Collagen turnover biomarkers and systemic right ventricle remodeling in adults with previous atrial switch procedure for transposition of the great arteries.

Abstract

Myocardial fibrosis is a potential pathophysiological mechanism leading to systemic right ventricular (SRV) deterioration. We hypothesize that circulating levels of collagen deposition markers are elevated in patients with SRV remodeling and this elevation may have a predictive value.We prospectively evaluated 56 patients with D-TGA after the atrial switch procedure (mean age 25.6 ± 4.8, range 18-37 years; 67% males). Serum levels of procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy-terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP), matrix metalloproteinase (MMP 1, MMP 9) and a tissue inhibitor of matrix metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured and compared with healthy controls. The relationship between these serum markers, echocardiographic and cardiac magnetic resonance parameters and the outcome at a follow-up of 61 months (range, 24-85 months) was determined.Compared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP (p<0.05, each). The levels of PIIINP and CITP were significantly higher among patients with an SRV mass index above the mean value. The level of PIIINP was significantly higher among patients with an SRV EDV index above the mean value. CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an adverse clinical outcome on univariate Cox proportional hazard survival analysis in addition to well proven predictors of outcome (SRV EF and NYHA).We demonstrated a pattern of altered collagen turnover adversely related with the indices of SRV remodeling and an adverse clinical outcome in patients with SRV.