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

Abstract

AimsMatrix 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 resultsA 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.ConclusionTIMP-1 is an independent predictor of non-response in patients treated with CRT.

Biomarkers in electrophysiology: role in arrhythmias and resynchronization therapy

“…A recent work has suggested that a significant decrease in MMP-9 levels correlates with CRT-associated RR* over a 6-month follow-up period [111]. Furthermore, higher TIMP-1 levels have been shown to be an independent predictor of nonresponse to CRT [112]. Increased collagen production resulting in excessive fibrosis can exert a deleterious effect on ventricular function.…”

Circulating biomarkers of collagen type I metabolism mark the right ventricular fibrosis and adverse markers of clinical outcome in adults with repaired tetralogy of Fallot

“…The PICP:CITP ratio was considered an index of the degree of coupling between the synthesis and degradation of collagen type I [7]. Serum levels of MMP-1, -2 -3, and -9, and TIMP-1 were analyzed using commercially available 2-site sandwich enzyme-linked immunosorbent assay (Quantikine R&D Systems, Minneapolis, Minnesota, USA) [8]. Intra-and inter-assay variations for determining MMPs and TIMP-1 were all b8%.…”

Biochemical aspects of gender differences in response to cardiac resynchronization therapy

“…Дисбаланс в системе цитокинов может приве-сти к ремоделированию миокарда вследствие активации матриксных металлопротеиназ (MMPs), вызывающих деградацию коллагена и ремоделирование экстрацел-люлярного кардиального матрикса (ЭКМ) [19], а также к развитию фиброза миокарда [20,21]. Известно влияние СРТ на процессы воспаления [22][23][24][25], ремоделирования экстрацеллюлярного кардиального матрикса (ЭКМ) [26][27][28], фиброобразования [29,30]. Однако влияние этих процессов на гендерную специфику ремоделирова-ния миокарда на фоне СРТ не изучено.…”

“…Имеются сведения о влиянии СРТ на активность систе-мы MMPs и их тканевых ингибиторов (TIMPs), играю-щих ключевую роль в ремоделировании ЭКМ [26][27][28]. Модернизация ЭКМ по сути является адаптивным про-цессом, ведущим к изменению растяжимости миокарда, сохранению геометрической формы сердца или формиро-ванию новой конструкции камер сердца.…”