Tag: CPET

Two-Day Cardiopulmonary Exercise Testing in Long COVID Post-Exertional Malaise Diagnosis

Abstract:

Background: Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.

Methods: 15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m2] performed a pulmonary function test and two ramp-incremental CPETs separated by 24hr. CPET variables included gas exchange threshold (GET), V̇O2peak and WRpeak. Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0-10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample t-tests were used to test significance of mean difference between days (p<0.05).

Results: mDSQ revealed PEM in 80% of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40% of patients (V̇O2peak <80% predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).

Conclusion: Post exertional malaise symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24hours, suggests that post-exertional malaise is not due to impaired recovery of exercise capacity between days.

Source: Gattoni C, Abbasi A, Ferguson C, Lanks CW, Decato TW, Rossiter HB, Casaburi R, Stringer WW. Two-Day Cardiopulmonary Exercise Testing in Long COVID Post-Exertional Malaise Diagnosis. Respir Physiol Neurobiol. 2024 Oct 25:104362. doi: 10.1016/j.resp.2024.104362. Epub ahead of print. PMID: 39490617. https://www.sciencedirect.com/science/article/pii/S1569904824001551 (Full text)

Comparison of the muscle oxygenation during submaximal and maximal exercise tests in patients post-coronavirus disease 2019 syndrome with pulmonary involvement

Abstract:

Introduction: Pulmonary involvement is prevalent in patients with coronavirus disease 2019 (COVID-19). Arterial hypoxemia may reduce oxygen transferred to the skeletal muscles, possibly leading to impaired exercise capacity. Oxygen uptake may vary depending on the increased oxygen demand of the muscles during submaximal and maximal exercise.

Objective: This study aimed to compare muscle oxygenation during submaximal and maximal exercise tests in patients with post-COVID-19 syndrome with pulmonary involvement.

Methods: Thirty-nine patients were included. Pulmonary function (spirometry), peripheral muscle strength (dynamometer), quadriceps femoris (QF) muscle oxygenation (Moxy® device), and submaximal exercise capacity (six-minute walk test (6-MWT)) were tested on the first day, maximal exercise capacity (cardiopulmonary exercise test (CPET)) was tested on the second day. Physical activity level was evaluated using an activity monitor worn for five consecutive days. Cardiopulmonary responses and muscle oxygenation were compared during 6-MWT and CPET.

Results: Patients’ minimum and recovery muscle oxygen saturation were significantly decreased; maximum total hemoglobin increased, heart rate, blood pressure, breathing frequency, dyspnea, fatigue, and leg fatigue at the end-of-test and recovery increased in CPET compared to 6-MWT (p < .050). Peak oxygen consumption (VO2peak) was 18.15 ± 4.75 ml/min/kg, VO2peak; percent predicted < 80% was measured in 51.28% patients. Six-MWT distance and QF muscle strength were less than 80% predicted in 58.9% and 76.9% patients, respectively.

Conclusions: In patients with post-COVID-19 syndrome with pulmonary involvement, muscle deoxygenation of QF is greater during maximal exercise than during submaximal exercise. Specifically, patients with lung impairment should be evaluated for deoxygenation and should be taken into consideration during pulmonary rehabilitation.

Source: Kavalcı Kol B, Boşnak Güçlü M, Baytok E, Yılmaz Demirci N. Comparison of the muscle oxygenation during submaximal and maximal exercise tests in patients post-coronavirus disease 2019 syndrome with pulmonary involvement. Physiother Theory Pract. 2024 Mar 12:1-14. doi: 10.1080/09593985.2024.2327534. Epub ahead of print. PMID: 38469863. https://pubmed.ncbi.nlm.nih.gov/38469863/

Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance

Abstract:

Background Post-acute sequelae of COVID-19 (PASC) affects a significant portion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom.

Study Objective This study aimed to characterize the invasive hemodynamic abnormalities of PASC-related exertional intolerance using a larger data set from invasive cardiopulmonary exercise testing (iCPET).

Study Design & Intervention Fifty-five patients were recruited from the Yale Post-COVID-19-Recovery-Program, with most experiencing mild acute illness. Supine right heart catheterization (RHC) and iCPET were performed on all participants.

Main results The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group), On average, the PASC alone group exhibited a “normal” peak exercise capacity, VO2 (89±18% predicted). Approximately 25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise HFpEF and 2 with exercise PH). PASC patient with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak VO2 and cardiac output >80% respectively) despite aberrant central cardiopulmonary exercise hemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m−2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group compromising of obese non-PASC group (n=61) derived from historical iCPET cohort was used. The non-PASC obese patients with preserved peak VO2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10%predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19).

Conclusions This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of current study also highlights the prevalence of a distinct high output failure HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

Source: Peter A. Kahn, Phillip Joseph, Paul M. Heerdt, Inderjit Singh. Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance. ERJ Open Research Jan 2023, 00714-2023; DOI: 10.1183/23120541.00714-2023 https://openres.ersjournals.com/content/early/2023/12/07/23120541.00714-2023 (Full text available as PDF file)

Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores

Abstract:

Purpose: Myalgic encephalomyelitis, commonly referred to as chronic fatigue syndrome (ME/CFS), is a severe, disabling chronic disease and an objective assessment of prognosis is crucial to evaluate the efficacy of future drugs. Attempts are ongoing to find a biomarker to objectively assess the health status of (ME/CFS), patients. This study therefore aims to demonstrate that oxygen consumption is a biomarker of ME/CFS provides a method to classify patients diagnosed with ME/CFS based on their responses to the Short Form-36 (SF-36) questionnaire, which can predict oxygen consumption using cardiopulmonary exercise testing (CPET).

Methods: Two datasets were used in the study. The first contained SF-36 responses from 2,347 validated records of ME/CFS diagnosed participants, and an unsupervised machine learning model was developed to cluster the data. The second dataset was used as a validation set and included the cardiopulmonary exercise test (CPET) results of 239 participants diagnosed with ME/CFS. Participants from this dataset were grouped by peak oxygen consumption according to Weber’s classification. The SF-36 questionnaire was correctly completed by only 92 patients, who were clustered using the machine learning model. Two categorical variables were then entered into a contingency table: the cluster with values {0,1} and Weber classification {A, B, C, D} were assigned. Finally, the Chi-square test of independence was used to assess the statistical significance of the relationship between the two parameters.

Findings: The results indicate that the Weber classification is directly linked to the score on the SF-36 questionnaire. Furthermore, the 36-response matrix in the machine learning model was shown to give more reliable results than the subscale matrix (p – value < 0.05) for classifying patients with ME/CFS.

Implications: Low oxygen consumption on CPET can be considered a biomarker in patients with ME/CFS. Our analysis showed a close relationship between the cluster based on their SF-36 questionnaire score and the Weber classification, which was based on peak oxygen consumption during CPET. The dataset for the training model comprised raw responses from the SF-36 questionnaire, which is proven to better preserve the original information, thus improving the quality of the model.

Source: Lacasa M, Launois P, Prados F, Alegre J, Casas-Roma J. Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores. Clin Ther. 2023 Oct 4:S0149-2918(23)00352-1. doi: 10.1016/j.clinthera.2023.09.007. Epub ahead of print. PMID: 37802746. https://www.clinicaltherapeutics.com/article/S0149-2918(23)00352-1/fulltext (Full text)

Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of SARS-CoV-2 infection

Abstract:

Background: Following acute COVID-19, a substantial proportion of patients showed symptoms and sequelae for several months, namely the post-acute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle.

Methods: At least 3 months after infection, non-hospitalized patients with PASC (n=11,ys:54±11; PASC) and patients without long-term symptoms (n=12,ys:49±9; CTRL) visited the laboratory on four non-consecutive days. Spirometry, lung diffusion capacity and quality of life were assessed at rest. Cardiopulmonary incremental exercise test was performed. Oxygen consumption (VO2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies.

Results: Pulmonary and cardiac functions were within normal range in all patients. VO2peak was lower in PASC than CTRL (24.7±5.0vs32.9±7.4mL*min-1*kg-1, respectively, P<.05). VO2 kinetics was slower in PASC than CTRL (41±12vs30±9s-1, P<.05). k was lower in PASC than CTRL (1.54±0.49vs2.07±0.51min-1, P<.05). Citrate synthase, PGC1alfa and JO2 for mitochondrial complex II were significantly lower in PASC vs CTRL (all P<.05).

Conclusion: In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to “peripheral” determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome appears to negatively impact skeletal muscle function, although the disease is an heterogenous condition.

Source: Colosio M, Brocca L, Gatti M, Neri M, Crea E, Cadile F, Canepari M, Pellegrino MA, Polla B, Porcelli S, Bottinelli R. Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of SARS-CoV-2 infection. J Appl Physiol (1985). 2023 Sep 7. doi: 10.1152/japplphysiol.00158.2023. Epub ahead of print. PMID: 37675472. https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00158.2023 (Full text available as PDF file)

Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue

Abstract:

Introduction: Fatigue is a common symptom in post-COVID-19 patients. Individuals with fatigue often perform less well compared to healthy peers or without fatigue. It is not yet clear to what extent fatigue is related to the inability to reach maximum exhaustion during physical exercise.

Methods: A symptom-based questionnaire based on the Carruthers guidelines (2003) was used for reporting the presence of fatigue and further symptoms related to COVID-19 from 85 participants (60.0% male, 33.5 ± 11.9 years). Cardiopulmonary exercise testing (CPET) and lactate measurement at the end of the test were conducted. Objective and subjective exhaustion criteria according to Wasserman of physically active individuals with fatigue (FS) were compared to those without fatigue (NFS).

Results: Differences between FS and NFS were found in Peak V̇O2/BM (p < 0.001) and Max Power/BM (p < 0.001). FS were more likely to suffer from further persistent symptoms (p < 0.05). The exhaustion criterion Max. lactate was reached significantly more often by NFS individuals.

Conclusion: Although the aerobic performance (Max Power/BM) and the metabolic rate (Peak V̇O2/BM and Max. lactate) of FS were lower compared to NFS, they were equally able to reach objective exhaustion criteria. The decreased number of FS who reached the lactate criteria and the decreased V̇O2 peak indicates a change in metabolism. Other persistent post-COVID-19 symptoms besides fatigue may also impair performance, trainability and the ability to reach objective exhaustion.

Trial registration: Trial registration: DRKS00023717; date of registration: 15.06.2021 (retrospectively registered).

Source: Vollrath S, Matits L, Schellenberg J, Kirsten J, Steinacker JM, Bizjak DA. Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue. Eur J Med Res. 2023 Aug 26;28(1):298. doi: 10.1186/s40001-023-01274-5. PMID: 37633931; PMCID: PMC10464445. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464445/ (Full text)

A Unique Circular RNA Expression Pattern in the Peripheral Blood of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with obscure aetiology. The underdiagnosis rate of ME/CFS is high due to the lack of diagnostic criteria based on objective markers. In recent years, circRNAs have emerged as potential genetic biomarkers for neurological diseases, including Parkinson’s disease and Alzheimer’s disease, making them likely to have the same prospect of being biomarkers in ME/CFS. However, despite the extensive amount of research that has been performed on the transcriptomes of ME/CFS patients, all of them are solely focused on linear RNAs, and the profiling of circRNAs in ME/CFS has been completely omitted. In this study, we investigated the expression profiles of circRNAs, comparing ME/CFS patients and controls before and after two sessions of cardiopulmonary exercise longitudinally.

In patients with ME/CFS, the number of detected circRNAs was higher compared to healthy controls, indicating potential differences in circRNA expression associated with the disease. Additionally, healthy controls showed an increase in the number of circRNAs following exercise testing, while no similar pattern was evident in ME/CFS patients, further highlighting physiological differences between the two groups. A lack of correlation was observed between differentially expressed circRNAs and their corresponding coding genes in terms of expression and function, suggesting the potential of circRNAs as independent biomarkers in ME/CFS.

Specifically, 14 circRNAs were highly expressed in ME/CFS patients but absent in controls throughout the exercise study, indicating a unique molecular signature specific to ME/CFS patients and providing potential diagnostic biomarkers for the disease. Significant enrichment of protein and gene regulative pathways were detected in relation to five of these 14 circRNAs based on their predicted miRNA target genes. Overall, this is the first study to describe the circRNA expression profile in peripheral blood of ME/CFS patients, providing valuable insights into the molecular mechanisms underlying the disease.

Source: Yuning Cheng, Si-Mei Xu, Konii Takenaka, Grace Lindner, Ashton Curry-Hyde, Michael Janitz. A Unique Circular RNA Expression Pattern in the Peripheral Blood of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Gene. Available online 15 June 2023, 147568. https://doi.org/10.1016/j.gene.2023.147568 https://www.sciencedirect.com/science/article/abs/pii/S0378111923004092

Cardiopulmonary testing in long COVID-19 versus non-COVID-19 patients with undifferentiated Dyspnea on exertion

Abstract:

Background: Dyspnea and fatigue are characteristics of long SARS-CoV-2 (COVID)-19. Cardiopulmonary exercise testing (CPET) can be used to better evaluate such patients.

Research question: How significantly and by what mechanisms is exercise capacity impaired in patients with long COVID who are coming to a specialized clinic for evaluation?

Study design and methods: We performed a cohort study using the Mayo Clinic exercise testing database. Subjects included consecutive long COVID patients without prior history of heart or lung disease sent from the Post-COVID Care Clinic for CPET. They were compared to a historical group of non-COVID patients with undifferentiated dyspnea also without known cardiac or pulmonary disease. Statistical comparisons were performed by t-test or Pearson’s chi2 test controlling for age, sex, and beta blocker use where appropriate.

Results: We found 77 patients with long COVID and 766 control patients. Long COVID patients were younger (47 ± 15 vs 50 ± 10 years, P < .01) and more likely female (70% vs 58%, P < .01). The most prominent difference on CPETs was lower percent predicted peak V̇O2 (73 ± 18 vs 85 ± 23%, p < .0001). Autonomic abnormalities (resting tachycardia, CNS changes, low systolic blood pressure) were seen during CPET more commonly in long COVID patients (34 vs 23%, P < .04), while mild pulmonary abnormalities (mild desaturation, limited breathing reserve, elevated V̇E/V̇CO2) during CPET were similar (19% in both groups) with only 1 long COVID patient showing severe impairment.

Interpretation: We identified severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Though mild pulmonary and autonomic impairment were common in long COVID patients, marked limitations were uncommon. We hope our observations help to untangle the physiologic abnormalities responsible for the symptomatology of long COVID.

Source: Contreras AM, Newman DB, Cappelloni L, Niven AS, Mueller MR, Ganesh R, Squires RW, Bonikowske AR, Allison TG. Cardiopulmonary testing in long COVID-19 versus non-COVID-19 patients with undifferentiated Dyspnea on exertion. Prog Cardiovasc Dis. 2023 May 19:S0033-0620(23)00053-1. doi: 10.1016/j.pcad.2023.05.005. Epub ahead of print. PMID: 37211198; PMCID: PMC10198738. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198738/ (Full text)

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Abstract:

Background: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.

Methods: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in a post-COVID cohort, compared those with or without symptoms, and correlated findings with previously measured biomarkers.

Results: Sixty participants (median age 53, 42% female, 87% non-hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted) compared to 3/19 (16%) without symptoms (p = 0.02). Adjusted peak VO2 was 5.2 ml/kg/min lower (95%CI 2.1-8.3; p = 0.001) or 16.9% lower percent predicted (95%CI 4.3-29.6; p = 0.02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias were absent.

Conclusions: Cardiopulmonary symptoms >1 year following COVID-19 were associated with reduced exercise capacity, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary Long COVID.

Source: Durstenfeld MS, Peluso MJ, Kaveti P, Hill C, Li D, Sander E, Swaminathan S, Arechiga VM, Lu S, Goldberg SA, Hoh R, Chenna A, Yee BC, Winslow JW, Petropoulos CJ, Kelly JD, Glidden DV, Henrich TJ, Martin JN, Lee YJ, Aras MA, Long CS, Grandis DJ, Deeks SG, Hsue PY. Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID. J Infect Dis. 2023 May 11:jiad131. doi: 10.1093/infdis/jiad131. Epub ahead of print. PMID: 37166076. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad131/7159960 (Full text available as PDF file)

Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation

Abstract:

Abstract available online: https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

Source: S. Jothi, G. Claessen, M. Insel, S. Kubba, E. Howden, S.-R. Carmona, F.P. Rischard. Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470