Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance

Background: Following the worldwide coronavirus disease 2019 (COVID-19) pandemic, many patients reported ongoing severe cardiovascular symptoms after the acute phase. This multisystemic condition has been named long COVID syndrome. While cardiovascular magnetic resonance (CMR) imaging is the gold st...

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Main Authors: Lukas D. Weberling, Elizabeth Hillier, Matthias G. Friedrich, Marc Zahlten, Norbert Frey, Florian André, Henning Steen
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Cardiovascular Magnetic Resonance
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Online Access:http://www.sciencedirect.com/science/article/pii/S1097664725000523
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author Lukas D. Weberling
Elizabeth Hillier
Matthias G. Friedrich
Marc Zahlten
Norbert Frey
Florian André
Henning Steen
author_facet Lukas D. Weberling
Elizabeth Hillier
Matthias G. Friedrich
Marc Zahlten
Norbert Frey
Florian André
Henning Steen
author_sort Lukas D. Weberling
collection DOAJ
description Background: Following the worldwide coronavirus disease 2019 (COVID-19) pandemic, many patients reported ongoing severe cardiovascular symptoms after the acute phase. This multisystemic condition has been named long COVID syndrome. While cardiovascular magnetic resonance (CMR) imaging is the gold standard to diagnose acute myocardial damage, no specific changes have been shown in long COVID patients. However, endothelial dysfunction has been hypothesized to contribute to its pathogenesis. Oxygenation-sensitive CMR during breathing exercise is a simple, non-invasive, and accurate test to objectify vascular function, which has not been applied to long COVID patients yet. Methods: After receiving approval from the local ethics committee, this prospective observational case-control study enrolled (i) patients reporting symptoms for ≥6 weeks following an acute COVID-19 infection or vaccination, and (ii) healthy volunteers with neither symptoms nor history of cardiovascular disease. Participants completed a questionnaire, point-of-care testing of cardiac biomarkers, a standard non-contrast CMR, and an oxygenation-sensitive CMR. Heart rate response and breathing-induced myocardial oxygenation reserve (B-MORE) were assessed during metronome-paced hyperventilation and apnea. Results: Thirty-one patients (17 female; age 39.4 [30.3; 51.6] years) and 27 controls (12 female; age 33.3 [27.3; 46.8] years) were included with comparable demographics and cardiovascular risk factors between groups. Laboratory testing and standard CMR did not reveal any pathologies in either of the groups. Indexed left ventricular stroke volume was significantly lower in patients (44.5 mL [41.2; 46.6] vs 55.9 mL [49.2; 59.2]; p < 0.001), while ejection fraction and longitudinal strain of both ventricles were comparable (p > 0.05 for all). Vasoactive breathing exercises induced a significant increase in heart rate (+35/min [21; 45]) and B-MORE (9.8% [4.3; 17.2]) in controls. In patients, however, heart rate increase was blunted (+15/min [7; 26]; p < 0.001) and B-MORE was significantly lower (7.3% [3.4; 10.4], p = 0.044). Conclusion: This pilot study is the first to show a blunted hemodynamic and myocardial oxygenation response to vasoactive breathing maneuvers during oxygenation-sensitive CMR in long COVID patients. This simple, non-invasive test may be the first to objectify complaints of affected patients and indicates evidence for the crucial role of the endothelium in the pathophysiology of long COVID.
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spelling doaj-art-5e0fc616be4e4541b4e1371a150ac7832025-08-20T02:08:57ZengElsevierJournal of Cardiovascular Magnetic Resonance1097-66472025-01-0127110189010.1016/j.jocmr.2025.101890Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonanceLukas D. Weberling0Elizabeth Hillier1Matthias G. Friedrich2Marc Zahlten3Norbert Frey4Florian André5Henning Steen6Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany; Corresponding author.Faculty of Medicine and Health Sciences, Division of Experimental Medicine, McGill University, Montreal, Quebec, CanadaFaculty of Medicine and Health Sciences, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada; Division of Cardiology, Departments of Medicine and Diagnostic Radiology, McGill University, Montreal, Quebec, CanadaDepartment of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, GermanyBackground: Following the worldwide coronavirus disease 2019 (COVID-19) pandemic, many patients reported ongoing severe cardiovascular symptoms after the acute phase. This multisystemic condition has been named long COVID syndrome. While cardiovascular magnetic resonance (CMR) imaging is the gold standard to diagnose acute myocardial damage, no specific changes have been shown in long COVID patients. However, endothelial dysfunction has been hypothesized to contribute to its pathogenesis. Oxygenation-sensitive CMR during breathing exercise is a simple, non-invasive, and accurate test to objectify vascular function, which has not been applied to long COVID patients yet. Methods: After receiving approval from the local ethics committee, this prospective observational case-control study enrolled (i) patients reporting symptoms for ≥6 weeks following an acute COVID-19 infection or vaccination, and (ii) healthy volunteers with neither symptoms nor history of cardiovascular disease. Participants completed a questionnaire, point-of-care testing of cardiac biomarkers, a standard non-contrast CMR, and an oxygenation-sensitive CMR. Heart rate response and breathing-induced myocardial oxygenation reserve (B-MORE) were assessed during metronome-paced hyperventilation and apnea. Results: Thirty-one patients (17 female; age 39.4 [30.3; 51.6] years) and 27 controls (12 female; age 33.3 [27.3; 46.8] years) were included with comparable demographics and cardiovascular risk factors between groups. Laboratory testing and standard CMR did not reveal any pathologies in either of the groups. Indexed left ventricular stroke volume was significantly lower in patients (44.5 mL [41.2; 46.6] vs 55.9 mL [49.2; 59.2]; p < 0.001), while ejection fraction and longitudinal strain of both ventricles were comparable (p > 0.05 for all). Vasoactive breathing exercises induced a significant increase in heart rate (+35/min [21; 45]) and B-MORE (9.8% [4.3; 17.2]) in controls. In patients, however, heart rate increase was blunted (+15/min [7; 26]; p < 0.001) and B-MORE was significantly lower (7.3% [3.4; 10.4], p = 0.044). Conclusion: This pilot study is the first to show a blunted hemodynamic and myocardial oxygenation response to vasoactive breathing maneuvers during oxygenation-sensitive CMR in long COVID patients. This simple, non-invasive test may be the first to objectify complaints of affected patients and indicates evidence for the crucial role of the endothelium in the pathophysiology of long COVID.http://www.sciencedirect.com/science/article/pii/S1097664725000523CMRCardiovascular imagingOS-CMROxygenation-sensitive CMRCOVID-19Long COVID syndrome
spellingShingle Lukas D. Weberling
Elizabeth Hillier
Matthias G. Friedrich
Marc Zahlten
Norbert Frey
Florian André
Henning Steen
Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance
Journal of Cardiovascular Magnetic Resonance
CMR
Cardiovascular imaging
OS-CMR
Oxygenation-sensitive CMR
COVID-19
Long COVID syndrome
title Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance
title_full Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance
title_fullStr Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance
title_full_unstemmed Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance
title_short Abnormal coronary vascular response in patients with long COVID syndrome – a case‐control study using oxygenation‐sensitive cardiovascular magnetic resonance
title_sort abnormal coronary vascular response in patients with long covid syndrome a case control study using oxygenation sensitive cardiovascular magnetic resonance
topic CMR
Cardiovascular imaging
OS-CMR
Oxygenation-sensitive CMR
COVID-19
Long COVID syndrome
url http://www.sciencedirect.com/science/article/pii/S1097664725000523
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