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Imbalance in the autonomic nervous system can lead to orthostatic intolerance manifested by dizziness, lightheadedness, and a sudden loss of consciousness (syncope); these are common conditions, but they are challenging to diagnose correctly. Uncertainties about the triggering mechanisms and the underlying pathophysiology have led to variations in their classification. This study uses machine learning to categorize patients with orthostatic intolerance. We use random forest classification trees to identify a small number of markers in blood pressure, and heart rate time-series data measured during head-up tilt to (a) distinguish patients with a single pathology and (b) examine data from patients with a mixed pathophysiology. Next, we use Kmeans to cluster the markers representing the time-series data. We apply the proposed method analyzing clinical data from 186 subjects identified as control or suffering from one of four conditions: postural orthostatic tachycardia (POTS), cardioinhibition, vasodepression, and mixed cardioinhibition and vasodepression. Classification results confirm the use of supervised machine learning. We were able to categorize more than 95% of patients with a single condition and were able to subgroup all patients with mixed cardioinhibitory and vasodepressor syncope. Clustering results confirm the disease groups and identify two distinct subgroups within the control and mixed groups. The proposed study demonstrates how to use machine learning to discover structure in blood pressure and heart rate time-series data. The methodology is used in classification of patients with orthostatic intolerance. Diagnosing orthostatic intolerance is challenging, and full characterization of the pathophysiological mechanisms remains a topic of ongoing research. This study provides a step toward leveraging machine learning to assist clinicians and researchers in addressing these challenges. Graphical abstract Machine learning tools utilized to analyze heart rate (HR) and blood pressure (BP) time-series data from syncope and control patients. Results show that machine learning can provide accurate classification of disease groups for 98% of patients and we identified two subgroups within the control patients differentiated by their BP response.

The current definition of postural orthostatic tachycardia syndrome (POTS) dates back to a small case series of patients with a subacute illness who presented with excessive orthostatic tachycardia and orthostatic intolerance, in the absence of another recognized disease. Conventional POTS criteria require an excessive orthostatic tachycardia in the absence of substantial orthostatic hypotension, and predominant symptoms of orthostatic intolerance, worse with upright posture and better with recumbence. POTS is a heterogeneous syndrome with likely several underlying pathophysiological processes, and not a specific disease. The primary panel for this Canadian Cardiovascular Society position statement sought to provide a contemporary update of the best evidence for the evaluation and treatment of POTS. We performed a systemic review of evidence for the evaluation of treatment of POTS using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, and developed recommendations on the basis of the Canadian Cardiovascular Society approach to position statements. One identified problem was that numerous patients who did not meet criteria for POTS would still be given that diagnoses by providers to validate the illness even though this diagnosis is incorrect. This includes patients with postural symptoms without tachycardia, orthostatic tachycardia without symptoms, and those with orthostatic tachycardia but another overt cause for excessive tachycardia. We developed a novel nomenclature ecosystem for orthostatic intolerance syndromes to increase clarity. We also provide more clarity on how to interpret the orthostatic vital signs. These concepts will need to be prospectively assessed.

Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension. The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Patients often will exhibit overlapping characteristics from more than one of these mechanisms. The approach to the treatment of POTS centers on treating the underlying pathophysiologic mechanism. Stockings, abdominal binders, and vasoconstrictors are used to enhance venous return in partial neuropathic POTS. Exercise and volume expansion are the main treatment strategies for hypo-volemic POTS. For hyperadrenergic POTS, beta-blockers and avoidance of norepinephrine reuptake inhibitors is important. Attempts should be made to discern which pathophysiologic mechanism(s) may be afflicting patients so that treatment regimens can be individualized.

Background Orthostatic intolerance (OI) is a significant problem for those with chronic fatigue syndrome (CFS). We aimed to characterize orthostatic intolerance in CFS and to study the effects of exercise on OI. Methods CFS (n = 39) and control (n = 25) subjects had recumbent and standing symptoms assessed using the 20-point, anchored, ordinal Gracely Box Scale before and after submaximal exercise. The change in heart rate (ΔHR ≥ 30 bpm) identified Postural Orthostatic Tachycardia Syndrome (POTS) before and after exercise, and the transient, exercise-induced postural tachycardia Stress Test Activated Reversible Tachycardia (START) phenotype only after exercise. Results Dizziness and lightheadedness were found in 41% of recumbent CFS subjects and in 72% of standing CFS subjects. Orthostatic tachycardia did not account for OI symptoms in CFS. ROC analysis with a threshold ≥ 2/20 on the Gracely Box Scale stratified CFS subjects into three groups: No OI (symptoms Conclusions Dizziness and Lightheadedness symptoms while recumbent are an underreported finding in CFS and should be measured when doing a clinical evaluation to diagnose orthostatic intolerance. POTS was found in 6 and START was found in 10 CFS subjects. Persistent OI had symptoms while recumbent and standing, highest symptom severity, and lability in symptoms after exercise. Trial registration The trial was registered at the following: https://clinicaltrials.gov/ct2/show/NCT03567811

Objective Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been suggested to be the main cause of chronic fatigue syndrome. In animal models of chronic fatigue, minocycline was reported to act as a suppressor of neural inflammation. Minocycline may thus exert favorable therapeutic effects in patients with ME. Methods Oral minocycline (100 mg ×2 on the first day, followed by 100 mg/day for 41 days) was administered to 100 patients with ME. The performance status score (0-9), orthostatic intolerance during the 10-min standing test, neurologic disequilibrium, and neuropathic pain were compared before and after treatment. Results After therapy completion, favorable effects were observed with a decrease in the performance status score of ≥2 points in 27 patients (27%). Before treatment, 6 of the 27 patients had orthostatic intolerance with an inability to complete the 10-min standing test; after treatment, this symptom resolved in 4 and improved in 2 patients. In addition, after treatment, postural orthostatic tachycardia resolved in five of eight patients, disequilibrium resolved in five of eight patients, and fibromyalgia or neuropathic pain was attenuated in four of five patients. The favorable effects appeared dependent on a shorter disease duration, primarily for a duration of less than three years and most frequently within six months of the disease onset. However, acute adverse effects with nausea and/or dizziness caused 38 patients (38%) to discontinue treatment in the first few days. Conclusion Oral minocycline therapy may be an effective treatment option for patients with ME, especially in the initial stage of the disease.

BACKGROUND: High sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available. OBJECTIVES: We tested whether a high sodium (HS) diet reduces orthostatic tachycardia (ΔHR) and upright heart rate (HR) compared with low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine. METHODS: We enrolled 14 POTS patients and 13 healthy controls (HC), 23–49 years old, in a crossover study with six days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. We measured supine and standing HR, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine. RESULTS: In POTS, HS diet reduced upright HR and ΔHR compared with LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with HS compared with LS diet However, upright HR, ΔHR and upright norepinephrine remained higher in POTS than in HC on HS diet [117 (98–121) beats per minute (bpm), 46 (32–55) bpm, and 753 (498–919) pg/mL in POTS vs. 85 (77–95) bpm, 19 (11–32) bpm, and 387 (312–433) pg/mL in HC], despite no difference in the measured PV. CONCLUSIONS: In POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases ΔHR. CONDENSED ABSTRACT: Postural Tachycardia Syndrome (POTS) is a chronic form of orthostatic intolerance. Augmented oral sodium intake is a frequently prescribed treatment and recommended in professional society scientific statements on POTS, but evidence supporting the effectiveness was lacking. We evaluated one week of a very high sodium diet compared to a very low sodium diet in POTS patients. The high sodium diet expanded the plasma volume and total blood volume, reduced standing plasma norepinephrine levels (a marker of sympathetic nervous system tone), and reduced the orthostatic tachycardia. These data provide supporting evidence for the use of high sodium diets in POTS patients. ClinicalTrials.gov Identifier: NCT01547117

The current surge of interest in postural orthostatic tachycardia syndrome commonly known as POTS requires good knowledge of the very complex physiology involved, but this is currently lacking. The often overlooked normal physiology of orthostasis is reviewed including the definition of normal postural orthostatic tachycardia. An illustrated functional anatomy that embeds orthostatic tachycardia within the learned and skilful motor functions in the human population is presented. The four physiological phases of orthostasis and the role of tachycardia are described in a laboratory‐controlled and progressive orthostatic stress in normal human volunteers. Standardized surrogate measures of autonomic control were used to quantify the trigger level for excessive tachycardia and the minimum autonomic control required to sustain viable arterial blood pressure during severe orthostatic stress in normal human volunteers. Tachycardia during orthostasis is part of a “democratic” contribution by four cardiovascular parameters of which the chronotropic function of the heart is just one of the parameters contributing toward cardiovascular compensation. It is adjusted during orthostasis in proportion to contributions from the other three parameters, namely inotropic function of the heart, windkessel vascular resistance and venous vascular capacitance. The physiological effects of the two stressors during orthostasis, gravity and isometric contraction of skeletal muscles are reviewed. A model of how the four cardiovascular parameters are regulated during orthostasis to achieve proportionate contributions is proposed emphasizing the necessity to quantify individual contributions from all these four parameters. Any one or more of these parameters may be compromised due to disease requiring disproportionate contribution of the prevailing magnitude of orthostatic tachycardia in an individual. It therefore requires neurophysiological assessment of the autonomic regulation of all the four cardiovascular parameters to assess the condition fully. We recommend here some current and novel neurophysiological methods that use modern medical technology to quantify laboratory standardized surrogate measures of some of these cardiovascular parameters including central parasympathetic regulation in postural orthostatic tachycardia syndrome., A four‐parameter model of cardiovascular regulation, two each in the cardiac zone C and vascular zone D to explain the normal physiology of postural orthostatic tachycardia in the human population. The International Consensus definition of an autonomic disorder known as Postural Orthostatic Tachycardia Syndrome (POTS) conversely describes a natural and physiological cardiovascular compensation in Phase 2 of severe orthostatic stress. The functional anatomy of orthostasis shows that it is part of a learned skilful motor function in the human population including the associated tachycardia.

Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes.We conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate.A total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by -3.97 beats per minute (95% CI, -4.08 to -3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses.Our meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes.

Aim: To estimate the incidence of postural orthostatic tachycardia syndrome (POTS) in the population of Zagreb, Croatia, and to determine the patients' demographic and clinical characteristics. ----- Methods: From 2012-2017, we identified patients with POTS by a retrospective analysis of medical records at University Hospital Center Zagreb. Crude incidence rates were directly standardized by age according to the European and World Standard Population. ----- Results: Out of 385 patients with suspected POTS, 23 had a definitive POTS diagnosis. The annual incidence ranged from 3.3 to 14.8 per 1000000 for both sexes combined. The highest incidence rates were in the age groups 18-29 and 30-39 years, with female predominance. The mean age at diagnosis was 30.7 years (standard deviation ±9.2, range 18-52). The median duration of symptoms at diagnosis was 7.5 months (range 3-180 months). Regarding associated comorbidities, two patients had chronic gastritis and one patient had each of the following: epilepsy, prior subarachnoid hemorrhage, anxiety, mitral insufficiency, obstructive sleep apnea, hypothyreosis, and irritable bowel syndrome. In patients not fulfilling the criteria for POTS, the most common alternative diagnoses were autonomic dysfunction due to multiple sclerosis in 22, anxiety disorder in 17, epilepsy in 16, and orthostatic tachycardia due to deconditioning in 13 patients. ----- Conclusion: The data obtained in this study can be used to optimize disease surveillance in population, comprehensive assessment of disease burden, and organization of health care services.

Postural tachycardia syndrome (POTS) is a heterogeneous clinical syndrome that has gained increasing interest over the past few decades due to its increasing prevalence and clinical impact on health-related quality of life. POTS is clinically characterized by sustained excessive tachycardia upon standing that occurs in the absence of significant orthostatic hypotension and other medical conditions and or medications, and with chronic symptoms of orthostatic intolerance. POTS represents one of the most common presentations of syncope and presyncope secondary to autonomic dysfunction in emergency rooms and in cardiology, neurology, and primary care clinics. The most sensitive method to detect POTS is a detailed medical history, physical examination with orthostatic vital signs or brief tilt table test, and a resting 12-lead electrocardiogram. Additional diagnostic testing may be warranted in selected patients based on clinical signs. While the precise etiology remains unknown, the orthostatic tachycardia in POTS is thought to reflect convergence of multiple pathophysiological processes, as a final common pathway. Based on this, POTS is often described as a clinical syndrome consisting of multiple heterogeneous disorders, with several underlying pathophysiological processes proposed in the literature including partial sympathetic neuropathy, hyperadrenergic state, hypovolemia, mast cell activation, deconditioning, and immune-mediated. These clinical features often overlap, however, making it difficult to categorize individual patients. Importantly, POTS is not associated with mortality, with many patients improving to some degree over time after diagnosis and proper treatment. This review will outline the current understanding of diagnosis, pathophysiology, and prognosis in POTS.

Orthostatic intolerance (OI) causes a marked reduction in the activities of daily living in patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome. Most symptoms of OI are thought to be related to cerebral hypo-perfusion and sympathetic activation. Because postural stability is an essential element of orthostatic tolerance, disequilibrium may be involved in the etiology of OI.The study comprised 44 patients with ME (men, 11 and women, 33; mean age, 37±9 years), who underwent neurological examinations and 10-min standing and sitting tests. Symptoms of OI were detected in 40 (91%) patients and those of sitting intolerance were detected in 30 (68%). Among the 40 patients with OI, disequilibrium with instability on standing with their feet together and eyes shut, was detected in 13 (32.5%) patients and hemodynamic dysfunction during the standing test was detected in 19 (47.5%); both of these were detected in 7 (17.5%) patients. Compared with 31 patients without disequilibrium, 13 (30%) patients with disequilibrium more prevalently reported symptoms during both standing (100% vs. 87%, p=0.43) and sitting (92% vs. 58%, p=0.06) tests. Several (46% vs. 3%, p0.01) patients failed to complete the 10-min standing test, and some (15% vs. 0%, p=0.15) failed to complete the 10-min sitting test. Among the seven patients with both hemodynamic dysfunction during the standing test and disequilibrium, three (43%) failed to complete the standing test. Among the 6 patients with disequilibrium only, 3 (50%) failed while among the 12 patients with hemodynamic dysfunction only, including 8 patients with postural orthostatic tachycardia, none (0%, p=0.02) failed.Patients with ME and disequilibrium reported not only OI but also sitting intolerance. Disequilibrium should be recognized as an important cause of OI and appears to be a more influential cause for OI than postural orthostatic tachycardia in patients with ME.

The aim of this study was to investigate the performance of the Composite Autonomic System Score-31 (COMPASS-31) questionnaire in a real- life setting in consecutive patients referred to the laboratory for objective testing of the autonomic nervous system (ANS), with the hypothesis that COMPASS-31 results differ depending on medications and findings of the tilt table test results. One hundred seventy- one consecutive patients (125 females, mean age 41.5 ± 19.3) referred for testing of the ANS were enrolled. Before testing, all patients completed the recently validated Croatian version of COMPASS-31. The following data were systematically collected for all patients: age, sex, diagnoses, and medications. Results of COMPASS-31 were significantly higher in patients taking medications with a known influence on the ANS (p < 0.001). Patients with postural orthostatic tachycardia had significantly higher orthostatic intolerance and vasomotor domains of COMPASS-31 (p = 0.048 and p = 0.022, respectively). Patients with a cardiovagal score ≥ 1 had a significantly higher vasomotor domain of COMPASS-31 compared to patients with normal results of ANS tests (p = 0.030). These findings suggest the COMPASS-31 might be a valuable screening tool for autonomic dysfunctions, as it is associated with impaired ANS tests, but usage of medications that modify the ANS should always be taken into account.

BackgroundPostural orthostatic tachycardia syndrome encompasses multiple disabling symptoms that interfere with daily activities. Non-pharmacologic approaches can be insufficient and can require adjunctive medications to manage symptoms. Minimal data exist in the literature on medication outcomes in these patients. We reviewed our database for medication management outcomes.Materials and MethodsPatients aged 18 years and younger at initial diagnosis met the inclusion criteria. All prescribed patient medications were extracted from the electronic health record, excluding medications for unrelated symptoms or comorbid diseases. Medications were grouped by symptom class consistent with our programme utilisation protocol. Within symptom classification, therapy was deemed successful when a specific dose was prescribed at least five consecutive times without changes; this was confirmed by chart review. Individual medications and overall percentage of successful therapies within symptom classifications were assessed, with further analysis by gender. t-Test, χ2, and Mann–Whitney U-test were used to assess for differences in specific variables, as appropriate.ResultsA total of 708 patients met the study criteria. The percentage of patients with effective therapy by symptom includes light-headedness (52.2%), headache (48.2%), nausea (39.1%), dysmotility (43.4%), pain (53.4%), and insomnia (42.8%). Insomnia therapy was better for females; all other therapies showed no gender difference. The median number of therapies prescribed per patient per symptom was 2 for light-headedness, headache, and insomnia, and 1 for nausea, dysmotility, and pain.DiscussionSymptoms associated with this disorder can be effectively managed with various medications. Further randomised studies are needed to better ascertain true efficacy compared with placebo.

Objective To investigate whether there is a difference in the neuro-autonomic and hemodynamic parameters in patients with postural tachycardia syndrome (POTS) according to onset time of orthostatic tachycardia during the Head-up tilt (HUT) test. Methods We retrospectively reviewed neuro-autonomic and hemodynamic data from patients with orthostatic intolerance. A standardized battery of neuro-autonomic tests, including the HUT, Valsalva maneuver, heart rate deep breathing and quantitative sudomotor axon reflex test, was performed. The beat-to-beat derived hemodynamic parameters, including systolic blood pressure (BP) (SBP), mean BP (MBP), diastolic BP, heart rate (HR), total peripheral resistance, stroke volume, and cardiac output, were also extracted from HUT test. According to onset time of orthostatic tachycardia (OT), we divided patients into two groups; HR increase “within 10 minutes” (i.e., early OT) and HR increase “after 10 minutes” (i.e., late OT). Results We identified 210 patients with OT during HUT test. Forty-three percent of patients were included in early OT group and 57% were late OT group. Patients in late OT group were older than early OT group. Late OT group tended to have baseline hypertension more frequently compared to early OT group. After adjusting for age, late OT group showed higher baseline SBP and MBP, and lower increase of HR during HUT test than early OT group. However, other neuro-autonomic and hemodynamic parameters did not show significant differences between two groups. Conclusion Orthostatic tachycardia might be developed in the late period during the HUT test. There were no remarkable differences in neuro-autonomic and hemodynamic parameters between early and late OT groups. It seems reasonable to extend the duration of HUT test to at least 20 min, to increase the diagnostic yield in patients with a history of orthostatic intolerance suspected as having POTS.

Introduction It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS. Methods Patients with POTS + hEDS ( n = 20) and POTS controls without hypermobility ( n = 20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year. Results Patients with hEDS had twice as many outpatient visits (21 v. 10, p = 0.012), were taking more prescription medications (8 vs. 5.5, p = 0.030), and were more likely to see a pain physician (70% vs 25%, p = 0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46 bpm vs 39 bpm, p = 0.018). Abnormal QSweat responses were common in both groups (38% of POTS + hEDS and 36% of POTS controls). Conclusions While autonomic testing results were not significantly different between groups, patients with POTS + hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role.

Postural tachycardia syndrome (POTS) can cause orthostatic headache. However, it is difficult to differentiate POTS from spontaneous intracranial hypotension (SIH) caused by cerebrospinal fluid (CSF) leaks. We herein report a 53-year-old woman who presented with SIH associated with POTS. A cervicothoracic and lumbar epidural blood patch rapidly improved not only the headache but also the orthostatic tachycardia, suggesting POTS secondary to SIH. This case suggests that a CSF leak can cause secondary POTS. Therefore, POTS should be considered in patients with orthostatic headaches, even in the presence of a CSF leak.

Compression garments are used by patients with lower extremity edema to help regulate fluid distribution and to prevent orthostatic symptoms. Current compression stockings are often reported as uncomfortable and adherence is poor. The current study was conducted to assess the efficacy of a novel active compression garment on healthy individuals undergoing 60‐degree head‐up tilts for 10 min to induce venous pooling and subsequent physiological responses. During tilts while garments were on, participants’ absolute change in heart rate relative to baseline was lower (16.7 ± 8.7 BPM) compared to control (20.9 ± 11.47 BPM, P = 0.002). There were no differences in changes in mean arterial blood pressure between conditions (P = 0.303). One participant had a pre‐syncopal event which occurred during a tilt without garments. This participant did not experience pre‐syncopal symptoms with the garments on. All together, these data suggest that a novel active compression garment is capable of blunting increases in heart rate during head‐up tilt. While untested thus far in patient populations, these garments may prove efficacious in preventing orthostatic intolerance.

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.

OBJECTIVE: To investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobility type (EDS-HT). METHODS: Eighty patients with EDS-HT and 52 controls participated in the first part of the study, which consisted of questionnaires. Fatigue was evaluated using the Checklist Individual Strength (CIS). As possible fatigue determinants OI [Autonomic Symptom Profile (ASP)], habitual physical activity (Baecke), affective distress [Hospital Anxiety and Depression Scale (HADS)], pain (SF36), medication use and generalized hypermobility (5-point score of Grahame and Hakim regarding generalized joint hypermobility) were studied. Next, a 20 min head-up tilt (70°) was performed in a subsample of 39 patients and 35 controls, while beat-to-beat heart rate and blood pressure were monitored (Holter, Finometer Pro). Before and after tilt, fatigue severity was assessed using a numeric rating scale. RESULTS: Patients scored significantly higher on the CIS [total score: EDS: 98.2 (18.63)vscontrols: 45.8 (16.62), P < 0.001] and on the OI domain of the ASP [EDS: 22.78 (7.16)vscontrols: 6.5 (7.78)]. OI was prevalent in EDS-HT (EDS: 74.4%, controls: 34.3%, P = 0.001), and frequently expressed as postural orthostatic tachycardia (41.0% of the EDS group). Patients responded to tilt with a higher heart rate and lower total peripheral resistance (p < 0.001; p = 0.032). This altered response correlated with fatigue in daily life (CIS). In the EDS-HT group, tilt provoked significantly more fatigue [numeric rating scale increase: EDS: +3.1 (1.90), controls: +0.5 (1.24), P < 0.001]. Furthermore, the factors OI, pain, affective distress, decreased physical activity and sedative use explained 47.7% of the variance in fatigue severity. CONCLUSION: OI is an important determinant of fatigue in EDS-HT.

We investigated how the diagnosis of postural orthostatic tachycardia syndrome (POTS) would be changed due to diurnal variability in orthostatic tachycardia. The orthostatic vital sign test was administered to each patient twice, in the afternoon of the day of admission and the next morning (n = 113). Forty-six patients were diagnosed with POTS, and the remaining 67 patients were assigned to non-POTS group. Heart rate increments after standing were larger in the morning than in the afternoon in every group (all P < .001). Among the POTS patients, 82.6% fulfilled the diagnostic criteria for POTS in the morning and 52.2% in the afternoon. Most POTS group (65.2%) displayed normal result on single orthostatic vital sign test. Orthostatic intolerance symptoms were provoked in only 45.7% of the POTS patients, more frequently in the morning. In conclusion, diurnal variability in hemodynamic parameters and provoked symptoms significantly challenged the diagnosis of POTS.

24-year-old Japanese man with type 2 diabetes mellitus and diabetic neuropathy was admitted to our ward to evaluate the cause of orthostatic intolerance. During a head-up tilt test, his heart rate increased from 105 to 155 beats/minute within 3 minutes, and chest discomfort began. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), and orthostatic intolerance disappeared after β-blocker treatment. Scintigraphy using123I-metaiodobenzylguanidine showed decreased cardiac uptake. Power spectral analysis of heart rate variability for 24 hours in Holter electrocardiography demonstrated decreases in both sympathetic and parasympathetic nervous system activities, with a greater decrease in parasympathetic activity than sympathetic activity. The relative sympathetic hyperactivity in the present patient with diabetic neuropathy seemed to be related to POTS., International Heart Journal, 59(6), pp.1488-1490; 2018

BACKGROUND: Chronic nausea in pediatrics is a debilitating condition with unclear etiology. We aimed to define hemodynamic and neurohumoral characteristics of chronic nausea associated with orthostatic intolerance in order to improve identification and elucidate mechanism. METHODS: Children (10–18 years) meeting Rome III criteria for functional dyspepsia with nausea and symptoms of orthostatic intolerance (OI) completed a Nausea Profile Questionnaire followed by prolonged (45 minutes rather than the traditional 10 minutes) head-upright tilt (HUT)(70 degree tilt up) test. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured supine and after 15 minutes into HUT. Beat-to-beat heart rate and blood pressure were continuously recorded to calculate their variability and baroreflex sensitivity. KEY RESULTS: Within 10 and 45 minutes of HUT, 46% and 85% of subjects, respectively, had an abnormal tilt test (orthostatic hypotension, postural orthostatic tachycardia, or syncope). At 15 and 45 minutes of HUT, nausea was elicited in 42% and 65% of subjects, respectively. Higher Nausea Profile Questionnaire scores correlated with positive HUT testing at 10 minutes (p=0.004) and baroreflex sensitivity at 15 minutes (p≤0.01). Plasma vasopressin rose 33-fold in subjects with HUT-induced nausea compared to 2-fold in those who did not experience HUT-induced nausea (p

Orthostatic intolerance (OI) is common in teenagers (T) and young adults (A). Despite treatment with oral fluids, medication, and exercise, a significant number have symptoms from multiple organ systems and suffer low quality of life (QOL). Previous studies showed that acute intravenous (IV) hydration (IH) could help restore orthostatic tolerance; however, no data are available about the intermediate-term effects of IH. We therefore studied the efficacy of IH to improve QOL and manage medication-refractory OI patients. Our study population consisted of 39 patients (mean age = 16.1 ± 3.3) years; thirty-two were female. Average number of medications failed = 3.1. Average QOL score on self-reported OI questionnaire was 4.2 (normal QOL = 10). IV hydration consisted of normal saline (1-2 l/day, 3-7 days/week). 1) Orthostatic testing revealed Postural Orthostatic Tachycardia (24), Neurally Mediated Hypotension (14) or OI (1). 2) Average orthostatic change in heart rate was 48 ± 18 bpm. 3) IH was performed via intermittent IV access (10), PICC line (22), and Port (7). 4) Duration of IH varied from 1 week to 3.8 years (mean = 29 ± 47 weeks). 5) Overall, 79 % (n = 31) demonstrated clinically improved self-reported QOL. 6) Six patients who discontinued IH requested to restart treatment. (7) Complications consisted of upper extremity deep vein thrombosis (n = 3) and infection (n = 4). IH is an effective therapy to improve QOL in T&A with medication-resistant OI. Most patients continued to report improved QOL once IH was discontinued. IH should be considered a therapeutic option in medication-resistant OI patients with low QOL.

The school nurse is often the first person with whom a student may discuss untoward health symptoms and concerns. Being cognizant of the clinical features of postural orthostatic tachycardia syndrome (POTS) will help the nurse alleviate some of the student’s anxiety. Due to misunderstandings and misconceptions about POTS, family and peers may disbelieve a student who is experiencing symptoms. Displaying compassion and support will help the student understand that someone does believe his or her symptoms. As the student’s advocate, the school nurse will champion a plan for the student’s health and safety in the academic environment.

Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes ( 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN.The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.

Background. Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests.Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group.Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls.Conclusions.This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

Background/Aims: There have been suggestions that interactions exist between the autonomic nervous system (ANS) and the immune system functions in multiple sclerosis (MS). We aimed to evaluate the ANS dysfunction, more specifically postural orthostatic tachycardia syndrome (POTS), as a possible predictor of conversion to MS in patients with clinically isolated syndrome (CIS). Methods: In this observational, prospective, longitudinal study, 84 patients were enrolled (56 females, mean age 32.9 ± 8.9 years). Disease activity during a 6-month period was monitored (relapses and/or MRI disease activity indicated by new T2 or T1 enhancing lesions), and the following predictors analyzed: age, Expanded Disability Status Scale, MRI midbrain, pontine or medulla oblongata lesions, and POTS on the head up tilt test. Results: POTS was identified in 8 (9.5%) patients. Of 84 patients, 62 (73.8%) completed the 6-month follow-up, and 28 (45.2%) patients converted to MS. Results of the multivariate regression analysis revealed age (10-year increase) and POTS as significant predictors of early conversion to MS (OR 2.34, 95% CI 1.15-4.78, p = 0.019 and OR 12.40, 95% CI 1.13-136.62, p = 0.040). The logistic model was statistically significant, χ2 (6) = 13.885, p = 0.031. Conclusion: POTS may be an indicator of a more active disease course in CIS patients and possibly be used as a prognostic factor.

Item does not contain fulltext BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is considered a diagnostic marker for chronic fatigue syndrome (CFS). OBJECTIVES: The aims of this study were to (i) compare POTS prevalence in a CFS cohort with fatigued patients not meeting CFS criteria, and (ii) assess activity, impairment and response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS-CFS) and without POTS (non-POTS-CFS). METHODS: Prospective cohort study at the Radboud University Medical Centre in the Netherlands. Between June 2013 and December 2014, 863 consecutive patients with persistent fatigue were screened. Patients underwent an active standing test, filled out questionnaires and wore an activity-sensing device for a period of 12 days. RESULTS: A total of 419 patients with CFS and 341 non-CFS fatigued patients were included in the study. POTS prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P = 0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P = 0.93). Adult patients with POTS-CFS were younger (30 +/- 12 vs. 40 +/- 13 years, P = 0.001) and had a higher supine heart rate (71 +/- 11 vs. 65 +/- 9 beats per min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity patterns did not differ between groups. In patients with CFS, criteria for Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of adolescents. In these patients with CFS fulfilling the SEID criteria, the prevalence of POTS was not different from that in the overall CFS population. POTS-CFS adolescents had less clinically significant improvement after CBT than non-POTS-CFS adolescents (58% vs. 88%, P = 0.017). CONCLUSION: In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

Postural tachycardia syndrome is defined by a heart rate increment of 40 beats/minute (bpm) (or a heart rate that exceeds 125 bpm) within 10 minutes of change from the supine position to an upright position in the absence of obvious orthostatic hypotension. There are multiple pathophysiological mechanisms that underlie postural tachycardia syndrome, including peripheral denervation, β-receptor supersensitivity, hypovolaemia, and impaired muscle pump. Some children afflicted with postural orthostatic tachycardia syndrome and hypovolaemic dysregulation have been found to have perturbed renin–angiotensin–aldosterone profile, disturbed vascular endothelial function, and abnormal vasodilation. The hyperadrenergic state in some postural tachycardia syndrome patients is likely a driver for orthostatic tachycardia. Other mechanisms include the presence of treatable autonomic neuropathies. An understanding of these pathophysiological mechanisms might be helpful for the effective treatment of postural tachycardia syndrome.

Background Patients with postural tachycardia syndrome often appear depressive and report diminished quality of life (QOL). In the current study, we first evaluated if the maximal heart rate (HR) increment after standing is associated with the clinical symptoms in patients with excessive orthostatic tachycardia (OT). Next, we investigated the correlations among the symptoms of orthostatic intolerance (OI), depression, and health-related QOL in these patients. Finally we assessed if patients with minimal OI symptoms suffer from depression or diminished QOL. Methods We performed a comprehensive questionnaire-based assessment of symptoms in 107 patients with excessive OT with a ≥ 30 beats/min heart rate increment (or ≥ 40 beats/min in individuals aged between 12 and 19) within 10 min after standing up. An existing orthostatic intolerance questionnaire (OIQ), the Beck depression inventory-II (BDI-II), and the 36 Item Short-Form Health Survey were completed prior to any treatment. Correlation analyses among the items of the questionnaires and other parameters were performed. Additionally, patients with minimal OI symptoms were analysed separately. Results The maximal orthostatic HR increment was not associated with the clinical symptoms. The OI symptoms were significantly correlated with depression and diminished QOL. The BDI-II score demonstrated a positive linear relationship with total OIQ score (r = 0.516), and both physical and mental component summary scales of SF-36 showed a negative linear relationship with total OIQ score (r = -0.542 and r = -0.440, respectively; all p

Sympathetic circulatory control is key to the rapid cardiovascular adjustments that occur within seconds of standing upright (orthostasis) and which are required for bipedal stance. Indeed, patients with ineffective sympathetic adrenergic vasoconstriction rapidly develop orthostatic hypotension, prohibiting effective upright activities. One speaks of orthostatic intolerance (OI) when signs, such as hypotension, and symptoms, such as lightheadedness, occur when upright and are relieved by recumbence. The experience of transient mild OI is part of daily life. However, many people experience episodic acute OI as postural faint or chronic OI in the form of orthostatic tachycardia and orthostatic hypotension that significantly reduce the quality of life. Potential mechanisms for OI are discussed including forms of sympathetic hypofunction, forms of sympathetic hyperfunction, and OI that results from regional blood volume redistribution attributable to regional adrenergic hypofunction.

The present study was designed to analyse the usefulness of a modified Calgary score system during differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope through a large sample sized clinical investigation. The study included 213 children, including 101 boys and 112 girls, with cardiac syncope or postural orthostatic tachycardia syndrome-associated syncope in the age group of 2–19 years (mean 11.8 ± 2.9 years). A modified Calgary score was created, which was analysed to predict differential diagnoses between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope using a receiver operating characteristic curve. The median of modified Calgary scores for cardiac syncope was −5.0, which significantly differed from that of postural orthostatic tachycardia syndrome (0.0; p < 0.01). The sensitivity and specificity of a differentiation score of less than −2.5 was 96.3% and 72.7%, respectively. Owing to the fact that the modified Calgary score was an integer, when less than −3.0 the diagnosis could be considered as cardiac syncope. The modified Calgary score could be used to make an initial differential diagnosis between cardiac syncope and postural orthostatic tachycardia syndrome-associated syncope in the clinic.

To study the frequency and degree of deconditioning, clinical features, and relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance.We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing.A total of 184 patients (84 with postural orthostatic tachycardia syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion criteria. Of these, 89% were women, and median age was 27.5 years (interquartile range [IQR] 22-37 years). Symptom duration was 4 years (IQR 2-7.8). Of the patients, 90% had deconditioning (reduced maximum oxygen uptake [VO(2max)%]85%) during exercise. This finding was unrelated to age, gender, or duration of illness. The prevalence of deconditioning was similar between those with POTS (95%) and those with orthostatic intolerance (91%). VO(2max)% had a weak correlation with a few autonomic and laboratory parameters but adequate predictors of VO(2max)% could not be identified.Reduced VO(2max)% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning.

To assess differences in gynecologic history and lightheadedness during menstrual cycle phases among patients with POTS and healthy control women.In a prospective, questionnaire-based study carried out at Paden Autonomic Dysfunction Center, Vanderbilt University, between April 2005 and January 2009, a custom-designed questionnaire was administered to patients with POTS (n=65) and healthy individuals (n=95). The results were analyzed via Fisher exact test and Mann-Whitney U test.Patients with POTS reported increased lightheadedness through all phases of the menstrual cycle phases as compared with healthy controls. Both groups experienced the greatest lightheadedness during menses, and a decrease in lightheadedness during the follicular phase. Patients with POTS reported a higher incidence of gynecologic diseases as compared with healthy controls.The severity of lightheadedness was found to vary during the menstrual cycle, which may relate to changes in estrogen levels. Patients with POTS also reported an increase in estrogen-related gynecologic disease.

Background— 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. Methods and Results— 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. Conclusions— 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.

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.

While orthostatic tachycardia is the hallmark of postural tachycardia syndrome (POTS), orthostasis also initiates increased minute ventilation (V̇e) and decreased end-tidal CO2 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% O2), eucapneic hypoxia (10% O2), and hypercapnic hyperoxia (30% O2 + 5% CO2) while supine and during 70° head-upright tilt. Heart rate, mean arterial pressure, O2 saturation, end-tidal CO2, and V̇e were measured. Peripheral chemoreflex sensitivity was calculated as the difference in V̇e during hypoxia compared with room air divided by the change in O2 saturation. Central chemoreflex sensitivity was determined by the difference in V̇e during hypercapnia divided by the change in CO2. 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) CO2 response (0.49 ± 0.38 vs. 1.04 ± 0.18) compared with controls. CO2 sensitivity was also reduced in POTS subjects when supine. POTS patients are markedly sensitized to hypoxia when upright but desensitized to CO2 while upright or supine. The interactions between orthostatic baroreflex unloading and altered chemoreflex sensitivities may explain the hyperventilation in POTS patients.

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

A 26-year-old woman experienced syncope on standing 2–3 times a year for more than 15 years. The attack was typically associated with palpitations and frequently accompanied by a feeling of intense fear. The patient underwent head-up tilt table testing at 70°for 40 min to determine the cause of the syncope. The tilt test results suggested that the etiology of the syncope was orthostatic tachycardia syndrome complicated by panic attack-associated hypocapnic hyperventilation, which presumably caused a greater degree of deep cerebral hypoperfusion than would be expected with orthostatic tachycardia syndrome alone, ultimately leading to the patient’s symptoms, including syncope. In conclusion, monitoring the ventilation and/or arterial CO2 level during head-up tilt table testing is occasionally required when evaluating patients with postural syncope.

Orthostatic tachycardia (POTS) can occur after space flights. We determined orthostatic heart rate responses in 18 cosmonauts before and 3-5 days after long-term space missions. Cosmonauts undergoing a cardiovascular training program in space experienced only moderate POTS after their return to earth. Cardiovascular countermeasures may have attenuated POTS. Another possible interpretation is that cardiovascular deconditioning is not sufficient to elicit full blown POTS in the absence of additional genetic or environmental factors.

Background Disturbances in autonomic nervous system function have been reported to occur in patients suffering from mitochondrial cytopathies. However, there is paucity of literature on the occurrence of orthostatic intolerance (OI) in these patients. We report on a series of patients diagnosed with mitochondrial cytopathy who developed features of autonomic dysfunction in the form of OI. Methods This was a single-center report on a series of 6 patients who were followed in our clinic for orthostatic intolerance. All of these patients had a diagnosis of mitochondrial cytopathy on the basis of muscle biopsy and were being followed at a center specializing in the treatment of mitochondrial disorders. This study was approved by our local institutional review board. Each of the patients had suffered from symptoms of fatigue, palpitations, near syncope, and syncope. The diagnosis of OI was confirmed by head-up tilt test. Collected data included demographic information, presenting symptoms, laboratory data, tilt-table response, and treatment outcomes. Results Six patients (3 females) were identified for inclusion in this report. The mean age of the group was 48 ± 8 years (range, 40–60 years). All of these patients underwent head-up tilt table testing and all had a positive response that reproduced their clinical symptoms. Among those having an abnormal tilt-table pattern, 1 had a neurocardiogenic response, 1 had a dysautonomic response, and 4 had a postural orthostatic tachycardia response. All but 1 patient reported marked symptom relief with pharmacotherapy. The patient who failed pharmacotherapy received a dual-chamber closed-loop pacemaker and subsequently reported marked improvement in her symptoms with elimination of her syncope. Conclusions Orthostatic intolerance might be a significant feature of autonomic nervous system dysfunction in patients suffering from mitochondrial cytopathy. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Background Autonomic dysfunction presenting as inappropriate sinus tachycardia has been reported to occur following slow pathway ablation for atrioventricular node tachycardia. We report on a series of patients who developed new onset postural orthostatic tachycardia syndrome (POTS) following successful radiofrequency ablation of atrioventricular nodal reentrant tachycardia (AVNRT). Methods The study was a retrospective analysis that was approved by our Institutional Review Board. Patients were identified from those seen at our Syncope and Autonomic Disorders Clinic. A total of six patients were identified who were previously healthy except for supraventricular tachycardia. Each was found to have AVNRT during electrophysiology study and each underwent successful radiofrequency modification of the slow atrioventricular nodal pathway. Following ablation each patient developed the new onset of symptoms of orthostatic intolerance consistent with POTS. Results After aninitial symptom-free period(3‐6 weeks)post ablation each patient began to experience symptoms of orthostatic intolerance. All six patients began to experience progressive severe fatigue. Orthostatic tachycardia was reported by five patients, syncope by three patients, and presyncope by all six patients. Each patient reported the occurrence of symptom while upright that were relieved by becoming supine. Each patient had experienced symptoms for greater than 6 months prior to being seen at our center. Three patients reported such severe symptoms of orthostatic tachycardia that they underwent repeat electrophysiology study; however, none had evidence of AVNRT. Each patient demonstrated a POTS response within the first 10 min of upright tilt with reproduction of their clinical symptoms that had occurred post ablation. Conclusion POTS may be a complication of radiofrequency ablation of AVNRT.

ObjectivesThe purpose of this study was to test the hypothesis that a small heart coupled with reduced blood volume contributes to the postural orthostatic tachycardia syndrome (POTS) and that exercise training improves this syndrome.BackgroundPatients with POTS have marked increases in heart rate during orthostasis. However, the underlying mechanisms are unknown and the effective therapy is uncertain.MethodsTwenty-seven POTS patients underwent autonomic function tests, cardiac magnetic resonance imaging, and blood volume measurements. Twenty-five of them participated in a 3-month specially designed exercise training program with 19 completing the program; these patients were re-evaluated after training. Results were compared with those of 16 healthy controls.ResultsUpright heart rate and total peripheral resistance were greater, whereas stroke volume and cardiac output were smaller in patients than in controls. Baroreflex function was similar between groups. Left ventricular mass (median [25th, 75th percentiles], 1.26 g/kg [1.12, 1.37 g/kg] vs. 1.45 g/kg [1.34, 1.57 g/kg]; p < 0.01) and blood volume (60 ml/kg [54, 64 ml/kg] vs. 71 ml/kg [65, 78 ml/kg]; p < 0.01) were smaller in patients than in controls. Exercise training increased left ventricular mass and blood volume by approximately 12% and approximately 7% and decreased upright heart rate by 9 beats/min [1, 17 beats/min]. Ten of 19 patients no longer met POTS criteria after training, whereas patient quality of life assessed by the 36-item Short-Form Health Survey was improved in all patients after training.ConclusionsAutonomic function was intact in POTS patients. The marked tachycardia during orthostasis was attributable to a small heart coupled with reduced blood volume. Exercise training improved or even cured this syndrome in most patients. It seems reasonable to offer POTS a new name based on its underlying pathophysiology, the “Grinch syndrome,” because in this famous children's book by Dr. Seuss, the main character had a heart that was “two sizes too small.”

Background: Autonomic dysfunction is common in patients suffering from multiple sclerosis (MS) and orthostatic dizziness occurs in almost 50% of these patients. However, there have been no reports on postural orthostatic tachycardia syndrome (POTS) in patients suffering from MS. Methods: The patients were included for analysis in this study if they had POTS with either a prior history of MS or having developed MS while being followed for POTS. Postural orthostatic tachycardia (POTS) is defined as symptoms of orthostatic intolerance(>6months) accompanied by a heart rate increase of at least 30 beats/min (or a rate that exceeds 120 beats/min) that occurs in the first 10 minutes of upright posture or head up tilt test (HUTT) occurring in the absence of other chronic debilitating disorders. We identified nine patients with POTS who were suffering from MS as well. Each of these patients had been referred from various other centers for second opinions. Results: The mean age at the time of diagnosis of POTS was 49±9 years and eight of the 9 patients were women. Five patients (55%) had hyperlipidemia, 3 (33%) migraine and 2 (22%) patients had coronary artery disease and diabetes each. Fatigue and palpitations (on assuming upright posture) were the most common finding in our patients (9/9). All patients also had orthostatic dizziness. Syncope was seen in 5/9(55%) of patients. Four patients (44%), who did not have clear syncope, were having episodes of near syncope. The presence of POTS in our study population resulted in substantial limitation of daily activities. Following recognition and treatment of POTS, 6/9(66%), patients were able to resume daily activities of living. Their symptoms (especially fatigue and orthostatic intolerance) improved. The frequency and severity of syncope also improved. Three (33%) patients failed to show a good response to treatment. Conclusion: Patients suffering from MS may manifest autonomic dysfunction by developing POTS. Early recognition and proper management may help improve the symptoms of POTS.

Although fibromyalgia (FM) syndrome is defined by chronic widespread pain and tenderness, additional symptoms, including disabling fatigue and dizziness, are often reported by patients with this chronic illness. Although nonrestorative sleep may play an important role for chronic fatigue in FM, other mechanisms, including dysfunction of the autonomic nervous system (ANS), need to be considered. Many important biological functions, such as heart rate, blood pressure, respirations, and bowel function, are tightly regulated by the ANS. However, dysfunction of the ANS is common in FM and often becomes quite apparent after positional changes from supine to upright. Although such positional changes sometimes result in syncope, they are more often associated with palpitations and dizziness. Head-up tilt table testing can be used to evaluate autonomic dysfunction and is frequently helpful for the work-up of FM complaints, including fatigue, dizziness, and palpitations. One of the most common events experienced by FM patients during tilt table testing is postural orthostatic tachycardia syndrome, which is defined as a heart rate increase of more than 30 beats per minute after more than 3 minutes of standing upright.

The types of patients different subspecialists jointly manage often provide insights regarding shared pathophysiology and common treatment strategies. During the past decade, as cardiologists have increasingly recognized the subset of adolescents with multiple somatic symptoms and marked orthostatic

Postural tachycardia syndrome (POTS) is characterized by the presence of orthostatic tachycardia in the absence of orthostatic hypotension with a heart rate increase of >or=30 bpm. Patients often relate complaints of palpitations, exercise intolerance, fatigue and near-syncope or syncope, other non-specific symptoms such as headache and nausea may be present as well to varying degrees. Myocardial bridging is rare occurring in 0.5-16% in angiographic studies. Clinical presentation is protean and can manifest as atrioventricular blockade, ventricular tachycardia, myocardial ischaemia, sudden cardiac death, and myocardial infarction. However, the majority of patients with myocardial bridging are asymptomatic. We describe a case of POTS syndrome and myocardial bridging co-existing and presenting a therapeutic challenge.

To evaluate the prevalence and pathogenetic mechanisms of postural orthostatic tachycardia syndrome (POTS).We reviewed the medical records of patients with POTS seen at the Mayo Clinic in Rochester, Minn, from January 1, 1993, through December 31, 2003. All patients were required to have had a full autonomic reflex screen. The results of the following additional tests were evaluated: thermoregulatory sweat test, plasma catecholamine measurement, serum ganglionic (a3) acetylcholine receptor antibody detection, and 24-hour urinary sodium measurement.We identified 152 patients (86.8% female; mean +/- SD age, 30.2+/-10.3 years) with a mean duration of symptoms of 4.1 years. The mean orthostatic heart rate increment was 44 beats/min. Half the patients had sudomotor abnormalities (apparent on both the quantitative sudomotor axon reflex test and thermoregulatory sweat test), and 34.9% had significant adrenergic impairment, indicating that at least half of the patients had a neuropathic pattern of POTS. In 13.8% of patients, onset was subacute, and ganglionic acetylcholine receptor antibody was detected in 14.6%, suggesting an autoimmune origin in at least 1 in 7 patients. Hyperadrenergic status was documented in 29.0% of patients (standing plasma norepinephrine level 2600 pg/mL), and at least 28.9% were presumably hypovolemic (24-hour urinary sodium level100 mEq/24h). The lack of correlation between urinary sodium and standing norepinephrine levels suggests that mechanisms other than hypovolemia accounted for the hyperadrenergic state.Our findings suggest a neuropathic basis for at least half the cases of POTS and that a substantial percentage of cases may be autoimmune. Hyperadrenergic and hypovolemic correlates are likely compensatory or exacerbating.

Bevezetés: Az orthostasis intolerancia, az orthostaticus tachycardia gyakran jelez hypovolemiát, gyógyszermellékhatást vagy autonóm elégtelenséget. Az orthostasisszal provokálható tachyarrhythmia ritka jelenség, emelt fejvégű billenőasztal vizsgálatsorozatokban csak elvétve fordul elő. Célkitűzés: A szerzők egy olyan beteget mutatnak be, akinek AV-csomó reentry tachycardiás paroxysmusait függőleges testhelyzet provokálta. Módszer: Vagusmanőverekkel az anterográd lassú pálya vezetésének blokkolása révén sikeresen szüntették a tachycardiát. Eredmények: Figyelemre méltó, hogy a vagusmanőverek csak vízszintes testhelyzetben bizonyultak hatásosnak. Következtetés: Ez a megfigyelés felhívja a figyelmet a manőverek pontos kivitelezésének fontosságára.