The long and winding road of postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is widely described as a chronic disorder of cardiovascular autonomic regulation, characterized by an exaggerated increase in heart rate upon standing [1]. The condition disproportionately affects women of reproductive age [2]. However, the clinical manifestations of POTS extend far beyond the cardiovascular system. Patients frequently experience a broad spectrum of symptoms, including exercise intolerance, cognitive difficulties such as impaired memory and concentration, gastrointestinal disturbances, and sleep disruption—often as prominently as palpitations and orthostatic intolerance [3].

Despite its substantial impact on quality of life, the long‐term trajectory of POTS remains uncertain: Is it a lifelong condition or one from which patients may recover spontaneously?

The relevance of this question has grown substantially in the wake of the COVID‐19 pandemic [4]. The incidence and, consequently, prevalence of POTS have increased markedly post‐pandemic, with estimates suggesting up to a six‐fold rise of the total POTS prevalence in population [5]. Among individuals with long COVID, approximately one third meet diagnostic criteria for POTS, sharing the multi‐systemic symptom burden of long COVID with circulatory dysregulation characteristic for POTS [6]. Notably, the presence of POTS is associated with more severe long COVID manifestations, yet its impact on long‐term prognosis remains unclear [7].

In this issue, Bourne et al. present data from a very long follow‐up of POTS patients [8]. The authors contacted around 120 patients previously investigated and diagnosed with POTS at the Vanderbilt Autonomic Center in Nashville, USA, between 1987 and 2014. The majority responded, and more than one third completed the online survey, exploring the symptom evolution and applied measures between the onset of POTS, the diagnosis, and the time point for survey.

Here, a word of caution is needed: Individuals with persistent symptoms may have been more motivated to participate, whereas those with full recovery—or, conversely, those most severely affected—may have been underrepresented. Thus, it is impossible to assess in an objective way how representative this rather small patient sample is for the general population of POTS patients.

In the final cohort of 46 patients with POTS who completed the study, the median disease duration was 23 years, whereas the median time between diagnosis and the survey was 17 years, offering a very long follow‐up time, by far exceeding the current studies on long COVID, which also include POTS patients.

The most striking observation was the persistence symptom over decades in nearly all participants. However, the disease trajectories differed: just over half reported a gradual improvement, whereas the rest declared worsening of symptoms or no change at all over time.

Against this background, the survey by Bourne et al. provides a rare opportunity to examine the long‐term course of POTS. The vast majority of patients were women, as expected, with a median age of symptom onset at 26 years, while being approximately 48 years old at the time of survey. In a recent similar study performed by Boris et al., including pediatric patients from the Children's Hospital of Philadelphia POTS Program, approximately one‐fourth of 862 responded to the survey [9]. These patients had a mean age of 12 years at the symptom onset and were 22 years old when the survey was completed. Thus, the follow‐up period was about 10 years, and their age was still below the onset of symptoms in Bourne's study. Half of patients missed >100 school days due to their symptoms, only 26% were able to work >40 h/week, and nearly half of all working patients had to adapt their working hours and job due to limitations imposed by POTS. Consequently, the substantial impact of POTS, regardless of whether the symptoms begin in adolescence or in adults, persists in almost all patients for years after disease onset.

In this place, it is important to mention that the spectacular post‐pandemic increase in new POTS cases all over the world conferred some shift in the age of POTS onset: As POTS is a part of long COVID phenomenon, it also partly shares long COVID's demographics. The female predominance is still there, but the average age at POTS (and long COVID) diagnosis has shifted up to about 40 years of age [7]. Like the above‐mentioned POTS surveys, the symptoms of long COVID seem to persist over time, with substantial proportion of patients being affected by POTS in parallel to long COVID [10].

In summary, although only a subset of the original population responded and completed the survey, which unavoidably has introduced selection bias, the resulting data offer a unique window into long‐term trajectories of POTS extending beyond two decades, probably the longest POTS follow‐up ever performed. Several important observations stand out. First, symptom persistence was the rule rather than the exception, with nearly all respondents reporting ongoing manifestations decades after diagnosis. Second, the disease course was heterogeneous: Although just over half described gradual improvement, a substantial proportion reported either no change or worsening over time. For the former, this may reflect appropriate diagnostic evaluation, adequate patient education, and the implementation of effective non‐pharmacological and pharmacological strategies—or simply that patients adapt to living with POTS, as is seen in many chronic conditions such as rheumatoid arthritis, heart failure, or multiple sclerosis. Accordingly, we cannot categorically conclude that the disease is self‐limiting in a subset of patients, as it is equally possible that observed improvement reflects effective interventions and self‐education. Even more importantly, these findings challenge the common perception of POTS as a predominantly self‐limiting condition and instead support a model of chronic, albeit variable, disease. It should also be borne in mind that POTS is conceptualized as a chronic condition from the point of diagnosis, as symptoms must be present for at least three months, the fact frequently forgotten by the proponents of self‐limiting disease hypothesis [2].

In the context of long COVID, these data are particularly sobering. If similar mechanisms underlie POTS in long COVID, a large subset of patients may face symptoms that persist for decades rather than years.

It is now essential to better understand the upstream mechanisms of POTS, develop disease‐modifying treatments, and identify preventive strategies for future post‐viral syndromes such as long COVID–associated POTS, which appear increasingly likely in light of recent developments. The question, therefore, is no longer whether POTS can be chronic, but in whom—and whether its course can be altered. This remains a major challenge for scientists, physicians, and those affected by this debilitating condition. The long and winding road of POTS has come to our door, and we have seen this road before. Perhaps the more pressing question is not whether it disappears, but how we learn to alter its course.

Author contributions

Artur Fedorowski: conceptualization; writing—original draft; validation.

Conflict of interest statement

Artur Fedorowski is supported by the Swedish Heart Lung Foundation (Grant no. 20220317). Artur Fedorowski reports consultancy and lecture fees from ArgenX BV (for POTS), Finapres Medical Systems (for syncope), Medtronic Inc. (for syncope), and Regeneron (for POTS).

Funding information

Artur Fedorowski is supported by the Swedish Heart Lung Foundation (Grant no. 20220317).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.