title: Release of growth-differentiation factor 15 and associations with cardiac function in adult patients with congenital heart disease.
abstract: BACKGROUND
  Growth-differentiation factor-15 (GDF-15), a cytokine with broad cardiac and non-cardiac activity, has diagnostic and prognostic value in various diseases, including heart failure. We aimed to investigate the release of GDF-15 in adults with congenital heart disease (ConHD), and assess the association with cardiac function and functional capacity.
  
  
  METHODS
  A total of 587 consecutive adults with ConHD (median age 33 [IQR 25-41] years, 59% men, and 90% NYHA I) underwent electrocardiography, echocardiography, venepuncture and were seen by a cardiologist. A subset of 143 patients underwent bicycle ergometry on the same day.
  
  
  RESULTS
  Median plasma GDF-15 was 618 [IQR 487-867] ng/L. In 87 patients (15%), GDF-15 was above the reference value of normal (1109 ng/L). GDF-15 levels were higher in older patients (r=0.367, p<0.001). GDF-15 was higher in patients with elevated pulmonary pressure (median 1114 [IQR 796-2320 ng/L) than in patients with normal pulmonary pressure (median 606 [IQR 481-826] ng/L, p<0.001). GDF-15 correlated positively with NT-proBNP (r=0.445, p<0.001). In multivariate analysis adjusting for age, sex, and NT-proBNP, hs-TnT and hs-CRP, GDF-15 above the reference value was associated with NYHA class (odds ratio for NYHA≥II: 3.5 [95% CI 1.8-6.8], p<0.001), and decreased exercise capacity (odds ratio for workload >85%:0.2 [95% CI 0.06-0.8], p=0.018), but not with systolic ventricular function or ECG rhythm.
  
  
  CONCLUSIONS
  GDF-15 is elevated in a substantial number of patients and higher in those with elevated pulmonary pressures, regardless of underlying congenital diagnosis. GDF-15 is associated with NYHA class, NT-proBNP and exercise capacity, suggesting the marker has diagnostic and potential prognostic value in adults with ConHD.
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Eindhoven
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: A E
authors.initials: AE
authors.lastname: van den Bosch
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Oemrawsingh
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: V J
authors.initials: VJ
authors.lastname: Baggen
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Kardys
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Cuypers
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Witsenburg
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: van Schaik
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands. Electronic address: j.roos@erasmusmc.nl.
authors.forename: J W
authors.initials: JW
authors.lastname: Roos-Hesselink
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Boersma
mesh_terms: D000328:Adult; D018450:Disease Progression; D004452:Echocardiography; D004562:Electrocardiography; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006330:Heart Defects, Congenital / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D008297:Male; D011669:Pulmonary Wedge Pressure / Q000502:physiology*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016276:Ventricular Function / Q000502:physiology*
chemical_list: D055436:Growth Differentiation Factor 15
keywords: Adult congenital heart disease; Echocardiography; Growth differentiation factor 15; Ventricular function