Plasma VEGF-D and sFLT-1 are potential biomarkers of hemodynamics and congestion in heart failure and following heart transplantation

Abstract

BackgroundInflammation and tyrosine-kinases are known mediators in the pathobiology of cardiovascular disease. Plasma biomarkers reflecting these systems may provide a non-invasive complement reflecting haemodynamics, aiding in clinical decision-making. We therefore aimed to investigate the plasma levels of vascular and inflammatory proteins, and their associations with invasive haemodynamics in advanced heart failure (HF) before, and at multiple follow-ups after heart transplantation (HT). MethodsUsing multiplex sandwich immunoassays, absolute plasma concentrations of nine vascular and inflammatory proteins were assessed in 26 patients with advanced HF, before-HT, and at four-weeks, six-months, and one-year after-HT. Right heart catheterization (RHC) haemodynamics were assessed at the time of blood sampling. Repeated measures correlations were performed to evaluate the overall intra-individual development of plasma protein levels in relation to haemodynamics’ development over time. ResultsOut of nine proteins included initially, in advanced HF, elevated plasma levels of vascular endothelial growth factor D (VEGF-D) and soluble fms-like tyrosine kinase-1 (sFlt-1) decreased most markedly, at four-weeks (p<0.0001), and decreased further at six-months (p<0.05) and at the one-year follow-ups after-HT (p<0.05). Over time, plasma VEGF-D correlated strongest with haemodynamic parameters including pulmonary arterial wedge pressure (PAWP) (rmr= 0.75, 95% bootstrapped confidence interval (CI) 0.61-0.84, p<0.0001), followed by mean right atrial pressure (MRAP) (rmr= 0.74, 95% CI 0.61-0.82, p<0.0001), and mean pulmonary arterial pressure (mPAP) (rmr= 0.74, 95% CI 0.58-0.82, p<0.0001). Plasma sFlt-1 correlated also with multiple haemodynamic parameters including PAWP (rmr= 0.66, 95% CI 0.58-0.79, p<0.0001), MRAP (rmr= 0.64, 95% CI 0.58-0.81, p<0.0001), and mPAP (rmr= 0.61, 95% CI 0.51-0.76, p<0.0001). ConclusionsIn advanced HF, elevated plasma VEGF-D and sFlt-1 levels decrease early, already within four weeks after HT, and further throughout the first year postoperatively. Our findings support that high plasma VEGF-D and sFlt-1 concentrations before HT are related to congestion, and overall haemodynamic improvement. Plasma VEGF-D and sFlt-1 may consequently be potential non-invasive biomarkers for monitoring hemodynamic deterioration and congestion in HF, and surveillance after HT.