Postural orthostatic tachycardia syndrome
|Classification and external resources|
Postural orthostatic tachycardia syndrome (POTS, also postural tachycardia syndrome) is a condition in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia. It is thought to be a condition of partial dysautonomia, specifically a form of orthostatic intolerance (OI). 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.
Signs and symptoms
As with OI, the primary symptom is lightheadedness or fainting when standing up from a supine position. In addition, the hallmark symptom of POTS is an increase in heart rate 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.
Symptoms of POTS may include:
- Postural tachycardia
- Abdominal discomfort
- Sleep disorder
- Exercise intolerance
- Many people affected with POTS exhibit comorbid small fiber peripheral neuropathy - both autonomic and in some cases sensory.
- POTS is often accompanied by vasovagal syncope, with a 25% overlap being reported.
- There is significant overlap between POTS and chronic fatigue syndrome, with evidence of POTS in 25-50% of CFS cases. Fatigue and reduced exercise tolerance are prominent symptoms of both conditions, and dysautonomia may underlie both conditions.
- Patients with Ehlers-Danlos syndrome may also have POTS. Joint hypermobility is a feature of the most common subtype of Ehlers-Danlos.
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.
- Abnormalities in cerebral autoregulation are a consistent findings in POTS.
- 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.
- Levels or activation of endothelial vasodilating molecules such as nitric oxide or hydrogen sulfide may be increased in some POTS patients.
- Vasoactive diuretic peptides may play a role in the pathophysiology of some POTS patients.
- "Hyperadrenergic" POTS has been associated with Mast Cell Disorders in some patients.
- POTS may also appear as a secondary manifestation of systemic autoimmune diseases such as Multiple Sclerosis, Sjogren's Syndrome, Rheumatoid Arthritis and Lupus. POTS has also been associated with Sarcoidosis. It is presumed that in these cases POTS may have an autoimmune or neuropathic basis.
- 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.
People with POTS will show a marked rise in heart rate within 10 minutes of standing or being tilted 60° head-up on a tilt table, without a corresponding decrease in blood pressure. A variety of autonomic tests are employed to exclude autonomic disorders that could underlie symptoms, while endocrine testing is used to exclude hyperthyroidism and rarer endocrine conditions. Electrocardiography is normally performed on all patients to exclude other possible causes of tachycardia. In cases where a particular associated condition or complicating factor are suspected, other non-autonomic tests may be used: echocardiography to exclude mitral valve prolapse, neuroimaging for suspected Chiari malformation, and thermal threshold tests for small-fiber neuropathy.
Testing the cardiovascular response to prolonged head-up tilting, exercise, eating, and heat stress may help determine the best strategy for managing symptoms. POTS has also been divided into several types, which may benefit from distinct treatments. People with neuropathic POTS show a loss of sweating in the feet during sweat tests, as well as impaired norepinephrine release in the leg, but not arm. This is believed to reflect peripheral sympathetic denervation in the lower limbs. People with hyperadrenergic POTS show a marked increase of blood pressure and norepinephrine levels when standing, and are morely likely to suffer from prominent palpitations, anxiety, and tachycardia.
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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.
- Ethanol has been shown to drastically exacerbate all types of orthostatic intolerance due to its vasodilation and dehydration properties. In addition to its adverse effects, it interacts unfavorably with many of the medications prescribed for POTS patients.
- 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.
- Eating large meals, especially ones high in carbohydrates, can cause a reduction in blood pressure and exacerbate symptoms in POTS patients.
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.
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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.
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.
Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), and paroxetine (Paxil), can be extremely effective in re-regulating the autonomic nervous system and raising blood pressure. Some studies indicate that serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta) are even more effective. Tricyclic antidepressants, tetracyclic antidepressants, and monoamine oxidase inhibitors are also occasionally, but rarely, prescribed. A combination of two antidepressants, usually an SSRI or SNRI with bupropion (Wellbutrin) or mirtazapine (Remeron), is also shown to be very effective.
Medications used to treat attention deficit disorder and attention deficit hyperactivity disorder such as methylphenidate (Ritalin) and Adderall effectively increase norepinehprine and dopamine levels, thereby increasing vasoconstriction and blood pressure.
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.
In the UK, Ivabradine has been used to treat patients with POTS symptoms with good effect. Ivabradine acts by reducing the heart rate in a mechanism different from that of beta blockers and calcium channel blockers, two commonly prescribed antianginal drugs. It is classified as a cardiotonic agent.
Trials are planned for other novel potential therapies for POTS.
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.
There are anecdotal reports of benefit being derived from Horse Chestnut seed extract (Aescin), Rehmannia glutinosa, Licorice root, Eucommia ulmoides, Diosmin and Ruscus aculeatus (Butcher Broom) however there is currently no research to support the efficacy of these herbal remedies that is specific to POTS.
External body pressure
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.
POTS has a favorable prognosis when managed appropriately. Symptoms improve within five years of diagnosis for many patients, and 60% return to their original level of functioning. 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. Outcomes are more guarded for adults newly diagnosed with POTS.
The prevalence of POTS is unknown. One study estimated a minimal rate of 170 POTS cases per 100,000 individuals, but the true prevalence is likely higher due to underdiagnosis. Another study estimated that there were millions of cases in the United States. POTS is more common in women, with a female-to-male ratio of 5:1. Most people with POTS are aged between 20 and 40, with an average onset of 30. Diagnoses of POTS beyond age 40 are rare, perhaps because symptoms improve with age.
In 1871, physician Jacob Mendes Da Costa described a condition that resembled the modern concept of POTS. He named it irritable heart syndrome. Cardiologist Thomas Lewis expanded on the description, coining the term soldier's heart because it was often found among military personnel. The condition came to be known as Da Costa syndrome, which is now recognized as several distinct disorders, including POTS.
Postural tachycardia syndrome was coined in 1982 in a description of a patient who had postural tachycardia, but not orthostatic hypotension. Ronald Schondorf and Phillip A. Low of the Mayo Clinic first used the name postural orthostatic tachycardia syndrome in 1993.
It is currently known that some species of ectothermic vertebrates also present orthostatic-tachycardia, and although there is no known relationship between this heart rate adjustment and POTS in these animals, it seems that such heart rate increase are mediated exclusively by the parasympathetic subdivision of the autonomic nervous system in snakes - a mediation that can be evolutionarily conserved in all vertebrates.
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- Dysautonomia International
- National Dysautonomia Research Foundation (NDRF)
- Dysautonomia Youth Network of America, Inc.
- Dysautonomia Information Network (aka POTS Place)
- Mik's Hidden Hearts Alliance for Dysautonomia