Abstract 11580: A Remodeling Paradox? Circulating Concentrations of the Novel Biomarker Mimecan Predict Both Adverse Events and Favorable Reverse Ventricular Remodeling in Chronic Heart Failure
Introduction: Myocardial remodeling is a pivotal aspect of the progression and complications of chronic heart failure (HF). Mimecan is a proteoglycan that has been associated with cardiac remodeling in basic science models.
Hypothesis: We assessed the hypothesis that mimecan concentrations predict clinical outcomes and ventricular remodeling in patients with HF due to left ventricular systolic dysfunction (LVSD).
Methods: A total of 142 subjects were followed through 882 visits over 10 ± 3 months. Mimecan values were considered across study visits, and used to assess risk for adverse cardiovascular (CV) events and LV remodeling.
Results: Median mimecan values at 9 months of follow up were higher in patients with CV events than in those without CV events (51.2 vs. 37.8 ng/mL, p = 0.02), with comparable trends noted at baseline, 3 months, 6 months and 12 months. Baseline elevated mimecan level was significantly associated with shorter time to first event (p < 0.001); those subjects with elevated mimecan concentrations across study visits had the highest CV event rate (65%) and were less likely to show favorable reverse LV remodeling. Conversely, rise in mimecan concentration from an initially low value was associated with significantly lower event rates (11.5%; p < 0.001), as well as greater decrease in LV end diastolic (p = 0.07) and systolic (p = 0.01) volume indices, and greater increase in LV ejection fraction (p = 0.02) (Figure, A). Changes in remodeling parameters were proportional to the magnitude of rise in mimecan concentration (Figure, B).
Conclusions: In chronic LVSD, mimecan concentrations predict outcomes and LV remodeling. While constitutive elevation of mimecan is associated with adverse outcome and less reverse remodeling, a rising mimecan paradoxically is associated with improved outcome and favorable reverse LV remodeling. These data suggest that mimecan expression represents an adaptive anti-remodeling response, whose benefits may wane over time.
- © 2013 by American Heart Association, Inc.