Abstract 13781: The Impact of Mechanical Unloading Through Ventricular Assist Device Placement on Cardiac ST2/IL-33 Signaling in Patients with Advanced Heart Failure
Introduction: Patients with heart failure (HF) experience progressive myocardial remodeling and failure. Circulating levels of soluble ST2 (sST2), a molecular marker of strain, indicate the degree of cardiac volume and pressure load and also predict outcomes and mortality in HF patients. Interleukin (IL)-33 neutralizes circulating sST2 and has been linked to a decrease in myocardial strain. The present study aims to determine if mechanical unloading through left ventricular assist device (LVAD) placement corrects circulating sST2 and IL-33 levels in patients (pts) with advanced HF.
Methods: Blood was obtained from 28 pts with stable HF (mean age: 58.9 yrs, BMI: 29.0 kg/m2), 31 pts with advanced HF before LVAD implantation (age: 52.9 yrs, BMI: 26.6 kg/m2) and 32 pts with advanced HF after LVAD implantation (age: 52.6 yrs, BMI: 26.0 kg/m2). Serum from 17 pts without HF served as controls (age: 42.6 yrs, BMI: 28.1 kg/m2). Clinical data were obtained from institutional medical records. Levels of sST2 and IL-33 were measured by ELISA (MBL, R&D).
Results: sST2 and IL-33 levels were elevated in pts undergoing LVAD implantation relative to stable HF patients and controls (sST2: 1.10 ng/mL vs 0.51 ng/mL and 0.44 ng/mL, p<0.01; IL-33: 0.59 ng/mL vs. 0.14 ng/mL and 0.28 ng/mL, p<0.05). sST2 levels showed correlation with serum BNP levels (r=0.44, p=0.001). Levels of sST2 in pts at LVAD explantation were lower compared to the time of LVAD implantation (0.58±0.28 ng/mL at explantation vs. 1.10±1.20 ng/mL at implantation, p<0.01); there were no significant changes in IL-33. Mean duration of LVAD support was 166±123 days. The IL-33/ST2 ratio was decreased in HF pts compared to controls (0.26 vs. 0.64, p=0.07) and increased in LVAD explant pts relative to implants (1.33 vs. 0.71, p=0.12).
Conclusions: Levels of sST2 correspond to worsening HF disease state, are elevated in advanced HF pts and normalize after mechanical unloading through LVAD placement. Our findings suggest a competitive interplay between IL-33 and sST2 indicated by a decreased IL-33/ST2 ratio in advanced HF pts. Further, the rise in IL-33 relative to sST2 after mechanical unloading may indicate the reversibility of abnormal sST2/IL33 signaling in advanced HF and normalization of cardiac load and ventricular strain.
- © 2011 by American Heart Association, Inc.