While orthostatic tachycardia is the hallmark of postural tachycardia syndrome (POTS), orthostasis also initiates increased minute ventilation (Ve) and decreased end-tidal CO(2) in many patients. We hypothesized that chemoreflex sensitivity would be increased in patients with POTS. We therefore measured chemoreceptor sensitivity in 20 POTS (16 women and 4 men) and 14 healthy controls (10 women and 4 men), 16-35 yr old by exposing them to eucapneic hyperoxia (30% O(2)), eucapneic hypoxia (10% O(2)), and hypercapnic hyperoxia (30% O(2) + 5% CO(2)) while supine and during 70° head-upright tilt. Heart rate, mean arterial pressure, O(2) saturation, end-tidal CO(2), and Ve were measured. Peripheral chemoreflex sensitivity was calculated as the difference in Ve during hypoxia compared with room air divided by the change in O(2) saturation. Central chemoreflex sensitivity was determined by the difference in Ve during hypercapnia divided by the change in CO(2). POTS subjects had an increased peripheral chemoreflex sensitivity (in l·min(-1)·%oxygen(-1)) in response to hypoxia (0.42 ± 0.38 vs. 0.19 ± 0.17) but a decreased central chemoreflex sensitivity (l·min(-1)·Torr(-1)) CO(2) response (0.49 ± 0.38 vs. 1.04 ± 0.18) compared with controls. CO(2) sensitivity was also reduced in POTS subjects when supine. POTS patients are markedly sensitized to hypoxia when upright but desensitized to CO(2) while upright or supine. The interactions between orthostatic baroreflex unloading and altered chemoreflex sensitivities may explain the hyperventilation in POTS patients.

A 37-year-old male was admitted with history of syncope and fall leading to right temporal bone fracture with extradural haemorrhage. He underwent craniotomy and clot evacuation. Postoperatively during inpatient rehabilitation, he was progressing well with his physical and cognitive rehabilitation, when he had resting tachycardia of between 90 and 100 per minute. Investigations to rule out cardio-pulmonary and endocrine causes of tachycardia were normal. He was further investigated for suspected postural orthostatic tachycardia syndrome (POTS). A tilt table test was done which revealed rise in baseline heart rate from 90/min to 130/min on 70 with no postural drop in blood pressure. Subsequently plasma norepinephrine level in erect posture was analysed which was 721 pg/ml. A working diagnosis of POTS was made. Initially, after an increase in water intake by 1.5-2 l/day, his baseline and postural tachycardia reverted back to 76/min. He is being followed up.

More than 10% of adolescents suffer from severe fatigue and/or orthostatic intolerance. Adult studies show correlations between iron insufficiency and fatigue as well as between hypovitaminosis D and non-specific pain. We sought to determine whether there were correlations between nutritional factors (iron status, and serum vitamin D levels) and chronic ill health. We reviewed records of 188 adolescents with symptoms of fatigue and/or orthostatic intolerance and who underwent autonomic reflex screening. Of the 188 patients, 130 patients (69%) had excessive postural tachycardia (PT) with a heart rate (HR) change of ≥30 bpm. 62 patients (47%, n = 131) had iron insufficiency with low iron stores, and 29 patients (22%, n = 131) were iron deficient. HR change did not correlate to ferritin level (P = 0.15). 21 patients (22%, n = 95) had hypovitaminosis D (25-hydroxyvitamin D ≤20 ng/mL). There was a significant association with hypovitaminosis D and orthostatic intolerance (P = 0.024). In patients presenting with chronic fatigue and/or orthostatic intolerance, low ferritin levels and hypovitaminosis D are common, especially in patients with PT.

To investigate whether patients with postural orthostatic tachycardia syndrome (POTS) developed unexpected perioperative complications. Retrospective case series. Academic medical center. The records of 13 patients with POTS, who underwent surgical procedures during general anesthesia, were studied. Details of disease management, anesthetic induction, hemodynamic response to induction and intubation, intraoperative course, and immediate postoperative management were analyzed. Three patients developed prolonged intraoperative hypotension, which was not associated with induction of anesthesia. All 13 patients were successfully treated and they recovered without complications. There were no unplanned hospital or intensive care admissions. Intraoperative hypotension, but not tachycardia, was observed in three of 13 patients with POTS who received general anesthesia for a variety of surgical procedures using multiple medications and techniques.

We have found recently that exercise training is effective in the treatment of the postural orthostatic tachycardia syndrome (POTS). Whether this nondrug treatment is superior to "standard" drug therapies, such as β-blockade, is unknown. We tested the hypothesis that exercise training but not β-blockade treatment improves symptoms, hemodynamics, and renal-adrenal responses in POTS patients. Nineteen patients (18 women and 1 man) completed a double-blind drug trial (propranolol or placebo) for 4 weeks, followed by 3 months of exercise training. Fifteen age-matched healthy individuals (14 women and 1 man) served as controls. A 2-hour standing test was performed before and after drug treatment and training. Hemodynamics, catecholamines, plasma renin activity, and aldosterone were measured supine and during 2-hour standing. We found that both propranolol and training significantly lowered standing heart rate. Standing cardiac output was lowered after propranolol treatment (P=0.01) but was minimally changed after training. The aldosterone:renin ratio during 2-hour standing remained unchanged after propranolol treatment (4.1±1.7 [SD] before versus 3.9±2.0 after; P=0.46) but modestly increased after training (5.2±2.9 versus 6.5±3.0; P=0.05). Plasma catecholamines were not affected by propranolol or training. Patient quality of life, assessed using the 36-item Short-Form Health Survey, was improved after training (physical functioning score 33±10 before versus 50±9 after; social functioning score 37±9 versus 48±6; both P<0.01) but not after propranolol treatment (34±10 versus 36±11, P=0.63; 39±7 versus 39±5, P=0.73). These results suggest that, for patients with POTS, exercise training is superior to propranolol at restoring upright hemodynamics, normalizing renal-adrenal responsiveness, and improving quality of life.

Reports of the outcomes of syncope assessment across a broad spectrum of ages in a single population are scarce. It is our objective to chart the varying prevalence of orthostatic and neurocardiogenic syncope (NCS) as a patient ages. This was a retrospective study. All consecutive patients referred to a tertiary referral syncope unit over a decade were included. Patients were referred with recurrent falls or orthostatic intolerance. Tilt tests and carotid sinus massage (CSM) were performed in accordance with best practice guidelines. A total of 3002 patients were included (1451 short tilt, 127 active stand, 1042 CSM and 382 prolonged tilt). Ages ranged from 11 to 91 years with a median (IQR) of 75 (62-81) years. There were 1914 females; 1088 males. Orthostatic hypotension (OH) was the most commonly observed abnormality (test positivity of 60.3%). Those with OH had a median (IQR) age of 78 (71-83) years. Symptomatic patients were significantly younger than asymptomatic (P = 0.03). NCS demonstrated a bimodal age distribution. Of 194 patients with carotid sinus hypersensitivity, the median age (IQR) was 77 (68-82) years. Those with vasovagal syncope (n = 80) had a median (IQR) age of 30 (19-44) years. There were 57 patients with isolated postural orthostatic tachycardia syndrome. Of the total patients, 75% were female. They had a median (IQR) age of 23 (17-29) years. We have confirmed, in a single population, a changing pattern in the aetiology of syncope as a person ages. The burden of disease is greatest in the elderly.

Models of microgravity are linked to excessive constitutive nitric oxide (NO) synthase (NOS), splanchnic vasodilation, and orthostatic intolerance. Normal-flow postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance associated with splanchnic hyperemia. To test the hypothesis that there is excessive constitutive NOS in POTS, we determined whether cutaneous microvascular neuronal NO and endothelial NO are increased. We performed two sets of experiments in POTS and control subjects aged 21.4 ± 2 yr. We used laser-Doppler flowmetry to measure the cutaneous response to local heating as an indicator of bioavailable neuronal NO. To test for bioavailable endothelial NO, we infused intradermal acetylcholine through intradermal microdialysis catheters and used the selective neuronal NOS inhibitor l-N(ω)-nitroarginine-2,4-L-diamino-butyric amide (N(ω), 10 mM), the selective inducible NOS inhibitor aminoguanidine (10 mM), the nonspecific NOS inhibitor nitro-l-arginine (NLA, 10 mM), or Ringer solution. The acetylcholine dose response and the NO-dependent plateau of the local heating response were increased in POTS compared with those in control subjects. The local heating plateau was significantly higher, 98 ± 1%maximum cutaneous vascular conductance (%CVC(max)) in POTS compared with 88 ± 2%CVC(max) in control subjects but decreased to the same level with N(ω) (46 ± 5%CVC(max) in POTS compared with 49 ± 4%CVC(max) in control) or with NLA (45 ± 3%CVC(max) in POTS compared with 47 ± 4%CVC(max) in control). Only NLA blunted the acetylcholine dose response, indicating that NO produced by endothelial NOS was released by acetylcholine. Aminoguanidine was without effect. This is consistent with increased endothelial and neuronal NOS activity in normal-flow POTS.

Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVC(max)) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVC(max)). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.

Incidence and rate of cardiovascular disease differ between men and women across the life span. Although hypertension is more prominent in men than women, there is a group of vasomotor disorders [i.e. Raynaud's disease, postural orthostatic tachycardia syndrome and vasomotor symptoms (hot flashes) of menopause and migraine] with a female predominance. Both sex and hormones interact to modulate neuroeffector mechanisms including integrated regulation of the Sry gene and direct effect of sex steroid hormones on synthesis, release and disposition of monoamine neurotransmitters, and distribution and sensitivity of their receptors in brain areas associated with autonomic control. The interaction of the sex chromosomes and steroids also modulates these effector tissues, that is, the heart, vascular smooth muscle and endothelium. Although involvement of central serotonergic centres has been studied in regard to mood disorders such as depression, their contribution to cardiovascular risk is gaining attention. Studies are needed to further evaluate how hormonal treatments and drugs used to modulate adrenergic and serotonergic activity affect progression and risk for cardiovascular disease in men and women.

Postural orthostatic tachycardia syndrome (POTS) is a common clinical problem in children and adolescents. The previous diagnostic approach to POTS of children and adolescents is based on a series of tests to exclude all other causes, which is time and medical resource consuming. Recently, a new diagnostic approach has been developed. The present study was designed to statistically analyze the results of clinical investigation items and the cost for the diagnosis of POTS in children patients, and evaluate cost changes in the diagnosis of POTS. A total of 315 children patients were divided into two groups according to diagnosis period, including group I diagnosed in 2002 - 2006 (100 cases) and group II in 2007 - 2010 (215 cases) and the diagnostic item-based distribution of the cost was analyzed. The diagnostic costs were compared between two groups using SPSS17.0. The per-capita cost of diagnosis in group I was (621.95 ± 21.10) Yuan, costs of diagnostic tests (head-up tilt test, standing test, etc) accounted for 8.68% and the exclusive tests for 91.32%. The per-capita cost of diagnosis in group II was (542.69 ± 23.14) Yuan, diagnostic tests accounted for 10.50% and exclusive tests for 89.50%. Comparison of the total cost of diagnostic tests between the two groups showed significant differences (P < 0.05). The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part.

We studied the cerebral autoregulation in a subgroup of patients with orthostatic intolerance, who exhibited excessively decreased middle cerebral artery flow velocity (MCAFV) on transcranial Doppler sonography (TCD) during head-up tilt (HUT) test but without orthostatic hypotension or postural tachycardia. Twenty patients and 20 age- and sex-matched controls underwent Valsalva maneuver (VM) and HUT test with simultaneous monitoring of MCAFV by TCD and blood pressure, heart rate recordings. The pulsatility index (PI), cerebrovascular resistance (CVR) and autoregulatory indices were calculated. During HUT, patients had marked MCAFV reduction (-29.0 ± 5.25% vs. -8.01 ± 4.37%), paradoxically decreased PI (0.68 ± 0.17 vs. 0.96 ± 0.28) but increased CVR (45.7 ± 16.7% vs. 14.3 ± 12.6%). The MCAFV decreased similarly during early phase II of VM in both groups but did not recover to baseline in patients during late phase II, phase III and less overshoot in phase IV (-11 ± 16.7% vs. +2.2 ± 17.9 %; -15.4 ± 16.5% vs. -2.4 ± 17.8% and 16.7 ± 22.9% vs. 38.7 ± 26.5%, respectively). We concluded that in these patients, cerebrovascular vasoconstriction in response to physiologic stimulation was normal but relaxation during and after stimulation were impaired, indicating prolonged cerebral vasoconstriction.

Syncope occurs frequently in adolescents, and is often benign. Potential worrisome syncopal events include those occurring with exertion, concurrent chest pain, dyspnoea or palpitations, and those with focal or diffuse neurologic changes. A 16-year-old female was referred to our institution for a history of exercise-induced spells. She was diagnosed since the age of 2 years with neurocardiogenic syncope and postural orthostatic tachycardia syndrome. She had been evaluated at multiple institutions, and was followed by pediatric neurology for a diagnosis of migraines. Owing to recurrent worsening symptoms and a syncopal episode requiring resuscitation, an echocardiogram was performed. The right coronary was normal, but the left coronary artery ostium could not be identified well. Doppler patterns were suspicious of an abnormal left coronary artery, and computed tomography angiography was performed. This revealed a single coronary artery arising from the right aortic sinus, with the left coronary artery arising from the proximal coronary trunk and coursing through the infundibular septum. This was surgically treated utilising a left internal mammary artery bypass graft to the left anterior descending coronary artery. A year later, she has not experienced any recurrence of syncope, and has returned to athletic activity. This case highlights the index of suspicion that must be present when evaluating any patient with syncope, both clinically and via echocardiography. A computed tomography angiogram is indicated for better evaluation of coronary artery anatomy when an anomalous coronary cannot be ruled out by echocardiography.

Ablate and pace for POTS. A 42-year-old woman with postural tachycardia syndrome (POTS) was admitted to our hospital with severe palpitations, light-headedness, and syncope. Several drugs had been administered previously, but all had been discontinued due to intolerable adverse effects or limited efficacy. One of the drugs, the I(f) current inhibitor ivabradine, effectively slowed the patient's heart rate and relieved the symptoms, but was discontinued due to allergy. After unsuccessful sinus node ablation, atrioventricular node ablation and dual chamber pacemaker implantation was performed, which dramatically improved her symptoms and eliminated syncope. Atrioventricular node ablation could modify the cardiac autonomic balance and thereby suppressed the excessive orthostatic sympathetic activity.

The aim of this study was to determine whether patients who faint earlier in the course of a tilt table study represent a separate population with a poorer prognosis or different pathophysiology. We analyzed differences across patients with different syncopal times on the tilt-table study to answer this question. This was a retrospective, approved, chart review. From our database of over 6000 patients, we identified 1222 patients with syncope. After excluding patients with orthostatic hypotension, postural tachycardia syndrome and diabetes, we were left with 131 patients with pure reflex syncope. We divided fainters into an early (<20 minutes) and late (>20 minutes) faint times. Along with the tilt table test all patients underwent heart rate response for deep breathing, Valsalva maneuver and quantitative sudomotor axon reflex tests. By 10 minutes in the tilt study, only 18% of subjects had fainted, 65% by 20 minutes, 92% by 30 minutes and 96% by 35 minutes. Age was evenly distributed across all syncopal times. Neither the 14 abnormal cardiac responses to deep breathing nor the 20 abnormal Valsalva maneuvers, nor the 28 abnormal axon reflex responses clustered with an early or late faint time. A 10-minute tilt will miss 82% of syncopal episodes, while a 30- minute tilt increases the yield 10-fold, missing only 8%. Patients with early faint times did not differ from patients with late fainting times with regard to age or autonomic test abnormalities. Timing of syncope during the tilt table test does not associated with more severe dysautonomia. A prospective study is needed to confirm these observations.

Postural tachycardia syndrome (PoTS) is a poorly understood but important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. PoTS is distinct from the syndromes of autonomic failure usually associated with orthostatic hypotension, such as pure autonomic failure and multiple system atrophy. Individuals affected by PoTS are mainly young (aged between 15 years and 40 years) and predominantly female. The symptoms--palpitations, dizziness and occasionally syncope--mainly occur when the patient is standing upright, and are often relieved by sitting or lying flat. Common stimuli in daily life, such as modest exertion, food ingestion and heat, are now recognized to be capable of exacerbating the symptoms. Onset of the syndrome can be linked to infection, trauma, surgery or stress. PoTS can be associated with various other disorders; in particular, joint hypermobility syndrome (also known as Ehlers-Danlos syndrome hypermobility type, formerly termed Ehlers-Danlos syndrome type III). This Review describes the characteristics and neuroepidemiology of PoTS, and outlines possible pathophysiological mechanisms of this syndrome, as well as current and investigational treatments.

OBJECTIVE. To describe the reasons for referral, autonomic diagnoses, test results, and patient management in a large pediatric population referred for testing for an autonomic disorder. DESIGN. The authors reviewed autonomic testing data and medical records for patients aged 18 years and younger who underwent testing between 1993 and 2007 and who had adequate clinical data. Relevance of test results to clinical symptoms was ranked on a 3-point scale. Treatments were noted and their benefit ranked on a 5-point scale. RESULTS. Among 142 pediatric patients identified, postural tachycardia syndrome was most common (71%) while orthostatic hypotension was rare (5%). Testing provided relevant information regarding the patient's symptoms in 88% of the cases. Beta-blockers were the most commonly prescribed medication (59%); 73% improved. CONCLUSIONS. Postural tachycardia syndrome was common in this large pediatric population, whereas orthostatic hypotension was infrequent. The symptomatic improvement in the majority bears an unclear relationship to treatment. Prospective studies are needed.

Patients with POTS (postural tachycardia syndrome) have excessive orthostatic tachycardia (>30 beats/min) when standing from a supine position. HR (heart rate) and BP (blood pressure) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR and BP is not known. In the present study, we tested the hypothesis that there is diurnal variation of orthostatic HR and BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR and BP were obtained in the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning (102±3 beats/min) than in the evening (93±2 beats/min; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 beats/min in the morning compared with 100±3 beats/min in the evening; P=0.012) and controls (89±3 beats/min in the morning compared with 80±2 beats/min in the evening; P=0.005) when analysed separately. There was no diurnal variability in orthostatic BP in POTS. A greater number of subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared with the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.

There have been reports on the use of octreotide in patients with orthostatic hypotension, postural tachycardia syndrome, and orthostatic syncope. However, there are little if any data on the use of octreotide in patients who have failed multiple other medications. This study was a retrospective chart analysis and was approved by our Institutional Review Board. A total of 12 patients were identified for inclusion in this study. The diagnosis of orthostatic intolerance was based on patient history, physical examination, and response to Head Up Tilt Table testing. These patients had failed multiple medications and were ultimately treated with octreotide. In a retrospective chart review, we collected data, including demographic information, presenting symptoms, laboratory data, tilt-table response, standing heart rate, standing blood pressure before and after treatment (wherever available), and treatment outcomes. Twelve patients aged 33 ± 18 years, eight (66.7%) females, were found to have symptoms of refractory orthostatic intolerance and failed multiple regimens of medication and were ultimately treated with octreotide administration. Five patients (41.7%) had demonstrated a postural tachycardia syndrome pattern, five (41.7%) a neurocardiogenic, and two (16.6%) a dysautonomic response on a Head Up Tilt Table. Symptoms of syncope and orthostatic palpitations improved in six (50%) of the patients. Standing heart rate was significantly reduced after octreotide administration (80 ± 8 versus 108 ± 13; P < 0.05). The standing systolic blood pressure was increased after octreotide administration (107 ± 26 versus 116 ± 22). Three patients (25%) reported complete elimination of syncope, whereas another three had reduction in the frequency of their syncope. However, symptoms of fatigue improved only in two (29%) of the seven patients. Octreotide may improve symptoms in some patients with refractory orthostatic intolerance.

Methylphenidate has been shown to be an effective therapy in patients with refractory neurocardiogenic syncope. However, the role of methylphenidate in patients suffering from postural orthostatic tachycardia (POTS) has not been reported. The study was approved by the institutional review board. A retrospective nonrandomized analysis was preformed on 24 patients evaluated at our autonomic center for POTS from 2003 to 2010. The diagnosis of POTS was based on patient history, physical examination, and response to head up tilt table testing. The mean follow-up period was 9 ± 3 months. The patients were included in the current study if they had a diagnosis of POTS with severe symptoms of orthostatic intolerance and were refractory to the commonly used medications. All of these patients were started on methylphenidate and the response to therapy was considered successful if it provided symptomatic relief. Twenty-four patients (age 28 ± 12, 20 women) met inclusion criterion for this study. The response to treatment was assed subjectively in each patient and was collected in a retrospective fashion from patient charts and physician communications. Four patients reported side effects in the form of nausea and 2 ultimately had to discontinue the treatment. Another 4 patients had a follow-up of less than 6 months. Thus, only 18 patients who received methylphenidate completed the follow-up of 6 months. Out of these 18 patients, 14 (77%) patients reported marked improvement in their symptoms. Nine out of 12 patients who had recurrent episodes of syncope reported no syncope at 6 months of follow-up. Fourteen (77%) patients reported marked improvement in their symptoms of fatigue and presyncope. Four patients continue to have symptoms of orthostatic intolerance and 3 continued to have recurrent episodes of syncope. Methylphenidate may be beneficial in patients with otherwise refractory postural tachycardia syndrome.

This article reviews microneurographic research on sympathetic neural control in women under both physiological and pathophysiological conditions across the lifespan. Specifically, the effects of sex, age, race, the menstrual cycle, oral contraceptives, estrogen replacement therapy, and normal pregnancy on neural control of blood pressure in healthy women are reviewed. In addition, sympathetic neural activity during neurally mediated (pre)syncope, the Postural Orthostatic Tachycardia Syndrome (POTS), obesity, the Polycystic Ovary Syndrome (PCOS), gestational hypertension, and preeclampsia, chronic essential hypertension, heart failure, and myocardial infarction in women are also reviewed briefly. It is suggested that microneurographic studies provide valuable information regarding autonomic circulatory control in women of different ages and in most cases, excessive sympathetic activation is associated with specific medical conditions regardless of age and sex. In some situations, sympathetic inhibition or withdrawal may be the underlying mechanism. Information gained from previous and recent microneurographic studies has significant clinical implications in women's health, and in some cases could be used to guide therapy if more widely available.

Postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia and significant functional disability. We have previously found that patients with POTS have increases in plasma angiotensin II (Ang II) that are twice as high as healthy subjects despite normal blood pressures (BPs). In this study, we assess systemic and renal hemodynamic and functional responses to Ang II infusion in patients with POTS compared with healthy controls. Following a 3-day sodium-controlled diet, we infused Ang II (3 ng/kg per minute) for 1 hour in patients with POTS (n=15) and healthy controls (n=13) in the supine position. All study subjects were women with normal BP. Ages were similar for patients with POTS and controls (mean±SEM, 30±2 versus 26±1 years; P=0.11). We measured the changes from baseline mean arterial pressure, renal plasma flow, plasma renin activity, aldosterone, urine sodium, and baroreflex sensitivity in both groups. In response to Ang II infusion, patients with POTS had a blunted increase compared with controls in mean arterial pressure (10±1 versus 14±1 mm Hg, P=0.01) and diastolic BP (9±1 versus 13±1 mm Hg, P=0.01) but not systolic BP (13±2 versus 15±2 mm Hg, P=0.40). Renal plasma flow decreased similarly with Ang II infusion in patients with POTS versus controls (-166±20 versus -181±17 mL/min per 1.73 kg/m(2), P=0.58). Postinfusion, the decrease in plasma renin activity (-0.9±0.2 versus -0.6±0.2 ng/mL per hour, P=0.43) and the increase in aldosterone (17±1 versus 15±2 pg/mL, P=0.34) were similar in both groups. The decrease in urine sodium excretion was similar in patients with POTS and controls (-49±12 versus -60±16 mEq/g creatinine, P=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in patients with POTS compared with controls (10.1±1.2 versus 16.8±1.5 ms/mm Hg, P=0.003), and it was further reduced with Ang II infusion. Patients with POTS have blunted vasopressor response to Ang II and impaired baroreflex function. This impaired vasoconstrictive response might be exaggerated with upright posture and may contribute to the subsequent orthostatic tachycardia that is the hallmark of this disorder. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962949.

To evaluate whether the use of adult heart rate (HR) criteria is appropriate for diagnosing orthostatic intolerance (OI) and postural tachycardia syndrome (POTS) in children and adolescents, and to establish normative data and diagnostic criteria for pediatric OI and POTS. A total of 106 normal controls aged 8-19 years (mean age, 14.5±3.3 years) underwent standardized autonomic testing, including 5 minutes of 70-degree head-up tilt. The orthostatic HR increment and absolute orthostatic HR were assessed and retrospectively compared with values in 654 pediatric patients of similar age (mean age, 15.5±2.3 years) who were referred to our Clinical Autonomic Laboratory with symptoms of OI. The HR increment was mildly higher in patients referred for OI/POTS, but there was considerable overlap between the patient and control groups. Some 42% of the normal controls had an HR increment of ≥30 beats per minute. The 95th percentile for the orthostatic HR increment in the normal controls was 42.9 beats per minute. There was a greater and more consistent difference in absolute orthostatic HR between the 2 groups, although there was still considerable overlap. The diagnostic criteria for OI and POTS in adults are unsuitable for children and adolescents. Based on our normative data, we propose new criteria for the diagnosis of OI and POTS in children and adolescents.

To explore the predictive value of plasma hydrogen sulfide (H(2)S) in differentiating between vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children. Patients were divided between the POTS group (n=60) and VVS group (n=17) by using either the head-up test or head-up tilt test. Twenty-eight healthy children were selected for the control group. Plasma concentrations of H(2)S were determined for children in all groups (POTS, VVS, and control). Plasma levels of H(2)S were significantly higher in children with VVS (95.3±3.8 μmol/L) and POTS (100.9±2.1 μmol/L) than in children in the control group (82.6±6.5 μmol/L). Compared with the VVS group, the POTS group had plasma levels of H(2)S that were significantly increased. The receiver operating characteristic curve for the predictive value of H(2)S differentiation of VVS from POTS showed a H(2)S plasma level of 98 μmol/L as the cutoff value for high probability of distinction. Such a level produced both high sensitivity (90%) and specificity (80%) rates of correctly discriminating between patients with VVS and patients with POTS. H(2)S plasma level has both high sensitivity and specificity rates to predict the probability of correctly differentiating between patients with VVS and patients with POTS.

Several studies recognized an overlap between CFS (chronic fatigue syndrome) and POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal phenotype of POTS patients with CFS (CFS-POTS) to those without CFS (non-CFS-POTS), to determine whether CFS-POTS represents a unique clinical entity with a distinct pathophysiology. We recruited 58 patients with POTS, of which 47 were eligible to participate. A total of 93% of them reported severe fatigue [CIS (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30) fulfilled criteria for CFS (CFS-POTS). The prevalence of CFS symptoms (Centers for Disease Control and Prevention criteria) was greater in the CFS-POTS group, but the pattern of symptoms was similar in both groups. Physical functioning was low in both groups (RAND-36 Health Survey, 40±4 compared with 33±3; P=0.153), despite more severe fatigue in CFS-POTS patients (CIS fatigue subscale 51±1 compared with 43±3; P=0.016). CFS-POTS patients had greater orthostatic tachycardia than the non-CFS-POTS group (51±3 compared with 40±4 beats/min; P=0.030), greater low-frequency variability of BP (blood pressure; 6.3±0.7 compared with 4.8±1.0 mmHg2; P=0.019), greater BP recovery from early to late phase II of the Valsalva manoeuvre (18±3 compared with 11±2 mmHg; P=0.041) and a higher supine (1.5±0.2 compared with 1.0±0.3 ng/ml per·h; P=0.033) and upright (5.4±0.6 compared with 3.5±0.8 ng/ml per h; P=0.032) PRA (plasma renin activity). In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.

A 28-year-old female with a history of situational syncope and a new-onset right sided hemiparesis is described. Tilt-up table test revealed the postural orthostatic tachycardia syndrome followed by vasovagal syncope. Neurological and internal medicine tests showed no particular disorders. The patient underwent autonomic physical training and the tilt-up test performed three months later showed improvement of the autonomic system in terms of lower heart beat rate of the postural orthostatic tachycardia syndrome and longer duration of the test. This case report describes longstanding idiopathic dysautonomia that can be improved by nonpharmacological treatment, while reminding that this medical condition may also be the cause of syncope.