Excessive Heart Rate Increase Research Articles

Individual tailored physical training in patients with postural orthostatic tachycardia syndrome after COVID-19 - a feasibility study

Abstract Background A significant proportion of patients with COVID-19 have developed persistent symptoms, described as post-acute COVID-19 syndrome (PACS ). A specific PACS variant is the postural orthostatic tachycardia syndrome (POTS). POTS is a cardiovascular autonomic dysfunction characterized by an excessive increase in heart rate in standing, deconditioning and low quality of life. Studies that have evaluated the effect and feasibility of individual tailored physical training in POTS associated with COVID-19 are sparse. Purpose To evaluate the effects and feasibility of individualized exercise on physical and psychological function in patients with POTS after COVID-19. Method Patients with POTS + PACS were enrolled between Dec 2021 and Dec 2022. The intervention consisted of individually tailored training, including endurance and muscle-strengthening exercises with a gradual progression of time, dose and position. The training was based on the study subject's heart rate and/or self-estimated exertion using BORG RPE. The intervention lasted 12 weeks. Progression of the exercise was halted if the study subject described increased symptoms >24h after the last exercise session. Measurements were carried out at baseline and after intervention: 6-minute walking test (6MWT), Active Standing Test (AST) and self-assessment of symptoms through forms; Malmö POTS scale (MaPS), Vanderbilt Orthostaic Symptom Score (VOSS), Fatigue Severity Scale (FSS) health-related quality of life (EQ-5D-5L), anxiety (GAD) and depression (PHQ-9). Physical activity and time in different positions (lying, sitting, standing and walking) were measured using accelerometers (ActivPAL). Recruitment rate, compliance and adverse events was registered as feasibility. Results A total of 24 patients were enrolled and 23 patients completed the intervention (19 women; mean age, 40.9 years (SD 10.7). No severe adverse events occurred however some of the patients described symptoms as post exertion malaise (PEM). After the intervention, patients demonstrated improvement in physical (6MWT, p<0.005) and psychological functions (PHQ-9, p<0.001), less symptoms related to POTS (MaPS p<0.01, VOSS p<0.02, FSS p<0.045) and improved HrQoL (EQ-5D p<0.001) (Table 1). The primary outcome, time spent in upright position increased by 1.5h/day i.e. by 49% (Figure 1). Conclusion In patients with COVID-19-related POTS, an individually tailored training seem to contribute to increased time in upright position, reduction of POTS-specific symptoms and improved functions. The intervention seems to be feasible in terms of recruitment, compliance and safety. Further studies are needed to verify these results and compare disease progression with and without intervention.Table 1Figure 1

Individual tailored physical training in patients with postural orthostatic tachycardia syndrome associated with post-acute COVID-19 syndrome - a feasibility study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Hjärt-Lungfonden Vetenskapsrådet Background The number of people that has been affected by COVID-19 is high and has continued to increase throughout the pandemic. A significant proportion of patients with COVID-19 have developed persistent symptoms, described as post-acute COVID-19 syndrome (PACS). A specific PACS variant is the postural orthostatic tachycardia syndrome (POTS). POTS is a cardiovascular dysautonomia characterized by an excessive increase in heart rate in standing and deconditioning. Studies evaluating effect and feasibility of individual tailored physical exercises in POTS associated with PACS are sparse. Purpose To evaluate the effects and feasibility of a individually tailored exercise on physical and psychological function in patients with POTS associated with PACS. Method Patients with POTS + PACS and diagnosed between Dec 2021-Sep 2022 were enrolled. Measurements were carried out at baseline and after intervention: 6-minute walking test (6MWT), Active Standing Test (AST) and self-assessment of symptoms through forms; Malmö POTS scale (MaPs), Vanderbilt Orthostatic Symptom Score (VOSS), health-related quality of life (EQ-5D-5L), anxiety (GAD) and depression (PHQ-9). Physical activity and time in different positions (lying, sitting, standing and walking) were measured using accelerometers (ActivPAL). The intervention consisted of 12 weeks individually tailored training, including both endurance and muscle-strengthening exercises with a gradual progression of time, dose, and position (supine-upright). The training was adapted based on the study subject's heart rate and/or self-estimated exertion using BORG reported perceived excertion. Progression of the exercise was halted if the study subject described increased symptoms >24h after the last exercise session indicating post exertional malaise (PEM). Recruitment rate, compliance and adverse events was registered. Results A total of 15 patients were enrolled and 14 patients completed the intervention (9 women; mean age, 41.6 years (SD 12.3). No severe adverse events occurred however some of the patients’ described PEM. After completing the intervention period, patients demonstrated improvement in physical (6MWT p<0.004) and psychological functions (PHQ-9 p<0.001) and less symptoms related to POTS (MaPS p<0.03) (Table 1). The primary outcome, time spent in upright position increased by 1.5h/day (Figure 1). Conclusion In patients with COVID-19-related POTS, individually tailored exercise was associated with increased time in upright position, reduction of POTS-specific symptoms and improved function. The intervention seems to be feasible in terms of recruitment, compliance and safety. Further studies are needed to verify these results and compare disease progression with and without intervention.

0586 An observational retrospective study of the prevalence of comorbid postural orthostatic tachycardia syndrome (POTS) in narcolepsy

Abstract Introduction Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of dysautonomia associated with an excessive increase in heart rate following a shift to standing posture. As of 2019, POTS has a prevalence of 1-3 million (0.3-0.9%) in the United States. Narcolepsy is a chronic neurologic condition of persistent hypersomnolence irrespective of total sleep time that also is associated with REM-sleep dissociative features (i.e., cataplexy, sleep paralysis, sleep-related hallucinations). In recent years, viral infections have been established as a trigger for both neurologic conditions. Methods A manual chart review was performed for records from 11/1/2020 to 12/20/2022. The overall clinic population of narcolepsy was identified by searching the electronic medical record for the ICD-10 codes G47.411 (narcolepsy type 1 [NT1]), and G47.419 (narcolepsy type 2 [NT2]). The past medical history of these charts then was searched for a history of POTS to identify patients with both conditions. A separate chart review was performed to identify all patients with POTS in the clinic. Results Of the 1,433 total patients in the clinic population, 207 narcolepsy patients (NT1=73, 35.3%; NT2=134, 64.7%) and 24 POTS patients were identified. The co-morbid prevalence of narcolepsy with POTS was 8.7% (18, 95% CI 5.2-13.4%); of those patients with POTS, 75% had narcolepsy (95% CI 53.3-90.2%). Co-morbid prevalence was higher in NT1 (13, 17.8% with 95% CI 9.8-28.5%) than NT2 (5, 3.7% with 95% CI 1.2-8.5%). The overall co-morbid prevalence and the NT1 co-morbid prevalence was significantly higher than the overall clinic POTS population (1.26% with 95% CI 0.75-1.98%) and the general population. Conclusion The prevalence of POTS is significantly higher in narcolepsy patients than the overall general population, especially in the NT1 subgroup. Clinicians should consider screening POTS patients for narcolepsy, and vice versa. Further studies are warranted to explore the etiology of co-morbid narcolepsy and POTS. Support (if any) N/A

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.

1055 MALMÖ POTS SYMPTOM SCORE: ASSESSING SYMPTOM BURDEN IN POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

Abstract Background Postural orthostatic tachycardia syndrome (POTS) is a common cardiovascular autonomic disorder characterized by excessive heart rate increase on standing and symptoms of orthostatic intolerance, posing significant limitations on functional capacity. No objective tool exists to classify symptom burden in POTS. Methods We conducted a case-control study in 62 POTS patients and 50 healthy controls to compare symptom burden between groups using the newly developed, self-rating, 12-item, Malmö POTS Score (MAPS; 0-10 per item, total range 0-120) based on patients’ own perception of symptoms through visual analogue scale assessment. We have also explored correlations between symptom severity assessed by MAPS, basic clinical parameters and postural haemodynamic changes. Results POTS patients showed significantly higher total MAPS score (78±20 vs. 14±12, p<0.001), higher baseline systolic blood pressure (BP), diastolic BP and heart rate (HR)(p<0.001) compared with healthy controls. The most prominent symptoms in POTS were palpitations, fatigue, and concentration difficulties. Haemodynamic parameters on standing were significantly correlated with palpitations in POTS after adjustment for age and sex (lower systolic and diastolic BP, and higher HR) (p<0.001 for all). Orthostatic HR was significantly associated with concentration difficulties and total MAPS score. The optimal cut-point value of MAPS to differentiate POTS and healthy controls was ≥42 (sensitivity, 97%; specificity, 98%). Conclusions Symptom severity, as assessed by MAPS score, is 5-fold higher in POTS compared with healthy individuals. The new MAPS score can be useful as a semi-quantitative system to assess symptom burden, monitor disease progression and evaluate pre-test likelihood of disease.

Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder characterized by excessive heart rate increase on standing, leading to debilitating symptoms with limited therapeutic possibilities. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification of patients based on their protein background. The aim of the present study was to determine plasma protein biomarkers of POTS and to reveal proteomic pathways differentially regulated in POTS. We performed an age- and sex-matched, case–control study in 130 individuals (case–control ratio 1:1) including POTS and healthy controls. Mean age in POTS was 30 ± 9.8 years (84.6% women) versus controls 31 ± 9.8 years (80.0% women). We analyzed plasma proteins using data-independent acquisition (DIA) mass spectrometry. Pathway analysis of significantly differently expressed proteins was executed using a cutoff log2 fold change set to 1.2 and false discovery rate (p-value) of < 0.05. A total of 393 differential plasma proteins were identified. Label-free quantification of DIA-data identified 30 differentially expressed proteins in POTS compared with healthy controls. Pathway analysis identified the strongest network interactions particularly for proteins involved in thrombogenicity and enhanced platelet activity, but also inflammation, cardiac contractility and hypertrophy, and increased adrenergic activity. Our observations generated by the first use a label-free unbiased quantification reveal the proteomic footprint of POTS in terms of a hypercoagulable state, proinflammatory state, enhanced cardiac contractility and hypertrophy, skeletal muscle expression, and adrenergic activity. These findings support the hypothesis that POTS may be an autoimmune, inflammatory and hyperadrenergic disorder.

Postural orthostatic tachycardia syndrome explained using a baroreflex response model.

Patients with postural orthostatic tachycardia syndrome (POTS) experience an excessive increase in heart rate (HR) and low-frequency (∼0.1 Hz) blood pressure (BP) and HR oscillations upon head-up tilt (HUT). These responses are attributed to increased baroreflex (BR) responses modulating sympathetic and parasympathetic signalling. This study uses a closed-loop cardiovascular compartment model controlled by the BR to predict BP and HR dynamics in response to HUT. The cardiovascular model predicts these quantities in the left ventricle, upper and lower body arteries and veins. HUT is simulated by letting gravity shift blood volume (BV) from the upper to the lower body compartments, and the BR control is modelled using set-point functions modulating peripheral vascular resistance, compliance, and cardiac contractility in response to changes in mean carotid BP. We demonstrate that modulation of parameters characterizing BR sensitivity allows us to predict the persistent increase in HR and the low-frequency BP and HR oscillations observed in POTS patients. Moreover, by increasing BR sensitivity, inhibiting BR control of the lower body vasculature, and decreasing central BV, we demonstrate that it is possible to simulate patients with neuropathic and hyperadrenergic POTS.

COVID-19 Increases the Prevalence of Postural Orthostatic Tachycardia Syndrome: What Nutrition and Dietetics Practitioners Need to Know

Postural orthostatic tachycardia syndrome (POTS) is a common complex disorder of the autonomic nervous system, also known as dysautonomia, which was estimated to affect 1 to 3 million people in the United States as of 2019.1 POTS is defined as a clinical syndrome marked by an excessive increase in heart rate (ie, tachycardia) after a shift to standing posture.1 Viral infections are an established trigger for POTS, and an unprecedented number of people have contracted viral infections due to SARS-CoV-2.

The Gut Microbiota and Short-Chain Fatty Acids Profile in Postural Orthostatic Tachycardia Syndrome

Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients (N = 25) compared to healthy control (N = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. Lachnoclostridium genus were higher in POTS when compared to the control group. On the other hand, Coprococcus and Coprobacter, were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.

Cardiorespiratory Responses During High-Intensity Interval Training Prescribed by Rating of Perceived Exertion in Patients After Myocardial Infarction Enrolled in Early Outpatient Cardiac Rehabilitation.

Objective: We aimed to determine the cardiorespiratory responses during, and adaptations to, high-intensity interval training (HIIT) prescribed using ratings of perceived exertion (RPE) in patients after myocardial infarction (MI) during early outpatient cardiac rehabilitation (CR).Methods: We prospectively recruited 29 MI patients after percutaneous coronary intervention who began CR within 2 weeks after hospital discharge. Eleven patients (seven men; four women; age: 61 ± 11 yrs) who completed ≥24 supervised HIIT sessions with metabolic gas exchange measured during HIIT once weekly for 8 weeks and performed pre- and post- CR cardiopulmonary exercise tests were included in the study. Each HIIT session consisted of 5–8 high-intensity intervals [HIIs, 1-min RPE 14–17 (Borg 6–20 scale)] and low-intensity intervals (LIIs, 4-min RPE < 12). Metabolic gas exchange, heart rate (HR), and blood pressure during HIIT were measured.Results: The mean oxygen uptake (2) during HIIs across 88 sessions of HIITs [91 (14)% of 2peak, median (interquartile range, IQR)] was significantly higher than the lower limit of target 2 zone (75% of 2peak) recommended for the HII (p < 0.001). Exercise intensity during RPE-prescribed HIITs, determined as %2peak, was highly repeatable with intra-class correlations of 0.95 (95% CI 0.86– 0.99, p < 0.001). For cardiorespiratory adaptations from the first to the last session of HIIT, treadmill speed, treadmill grade, treadmill power, 2HII, %2peak, and VE during HIIs were increased (all p < 0.05), while no difference was found for HR, %HRpeak and systolic blood pressure (all p > 0.05). 2peak increased by an average of 9% from pre-CR to post-CR. No adverse events occurred.Conclusion: Our results demonstrate that HIIT can be effectively prescribed using RPE in MI patients during early outpatient CR. Participation in RPE-prescribed HIIT increases exercise workload and 2 during exercise training without increased perception of effort or excessive increases in heart rate or blood pressure.

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 (&gt;= 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 &amp; Ray, 2002; Ray &amp; 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&lt;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.

Dexmedetomidine as a Heart Rate Control for Off-Pump Coronary Artery Bypass Surgery

Introduction: The traditional surgical approach is performed under cardiac arrest with cardiopulmonary bypass (CPB), which has the potential to result in myocardial injuries. In 1990s, when researchers developed efficient mechanical stabilizer devices, Off-pump coronary artery bypass (OPCAB) gained more widespread interest, as it’s associated with many significant benefits. Avoidance of tachycardia is a goal for anesthetic management during OPCAB surgery. A short-acting Beta-blocker is needed for lowering excessive increases in heart rate. However, in some hospitals these drugs were not available. Case: A 53-yr-old, 73 kg man with a three-vessel coronary arterial disease with left main disease was scheduled for elective OPCAB surgery. Patient has a medical history of heart attack and hypertension. Preoperative echocardiography shows reduced LV systolic function, diastolic dysfunction grade I, with LVEF 47%. Throughout the hour after induction, HR increased in a constant manner to a persistent of 85-90 bpm despite additional fentanyl given. We didn’t have any intravenous beta blocker drug and therefore we started dexmedetomidine. HR decreased to 55-60 bpm and remained at that value throughout the surgical procedure. Patient extubated in OR and transferred to ICU. After 6 days, he was discharged from the hospital without any complications. Conclusion: Perioperative administration of Dexmedetomidine is an effective adjuvant to general anaesthesia, attenuates the stress response to intubation, provides minimal heart rate variations, enabling smooth extubation, also provides adequate sedation in the post-operative period.

Downregulation of growth hormone in postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort

Abstract Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial. Purpose We aimed to investigate the alterations in circulating growth hormone level in POTS. Methods We conducted an age-matched case-control study enrolling 42 patients with POTS (age 31±9 years; 36 women) verified by positive head-up tilt testing and cardiovascular autonomic tests, and 46 controls (32±9 years; 35 women) with negative active standing test and no history of syncope, orthostatic intolerance and endocrine disease. We measured plasma levels of growth hormone using a high-sensitivity chemiluminescence immunoassay in relation to presence of POTS diagnosis. All study participants completed the validated Orthostatic Hypotension Questionnaire (OHQ), consisting of two components: the symptoms assessment scale (OHSA) and daily activity scale (OHDAS) to evaluate the burden of symptoms. We applied standard statistical tests for group differences. Growth hormone values were log-transformed and standardized before the group comparison. Results POTS patients had significantly lower plasma levels of growth hormone (ng/mL) (median=0.53, IQR, 0.10–2.83 vs. median=2.33, IQR, 0.26–7.2, p=0.04) than controls. Levels of growth hormone were reversely related to OHDAS (p=0.049) among POTS patients. Supine heart rate was significantly higher in POTS patients (69.0±11.1 beats/min vs. 63.3±10.8 beats/min, p=0.02), as well as diastolic blood pressure (72.9±9.1 mmHg vs. 69.0±8.5 mmHg, p=0.04). We observed no significant difference in supine systolic blood pressure (116.6±13.3 mmHg vs. 115.2±10.0 mmHg, p=0.60). POTS patients had a significantly higher composite OHQ score than controls (60.0±18.6 vs. 4.2±7.5, p&amp;lt;0.001), as well as OHSA (36.2±10.0 vs. 3.6±6.4, p&amp;lt;0.001) and OHDAS (23.8±9.7 vs. 0.6±1.3, p&amp;lt;0.001). Conclusion(s) Our study shows that patients with POTS have significantly reduced plasma levels of circulating growth hormone. Lower growth hormone levels among POTS patients are associated with increased impairment of daily life activities. Further studies are necessary to confirm our findings in the independent populations and explain the mechanisms behind this alteration. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Crafoord Foundation, Swedish Heart and Lung Foundation

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.

Serum Activity Against G Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome.

BackgroundPostural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein–coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell‐based assay.Methods and ResultsForty‐eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10‐item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein–coupled receptor: adrenergic α1 receptor, adrenergic β2 receptor, cholinergic muscarinic type 2 receptor, and opioid receptor‐like 1 were treated with sera from all patients. Receptor response was analyzed using a β‐arrestin–linked transcription factor driving transgenic β‐lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein–coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls (P<0.01 for all). The area under the curve was 0.88 (0.80–0.97, P<0.001) combining all 4 receptors. Adrenergic α1 receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity, P=0.009) and with reduced tolerability for prolonged standing (P=0.037) and walking for short (P=0.042) or long (P=0.001) periods. All 4 receptors were associated with vision problems (P<0.05 for all).ConclusionsOur results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum‐mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α1 receptor is associated with orthostatic symptoms severity in patients with POTS.

Efficacy of Gradient Compression Garments in the Hours After Long-Duration Spaceflight.

The incidence of presyncopal events is high soon after a long-duration spaceflight;>60% of returning astronauts could not complete a 10-min 80° head-up tilt test on landing day (R+0) after ~6 months of spaceflight. The objective of this study was to demonstrate the ability of a lower body gradient compression garment (GCG) to protect against an excessive increase in heart rate and a decrease in blood pressure during standing after long-duration spaceflight. Methods: Eleven astronauts (9 M, 2 F) volunteered to participate. The stand test protocol consisted of 2 min of prone rest followed by 3.5 min of standing. Subjects completed one familiarization session, two preflight data collection sessions in standard clothing, and three tests on landing day while wearing GCG. Postflight tests were conducted 1–4 h (R+0A), ~12 h (R+0B), and ~28 h after landing (R+0C). Results: All astronauts completed the stand test preflight. Three astronauts were unable to attempt the stand test at R+0A, and one of these was unable to start the test at R+0B. One astronaut was unable to complete 3.5 min of standing at R+0B (test ended at 3.3 min). Review of the individual’s blood pressure data revealed no hypotension but the astronaut reported significant motion sickness. Of the astronauts who participated in testing on landing day, the heart rate and mean arterial pressure responses to standing (stand-prone) were not different than preflight at any of the postflight sessions. Conclusion: Wearing the GCG after spaceflight prevented the tachycardia that normally occurs while standing after spaceflight without compression garments and protected against a decrease in blood pressure during a short stand test.

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome

BackgroundPostural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.MethodsWe conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction.ResultsPOTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS.ConclusionsCardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

P4441Serum activity against specific G-protein coupled receptors is associated with the severity of orthostatic symptoms in patients with POTS

Abstract Background Postural orthostatic tachycardia syndrome (POTS) is characterised by an excessive heart rate increase upon standing and orthostatic intolerance. Previous studies indicate autoimmune involvement mediated via G-protein coupled receptors (GPCRs) as a possible aetiology. Purpose To test if serum from POTS patients and controls activates selected GPCRs and if the activation associates with the severity of symptoms. Methods A total of 34 POTS patients (age 28.9 [9.9] years; 29 women) and a population-based control group of 25 healthy subjects (age 30.7 [8.6] years; 21 women) were included. The subjects performed an active standing test and completed the orthostatic hypotension questionnaire (OHQ) including ten items related to orthostatic intolerance. The OHQ composite score was calculated (range 0–10). Sera were analysed by a FRET-based reporter system (Tango GeneBLAzer, Thermo Fischer) based on a beta-arrestin-linked transcription factor driving transgenic betalactamase transcription. HEK293M-cells over-expressing one of the GPCRs, adrenergic alpha-1 (ADRA1), adrenergic beta-2 (ADRB2), muscarinic type-2 (CHRM2) and opioid-receptor-like 1 (OPRL1) receptor were plated in 96-well optical plates and allowed to re-attach during 48 hrs. The cells were treated with 10% sera diluted in RPMI for 5 hours, followed by addition of the FRET-substrate, incubation for 60 min and quantification analysis in a CLARIOStar multi-purpose plate reader. Quantification of the activation of the GPCRs was log-transformed and related to the OHQ composite and individual scores in age-adjusted linear regression models. OHQ scores were compared according to the median of sera activation, using independent samples t-test. Results Serum ADRA1 activation associated with the OHQ composite score (beta 0.77 OHQ points per SD of activity; p=0.009), whereas there were no significant associations among controls (p=0.953). The association between ADRA1 and total OHQ was significant also after adjusting for heart rate and systolic blood pressure at 3 min (p=0.024). The OHQ composite score was higher in with above median serum ADRA1 activation (Figure 1). ADRA1 activation associated with a higher score for vision problems (p&lt;0.001) and symptoms during prolonged standing (p=0.037) and walking for short (p=0.042) or long periods (p=0.001). The activity of ARB2, CHRM2 and OPRL1 did not associate with OHQ composite score in neither POTS patients nor controls. Figure 1. OHQ according to ADRA1 activation Conclusions Activating serum proteins for the adrenergic alpha-1 receptor are associated with the severity of orthostatic symptoms in POTS patients, partly independent of the orthostatic hemodynamic response. Serum activity against alpha1 receptors is related particularly to symptoms of disturbed vision and symptoms during walking or prolonged standing. Serum activity against the adrenergic alpha 1 receptor may be a one factor underlying the orthostatic symptoms in POTS. Acknowledgement/Funding The Swedish Heart-Lung Foundation, The Swedish Heart and Lung Association, Solidex, ALF funds, Crafoord Foundation, Ernhold Lundströms Foundation.

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management.

Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affectsyounger individuals 15-45years old with a distinct female predominance (≈80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, 'brain fog', dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring. Although long-term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1-3years. After the diagnosis has been established, patient should be thoroughly educated about non-pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.

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.