OC 34.1 - Elevated NET biomarkers and reduced DNase 1 activity in patients with a systemic right ventricle

Monday, June 24, 2024

09:30 – 09:45 ICT

Room: Ballroom B4

Presenting Author(s)

Valérie Spalart, MD- PhD candidate

Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences - KU Leuven (Belgium). Department of Cardiology, University Hospitals Leuven, Leuven, Belgium.
Leuven, Vlaams-Brabant, Belgium

Co-Author(s)

AC

Aleksandra Cieplucha

MD
Congenital and Structural Cardiology, University Hospitals Leuven, Leuven, Belgium.
Leuven, Vlaams-Brabant, Belgium
WB

Werner Budts

Professor
Congenital and Structural Cardiology, University Hospitals Leuven, Leuven, Belgium. Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
PD

Pieter De Meester

Professor
Congenital and Structural Cardiology, University Hospitals Leuven, Leuven, Belgium.
Leuven, Vlaams-Brabant, Belgium
ET

Els Troost

MD
Congenital and Structural Cardiology, University Hospitals Leuven, Leuven, Belgium.
Leuven, Vlaams-Brabant, Belgium
WD

Walter Droogne

MD
Department of Cardiology, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
LV

Lucas Van Aelst

Professor
Department of Cardiology, University Hospitals Leuven, Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
ML

Magalie Ladouceur

MD-PhD
Department of Cardiology, Medical department, Hôpitaux Universitaires de Genève, 1205 Genève. Centre de Recherche Cardiovasculaire de Paris, INSERM U970, Paris, France.
Geneve, Geneve, Switzerland
TW

Thilo Witsch

MD
Department of Cardiology and Angiology, University Heart Center Freiburg - Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Freiburg, Baden-Wurttemberg, Germany
AV

Alexander Van De Bruaene

Professor
Congenital and Structural Cardiology, University Hospitals Leuven, Leuven, Belgium.
Leuven, Vlaams-Brabant, Belgium
Kimberly Martinod

Assistant Professor
Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences - KU Leuven (Belgium)
Leuven, Vlaams-Brabant, Belgium

Background: Patients with a systemic right ventricle (sRV) are prone to develop heart failure (HF) with poor prognosis due to lack of evidence for classic HF therapies and extensive fibrosis of non-ischemic origin. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of cardiac fibrosis, yet their impact in HF is currently unknown. DNase 1 is an enzyme involved in the extracellular breakdown of NETs and decreased activity in plasma may promote elevated NET levels and immunothrombosis.

Aims: To assess systemic NET levels and DNase 1 activity in patients with a sRV and compare these values to patients with a normal anatomy (systemic left ventricle) and HF (sLV-HF) to gain more insight into the pathophysiology of HF in sRV patients.

Methods: In total, 87 sRV and 40 sLV-HF patients were prospectively enrolled at the outpatient clinic of the University Hospitals Leuven. Additionally, 50 age- and sex-matched healthy controls were included. Citrullinated histone H3-DNA (H3Cit-DNA) and myeloperoxidase-DNA (MPO-DNA) were measured as NET biomarkers in plasma using in-house ELISAs. A kinetic fluorometric assay was used to assess DNase 1 activity. Statistical analysis was performed with Kruskal-Wallis test with post-hoc Dunn’s correction.

Results: NET biomarkers were significantly higher in sRV patients compared to sLV-HF patients and healthy controls: H3Cit-DNA (0.87 vs 0.28 vs 0.611, P< 0.001 and P=0.0162) and MPO-DNA (1.21 vs 0.51 vs 0.84, both P< 0.001). Interestingly, this was independent of HF in sRV. Relative DNase 1 activity was significantly lower in sRV patients compared to healthy controls (0.98 vs 1.20, P=0.04), but not significantly different with sLV-HF patients (0.98 vs 1.12, P=0.12).

Conclusion(s): sRV patients have increased NET biomarkers compared to healthy controls and sLV-HF patients. A decreased DNase 1 activity could be a possible explanation. Further investigation into the potential role of NETs in HF pathophysiology is warranted and could provide novel therapeutic targets.