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

BACKGROUND

Inflammation and tyrosine-kinases are known mediators in the pathobiology of cardiovascular disease. Plasma biomarkers reflecting these systems may provide a noninvasive complement reflecting hemodynamics, aiding in clinical decision-making. We therefore aimed to investigate the plasma levels of vascular and inflammatory proteins, and their associations with invasive hemodynamics in advanced heart failure (HF) before, and at multiple follow-ups after heart transplantation (HT).

METHODS

Using multiplex sandwich immunoassays, absolute plasma concentrations of 9 vascular and inflammatory proteins were assessed in 26 patients with advanced HF, before HT, and at 4 weeks, 6 months, and 1year after HT. Right heart catheterization hemodynamics 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 hemodynamics' development over time.

RESULTS

Out of 9 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 4 weeks ( < 0.0001), and decreased further at 6 months ( < 0.05) and at the 1 year follow-ups after-HT ( < 0.05). Over time, plasma VEGF-D correlated strongest with hemodynamic parameters including pulmonary arterial wedge pressure (PAWP) ( = 0.75, 95% bootstrapped confidence interval (CI) 0.61-0.84,  < 0.0001), followed by mean right atrial pressure (MRAP) ( = 0.74, 95% CI 0.61-0.82,  < 0.0001), and mean pulmonary arterial pressure (mPAP) ( = 0.74, 95% CI 0.58-0.82,  < 0.0001). Plasma sFlt-1 correlated also with multiple hemodynamic parameters including PAWP ( = 0.66, 95% CI 0.58-0.79,  < 0.0001), MRAP ( = 0.64, 95% CI 0.58-0.81,  < 0.0001), and mPAP ( = 0.61, 95% CI 0.51-0.76,  < 0.0001).

CONCLUSIONS

In advanced HF, elevated plasma VEGF-D and sFlt-1 levels decrease early, already within 4 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 hemodynamic improvement. Plasma VEGF-D and sFlt-1 may consequently be potential noninvasive biomarkers for monitoring hemodynamic deterioration and congestion in HF, and surveillance after HT.