Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young

Abstract

Hypertrophic cardiomyopathy (HCM) remains the leading cause of sudden cardiac death in the young. Early markers for HCM are important to identify individuals at risk. The aim of this study was to investigate novel serum biomarkers reflecting myocardial remodeling, microfibrosis, and vascular endotheliopathy in the early stages of familial HCM in young patients. Twenty-three HCM patients, 16 HCM-risk individuals, and 66 controls (median 15 years) underwent echocardiography and serum analysis for cathepsin S, endostatin, myostatin, type I collagen degradation marker (ICTP), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor receptor (VEGFR)-1, and vascular and intercellular adhesion molecules (VCAM, ICAM). In a subset of the population, global myocardial perfusion was performed by magnetic resonance imaging. Cathepsin S (p = 0.0009), endostatin (p < 0.0001), MMP-9 (p = 0.008), and VCAM (p = 0.04) were increased in the HCM group and correlated to left ventricular mass index and mitral E/e′ (p < 0.01). In the HCM-risk group, myostatin was decreased (p = 0.004), whereas ICAM was increased (p = 0.002). Global perfusion was decreased in the HCM group (p < 0.05) versus controls. Endostatin and mitral E/e′ correlated inversely to myocardial perfusion (p ≤ 0.05). This is the first study demonstrating adverse changes in biomarkers reflecting myocardial matrix remodeling, microfibrosis, and vascular endotheliopathy in early stage of hypertrophic cardiomyopathy in the young.

Serum Matrix Metalloproteinases as Quantitative Biomarkers for Myocardial Fibrosis and Sudden Cardiac Death Risk Stratification in Patients With Hypertrophic Cardiomyopathy

“…MMP-9 has previously shown to be associated with LV wall thickness and decreased LVEF in symptomatic HCM (7,8). In patients with myocardial infarction, MMP-9 correlated with LV dysfunction and remodeling, indicating a pivotal role in cardiac fibrosis (9).…”

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

“…Fernandez-Sola et al, demonstrated cardiac myostatin upregulation in hearts with cardiomyopathy of hypertensive, alcoholic, valve and coronary origins [ 172 ]. Furthermore, Fernlund et al, discovered no difference regarding circulating myostatin concentration in the serum of young patients with hypertrophic cardiomyopathy in comparison to healthy controls, despite lower myostatin levels in patients at risk of this disorder, which indicates a potential role of myostatin in the development of hypertrophic cardiomyopathy [ 173 ].…”

Coronary arterial vasculature in the pathophysiology of hypertrophic cardiomyopathy

“…Given these facts, it is of interest to seek evidence for prehypertrophic processes affecting fibrotic and vascular remodeling. Current evidence in humans indicates an early remodeling process with increases in circulating cathepsin S and endostatin correlating with diastolic dysfunction [34]. Others have shown increases in collagen synthesis detected by increased PICP, an unusual finding in a pressure-overloaded system without significant hypertrophy [54].…”