Circulating levels of biomarkers of collagen synthesis and ventricular function and dyssynchrony in adolescents and young adults after repair of tetralogy of Fallot

Abstract

BACKGROUND: Circulating carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) are biomarkers of collagen synthesis. We tested the hypothesis that circulating PICP and PIIINP are altered and may correlate with ventricular volume load and function in patients with repaired tetralogy of Fallot (TOF). METHODS AND RESULTS: Serum PICP and plasma PIIINP levels were determined in 39 patients with repaired TOF aged 17.7 +/- 4.1 years and 25 healthy controls and correlated with right ventricular (RV) and left ventricular (LV) volumes, functional indices, and mechanical dyssynchrony as assessed by 3-dimensional and tissue Doppler echocardiography. Compared with controls, patients had significantly higher circulating PICP (P = .016) and PIIINP (P = .008) levels, worse RV function with intra-RV mechanical delay (all P < .001), impaired LV systolic functional indices (all P < .05), and greater LV systolic dyssynchrony index (SDI) (P < .001). For the whole cohort, circulating PICP and PIIINP levels correlated with age (P = .001 and P < .001, respectively), body mass index (P = .033 and P = .012, respectively), LV eccentricity (P = .035 and P = .046, respectively), RV end-diastolic volume (P = .029 and P = .047, respectively), and LV SDI (both P < .001). In addition, PICP levels correlated negatively with RV and LV isovolumic acceleration and RV ejection fraction. Multiple linear regression analysis identified LV SDI as a significant independent correlate of circulating levels of PICP (beta = .31, P = .045) and PIIINP (beta = .37, P = .004). CONCLUSION: Circulating levels of PICP and PIIINP correlate positively with LV mechanical dyssynchrony in patients after TOF repair, implicating a possible role of increased collagen synthesis in its pathogenesis.