title: Diagnostic performance and reference values of novel biomarkers of paediatric heart failure.
abstract: Biomarkers play a pivotal role in heart failure (HF) management. Reference values and insights from studies in adults cannot be extrapolated to the paediatric population due to important differences in pathophysiology and compensatory reserve. We assessed the diagnostic utility of four novel biomarkers in paediatric HF.
  
  
  
  Midregional (MR) pro-atrial natriuretic peptide (proANP), soluble ST2 (sST2), growth differentiation factor-15 (GDF-15), MR-pro-adrenomedullin (proADM) and N-terminal pro-B natriuretic peptide (NT-proBNP) were measured in 114 patients and 89 controls. HF was defined as the presence of HF symptoms and/or abnormal systolic ventricular function. Receiver-operating characteristics were plotted, and the area under the curve (AUC) was measured. This was repeated for subgroups with cardiomyopathy and congenital heart disease (CHD). Ventricular systolic function was measured by magnetic resonance or echocardiography. Reference values were calculated according to the current guidelines.
  
  
  
  The AUC for diagnosing HF was 0.76 for MR-proANP (CI 0.70 to 0.84) and 0.82 for NT-proBNP (CI 0.75 to 0.88). These parameters performed similarly in the subgroups with CHD and cardiomyopathy. By contrast, MR-proADM, GDF-15 and sST2 performed poorly. When used in conjunction with NT-proBNP, no parameter added significantly to its diagnostic accuracy. NT-proBNP, MR-proANP, GDF-15 and sST2 could accurately discriminate between patients with preserved and patients with poor functional status. In a subset of patients with dilated cardiomyopathy, NT-proBNP, MR-proANP, MR-proADM and GDF-15 were associated with poor LV function.
  
  
  
  MR-proANP could accurately detect HF in children and adolescents. Its diagnostic performance was comparable with that of NT-proBNP, regardless of the underlying condition. Reference values are presented.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Paediatric Cardiology, Medical University of Vienna, Vienna, Austria University College London, Institute of Cardiovascular Science, Centre for Cardiovascular Imaging, London, UK Cardiorespiratory Division, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Jakob A
authors.initials: JA
authors.lastname: Hauser
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Demyanets
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Paediatric Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Rusai
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Paediatric Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Clara
authors.initials: C
authors.lastname: Goritschan
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.affiliation: University College London, Institute of Cardiovascular Science, Centre for Cardiovascular Imaging, London, UK Cardiorespiratory Division, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Dilveer
authors.initials: D
authors.lastname: Panesar
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Paediatric Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rindler
authors.affiliation: University College London, Institute of Cardiovascular Science, Centre for Cardiovascular Imaging, London, UK Cardiorespiratory Division, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Taylor
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Rodrig
authors.initials: R
authors.lastname: Marculescu
authors.affiliation: Cardiorespiratory Division, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Burch
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria Medical University of Vienna, Core Facilities, Vienna, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Paediatric Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ina
authors.initials: I
authors.lastname: Michel-Behnke
mesh_terms: D000293:Adolescent; D053607:Adrenomedullin / Q000097:blood*; D000367:Age Factors; D019540:Area Under Curve; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001317:Austria; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D012016:Reference Values; D015203:Reproducibility of Results; D006113:United Kingdom; D055815:Young Adult
chemical_list: C507862:ADM protein, human; D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); C088633:proadrenomedullin; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor