Postural orthostatic tachycardia syndrome

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To be distinguished from Pott's Disease.
Autonomic dysfunction
Classification and external resources
ICD-10 G90.9
ICD-9 337.9
MeSH D054972

Postural orthostatic tachycardia syndrome (POTS, also postural tachycardia syndrome) is thought to be a condition of partial dysautonomia,[1] to be more specific orthostatic intolerance (OI), 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.[2] 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.

Types[edit]

There are two known types of POTS, the neurally mediated, as well as the hyperadrenergic form. They share the same diagnostic criteria, that there is an increase of 30 or more BPM when the person stands up. However, the hyperadrenergic form, is related to increased amount of cathecolamines, that increase the blood pressure upon standing. [3]

Overview[edit]

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.[4]

Symptoms[edit]

Symptoms of POTS include: [5]

  • Postural tachycardia
  • Headache
  • Abdominal discomfort
  • Dizziness/presyncope
  • Nausea
  • Fatigue[6]
  • Lightheadedness
  • Sweating
  • Tremor
  • Anxiety
  • Palpitations
  • Exercise intolerance

Associated conditions[edit]

Causes[edit]

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.[9] 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.[10]

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.[7][11][12] Small fiber peripheral neuropathy may be associated with autoimmune illnesses, exposure to toxins, certain medications, and in many cases are considered idiopathic.[13]
  • 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.[10] 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.[14][15]
  • Low blood volume or hypovolemia is a frequent finding in POTS, often coupled with an abnormal renin-aldosterone response to this volume deficit.[16]
  • Expression of Norepinephrine transporter (NET) protein appears to be reduced in some POTS patients.[17] 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.[18]
  • 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.[19]
  • 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.[20][21][22]
  • 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.[23][24]
  • 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.[25] However, norepinephrine transporter inhibition may create a phenotype with similarities to this finding.[26]
  • Levels or activation of endothelial vasodilating molecules such as nitric oxide or hydrogen sulfide may be increased in some POTS patients.[27][28]
  • Vasoactive diuretic peptides may play a role in the pathophysiology of some POTS patients.[29]
  • "Hyperadrenergic" POTS has been associated with Mast Cell Disorders in some patients.[30]
  • POTS may also appear as a secondary manifestation of systemic autoimmune diseases such as Multiple Sclerosis,[31] Sjogren's Syndrome,[32] 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.[33] Alpha-1 receptors cause peripheral vasoconstriction when stimulated. Alpha-1 receptor supersensitivity may be causing dysautonomia in some patients.[34]
  • Beta-receptor supersensitivity may occur with hyperadrenergic states in some people with POTS.[35]
  • 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.[36]

Diagnosis[edit]

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.[citation needed] 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.

Prognosis[edit]

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.[37] 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.[citation needed] 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.[38] 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.

Treatment[edit]

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.

Dietary/Lifestyle changes[edit]

  • 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.[35][39]
  • Eating large meals, especially ones high in carbohydrates, can cause a reduction in blood pressure and exacerbate symptoms in POTS patients.[40]

Physical therapy and exercise[edit]

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.[41] 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.[39] 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.

Medications[edit]

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.[citation needed]

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.[citation needed]

Dietary increases in sodium and sodium supplements are often used.[citation needed]

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.[citation needed]

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.[citation needed]

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.[citation needed]

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.

Modafinil has recently been reported to also be effective - particularly for fatigue.[42][43]

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.[16][44] 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.[45][46] 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.[47]

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)[48] however there is currently no research to support the efficacy of these herbal remedies that is specific to POTS.

External body pressure[edit]

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.[49] 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.

History[edit]

POTS was first named and identified by Schondorf and Low in 1993;[50] 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[citation needed] and as "idiopathic hypovolemia" by Fouad.[51] Hypotension associated with POTS has been previously described as the "neurally mediated hypotension" form of POTS.

References[edit]

  1. ^ a b c Carew, S.; Connor, M. O.; Cooke, J.; Conway, R.; Sheehy, C.; Costelloe, A.; Lyons, D. (12 November 2008). "A review of postural orthostatic tachycardia syndrome". Europace 11 (1): 18–25. doi:10.1093/europace/eun324. 
  2. ^ Hermosillo, A. G.; Jordan, JL; Vallejo, M; Kostine, A; Márquez, MF; Cárdenas, M (2006). "Cerebrovascular blood flow during the near syncopal phase of head-up tilt test: A comparative study in different types of neurally mediated syncope". Europace 8 (3): 199–203. doi:10.1093/europace/eul001. PMID 16627440. 
  3. ^ http://www.patient.co.uk/health/postural-orthostatic-tachycardia-syndrome
  4. ^ http://www.ninds.nih.gov/disorders/postural_tachycardia_syndrome/postural_tachycardia_syndrome.htm
  5. ^ "Postural Orthostatic Tachycardia Syndrome". 
  6. ^ Johnson, Jonathan N.; Mack, Kenneth J.; Kuntz, Nancy L.; Brands, Chad K.; Porter, Coburn J.; Fischer, Philip R. "Postural Orthostatic Tachycardia Syndrome: A Clinical Review". Pediatric Neurology 42 (2): 77–85. doi:10.1016/j.pediatrneurol.2009.07.002. 
  7. ^ a b Peltier, A. C.; Garland, E.; Raj, S. R.; Sato, K.; Black, B.; Song, Y.; Wang, L.; Biaggioni, I.; Diedrich, A.; Robertson, D. (2009). "Distal sudomotor findings in postural tachycardia syndrome". Clinical Autonomic Research 20 (2): 93–99. doi:10.1007/s10286-009-0045-y. PMC 3089763. PMID 20035362. 
  8. ^ Gazit, Yael; Nahir, A.Menahem; Grahame, Rodney; Jacob, Giris. "Dysautonomia in the joint hypermobility syndrome". The American Journal of Medicine 115 (1): 33–40. doi:10.1016/S0002-9343(03)00235-3. 
  9. ^ Kanjwal K, Karabin B, Kanjwal Y, Grubb BP (2011). "Postural orthostatic tachycardia syndrome following Lyme disease". Cardiology Journal 18 (1): 63–66. PMID 21305487. 
  10. ^ a b Thieben, Mark J.; Sandroni, Paola; Sletten, David M.; Benrud-Larson, Lisa M.; Fealey, Robert D.; Vernino, Steven; Lennon, Phillip A.; Shen, Vanda A.; Low, Win-Kuang (2007). "Postural Orthostatic Tachycardia Syndrome: The Mayo Clinic Experience". Mayo Clinic Proceedings 82 (3): 308–13. doi:10.4065/82.3.308. PMID 17352367. 
  11. ^ Peltier, A. C.; Garland, E.; Raj, S. R.; Sato, K.; Black, B.; Song, Y.; Wang, L.; Biaggioni, I.; Diedrich, A.; Robertson, D. (2009). "Distal sudomotor findings in postural tachycardia syndrome". Clinical Autonomic Research 20 (2): 93–99. doi:10.1007/s10286-009-0045-y. PMC 3089763. PMID 20035362. 
  12. ^ "Autonomic Innervation in Neuropathic and Non-Neuropathic Postural Tachycardia Syndrome (S37.005) - Wang et al. 80 (1001): S37.005". Neurology. 2013-02-12. Retrieved 2013-06-18. 
  13. ^ "Small fiber neuropathy: A burning problem". Ccjm.org. 2009-05-01. Retrieved 2013-06-18. 
  14. ^ "Autonomic Autoantibodies with Allosteric Activity in Idiopathic Postural Orthostatic Hypotension (IOH) and Tachycardia Syndrome (POTS): A New Mechanism - Li et al. 33 (3): OR48-1 - Endocrine Reviews". Edrv.endojournals.org. Retrieved 2013-06-18. 
  15. ^ Wang, X. L.; Chai, Q.; Charlesworth, M. C.; Figueroa, J. J.; Low, P.; Shen, W. K.; Lee, H. C. (2012). "Autoimmunoreactive IgGs from patients with postural orthostatic tachycardia syndrome". PROTEOMICS - Clinical Applications 6 (11–12): 615–625. doi:10.1002/prca.201200049. PMC 3786406. PMID 23002038. 
  16. ^ a b Raj, S. R.; Biaggioni, I; Yamhure, PC; Black, BK; Paranjape, SY; Byrne, DW; Robertson, D (2005). "Renin-Aldosterone Paradox and Perturbed Blood Volume Regulation Underlying Postural Tachycardia Syndrome". Circulation 111 (13): 1574–82. doi:10.1161/01.CIR.0000160356.97313.5D. PMID 15781744. 
  17. ^ Lambert, E.; Eikelis, N.; Esler, M.; Dawood, T.; Schlaich, M.; Bayles, R.; Socratous, F.; Agrotis, A.; Jennings, G.; Lambert, G.; Vaddadi, G. (2008). "Altered Sympathetic Nervous Reactivity and Norepinephrine Transporter Expression in Patients with Postural Tachycardia Syndrome". Circulation: Arrhythmia and Electrophysiology 1 (2): 103. doi:10.1161/CIRCEP.107.750471. 
  18. ^ Haensch, C.-A.; Lerch, H.; Schlemmer, H.; Jigalin, A.; Isenmann, S. (2009). "Cardiac neurotransmission imaging with 123I-meta-iodobenzylguanidine in postural tachycardia syndrome". Journal of Neurology, Neurosurgery & Psychiatry 81 (3): 339. doi:10.1136/jnnp.2008.168484. 
  19. ^ Bayles, R.; Kn, H.; Lambert, E.; Baker, E. K.; Agrotis, A.; Guo, L.; Jowett, J. B. M.; Esler, M.; Lambert, G.; El-Osta, A. (2012). "Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome". Arteriosclerosis, Thrombosis, and Vascular Biology 32 (8): 1910–1916. doi:10.1161/ATVBAHA.111.244343. PMID 22723437. 
  20. ^ Glover, June L.; Glover, Julian M.; Medow, Marvin S. (2006). "Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume". Clinical Science 110 (2): 255–63. doi:10.1042/CS20050254. PMID 16262605. 
  21. ^ Mustafa, Hossam I.; Garland, Emily M.; Biaggioni, Italo; Black, Bonnie K.; Dupont, William D.; Robertson, David; Raj, Satish R. (2011). "Abnormalities of angiotensin regulation in postural tachycardia syndrome". Heart Rhythm 8 (3): 422–8. doi:10.1016/j.hrthm.2010.11.009. PMC 3050076. PMID 21266211. 
  22. ^ Stewart, J. M.; Ocon, A. J.; Clarke, D.; Taneja, I.; Medow, M. S. (2009). "Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome". Hypertension 53 (5): 767–74. doi:10.1161/HYPERTENSIONAHA.108.127357. PMC 2765216. PMID 19289653. 
  23. ^ Ocon, AJ; Medow, MS; Taneja, I; Clarke, D; Stewart, JM (2009). "Decreased upright cerebral blood flow and cerebral autoregulation in normocapnic postural tachycardia syndrome". American Journal of Physiology - Heart and Circulatory Physiology 297 (2): H664–H673. doi:10.1152/ajpheart.00138.2009. PMC 2724195. PMID 19502561. 
  24. ^ Stewart, JM; Medow, MS; Messer, ZR; Baugham, IL; Terilli, C; Ocon, AJ (2012). "Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome". American journal of physiology. Heart and circulatory physiology 302 (5): H1185–94. doi:10.1152/ajpheart.00994.2011. PMC 3311460. PMID 22180650. 
  25. ^ Fu, Q.; Vangundy, T. B.; Galbreath, M. M.; Shibata, S.; Jain, M.; Hastings, J. L.; Bhella, P. S.; Levine, B. D. (2010). "Cardiac Origins of the Postural Orthostatic Tachycardia Syndrome". Journal of the American College of Cardiology 55 (25): 2858–2868. doi:10.1016/j.jacc.2010.02.043. PMC 2914315. PMID 20579544. 
  26. ^ "Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation". Jap.physiology.org. 2008-01-10. Retrieved 2013-06-18. 
  27. ^ Stewart, J. M.; Nafday, A.; Ocon, A. J.; Terilli, C.; Medow, M. S. (2011). "Cutaneous constitutive nitric oxide synthase activation in postural tachycardia syndrome with splanchnic hyperemia". AJP: Heart and Circulatory Physiology 301 (3): H704. doi:10.1152/ajpheart.00171.2011. 
  28. ^ Zhang, Fengwen; Li, Xueying; Stella, Chen; Chen, Li; Liao, Ying; Tang, Chaoshu; Jin, Hongfang; Du, Junbao (2012). "Plasma Hydrogen Sulfide in Differential Diagnosis between Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome in Children". The Journal of Pediatrics 160 (2): 227–31. doi:10.1016/j.jpeds.2011.08.008. PMID 21920536. 
  29. ^ http://content.onlinejacc.org/article.aspx?articleid=1217866
  30. ^ "Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders". Hyper.ahajournals.org. 2005-02-14. Retrieved 2013-06-18. 
  31. ^ "Autonomic Dysfunction Presenting as Postural Orthostatic Tachycardia Syndrome in Patients with Multiple Sclerosis". Medsci.org. doi:10.7150/ijms.7.62. Retrieved 2013-06-18. 
  32. ^ "The Postural Tachycardia Syndrome: A Concise Guide: Classification". Medscape.com. Retrieved 2013-06-18. 
  33. ^ Gordon, Victor M.; Opfer-Gehrking, Tonette L.; Novak, Vera; Low, Phillip A. (2000). "Hemodynamic and symptomatic effects of acute interventions on tilt in patients with postural tachycardia syndrome". Clinical Autonomic Research 10 (1): 29–33. doi:10.1007/BF02291387. PMID 10750641. 
  34. ^ Stewart, Julian M; Medow, Marvin S (Jan 6, 2011). "Orthostatic Intolerance". In Neish, Steven R. Medscape. 
  35. ^ a b Low, P. A. (2000, July). Orthostatic intolerance. National Dysautonomia Research Foundation Patient Conference. Minneapolis, Minnesota.
  36. ^ http://jms.ndmctsgh.edu.tw/fdarticlee%5C3003127.pdf
  37. ^ Agarwal, AK; Garg, R; Ritch, A; Sarkar, P (July 2007). "Postural orthostatic tachycardia syndrome". Postgrad Med J. 83 (981): 478–480. doi:10.1136/pgmj.2006.055046. PMC 2600095. PMID 17621618. 
  38. ^ "Ehlers-Danlos Syndrome, Hypermobility Type". National Center for Biotechnology Information. U.S. National Library of Medicine. Retrieved 6 July 2014. 
  39. ^ a b Grubb, Blair P.; Kanjwal, Yousuf; Kosinski, Daniel J. (2005). "The Postural Tachycardia Syndrome: A Concise Guide to Diagnosis and Management". Journal of Cardiovascular Electrophysiology: 051123074027005. doi:10.1111/j.1540-8167.2005.00318.x. 
  40. ^ Freeman, Roy; Wieling, Wouter; Axelrod, Felicia B.; Benditt, David G.; Benarroch, Eduardo; Biaggioni, Italo; Cheshire, William P.; Chelimsky, Thomas; Cortelli, Pietro; Gibbons, Christopher H.; Goldstein, David S.; Hainsworth, Roger; Hilz, Max J.; Jacob, Giris; Kaufmann, Horacio; Jordan, Jens; Lipsitz, Lewis A.; Levine, Benjamin D.; Low, Phillip A.; Mathias, Christopher; Raj, Satish R.; Robertson, David; Sandroni, Paola; Schatz, Irwin; Schondorff, Ron; Stewart, Julian M.; Dijk, J. Gert (24 March 2011). "Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome". Clinical Autonomic Research 21 (2): 69–72. doi:10.1007/s10286-011-0119-5. 
  41. ^ "Exercise training program improves outcomes in "Grinch Syndrome" patients | American Heart Association". Newsroom.heart.org. 2011-06-20. Retrieved 2013-06-18. 
  42. ^ http://www.dynakids.org/Documents/ModafinilPOTS.pdf
  43. ^ http://conference-cast.com/HRS/common/presentation-detail.aspx/8/28/1040/6057
  44. ^ Raj, SR (2006). "The Postural Tachycardia Syndrome (POTS): Pathophysiology, diagnosis & management". Indian pacing and electrophysiology journal 6 (2): 84–99. PMC 1501099. PMID 16943900. 
  45. ^ Hersi, Ahmad (2010). "Potentially New Indication of Ivabradine: Treatment of a Patient with Postural Orthostatic Tachycardia Syndrome". The Open Cardiovascular Medicine Journal 4: 166–7. doi:10.2174/1874192401004010166. PMC 2995161. PMID 21127745. 
  46. ^ McDonald, C.; Frith, J.; Newton, J. L. (2010). "Single centre experience of ivabradine in postural orthostatic tachycardia syndrome". Europace 13 (3): 427–30. doi:10.1093/europace/euq390. PMC 3043639. PMID 21062792. 
  47. ^ Stewart, J. M. (2012). "Mechanisms of sympathetic regulation in orthostatic intolerance". Journal of Applied Physiology 113 (10): 1659–1668. doi:10.1152/japplphysiol.00266.2012. PMC 3524660. PMID 22678960. 
  48. ^ Redman, D. A. (2000). "Ruscus aculeatus (butcher's broom) as a potential treatment for orthostatic hypotension, with a case report". Journal of alternative and complementary medicine 6 (6): 539–549. doi:10.1089/acm.2000.6.539. PMID 11152059. 
  49. ^ Grubb, Blair P.; Karas, Barry (1999). "Clinical Disorders of the Autonomic Nervous System Associated with Orthostatic Intolerance: An Overview of Classification, Clinical Evaluation, and Management". Pacing and Clinical Electrophysiology 22 (5): 798–810. doi:10.1111/j.1540-8159.1999.tb00546.x. PMID 10353141. 
  50. ^ Schondorf, R; Low, PA (1993). "Idiopathic postural orthostatic tachycardia syndrome: An attenuated form of acute pandysautonomia?". Neurology 43 (1): 132–7. doi:10.1212/WNL.43.1_Part_1.132. PMID 8423877. 
  51. ^ Fouad, FM; Tadena-Thome, L; Bravo, EL; Tarazi, RC (1986). "Idiopathic hypovolemia". Annals of Internal Medicine 104 (3): 298–303. doi:10.7326/0003-4819-104-3-298. PMID 3511818. 

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