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

Ahmed, Salaheldin LU orcid ; Lundgren, Jakob LU ; Ahmed, Abdulla LU orcid and Rådegran, Göran LU (2023) In JHLT Open 2.
Abstract
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... (More)
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 (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).

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. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JHLT Open
volume
2
article number
100013
publisher
Elsevier
ISSN
2950-1334
DOI
10.1016/j.jhlto.2023.100013
language
English
LU publication?
yes
id
f416e6c2-d8f7-4d3c-aacd-82253452c930
date added to LUP
2025-03-26 14:10:14
date last changed
2025-04-04 14:12:55
@article{f416e6c2-d8f7-4d3c-aacd-82253452c930,
  abstract     = {{Background<br/>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).<br/><br/>Methods<br/>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.<br/><br/>Results<br/>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 &lt; 0.0001), and decreased further at 6 months (p &lt; 0.05) and at the 1 year follow-ups after-HT (p &lt; 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 &lt; 0.0001), followed by mean right atrial pressure (MRAP) (rmr = 0.74, 95% CI 0.61-0.82, p &lt; 0.0001), and mean pulmonary arterial pressure (mPAP) (rmr = 0.74, 95% CI 0.58-0.82, p &lt; 0.0001). Plasma sFlt-1 correlated also with multiple hemodynamic parameters including PAWP (rmr = 0.66, 95% CI 0.58-0.79, p &lt; 0.0001), MRAP (rmr = 0.64, 95% CI 0.58-0.81, p &lt; 0.0001), and mPAP (rmr = 0.61, 95% CI 0.51-0.76, p &lt; 0.0001).<br/><br/>Conclusions<br/>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.}},
  author       = {{Ahmed, Salaheldin and Lundgren, Jakob and Ahmed, Abdulla and Rådegran, Göran}},
  issn         = {{2950-1334}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{Elsevier}},
  series       = {{JHLT Open}},
  title        = {{Plasma VEGF-D and sFLT-1 are potential biomarkers of hemodynamics and congestion in heart failure and following heart transplantation}},
  url          = {{http://dx.doi.org/10.1016/j.jhlto.2023.100013}},
  doi          = {{10.1016/j.jhlto.2023.100013}},
  volume       = {{2}},
  year         = {{2023}},
}