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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Circulating biomarkers of collagen type I metabolism mark the right ventricular fibrosis and adverse markers of clinical outcome in adults with repaired tetralogy of Fallot.
International Journal of Cardiology 2013 September 11
BACKGROUND: Right ventricular (RV) fibrosis is common in patients with repaired tetralogy of Fallot (rTOF). Although accumulating evidence indicates the role of circulating biomarkers of collagen metabolism in left ventricular fibrosis, rTOF data are lacking. This study examined the expression profile and clinical relevance of circulating biomarkers of collagen type I metabolism in rTOF patients.
METHODS: Serum biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I, PICP), degradation (carboxy-terminal telopeptide of collagen type I, CITP), and enzymes regulating collagen degradation (matrix metalloproteinases, and type I tissue inhibitor, TIMP-1) were measured in 70 rTOF and 91 control adults. All patients had complete clinical data and received cardiovascular magnetic resonance scans with late gadolinium enhancement (LGE).
RESULTS: Compared to the controls, rTOF patients had higher PICP levels (p<0.001), PICP:CITP ratios (p<0.001), and TIMP-1 concentrations (p<0.001). Increasing PICP levels correlated with higher RV LGE scores (r=0.427, p<0.001), lower VO2max (r=-0.428, p=0.002), and larger RV volumes. Furthermore, stepwise multivariate linear regression analysis identified RV end-diastolic volume index >150mL/m(2) (β=40.52, p=0.016), RV LGE score (β=3.94, p=0.008), and age (β=-1.77, p=0.011) as independent correlates of circulating PICP levels.
CONCLUSIONS: Patients with rTOF exhibited a profibrotic state with excessive collagen type I synthesis and dysregulated degradation. Elevated circulating PICP levels might reflect RV fibrosis, and link to adverse markers of clinical outcome.
METHODS: Serum biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I, PICP), degradation (carboxy-terminal telopeptide of collagen type I, CITP), and enzymes regulating collagen degradation (matrix metalloproteinases, and type I tissue inhibitor, TIMP-1) were measured in 70 rTOF and 91 control adults. All patients had complete clinical data and received cardiovascular magnetic resonance scans with late gadolinium enhancement (LGE).
RESULTS: Compared to the controls, rTOF patients had higher PICP levels (p<0.001), PICP:CITP ratios (p<0.001), and TIMP-1 concentrations (p<0.001). Increasing PICP levels correlated with higher RV LGE scores (r=0.427, p<0.001), lower VO2max (r=-0.428, p=0.002), and larger RV volumes. Furthermore, stepwise multivariate linear regression analysis identified RV end-diastolic volume index >150mL/m(2) (β=40.52, p=0.016), RV LGE score (β=3.94, p=0.008), and age (β=-1.77, p=0.011) as independent correlates of circulating PICP levels.
CONCLUSIONS: Patients with rTOF exhibited a profibrotic state with excessive collagen type I synthesis and dysregulated degradation. Elevated circulating PICP levels might reflect RV fibrosis, and link to adverse markers of clinical outcome.
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