Associations between blood biomarkers, cardiac function and adverse outcome in a young tetralogy of Fallot cohort

Eva van den Bosch, Wouter J. van Genuchten, Saskia E. Luijnenburg, Nienke Duppen, Vivian P. Kamphuis, Jolien W. Roos-Hesselink, Beatrijs Bartelds, Arno A.W. Roest, Johannes M.P.J. Breur, Nico A. Blom, Eric Boersma, Laurens P. Koopman, Willem A. Helbing*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: To determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF). Methods: In the setting of multicenter prospective research studies TOF patients underwent blood sampling, cardiopulmonary exercise testing and low-dose dobutamine stress cardiac magnetic resonance (CMR) imaging. In the blood sample NT-proBNP, GDF-15, Galectin-3, ST-2, DLK-1, FABP4, IGFBP-1, IGFBP-7, MMP-2, and vWF were assessed. During subsequent follow-up, patients were evaluated for reaching the study endpoint (cardiac death, arrhythmia-related hospitalization or cardioversion/ablation, VO2 max ≤65% of predicted). Regression analysis was used to explore the correlation between blood biomarkers (corrected for age and gender) and other clinical parameters. The potential predictive value of blood biomarkers and events were assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. Results: We included 137 Fallot patients, median age 19.2 (interquartile range: 14.6–25.7) years, median age at TOF-repair 0.9 (0.5–1.9) years. After a median follow-up of 8.7 (6.3–10.7) years, 20 (14.6%) patients reached the composite endpoint. In a multivariable cox-regression analysis corrected for age at study baseline, elevated IGFBP-7 and MMP-2 levels were associated with the composite endpoint. We also noted a correlation between DLK-1 and relative change in right ventricular end systolic volume during dobutamine stress CMR (β = −0.27, p = 0.010), a correlation between FABP4 and Max VO2 (β = −0.41, p ≤0.001 and between MMP-2 and tricuspid valve E/A ratio (β = −0.15, p = 0.037). Conclusions: IGFBP-7, MMP-2 and DLK-1 levels are related to cardiac function and long-term outcome in TOF patients.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalInternational Journal of Cardiology
Volume361
Early online date26 Apr 2022
DOIs
Publication statusPublished - 15 Aug 2022

Bibliographical note

Funding Information:
E. van den Bosch, W.J. van Genuchten, V.P. Kamphuis, J.W. Roos-Hesselink, N. Duppen and S. E. Luijnenburg were supported by research grants from the Dutch Heart Foundation (grant 2013T091 , grant 2013T093 , grant 2008B026 and grant 2006B095 ).

Publisher Copyright:
© 2022 The Authors

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