postural orthostatic tachycardia syndrome postural orthostatic tachycardia syndrome postural orthostatic tachycardia syndrome (pots) is a condition characterized by an abnormally large increase in heart rate upon standing. pots is a disorder of the autonomic nervous system that can lead the individual to experience a variety of symptoms. symptoms may include lightheadedness, brain fog, blurred vision, weakness, fatigue, headaches, heart palpitations, exercise intolerance, nausea, diminished concentration, tremulousness (shaking), syncope (fainting), coldness or pain in the extremities, chest pain and shortness of breath. other conditions associated with pots include ehlers–danlos syndrome, mast cell activation syndrome, irritable bowel syndrome, insomnia, chronic headaches, chronic fatigue syndrome, and fibromyalgia. pots symptoms may be treated with lifestyle changes such as increasing fluid and salt intake, wearing compression stockings, gentler and slow postural changes, avoiding prolonged bedrest, medication and physical therapy. not to be confused with pott disease. postural orthostatic tachycardia syndromeother namespotsacrocyanosis in a male norwegian pots patientspecialtycardiology, neurologysymptomsmore often with standing: lightheadedness, trouble thinking, tachycardia, weakness, palpitations, heat intolerance, acrocyanosisusual onsetmost common (modal) age of onset is 14 yearstypesneuropathic pots, hyperadrenergic pots, secondary pots.causesantibodies against the alpha 1 adrenergic receptor and muscarinic acetylcholine m4 receptorrisk factorsfamily history, ehlers danlos syndromediagnostic methodan increase in heart rate by 30 beats/min with standingdifferential diagnosisdehydration, heart problems, adrenal insufficiency, epilepsy, parkinson disease, anemiatreatmentavoiding factors that bring on symptoms, increasing dietary salt and water, compression stockings, exercise, medicationsmedicationoff label medications: beta blockers, ivabradine, midodrine, and fludrocortisone. selective serotonin reuptake inhibitors (ssris) may also be used in treatment for pots.prognosisc. 90% improve with treatment, 25% of patients unable to workfrequency~ 500,000 - 1,000,000 (us) the causes of pots are varied. pots may develop after a viral infection, surgery, trauma or pregnancy. it has been shown to emerge in previously healthy patients after covid-19, or in rare cases after covid-19 vaccination. risk factors include a family history of the condition. a pots diagnosis in adults is characterized by an increased heart rate of 30 beats per minute within ten minutes of standing up, while accompanied by symptoms. this increased heart rate should occur in the absence of orthostatic hypotension (>20 mm hg drop in systolic blood pressure) to be considered pots. a spinal fluid leak (called spontaneous intracranial hypotension) may have the same signs and symptoms as pots and should be excluded. prolonged bedrest may lead to multiple symptoms, including blood volume loss and postural tachycardia. other conditions which can cause similar symptoms, such as dehydration, orthostatic hypotension, heart problems, adrenal insufficiency, epilepsy, and parkinson's disease, must not be present. treatment may include avoiding factors that bring on symptoms, increasing dietary salt and water, small and frequent meals, avoidance of immobilization, wearing compression stockings, and taking medications. medications used may include beta blockers, pyridostigmine, midodrine or fludrocortisone. more than 50% of patients whose condition was triggered by a viral infection get better within five years. about 80% of patients have symptomatic improvement with treatment, while 25 percent of patients are so disabled they are unable to work. a retrospective study on patients with adolescent-onset has shown that five years after diagnosis, 19% of patients had a full resolution of symptoms. it is estimated that 500,000 people in the united states have pots. the average age for pots onset is 20 years old, and it occurs about five times more frequently in females than in males. signs and symptoms person standing and measuring heart rate with a pulse oximeter which shows tachycardia of 108 bpm in adults, the primary manifestation is an increase in heart rate of more than 30 beats per minute within ten minutes of standing up. the resulting heart rate is typically more than 120 beats per minute. for people between ages 12 and 19, the minimum increase for a pots diagnosis is 40 beats per minute. pots is often accompanied by common features of orthostatic intolerance—in which symptoms that develop while upright are relieved by reclining. these orthostatic symptoms include palpitations, light-headedness, chest discomfort, shortness of breath, nausea, weakness or "heaviness" in the lower legs, blurred vision, and cognitive difficulties. symptoms may be exacerbated with prolonged sitting, prolonged standing, alcohol, heat, exercise, or eating a large meal. up to one-third of pots patients experience fainting for many reasons, including but not limited to standing, physical exertion, or heat exposure. pots patients may also experience orthostatic headaches. some pots patients may develop blood pooling in the extremities, characterized by a reddish-purple color of the legs and/or hands upon standing. 48% of people with pots report chronic fatigue and 32% report sleep disturbances. other pots patients only exhibit the cardinal symptom of orthostatic tachycardia. additional signs and symptoms are varied, and may include excessive sweating, lack of sweating, heat intolerance, digestive issues such as nausea, indigestion, constipation, and diarrhea, post-exertional malaise, coat-hanger pain, brain fog, and syncope or presyncope. brain fog one of the most disabling and prevalent symptoms in pots is "brain fog", a term used by patients to describe the cognitive difficulties they experience. in one survey of 138 pots patients, brain fog was defined as "forgetful" (91%), "difficulty thinking" (89%), and "difficulty focusing" (88%). other common description was "difficulty processing what others say" (80%), confusion (71%), lost (64%), and "thoughts moving too quickly" (40%). the same survey described the most common triggers of brain fog to be fatigue (91%), lack of sleep (90%), prolonged standing (87%) and dehydration (86%). neuropsychological testing has shown that a pots patient has reduced attention (ruff 2&7 speed and wais-iii digits forward), short-term memory (wais-iii digits back), cognitive processing speed (symbol digits modalities test) and executive function (stroop word color and trails b). a potential cause for brain fog is a decrease in cerebral blood flow (cbf), especially in upright position. there may be a loss of neurovascular coupling and reduced functional hyperemia in response to cognitive challenge under orthostatic stress – perhaps related to a loss of autoregulatory buffering of beat-by-beat fluctuations in arterial blood flow. causes the symptoms of pots can be caused by several distinct pathophysiological mechanisms. these mechanisms are poorly understood, and can overlap, with many patients showing features of multiple pots types. many people with pots exhibit low blood volume (hypovolemia), which can decrease the rate of blood flow to the heart. to compensate for low blood volume, the heart increases its cardiac output by beating faster (reflex tachycardia), leading to the symptoms of presyncope. in the 30% to 60% of cases classified as hyperadrenergic pots, norepinephrine levels are elevated on standing, often due to hypovolemia or partial autonomic neuropathy. a smaller minority of people with pots have (typically very high) standing norepinephrine levels that are elevated even in the absence of hypovolemia and autonomic neuropathy; this is classified as central hyperadrenergic pots. the high norepinephrine levels contribute to symptoms of tachycardia. another subtype, neuropathic pots, is associated with denervation of sympathetic nerves in the lower limbs. in this subtype, it is thought that impaired constriction of the blood vessels causes blood to pool in the veins of the lower limbs. heart rate increases to compensate for this blood pooling. in up to 50% of cases, there was an onset of symptoms following a viral illness. it may also be linked to vaccination, physical trauma, concussion, pregnancy, or surgery. it is believed that these events could act as a trigger for an autoimmune response that result in pots. covid has been implicated as has more rarely, the vaccine for covid. it has been shown to emerge in previously healthy patients after covid-19, or in rare cases after covid-19 vaccination. pots is more common in females than males. it has also been shown to be linked in patients with acute stressors such as pregnancy, recent surgery, or recent trauma. pots also has been linked to patients with a history of autoimmune diseases, long covid, irritable bowel syndrome, anemia, hyperthyroidism, fibromyalgia, diabetes, amyloidosis, sarcoidosis, systemic lupus erythematosus, and cancer. genetics likely plays a role, with one study finding that one in eight pots patients reported a history of orthostatic intolerance in their family. autoimmunity there is an increasing number of studies indicating that pots is an autoimmune disease. a high number of patients has elevated levels of autoantibodies against the adrenergic alpha 1 receptor and against the muscarinic acetylcholine m4 receptor. elevations of autoantibodies targeting adrenergic α1 receptor has been associated with symptoms severity in patients with pots. more recently, autoantibodies against other targets have been identified in small cohorts of pots patients. signs of innate immune system activation with elaboration of pro-inflammatory cytokines has also been reported in a cohort of pots patients. secondary pots if pots is caused by another condition, it may be classified as secondary pots. chronic diabetes mellitus is one common cause. pots can also be secondary to gastrointestinal disorders that are associated with low fluid intake due to nausea or fluid loss through diarrhea, leading to hypovolemia. systemic lupus erythematosus and other autoimmune diseases have also been linked to pots. there is a subset of patients who present with both pots and mast cell activation syndrome (mcas), and it is not yet clear whether mcas is a secondary cause of pots or simply comorbid, however, treating mcas for these patients can significantly improve pots symptoms. pots can also co-occur in all types of ehlers–danlos syndrome (eds), a hereditary connective tissue disorder marked by loose hypermobile joints prone to subluxations and dislocations, skin that exhibits moderate or greater laxity, easy bruising, and many other symptoms. a trifecta of pots, eds, and mast cell activation syndrome (mcas) is becoming increasingly more common, with a genetic marker common among all three conditions. pots is also often accompanied by vasovagal syncope, with a 25% overlap being reported. there are some overlaps between pots and chronic fatigue syndrome, with evidence of pots in 10–20% of cfs cases. fatigue and reduced exercise tolerance are prominent symptoms of both conditions, and dysautonomia may underlie both conditions. pots can sometimes be a paraneoplastic syndrome associated with cancer. there are case reports of people developing pots and other forms of dysautonomia post-covid. there is no good large-scale empirical evidence yet to prove a connection, so for now the evidence is preliminary. diagnosis results of a tilt table test positive for pots pots is most commonly diagnosed by a cardiologist (41%), cardiac electrophysiologist (15%), or neurologist (19%). the average number of physicians seen before receiving diagnosis is seven, and the average delay before diagnosis is 4.7 years. diagnostic criteria a pots diagnosis requires the following characteristics: for patients age 20 or older, increase in heart rate ≥30 bpm within ten minutes of upright posture (tilt table test or standing) from a supine position for patients age 12–19, heart rate increase must be >40 bpm associated with related symptoms that are worse with upright posture and that improve with recumbence chronic symptoms that have lasted for longer than six months in the absence of other disorders, medications, or functional states that are known to predispose to orthostatic tachycardia orthostatic intolerance an increase in heart rate upon moving to an upright posture is known as orthostatic (upright) tachycardia (fast heart rate). it occurs without any coinciding drop in blood pressure, as that would indicate orthostatic hypotension. certain medications to treat pots may cause orthostatic hypotension. it is accompanied by other features of orthostatic intolerance—symptoms that develop in an upright position and are relieved by reclining. these orthostatic symptoms include palpitations, light-headedness, chest discomfort, shortness of breath, nausea, weakness or "heaviness" in the lower legs, blurred vision, and cognitive difficulties. differential diagnoses 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, 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 (see § causes), 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