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Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2.

ABSTRACT: The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.

SUBMITTER: Raj SR

PROVIDER: S-EPMC8455430 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2.

Raj Satish R SR Bourne Kate M KM Stiles Lauren E LE Miglis Mitchell G MG Cortez Melissa M MM Miller Amanda J AJ Freeman Roy R Biaggioni Italo I Rowe Peter C PC Sheldon Robert S RS Shibao Cyndya A CA Diedrich Andre A Systrom David M DM Cook Glen A GA Doherty Taylor A TA Abdallah Hasan I HI Grubb Blair P BP Fedorowski Artur A Stewart Julian M JM Arnold Amy C AC Pace Laura A LA Axelsson Jonas J Boris Jeffrey R JR Moak Jeffrey P JP Goodman Brent P BP Chémali Kamal R KR Chung Tae H TH Goldstein David S DS Darbari Anil A Vernino Steven S

Autonomic neuroscience : basic & clinical 20210630

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomi ...[more]

PMID: 34246578

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Project description:BackgroundNon-cephalgic symptoms including orthostatic intolerance, fatigue, and cognitive impairment, are common in patients with chronic headache disorders and may result from alterations in the autonomic nervous system. However, little is known about the function of autonomic reflexes, which regulate cardiovascular homeostasis and cerebral perfusion in patients with headache.MethodsAutonomic function testing data from patients with headache collected between January 2018 and April 2022 was retrospectively analyzed. Through review of EMR we determined headache pain chronicity and patient self-report of orthostatic intolerance, fatigue, and cognitive impairment. Composite Autonomic Severity Score (CASS), CASS subscale scores, and cardiovagal and adrenergic baroreflex sensitivities were used to quantify autonomic reflex dysfunction. Descriptive analyses (Mann-Whitney-U or χ2, as appropriate) determined associations between autonomic reflex dysfunction and POTS as well as chronic headache. Binomial logistic regression adjusted for age and sex. Spearman's rank correlation determined the association between the total CASS score and the number of painless symptoms reported by each participant.ResultsWe identified 34 patients meeting inclusion criteria, of whom there were 16 (47.0%) with orthostatic intolerance, 17 (50.0%) with fatigue, 11 (32.4%) with cognitive complaints, and 11 (32.4%) with Postural Orthostatic Tachycardia Syndrome (POTS). The majority of participants had migraine (n = 24, 70.6%), were female (n = 23, 67.6%) and had a chronic (>15 headache days in a month) headache disorder (n = 26, 76.5%). Reduced cardiovagal baroreflex sensitivity (BRS-V) independently predicted chronic headache [aOR: 18.59 (1.16, 297.05), p = 0.039] and POTS [aOR: 5.78 (1.0, 32.5), p = 0.047]. The total CASS was correlated with the total number of non-painful features in the expected direction (r = 0.46, p = 0.007).ConclusionAbnormal autonomic reflexes may play an important role in pain chronification and the development of POTS in patients with headache.

Project description:Postural orthostatic tachycardia syndrome (POTS) is a chronic neurological disorder of the autonomic nervous system (ANS) that is characterized by an excessive increase in heart rate upon orthostatic challenge. The symptoms of POTS are often debilitating, and it primarily affects young females. Even prior to coronavirus disease 2019 (COVID-19) pandemic, POTS was prevalent, affecting an estimated 0.5% to 1% of the entire population in the United States (US). Since the COVID-19 pandemic, the incidence of POTS has acutely risen, adding roughly 6-7 million POTS patients in the US alone. Despite its importance, there is currently no reliable serum biomarker for POTS. One of the major hurdles in identifying biomarkers of POTS is the heterogenous nature of the clinical syndrome. To address this challenge, we focused our analysis on patients from the recent increase in cases of post-COVID-19 onset POTS (PC-POTS). We hypothesized that PC-POTS represents a relatively homogeneous subgroup of POTS, likely triggered by the same pathogen, and presents with symptoms that are more pronounced compared to those in healthy controls. We identified 752 proteins from 18 serum proteome samples composed of 9 PC-POTS patients and 9 health control (HC) individuals, and 31 proteins showed a significant protein abundance difference in PC-POTS. Notably, the majority of the elevated proteins are associated with either actin filaments or immune functions/inflammation. The Weighted Gene Co-Expression Network Analysis (WGCNA) revealed that the module 7 (M7) most highly correlated with the diagnosis also exhibited strong correlations with various sample traits such as the Orthostatic Intolerance Score, Gastrointestinal Score, Pupillomotor Score, and the COMPASS-31 score. The proteins MTPN, TAGLN2, ADP-ribosylation factor 1, PDLIM1, PPIA, CNN2, LGALSL, TXN, TLN1, TUBA4A, IL4, TREML1, GP1BA, and GP6 were identified as common proteins overlapping in various sample traits. Cell-type enrichment analysis revealed that M7 is highly associated with immune and neuronal cells. The main pathways identified in this module include the integrin signaling pathway, blood coagulation, and glycolysis. This suggests that these proteins could potentially serve as biomarkers for PC-POTS. This study utilizes mass spectrometry-based proteomic analysis to identify serum biomarkers that differentiate patients with PC-POTS from HC individuals, thus establishing a foundation for further research and validation.

Dataset Information

Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2.

Publications

Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2.

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