Association of interleukin 8 and myocardial recovery in patients with ST-elevation myocardial infarction complicated by acute heart failure

PLoS One. 2014 Nov 12;9(11):e112359. doi: 10.1371/journal.pone.0112359. eCollection 2014.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00324766.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein
  • Cardiotonic Agents / therapeutic use
  • Female
  • Heart Failure / blood*
  • Heart Failure / complications
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Humans
  • Hydrazones / therapeutic use
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood*
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Morpholines / blood
  • Myocardial Contraction / physiology*
  • Myocardial Infarction / blood*
  • Myocardial Infarction / complications
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / physiopathology
  • Pyridazines / therapeutic use
  • Receptors, Interleukin-6 / blood
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Simendan
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Cell Adhesion Molecule-1 / blood
  • Ventricular Function, Left / physiology*

Substances

  • Biomarkers
  • Cardiotonic Agents
  • Hydrazones
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • Morpholines
  • Pyridazines
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Simendan
  • 2-phenyl-5,5-dimethyltetrahydro-1,4-oxazine
  • C-Reactive Protein
  • Matrix Metalloproteinase 9

Associated data

  • ClinicalTrials.gov/NCT00324766

Grants and funding

The Centre for Heart Failure Research University of Oslo, South-Eastern Norway Regional Health Authority, The Scientific Council at Oslo University Hospital Ullevål, an unrestricted grant from Orion Pharma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.