A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients ( = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. Patients with autoimmune disorders have been reported with a variety of elevated cytokines and cytokines (such as rheumatoid arthritis); thus, we evaluated a limited number of cytokines/chemokines in POTS patients with elevated adrenergic and muscarinic receptor autoantibodies. We utilized the plasma of 34 patients from a previous study; all of the patients (100%) had autoantibodies against the A1 adrenergic receptor and 55.9% (19/34) had autoantibodies against the M4 muscarinic acetylcholine receptor. In particular, the plasma cytokine/chemokine levels were measured as biomarkers of inflammation by Quantibody technology (Raybiotech, Peachtree Corners, GA, USA). We also evaluated the platelet dense granule numbers, as these patients frequently complain of symptoms related to platelet dysfunction. Patients were predominantly young females who displayed a multitude of co-morbidities but generally reported viral-like symptoms preceding episodes of syncope. Eighty five percent (29/34) had platelet storage pool deficiency. Patients had elevations in five of ten cytokine/chemokines biomarkers (IL1β, IL21, TNFα, INFγ, and CD30), whereas two biomarkers had decreased levels (CD40L and RANTES). Our observations demonstrate that POTS patients known to have autoantibodies against the G-protein-coupled adrenergic A1 receptor have abnormal plasma concentrations of inflammatory cytokines.

Postural orthostatic tachycardia syndrome (POTS) and supraventricular tachycardia (SVT) are disease states with distinctive features but overlapping clinical manifestations. Currently, studies on the presence of underlying SVT in patients with POTS are lacking. This retrospective study analyzed 64 patients [mean age: 43 years; 41 (61%) women] who had a POTS diagnosis and were found to have concomitant SVT during rhythm monitoring from September 1, 2013 to September 30, 2019 at our Syncope and Autonomic Disorders Clinic. The outcomes assessed were changes in disease severity, frequency of symptoms, heart rate, and blood pressure between before and after SVT ablation. The most frequent types of SVT noted on the electrophysiologic study were atrioventricular nodal reentrant tachycardia (57.81%), atrial flutter (29.68%), atrioventricular reentrant tachycardia (9.37%), atrial tachycardia (1.56%), and junctional tachycardia (1.56%). After SVT ablation, all 64 patients experienced an improvement in symptoms. Palpitations and lightheadedness experienced the most improvement after the procedure (72% vs. 31%; p < 0.001 and 63% vs. 22%; p < 0.001, respectively). There was a significant improvement in the resting heart rate (81.1 ± 12.8 vs. 75.8 ± 15.6 bpm; p < 0.002), but the orthostatic tachycardia on standing persisted (93.6 ± 16.5 vs. 77.3 ± 19.8 bpm; p = 0.14). Underlying SVT in patients with POTS can be missed easily. A strong suspicion and long-term ambulatory cardiac rhythm monitoring can help in diagnosing the condition.

Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterised by an excessive heart rate on standing and orthostatic intolerance. We present a rare case of a 38-year-old man who underwent open repair of a thoracoabdominal aortic aneurysm for a chronic Stanford type B aortic dissection whose recovery was complicated by POTS. He received blood transfusions and was commenced on metoprolol, fludrocortisone and ivabradine with significant improvement in his symptoms. Correct assessment of postoperative tachycardia including postural telemetry is the key to identifying this condition and its successful management.

Some patients with postural orthostatic tachycardia syndrome (POTS) demonstrate improved dysautonomic symptoms following treatment for pelvic venous insufficiency (PVI). This study assessed the prevalence of significant left common iliac vein (LCIV) compression in POTS patients. Radiologists retrospectively reviewed CT images of pelvic veins for 216 women (191 with POTS and 25 age-comparable controls).Quantitative vascular analysis identified percent-diameter compression of the LCIV by the right common iliac artery. Significant LCIV compression was defined as >50%. Significant LCIV compression was found in 69% (131/191) of females with POTS versus 40% (10/25) in controls. The hypothesis that venous compression and presence of POTS are independent was rejected ( = .005). Significant LCIV compression was noted in a majority of female POTS patients, suggesting that incidence of iliac venous obstruction may be higher than the general population. Patients with POTS and symptoms of PVI may benefit from assessment for venous outflow obstruction.

Orthostatic intolerance (OI) is a common manifestation of autonomic dysfunction. It is characterized by light-headedness and palpitations in the upright position, with relief when supine. It can affect the quality of life. Other symptoms that may accompany OI include headache, fatigue, nausea, palpitations and abdominal pain. The prevalence and characteristics of autonomic symptoms in childhood hypersomnia disorders of childhood has not been examined, and hence were studied. The medical records of children and adolescents with hypersomnia disorders were reviewed. Subjects had been diagnosed with narcolepsy types 1 or 2 (NT1 or NT2), idiopathic hypersomnia (IH) or the KLS, or hypersomnia related to medical conditions, were under 18 years of age at sleep diagnosis, and had been evaluated at our sleep center between 2000 and 2018. Those with comorbidities such as obstructive sleep apnea and major depression were excluded. The medical records were reviewed for symptoms at initial presentation suggestive of autonomic dysfunction, such as orthostatic intolerance, headache, fatigue, nausea, palpitations and abdominal pain. If these symptoms had been recorded, the chart was examined further to determine if an autonomic reflex screen (ARS) battery had been conducted. The ARS battery examines both sympathetic and parasympathetic function. It is composed of a tilt table test, heart rate and blood pressure responses to the Valsalva maneuver and deep breathing, a quantitative sudomotor axon reflex test and beat-to-beat blood pressure measurements during the Valsalva maneuver. Results of the ARS battery were interpreted by an autonomic neurology specialist (WS), who was not otherwise involved in the care of the patients. Medications taken at the time of autonomic testing were recorded. There were 89 patients with hypersomnia disorders. Forty six patients had NT1, 17 had NT2, 18 had IH, 1 with KLS, and 7 had hypersomnia associated with medical disorders. Thirty three of 89 subjects (37%) had the symptom of OI at initial presentation, hence had undergone autonomic reflex screen testing. The median age at diagnosis of hypersomnia in the 33 subjects with the OI symptom was 14.5 years (interquartile range 12-16) and similar (14.5 years, interquartile range 11.5-16) in the 56 subjects without OI. In the group with OI, 25/33 had not received medications for treating hypersomnia at the time of autonomic testing. OI was not related to the degree of sleepiness- the mean sleep latency in the subjects with OI was 5.3 ± 2.9 min while in those without OI it was 4.5 ± 3.8 min. The symptom of OI was not more likely to occur in any specific type of hypersomnia. OI however tended to occur predominantly in females - the female: male ratio in the OI subgroup was 2:1 (n = 33) while in the subgroup without OI, it was 1: 2.1 (n = 56; p = 0.0015). Additional symptoms recorded in the OI subgroup included lightheadedness in 25/33, palpitations in 6/33, nausea and vomiting in 4/33, fatigue in 25/33, headache in 15/33 and constipation in 3/33. The symptoms of OI were reproduced during the tilt table test in 17/33 subjects; 5 of these patients had a rise in heart rate consistent with postural orthostatic tachycardia syndrome (POTS). In this retrospective sample, one third of children with hypersomnia disorders exhibited the symptom of OI at initial presentation, with female predominance. A smaller subgroup met criteria for POTS. Screening for autonomic symptoms in children with hypersomnia is important because the former seems to be a treatable co-morbidity that impacts the sense of well-being.

Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance associated with a significant symptom burden. Compression garments are a frequently prescribed treatment, but the effectiveness of waist-high compression has not been evaluated in adults with POTS. This study evaluated compression garments as a treatment for POTS using a head-up tilt test (HUT), and a noninflatable core and lower body compression garment. Thirty participants completed 10-min HUT with each of 4 compression conditions in a randomized crossover design. The conditions were no compression (NONE), lower leg compression (LEG), abdominal/thigh compression (ABDO), and full abdominal/leg compression (FULL). Heart rate, beat-to-beat blood pressure, and Vanderbilt Orthostatic Symptom Score ratings were measured during each HUT. The compression garment reduced heart rate (NONE: 109 ± 19 beats/min; LEG: 103 ± 16 beats/min; ABDO: 97 ± 15 beats/min; FULL: 92 ± 14 beats/min; p < 0.001) and improved symptoms (p < 0.001) during HUT in a dose-dependent manner. During HUT, stroke volume and systolic blood pressure were better maintained with FULL and ABDO compression compared with LEG and NONE compression. Abdominal and lower body compression reduced heart rate and improved symptoms during HUT in adult patients with POTS. These effects were driven by improved stroke volume with compression. Abdominal compression alone might also provide a clinical benefit if full lower body compression is not well tolerated. (Hemodynamic Effects of Compression in POTS; NCT03484273).

A Postural orthostatic tachycardia syndrome (POTS) is infrequently diagnosed in routine practice because of the variable range of symptoms that could be seen in cardiac rhythm disorders, vertigo, chronic fatigue syndrome and anxiety panic disorder. POTS is a chronic debilitating condition that affects day to day efficient working of an individual. We have planned a study to look for POTS in patients who are having orthostatic intolerance symptoms and underwent a head-up tilt table test (HUTT). To study the prevalence of POTS in patients of orthostatic intolerance (OI) symptoms and to analyze symptomatology, its association with neurocardiogenic syncope (NCS), and its outcome. We reviewed the medical records of 246 patients presented with symptoms of OI seen at our centre from January 2010 till March 2019. Out of them, 40 patients included, those qualifying the criteria for POTS on HUTT. The mean age of the cohort was 25.90 ± 10.33 years with a range of 15 to 55 years, and males comprised 52.5% (21/40) of total patients. The most frequent presenting orthostatic symptoms of POTS patients are loss of consciousness (77.5%), lightheadedness (75%), and palpitation (67.5%). A total of 18 patients (45%) had coexisting neurocardiogenic syncope. POTS is a prevalent condition and have a significant impact on the quality of life, and the majority of patients may not present with OI symptoms during HUTT. We have to keep this possibility in young patients of transient loss of consciousness because it may coexist with NCS.

This is the first case report of a patient with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) with multiple persistent antiphospholipid antibody (aPL)-positivity more than a year after illness onset who also meets Global Consensus-2 criteria for mast cell activation syndrome (MCAS), suggesting pathological activation of the acquired and innate immune systems by SARS-CoV-2. While the patient continues to meet criteria for POTS 1 year on, her functional ability has improved significantly with therapy directed at MCAS, POTS and aPL-positivity. A subset of long-haul COVID-19 patients have postural orthostatic tachycardia syndrome (POTS), which can be diagnosed by a 10-minute in-office stand test.Antiphospholipid antibodies may be associated with POTS in patients with long-haul COVID-19 and have important clinical implications.Mast cell activation syndrome (MCAS) may be associated with long-haul COVID-19 (with or without POTS) and can often be easily treated, including with over-the-counter medications, supplements and dietary changes.

Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (AABs) targeting G-protein coupled receptors (GPCR-AABs) has been discussed to be involved. We, therefore investigated, whether GPCR-AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-AABs that acted as receptor agonists. Some of those GPCR-AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-AAB detection). Other GPCR-AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-AABs identified in the blood of Long-COVID patients targeted the β-adrenoceptor (β-AAB), the α-adrenoceptor (α-AAB), the angiotensin II AT1-receptor (AT1-AAB), and the nociceptin-like opioid receptor (NOC-AAB). The negative chronotropic GPCR-AABs identified targeted the muscarinic M-receptor (M-AAB), the MAS-receptor (MAS-AAB), and the ETA-receptor (ETA-AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.

Soluble cluster of differentiation 26 (sCD26) has a wide range of enzymatic functions affecting immunological, metabolic and vascular regulation. Diminished sCD26 concentrations have been reported in various autoimmune diseases and also in Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). Here we re-evaluate sCD26 as a diagnostic marker and perform a comprehensive correlation analysis of sCD26 concentrations with clinical and paraclinical parameters in ME/CFS patients. Though this study did find significantly lower concentrations of sCD26 only in the female cohort and could not confirm diagnostic suitability, results from correlation analyses provide striking pathomechanistic insights. In patients with infection-triggered onset, the associations of low sCD26 with elevated autoantibodies (AAB) against alpha1 adrenergic (AR) and M3 muscarinic acetylcholine receptors (mAChR) point to a pathomechanism of infection-triggered autoimmune-mediated vascular and immunological dysregulation. sCD26 concentrations in infection-triggered ME/CFS were found to be associated with activated T cells, liver enzymes, creatin kinase (CK) and lactate dehydrogenase (LDH) and inversely with Interleukin-1 beta (IL-1b). Most associations are in line with the known effects of sCD26/DPP-4 inhibition. Remarkably, in non-infection-triggered ME/CFS lower sCD26 in patients with higher heart rate after orthostatic challenge and postural orthostatic tachycardia syndrome (POTS) suggest an association with orthostatic regulation. These findings provide evidence that the key enzyme sCD26 is linked to immunological alterations in infection-triggered ME/CFS and delineate a different pathomechanism in the non-infectious ME/CFS subset.

Joint hypermobility syndrome refers to increased joint flexibility beyond the normal range of motion. This syndrome has a benign form known as Ehlers-Danlos syndrome type 3. This is a disorder in which hypermobility is accompanied by clinical manifestations in the absence of any systemic disease. A clinical finding associated with this condition is postural orthostatic tachycardia syndrome. The following is a rare case of joint hypermobility syndrome and postural orthostatic tachycardia syndrome. The relevance of this case report lies in the impact that this disease had on the patient's quality of life and the limitation in the performance of activities of daily living.

Antiphospholipid syndrome is a rare complication of postural orthostatic tachycardia syndrome. Clinically, the presentation has overlapping symptoms of both diseases, with lightheadedness or syncope when moving from a supine to a standing position as well as blood clots, headache, or pregnancy complications in women. This case presentation involves a 39-year-old patient identified as female who has been diagnosed with POTS and elevated anticardiolipin antibodies.

To develop and implement criteria for description of post COVID syndrome based on analysis of patients presenting for evaluation at Mayo Clinic Rochester between November 2019 and August 2020. A total of 465 patients with a history of testing positive for COVID-19 were identified and their medical records reviewed. After a thorough review, utilizing the DELPHI methods by an expert panel, 42 (9%) cases were identified with persistent central sensitization (CS) symptoms persisting after the resolution of acute COVID-19, herein referred to as Post COVID syndrome (PoCoS). In this report we describe the baseline characteristics of these PoCoS patients. Among these 42 PoCoS patients, the mean age was 46.2 years (median age was 46.5 years). Pain (90%), fatigue (74%), dyspnea (43%), and orthostatic intolerance (38%) were the most common symptoms. The characteristics of an initial 14 patients were utilized for the development of clinical criteria via a modified Delphi Method by a panel of experts in central sensitization disorders. These criteria were subsequently applied in the identification of 28 additional cases of suspected PoCoS. A 2-reviewer system was used to analyze agreement with using the criteria, with all 28 cases determined to be either probable or possible cases by the reviewers. Inter-reviewer agreement using these proposed defining criteria was high with a Cohen's alpha of .88. Here we present what we believe to be the first definitional criteria for Post COVID syndrome. These may be useful in clinical phenotyping of these patients for targeted treatment and future research.

A 32-year-old woman with a history of symptomatic supraventricular tachycardia, inappropriate sinus tachycardia, and hyperadrenergic POTS was treated with ivabradine and metoprolol. She then presented with bradycardia and Mobitz II second-degree AV block on event monitoring six weeks after COVID-19 infection. Her post-viral workup revealed normalization of catecholamine levels and significant symptomatic improvement in heart rate. To the authors' knowledge, this is the first reported case of improvement in POTS after COVID-19 infection. As our understanding of COVID-19 continues to improve, it will be vital to better understand the impact of COVID-19 dysautonomia on cardiac patients.

Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients. 60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 min post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound). End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥ 30 mmHg) versus hypocapnia (end-tidal PCO2 < 30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all < 0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients. During tilt testing, extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients. The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.

Postural orthostatic tachycardia syndrome (POTS) is a disorder epitomized by the story of the blind men and the elephant. Patients may see primary care internists or pediatricians due to fatigue, be referred to neurologists for "spells", to cardiologists for evaluation of pre-syncope or chest pain, to gastroenterologists for nausea or dyspepsia, and even pulmonologists for dyspnea. Adoption of a more systematic approach to their evaluation and better characterization of patients has led to greater understanding of comorbidities, hypotheses prompting mechanistic investigations, and pharmacologic trials. Recent work has implicated disordered sympathetic nervous system activation in response to central (thoracic) hypovolemia. It is this pathway that leads one zero in on a putative focal point from which many of the clinical manifestations can be explained - specifically the carotid body. Despite heterogeneity in etiopathogenesis of a POTS phenotype, we propose that aberrant activation and response of the carotid body represents one potential common pathway in evolution. To understand this postulate, one must jettison isolationist or reductionist ideas of chemoreceptor and baroreceptor functions of the carotid body or sinus, respectively, and consider their interaction and interdependence both locally and centrally where some of its efferents merge. Doing so enables one to connect the dots and appreciate origins of diverse manifestations of POTS, including dyspnea for which the concept of neuro-mechanical uncoupling is wanting, thereby expanding our construct of this symptom. This perspective expounds our premise that POTS has a prominent respiratory component.

To report the first case, to our knowledge, of intermittent pancytopenia and cardiac tamponade occurring together in association with Autoimmune Addison's Disease (AAD). A 21 year-old woman presented on three different occasions with multiple complaints. Her evaluation was significant for intermittent pancytopenia (white blood cell, 1.3-3.0 × 10/μL [normal 4.5-11 × 10]; hemoglobin, 8.8-9.6 g/dL [11-16]; and platelets, 102-117 × 10/μL [150-400 × 10/μL]) and pericardial effusion with cardiac tamponade. Further investigation including a morning serum cortisol level of 0.6 μg/dL (5.27-22.45 μg/dL), adrenocorticotropic hormone level of 1027 pg/mL (normal 6-50 pg/mL), and positive 21-hydroxylase antibodies confirmed the diagnosis of primary adrenal insufficiency due to AAD. Treatment with steroids resulted in prompt hemodynamic recovery with normalization of all blood cell lines. The diagnosis of AAD is often delayed or overlooked. Pancytopenia occurring in AAD is most likely due to either marrow suppression in the setting of acute illness and exacerbated by hypoadrenalism or possibly an autoimmune-mediated marrow reaction. Pericarditis with cardiac tamponade has been described in AAD occurring in the setting of polyglandular autoimmune syndrome type II. The pathogenesis involves autoimmune inflammation of the pericardium, which precipitates an acute inflammatory reaction and rapid fluid accumulation. Pericarditis with cardiac tamponade and intermittent neutropenia may be rare manifestations of an Addisonian crisis.

Individuals with generalised joint hypermobility (GJH, present in 10-20% of the general population) are at increased risk of being diagnosed with a range of psychiatric and rheumatological conditions. It is unknown whether Paediatric acute-onset neuropsychiatric syndrome (PANS), characterised by childhood onset obsessive-compulsive disorder or restricted eating and typically associated with several comorbid neuropsychiatric symptoms, is associated with GJH. It is also unknown whether extensive psychiatric comorbidity is associated with GJH. This is a case-control study including 105 participants. We compared three groups: Individuals with PANS, individuals with other mental disorders and healthy controls. Joint mobility was assessed with the Beighton scoring system, psychiatric comorbidity with the M.I.N.I. or MINI-KID interview and symptoms of PANS with the PsychoNeuroInflammatory related Signs and Symptoms Inventory (PNISSI). Hypermobility was similar across groups, and high rates of psychiatric comorbidity was not associated with higher Beighton scores. Although GJH is associated with several psychiatric conditions, such as ADHD and anxiety, this does not seem to be the case for PANS according to this preliminary study.

A 25-year-old woman with a background history of bronchial asthma and intellectual disability presented to hospital with progressively worsening dyspnoea. Despite testing negative four times for coronavirus disease infection by nasopharyngeal swab reverse-transcriptase polymerase chain reaction, her clinical symptoms of hypoxaemic respiratory failure and radiological findings on computed tomography pulmonary angiogram were consistent with coronavirus disease pneumonia. Although she made a quick recovery in the intensive care unit with a combination of empirical antibiotics, corticosteroids, high flow nasal oxygen, therapeutic anticoagulation and awake semi proning, her protracted hospital course due to persistent sinus tachycardia remained challenging. A diagnosis of potential postural orthostatic tachycardia syndrome was explored during the acute phase of illness following an active stand test and exclusion of other causes. She was treated with beta blockers as she failed to improve with non-pharmacological measures. We searched for similar cases by analysing the literature databases. Our case aims to stress the importance of recognising and treating patients with negative nasal reverse-transcriptase polymerase chain reaction swabs as coronavirus disease infection, especially if there is strong evidence of clinical and radiological findings where diagnosis is often under recognised in asthmatics with intellectual disability.

The coronavirus pandemic remains a major public health burden with multisystem disease manifestations. There has been an ongoing global effort to better understand the unique cardiovascular manifestations of this disease and its associated arrhythmias. In this review, we summarize the current data on incidence and outcomes of arrhythmias in the acute and convalescent period, possible pathophysiologic mechanisms, and medical management. Sinus bradycardia-reported in multiple observational studies in the acute infectious period-stands out as an unexpected inflammatory response. Atrial fibrillation has been noted as the most common pathologic arrhythmia and has been shown to be a poor prognostic marker in multiple cohorts. In the convalescent period, long-term complications such as postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia have been described.

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.

To report a case series of dysautonomia associated with COVID-19 infection. This is a retrospective review of patients evaluated in the autonomic clinic at our institution with suspected signs and symptoms of dysautonomia who underwent formal evaluation, including autonomic testing. Six patients were identified with signs and symptoms suggestive of dysautonomia who underwent autonomic testing. All patients had symptoms typical of COVID-19 infection, though none were hospitalized for these or other symptoms. All patients reported symptoms of postural lightheadedness and near-syncope, fatigue, and activity intolerance. Five patients reported the onset of autonomic symptoms concomitant with other COVID-19 symptoms, with the other patient reporting symptom onset 6 weeks following initial COVID-19 symptoms. Autonomic testing demonstrated an excessive postural tachycardia in 4 patients, a hypertensive response with head-up tilt in 3 patients, orthostatic hypotension in 1 patient, and sudomotor impairment in 1 of the patients with excessive postural tachycardia. We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.

Fatigue is a common acute symptom following SARS-CoV-2 infection (COVID-19). The presence of persistent fatigue and impaired daily physical and cognitive function has led to speculation that like SARS-CoV-1 infection, COVID-19 will be followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We describe three adolescent and young adult patients who had confirmed or probable COVID-19 infections early on during the pandemic and were referred for evaluation to the Chronic Fatigue Clinic at the Johns Hopkins Children's Center. All patients reported orthostatic intolerance symptoms within the first 2 weeks of illness, and 10-min passive standing tests were consistent with postural tachycardia syndrome. After 6 months of illness, all three patients met criteria for ME/CFS. Clinical features of interest included strong histories of allergies in all three patients, two of whom had elevations in plasma histamine. Each demonstrated limitations in symptom-free range of motion of the limbs and spine and two presented with pathological Hoffman reflexes. These comorbid features have been reported in adolescents and young adults with ME/CFS. ME/CFS can be triggered by COVID-19 in adolescents and young adults. Further work is needed to determine the pathogenesis of ME/CFS after COVID-19 and optimal methods of treating these patients. Our preliminary study calls attention to several comorbid features that deserve further attention as potential targets for intervention. These include neuromuscular limitations that could be treated with manual forms of therapy, orthostatic intolerance and POTS for which there are multiple medications and non-pharmacologic therapies, treatable allergic and mast cell phenomena, and neurologic abnormalities that may require specific treatment. Larger studies will need to ascertain the prevalence of these abnormalities.

This study aims to investigate the diurnal variability of heart rate (HR) increment after standing (ΔHR) in pediatric postural tachycardia syndrome (POTS) and explore appropriate cutoff values of ΔHR at different times for the POTS diagnosis. Seventy-eight patients (9-14 years) who presented with orthostatic intolerance symptoms were enrolled. Forty-three patients were diagnosed as POTS (ΔHR ≥40 bpm), and 35 patients were assigned to the non-POTS group (ΔHR <40 bpm). Twenty-six healthy children served as the control group. All subjects completed three standing tests in the morning, afternoon, and evening. Orthostatic HR parameters were analyzed to predict the diagnosis of POTS. Additionally, 41 patients were recruited as an external validation group. Orthostatic HR increments in both the POTS and non-POTS groups exhibited diurnal variability, which was markedly larger in the morning ( < 0.05), whereas it did not differ with the time of day in the control group. Among the POTS patients, 100% met the diagnostic criteria for POTS in the morning, 44.2% in the afternoon, and 27.9% in the evening. Almost half of the POTS patients (51.2%) displayed a positive result only in the morning standing test. However, in the three standing tests at different times, ΔHR from 1 to 10 min after standing and ΔHR were the highest in the POTS group compared with in the non-POTS and control groups ( < 0.05). Furthermore, the maximum ΔHR (ΔHR) and ΔHR at 5 and 10 min in the afternoon and evening standing tests yielded moderate predictive values for the POTS diagnosis. The external validation test showed that the afternoon ΔHR ≥30 bpm to diagnose POTS yielded sensitivity, specificity, and accuracy of 85, 71.4, and 78%, respectively, and the evening ΔHR ≥25 bpm yielded sensitivity, specificity, and accuracy of 85, 76.2, and 80.5%, respectively. The orthostatic HR increment exhibits diurnal variability in children and adolescents with POTS that may affect the diagnosis of POTS. Supplementary criteria are proposed for the POTS diagnosis based on diurnal variability.

We describe the disease course of a 35-year-old female with an autoimmune mediated neuropathic postural tachycardia syndrome (PoTS), who responded to immunoglobulin therapy and stabilized on maintenance therapy with subcutaneous immunoglobulin (SCIg). We provide longitudinal data of clinical scores, tilt-table results and antibody titers. Initial treatment with intravenous immunoglobulin caused infusion-related side-effects whereas SCIg was well tolerated and improved clinical symptoms and quality of life. Clinical improvement correlated with the reduction of serum antibody titers 22 months after first infusion. These findings suggest that autoimmune-mediated neuropathic PoTS can be treated sufficiently with IVIg whereas SCIg minimizes side-effects.