Postural orthostatic tachycardia syndrome (POTS, also postural tachycardia syndrome) is a condition of dysautonomia, to be more specific orthostatic intolerance, in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia. Several studies show a decrease in cerebral blood flow with systolic and diastolic cerebral blood flow (CBF) velocity decreased 44% and 60%, respectively. People with POTS have problems maintaining homeostasis when changing position, e.g. moving from one chair to another or reaching above their heads. Many also experience symptoms when stationary or even while lying down.
Symptoms present in various degrees of severity depending on the individual. POTS can be severely debilitating. Some afflicted individuals are unable to attend school or work and for especially severe cases, they are completely incapacitated.
The hallmark symptom of POTS is an increase in heart rate from the supine to upright position of more than 30 beats per minute or to a heart rate greater than 120 beats per minute within 10 minutes of head up tilt.
This tachycardic response is sometimes accompanied by a decrease in blood flow to the brain and a wide variety of symptoms associated with cerebral hypoperfusion. Decreased cerebral perfusion may promote the following:
Symptoms of POTS overlap considerably with those of generalized anxiety disorder, and a misdiagnosis of an anxiety disorder is not uncommon. Some patients may be able to show a marked, and speedy, reddening of hands on lowering to resting position to challenge this misdiagnosis.
POTS is often accompanied by vasovagal syncope, also called "neurally mediated hypotension" (NMH) or "neurocardiogenic syncope" (NCS). Vasovagal syncope is a fainting reflex due to a profound drop in blood pressure. Autonomic dysfunction that occurs with these disorders causes blood to inappropriately pool in the limbs away from the heart, lungs, and brain. The combination of misdirected bloodflow and hypotension will invoke syncope. Tachycardia associated with POTS may be a cardiac response to restore cerebral perfusion. However, a characteristic of POTS is normotension or even hypertension when presyncope or syncope is experienced, suggesting cerebral vasospasm or autoregulatory failure may account for syncope.
Some people experience symptoms associated with restless leg syndrome. Treating POTS should also relieve these symptoms.
A small percentage of pediatric cases of POTS have been associated with moderate to severe memory loss.
The primary causal mechanisms in POTS remain unclear and are likely heterogeneous. Some people develop symptoms in their teenage years during a period of rapid growth and see gradual improvement into their mid-twenties. Others develop POTS after a viral or bacterial infection such as mononucleosis, pneumonia, or Lyme disease while others develop symptoms after experiencing some sort of trauma such as a car accident or injury. Women can also develop POTS during or after pregnancy.
In one large test, 12.5% of 152 people with POTS reported a family history of orthostatic intolerance, suggesting that there is a genetic inheritance associated with POTS.
While the primary causal mechanisms remain unclear, a number of theories have been offered based on preliminary research findings:
Abnormal distal sudomotor findings are frequently reported suggesting patchy small fiber neuropathy in a large subset of POTS patients. The finding of abnormal quantitive sudomotor axon test results or skin biopsies in this subset have been interpreted as supporting an autonomic neuropathic process.Small fiber peripheral neuropathy may be associated with autoimmune illnesses, exposure to toxins, certain medications, and in many cases are considered idiopathic.
An autoimmune process has been suggested as a causal mechanism for some POTS patients, supported by the finding of autoantibodies against ganglionic alpha 3 acetylcholine receptors. Anecdotally it has been suggested that POTS patients exhibit a higher incidence of comorbid autoimmune diseases than the general population and frequently report a family history of autoimmunity or migraine. More recently, alternative autoantibodies in POTS have been identified.
Low blood volume or hypovolemia is a frequent finding in POTS, often coupled with an abnormal renin-aldosterone response to this volume deficit.
Expression of Norepinephrine transporter (NET) protein appears to be reduced in some POTS patients. Cardiac neurotransmission imaging of norepinephrine reuptake measured utilising MIBG has also been found to be abnormal in some POTS patients, suggesting cardiac denervation or NET deficiency.
Recently, an epigenetic mechanism (chromatin remodelling and gene suppression of the norepinephrine transporter gene) that results in reduced expression of the norepinephrine transporter and consequently a phenotype of impaired neuronal reuptake of norepinephrine has been implicated in the postural orthostatic tachycardia syndrome.
Recent studies have described a subset of POTS patients with elevated angiotensin II levels coupled with paradoxically reduced absolute blood volume, signs of increased sympathetic activity and reduced peripheral blood flow. This subset appears to have abnormal catabolism of Angiotensin II that may contribute to reduced blood volume and orthostatic intolerance.
Reduced venous return is one of the main mechanisms that cause POTS symptoms. Venous return can be reduced due to conditions such as hypovolemia (low plasma volume/low blood volume), venous pooling, and denervation. A hyperadrenergic state may result as the body attempts to compensate for these abnormalities.
Deconditioning either as a primary pathophysiology or an epimechanism have been suggested based on the frequent finding of low stroke volume and blood volume in POTS patients. However, norepinephrine transporter inhibition may create a phenotype with similarities to this finding.
Alpha-receptor dysfunction may be occurring in some POTS patients. Alpha-1 receptors cause peripheral vasoconstriction when stimulated. Alpha-1 receptor supersensitivity may be causing dysautonomia in some patients.
Beta-receptor supersensitivity may occur with hyperadrenergic states in some people with POTS.
A case of Vagal Palsy and associated Postural Tachycardia Syndrome has been reported, presumed in this case to be the result of reduced central parasympathetic activity and consequential reductions in cerebral blood flow and tachycardia.
POTS can be difficult to diagnose. A routine physical examination and standard blood tests will not indicate POTS. A tilt table test is vital to diagnosing POTS, although all symptoms must be considered before a final diagnosis is made. Tests to rule out Addison's Disease, pheochromocytoma, electrolyte imbalance, Lyme Disease, Celiac Disease, and various food allergies are usually performed. A blood test may be performed to verify abnormally high levels of norepinephrine present in some POTS patients.
Between 75 and 80 percent of POTS patients are female and of the menstruating age. Some women also develop POTS symptoms during or after pregnancy.
Many POTS patients will see symptom improvement over the course of several years. Those who develop POTS in their early to mid teens during a period of rapid growth will most likely see complete symptom resolution in two to five years. Patients with post-viral POTS will sometimes improve greatly or even see a full symptom resolution. Adults who develop POTS, especially women during or after pregnancy, usually see milder improvement and can be plagued with their condition for life. Rarely, a teenager who develops POTS will gradually worsen over time and have lifelong symptoms. Patients with secondary POTS as a consequence of Ehlers-Danlos Syndrome will also usually struggle with symptoms for life. In some patients the only cure for POTS is time.
Many adult patients report a relapsing/remitting course characterised by periods of partial remission and occasional 'flare-ups' or exacerbations.
Recovered individuals do complain of occasional, non-debilitating recurrence of symptoms associated with autonomic dysfunction including dizzy spells, lightheadedness, flushing, and transient syncope, as well as symptoms of irritable bowel syndrome. These symptoms are consistent with B12 deficiency in absence of anemia, which should always be ruled out directly by checking B12, homocysteine and methylmalonic acid.
Most patients will respond to some form of treatment. Lifestyle changes, in particular drinking extra water and avoiding trigger situations such as standing still or getting hot are necessary for all patients. Some patients also benefit from the addition of other treatments, such as certain medications.
Drinking more water improves symptoms for nearly all patients. Most patients are encouraged to drink at least 64 ounces (two liters) of water or other hydrating fluids each day.
Eating frequent, small meals can reduce gastrointestinal symptoms associated with POTS by requiring the diversion of less blood to the abdomen.
Increasing salt intake, by adding salt to food, taking salt tablets, or drinking sports drinks and other electrolyte solutions is a treatment used for many people with POTS; however, salt is not recommended for all patients. Increasing salt is an effective way to raise blood pressure in many patients with orthostatic hypotension by helping the body retain water and thereby expanding blood volume. Different physicians recommend different amounts of sodium to their patients.
Diets high in carbohydrates have been connected to impaired vasoconstrictive action. Eating foods with lower carbohydrate levels can mildly improve POTS symptoms.
Caffeine helps some POTS patients due to its stimulant effects. However, other patients report a worsening of symptoms with caffeine intake. This could be due in part to its diuretic effect (by inhibiting anti-diuretic hormone).
Some POTS patients find it helpful to sleep at a slight incline (usually a 20 or 30 degree increase). This can be accomplished by either propping one's head up with a pillow or using bed risers on only two of the four legs of the frame. The logic behind this is as follows... The morning is often the POTS patient's worst enemy due to the fact that human blood volume is usually lowest upon waking (after a night of negligible fluid intake and trips to the bathroom). When you stand upright, your cerebral blood flow (CBF) drops slightly and cerebral auto-regulation (which maintains CBF) ensures the swift release of vasopressin. Vasopressin (a.k.a. anti-diuretic hormone) acts on the kidneys to increase free water re-absorption (and therefore, increased blood volume) and also causes an increase in total peripheral resistance (increased blood pressure). Conversely, when you lie down, your CBF increases slightly and thus causes a decrease in vasopressin levels. In healthy individuals, these small changes in vasopressin concentrations are fairly insignificant. However in POTS patients, this can worsen symptoms dramatically. Therefore, if you sleep at a slight incline, you can achieve the same increase in vasopressin levels without having to stand up. By increasing vasopressin levels, you can actually retain more blood volume overnight due to the hormone's fluid retaining effect. Vasopressin will also decrease the number of nightly trips to the bathroom and therefore allow you to conserve fluid.
Physical therapy and exercise
Exercise is very important for maintaining muscle strength and avoiding deconditioning. Though many POTS patients report difficulty exercising, some form of exercise is essential to controlling symptoms and, eventually, improving the condition. Exercises that improve leg and abdominal strength may aid in improving the muscle pump and, therefore, preventing pooling of blood in the abdomen and lower extremities.
Aerobic exercise performed for 20 minutes a day, three times a week, is sometimes recommended for patients who can tolerate it. Certain modalities of exercise may be more tolerable initially, such as riding a recumbent bicycle or swimming. However, as tolerable, upright exercise may benefit the participant through orthostatic training. All exercise programs for POTS patients should begin with low-intensity exercises for a short duration and progress slowly.
Several classes of drugs often provide symptom control and relief for POTS patients. Treatments must be carefully tested due to medication sensitivity often associated with POTS patients, and each patient will respond to different therapies in different ways.
The first drug of choice for symptomatic relief of POTS is usually fludrocortisone, or Florinef, a mineralcorticoid used to increase sodium retention and thus increase blood volume and blood pressure. An increase in sodium and water intake must coincide with fludrocortisone therapy for effective treatment.
Dietary increases in sodium and sodium supplements are often used.
An 80 mg capsule of Propranolol.
Beta blockers such as atenolol, metoprolol and propanolol are often prescribed to treat POTS. These medications slow down the rapid heart rate (tachycardia) that POTS patients experience. They make the heart more efficient by increasing the time spent in diastole, thus allowing more time for the left ventricle to fill with blood. However, beta blockers are a double-edged sword in POTS. This is because they also inhibit the release of renin from the Juxtaglomerular Apparatus in the kidneys. This decreases the amount of circulating aldosterone, which will decrease blood volume due to increased sodium excretion. That being said, beta blockers are first-line drugs for POTS and are often helpful due to their ability to mitigate some of the more distressing symptoms (e.g. reflex tachycardia). Unfortunately, they also decrease blood pressure (BP) by decreasing the heart rate and myocardial contractility. This decrease in BP can be offset by another common POTS medication, midodrine. Some beta blockers, such as acebutolol and pindolol, have intrinsic sympathomimetic activity (ISA). This basically means that they are partial agonists. They will act like antagonists (regular beta blockers) in the presence of excessive endogenous norepinephrine but will actually activate beta receptors when sympathetic tone is low. These characteristics could be useful in some POTS patients (not the hyperadrenergic variety) because of the fact that they wouldn't cause as much of a decrease in heart rate or blood pressure at rest. But they would most definitely block the catecholamine surge that assaults these patients during orthostasis.
Midodrine (Proamatine), is approved by the U.S. Food and Drug Administration (FDA) to treat orthostatic hypotension, which is one of the hallmark signs/symptoms of POTS. It is a non-CNS stimulant that causes vasoconstriction and thereby increases blood pressure and allows more blood to return to the upper parts of the body. Use of midodrine is often discontinued due to intolerable side-effects (i.e. goosebumps, itchy scalp), and it is known to cause supine hypertension (high blood pressure when lying down). Some doctors prefer to start patients on midodrine without the concomitant use of Beta blockers and then add Beta blockers once the dose of midodrine has been properly adjusted. This gives the midodrine time to start raising the patient's blood pressure which often helps avoid the hypotension that is a common side effect of Beta blockers. Obviously lowering the blood pressure of a POTS patient would exacerbate any existing orthostatic hypotension or worsen orthostatic intolerance. Additionally, midodrine's vasoconstrictive actions can trigger a reflex bradycardia, therefore it is best to see how an individual's heart is affected by the drug before giving a beta blocker which will further decrease the heart rate.
Modafinil has recently been reported to also be effective - particularly for fatigue.
In some cases, when increasing oral fluids and salt intake is not enough, intravenous saline is used to help increase blood volume, as many POTS patients suffer from hypovolemia. Increasing blood volume can decrease POTS symptoms caused or worsened by low blood volume such as tachycardia, low blood pressure, fatigue, and syncope. Infusions can be taken on an as-needed basis in an Emergency Room, or on a regularly scheduled manner at an infusion center or at home with the assistance of a home-care nurse. Many patients report a profound though short-lived improvement in their symptoms from saline infusions.
Erythropoietin, used to treat anemia via intravenous infusion, is very effective at increasing blood volume. It is seldom used, however, due to the dangers of increasing the hematocrit, the inconvenience of intravenous infusion, and its prohibitively expensive cost.
Pregabalin (Lyrica), an anticonvulsant drug, has been shown to be especially effective in treating neuropathic pain associated with POTS. In fact, Lyrica was the first and, for its first year on the market, the only prescription drug approved by the FDA to treat fibromyalgia. Some POTS patients also report improvement in concentration and energy while on Lyrica.
Pyridostigmine (Mestinon), inhibits the breakdown of acetylcholine, promoting autonomic nervous system activity. It is especially effective in increasing both parasympathetic and sympathetic activity.
Theophylline, a drug used to treat respiratory diseases such as COPD and asthma, is occasionally prescribed at low doses for POTS patients. Theophylline increases cardiac output, increases blood pressure, and stimulates epinephrine and norepinephrine production. Due to its very narrow therapeutic index, Theophylline is known to cause a wide variety of side-effects and even toxicity.
Women who report a worsening of symptoms during menstruation will often use combined (containing both estrogen and progestin) forms of hormonal contraception to prevent hormonal changes and an aggravation of their condition.
IVIG (Intravenous Immunoglobulin) infusions may be helpful for patients whose POTS is caused by autonomic neuropathy associated with Guillain Barre Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Sjogren's Syndrome or other autoimmune diseases. More recently, immunosuppressive treatment has show utility in syndromes of orthostatic tolerance that are presumed autoimmune in etiology even where pathological autoantibodies can not be identified.
Dihydroergotamine or DHE may be useful in some patients as a selective venoconstrictor through serotoninic receptor agonism.
Synephrine has been used 'off-label' for treatment of POTS.
Piracetam may improve cerebral blood flow in POTS according to one study.
Trials are planned for other novel potential therapies for POTS.
Patients whose POTS symptoms are due to B12 deficiency need pharmacological doses of B12 for repletion of tissues.
Recently it has become a popular belief that medical marijuana may have positive effects on POTS patients. However, there is little evidence supporting its efficacy, and the active constituents of marijuana are often associated with postural hypotension.
Pressure garments can reduce symptoms associated with orthostatic intolerance by constricting blood pressures with external body pressure.
Compression devices, such as abdominal binders and compression stockings, help to reduce the amount of pooling blood. Compression stockings should be at least 30–40 mm Hg and will work best if they are waist-high. Compression stockings should be fitted to achieve the greatest benefit. If the patient finds compression stockings of 30-40 mmHg to be too uncomfortable, consider a lesser compression such as 20-30 mmHg. Many patients see improvement with that level of compression, with full-length/waist-high stockings.
Compressions suits (G-Suits) have also been used with some good results.
Changes in environment
Some patients report that symptoms worsen with changes in barometric pressure (for instance, before a thunderstorm) and changes from outdoors to indoors (it is presumed that barometric pressure is higher inside) and depending on weight of clothes and coverage. These patients may find relief by moving to a new location where barometric pressure is relatively stable, e.g. San Diego.
POTS was first named and identified by Schondorf and Low in 1993; however, the syndrome has been described in medical studies dating back to at least 1940. Hypertension associated with POTS has been previously described as the "hyperadrenergic syndrome" by Streeten and as "idiopathic hypovolemia" by Fouad. Hypotension associated with POTS has been previously described as the "neurally mediated hypotension" form of POTS.
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