Background: Neutrophil extracellular traps (NETs) are complex structures of nuclear chromatin and cellular proteins released from neutrophils following activation or apoptosis, and are thought to have prothrombotic properties. Experimental models have implicated NETs in ischaemia-reperfusion (IR) injury. Very little is known about the role of NETs in myocardial infarction (MI), but both high levels of circulating NETs and increased burden of NETs in coronary thrombi have been reported to be associated with larger infarct size in patients with ST-elevation MI (STEMI).
Purpose: We hypothesized that NETs measured in the acute phase of STEMI are associated with IR-injury, infarct size and left ventricular (LV) function, and used serial measurements of the NETs marker double-stranded DNA (dsDNA) as well as repeated cardiac magnetic resonance imaging (CMR), to evaluate: 1) the temporal profile of dsDNA during STEMI, 2) possible associations between dsDNA and microvascular obstruction (MVO), myocardial salvage, infarct size, and LV function and remodeling, and 3) possible associations with adverse clinical events.
Methods: 258 patients with first-time STEMI, treated with primary percutaneous coronary intervention (PCI) were included. Blood samples for measurement of dsDNA were drawn before and immediately after the PCI procedure, at Day 1 and at 4-month follow-up. dsDNA was quantified in serum by use of a fluorescent nucleic acid stain. CMR was performed in the acute phase and after 4 months. Clinical events were registered during 12 months' follow-up.
Results: There was a gradual and significant decrease in dsDNA levels from admission to Day 1 with a subsequent decline to 4-month follow-up. Patients with high (>median) levels of dsDNA measured at Day 1 had significantly higher frequency of MVO in the acute phase, and larger final infarct size, decreased myocardial salvage, lower LV ejection fraction (LVEF), and larger increase in indexed LV end-diastolic volume (LVEDVi) at 4-month follow-up, compared to patients with low levels of dsDNA (Figure 1, panels a-e). In multivariable linear regression analyses dsDNA remained associated with infarct size, LVEF, myocardial salvage and change in LVEDVi after adjustment for relevant clinical variables, but not after adjustment for peak troponin T. A total of 19 adverse clinical events were registered during 12 months of follow-up. Patients with high levels of dsDNA at Day 1 had significantly more adverse events compared to patients with low levels (Figure 1, panel f). No significant associations were observed between dsDNA levels measured during PCI and at 4-month follow-up, and the different outcome variables determined by CMR or adverse clinical events.
Conclusions: High circulating levels of dsDNA measured the following day after admission with STEMI were associated with MVO, large infarct size, decreased myocardial salvage, LV remodelling and adverse clinical outcome.