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Biomarkers of Myocardial Fibrosis: Revealing the Natural History of Fibrogenesis in Fabry Disease Cardiomyopathy

Aguiar, P; Azevedo, O; Pinto, R; Marino, J; Cardoso, C; Sousa, N; Cunha, D; ... Ducla Soares, JL; + view all (2018) Biomarkers of Myocardial Fibrosis: Revealing the Natural History of Fibrogenesis in Fabry Disease Cardiomyopathy. Journal of the American Heart Association , 7 (6) 10.1161/JAHA.117.007124. Green open access

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Abstract

BACKGROUND: Cardiomyopathy is a major determinant of overall Fabry disease (FD) prognosis, with the worst outcomes in patients with myocardial fibrosis. Late gadolinium enhancement is currently the gold standard for evaluation of replacement myocardial fibrosis; however, this event is irreversible, thus identification of biomarkers of earlier diffuse fibrosis is paramount. METHODS AND RESULTS: Type I collagen synthesis and degradation biomarkers (PICP [carboxyterminal propeptide of procollagen type I], ICTP [carboxyterminal telopeptide of type I collagen], and MMP1 [matrix metalloproteinase 1] and MMP2) and markers of bone synthesis and degradation were evaluated (to adjust type I collagen metabolism to bone turnover) in FD patients and controls. FD patients were grouped by cardiomyopathy severity, according to echocardiogram: (1) normal, (2) tissue Doppler abnormalities, (3) left ventricular hypertrophy. A significant increase in PICP and a significant decrease in matrix metalloproteinases were observed in FD patients; even the group with normal echocardiogram had a significant increase in PICP. We also found a significant correlation between left ventricular mass and PICP (ρ=0.378,P=0.003) and MMP1 (ρ=-0.484,P<0.001). PICP (adjusted for bone turnover) was the better predictor of left ventricular mass in multivariable regression, and its diagnostic accuracy to predict late gadolinium enhancement was also significant. CONCLUSIONS: Collagen type I synthesis is increased in FD cardiomyopathy, even in the earlier stages of the disease, and this profibrotic state has good predictive value for and is likely to be critical to the development of overt left ventricular hypertrophy. Moreover, inhibition of enzymes involved in collagen type I cleavage also seems crucial to myocardial collagen deposition.

Type: Article
Title: Biomarkers of Myocardial Fibrosis: Revealing the Natural History of Fibrogenesis in Fabry Disease Cardiomyopathy
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/JAHA.117.007124
Publisher version: http://doi.org/10.1161/JAHA.117.007124
Language: English
Additional information: Copyright © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifications or adaptations are made.
Keywords: Fabry disease cardiomyopathy, biomarkers, carboxyterminal propeptide of procollagen type I, cardiac fibrosis, matrix metalloproteinases
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10045974
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