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.This study has been supported by an investigator-initiated research grant from Shire Pharmaceuticals. The funder did not have a role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.info:eu-repo/semantics/publishedVersio

Aguiar, Patrício

Azevedo, Olga

Cardoso, Carlos

Cunha, Damião

Ducla Soares, José Luís

Hughes, Derralynn

Marino, Jacira

Pinto, Rui

Sousa, Nuno

Journal of the American Heart Association

English

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

Aguiar, P

Azevedo, O

Pinto, R

Marino, J

Cardoso, C

Sousa, N

Cunha, D

Hughes, D

Ducla Soares, JL

UCL Discovery

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


            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
              MMP
              1 (ρ=−0.484,
              P
              &lt;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.
            
          </jats:sec

Patrício Aguiar

Olga Azevedo

Rui Pinto

Jacira Marino

Carlos Cardoso

Nuno Sousa

Damião Cunha

Derralynn Hughes

José Luís Ducla Soares

Crossref

Universidade do Minho: RepositoriUM

Biomarkers of myocardial fibrosis: Revealing the natural history of fibrogenesis in fabry disease cardiomyopathy

http://discovery.ucl.ac.uk/10045974/1/e007124.full.pdf

Biomarkers of myocardial fibrosis: Revealing the natural history of fibrogenesis in fabry disease cardiomyopathy

Abstract

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UCL Discovery

Crossref

Universidade do Minho: RepositoriUM