Abstract 3158: Changes In Exracellular Matrix Regulation During Episodes Of Clinical Decompensation In Patients With Systolic Heart Failure

Abstract

Introduction: The extracellular matrix (ECM) plays an active role in myocardial remodeling in heart failure (HF). Episodes of decompensation are associated with increased levels of neurohormones, inflammation and oxidative stress that are known to affect ECM regulation, and may contribute to progression of HF. We hypothesized that HF decompensation is associated with dysregulation of ECM turnover, as reflected by markers of degradation (matrix metalloproteinases [MMPs] and their tissue inhibitors [TIMPs]) and synthesis (pro-collagen N-terminal types I [PINP] and III [PIIINP]). Methods: Blood levels of MMP-2 and -9, TIMP-1, -2 and -4, and PI- and PIIINP were measured in 80 patients in 3 groups: 20 controls without HF, 21 patients with chronic stable systolic HF (no recent admission and no congestion by clinical examination), and 39 patients with acute HF decompensation, in whom measures were done on admission, at discharge, and chronically at least 2 months later. Results: In chronic stable HF, ECM markers were not increased vs. controls. In contrast, in patients with decompensated HF, MMP-2, TIMP-1 and PIIINP levels were increased (vs. stable HF or controls; Table ), while MMP-9, TIMP-2 and -4 or PINP were unchanged. Likewise, following effective therapy and return to clinical compensation (chronically but not at discharge) MMP-2, TIMP-1 and PIIINP levels returned to chronic stable HF levels, whereas MMP-9, TIMP-2 and -4 or PINP remained unchanged. Conclusion: A transient ECM dysregulation occurs during acute episodes of HF decompensation and may contribute to adverse ventricular remodeling. While HF decompensation is associated with certain markers of degradation and synthesis (MMP-2, TIMP-1 and PIIINP), other markers (MMP-9, TIMP-2 and -4 or PINP) are unchanged, suggesting selective pattern of ECM activation. The observation that matrix turnover is increased in decompensated but not stable HF may have implication for the timing of anti-remodeling therapy. ECM markers in controls, stable and decompensated HF