Abstract 10910: The Role of Extracellular Matrix Biomarkers in Phenotypes of Subclinical Heart Failure

Abstract

Introduction: The extracellular matrix (ECM) plays a pivotal role in the development of heart failure (HF). Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are key regulators of collagen turnover; several MMP and TIMP enzymes are associated with fibrosis and clinical HF. Hypothesis: This study compared ECM biomarkers with clinical biomarkers of cardiac function (N-terminal pro-brain natriuretic peptide [NTpBNP] and troponin-T [tropT]) in subclinical HF. Methods: 316 asymptomatic patients (71±5 years; 58% female) with at least one HF risk factor (hypertension, obesity, type 2 diabetes mellitus) from two community-based populations underwent a comprehensive echo, including global longitudinal strain (GLS), diastolic function (annular velocity [e’]) and LV geometry (LV mass index [LVMi], relative wall thickness [RWT]). ECM was assessed with MMP-2 and -9, and TIMP-1 and -2. Results: In the cohort, systolic function was preserved (GLS -18.4±3%), myocardial relaxation was slightly reduced (7.8±2cm/s) and LVMi was within normal limits (78.7±19g/m 2 ). Abnormal GLS (>-16%) was associated with elevated TropT ( p =0.007) and NTpBNP ( p =0.008; Table), but no association was found with ECM biomarkers. However, elevated RWT and LVMi were associated with lower MMP-2, MMP-9 and TIMP-1, but not TropT or NTpBNP (Table). In multivariable regression analyses, there were weak negative associations observed between LVMi and MMP-2 (β=-0.05 [95% CI -0.09, -0.02], p =0.003), MMP-9 (β=-0.017 [-0.028, -0.007], p =0.001) and TIMP-1 (β=-0.03 [-0.05, -0.01], p =0.001). However, all ECM biomarkers had poor diagnostic utility in detecting elevated LVMi (AUC MMP-2 61%; MMP-9 58%; TIMP-1 61%). Similar trends were observed with RWT (AUC MMP-2 58%; MMP-9 64%; TIMP-1 61%). Conclusions: Although ECM biomarkers are associated mechanistically with cardiac remodelling, they lack clinical utility in recognition of subclinical HF.