Poor health-related quality of life in postural orthostatic tachycardia syndrome in comparison with a sex- and age-matched normative population

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder identified by its hallmark manifestation of postural-induced tachycardia in the absence of orthostatic hypotension [1, 2]. The syndrome has a high female predominance (> 80%) and appears to mostly affect those of childbearing age [3‐5]. Patients with POTS often experience diverse and multisystemic symptomatology with variable impact on activities of daily living including ability to self-care or engage in education and employment [6]. POTS remains poorly recognized among clinicians, with reports of protracted delay in diagnosis [5, 6]. The impact of this condition has not been well characterized to date, with few studies reporting on health-related quality of life (HrQoL) in those affected [7, 8]. Furthermore, the effect of POTS on HrQoL, including restriction of activity and societal participation in comparison with normative age-matched populations, has not been evaluated. The lack of such information prevents healthcare agencies from understanding the true impact of POTS and limits their ability to allocate health resources equitably. Therefore, the primary objective of this study was to delineate the disutility of POTS in comparison with a normative age- and sex-matched population.

The Euroquol five-dimensional instrument (EQ-5D) is the most ubiquitously applied generic multi-attribute utility instrument for indirect measurement of health utilities by assessing five domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as the global health status in an individual [9‐11]. Here, we used the contemporary five-response version of the Euroquol tool (EQ-5D-5L), which has demonstrated strong sensitivity in detecting clinically meaningful differences in HrQoL, to evaluate the health status of patients with POTS. These were compared with local normative age- and sex-matched data from participants in the South Australian Health Omnibus Study [10].

This study has institutional human research and ethics committee approval (approval number H-2021–052) and was performed in accordance with the 1964 Declaration of Helsinki standards for human research. All participants gave informed consent prior to their inclusion in the study.

Consecutive participants ≥ 16 years of age and enrolled in the Australian POTS patient registry (Australian New Zealand Clinical Trials Registry: ACTRN12621001034820) between 5 August 2021 and 30 June 2022, who provided written, informed consent were included. Health and quality of life surveys, including the composite autonomic symptom score (COMPASS-31) and fatigue severity (FSS) were completed via a password protected, electronic link to a Research Electronic Data Capture (REDCap) database. The REDCap self-complete digital version of the EQ-5D-5L was utilized to capture quality of life responses. To be eligible, all participants had their POTS diagnosed or confirmed by an experienced multidisciplinary team at a specialist clinic in Adelaide, South Australia, according to the international criteria, which included a sustained heart rate rise of ≥ 30 beats per minute (bpm) (≥ 40 bpm in adolescents) on 10 min standing test or head-up tilt table; absence of orthostatic hypotension as defined by a drop of ≥ 20 mmHg systolic or 10 mmHg diastolic blood pressure in the first 3 minutes of standing; as well as accompanying symptoms of orthostatic intolerance and chronicity of symptomology for ≥ 6 months [2]. All comorbidities were clinically verified and most of the individuals with POTS were treatment naive. Data were compared with those of local normative age- and sex-matched participants from the South Australian Health Omnibus Study for this comparative study. In brief, this database consists of 2908 individuals randomly selected from both metropolitan Adelaide and country towns with population of at least 1000 people. The interviewer-administered, face-to-face, cross-sectional study was undertaken in 2013 where deidentified sociodemographic and EQ-5D-5L responses were collected [10].

From a total of 256 participants enrolled in the Australian POTS patient registry during the study period, 54 were excluded due to incomplete surveys. This study therefore included 202 consecutive participants with POTS and 202 age and sex propensity matched normative participants. The median age of these patients was 28 years (range 16–66 years). The majority of the participants were female (90.6%) and Caucasian (95%). POTS patients were less likely to be undertaking any employment (47% versus 62%, P < 0.001) and more likely to be unemployed due to disability or injury (15% versus 4%, P < 0.001) than the normative population. The POTS cohort reported onset of POTS symptoms at median age of 23 years (IQR 16 years) with median symptom duration of 3 years (IQR 9 years). As presented in Table 1, 40% of the individuals with POTS demonstrate no identifiable trigger, while preceding infection was reported in 30%. Other less common triggers are trauma or concussion, post-surgical, and vaccination. Common comorbidities include anxiety or depression, migraine, Ehlers–Danlos syndrome or hypermobile spectrum disorder, irritable bowel syndrome, iron deficiency, and myalgic encephalomyelitis or chronic fatigue syndrome (Table 1).

This is the first study to report comparative HrQoL data in individuals with POTS and a normative, age- and sex-matched population. First, our data demonstrate new findings of significantly reduced HrQoL in the POTS cohort as compared with a normative population in the form of significantly lower EQ-5D-5L scores in all five subdomains, with “usual activities” being the worst affected, followed by “pain and discomfort,” “mobility,” “anxiety and depression,” and “self-care.” Second, individuals with POTS reported significantly lower global health rating and higher health disutility. Third, there is no sparing of these effects with similarly affected HrQoL scores among different age categories. Last, severity of orthostatic intolerance symptoms, female sex, and comorbid diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were independent predictors of lower utility scores. Our findings provide new understanding on the disutility associated with POTS and calls for improved health response to this condition.

This is the first comprehensive comparison of HrQoL in POTS with an age- and sex-matched normative population demonstrating a significant HrQoL burden exerted by POTS on a young, predominantly female population, including significant problems with usual activities, pain and discomfort, mobility, anxiety and depression, and self-care. Effective strategies to manage, improve, and support the reduced HrQoL in those with POTS are urgently needed.