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Bioactive adrenomedullin (bio-ADM) is associated with endothelial dysfunction in infants and children with complex congenital heart disease undergoing open-heart surgery on cardiopulmonary bypass

  • Maike Schaefer , Andreas Stein , Bettina Ruf , Gunter Balling , Jonas Palm ORCID logo , Andreas Simmelbauer , Julie Cleuziou , Michaela Sander , Josef Auer , Kristina Borgmann , Joachim Struck , Oliver Hartmann , Janin Schulte , Jürgen Hörer , Peter Tassani-Prell , Peter Ewert , Stefan Holdenrieder and Cordula M. Wolf ORCID logo EMAIL logo
Published/Copyright: October 24, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 3

Abstract

Objectives

Children with congenital heart disease (CHD) undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at risk for systemic inflammation leading to endothelial dysfunction associated with increased morbidity. Bioactive adrenomedullin (bio-ADM) is a peptide regulating vascular tone and endothelial permeability. The aim of this study was to evaluate the dynamics of plasma bio-ADM in this patient cohort and its role in capillary leak.

Methods

Plasma samples from 73 pediatric CHD patients were collected for bio-ADM measurement at five different timepoints (TP) in the pre-, intra-, and post-operative period. The primary endpoint was a net increase in bio-ADM levels after surgery on CPB. Secondary endpoints included association of bio-ADM levels with clinical signs for endothelial dysfunction.

Results

Bio-ADM levels increased after surgery on CPB from pre-operative median of 12 pg/mL (IQR [interquartile range] 12.0–14.8 pg/mL) to a maximum post-operative median of 48.8 pg/mL (IQR 34.5–69.6 pg/mL, p<0.001). Bio-ADM concentrations correlated positively with post-operative volume balance, (r=0.341; p=0.005), increased demand for vasoactive medication (duration: r=0.415; p<0.001; quantity: TP3: r=0.415, p<0.001; TP4: r=0.414, p<0.001), and hydrocortisone treatment for vasoplegia (bio-ADM median [IQR]:129.1 [55.4–139.2] pg/mL vs. 37.9 [25.2–64.6] pg/mL; p=0.034). Patients who required pleural effusion drainage revealed higher bio-ADM levels compared to those who did not (median [IQR]: 66.4 [55.4–90.9] pg/mL vs. 40.2 [28.2–57.0] pg/mL; p<0.001).

Conclusions

Bio-ADM is elevated in children after cardiac surgery and higher levels correlate with clinical signs of capillary leakage. The peptide should be considered as biomarker for endothelial dysfunction and as potential therapeutic target in this indication.

Keywords: bioactive adrenomedullin; biomarker; capillary leak; cardiopulmonary bypass; congenital heart disease; endothelial dysfunction
Corresponding author: Cordula M. Wolf, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, School of Medicine & Health, Lazarettstr. 36 80636 Munich, Germany; and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany, E-mail:

  1. Research ethics: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board (Ethical Committee of Technical University Munich, protocol number 190/19S-SR from 07/15/2019).

  2. Informed consent: Informed consent was obtained from all individuals included in this study or their legal representatives.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: CMW is a consultant to Adrenomed AG. JSt is employed by Adrenomed AG, a biopharmaceutical company developing Adrecizumab, an anti-Adrenomedullin antibody, as a drug candidate. OHa is employed by SphingoTec GmbH, a biomarker company having patent rights in and commercializing the bio-ADM assay. JSc is employed by SphingoTec GmbH, a biomarker company having patent rights in and commercializing the bio-ADM assay.

  5. Research funding: The study was supported by a sponsored research agreement by Adrenomed AG.

  6. Data availability: The raw data in anonymized form can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0511).

Received: 2023-05-15
Accepted: 2023-10-10
Published Online: 2023-10-24
Published in Print: 2024-02-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-0511
Keywords for this article
bioactive adrenomedullin; biomarker; capillary leak; cardiopulmonary bypass; congenital heart disease; endothelial dysfunction

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Unraveling the mystery of blood groups and COVID-19
  4. Reviews
  5. Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis
  6. Platelet distribution width (PDW) as a significant correlate of COVID-19 infection severity and mortality
  7. Mini Reviews
  8. ABO blood group-related mechanism of infection of SARS-CoV-2: an overview of systematic reviews
  9. Opinion Paper
  10. Personalized laboratory medicine in the digital health era: recent developments and future challenges
  11. Guidelines and Recommendations
  12. Algorithm of differential diagnosis of anemia involving laboratory medicine specialists to advance diagnostic excellence
  13. General Clinical Chemistry and Laboratory Medicine
  14. Rescaling creatinine makes GFR estimation equations generally applicable across populations – validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry
  15. Periodic verification of results’ comparability between several analyzers: experience in the application of the EP31-A-IR guideline
  16. Machine learning to optimize cerebrospinal fluid dilution for analysis of MRZH reaction
  17. Diagnostic performance of automated red cell parameters in predicting bone marrow iron stores
  18. Reliability of hemoglobin A2 value as measured by the Premier Resolution system for screening of β-thalassemia carriers
  19. Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study
  20. Development of high-performance point-of-care aqueous VEGF detection system and proof-of-concept validation in RVO patients
  21. Detection rate of IGF-1 variants and their implication to protein binding: study of over 240,000 patients
  22. Analysis of a second-tier test panel in dried blood spot samples using liquid chromatography-tandem mass spectrometry in Catalonia’s newborn screening programme
  23. Targeted quantitative lipidomic uncovers lipid biomarkers for predicting the presence of compensated cirrhosis and discriminating decompensated cirrhosis from compensated cirrhosis
  24. Reference Values and Biological Variations
  25. Establishment of reference intervals for free light chains and immunoglobulins in Saudi population
  26. Cancer Diagnostics
  27. A predictive and prognostic model for surgical outcome and prognosis in ovarian cancer computed by clinico-pathological and serological parameters (CA125, HE4, mesothelin)
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  31. Infectious Diseases
  32. Monocyte distribution width as an early predictor of short-term outcome in adult patients with sepsis
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