title: Plasma tissue inhibitor of matrix metalloproteinase-1 a predictor of long-term mortality in patients treated with cardiac resynchronization therapy.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in cardiac remodelling. Available information regarding their prognostic utility in heart failure (HF) and cardiac resynchronization therapy (CRT) is controversial. The aim of this study was to analyse MMP-2 and TIMP-1 levels as predictors of long-term mortality in HF patients treated with CRT.
  
  
  RESULTS
  We prospectively included 42 consecutive patients with successfully implanted CRT. Matrix metalloproteinase-2 and TIMP-1 assays were performed prior to implant. Patients were evaluated at baseline and at the outpatient clinic at 6-month intervals. Clinical response, left ventricular (LV) remodelling, and mortality were analysed. During a mean follow-up of 60 ± 34 months, long-term mortality from any cause was 36% (15 patients). The cause of death was end stage of HF in 12 patients, sudden death in 2 patients, and 1 unknown. After adjustment using a Cox regression model, the independent predictors of long-term mortality were baseline TIMP-1, hazard ratio (HR) 1.18 (95% confidence interval (95% CI) [1.05-1.33], P = 0.007), baseline glomerular filtration rate (GFR), HR 0.97 (95% CI [0.94-1.00], P = 0.05), and permanent atrial fibrillation (AF), HR 3.14 (95% CI [1.02-9.67], P = 0.04). Area under receiver operating characteristic curve for TIMP-1 was 0.79 (95% CI [0.63-0.94]). Tissue inhibitor of matrix metalloproteinase-1 ≥ 248 ng/mL predicts mortality with 80% sensitivity and 71% specificity.
  
  
  CONCLUSIONS
  Tissue inhibitor of matrix metalloproteinase-1 is a powerful predictor of long-term mortality in HF patients treated with CRT.
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Emilce
authors.initials: E
authors.lastname: Trucco
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain tolosana@clinic.ub.es.
authors.forename: José M
authors.initials: JM
authors.lastname: Tolosana
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Castel
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Borràs
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Sitges
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Guash
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Matas
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Arbelo
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Berruezo
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Thorax Institute, Cardiology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Mont
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy / Q000009:adverse effects / Q000401:mortality*; D002423:Cause of Death; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy*; D016027:Heart Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Cardiac resynchronization therapy; Heart failure mortality; Inhibitors of matrix metalloproteinases