Release of growth-differentiation factor 15 and associations with cardiac function in adult patients with congenital heart disease

Int J Cardiol. 2016 Jan 1:202:246-51. doi: 10.1016/j.ijcard.2015.09.010. Epub 2015 Sep 14.

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.

Keywords: Adult congenital heart disease; Echocardiography; Growth differentiation factor 15; Ventricular function.

MeSH terms

  • Adult
  • Disease Progression
  • Echocardiography
  • Electrocardiography
  • Exercise Test
  • Exercise Tolerance / physiology*
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factor 15 / blood*
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Male
  • Pulmonary Wedge Pressure / physiology*
  • Retrospective Studies
  • Severity of Illness Index
  • Ventricular Function / physiology*

Substances

  • Growth Differentiation Factor 15