The Present and Future
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Circulating Biomarkers of Myocardial Fibrosis: The Need for a Reappraisal

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Abstract

Myocardial fibrosis impairs cardiac function, in addition to facilitating arrhythmias and ischemia, and thus influences the evolution and outcome of cardiac diseases. Its assessment is therefore clinically relevant. Although tissue biopsy is the gold standard for the diagnosis of myocardial fibrosis, a number of circulating biomarkers have been proposed for the noninvasive assessment of this lesion. A review of the published clinical data available on these biomarkers shows that most of them lack proof that they actually reflect the myocardial accumulation of fibrous tissue. In this “call to action” article, we propose that this absence of proof may lead to misinterpretations when considering the incremental value provided by the biomarkers with respect to traditional diagnostic tools in the clinical handling of patients. We thus argue that strategies are needed to more strictly validate whether a given circulating biomarker actually reflects histologically proven myocardial fibrosis before it is applied clinically.

Key Words

biomarker
collagen
endomyocardial biopsy
fibrosis
heart failure

Abbreviations and Acronyms

CIVF
myocardial collagen type I volume fraction
CIIIVF
myocardial collagen type III volume fraction
CVF
collagen volume fraction
DCM
dilated cardiomyopathy
HF
heart failure
HHD
hypertensive heart disease
LV
left ventricular
LVAD
left ventricular assist device
MMP
matrix metalloproteinase
PICP
carboxy-terminal propeptide of procollagen type I
PIIINP
amino-terminal propeptide of procollagen type III
TGF
transforming growth factor

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This work was funded through the Ministry of Economy and Competitiveness, Spain (Instituto de Salud Carlos III grant RD12/0042/0009), and the European Commission FP7 Programme (MEDIA project grant FP7-HEALTH-2010-261409, EU-MASCARA project grant FP7-HEALTH-2011-278249, HOMAGE project grant FP7-HEALTH-2012-305507, and FIBRO-TARGETS project grant FP7-HEALTH-2013-602904). Dr. González is the recipient of a Ramón y Cajal contract from the Ministry of Economy and Competitiveness, Spain (RYC-2010-05797). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.