Abstract 12653: Plasma LTBP-2 is Associated With Myocardial LTBP-2 and Poor Prognosis in Dilated Cardiomyopathy

Abstract

Introduction: Cardiac extracellular matrix proteins provide structural support to the heart function and are associated with fibrosis in dilated cardiomyopathy (DCM). Latent transforming growth factor beta-binding protein 2 (LTBP-2) is a type of extracellular matrix protein, but the significance of LTBP-2 in patients with dilated cardiomyopathy is still unclear. Objective: To elucidate the significance of LTBP-2 in dilated cardiomyopathy. Methods: Plasma LTBP-2 levels were measured by Enzyme-linked immunosorbent assay in 131 DCM patients who underwent endomyocardial biopsy and 44 controls who had no history of cardiac diseases. Immunohistochemistry for LTBP-2, LTBP-1 (another LTBP family member), and Elastica-Masson staining were performed in endomyocardial biopsy specimens. DCM patients were followed up for cardiac death or ventricular assist device (VAD) implantation. Results: DCM patients had elevated plasma LTBP-2 levels compared to controls (104 vs. 57 ng/mL, P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen (R = 0.311, P < 0.001). Myocardial LTBP-2-positive fraction was positively correlated with myocardial LTBP-1-positive fraction (R = 0.444, P = 0.014) and fibrosis fraction estimated by Elastica-Masson staining (R = 0.387, P < 0.001). In the Kaplan-Meier analysis, the high plasma LTBP-2 concentration group and the high myocardial LTBP-2-positive fraction group had more cardiac deaths or VAD implantations than low groups (P = 0.008 and P < 0.001, respectively). Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with cardiac death or VAD implantation. Conclusion: Plasma LTBP-2 reflects myocardial LTBP-2 and can be a biomarker to predict adverse outcomes in DCM patients.