Evaluating the Utility of Circulating Biomarkers of Collagen Synthesis in Hypertrophic Cardiomyopathy
Background—In hypertrophic cardiomyopathy (HCM), accumulation of myocardial collagen may play a central role in the pathogenesis of diastolic dysfunction and arrhythmia. Previous studies have suggested that peripheral levels of byproducts of collagen synthesis are reflective of myocardial extracellular matrix metabolism although this has not been validated in detail. Given the potential clinical utility of such biomarkers, we sought to validate the assumed relationship between peripheral markers and myocardial fibrosis in HCM.
Methods and Results—Fifty patients with HCM and twenty-five healthy control subjects underwent peripheral venous sampling to determine the plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance (CMR) imaging was performed to quantify regional (by late gadolinium enhancement [LGE]) and diffuse (by T1 mapping) myocardial fibrosis. Nineteen subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac concentration gradients of PINP, PIIINP and C-terminal telopeptide of type I collagen [ICTP]) and right heart catheterization. Despite CMR evidence of regional (LGE quantity: 6.4±8.0%) and diffuse (T1 time: 478±79 ms) myocardial fibrosis 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 μg/L, p=0.26). No significant net positive transcardiac concentration gradient was detected for either biomarker of collagen synthesis.
Conclusions—The cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM is insignificant. Furthermore, peripheral levels of these biomarkers do not accurately reflect myocardial collagen content in these patients.
- coronary sinus sampling
- procollagen propeptides
- hypertrophic cardiomyopathy
- myocardial fibrosis
- cardiac magnetic resonance imaging
- Received July 24, 2013.
- Accepted January 23, 2014.