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The plasma levels of growth hormone (GH) (panel A) and myoglobin (panel B), expressed on Normalised Protein Expression (NPX) on a log2 scale, are presented in relation to POTS and sex status. Data are shown as a box and whisker plot with median in the box and the whiskers representing the 5th and 95th percentiles in relation to plasmatic biomarker level
Source publication
Background:
Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.
Methods:
We cond...
Contexts in source publication
Context 1
... of biomarker verification analysis, nine PCA-selected proteins differed significantly in pairwise comparison, but only GH and MB attained significance after Bonferroni correction (Table 2). Plasma levels of GH were significantly higher in POTS women compared with POTS men (p = 0.0002), and both male (p < 0.0001) and female controls (p = 0.003) (Fig. 2). Conversely, plasma level of MB were significantly lower in POTS men compared with male controls (p = ...
Context 2
... of biomarker verification analysis, nine PCA-selected proteins differed significantly in pairwise comparison, but only GH and MB attained significance after Bonferroni correction (Table 2). Plasma levels of GH were significantly higher in POTS women compared with POTS men (p = 0.0002), and both male (p < 0.0001) and female controls (p = 0.003) (Fig. 2). Conversely, plasma level of MB were significantly lower in POTS men compared with male controls (p = ...
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Background
To evaluate the short-term effectiveness of reduced-osmolarity oral rehydration salt formulation (ORS) and propranolol in children diagnosed with postural orthostatic tachycardia syndrome (POTS) in head-up tilt testing (HUTT).
Methods
Children were admitted with symptoms of orthostatic intolerance (OI) occurring in a standing position a...
Background:
A Postural orthostatic tachycardia syndrome (POTS) is infrequently diagnosed in routine practice because of the variable range of symptoms that could be seen in cardiac rhythm disorders, vertigo, chronic fatigue syndrome and anxiety panic disorder. POTS is a chronic debilitating condition that affects day to day efficient working of an...
Objective
To develop an orthostatic intolerance symptom scoring system to assess orthostatic intolerance and then to compare the symptom score among different head-up tilt test responses.
Methods
272 subjects (5-18 years) presenting with orthostatic intolerance symptoms finished questionnaire and head-up tilt test. According to head-up tilt test h...
Background
Guidelines recommend increased salt intake as first-line in the management of orthostatic hypotension and syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for this recommendation in patients with orthostatic intolerance.
Methods
We planned a systematic review and meta-analysis of s...
Citations
... Additionally, skeletal-muscular pump dysfunction may occur due to a venous valve defect or the congenital absence of a valve. The plasma myoglobin level in patients with POTS was lower than that in controls and the reduced myoglobin level in the patient was correlated with the severity of POTS, suggesting that there might be a relationship between abnormal skeletal muscle status and the development of POTS [39]. ...
Postural orthostatic tachycardia syndrome (POTS) is common in children, with an excessive increment in heart rate when moving from the supine to upright position. It has significant negative impacts on the daily life of pediatric patients. The pathogenesis of POTS includes peripheral vascular dysfunction, central hypovolemia, abnormal autonomic function, a high-adrenergic state, impaired skeletal-muscle pump function, the abnormal release of vasoactive factors, and autoimmune abnormalities. Therefore, the empirical use of pharmacological treatments has limited therapeutic efficacy due to the diversity of its mechanisms. A crucial aspect of managing POTS is the selection of appropriate treatment targeting the specific pathogenesis. This review summarizes the commonly used pharmacological interventions, with a focus on their predictive indicators for treatment response. Factors such as heart rate variability, plasma biomarkers, and cardiac-function parameters are discussed as potential predictors of therapeutic efficacy, enabling the implementation of individualized treatment to improve therapeutic effectiveness. This review consolidates the current knowledge on POTS, encompassing its clinical characteristics, epidemiological patterns, underlying pathogenic mechanisms, and predictive indicators for treatment response. Further research is warranted to enhance the understanding of POTS and facilitate the development of more effective therapeutic approaches for this challenging syndrome.
... Potential mechanisms are the hormonal effects on vasculature, differences in heart and skeletal muscle size or the fact that oestrogen exposure and concomitant infection can synergistically trigger autoimmunity [60,64]. Finally, inflammatory, immune and neuroendocrine protein biomarkers are altered in individuals with POTS compared with controls [65][66][67]. ...
Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.
... 62,66 Finally, inflammatory, immune and neuroendocrine protein biomarkers are altered in individuals with POTS compared with controls. [67][68][69] The response to standing in POTS is a form of orthostatic stress. However, other forms of stress can also increase autoimmunity risk: a large population-and sibling-matched retrospective cohort study in Sweden found that exposure to life stressors confers a 36% increased risk of autoimmune disease. ...
Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalised immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but prevalence with its supporting evidence is compelling.
... Faulty regulation in myogenesis leads to deconditioning-related changes characterized by decreased muscle mass 33 . These findings are in line with the previous identification of upregulation of myoglobin in POTS 34 . In POTS, differences in sympathetic nerve discharge and fiber loss from skeletal muscles is observed 35 , which could putatively explain muscle fatiguability and deconditioning associated with POTS. ...
Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder characterized by excessive heart rate increase on standing, leading to debilitating symptoms with limited therapeutic possibilities. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification of patients based on their protein background. The aim of the present study was to determine plasma protein biomarkers of POTS and to reveal proteomic pathways differentially regulated in POTS. We performed an age- and sex-matched, case–control study in 130 individuals (case–control ratio 1:1) including POTS and healthy controls. Mean age in POTS was 30 ± 9.8 years (84.6% women) versus controls 31 ± 9.8 years (80.0% women). We analyzed plasma proteins using data-independent acquisition (DIA) mass spectrometry. Pathway analysis of significantly differently expressed proteins was executed using a cutoff log2 fold change set to 1.2 and false discovery rate (p-value) of < 0.05. A total of 393 differential plasma proteins were identified. Label-free quantification of DIA-data identified 30 differentially expressed proteins in POTS compared with healthy controls. Pathway analysis identified the strongest network interactions particularly for proteins involved in thrombogenicity and enhanced platelet activity, but also inflammation, cardiac contractility and hypertrophy, and increased adrenergic activity. Our observations generated by the first use a label-free unbiased quantification reveal the proteomic footprint of POTS in terms of a hypercoagulable state, proinflammatory state, enhanced cardiac contractility and hypertrophy, skeletal muscle expression, and adrenergic activity. These findings support the hypothesis that POTS may be an autoimmune, inflammatory and hyperadrenergic disorder.
... 50,51 Interestingly, a recent proteomic analysis of patients with POTS found sexspecific biomarker signatures, with higher growth hormone levels in females and lower myoglobin levels in males. 52 A more powerful effect of growth hormone on the manifestation of OT in females, compared with males, could explain why more females presented during or after puberty, while males presented at a younger age. ...
Background: Orthostatic tachycardia (OT) affects some patients after concussion/mild traumatic brain injury (mTBI). In this study, we sought to identify the factors associated with increased risk for OT in patients with mTBI. Methods: We conducted a retrospective review of 268 patients (8-25 years) with mTBI/concussion to determine the prevalence of OT, defined as orthostatic heart rate change ≥40 bpm for those ≤19 years of age and ≥30 bpm on active standing test for those >19 years of age. Results: Among the study population, 7% (n = 19) exhibited post-concussive OT. The only significant difference between OT and non-OT groups was that history of prior concussion was more prevalent in the OT group. Conclusion: A substantial subset (7%) of concussion clinic patients exhibit OT. While POTS literature describes female and adolescent predominance, post-concussive OT had similar prevalence across age and gender groups in this study, suggesting that it may be distinct from POTS.
... ng/ml), adiponectin (2.4-17.9 ug/ml), trisulfated heparin disaccharide (TS-HDS) antibody (<10,000 titers), 26 fibroblast growth factor receptor 3 (FGFR3) antibody (<3,000 titers), 26 acetylcholine receptor binding antibody (< = 0.02 nmol/L), ganglionic acetylcholine receptor antibody (< = 0.02 nmol/L), 27 neuronal VGKC antibody (< = 0.02 nmol/L), calcium channel P/Q binding antibody (<= 0.02 nmol/L), myoglobin (<= 71 ng/ml), 28 and human growth hormone (0.01-3.61 ng/mL). 28 We also evaluated norepinephrine supine (70-750 pg/ml) and standing (200-1,700 pg/ml), which is useful in the assessment of the hyperadrenergic form of POTS. 10 The TS-HDS and FGFR3 antibodies were obtained from Washington University School of Medicine (St. Louis, MO), remaining antibodies as well as TNF-α, IL-10, human growth hormone were obtained from Mayo Clinic laboratories (Rochester, MN). ...
... ug/ml), trisulfated heparin disaccharide (TS-HDS) antibody (<10,000 titers), 26 fibroblast growth factor receptor 3 (FGFR3) antibody (<3,000 titers), 26 acetylcholine receptor binding antibody (< = 0.02 nmol/L), ganglionic acetylcholine receptor antibody (< = 0.02 nmol/L), 27 neuronal VGKC antibody (< = 0.02 nmol/L), calcium channel P/Q binding antibody (<= 0.02 nmol/L), myoglobin (<= 71 ng/ml), 28 and human growth hormone (0.01-3.61 ng/mL). 28 We also evaluated norepinephrine supine (70-750 pg/ml) and standing (200-1,700 pg/ml), which is useful in the assessment of the hyperadrenergic form of POTS. 10 The TS-HDS and FGFR3 antibodies were obtained from Washington University School of Medicine (St. Louis, MO), remaining antibodies as well as TNF-α, IL-10, human growth hormone were obtained from Mayo Clinic laboratories (Rochester, MN). IL-6 was obtained at Mayo Clinic laboratories (Rochester, MN) or at BWH Clinical laboratories (Boston, MA). ...
Objective
To describe cerebrovascular, neuropathic and autonomic features of post-acute sequelae of COVID-19 (PASC).
Methods
This retrospective study evaluated consecutive patients with chronic fatigue, brain fog and orthostatic intolerance consistent with PASC. Controls included postural tachycardia syndrome patients (POTS) and healthy participants. Analyzed data included surveys and autonomic (Valsalva maneuver, deep breathing, sudomotor and tilt tests), cerebrovascular (cerebral blood flow velocity (CBFv) monitoring in middle cerebral artery), respiratory (capnography monitoring) and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/autoimmune markers.
Results
Nine PASC patients were evaluated 0.7±0.3 years after a mild COVID-19 infection, treated as home observations. Autonomic, pain, brain fog, fatigue and dyspnea surveys were abnormal in PASC and POTS (n=10), compared to controls (n=15). Tilt table test reproduced the majority of PASC symptoms. Orthostatic CBFv declined in PASC (-20.0±13.4%) and POTS (-20.3±15.1%), compared to controls (-3.0±7.5%,p=0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS. Reduced orthostatic CBFv in PASC included both subjects without (n=6) and with (n=3) orthostatic tachycardia. Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p=0.013). PASC and POTS cohorts diverged in frequency of small fiber neuropathy (89% vs. 60%) but not in inflammatory markers (67% vs. 70%). Supine and orthostatic hypocapnia was observed in PASC.
Interpretation
PASC following mild COVID-19 infection is associated with multisystem involvement including: 1) cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction; 2) small fiber neuropathy and related dysautonomia; 3) respiratory dysregulation; 4) chronic inflammation.
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... A previous study has reported elevated plasma levels of GH in POTS, by using a proteomics approach and analyzing simultaneously over 90 cardiovascular plasma biomarkers in one plasma sample 8 . In our study, we observed lower levels of GH in POTS patients, by using a highly specific immunoassay method. ...
Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case–control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.
... This is largely due to the fact that POTS is a heterogenous syndrome with many potential etiologies, creating significant challenges for physicians striving to provide targeted treatment options for patients. In a recent study, Spahic and colleagues aimed to isolate POTS-specific proteomic markers from 994 consecutive patients of their syncope unit in Malmö, Sweden [1]. Patients were referred for either unexplained syncope or symptoms of orthostatic intolerance, and all patients underwent head-up tilt testing (HUT). ...
Orthostatic intolerance (OI) is defined as a group of diseases which symptoms are typically manifested in a standing position. These symptoms result from cerebral hypoperfusion and disappear in the supine position. We include postural orthostatic intolerance syndrome (POTS), orthostatic hypotension (OH) and vasovagal orthostatic syncope in this group of diseases. Each of them have similar clinical presentation (blurred vision, weakness, dizziness, nausea, headaches, fatigue). However, they vary from each other in biochemical, autonomic and hemodynamic characteristics. The aim of the work is to provide an overview of humoral and non-human markers that are involved in the etiopathogenesis of orthostatic intolerance.
