Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort. (With apologies to authors of last article)

van den Bosch E; Bossers SSM; Kamphuis VP; Boersma E; Roos-Hesselink JW;
Breur JMPJ; Ten Harkel ADJ; Kapusta L; Bartelds B; Roest AAW; Kuipers IM;
Blom NA; Koopman LP; Helbing WA

Journal of the American Heart Association. 10(5):e015022, 2021 02.

Background Patients who have undergone the Fontan procedure are at high
risk of circulatory failure. In an exploratory analysis we aimed to
determine the prognostic value of blood biomarkers in a young cohort who
have undergone the Fontan procedure. Methods and Results In multicenter
prospective studies patients who have undergone the Fontan procedure
underwent blood sampling, cardiopulmonary exercise testing, and stress
cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP
(N-terminal pro-B-type natriuretic peptide), GDF-15 (growth
differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of
tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty
acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding
protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von
Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after
Fontan completion. After this baseline study measurement, follow-up
information was collected on the incidence of adverse cardiac events,
including cardiac death, out of hospital cardiac arrest, heart
transplantation (listing), cardiac reintervention (severe events),
hospitalization, and cardioversion/ablation for arrhythmias was collected
and the relation with blood biomarkers was assessed by Cox proportional
hazard analyses. The correlation between biomarkers and other clinical
parameters was evaluated. We included 133 patients who have undergone the
Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years,
median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2
(4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13
(9.8%) had a severe event. NT-proBNP was associated with (all) events
during follow-up and remained predictive after correction for age, sex,
and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe
event-free survival was better in patients with low levels of GDF-15
(P=0.005) and vWF (P=0.008) and high levels of DLK-1 (P=0.041). There was
a positive correlation (beta=0.33, P=0.003) between DLK-1 and stress
cardiac magnetic resonance imaging functional reserve. Conclusions
NT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to
long-term outcome in young patients who have undergone the Fontan