Katie Goff, who lives with POTS, and her dog Luna

Decoding the Mysteries of Postural Orthostatic Tachycardia Syndrome

When Katie Goff was a freshman in college, she began to suffer a myriad of seemingly unrelated symptoms – respiratory infections, heartburn, headaches, fatigue, insomnia, and relentless nausea. Visits to the doctor didn’t seem to help. At one visit, the doctor told her she had allergies. At another, she was given a prescription for an antidepressant.

During her sophomore year, Goff’s health worsened. She started feeling like her heart was racing—a condition called tachycardia–which her doctor diagnosed as panic attacks and treated her with anti-anxiety medications. But she felt light-headed, and the medications seemed to make her persistent insomnia even worse. Whenever Goff did sleep, she had surreal dreams and restless legs. She eventually left school that year and returned to her parents’ home on medical leave.

It felt like a stroke of luck when Goff’s mother happened to be describing her daughter’s symptoms to a neighbor, a pediatric gastroenterologist with expertise in a condition known as postural orthostatic tachycardia syndrome (POTS). The neighbor suggested conducting a tilt table test on Ms. Goff—a type of diagnostic procedure in which a person is safely strapped to a table that is designed to mimic the act of moving from lying flat to sitting up or standing up. The person is connected to electrocardiogram and blood pressure monitors. If the change in posture causes syncope (fainting) or a rapid heart rate change, a doctor may point to a POTS diagnosis.

“It felt like a roller coaster to get the right diagnosis,” Goff said. “But when our neighbor did the tilt table test on me, I fainted pretty quickly. He felt it was conclusive.”

Ms. Goff’s disabling symptoms, journey toward a diagnosis, and test results are common among those who live with POTS. Typically, when a person moves from lying down to standing up, blood moves to the lower extremities, causing a temporary reduction in blood flow to the heart and brain. Usually this does not cause a problem – the heart briefly speeds up its pumping to compensate. But in people with POTS, this “orthostasis” is abnormal. It’s as if the heart overcompensates, beating at a frenetic pace for longer than it should.

In addition to Goff’s specific symptoms, POTS can be associated with neurocognitive impairments or “brain fog”; problems with body temperature regulation; gastroenterological symptoms like nausea, abdominal pain, diarrhea, or constipation; and dark red-blue discoloration of the legs. Some people with POTS also may have one or more associated conditions, including migraine, irritable bowel syndrome, and joint hypermobility syndrome. Many people with POTS also have a personal or family history of autoimmune disease, in which the immune system attacks the body’s own tissues.

Now, the NHLBI is stepping up efforts that could lead to a better understanding of this often-debilitating condition. POTS currently has no cure, but with more knowledge will come better treatments – and hopefully, a way to help doctors know what they’re seeing when they see it.

A puzzle still unsolved

Exactly what causes POTS is unclear, but researchers believe the condition likely has multiple underlying mechanisms that vary from person to person. POTS may arise from problems with the autonomic nervous system or immune system. It may result when blood volume is reduced or blood flow gets disrupted throughout the body when a person goes from lying down to an upright position. Or, it could occur as a result of a combination of these factors.

Genetic factors may also play a role. And some people report having a preceding health event or disruption, such as a viral infection, concussion, surgery, pregnancy, or the start of puberty, before experiencing POTS symptoms. Many others cannot pinpoint any specific event that could have triggered the onset of POTS.

Because the signs and symptoms of POTS tend to vary, doctors still do not know whether it is best defined as a single syndrome or as a syndrome with several subtypes that have distinct underlying causes.

Julian Stewart, M.D., Ph.D., a pediatric cardiologist at New York Medical College, believes POTS can be categorized as primary or secondary. “Primary POTS,” he said, results from a disruption in the autonomic and circulatory systems that can’t be explained by other conditions. Those with an existing or identified underlying condition – such as heart failure, a thyroid condition, or another condition in which there is a loss of blood volume – may experience “secondary POTS” as a consequence of their primary condition. But Stewart said he is unsure if these secondary cases can truly be considered POTS. “Just because you think someone has POTS doesn’t mean you should stop looking for another underlying disease,” he suggested.

Satish Raj, M.D., a heart rhythm cardiologist at the University of Calgary and past president of the American Autonomic Society, believes there may, in fact, be subtypes of the condition. “The key to defining POTS is to focus on the “S” for syndrome,” said Raj, who chaired a 2019 NIH workshop on the state of the science, clinical care and research for POTS. “From a patient point of view, POTS is a cluster of symptoms, but we need better ways of defining and understanding it. We need good biomarkers. Ultimately, we want to tease out the different mechanisms associated with it.”

Limits to treatment

Until there is a cure, people like Goff are working to feel as well as they can with treatments focused on controlling symptoms. Many patients, for example, benefit by making sure they get enough salt in their diets and by staying well hydrated. Their doctors may prescribe medications that help them maintain normal blood pressure, expand their blood volume, and lower their heart rate. Many see improvement from exercise training, with a focus on aerobic reconditioning.

To manage her own condition, Goff takes fludrocortisone, a steroid and frequent treatment choice for POTS patients. “It helps a lot, and it’s manageable – I was able to get my stamina back,” Goff said. She has to be mindful, however. “When I exercise, I have to make sure my heart rate stays in a healthy range,” she noted. She also drinks plenty of liquids and makes sure she doesn’t stand in one place for too long without moving around. And because she is highly sensitive to heat, she needs to keep cool.

A future for POTS research

As a person living with POTS, Goff wants to see researchers focus more on why POTS happens. “I feel like current treatments aren’t really getting to the root problem, and I also worry about the effects of taking steroids long term,” Goff said. “I’d like to see possibly better treatments that get to the reason for the condition.” Raj agrees. “We still have an incomplete picture of the underlying mechanisms of POTS,” he said. “If we understand [the mechanisms] better, we can come up with better targeted treatments. We also need objective tests that clearly differentiate POTS from other distinct syndromes like chronic fatigue, myalgic encephalomyelitis, and fibromyalgia,” he added.

Raj noted that Long COVID – lingering symptoms experienced by many survivors of COVID-19 – can sometimes look like POTS. But while researchers can’t yet say what, if any, mechanisms the two conditions have in common, Raj thinks that strategies being developed to treat POTS could potentially be used to treat Long COVID patients, and vice versa.

He also agrees that better treatments are needed, and points to the problems that patients can encounter when trying to access medications. Because there are no FDA-approved treatments specifically for POTS, doctors prescribe medications off-label to treat its symptoms, and that can sometimes result in problems with insurance coverage and patient access.

Dr. Raj also would like to see more epidemiological research on POTS. “The WHO’s ICD-10, which is currently in use in the United States, does not include a POTS designation,” he noted, referring to the World Health Organization’s coding system for diseases used both domestically and internationally, which limits doctors’ ability to diagnose the syndrome officially for tracking purposes. This means that our estimates of prevalence are inexact, and the data are not uniformly collected, he said. It also can result in insurance coverage challenges. The WHO’s ICD-11 does include a code for POTS.

In addition to better understanding the fundamental aspects of POTS, Stewart of the New York Medical College is interested in why POTS seems to impact girls and women almost exclusively. Indeed, POTS primarily affects women of child-bearing age, with most studies reporting around 80-90 percent female predominance. “It is thought to be related to estrogen and other female hormones, but a close link hasn’t been shown. Some have found that POTS may cycle along with the menstrual cycle, but some have found the exact opposite,” Stewart said. He is also interested in further exploring the potential association between POTS and iron deficiency often seen in menstruating women.

Recognizing the gap in the understanding and treatment of POTS, the NHLBI and the National Institute of Neurological Disorders and Stroke have issued a Notice of Special Interest to encourage researchers to submit proposals designed to answer fundamental questions about POTS. Initial applications are due June 5, 2021.

For more information:

Postural Orthostatic Tachycardia Syndrome (POTS): State of the Science, Clinical Care, and Research Workshop Report

Notice of Special Interest (NOSI): Stimulate Research on the Diagnosis, Treatment, and Mechanistic Understanding of Postural Orthostatic Tachycardia Syndrome (POTS)