Association of IL-8 With Infarct Size and Clinical Outcomes in Patients With STEMI.

Little is known about the role of interleukin (IL)-8 in patients with acute ST-segment elevation myocardial infarction (STEMI). The aims of this study were to evaluate, in STEMI patients, the temporal profile of IL-8 and possible associations with left ventricular (LV) function and remodeling, infarct size, microvascular obstruction, myocardial salvage, and future clinical events. A total of 258 patients with STEMI were included. Blood samples were drawn before and immediately after percutaneous coronary intervention (PCI), at day 1, and after 4 months. Cardiac magnetic resonance imaging was performed in the acute phase and after 4 months. Clinical events were registered during 12 months' follow-up and all-cause mortality after median 70 months' follow-up. Patients with IL-8 levels greater than the median measured both immediately after PCI and at day 1 had larger final infarct size, lower LV ejection fraction, larger increase in LV end-diastolic volume, and higher frequency of microvascular obstruction. After multivariate adjustment, high IL-8 levels at day 1 were associated with an increased risk of developing a large MI and having reduced LV ejection fraction at 4 months, also after adjustment for peak troponin value. Patients with IL-8 levels in the highest quartile measured at all sampling points were more likely to have a clinical event during the first 12 months after the MI and had lower overall survival during long-term follow-up. High levels of circulating IL-8 were associated with large infarct size, impaired recovery of LV function, and adverse clinical outcome in patients with STEMI, suggesting IL-8 as a future therapeutic target based on its important role in post-infarction inflammation.

Shetelig C ，Limalanathan S ，Hoffmann P ，Seljeflot I ，Gran JM ，Eritsland J ，Andersen GØ ... -  《-》

High levels of interleukin-6 are associated with final infarct size and adverse clinical events in patients with STEMI.

Inflammation has emerged as a new treatment target in patients with coronary artery disease and inflammation seems to play an important role in ischaemia/reperfusion injury that follows ST-elevation myocardial infarction (STEMI). We aimed to explore the role of acute and sustained interleukin 6 (IL-6) signalling, including soluble IL-6 receptor (IL-6R), with regard to infarct size, adverse remodelling and future cardiovascular events in patients with STEMI. We included 269 patients with first-time STEMI, symptom duration <6 hours and treated with percutaneous coronary intervention. Blood sampling and cardiac MRI were performed in the acute phase and after 4 months. Clinical events and all-cause mortality were registered during 12-month and 70-month follow-up, respectively. IL-6 levels above median at all sampling points were significantly associated with increased infarct size and reduced left ventricular ejection fraction (LVEF). IL-6 levels in the highest quartile were at all sampling points associated with an increased risk of having an adverse clinical event during the first 12 months and with long-term all-cause mortality. IL-6R was not associated with infarct size, LVEF, myocardial salvage or long-term all-cause mortality. Acute and sustained elevation of IL-6 measured 4 months after STEMI were associated with larger infarct size, reduced LVEF and adverse clinical events including all-cause mortality. The results add important information to the sustained role of inflammation in patients with STEMI and IL-6 as a potential target for long-term intervention. NCT00922675.

Tøllefsen IM ，Shetelig C ，Seljeflot I ，Eritsland J ，Hoffmann P ，Andersen GØ ... -  《Open Heart》

ST2 and left ventricular remodeling after ST-segment elevation myocardial infarction: A cardiac magnetic resonance study.

The association of soluble interleukin-1 receptor-like 1 (ST2) with left ventricular (LV) remodeling is unclear in patients with a first ST-segment elevation myocardial infarction (STEMI). The objective of this work was to assess the relationship between ST2, a marker of inflammation, and cardiac magnetic resonance (CMR) imaging-derived LV remodeling after a first STEMI. We prospectively evaluated 109 patients with a first STEMI treated with primary percutaneous coronary intervention who had ST2 assessed 24 h post-reperfusion. All patients underwent CMR imaging 1 week and 6 months after STEMI. The independent associations between ST2, LV diastolic and systolic volume indices, and LV ejection fraction (LVEF) were evaluated by linear mixed models. The mean age of the sample was 59 ± 12 years, 85 patients (78%) were male, and 13 (11.9%) had a LVEF ≤40%. The median (IQR) of ST2 was 55.3 (38.7-94.1) pg/mL. At 1-week CMR higher ST2 was related to more infarct size and less myocardial salvage index (p < 0.01). Overall, after comprehensive multivariable adjustment, higher baseline ST2 was associated with progressive LV volume indices dilation and LVEF deterioration (p < 0.05). This effect was stronger in patients with severe 1-week structural damage, namely those with large infarct size, extensive microvascular obstruction or LVEF ≤40%. In patients with a first STEMI treated with primary percutaneous coronary intervention, soluble ST2 predicts dynamic changes in CMR-derived LV volumes and LVEF. Future studies must assess whether targeting interleukin-1 leads to lower ST2 levels and less LV remodeling.

Miñana G ，Núñez J ，Bayés-Genís A ，Revuelta-López E ，Ríos-Navarro C ，Núñez E ，Chorro FJ ，López-Lereu MP ，Monmeneu JV ，Lupón J ，Bodí V ... -  《-》

Increased interleukin-1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

To assess the relationship between interleukin (IL)-1-related molecules, infarct size and left ventricular (LV) remodelling following acute myocardial infarction (MI). Forty-two patients with first-time diagnosis of ST segment elevation MI (STEMI), with a single occluded vessel successfully revascularized by primary percutaneous coronary intervention (PCI), were recruited to this observational study conducted at a university teaching hospital and followed for 1 year. Plasma levels of IL-1β, IL-1 receptor antagonist (IL-1Ra), IL-18 and caspase-1 were analysed before and 2 days, 1 week and 2 months after PCI. Serial cardiac magnetic resonance imaging (CMR) was used for the assessment of infarct size and LV remodelling. CMR findings at 1 year was the primary outcome variable. Univariate analysis showed that IL-1-related mediators were strongly (IL-1 β), moderately (caspase-1) and weakly (IL-1Ra) associated with impaired myocardial function and noninfarct mass, but not infarct size, 1 year after reperfused STEMI. In multivariate analyses, troponin T predicted LV ejection fraction (LVEF), infarct size and LV end-diastolic (LVEDVi) and end-systolic volume index (LVESVi). However, significant additional variance was explained by IL-1β, IL-18 and caspase-1. IL-1β levels at 2 months, IL-18 at 2 days and pre-PCI caspase-1 were predictors of LVEF. Caspase-1 and in particular IL-1β at 2 days were the only predictors of noninfarct mass. IL-1β and IL-18 at 2 days were predictors of LVEDVi, whilst pre-PCI levels of IL-1β contributed to prediction of LVESVi. By contrast, pro-B-type natriuretic peptide, C-reactive protein, IL-6 and transforming growth factor-β1 (TGF-β1) had no or only a weak (TGF-β1) association with these CMR parameters in multivariate analyses. IL-1β levels after STEMI were strongly associated with impaired myocardial function and noninfarct LV mass after 1 year, suggesting a potential role for IL-1β as a predictor of maladaptive myocardial remodelling following reperfused MI.

Ørn S ，Ueland T ，Manhenke C ，Sandanger Ø ，Godang K ，Yndestad A ，Mollnes TE ，Dickstein K ，Aukrust P ... -  《-》

Predictors of left ventricular remodeling after ST-elevation myocardial infarction.

Hendriks T ，Hartman MHT ，Vlaar PJJ ，Prakken NHJ ，van der Ende YMY ，Lexis CPH ，van Veldhuisen DJ ，van der Horst ICC ，Lipsic E ，Nijveldt R ，van der Harst P ... -  《-》