Postural tachycardia syndrome: a heterogeneous and multifactorial disorder
A Heterogeneous and Multifactorial Disorder
Postural tachycardia syndrome (POTS) is defined by a heart rate increment of 30 beats/min or more within 10 minutesof standing or head-up tilt in the absence of orthostatic hypotension; the standing heart rate is often 120 beats/min orhigher. POTS manifests with symptoms of cerebral hypoperfusion and excessive sympathoexcitation. The pathophys-iology of POTS is heterogeneous and includes impaired sympathetically mediated vasoconstriction, excessive sympa-thetic drive, volume dysregulation, and deconditioning. POTS is frequently included in the differential diagnosis ofchronic unexplained symptoms, such as inappropriate sinus tachycardia, chronic fatigue, chronic dizziness, or unex-plained spells in otherwise healthy young individuals. Many patients with POTS also report symptoms not attributable toorthostatic intolerance, including those of functional gastrointestinal or bladder disorders, chronic headache, fibromyalgia,and sleep disturbances. In many of these cases, cognitive and behavioral factors, somatic hypervigilance associated withanxiety, depression, and behavioral amplification contribute to symptom chronicity. The aims of evaluation in patients withPOTS are to exclude cardiac causes of inappropriate tachycardia; elucidate, if possible, the most likely pathophysiologic basisof postural intolerance; assess for the presence of treatable autonomic neuropathies; exclude endocrine causes of ahyperadrenergic state; evaluate for cardiovascular deconditioning; and determine the contribution of emotional andbehavioral factors to the patient’s symptoms. Management of POTS includes avoidance of precipitating factors, volumeexpansion, physical countermaneuvers, exercise training, pharmacotherapy (fludrocortisone, midodrine, -blockers,and/or pyridostigmine), and behavioral-cognitive therapy. A literature search of PubMed for articles published fromJanuary 1, 1990, to June 15, 2012, was performed using the following terms (or combination of terms): POTS; posturaltachycardia syndrome, orthostatic; orthostatic; syncope; sympathetic; baroreceptors; vestibulosympathetic; hypovolemia; vis-ceral pain; chronic fatigue; deconditioning; headache; Chiari malformation; Ehlers-Danlos; emotion; amygdala; insula; anteriorcingulate; periaqueductal gray; fludrocortisone; midodrine; propranolol; -adrenergic; and pyridostigmine. Studies werelimited to those published in English. Other articles were identified from bibliographies of the retrieved articles.
2012 Mayo Foundation for Medical Education and Research Ⅲ Mayo Clin Proc. 2012;87(12):1214-1225
From the Department ofNeurology, Mayo Clinic,Rochester, MN.
P osturaltachycardiasyndrome(POTS)isone drenandadolescents,andnewcriteriaforthesedis-
of the most common manifestations of ortho-
orders in this age group have been recently
criteria for POTS is defined by a heart rate
(female:male ratio, 4.5:1), and most cases occur be-
increment of 30 beats/min or more within 10 min-
tween the ages of 15 and 25 years. Up to 50% of
utes of standing or head-up tilt (HUT) in the absence
cases have antecedent viral illness, and 25% have a
of orthostatic hypotension; the standing heart rate is
often 120 beats/min or higher. These criteria may
rience from extensive series indicates that POTS is
not be applicable for individuals with low resting
pathophysiologically heterogeneous. Many patients
heart rate. For individuals aged 12 to 19 years, the
with POTS present with multiple chronic symptoms
that are not directly related to orthostatic stress, and
orthostatic tachycardia may be accompanied by
only a small subgroup of patients with POTS have a
symptoms of cerebral hypoperfusion and sympa-
defined autonomic disorder. Physical decondition-
thetic hyperactivity that are relieved by recum-
ing and psychological factors have an important role
bency. Symptoms of cerebral hypoperfusion include
in these patients. Therefore, the evaluation and
light-headedness, blurred vision, cognitive difficul-
management of POTS should be multidisciplinary.
ties, and generalized weakness; symptoms of exces-
These patients pose a particular challenge in man-
sive sympathoexcitation include palpitations, chest
agement, which reflects the pathophysiologic hetero-
pain, and tremulousness. The term orthostatic intol-
geneity of orthostatic intolerance, the presence of
erance is used to describe a condition in which pa-
multiple comorbidities not directly related to ortho-
tients develop symptoms on standing or HUT but
static stress, and the lack of recognition that patients
do not fulfill the heart rate criteria for the diagnosis
with POTS frequently require exercise training and
of The diagnostic criteria for orthostatic in-
behavioral-cognitive approaches to obtain long-
tolerance and POTS in adults are unsuitable for chil-
term control of their symptoms. There have been
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
www.mayoclinicproceedings.org Ⅲ 2012 Mayo Foundation for Medical Education and Research
many recent reviews on This review willfocus on (1) the pathophysiologic heterogeneity of
POTS, (2) comorbid conditions commonly associ-
Postural tachycardia syndrome (POTS) is not a unique nosological
ated with POTS, (3) an expanded view of POTS
entity, and its treatment should be individualized.
pathophysiology, and (4) the evaluation and ratio-nale for a multimodal approach to these patients.
The pathophysiologic mechanisms of orthostatic intolerance in POTS
A literature search of PubMed for articles pub-
are multifactorial and include hypovolemia, venous pooling, hyperad-
lished from January 1, 1990, to June 15, 2012, was
renergic states, and restricted adrenergic neuropathies in the lower
performed using the following terms (or combina-
tion of terms): POTS; postural tachycardia syndrome,
Many symptoms reported by patients with POTS, including visceral
orthostatic; orthostatic; syncope; sympathetic; barore-ceptors; vestibulosympathetic; hypovolemia; visceral
symptoms and chronic pain disorders, are not due to orthostatic
pain; chronic fatigue; deconditioning; headache; Chiari
intolerance and therefore are not, in the strict sense, part of the
malformation; Ehlers-Danlos; emotion; amygdala; in-sula; anterior cingulate; periaqueductal gray; fludrocor-
Most patients with POTS and evidence of a sympathetic neuropathy
tisone; midodrine; propranolol; -adrenergic; and pyri-
restricted to the lower limbs have no identifiable cause of neuropathy;
dostigmine. Studies were limited to those published
pheochromocytoma should be excluded in patients with excessive
in English. Other articles were identified from bib-liographies of the retrieved articles.
Except for effects of chronic pain and physical deconditioning, there is
no clear mechanistic relationship between Ehlers-Danlos syndrome or
POTS AS A SYNDROME OF ORTHOSTATICINTOLERANCE
The management of POTS includes patient education, volume restitution,
Symptoms Reflecting Orthostatic Intolerance
physical countermaneuvers, graded exercise training, and pharmacotherapy
POTS is one of the most common syndromes of
(fludrocortisone, midodrine, -blockers, and/or pyridostigmine).
orthostatic intolerance; others include reflex (neu-
Cognitive-emotional factors, including behavioral conditioning and am-
rally mediated, vasovagal) syncope and orthostatichypotension in its several The manifesta-
plification, have a key role in POTS.
tions of POTS that reflect orthostatic intolerance(POTS in the strict sense) include those of cerebralhypoperfusion and reflex sympathetic activation.
of sweating in the feet on thermoregulatory sweat
Up to one-third of patients may develop secondary
tests and quantitative sudomotor axon reflex test-
orthostatically triggered vasovagal (reflex, neurally
and impaired increase of NE release in the
lower limb in response to orthostatic In a
intolerance, typical exacerbating factors include
large 54% of patients had evidence of pe-
heat exposure, physical exertion, heavy meals, pro-
ripheral sudomotor denervation. The primary
longed recumbency, menses, and drugs such as di-
pathophysiologic mechanism of postural intoler-
ance in this subgroup of patients is presumed to beimpaired peripheral vasoconstriction, leading to ve-
Classic Pathophysiology and POTS Subtypes
nous pooling in the lower limbs. Consistent with
Exaggerated postural tachycardia may reflect several
this possibility, a subgroup of patients with POTS
have impaired indirect measures of sympathetic va-
soconstriction assessed by the blood pressure profile
norepinephrine (NE) levels, POTS has been classi-
during the Valsalva maneuver or and venous
fied into several subtypes, including neuropathic
pooling in the absence of venous compliance defects
surement of leg venous pressure and calf blood flow,
corresponds to the so-called high-flow POTS sub-
group, characterized by reduced total peripheral re-
 -Adrenoreceptor polymorphisms may contribute
sistance while supine and venous pooling in the legs
to the hemodynamic diversity of patients with
benzylguanidine uptake has been reported in pa-tients with However, the relationship be-tween this finding and peripheral adrenergic
Neuropathic POTS. The term neuropathic
denervation of the lower limb is still undeter-
describes a subgroup of patients with indirect evi-
mined. The frequent onset after a viral illness and
dence of peripheral sympathetic denervation in the
the presence of a ganglionic acetylcholine recep-
lower limbs. This condition is characterized by loss
tor antibody in 14% of patients suggest an auto-
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
TABLE 1. Pathophysiologic Mechanisms of Orthostatic Intolerance in POTS
Impaired sympathetically mediated vasoconstriction
Restricted postviral or autoimmune neuropathies
Excessive cardiac sympathoexcitatory responses
Impaired renal control of fluid secretion
HUT ϭ head-up tilt; MIBG ϭ meta-iodobenzylguanidine; NE ϭ norepinephrine; POTS ϭ postural tachycardia syndrome; RAA ϭ renin-angiotensin-aldosterone; VGKC ϭvoltage-gated potassium channel; VM ϭ Valsalva maneuver; V˙O
possibility of hyperthyroidism or a catecholamine-se-
creting tumor, such as pheochromocytoma, should beconsidered. Laboratory studies should include deter-mination of plasma and urinary metanephrine levels,
Hyperadrenergic POTS. Between 30% and 60% of
and if they are elevated, imaging studies to detect
patients with POTS have evidence of increased cen-
tral sympathetic drive, as reflected by standing
Hyperadrenergic states may also be secondary
plasma NE levels of 600 pg/mL or more (to convert
to immune disorders associated with antibodies
to pmol/L, multiply by 5.911); fluctuating blood
against components of the voltage-gated potas-
pressure or hypertensive response during HUT; and
sium channel complex in the setting of limbic
episodes of tachycardia, hypertension, and hyperhi-
hyperadrenergic POTS as the only manifestation
triggered not only by orthostatic stress but also by
of anti–voltage-gated potassium channel complex
emotional stimuli and physical activity. This sub-
autoimmunity has not yet been convincingly
group of patients may correspond to the so-called
low-volume POTS characterized by supine vasocon-striction, supine tachycardia, pale and cold skin,and increased supine muscle sympathetic nerve ac-
POTS and Volume Dysregulation. Many patients
These patients have been categorized into a
with POTS have low plasma, red cell, and total
primary or central hyperadrenergic subgroup with
blood volumes as assessed using various tech-
plasma NE levels often between 1000 and 2000
niques.In one study, 28.9% of patients ex-
pg/mL that compromises approximately 5% to 10%
creted less than 100 mEq/L of sodium in 24 hours,
of cases and a heterogeneous group of secondary
which was interpreted as consistent with a hypovo-
lemic In many cases, these patients have low
quence variation of the norepinephrine transporter
levels of standing plasma renin activity and aldoste-
(NET) and reduced clearance of synaptic NE were
rone compared with controls. However, some pa-
tients have a low-flow phenotype associated with
ever, increased NE levels more commonly reflect
inappropriately high plasma angiotensin II levels,
pharmacological NET blockade by drugs such as
reflecting reduced estimated angiotensin-convert-
tricyclic antidepressants, selective NET inhibitors,
and amphetaminelike drugs such as methylpheni-
disorders associated with poor water intake due to
date. Secondary hyperadrenergic POTS has also
nausea or excess fluid loss due to diarrhea may re-
been associated with mast cell activation disor-
sult in hypovolemia with secondary orthostatic
In patients with hyperadrenergic POTS, the
symptoms and tachycardia. In this case, POTS
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
should be considered a consequence of the gastro-
parasympathetic or sympathetic output via the
vagus, pelvic, or splanchnic nerves.
POTS and Physical Deconditioning. Most patients
Chronic Fatigue, Insomnia, and Fibromyalgia
with POTS exhibit greater and more persistent
tachycardia, reduced stroke volume, reduced left
turbanceshave been frequently associated with
ventricular mass, and reduced peak oxygen uptake
POTS. In a large series of adult patients with POTS,
when upright and during and after exercise com-
many reported chronic fatigue (48%), sleep distur-
bance (32%), and myofascial pain There is an
dicate the presence of physical deconditioning,
overlap between chronic fatigue syndrome and POTS.
which may be an important factor in the develop-
Patients with POTS who have chronic fatigue syn-
ment of orthostatic symptoms, regardless of the un-
drome have higher laboratory markers of sympathetic
activation than patients without chronic
tioning also decreases the gain of the vasoconstrictorbaroreceptor and the vestibulosympa-
thetic which could also predispose patients
Ehlers-Danlos syndrome (EDS) is a heterogeneous dis-
to orthostatic intolerance. However, there is evi-
order that includes several forms, all linked to se-
dence that bed rest or deconditioning does not pri-
quence variations in genes encoding for fibrillar pro-
marily affect the reflex control of muscle sympa-
teins and/or collagen processing enzymes leading to
reduced structural integrity of connective tissue. Joint hypermobility, which is characteristic of EDStype III associated with sequence variations in tenas-
cin X, has been frequently associated with
Many patients with POTS experience chronic symp-
toms that cannot be mechanistically explained by pos-
between these 2 entities is incompletely defined.
Whereas tenascin X sequence variations affect car-
these symptoms are also prevalent in patients without
diovascular tissue leading to valvular the
orthostatic intolerance; in these cases, excessive pos-
hypothesis that impaired integrity of vascular con-
tural tachycardia is secondary to hypovolemia, pro-
nective tissue leads to impaired venous return and
longed bed rest, physical deconditioning, and anxiety,
secondary orthostatic tachycardia has not yet been
convincingly tested. EDS III is also characterized byearly onset of chronic pain, particularly in the shoul-ders, hands, and which may be disabling
due to associated anxiety, depression, and a somato-
A percentage of patients with POTS experience vis-
sensory amplification this may lead to sec-
ceral symptoms referred to the upper or lower gas-
ondary hypersympathetic responses triggered by
trointestinal tract, bladder, and other organs. In a
large series of adult patients with nausea waspresent in 39%, bloating in 24%, diarrhea in 18%,constipation in 15%, abdominal pain in 15%, and
bladder symptoms in 9% of cases. These symptoms
Chronic headache, including migraine, is a common
are similar to those typically reported by patients
with functional motility disorders such as functional
static headaches also occur in patients with
dyspepsia, gastric emptying disorders, irritable
even in the absence of intracranial hypo-
bowel syndrome, and interstitial cystitis, among
volemia or cerebrospinal fluid The relation-
ship between POTS and orthostatic headache is un-
these disorders includes mucosal inflammation, vis-
certain because treatment of orthostatic tachycardia
ceral hypersensitivity, secondary visceromotor dys-
with volume expansion is only partially effective in
function, and, in most cases, behavioral amplifica-
been reported in patients with type I Chiari malfor-
frequently reported in patients with neuropathic
they should not necessarily be considered
a manifestation of a primary underlying auto-
incidental type I Chiari malformation and ortho-
nomic disorder (dysautonomia) because these are
static intolerance has not been convincingly dem-
disorders of visceral sensitivity mediated by vis-
ceral afferents and not due to primary involve-
tients with a remote history of traumatic head
ment of the enteric nervous system or efferent
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
direct damage of central autonomic areas as the
primary cause of orthostatic intolerance.
ceptors (including cardiovascular, gastrointestinal,and genitourinary receptors) as well as visceral and
somatic nociceptors is conveyed to this network viathe dorsal horn of the spinal cord, nucleus of the
solitary tract, and parabrachial nucleus of the
vestibular receptors activate this network
The persistence of orthostatic symptoms despite
via relay in the vestibular This information
adequate control of the heart rate and the coexis-
is referred to as interoception because it reflects the
tence of many nonorthostatic symptoms com-
physiological state of the body.These inputs trig-
monly reported by patients with POTS suggest that
ger homeostatic reflexes integrated at the level of the
impaired processing of viscerosensory (including
cardiovascular) information, conditioning, and be-
havioral amplification also play a contributory role
static stress and mediated by sympathoexcitatory
in this disorder. For example, many triggers, such as
viral illness (particularly if associated with gastroin-
These interoceptive inputs also relay, either directly or
testinal fluid loss), prolonged bed rest, or both, may
via the thalamus, to forebrain areas such as the hypo-
result in relatively rapid development of symptoms
thalamus, amygdala, insular cortex, and anterior cin-
of orthostatic intolerance and sympathoexcitation.
gulate All these areas are reciprocally inter-
This pattern of responses may become conditioned,
connected and control sympathetic cardiovascular
leading to failure of the viscerosensory and sympa-
output via projections to the rostral ventrolateral me-
thetic systems to readapt to the routine demands
The amygdala automatically attributes emo-
of standing and exercise after the acute illness.
tional valence to the stimulus and is involved in
This situation would be akin to the case of chronic
associative learning and conditioned fear re-
subjective dizziness, in which there is failure of the
The anterior insular cortex is required for
postural and ocular motor control systems to re-
adapt to the routine demands of locomotion after an
ample, functional magnetic resonance imaging
acute episode of vertigo and postural instabil-
studies showed increased activity of the anterior in-
Because standing up not only produces ac-
sula during tasks in which subjects attend to the
tivation of the baroreflex but also triggers a vestibu-
timing of their heartbeats.The dorsal anterior cin-
gulate (also called the midcingulate) cortex is acti-
responses to vestibular inputs and lack of readapta-
vated during tasks that involve awareness, attention,
tion of the vestibulosympathetic responses may also
and behavioral engagement that are associated with
contribute to persistence of posture-induced symp-
an increase in sympathetic These areas proj-
toms and tachycardia in these patients. Abnormal
ect to the hypothalamus and periaqueductal gray
processing of sensory information, including so-
region, which orchestrate coordinated autonomic
and pain modulatory responses in the setting of
tion, may also contribute to persistence of symp-
emotion and stress. Functional neuroimaging stud-
toms, including those not triggered by orthostatic
ies also indicate that the insular and anterior cingu-
late cortex may also be involved in modulation of
and chronic dizziness. Furthermore, decondition-
baroreflex-mediated sympathetic and cardiovascu-
ing, poor sleep, and psychological factors such as
anxiety or depression may all lead to relative pre-
There is a reciprocal interaction between these
dominance of sympathetic over vagal control the
areas and areas of the prefrontal cortex involved in
focused attention and emotional modulation.Theinsular, midcingulate, and dorsolateral prefrontal
cortex are also components of the cortical network
The central circuits involved in visceral sensation,
that is activated in response to pain and visceral
aversive conditioning, behavioral arousal, stress re-
sensations, referred to as the pain matrixThis
sponses, and pain processing and modulation may
network exhibits considerable use-dependent syn-
all be involved in the maintenance of the symptoms
aptic plasticity, which may be maladaptive, for ex-
ample in the setting of chronic stress or
this network include the brainstem sensory relay nu-
Functional neuroimaging studies also show that the
clei, amygdala, insula, anterior cingulate cortex, hy-
connectivity among the amygdala, cingulate, and pre-
pothalamus (particularly the paraventricular nu-
frontal cortex is affected in disorders such as anxiety
cleus and lateral hypothalamic area), periaqueductal
gray region, medullary raphe, and ventrolateral me-
ditions in patients with symptoms associated with
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
Anterior cingulate cortex (behavioral arousal)
Amygdala (emotional tagging of sensation)
-Visceral pain/dysmotility-Myofascial pain
FIGURE. Complex pathophysiology of postural tachycardia syndrome (POTS). The mechanisms of orthostatic intolerance inPOTS include impaired sympathetic vasoconstriction leading to venous pooling, hypovolemia, deconditioning, and hyperadrenergicstate. Excessive reflex sympathoexcitation may be triggered by orthostatic stress via reduced baroreceptor input to the nucleusof the solitary tract (NTS) and activation of vestibulosympathetic reflexes (VSR) relayed via the medial vestibular nucleus (MVN),resulting in increased activity of sympathoexcitatory neurons of the rostral ventrolateral medulla. Many comorbidities of POTS,including visceral pain and dysmotility, other chronic pain conditions, and dizziness may reflect abnormal processing of interoceptiveinformation, relayed via the NTS and parabrachial nucleus (PBN) via the ventromedial portion of the thalamus to a central networkthat includes the anterior cingulate cortex, insula, amygdala, hypothalamus, and periaqueductal gray region.
POTS, including those of visceral pain and dysmotility,
tating or aggravating factors; presence of associated
chronic fatigue, fibromyalgia, and insomnia.
nonorthostatic symptoms; fluid and caffeine intake;level of physical activity; sleep pattern; response toprevious attempted treatments; and current drug
EVALUATION AND MANAGEMENT OF PATIENTSWITH POTS
therapy. The patient should undergo a comprehen-sive cardiac and neurologic examination in addition
Patients with POTS require a multidisciplinary eval-
to measurements of supine and standing heart rate
and blood pressure. Examination could also revealindirect evidence of venous pooling (such as lower
extremity edema) or excessive sympathetic activity
Elicitation of the clinical history of patients with
(such as cold, clammy hands). The main aspects of
POTS should address the trigger, timing of onset,
laboratory evaluation in patients with POTS are
and progression of orthostatic symptoms; precipi-
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
TABLE 2. Laboratory Evaluation in Patients With POTS
Cardiac evaluation (ECG, echocardiogram, Holter monitoring)
Head-up tilt (at a 60° angle for 10 min)
Plasma catecholamine, both supine and during standing or
Assessment of baroreflex sympathoexcitation
24-Hour blood pressure and heart rate monitoring
Correlate the timing of the patient’s symptoms
Autoantibodies (VGKC complex, ganglionic AChR)
AChR ϭ acetylcholine receptor; ECG ϭ electrocardiogram; MRI ϭ magnetic resonance imaging; OI ϭ orthostatic intolerance; POTS ϭpostural tachycardia syndrome; VGKC ϭ voltage-gated potassium channel.
primary cardiac causes of inappropriate tachycardia;
into the different pathophysiologic subtypes
determine, if possible, the most likely primary
(neuropathic, hyperadrenergic, or hypovolemic).
pathophysiologic basis of postural intolerance;identify treatable causes of autonomic neuropathy
in patients with neuropathic POTS; exclude endo-crine or other systemic causes of a hyperadrenergic
The management of POTS involves nonpharmaco-
state in patients with hyperadrenergic POTS; assess
the degree of cardiovascular conditioning; investi-
gate the mechanisms of gastrointestinal and otherassociated symptoms; and address possible psychi-
atric comorbidities. The basic evaluation should in-
Patient education is a fundamental aspect of POTS
clude a cardiac evaluation, autonomic reflex testing,
management. Patients should be informed about the
and measurement of supine and standing plasma
differences between the symptoms that are due to
catecholamine levels. Screening HUT table testing
orthostatic intolerance and those that are not and
has been shown to be helpful in the evaluation of
about potential aggravating or precipitating factors
patients with syncope of unknown cause, including
that may exacerbate their postural and exercise
pressure and heart rate monitoring allows a carefulexamination of the beat-to-beat systolic and dia-stolic blood pressure and heart rate responses dur-
ing HUT. Data regarding stroke index and total
Regardless of the basic pathophysiologic mecha-
peripheral resistance, as well as heart rate vari-
nism, most patients require volume expansion with
ability, can also be obtained from these record-
adequate daily water (1.5-2 L) and sodium intake. This
ings. This information provides a more thorough
is particularly important on awakening or before a pre-
picture of the hemodynamic and reflex responses
dictable orthostatic stress. Excessive caffeine intake
associated with orthostatic stress and allows a
should be avoided because it may increase diuresis
more precise categorization of patients with POTS
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
TABLE 3. Nonpharmacological Management of POTS
Physical countermaneuvers, such as leg crossing,bending forward and placing a foot on a chair, mak-
ing a fist, or active contraction of abdominal or but-
tock muscles may produce small increases in mean
arterial pressure to maintain an adequate cerebral
blood flow and prevent fainting in patients with all
forms of orthostatic intolerance, including neuro-
Avoid blood pooling in mesenteric vessels
Because blood pooling on standing occurs both in
the abdomen and lower limbs, some patients with
POTS may benefit from wearing support garments,
such as thigh- or waist-high tight support stockings
As in all causes of physical deconditioning, reduced
stroke volume is a key component in the pathogen-
short-term exercise training improves physical fit-
ness and cardiovascular responses during exercise
NE ϭ norepinephrine; POTS ϭ postural tachycardia syndrome.
in patients with POTS. Given that deconditionedpatients with POTS may rapidly become symptom-atic during exercise, they should begin with a verysmall amount of exercise, using either a recumbent
intravascular volume. Pyridostigmine may poten-
cycle or treadmill and gradually increasing the reg-
tiate muscarinic receptor activation in the gastro-
imen over the next 6 to 8 weeks. Patients also benefit
intestinal tract, exacerbating nausea, vomiting,
from light strengthening exercises for the major
abdominal cramps, and diarrhea, and in the blad-
muscle groups using weight machines.
der, potentiating the symptoms of detrusorhyperactivity.
Pharmacological TherapyDrug therapy of POTS includes the mineralocorti-
Why Are Some Patients With POTS So Difficult to
ume expansion, the ␣ -adrenergic agonist mido-
Several factors contribute to the difficulties in the
to elicit peripheral vasoconstriction and
management of patients with POTS. First is the lack
reduce venous pooling, -blockers including pro-
of patient education (or, worse, patient misinforma-
tion) about the disorder. This leads to unrealistic
to control the excessive sinus tachycardia,
expectations about the beneficial effects of treatment
aimed to correct the postural tachycardia and sec-
prolong the phasic effects of acetylcholine on the
ondary frustration and symptom amplification. A
autonomic ganglia, leading to peripheral sympa-
second factor is the failure to recognize the hetero-
thetic vasoconstrictor output (and potentiating va-
geneous pathophysiologic basis of orthostatic tachy-
gal effects) on standing However, adverse
cardia in POTS. Drug treatment may need to be in-
effects of these drugs can limit their use in patients
dividualized, depending on whether impaired
with POTS because of the presence of comorbid
peripheral vasoconstriction and venous pooling, hy-
symptoms. Fludrocortisone may exacerbate head-
peradrenergic state, or hypovolemia is thought to be
ache and vertigo, particularly in patients with mi-
the most prominent trigger. A complicating factor is
graine. Midodrine can increase the risk of urinary
that the doses of fludrocortisone, midodrine,
retention in patients with functional bladder disor-
-blockers, or pyridostigmine used for treatment of
ders by increasing contraction of the smooth muscle
other conditions such as neurogenic orthostatic hy-
of the bladder neck. Propranolol and other -block-
potension or inappropriate sinus tachycardia may
ers may exacerbate fatigue and exercise intolerance
not be tolerated by many patients with POTS, par-
and may produce hypotension in patients with low
ticularly those with physical deconditioning and
Mayo Clin Proc. Ⅲ December 2012;87(12):1214-1225 Ⅲ
TABLE 4. Pharmacological Management of POTS
Special considerations in patients with POTS
Vasoconstriction (reduces venous pooling)
May worsen GI symptoms or urinary retention
Reduce sympathetic influence on the sinus node
Propranolol may be potentially useful to treat comorbidities
All -blockers should be started at low doses because
patients may have -adrenoceptor supersensitivity
-Blockers may exacerbate fatigue or produce hypotension
if used without concomitant nonpharmacological
Potentiates ganglionic sympathoexcitation during
May help visceral hypomotility but may exacerbate
GI ϭ gastrointestinal; POTS ϭ postural tachycardia syndrome.
comorbid conditions. Drugs used to treat POTS
eas involved in processing of interoceptive (vis-
comorbidities may also exacerbate orthostatic
ceral and somatic nociceptive) information,
tachycardia; these include amphetaminelike psy-
interoceptive awareness, behavioral arousal, and
chostimulants used to treat chronic fatigue and an-
tidepressants such as amitriptyline used to treat in-
somnia, migraine, fibromyalgia, or visceral pain.
drome; HUT ؍ head-up tilt; NE ؍ norepinephrine; NET ؍
Another reason for symptom persistence is the fail-
norepinephrine transporter; POTS ؍ postural tachycardia
ure to address physical deconditioning with a grad-
ual exercise program. Although many patients are
Correspondence: Address to Eduardo E. Benarroch, MD,
motivated to exercise, they may initially exercise too
Department of Neurology, Mayo Clinic, 200 First St SW,
vigorously, leading to worsening of symptoms. Fi-
nally and perhaps most importantly is the funda-mental role of somatic hypervigilance, behavioralarousal, and emotional conditioning in the main-
tenance of the patient’s orthostatic, as well as non-
Low PA, Opfer-Gehrking TL, Textor SC, et al. Postural tachy-
orthostatic, symptoms. Both the patient and the
cardia syndrome (POTS). Neurology. 1995;45(4, suppl 5):S19-
physician should realize that, as in many other
chronic conditions, realistic expectations and be-
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Az izlám-nők jogi helyzete Évszázados előítélet, hogy a mohammedán nőnek tulaj- donképpen nincs is jogi helyzete. Socialis szerepe és fontossága semmi, férjével szemben rabszolga és semmi más. Alá- rendelt helyzetét az idők hosszú folyama alatt szinte termé- szetesnek kezdtük találni mindannyian egész a legújabb időkig, mikor is Törökország egyes modern politikai