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Antiadrenergic autoimmunity in postural tachycardia syndrome
Open accessAbstract
AIMS: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). METHODS AND RESULTS: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity. CONCLUSION: These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.
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TL;DR
IgG from patients with postural tachycardia syndrome (POTS) showed higher direct activation of α1-adrenergic and β1/2-adrenergic receptors than IgG from recurrent vasovagal syncope (VVS) patients or healthy controls, and also altered receptor responsiveness to phenylephrine and isoproterenol. These antiadrenergic autoantibody effects correlated with upright heart rate and support an autoimmune contribution to POTS pathophysiology.
Key findings
- Among 17 POTS patients, direct receptor activation was found in 8/17 for α1AR (47%), 11/17 for β1AR (65%), and 12/17 for β2AR (71%); none of these autoantibodies were found in VVS patients or healthy controls.
- Mean autoantibody activity was significantly higher in POTS than in VVS and controls for α1AR (0.31 ± 0.07 vs. 0.24 ± 0.04 and 0.23 ± 0.04; P=0.029 and 0.004), β1AR (1840 ± 186 vs. 1578 ± 117 and 1608 ± 127; P=0.002 and 0.001), and β2AR (1104 ± 230 vs. 816 ± 73 and 837 ± 72; P=0.007 and 0.001).
- POTS IgG decreased phenylephrine-induced α1AR activation in 8/17 patients and increased isoproterenol-induced β1AR activation in 13/17 patients; 13/17 POTS IgG also increased contractility in isolated rat cremaster arterioles, which was reversed by α1AR blockade with phentolamine.
- Upright heart rate correlated with IgG-mediated β1AR activity (3 min P=0.0009; maximal P=0.0006) and α1AR activity (maximal P=0.039), but not with β2AR activity (P=0.11).
Methods
- Case-control functional study using serum IgG from 17 POTS patients (16 females; age 26 ± 9 years), 7 recurrent VVS patients (5 females; age 31 ± 9 years), and 11 healthy controls (10 females; age 31 ± 6 years) recruited from the SYSTEMA cohort in Malmö, Sweden.
- IgG was tested in cell-based assays for α1AR activation (FRET β-lactamase reporter in α1AR-NFAT-bla CHO-K1 cells) and β1AR/β2AR activation (cAMP Hunter eXpress GPCR assay in transfected CHO cells), with blockade by prazosin or propranolol, and in an isolated rat cremaster arteriole contractility assay with phentolamine.
- Group comparisons used Student’s t-test, one-way ANOVA with Tukey post hoc, Pearson’s χ2, and linear regression; autoantibody positivity was defined as above mean + 2SD or below mean − 2SD of controls.
Limitations
- The paper states that parasympathetic tonus was not assessed during head-up tilt and that possible autoantibodies against muscarinic receptors and/or the acetylcholine system were not investigated.
- The paper states that study groups were not strictly age matched, although the age difference was not significant.
- Evident from the text: the study has small group sizes (17 POTS, 7 VVS, 11 controls), and the authors note that the cremaster arteriolar bioassay is not suitable for large numbers of samples.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively.”
- Also stated in: § Autoantibody activity · plain
“Among the 17 patients with POTS, 8, 11, and 12 showed direct activation of α1AR (47%), β1AR (65%), and β2AR (71%), respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Autoantibody activity · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively.”
- Also stated in: § Autoantibody activity · plain
“Among the 17 patients with POTS, 8, 11, and 12 showed direct activation of α1AR (47%), β1AR (65%), and β2AR (71%), respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Autoantibody activity · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“β2AR: POTS 1104 ± 230 vs. VVS 816 ± 73 and control 837 ± 72, P= 0.007 and 0.001, respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“β1AR: POTS 1840 ± 186 vs. VVS 1578 ± 117 and control 1608 ± 127, P= 0.002 and 0.001, respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively.”
- Also stated in: § Autoantibody activity · plain
“Among the 17 patients with POTS, 8, 11, and 12 showed direct activation of α1AR (47%), β1AR (65%), and β2AR (71%), respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Autoantibody activity · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“α1AR: POTS 0.31 ± 0.07(SD) vs. VVS 0.24 ± 0.04 and control 0.23 ± 0.04, P= 0.029 and 0.004, respectively”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of these autoantibodies were found in the patients with VVS or healthy controls.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on these direct assays, 6 of these 17 POTS patients (35%) harboured both α1AR- and β1AR-AAb (Table 2).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in Figure 3B, POTS IgG-induced contractility was largely returned to baseline level by addition of the α1AR blocker phentolamine (10 µM, from 88.9 ± 3.0% to 96.5 ± 2.1%, P= 0.0006).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Abstract > Methods and results
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- It may state two separate claims as one. 28
- Probably not a substantial claim. 18
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“β1/2AR autoantibody activity was increased in POTS but not in VVS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the linear regression analysis, IgG-mediated β1AR activity was strongly correlated with both 3 min (P= 0.0009) and maximal upright heart rate (P= 0.0006), whereas the latter was also correlated with α1AR activity (P= 0.039) but not with β2AR activity (P= 0.11).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither shift was observed using control IgG.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We have demonstrated that serum from subjects with POTS contains circulating autoantibodies, some with a direct stimulatory effect on adrenergic receptors.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
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In the paper
“There was no significant difference between the latter two groups.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a significant decrease in phenylephrine-induced α1AR activation with POTS IgG (0.13 ± 0.02) compared with phenylephrine alone (0.18 ± 0.03, P< 0.0036) or IgG from normal controls (0.17 ± 0.02, P< 0.0005) (Figure 2C).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither SBP nor DBP were correlated with adrenergic receptor stimulation.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The VVS group reported a longer history of syncopal symptoms (P= 0.017), but the number of syncope episodes, proportions of characteristic precipitating symptoms, and self-reported dizziness on standing did not differ between POTS and VVS patients.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The isoproterenol-stimulated β1AR activation, on the other hand, was significantly increased with POTS IgG (1835 ± 309) compared with isoproterenol alone (1479 ± 86, P< 0.037) or IgG from normal controls (1508 ± 80, P< 0.032) (Figure 2D).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was some overlap for the α1AR and considerable overlap for the β1AR with the other tests (Table 2).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the primary objective, we found that antiadrenergic α1AR autoantibody activity was evident in POTS, while the VVS subjects were not different from normal subjects.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the presence of POTS IgG, the phenylephrine response curve was shifted to the right, demonstrating a decreased α1AR response (Figure 2A).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Autoantibody activity
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A majority also exerted an allosterically mediated positive modulatory effect upon β1AR and a negative modulatory effect on α1AR activity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“As previously reported,8 these data confirmed the active α1AR autoantibodies inhibited the phenylephrine response and shifted the phenylephrine dosage response curve to the right.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Moreover, β1AR autoantibodies enhanced the isoproterenol response and most importantly shifted the isoproterenol dosage response curves to the left, confirming our previous observations.8”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the β1AR effect was just the opposite and shifted the β1AR agonist dosage response curve to the left.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
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In the paper
“Since the pathophysiological basis for POTS is unclear, therapeutic interventions are empirical.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This procedure was approved by the Oklahoma University Health Sciences Center Institutional Animal Care and Use Committee.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Isolated cremaster arteriole assay
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A number of treatment options have been proposed in POTS but their efficacy in the more severe forms is limited and often questioned.2,7”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [2] Sheldon, 2015, 2015 Heart Rhythm Society Expert Consensus Statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source
- Not checked yetcites [7] Fedorowski, 2013, Syndromes of orthostatic intolerance: a hidden danger, J Intern Med source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All samples were assayed in triplicate.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Cell-based α1AR assay
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Receipt and assay of these de-identified samples was approved by the University of Oklahoma Health Sciences Center Institutional Review Board.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Sample preparation
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean age for the POTS patients was not significantly different from those with VVS and control subjects.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Results > Clinical characteristics
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In the paper
“In order to ascertain the accuracy of diagnoses, the digital test records were subsequently inspected off-line using Nexfin@PC (BMEYE, Amsterdam, the Netherlands), dedicated software provided by the manufacturer.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Diagnostic criteria of postural tachycardia syndrome and classic vasovagal syncope
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In the paper
“Li et al. recently reported that activating autoantibodies (AAb) to the α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR) might play a pathophysiological role in POTS.8”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [8] Li, 2014, Autoimmune basis for postural tachycardia syndrome, J Am Heart Assoc source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Negative (buffer) and positive (phenylephrine) controls were included in each assay.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Cell-based α1AR assay
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Its onset may follow an acute infection or vaccination but more commonly appears without antecedent causative events.2,6”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Introduction
What the sources say
- Not checked yetcites [2] Sheldon, 2015, 2015 Heart Rhythm Society Expert Consensus Statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source
- Not checked yetcites [6] Brinth, 2015, Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus, Vaccine source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the SYSTEMA cohort, we randomly selected 17 patients with a confirmed diagnosis, by clinical history and tilt testing, of POTS (16 females; age, 26 ± 9 years), and 7 with recurrent VVS (5 females; age: 31 ± 9 years).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Study patients
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In the paper
“The Regional Ethical Review Board in Lund, Sweden approved the study protocol (ref no 82/2008), and all study participants gave their written informed consent including serum analyses.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Examination protocol
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These and possibly other yet-to-be identified immunoglobulins with different target epitopes may exert varying biological effects in particular patients, which may explain different constellations of symptoms in POTS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Within the SYSTEMA cohort, we randomly selected 17 patients with a confirmed diagnosis, by clinical history and tilt testing, of POTS (16 females; age, 26 ± 9 years), and 7 with recurrent VVS (5 females; age: 31 ± 9 years).”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Methods > Study patients
Strength:plain· not yet calibratedn = 17Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, the study groups were not strictly age matched, although the age difference was not significant.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The catecholamine surge may be seen as a compensatory mechanism to override the α1AR malfunction associated with the proposed autoimmune blockade as present in POTS patients but this explanation is unlikely in those with recurrent VVS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
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In the paper
“This report more than doubles the number of our previous observations, and focuses on a tightly characterized group of patients and controls.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diagnostic criteria based on measuring the autoantibodies' impact on an allosteric-mediated receptor response to the natural ligand may provide a more favourable estimate of autoantibody involvement in the complex pathophysiology of POTS.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This cremaster arteriolar bioassay is not suitable for use in large numbers of samples and the specific cell-based assays are an improvement with regard to numbers.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It seems apparent that the high percentage of POTS subjects examined by our group present with an apparent autoimmune diathesis that supports the concept that these autoantibodies play important role in the pathophysiology of this entity.”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: There is a paucity of concrete evidence for other pathophysiological bases for POTS for the vast majority of patients.
In the paper
“The vagal drive may have an important implication in related POTS symptomatology.20”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion > Strengths and limitations
What the sources say
- Not checked yetcites [20] Yoshida, 2014, Variant cardiovascular regulation in children with postural tachycardia syndrome, Pediatr Int source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Both POTS and IST share abnormal sinus tachycardia tendency, and differ in regard to resting heart rate control that is usually preserved in POTS but not in IST.2”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [2] Sheldon, 2015, 2015 Heart Rhythm Society Expert Consensus Statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope, Heart Rhythm source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This spectrum would certainly range from subclinical to overt expressions that may overlap with other entities such as inappropriate sinus tachycardia (IST), where circulating antibodies against cardiac β-receptors have been previously reported.18”
§ Antiadrenergic autoimmunity in postural tachycardia syndrome > Discussion
What the sources say
- Not checked yetcites [18] Chiale, 2006, Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac beta andrenergic receptors, Heart Rhythm source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The POTS patients selected from the SYSTEMA cohort are representative of POTS patients generally.
“we planned to examine the AAb profile of a larger, well-characterized, and representative cohort of patients with POTS from an independent European institution whose selection was completely separate from the originating laboratory.”
The paper relies on this without support.
There is a paucity of concrete evidence for other pathophysiological bases for POTS for the vast majority of patients.
“Although it is likely that POTS has multiple causes, there has been a paucity of concrete evidence for other pathophysiological bases for an underlying pathophysiology to date for the vast majority of patients.”
The paper relies on this without support.
The isolated rat cremaster arteriole assay is a valid measure of α1AR autoantibody-mediated contractile activity in POTS.
“Immunoglobulin G (0.05 mg/mL) from each subject with POTS and 8 controls were tested for α1AR autoantibody-mediated contractile activity using an isolated rat cremaster arteriole assay.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Although altered GPCR activity in people with POTS has been observed (Fedorowski et al., 2017”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Fedorowski et al., 2017
In the citing paper
“Serum immunoglobulins isolated from POTS patients have been reported to act as partial agonists to both α- and β-adrenergic receptors in vitro (Fedorowski et al., 2017; Li et al., 2014), a finding independently confirmed by several other groups (Vernino and Stiles, 2018) and expanded to include a wider range of G-protein coupled receptors (GPCRs) as targets (Kharraziha et al., 2020).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Fedorowski et al., 2017
In the citing paper
“Higher levels of autoantibodies against beta-1 and beta-2 adrenoreceptors have been detected in POTS patients versus healthy controls in serologic studies (32, 44).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [44]
In the citing paper
“This group also demonstrated that autoantibody affinity toward beta-receptors positively correlated with a greater degree of orthostatic tachycardia (44).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [44]
In the citing paper
“Fedorowski et al. (44) demonstrated that these autoantibodies, in addition to acting like a direct beta-agonist, can also upregulate sympathetic nervous activity through allosteric interactions with the beta-receptors.”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [44]
In the citing paper
“Circulating antibodies to α1-and β-adrenergic receptors and cardiac lipid raft-associated proteins have also been discovered in POTS (Fedorowski et al., 2017;Wang et al., 2013;Li et al., 2014).”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Fedorowski et al., 2017
In the citing paper
“A specific focus was given cardiovascular G-protein-coupled membrane complexes, such as adrenergic, muscarinic and angiotensin II type-1 receptors The symptoms of POTS, especially [43,45] (Fig. 1).”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [45]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
POTS sex counts disagree
MinorThe Methods describe 16 female POTS patients among 17, whereas Table 1 lists 15 females and 2 males among 17.
“17 patients with a confirmed diagnosis, by clinical history and tilt testing, of POTS (16 females; age, 26 ± 9 years)”
“| Sex M/F | 2/15 | 2/5 | 1/10 | 0.55/0.98 |”
Fewer than half showed the stated α1AR modulation
MinorThe Discussion says a majority exerted a negative modulatory effect on α1AR activity, but Table 2 reports that effect in only 8 of 17 POTS patients.
“A majority also exerted an allosterically mediated positive modulatory effect upon β1AR and a negative modulatory effect on α1AR activity.”
“| Total | 8/17 | 8/17 | 11/17 | 13/17 | 12/17 |”
POTS age summary disagrees with Table 1
MinorThe Methods give the POTS group's age as 26 ± 9 years, but Table 1 gives 25 ± 7.
“POTS (16 females; age, 26 ± 9 years)”
“| Age | 25 ± 7 | 31 ± 9 | 31 ± 6 | 0.17/0.063 |”
Citations
Cites
Developed in collaboration with, European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), and Heart Rhythm Society (HRS), societies, E. B. T. F., European Society of Emergency Medicine (EuSEM), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), American Geriatrics Society (AGS), European Neurological Society (ENS), et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp298 · Cited by 2,040
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Sheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W.-K., Calkins, H., Brignole, M., Raj, S. R., Krahn, A. D., Morillo, C. A., Stewart, J. M., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.03.029 · Cited by 1,013
Self-citationPostural tachycardia syndrome: a heterogeneous and multifactorial disorder
Benarroch, E. E. (2012) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2012.08.013 · Cited by 370 · cited 4×
“It often leads to debilitating symptoms and uncertain long-term prognosis.(1) A number of treatment options have been proposed in POTS but their efficacy in the more severe forms is limited and often questioned.”
BackgroundInfluentialHemodynamic Response to the Upright Posture
Smith, J. J., Porth, C. M., & Erickson, M. (1994) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1994.tb04977.x · Cited by 320 · cited 1×
“pulse increase ,30 bpm and absence of orthostatic hypotension).(10,11) All the patients and controls were recruited from the same community of Malmö or neighbouring municipalities in Skåne Region, Southern Sweden.”
BackgroundBartoletti, A. (2000) · Europace · doi:10.1053/eupc.2000.0125 · Cited by 315 · cited 1×
“The head-up tilt (HUT) test for SYSTEMA patients was performed according to the Italian protocol.(12) The tilt table was raised at constant speed to 708 in 18 s, and had the same lowering time.”
MethodPostural tachycardia syndrome (POTS)
Lamotte, G., & Low, P. A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-85492-4.00118-6 · Cited by 301
Guía de práctica clínica para el diagnóstico y manejo del síncope (versión 2009)
Moya‐Mitjans, À., Sutton, R., Ammirati, F., Blanc, J., Brignole, M., Dahm, J. B., Deharo, J., Gajek, J. J., Gjesdal, K., Krahn, A. D., et al. (2009) · Revista Española de Cardiología (English Edition) · doi:10.1016/s1885-5857(09)73541-8 · Cited by 277
Self-citationAutoimmune Basis for Postural Tachycardia Syndrome
Li, H., Yu, X., Liles, C., Khan, M., Vanderlinde‐Wood, M., Galloway, A., Zillner, C., Benbrook, A., Reim, S., Collier, D., et al. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.113.000755 · Cited by 255 · cited 12×
“Immunoglobulin G-mediated b1AR and b2AR activation of cAMP production in transfected CHO cells (with either b1AR or b2AR stimulation) was measured using the cAMP Hunter eXpress GPCR Assay kit (DiscoveRx) as described.(8,15) Briefly, b1AR- or b2AR-CHO cells were dispensed into 96-well plates and incubated overnight.”
BackgroundMethodResultInfluentialSelf-citation
Flagged first, then by citations
1 of the 22 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–151 of 151
Kakavand, B., Maul, T. M., Madueme, P. C., & Dadlani, G. H. (2023) · Pediatric Cardiology · doi:10.1007/s00246-023-03113-0 · Cited by 5
“Postviral onset [16], association with autoimmune disorders [17, 18], and genetic causes [19, 20] have been implicated.”
BackgroundMalkova, A. M., & Shoenfeld, Y. (2022) · Autoimmunity Reviews · doi:10.1016/j.autrev.2022.103231 · Cited by 5
RetractedPathophysiology and Classification of PoTS
Lloyd, M., & Raj, S. (2020) · Postural Tachycardia Syndrome · doi:10.1007/978-3-030-54165-1_5 · Cited by 4
Postural orthostatic tachycardia syndrome explained using a baroreflex response model
Geddes, J. R., Ottesen, J. T., Mehlsen, J., & Olufsen, M. S. (2022) · Journal of The Royal Society Interface · doi:10.1098/rsif.2022.0220 · Cited by 5
“Additionally, autoantibodies against b1,b2,a1,M1,M2 receptors may be responsible for some cases of POTS [1,56].”
BackgroundHofmann, S., Lucio, M., Wallukat, G., Hoffmanns, J., Schröder, T., Raith, F., Szewczykowski, C., Skornia, A., Rech, J., Schottenhamml, J., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146746 · Cited by 4
Gunning, W. T., Khan, S. E. A., Spatafore, J. W., Karabin, B. L., & Grubb, B. P. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1560120 · Cited by 4
“Hypotheses regarding pathophysiology include abnormally increased sympathetic activity, sympathetic denervation leading to hypovolemia and reflex tachycardia, and autoimmunity to G-protein coupled receptors (2, 3, 79, 81, 82).”
Goto, Y., Sunami, Y., Sugaya, K., Nakane, S., & Takahashi, K. (2021) · Rinsho Shinkeigaku · doi:10.5692/clinicalneurol.cn-001598 · Cited by 4
Mantovani, M., Grossi, R., Fede, G. D., & Bellavite, P. (2024) · Cureus · doi:10.7759/cureus.60019 · Cited by 4
“This hypothesis is supported by the fact that most patients with POTS possessed autoantibodies that activated ADRA1, ADRB1, and ADRB2 receptors [21].”
ResultMiglis, M. G., & Muppidi, S. (2020) · Clinical Autonomic Research · doi:10.1007/s10286-019-00661-5 · Cited by 4
Treatment Updates in Postural Tachycardia Syndrome
Goodman, B. P. (2020) · Current Treatment Options in Neurology · doi:10.1007/s11940-020-00643-3 · Cited by 3
González-Hermosillo, J. A., Rubio-Vega, A., González-Olvera, K. A. F., Sierra-Beltrán, M., Kostine, A., & Lerma, C. (2021) · Revista de investigaci�n Cl�nica · doi:10.24875/ric.21000199 · Cited by 4
Hop to It: The First Animal Model of Autoimmune Postural Orthostatic Tachycardia Syndrome
Miller, A. J., & Doherty, T. A. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.119.014084 · Cited by 3
“adrenergic receptors in all patients with POTS tested from 2 different countries.(4,5) These studies found antibodies that activate the b1 adrenergic receptor in most participants with POTS (n=28/32), and a smaller subset of participants”
BackgroundHen, O., David, P., & Shoenfeld, Y. (2021) · Medicina · doi:10.3390/medicina57121333 · Cited by 2
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Rowe, P. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-75608-2.00200-7 · Cited by 2
Moyano, E. G., Pavón, F. J., Rodríguez‐Capitán, J., Bardán-Rebollar, D., Ramos-Carrera, T., Sánchez, A. V., de Pedro, I. P., Ruiz-García, F., Mora-Robles, J., Sampalo, A. L., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13082405 · Cited by 2
Jost, K., Rodriguez, B., Söll, N., Hoepner, R., & Z'Graggen, W. J. (2022) · F1000Research · doi:10.12688/f1000research.109373.1 · Cited by 1
Blitshteyn, S., & Fries, D. (2017) · Clinical Autonomic Research · doi:10.1007/s10286-017-0397-7 · Cited by 2
Autoimmune Antibodies in Orthostatic Intolerance Syndromes
Lukáčová, M., Mitro, P., Lazúrová, Z., Hijová, E., Bertková, I., & Valová, K. (2025) · Physiological Research · doi:10.33549/physiolres.935504 · Cited by 1
“To date, there have been some studies concerning autoimmune antibodies against adrenergic, cholinergic, and angiotensin II type I receptors in POTS patients with different results, and very few available studies regarding these autoimmune antibodies in VVS patients [7,8].”
Autonomic nervous system autoimmunity and proposed immunotherapies
Goodman, B. P. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-323-90887-0.00026-2 · Cited by 1
Is PoTS an Autoimmune Condition?
Rull, G., & Lobo, M. (2020) · Springer eBooks · doi:10.1007/978-3-030-54165-1_20 · Cited by 1
Autonomic Dysfunction in the Central Nervous System Hypersomnias
Miglis, M. G. (2023) · Current Sleep Medicine Reports · doi:10.1007/s40675-023-00247-8 · Cited by 1
Kluczna, A., Mularska, E., & Dzierżanowski, T. (2022) · European journal of medical research · doi:10.1186/s40001-022-00685-0 · Cited by 1
“, towards a-/b-adrenoreceptors and muscarinic receptors [26, 27].”
LC, POTS, and ME/CFS: Lifting the FogPreprint
Chambers, P. W. (2023) · Preprints.org · doi:10.20944/preprints202303.0418.v1
Long Covid, POTS, and ME/CFS: Lifting the FogPreprint
Chambers, P. W. (2023) · Preprints.org · doi:10.20944/preprints202303.0418.v2
Long COVID, POTS, CFS and MTHFR: Linked by Biochemistry and NutritionPreprint
Chambers, P. W. (2023) · Preprints.org · doi:10.20944/preprints202303.0418.v3
OBSOLETE: Sinus Tachycardias: Inappropriate Sinus Tachycardia and Postural Tachycardia Syndrome
Raj, S. R. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.99799-x
Beta-blockers as Antiarrhythmic Agents
Buzea, A., Dan, A. R., & Dan, G. (2020) · Springer eBooks · doi:10.1007/978-3-030-34893-9_4
Erolu, E. (2020) · Haydarpasa Numune Training and Research Hospital Medical Journal · doi:10.14744/hnhj.2020.04557
“The incidence of autoimmune diseases in HLADQ2- positivity has increased compared to the normal population[14,17].”
BackgroundUpdates in postural tachycardia syndrome
Moon, J. (2021) · Annals of Clinical Neurophysiology · doi:10.14253/acn.2021.23.1.1
“One group found that most patients with POTS harbored antibodies that activate the β1 adrenergic receptor, while a smaller proportion of patients had antibodies that activate the β2 adrenergic receptor and also act as partial agonists/antagonists to α1 receptors.(18,27) Moreover, patients with POTS have a higher posit…”
BackgroundNunura, F., Tulloch-Reid, E., Soliman, A., Weekes, S., Basil, E., Baugh, D. S., & Madu, E. C. (2021) · Acta Scientific Medical Sciences · doi:10.31080/asms.2020.05.0990
Postural Orthostatic Tachycardia Syndrome explained using abaroreflex response modelPreprint
Geddes, J. R., Ottesen, J. T., Mehlsen, J., & Olufsen, M. S. (2021) · arXiv (Cornell University) · doi:10.48550/arxiv.2109.14558
“Additionally, autoantibodies against b1,b2,a1,M1,M2 receptors may be responsible for some cases of POTS [1,56].”
BackgroundDETERMINATION OF A PLASMA EMITTER FORM IN AN ACCELERATING ELECTRIC FIELD.
Volkov, B. I., Sveshnikov, A. G., & Semashko, N. N. (1971) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information)
Endothelial and Autonomic Assessments in the Management of COVID-19
Maarek, A. (2021) · Open Journal of Preventive Medicine · doi:10.4236/ojpm.2021.1112033
“On the other hand, the autonomic dysfunction in COVID-19 patients could be caused by the virus itself [40] [41] [42] [43].”
BackgroundPostural orthostatic tachycardia syndrome in children and adolescents
Lee, J. (2022) · Journal of Korean Medical Association · doi:10.5124/jkma.2022.65.2.101
“다 른 연구에서는 전체 소아청소년 POTS 환자의 약 5-10%에 서 셀리악병, 크론병, 염증장질환, 쇼그랜 증후군, 자가면역 성 갑상선염증 등이 같이 있는 것으로 알려져 있어서 최근에 는 경한 자가면역질환의 하나로 인식이 되고 있다[5,15,25].”
Sinus Tachycardias: Inappropriate Sinus Tachycardia and Postural Tachycardia Syndrome
Shaw, B. H., Ng, J., & Raj, S. R. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809657-4.99799-0
LC, POTS, and ME/CFS: Lifting the FogPreprint
Chambers, P. W. (2023) · doi:10.32388/nlr1k8
LC, POTS, and ME/CFS: Lifting the FogPreprint
Chambers, P. W. (2023) · doi:10.32388/nlr1k8.2
Taquicardia ortostática postural y trastornos autonómicos en el síndrome post COVID-19
Hernández-Perera, A., Chuisent-Gómez, I. T., Suarez-Renol, D., & Nodarse-Amaya, E. D. L. C. (2023) · REVISTA BIOMÉDICA · doi:10.32776/revbiomed.v34i3.1125
Psychological stress in postural orthostatic tachycardia syndrome: A pilot pre-COVID survey
Firth, K., Daukantaité, D., Hamrefors, V., Sutton, R., & Fedorowski, A. (2023) · Heart and Mind · doi:10.4103/hm.hm-d-23-00051
Self-citationSinus Tachycardias: Inappropriate Sinus Tachycardia and Postural Orthostatic Tachycardia Syndrome
Talati, A., Uppal, J., Sheldon, R. S., & Raj, S. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15734-9.00016-9
Tackling POTS Needs More Than Just a Sympathetic Approach
Dani, M., & Fedorowski, A. (2024) · Hypertension · doi:10.1161/hypertensionaha.124.23716
Self-citationDziedzic, A., Furtak, D., Grela, W., Niewiadomska, J., Głogowska, P., Tulej, D., Marciniuk, D., Gniaź, N., Górska, A., & Marko, N. (2024) · Journal of Education Health and Sport · doi:10.12775/jehs.2024.71.56193 · Cited by 1
Case report: Treatable immune-mediated severe orthostatic hypotension in SARS-CoV-2 infection
Theiler, K., Bronchain, M., Grouzmann, E., Duflon, S., Hirt, L., Pasquier, R. D., Waeber, G., Wuerzner, G., Diserens, K., & Bally, J. F. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1505727 · Cited by 4
Positionspapier zum Post-COVID-Syndrom
Schieffer, E., Hilfiker‐Kleiner, D., Schlitt, A., Laufs, U., Eckardt, L., & Schieffer, B. (2025) · Die Kardiologie · doi:10.1007/s12181-024-00722-8
Beta-Blockers as Antiarrhythmic Agents
Buzea, A., & Dan, A. R. (2024) · Springer eBooks · doi:10.1007/978-3-031-74046-6_4 · Cited by 2
Medic Spahic, J., Ricci, F., Aung, N., Hallengren, E., Axelsson, J., Hamrefors, V., Melander, O., Sutton, R., & Fedorowski, A. (2020) · Figshare · doi:10.6084/m9.figshare.12177873
Self-citationWang, S., Zhao, T., Li, F., Wang, Y., Hong, C., Liu, L., Wen, C., Zou, R., & Wang, C. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15051798
POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME (POTS) IN PRIMARY CARE: DIAGNOSIS AND MANAGEMENT
Sumlet, P., Małajewicz, I., Spychalska, W., Kurasińska, W., Kolm, M., Chmielewska, Z., Drzewińska, K., Suszczyńska, W., Gofron, M., & Duliński, M. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(51).2026.6253
Trout, J., Lamotte, G. J., Langford, J. S., Heyliger, L., & Cortez, M. M. (2026) · Clinical Autonomic Research · doi:10.1007/s10286-026-01239-8
Azola, A. M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-23516-0.00124-0
Metadata
- Authors
- Fedorowski, A., Li, H., Yu, X., Koelsch, K. A., Harris, V. M., Liles, C., Murphy, T. A., Quadri, S. M. S., Scofield, R. H., Sutton, R., Melander, O., & Kem, D. C.
- Affiliations
- Lund University (SE)
- University of Oklahoma Health Sciences Center (US)
- Oklahoma Medical Research Foundation (US)
- Imperial College London (GB)
- Corresponding author
- Fedorowski, Artur
- ORCID
- Venue
- EP Europace
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-10-04
- Volume
- 19
- Issue
- 7
- Pages
- 1211-1219
- ISSN
- 1099-5129 (ISSN-L)
- 1532-2092
- PMC
- PMC5834103
- OpenAlex
- W2528071726
- Semantic Scholar
- 31fdba9a6b101b72fdc3c4780b2b82249e111255
- Cited by
- 151
- References
- 22
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 16 · 2023: 23 · 2022: 24 · 2021: 18 · 2020: 21 · 2019: 11 · 2018: 14 · 2017: 8
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- EP Europace (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- European Society of Cardiology
- Lunds Universitet
- Medical Research Council
- National Heart, Lung, and Blood Institute (R01HL128393, R56HL128393)
- National Institute of General Medical Sciences (U54GM104938)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- postural orthostatic tachycardia syndrome, autoantibodies, adrenergic receptors, alpha1-adrenoceptors, beta1-adrenergic receptor, beta2-adrenergic receptor, vasovagal syncope, orthostatic intolerance, autonomic dysfunction
- MeSH terms
- Abdominal Muscles, Adolescent, Adult, Animals, Arterioles, Autoantibodies, Cricetulus, Dose-Response Relationship, Drug, Female, Humans, Immunoglobulin G, Male, Transfection, Vasoconstriction, Autoimmunity, Case-Control Studies, CHO Cells, Receptors, Adrenergic, alpha-1, Receptors, Adrenergic, beta-1, Receptors, Adrenergic, beta-2, Rats, Postural Orthostatic Tachycardia Syndrome, Young Adult, Adrenergic alpha-1 Receptor Agonists, Adrenergic beta-1 Receptor Agonists, Adrenergic beta-2 Receptor Agonists, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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