Growth differentiation factor 15: an additional diagnostic tool for the risk stratification of developing heart failure in patients with operated congenital heart defects?

Abstract

Background: Many young adults who have congenital heart defects develop heart failure despite corrective surgeries. Growth differentiation factor 15 (GDF-15) has an established role as a marker for risk stratification and mortality both in patients after acute myocardial infarction and in patients with heart failure. Our aim was to establish a role for GDF-15 for monitoring heart failure in operated congenital heart defects (ACHD). This potential biomarker was validated through comparison with maximal oxygen uptake (VO(2max)) and to another biomarker, N-terminal pro-brain natriuretic peptide (NT-proBNP).

Methods: A total of 317 ACHD patients (129 females) with an average age of 26.5 ± 8.5 years (mean ± SD) enrolled in the study. We studied the relation between GDF-15 and NT-proBNP and VO(2max%) (percent predicted for age and gender). The cutoffs for the groups were as follows: NT-proBNP <100, 100 to 300, and >300 pg/mL; VO(2max%) <65%, 65% to 85%, and >85% of predicted normal.

Results: Significant differences in mean GDF-15 levels were found between the NT-proBNP <100 and NT-proBNP >300 groups, as well as between the 100 to 300 and the >300 groups. For VO(2max%), significant differences were found in GDF-15 levels between <65% and >85% and between <65% and 65% to 85%, respectively. The lowest mean GDF-15 was found in groups with NT-proBNP <100 pg/mL and VO(2max%) >85%. The highest mean GDF-15 was found in the groups with NT-proBNP >300 pg/mL and VO(2max%) <65%. A subgroup analysis, including 82 patients with operated tetralogy of Fallot, showed that patients in the New York Heart Association I class have significantly lower NT-proBNP and GDF-15 level and markedly higher VO(2max) compared with the patients in higher New York Heart Association class.

Conclusion: Growth differentiation factor 15 might be used as a surrogate marker for latent heart failure and could help to identify patients with ACHD who are at risk for developing heart failure, even if they are clinically asymptomatic.