title: Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover.
abstract: OBJECTIVE
  Heart failure with preserved ejection fraction (HF-PEF) can be difficult to diagnose in clinical practice. Myocardial fibrosis is a major determinant of diastolic dysfunction (DD), potentially contributing to the progression of HF-PEF. The aim of this study was to analyse whether serological markers of collagen turnover may predict HF-PEF and DD.
  
  
  RESULTS
  We included 85 Caucasian treated hypertensive patients (DD n=65; both DD and HF-PEF n=32). Serum carboxy (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I, amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and tissue inhibitor of MMP levels were assayed. Using receiver operating characteristic curve analysis, MMP-2 (AUC=0.91; 95% CI: 0.84, 0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B-type natriuretic peptide (BNP) (0.82; 0.73, 0.91), MMP-9 (0.79; 0.68, 0.89), and PIIINP (0.78; 0.66, 0.89) levels were significant predictors of HF-PEF (P<0.01 for all). Carboxytelo peptides of procollagen type I (AUC=0.74; 95% CI: 0.62, 0.86), MMP-2 (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP (0.66; 0.54, 0.78) levels were significant predictors of DD (P<0.05 for all). A cutoff of 1585 ng/mL for MMP-2 provided 91% sensitivity and 76% specificity for predicting HF-PEF and combinations of biomarkers could be used to adjust either sensitivity or specificity.
  
  
  CONCLUSIONS
  Markers of collagen turnover identify patients with HF-PEF and DD. Matrix metalloproteinase 2 may be more useful than BNP in the identification of HF-PEF. This suggests that these new biochemical tools may assist in identifying patients with these diagnostically challenging conditions.
authors.affiliation: Heart Failure Unit, School of Medicine and Medical Science, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: Ramón
authors.initials: R
authors.lastname: Martos
authors.forename: John
authors.initials: J
authors.lastname: Baugh
authors.forename: Mark
authors.initials: M
authors.lastname: Ledwidge
authors.forename: Christina
authors.initials: C
authors.lastname: O'Loughlin
authors.forename: Niamh F
authors.initials: NF
authors.lastname: Murphy
authors.forename: Carmel
authors.initials: C
authors.lastname: Conlon
authors.forename: Anil
authors.initials: A
authors.lastname: Patle
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
authors.forename: Kenneth
authors.initials: K
authors.lastname: McDonald
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood; D024061:Collagen Type III / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D054144:Heart Failure, Diastolic / Q000175:diagnosis; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D012680:Sensitivity and Specificity; D013318:Stroke Volume; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D020782:Matrix Metalloproteinases