Effect of pirfenidone on plasma markers of collagen turnover in patients with heart failure, preserved left ventricular ejection fraction and myocardial fibrosis.

Black, Nicholas ORCID: 0000-0002-0089-6180, Lewis, Gavin, Soltani, Fardad ORCID: 0000-0003-2030-9761, Dodd, Susanna ORCID: 0000-0003-2851-3337, Schelbert, Erik B, Ravassa, Susana, López, Begoña, González, Arantxa ORCID: 0000-0001-5986-6528, Cleland, John G ORCID: 0000-0002-1471-7016 and Miller, Christopher A (2026) Effect of pirfenidone on plasma markers of collagen turnover in patients with heart failure, preserved left ventricular ejection fraction and myocardial fibrosis. Open heart, 13 (1). e003596-. ISSN 2053-3624, 2053-3624

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Abstract

<h4>Background</h4>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).<h4>Methods</h4>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).<h4>Results</h4>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 (R² 0.16, p=0.01) and log CITP (R² 0.12, p=0.04), but not log PICP:CITP ratio (p=0.56).<h4>Conclusions</h4>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.

Item Type:	Article
Uncontrolled Keywords:	Myocardium, Humans, Fibrosis, Pyridones, Collagen Type I, Peptides, Peptide Fragments, Procollagen, Magnetic Resonance Imaging, Cine, Stroke Volume, Treatment Outcome, Double-Blind Method, Ventricular Function, Left, Ventricular Remodeling, Time Factors, Aged, Middle Aged, Female, Male, Heart Failure, Biomarkers, Antifibrotic Agents
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Population Health Faculty of Health & Life Sciences > Inst. Population Health > Health Data Science Faculty of Health & Life Sciences > Inst. Population Health > Inst. Population Health (T&R Staff)
Depositing User:	Symplectic Admin
Date Deposited:	17 Feb 2026 08:24
Last Modified:	17 Feb 2026 08:24
DOI:	10.1136/openhrt-2025-003596
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3197063
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