Abstract
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)).
Highlights
Despite today’s state-of-the-art management of acute STelevation myocardial infarction (STEMI), including rapid revascularization with percutaneous coronary intervention (PCI) and modern antithrombotic treatment, one-year mortality still remains approximately 10% [1]
Epidemiological data reporting that increased neutrophil count after PCI in ST-elevation myocardial infarction (STEMI) patients associates with larger infarct size and deteriorated left ventricular function underpin the clinical importance of neutrophil actions in the early postinfarction phase [6]
While Double-stranded deoxyribonucleic acid (dsDNA) levels were significantly reduced at all subsequent time points, MPO-DNA levels were significantly reduced after PCI and at 4 months (Figure 1)
Summary
Despite today’s state-of-the-art management of acute STelevation myocardial infarction (STEMI), including rapid revascularization with percutaneous coronary intervention (PCI) and modern antithrombotic treatment, one-year mortality still remains approximately 10% [1]. High day 1 dsDNA levels 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, when adjusting for peak troponin T (hazard ratio 5.1, p = 0:012). No such observations were encountered for MPO-DNA. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008))
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