title: Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow-up in heart failure patients with reduced ejection fraction: Comparison with soluble AXL and BNP.
abstract: BACKGROUND
  Prognostic biomarkers are needed to improve the management of the heart failure (HF) epidemic, being the brain natriuretic peptides the most valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT), galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP), compare them with a recently described new candidate (sAXL), and analyze their relationship with BNP.
  
  
  METHODS
  HF patients with reduced ejection fraction (n=192) were included in this prospective observational study, with measurements of candidate biomarkers, functional, clinical and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events, i.e. all-cause mortality and heart transplantation.
  
  
  RESULTS
  Hs-TnT circulating values were correlated to clinical characteristics indicative of more advanced HF. When analyzing the event-free survival at a mean follow-up of 3.6years, patients in the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent risk factors for clinical events.
  
  
  CONCLUSIONS
  In this HF cohort, hs-TnT is a good HF marker and has a very significant prognostic value. The prognostic value of CICP and sAXL was of less significance. However, hs-TnT did not add predictive value to BNP, while sAXL did. This suggests that elevated troponin has a common origin with BNP, while sAXL could represent an independent pathological mechanism.
authors.affiliation: Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) and the Cardiovascular Clinic Institute, Hospital Clínic de Barcelona, Spain. Electronic address: mbatlle@clinic.cat.
authors.forename: M
authors.initials: M
authors.lastname: Batlle
authors.affiliation: Department of Public Health, Universitat de Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Campos
authors.affiliation: Heart Failure and Transplant Unit, Cardiovascular Clinic Institute, Hospital Clínic de Barcelona and researcher at Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Spain.
authors.forename: M
authors.initials: M
authors.lastname: Farrero
authors.affiliation: Heart Failure and Transplant Unit, Cardiovascular Clinic Institute, Hospital Clínic de Barcelona and researcher at Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cardona
authors.affiliation: Core Laboratory, Hospital Clínic de Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: González
authors.affiliation: Heart Failure and Transplant Unit, Cardiovascular Clinic Institute, Hospital Clínic de Barcelona and researcher at Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Castel
authors.affiliation: Heart Failure and Transplant Unit, Cardiovascular Clinic Institute, Hospital Clínic de Barcelona and researcher at Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ortiz
authors.affiliation: Heart Failure Unit at the Cardiology Department, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Biomèdica (IIB Sant Pau), Universitat Autònoma de Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Roig
authors.affiliation: Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) and the Cardiovascular Clinic Institute, Hospital Clínic de Barcelona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pulgarín
authors.affiliation: Pathological Anatomy Department, Hospital Clínic de Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ramírez
authors.affiliation: Core Laboratory, Hospital Clínic de Barcelona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Bedini
authors.affiliation: Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) and the Cardiovascular Clinic Institute, Hospital Clínic de Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sabaté
authors.affiliation: Department of Cell Death and Proliferation at Institut d'Investigacions Biomèdiques de Barcelona (IIBB-CSIC) and IDIBAPS, Spain.
authors.forename: P
authors.initials: P
authors.lastname: García de Frutos
authors.affiliation: Heart Failure and Transplant Unit, Cardiovascular Clinic Institute, Hospital Clínic de Barcelona and researcher at Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Spain.
authors.forename: F
authors.initials: F
authors.lastname: Pérez-Villa
mesh_terms: D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D013318:Stroke Volume / Q000502:physiology; D020107:Troponin T / Q000097:blood*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D010446:Peptide Fragments; D011347:Procollagen; D011518:Proto-Oncogene Proteins; D020107:Troponin T; C042813:procollagen type I carboxy terminal peptide; D020097:Natriuretic Peptide, Brain; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: AXL receptor tyrosine kinase; C-terminal propeptide of type I procollagen; Galectin-3; Heart failure; High sensitivity troponin T; Myocardial damage; Prognosis