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.


RESULTS
Fifty patients with HCM and 25 healthy controls underwent peripheral venous sampling to determine plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance imaging was performed to quantify regional (by late-gadolinium enhancement) 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) and right heart catheterization. Despite cardiac magnetic resonance evidence of regional (late-gadolinium enhancement quantity, 6.4±8.0%) and diffuse (T1 time, 478±79 ms) myocardial fibrosis in patients with HCM, peripheral levels of collagen precursors were similar compared with control subjects (PINP, 45.9±22.9 versus 53.4±25.9 μg/L; P=0.21; PIIINP, 4.8±1.7 versus 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.
Heart Centre, Alfred Hospital, Melbourne, Australia.
Andris H
AH
Ellims
Andrew J
AJ
Taylor
Justin A
JA
Mariani
Liang-Han
LH
Ling
Leah M
LM
Iles
Micha T
MT
Maeder
David M
DM
Kaye
D015415:Biomarkers / Q000097:blood*; D006328:Cardiac Catheterization; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D003094:Collagen / Q000096:biosynthesis*; D004452:Echocardiography; D005260:Female; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011863:Radioimmunoassay; D012720:Severity of Illness Index; D016277:Ventricular Function, Left / Q000502:physiology
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen
cardiomyopathy, hypertrophic; collagen; endomyocardial fibrosis; magnetic resonance imaging