Husebye Trygve, Eritsland Jan, Arnesen Harald, Bjørnerheim Reidar, Mangschau Arild, Seljeflot Ingebjørg, Andersen Geir Øystein
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
PLoS One. 2014 Nov 12;9(11):e112359. doi: 10.1371/journal.pone.0112359. eCollection 2014.
No data from controlled trials exists regarding the inflammatory response in patients with de novo heart failure (HF) complicating ST-elevation myocardial infarction (STEMI) and a possible role in the recovery of contractile function. We therefore explored the time course and possible associations between levels of inflammatory markers and recovery of impaired left ventricular function as well as levosimendan treatment in STEMI patients in a substudy of the LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial.
A total of 61 patients developing HF within 48 hours after a primary PCI-treated STEMI were randomised double-blind to a 25 hours infusion of levosimendan or placebo. Levels of IL-6, CRP, sIL-6R, sgp130, MCP-1, IL-8, MMP-9, sICAM-1, sVCAM-1 and TNF-α were measured at inclusion (median 22 h, interquartile range (IQR) 14, 29 after PCI), on day 1, day 2, day 5 and 6 weeks. Improvement in left ventricular function was evaluated as change in wall motion score index (WMSI) by echocardiography.
Only circulating levels of IL-8 at inclusion were associated with change in WMSI from baseline to 6 weeks, r = ÷ 0.41 (p = 0.002). No association, however, was found between IL-8 and WMSI at inclusion or peak troponin T. Furthermore, there was a significant difference in change in WMSI from inclusion to 6 weeks between patients with IL-8 levels below, compared to above median value, ÷ 0.44 (IQR ÷ 0.57, ÷ 0.19) vs. ÷ 0.07 (IQR ÷ 0.27, 0.07), respectively (p < 0.0001). Levosimendan did not affect the levels of inflammary markers compared to control.
High levels of IL-8 in STEMI patients complicated with HF were associated with less improvement in left ventricular function during the first 6 weeks after PCI, suggesting a possible role of IL-8 in the reperfusion-related injury of post-ischemic myocardium. Further studies are needed to confirm this hypothesis.
ClinicalTrials.gov NCT00324766.
关于初发性心力衰竭（HF）合并ST段抬高型心肌梗死（STEMI）患者的炎症反应及其在收缩功能恢复中可能发挥的作用，尚无来自对照试验的数据。因此，在心肌梗死后急性心力衰竭中使用左西孟旦（LEAF）试验的一项子研究中，我们探讨了STEMI患者炎症标志物水平与受损左心室功能恢复之间的时间进程及可能的关联，以及左西孟旦治疗的影响。
共有61例在接受直接经皮冠状动脉介入治疗（PCI）的STEMI后48小时内发生HF的患者被随机双盲分为接受25小时左西孟旦输注或安慰剂输注的两组。在纳入时（PCI后中位数22小时，四分位数间距（IQR）为14, 29）、第1天、第2天、第5天和6周时测量白细胞介素-6（IL-6）、C反应蛋白（CRP）、可溶性IL-6受体（sIL-6R）、可溶性糖蛋白130（sgp130）、单核细胞趋化蛋白-1（MCP-1）、IL-8、基质金属蛋白酶-9（MMP-9）、可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）和肿瘤坏死因子-α（TNF-α）的水平。通过超声心动图评估左心室功能的改善情况，以室壁运动评分指数（WMSI）的变化来衡量。
仅纳入时的循环IL-8水平与从基线到6周时WMSI的变化相关，r = -0.41（p = 0.002）。然而，在纳入时或肌钙蛋白T峰值时，未发现IL-8与WMSI之间存在关联。此外，IL-8水平低于中位数与高于中位数的患者相比，从纳入到6周时WMSI的变化存在显著差异，分别为-0.44（IQR -0.57, -0.19）和-0.07（IQR -0.27, 0.07）（p < 0.0001）。与对照组相比，左西孟旦不影响炎症标志物水平。
合并HF的STEMI患者中高水平的IL-8与PCI后最初6周内左心室功能改善较少相关，提示IL-8在缺血后心肌再灌注相关损伤中可能发挥作用。需要进一步研究来证实这一假说。
ClinicalTrials.gov NCT00324766
