Abstract
BACKGROUND: Plasma concentrations of procollagen type-I C-terminal pro-peptide (PICP) and collagen type-I C-terminal telopeptide (CITP) may reflect collagen turnover and systemic fibrosis. We investigated the effect of pirfenidone, an anti-fibrotic agent, on PICP and CITP, and their association with myocardial fibrosis, using cardiovascular magnetic resonance to measure extracellular volume (ECV). METHODS: In the trial (Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction), PICP, CITP and PICP:CITP ratio were measured at baseline and follow-up in patients with ECV≥27% randomised (n=94) to pirfenidone or placebo, and at baseline only in patients who were not randomised because of ECV<27% (n=13). RESULTS: There was no association between baseline myocardial ECV and baseline log PICP, log CITP and log PICP:CITP ratio (p=0.19, p=0.13, p=0.60, respectively). Treatment with pirfenidone did not alter PICP, but reduced CITP and increased PICP:CITP ratio at 13 and 26 weeks (all p<0.05) but not at 52 weeks. After multivariable adjustment, there was a weak relationship between change in myocardial ECV and change in log PICP (R(2) 0.16, p=0.01) and log CITP (R(2) 0.12, p=0.04), but not log PICP:CITP ratio (p=0.56). CONCLUSIONS: In patients with stable heart failure with preserved ejection fraction, pirfenidone treatment had no sustained effect on plasma levels of PICP and CITP at 52 weeks. Changes in ECV during treatment with pirfenidone are associated with changes in plasma PICP and CITP, suggesting a weak association between changes in collagen volume/mass and plasma markers of collagen turnover.