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


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.


CONCLUSIONS
TIMP-1 is an independent predictor of non-response in patients treated with CRT.
Tolosana
Jose María
JM
Cardiology Department, Arrhythmia Section, Institut Clínic del Torax (ICT), Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, Barcelona, Spain.
Mont
Lluís
L
Sitges
Marta
M
Berruezo
Antonio
A
Delgado
Victoria
V
Vidal
Bàrbara
B
Tamborero
David
D
Morales
Manel
M
Batlle
Montserrat
M
Roig
Eulalia
E
Castel
M Angeles
MA
Pérez-Villa
Félix
F
Godoy
Miguel
M
Brugada
Josep
J
D000368:Aged; D002304:Cardiac Pacing, Artificial; D016001:Confidence Intervals; D017147:Defibrillators, Implantable; D004452:Echocardiography; D018618:Echocardiography, Doppler, Color; D005080:Exercise Test; D005260:Female; D006305:Health Status Indicators; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000378:metabolism; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011788:Quality of Life; D013223:Statistics as Topic; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000378:metabolism; D017211:Treatment Failure; D020257:Ventricular Remodeling; D016138:Walking
D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2