Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover
1 Heart Failure Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
2 School of Medicine and Medical Science, St Vincent's University Hospital, Dublin 4, Ireland
3 Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
* Corresponding author. Tel: +353 1 230 4629, Fax: +353 1 230 4639, Email: kenneth.mcdonald{at}ucd.ie
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Abstract |
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Aims: 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.
Methods and 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.
Conclusion: 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.
Key Words: Diastolic dysfunction • Heart failure with preserved ejection fraction • Markers of collagen turnover • B-type natriuretic peptide
Received June 12, 2008; Revised October 20, 2008; Accepted November 24, 2008
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