In addition to the endurance training, resistance training such as weight lifting was also

used. Weight lifting started from once weekly, 15 to 20 min per session and gradually increased to

twice weekly, 30 min per session. Additionally, patients were encouraged to increase water intake,

3 liters per day, and increased salt intake, with a goal of 7-10 grams per day. A slow, progressive

increase of salt was suggested so it would not upset the gastrointestinal system. Salt tablets were
JHRM-D-15-01387 Revision 2 8

discouraged. Patients were also encouraged to elevate the head of the bed 4-6 inches during

sleeping at night. Remaining upright while awake as much as tolerated was strongly recommended.

A variation for those who were too disabled and consequently unable to start the 3 month

program was to start with a “pre-month” 1 and 2. These daily exercise schedules were provided in

the event month 1 was too difficult. The main difference in the pre-months was this provided

shorter duration of the base pace and maximal steady state workouts.

Post Training Follow Up

The 10-min stand tests with physician oversight, and the SF-36 were measured again at ~3

months, on completion of the training program, achieving the training schedule provided during the

last week of the 3 month calendar. Some patients required additional time to complete the 3 month

program. Their data were accepted and included, as long as all 3 month training sessions were

completed in proper succession.

If we were unable to receive follow up data from the patient or doctor, both were contacted.

Before someone was considered a drop out from the registry, we contacted the patient and physician

at least 3 times with phone calls and emails.

Main Outcomes

We evaluated the efficacy of exercise/lifestyle intervention with two endpoints: objective

quantification of change in heart rate by the stand test and subjective evaluation with the SF-36

quality of life questionnaire.

JHRM-D-15-01387 Revision 2 9

Data and Statistical Analysis

The SF-36 (version 2.0) uses a norm-based scoring algorithm for each domain and linear

transformations are performed to transform scores to a mean of 50 and standard deviations of 10 in

the general US population 17. This transformation achieves the same mean and standard deviation

for all eight scales and for the physical component summary and mental component summary

measures 17.

Data are expressed as mean ± standard deviation. A 2-way repeated measures analysis of

variance was used to compare supine and standing heart rate and blood pressure before and after

exercise training. In the case of a significant difference, the Holm-Sidak method was used post hoc

for multiple comparisons. Effects of exercise training on the change in heart rate from supine to 10-

min stand and the SF-36 scores were analyzed using Wilcoxon signed-rank tests. All statistical

analyses were performed with a personal computer-based analysis program (Sigma Plot Version

12.0, Systat Software, Inc.). A p value <0.05 was considered statistically significant.

RESULTS

Patient Characteristics

Table 1 depicts the demographic profile of patients enrolled in the POTS registry. The vast

majority of these patients were young Caucasian women.

Figure 1 depicts the participant flow diagram. Among all patients enrolled, 103 of them

completed the 3-month training program. Thus, the completion rate of our program administered in

a community setting was 41%. We were able to obtain full data sets on 78 of the 103 patients that

completed the exercise program. Of the remaining 25, 11 patients provided only the stand test or

the SF-36 questionnaire after 3 months of training. Fourteen patients were in contact with us, and
JHRM-D-15-01387 Revision 2 10

assured us they completed the 3 month program; however, they did not provide the results of either

the stand test or the SF-36 questionnaire upon completion.

Although each medical decision was left to the primary physician, most physicians were

able to wean patients from POTS medications prior to beginning the program. We found that the

vast majority of patients were able to train off of medications; however, the individual choice of

whether or not to continue a medication was left to the primary physician. In the registry, 2 patients

were on β-blockers, 1 was on midodrine (α1-agonist), 2 were on florinef (volume expander), and 2

patients were on both midodrine and florinef during 3-month training.

Our dropout rate (148/251) was 59%. Of the 148 patients that did not complete the

program, 35 (24%) did not finish because of other medical problems. According to the patients,

these issues ranged from connective tissue disease, mitochondrial disorders that may have affected

POTS symptoms, Lyme disease, epilepsy, celiac disease, intractable migraines, supraventricular

tachycardia unrelated to POTS, and hospitalizations for unknown reasons. Other medical problems

also included trauma, such as broken bones, and surgeries (cholecystectomy, spine, jaw, etc.),

preventing exercise. Twenty-three (16%) patients stopped for personal reasons including inability

to afford a gym membership or lack of access to workout equipment or other unknown reasons.

Fifty-nine (40%) patients stopped because the training was considered “too difficult”. Of these 59

patients, 7 were able to train, but at a lower intensity but were still included in this drop out category

because of inability to complete the standard 3 month program. Thirty-one (21%) patients were

unable to be contacted after multiple attempts, we received no follow up data, and it was assumed

they did not complete the program.

JHRM-D-15-01387 Revision 2 11

Effects of Exercise Training on Orthostatic Tachycardia

Figure 2 shows heart rate and blood pressure in the supine position and during 10-min

standing in patients who completed the 3 month training and had the full data set (n=78). Short-

term exercise training markedly reduced standing heart rate in POTS patients. The change in heart

rate from supine to 10-min stand was significantly smaller after training compared with before

training. Of those that completed the program, 71% no longer qualified for POTS criteria and were

thus effectively in remission. These patients also remitted their clinical symptoms. Exercise

training did not affect supine and standing blood pressure in these patients.

A subset of patients continued the program for longer periods of time after completion of

our study. Figure 3 shows heart rate responses in these patients before and after 3, 6 and/or 12

months of training (n=31) and showed no evidence of decay in the efficacy of the intervention over

time. These data imply continued exercise leads to continued relief from POTS symptoms.

Impact of Exercise Training on Patient Quality of Life

Table 3 shows patient quality of life. The SF-36 scores were markedly increased under all

categories in virtually all patients, suggesting a significant improvement in overall well-being and

quality of life after completing 3 months of exercise training/lifestyle intervention. Furthermore,

these results appeared to persist when patients were able to continue training out to 6 and 12 months

(Figure 3).

DISCUSSION

Data from our POTS registry demonstrate that 1) if patients can complete the prescribed 3

month training/lifestyle intervention program under the supervision of their primary care

physicians, they have a very good chance to effectively remit their postural orthostatic tachycardia
JHRM-D-15-01387 Revision 2 12

with a substantial reduction in standing heart rate; 2) exercise training improves quality of life (the

SF-36 scores ) in virtually all patients; and 3) if the training is continued, the success appears to

persist with no evidence of decay of efficacy. These results suggest that our exercise

training/lifestyle intervention program can be implemented safely in a community environment with

physician supervision and is effective in the treatment of POTS.

Efficacy of the Training Program in a Community Setting

Targeting treatment to the underlying physiology of a small heart, reduced blood volume

and small standing stroke volume leading to reflex tachycardia 5, 6, 10 explains why exercise is

effective for patients with POTS 8, 18, 19. Conversely, the success of this type of intervention

program reaffirms the cardiac origin of POTS in a much larger number (than in our original

research study) of unselected patients from the community who have been diagnosed with POTS.

Endurance exercise training has been shown to expand blood and plasma volumes 20, increase

cardiac size and mass 21, prevent cardiac atrophy and increase orthostatic tolerance in healthy

women after a prolonged period of bed rest (i.e., physical deconditioning) 21. Though heart size and

blood volume were not measured in the current study, previous investigations from our laboratory

showed that in a research setting 3-month exercise training significantly increased these variables in

POTS patients 5, 6. In that study, we also found that peak oxygen uptake was increased by 11% after

training, confirming an increase in physical fitness 5, 6, 10.

In the POTS registry, 71% of those that completed the training program no longer qualified

for POTS criteria and thus effectively remitted their orthostatic tachycardia. This remission rate

was higher than that in our previous study in the research setting (i.e., 53%) 5. Furthermore, the

training-induced reduction in standing heart rate was greater in the POTS registry (124±23 before

training versus 98±15 beats/min after training, P<0.001) compared with the previous research study
JHRM-D-15-01387 Revision 2 13

(120±19 versus 108±21 beats/min) 5, 6. These observations are not attributable to the difference in

severity of the disorder. In fact, more patients had moderate-to-severe POTS (i.e., an increase in

heart rate >35 beats/min) in the registry than in the research study (63% versus 45%) 5. It is

possible that use of medications could have affected the heart rate response during standing in this

registry. Indeed, in the previous study patients enrolled in the training program did not take any

medications for POTS. Nevertheless, the number of patients being treated with POTS medications

during 3-month training was small in the current study, and the results remained unchanged after

these patients were removed (10-min standing heart rate: 122±22 before training versus 97±15

beats/min after training).

The results from the stand test provide objective evidence that this exercise based lifestyle

intervention program is effective in the community setting, while the SF-36 data confirm that POTS

patients actually feel better after completing the program. Indeed, patient overall well-being and

quality of life, assessed by the SF-36 questionnaire, were significantly improved after training in

virtually all patients including those who were also on drug treatment. These results are indicative

of successful treatment, and lack of symptoms with upright posture. Aside from treating POTS

physiology, it is possible that regular exercise contributes to patients’ subjective improvement as

there is compelling evidence that exercise changes the neurochemistry of the brain 22, a

phenomenon popularly termed “the runners high”. Therefore many exercisers, not only POTS

patients, feel better when they exercise regularly. In contrast, bed rest or physical deconditioning

seems to make people feel worse. There is anecdotal evidence prolonged bed rest leads to increased

pain sensitivity and could contribute to the downward spiral of hypervigilance, and increased

sensitivity to multiple stimuli 3.

JHRM-D-15-01387 Revision 2 14

Patient Adherence to Exercise Training in Clinical Practice

In the POTS registry 41% of patients completed the training program, whereas in the

previous research study the completion rate was 76% 5. This difference is not surprising. All of the

training sessions in the research study were supervised closely by an experienced exercise

physiologist, heart rate was recorded during every training session using a Polar heart rate monitor,

and the training progress was evaluated weekly. Conversely, in the POTS registry the training

program was delivered directly to the primary physicians, who oversaw exercise training in their

patients with no input from the research team. It is possible that if physicians and health care

providers, perhaps with increasing assistance by exercise professionals 23-26, develop health care

delivery systems to take additional responsibility to monitor patients more frequently, one could

expect a higher rate of completion of the training program.

However, it is important to emphasize that the completion rate of exercise training in the

POTS registry is quite similar to patients going through traditional cardiac rehabilitation as well as

that reported in the HF-ACTION trial (a trial of exercise in patients with heart failure), which

ranged from 38-42% for full adherence depending on their time points 27-29. Completion rates for

supervised cardiac rehab vary greatly. Current studies appear to be around 30-50% 30, 31, with some

completion rates as low as 4% 32. Completion rates even for taking daily medications can be

strikingly low; many studies report less than 40% adherence rate 33-35. These comparisons highlight

that compliance with any long term therapy is difficult, and exercise training is no exception.

Nevertheless, patient adherence to exercise training is one of the important measures of treatment

effectiveness. Plans to improve adherence to intervention should be developed and implemented in

future community-based clinical trials. Approaches such as regular telephone or text message

follow-up, cell phone applications, family member involvement in patient physical activity
JHRM-D-15-01387 Revision 2 15

monitoring at home, or patient support groups though Facebook and Twitter may be considered in

long-term drug and non-drug therapy.

Study Limitations

Firstly, the current study was observational and descriptive, and there was no control group

for patients enrolled in the training program. However all these patients had symptoms lasting at

least 6 months and many for much longer, so there is little reason to suspect that continued

observation without an intervention would have had such a profound effect. For comparison, we

have compared the therapeutic effects of exercise training versus standard drug therapies (such as β-

blockers) for POTS in the previous research study, and found that although β-blockers reduced

supine and standing heart rate, there was no improvement in quality of life 6. Moreover the placebo

controlled arm of this study had no improvement in either symptoms or standing heart rate.

Together, these observations provide supportive evidence against a placebo effect or regression to

the mean causing the improvement in both standing heart rate and quality of life. Nevertheless, our

findings from the current and previous studies should be confirmed in a large randomized,

controlled, community-based clinical trial. Secondly, we reported results only from patients that

completed the 3-month training program and had a full data set. There certainly could be selection

bias due to loss to follow-up or withdrawal from the study in some patients. Strategies to improve

patient retention and adherence to exercise intervention are necessary in future studies to verify our

findings and optimize the intervention approach to the largest number of patients. In this context, it

is important to emphasize that there are many pathways to POTS with multiple possible

precipitating causes 36. However in the chronic state, after these complicating disorders have been

ruled out or treated, much of the disability associated with POTS appears to be related to the broad

pathophysiology of cardiovascular deconditioning, and can be ameliorated with an intervention

JHRM-D-15-01387 Revision 2 16

based on exercise training. Thirdly, we cannot exclude the possibility that patients who completed

the program might have a favorable natural history compared with those who dropped out. In the

previous laboratory-based research trials however, we compared the characteristics of patients who

completed the 3-month exercise training versus those who dropped out, and found that the severity

of POTS was similar prior to training between the groups. Unfortunately, the lack of direct control

of the circumstances of the intervention was both a strength and weakness of this study. We wanted

to have as little control as possible to test its efficacy in a “real world” setting, much as we currently

do when requested by other health care providers. Fourthly, there may be other mechanisms by

which heart rate might have been reduced in these patients other than by exercise training.

Regardless of the mechanism however, the study confirms the results of previous studies in a

community setting.

Conclusions

In the POTS registry, the vast majority of patients who completed 3 months of exercise

training/lifestyle intervention no longer qualified for POTS criteria and were thus effectively in

remission. Quality of life was improved significantly after training in virtually all patients. These

results suggest that this training program can be implemented in the community setting with

physicians’ supervision and is effective in the treatment of POTS. It remains to be determined

whether exercise can be an effective long-term treatment strategy for this condition, though our

patients are encouraged to maintain an active lifestyle indefinitely.

JHRM-D-15-01387 Revision 2 17

ACKNOWLEDGEMENTS

The time and effort put forth by patients and their primary physicians is greatly appreciated.

The authors thank Debbie Moreno and Sheryl Livingston for their valuable laboratory assistance.

FIGURE LEGENDS

Figure 1. Participant Flow Diagram.

Figure 2. Effects of Short-Term Exercise Training on Heart Rate and Blood Pressure in the Supine

Position and during 10-min Stand. HR, heart rate. ∆HR, the change in heart rate from supine to 10-

min stand. SBP and DBP, systolic and diastolic blood pressure.

Figure 3. Effects of Prolonged Exercise Training on Heart Rate and Quality of Life in A Subset of

Patients. HR, heart rate. ∆HR, the change in heart rate from supine to 10-min stand. SF-36, the

36-item Short-Form health Survey. **P<0.001.

JHRM-D-15-01387 Revision 2 18

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urge to block beta-receptors? Hypertension.58(2):136-137.

JHRM-D-15-01387 Revision 2 20

19. Joyner MJ. Standing up for exercise: should deconditioning be medicalized? The Journal of

physiology.590(Pt 15):3413-3414.

20. Saltin B, Blomqvist G, Mitchell JH, Johnson RL, Jr., Wildenthal K, Chapman CB. Response

to exercise after bed rest and after training. Circulation. 1968;38(5 Suppl):VII1-78.

21. Dorfman TA, Levine BD, Tillery T, Peshock RM, Hastings JL, Schneider SM, Macias BR,

Biolo G, Hargens AR. Cardiac atrophy in women following bed rest. J Appl Physiol.

2007;103(1):8-16.

22. Lechin F, van der Dijs B, Orozco B, et al. Plasma neurotransmitters, blood pressure, and

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23. Blair SN, Sallis RE, Hutber A, Archer E. Exercise therapy - the public health message.

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24. Sallis R. Exercise is medicine: a call to action for physicians to assess and prescribe

exercise. Phys Sportsmed.2015;43(1):22-26.

25. Sallis R, Franklin B, Joy L, Ross R, Sabgir D, Stone J. Strategies for promoting physical

activity in clinical practice. Prog Cardiovasc Dis. 2015;57(4):375-386.

26. Sallis RE. Exercise is medicine and physicians need to prescribe it! Br J Sports Med.

2009;43(1):3-4.

27. Blumenthal JA, Babyak MA, O'Connor C, Keteyian S, Landzberg J, Howlett J, Kraus W,

Gottlieb S, Blackburn G, Swank A, Whellan DJ. Effects of exercise training on depressive

symptoms in patients with chronic heart failure: the HF-ACTION randomized trial. JAMA.

2012;308(5):465-474.
JHRM-D-15-01387 Revision 2 21

28. Flynn KE, Pina IL, Whellan DJ, et al. Effects of exercise training on health status in patients

with chronic heart failure: HF-ACTION randomized controlled trial. JAMA.

2009;301(14):1451-1459.

29. O'Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in

patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA.

2009;301(14):1439-1450.

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32. Lemstra ME, Alsabbagh W, Rajakumar RJ, Rogers MR, Blackburn D. Neighbourhood

income and cardiac rehabilitation access as determinants of nonattendance and

noncompletion. Can J Cardiol. 2013;29(12):1599-1603.

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JHRM-D-15-01387 Revision 2 22

36. Raj SR, Levine BD. Postural tachycardia syndrome (POTS) diagnosis and treatment: basics

and new developments. Last accessed February 8, 2013. http://crm.cardiosource.org/Learnfrom-

the-Experts/2013/02/POTS-Diagnosis-and-Treatment.aspx

Clinical Perspectives:

The postural orthostatic tachycardia syndrome (POTS) causes debilitating orthostatic

intolerance predominantly in premenopausal women. The underlying mechanisms are not well

understood, and few effective therapies are available. Previous research suggested that physical

deconditioning (i.e., cardiac atrophy and hypovolemia) and reduced standing stroke volume may

underlie the pathophysiology of POTS by demonstrating marked improvement from a carefully

controlled period of exercise training (beginning in the seated position to avoid orthostatic stress)

and life style modification. In this study, the first international registry of patients with POTS was

established and detailed instructions on how to implement an exercise based intervention was

delivered to the patients’ own primary care physician or health care team. This current community

based study extends previous laboratory based work by demonstrating that similar efficacy (71%

remission for those that adhered to the prescription) can be obtained by implementing this therapy

in a primary health care setting. Moreover, patients who continued to adhere to the program

showed a persistence improvement with no evidence of loss of efficacy. Thus patients with this

incapacitating syndrome can be markedly improved by a non-pharmacologic intervention without

the requirement for a specialized center or equipment. Future efforts to engage exercise specialists,

physical therapists, personal trainers, social media experts, and other health care providers should

be made to improve access, adherence, and long term life style modification for maximal

improvement in functional capacity and quality of life.

JHRM-D-15-01387 Revision 2 23

Table 1. Patient Characteristics

All Participants

Variables (n=251)

Age (years) 26±11

Sex (Men/Women) 35/216

Height (cm) 168±10

Weight (kg) 64±16

Body Mass Index (kg/m2) 23±5

Heart Rate (beats/min) Supine 78±15

10-min Stand 120±21

Change (∆) from Supine to 10-min Stand 43±17

Blood Pressure (mmHg) Supine 115±14 (Systolic) /69±9 (Diastolic)

10-min Stand 111±19/72±14

Race (n)

Caucasian 234

African American 2

American Indian 1

Hispanic 4

Indian 1

Asian 2

Unknown 7

Data are expressed as mean ± standard deviation.

JHRM-D-15-01387 Revision 2 24

Table 2. Short-Term Exercise Training Program

Training Type Month 1 Month 2 Month 3

Base Pace 10 × 30 min 6 × 30 min 5 × 35 min

(RPE 13-15) 3 × 35-40 min 4 × 45-60 min

Maximal Steady State 1 × 20min 1 × 25 min 1 × 30 min

(RPE 16-18) 1 × 25 min 1 × 30 min 1 × 35 min

1 × 35 min 1 × 40 min

Recovery 2 x 40min 1 × 40 min 3 × 25 min

(RPE 6-12) 1 × 30 min

Strength Training 8 × 15-20 min 8 × 20-25 min 8 × 30 min

Cardiovascular Modes Recumbent Bike Month 1 Modes Plus Month 1 and 2 Modes

Swimming Upright Bike Plus Elliptical and

Rowing Treadmill Walking

RPE, rating of perceived exertion. Subjective rating of the entire cardio workout on a scale of 6
to 20: 6 is very, very easy; 11 is fairly easy; 13 is somewhat hard; 15 is hard; 17 is very hard;
19 is very very hard.
 JHRM-D-15-01387 Revision 2 25

Table 3. Patient Quality of Life

Before Training Before Training After Training P Value

Variables A B C C vs. B
(n=251) (n=78) (n=78)

Transform Physical 30±9 29±9 42±10 <0.001

Transform Mental 40±12 41±11 48±9 <0.001

Physical Functioning 32±9 32±8 46±9 <0.001

Role Physical 27±9 26±8 40±12 <0.001

Bodily Pain 40±11 42±11 49±10 <0.001

General Health 31±8 31±8 40±10 <0.001

Vitality 32±9 31±8 44±11 <0.001

Social Functioning 28±11 28±11 41±13 <0.001

Role Emotional 41±13 43±12 49±9 <0.001

Mental Health 42±12 42±11 49±9 <0.001

 Screened Figure 1
(n=304)
Excluded (n=48); Enrolled Withdrew prior to enrollment
DNQ per stand test (n=35) (n=5)
(n=251)
DNQ tilt test (n=5)
Age (n=3)
Incomplete data (n=5)
Completed
Did not finish program
(n=103)
(n=117)
Unable to
contact
(lost to
follow up)
Full data Partial Completed Other Personal Training (n=31)
(n=78) data training, no medical reasons difficulty
(n=11) follow-up data problem (n=23) (n=59)
(n=14) (n=35)
Continued training
at lower intensity
(n=7)
 160
Figure 2
Before training 70 P<0.001
After training
140 60
∆HR (beats/min)
HR (beats/min)

50
120
40
100
30
80
20
P<0.001 for posture
60 P<0.001 for training 10
P<0.001 for interaction
0 0
Before After
140 100
130 90

DBP (mmHg)
SBP (mmHg)

120 80
110 70
100 60
P=0.080 for posture P<0.001 for posture
90 P=0.759 for training 50 P=0.220 for training
P=0.391 for interaction P=0.047 for interaction
0 0
Supine 1min 3min 5min 10min Supine 1min 3min 5min 10min
Stand Stand
 **
Figure 3
**
160 70 **
**
140 60
∆HR (beats/min)
10 min Stand HR

120
50
(beats/min)

100
40
80
30
60
20
40
20 10
0 0
**
SF-36 Transform Physical

60 70 **
**

SF-36 Transform Mental

60 **
50
50
40
40
30
30
20
20
10 10
0 0
Before 3 months 6/12 months Before 3 months 6/12 months
After After