Biomarkers of Collagen Metabolism Are Associated with Left Ventricular Function and Prognosis in Dilated Cardiomyopathy: A Multi-Modal Study

J Clin Med. 2023 Sep 1;12(17):5695. doi: 10.3390/jcm12175695.

Abstract

Background: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM.

Methods: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5-8).

Results: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = -0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = -0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002-1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004).

Conclusion: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients.

Keywords: CITP/MMP-1; cardiovascular magnetic resonance; dilated cardiomyopathy; feature tracking; fibrosis; global longitudinal strain.

Grants and funding

This work was supported by the Instituto de Salud Carlos III (CIBERCV CB16/11/00483, PI18/01469, and PI21/00946 co-financed by ERDF funds); Kootstra Talented Post-Doctoral Fellowship; and the European Union Commission’s Seventh Framework Program under grant agreement no. 305507 (HOMAGE [Heart OMics in AGEing consortium]).