Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI

Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Me...

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Main Authors: Ragnhild Helseth, Christian Shetelig, Geir Øystein Andersen, Miriam Sjåstad Langseth, Shanmuganathan Limalanathan, Trine B. Opstad, Harald Arnesen, Pavel Hoffmann, Jan Eritsland, Ingebjørg Seljeflot
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/7816491
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author Ragnhild Helseth
Christian Shetelig
Geir Øystein Andersen
Miriam Sjåstad Langseth
Shanmuganathan Limalanathan
Trine B. Opstad
Harald Arnesen
Pavel Hoffmann
Jan Eritsland
Ingebjørg Seljeflot
author_facet Ragnhild Helseth
Christian Shetelig
Geir Øystein Andersen
Miriam Sjåstad Langseth
Shanmuganathan Limalanathan
Trine B. Opstad
Harald Arnesen
Pavel Hoffmann
Jan Eritsland
Ingebjørg Seljeflot
author_sort Ragnhild Helseth
collection DOAJ
description Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p≤0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p<0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p≤0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p<0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p=0.012). No such observations were encountered for MPO-DNA. Conclusions. High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)).
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spelling doaj-art-2f4099584d30414d8bf3d9f0c8f294a92025-02-03T05:53:02ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/78164917816491Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMIRagnhild Helseth0Christian Shetelig1Geir Øystein Andersen2Miriam Sjåstad Langseth3Shanmuganathan Limalanathan4Trine B. Opstad5Harald Arnesen6Pavel Hoffmann7Jan Eritsland8Ingebjørg Seljeflot9Center for Clinical Heart Research, Oslo University Hospital Ullevål, NorwayDepartment of Cardiology, Oslo University Hospital Ullevål, NorwayDepartment of Cardiology, Oslo University Hospital Ullevål, NorwayCenter for Clinical Heart Research, Oslo University Hospital Ullevål, NorwayThe National Association for Heart and Lung Disease (LHL) Hospital, Gardermoen, NorwayCenter for Clinical Heart Research, Oslo University Hospital Ullevål, NorwayCenter for Clinical Heart Research, Oslo University Hospital Ullevål, NorwayDepartment of Cardiology, Oslo University Hospital Ullevål, NorwayDepartment of Cardiology, Oslo University Hospital Ullevål, NorwayCenter for Clinical Heart Research, Oslo University Hospital Ullevål, NorwayBackground. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p≤0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p<0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p≤0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p<0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p=0.012). No such observations were encountered for MPO-DNA. Conclusions. High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)).http://dx.doi.org/10.1155/2019/7816491
spellingShingle Ragnhild Helseth
Christian Shetelig
Geir Øystein Andersen
Miriam Sjåstad Langseth
Shanmuganathan Limalanathan
Trine B. Opstad
Harald Arnesen
Pavel Hoffmann
Jan Eritsland
Ingebjørg Seljeflot
Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
Mediators of Inflammation
title Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
title_full Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
title_fullStr Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
title_full_unstemmed Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
title_short Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI
title_sort neutrophil extracellular trap components associate with infarct size ventricular function and clinical outcome in stemi
url http://dx.doi.org/10.1155/2019/7816491
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