Tag: POTS

High incidence of autonomic dysfunction and postural orthostatic tachycardia syndrome in patients with long-COVID: Implications for management and healthcare planning

Abstract:

Background: Autonomic 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.

Methods: All participants were prospectively enrolled between 5th August 2021 and 31st October 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.

Results: A total of 99 participants (n=33 PASC, n=33 POTS and n=33 healthy controls; median age 32 [18], 85.9% females) were included. Compared to healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (p<0.001), greater heart rate increase during 10-minute active standing test (p<0.001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all p<0.001) and poor HrQoL across all EQ-5D-5L domains (all p<0.001), lower median EQ-VAS (p<0.001) and lower utility scores (p<0.001). The majority (79%) of those with PASC met the internationally established criteria for POTS.

Conclusion: The prevalence of autonomic symptomology or 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.

Trial registration: ANZCTR 12621000476831.

Source: Seeley MC, Gallagher C, Ong E, Langdon A, Chieng J, Bailey D, Page A, Lim HS, Lau DH. High incidence of autonomic dysfunction and postural orthostatic tachycardia syndrome in patients with long-COVID: Implications for management and healthcare planning. Am J Med. 2023 Jun 28:S0002-9343(23)00402-3. doi: 10.1016/j.amjmed.2023.06.010. Epub ahead of print. PMID: 37391116. https://www.amjmed.com/article/S0002-9343(23)00402-3/fulltext (Full text)

Clinical Features of Post-Covid Syndrome

Abstract:

There is no common understanding of the clinical picture of post-covid syndrome. The US regulator CDC proposes to highlight:

(A) persistent symptoms and conditions that begin during acute COVID-19 illness;

B) new onset late complications after asymptomatic disease or a period of acute symptomatic relief or remission;

(C) the evolution of symptoms and conditions that include some persistent symptoms (eg, shortness of breath) with the addition of new symptoms or conditions over time (eg, cognitive difficulties).

Some manifestations may resemble other postviral syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia (eg, postural orthostatic tachycardia syndrome), or mast cell activation syndrome.

Source: Sayfulloyevich, P. S. ., & Musayevich, U. R. . (2023). Clinical Features of Post-Covid Syndrome. EUROPEAN JOURNAL OF INNOVATION IN NONFORMAL EDUCATION, 3(6), 34–36. Retrieved from http://inovatus.es/index.php/ejine/article/view/1786 http://inovatus.es/index.php/ejine/article/view/1786/1794 (Full text)

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

Abstract:

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<0.05) and (3) a higher number of HR spikes per h (1.4 +/-0.8 vs. 0.8 +/-0.7/h, p<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.

Source: D Hupin and others, Diagnostic value of 24-h ECG recording in Long COVID patients with postural orthostatic tachycardia syndrome, EP Europace, Volume 25, Issue Supplement_1, June 2023, euad122.626, https://doi.org/10.1093/europace/euad122.626 (Full text available as PDF file)

Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients

Abstract:

Introduction: During a standard 70-degree head-up tilt test, 90% of adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develop an abnormal reduction in cerebral blood flow (CBF). A 70-degree test might not be tolerated by young ME/CFS patients because of the high incidence of syncopal spells. This study examined whether a test at 20 degrees would be sufficient to provoke important reductions in CBF in young ME/CFS patients.

Methods: We analyzed 83 studies of adolescent ME/CFS patients. We assessed CBF using extracranial Doppler measurements of the internal carotid and vertebral arteries supine and during the tilt. We studied 42 adolescents during a 20 degree and 41 during a 70 degree test.

Results: At 20 degrees, no patients developed postural orthostatic tachycardia (POTS), compared to 32% at 70 degrees (p = 0.0002). The CBF reduction during the 20 degree tilt of -27(6)% was slightly less than during the reduction during a 70 degree test [-31(7)%; p = 0.003]. Seventeen adolescents had CBF measurements at both 20 and 70 degrees. The CBF reduction in these patients with both a 20 and 70 degrees test was significantly larger at 70 degrees than at 20 degrees (p < 0.0001).

Conclusions: A 20 degree tilt in young ME/CFS patients resulted in a CBF reduction comparable to that in adult patients during a 70 degree test. The lower tilt angle provoked less POTS, emphasizing the importance of using the 70 degree angle for that diagnosis. Further study is needed to explore whether CBF measurements during tilt provide an improved standard for classifying orthostatic intolerance.

Source: van Campen CLMC, Rowe PC, Visser FC. Comparison of a 20 degree and 70 degree tilt test in adolescent myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients. Front Pediatr. 2023 May 12;11:1169447. doi: 10.3389/fped.2023.1169447. PMID: 37252045; PMCID: PMC10213432. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213432/ (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators?

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA), dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber neuropathy (SFN). The causes of these syndromes and the reason for their frequent association are not yet fully understood.

We previously published a comprehensive hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms, findings and chronicity of the disease. We wondered whether some of the identified key pathomechanisms in ME/CFS are also operative in MCA, endometriosis and dysmenorrhea, POTS, decreased cerebral blood flow and SFN, and possibly may provide clues on their causes and frequent co-occurrence.

Our analysis indeed provides strong arguments in favor of this assumption, and we conclude that the main pathomechanisms responsible for this association are excessive generation and spillover into the systemic circulation of inflammatory and vasoactive tissue mediators, dysfunctional β2AdR, and the mutual triggering of symptomatology and disease initiation. Overall, vascular dysfunction appears to be a strong common denominator in these linkages.

Source: Wirth KJ, Löhn M. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators? Medicina. 2023; 59(5):978. https://doi.org/10.3390/medicina59050978  https://www.mdpi.com/1648-9144/59/5/978 (Full text)

Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Highlights:

  • Adults with ME/CFS experience a 3-fold greater reduction in cerebral blood flow during end-tilt tilt compared to healthy controls, confirming orthostatic intolerance.
  • During tilt testing we found that in 134/362 (37%) patients with ME/CFS without POTS or hypotension, the heart rate increase was below the lower limit of the 95% prediction interval of the heart rate increase of controls, indicative of orthostatic chronotropic incompetence.
  • These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing, confirming another abnormality in the circulatory response to upright posture in ME/CFS.

Abstract:

Background: Orthostatic intolerance (OI) is a core diagnostic criterion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The majority of ME/CFS patients have no evidence of hypotension or postural orthostatic tachycardia syndrome (POTS) during head-up tilt, but do show a significantly larger reduction in stroke volume index (SVI) when upright compared to controls. Theoretically a reduction in SVI should be accompanied by a compensatory increase in heart rate (HR). When there is an incomplete compensatory increase in HR, this is considered chronotropic incompetence.

This study explored the relationship between HR and SVI to determine whether chronotropic incompetence was present during tilt testing in ME/CFS patients.

Methods: From a database of individuals who had undergone tilt testing with Doppler measurements for SVI both supine and end-tilt, we selected ME/CFS patients and healthy controls (HC) who had no evidence of POTS or hypotension during the test.

To determine the relation between the HR increase and SVI decrease during the tilt test in patients, we calculated the 95% prediction intervals of this relation in HC. Chronotropic incompetence in patients was defined as a HR increase below the lower limit of the 95th % prediction interval of the HR increase in HC.

Results: We compared 362 ME/CFS patients with 52 HC. At end-tilt, tilt lasting for 15 (4) min, ME/CFS patients had a significantly lower SVI (22 (4) vs. 27 (4) ml/m2; p<0.0001) and a higher HR (87 (11) vs. 78 (15) bpm; p<0.0001) compared to HC. There was a similar relationship between HR and SVI between ME/CFS patients and HC in the supine position.

During tilt ME/CFS patients had a lower HR for a given SVI; 37% had an inadequate HR increase. Chronotropic incompetence was more common in more severely affected ME/CFS patients.

Conclusion: These novel findings represent the first description of orthostatic chronotropic incompetence during tilt testing in ME/CFS patients.

Source: C. (Linda) M.C. van Campen, Freek W.A. Verheugt, Peter C. Rowe, Frans C. Visser. Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). IBRO Neuroscience Reports [In Press, Journal Pre-proof]  Available online 2 May 2023 https://www.sciencedirect.com/science/article/pii/S2667242123000374 (Full text)

Autonomic Dysfunction related to Post-Acute SARS-CoV-2 Syndrome

Introduction:

The SARS-CoV-2 virus, a member of the coronavirus family, has been responsible for the Coronavirus Disease-19 (COVID-19) pandemic with an acute phase causing pneumonia and pulmonary disorders, but it has been shown to extrapulmonary manifestations including cardiovascular and neurological diseases. Moreover, residual symptoms have been reported to persist past the acute phase. In a cross-sectional study of SARS-CoV-2 positive patients, at 48 days post-discharge the most common persistent symptoms were fatigue, difficulty breathing, and psychological distress.
 In a cohort study of 1,733 COVID-19 patients from Wuhan, China, patients reported persistence of fatigue, muscle weakness, sleeping difficulties, palpitations, anxiety, or depression at 6 months after initial onset.
 Numerous other studies now indicate the presence of persistent symptoms following COVID-19 infection, with over 200 symptoms reported. This syndrome has been coined as the Post-Acute SARS-CoV-2 Syndrome (PASC) and has been defined as the persistence of symptoms or development of new symptoms after the time of infection, which can include fatigue, brain fog, palpitations, and a plethora of other manifestations.
Source: Justin Haloot, DO, MS, MS, Ratna Bhavaraju-Sanka, MD, Jayasree Pillarisetti, MD Msc, Monica Verduzco-Gutierrez, MD. Autonomic Dysfunction related to Post-Acute SARS-CoV-2 Syndrome. Physical Medicine and Rehabiliation Clinics. Published: April 18, 2023. DOI:https://doi.org/10.1016/j.pmr.2023.04.003 (Full text)

Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID’s impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation.

Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID.

These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause.

We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

Source: Pollack Beth, von Saltza Emelia, McCorkell Lisa, Santos Lucia, Hultman Ashley, Cohen Alison K., Soares Letícia. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Frontiers in Rehabilitation Sciences, Vol 4, 2023, ISSN=2673-6861. DOI: 10.3389/fresc.2023.1122673 https://www.frontiersin.org/articles/10.3389/fresc.2023.1122673 (Full text)

Cardiovascular Considerations in the Management of People with Suspected Long COVID

Abstract:

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks post-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 may 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 (ME/CFS), post-exertional malaise and post-exertional symptom exacerbation (PEM/PESE), cardiac dysautonomia such as Inappropriate Sinus Tachycardia (IST), and Postural Orthostatic Tachycardia Syndrome (POTS), and occasionally Mast Cell Activation Syndrome (MCAS).

This paper summarizes the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, this review includes a Canadian perspective, consisting of a panel of expert opinions from 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.

Source: Quinn KL, Lam GY, Walsh JF, Bhéreur A, Brown AD, Chow CW, Christie Chung KY, Cowan J, Crampton N, Décary S, Falcone EL, Graves L, Gross DP, Hanneman K, Harvey PJ, Holmes S, Katz GM, Parhizgar P, Sharkawy A, Tran KC, Waserman S, Zannella VE, Cheung AM. Cardiovascular Considerations in the Management of People with Suspected Long COVID. Can J Cardiol. 2023 Apr 6:S0828-282X(23)00303-3. doi: 10.1016/j.cjca.2023.04.003. Epub ahead of print. PMID: 37030518. Quinn KL, Lam GY, Walsh JF, Bhéreur A, Brown AD, Chow CW, Christie Chung KY, Cowan J, Crampton N, Décary S, Falcone EL, Graves L, Gross DP, Hanneman K, Harvey PJ, Holmes S, Katz GM, Parhizgar P, Sharkawy A, Tran KC, Waserman S, Zannella VE, Cheung AM. Cardiovascular Considerations in the Management of People with Suspected Long COVID. Can J Cardiol. 2023 Apr 6:S0828-282X(23)00303-3. doi: 10.1016/j.cjca.2023.04.003. Epub ahead of print. PMID: 37030518. https://www.onlinecjc.ca/article/S0828-282X(23)00303-3/fulltext (Full text)

LC, POTS, and ME/CFS: Lifting the Fog

Abstract:

These three syndromes – long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – have many symptoms in common. The common denominator remains elusive.
The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis.
In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT).
The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.
Source: Chambers, P. LC, POTS, and ME/CFS: Lifting the Fog. Preprints.org 2023, 2023030418. https://doi.org/10.20944/preprints202303.0418.v1 (Full text available as PDF file)