Welcome to the
Postural Tachycardia Study website. Researchers at the Center
for Hypotension at New York Medical College in Valhalla NY
have received renewed funding from the National Institutes of Health (NIH) to
study whether neurovascular problems that can explain the findings of
postural tachycardia syndrome
in teenagers and young adults. Our recent data indicate that
modulation of the sympathetic nervous system by
nitric oxide of nNOS origin
explain many of the features of POTS including
in important subsets of POTS.
Investigator for this study is Julian M. Stewart MD, PhD,
Professor of Pediatrics and of Physiology at
New York Medical College.
comprises the study population?
is the hypothesis and importance of the study?
are the symptoms and findings in patients?
is the goal of the study?
your own doctor can do to help diagnose POTS.
do I know if I’m eligible to be in this study?
pays for the exams, testing, and travel?
can I get a questionnaire for this study?
I decide to participate what does the study entail?
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.
currently two sets of experiments: one focussing on skin to look at local
vascular regulation by nitric oxide, angiotensin-II and oxidative stress
and the other to look at sympathetic activation in
POTS and its relation to NO, angiotensin, and oxidative stress. You will need to be over
years old (i.e. 15-29 years old) to enroll in the studies.
is the hypothesis and importance
A major subset of POTS has increased peripheral
resistance and low blood flow (LFP) related to increased angiotensin-II
(Ang-II), and decreased nitric oxide (NO). NO deficits are reversed by
Ang-II type-1 receptor (AT1R) blockade, ascorbic acid (AA) and
tetrahydrobiopterin in skin suggesting the importance of oxidative
stress. Preliminary data also suggest that the coupling of sympathetic
nerve activity to blood vessel contraction is enhanced via ↑Ang-II
and ↓NO. We hypothesize that this is due to activation of reactive
oxygen species (ROS) including superoxide, which scavenges NO to
generate peroxynitrite, and hydrogen peroxide. Combined measurements in
the skin and the systemic circulation will be combined with local
measurement of ROS production and sympathetic nerve activity will enable
us to determine precisely how the autonomic nervous system is affected
by the illness. Methods include cutaneous microdialysis to measure ROS,
skin biopsy and blood tests to measure gene expression of nitric oxide
synthase and Ang-II receptors, and peroneal microneurography to measure
muscle sympathetic nerve activity (MSNA). Combined with ultrasonic
femoral artery blood flow this will yield assessment of the
interactions of nerves with the blood vessels that they control.
we discover specific biochemical mechanisms of POTS in patients, then we
may be able to specifically treat the defect.
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
with the case definition of chronic fatigue syndrome (CFS) and POTS is
often found in CFS in the young. Fainting is relatively uncommon during
is the goal of the study
study will determine how often blood flow regulation abnormalities
and abnormalities of sympathetic regulation produced by nitric oxide,
angiotensin-II, and oxidative stress 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. There is a treatment arm with a medication (losartan) that
reduces the binding of angiotensin and increases NO. If we know the specific biochemical mechanism we may be able
to offer further specific treatments to specific patients.
Our Specific Aims
1 In Microvascular Studies - to test whether cutaneous microvascular NO
is increased in VVS and NFP and inhibits pre- and post-junctional
2 Microvascular Studies - to test whether nitric oxide synthase (NOS)
isoforms (eNOS, iNOS and nNOS) gene expression and protein content are
increased in OI
3Macrovascular Studies - to test whether systemic NO is increased in VVS
and NLP, inhibits pre and post junctional adrenergic activity, and
alters the hemodynamic response to orthostatic stress.
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 a standard means to diagnose POTS and has been used to assess
VVS. Thus, in most cases POTS and VVS will have been
diagnosed during a clinical assessment by your own doctors.
The tests we will be
performing are not ordinarily available to your doctor. They are,
however, all approved ways of measuring how blood vessels and the
autonomic nervous system work. If there is NO excess, the tests performed during the study
may help us determine a specific treatment. We will provide
you and your doctor with all test results.
do I know if I’m eligible to be in this study?
All postural VVS
patients are eligible if they have had 3 or more episodes in the past 12
months. All "normal flow", splanchnic pooling neuropathic POTS patients
are eligible. It can be difficult to
distinguish those with different causes of POTS prior to entry into
a study. However, our concurrent study entitled "Local
Vasoconstriction in Low Flow POTS" can make this distinction in one
day of testing. Therefore prior POTS subjects diagnosed with
neuropathic or current subjects will be eligible.
The diagnosis of
VVS or POTS may be made by your doctor or your consulting doctors. The diagnosis of
neuropathic POTS may also be made through
contact with our center which will include a standard tilt table
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.
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.
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 a daily fee to help defray any expenses in
participating in the study.
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 firstname.lastname@example.org 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.
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 nurse study coordinator, Courtney
Terilli will contact you to go over
questionnaire material and discuss arranging for the study. She 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
most of a week and you will also be asked to have a measurement of blood
volume. We will make
appointments to come to our center for your visits. You’ll arrive at
9:30 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 our nurse coordinator Courtney Terilli, and Drs. Julian Stewart
and Marvin Medow who, along with other staff, will review the study with you, and answer any questions you may
have. After obtaining your or your parents informed consent 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.
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. On another day we
will measure the impact of gradual tilting on memory.
currently two active sets of experiments: one to look strictly at local
regulation in the skin and the other to look at sympathoactivation in POTS and its
relation to NO and angiotensin. We will test whether antioxidant therapy
can reduce overall abnormalities in blood flow and sympathetic
activation. We will
also sample blood for certain biochemicals, for nitric oxide, and for
the expression of gene activity (not measuring DNA) which may be important in
POTS. If you are in the "low flow" group of POTS patients we
will request that you enroll in a study of the effects of the
angiotensin receptor blocker, losartan, on chronic POTS and ask that you
return for follow up visits.
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 five probes placed on the first day of testing and
five probes on the
second day. This will enable us to measure how much NO, angiotensin, and
ROS 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. These are FDA approved. 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 by
using gentle local heat over a small area of skin. These tests take a
number of hours and are more boring than anything else.
Later on and
after local anesthesia, we will also obtain two tiny amounts of skin
from your leg to look for genetic expression related to nitric oxide and
angiotensin. thus, we will have laser blood flow measurements, response
to medications and antioxidants, and gene expression from the same organ
(skin) at one time.
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 can measure changes in blood flow regulation
and autonomic nervous system control during the administration of drugs that can increase or decrease nitric
oxide and angiotensin-II in the central nervous system. An ultrasound of
the femoral (leg) artery on the opposite side will enable us to tell
whether the problems in blood flow regulation arise from the nerve
itself or from the conversion of the sympathetic nerve signal into blood
If you have
further questions about the study, please feel free to call:
or Email at email@example.com