Inappropriate sinus tachycardia is an ill-defined clinical syndrome with diverse clinical manifestations. Clinical symptoms can range from intermittent palpitations to multisystem complaints. Although there is a general consensus that when the heartbeat exceeds 100 beats per minute at rest or with minimal physiologic challenge, it is considered "inappropriate," this quantitative differentiation is quite arbitrary, while validation of the reproducibility of the heart rate/activity correlation can be challenging. Once the clinical diagnosis of inappropriate sinus tachycardia is expected, other supraventricular tachyarrhythmias and medical conditions causing sinus tachycardia should be excluded. The underlying mechanism of inappropriate sinus tachycardia is not well understood. "Intracardiac" mechanisms such as enhanced intrinsic automaticity, enhanced sympathetic tone, increased sympathetic receptor sensitivity, and blunted parasympathetic tone have been proposed. Evidences for "extracardiac" mechanisms such as length-dependent autonomic neuropathy, excessive venous pooling, beta-receptor hypersensitivity, alpha-receptor hyposensitivity, altered sympathovagal balance, and brainstem dysregulation have also been reported. Currently, our ability to differentiate primary (intracardiac) from secondary (extracardiac) mechanisms of inappropriate sinus tachycardia is limited. It has been reported that ablative therapy of sinus node is effective in treating patients with symptomatic inappropriate sinus tachycardia. Acute success of sinus node modification/ablation can be accomplished in 70%-100% of the various study populations. Although long-term successful outcome may be accomplished in a few patients, symptoms of palpitations and autonomic characteristics frequently persist. Identification and differentiation of patients who are suitable for ablative therapy versus medical therapy should be one of the central clinical research issues in this patient population. This brief review first considers the clinical and electrophysiologic diagnosis of inappropriate tachycardia and then summarizes the mechanisms of inappropriate sinus tachycardia and related syndromes such as postural orthostatic tachycardia syndrome. Techniques of mapping and ablation of sinus node are discussed briefly. A critical review of the acute and long-term clinical outcomes following sinus node ablation and modification is updated. In conclusion, the precise role of sinus node modification in patients with inappropriate sinus tachycardia remains to be determined. Sinus node modification could be considered in patients with inappropriate sinus tachycardia with persistently increased heart rate in the absence of any autonomic abnormalities. Autonomic laboratory testing should be performed to exclude any evidence of autonomic dysregulation. Clinical research on the pathophysiology of inappropriate sinus tachycardia should be pursued vigorously.

Adrenergic agents are commonly used in the treatment of chronic orthostatic intolerance with postural tachycardia syndrome (POTS). POTS may be associated with increased limb blood flow ("high flow") and defective orthostatic vasoconstriction or decreased limb blood flow ("low flow") and potentially with small blood volume. We investigated the consequences of short-term intravenous administration of an alpha-1 adrenergic agonist, phenylephrine, and a beta-1 adrenergic antagonist, esmolol, in 14 patients with POTS aged 13 to 19 years. Indices of heart rate and blood pressure variability, peripheral blood flow, and arterial resistance were assessed, and the capacitance relation was computed for every subject using venous occlusion plethysmography. Patients were tilted to 35 degrees upright while medicated and while unmedicated, and measurements were repeated. Phenylephrine improved orthostatic tolerance and normalized hemodynamics and indices of heart rate/blood pressure variability while supine and while upright, producing significant peripheral vasoconstriction and venoconstriction (20% capacitance change). Esmolol did not improve orthostatic tolerance or hemodynamics. A subgroup of low-flow POTS patients had exaggerated venoconstriction to phenylephrine (50% capacitance change) but others had no response. Phenylephrine, but not esmolol, improves orthostatic tolerance and hemodynamics in POTS. This lends support to the use of oral alpha-1 agonists in the treatment of patients with chronic orthostatic intolerance.

During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress. Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD. NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002). The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

We recently published data suggesting the presence of an intrinsic sinus node abnormality in a subgroup of patients with the postural tachycardia syndrome (POTS). Based on the hypothesis that more widespread abnormalities of cardiac electrophysiologic properties may be present in POTS, we undertook a study to compare cardiac conduction and repolarization at different heart rate levels in patients with POTS and healthy controls. Eleven healthy controls and fourteen patients with POTS participated in the study. Acquisition of 12-lead electrocardiogram recordings were made during supine rest and during gradual head-up tilt. The heart rate of controls was titrated by isoproterenol infusion to match the heart rate of patients. Indices for cardiac conduction (PR interval, QRS duration, and R wave axis) and repolarization (QT interval, QTc interval, and T wave axis) were then compared at different heart rate levels. The PR interval decreased with increasing heart rate in controls more than in patients, resulting in a significantly longer PR interval in patients at the fastest heart rate level. The QT and QTc intervals were significantly shorter in POTS over the entire analyzed heart rate range. The T wave axis decreased with increasing heart rate in patients only. This resulted in a significantly lower T wave axis in patients at the fastest heart rate level. Our data suggest abnormalities of atrioventricular conduction and ventricular repolarization in patients with POTS. These findings may reflect intrinsic cardiac electrophysiologic abnormalities or may be secondary due to abnormalities of cardiac autonomic innervation.

Orthostatic intolerance (OI) is a syndrome that is characterised by headache, concentration difficulties, palpitation of the heart, dizziness associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high when the sufferer is in the upright posture. In contrast to other forms of orthostatic dysregulation - orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS) - OI, hitherto, could be diagnosed only by a tilt table examination, with high expenditure. In this paper we examine the reliability and validity of a questionnaire as a screening instrument for OI. We studied 138 young men (mean age 21.6 years) who were undergoing military service. After a medical check and filling in the questionnaire, the participants underwent a tilt table test including monitoring of blood pressure, heart rate and plasma catecholamines, in the supine position and during 30 min of standing. The questionnaire consisted of ten items registering presence and frequency of typical OI symptoms. Probands (104) showed normal tilt table test results. OI was diagnosed in 14 probands, OH in 6 and POTS in 14. The OI participants scored significantly higher in the questionnaire than the healthy subjects did: the mean score of the OI group was 22.6, the healthy participants had a mean score of 3.9. Participants with POTS had a mean score of 13.5 and subjects with OH had a mean score of 17.0. Reliability analysis showed a Cronbach's alpha of 0.888. Validity analysis showed that 93.5% of the probands with any kind of orthostatic dysregulation can be detected. We were able to establish a short questionnaire as a reliable and valid screening instrument for OI. Usage of this questionnaire can simplify enormously the diagnostic management of patients with suspected OI.

Simple faint (neurocardiogenic syncope) and postural tachycardia syndrome (POTS) characterize acute and chronic orthostatic intolerance respectively. We explored the hypothesis that vascular function is similar in the two conditions. We studied 29 patients with POTS and compared them with 20 patients with neurocardiogenic syncope who were otherwise well, and with 15 healthy control subjects. We measured continuous heart rate, respiration and blood pressure, and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow, peripheral arterial resistance, peripheral venous resistance and venous pressure ( P (v)). Upright tilt was performed to 70 degrees for 10 min, during which calf blood flow and volume were measured. Calf P (v) was increased (to 27.2+/-2.0 mmHg) in a subgroup of POTS patients, who also had increased arterial resistance (57+/-6 mmHg.ml(-1).min(-1).100 ml(-1) tissue), increased venous resistance (2.4+/-0.3 mmHg.ml(-1).min(-1).100 ml(-1) tissue), and decreased peripheral flow (1.0+/-0.2 ml.min(-1).100 ml(-1) tissue) in the calf; other POTS patients with a normal P (v) had decreased arterial resistance (18+/-2 mmHg.ml(-1).min(-1).100 ml(-1) tissue) and increased blood flow (3.8+/-0.3 ml.min(-1).100 ml(-1) tissue). Syncope patients were not different from controls ( P (v)=11.4+/-0.5 mmHg; calf flow=3.1+/-0.2 ml.min(-1).100 ml(-1) tissue; arterial resistance=27+/-2 mmHg.ml(-1).min(-1).100 ml(-1) tissue; venous resistance=1.2+/-0.3 mmHg.ml(-1).min(-1).100 ml(-1) tissue). When upright, syncope patients and control subjects had similar increases in heart rate and calf volume, stable blood pressure, and decreases in blood flow. POTS patients had markedly increased heart rate and calf blood flow, unstable blood pressure, and pooling in the lower extremities, regardless of subgroup. We conclude that peripheral vascular physiology in patients with POTS is abnormal, in contrast with normal peripheral vascular physiology in neurocardiogenic syncope.

In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with OH due to MSA or PAF. A total of 28 patients with OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with Alzheimer's disease, 18 patients with dysautonomia (postural tachycardia syndrome or neurocardiogenic syncope) and six patients with MSA in the absence of OH. Patients with OH had lower cerebrospinal fluid concentrations of noradrenaline (0.53+/-0.07 nmol/l) and dihydroxyphenylglycol (6.52+/-0.46 nmol/l) than did control subjects (0.90+/-0.09 and 9.64+/-0.46 nmol/l respectively; P =0.0001). The MSA+OH group had higher plasma levels of both catechols (noradrenaline, 1.31+/-0.16 nmol/l; dihydroxyphenylglycol, 5.08+/-0.43 nmol/l) than did the PAF group (noradrenaline, 0.38+/-0.08 nmol/l; dihydroxyphenylglycol, 2.53+/-0.30 nmol/l; P <0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with OH had lower cerebrospinal fluid levels of noradrenaline and dihydroxyphenylglycol than those without OH (noradrenaline, 1.71+/-0.64 nmol/l; dihydroxyphenylglycol, 10.41+/-1.77 nmol/l respectively; P =0.006). The findings are consistent with central noradrenergic deficiency in both MSA+OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to OH.

A relatively novel group of drugs that inhibit the funny current in the sinus node pacemaker cells, the so-called specific bradycardic agents, are likely to play a significant role in the management of a wide range of cardiovascular disorders, including the sinus tachyarrhythmias. This comprehensive review initially provides an insight into these agents, their historical background, and their mechanism of action. It then discusses the differential diagnosis of the sinus tachyarrhythmias (normal sinus tachycardia, inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome, and sinus node reentry tachycardia), elaborates on their pathophysiologic basis, and provides up-to-date evidence-based information on their optimum management. The specific bradycardic agents, by the very nature of their mode of action, may prove ideal therapies for the management of the sinus tachyarrhythmias, and this is explored at every stage.

Postural tachycardia syndrome (POTS) is related to defective peripheral vasoconstriction of dependent extremities with redistributive hypovolemia. To test whether enhanced microvascular filtration produces leg enlargement, we studied 12 patients 13 to 19 years of age with POTS and defective leg vasoconstriction and 13 age-matched healthy control subjects, with strain-gauge plethysmography used to measure venous pressure (Pv), forearm and calf blood flow, vascular capacitance, and the microvascular filtration coefficient (Kf). Measurements were made while the patient was supine and at steady state during upright tilt to 35 degrees. Supine Pv was not different in POTS, but upright leg Pv tended to be increased above control. Arm and leg peripheral arterial resistance was decreased in the supine and upright positions in patients with POTS compared with control subjects (P=0.01, upright legs). Supine Kf was not significantly increased in the forearm in patients with POTS but was increased in the calf (9.3+/-2.2 versus 5.7+/-2.4 [10(-3)] mL/100 mL per minute per mm Hg, P=0.04), correlating with calf blood flow (rs=0.84, P=0.002). Kf was invariant with orthostasis. The hydraulic contribution to upright filtered flow at 35 degrees tilt, the product of Kf and Pv, was approximately twice that of control (0.41+/-0.09 versus 0.19+/-0.04 mL/100 mL per minute, P=0.04). Increased microvascular filtration accounts for enhanced leg swelling in patients with POTS with increased arterial blood flow.

Extraarticular manifestations of the joint hypermobility syndrome may include the peripheral nervous system. The purpose of this study was to investigate autonomic function in patients with this syndrome. Forty-eight patients with the joint hypermobility syndrome who fulfilled the 1998 Brighton criteria and 30 healthy control subjects answered a clinical questionnaire designed to evaluate the frequency of complaints related to the autonomic nervous system. Next, 27 patients and 21 controls underwent autonomic evaluation: orthostatic testing, cardiovascular vagal and sympathetic functions, catecholamine levels, and adrenoreceptor responsiveness. Symptoms related to the autonomic nervous system, such as syncope and presyncope, palpitations, chest discomfort, fatigue, and heat intolerance, were significantly more common among patients. Orthostatic hypotension, postural orthostatic tachycardia syndrome, and uncategorized orthostatic intolerance were found in 78% (21/27) of patients compared with in 10% (2/21) of controls. Patients with the syndrome had a greater mean (+/- SD) drop in systolic blood pressure during hyperventilation than did controls (-11 +/- 7 mm Hg vs. -5 +/- 5 mm Hg, P = 0.02) and a greater increase in systolic blood pressure after a cold pressor test (19 +/- 10 mm Hg vs. 11 +/- 13 mm Hg, P = 0.06). Patients with the syndrome also had evidence of alpha-adrenergic (as assessed by administration of phenylephrine) and beta-adrenergic hyperresponsiveness (as assessed by administration of isoproterenol). The autonomic nervous system-related symptoms of the patients have a pathophysiological basis, which suggests that dysautonomia is an extraarticular manifestation in the joint hypermobility syndrome.

Postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia are two clinically different entities but with significant overlap of symptoms. Treatment by and large is medical; however, other modalities of treatment are being evaluated.

Four women age 17 to 28 years presented with orthostatic headaches as the most prominent feature of their symptom complex. None had CSF leak or intracranial hypotension. Autonomic studies showed evidence of orthostatic intolerance with tachycardia in all cases. Treatment of orthostatic intolerance, mainly with volume expansion, was only partially effective. Orthostatic headaches are not always caused by CSF leak or supine intracranial hypotension. Occasionally they may be the major clinical manifestation of postural tachycardia syndrome or orthostatic intolerance.

The study investigated correlates of functional disability in 94 patients (89.4% women, 10.6% men; mean age=34.2 years) with postural tachycardia syndrome (POTS), a clinical syndrome of orthostatic intolerance characterized by significant functional limitations. Path analysis supported a model in which, controlling for demographic and disease variables, catastrophic cognitions were directly related to the latent variable functional disability, whereas somatic vigilance, anxiety sensitivity, and neuroticism were indirectly associated with functional disability through their relationship with catastrophic cognitions. Results suggest that modifiable psychological factors play a role in the functional limitations experienced by patients with POTS. Longitudinal research is necessary to confirm these relationships.

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.

Postural Orthostatic Tachycardia Syndrome (POTS) is a type of orthostatic intolerance that is characterized by excessive tachycardia and decreased cerebral blood flow in the upright position. This can result in significant symptoms of dizziness and light-headedness that can eventually lead to syncope. In this review, we describe two patients with POTS that varied in their degree of symptoms and treatment. One patient was able to be treated as an outpatient, while the other required hospitalization and extensive medical therapy. We would like to emphasize with this review that POTS is probably more common than it is diagnosed and is often confused with other conditions, such as chronic fatigue syndrome or functional syncope. It is important to make the correct diagnosis in order to allow appropriate treatment and to improve the quality of life for these patients.

This paper discusses the development of a system to measure continuous cardiac baroreceptor measurement during a 45-minute 70-degree head-up tilt (HUT) of five groups of subjects suffering the following: chronic fatigue syndrome (CFS), CFS with fibromyalgia (CFS-FM), CFS with postural orthostatic tachycardia syndrome (CFS-POTS), controls with POTS (CON-POTS), and controls (CON). The duration of the test was 56-minutes, which included a five-minute supine baseline, a 45-minute HUT and a six-minute recovery period. The system was developed in LabView, and can provide a comparative time analyses of weighted BRSI averages. Baroreflex effectiveness index (BEI) was also investigated over the course of lags 0, 1 and 2 as well as an assessment of overall BEI performance between groups.

There are a number of distal and generalized small-fiber neuropathies. The neuropathologic basis is poorly understood as somatic and autonomic C fibers are not usually studied in the same region of the body. To evaluate prospective somatic and autonomic C-fiber function in 11 healthy control subjects and 38 patients with different clinical patterns of neuropathy. Distal small-fiber neuropathy (DSFN), peripheral neuropathy (PN), diabetic neuropathy (DN), neuropathic postural tachycardia syndrome (POTS), and idiopathic autonomic neuropathy (IAN) were evaluated. Intraepidermal nerve fiber density was used to evaluate distal somatic C fibers. Both quantitative sudomotor axon reflex test and skin norepinephrine content were measured for the biopsy site to assess distal autonomic C-fiber function. Postganglionic sudomotor, adrenergic, and cardiovagal functions were evaluated by autonomic reflex testing and quantified using a Composite Autonomic Severity Scale. Skin norepinephrine concentration was significantly related to CASS. DN was associated with somatic and autonomic C-fiber impairment with good agreement. POTS was associated with selective distal autonomic deficit. DSFN had combined distal somatic and C-fiber impairment. IAN showed combined and selective distal and generalized autonomic C-fiber impairment. The somatic neuropathies had C-fiber impairment affecting both populations to varying degrees. Although a general agreement exists between the loss of somatic C fibers and autonomic deficits, selective involvement occurs for specific autonomic neuropathies.

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 +/- 1 vs. 39 +/- 3 and 43 +/- 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 +/- 0.07 vs. 0.76 +/- 0.07 and 0.80 +/- 0.06). We found that blood flow was linearly correlated (r(p) = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 +/- 0.3 in low-flow POTS vs. 2.6 +/- 0.5 in controls (P = 0.17) and 2.4 +/- 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients.

Autonomic imbalance may work as a modifying factor for initiating lethal arrhythmia in patients with Brugada syndrome. A 26-year-old man with episodes of near syncope was given a diagnosis of an autonomic disorder, postural orthostatic tachycardia syndrome (POTS). The patient spontaneously showed typical Brugada-type ECG, and ventricular fibrillation was induced by programmed electrical stimulation, which allowed the further diagnosis of Brugada syndrome. Although it seems that Brugada syndrome is asymptomatic, its uncommon association of POTS may increase the risk for future arrhythmic events in this patient.

The aim of this study was to assess the presence of dysautonomia, as manifested in abnormal cardiovascular reactivity, in patients with familial Mediterranean fever (FMF). Fifty-five consecutive patients with FMF and 23 age- and sex-matched healthy controls were evaluated. Cardiovascular reactivity was studied: (1) using recordings of blood pressure (BP) and heart rate (HR) during 10 min of recumbence and 30 min of head-up tilt test to identify clinical endpoints and (2) during tilt-test, identifying parameters acting as independent predictors of FMF reactivity and enabling computation of a cardiovascular reactivity score (CVRS). Clinically, vasovagal reaction, postural tachycardia syndrome, and/or orthostatic hypotension were observed in ten patients (18.1%). Utilizing a derived equation, the group average CVRS in FMF was 5.83+/-1.78 (healthy group -7.60+/-5.41) ( P=<0.0001). A CVRS of >3.25 was associated with FMF, with 98% sensitivity and 100% specificity. A very high percentage of FMF patients exhibit abnormal cardiovascular reactivity which is clinically occult but can be detected on autonomic challenge and application of the CVRS.

Fibromyalgia (FM) is a major determinant of poor health status in systemic lupus erythematosus (SLE). FM has been shown to be associated with neurally mediated hypotension (NMH) in the general population, in which effective treatments exist. We explored whether NMH was more common in SLE patients with FM than those without. Seventy-six SLE patients (4 male, 72 female; 1 ethnic Indian, 28 African American, 47 Caucasian; mean age 40.2 +/- 9.4 yr) were recruited and their FM status ascertained using American College of Rheumatology (ACR) classification criteria. Patients who were pregnant or deconditioned were excluded. A two-stage tilt-table test was used to detect NMH. All patients completed the SF-36 Heath Status Inventory (SF-36) and the Krupp Fatigue Severity Scale (KFSS) to evaluate their quality of life. Serological markers and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were recorded. Medications that might interfere with testing were temporarily withheld before the tilt-table test. The prevalence of NMH (first stage) in SLE patients was 47.9%. Seven patients had both NMH and postural orthostatic tachycardia syndrome. Two patients had borderline results with symptoms reproduced but an inadequate drop in systolic blood pressure by definition (a drop of at least 25 mmHg defines an abnormal response). Eighteen (23.7%) SLE patients had FM and 51 (67.1%) had at least one tender point (TP). The frequency of NMH (first or second stage) in SLE with FM was 58.3% compared with 69.4% in SLE without FM (odds ratio 0.62, 95% CI 0.16-2.37). SF-36 and KFSS scores were not significantly different in SLE patients with and without NMH. However, both scores were found to be associated with FM status (P<0.001 and P = 0.014), reflecting poor health status in the FM group. No confounding variable was found to be significantly associated with both NMH and FM. NMH is common in SLE patients with a high prevalence rate. The large increase in NMH, a form of autonomic neuropathy, in SLE, has not been explained. However, NMH has no impact on quality of life above that determined by FM, and has no statistically significant association with FM status. Identification of NMH may be important in selected patients with SLE who have chronic fatigue, but NMH cannot explain the increased prevalence of FM in SLE.

Water drinking recently has been shown to raise blood pressure in normal subjects and in patients with autonomic failure who have orthostatic hypotension. However, in normal young subjects, ingestion of approximately 500 ml has no pressor effect; but in older subjects there is an increase in blood pressure. An even greater rise in blood pressure occurs in cases with autonomic failure. The possible mechanisms responsible for the pressor response to water include neural and humoral factors; fluid redistribution also needs to be considered. This review will concentrate on the water pressor response in normal subjects and different groups of patients with autonomic diseases who have orthostatic intolerance, on the mechanisms that could be involved, and on whether this pressor response may be used in the management of orthostatic hypotension, vasovagal syncope and the postural tachycardia syndrome.

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.

Increased central sympathetic activity and/or deficient peripheral sympathetic nerve function are among the proposed pathophysiological changes in patients with the postural tachycardia syndrome (POTS). Little is known about sympathetic nerve outflow and its role in hemodynamic control in this disorder. We recorded peroneal muscle sympathetic nerve activity in 9 POTS patients and 9 control subjects at rest and during a nitroprusside-induced hypotensive stimulus. Baseline blood pressure (BP) and heart rate were significantly higher in POTS patients than in controls. At rest, the burst frequency was similar in POTS patients and controls (18.1+/-6.2 and 20.1+/-7.9 bursts/min, respectively; P=NS), whereas the burst incidence was significantly lower (23.1+/-6.8 versus 32.2+/-11.4 bursts/100 heartbeats, P<0.05). Nitroprusside increased sympathetic outflow significantly more in POTS patients than in controls despite a similar BP decrease (burst frequency 20.4+/-7.5 versus 12.1+/-4.1 bursts/min, P=0.008, and burst incidence 21.8+/-8.4 versus 14.4+/-5.2 bursts/100 heartbeats, P=0.03). The change in mean burst area, a measure of the number of actively firing sympathetic neurons, was similar in patients and controls (117+/-15% versus 114+/-21%, P=NS). At rest, the tachycardia and normal burst frequency result in normal or even elevated BP in POTS patients. During a hypotensive stimulus, cardiovascular homeostasis is maintained by the increased sympathetic outflow and normal heart rate response despite the lack of concomitant increase in mean burst area that is most likely due to sympathetic denervation.

Recurrent syncope may be either a sign or a symptom and may occur due to a wide variety of very different causes. Extensive investigations into the nature of this disorder soon uncovered that it represents only one aspect of a broad, heterogenous group of disturbances of the autonomic nervous system (ANS) that can result in hypotension, orthostatic intolerance, and often syncope. Disorders of orthostatic regulation may be subgrouped into both primary and secondary forms. In primary autonomic failure syndromes, as opposed to the intermittent periods of hypotension seen in the reflex syncopes, patients could develop orthostatic intolerance due to a failure of the ANS to function under normal circumstances. Chronic autonomic insufficiency has two entities: Pure Autonomic Failure (PAF) and Multiple System Atrophy (MSA). Over the last several years, it has become apparent that a milder form of autonomic insufficiency occurs that is now referred to as the Postural Orthostatic Tachycardia Syndrome (POTS). The secondary forms of autonomic failure occur in association with a particular disease process. One of the most important things to remember are the vast number of pharmacologic agents that may either cause or worsen orthostatic hypotension. The principal feature that all of these conditions share is that normal cardiovascular regulation is disturbed resulting in postural hypotension. The comerstone of evaluation is a detailed history and physical examination. One of the physician's most important tasks is to identify whether hypotensive syncope is primary or secondary in nature, and to determine if there are any potentially reversible causes (i.e., drugs, anemia, volume depletion). It is equally important to educate the patient. Nonpharmacologic therapies are useful. Pharmacotherapy should be used cautiously in selected cases.