Circulating levels of biomarkers of collagen synthesis correlate with left ventricular mechanical dyssynchrony in adolescents after repair of tetralogy of fallot

Abstract

BACKGROUND: Abnormal remodelling of myocardial architecture may potentially lead to alteration of ventricular function in patients after repair of tetralogy of Fallot (TOF). Circulating carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) are candidate biomarkers of myocardial collagen synthesis. OBJECTIVE: We tested the hypothesis that circulating levels of PICP and PIIINP may correlate with ventricular function and synchronicity of ventricular contraction in adolescents after TOF repair. METHODS: Right ventricular (RV) and left ventricular (LV) function and LV mechanical dyssynchrony were assessed by tissue Doppler and 3-dimensional echocardiography in 18 postoperative TOF patients aged 14.5±2.2 years and 11 age-matched controls. Serum PICP and plasma PIIINP levels were determined and correlated with indices of ventricular function and LV systolic dyssynchrony index (SDI). RESULTS: Compared with control, patients had significantly higher circulating PICP (482±194 μg/l vs 313±119 μg/l, p=0.015) and PIIINP (11.4±5.22 μg/l vs 7.6±3.19 μg/l, p=0.04) levels, greater RV end diastolic volume (p=0.013) with increased LV eccentricity (p<0.001), decreased RV ejection fraction (p=0.042), reduced RV IVA (p<0.001), reduced LV IVA (p=0.003), and worse LV SDI (p<0.001). Circulating PICP and PIIINP levels correlated with age (r=-0.44, p=0.016 and r=-0.58, p=0.001, respectively), body mass index (r=-0.43, p=0.019 and r=-0.50, p=0.006, respectively), and LV SDI (r=0.61, p=0.001 and r=0.47, p=0.014, respectively). Additionally, PICP levels correlated negatively with LV IVA (r=-0.42, p=0.025). Multiple linear regression analysis identified LV SDI as a significant independent correlate of circulating levels of PICP (β=0.46, p=0.021) and PIIINP (β=0.36, p=0.034) after adjustment for age and body mass index. CONCLUSION: Circulating levels of PICP and PIIINP correlate positively with LV mechanical dyssynchrony in adolescent patients after TOF repair, implicating a possible role of increased collagen synthesis in the pathogenesis of dyssynchronous LV contraction.