Patients with postural tachycardia syndrome (POTS) are characterized by development of symptoms of orthostatic intolerance during standing that are not because of hypotension but are associated with tachycardia. The goal of this study was to compare the cardiac and vascular responses to orthostatic stress for patients with POTS (n = 8) with those for patients with low orthostatic tolerance (n = 29) and for healthy control subjects (n = 12). Responses of heart rate (ECG), arterial blood pressure, and brachial artery blood velocity (Doppler) were determined during a progressive orthostatic stress test of head-up tilt and lower body suction. Changes in forearm vascular resistance (mean arterial pressure/brachial velocity) were less for patients with POTS than for healthy persons, and also less than for most of the patients with low orthostatic tolerance. However, patients with POTS did not have a low tolerance to orthostatic stress (measured as time to discontinuation of the test). For the patients with POTS, the test was discontinued often because of symptoms associated with tachycardia but not hypotension, whereas for the other two groups, the test was discontinued because of hypotension. This study shows that for patients with POTS, abnormal sympathetic responses exist, with an increased sympathetic drive to the heart but deficient peripheral vascular responses, as measured in the forearm. This supports the hypothesis that patients with POTS may have a selective peripheral neuropathy, with small responses in some regions being compensated by overactivity in other regions.

To compare the hemodynamic and ventilatory responses to autonomic challenge evoked by upright tilt table testing in patients with chronic fatigue syndrome (CFS) to healthy individuals. Thirty-two consecutive patients with CFS and 32 healthy volunteers were evaluated with the aid of the recently introduced capnography head-up tilt test (CHUTT). The main outcome measures were values of blood pressure (BP), heart rate (HR), respiratory rate (RR), and end-tidal pressure of co2 (ETPco2) recorded during recumbence and tilt. In addition, the end points of vasodepressor and cardioinhibitory reactions, hyperventilation (defined by ETPco2 <25 mm Hg) and the postural tachycardia syndrome, were recorded. The BP, HR, RR, and ETPco2 recorded during recumbence were similar in both groups. During tilt, patients with CFS developed significantly lower systolic BP, diastolic BP, and ETPco2, and a significant rise in HR and RR (P<.01). In CFS patients, the postural tachycardia syndrome occurred in 44%, vasodepressor reaction in 41%, cardioinhibitory reaction in 13%, and hyperventilation in 31% of cases. One or more end points of the CHUTT were reached in 78% of patients with CFS but in none of the controls (P<.0001). In most patients with CFS, a spectrum of abnormal homeostatic reactions is diagnosed with the aid of the CHUTT. Data provided by the CHUTT may reinforce the clinical diagnosis by adding objective and unbiased criteria to the subjective assessment of CFS.

Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(-1)) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.

The postural tachycardia syndrome is a common disorder that is characterized by chronic orthostatic symptoms and a dramatic increase in heart rate on standing, but that does not involve orthostatic hypotension. Several lines of evidence indicate that this disorder may result from sympathetic denervation of the legs. We measured norepinephrine spillover (the rate of entry of norepinephrine into the venous circulation) in the arms and legs both before and in response to exposure to three stimuli (the cold pressor test, sodium nitroprusside infusion, and tyramine infusion) in 10 patients with the postural tachycardia syndrome and in 8 age- and sex-matched normal subjects. At base line, the mean (+/-SD) plasma norepinephrine concentration in the femoral vein was lower in the patients with the postural tachycardia syndrome than in the normal subjects (135+/-30 vs. 215+/-55 pg per milliliter [0.80+/-0.18 vs. 1.27+/-0.32 nmol per liter], P=0.001). Norepinephrine spillover in the arms increased to a similar extent in the two groups in response to each of the three stimuli, but the increases in the legs were smaller in the patients with the postural tachycardia syndrome than in the normal subjects (0.001+/-0.09 vs. 0.12+/-0.12 ng per minute per deciliter of tissue [0.006+/-0.53 vs. 0.71+/-0.71 nmol per minute per deciliter] with the cold pressor test, P=0.02; 0.02+/-0.07 vs. 0.23+/-0.17 ng per minute per deciliter [0.12+/-0.41 vs. 1.36+/-1.00 nmol per minute per deciliter] with nitroprusside infusion, P=0.01; and 0.008+/-0.09 vs. 0.19+/-0.25 ng per minute per deciliter [0.05+/-0.53 vs. 1.12+/-1.47 nmol per minute per deciliter] with tyramine infusion, P=0.04). The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.

Orthostatic intolerance refers to the development upon assuming an upright posture of disabling symptoms, which are partly relieved by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations due to excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurological and psychiatric evaluation, which usually fails to identify a specific abnormality. We investigated the autonomic and hemodynamic profile of POTS patients and the efficacy of bisoprolol and or fludrocortisone. We evaluated eleven female patients with POTS before and after medical treatment with a cardio-selective beta blocker (bisoprolol) and/or fludrocortisone, and eleven age-matched controls. Variability of heart rate and systolic blood pressure was assessed by Fast Fourier Transform, and spontaneous baroreceptor gain by temporal sequences slope and alpha index. Modelflow was used to quantify hemodynamics. All patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol and/or fludrocortisone. These results need further confirmation in a controlled double-blind study. Proper medical treatment dramatically improves the clinical and autonomic/hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is due to a hyperadrenergic activation and/or hypovolemia during orthostasis.

Gastroenterologic symptoms are common in the postural tachycardia syndrome (POTS), and postprandial worsening of orthostatic symptoms often occurs. We, therefore, investigated splanchnic-mesenteric vasoregulation in POTS. Eleven patients with POTS (one man, 10 women, 29.4 +/- 7.7 (S.D.) years) and 10 controls (two men, eight women, 27.9 +/- 5.6 years) participated in this study. The protocol included 5 min of 70 degrees head-up tilt (HUT) before and after a liquid meal, as well as 1.5 min of hyperventilation. Blood pressure (BP), heart rate (HR), endtidal CO2, and cardiovascular indices derived from thoracic electrical bioimpedance were continuously monitored. Superior mesenteric artery (SMA) blood flow was measured by real time Doppler ultrasound and analyzed off-line. Cross-sectional area of SMA (SMA-area) and time-averaged velocity (SMA-TAV) were measured; SMA blood flow (SMA-BF) and vascular resistance (SMA-VR) were derived. The following significant results were found: at supine rest, the POTS group had higher HR, BP, SMA-TAV and SMA-BF and a lower SMA-VR than the control group. HUT resulted in a reduction of pulse pressure, CO2 level, SMA-area, SMA-TAV and SMA-VF and increment of HR and SMA-VR in both groups. The POTS group underwent greater increment of HR and greater reduction of CO2 than controls. Hyperventilation induced increment of HR and cardiac index (CI) and reduction of SMA-VR in controls; no significant change occurred in POTS. The test meal induced increments of HR, CI, SMA-area, SMA-TAV and SMA-VF and reduction of SMA-VR in patients and controls for both supine rest and HUT. The main novel observations of increased resting SMA-BF, SMA-TAV supine, and reduced SMA-VR when compared with controls support the notion that there is excessive splanchnic capacity (pooling) at rest in POTS.

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Inappropriate sinus tachycardia and postural orthostatic tachycardia are ill-defined syndromes with overlapping features. Although sinus node modification has been reported to effectively slow the sinus rate, long-term clinical response has not been adequately assessed. Furthermore, whether patients with postural orthostatic tachycardia would benefit from sinus node modification is unknown. The study prospectively assessed the short- and long-term clinical outcomes of seven consecutive female patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia who were treated with sinus node modification. The study was conducted in a tertiary care center. The electrophysiological and clinical responses were prospectively assessed as defined by autonomic function testing, including Valsalva maneuver, deep breathing, tilt table testing, and quantitative sudomotor axonal reflex testing. Among the study population (mean age was 41+/-6 years), 5 (71%) patients had successful sinus node modification. At baseline, heart rates were 101+/-12 beats/min before modification and 77+/-9 beats/min after modification (P = 0.001). With isoproterenol, heart rates were 136+/-9 and 105+/-12 beats/min (P = 0.002) before and after modification, respectively. The mean heart rate during 24-hour Holter monitoring was also significantly reduced: 96+/-9 and 72+/-6 beats/min (P = 0.005) before and after modification, respectively. Despite the significant reduction in heart rate, autonomic symptom score index (based on ten categories of clinical symptoms) was unchanged before (15.6+/-4.1) and after (14.6+/-3.6) sinus node modification (P = 0.38). Sinus rate can be effectively slowed by sinus node modification. Clinical symptoms are not significantly improved after sinus node modification in patients with inappropriate sinus tachycardia and postural orthostatic tachycardia. A primary subtle autonomic disregulation is frequently present in this population. Sinus node modification is not recommended in this patient population.

The head-upright tilt-table (HUT) test is used primarily for the investigation of orthostatic symptoms. Although this test is frequently the gold standard for the evaluation of neurocardiogenic syncope, dysautonomia and postural orthostatic tachycardia syndrome, there is a debate over its diagnostic value and method. The authors review the physiologic basis of the HUT test, the method, patterns of response, indications and contraindications, and diagnostic validity. Despite its limitations, the HUT test is useful in patients with a variety of clinical manifestations induced by orthostatism. It is most useful in documenting objective measures of orthostatic hypertension that cannot be obtained in a clinical setting.

Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms of lightheadedness, fatigue, and signs of edema, acrocyanosis, and exaggerated tachycardia within 10 minutes of upright posture. Our objective was to determine how vascular properties contribute to the pathophysiology of POTS in adolescents. We compared 11 patients aged 13 to 18 years with 8 members of a control group, recording continuous heart rate and blood pressure and using strain-gauge plethysmography to measure forearm and calf blood flow and to estimate venous pressure while the subjects were supine. Calf blood flow and size change were measured during 70 degrees head-up tilt. Resting calf venous pressure was higher in the POTS group compared with the control group. Resting resistance was decreased in both the forearm (15 +/- 2 vs 30 +/- 4) and calf (27 +/- 2 vs 42 +/- 5) in the POTS group. Calf blood flow 60 seconds after tilt increased from 1.9 +/- 0.4 mL/100 mL/min to 6.6 +/- 2.3 mL/100 mL/min in the POTS group but only by half in the control group. Flow remained elevated in the POTS group but decreased to 70% baseline in the control group. Calf volume increased twice as much in the POTS group compared with the control group over a shorter time (13 vs 30 minutes). Lower resistance at baseline reflects a defect in arterial vasoconstriction in POTS, further exacerbated during upright posture.

Orthostatic intolerance (OI) or postural tachycardia syndrome (POTS) is a syndrome primarily affecting young females, and is characterized by lightheadedness, palpitations, fatigue, altered mentation, and syncope primarily occurring with upright posture and being relieved by lying down. There is typically tachycardia and raised plasma norepinephrine levels on upright posture, but little or no orthostatic hypotension. The pathophysiology of OI is believed to be very heterogeneous. Most studies of the syndrome have focused on abnormalities in norepinephrine release. Here the hypothesis that abnormal norepinephrine transporter (NET) function might contribute to the pathophysiology in some patients with OI was tested. In a proband with significant orthostatic symptoms and tachycardia, disproportionately elevated plasma norepinephrine with standing, impaired systemic, and local clearance of infused tritiated norepinephrine, impaired tyramine responsiveness, and a dissociation between stimulated plasma norepinephrine and DHPG elevation were found. Studies of NET gene structure in the proband revealed a coding mutation that converts a highly conserved transmembrane domain Ala residue to Pro. Analysis of the protein produced by the mutant cDNA in transfected cells demonstrated greater than 98% reduction in activity relative to normal. NE, DHPG/NE, and heart rate correlated with the mutant allele in this family. These results represent the first identification of a specific genetic defect in OI and the first disease linked to a coding alteration in a Na+/Cl(-)-dependent neurotransmitter transporter. Identification of this mechanism may facilitate our understanding of genetic causes of OI and lead to the development of more effective therapeutic modalities.

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Dependent pooling occurs in postural orthostatic tachycardia syndrome (POTS) related to defective vasoconstriction. Increased venous pressure (Pv) >20 mmHg occurs in some patients (high Pv) but not others (normal Pv). We compared 22 patients, aged 12-18 yr, with 13 normal controls. Continuous blood pressure and strain-gauge plethysmography were used to measure supine forearm and calf blood flow, resistance, venous compliance, and microvascular filtration, and blood flow and swelling during 70 degrees head-up tilt. Supine, high Pv had normal resistance in arms (26 +/- 2 mmHg x ml(-1) x 100 ml x min) and legs (34 +/- 3 mmHg x ml(-1) x 100 ml x min) but low leg blood flow (1.5 +/- 0.4 ml x 100 ml(-1) x min(-1)). Supine leg Pv (30 +/- 2 vs. 13 +/- 1 mmHg in control) exceeded the threshold for edema (isovolumetric pressure = 19 +/- 3 mmHg). Supine, normal Pv had high blood flow in arms (4.1 +/- 0.2 vs. 3.5 +/- 0.2 ml x 100 ml(-1) x min(-1) in control) and legs (3.8 +/- 0.4 vs. 2.7 +/- 0.3 ml x 100 ml(-1) x min(-1) in control) with low resistance. With tilt, calf blood flow increased steadily in POTS with high Pv and transiently increased in normal Pv. Calf volume increased in all POTS patients. Arm blood flow increased in normal Pv only with forearm maintained at heart level. These data suggest that there are (at least) two subgroups of POTS characterized by high Pv and low flow or normal Pv and high flow. These may correspond to abnormalities in local or baroreceptor-mediated vasoconstriction, respectively.

Instantaneous orthostatic hypotension (INOH) has been reported in children and adolescents as a new entity of orthostatic intolerance in children who underwent rapid standing as an orthostatic stress test. Children with INOH were discovered among patients presenting with symptoms of chronic orthostatic intolerance, which is often related to orthostatic tachycardia. We used head-up tilt table testing at 70 degrees to investigate children presenting with symptoms of chronic orthostatic intolerance. We compared 24 patients aged 12-17 y, with chronic orthostatic intolerance and symptoms for >or=3 mo, with 13 healthy normal control patients. We recorded continuous heart rate, blood pressure, and respiratory rate and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow while supine and calf blood flow during head-up tilt. Patients with chronic orthostatic intolerance fulfilled criteria for the postural orthostatic tachycardia syndrome. Postural orthostatic tachycardia syndrome patients were divided into two groups by the occurrence of INOH. Supine forearm and calf arterial resistance was decreased in patients with INOH (n = 8) compared with postural orthostatic tachycardia syndrome patients without INOH (n = 16) and compared with control (n = 13). Resting calf venous pressure was elevated, suggesting excess venous filling because of vasodilation. During early head-up tilt, calf blood flow increased markedly in INOH, less in No-INOH, postural orthostatic tachycardia syndrome patients and least in control patients. Flow was temporally related to calf swelling and negatively correlated to hypotension. The data suggest that INOH occurs in patients with chronic orthostatic intolerance and orthostatic tachycardia and is related to rapid caudal blood flow when upright because of a vasoconstrictor defect.

Orthostatic intolerance is occasionally reported by patients with syringomyelia and is usually attributed to vestibular symptoms or neurogenic orthostatic hypotension. Postural tachycardia syndrome has not been previously described in syringomyelia. A patient with long-standing syringomyelia and a Chiari type I anomaly developed disabling "panic-like" attacks associated to orthostatic intolerance five years after posterior fossa decompression and shunting of the syrinx. A head-up tilt test showed an early phase of postural orthostatic tachycardia followed by progressive arterial hypotension and bradycardia as seen in neurally mediated syncope. A magnetic resonance imaging scan showed a collapsed syrinx from the 3rd cervical to the 12th thoracic vertebra without syringobulbia. Fludrocortisone and beta-blockers led to resolution of symptoms. Partial sympathetic denervation of the legs in syringomyelia might explain the occasional occurrence of postural tachycardia syndrome. Postural tachycardia syndrome may be included as a possible cause of orthostatic symptoms in syringomyelia patients.

Postural tachycardia syndrome is defined as the development of orthostatic symptoms without orthostatic hypotension. We report a 28-year-old female patient with postural tachycardia syndrome who exhibited palpitation, low-grade fever and weight loss. Evaluation of autonomic nervous system functions showed that cardiovagal function was normal. Sweat response to acetylcholine was decreased. Excessive blood pressure elevation was seen in phase IV of the Valsalva maneuver. Pathophysiologic factors in this case were considered to be alpha adrenergic denervation and beta adrenergic hyperresponsiveness. It is important that this syndrome be widely recognized and properly diagnosed.

This is the first report of neurovesical dysfunction in a woman with postural tachycardia syndrome (POTS). The patient had both symptoms and urodynamic findings diagnostic of detrusor hyperreflexia. Management consisted of anticholinergic medication and timed voiding. Lower urinary tract dysfunction may be underrecognized in POTS.

Transient orthostatic hypotension is a common experience of many healthy adolescents and is the expected outcome of relatively dilated-dependent vascular tone. These children may experience brief symptoms of orthostatic intolerance when standing up rapidly, but they have no chronic symptoms or diseases. However, persistent orthostatic hypotension and chronic symptoms of orthostatic intolerance indicate postural tachycardia syndrome.

To determine whether an intrinsic sinus node abnormality is involved in the pathophysiology of the postural tachycardia syndrome (POTS). SUBJECTS, PATIENTS, AND METHODS: In this prospective study, we compared the relationship between P-wave axis (PWA) and heart rate (HR) in 11 healthy controls and 14 patients with POTS by obtaining 12-lead electrocardiographic recordings during supine rest and during gradual head-up tilt. The HR of controls was titrated with isoproterenol infusion to match the HR of patients. The PWA was compared at different HR levels, and the relationship between HR and PWA was assessed for patients and controls. Primary end points were the PWA-HR relationship in healthy controls, comparison of these data with data from patients with POTS as a group, and identification of a possible subgroup of patients with POTS with irregular PWA-HR relationship. The PWA increased with increasing HR following a similar logarithmic trendline in both groups. The PWA of patients was significantly lower at the lowest comparable HR level but not different at faster HR levels. Three patients (21%) had a clearly abnormal HR-PWA relationship with substantial shift toward lower PWA. Our data support the hypothesis of a primary sinus node abnormality in a subset of patients with POTS. The ability to identify patients with primary sinus node abnormality may have important therapeutic implications.

To compare the hemodynamic responses to autonomic challenge evoked by upright tilt table testing in patients with familial Mediterranean fever (FMF). Forty consecutive patients with FMF and 25 age and sex matched healthy controls were evaluated using the head-up tilt test (HUTT). The main outcome measures were the values of blood pressure (BP) and heart rate (HR) recorded during recumbence and tilt. The endpoints of vasodepressor and cardioinhibitory reactions, orthostatic tachycardia, and postural tachycardia syndrome were recorded. Patients with FMF exhibited significantly higher diastolic BP during supine and tilt measurements (p = 0.003 and 0.04, respectively). In response to tilt, patients showed significant increases in HR compared to healthy subjects (p = 0.02). Pathological endpoints on tilt were observed in the FMF group in 7 patients (17%) and in no controls. FMF severity, genotype, duration of illness, response to therapy, and associated amyloidosis did not correlate with pathological reactions on HUTT. FMF patients exhibit an abnormal cardiovascular reactivity, which is clinically occult, but can be detected on autonomic challenge. The abnormal autonomic activity in FMF is similar to dysautonomia described in a variety of rheumatic disorders.

Orthostatic intolerance is characterized by postural tachycardia syndrome (POTS) with exaggerated tachycardia, orthostatic symptoms, and "pooling" (which comprises acrocyanosis and dependent edema when upright). My colleagues and I tested the hypothesis that pooling results from increased venous compliance in POTS patients. Fifteen patients aged 13 to 19 years were compared with 11 healthy, age-matched controls. The POTS group was divided into patients with high venous pressure (P(v)>20 mm Hg) and normal P(v) on the basis of resting supine P(v) obtained in previous work. Subjects were studied using strain gauge plethysmography to measure blood flow, P(v), and the venous compliance volume-pressure relation while supine and during incremental head-up tilt testing at -10 degrees, 0 degrees, 20 degrees, and 35 degrees. Volume-pressure relations of controls and POTS patients with normal P(v) and high P(v) were not different and were unchanged by orthostasis. Supine leg peripheral resistance was greater than control resistance in patients with high P(v) (54+/-9 versus 30+/-6 mm Hg x mL(-1) x 100 mL(-1) x min(-1)) and less than control resistance in patients with normal P(v) (17+/-2 mm Hg x mL(-1) x 100 mL(-1) x min(-1)). On upright tilt, resistance decreased in high P(v) to approximate resistance in normal P(v). Resistance in controls increased throughout tilt. Leg P(v) increased in patients with normal P(v) and in controls but remained unchanged in the high P(v) group. The findings suggest that pooling in POTS is due to blunted arterial vasoconstriction, which produces passive redistribution of blood within peripheral venous capacitance beds. Venous compliance in POTS is similar to that in control subjects.

To quantify quality of life and identify demographic and clinical correlates of functioning in a well-characterized sample of patients with postural tachycardia syndrome (POTS). Prospective patients were those seen at the Mayo Clinic Autonomic Disorders Laboratory from September 2000 to June 2001. Neurologists made diagnoses of POTS according to established criteria. Patients completed a questionnaire packet that included measures of quality of life (36-Item Short-Form Health Survey [SF-36]) and symptom severity (Autonomic Symptom Profile). Additional clinical information was abstracted from medical records. Ninety-four patients (89% female; mean age, 34.2 years) were enrolled in the study. Patients with POTS reported impairment across multiple domains on the SF-36. Physical functioning, role functioning, bodily pain, general health, vitality, and social functioning were all significantly impaired compared with a healthy population (P<.01 for all) and similar to that reported by patients with other chronic, disabling conditions. Hierarchical regression analyses revealed that symptom severity (beta = -.36, P<.001) and disability status (beta = -36, P<.001) were independent predictors of SF-36 physical component scores, with the full model accounting for 54% of the variance (P<.001). None of the variables examined accounted for a significant amount of the variance in SF-36 mental component scores. Patients with POTS experience clear limitations across multiple domains of quality of life, including physical, social, and role functioning. Treatment should address the multiple and varied impairments experienced by these patients and may require a multidisciplinary approach. Future research must further delineate factors, both disease related and psychosocial, that predict functioning and adjustment in this population.

We describe a 20-year-old woman suffering from right temporal epilepsy, behavioral disorder, and a complaint of paroxysmal palpitations accompanied by anxiety. Detailed cardiac evaluation revealed that the palpitations were due to episodes of marked sinus tachycardia secondary to a concomitant postural orthostatic tachycardia syndrome (POTS) and not of psychogenic origin as initially thought. Treatment with a beta-blocker resulted in the disappearance of palpitations and the associated anxiety. This is the first report of the coexistence of partial epilepsy and POTS. The recognition of such a syndrome in epileptic patients is important in order to offer appropriate therapy.

In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear. Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating (3)H-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[(18)F]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171+/-30 pmol/min, N=16) was higher and in NCS (62+/-9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102+/-9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106+/-18 pmol/min, N=11). Both patient groups had normal cardiac extraction of (3)H-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[(18)F]fluorodopamine-derived radioactivity. POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia.

In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the 'hemodynamic instability score' (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope. Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified 'clinical outcomes' (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and 'HIS endpoint', i.e. HIS >-0.98. The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects. The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS.