Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): An independent predictor of poor response to cardiac resynchronization therapy

Abstract

Aim: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular structural remodelling. The aim of our study was to analyse MMP-2 and TIMP-1 levels as predictors of poor response to cardiac resynchronization therapy (CRT). Methods and results: A cohort of 42 CRT patients from our centre was prospectively evaluated at baseline and after 12-month follow-up. MMP-2 and TIMP-1 assays were performed prior to CRT implant. Cardiac resynchronization therapy responders were defined as patients who survived, were not transplanted, and increased their basal 6 min walking distance test (6MWDT) by >10% or improved their NYHA functional class. Overall, 25 patients (60%) were classed as responders. At 12-month follow-up, six patients (14.2%) had died and one (2.4%) patient had been transplanted. Compared with responders, non-responders had higher levels of TIMP-1 (277±59 vs. 216±46 ng/mL, P = 0.001), MMP-2 (325±115 vs. 258±56 ng/mL, P = 0.02), and creatinine (1.76±0.8 vs. 1.25±0.3 mg/dL, P = 0.01). In a multivariate analysis, TIMP-1 was the only independent predictor of non-response to CRT [OR 0.97, 95% (CI 0.96-0.99) P = 0.005]. TIMP-1>248 ng/mL predicted non-response with 71% sensitivity and 72% specificity. Conclusion: TIMP-1 is an independent predictor of non-response in patients treated with CRT. © The Author 2010.