Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

Ambrosino, Pasquale; Parrella, Paolo; Formisano, Roberto; Perrotta, Giovanni; D’Anna, Silvestro Ennio; Mosella, Marco; Papa, Antimo; Maniscalco, Mauro

doi:10.3390/jcm11051452

Cited by 23 publications

(28 citation statements)

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“…45, 46 Abnormal endothelial function assessed with non-invasive brachial artery flow-mediated dilation may be associated with reduced VO 2 in PASC. 47 Coronary microvascular dysfunction, present in some people recovering from COVID-19, 48 is also associated with chronotropic incompetence in the general population with microvascular dysfunction. 49, 50…”

Section: Discussionmentioning

confidence: 99%

“…45,46 Abnormal endothelial function assessed with non-invasive brachial artery flowmediated dilation may be associated with reduced VO2 in PASC. 47 Coronary microvascular dysfunction, present in some people recovering from COVID-19, 48 is also associated with chronotropic incompetence in the general population with microvascular dysfunction. 49,50 Autonomic Function in PASC Consistent with Ladlow et al's findings, altered autonomic function is the most likely unifying explanation for the constellation of findings observed in our study.…”

Section: Findings Of Vascular Dysfunctionmentioning

confidence: 99%

“…48 Endothelial and coronary microvascular dysfunction are associated with chronotropic incompetence in the general population [49][50][51] and have been demonstrated in early PASC. [52][53][54] Endothelial dysfunction may be associated with reduced VO2 in PASC; 55 57 preload failure 58 or inadequate stroke volume augmentation, 23,24 and disordered breathing. [58][59][60] Autonomic Function, Sinus Node Function, and Inflammation in PASC Altered autonomic function is the most likely unifying explanation for the constellation of findings we observed.…”

Section: Connections Between Inflammation Reduced Exercise Capacity A...mentioning

confidence: 99%

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

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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BACKGROUNDMechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.METHODSIn the Long-Term Impact of Infection with Novel Coronavirus (LIINC) Cohort, we performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection. We used logistic and linear regression to compare those with and without cardiopulmonary symptoms (dyspnea, chest pain, palpitations) adjusting for confounders.RESULTSOne hundred twenty individuals were studied, among whom 46 participants (unselected for symptom status) had at least one advanced test performed at median 17 months (IQR 15-18). Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), smaller RV volume and stroke volume and higher extracellular volume were present among those with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/15 (87%) participants with reduced exercise capacity (<85% predicted) reported cardiopulmonary symptoms or fatigue (p=0.008). Adjusted peak VO2 was 2.7 ml/kg/min lower among those with cardiopulmonary symptoms (95%CI −6.9 to 1.5; p=0.20) or −11% predicted (95%CI −27 to 5, p=0.17). Including fatigue along with cardiopulmonary symptoms, the adjusted difference in peak VO2 was −5.9 ml/kg/min (−9.6 to −2.3; p=0.002) or −21% predicted (−35 to −7; p=0.006). Chronotropic incompetence was the primary abnormality among 9/15 with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Those with chronotropic incompetence had higher hsCRP, lower heart rate recovery, and lower heart rate variability suggestive of autonomic dysfunction.CONCLUSIONSReduced exercise capacity and reduced heart rate response to exercise, and hsCRP are associated with persistent cardiopulmonary symptoms more than 1 year following COVID-19. Chronic inflammation and autonomic dysfunction may underlie cardiopulmonary PASC.Clinical PerspectiveWhat is New?Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection.Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRIfindings argue against myocardial dysfunction and myocarditis.Clinical ImplicationsCardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or “Long COVID” should be performed in a manner that allows for assessment of heart rate response to exercise.Therapeutic trials of antiviral, anti-inflammatory, and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

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Section: Discussionmentioning

confidence: 99%

Section: Findings Of Vascular Dysfunctionmentioning

confidence: 99%

Section: Connections Between Inflammation Reduced Exercise Capacity A...mentioning

confidence: 99%

See 1 more Smart Citation

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

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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“…Dennoch zeichnet sich ab, dass Personen mit anhaltenden Symptomen sowohl im Vergleich mit einer gesunden Kontrollgruppe als auch gemessen an ihrer zu erwartenden Leistungsfähigkeit eine reduzierte aerobe Kapazität aufweisen. Unabhängig vom Schweregrad der akuten Covid-19-Erkrankung wurden zum Beispiel eine reduzierte Sauerstoffaufnahme bei Beendigung des Tests und eine Akkumulation von Laktat im arteriellen Blut festgestellt 1 , 8 , 18 , 24 , 26 . Dies geht einher mit einer möglichen Linksverschiebung der Sauerstoffbindungskurve, wodurch die Sauerstoffabgabe von Hämoglobin im Gewebe beeinträchtigt wird, was einen früheren Übergang zum anaeroben Metabolismus erklären könnte 2 .…”

Section: Persistierende Belastungsintoleranzunclassified

“…Unklar ist, ob die beschriebenen spiroergometrischen Befunde bei Long Covid eine Folge spezifischer Virus-Wirt-Interaktionen sind. Ambrosino et al 1 liefern in diesem Zusammenhang Hinweise bezüglich potenzieller pathophysiologischer Mechanismen. Von 36 untersuchten Probanden mindestens 2 Monate nach der Infektion zeigten 78 % eine reduzierte kardiopulmonale Leistungsfähigkeit gemessen an der Sauerstoffaufnahme bei maximaler Belastung.…”

Section: Persistierende Belastungsintoleranzunclassified

Genesen, aber nicht gesund – Long Covid und die Auswirkungen auf die körperliche Leistungsfähigkeit

Haunhorst¹,

Bloch²,

Ellert³

et al. 2022

Sportphysio

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Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults

et al. 2022

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ImportanceReduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.ObjectivesTo estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.Data SourcesA search of PubMed, EMBASE, Web of Science, preprint servers, conference abstracts, and cited references was performed on December 20, 2021, and again on May 24, 2022. A preprint search of medrxiv.org, biorxiv.org, and researchsquare.com was performed on June 9, 2022.Study SelectionStudies of adults with SARS-CoV-2 infection more than 3 months earlier that included CPET-measured peak oxygen consumption (V̇o2) were screened independently by 2 blinded reviewers; 72 (2%) were selected for full-text review, and 35 (1%) met the inclusion criteria. An additional 3 studies were identified from preprint servers.Data Extraction and SynthesisData extraction was performed by 2 independent reviewers according to the PRISMA reporting guideline. Data were pooled using random-effects models.Main Outcomes and MeasuresDifference in peak V̇o2 (in mL/kg/min) among individuals with and without persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection.ResultsA total of 38 studies were identified that performed CPET on 2160 individuals 3 to 18 months after SARS-CoV-2 infection, including 1228 with symptoms consistent with LC. Most studies were case series of individuals with LC or cross-sectional assessments within posthospitalization cohorts. Based on a meta-analysis of 9 studies including 464 individuals with LC symptoms and 359 without symptoms, the mean peak V̇o2 was −4.9 (95% CI, −6.4 to −3.4) mL/kg/min among those with symptoms with a low degree of certainty. Deconditioning and peripheral limitations (abnormal oxygen extraction) were common, but dysfunctional breathing and chronotropic incompetence were also described. The existing literature was limited by small sample sizes, selection bias, confounding, and varying symptom definitions and CPET interpretations, resulting in high risk of bias and heterogeneity.Conclusions and RelevanceThe findings of this systematic review and meta-analysis study suggest that exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among individuals with symptoms consistent with LC compared with individuals without LC symptoms, with low confidence. Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.

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Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

Cited by 23 publications

References 50 publications

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

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

Genesen, aber nicht gesund – Long Covid und die Auswirkungen auf die körperliche Leistungsfähigkeit

Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults

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