Plasma TIMP-4 Predicts Left Ventricular Remodeling After Acute Myocardial Infarction

Background: Alterations in the balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) are associated with left ventricular (LV) remodeling after acute myocardial infarction (AMI). No relationships have been identified between TIMPs and serial postinfarction change in LV function. Methods and Results: Plasma concentrations of TIMP-1, -2, -4 were measured at baseline (mean 46 h) and at 24 weeks in 100 patients (age 58.9 +/- 12 years, 77% male) admitted with AMI and LV dysfunction, with cardiac magnetic resonance imaging at each time point. TIMP-1 concentration was reduced, whereas TIMP-2 and -4 concentrations were elevated at baseline compared with a reference control population. TIMP-1 decreased and TIMP-2 increased significantly over time; there was an incremental trend in TIMP-4 concentration. Baseline TIMP-4 correlated with change in LV end-systolic volume index (Delta LVESVI; r = 0.24; P = .023) and change in LV end-diastolic volume index (Delta LVEDVI; r = 0.25; P = .015). Delta TIMP-4 also correlated with Delta LVESVI and with Delta LVEDVI, as did Delta TIMP-2. On multivariable analysis, baseline TIMP-4 concentration was an independent predictor of Delta LVESVI. Conclusions: Plasma TIMP-4 concentration, measured early after AMI, may assist in the prediction of LV remodeling and therefore in the assessment of prognosis. Further study of the role of the TIMPs in the pathophysiology of postinfarction remodeling is warranted. (J Cardiac Fail 2011;17:465-471)