Absence Of Orthostatic Hypotension Research Articles

Overview of Postural Orthostatic Tachycardia Syndrome (POTS) for General Cardiologists

Postural tachycardia syndrome (POTS) is a chronic autonomic disorder characterized by excessive heart rate elevation upon standing or head-up tilt, in the absence of orthostatic hypotension. This debilitating condition affects primarily young to middle-aged individuals, particularly women, and substantially influences quality of life. The main presenting symptoms are lightheadedness, palpitations, exercise intolerance, and cognitive impairment. POTS is of particular importance to cardiologists, given its prominent cardiovascular symptoms. The diagnostic criteria for POTS include a sustained heart rate increase of more than 30 beats per minute upon standing or head-up tilt; symptoms of orthostatic intolerance lasting at least 3 months; and exclusion of other causes. The exact etiology of POTS is unknown, but multiple possible etiologies leading to a similar clinical phenotype have been proposed. Early intervention and appropriate management can improve symptoms. Treatment strategies include lifestyle modifications, pharmacotherapy, and tailored conditioning programs. Non-pharmacologic options are the first line treatment. Prognosis varies widely: POTS can be a temporary condition for some individuals but a chronic and debilitating condition for others. Further research is necessary to elucidate the pathophysiology and optimize treatment strategies for this condition.

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.

Post-acute sequelae of SARS-CoV-2 syndrome presenting as postural orthostatic tachycardia syndrome.

The novel SARS-CoV-2 emerged in 2019, and the global COVID-19 pandemic continues into 2022. It has been known that a subset of patients develops chronic, debilitating symptoms after otherwise complete recovery from acute infection of COVID-19. Multiple terms have been used to describe this constellation of symptoms, including long COVID, long-haul COVID, and postacute sequelae of SARS-CoV-2 syndrome (PASC). PASC is broadly defined as a wide range of new, returning, or ongoing symptoms at least four weeks after infection. Those patients are often seen in emergency departments after acute COVID-19 infection, but their symptoms are not adequately managed because the underlying pathophysiology of PASC is not well understood. Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. POTS is one of the most common forms of autonomic dysfunction and defined by a sustained orthostatic tachycardia during active standing or head-up tilt test in the absence of orthostatic hypotension or other cardiopulmonary diseases. Because POTS is a treatable condition, it is important to recognize POTS among PASC patients. Herein, we reviewed the current literature on POTS and dysautonomia in PASC in order to better understand the overlap and distinction between these pathologies.

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.

Orthostatic hemodynamics in the vertebral artery and blood pressure in patients with orthostatic dizziness/vertigo

ObjectivesOrthostatic dizziness/vertigo (ODV) is a common symptom and is believed to occur due to the cerebral hypoperfusion caused by orthostatic hypotension (OH). However, the detailed mechanism underlying ODV onset is poorly understood. The vertebral artery (VA) mainly supplies blood to the central vestibular system; therefore, the orthostatic decrease of VA blood flow could possibly lead to ODV. This study investigated the orthostatic blood pressure and VA hemodynamics in ODV patients to elucidate the hemodynamic mechanism underlying ODV onset. Furthermore, the influence of orthostatic hypotension (OH) on VA hemodynamics was examined because OH is probably the most common cause of ODV. MethodsThis study included 181 patients with ODV and 73 control patients without ODV. All subjects underwent an active standing test to measure the extracranial Doppler (ECD) sonography spectrum of the VA and blood pressure (BP). VA blood flow velocity and BP were simultaneously measured for each patient in the supine static position and then in the upright standing positions following 3 min of standing. We investigated the orthostatic change in the average of flow velocity in bilateral VAs (VAFV) and BP for ODV patients compared with the control patients. ResultVAFV in ODV patients was significantly reduced when standing up compared with the control patients. In the ODV patients, there was no difference in orthostatic decrease in VAFV between patients those with OH and without OH. However, the VAFV in the standing position was significantly lower in patients with OH than without OH. In cases with OH, the ODV patients exhibited a greater decrease in VAFV compared with the control patients, but this was not statistically significant. In the absence of OH, a significantly greater orthostatic decrease in VAFV was observed in ODV patients compared with the controls. ConclusionOur findings suggest that the orthostatic decrease of VA blood flow is deeply involved in the hemodynamic mechanism underlying ODV onset and is possibly associated with OH and other etiologies.

An Unusual Case of Polyautoimmunity with Concomitant Presentation of Postural Tachycardia Syndrome, Antiphospholipid Syndrome and Hashimoto’s Thyroiditis

Introduction: Postural tachycardia syndrome (POTS) is a chronic form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. In a subgroup of patients with POTS, autoantibodies against adrenergic or cholinergic receptors suggest an immune-mediated etiology. Antiphospholipid syndrome (APS) is a hypercoagulative autoimmune disorder associated with anti-phospholipid-antibodies that causes arterial and venous thromboses. Concurrent occurrence of APS and immune-mediated POTS is rare. Methods and Results: Here, we report a 28-year-old female that experiences symptoms of orthostatic intolerance, vasovagal syncopes, gastrointestinal dysmotility and sudomotor dysfunction. She fulfills the formal diagnostic criteria of POTS showing a heart rate increment of ≥30 beats per minute (bpm) within 10 m of head-up tilt in the absence of orthostatic hypotension, accompanied by symptoms of orthostatic intolerance. The thermoregulatory sweat test reveals severe patchy anhidrotic areas. Gastric emptying scintigraphy shows an impaired gastrointestinal motility. Plasma norepinephrine levels and a skin biopsy appear normal. Finally, serological persistence of anti-alpha-1-adrenergic autoantibodies suggest an immune-mediated pathogenesis. Several years after initial presentation of POTS symptoms, the patient develops APS with recurrent venous emboli and persistent anti-phospholipid-antibodies. Recently the patient is diagnosed with Hashimoto’s thyroiditis (HT) expressing high levels of thyroid-stimulating hormone and high titers of anti-thyroid antibodies. Conclusion: To our knowledge, this is the first report of consecutive immune-mediated POTS, APS and HT in a young woman, possibly displaying a unique combination of three disorders of autoimmune etiology.

Abstract P204: Sinusoidal Galvanic Stimulation Improves Orthostatic Symptoms In Patients With Postural Tachycardia.

Postural Tachycardia Syndrome (POTS) is characterized by frequent orthostatic symptoms and excessive heart rate increase (>= 30 bpm) on standing in the absence of orthostatic hypotension for more than 6 months. We and others have described a vestibulo-sympathetic reflex that can be engaged by galvanic vestibular stimulation to modulate sympathetic activity (Biaggioni et al., 2000; Kaufmann et al., 2002; Monahan & Ray, 2002; Ray & Carter, 2003, Bent, Macefield et al. 2006). We hypothesize that habituation to sinusoidal galvanic vestibular stimulation will improve orthostatic tolerance. We studied 6 patients with POTS (30.5+/6.0 years, BMI 22.8+/-2.9 kg/m 2 ) in two sessions using sinusoidal galvanic vestibular stimulation (sGVS 0.025 Hz, 2mA) or sham (0.01 mA). Stimulation was applied near mastoid process for 30 min in semi-recumbent position before orthostatic challenge. Patient were upright for a maximum of 15 minutes after each stimulation. Orthostatic change in Vanderbilt Orthostatic Symptom Score (dVOSS), orthostatic heart rate increase (dHR) and blood pressure response were recorded. Non-parametric Wilcoxon test for paired measures with significance level p<0.05 was used. sGVS stimulation reduced overall orthostatic symptom score (dVOSS sham: 32.5+/-9.3 bpm vs dVOSS sGVS: 10.5+/-5.5, p=0.03) and tended to reduce orthostatic HR increase (dHR sham: 65.83+/-11.5 vs dHR sGVS: 46.5+/-10.7 bpm, p=0.06). Blood pressure and tilt time did not change. This pilot study suggests that habituation to sinusoidal vestibular could be used to improve orthostatic symptoms and orthostatic tolerance.

O-AD003. Postural Orthostatic Tachycardia Syndrome (POTS): A case series from India

Introduction . POTS (Postural Orthostatic Tachycardia Syndrome) is defined as the presence of chronic symptoms of orthostatic intolerance (≥6 months) accompanied by an increased heart rate (HR) ≥30 bpm within 10 minutes of assuming an upright posture in the absence of orthostatic hypotension. It is diagnosed by tilt table testing where the heart rate at base line and on standing is recorded. The incidence and presenting complaints of this disease has not been studied in the Indian subcontinent. Methods . This is a retrospective study where we looked into the data of patients with diagnosis of POTS over a period of 3 years (August 2014–August 2017). We are describing the baseline demographics, clinical presentations, investigations, treatment and follow up of these patients. POTS was diagnosed based on inclusion criteria with a tilt table. Heart rate was recorded in supine position and then in upright position. Continuous heart rate and BP recording was done every minute for 10 minutes and if patient had symptoms it was noted. Results . During the study period from August 2015–August 2017 we had 42 patients with POTS. This was 7.7% of all patients who had positive tilt table testing during this period. The cohort had 24 males and 18 females. Commonest symptoms were postural giddiness in 18 patients, palpitation on standing and walking in 13 patients and postural syncope in 12 patients. 13 patients had improvement with excess fluid intake, while 29 patients required drug therapy. Conclusion . This is the only series of POTS from India. POTS is not a rare cause of orthostatic intolerance as previously reported. High index of suspicion can help in early identification and treatment of this syndrome.

Abstract MP35: Association Of Orthostatic Blood Pressure Response With Incident Heart Failure: The Framingham Heart Study

Introduction: Orthostatic hypotension (OH) and hypertension (OHT) are associated with cardiovascular disease and mortality. The relation of OH and OHT with heart failure (HF) in the community is not well explored, particularly among the elderly and those with hypertension. Moreover, there remains a paucity of longitudinal data on the development of HF subtypes (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]) in those with OH and OHT. Hypothesis: We hypothesized that OH and OHT are associated with a higher risk of HF. Methods: We evaluated 1914 Framingham Heart Study participants (mean age 72 years, 1159 women [61%]), with available orthostatic blood pressure (BP) measurements. OH was defined as a decrease and OHT as an increase of 20/10 mmHg in systolic/diastolic BP from supine to standing position, respectively. We used a categorical variable (OH, OHT, absence of OH and OHT [referent]). Using Cox proportional hazards regression, we related OH and OHT to risk of HF and its subtypes (HFrEF, HFpEF), compared to the referent group, adjusting for age, sex, body mass index, systolic BP, diastolic BP, hypertension treatment, smoking, and diabetes. Results: There were 275 participants with OH (181 women, 66%) and 411 with OHT (236 women, 57%). On median follow-up of 13 years, 492 developed HF (292 women, 59%). In multivariable-adjusted analyses, OH was associated with higher risk of HF (Hazards Ratio [HR] 1.47; 95% CI, 1.13-1.92; Figure ) compared to referent. Further, OH was associated with higher risk of HFrEF (HR 2.56; 95% CI, 1.46-4.48), but not HFpEF. OHT was not associated with incident HF. Conclusions: Assessment of orthostatic BP response in the elderly may identify future HF risk. Further studies are warranted to investigate mechanisms underlying the observed associations.

Investigation of Vestibular Function in Adult Patients with Gitelman Syndrome: Results of an Observational Study.

Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene, encoding the thiazide-sensitive sodium chloride cotransporter (NCC). Patients with GS frequently complain of vertigo, usually attributed to hypovolemia. Because NCC is also located in the endolymphatic sac, we hypothesized that patients with GS might have vestibular dysfunction. Between April 2013 and September 2016, 20 (22%) out of 90 patients followed at the reference center complained of vertigo in the absence of orthostatic hypotension. Sixteen of them were referred to an otology department for investigation of vestibular function. The vertigo was of short duration and triggered in half of them by head rotation. Seven patients (44%) had a vestibular syndrome. Vestibular syndrome was defined: (1) clinically, as nystagmus triggered by the head shaking test (n = 5); and/or (2) paraclinically, as an abnormal video head impulse test (n = 0), abnormal kinetic test (n = 4) and/or abnormal bithermal caloric test (n = 3). Five patients had associated auditory signs (tinnitus, aural fullness or hearing loss). In conclusion, we found a high frequency of vestibular disorder in GS patients suffering from vertigo, suggesting a role of NCC in the inner ear. Referent physicians of these patients should be aware of this extrarenal manifestation that requires specific investigations and treatment.

Prevalence and factors related to orthostatic syndromes in recently diagnosed, drug-naïve patients with Parkinson disease.

The aim of this study was to explore the prevalence of and factors related to orthostatic syndromes in recently diagnosed drug-naïve patients with Parkinson disease (PD). This was a cross-sectional study that included 217 drug-naïve patients with PD and 108 sex- and age-matched non-parkinsonian controls from the Parkinson's Progression Markers Initiative (PPMI) prospective cohort study who were devoid of diabetes, alcoholism, polyneuropathy, amyloidosis, and hypotension-inducing drugs. Orthostatic symptoms were evaluated using the Scales for Outcomes in PD-Autonomic Dysfunction (SCOPA-AUT). Ioflupane-I123 single-photon emission computerized tomography was used to evaluate striatal dopamine active transporter (DaT) levels. Blood pressure was assessed both in the supine position and 1-3min after the switch to a standing position. Orthostatic hypotension (OH) was defined by international consensus, and orthostatic intolerance (OI) was defined as the presence of orthostatic symptoms in the absence of OH. Compared with non-parkinsonian controls, patients with PD experienced a mild fall in systolic blood pressure upon standing (p = 0.082). The prevalence of OH was 11.1% in PD patients and 5.6% in controls (p = 0.109). The prevalence of OI was higher in patients with PD than in controls (31.3 vs. 13.3%; p = 0.003). Logistic regression revealed that OH and OI were related to a lower striatal DaT level and higher SCOPA-AUT gastrointestinal score. Orthostatic syndromes were common in the recently diagnosed drug-naïve patients with PD enrolled in the study, but only the prevalence of OI was higher in PD patients than in the non-parkinsonian controls. Unlike motor or functional disability indicators, markers of dopaminergic striatal deficit and gastrointestinal dysfunction were associated with OH and OI.

M350 PERIODIC FACIAL ERYTHEMA IN A PATIENT WITH POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

Periodic facial erythema is associated with postural orthostatic tachycardia syndrome (POTS), an abnormal response of the autonomic nervous system. This syndrome of orthostatic intolerance is characterized by tachycardia in the absence of orthostatic hypotension, light-headedness, palpitations, and rarely facial erythema. Resolution of symptoms occurs with recumbence. Here we present a case of periodic facial erythema secondary to POTS.

Incidence of Thoracic Outlet Syndrome in Patients With Postural Orthostatic Tachycardia Syndrome

Thoracic outlet syndrome (TOS) refers to a constellation of symptoms resulting from neurovascular compression at the thoracic outlet, causing some combination of pain in the neck and upper extremity, weakness, sensory loss, paresthesia, swelling, and discoloration. Classification of TOS would depend on the anatomical structure that is compressed: venous TOS (VTOS)—compression of Subclavian vein; arterial TOS (ATOS)—compression of subclavian artery; and neurogenic TOS (NTOS)—compression of brachial plexus. Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by orthostatic tachycardia that develops in the absence of orthostatic hypotension, with a symptom duration of >6 months. POTS is now known to be commonly associated with Ehlers-Danlos Syndrome (EDS), thereby raising speculation about the extent of prevalence of TOS symptoms in EDS patients. The aim of the study was to quantify the influx of patients with POTS, reporting symptoms of arm fatigue with or without numbness and tingling. The symptoms were quantified initially by conducting postural maneuvers that would reproduce the symptoms, to rule-in the possibility of TOS and further confirmed by using ultrasonography in upper limbs as the imaging modality of choice to evaluate arterial and/or venous compression. This study also looks at the presence of a concurrent diagnosis of EDS among the symptomatic patients who test positive for TOS.

Orthostatic hypotension and health-related quality of life among community-living older people in Korea.

To investigate the association of orthostatic hypotension (OH) with health-related quality of life (HRQoL) in older people living in the community. A cross-sectional design was used. A total of 217 participants aged 65 and older were classified as having OH if their systolic or diastolic blood pressure showed a drop of ≥ 20mmHg systolic blood pressure or ≥ 10mmHg diastolic blood pressure, respectively, within 3min of standing. Participants provided demographic and medical information and responded to questionnaires about their HRQoL (EuroQoL-5D-3L), as well as depression, anxiety, cognitive function, and recent physical activities. The number of participants with OH was 117, and those without OH numbered 100. The mean HRQoL levels were 0.56 (SD 0.29) in the OH group and 0.74 (SD 0.25) in the non-OH group (p < .001). Participants with OH were more likely to be older, women, and smokers. These participants had fewer years of education, a greater history of stroke and hypertension, and a greater number of comorbidities. The absence of OH, a higher physical activity level, a lower degree of depression, an absence of stroke history, and younger age were all significant determinants of greater HRQoL. The level of HRQoL of older people with OH was significantly lower than that of older people without. The presence of OH was an independent determinant of HRQoL in older adults after adjusting for covariates. This finding suggests that strategies for relieving OH could improve HRQoL in affected older adults.

Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension.

To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology. Autopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic. The absence of orthostatic hypotension (OH) was the strongest autonomic parameter that distinguished PSP from α-synucleinopathies (0% vs 69%, p < 0.0001). Tests of adrenergic failure, which distinguish neurogenic OH, also differentiated PSP from other groups. These included the pressure recovery time (p = 0.0008), adrenergic impairment score (p = 0.001), and magnitude of change of systolic (p = 0.0002) and diastolic (p = 0.0001) blood pressures (BPs) during upright tilt. In addition, REM sleep behavior disorder was seen less frequently (p = 0.006) in PSP (33%) compared to MSA (87%) and LBD (90%). Antemortem clinical diagnostic accuracy for these phenotypically variable disorders was 57% for PSP and 83% for α-synucleinopathies. Our results suggest that the cardiovascular adrenergic system, which sustains BP during standing, is relatively unaffected, if not spared, in PSP. These findings increase our understanding of the clinical signature of PSP and have the potential to improve diagnostic accuracy in atypical parkinsonisms by distinguishing PSP from the α-synucleinopathies.

MON-LB009 Renin Angiotensin Aldosterone System Inactivation in Postural Orthostatic Tachycardia Syndrome

Postural Orthostatic Tachycardia Syndrome (POTS) is a clinical syndrome characterized by the presence of tachycardia in the absence of orthostatic hypotension; symptoms of orthostatic intolerance (presyncope and syncope) are present secondary to autonomic dysfunction (1). It is thought that one of the implications for POTS involves plasma volume disturbances leading to blood pooling. The Renin Angiotensin Aldosterone System (RAAS) is one system that assists in plasma volume regulation (2). In this study we hypothesized that these disturbances are brought about by an inactivation of RAAS. This was done by retrospectively reviewing the medical records of POTS patients. In these patients, diagnosis of POTS was established by an increase in Heart Rate of over 30 bpm within 10 minutes of tilt. Stroke Volume was used as a measure of volume disturbances; those POTS patients whose stroke volumes had not increased by the End of the Tilt as compared to their 6 minute supine baseline were considered to have an inactivation of RAAS. Our total sample of POTS patients numbered at 447, out of which 417 patients had lower stroke volumes at the end of their tilt table tests when compared to their baseline; this makes for 92.87% of our POTS Patient Sample. The average Stroke Volume at the 6 minute mark was calculated to be 74.67; the average stroke volume at the end of the tilt table test (30 minutes) was calculated to be 46.33 mL; . The results seen in this study show that more than 90% of our POTS Patient Sample there is no recovery of the stroke volume by the end of the tilt table test, this volume disturbance can be the result of decreased RAAS activation. This observation is supported by the difference found between average stroke volumes seen at 6 minute baseline and at 30 minutes of tilt. In normal individuals, we should see an increase in stroke volume at the end of the tilt as RAAS is activated. However, as patients with POTS are known to have lower plasma volumes (2), compounded with the inactivation of RAAS; the resulting hypovolemia will amplify the symptoms of POTS, increasing their severity. These patients should respond well to fludrocortisone, as there will be a correction of hemodynamic impairments (RAAS inactivation) leading to symptomatic relief (3). Further studies and analyses are needed to look into the levels of Renin and Aldosterone at Baseline & at Tilt, as well as the effects of fludrocortisone on such patients with RAAS inactivation.

Clinical profile and cardiovascular autonomic function tests in patients with postural orthostatic tachycardia syndrome

Background: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by the clinical symptoms of orthostatic intolerance such as light-headedness, fatigue, sweating, tremor, anxiety, palpitation, exercise intolerance, and near syncope on standing in the absence of orthostatic hypotension. Objective: The objective of this study is to evaluate the clinical profile and autonomic parameters in patients with POTS. Materials and Methods: A total of 70 patients with POTS underwent cardiovascular autonomic function tests, i.e., heart rate (HR) response to deep breathing, heart rate and blood pressure (BP) changes in Valsalva maneuver and tilt study in the autonomic laboratory of the Department of Neurology from January 2014 to February 2016 using WR Medical Works, USA. Results: Mean age of cohort was 28.07 ± 10.64 years, and there were 36 (51%) women. Light-headedness 59 (84.3%) was the most common orthostatic symptom, followed by dizziness 56 (80%), palpitation 41 (58.57%), anxiety 26 (37.14%), loss of consciousness 21 (30%), disequilibrium 19 (27.14%), visual symptoms 12 (17.14%), weakness 8 (11.43%), and shortness of breath 2 (2.86%). The average heart rate response to deep breathing was 24.79 ± 7.20 bpm. Average Valsalva ratio was 1.78 ± 0.30. During the tilt, average maximum HR increase was 43.47 ± 11.19 bpm. Conclusion: POTS is an underrecognized disorder and majority of them present with vague orthostatic symptoms ways, hence clinicians should be made aware of the symptomatology. The tilt table test with beat-to-beat monitoring of HR and BP is the standard test for diagnosis.

Chapter 29 - Clinical neurophysiology of postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is one of several disorders of orthostatic intolerance (OI). It is defined by the development of symptoms of cerebral hypoperfusion or sympathetic activation and a sustained heart rate increment of 30 beats/min or more (40 beats/min for teenagers) within 10min of standing or head-up tilt in the absence of orthostatic hypotension; the standing heart rate is often 120 beats/min or higher. POTS is approximately five times more common in women than men. This heterogeneous syndrome is caused by several pathophysiologic mechanisms (limited autonomic neuropathy, hyperadrenergic state, hypovolemia, venous pooling, deconditioning), which are not mutually exclusive. Anxiety and somatic hypervigilance play significant roles in POTS. Common comorbidities include visceral pain and dysmotility, chronic fatigue and fibromyalgia, migraine, joint hypermobility, mitral valve prolapse, and inappropriate sinus tachycardia. Patients with suspected POTS should undergo comprehensive cardiac and neurologic examinations and autonomic and laboratory tests to determine the most likely pathophysiologic basis of OI. The objectives of POTS management are to (1) increase the time that patients can stand, perform daily activities, and exercise and (2) avoid syncope. Management involves nonpharmacologic (fluid and salt loading, physical countermaneuvers, compression garments, exercise training) and pharmacologic (β-blockers, pyridostigmine, fludrocortisone, midodrine) approaches.

Abstract P387: Sub-Perception Transdermal Vagal Stimulation in Postural Tachycardia Syndrome

Postural Tachycardia Syndrome (POTS) is a clinical syndrome characterized by an excessive increase in heart rate (&gt;= 30 bpm) on standing in the absence of orthostatic hypotension, and frequent orthostatic symptoms for more than 6 months. While most researchers focus on the hyperadrenergic features of POTS, these patients also have significant cardio-vagal (parasympathetic) impairment. We tested the hypothesis that transdermal electrical stimulation of the auricular branch of the vagus nerve will enhance cardio-vagal modulation, reduce heart rate, upright symptoms, and improve orthostatic tolerance. We studied 14 patients with POTS (31.5+/-11.7 years, BMI 22.6+/-3.9 kg/m 2 ). Sham or sub-perception threshold transdermal electrical vagal stimulation was applied in random order to the auricular branch in the right ear in supine and during graded tilt maneuver. Patients with low vagal modulation (low high frequency HF &lt; 200 ms 2 ) responded to vagal stimulation (Kruskal Wallis p=0.01, n=7, Fig left) with significant increase in HF power (eg @50Hz: +51+/-10 ms 2 , p=0.0032). Vagal stimulation during upright tilt tended to reduce orthostatic tachycardia and overall orthostatic symptom score. It improved significantly tilt time (+5.3+/-2.6 min, p=0.0156, Fig right). Patients with higher baseline vagal modulation (HF &gt;= 200 ms 2 ) did not respond to vagal stimulation (interaction p=0.41). This proof of concept study indicates that auricular transdermal vagal stimulation improves supine cardio-vagal function in POTS patients with low vagal modulation. Further research will determine if this approach can be used therapeutically, alone or in combination with other therapies.

P4427Detection of inflammatory biomarkers associated with postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular dysautonomic condition affecting predominantly young women. POTS is defined as the presence of chronic symptoms of orthostatic intolerance associated with an increased heart rate ≥30 bpm, or heart rate exceeding 120 bpm, within 10 minutes of standing or head-up tilt in the absence of orthostatic hypotension. The etiology is still unknown though autoimmunity has been hypothesized to play an important role. Purpose: To investigate whether an inflammatory biomarker signature is associated with POTS. Methods: We performed a cross-sectional study enrolling 475 patients aged between 15 and 55 years with unexplained syncope or symptoms of orthostatic intolerance. Of these 118 have been diagnosed with POTS and 357 controls demonstrated normal hemodynamic response during passive phase of HUT i.e. no orthostatic hypotension or POTS. A total of 318 patients provided supine blood plasma samples that were analyzed through the antibody-based Proximity Extension Assay technique, simultaneously measuring 53 inflammatory and cancer-related human protein biomarkers. After excluding 5 biomarkers with low call rate <65% (VEstatin, LITAF, MYD88, MICA, CEA) and 9 patients with missing data, the final study sample consisted of 309 patients (POTS, n=78; no POTS n=231). The discovery algorithm was a sequential two-step process of biomarker signature identification by multivariate principal component analysis (PCA), and verification by univariate ANOVA with Bonferroni correction. Results: POTS patients were younger (28 vs. 35 years; p<0.001) compared with controls. PCA and Bonferroni-adjusted ANOVA identified furin and FADD as the most robust targeted biomarker signature for POTS. The plasma concentration of furin was significantly lower (6.39 (0.5) vs 6.64 (0.4), p<0.001), whereas FADD levels were significantly higher (2.37 (0.72) vs 2.14 (0.69), p=0.01) in POTS patients compared with controls. In multivariable regression analysis, adjusting for age and sex, the results remained significant. Conclusion: Targeted protein profiling in POTS revealed a biomarker signature associated with immunoregulatory functions. Circulating levels of furin were downregulated, whereas circulating levels of FADD were elevated in POTS, suggesting the presence of a characteristic inflammatory signature in this unexplained condition.