TY - JOUR
T1 - Biomarkers of Collagen Metabolism Are Associated with Left Ventricular Function and Prognosis in Dilated Cardiomyopathy
T2 - A Multi-Modal Study
AU - Raafs, Anne G.
AU - Adriaans, Bouke P.
AU - Henkens, Michiel T.H.M.
AU - Verdonschot, Job A.J.
AU - Abdul Hamid, Myrurgia A.
AU - Díez, Javier
AU - Knackstedt, Christian
AU - van Empel, Vanessa P.M.
AU - Brunner-La Rocca, Hans Peter
AU - González, Arantxa
AU - Wildberger, Joachim E.
AU - Heymans, Stephane R.B.
AU - Hazebroek, Mark R.
N1 - Funding Information:
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]).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - 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.
AB - 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.
KW - cardiovascular magnetic resonance
KW - CITP/MMP-1
KW - dilated cardiomyopathy
KW - feature tracking
KW - fibrosis
KW - global longitudinal strain
U2 - 10.3390/jcm12175695
DO - 10.3390/jcm12175695
M3 - Article
SN - 2077-0383
VL - 12
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 17
M1 - 5695
ER -