Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome.

BACKGROUND: High sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available. OBJECTIVES: This study tested whether a high sodium (HS) diet reduces orthostatic tachycardia (Δ heart rate) and upright heart rate compared with a low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine. METHODS: A total of 14 POTS patients and 13 healthy control subjects (HC), age 23 to 49 years, were enrolled in a crossover study with 6 days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. Supine and standing heart rate, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine were measured. RESULTS: In POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in HC on the HS diet (median 117 beats/min [interquartile range: 98 to 121 beats/min], 46 beats/min [interquartile range: 32 to 55 beats/min], and 753 pg/ml [interquartile range: 498 to 919 pg/ml] in POTS vs. 85 beats/min [interquartile range: 77 to 95 beats/min], 19 beats/min [interquartile range: 11 to 32 beats/min], and 387 pg/ml [interquartile range: 312 to 433 pg/ml] in HC, respectively), despite no difference in the measured PV. CONCLUSIONS: In POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases Δ heart rate. (Dietary Salt in Postural Tachycardia Syndrome; NCT01547117).

Circulating levels of growth hormone in postural orthostatic tachycardia syndrome.

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.

gAChR antibodies in children and adolescents with acquired autoimmune dysautonomia in Japan.

OBJECTIVE: Patients with acquired autonomic dysfunction may have antibodies specific to the ganglionic nicotinic acetylcholine receptor (gAChR). However, the clinical features of children and adolescents with acquired autonomic dysfunction (AAD) remain unclear. This study aimed to determine the clinical features of pediatric patients with acquired autonomic dysfunction. METHODS: This study retrospectively examined a series of patients of AAD with serum gAChR antibodies who were referred to our laboratory for antibody testing between January 2012 and April 2019. The study included 200 patients (<20 years, 20 cases; ≥20 years, 175 cases) with clinical features of AAD. RESULTS: Upon comparing pediatric and adult patients, we found that antecedent infection and autonomic symptoms at onset with gastrointestinal symptoms occurred more frequently in children with AAD. We confirmed that four children (20.0%) met the diagnostic criteria for postural orthostatic tachycardia syndrome (POTS). A significantly higher number of children than adults had POTS (P = 0.002). In addition, upper GI dysfunction was more prevalent in children than in adults (P = 0.042). In particular, nausea and vomiting occurred in 60.0% of children with AAD and in 21.1% of adults (P < 0.001). The frequency of paralytic ileus was significantly higher in children with AAD (20.0%) relative to adults (6.3%) (P = 0.030). Regarding extra-autonomic manifestations, encephalopathy was more frequent in children (15.0%) than in adults (1.1%) (P < 0.001). INTERPRETATION: Pediatric AAD patients have their own clinical characteristics, and these features may be unique to children and adolescents.

Serum Activity Against G Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome.

Background Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein-coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell-based assay. Methods and Results Forty-eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10-item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein-coupled receptor: adrenergic α1 receptor, adrenergic ß2 receptor, cholinergic muscarinic type 2 receptor, and opioid receptor-like 1 were treated with sera from all patients. Receptor response was analyzed using a ß-arrestin-linked transcription factor driving transgenic ß-lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein-coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls (P<0.01 for all). The area under the curve was 0.88 (0.80-0.97, P<0.001) combining all 4 receptors. Adrenergic α1 receptor activation associated with OHQ composite score (ß=0.77 OHQ points per SD of activity, P=0.009) and with reduced tolerability for prolonged standing (P=0.037) and walking for short (P=0.042) or long (P=0.001) periods. All 4 receptors were associated with vision problems (P<0.05 for all). Conclusions Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum-mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α1 receptor is associated with orthostatic symptoms severity in patients with POTS.

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome.

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 conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. RESULTS: POTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. CONCLUSIONS: Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

Adrenergic Autoantibody-Induced Postural Tachycardia Syndrome in Rabbits.

Background Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits. Methods and Results Eight New Zealand white rabbits were coimmunized with peptides from the α1-adrenergic receptor and ß1-adrenergic receptor (ß1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope-mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the ß-adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of ß1AR antibodies. In contrast, the blood pressure response to infusion of the α1-adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1-adrenergic receptor antibodies. Injections of antibody-neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays. Conclusions The differential allosteric effect of α1-adrenergic receptor and ß1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac ß1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.

Vagal and Sympathetic Function in Neuropathic Postural Tachycardia Syndrome.

The diagnosis of neuropathic postural tachycardia syndrome (POTS) requires research techniques not available clinically. We hypothesized that these patients will have impaired vagal and sympathetic cardiovascular control that can be characterized with clinical autonomic tests. We included 12 POTS patients with possible neuropathic subtype because of normal plasma norepinephrine and no increase in upright blood pressure. We compared them to 10 healthy subjects. We assessed hemodynamics, heart rate and blood pressure variability, baroreflex sensitivity, raw and integrated muscle sympathetic nerve activity, and blood volume. To understand the vagal/sympathetic control, we dissected the phase 2 of Valsalva maneuver (VM) into early (VM2e) and late (VM2l). POTS' upright heart rate increased 43±3 bpm. Patients had normal plasma volume but reduced red blood cell volume (1.29 L versus predicted normal values 1.58 L; P=0.02). Vagal indices of heart rate variability, HFRRI (430±130 versus 1680±900; P=0.04), PNN50, and root mean squared of successive differences were lower in POTS. Patients showed a decrease in vagal baroreflex sensitivity (VM2e; P=0.04). In POTS, integrated muscle sympathetic nerve activity was lower at rest (12±1.5 versus 20±2 burst/min; P=0.004) and raw muscle sympathetic nerve activity spike analysis showed blunted responses during VM2e, despite a greater drop in systolic blood pressure (34±5 in POTS and 14±6 mm Hg in controls; P=0.01). This cohort of POTS patients enriched for possible neuropathic subtype had lower resting muscle sympathetic nerve activity, impaired vagal cardiac control, and exaggerated drop in blood pressure in response to VM and a delay in the sympathetic cardiovascular responsiveness during hypotensive challenge.

Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome.

BACKGROUND: Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and ß1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS. METHODS AND RESULTS: Serum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1-adrenergic receptor. CONCLUSIONS: Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS.

Vascular dysfunction of postural tachycardia syndrome in children.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance, and its incidence in children is approximately 6.8% [1]. The pathogenesis of POTS is complex with multiple, overlapping, interacting pathophysiological mechanisms. Although the specific pathogenic mechanism has remained perplexing, with the discovery of various gasotransmitters and biological peptides, the vascular dysfunction has aroused overwhelming attention. DATA SOURCES: On the basis of searching in a wide range of recent original literatures, we reviewed the pathogenesis of vascular dysfunction in children with POTS. RESULTS: The flow-mediated vasodilation of POTS patients was greater than that of healthy controls, and the vasodilator factors were increased in patients with POTS under basal condition or under a standing position, while the vasoconstriction factors were reduced. CONCLUSIONS: Vascular dysfunction, as one of pathogenesis in pediatric POTS patients, affects the occurrence and development of diseases through a variety of factors.

Serum Resistin Negatively Correlates with Clinical Severity of Postural Tachycardia Syndrome in Children.

This study was designed to analyse the serum resistin level in children with postural tachycardia syndrome (POTS) and its clinical significance. Twenty-one children with POTS and 31 healthy children as controls participated in the study. Clinical characteristics, heart rate and blood pressure in the supine and upright positions were monitored and collected during an upright test, and the symptom scoring of POTS patients was recorded. The serum resistin levels of patients in both groups were determined by enzyme-linked immunosorbent assay. The change in serum resistin levels in the POTS group before and after standing, as well as its correlation with symptom scores and change in heart rate after standing, was analysed. Compared with the control group, the serum resistin levels in the POTS group were significantly increased (P < 0.01). The serum resistin levels in the POTS group before and after standing did not differ (P > 0.05). There was a negative correlation between the serum resistin levels and a change in heart rate from the supine to upright position (correlation coefficient = -0.615, P < 0.01). Moreover, serum resistin levels were negatively correlated with symptom scores (correlation coefficient = -0.493, P < 0.05). Serum resistin levels in children with POTS were significantly higher than those in healthy children and negatively correlated with a change in heart rate from the supine to upright position and symptom scores. These results suggest a protective role of increased resistin in the pathogenesis of POTS.

Vitamin B1 deficiency in patients with postural tachycardia syndrome (POTS).

OBJECTIVE: POTS is a heterogeneous disorder of the autonomic nervous system that can result from multiple etiologies. An increased prevalence of vitamin B12, vitamin D 25-OH and iron deficiencies has been observed in patients with POTS. This study examined the prevalence of vitamin B1 deficiency and assessed response to vitamin B1 supplementation in the deficient POTS patients. METHODS AND RESULTS: Medical records of 65 consecutive patients with POTS evaluated at our clinic were reviewed. In this cohort (mean age 32, range 13-54 years; 89% female), 6% had vitamin B1 deficiency, and one of four deficient patients experienced significant improvement of POTS after oral vitamin B1 supplementation. CONCLUSION: A small subset of patients with POTS may have vitamin B1 deficiency. Testing for vitamin B1 deficiency and correcting the deficiency is recommended.

Postural tachycardia syndrome (POTS) with anti-NMDA receptor antibodies after human papillomavirus vaccination.

We describe a young woman who developed POTS with positive serum anti-NMDA receptor antibodies and no evidence of encephalitis after vaccination with HPV vaccine, Cervarix. Her symptoms improved significantly with immunomodulatory therapy and re-occurred after immunomodulatory therapy was stopped, suggesting an autoimmune etiology of POTS after vaccination.

Antiadrenergic autoimmunity in postural tachycardia syndrome.

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 ß1/2-adrenergic receptors (ß1/2AR). 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 ß1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and ß1/2AR 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, ß1AR and ß2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and ß1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the ß1AR 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 ß1AR and α1AR activity but not with ß2AR 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 ß1AR responsiveness are important in the pathophysiology of postural tachycardia.

Postural orthostatic tachycardia syndrome is associated with platelet storage pool deficiency.

Mechanisms have been postulated to explain postural orthostatic tachycardia syndrome (POTS), however, the etiology of this often debilitating disorder remains unknown. We conducted a retrospective case-control study of 181 POTS patients who exhibited/reported bleeding symptoms for a specific platelet (PL) dysfunction disorder, delta granule storage pool deficiency (δ-SPD).Patients were included only if results of blood tests for δ-SPD were available. Electron microscopy was utilized to diagnose δ-SPD. An ELISA assay was used to determine serotonin (5HT) concentration in PLs and medical record review was employed to collect patients' clinical symptoms.The most common bleeding symptom was easy bruising (71%) but frequent nose bleeds, heavy menstrual bleeding, and a family history of bleeding were also commonly reported. Of the patients studied, 81% were diagnosed with δ-SPD. Our investigation of 5HT concentration extracted from PLs revealed significantly lower levels of 5HT in POTS patients when compared to that of control subjects. Our data suggest that patients with POTS have significant comorbidities including bleeding symptoms and/or family bleeding histories, and have diminished PL 5HT levels supporting the hypothesis that POTS is a low 5HT level disorder. While we describe a significant relationship with POTS and δ-SPD, this finding does not constitute an etiology for POTS.Our results establish an additional comorbidity frequently seen in POTS that could explain a number of disparate symptoms often affecting the severity of POTS.

Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.

Autonomic activity and biomarker behavior in supine position and after passive postural stress in different orthostatic intolerance syndromes.

INTRODUCTION AND OBJECTIVES: Orthostatic intolerance (OI) syndromes are a confusing topic and determining a specific diagnosis to achieve optimal treatment can be troublesome. We sought to assess biomarker, hemodynamic and autonomic variables in OI patients (autonomic dysfunction [AD], postural orthostatic tachycardia syndrome [POTS] and neurally mediated syncope [NMS]) and healthy controls during supine and head-up tilt position in order to achieve a better diagnosis. RESULTS: In response to head-up tilt, patients with AD presented a marked decrease in systolic blood pressure (SBP) (p=0.002), and a blunted increase in heart rate (HR) (p=0.04). Baroreceptor gain was almost absent in supine position and did not change in response to tilt. Patients with POTS had lower values of atrial natriuretic peptide (p=0.03) but similar neurohormonal biomarkers and hemodynamic and baroreceptor function in supine position compared to healthy subjects. However, in response to head-up tilting greater reductions in stroke volume (p=0.008) and baroreceptor gain (p=0.002) and greater rises in HR (p=0.001), total peripheral resistance (p=0.008), low frequency component of SBP variability (LF-SBP) (p=0.003) and plasma noradrenaline (p=0.03) were observed. Patients with NCS had similar biomarkers and autonomic indices to healthy subjects in supine position, but a larger decrease in baroreceptor gain (p=0.007) and a greater rise in LF-SBP (p=0.004) and plasma adrenaline (p=0.003) response to head-up tilting. CONCLUSION: Although different OI syndromes share similar symptoms, including blurred vision, syncope and dizziness particularly during orthostatism, they differ markedly regarding biochemical, autonomic and hemodynamic parameters. Assessment of these differences may be helpful for better diagnosis and management.

Total peripheral vascular resistance, cardiac output, and plasma C-type natriuretic Peptide level in children with postural tachycardia syndrome.

OBJECTIVE: To investigate the total peripheral vascular resistance (TPVR), cardiac output (CO), and plasma C-type natriuretic peptide (CNP) levels in children with postural tachycardia syndrome (POTS) during supine, upright, and return to supine. STUDY DESIGN: Twenty-nine children with POTS, aged 12 ± 3 years, were recruited, and 32 healthy children, aged 11 ± 2 years, served as controls. Heart rate (HR), blood pressure, TPVR, and CO were continuously monitored with Finapres Medical System, and plasma CNP levels were detected with Sandwich immunoluminescence assay. RESULTS: In children with POTS, upright TPVR and CO were significantly lower than those in supine position, and they rose again when they returned to supine position. However, in healthy control patients, both TPVR and CO did not change during supine, upright, and supine again positions. Also, in the supine position, there was no significant difference in TPVR and CO between POTS children and control subjects (P > .05). When upright, however, TPVR and CO in children with POTS were significantly lower than those of controls. Plasma CNP levels were significantly greater in children with POTS than that of controls (32.8 ± 9.7 vs 24.2 ± 8.4 [pg/mL], P < .01), and symptom scores and ΔHR positively correlated with plasma CNP levels in children with POTS (symptom scores: r = 0.490, P < .01; ΔHR: r = 0.508, P < .001), but CO negatively correlated with plasma CNP levels (r = -0.446, P < .01). CONCLUSION: Reduced TPVR and CO associated with the elevated plasma CNP might be involved in the pathogenesis of POTS.