Welcome

Welcome to the Postural Tachycardia Study website. Researchers at the Center for Hypotension at New York Medical College in Valhalla NY have received funding from the National Institutes of Health (NIH) to study whether local circulatory problems explain the findings of postural tachycardia syndrome in teenagers and young adults. Our most recent data indicate that modulation of the sympathetic nervous system by angiotensin-II and nitric oxide of nNOS origin explain many of the features of POTS including exercise intolerance in important subsets of POTS.

The Principal Investigator for this study is Julian M. Stewart  MD, PhD, Professor of Pediatrics and of Physiology at  New York Medical College.

What comprises the study population? 
What is the hypothesis and importance of the study?
What are the symptoms and findings in patients?
What is the goal of the study?
What your own doctor can do to help diagnose POTS.
How do I know if I’m eligible to be in this study? 
Who pays for the exams, testing, and travel? 
How can I get a questionnaire  for this study? 
If I decide to participate what does the study entail?
 

What comprises the study population? 

We are seeking patients aged 15-29 years old with postural tachycardia syndrome (POTS) who may benefit from an investigation of abnormalities of regulation of blood flow. Many people are unable to remain upright for long because of symptoms such as dizziness, nausea and headache or fainting. This may occur on a day-to-day basis and may severely compromise lifestyle. The most common cause of this condition is the postural tachycardia syndrome (POTS), which is believed to affect at least a million Americans. POTS is defined by an abnormal increase in heart rate (“tachycardia”) that occurs when upright (therefore “postural”). POTS has many causes and we are attempting to determine the precise biochemical basis for POTS in patients.

There are currently two active sets of experiments: one to look strictly at local regulation by nitric oxide and angiotensin and the other to look at sympathoactivation in POTS and its relation to NO and angiotensin. You will need to be over 18 years old (i.e. 18-29 years old) to enroll in the second study. We are trying to actively recruit older subjects (18-29 years) because the data collection from the first set of local experiemnts are nearly complete. In both sets we will measure blood volume by dye dilution technique which requires an intravenous catheter (IV). We will also sample blood for certain biochemicals which may be important in POTS. This will only be performed on the first day of testing.

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What is the hypothesis and importance

POTS has many causes, all related to an abnormal decrease in the amount of blood returning to the heart especially when patients are standing upright. Thus, it is a problem in blood flow regulation. Blood flow regulation is partly due to the autonomic nervous system and partly due to local factors. It is these local factors which we are studying. Our data indicate that there is impairment in nitric oxide or NO whose job it is to control blood vessel size with changes in blood flow, changes in blood vessels during inflammation and blood vessel leakiness. In addition it appears that NO also originates in other tissues where it can exert a potent regulatory ability on the sympathetic nervous system. There is new data indicating both local regulation changes through the innermost wall of the blood vessel called the endothelium. There is also evidence that a defect in NO production within the central nervous system and an excess of angiotensin-II produce sympathoexcitation. We propose to test whether there are abnormalities in NO and angiotensin-II production causing POTS. In one set of experiments we will perform tests to measure NO, tests to stimulate the release of NO and tests of the effects of chemicals, which may be blocking NO release or can replace NO if it is missing. In another set of experiments we measure the effects of alteration of nitric oxide and angiotensin-II on the outflow of sympathetic nerves from the central nervous system.

If we discover specific biochemical mechanisms of POTS in patients, then we may be able to specifically treat the defect.

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What are the symptoms of POTS

The key feature of POTS is symptoms which are most prominent when standing. However, in some, findings are present supine (lying down)  but worsened standing. Symptoms of POTS include dizziness in all patients, exercise provoked symptoms and thus exercise intolerance, excessive fatigue, nausea and abdominal pain, headache, shortness of breath and deep breathing, weakness, shakiness and postural anxiety, pallor, and neurocognitive loss (difficulty thinking). These occur on a day-to-day basis. The symptoms overlap with the case definition of chronic fatigue syndrome (CFS) and POTS is often found in CFS in the young. Fainting is relatively uncommon during daily life. 

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What is the goal of the study

Our study will determine how often blood flow regulation abnormalities and abnormalities of sympathetic regulation produced by nitric oxide and angiotensin-II occur in POTS and the mechanism(s) of POTS in individual patients. Specific causes for POTS may vary from patient to patient. Patients will be compared to healthy control subjects. If we know the specific biochemical mechanism we may be able to offer specific treatment to specific patients.

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What can your own doctor do

Your doctor can rule out other illnesses such as infectious and inflammatory conditions which can produce similar symptoms. For example, most blood tests can be performed by your own physician. In addition you may have seen a cardiologist, a neurologist, or an endocrinologist. Tests such as tilt table tests may have been performed which is the standard means to diagnose POTS: POTS may have been diagnosed during a preliminary laboratory session by an increase in sinus heart rate of greater than 30 bpm within 10 minutes after upright tilt to 70^° associated with symptoms of orthostatic intolerance.

However, the tests we will be performing are not ordinarily available to your doctor. They are, however, all approved ways of measuring how blood vessels work. POTS can be treated by a combination of lifestyle adjustments such as avoidance maneuvers and by medication which your doctor can administer. The tests performed during the study may help us determine what treatment is best for you. We will provide you and your doctor with test results and treatment information.

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How do I know if I’m eligible to be in this study? 

All POTS patients are elligible. It can be difficult to distinguish those with different causes of POTS prior to entry into the study. At this time we cannot accurately predict who has local circulatory dysfunction, or who has sympathetic activation. Therefore all patients who fulfill the criteria for POTS and are between 15 and 29 years old can enroll.

The diagnosis of POTS may be made by your doctor or your consulting doctors. However,  this requires documentation of a standard tilt test demonstrating the changes in heart rate associated with symptoms of OI that are characteristic of POTS. The diagnosis of POTS may also be made through contact with our center which will include a standard tilt table evaluation. The diagnosis of POTS is prerequisite to the the study proper.

Exclusion:  Criteria for initial exclusion will include a condition known to be associated with endothelial dysfunction, an active medical condition that may explain the diagnosis, a previous medical condition with undocumented resolution that may explain the diagnosis, past or present major psychiatric disorder, or substance abuse within 2 years before onset of symptoms.

Inclusion: Cases will be between the ages of 15 and 29 years old referred for evaluation of orthostatic intolerance with 3 or more of the following symptoms for at least 3 months: dizziness, nausea and vomiting, palpitations, fatigue, headache, exercise intolerance, blurred vision, abnormal sweating, heat. Cases will have the diagnosis of symptomatic postural tachycardia made during a screening tilt table test. Cases will have normal physical examination, and normal electrocardiographic and echocardiographic evaluations. Only those free from heart disease, and from systemic illness will be eligible to participate. This excludes patients with illnesses and disease states known to be associated with endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, morbid obesity and peripheral vascular disease. At the time of testing all patients and control subjects must refrain from vasoactive drugs for two weeks. Please check with us about any medication that you are taking.

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Who pays for the exams, or testing?

The diagnosis of POTS is a clinical diagnosis that may be made by your doctors or by our center. In either case clinically appropriate fees may be incurred. There is no charge to you for any of the the testing  directly related to this study. We will pay each participant who completes the study $300 as a token of appreciation for their time.

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How can I get a questionnaire for this study? 

You can click on the Questionnaire icon, and download and print out the application and mail it to us. The mailing address is on the last page of the form. Alternatively you can email the application to stewart@nymc.edu or you can also fax us the application at 914-593-8890. Or, you can call us at 914-593-8888, leave your name and address on the voicemail and we’ll mail you an application. 

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What happens if I’m eligible to be in the study and decide to participate? 

If you would like to take part in these studies, the study coordinator will contact you to go over questionnaire material and discuss arranging for the study. The study coordinator will review the consent form with you and we will also review the consent and any questions you may have when you arrive for the study. You and your parents (if applicable) should understand the study, and its risks and benefits. You can click on the icon for Consent Form to read about our study. 

Testing lasts two days usually on a Monday and a Tuesday. We will make appointments to come to our center for your visits. You’ll arrive at 10 AM on the day of your appointment. We ask that you not eat or drink anything after 6 AM that morning. Please wear comfortable clothing and bring along a pair of shorts and a short sleeve shirt. 

We will meet you at the Bradhurst Building and take you to the laboratory area. Here then you will meet Dr. Marvin Medow and Dr. Julian Stewart who, along with the coordinator or a technician, will review the study with you, and answer any questions you may have. After obtaining your or your parents informed consent and informed assent if appropriate,  you’ll answer a few questions, have a brief physical examination, give a urine sample, and be taken to the laboratory area.

You will undergo tests of how the blood vessels function.  We will measure blood flow properties of the leg and arm vein using noninvasive techniques while lying flat. You will then have a brief tilt table test for at most 10 minutes so that we can confirm POTS and measure whether there are important fluid shifts when upright. 

There are currently two active sets of experiments: one to look strictly at local regulation and the other to look at sympathoactivation in POTS and its relation to NO and angiotensin. We will likely ask you to enroll in the second set of experiments since data from the first are complete. In both sets we will measure blood volume by dye dilution technique which requires an intravenous catheter (IV). We will also sample blood for certain biochemicals which may be important in POTS. This will only be performed on the first day of testing.

In the first set of experiments we use Laser-Doppler flowmetry (LDF) to measure skin blood flow while lying flat. This uses a small beam of reflected light which you cannot feel. LDF will be combined with microdialysis in which we put tiny tubes called microdialysis probes within the skin of the leg using a small needle. There will be four probes placed on the first day of testing and four probes on the second day. This will enable us to measure how much NO and related biochemicals are being locally produced and will allow us to administer small amounts of chemicals into the skin, testing the ability of the blood vessels to react normally.  The method only affects the tiny area of skin tested and has no effect on overall circulation. Thus, we can test how blood vessels work without disturbing the natural workings of the heart and circulation. We will stimulate local blood flow in two ways: One uses gentle local heating over a small area of skin. The other uses a blood pressure cuff that is inflated for 4 minutes on your leg to a pressure above your highest blood pressure. This causes blood vessels to widen and stimulates the production of NO. On the second day of testing we will also examine blood flow in response to acetylcholine in combination with other medications. We believe that this study will help to determine the specific biochemical causes of POTS and will point towards improved medical therapy for young patients.

The second set of experiments investigates more specific regulation of sympathetic outflow from the central nervous system by nitric oxide and angiotensin-II. In these experiments sympathetic nerve activity is measured in a leg nerve using a tiny electrode. We then measure changes in blood flow regulation during the administration of drugs that can increase or decrease nitric oxide and angiotensin-II in the central nervous system.

 We expect that each visit will take about 6-7 hours.

If you have further questions about the study, please feel free to call:
914-593-8888 for more information. 
or Email at stewart@nymc.edu

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