Evaluating the Utility of Circulating Biomarkers of Collagen Synthesis in Hypertrophic Cardiomyopathy

Study Questions:

What is the relationship between circulating markers of collagen synthesis and myocardial fibrosis in hypertrophic cardiomyopathy (HCM)?

Methods:

The study cohort, comprised of 50 HCM patients and 25 healthy controls, underwent peripheral venous sampling to determine the plasma concentrations of collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Late gadolinium-enhanced (LGE) mapping, with cardiac magnetic resonance (CMR) imaging, was utilized to quantify regional myocardial fibrosis. A total of 19 subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac PINP, telopeptide of type I collagen), and right heart catheterization.

Results:

The investigators reported that despite evidence of regional (LGE quantity: 6.4 ± 8.0%) and diffuse (T1 time: 478 ± 79 ms) myocardial fibrosis, on CMR, in HCM patients, peripheral levels of collagen precursors were similar compared to control subjects (PINP 45.9 ± 22.9 μg/L vs. 53.4 ± 25.9 μg/L, p = 0.21; PIIINP 4.8 ± 1.7 μg/L vs. 4.4 ± 1.1 μ g/L, p = 0.26). They found no significant net positive transcardiac concentration gradient for either biomarker of collagen synthesis.

Conclusions:

The authors concluded that cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM was not insignificant. They also concluded that peripheral levels of biomarkers of collagen synthesis and myocardial fibrosis do not accurately reflect myocardial collagen content in HCM patients.

Perspective:

This is an important study, which suggests that the traditional biomarkers of collagen synthesis and turnover are not good predictors of myocardial fibrosis that occurs in HCM. This study should prompt investigation into novel biomarkers associated with myocardial fibrosis and remodeling, such as ST2 and galectin-3.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging

Keywords: Collagen Type I, Biological Markers, Cardiomyopathy, Hypertrophic, Gadolinium, Magnetic Resonance Imaging, Procollagen


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