Abstract 16662: GDF-15: Association With Pulmonary Hemodynamic Indices and Reduction With Serelaxin in Acute Heart Failure
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.
Author Disclosures: M.F. Prescott: Employment; Significant; employee Novartis Pharma. Ownership Interest; Significant; stock in Novartis as part of compensation. P. Ponikowski: Research Grant; Modest; received research grant from Vifor Pharma Ltd. Honoraria; Modest; received honoraria from Vifor Pharma Ltd, Amgen, Servier, Novartis, Bayer, Pfizer, Merck-Serono, Berlin-Chemie, Pfizer, Abbott Vascular, Coridea and Respicardia. Consultant/Advisory Board; Modest; Served on advisory boards for Vifor Pharma Ltd, Amgen, Servier, Novartis, Bayer, Abbott Vascular, Coridea and Respicardia. Other; Modest; Member of the Executive Committee of the Novartis RELAX AHF studies. V. Mitrovic: Other Research Support; Modest; VM has received research support from Bayer and Novartis. Honoraria; Modest; VM has received honoraria from Bayer, Novartis and GlaxoSmithKline. Consultant/Advisory Board; Modest; VM has provided consultancy to Cardiorentis, and board member of DAIICHI Sankyo. M. Ruda: Other Research Support; Modest; Pricincipal investigator for Novartis clinical trial. A. Fernandez: Other Research Support; Modest; Principqal investigator for Novartis, Sanofi, Jannsen, Astra Zeneca and Servier clinical trials. Speakers Bureau; Modest; Served as a speaker for Jansen. A.A. Voors: Research Grant; Modest; AAV received consultancy fees and/or research grants from: Alere, AstraZeneca, Bayer, Cardio3Biosciences, Celladon, Merck/MSD, Novartis, Servier, Torrent, Trevena, Vifor.. Other Research Support; Modest; AAV is supported by a grant from the European Commission: FP7-242209-BIOSTAT-CHF and • AAV is Clinical Established Investigator and by other grants of the Dutch Heart Foundation. Consultant/Advisory Board; Modest; Received consultancy fees and/or research grants from: Alere, AstraZeneca, Bayer, Cardio3Biosciences, Celladon, Merck/MSD, Novartis, Servier, Torrent, Trevena, Vifor. M. Metra: Speakers Bureau; Modest; MM has served as a speaker for Novartis. Honoraria; Modest; MM received honoraria from Bayer, Novartis, Servier as member or chair of committees involved in clinical trials. Consultant/Advisory Board; Modest; MM has received consultancy fees from Mast- therapeutics and Stealth Peptides.. Other; Modest; MM is a Co-Chair of the Executive Committee of the Novartis RELAX AHF studies. G. Cotter: Employment; Modest; GD is an employee of Momentum Research Inc (MRI). Research Grant; Modest; MRI has received research grants from non-for-profit-non governmental organizations and NIH. Consultant/Advisory Board; Modest; MRI received compensation for coordinating research activities or participated in designing AHF programs for Merck & Co, Corthera, Novartis, Nile, Travena, Cardio3, Sorbent, Amgen/Cytokinetics, Chan. Other; Modest; GD is a member of the Executive Committee of the Novartis RELAX AHF studies. Y. Zhang: Employment; Significant; YZ is an employee of Novartis. M. Dahlke: Employment; Significant; MD is an employee of Novartis.
- © 2014 by American Heart Association, Inc.