Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies.

Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension. The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Patients often will exhibit overlapping characteristics from more than one of these mechanisms. The approach to the treatment of POTS centers on treating the underlying pathophysiologic mechanism. Stockings, abdominal binders, and vasoconstrictors are used to enhance venous return in partial neuropathic POTS. Exercise and volume expansion are the main treatment strategies for hypo-volemic POTS. For hyperadrenergic POTS, beta-blockers and avoidance of norepinephrine reuptake inhibitors is important. Attempts should be made to discern which pathophysiologic mechanism(s) may be afflicting patients so that treatment regimens can be individualized.

Daily Functionality in Adults with POTS: Predictive Factors.

Symptoms associated with postural orthostatic tachycardia syndrome (POTS) hinder overall functionality. This study examined factors that impacted daily life and contributed to overall daily functionality in adults with POTS (n = 958, ages 18-60). Descriptive and multiple linear regression analyses indicated that participants with fewer challenges in ADLs, IADLs, work, school, leisure, and socializing had overall better functionality. Furthermore, 'younger age with exercise tolerance', 'having a job', and 'no falls in the last year' were predictors of better functionality. A comprehensive approach to addressing physical, environmental, and psychological factors could help improve overall functionality and enhance quality of life in individuals with POTS.

Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy.

Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and researchers. Both the pathogenesis and treatment of these disorders require further study. In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy. Sjogren's syndrome, which is a classical autoimmune disease, could serve as a disease model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may most benefit from the immunotherapy.

The face of postural tachycardia syndrome - insights from a large cross-sectional online community-based survey.

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

Neurocognitive Difficulties Among Youth with POTS within an Intensive Pain Rehabilitation Program.

OBJECTIVE: Adolescents and young adults (AYAs) with postural orthostatic tachycardia syndrome (POTS) commonly report cognitive difficulties, though there is limited information regarding the objective measurement of neurocognitive deficits in this population. This study described the rates of subjectively experienced and objectively measured neurocognitive difficulties and explored effects of medications on neurocognitive functioning among AYAs with POTS admitted to an intensive outpatient pain rehabilitation program. METHODS: Participants in a pain rehabilitation program diagnosed with POTS (N = 96; ages 12-22) were included in the study. Medical characteristics, reported cognitive complaints, and neurocognitive assessment results were collected through retrospective medical record review. We calculated descriptive statistics and Pearson's χ2 or Fisher's exact tests, where appropriate. RESULTS: While 96% of this sample reported subjective cognitive complaints, as a group, they performed in the Average range on standardized measures of intellectual functioning, attention, and memory. The majority did not demonstrate any normative (73%) or relative (54%) weaknesses in attention or memory. Those prescribed an antiepileptic (n = 19) were less likely to have visual-spatial memory weaknesses but more likely to have attention weaknesses. CONCLUSIONS: Despite a high frequency of reported cognitive difficulties, most AYAs with POTS did not demonstrate neurocognitive impairment on standardized, one-on-one assessment. Suggestions for further study of biopsychosocial contributors to neurocognitive difficulties and for clinical use of neurocognitive assessments in this population were provided.

Youth with Chronic Pain and Postural Orthostatic Tachycardia Syndrome (POTS): Treatment Mediators of Improvement in Functional Disability.

Intensive pain rehabilitation programs are effective in increasing functioning for youth with chronic pain (CP). However, the utility of such programs for youth with CP and co-morbid postural orthostatic tachycardia syndrome (POTS) is rarely examined. In addition, studies examining mediators of treatment for CP are sparse. This paper compares treatment outcomes for youth with CP (n = 117) and youth with CP + POTS (n = 118). Additionally, depression and pain catastrophizing were tested as potential mediators of treatment effects. Significant treatment improvements were found for functional disability, depression, pain catastrophizing, and perceived pain intensity but with no differences between groups. Improvements in depressed mood, pain catastrophizing (helplessness subscale), and pain severity partially mediated functioning improvement. Pain severity was not a significant mediator in the CP + POTS group. We concluded that depression and pain catastrophizing, especially the helplessness domain, can impact functioning improvement in adolescents with CP and POTS and are particularly important to target in treatment.

Health-related quality of life and suicide risk in postural tachycardia syndrome.

PURPOSE: Postural tachycardia syndrome (POTS) is a disorder featured by orthostatic intolerance. The purpose of this study was to investigate the severity of quality of life issues in POTS patients. METHODS: Online surveys for health related quality of life, sleep quality, fatigue, pain, and suicidal ideation were completed by 624 POTS patients and 139 controls. RESULTS: People with POTS have significantly more days of poor physical health (p < 0.001), fewer days with good energy (p < 0.001), and significantly more days with activity limitations (p < 0.001) than controls. Pain severity was significantly higher for those with POTS (p < 0.001) while feelings of control over life was lower than controls (p < 0.001). Sleep quality and daytime fatigue were also significantly worse for those with POTS than controls (p < 0.001). Finally, those with POTS have a significantly higher risk of suicide compared with controls (p < 0.001). INTERPRETATION: The myriad of symptoms from which many POTS patients suffer is associated with a decreased quality of life. Nearly half of our sample with POTS was at high risk for suicide. More work needs to be done to determine the underlying issues surrounding suicide in POTS so that an appropriate treatment regimen can be developed.

Interdisciplinary Treatment of Maladaptive Behaviors Associated with Postural Orthostatic Tachycardia Syndrome (POTS): A Case Report.

The prevalence of postural orthostatic tachycardia syndrome (POTS) in adolescents and young adults has been increasing during the past decade. Despite this increase, documentation regarding treatment of these patients is just beginning to emerge. In addition, despite a call for a multidisciplinary or interdisciplinary approach, no studies have examined the efficacy of such an approach to treatment. This paper describes a case study of a 19-year-old male with debilitating POTS seen at a tertiary clinic for evaluation and subsequent intensive interdisciplinary treatment. The treatment approach is described and outcomes are presented.

Understanding the placebo effect in clinical trials for postural tachycardia syndrome.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) upon standing. Previous studies have shown that standing HR decreases over time in POTS patients given placebo. We hypothesized that this reduction is due to cardiovascular physiological alteration, as opposed to psychological benefit from perceived therapy. To prospectively test this hypothesis, we examined the effects of an open-label 'no treatment' intervention (NoRx) compared with a patient-blinded placebo on standing HR in POTS patients. Twenty-one POTS patients participated in a randomized cross-over trial with oral placebo versus NoRx administered at 0900 h. Seated blood pressure (BP) and HR were measured at baseline and every hour for 4 h. Similarly, BP and HR were measured while patients stood for 10 min at these time points. Standing HR decreased significantly over time with both NoRx (112±13 and 103±16 b.p.m. at baseline and 4 h, respectively) and placebo (112±14 and 102±16 b.p.m. at baseline and 4 h, respectively; Ptime<0.001), but this effect was not different between interventions (Pdrug=0.771). Postural tachycardia syndrome patients have exaggerated orthostatic tachycardia in the morning that decreases over time with either placebo or NoRx interventions, suggesting this phenomenon is due to cardiovascular physiological variation. These data highlight the need for a placebo arm in haemodynamic clinical trials in POTS and may have important implications for the diagnosis of these patients.

[Postural orthostatic tachycardia syndrome (POTS)--pathophysiology, diagnostics, and treatment]. / Zespól posturalnej tachykardii ortostatycznej (POTS)--patofizjologia, rozpoznanie i leczenie.

Postural orthostatic tachycardia syndrome (POTS) is one of the most common presentation of orthostatic intolerance. The syndrome is described as a multifactorial affliction. Main symptoms consist of persistent orthostatic tachycardia (heart rate increase at least 30 beats/min, lasting at least 10 min after assumic vertical position) with high noradrenalin serum concentration (measured in stand-up position). Additionally patients with POTS tend to have lover total blood volume. POTS is generally classified into dysatonomia disorders Symptoms in patients affected with POTS are chronic. The syndrome occurs predominantly in young women (approximately 80%). Due to complexity and variable intensity of symptoms POTS can severely impair daily activity and quality of life in otherwise healthy people. The correct diagnosis and identification of potential pathophysiological mechanisms of POTS is necessary before treatment administration. Adequate therapy can significantly reduce symptoms giving the patients a chance for a normal life.

The Contribution of Psychological Symptoms to Cognitive Difficulties in Youth With Postural Orthostatic Tachycardia Syndrome and Chronic Pain.

INTRODUCTION: Subjectively experienced cognitive difficulties are common in youth with postural orthostatic tachycardia syndrome. The pathophysiological and psychological contributions of these cognitive impairments remain unclear. METHOD: Participants were 96 adolescents and young adults diagnosed with postural orthostatic tachycardia syndrome and admitted to an intensive pain treatment program. Participants completed cognitive assessment and measures of postural orthostatic tachycardia syndrome symptoms, pain intensity, pain catastrophizing, anxiety, depression, and functional disability. RESULTS: Self-reported autonomic symptom intensity, but not severity of heart rate change, was associated with cognitive performance. Symptoms of depression were associated with decreases in most measures of cognitive functioning. Pain intensity, pain catastrophizing, and depression but not cognitive scores and physiological measures, were significant predictors of disability. CONCLUSION: Depression appears to be a significant contributor to the cognitive difficulties in youth with postural orthostatic tachycardia syndrome. These findings highlight the importance of assessing and treating affective symptoms in this population along with medical and lifestyle approaches to treating postural orthostatic tachycardia syndrome symptoms.

[Anxiety in patients with postural tachycardia syndrome (POTS)]. / Ängstlichkeit bei Patienten mit posturalem Tachykardiesyndrom (POTS).

BACKGROUND: The postural tachycardia syndrome (POTS) is a condition of the autonomic nervous system with symptoms of orthostatic intolerance. In POTS patients, orthostatic stress leads to an overshoot of heart rate increase without a fall in blood pressure. The purpose of this study is to distinguish between anxiety disorders and anxiety as a concomitant phenomenon of orthostatic stress. METHODS: 50 patients fulfilling the diagnostic criteria (orthostatic symptoms, heart rate increase of > 30 bpm or up to > 120 bpm by testing with tilt-table) were included. The study design included a thorough medical history as well as standardised questionnaires about anxiety. RESULTS: The average heart rate increase was 36 bpm after ten minutes of standing and 42 bpm after maximal standing time (max. 45 minutes). POTS patients scored significantly higher than a comparison group in a range of anxiety disorders by using anxiety questionnaires like "Beck Angst-Inventar" (BAI) and trait test of "State-Traits-Angstinventar" which include autonomic items. When questionnaires were used that exclude autonomic items (anxiety sensitivity index: ASI; Interaktions-Angst-Fragebogen: IAF) there was no difference. CONCLUSION: POTS patients do not exhibit signals of anxiety disorders more often than control groups, provided that questionnaires without autonomic items are used.

Psychological correlates of patients with postural orthostatic tachycardia syndrome (POTS).

Psychological symptoms are frequently reported in patients with Postural Orthostatic Tachycardia Syndrome (POTS); however, the nature of these symptoms is not well understood. The current study described baseline psychological symptoms in patients with POTS, and examined associations between psychological and self-report autonomic symptoms. Participants reported mild anxiety symptoms, moderate depressive symptoms, severe somatization, and elevated anxiety sensitivity. Depressive symptoms and pain catastrophizing were significantly associated with autonomic symptoms. The current study adds to the literature by documenting elevated levels of anxiety sensitivity, and relationships between psychological and autonomic symptoms.

Dimensional latent factor structure of psychopathology in adults with chronic illness.

The goal of the present study was to determine if the internalizing and externalizing model of psychopathology is applicable in a sample of adults with chronic illness. Confirmatory factor analyses were used to examine the factor structure of internalizing and externalizing symptoms in a sample of adults (N = 172) with a unique chronic physical health condition (postural orthostatic tachycardia syndrome; POTS) and in a sample of adults without any chronic illness diagnoses (N = 199). Measurement invariance was used to compare levels of internalizing and externalizing symptoms across samples. Confirmatory factor analyses suggested that psychological distress in individuals with chronic illness can be effectively characterized by an internalizing dimension composed of distress and fear subcomponents as well as an externalizing dimension. Measurement invariance testing reached adequate levels of fit, allowing for examination of latent means; individuals with chronic illness had higher scores on the internalizing dimension and lower scores on the externalizing dimension than healthy controls. Regression analyses suggested that among those with a chronic illness, internalizing symptoms were significantly, negatively related to acceptance of illness and higher health-related quality of life. Findings suggest that assessing internalizing symptoms broadly may allow for better identification of chronically ill individuals experiencing psychological distress than a focus on categorical diagnoses. However, professionals also need to be aware of the overlap between physical and psychological symptoms in adults with chronic illnesses in order to avoid inaccurate diagnoses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test.

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end-tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30-minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5-minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age- and sex-matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P≥0.4). The CBFv decreased in both groups (condition, P=0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (-7.8% versus -1.8%; interaction, P=0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P=0.027) and a greater increase in symptom scores at study completion (interaction, P<0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end-tidal carbon dioxide) did not differ between groups after PCST (all P>0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.

Psychiatric profile and attention deficits in postural tachycardia syndrome.

OBJECTIVES: Patients with postural tachycardia syndrome (POTS) often appear anxious and report inattention. Patients with POTS were formally assessed for psychiatric disorders and inattention and compared with patients with attention deficit hyperactivity disorder (ADHD) and control subjects. METHODS: Patients with POTS (n = 21), ADHD (n = 18) and normal control subjects (n = 20) were assessed for DSM-IV psychiatric disorders and completed a battery of questionnaires that assessed depression, anxiety and ADHD characteristics. RESULTS: Patients with POTS did not have an increased prevalence of major depression or anxiety disorders, including panic disorder, compared with the general population. Patients with POTS had mild depression. They scored as moderately anxious on the Beck Anxiety Inventory but did not exhibit a high level of anxiety sensitivity. Patients with POTS scored significantly higher on inattention and ADHD subscales than control subjects. These symptoms were not present during childhood. CONCLUSIONS: Patients with POTS do not have an increased lifetime prevalence of psychiatric disorders. Although they may seem anxious, they do not have excess cognitive anxiety. They do experience significant inattention which may be an important source of disability.

POTS versus deconditioning: the same or different?

The 2007 Streeten Lecture focused on the idea that physical deconditioning plays a key role in the symptomology and pathophysiology of POTS. Parallels were drawn between the physiological responses to orthostatic stress seen in POTS patients and the physiological responses seen in "normal" humans after prolonged periods of bedrest, deconditioning, or space flight. Additionally, the idea that endurance exercise training might ameliorate some of these symptoms was also advanced. Finally, potential parallels between POTS, chronic fatigue syndrome, and fibromyalgia were also drawn and the potential role of exercise training as a "therapeutic intervention" in all three conditions was raised. The conceptual model for the lecture was that after some "initiating event" chronic deconditioning plays a significant role in the pathophysiology of these conditions, and these physiological changes in conjunction with "somatic hypervigilence" explain many of the complaints that this diverse group of patients have. Additionally, the idea that systematic endurance exercise training might be helpful was advanced, and data supportive of this idea was reviewed. The main conclusion is that the medical community must retain their empathy for patients with unusual conditions but at the same time send a firm but empowering message about physical activity. As always, we must also ask what do the ideas about physical activity and inactivity and the conditions mentioned above not explain?

The patient perspective: What postural orthostatic tachycardia syndrome patients want physicians to know.

Diagnosing and treating postural orthostatic tachycardia syndrome (POTS) can be a frustrating experience for patients and physicians alike. Experienced patient leaders solicited input from the large online POTS community to identify patient suggestions and concerns, with the goal of improving the patient-physician relationship and outcomes in POTS. This review article offers practical tips to improve POTS patient care and links to credible resources for your patients. The authors emphasize the urgent need for improved physician education, a tailored treatment approach, and expanded research efforts.

Parental Perceptions of Pediatric Pain and POTS-Related Disability.

Adolescents with postural orthostatic tachycardia syndrome (POTS) often have pain and functional impairment. This study evaluated how parental attributions of children's symptoms relate to child functional impairment. Adolescents with chronic pain and clinical symptoms suggestive of autonomic dysfunction (fatigue, dizziness, nausea) that attended a multidisciplinary chronic pain clinic completed measures of depression, anxiety, and functioning (n = 141). Parents of 114 of these patients completed the Parent Pain Attribution Questionnaire (PPAQ), a measure indicating the extent they believe physical and psychosocial factors account for their child's health condition. Patients were retrospectively grouped as to whether or not they had significant POTS on tilt table testing (n = 37). Greater parental attribution to physical causes was associated with increased levels of functional disability whether patients had POTS ( r = 0.45, P = .006) or not ( r = 0.25, P = .03). These results suggest that providers should advocate a more comprehensive family-oriented rehabilitative approach to treatment.