Abstract 2569: Matrix Metalloproteinase-9 in the Pathogenesis of Left Ventricular Remodelling and Heart Failure Post Acute Myocardial Infarction
Introduction.Matrix metalloproteinases(MMP’s)are implicated in adverse ventricular remodel-ling.We investigated the temporal profile of the gelatinase MMP-9,its relationship to LV remodelling and heart failure following acute myocardial infarction (AMI) and compared with N-BNP as a predictor of such changes.
Methods.We studied 91 patients with AMI (85%STEMI).MMP-9 was measured at 0 –12,12–24&24hr periods after symptom onset,and N-BNP at discharge.Echocardiographic assessment of LV function via bi-planar ejection fraction(LVEF)and wall motion index scoring (WMIS),LV volumes-end systolic (LVESV),end diastolic volume(LVEDV)and the change in volume(Δ,%)was performed pre-discharge and at a median of 176(138 –262)days,patients were followed for episodes of heart failure for a median of 531 days(range 1– 614).
Results:MMP-9 peaked 12 hours post AMI then fell to a plateau(0 –12hrsv12–24hrs,p=0.03).MMP-9 within the first 12 hours was higher in smokers(p=0.029) and correlated with plasma neutrophil count(r=.409, p<0.001).Higher MMP-9 was associated with more severe LV dysfunction pre-discharge,(LVEF r=-.324,p=.003;WMIS r=.231,p=.03).There was correlation between peak MMP-9 and ΔEDV(r=.324,p=.017)remaining on multi-variant analysis.Paradoxically there was inverse correlation between trough MMP-9 and ΔEDV and ΔESV(r=-.290,p=.034r=-.454,p<0.001)the latter maintained on multivariate analysis.Over our follow up period there were 10 patients with heart failure episodes,lower MMP-9 trough levels predicting these patients(median 24.2v37.48, p=0.021)this observation being maintained in a logistic model(OR.47,p=0.047)and on Cox proportional hazards(HR.01,p<0.001).N-BNP did not correlate with Δ volumes but correlated with both admission and follow up WMIS and LVEF and was raised in heart failure group.
Conclusion:Individual temporal profiles of plasma MMP occur after AMI.Correlation of peak MMP-9 with increasing LV volumes implicates these enzymes in remodelling.The negative correlations seen between trough levels of MMP-9 and changes in LV volumes and heart failure suggests that a basal level may be required to maintain LV integrity.Circulating neutrophils may be the source of plasma MMPs seen after AMI.