Abstract 16662: GDF-15: Association With Pulmonary Hemodynamic Indices and Reduction With Serelaxin in Acute Heart Failure

Abstract

Background: Growth differentiation factor 15 (GDF-15) appears to have a role in regulating inflammation and apoptosis and is up-regulated following injury to the liver, kidney, heart and lung. Elevated baseline (BL) levels of GDF-15 and increases over time have been shown to be associated with adverse events in heart failure (HF). GDF-15 was decreased following LVAD implantation and cardiac unloading in end stage HF. As previously reported, serelaxin improved Pulmonary Capillary Wedge Pressure (PCWP), mean Pulmonary Artery Pressure (mPAP), and Pulmonary Vascular Resistance (PVR) during a 20 h infusion period (all p<0.005 vs. placebo [PBO]). A post-hoc analysis was performed to explore serelaxin effects on GDF-15 in acute HF (AHF) and whether GDF-15 is associated with pulmonary hemodynamics. Methods: Following serelaxin (30 ug/kg/d) or PBO infusion for 20 h in AHF patients, PCWP, mPAP, PVR, NTproBNP (Roche Diagnostics) and GDF-15 (pre-commercial kit, Roche Diagnostics) were measured in 32 serelaxin and 31 PBO treated patients. The effect of serelaxin on GDF-15 and NTproBNP was analyzed and the potential association of GDF-15 or NTproBNP with selected hemodynamic indices was explored combining treatment data from the two treatment arms. Results: Following the 20 h infusion period, serelaxin reduced GDF-15 vs BL (BL median 3192 pg/ml) by 16% (serelaxin vs PBO p=0.021) and reduced NTproBNP (BL median 3262 pg/ml) by 13% (serelaxin vs PBO p=0.021). GDF-15 at BL and 20 h was significantly associated with BL and 20 h NTproBNP (both p<0.001), mPAP (both p<0.025), and PVR (both p<0.001). At 20 h GDF-15 and PCWP were significantly associated (p<0.02) but their association at BL was not statistically significant (p=0.70). The association of NTproBNP at BL and 20 h was not statistically significant for BL or 20 h PCWP, mPAP or PVR (all p >0.05). Conclusions: In this small invasive hemodynamic study in patients with AHF, serelaxin significantly reduced GDF-15 and NTproBNP and had favorable effects on pulmonary hemodynamics. GDF-15 levels at BL and 20 h showed a strong correlation with BL and 20 h values of mPAP and PVR. Additional studies measuring GDF-15 levels in acute HF patients with pulmonary congestion appear warranted.