Tag: POTS

Autonomic dysfunction post-acute COVID-19 infection

Introduction:

SARS-CoV-2 infection which causes the disease COVID-19 is most known for its severe respiratory complications. However, a variety of extrapulmonary effects have since been described, with cardiovascular complications being amongst the most common [ 1 ]. Those who recover from the acute phase of COVID-19 may be left with residual symptoms such as chest pain and dyspnea, resulting in a decreased quality of life and a syndrome sometimes described as “long COVID”[ 2 ].

Recent evidence suggests that survivors with some of these chronic symptoms may have autonomic dysfunction with features of postural orthostatic tachycardia syndrome (POTS) and/or inappropriate sinus tachycardia (IST)3 , 4. POTS is characterized by symptoms that occur with standing, an increase in heart rate of ≥30 beats per minute (or heart rate >120 bpm) when moving from a supine to a standing position, and the absence of orthostatic hypotension[ 5 ]. IST is defined as a sinus heart rate >100 beats per minute at rest without an identifiable cause of sinus tachycardia[ 6 ]. Cardiac manifestations of autonomic dysfunction lie on a wide spectrum and can therefore be classified as either POTS, IST, or other unspecified symptoms such as tachycardia and palpitations without a clear, single underlying pathological mechanism.[ 7 ]

The treatment of these arrhythmias includes nonpharmacologic management, such as increasing salt and fluid intake, as well as the use of oral medications. Beta-blockers or off label use of ivabradine have used reported to be used in both syndromes with the goal of controlling heart rate to reduce the symptoms 8 , 9. Other therapies more common in POTS include fludrocortisone, midodrine, pyridostigmine, and alpha-2 agonists[ 8 ].

There is a need to understand the patient characteristics and risk factors for developing AD as a sequela of COVID-19. Furthermore, there is limited management information specific to patients suffering from AD following COVID-19. It is unclear how treatment of these patients and their prognoses may differ from other cases of POTS or IST. In this study, we investigated a small cohort of patients diagnosed with suspected AD post SARS-CoV-2 infection to elucidate possible risk factors and treatment strategies in this population.

Source: Desai AD, Boursiquot BC, Moore CJ, Gopinathannair R, Waase MP, Rubin GA, Wan EY. Autonomic dysfunction post-acute COVID-19 infection. HeartRhythm Case Rep. 2021 Nov 27. doi: 10.1016/j.hrcr.2021.11.019. Epub ahead of print. PMID: 34868880; PMCID: PMC8626157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626157/ (Full text)

Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome

Abstract:

In this paper we highlight the presence of tachycardia in post-acute COVID-19 syndrome by introducing a new label for this phenomenon—post-COVID-19 tachycardia syndrome—and argue that this constitutes a phenotype or sub-syndrome in post-acute COVID-19 syndrome. We also discuss epidemiology, putative mechanisms, treatment options, and future research directions in this novel clinical syndrome.

Source: Ståhlberg M, Reistam U, Fedorowski A, et al. Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome [published online ahead of print, 2021 Aug 11]. Am J Med. 2021;S0002-9343(21)00472-1. doi:10.1016/j.amjmed.2021.07.004  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356730/ (Full text)

Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

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.

Source: Szklarski M, Freitag H, Lorenz S, Becker SC, Sotzny F, Bauer S, Hartwig J, Heidecke H, Wittke K, Kedor C, Hanitsch LG, Grabowski P, Sepúlveda N, Scheibenbogen C. Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Immunol. 2021 Apr 6;12:644548. doi: 10.3389/fimmu.2021.644548. PMID: 33889154; PMCID: PMC8056217. https://www.frontiersin.org/articles/10.3389/fimmu.2021.644548/full  (Full text)

A report on comorbidity of chronic fatigue syndrome, postural tachycardia syndrome, and narcolepsy with 5,10-methylenetetrahydrofolate reductase (MTHFR) mutation in an adolescent

A 16-year-old male adolescent was hospitalized complaining of intermittent dizziness, drowsiness, and fatigue for approximately 2 years. The patient had an episode of fever and pharyngalgia lasting nearly 2 weeks and had undergone appendectomy because of acute appendicitis before the presentation of the above symptoms. He suffered from severe dizziness mostly after switching from a supine to an upright posture when he was getting up in the morning. The symptom of dizziness usually persisted for minutes to hours and could be partially alleviated by recumbency. In addition, he felt drowsy and fatigued all day despite a total sleep duration of 14 to 15 h per day. All the symptoms could be partially mitigated by complete bed rest for 1 or 2 weeks, but he relapsed after taking part in normal school life again. Additionally, the feeling of fatigue was obviously aggravated after exertion or infection. He was unable to focus on his studies and had to withdraw from school for a long time. As a result, there was a decline in academic performance after the onset of illness. He used to benefit from taking carnitine and folate; however, the improvement was limited in enabling him to take part in normal social and school life. He was physically and mentally healthy before the presentation and did not feel disgusted with learning in the past. No family history of cardiovascular or nervous system disease was evident. The study was approved by the Ethics Committee of Peking University First Hospital (No. 2020- 415).

Source: Liao, Ying; Qi, Jian-Guang; Yan, Hui; Zhang, Qing-You; Ji, Tao-Yun; Chang, Xing-Zhi; Yang, Hai-Po; Jin, Hong-Fang; Du, Jun-Bao A report on comorbidity of chronic fatigue syndrome, postural tachycardia syndrome, and narcolepsy with 5,10-methylenetetrahydrofolate reductase (MTHFR) mutation in an adolescent, Chinese Medical Journal: March 25, 2021 – Volume Publish Ahead of Print – Issue – doi: 10.1097/CM9.0000000000001387  https://journals.lww.com/cmj/Citation/9000/A_report_on_comorbidity_of_chronic_fatigue.98688.aspx (Full text)

Insights from Invasive Cardiopulmonary Exercise Testing of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affects tens of millions worldwide; the causes of exertional intolerance are poorly understood. The ME/CFS label overlaps with postural orthostatic tachycardia (POTS) and fibromyalgia, and objective evidence of small fiber neuropathy (SFN) is reported in ∼50% of POTS and fibromyalgia patients.

Research Question

Can invasive cardiopulmonary exercise testing (iCPET) and PGP9.5-immunolabeled lower-leg skin biopsies inform the pathophysiology of ME/CFS exertional intolerance and potential relationships with SFN?

Study Design and Methods

We analyzed 1516 upright invasive iCPETs performed to investigate exertional intolerance. After excluding patients with intrinsic heart or lung disease and selecting those with right atrial pressures (RAP) <6.5 mmHg, results from 160 patients meeting ME/CFS criteria who had skin-biopsy test results were compared to 36 controls. Rest-to-peak changes in cardiac output (Qc) were compared to oxygen uptake (Qc/VO 2 slope) to identify participants with low, normal, or high pulmonary blood flow by Qc/VO 2 tertiles.

Results

During exercise, the 160 ME/CFS patients averaged lower RAP (1.9±2 vs. 8.3±1.5; P<0.0001) and peak VO 2 (80%±21 vs. 101.4%±17; P<0.0001) than controls. The low-flow tertile had lower peak Qc than the normal and high-flow tertiles (88.4±19% vs. 99.5±23.8% vs. 99.9±19.5% predicted; P<0.01). In contrast, systemic oxygen extraction was impaired in high-flow versus low and normal-flow participants (0.74±0.1% vs. 0.88±0.11 vs. 0.86±0.1; P<0.0001) in association with peripheral left-to-right shunting. Among the 160 ME/CFS patient biopsies, 31% was consistent with SFN (epidermal innervation ≤5.0% of predicted; P < 0.0001). Denervation severity did not correlate with exertional measures.

Interpretation

These results identify two types of peripheral neurovascular dysregulation that are biologically plausible contributors to ME/CFS exertional intolerance–depressed Qc from impaired venous return, and impaired peripheral oxygen extraction. In patients with small-fiber pathology, neuropathic dysregulation causing microvascular dilation may limit exertion by shunting oxygenated blood from capillary beds and reducing cardiac return.

Abbreviation:

Ca-vO2/[Hb] ( Arterial–mixed venous oxygen content difference/hemoglobin concentration), iCPET ( Invasive cardiopulmonary exercise test), NAM ( National Academy of Medicine, formerly the Institute of Medicine), ME/CFS ( Myalgic encephalomyelitis/chronic fatigue syndrome), MM ( Mitochondrial myopathy), mPAP ( Mean pulmonary artery pressure), PAWP ( Pulmonary arterial wedge pressure), PLF ( Preload failure), POTS ( Postural orthostatic tachycardia syndrome), PVR ( Pulmonary vascular resistance), RAP ( Right atrial pressure), Qc ( Cardiac output), SFN ( Small fiber neuropathy), VO2 ( Oxygen uptake), vPO2 ( Venous oxygen tension)

Source: Phillip Joseph, MD, Carlo Arevalo, MD, Rudolf K.F. Oliveira, MD, PhD, Donna Felsenstein, MD, Anne Louise Oaklander, MD, PhD, David M. Systrom, MD. Insights from Invasive Cardiopulmonary Exercise Testing of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. February 09, 2021. DOI:https://doi.org/10.1016/j.chest.2021.01.082 https://journal.chestnet.org/article/S0012-3692(21)00256-7/fulltext

Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study

Abstract:

Background: 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).

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Source: Chouksey D, Rathi P, Sodani A, Jain R, Ishar HS. Postural orthostatic tachycardia syndrome in patients of orthostatic intolerance symptoms: an ambispective study. AIMS Neurosci. 2020 Dec 8;8(1):74-85. doi: 10.3934/Neuroscience.2021004. PMID: 33490373; PMCID: PMC7815479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815479/ (Full text)

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008).

Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Source: C (Linda) MC van Campen, Peter C. Rowe, and Frans C Visser. Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare 2020, 8(4), 394; https://doi.org/10.3390/healthcare8040394 https://www.mdpi.com/2227-9032/8/4/394/htm (Full text)

Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

Abstract:

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise.

One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI).

The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks.

These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction.

Source: Clarke T, Jamieson JD, Malone P, Rayhan RU, Washington S, VanMeter JW, et al. (2019) Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention. PLoS ONE 14(12): e0226481. https://doi.org/10.1371/journal.pone.0226481 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226481 (Full text)

Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy

Abstract:

Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and researchers. Both the pathogenesis and treatment of these disorders require further study.

In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy.

Sjogren’s syndrome, which is a classical autoimmune disease, could serve as a diseases model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may mostly benefit from the immunotherapy.

Copyright © 2020. Published by Elsevier Inc.

Source: Shoenfeld Y, Ryabkova VA, Sheibenbogen C, Brinth L, Martinez-Lavin M, Ikeda S, Heidecke H, Watad A, Bragazzi NL, Chapman J, Churilov LP, Amital H. Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy. Clin Immunol. 2020 Mar 11:108384. doi: 10.1016/j.clim.2020.108384. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32171889

Syncope and hypermobile joints: Not rare, but rarely diagnosed

Abstract:

Postural orthostatic tachycardia syndrome (POTS) is a chronic, debilitating condition characterized by heterogeneous symptoms, such as lightheadedness, palpitations, pre-syncope, syncope, and weakness or heaviness, especially of the legs. It is frequently associated with hypermobile joints or conditions such as chronic fatigue syndrome, chronic abdominal pain, migraine headache, and diabetes mellitus. Described is a case of POTS, which though it is not rare, is rarely diagnosed. It can be diagnosed quickly with simple methods.

Source: Tahirovic E. Syncope and hypermobile joints: Not rare, but rarely diagnosed. Turk Kardiyol Dern Ars. 2020 Mar;48(2):177-179. doi: 10.5543/tkda.2019.32624. https://archivestsc.com/jvi.aspx?un=TKDA-32624 (Full text)