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

TL;DR

VEGF-D and sFlt-1 are potential noninvasive biomarkers for tracking heart failure and recovery after heart transplantation.

Contribution

VEGF-D and sFlt-1 are shown to correlate strongly with hemodynamic changes in heart failure and post-transplant recovery.

Findings

VEGF-D and sFlt-1 levels drop significantly within 4 weeks after heart transplantation.

VEGF-D shows the strongest correlation with pulmonary and right heart pressures in advanced heart failure.

Both biomarkers continue to decrease over the first year post-transplant, reflecting hemodynamic improvement.

Abstract

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).

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.

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 (p < 0.0001), and decreased further at 6 months (p < 0.05) and at the 1 year follow-ups after-HT (p < 0.05). Over time, plasma VEGF-D correlated strongest with hemodynamic 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 hemodynamic 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).

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.

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