Patients with POTS fear that data on abnormal haemodynamic physiology have been ignored

Norcliffe-Kaufmann et al.1 recently reported that patients with postural orthostatic tachycardia syndrome (POTS) had an exaggerated anticipatory heart rate (HR) increase in the 30 s prior to head-up tilt (HUT). Based largely on these findings, the authors conclude that patients with POTS suffer from a ‘fear-conditioning behavioural response’ to the thought of standing, and that POTS is a ‘functional psychogenic disorder’ that would best be treated by mental health professionals. Their basic finding is of potential interest; unfortunately their conclusions ignore limitations in their participant selection, methodological approach, and prior research into POTS pathophysiology, and they illustrate their lack of knowledge of psychiatric diagnosis and care. A major study limitation is the choice to compare POTS patients with a healthy control group. In a previous report,2 participants with POTS scored higher on the anxiety sensitivity index than healthy control participants, but scores were not significantly different compared to the general population.2 Patients with chronic illness have elevated depression, anxiety and health anxiety scores compared to healthy controls.3 Consequently, Norcliffe-Kaufmann et al.1 should have chosen a control group with chronic illness but without an orthostatic disorder. Without this control group, the study finding of exaggerated anticipatory tachycardia to a tilt stimulus may simply reflect elevated somatic anxiety due to chronic illness. Importantly, POTS patients very often have symptomatic postural sinus tachycardia throughout the day. Norcliffe-Kaufmann et al.1 would do well to explain how anticipation of a tilt test could cause hours of symptoms every day for months. They might also reflect on the numerous and well documented symptoms and signs of POTS patients such as daily headache, brain fog, patchy sympathetic denervation and dependent acrocyanosis. The magnitude of the anticipatory HR increase is barely ‘exaggerated’. Figure 1B in Norcliffe-Kaufmann et al.1 shows the supine anticipatory HR increase was 8 bpm in POTS patients and 3.5 bpm in healthy controls, with all values in the normal range. If the HR increase is due to ‘anticipatory anxiety’, it may well be in anticipation of a medical procedure (the HUT), and not of simply standing. It is likely that many of the POTS patients have had a prior HUT, which most people describe as an unpleasant test, while most ‘healthy controls’ would have not undergone a previous tilt test. Therefore, the trigger for an anticipatory response was likely not equal between groups and may have been associated with anticipating a medical test and not day-to-day standing. Norcliffe-Kaufmann et al.1 ignore the large amount of literature that documents abnormal physiology in POTS patients including low blood volume4,5 and low stroke volume,4,5 especially when upright, compared to healthy participants. It is curious that the authors did not report the stroke volume in their patients, especially given that the Finometer® continuous blood pressure monitor that was used in this study can give estimates of stroke volume. Several strategies that target low blood volume and low stroke volume, but do not target ‘anticipatory anxiety’, will lower the upright HR and improve symptom burden in patients with POTS. These interventions include exercise training,5 a high sodium diet,4 lower body compression garments6 and ivabradine (a drug that affects sinus node automaticity).7 All these successful interventions target abnormal hemodynamic physiology, and none target a ‘fear of standing’. The lack of reported physiological data is at minimum an unfortunate omission. Perhaps the authors could clarify how anticipation of a tilt test has such a profound effect on blood volume and the response to interventions that target it. Masuki et al.8 conducted an elegant study to tease out the role of anxiety versus gravitational fluid shifts as the cause of excessive tachycardia in patients with POTS. They simulated standing using lower body negative pressure (LBNP), in which negative pressure (suction) is applied to the lower body, causing blood to shift from the thorax into the abdomen and legs. LBNP simulates the intravascular fluid shifts that occur with the assumption of upright posture. This simulated orthostatic stress reduces stroke volume, unloads the baroreceptors and activates the baroreflex, resulting in increased sympathetic nervous system activation and increased HR. When Masuki et al.8 applied LBNP, patients with POTS had a significantly higher HR increase compared to the healthy controls, without a change in blood pressure. When the protocol was repeated with the medical antishock trouser (MAST) pants inflated (to insulate the legs from suction), this HR increase was essentially eliminated. When the vacuum sound was applied without any negative pressure (negative control), the HR did not increase in patients with POTS.8 These data elegantly demonstrated that the increase in HR seen in patients with POTS was driven by the shift of fluids away from the thorax (baroreceptor unloading) and not the anticipation of LBNP. The authors are incorrect in labelling fear conditioning as a psychiatric disorder. The phenomenon of fear conditioning is an anxiety response to the threat of uncertainty following prior experience with an unpleasant stimulus,9 in this case tilt testing. POTS is not a functional psychogenic disorder as these ‘fear conditioning’ and ‘psychogenic disorders’ are very different entities. Psychogenic disorders are recognized by physical symptoms that are incompatible with or in gross excess of organic findings, along with variable health-related anxiety and insight. Treatment involves psychotherapy and prognosis is often limited. The wealth of data on physiological perturbations in POTS, and favourable response to non-psychological treatments, are not consistent with a psychogenic disorder. The authors suggest the optimal treatment for POTS should be led by psychiatric care. This has already failed. In a large survey of over 4800 POTS patients, prior to diagnosis, 77% of patients were told their symptoms could be the result of psychological or psychiatric problem, but only 28% felt that they were actually experiencing a psychological or psychiatric problem.10 After their POTS diagnosis, only 37% of participants had a doctor tell them their symptoms were the result of a psychological or psychiatric problem, and 31% were being treated for a psychological or psychiatric problem.10 If the authors’ conjecture is correct that the optimal treatment of POTS lies in the realm of psychiatric care, one would expect that most of these patients would get better with the high prevalence of psychiatry care. Unfortunately, that was not the case. The authors’ conjecture is too little, too late and too wrong. As providers and researchers for patients with POTS, we are interested in any interventions that could help these patients. We do agree that mental health should be considered in treating patients with POTS, as it is with many other disorders. The authors’ conclusion that POTS be recast as a ‘functional psychogenic disorder’ flies in the face of a vast body of published literature, and far outstrips their own results. If the authors truly believe that psychiatric care will make these patients better, we will eagerly look forward to their intervention study of psychiatric and psychological approaches to the treatment of patients with POTS. Data sharing is not applicable to this article as no new data were created or analysed in this study. This work was supported by the Canadian Institutes of Health Research (CIHR; Ottawa, ON, Canada) grant MOP142426, and the Vanderbilt Institute for Clinical and Translational Research (NIH UL1-TR000445). S.R.R. is a consultant to Lundbeck LLC, Theravance Biopharma and Amneal Pharma related to neurogenic orthostatic hypotension; consultant to Servier Affaires Medicales, Regeneron and argenx BV related to postural orthostatic tachycardia syndrome. Honoraria from Spire Learning and Medscape are received for developing CME materials on neurogenic orthostatic hypotension. S.S.R. is DMSB Chair for a Phase 2 study of an irritable bowel syndrome medication for Arena Pharmaceuticals with compensation and Past-President of the American Autonomic Society without financial compensation. The other authors report no competing interests.

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