Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormal increase in heart rate upon sitting up or standing. POTS in adults is characterized by a heart rate increase of 30 beats per minute within ten minutes of standing up, accompanied by other symptoms. This increased heart rate should occur in the absence of a significant drop in blood pressure. POTS is a disorder of the autonomic nervous system that can lead to a variety of symptoms. Upon standing, individuals can experience lightheadedness, blurred vision, heart palpitations, weakness and tremor (shaking). In addition, individuals can experience fatigue, headaches, brain fog, exercise intolerance, nausea, difficulty concentrating, chest pain, and shortness of breath.
POTS is thought to be caused by problems in the autonomic nervous system, which controls heart rate and blood flow. These problems may include blood pooling in the legs, reducing blood return to the heart, or the heart beating faster to make up for low blood pressure. It can develop after a viral infection, surgery, trauma, autoimmune disease, or pregnancy. For instance, it can emerge after contracting COVID-19, as part of long COVID, or possibly in rare cases after COVID-19 vaccination, though causative evidence is limited and further study is needed. POTS is more common among people who got infected with SARS-CoV-2 than among those who got vaccinated against COVID-19. Risk factors include a family history of the condition.
Treatment may include:
avoiding factors that bring on symptoms, increasing dietary salt and water, small and frequent meals, wearing compression garments, and medication. Medications used may include: beta blockers, pyridostigmine, midodrine, fludrocortisone, or ivabradine.
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% 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 full resolution of symptoms.
An estimated 1–3 million people in the United States have POTS. The average age for POTS onset is 20, and it occurs about five times more frequently in females than in males.
Signs and symptoms
Individuals with POTS can have a large array of symptoms, which may differ significantly between people. Individuals living with POTS experience a diminished quality of life compared to healthy individuals, due to disruptions in various domains such as standing, playing sports, symptom anxiety, and impacts on school, work, or spiritual (religious) domains—these disruptions affect their daily life and overall well-being.
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 the ages of 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, lightheadedness, 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 or hands upon standing. 48% of people with POTS report chronic fatigue and 32% report sleep disturbances.
POTS and dysautonomia sometimes present with narrowed pulse pressures. In such cases, patients experience a drop in pulse pressure to 0 mm Hg upon standing, rendering them practically pulseless while upright. This condition leads to significant morbidity, as many affected individuals struggle to stand at all.
Additional signs and symptoms are varied, and may include excessive sweating, lack of sweating, heat intolerance, digestive issues such as nausea, indigestion, bloating, constipation or diarrhea, post-exertional malaise, coat-hanger pain, brain fog, and syncope or presyncope.
Whereas POTS is primarily characterized by its impact on the autonomic and cardiovascular systems, it can lead to substantial functional impairment. This impairment, often manifesting as symptoms such as fatigue, cognitive dysfunction, and sleep disturbances, can significantly diminish the patient's quality of life.
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 descriptions were "difficulty processing what others say" (80%), "confusion" (71%), "getting 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 the 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.
Comorbidities Conditions that are commonly reported with POTS include: Migraine headaches (40%) Irritable bowel syndrome (30%) Ehlers–Danlos syndrome (18–25%) Asthma (20%) Fibromyalgia (20%) Reynaud's syndrome (16%) Iron deficiency anemia (16%) Autoimmune disease (16%) Gastroparesis (14%) Vasovagal syncope (13-25%) Inappropriate sinus tachycardia (11%) Mast cell activation disorder (9%) There are some overlaps between POTS and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with evidence of POTS in 10–20% of ME/CFS cases. Fatigue and reduced exercise tolerance are prominent symptoms of both conditions, and dysautonomia may underlie both conditions.
Causes In up to 50% of cases, symptom onset followed a viral illness. It may also be linked to physical trauma, concussion, pregnancy, surgery, menarche, or psychosocial stress. These events could act as a trigger for an autoimmune response that result in POTS. It has been shown to emerge in previously healthy patients after COVID-19, or after COVID-19 vaccination.
A 2023 review found that the chances of being diagnosed with POTS within 90 days after mRNA vaccination were 1.33 times higher compared to 90 days before vaccination. Still, the results are inconclusive due to a small sample size; only 12 cases of newly diagnosed POTS after mRNA vaccination were reported, all these 12 patients having autoimmune antibodies. However, the risk of POTS-related diagnoses was 5.35 times higher after getting infected with SARS-CoV-2 compared to after mRNA vaccination. Possible mechanisms for COVID-induced POTS are hypovolemia, autoimmunity/inflammation from antibody production against autonomic nerve fibers, and direct toxic effects of COVID-19, or secondary sympathetic nervous system stimulation.
POTS is more common in females than males with up to 94% of patients being female. 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.
Physical deconditioning may be a factor involved in POTS. It has been proposed that there are parallels between POTS and physical deconditioning or people who have undergone prolonged periods of bed rest. Both POTS and deconditioning are marked by cardiac atrophy, reduced blood volume, and other physical changes. There are however distinct differences between classic cardiovascular deconditioning and POTS in most cases.
Mechanisms
The pathophysiology of POTS is not attributable to a single cause or unified hypothesis—it is the result of multiple interacting mechanisms, each contributing to the overall clinical presentation; the mechanisms may include autonomic dysfunction, hypovolemia, deconditioning, hyperadrenergic states, etc. These mechanisms are poorly understood, and can overlap, with many patients showing features of multiple POTS types.
Hypovolemic POTS 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.
Hyperadrenergic POTS 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.
Neuropathic POTS Another subtype, neuropathic POTS, is associated with denervation of sympathetic nerves in the lower limbs. In this subtype, 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.
A subset of POTS patients have markedly reduced myocardial MIBG reuptake via MIBG myocardial scintigraphy, interpreted to be a potential manifestation of autonomic cardiac neuropathy, although reduced expression of the norepinephrine transporter may also result in impaired MIBG reuptake and has been implicated in POTS.
Autoimmunity There is an increasing number of studies indicating that POTS is an autoimmune disease. A high number of patients have elevated levels of autoantibodies against the α1-adrenergic receptor and against the muscarinic acetylcholine M4 receptor.
Elevations of autoantibodies targeting the α1-adrenergic receptor have been associated with symptom 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. Studies suggest the involvement of adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. These autoantibodies are thought to interfere with the normal functioning of the autonomic nervous system, leading to the symptoms observed in POTS. There is thus a growing interest in the use of immunomodulation therapy, which aims to regulate or normalize the immune response to reduce the production of harmful autoantibodies, as a potential treatment strategy for POTS.
Secondary POTS