Postural Tachycardia Research Articles

Long COVID and its cardiovascular consequences: What is known?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Predicting Therapeutic Efficacy of Pharmacological Treatments in Children with Postural Orthostatic Tachycardia Syndrome: A Mini-Review.

Postural orthostatic tachycardia syndrome (POTS) is common in children, with an excessive increment in heart rate when moving from the supine to upright position. It has significant negative impacts on the daily life of pediatric patients. The pathogenesis of POTS includes peripheral vascular dysfunction, central hypovolemia, abnormal autonomic function, a high-adrenergic state, impaired skeletal-muscle pump function, the abnormal release of vasoactive factors, and autoimmune abnormalities. Therefore, the empirical use of pharmacological treatments has limited therapeutic efficacy due to the diversity of its mechanisms. A crucial aspect of managing POTS is the selection of appropriate treatment targeting the specific pathogenesis. This review summarizes the commonly used pharmacological interventions, with a focus on their predictive indicators for treatment response. Factors such as heart rate variability, plasma biomarkers, and cardiac-function parameters are discussed as potential predictors of therapeutic efficacy, enabling the implementation of individualized treatment to improve therapeutic effectiveness. This review consolidates the current knowledge on POTS, encompassing its clinical characteristics, epidemiological patterns, underlying pathogenic mechanisms, and predictive indicators for treatment response. Further research is warranted to enhance the understanding of POTS and facilitate the development of more effective therapeutic approaches for this challenging syndrome.

Poor health-related quality of life in postural orthostatic tachycardia syndrome in comparison with a sex- and age-matched normative population

PurposeThe effect of postural orthostatic tachycardia syndrome (POTS) on health-related quality of life (HrQoL) remains poorly studied. Here, we sought to compare the HrQoL in individuals with POTS to a normative age-/sex-matched population.MethodsParticipants enrolled in the Australian POTS registry between 5 August 2021 and 30 June 2022 were compared with propensity-matched local normative population data from the South Australian Health Omnibus Survey. The EQ-5D-5L instrument was used to assess HrQoL across the five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with global health rating assessed with a visual analog scale (EQ-VAS). A population-based scoring algorithm was applied to the EQ-5D-5L data to calculate utility scores. Hierarchical multiple regression analyses were undertaken to explore predictors of low utility scores.ResultsA total of 404 participants (n = 202 POTS; n = 202 normative population; median age 28 years, 90.6% females) were included. Compared with the normative population, the POTS cohort demonstrated significantly higher burden of impairment across all EQ-5D-5L domains (all P < 0.001), lower median EQ-VAS (p < 0.001), and lower utility scores (p < .001). The lower EQ-VAS and utility scores in the POTS cohort were universal in all age groups. Severity of orthostatic intolerance symptoms, female sex, fatigue scores, and comorbid diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were independent predictors of reduced HrQoL in POTS. The disutility in those with POTS was lower than many chronic health conditions.ConclusionsThis is the first study to demonstrate significant impairment across all subdomains of EQ-5D-5L HrQoL in the POTS cohort as compared with a normative population.Trial registrationACTRN12621001034820

Microvasular Dysfunction and Reduced Cardiac Stress Reactivity in Postural Orthostatic Tachycardia Associated With Postacute COVID-19.

HomeCirculation: Arrhythmia and ElectrophysiologyAhead of PrintMicrovasular Dysfunction and Reduced Cardiac Stress Reactivity in Postural Orthostatic Tachycardia Associated With Postacute COVID-19 No AccessResearch ArticleRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessMicrovasular Dysfunction and Reduced Cardiac Stress Reactivity in Postural Orthostatic Tachycardia Associated With Postacute COVID-19 Ali Mahdi, Klara Lodin, Ulrika Reistam, Artur Fedorowski, Malin Nygren-Bonnier, Michael Runold, Judith Bruchfeld, Liyew Desta, John Pernow, Jannike Nickander and Marcus Ståhlberg Ali MahdiAli Mahdi Correspondence to: Ali Mahdi, MD, PhD, Cardiovascular Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden. Email E-mail Address: [email protected] https://orcid.org/0000-0003-0386-7817 Division of Cardiology, Department of Medicine, Solna, Sweden (A.M., U.R., A.F., L.D., J.P., M.S.). Search for more papers by this author , Klara LodinKlara Lodin https://orcid.org/0009-0008-3759-5278 Department of Clinical Physiology, Karolinska University Hospital, Karolinska Institutet. (K.L.) Search for more papers by this author , Ulrika ReistamUlrika Reistam https://orcid.org/0000-0002-9192-8992 Division of Cardiology, Department of Medicine, Solna, Sweden (A.M., U.R., A.F., L.D., J.P., M.S.). Search for more papers by this author , Artur FedorowskiArtur Fedorowski https://orcid.org/0000-0002-5352-6327 Division of Cardiology, Department of Medicine, Solna, Sweden (A.M., U.R., A.F., L.D., J.P., M.S.). Search for more papers by this author , Malin Nygren-BonnierMalin Nygren-Bonnier Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska University Hospital, Stockholm, Sweden. (M.N.-B., J.N.). Search for more papers by this author , Michael RunoldMichael Runold Department of Respiratory and Allergic Diseases, Karolinska University Hospital, Stockholm, Sweden. (M.R.) Search for more papers by this author , Judith BruchfeldJudith Bruchfeld Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden. (J.B.) Division of Infectious Diseases, Department of Medicine, Solna (J.B.). Search for more papers by this author , Liyew DestaLiyew Desta Division of Cardiology, Department of Medicine, Solna, Sweden (A.M., U.R., A.F., L.D., J.P., M.S.). Search for more papers by this author , John PernowJohn Pernow https://orcid.org/0000-0003-4766-0922 Division of Cardiology, Department of Medicine, Solna, Sweden (A.M., U.R., A.F., L.D., J.P., M.S.). Search for more papers by this author , Jannike NickanderJannike Nickander https://orcid.org/0000-0001-5659-8142 Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska University Hospital, Stockholm, Sweden. (M.N.-B., J.N.). Search for more papers by this author and Marcus StåhlbergMarcus Ståhlberg Division of Cardiology, Department of Medicine, Solna, Sweden (A.M., U.R., A.F., L.D., J.P., M.S.). Search for more papers by this author Originally published19 Jun 2023https://doi.org/10.1161/CIRCEP.123.011881Circulation: Arrhythmia and Electrophysiology. 2023;0:e011881"Microvasular Dysfunction and Reduced Cardiac Stress Reactivity in Postural Orthostatic Tachycardia Associated With Postacute COVID-19." Circulation: Arrhythmia and Electrophysiology, , pp. FootnotesFor Sources of Funding and Disclosures, see page XXX.Correspondence to: Ali Mahdi, MD, PhD, Cardiovascular Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden. Email ali.[email protected]se Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.123.011881PMID: 37334702 Originally publishedJune 19, 2023 Keywordsperfusionvascular diseasesheart diseasespostacute COVID-19 syndromehumansPDF download Advertisement SubjectsAutonomic Nervous SystemEndothelium/Vascular Type/Nitric OxideMechanismsPathophysiology

WITHDRAWN: Usefulness of nabilone as an antiemetic in persistent vomiting due to refractory gastrointestinal disorders.

Nabilone, a synthetic analogue of delta-9-Tetrahydrocannabinol, is an agonist of cannabinoid receptors (CB-1 and CB-2) approved to treat chemotherapy-induced vomiting refractory to antiemetics. Its use in patients with refractory vomiting due to gastrointestinal dysmotility (GID) has not been reported. Our study aims are to assess nabilone usefulness and side-effects in patients with refractory vomiting due to GID. Patients prescribed nabilone at St. Mark's intestinal rehabilitation unit (January 2017 to September 2022) due to GID vomiting have been retrospectively reviewed. Descriptive analysis has been done. Variables measured: age, sex, comorbidities, antiemetics/prokinetics, enteral or parenteral nutrition, nabilone prescription, subjective symptom improvement and side-effects. Seven patients received nabilone. 5/7 (72%) were females. Median age:25 years (23-37). 3/7 (43%) had gastroparesis (1/3 related to postural orthostatic tachycardia syndrome -POTS- , 1/3 to Ehlers-Danlos' Syndrome, POTS, Crohn's Disease and adrenal insufficiency -AI- and 1/3 to sinus node ablation and AI), 2/7 (29%) had gastroparesis and intestinal dysmotility (1/2 related to POTS and 1/2 related to EDS and other connective tissue diseases) and 2/7 (29%) had intestinal dysmotility (1/2 because of polyglucosan body visceral myopathy and 1/2 to intestinal surgery). All patients had received antiemetics or prokinetics before (median of 5 drugs; 2-11). 1/7 (14%) received enteral supplements, 5/7 (72%) enteral nutrition through enteral tubes and 4/7 (57%) parenteral nutrition. 5/7 (72%) patients received 1mg of nabilone bd orally, 1/7 (14%) 2 mg bd through jejunostomy and 1/7 (14%) started nabilone at 2 mg bd orally, but had to be switched to 1 mg bd because of side-effects. The median treatment's duration was 9 days (7-35). Regarding the efficacy of nabilone, 3/7 (43%) had symptomatic improvement. In terms of side-effects 4/7 (57%) patients reported some incidence under the treatment such as headache, light-headedness, drowsiness, dizziness or hallucinations. Patients with refractory GID vomiting despite multiple anti-sickness are difficult to treat. Nabilone improved symptoms in almost half of the patients although adverse effects appeared in more than 50%. Doses higher than 1 mg bd po did not show benefit. Although our study has important limitations, nabilone might be a temporary measure in these patients. Side-effects should be taken into consideration.

Atrial electromechanical delay in post-COVID-19 postural orthostatic tachycardia: Innocent bystander or pathologic factor

BackgroundPost-COVID-19 syndrome represents a wide range of ongoing symptoms that persist beyond weeks or even months, after recovery from the acute phase. Postural orthostatic tachycardia (POT) is one of these symptoms with a poorly recognized underlying pathophysiology. PurposeWe aimed to investigate atrial electromechanical delay (AEMD), demonstrated by electrocardiographic P wave dispersion (PWD) and tissue Doppler echocardiography (TDE) in patients with POST-COVID-19 POT (PCPOT). Methods94 post-COVID-19 patients were enrolled and classified into two groups; PCPOT group, 34 (36.1%) patients, and normal heart rate (NR group), 60 (63.9%) patients. 31.9% of them were males and 68.1% were females, with a mean age of 35 ± 9 years. Both groups were compared in terms of PWD and AEMD. ResultsAs compared to the NR group, the PCPOT group showed a significant increase in PWD (49 ± 6 versus 25.6 ± 7.8, p < 0.001), higher CRP (37 ± 9 versus 30 ± 6, p = 0.04), prolonged left-atrial EMD, right-atrial EMD and inter-atrial EMD at (p = 0.006, 0.001, 0.002 respectively). Multivariate logistic regression analysis revealed that P wave dispersion (β 0.505, CI (0.224–1.138), p = 0.023), PA lateral (β 0.357, CI (0.214–0.697), p = 0.005), PA septal (β 0.651, CI. (0.325–0.861), p = 0.021), and intra-left atrial EMD (β 0.535, CI (0.353–1.346) p < 0.012) were independent predictors of PCPOT. ConclusionAtrial heterogenicity in the form of prolonged AEMD and PWD seems to be a reasonable underlying pathophysiology of PCPOT. This could provide a new concern during the management and novel pharmacological approaches in these patients.

Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study)

PurposeApproximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing.MethodsIn this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions.ResultsPatients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing.ConclusionCompared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS.Trial Registration InformationThe study was registered at ClinicalTrials.gov (NCT03681080).

High Incidence of Autonomic Dysfunction and Postural Orthostatic Tachycardia Syndrome in Patients with Long COVID: Implications for Management and Health Care Planning

BackgroundAutonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), has been reported in individuals with post-acute sequelae of COVID-19 (PASC). However, the degree of dysautonomia in PASC has not been compared to those with POTS and healthy controls. MethodsAll participants were prospectively enrolled between August 5, 2021 and October 31, 2022. Autonomic testing included beat-to-beat hemodynamic monitoring to assess respiratory sinus arrhythmia, Valsalva ratio, and orthostatic changes during a 10-minute active standing test, as well as sudomotor assessment. The Composite Autonomic Symptom Score (COMPASS-31) was used to assess symptoms and the EuroQuol 5-Dimension survey (EQ-5D-5L) was used to assess health-related quality of life (HrQoL) measures. ResultsA total of 99 participants (n = 33 PASC, n = 33 POTS, and n = 33 healthy controls; median age 32 years, 85.9% females) were included. Compared with healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (P < .001), greater heart rate increase during 10-minute active standing test (P < .001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all P < .001), and poor HrQoL across all EQ-5D-5L domains (all P < .001), lower median EuroQol-visual analogue scale (P < .001), and lower utility scores (P < .001). The majority (79%) of those with PASC met the internationally established criteria for POTS. ConclusionThe prevalence of autonomic symptomology for POTS was high in those with PASC, leading to poor HrQoL and high health disutility. Autonomic testing should be routinely undertaken in those with PASC to aid diagnosis and direct appropriate management to improve health outcomes.

Cardiovascular Considerations in the Management of People With Suspected Long COVID.

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks after acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection might present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat. When assessing patients with these symptoms, clinicians need to keep in mind myalgic encephalomyelitis/chronic fatigue syndrome, postexertional malaise and postexertional symptom exacerbation, dysautonomia with cardiac manifestations such as inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome, and occasionally mast cell activation syndrome. In this review we summarize the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, we include a Canadian perspective, consisting of a panel of expert opinions from people with lived experience and experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.

Objective Hemodynamic Cardiovascular Autonomic Abnormalities in Post-Acute Sequelae of COVID-19.

Many COVID-19 patients are left with symptoms several months after resolution of the acute illness; this syndrome is known as post-acute sequalae of COVID-19 (PASC). We aimed to determine the prevalence of objective hemodynamic cardiovascular autonomic abnormalities (CAA), explore sex differences, and assess the prevalence of CAA among hospitalized vs nonhospitalized patients with PASC. Patients with PASC (n= 70; female [F]= 56; 42 years of age; 95% confidence interval [CI], 40-48) completed standard autonomic tests, including an active stand test 399 days (338, 455) after their COVID-19 infection. Clinical autonomic abnormalities were evaluated. Most patients with PASC met the criteria for at least 1 CAA (51; 73%; F= 43). The postural orthostatic tachycardia syndrome hemodynamic (POTSHR) criterion of a heart rate increase of > 30 beats per minute within 5 to 10 minutes of standing was seen in 21 patients (30%; F= 20; P= 0.037 [by sex]). The initial orthostatic hypotension hemodynamic (IOH40) criterion of a transient systolic blood pressure change of > 40 mm Hg in the first 15 seconds of standing was seen in 43 (61%) patients and equally among female and male patients (63% vs 57%; P= 0.7). Only 9 (13%) patients were hospitalized; hospitalized vs nonhospitalized patients had similar frequencies of abnormalities (67% vs 74%; P= 0.7). Patients with PASC have evidence of CAA, most commonly IOH40, which will be missed unless an active stand test is used. Female patients have increased frequency of POTSHR, but IOH40 is equally prevalent between sexes. Finally, even nonhospitalized "mild" infections can result in long-term CAAs.

Evaluation of cardiovascular and cerebrovascular control mechanisms in postural orthostatic tachycardia syndrome via conditional transfer entropy: the impact of the respiratory signal type

Objective. Closed loop cardiovascular (CV) and cerebrovascular (CBV) variability interactions are assessed via transfer entropy (TE) from systolic arterial pressure (SAP) to heart period (HP) and vice versa and from mean arterial pressure (MAP) to mean cerebral blood velocity (MCBv) and vice versa. This analysis is exploited to assess the efficiency of baroreflex and cerebral autoregulation. This study aims at characterizing CV and CBV controls in postural orthostatic tachycardiac syndrome (POTS) subjects experiencing exaggerated sympathetic response during orthostatic challenge via unconditional TE and TE conditioned on respiratory activity (R). Approach. In 18 healthy controls (age: 28 ± 13 yrs; 5 males, 13 females) and 15 POTS individuals (age: 29 ± 11 yrs; 3 males, 12 females) we acquired beat-to-beat variability of HP, SAP, MAP and MCBv and two R signals, namely respiratory chest movement (RCM) and capnogram (CAP). Recordings were made at sitting rest and during active standing (STAND). TE was computed via vector autoregressive approach. Main results. We found that: (i) when assessing CV interactions, the increase of the TE from SAP to HP during STAND, indicating baroreflex activation, is detected solely when conditioning on RCM; (ii) when assessing CBV interactions, the impact of R on the TE computation is negligible; (iii) POTS shows baroreflex impairment during STAND; (iv) POTS exhibits a normal CBV response to STAND. Significance. TE is useful for detecting the impairment of specific regulatory mechanisms in POTS. Moreover, using different R signals highlights the sensitivity of CV and CBV controls to specific R aspects.

1014 The PANDA Monster Under the Bed

Abstract Introduction Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) is an acute-onset constellation of symptoms including obsessive-compulsive disorder and concurrent neuropsychiatric symptoms including anxiety, emotional lability, and behavioral regression. Sleep disturbances are common in PANDAS, suspected of post-infectious inflammation that can decrease serotonin, increase dopamine, and prevent the production of melatonin. OCD fears and rituals can create may impede sleep onset and impair sleep maintenance. Abnormal motor manifestations during sleep include restlessness, stereotypies, paroxysms or periodic limb movements during sleep. This case report highlights the clinical time course of sleep disorders found in chronic PANDAS, refractory to immunomodulatory interventions. Report of case(s) We present the case of an 11-year-old male who presented with behavioral insomnia of childhood sleep-onset association type in the setting of personality changes and deterioration of school performance coinciding with streptococcus infection two months earlier. The patient was supported with prophylaxis antistreptococcal therapy as well as Omega-3 fatty acids. Parents noted heightened anxiety during the day, fear of obsessive and intrusive thoughts about becoming sick, and social seclusion but refusal to sleep alone and be away from home. He was also diagnosed with a tic disorder, chronic migraine, and postural orthostatic tachycardia syndrome (POTS), which likely exacerbated insomnia. The patient was referred for Cognitive behavior therapy utilizing exposure/response prevention ERP modality and psychoeducation. However, it was not until clonidine was introduced that the patient demonstrated a significant clinical response. Clonidine was initiated at 50ug and increased to 100ug QHS. It likely promotes sedation by decreasing norepinephrine release via negative feedback by agonism of the α2-adrenergic receptors at the level of the locus coeruleus. Conclusion Sleep disorders in PANDAS syndrome remain elusive and challenging to manage due to the lack of well-developed pharmacologic guidelines to treat insomnia in children. Our case illustrates the importance of the integration of pharmacologic treatments to augment behavioral strategies and promote better patient outcomes. More studies are needed to investigate the pharmacologic management of sleep ­disorders in children in general, but appraise the safety and efficacy of specific medications such, as clonidine, in particular. Support (if any)

Cardiorespiratory dysautonomia in post-COVID-19 condition: Manifestations, mechanisms and management.

A significant proportion of COVID-19 patients experience debilitating symptoms for months after the acute infection. According to recent estimates, approximately one out of ten COVID-19 convalescents reports persistent health issues more than three months after initial recovery. This "post-COVID-19 condition" may include a large variety of symptoms from almost all domains and organs, and for some patients it may mean prolonged sick-leave, homestay, and strongly limited activities of daily life. In this narrative review, we focus on the symptoms and signs of post-COVID-19 condition in adults-particularly those associated with cardiovascular and respiratory systems, such as postural orthostatic tachycardia syndrome (POTS) or airway disorders-and explore the evidence for chronic autonomic dysfunction as a potential underlying mechanism. The most plausible hypotheses regarding cellular and molecular mechanisms behind the wide spectrum of observed symptoms-such as lingering viruses, persistent inflammation, impairment in oxygen sensing systems and circulating antibodies directed to blood pressure regulatory components-are discussed. In addition, an overview of currently available pharmacological and non-pharmacological treatment options is presented. This article is protected by copyright. All rights reserved.

Anticipatory central command on standing decreases cerebral blood velocity causing hypocapnia in hyperpneic postural tachycardia syndrome.

Fifty percent of patients with postural tachycardia syndrome (POTS) are hypocapnic during orthostasis related to initial orthostatic hypotension (iOH). We determined whether iOH drives hypocapnia in POTS by low BP or decreased cerebral blood velocity (CBv). We studied three groups; healthy volunteers (n = 32, 18 ± 3 yr) were compared with POTS, grouped by presence [POTS-low end-tidal CO2 (↓ETCO2), n = 26, 19 ± 2 yr] or absence [POTS-normal upright end-tidal carbon dioxide (nlCO2), n = 28, 19 ± 3 yr] of standing hypocapnia defined by end-tidal CO2 (ETCO2) ≤ 30 mmHg at steady-state, measuring middle cerebral artery CBv, heart rate (HR), and beat-to-beat blood pressure (BP). After 30 min supine, subjects stood for 5 min. Quantities were measured prestanding, at minimum CBv, minimum BP, peak HR, CBv recovery, BP recovery, minimum HR, steady-state, and 5 min. Baroreflex gain was estimated by α index. iOH occurred with similar frequency and minimum BP in POTS-↓ETCO2 and POTS-nlCO2. Minimum CBv was reduced significantly (P < 0.05) in POTS-↓ETCO2 (48 ± 3 cm/s) preceding hypocapnia compared with POTS-nlCO2 (61 ± 3 cm/s) or Control (60 ± 2 cm/s). The anticipatory increased BP was significantly larger (P < 0.05) in POTS (8 ± 1 mmHg vs. 2 ± 1) and began ∼8 s prestanding. HR increased in all subjects, CBv increased significantly (P < 0.05) in both POTS-nlCO2 (76 ± 2 to 85 ± 2 cm/s) and Control (75 ± 2 to 80 ± 2 cm/s) consistent with central command. CBv decreased in POTS-↓ETCO2 (76 ± 3 to 64 ± 3 cm/s) correlating with decreased baroreflex gain. Cerebral conductance [meanCBv/mean arterial blood pressure (MAP)] was reduced in POTS-↓ETCO2 throughout. Data support the hypothesis that excessively reduced CBv during iOH may intermittently reduce carotid body blood flow, sensitizing that organ and producing postural hyperventilation in POTS-↓ETCO2. Excessive fall in CBv occurs in part during prestanding central command and is a facet of defective parasympathetic regulation in POTS.NEW & NOTEWORTHY Dyspnea is frequent in postural tachycardia syndrome (POTS) and is associated with upright hyperpnea and hypocapnia that drives sinus tachycardia. It is initiated by an exaggerated reduction in cerebral conductance and decreased cerebral blood flow (CBF) that precedes the act of standing. This is a form of autonomically mediated "central command." Cerebral blood flow is further reduced by initial orthostatic hypotension common in POTS. Hypocapnia is maintained during the standing response and might account for persistent postural tachycardia.

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 &amp;gt;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&amp;lt;0.004) and psychological functions (PHQ-9 p&amp;lt;0.001) and less symptoms related to POTS (MaPS p&amp;lt;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.

Postural orthostatic tachycardia syndrome associated with post-acute covid-19 syndrome is not mediated through smaller hearts or contractile dysfunction

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Swedish Heart-Lung foundation Swedish Research Council Introduction Post-acute covid-19 syndrome (PACS) is a novel condition with persistent symptoms affecting different organs. We have previously reported postural orthostatic tachycardia syndrome (POTS) as one important long-term complication. The pathophysiological mechanisms behind PACS and associated POTS are largely unknown. It has previously been suggested that POTS patients have a smaller left ventricular mass (LVM) and volume contributing to the persistent symptoms of tachycardia, however it is currently unknown if these pathophysiological mechanisms are similar in PACS associated POTS. Furthermore, it has been shown that global longitudinal strain (GLS) and global circumferential strain (GCS) are more sensitive measures of contractile function compared to ejection fraction, however it is also currently unknown if GLS and GCS differs between PACS patients with and without POTS. Purpose To elucidate if patients with PACS associated POTS have a lower LVM compared to PACS without POTS, and if GLS and GCS differ between the groups. Methods In total, 31 patients that had suffered a mild SARS-CoV-2 infection diagnosed with PACS according to the WHO criteria were enrolled in this prospective cohort study. POTS was verified by head-up tilt test; 16 patients (age 40±10 years, 94% women) were POTS positive whereas 15 (45±11 years, 93% women) were POTS negative. All patients underwent cardiac magnetic resonance imaging, and global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated. Results There were no differences between the groups with regards to left ventricular dimensions or mass, Table 1. There were no differences in GLS and GCS between the two groups (GLS: PACS and POTS positive -18±2% vs PACS and POTS negative -19±2%, p=0.53; GCS: PACS and POTS positive -17±3% vs PACS and POTS negative -19±3%, p=0.16), Figure 1. Conclusions PACS-related POTS is not associated with contractile dysfunction nor differences in cardiac geometrics, providing mechanistic insights in the pathophysiology of PACS associated POTS. Other specific pathophysiological mechanisms that underlie POTS associated with PACS needs to be established.

Evidence of cytokine activation in patients with post-acute COVID-19 syndrome with- and without postural orthostatic tachycardia syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Research Council Swedish Heart- and Lungfoundation Introduction Post-acute COVID-19 syndrome (PACS) affects approximately 10% of non-hospitalized COVID-19 patients with mild primary infection and constitutes an increasing burden for society and healthcare systems. We have previously reported that a proportion of PACS patients develop postural orthostatic tachycardia syndrome (POTS). The pathophysiological mechanisms behind PACS and associated POTS remain largely unknown but cytokine activation and inflammation have been proposed. Purpose To test the hypothesis that PACS and POTS-specific phenotype are associated with cytokine activation. Methods We recruited 20 patients with PACS and POTS verified by head-up TILT test (95% female, 39±11 years, 18±3 months after acute SARS-CoV-2 infection) and 22 patients with PACS without POTS (100% female, 44±11years, 19±3 months after acute SARS-CoV-2 infection). Age- and sex matched healthy volunteers (n=21; 95% female, 43±6 years) without- (n=16) and with (n=5) a history of SARS-Cov-2 infection but without symptoms served as control group. Peripheral blood samples were collected and analyzed for concentrations of 45 cytokines and inflammatory markers using Proximity Extension Assay. Protein-protein interactions and signaling pathway analysis were assessed using String database, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Results Several cytokines and inflammatory biomarkers were overexpressed in patients with PACS compared to healthy controls irrespective of the presence of POTS (Figure 1). Protein-protein interaction analysis revealed a cluster including IL-7, CXCL12, CXCL11, CCL8 and CCL13. Cytokine-receptor activation, viral protein – cytokine receptor interaction and chemokine signaling were the most significantly upregulated KEGG pathways. Cytokine-mediated signaling, and cell- and leukocyte migration and chemotaxis were the most significantly upregulated GO biological processes. Conclusion PACS is associated with increased levels of circulating cytokines regardless of concomitant POTS up to 18 months after a mild primary SARS-CoV-2 infection. This suggests that PACS-associated POTS exist on a background of cytokine activation but other specific pathophysiological mechanisms for PACS induced POTS needs to be established. Whether the cytokine profile of PACS is associated with persistent viral load or prolonged activation of the innate immune system and chronic inflammation, constituting a potential treatment target should be explored in future studies.

Diagnostic value of 24-h ECG recording in Long COVID patients with postural orthostatic tachycardia syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular autonomic dysfunction (CVAD) is a major complication for a large proportion of Long COVID (LC) patients. The main phenotype of CVAD is postural orthostatic tachycardia syndrome (POTS), commonly observed as a sequalae of COVID infection, thus defining a subset of LC patients. POTS is a cardiovascular autonomic disorder characterized by an excessive heart rate (HR) increase and symptoms of orthostatic intolerance when assuming upright posture, occurring predominantly in young and middle-aged women. Since the start of COVID-19 pandemic it has been observed that up to 30% of patients with post-COVID-19 syndrome develop POTS with such symptoms as tachycardia, orthostatic intolerance, fatigue, and cognitive impairment. The heterogeneity of POTS symptoms makes the diagnosis and appropriate management of POTS more difficult and one of the first steps for clinicians is to develop and test relevant diagnostic methods for POTS. Methods Patients with persistent symptoms, 3 months after an acute SARS-CoV-2 infection were referred to the multi-disciplinary LC unit at a hospital in Sweden. Consecutive patients seen at this unit from 2021 to 2022 underwent a 24-h ECG recording. LC patients with POTS verified by active standing test and/or head-up tilt testing were prospectively enrolled in the study database and were compared with LC patients without POTS according to 3 specific analyses based on 24-h ECG recording : (1) cardiac autonomic activity expressed by heart rate variability, HRV (SDNN and RMSSD in ms) parameters, (2) awakening HR increase (HR mean 10 min before vs. 30 min after awakening) and (3) HR spikes (number/h if at least over than 30 bpm and at least during 30 s). Control group consisted of healthy subjects from 24-h ECG recordings database (HRV analysis) of a hospital in France. Data were expressed as mean (± standard deviation, SD) and frequencies (%). Results A total of 120 LC patients (mean age: 42.7 +/-9.97 y, 88% women) and 100 healthy subjects (mean age: 46.4 +/-10.2 y, 82% women) were included. LC with POTS (42%) was associated with (1) a decrease in most HRV parameters (mean SDNN: 86.8 +/-24.3 vs. 108.7 +/-24.1 ms, p=0.03), and the most reduced components were those related to the parasympathetic tone (mean RMSSD: 34,5 +/-20.4 vs. 45.6 +/-22.1 ms, p=0.04), (2) an abrupt and sustained increase in HR during the first 30 min after awakening (+30%, p&amp;lt;0.05) and (3) a higher number of HR spikes per h (1.4 +/-0.8 vs. 0.8 +/-0.7/h, p&amp;lt;0.001) compared with healthy subjects (HRV) and LC patients without POTS (awakenings and HR peaks) respectively. Conclusion A triple analysis of 24-h ECG recordings revealed presence of autonomic dysfunction in LC patients with POTS compared with those without POTS. This novel analysis may be introduced in the clinic for screening and therapy monitoring.

Novel inflammatory biomarkers in postural orthostatic tachycardia syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Postural Orthostatic Tachycardia Syndrome (POTS) is a disorder characterized by excessive orthostatic tachycardia and orthostatic intolerance. While traditional inflammatory biomarkers tend to be normal, a subclinical inflammatory process may be present in POTS. Purpose We aimed to analyse novel inflammatory biomarkers in POTS patients: Growth Differentiation Factor 15 (GDF15), Neutrophil Gelatinase Associated Lipocalin (NGAL), Intercellular Adhesion Molecule 1 (ICAM-1), Tumour Necrosis Factor Receptor 1 (TNFR1) and Tumour Necrosis Factor Receptor 2 (TNFR2) and compared them to healthy controls. These inflammatory biomarkers have been shown to be independent predictors of major adverse cardiovascular events in other populations. Methods An age- and sex-matched case-control study included 65 patients verified to have POTS by positive head-up tilt-testing and cardiovascular autonomic tests, and 65 healthy controls (mean age: 31.1 vs 31.5 years, 84% females) with negative active standing tests and no history of syncope, orthostatic intolerance, or endocrine disease. High-sensitivity chemiluminescence sandwich immunoassay was used to measure plasma levels of inflammatory biomarkers in a blinded fashion. Descriptive statistics compared groups and a univariate ANOVA was employed. Biomarker values were log-transformed. A score incorporating all biomarkers was generated to see if the totality of biomarkers discriminated POTS patients from controls. Results Baseline characteristics are displayed in Table 1. Mean levels of GDF15 (p=0.01), NGAL (p=0.003), ICAM-1 (p=0.04) and TNFR1 (p=0.03) were significantly higher in POTS vs controls, whereas TNFR2 (p=0.04) was significantly lower in POTS (p=0.04). The product of four upregulated biomarkers divided by TNFR2 produced a receiver operator curve (ROC) with an area under the curve (AUC) of 0.703 (p&amp;lt;0.001) (Fig.1). Conclusion POTS patients had increased GDF15, NGAL, TNFR1 and ICAM-1 levels and reduced TNFR2 levels suggesting underlying, yet undefined, subclinical inflammatory processes involving neutrophil and endothelial activation.

Psychological stress in postural tachycardia syndrome: results of an online survey

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Postural orthostatic tachycardia syndrome (POTS) is a chronic condition in which patients show a marked increase in heart rate on standing, but also suffer from a range of additional symptoms, which may include fatigue and unrefreshing sleep. A well accepted 10-item survey instrument, the Perceived Stress Scale (PSS; Cohen, et al., 1983), was used to investigate the levels of psychological stress experienced by POTS patients. Methods Sixty Swedish patients diagnosed with POTS at a tertiary investigation center were contacted by mail and a link was provided to respondents who signed the informed consent form. A 64-item, on-line survey was developed in five sections. One of the sections consisted of the ten items of the PSS scale. As an example, item three asks: "In the last month, how often have you felt nervous and ‘stressed’?". A five-point Likert scale is used with possible responses ranging from "never" to "very often". This study employed a previously translated Swedish language version, which has been validated in a sample of 3,406 respondents and showed good internal reliability (α =.84) and normative data for a Swedish population (Nordin &amp; Nordin, 2013). Symptoms were measured using the orthostatic hypotension questionnaire (Kaufmann et al. 2012). Results Twenty-four POTS patients (22 female gender; mean age 35 years, SD = 8.4) completed the survey. The average age at onset of symptoms was 20 years and four months with patients waiting an average of nine years and five months for a POTS diagnosis. Scores for the PSS ranged from three to 35. The mean PSS score for this cohort was 19.38 (SD = 8.88). Fourteen respondents were in the moderate range for perceived stress (14 to 26), whilst five can be considered to have a low perception of stress and five a high perception. Patients with POTS had a statistically significant higher score for perceived stress (M = 19.38, SD = 8.88, p &amp;lt; .01) than the general population of Sweden (M = 13.96, SD = 5.63). However, there was no correlation between perceptions of stress and symptom severity measured by the orthostatic hypotension questionnaire. Conclusions Swedish POTS patients have higher levels of perceived stress, similar to other disease states such as chronic pain and multiple sclerosis (Table 1). However, this survey found no correlation between perceptions of stress and symptom severity.