Abstract 9114: Circulating Biomarkers of Collagen Type I Metabolism Mark Right Ventricular Fibrosis and Indications for Pulmonary Valve Replacement in Adults with Repaired Tetralogy of Fallot
Background: Right ventricular (RV) fibrosis is common in patients with repaired tetralogy of Fallot (rTOF). Previous works have shown that cardiac fibrosis could be monitored from circulating biomarkers of collagen metabolism. We assessed the hypothesis that the expression of circulating biomarkers of collagen type I metabolism is altered in rTOF, and could mark in vivo cardiac fibrosis and adverse outcomes.
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 turnover (matrix metalloproteinases, MMPs, and type I tissue inhibitor, TIMP-1) were measured in 70 adults with rTOF and 91 age- and sex-matched controls. All patients underwent cardiac magnetic resonance (CMR) to evaluate biventricular function and late gadolinium enhancement (LGE). Patients were classified as with or without indications for pulmonary valve replacement (PVR) based on clinical symptoms, exercise capacity, and CMR-derived measurements.
Results: In patients with rTOF, PICP (median 87.7 [25%-75% percentile 68.9-115.6] vs. 58.9 [48.4-71.9] ng/mL, P < 0.001) and PICP:CITP ratio (23.1 [17.5-30.7] vs. 16.5 [13.6-21.7], P < 0.001) were significantly higher than in controls. TIMP-1 was elevated (168.4 [145.7-180.3] vs. 107.3 [91.8-124.2] ng/mL, P < 0.001) without concomitant increase in MMP-1, -2, -3, and -9. Patients with PVR indications had higher PICP (P = 0.009) and PICP:CITP ratio (P = 0.078) than those without. In addition, a higher PICP correlated with a higher RV LGE score (r = 0.427, P < 0.001) and a lower exercise capacity (r = -0.465, P = 0.001). In multivariate analysis, PICP was associated with the probability of the presence of indications for PVR (odds ratio 1.80 per 10 ng/mL, P = 0.003).
Conclusions: Collagen type I overproduction and uncoupled degradation were found in patients with rTOF. Circulating PICP not only correlated with RV LGE, but also linked to adverse markers of clinical outcome indicating the need for PVR. These findings may give us new insight into the pathophysiology of adverse RV remodeling in rTOF, and form the basis for the development of new therapeutic strategies in these patients.
- © 2011 by American Heart Association, Inc.