Chronic Orthostatic Intolerance Research Articles

Orthostatic intolerance with tachycardia (postural tachycardia syndrome) and without (hypocapnic cerebral hypoperfusion) represent a spectrum of the same disorder.

Spectrum of chronic orthostatic intolerance without orthostatic hypotension includes postural tachycardia syndrome (POTS), with orthostatic tachycardia and hypocapnic cerebral hypoperfusion (HYCH), without orthostatic tachycardia. This study compared autonomic, cerebrovascular, and neuropathic features of POTS and HYCH. This retrospective study evaluated patients with orthostatic intolerance referred for autonomic testing. Analyzed data included surveys (Survey of Autonomic Symptoms, Compass-31, Neuropathy Total Symptom Score-6, Central Sensitization Inventory) and autonomic tests (Valsalva maneuver, deep breathing, sudomotor and tilt tests), cerebrovascular (cerebral blood flow velocity (CBFv) monitoring in the middle cerebral artery), respiratory (capnography), neuropathic (skin biopsies for assessment of small fiber neuropathy) and invasive cardiopulmonary exercise testing (iCPET). A total of 127 HYCH, 125 POTS, and 42 healthy controls were analyzed. Compared HYCH to POTS patients, there was no difference in the duration of symptoms, the prevalence of younger women, comorbidities, sensory and autonomic complaints, central sensitization syndrome, supine/standing norepinephrine levels, inflammatory markers and medical therapy except for gastrointestinal medication. Autonomic testing showed widespread but similar abnormalities in POTS and HYCH that included: reduced orthostatic CBFv and end-tidal CO2, preload failure (assessed in 16/19 POTS/HYCH), mild autonomic failure, and frequent small fiber neuropathy. HYCH and POTS are syndromes of orthostatic intolerance with cerebral hypoperfusion associated with reduced orthostatic cerebral blood flow, hypocapnia, mild autonomic failure and small fiber neuropathy of a similar degree and distribution; except for tachycardia in POTS. Similarities in peripheral domain abnormalities that affect heart rate suggest that orthostatic tachycardia in POTS is driven by the central nervous system overcompensation of orthostatic challenge. These findings provide additional evidence that HYCH and POTS represent a spectrum of the same disorder. Reduced orthostatic cerebral blood flow is a key unifying feature of HYCH and POTS.

Acceleration index predicts efficacy of orthostatic training on postural orthostatic tachycardia syndrome in children.

Electrocardiographic acceleration index can be used to predict the effectiveness of orthostatic training in treating children with POTS. • Postural orthostatic tachycardia syndrome (POTS) is a chronic orthostatic intolerance involving multiple mechanisms. Autonomic dysfunction is one of the main mechanisms of POTS in children and could be treated with orthostatic training. • In order to improve the efficacy of orthostatic training in children with POTS, it is particularly important to identify the patients with autonomic dysfunction as the main mechanism before the treatment. • We found acceleration index of the electrocardiogram (ECG) can be used as a satisfactory index to predict the efficacy of orthostatic training in the treatment of POTS in children. • Using the acceleration index to predict the efficacy of orthostatic training on POTS in children is easy to be popularized in hospitals at all levels because it is non-invasive, convenient, and not expensive.

Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study

PurposeTo determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state. MethodsA cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests. ResultsIn CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process. ConclusionOur data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.

Linking the Extended Autonomic System with the Homeostat Theory: New Perspectives about Dysautonomias.

Dysautonomias are conditions in which altered functions of one or more components of the autonomic nervous system (ANS) adversely affect health. This essay is about how elucidating mechanisms of dysautonomias may rationalize personalized treatments. Emphasized here are two relatively new ideas-the "extended" autonomic system (EAS) and the "homeostat" theory as applied to the pathophysiology and potential treatments of dysautonomias. The recently promulgated concept of the EAS updates Langley's ANS to include neuroendocrine, immune/inflammatory, and central components. The homeostat theory builds on Cannon's theory of homeostasis by proposing the existence of comparators (e.g., a thermostat, glucostat, carbistat, barostat) that receive information about regulated variables (e.g., core temperature, blood glucose, blood gases, delivery of blood to the brain). Homeostats sense discrepancies between the information and response algorithms. The presentation links the EAS with the homeostat theory to understand pathophysiological mechanisms of dysautonomias. Feed-forward anticipatory processes shift input-output curves and maintain plateau levels of regulated variables within different bounds of values-"allostasis". Sustained allostatic processes increase long-term wear-and-tear on effectors and organs-allostatic load. They decreaseing thresholds for destabilizing and potentially fatal positive feedback loops. The homeostat theory enables mathematical models that define stress, allostasis, and allostatic load. The present discussion applies the EAS and homeostat concepts to specific examples of pediatric, adolescent/adult, and geriatric dysautonomias-familial dysautonomia, chronic orthostatic intolerance, and Lewy body diseases. Computer modeling has the potential to take into account the complexity and dynamics of allostatic processes and may yield testable predictions about individualized treatments and outcomes.

Abstract 15621: Pelvic Vein Compression in Patients Diagnosed With Postural Orthostatic Tachycardia Syndrome

Introduction: Postural Orthostatic Tachycardia Syndrome (POTS) is a condition characterized by chronic orthostatic intolerance and a significant increase in heart rate. Patients with POTS often exhibit symptoms suggestive of pelvic venous congestion. While venography is the standard method for diagnosing venous compression disorders in the abdomen and pelvis, its potential use in identifying undiagnosed venous abnormalities and its relationship in POTS patients has not been studied. Research Question: This study aimed to investigate the findings of antegrade venography and intravascular ultrasound in patients diagnosed with POTS with high suspicion of May-Thurner Syndrome (MTS) and/or pelvic congestion syndrome, based on initial diagnostic tools such as ultrasound, and who exhibited symptoms of pelvic venous insufficiency (PVI). Methods: Patients clinically diagnosed with POTS underwent antegrade venography and intravascular ultrasound due to a high suspicion of PVI. Demographic, clinical presentation, and venography findings were extracted from the electronic medical records of patients referred to Emory University for POTS/dysautonomia/long COVID evaluation. Patients were diagnosed with MTS if they demonstrated stenosis of the left common iliac vein of 50-70% with associated symptoms like pelvic pain and lower extremity swelling. Results: We identified 28 patients with POTS who had symptoms of PVI. The mean age was 31.6 years (range 18-54), and 96% were female. Doppler ultrasonography revealed venous reflux in the common femoral vein in 82% of the patients. All participants met the criteria for MTS and were referred for stenting. Additionally, 21% of those evaluated had significant bilateral iliac vein compression. Conclusions: This is the largest cohort of POTS patients with pelvic venous compression to date, and our findings suggest a potential association between venous disease and the pathophysiology of POTS. Further research is needed to establish a causal link and explore the clinical implications of venography findings after intervention with angioplasty and stenting. Understanding the venous component in POTS may aid clinicians in the earlier diagnosis and management of PVI.

Hypocapnia increases heart rate in patients with Postural Orthostatic Tachycardia Syndrome (POTS)

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by chronic orthostatic intolerance and significantly impacts quality of life of patients. POTS predominantly affects women of child-bearing age with an estimated prevalence of up to 1%. POTS is defined by an excessive increase in heart rate (HR) of ≥30 bpm within 10 minutes of upright posture, in the absence of orthostatic hypotension. POTS is associated with chronic symptoms (≥6 months) including hyperventilation (HV) in the form of hyperpnea. HV reduces arterial CO 2 (hypocapnia) and worsens tachycardia in POTS. Whether it is hypocapnia that increases HR in these patients is unclear. Studies have not investigated the effects of CO 2 on HR due to the confounding effects of posture and ventilation. Objective: We aimed to determine if hypocapnia exacerbates tachycardia in POTS patients. Hypothesis: We hypothesize that hypocapnia will increase HR in POTS. Methods: We conducted a randomized crossover trial of hypocapnic HV vs. eucapnic HV in 13 female POTS patients (34±9 y). Participants completed the supine breathing protocol: 1) HV with resultant hypocapnia, and 2) HV (with end-tidal CO 2 (ETCO 2 ) clamped at baseline). Breath-by-breath respiratory (ventilation (V E ), tidal volume (V T ), ETCO 2 , end-tidal O 2 (ETO 2 )) and beat-to-beat hemodynamics (HR, stroke volume (SV), cardiac output (CO)) were measured. Data are reported as mean±SD. Paired t-tests were used to compare respiratory and hemodynamic parameters between hypocapnic HV vs. eucapnic HV. Results: During HV, ETCO 2 was significantly lower during hypocapnia vs. eucapnia (19.6±3.7 mmHg vs. 37.4±3.5 mmHg; p<0.0001). ETO 2 was greater during hypocapnia vs eucapnia (117.4±4.7 mmHg vs. 114.6±3.1 mmHg; p<0.001). There was no difference in V E (22.2±6.5 L/min vs. 22.0±5.1 L/min; p=0.8) or V T (1.4±0.4 L vs. 1.4±0.3 L; p=0.9) between hypocapnia and eucapnia. HR was significantly greater during hypocapnia vs. eucapnia (99±12 bpm vs 82±10 bpm; p<0.001); SV was significantly lower during hypocapnia vs. eucapnia (66±14 mL vs. 74±13 mL; p=0.02); and there was no difference in CO between hypocapnia and eucapnia (6.4±1.3 L/min vs. 6.1±1.6 L/min; p=0.3). Conclusion: Independent of ventilation, hypocapnia increases HR in patients with POTS. Our findings suggests that hypocapnia causes a reduction in SV, perhaps due to increased blood pooling in the capacitance vessels leading to reduced venous return. This work was supported by Standing up to POTS. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypocapnic Orthostatic Intolerance with (POTS) and without (HYCH) Tachycardia Represent a Spectrum of the Same Disorder (S43.003)

<h3>Objective:</h3> To compare postural tachycardia syndrome (POTS) with hypocapnic cerebral hypoperfusion (HYCH). <h3>Background:</h3> Several chronic orthostatic intolerance syndromes are associated with hypocapnia-driven cerebral hypoperfusion. Common syndromes are POTS where orthostatic tachycardia is present, and HYCH, where orthostatic tachycardia is absent. <h3>Design/Methods:</h3> This retrospective study evaluated consecutive patients with POTS and HYCH. Analyzed data included surveys (autonomic and sensory), autonomic (Valsalva maneuver, deep breathing, sudomotor and tilt tests), cerebrovascular (cerebral blood flow velocity (CBFv) monitoring in the middle cerebral artery), respiratory (capnography), neuropathic (skin biopsies for assessment of small fibers) testing and metabolic/inflammatory/autoimmune markers. <h3>Results:</h3> Eighty-one POTS and seventy-two HYCH patients were evaluated and they were compared to 25 healthy controls. POTS and HYCH patients had similar ages, gender, disease duration, and survey scores. Orthostatic CBFv was reduced in HYCH (−22.1±9.4%) and POTS (−23.3±12.0%) compared to controls (−4.4±7.1%,p&lt;0.001). Orthostatic end-tidal CO₂ was reduced in HYCH (27.9±5.6 mmHg) and POTS (27.1±5.6 mmHg) compared to controls (35.3±4.8 mmHg, p&lt;0.001). Orthostatic heart rate was higher in POTS (117±19.3 BPM) compared to HYCH (88.5±15.0 BPM, p&lt;0.001). Mild autonomic failure was present in 91.7% of HYCH and 82.7% of POTS patients. Compared HYCH with POTS, there was no significant difference in the following QASAT scores: sympathetic sudomotor (1.7±1.6/1.3±1.8, HYCH/POTS), parasympathetic cardiovagal (0.4±0.7/0.3±0.6), sympathetic adrenergic (1.2±0.9/1.1±1.0), epidermal fiber density (EFD, 1.8±2.1/1.9/2.4) and sweat gland fiber density (SGF, 1.4±2.0/1.5±2.3). EFD/SGF was abnormal in 63.4%/41.5% of HYCH and 55.8%/43.1% of POTS. Autoimmune markers were positive in 75% of HYCH and 81.5% of POTS. There was no significant difference in supine and orthostatic norepinephrine in both conditions. <h3>Conclusions:</h3> POTS and HYCH have similar abnormalities on subjective and objective measures except for the presence of tachycardia in POTS. Considering that the POTS-grade orthostatic tachycardia (≥30 BPM) can be seen in healthy subjects, these results suggest that HYCH and POTS represent a spectrum of the same disorder. <b>Disclosure:</b> Dr. Novak has received personal compensation for serving as an employee of Dysimmune Disease Foundation. Dr. Novak has stock in Pfeizer. Dr. Novak has stock in Moderna. Dr. Novak has stock in Novavax. Dr. Novak has stock in Editas Medicine. Dr. Novak has stock in Prothena. Dr. Novak has received publishing royalties from a publication relating to health care. Miss Marciano has nothing to disclose.

Sympathetic toggled sinus rate acceleration as a mechanism of sustained sinus tachycardia in chronic orthostatic intolerance syndrome

The role of sympathetic nerve activity to maintain sinus rate acceleration remains unclear. The purpose of this study was to test the hypothesis that sustained (>30 seconds) sinus rate acceleration can be associated with either a sympathetic driven or a sympathetic toggled mechanism. We used a patch monitor to record skin sympathetic nerve activity (SKNA) and electrocardiogram over 24 hours. Study 1 included chronic orthostatic intolerance (OI) (n = 18), atrial fibrillation (n = 7), and asymptomatic normal control (n = 19) groups. Study 2 included 17 participants with chronic OI not treated with ivabradine, pyridostigmine, or β-blockers. While a majority of sinus rate acceleration was driven by persistent SKNA in study 1, some episodes were toggled on and off by SKNA bursts without persistent SKNA elevation. The sympathetic toggled sinus rate acceleration episodes were found in 7 of 18 participants with chronic OI (39%), 2 of 7 participants with atrial fibrillation (29%), and 6 of 19 normal control participants (32%) (P = .847) and were faster and longer in the chronic OI group than in other groups. In study 2, there were a total of 11 episodes of sinus rate acceleration that persisted for >200 seconds. Among these episodes, 6 (35%) were toggled on and off by SKNA bursts. Sustained sinus rate acceleration (may be toggled on or off) is associated with SKNA bursts in participants with chronic OI, participants with atrial fibrillation, and normal controls. Patients with OI had more frequent and longer episodes than did other groups.

Sleep Timing and Duration in Adolescents with Debilitating Chronic Orthostatic Intolerance

Sleep Timing and Duration in Adolescents with Debilitating Chronic Orthostatic Intolerance

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

Chronic orthostatic intolerance (OI) is characterizedby the development of tachycardia and other symptomswhen assuming an upright body position. The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or β-blockers. In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptomshad higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomaticin controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

Physical Symptoms, Distress, and Functional Disability in Youth With Chronic Orthostatic Intolerance.

Youth with chronic orthostatic intolerance (OI) can experience significant physical, social, and academic functional debilitation. Previous studies have indicated associations among symptom severity, psychosocial factors, and functional disability. However, empirically tested models explaining how different medical and psychosocial factors may contribute to functional disability are lacking. The current cross-sectional study aimed to evaluate mediation, moderation, and additive models of the effect of physical symptoms and psychological distress on functional disability. One hundred and sixty-five youth (13-22 years old) undergoing medical evaluation of chronic OI symptoms completed measures of autonomic dysfunction symptom severity, depressive and anxiety symptoms, and functional disability. Models were evaluated using tests of indirect effects and linear and logistic regression analyses. Results supported the mediation and additive effects models for depressive symptoms. Mediation, moderation, and additive models for hypothesized effects of anxiety symptoms were not supported. Results provide preliminary support for models in which OI symptoms affect functional debility via their effects on mood and in which depressive symptoms have unique and additive effects on functioning. Findings lay the foundation for longitudinal and experimental evaluation of biopsychosocial models of functional disability in youth with chronic OI and related conditions. Implications include the importance of a biopsychosocial conceptualization of OI symptoms and debility as a complex interplay of factors rather than as a purely physiological or psychological process.

Oral and intravenous hydration in the treatment of orthostatic hypotension and postural tachycardia syndrome.

Hydration with water and salt is the mainstay of treatment for autonomic nervous system disorders that impair orthostatic tolerance. The goal is to expand intravascular volume to compensate for the downward displacement of blood volume that occurs when standing and thereby sustain cerebral perfusion and restore quality of life. Despite strong consensus recommendations for salt supplementation as standard treatment of these disorders, published evidence of benefit is relatively weak, and no randomized clinical trials have occurred. This review summarizes the physiological rationale for hydration and evaluates the literature on oral and intravenous hydration in the treatment of neurogenic orthostatic hypotension, postural tachycardia syndrome, and recurrent vasovagal syncope. We conclude that oral salt replacement is indicated for treatment of neurogenic orthostatic hypotension because these patients have excessive renal sodium excretion, and for treatment of chronic orthostatic intolerance because these patients are often hypovolemic. As not all patients are able to tolerate sufficient oral hydration, there is also a role for intravenous volume-loading in severe cases of postural tachycardia syndrome. We offer guidance, based on review of the literature and the clinical judgment of a cardiologist and neurologist with experience treating autonomic disorders, regarding the option of ongoing intravenous hydration for treatment of severe, refractory cases of postural tachycardia syndrome.

Cardiovascular Autonomic Regulation, ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance.

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of ≥ 30bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO2 and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N = 108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO2 during 10min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO2 show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

Early Cerebral Hypoperfusion in Patients with Orthostatic Intolerance Without Tachycardia During Head-Up Tilt Test is Independent of Vasovagal Response.

Cerebral hypoperfusion before syncope has been shown in patients with chronic orthostatic intolerance (OI) without tachycardia, but it is unknown if an initial decrease of cerebral blood flow velocity (CBFv) could be related to the vasovagal response (VVR) to head-up tilt test (HUTT). The objective of the study was to compare cardiovascular, cerebrovascular, and autonomic variables during HUTT in OI patients with or without a VVR. We included 74 subjects (58% female, mean age 33 ± 12 years) who underwent a 30-min HUTT and were divided into three groups: OI with VVR positive (VVR+), OI without VVR negative (VVR-), and asymptomatic healthy subjects with negative HUTT (control group). Cardiovascular, cerebrovascular, and autonomic variables were assessed beat-to-beat during HUTT with a Task Force monitor and a trans-cranial Doppler. Mean values were evaluated at baseline and throughout the first 10 min of tilting. Cardiovascular variables were similar in the three groups. Systolic, diastolic, and mean CBFv were similar in VVR+ and VVR-, but both groups had lower CBFv than the control group. Systolic and diastolic CBFv decreased from baseline since min 1 in VVR+ and VVR- and since min 5 in the control group. The mean CBFv had a significant decrease since min 1 compared to baseline in all groups. Spectral indices of heart rate and blood pressure variability showed a similar autonomic response to HUTT in all groups. Patients with chronic OI without tachycardia have early postural cerebral hypoperfusion, regardless of the VVR during HUTT.

Postural Tachycardia Syndrome in Children and Adolescents: Pathophysiology and Clinical Management.

Postural tachycardia syndrome (POTS), characterized by chronic (≥6 months) orthostatic intolerance symptoms with a sustained and excessive heart rate increase while standing without postural hypotension, is common in children and adolescents. Despite the unclear pathogenesis of POTS, the present opinion is that POTS is a heterogeneous and multifactorial disorder that includes altered central blood volume, abnormal autonomic reflexes, “hyperadrenergic” status, damaged skeletal muscle pump activity, abnormal local vascular tension and vasoactive factor release, mast cell activation, iron insufficiency, and autoimmune dysfunction. A number of pediatric POTS patients are affected by more than one of these pathophysiological mechanisms. Therefore, individualized treatment strategies are initiated in the management of POTS, including basal non-pharmacological approaches (e.g., health education, the avoidance of triggers, exercise, or supplementation with water and salt) and special pharmacological therapies (e.g., oral rehydration salts, midodrine hydrochloride, and metoprolol). As such, the recent progress in the pathogenesis, management strategies, and therapeutic response predictors of pediatric POTS are reviewed here.

Orthostatic heart rate does not predict symptomatic burden in pediatric patients with chronic orthostatic intolerance.

Postural orthostatic tachycardia syndrome (POTS) in adults is defined as symptoms of chronic orthostatic intolerance (COI) and autonomic dysfunction (AD) with heart rate (HR) increase of 30 beats per minute (bpm), or HR > 120bpm, during prolonged upright position. However, in adolescents, POTS is defined as symptoms of OI and AD with HR increase of ≥ 40bpm, based on tilt table data. We assessed frequency of COI symptoms in pediatric patients versus HR criteria on prolonged standing to evaluate using criteria of increased HR of 30-39bpm versus ≥ 40bpm in our POTS Program. Patients with COI with symptoms for > 3months plus HR increase of ≥ 30bpm on 10 min stand aged ≤ 18years at diagnosis were included. Patients were divided into two groups: those with HR increase of 30-39bpm, and those with HR increase of ≥ 40bpm or upright HR of > 120bpm. A total of 28 symptoms described prior to diagnosis were evaluated using chi-square testing to assess for significant differences. Only insomnia was found to be significantly different between the two groups. The other 27 symptoms showed no significant difference as a function of HR. There are minimal statistically significant differences and no clinical differences between patients as a function of HR increase during standing. Thus, a 40-bpm threshold for adolescents on standing test may be too high, or a specific HR criteria threshold is neither predictive nor definitive in diagnosing POTS.

Autonomic uprising: the tilt table test in autonomic medicine.

This perspective piece on head-up tilt table testing is part of a series on autonomic function testing. The tilt table can be a useful diagnostic test, but methodologies vary, and the results are sometimes misinterpreted. The intent here is not to review comprehensively the utility of various tilt table testing protocols but to convey a number of general points that may give perspective and have practical clinical value, based on an understanding of autonomic physiology and our long clinical and research experience in the evaluation of autonomic disorders. The goals of tilt table testing are to assess orthostatic hypotension (OH), chronic orthostatic intolerance (COI), and unexplained syncope. The testing is useful for distinguishing neurogenic from non-neurogenic OH, identifying failure of the sympathetic noradrenergic system in autonomic neuropathies and ganglionopathies, and assessing baroreflex-sympathoneural function in α-synucleinopathies. For COI, the testing can provide objective data related to the patient's symptoms, diagnose postural tachycardia syndrome (POTS), and distinguish POTS from other causes of tachycardia. Provocative tilt table testing can help understand bases for recurrent transient loss of consciousness in patients with syncope, distinguish neurally mediated syncope from psychogenic pseudosyncope, and separate syncope-related convulsion from epileptic seizures. For each of these purposes, the goals, formats, endpoints, and clinical utility are different. As for any autonomic test, tilt table findings must be interpreted in the context of the patient's clinical presentation.

BS05. Orthostatic hypotension and syncope in patients with ehlers-danlos syndrome

Introduction Postural tachycardia Syndrome (POTS) is a form of chronic orthostatic intolerance where the hallmark physiological trait is an excessive increase in heart rate upon standing. POTS is a final common pathway for a number of overlapping conditions, including lower body autonomic neuropathy, elevated sympathetic tone, mast cell activation, deconditioning, the presence of certain antibodies and hypovolemia. It also has similarities to chronic fatigue syndrome, Ehlers-Danlos Syndrome (EDS), vasovagal syncope and inappropriate sinus tachycardia. EDS is an heterogeneous disorder associated with inherited abnormalities of collagen structure. Patients develop hyper-extensibility, joint hypermobility and fragile connective tissue. Patients with EDS type III frequently have symptoms of autonomic dysregulation such as palpitations, lightheadedness, chest pain, presyncope and syncope that are also common in patients with POTS. Connective tissue abnormalities in EDS could lead to vascular laxity, predipose patients to orthostatic blood pooling in the lower extremities and orthostatic intolerance. These patients might have a peripheral neuropahty that could contribute to autonomic impairment. Methods Clinical records of patients diagnosed with Ehlers Danlos treated at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran were reviewed retrospectively during a 10 year period (1987–2017). Results 29 patients were found to have a diagnosis of EDS. The female-to-male ratio was 3:1, while the mean age was 29. One patient died due to a ruptured aortic aneurysm. 9 (34.6%) patients had a history of presyncope, 14 patients (53%) had low blood pressure and 12 (46.15%) patients had heart rate values above 80 beats per minute. Mean systolic blood pressure was 107.2 ± 16, diastolic blood pressure 67.3 mmHg ± 10.8 with a mean heart rate of 80.1 ± 11.8. The most common Ehlers Danlos phenotype found was type III, which ocurred in 5 patients (40%). Type IV was found in 5 patients (26%), 3 patients (20%) presented with type VI and only two patients with type VII and type IX, respectively. We could not have the type of 14 patients. Conclusion Although is known that patients with the EDS may present with syncope or presyncopal episodes it is not known the percentage of patients who have dysautonomic cardiovascular symptoms and signs. We found that 53% of the patients have orthostatic intolerance, 34% had syncopal episodes and 46% could be diagnosed with POTS. One patient died due to a thoracic aortic aneurysm.

Cognitive and psychological issues in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is one of the most common forms of chronic orthostatic intolerance. In addition to orthostatic symptoms, many POTS patients report incapacitating cognitive dysfunction or "brain fog" even while lying down or seated. Consistent with these subjective reports, there is accruing objective evidence of specific cognitive difficulties in POTS, with studies showing mild to moderate cognitive impairment using standardized neuropsychological assessment batteries. The precise profile of cognitive dysfunction in POTS patients has been shown to vary among these studies potentially due to the neuropsychological tests used, postural position, comorbidities and length of illness, inclusion of adolescent versus adult patients, and sites of recruitment. The extent of the impact that this cognitive challenge has in patients justifies ongoing investigation and research into lifestyle and pharmacological treatments. Psychologically, patients face challenges congruent with many chronic illnesses, perhaps especially early in adjusting to the condition. POTS patients often exhibit mild to moderate depression symptoms as well as symptoms of anxiety disorders. Since even low levels of anxiety can exacerbate symptoms, and a high number of patients experience sub-clinical low mood and sleep disturbances, there is a likely role for psychotherapy in helping control adjustment-related issues, and possibly aberrant physiology, in POTS.

Neurohumoral and Hemodynamic Profile in Children with Chronic Nausea and Orthostatic Intolerance

Neurohumoral and Hemodynamic Profile in Children with Chronic Nausea and Orthostatic Intolerance