Celine Gallagher

Objectives: To characterise the symptom, comorbidity and diagnostic journey of adult and older adolescent patients with postural orthostatic tachycardia syndrome (POTS). Design: Cross-sectional observational cohort study. Setting: Participants ≥16 years old with physician-confirmed POTS who enrolled in the Australian POTS registry between 1 May 2021 and 30 April 2024 were included. Participants: 500 participants enrolled in the Australian POTS registry. Outcome measures: Health-related quality of life and symptom severity were assessed using validated patient-reported outcome measures, including the Composite Autonomic Symptom Score, EuroQol 5-Dimension-5 Level (EQ-5D), Gastroparesis Cardinal Symptom Index (GCSI), Fatigue Severity Scale (FSS) and the 5-point hypermobility index scores. Sociodemographics, diagnostic journey details and comorbidities were obtained via self-reported questionnaires and reconciled with medical records by the clinical team. Results: Among 500 participants (86.8% females, 92.7% White; mean age 31.3±11.7 years), the median diagnostic delay was 3.0 years (IQR 9.0; mean 6.7 years), with 25.5% experiencing a delay of ≥10 years. Despite being young and highly educated, 22.0% were unemployed or unable to attend education. Infection was the most frequently identified proximal trigger and accounted for 39.4% of cases. Higher autonomic symptom burden, as reported on the Composite Autonomic Symptoms Score (COMPASS-31) questionnaire, was associated with greater fatigue (FSS: 56.0±8.8 vs 48.0±14.5; p2 tests as appropriate. Conclusions: POTS is associated with significant diagnostic delays, high healthcare utilisation, substantial symptom burden, educational, social and occupational impacts. Patient-reported outcome measures such as the COMPASS-31 questionnaire can assist in identifying high-risk individuals. Systemic healthcare reform is urgently needed to improve access to timely diagnosis and effective treatment for individuals living with POTS. Trial registration number: ACTRN12621001034820.

Background: Postural orthostatic tachycardia syndrome (POTS) is increasingly recognized after SARS‐CoV‐2 infection. We compared autonomic phenotype, functional impact, and circulating immune markers in POTS, postacute sequelae of COVID‐19 (PASC), and healthy controls. Methods: In this cross‐sectional study (August 2021 to December 2022), we recruited patients with POTS (n=24) or PASC (n=24) and healthy controls (n=19). Participants underwent 10‐minute active stand testing, 24‐hour Holter monitoring, serum cytokine, and adrenergic autoantibody assays (cell‐based activation). Patient‐reported outcome measures were collected via secure electronic link. Results: The study included 67 participants (mean age, 32.4±8.9 years; 71% women). Compared with controls and participants with PASC, participants with POTS demonstrated significantly higher orthostatic tachycardia (active stand heart rate change from supine to standing, 46.3±14.0 bpm versus 12.7±6.6 bpm in controls and 34.6±13.7 bpm in PASC; P P =0.005). Among participants with PASC, 62.5% met formal POTS criteria. Cytokine analysis revealed lower interleukin‐2 and higher interleukin‐8 levels in POTS versus controls, with POTS cases showing elevated tumor necrosis factor‐α compared with those without POTS. Autoantibody activation measures did not differ significantly among groups, and multivariate biomarker models lacked predictive utility for POTS diagnosis. Patient‐reported outcome measures indicated greater fatigue, orthostatic intolerance, and autonomic symptom burden and reduced health‐related quality of life in POTS and PASC groups compared with controls. Conclusions: POTS and PASC exhibit overlapping autonomic symptomology and profound functional impairment. Alterations in cytokines suggest a possible cytokine‐linked or compartmentalized immune contribution, but cytokine and autoantibody measures alone do not predict POTS. Routine autonomic assessment in persistent postviral illness and larger longitudinal, multimodal studies are warranted. Registration: Australian New Zealand Clinical Trial Registry; ACTRN: 12621000476831.

Introduction: Spontaneous coronary artery dissection (SCAD) is frequently accompanied by persistent symptoms of unknown pathogenesis after the index event. Autonomic dysfunction is a plausible mechanism for these but has not been systematically characterized. We quantified antecedent and contemporary autonomic symptoms in survivors of SCAD and examined their associations with cardiac and extra-cardiac symptoms and health-related quality of life. Methods: This cross-sectional study recruited 227 volunteers from multiple countries with a self-reported history of SCAD. Participants completed validated patient-reported measures, including the Composite Autonomic Symptom Score-31 (COMPASS-31), Anxiety Sensitivity Index-3 (ASI–3), and EuroQol-5 Dimension-5L (EQ-5D-5L). They also completed an internally derived retrospective autonomic predisposition score assessing symptoms during adolescence and early adulthood. Results: Participants were predominantly female (97.8%), median age 53 (47–58) years, and were surveyed a median of 3 (1–5) years after their index SCAD event. 21.6% reported SCAD recurrence. Moderate autonomic symptom burden (COMPASS-31 ≥20) was present in 56.4% and severe burden (≥40) in 16.3%. History of antecedent autonomic symptoms was the strongest independent predictor of contemporary autonomic symptom burden after adjustment for demographic and clinical covariates ( β =0.514; P β =−0.150; P =0.029) and was associated with the ASI-3 ‘ physical concerns ’ ( β =0.232; P social concerns ’ domain. Autonomic symptoms were not associated with SCAD recurrence. Conclusion: Symptoms of autonomic dysregulation are common in survivors of SCAD and are associated with reduced quality of life. Their association with antecedent dysautonomic features during adolescence and early adulthood suggests a longstanding predisposition, the significance of which warrants further evaluation. Clinical Perspective: What Is New?: Self-reported antecedent and current autonomic symptoms are common in survivors of spontaneous coronary artery dissection and are associated with poorer health-related quality of life, greater fatigue, and greater psychological distress. What Are the Clinical Implications?: Autonomic symptoms warrant clinical recognition in patients with prior spontaneous coronary artery dissection, not only as a post-event complaint but also as a potential marker of pre-existing autonomic vulnerability that may influence recovery experience. Greater awareness of autonomic symptom burden may support more personalized follow-up, patient counseling, and rehabilitation planning to help patients return more safely and confidently to daily activities, work, and family life. Graphical