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

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...

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Veröffentlicht in:Journal of clinical medicine 2023-09, Vol.12 (17), p.5695
Hauptverfasser: Raafs, Anne G, Adriaans, Bouke P, Henkens, Michiel T. H. M, Verdonschot, Job A. J, Abdul Hamid, Myrurgia A, Díez, Javier, Knackstedt, Christian, van Empel, Vanessa P. M, Brunner-La Rocca, Hans-Peter, González, Arantxa, Wildberger, Joachim E, Heymans, Stephane R. B, Hazebroek, Mark R
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Sprache:eng
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Zusammenfassung: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.
ISSN:2077-0383
2077-0383
DOI:10.3390/jcm12175695