Tag: heart rate

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)

Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes

Introduction: Cognitive impairment is experienced by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of COVID-19 (PASC). Patients report difficulty remembering, concentrating, and making decisions. Our objective was to determine whether orthostatic hemodynamic changes were causally linked to cognitive impairment in these diseases.

Methods: This prospective, observational cohort study enrolled PASC, ME/CFS, and healthy controls. All participants underwent clinical evaluation and assessment that included brief cognitive testing before and after an orthostatic challenge. Cognitive testing measured cognitive efficiency which is defined as the speed and accuracy of subject’s total correct responses per minute. General linear mixed models were used to analyze hemodynamics and cognitive efficiency during the orthostatic challenge. Additionally, mediation analysis was used to determine if hemodynamic instability induced during the orthostatic challenge mediated the relationship between disease status and cognitive impairment.

Results: Of the 276 participants enrolled, 256 were included in this study (34 PASC, 71 < 4 year duration ME/CFS, 69 > 10 year ME/CFS duration, and 82 healthy controls). Compared to healthy controls, the disease cohorts had significantly lower cognitive efficiency scores immediately following the orthostatic challenge. Cognitive efficiency remained low for the >10 year ME/CFS 2 and 7 days after orthostatic challenge. Narrow pulse pressure less than 25% of systolic pressure occurred at 4 and 5 min into the orthostatic challenge for the PASC and ME/CFS cohorts, respectively. Abnormally narrow pulse pressure was associated with slowed information processing in PASC patients compared to healthy controls (−1.5, p = 0.04). Furthermore, increased heart rate during the orthostatic challenge was associated with a decreased procedural reaction time in PASC and < 4 year ME/CFS patients who were 40 to 65 years of age.

Discussion: For PASC patients, both their disease state and hemodynamic changes during orthostatic challenge were associated with slower reaction time and decreased response accuracy during cognitive testing. Reduced cognitive efficiency in <4 year ME/CFS patients was associated with higher heart rate in response to orthostatic stress. Hemodynamic changes did not correlate with cognitive impairment for >10 year ME/CFS patients, but cognitive impairment remained. These findings underscore the need for early diagnosis to mitigate direct hemodynamic and other physiological effects on symptoms of cognitive impairment.

Source: Day Heather, Yellman Brayden, Hammer Sarah, Rond Candace, Bell Jennifer, Abbaszadeh Saeed, Stoddard Greg, Unutmaz Derya, Bateman Lucinda, Vernon Suzanne D. Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes. Frontiers in Neuroscience, VOLUME=17, 2023. DOI=10.3389/fnins.2023.1203514. ISSN=1662-453X. https://www.frontiersin.org/articles/10.3389/fnins.2023.1203514 (Full text)

ME/CFS Pathophysiology Investigated by Invasive Cardiopulmonary Exercise Testing and Autonomic Function Testing

Abstract

Introduction: Mechanisms underlying exercise and orthostatic intolerance in myalgic encephalomyelitis/chronic
fatigue syndrome (ME/CFS) have been uncovered by invasive cardiopulmonary exercise testing (iCPET) and
autonomic function testing (AFT), but the relationships between the two are not known. This study aims to determine
if there is overlap of cardiovascular and respiratory pathophysiology in patients who have undergone both
tests.

Methods: Between January 2017 and April 2022, 62 patients were identified with a contemporary iCPET and
AFT. Key variables from the iCPET included peak oxygen uptake (pVO2), cardiac output (pQc), right atrial pressure
(pRAP), and systemic oxygen extraction (Ca-vOy/Hgb) at peak exercise. Key variables from the autonomic testing
included epidermal and sweat gland small fiber neurite density, electrochemical skin conductance, and change in
heart rate (AH) and end tidal carbon dioxide (AETCO2) from supine to upright during the tilt table test
(TTT).

Results: All 62 patients demonstrated preload failure (pRAP < 6.5mmHg). Of this group, 54 patients (87.1%) fulfilled NAM criteria for ME/CFS, with 32 testing positive (59.3%) for small fiber neuropathy (SFN) using either morphological and/or functional testing. Significant correlations were found between pVOg and both AH (r=-0.439. P<0.05) and AETCO, (r=0.474, P<0.05) during TTT. The same tilt table variables were found to be significantly correlated with pQc (r=-0.365, P<0.05 and r=0.351, P<0.05) from the iCPET. It should be noted that 8 of the ME/CFS SFN patients (25%) fulfilled diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) based on the tilt table test.

Conclusion: Decreased oxygen uptake and cardiac output at peak exercise during iCPET correlated with a greater change in heart rate and ETCO from supine to upright during TTT. There appears to be significant overlap of cardiopulmonary pathophysiology in ME/CFS underlying exercise and orthostatic symptoms.

Source: J. Squires, K. Wichmann Madsen, M.C. Stovall, S. Al-Zayer, W. Xiao, C.-J. Chang, P. Novak, D.M. Systrom. ME/CFS Pathophysiology Investigated by Invasive Cardiopulmonary Exercise Testing and Autonomic Function Testing. American Journal of Respiratory and Critical Care Medicine 2023;207:A2996. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A2996

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)

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

To assess biobehavioral sex differences in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) utilizing a low burden exercise protocol, 22 females and 15 males with ME/CFS and 14 healthy controls underwent two six-min walk tests.

Fifteen daily assessments were scheduled for fatigue and function ratings and heart monitoring. Six-min walk tests were conducted on days 8 and 9. The ME/CFS group showed high self-report fatigue and impaired physical function, whereas healthy controls did not show fatigue or function abnormalities.

In patients, no significant post-exercise changes were found for heart rate variability (HRV); however, heart rate decreased in ME/CFS males from Day 14 to Day 15 (p = 0.046). Female patients showed increased fatigue (p = 0.006) after the initial walk test, but a downward slope (p = 0.008) in fatigue following the second walk test. Male patients showed a decrease in self-report work limitation in the days after exercise (p = 0.046). The healthy control group evidenced a decrease in HRV after the walk tests from Day 9-14 (p = 0.038).

This pilot study did not confirm hypotheses that females as compared to males would show slower exercise recovery on autonomic or self-report (e.g. fatigue) measures. A more exertion-sensitive test may be required to document prolonged post-exertional abnormalities in ME/CFS.

Trial registration: NCT NCT03331419.

Source: Friedberg F, Adamowicz JL, Bruckenthal P, Milazzo M, Ramjan S, Zhang X, Yang J. Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. 2023 Apr 3;13(1):5442. doi: 10.1038/s41598-023-32581-w. PMID: 37012343. https://www.nature.com/articles/s41598-023-32581-w (Full text)

An international survey of experiences and attitudes towards pacing using a heart rate monitor for people with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis (ME) is a complex, multi-system neurological condition. The defining feature of ME is post-exertional malaise (PEM) with over 30 symptoms triggered by physical, cognitive, emotional and social activity.

The cause of PEM is unclear but one area of research using cardio-pulmonary exercise tests show a reduced ventilatory anaerobic threshold (VAT) with repeated tests leading to PEM.

Pacing with heart rate monitoring (HRM) provides feedback to maintain activity intensity below the VAT. There is only one piece of research investigating the use of HRM although a number of guidelines recommend it.

Objective: To identify the experiences and attitudes of people with ME towards HRM.

Methods: A 40 question online survey was devised and released on ME websites, Twitter and Facebook pages. People with ME read the information sheet and followed an online link to the survey. The survey was open for three weeks and all answers were anonymous.

Results: 488 people with ME completed the survey. Most participants were female, 35-50 years and with a reported illness of greater than 5 years. Over 100 types of HR monitor used. Over 30 benefits and over 30 negatives identified. HRM reduced severity of ME and severity and duration of PEM.

Conclusion: Although there are limitations, HRM has many benefits including helping PwME to understand and manage their PEM and support them to increase their activities, including work. There is a need for more research and education of healthcare professionals in the safe use of HRM.

Source: Clague-Baker N, Davenport TE, Madi M, Dickinson K, Leslie K, Bull M, Hilliard N. An international survey of experiences and attitudes towards pacing using a heart rate monitor for people with myalgic encephalomyelitis/chronic fatigue syndrome. Work. 2023 Mar 13. doi: 10.3233/WOR-220512. Epub ahead of print. PMID: 36938766. https://content.iospress.com/articles/work/wor220512 (Full text)

Orthostatic Intolerance and Chronotropic Incompetence in Patients With Myalgic Encephalomyelitis or Chronic Fatigue Syndrome

Abstract:

Background: Orthostatic intolerance markedly affects the day-to-day activities of patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome. Chronotropic incompetence (CI), defined as an impaired chronotropic response or reduced increases in heart rate during exercise and resulting in lower exercise capacity, may also be observed during orthostasis in patients with ME.

Methods and Results: In this study, the recordings of 101 adult patients with ME (36 men, 65 women; mean [±SD] age 37±12 years) who underwent conventional active 10-min standing tests at least 3 times to determine the presence of CI were analyzed. Recordings were selected for 13 patients who experienced tests both with and without exhibiting postural orthostatic tachycardia syndrome (POTS; an increase in heart rate of ≥30 beats/min or an actual heart rate of ≥120 beats/min) while also both successfully completing and failing to complete 10-min standing on different occasions. Subjects in whom failure without POTS was observed in any test(s) while success was associated with POTS on other occasions were considered positive for CI during orthostasis. Of the 13 patients, 12 (92%) were CI positive, 5 (38%) of whom exclusively failed the tests without experiencing POTS.

Conclusions: Some patients with ME were CI positive during standing tests, suggesting impaired sympathetic activation. The presence of POTS appears to be essential for maintaining orthostasis in these patients.

Source: Kunihisa Miwa. Orthostatic Intolerance and Chronotropic Incompetence in Patients With Myalgic Encephalomyelitis or Chronic Fatigue Syndrome. Circulation Reports, Article ID CR-22-0114. https://www.jstage.jst.go.jp/article/circrep/advpub/0/advpub_CR-22-0114/_html/-char/en (Full text)

Autonomic Nervous System Regulation Effects of Epipharyngeal Abrasive Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Associated With Chronic Epipharyngitis

Abstract:

Objective: To evaluate the autonomic nerve stimulation effect of epipharyngeal abrasive therapy (EAT) on myalgic encephalomyelitis/chronic fatigue syndrome (CFS) associated with chronic epipharyngitis. Heart rate variability analysis was performed. The study was conducted by analyzing heart rate variability.

Subjects and methods: A total of 29 patients with chronic epipharyngitis who underwent EAT from July 2017 to April 2018 were classified into two groups: 11 patients in the CFS group and 18 patients in the control group without CFS. The patients were classified as phase 1 during bed rest, phase 2 during nasal endoscopy, phase 3 during nasal abrasion, and phase 4 during oral abrasion. Electrocardiographic recordings were made, and autonomic function was compared and evaluated by measuring heart rate, coefficient of variation on R-R interval (CVRR), coefficient of component variance high frequency (ccvHF), and low frequency/ccvHF ratio (L/H) for each of the four phases. The Shapiro-Wilk test was performed to confirm the normality of the two groups, and the parametric test was selected. A repeated measures analysis of variance was performed to assess changes over time between the four events in the two groups. Multiple comparisons were corrected by the Bonferroni method. Comparisons between resting data and three events within each group were performed by paired t-test.

Results: The CFS group had an increased baseline heart rate compared to the control group, and the CFS group had a greater increase in parasympathetic activity and a decrease in heart rate with nasal abrasion. Oral abrasion elicited a pharyngeal reflex and increased heart rate and both sympathetic and parasympathetic activity.

Conclusion: The CFS group was in a state of dysautonomia due to autonomic overstimulation, with an elevated baseline heart rate. The CFS group was considered to be in a state of impaired autonomic homeostasis, with an increased likelihood that overstimulation would induce a pathological vagal reflex and the Reilly phenomenon would develop. The direct effects of EAT on the autonomic nervous system were considered to be vagus nerve stimulation and the regulation of autonomic function by opposing stimulation input to sympathetic and parasympathetic nerves. As an indirect effect, bleeding from the epipharyngeal mucosa due to abrasion was thought to restore the function of the cerebral venous and lymphatic excretory systems and the autonomic nerve center.

Source: Hirobumi I. Autonomic Nervous System Regulation Effects of Epipharyngeal Abrasive Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Associated With Chronic Epipharyngitis. Cureus. 2023 Jan 14;15(1):e33777. doi: 10.7759/cureus.33777. PMID: 36655156; PMCID: PMC9840732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9840732/ (Full text)

Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination

Abstract:

Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus (PASC)). More recently, comparable problems have been noticed after the SARS-CoV-2 vaccination (post-VAC). The pathophysiology of these problems is not well-understood.

Methods: In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19). The data were compared with a control group of 47 healthy age-matched patients, as recently published.

Results: All patients had a normal left ventricular function as measured by echocardiography. Significantly elevated diastolic blood pressure in all patient groups indicated a regulatory cardiovascular problem. Compared with the healthy control group, the patient groups showed significantly elevated heart rates whilst lying and standing, with significantly higher heart rate increases. The stress index was significantly enhanced in all patient groups whilst lying and standing. Significantly decreased pNN20 values, mostly whilst standing, indicated a lower vagus activity in all patient groups. The respiratory rates were significantly elevated in Groups 1 and 2.

Conclusion: The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.

Source: Buchhorn R. Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination. Vaccines (Basel). 2022 Oct 9;10(10):1686. doi: 10.3390/vaccines10101686. PMID: 36298551; PMCID: PMC9607162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607162/ (Full text)

Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Background: As complaints of long-haul COVID patients are similar to those of ME/CFS patients and as orthostatic intolerance (OI) plays an important role in the COVID infection symptomatology, we compared 14 long-haul COVID patients with 14 ME/CFS patients with a post-viral Ebstein-Barr (EBV) onset and 14 ME/CFS patients with an insidious onset of the disease.
Methods: In all patients, OI analysis by history taking and OI assessed during a tilt test, as well as cerebral blood flow measurements by extracranial Doppler, and cardiac index measurements by suprasternal Doppler during the tilt test were obtained in all patients.
Results: Except for disease duration no differences were found in clinical characteristics. The prevalence of POTS was higher in the long-haul patients (100%) than in post-EBV (43%) and in insidious-onset (50%) patients (p = 0.0002). No differences between the three groups were present in the prevalence of OI, heart rate and blood pressure changes, changes in cerebral blood flow or in cardiac index during the tilt test.
Conclusion: OI symptomatology and objective abnormalities of OI (abnormal cerebral blood flow and cardiac index reduction during tilt testing) are comparable to those in ME/CFS patients. It indicates that long-haul COVID is essentially the same disease as ME/CFS.
Source: van Campen CMC, Visser FC. Orthostatic Intolerance in Long-Haul COVID after SARS-CoV-2: A Case-Control Comparison with Post-EBV and Insidious-Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare. 2022; 10(10):2058. https://doi.org/10.3390/healthcare10102058 (Full text)