Abstract
IntroductionPostural (Orthostatic) Tachycardia Syndrome (PoTS) is a debilitating chronic disorder of the autonomic nervous system with many possible causes and symptoms, characterised by an unexplained excessive increase in heartbeat upon standing without change in blood pressure. The symptom burden is high but poorly delineated and there is little medical consensus regarding causes, symptoms, or treatment, meaning the journey to a PoTS diagnosis can be prolonged and fraught with complexity. This thesis aims to investigate the symptom burden in PoTS, but also understand how patients manage these symptoms in the context of multiple commonly co-occurring conditions, and where a clear diagnostic label may not always be provided. The aims of this thesis are therefore to investigate the symptom burden of PoTS (contextualising, measuring, and validating this quantitatively), and exploring the journey to diagnosis (in a qualitative manner) to better understand how this may influence the management of symptoms.
Methods
The first stage of the PhD was a published systematic review of 29 studies, which investigated factors and interventions associated with symptom burden in PoTS (I. Knoop et al., 2022). The second phase was a longitudinal mixed-methods project divided into four separate sub-studies. Patients (n=465) with suspected PoTS who were a month away from their first appointment with one of the largest specialist UK NHS PoTS clinics were invited by letter to participate in the studies. The first sub-study, published in the British Journal of Health Psychology, was a cross-sectional qualitative study which explored aspects of the Common-Sense-Model (CSM) in relation to the journey to a diagnosis of PoTS, and included those with a preliminary diagnosis of PoTS and those without (n=29). A second qualitative study due to be published in BMJ Open (Knoop et al., 2024), longitudinally explored the journey to a PoTS diagnosis from one month pre-specialist clinic appointment to 6 months later (Knoop et al., 2024). This study focused on those who did not have a preliminary diagnosis at baseline (n=15). A final, longitudinal quantitative study measured psychosocial and physiological correlates and predictors of symptom severity in patients under investigation for PoTS (n=149) at two timepoints; one month pre-specialist clinic appointment and 6 months later (n=98). A published nested psychometric validation study assessed the psychometric properties of the two main symptom outcome measures of the longitudinal quantitative study in the current study sample (n=149) (Knoop, A. S. Jones, et al., 2023).
Results
The systematic review (Study 1) suggested that adrenergic α1 receptor activation, reduced physical functioning, depression, and catastrophising were significantly associated with symptom burden in PoTS. This burden was however inconsistently measured as there is currently no validated standardised symptom measure for PoTS. We therefore nested a psychometric validation of two symptom burden measures for PoTS as part of the quantitative work. The systematic review also highlighted the paucity of work in this area, the lack of theoretical framing of the possible biopsychosocial aetiological factors investigated, and that no fully powered interventions have been conducted to date to reduce symptom burden in PoTS, and no behavioural or psychological interventions to reduce symptom burden have been trialled.
The qualitative studies (Studies 2 and 3) highlighted that diagnostic journeys were prolonged, complex, and added to patients’ cumulative burden of symptoms, co-occurring conditions, psychosocial impact, treatment, investigations, and dismissive attitudes (I. Knoop et al., 2023a). Moreover, the process did not always fully resolve patients’ search for further coherence, legitimacy, and diagnostic labels. The Common-Sense-Model would benefit from refinement to reflect this, or the 5-areas-CBT-model might provide a more suitable alternative framework.
Participants in the larger quantitative study (n=149) were predominantly female (90.5%) with a mean age of 33±12, reporting to have on average 3.8 co-occurring conditions. In Study 4, the orthostatic grading scale, and the symptom screen for small fibre polyneuropathy, were found to be valid and reliable measures of symptom burden in those under investigation for PoTS. The longitudinal questionnaire study (Study 5) showed that 48.6% of patients received a definitive diagnosis of PoTS, 22.3% had features of PoTS and were told they were PoTSie / orthostatic intolerant but did not meet the full diagnostic criteria, 28.8% remained under investigation without a confirmed diagnosis, and 0.7% received an alternative diagnosis, after 6 months follow-up. Psychosocial factors defined within a cognitive-behavioural model of persistent symptoms in PoTS in Study 5 explained a significant proportion (35-48%) of the variance of symptom burden at baseline. There was no change in symptom burden over time. At follow-up, physiological variables including relevant heart rate (HR) and blood pressure (BP) measures (HR delta from tilt test, average HR from Holter monitor, and diastolic BP) collectively explained a small (4%) but significant amount of variance of orthostatic symptoms. Due to the stability of symptom scores over time, only a small non-significant percentage of the variance in symptom severity over time was explained by psychosocial factors when controlling for demographic & haemodynamic factors, and baseline scores of the outcome measure. This was due to the baseline symptom scores explaining the vast majority of variance.
Conclusion
PoTS is an impactful condition, and this impact appears intensified by extensive investigations for the condition and its associated comorbidities, the lack of recognition the condition receives, and the persistence that is required by patients to receive appropriate diagnoses and care. Directions for future work include exploring the views of healthcare professionals to understand the challenges of caring for this patient group, identifying common symptoms across PoTS and comorbid conditions to inform which specific factors to target in the development of a complex tailored psychosocial/behavioural intervention that could be administered early on or prior to a diagnosis. These findings combined may contribute to a unified explanatory and treatment model for PoTS and associated comorbidities and provide directions for future interventions in this area.
| Date of Award | 1 Jul 2024 |
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| Original language | English |
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| Supervisor | Rona Moss-Morris (Supervisor) & Annie Jones (Supervisor) |