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

血浆基质金属蛋白酶-1 组织抑制剂 (TIMP-1):心脏再同步化治疗反应不佳的独立预测因子

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作者:Jose María Tolosana, Lluís Mont, Marta Sitges, Antonio Berruezo, Victoria Delgado, Bàrbara Vidal, David Tamborero, Manel Morales, Montserrat Batlle, Eulalia Roig, M Angeles Castel, Félix Pérez-Villa, Miguel Godoy, Josep Brugada

Aims

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).

Conclusion

TIMP-1 is an independent predictor of non-response in patients treated with CRT.

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 >or=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>or=248 ng/mL predicted non-response with 71% sensitivity and 72% specificity.

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