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


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov NCT00324766.
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.
Trygve
T
Husebye
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Jan
J
Eritsland
Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Harald
H
Arnesen
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Reidar
R
Bjørnerheim
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Arild
A
Mangschau
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Ingebjørg
I
Seljeflot
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway.
Geir Øystein
GØ
Andersen
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein; D002316:Cardiotonic Agents / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009025:Morpholines / Q000097:blood; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D011724:Pyridazines / Q000627:therapeutic use; D019947:Receptors, Interleukin-6 / Q000097:blood; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D000077464:Simendan; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D016277:Ventricular Function, Left / Q000502:physiology*
D015415:Biomarkers; D002316:Cardiotonic Agents; D006835:Hydrazones; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D009025:Morpholines; D011724:Pyridazines; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000077464:Simendan; C005759:2-phenyl-5,5-dimethyltetrahydro-1,4-oxazine; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9