Long-Term POTS Outcomes Survey: Diagnosis, Therapy, and Clinical Outcomes.

BACKGROUND: Limited data exist on long-term outcomes in individuals with postural orthostatic tachycardia syndrome (POTS). We designed an electronic questionnaire assessing various aspects of outcomes among patients diagnosed and treated in a single-center pediatric POTS clinical program. METHODS AND RESULTS: The LT-POTS (Long Term POTS Outcomes Survey) included questions about quality of life, symptoms, therapies, education, employment, and social impact of disease. Patients age≤18 years at POTS diagnosis who were managed in the Children's Hospital of Philadelphia POTS Program were included. A total of 227 patients with POTS responded with sufficient data for interpretation. The mean age of respondents was 21.8±3.5 years. The median age of symptom onset was 13 (interquartile range 11-14) years, with mean 9.6±3.4 years symptom duration. Multiple cardiovascular, neurologic, and gastrointestinal symptoms were reported. Symptom prevalence and severity were worse for female patients, with 99% of patients reporting ongoing symptoms. Quality of life showed moderate function and limitation, with more severe limitations in energy/fatigue and general health. Nearly three quarters of patients had diagnostic delays, and over half were told that their symptoms were "in their head." Multiple medications were used and were felt to be effective, whereas fewer nonpharmacologic interventions demonstrated efficacy. Nearly 90% of patients required continued nonpharmacologic therapy to control symptoms. CONCLUSIONS: POTS is a chronic disorder leading to significant disability with a range of multisystem problems. Although symptoms can be modifiable, it rarely spontaneously resolves. Improved understanding of POTS presentation and therapeutic approaches may inform provider education, improve diagnostic success, and help patients self-advocate for appropriate medical management approaches.

One or many labels? a longitudinal qualitative study of patients' journey to diagnosis at a specialist NHS Postural Tachycardia Syndrome (PoTS) clinic.

OBJECTIVES: Postural Tachycardia Syndrome (PoTS) is a poorly understood syndrome of multiple disabling symptoms. This study explored the process of seeking a diagnosis of PoTS. Analysis focused on changes before and after participants' first appointment with a national PoTS clinic, and explored whether a diagnosis is beneficial in the context of multiple co-occurring conditions and an absence of licenced treatments. DESIGN: A longitudinal, qualitative study. METHODS: Participants (n = 15) in this nested qualitative study were recruited from a larger study of people who had been newly referred to a National specialist NHS Cardiology PoTS service. Semi-structured interviews were conducted remotely before, and 6 months after their first appointment with the clinic. Data was analysed longitudinally and inductively using Reflexive Thematic Analysis. RESULTS: Three overarching themes were identified: "Slowly moving forward and finding positive gains", "Needing more pieces of the puzzle to see the bigger picture", and "The value and impact of investigations". Findings suggested that not much had changed in the 6 months between interviews. Participants were moving forward in terms of diagnoses, treatment and adjustment following their appointment, but many were still seeking further clarity and possible diagnoses. Investigations, appointments, and new-found problems, continued to have a substantial impact over time. CONCLUSIONS: The journey to diagnosis for patients with suspected PoTS appeared to promote acceptance of self, and of limitations posed by symptoms. However, many participants continued their search for an explanation for every symptom experience, and this may become increasingly complex, the more labels that have been acquired. Lack of clarity contributed to ongoing difficulties for this patient group alongside fraught relations with health care professionals (HCPs). A more coherent, integrated approach which is communicated clearly to patients is recommended.

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.

Autonomic Dysfunction from Diagnosis to Treatment.

Autonomic disorders can present with hypotension, gastrointestinal, genitourinary symptoms, and heat intolerance. Diabetes is the most common causes of autonomic failure, and management should focus on glucose control to prevent developing autonomic symptoms. The most prevalent cause of dysautonomia, or autonomic dysfunction, is Postural Orthostatic Tachycardia Syndrome (POTS). Autonomic testing characterizes causes for nonspecific symptoms but is not necessary in patients with classic presentations. Treatment for autonomic dysfunction and failure focus on discontinuing offending medications, behavioral modification, and pharmacologic therapy to decrease symptom severity. Autonomic failure has no cure; therefore, the focus remains on improving quality of life.

The use and effectiveness of exercise for managing postural orthostatic tachycardia syndrome in young adults with joint hypermobility and related conditions: A scoping review.

PURPOSE: Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia. It may occur in isolation, but frequently co-exists in individuals with hypermobile variants of Ehlers-Danlos Syndrome (EDS) and related conditions (chronic fatigue syndrome [CFS] and fibromyalgia). Exercise is recommended for non-pharmacological POTS management but needs to be individualised. This scoping review explores the current literature on use and effectiveness of exercise-based management for POTS, with specific focus on individuals with joint hypermobility and related conditions who experience hypermobility, and/or pain, and/or fatigue. METHODS: A systematic search, to January 2023, of Medline, EMBASE, AMED, CINAHL and the Cochrane library was conducted. Studies that reported on adolescents and adults who had been diagnosed with POTS using standard criteria and underwent an exercise-based training intervention were included. RESULTS: Following full-text screening, 10 articles were identified (2 randomised control trials, 4 comparative studies and 4 case reports). One comparative study reported a small subset of participants with EDS and one case report included an individual diagnosed with CFS; the remainder investigated a wider POTS population. Overall, 3 months of endurance followed by resistance exercise, graduating from the horizontal-to-upright position reduced POTS symptoms and improved quality-of-life. CONCLUSION: The findings highlight a paucity of higher-level studies documenting exercise for POTS management in people with joint hypermobility and related conditions. Results from the wider POTS population demonstrate exercise is safe and effective. Large, well-designed clinical studies exploring exercise for POTS management adapting to meet the complex musculoskeletal and non-musculoskeletal features of symptomatic joint hypermobility are needed.

Comorbid anxiety is associated with more changes in the Management of Postural Orthostatic Tachycardia Syndrome.

OBJECTIVE: Postural Orthostatic Tachycardia Syndrome (POTS) is not an anxiety disorder, but it shares similar symptomatology. The impact of this comorbidity on management is unknown. This information may lead to better strategies to improve the care of this subgroup. METHOD: The electronic medical records of 322 patients seen at our institution between 2018 and 2022 with confirmed POTS diagnoses were analyzed. Demographics, anxiety comorbidities, questionnaire responses, and treatment course changes were collected. Negative binomial regression models examined if the presence of an anxiety disorder was associated with the number of POTS treatment course changes offset by observation time. RESULTS: When adjusted for sex, age, baseline GAD-7 score, and baseline PROMIS global mental health score, those with a diagnosis of an anxiety disorder had2.6 times the incident rate of treatment changes for POTS management (IRR = 2.66 (95% CI: 1.43-4.95)). CONCLUSION: Individuals carrying the diagnosis of an anxiety disorder had an increase in the incident rate of treatment changes for POTS therapy. This finding may be due to the underlying pathophysiology and treatment of anxiety disorders, the effect of bias, and difficulty with symptom differentiation. More work needs to be done to determine how to best care for POTS patients with comorbid anxiety.

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial.

BACKGROUND: Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS). OBJECTIVES: In this study the authors conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of tVNS on POTS over a 2-month period relative to sham stimulation. METHODS: tVNS (20 Hz, 1 mA below discomfort threshold) was delivered using an ear clip attached to either the tragus (active; n = 12) or the ear lobe (sham; n = 14) for 1 hour daily over a 2-month period. Postural tachycardia was assessed during the baseline and 2-month visit. Heart rate variability based on 5-minute electrocardiogram, serum cytokines, and antiautonomic autoantibodies were measured at the respective time points. RESULTS: Mean age was 34 ± 11 years (100% female; 81% Caucasian). Adherence to daily stimulation was 83% in the active arm and 86% in the sham arm (P > 0.05). Postural tachycardia was significantly less in the active arm compared with the sham arm at 2 months (mean postural increase in heart rate 17.6 ± 9.9 beats/min vs 31.7 ± 14.4 beats/min; P = 0.01). Antiadrenergic autoantibodies and inflammatory cytokines were lower in the active arm compared with the sham arm at 2 months (P < 0.05). Heart rate variability was better in the active arm. No device-related side effects were observed. CONCLUSIONS: Our results support the emerging paradigm of noninvasive neuromodulation to treat POTS. Mechanistically, this effect appears to be related to reduction of antiautonomic autoantibodies and inflammatory cytokines, and improvement in autonomic tone. Further studies are warranted. (Autoimmune Basis for Postural Tachycardia Syndrome; NCT05043051).

Exploring the complexities of illness identity and symptom management in seeking a diagnostic label of postural orthostatic tachycardia syndrome (POTS): An inductive approach.

OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) is a debilitating and under-recognized condition of the autonomic nervous system. This study applied Leventhal's Common-Sense Model of Illness Representations to explore the journey to a diagnosis of POTS and to understand its relevance to poorly understood conditions which have common comorbidities. DESIGN: An inductive qualitative approach was used to explore the processes by which patients formulate explanations and management of symptoms within the search for a diagnostic label and to investigate illness identity in the context of existing diagnoses or multimorbidity. METHODS: Participants (n = 29) for this nested qualitative study were recruited from a larger longitudinal study of people who had been newly referred to a specialist POTS service. Semi-structured interviews were conducted via video call. Three researchers coded and analysed data using Reflexive Thematic Analysis and elements of Grounded Theory. RESULTS: The analysis resulted in three overarching themes: 'Seeking physiological coherence and validation', 'Individual persistence', and 'Navigating the cumulative burden'. 'Accessibility and disparities of health care' was noted as a contextual factor. Receiving a POTS diagnosis was regarded by participants as providing legitimacy and increased access to treatment. Overall, delays in the diagnostic journey and the lack of a clear diagnosis impacted negatively on patients through increased uncertainty and a lack of clear guidance on how to manage symptoms. Findings also suggested there were great complexities in assigning symptoms to labels in the context of multimorbidity. CONCLUSIONS: Participants' stories highlighted the urgent need for better recognition of POTS so that the self-regulatory process can be initiated from the early stages of symptom detection.

Recognizing postural orthostatic tachycardia syndrome in primary care.

ABSTRACT: Postural orthostatic tachycardia syndrome (POTS) is a complex autonomic disorder characterized by abnormal tachycardia on standing. This disorder predominantly affects young women, with a peak incidence between ages 20 and 30 years. POTS often is associated with a variety of symptoms, including dizziness, palpitations, fatigue, generalized weakness, anxiety, and exercise intolerance, which can significantly impair patient quality of life. Primary care providers (PCPs) often are the first healthcare professionals to whom patients present. This article provides an overview of POTS, including diagnostic criteria and the importance of a thorough clinical evaluation to rule out other causes of symptoms. PCPs play a critical role in the comprehensive approach to care, involving patient education, lifestyle modifications, and treatment to improve outcomes and enhance patient quality of life.

Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial.

PURPOSE: Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC). METHODS: Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions. RESULTS: The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09). CONCLUSION: Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.

Autoimmunity and postural orthostatic tachycardia syndrome: Implications in diagnosis and management.

Postural orthostatic tachycardia syndrome (POTS)-sustained tachycardia upon standing without orthostatic hypotension-can be diagnosed clinically without an extensive diagnostic evaluation unless certain atypical features suggest an alternative diagnosis. A unifying pathophysiologic mechanism has not been identified, although several have been proposed. Similarities between POTS and various autoimmune disorders suggest an immune mechanism in a subset of patients. However, no causative antibody has been identified, and associated antibodies are rarely clinically relevant. Moreover, immunotherapies are not currently recommended for POTS, although clinical trials are underway to clarify their utility.

Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.

The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.

Postural Orthostatic Tachycardia Syndrome After COVID-19: A Systematic Review of Therapeutic Interventions.

ABSTRACT: Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.

Patient-Centered Paradigm for Managing Autonomic Long COVID Symptoms During Sports and Exercise.

ABSTRACT: This report highlights a new, patient-centered paradigm for managing post-COVID-19 dysautonomia symptoms during sports and exercise. The patient was a healthcare worker exposed before vaccination. She experienced postural orthostatic tachycardia plus exertional tachycardia, with postexertional fatigue, beginning a few weeks after testing positive for COVID-19. Stress test, echo, and an extensive dysautonomia evaluation were negative. Recommended nonpharmacological and pharmacological interventions were poorly tolerated. Prescription of a novel regimen of "basal-dose" ivabradine, plus very low-dose metoprolol according to an exertional "sliding scale" managed symptoms to an acceptable level for work and recreation.

Postural orthostatic tachycardia syndrome: Recognition and treatment.

ABSTRACT: Postural orthostatic tachycardia syndrome (POTS) affects 3 million in the US and 11 million globally. Signs and symptoms can vary and greatly impact a patient's quality of life. This article focuses on the prevalence, clinical manifestations, diagnosis, treatment, and patient education surrounding POTS.

Postural orthostatic tachycardia syndrome: New concepts in pathophysiology and management.

Postural orthostatic tachycardia syndrome (POTS) is a common and therapeutically challenging condition affecting numerous people worldwide. Recent studies have begun to shed light on the pathophysiology of this disorder. At the same time, both non-pharmacologic and pharmacologic therapies have emerged that offer additional treatment options for those afflicted with this condition. This paper reviews new concepts in both the pathophysiology and management of POTS.

Gluten-free diet in postural orthostatic tachycardia syndrome (POTS).

OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) is a chronic disorder of the autonomic nervous system that is associated with orthostatic intolerance (OI) and gastrointestinal (GI) symptoms. We aimed to determine if a gluten-free diet (GFD) may be an effective treatment in patients with POTS. METHODS: Patients with confirmed POTS and without celiac disease who followed GFD for 4 weeks retrospectively completed pre- and post- GFD COMPASS-31 questionnaires. Paired-samples t-tests were conducted to compare COMPASS-31 scores before and after adopting GFD. RESULTS: All 20 patients (all females, age 16-62 years (mean age 33)), had POTS symptoms for 1-30 years (mean 10.8, SD = 10.23 years). Eleven patients had co-morbid mast cell activation syndrome, and 8 had hypermobile Ehlers-Danlos syndrome. Pre-GFD COMPASS-31 scores (mean 57.8) were significantly higher than post-GFD scores (mean 38.2, t(19) = -8.92, p < 0.00001), with the largest improvement noted in the OI (p < 0.00001), vasomotor, (p = 0.0034), and GI (p = 0.0004) domains and with a mean reduction in total COMPASS-31 score by 33.9% after implementing GFD. All patients reported improved symptoms on GFD with mean self-assessed improvement of 50.5% (range 10-99%). DISCUSSION: GFD may be effective in reducing the symptom burden in patients with POTS, particularly in the OI, vasomotor, and GI symptom domains. Large prospective studies are necessary to confirm whether GFD is an effective long-term treatment option for patients.

Transcutaneous vagus nerve stimulation attenuates autoantibody-mediated cardiovagal dysfunction and inflammation in a rabbit model of postural tachycardia syndrome.

PURPOSE: Previous studies demonstrated M2 muscarinic acetylcholine receptor-activating autoantibodies (M2R-AAb) were present in some patients with postural tachycardia syndrome (POTS). This study examines how these autoantibodies might contribute to the pathophysiology of POTS, and whether low-level tragus stimulation (LLTS) can ameliorate autoantibody-mediated autonomic dysregulation in the rabbit. METHODS: Five New Zealand white rabbits were immunized with a M2R second extracellular loop peptide to produce cholinomimetic M2R-AAb. Tilt test and infusion studies were performed on conscious rabbits before immunization, 6 weeks after immunization, and 8 weeks after immunization with 2-week daily LLTS treatment. Each rabbit served as its own control. RESULTS: Compared to preimmune state, an enhanced heart rate increase and decreased parasympathetic activity upon tilting were observed in immunized rabbits. Furthermore, these rabbits demonstrated an attenuated heart rate-slowing response to infusion of the M2R orthosteric agonist arecaidine propargyl ester (APE), suggesting an inhibitory allosteric effect of M2R-AAb. There was also a significant increase in serum inflammatory cytokines in immunized rabbits. LLTS treatment suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, reduced the levels of inflammatory cytokines, and reversed the attenuated heart rate response to APE in immunized rabbits. No suppression of M2R-AAb expression by LLTS was found during this short-term study period. Receptor-modulating activity of M2R-AAb produced in immunized rabbits was confirmed with in vitro bioassay. CONCLUSIONS: Autoantibody inhibition of cholinergic ligand activity may be involved in the development of cardiovagal dysfunction and inflammation associated with POTS, both of which can be improved by vagal stimulation.