Inappropriate sinus tachycardia (IST) and postural tachycardia syndrome (POTS) are 2 disorders characterized by sinus tachycardia. It is debated whether the pathophysiology of IST and POTS results from abnormal autonomic regulation or abnormal sinus node function. We hypothesized that intrinsic heart rate (IHR) after autonomic blockade would be increased in patients with IST but not POTS. We enrolled 48 POTS patients, 8 IST patients, and 17 healthy control (HC) subjects. Intravenous propranolol and atropine were given to block the sympathetic and parasympathetic limbs of the autonomic nervous system in order to determine the IHR. Patients with IST have a higher sympathetic contribution to heart rate when compared with POTS patients (31±13 bpm versus 12±7 bpm, P<0.001) and HC (8±4 bpm; P<0.001) and a trend to less parasympathetic contribution than POTS and HC (IST: 31±11 bpm versus POTS: 46±11 bpm versus HC: 48±11 bpm, ANOVA P=0.108). IHR was not significantly different between IST and either POTS or HC (IST: 111±11 bpm versus POTS: 108±11 bpm versus HC: 106±12 bpm, ANOVA P=0.237). IST patients have more sympathetic tone when compared with either POTS or HC, but IST patients do not have abnormal sinus node automaticity. These data suggest that the treatment of IST and POTS should focus on sympatholysis, reserving sinus node modification for patients with continued debilitating symptoms after beta-blockade and possibly ivabradine. http://clinicaltrials.gov/. Unique identifier: NCT00262470.

To compare children with primary, chronic idiopathic nausea to those with secondary nausea associated with functional abdominal pain. Retrospective chart review of 45 children with a primary complaint of chronic nausea several times per week. Comparisons were made to prospectively collected data on 49 children with functional abdominal pain and comorbid nausea. The majority of those affected were adolescent Caucasian females. Subjects with chronic nausea had a more severe presentation with daily 88% (vs 26%) and constant 60% (vs 10%) nausea (P < .001), one-half with peak morning intensity. In the chronic nausea group, 62% had migraines, and 71% (vs 22%) had familial migraines (P < .001), 36% had postural tachycardia syndrome and 27% cyclic vomiting syndrome. Both groups suffered comorbid symptoms (anxiety, dizziness, fatigue, and sleep problems). The chronic nausea cohort underwent extensive, negative medical evaluations. Chronic idiopathic nausea of childhood is a poorly described symptom. Patients with primary (vs secondary) chronic nausea were more likely Caucasian, older adolescent females with severe, daily nausea and comorbid conditions such as anxiety, dizziness, and fatigue as well as significantly more migraine features. Chronic nausea is a major, disabling symptom that requires increased recognition as a separate functional entity. Future studies may need to focus on comorbid conditions including migraine and dysautonomia.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) upon standing. Previous studies have shown that standing HR decreases over time in POTS patients given placebo. We hypothesized that this reduction is due to cardiovascular physiological alteration, as opposed to psychological benefit from perceived therapy. To prospectively test this hypothesis, we examined the effects of an open-label 'no treatment' intervention (NoRx) compared with a patient-blinded placebo on standing HR in POTS patients. Twenty-one POTS patients participated in a randomized cross-over trial with oral placebo versus NoRx administered at 0900 h. Seated blood pressure (BP) and HR were measured at baseline and every hour for 4 h. Similarly, BP and HR were measured while patients stood for 10 min at these time points. Standing HR decreased significantly over time with both NoRx (112±13 and 103±16 b.p.m. at baseline and 4 h, respectively) and placebo (112±14 and 102±16 b.p.m. at baseline and 4 h, respectively; Ptime<0.001), but this effect was not different between interventions (Pdrug=0.771). Postural tachycardia syndrome patients have exaggerated orthostatic tachycardia in the morning that decreases over time with either placebo or NoRx interventions, suggesting this phenomenon is due to cardiovascular physiological variation. These data highlight the need for a placebo arm in haemodynamic clinical trials in POTS and may have important implications for the diagnosis of these patients.

It is hypothesised that the autonomic nervous system responds differently to various stressors in patients with chronic fatigue syndrome (CFS) compared with healthy controls. The goal is to systematically review the scientific literature addressing the functioning of the autonomic nervous system in patients with CFS. All studies that were identified through electronic databases (PubMed and Web of Science) were screened for eligibility based on the selection criteria and assessed (two independent raters) for methodological quality using a methodological checklist for case-control studies. Twenty-seven case-control studies were included. The methodological quality varied between 50% and 71·4%. Some studies showed different responses to head-up tilt and other autonomous testing. Although comparison between the included case-control studies was difficult, we can conclude that there are differences in autonomous response between patients with CFS and healthy controls. The heart rate dynamic response during the head-up tilt test differs between patients with CFS and healthy controls, supporting the increased prevalence of postural orthostatic tachycardia syndrome. The autonomic response can be useful for the diagnosis of CFS.

This study examines a possible relationship between Ehlers-Danlos Syndrome (EDS) and Postural Tachycardia Syndrome (POTS). We retrospectively reviewed 109 medical records of patients suffering from autonomic dysfunction exhibiting at least one POTS symptom from one urban clinic for EDS and POTS diagnoses between 2006 and 2013. The presence of EDS within the POTS and non-POTS populations was calculated and compared to that of the general population. The review revealed 39 (36F:3M) patients with POTS (mean ± SD age, 32.5 ± 11.8 years) with 7 cases of EDS yielding a prevalence of 18% (95% exact CI: 8%, 34%), a statistically significant difference from the suggested prevalence of EDS in the general population of 0.02% (p<0.0001). 70 patients (53F:17M) without POTS (mean ± SD age, 51.1 ± 14.7 years) contained 3 cases of EDS, yielding a prevalence of 4% (95% exact CI: 1%, 12%), a statistically significant difference from the general population (p<0.0001). The prevalence of EDS was significantly higher in the POTS group compared to the non-POTS group (p=0.0329). The odds ratio comparing the odds of EDS for POTS versus non-POTS patients is 4.9 (95% CI: 1.2, 20.1). The presence of EDS may be significantly higher in patients with POTS than that of the general population and in autonomic patients without POTS. We suspect an additional underlying mechanism of POTS caused by EDS.

Hyperventilation and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. On the basis of our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects with 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis before blood pressure recovery; central blood volume and mean arterial pressure were reduced (P<0.025), resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05) when compared with controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS (P<0.01) and inversely proportional to end tidal CO2 and resulted in an increase in heart rate (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia, and a statistically significant increase in blood pressure.

Quantitative and qualitative abnormalities in visceral function have been demonstrated in postural orthostatic tachycardia syndrome. Joint hypermobility is frequently associated with both postural orthostatic tachycardia syndrome and gastrointestinal symptoms. Future studies in this area should appropriately and systematically control for the presence of joint hypermobility syndrome.

Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder that has been shown to cause a large number of cardiac and neurological manifestations. Two recent studies have demonstrated abnormalities in cardiovascular autonomic function testing in APS patients without other cardiovascular or autoimmune disease. However, an association between autonomic disorders such as postural tachycardia syndrome and APS has not previously been described. Data were obtained by retrospective chart review. We identified 15 patients who have been diagnosed with APS and an autonomic disorder. The median age of the patients at the time of data analysis was 39 years. The autonomic disorders seen in these patients included postural tachycardia syndrome, neurocardiogenic syncope and orthostatic hypotension. The majority of patients (14/15) were female and the majority (14/15) had non-thrombotic neurological manifestations of APS, most commonly migraine, memory loss and balance disorder. Many also had livedo reticularis (11/15) and Raynaud's phenomenon (nine of 15). In some patients, the autonomic manifestations improved with anticoagulation and/or anti-platelet therapy; in others they did not. Two patients with postural tachycardia syndrome who failed to improve with the usual treatment of APS have been treated with intravenous immunoglobulin with significant improvement in their autonomic symptoms. We believe that autonomic disorders in APS may represent an important clinical association with significant implications for treatment.

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate (HR) upon standing, and many POTS patients have a hyperadrenergic state. Medications that restrain HR are a promising approach to this problem. We tested the hypothesis that melatonin will attenuate the tachycardia and improve symptom burden in patients with POTS. Patients with POTS (n = 78) underwent acute drug trials with melatonin 3 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressure, HR, and symptoms were assessed while seated and after standing for up to 10 min prior to, and hourly for 4 h following study drug administration. The reduction in standing HR was significantly greater 2 h after melatonin compared with placebo (P = 0.017). There was no significant difference in the reduction of systolic blood pressure between melatonin and placebo, either with standing or while seated. The symptom burden was not improved with melatonin compared with placebo. Oral melatonin produced a modest decrease in standing tachycardia in POTS. Further research is needed to determine the effects of regular night-time use of this medication in POTS.

Postural tachycardia syndrome (POTS) manifests as marked tachycardia while standing. We noticed two forms of circulatory response to orthostatic stress in POTS. We investigated cardiovascular and autonomic nervous response to orthostatic stress in the two forms. We studied 79 patients with POTS and 38 healthy control subjects (Ct). Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. Autonomic nervous function was evaluated on power spectral analysis of HR variability and diastolic BP variability. We divided the subjects into two groups: standing-induced tachycardia (SI group; increase in HR ≥35 beats/min) and supine tachycardia (Su group; standing HR ≥115 beats/min with standing-induced HR increase <35 beats/min). The Su group had higher supine BP and HR compared with the other groups, indicating dominant sympathetic control of the heart in the supine position. While rising, the SI group had a higher increase in HR than the Ct group, indicating excessive withdrawal of vagal tone. The Su group had a smaller increase in HR and a greater decrease of systolic BP and cardiac index by standing compared with the SI group. These results suggest that compensatory mechanisms of sympathetic function during standing failed in the Su group, probably because of exhaustion by the nearly maximum effort to generate sympathetic drive even in the supine position with low central blood volume. There is a difference between the two types of POTS, in the balance of resting autonomic function and hemodynamic response to standing.

To examine a large UK cohort of patients with postural tachycardia syndrome (PoTS), to compare demographic characteristics, symptoms and treatment of PoTS at one centre compared to the largest patient group PoTS UK and to verify if their functional limitation is similar to patients with chronic fatigue syndrome (CFS). A cross-sectional study assessed the frequency of symptoms and their associated variables. Two PoTS cohorts were: (1) recruited via PoTS UK, (2) diagnosed at Newcastle Hospitals National Health Service (NHS) Foundation Trust 2009-2012. Patients with PoTS were then compared to a matched cohort with CFS. Patients' detailed demographics, time to diagnosis, education, disability, medications, comorbidity and precipitants. Symptom assessment tools captured, Fatigue Impact Scale, Epworth Sleepiness Scale, Orthostatic Grading Scale (OGS), Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, Cognitive Failures Questionnaire. 136 patients with PoTS participated (84 members of PoTS UK (170 cohort; 50% return) and 52 (87 cohort; 60%) from Newcastle Clinics). The PoTS UK population was significantly younger than the clinic patients, with significantly fewer men (p=0.005). Over 60% had a university or postgraduate degree. Significantly more of the PoTS UK cohort were working, with hours worked being significantly higher (p=0.001). Time to diagnosis was significantly longer in the PoTS UK cohort (p=0.04). Symptom severity was comparable between cohorts. The PoTS total group was compared with a matched CFS cohort; despite comparable levels of fatigue and sleepiness, autonomic symptom burden (OGS) was statistically significantly higher. The most common treatment regime included β-blockers. Overall, 21 treatment combinations were described. Up to 1/3 were taking no treatment. Patients with PoTS are predominantly women, young, well educated and have significant and debilitating symptoms that impact significantly on quality of life. Despite this, there is no consistent treatment.

We hypothesized that orthostatic intolerance (OI) is associated with gastric dysrhythmias, nausea, and abdominal pain, which improves using fludrocortisone to treat OI. Patients (n=16, girls) with OI completed questionnaires before and after fludrocortisone treatment (age 14.8 ± 2.8 years). Ten patients underwent electrogastrograms (EGGs) before fludrocortisone. All EGGs showed gastric dysrhythmias. Fludrocortisone reduced mean scores as follows: nausea, 3.1 ± 0.8 to 2.1 ± 1.1 (P=0.016); dizziness, 3.0 ± 1.0 to 2.2 ± 1.1 (P=0.0371); abdominal pain, 2.8 ± 1.3 to 1.9 ± 1.4 (P=0.0063); flushing, 2.3 ± 1.2 to 1.5 ± 1.4 (P=0.0476); and missing school, 2.2 ± 1.5 to 1.2 ± 1.5 (P=0.0078). Chronic nausea and abdominal pain accompany OI and improve with OI treatment.

Cognitive deficits are characteristic of postural tachycardia syndrome (POTS). Intact nitrergic nitric oxide (NO) is important to cerebral blood flow (CBF) regulation, neurovascular coupling, and cognitive efficacy. POTS patients often experience defective NO-mediated vasodilation caused by oxidative stress. We have previously shown dilation of the middle cerebral artery in response to a bolus administration of the NO donor sodium nitroprusside (SNP) in healthy volunteers. In the present study, we hypothesized a blunted middle cerebral artery response to SNP in POTS. We used combined transcranial Doppler-ultrasound to measure CBF velocity and near-infrared spectroscopy to measure cerebral hemoglobin oxygenation while subjects were in the supine position. The responses of 17 POTS patients were compared with 12 healthy control subjects (age: 14-28 yr). CBF velocity in POTS patients and control subjects were not different at baseline (75 ± 3 vs. 71 ± 2 cm/s, P = 0.31) and decreased to a lesser degree with SNP in POTS patients (to 71 ± 3 vs. 62 ± 2 cm/s, P = 0.02). Changes in total and oxygenated hemoglobin (8.83 ± 0.45 and 8.13 ± 0.48 μmol/kg tissue) were markedly reduced in POTS patients compared with control subjects (14.2 ± 1.4 and 13.6 ± 1.6 μmol/kg tissue), primarily due to increased venous efflux. The data indicate reduced cerebral oxygenation, blunting of cerebral arterial vasodilation, and heightened cerebral venodilation. We conclude, based on the present study outcomes, that decreased bioavailability of NO is apparent in the vascular beds, resulting in a downregulation of NO receptor sites, ultimately leading to blunted responses to exogenous NO.

Midodrine hydrochloride is used clinically to treat children with postural tachycardia syndrome (POTS), but it is not effective in all patients. This study was designed to explore the changes in plasma copeptin and its predictive value in assessing the therapeutic efficacy of midodrine hydrochloride in children with POTS. The study included 33 children with POTS and 26 healthy children. The group with POTS received midodrine hydrochloride treatment for 1.5-3 months. The plasma copeptin was measured using a sandwich immunoluminometric assay. A receiver operating characteristic curve was used to explore the predictive value of plasma copeptin. The plasma copeptin in the group with POTS was significantly higher than that of the control group (10.827±2.459 pmol/L vs 8.845±1.471 pmol/L, P<.001). The plasma copeptin in responders to midodrine hydrochloride was significantly higher than that of nonresponders (12.082±1.998 pmol/L vs 9.646±2.301 pmol/L, P=.003). Receiver operating characteristic analysis on the predictive value of plasma copeptin showed that the area under the curve was 0.800 with a 95% CI of 0.640-0.959. Using a plasma copeptin level of 10.482 pmol/L as the cutoff point produced both favorite sensitivity (81.3%) and specificity (76.5%) in predicting the efficacy of midodrine hydrochloride therapy in children with POTS. Plasma copeptin may be considered as a predictive biomarker for the likelihood of successful treatment of children with POTS with midodrine hydrochloride.

Little is known about the effectiveness of abdominal and lower-extremity compression in treating postural tachycardia syndrome, particularly in younger patients. This repeated-measures study of 20 young patients with postural tachycardia syndrome demonstrates that compression during head-upright tilt table testing decreases tachycardia (P<.001) and effectively attenuates orthostatic symptoms.

At present, the haemodynamic diagnosis of orthostatic intolerance is based mainly on the head-up tilt table test, which is sometimes risky for patients. Thus, it is important to find objective and safe methods to differentiate haemodynamic patterns of orthostatic intolerance cases. In all, 629 children with orthostatic intolerance, either vasovagal syncope or postural orthostatic tachycardia syndrome, were included in the multi-centre clinical study. We analysed the association between the clinical manifestation and haemodynamic patterns of the patients. Syncope after motion with a prodrome of chest distress or palpitations and the concomitant symptom(s) after a syncopal attack, with debilitation, dizziness or headache, were the most important variables in predicting the diagnosis of vasovagal syncope. The overall diagnostic accuracy was 71.5%. Complaint of syncope after motion with prodromal chest distress or palpitation and the concomitant symptom after a syncopal attack, with subsequent debilitation, dizziness or headache, were the most important variables in the diagnosis of vasovagal syncope in children with orthostatic intolerance.

Postural orthostatic tachycardia syndrome (POTS) is characterized by chronic fatigue and dizziness and affected individuals by definition have orthostatic intolerance and tachycardia. There is considerable overlap of symptoms in patients with POTS and chronic fatigue syndrome (CFS), prompting speculation that POTS is akin to a deconditioned state. We previously showed that adolescents with postural orthostatic tachycardia syndrome (POTS) have excessive heart rate (HR) during, and slower HR recovery after, exercise - hallmarks of deconditioning. We also noted exaggerated cardiac output during exercise which led us to hypothesize that tachycardia could be a manifestation of a high output state rather than a consequence of deconditioning. We audited records of adolescents presenting with long-standing history of any mix of fatigue, dizziness, nausea, who underwent both head-up tilt table test and maximal exercise testing with measurement of cardiac output at rest plus 2-3 levels of exercise, and determined the cardiac output () versus oxygen uptake () relationship. Subjects with chronic fatigue were diagnosed with POTS if their HR rose ≥40 beat·min(-1) with head-up tilt. Among 107 POTS patients the distribution of slopes for the , relationship was skewed toward higher slopes but showed two peaks with a split at ~7.0 L·min(-1) per L·min(-1), designated as normal (5.08 ± 1.17, N = 66) and hyperkinetic (8.99 ± 1.31, N = 41) subgroups. In contrast, cardiac output rose appropriately with in 141 patients with chronic fatigue but without POTS, exhibiting a normal distribution and an average slope of 6.10 ± 2.09 L·min(-1) per L·min(-1). Mean arterial blood pressure and pulse pressure from rest to exercise rose similarly in both groups. We conclude that 40% of POTS adolescents demonstrate a hyperkinetic circulation during exercise. We attribute this to failure of normal regional vasoconstriction during exercise, such that patients must increase flow through an inappropriately vasodilated systemic circulation to maintain perfusion pressure.

The postural orthostatic tachycardia syndrome is a disease characterized by excessively increased heart rate during orthostatic challenge associated with symptoms of orthostatic intolerance including dizziness, exercise intolerance, headache, fatigue, memory problems, nausea, blurred vision, pallor, and sweating, which improve with recumbence. Postural orthostatic tachycardia syndrome patients may present with a multitude of additional symptoms that are attributable to vascular vasoconstriction. Observed signs and symptoms in a patient with postural orthostatic tachycardia syndrome include tachycardia at rest, exaggerated heart rate increase with upright position and exercise, crushing chest pain, tremor, syncope, loss of vision, confusion, migraines, fatigue, heat intolerance, parasthesia, dysesthesia, allodynia, altered traditional senses, and thermoregulatory abnormalities. There are a number of possible dermatological manifestations of postural orthostatic tachycardia syndrome easily explained by its recently discovered pathophysiology. The author reports the case of a 22-year-old woman with moderate-to-severe postural orthostatic tachycardia syndrome with numerous dermatological manifestations attributable to the disease process. The cutaneous manifestations observed in this patient are diverse and most noticeable during postural orthostatic tachycardia syndrome flares. The most distinct are evanescent, hyperemic, sharply demarcated, irregular patches on the chest and neck area that resolve upon diascopy. This distinct "evanescent hyperemia" disappears spontaneously after seconds to minutes and reappears unexpectedly. Other observed dermatological manifestations of this systemic disease include Raynaud's phenomenon, koilonychia, onychodystrophy, madarosis, dysesthesia, allodynia, telogen effluvium, increased capillary refill time, and livedo reticularis. The treatment of this disease poses a great challenge. The author reports the unprecedented use of an oral angiotensin II type 1 receptor antagonist resulting in remarkable improvement.

Metoprolol is clinically used to treat postural tachycardia syndrome (POTS) in children, but its effectiveness is unsatisfactory. Biomarkers to predict therapeutic efficacy are needed. We aimed to explore changes in the plasma copeptin level for assessing the therapeutic efficacy of metoprolol for POTS in children. We included 49 children with POTS and 25 healthy children as controls. Patients received metoprolol for 1.5 to 3 months. The plasma copeptin level was measured by sandwich immunoluminometric assay. The area under the receiver operating characteristic curve was used to explore the predictive value of the plasma copeptin level. The baseline plasma copeptin level was higher in children with POTS than controls (10.524 ± 2.016 vs 8.750 ± 1.419 pmol/L, p <0.001) and was lower for responders than nonresponders to metoprolol (9.377 ± 1.411 vs 12.054 ± 1.662 pmol/L, p = 0.003). The area under the receiver operating characteristic curve was 0.889 (95% confidence interval 0.799 to 0.980). With a baseline plasma copeptin level of 10.225 pmol/L as a cutoff, the sensitivity was 90.5% and specificity 78.6% in predicting the efficacy of metoprolol in children with POTS. In conclusion, the baseline plasma copeptin level can be used as a biomarker to predict the therapeutic effectiveness of metoprolol in children with POTS.

Syncope is a common presenting complaint in both the inpatient and outpatient settings. The main goals in the clinical evaluation of syncope are to identify an underlying etiology, to stratify risk and to guide plans for therapeutic intervention. Testing begins with an initial electrocardiogram to screen for any cardiac rhythm abnormalities. Heart rate variability to paced breathing provides a standard measure of cardiac parasympathetic function and offers clues towards an autonomic cause of syncope. A Valsalva maneuver is used to evaluate for parasympathetic dysfunction through the Valsalva ratio. In addition, sympathetic adrenergic function is assessed through evaluation of blood pressure response during the Valsalva maneuver. Abnormalities to the Valsalva maneuver can suggest clues towards an autonomic cause of syncope. Head-up tilt table testing is an important part of the autonomic evaluation of patients with syncope, and can be diagnostic for many disorders that result in syncope including orthostatic hypotension, neurally mediated syncope, postural tachycardia syndrome or delayed orthostatic hypotension. Autonomic function testing provides a safe and controlled environment for evaluation of patients, and plays a pivotal role in the diagnosis of syncope, particularly in challenging cases. While the initial clinical evaluation of syncope involves a detailed history and physical examination; in situations where the diagnosis is unknown, the addition of autonomic testing is complementary and can lead to identification of autonomic causes of syncope.

Postural tachycardia syndrome (POTS) is a heterogeneous disorder that creates challenges for treatment. Beta-blocker was one of the most commonly used drugs, but it is inconsistently effective. The purpose of this study is to explore whether orthostatic plasma norepinephrine level could be an indicator of therapeutic effectiveness of metoprolol for POTS in children. Twenty-seven children with POTS were enrolled in our study. They received metoprolol treatment, and their orthostatic plasma norepinephrine levels were measured by high-performance liquid chromatography method. Three months after rmetoprolol treatment, 25 patients were followed up. A receiver-operating characteristic (ROC) curve was used to explore the predictive value of orthostatic plasma norepinephrine level. The symptom severity and increment of heat rate from supine position to upright of patients positively correlated with their orthostatic plasma norepinephrine level (r=0.599, P<0.001; r=0.633, P<0.001, respectively). Orthostatic plasma norepinephrine level in responders to metoprolol was significantly higher than that of nonresponders (P=0.028). A ROC curve on the predictive value of orthostatic plasma norepinephrine level showed that the area under the curve was 0.785. Using a cutoff value for orthostatic plasma norepinephrine level of 3.59 pg/ml yielded both sensitivity (76.9%) and specificity (91.7%) in predicting the efficacy of metoprolol therapy for POTS. Orthostatic plasma norepinephrine level of>3.59 pg/ml was an indicator of the effectiveness of metoprolol therapy for POTS in children and adolescents.

Postural tachycardia syndrome (POTS) is associated with exercise intolerance, hypovolemia, and cardiac atrophy, which may contribute to reduced stroke volume and compensatory exaggerated heart rate (HR) increases. Acute volume loading with intravenous (iv) saline reduces HR and improves orthostatic tolerance and symptoms in POTS, but its effect on exercise capacity is unknown. In this study, we determined the effect of iv saline infusion on peak exercise capacity (VO2peak) in POTS. Nineteen patients with POTS participated in a sequential study. VO2peak was measured on two separate study days, following administration of placebo or 1 liter of i.v. saline (NaCl 0.9%). Patients exercised on a semirecumbent bicycle with resistance increased by 25 W every 2 min until maximal effort was achieved. Patients exhibited blood volume deficits (-13.4 ± 1.4% ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline significantly increased stroke volume (saline 80 ± 8 ml vs. placebo 64 ± 4 ml; P = 0.010), increased cardiac output (saline 6.9 ± 0.5 liter/min vs. placebo 5.7 ± 0.2 liter/min; P = 0.021), and reduced systemic vascular resistance (saline 992.6 ± 70.0 dyn-s/cm(5) vs. placebo 1,184.0 ± 50.8 dyn-s/cm(5); P = 0.011), with no effect on HR or blood pressure. During exercise, saline did not produce differences in VO2peak (saline 26.3 ± 1.2 mg·kg(-1)·min(-1) vs. placebo 27.7 ± 1.8 mg·kg(-1)·min(-1); P = 0.615), peak HR [saline 174 ± 4 beats per minute (bpm) vs. placebo 175 ± 3 bpm; P = 0.672] or other cardiovascular parameters. These findings suggest that acute volume loading with saline does not improve VO2peak or cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function.

Whether non-dipping - the loss of the physiologic nocturnal drop in blood pressure - among patients with postural tachycardia syndrome (POTS) is secondary to autonomic neuropathy, a hyperadrenergic state, or other factors remains to be determined. In 51 patients with POTS (44 females), we retrospectively analyzed 24-hour ambulatory blood pressure recordings, laboratory indices of autonomic function, orthostatic norepinephrine response, 24-hour natriuresis and peak exercise oxygen consumption. Non-dipping (<10% day-night drop in systolic blood pressure) was found in 55% (n=28). Dippers and non-dippers did not differ in: 1) baseline characteristics including demographic and clinical profile, sleep duration, daytime blood pressure, 24-hour natriuresis, and peak exercise oxygen consumption; 2) severity of laboratory autonomic deficits (sudomotor, cardiovagal and adrenergic); 3) frequency of autonomic neuropathy (7/23 vs. 8/28, P=0.885); 4) supine resting heart rate (75.3±14.0bpm vs. 74.0±13.8bpm, P=0.532); or 5) supine plasma norepinephrine level (250.0±94.9pg/ml vs. 207.0±86.8pg/ml, P=0.08). However, dippers differed significantly from non-dippers in that they had significantly greater orthostatic heart rate increment (43±16bpm vs. 35±10bpm, P=0.007) and significantly greater orthostatic plasma norepinephrine increase (293±136.6pg/ml vs. 209±91.1pg/ml, P=0.028). Our data indicate that in patients with POTS, a non-dipping blood pressure profile is associated with a reduced orthostatic sympathetic reactivity not accounted for by autonomic neuropathy.

Postural tachycardia syndrome and vasovagal syncope are common causes of orthostatic intolerance in children. The supplementation with water, or salt, or midodrine, or β-blocker was applied to children with postural tachycardia syndrome or vasovagal syncope. However, the efficacy of such medication varied and was not satisfied. This review aimed to summarise the current biomarkers in the treatment of the diseases. Studies were collected from online electronic databases, including OVID Medline, PubMed, ISI Web of Science, and associated references. The main areas assessed in the included studies were clinical improvement, the cure rate, and the individualised treatment for postural tachycardia syndrome and vasovagal syncope in children. Haemodynamic change during head-up tilt test, and detection of 24-hour urinary sodium excretion, flow-mediated vasodilation, erythrocytic H₂S, and plasma pro-adrenomedullin as biological markers were the new ways that were inexpensive, non-invasive, and easy to test for finding those who would be suitable for a specific drug and treatment. With the help of biomarkers, the therapeutic efficacy was greatly increased for children with postural tachycardia syndrome and vasovagal syncope.

To determine whether there is altered autonomic function associated with elevated heart rate increments on head-up tilt (HUT) in younger individuals. A total of 149 subjects were enrolled in this study. Subjects underwent the autonomic reflex screen including HUT and completed the Autonomic Symptom Profile. Heart rate increment on HUT did not show a correlation with Composite Autonomic Severity Score (CASS) and the individual CASS scores were low (score 0/10, n=103; score 1/10, n=27; score 2/10, n=1; score 3/10, n=2). There was no correlation with multiple autonomic domains assessed by the Autonomic Symptom Profile. However, there were significant inverse correlations between heart rate increment and total COMPASS score including male sexual dysfunction (r=-0.318; p=0.011; n=64), bladder (r=-0.209; p=0.014; n=138), pupillomotor (r=-0.235; p=0.006; n=138) and male sexual dysfunction (r=-0.554; p<0.0001; n=64). These domains showed a positive correlation with age and a significant effect of age but not heart rate increment with regression analysis (except pupillomotor domain). These results argue against a reduction in autonomic function underlying the higher heart rate increments seen on HUT in younger individuals. These findings argue that the development of Postural Tachycardia Syndrome involves mechanisms that potentially occur independently of heart rate increment.