Biomarkers in Adult Congenital Heart Disease

Study Questions:

What is the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitive troponin-T (hs-TnT), and growth-differentiation factor 15 (GDF-15) with cardiovascular events in adult congenital heart disease (ACHD)?


A prospective study was performed at a single referral center. Clinically stable patients with ACHD of moderate or greater complexity seen for routine visits over a 2-year span were included. The primary endpoint was a composite endpoint including all-cause mortality, heart failure, hospitalization for cardiac reasons, arrhythmia, thromboembolic events, and cardiac re-interventions.


In total, 595 patients were included, with a median age of 33 [interquartile range (IQR) 25-41]. A majority (58%) was male and a large majority (90%) was identified as having New York Heart Association class I symptoms. Of the three biomarkers studied, NT-proBNP in the upper quartile (>33.3 pmol/L or 282 pg/ml using a conversion factor of 1 pg/ml = 0.118 pmol/L) was most associated with the composite endpoint (n = 165, adjusted hazard ratio [HR], 9.05 [3.24-25.3]; p < 0.01) and with death or heart failure (n = 50, adjusted HR, 16.0 [2.04-126]; p < 0.001). The cumulative proportion of patients with death and heart failure was 1% in the lowest two NT-proBNP quartiles. In patients with elevated NT-proBNP (>14 pmol/L or 118.6 pg/ml), elevated hs-TnT (>14 ng/L) and elevated GDF-15 (>1109 ng/L) identified those patients at highest risk of cardiovascular events (log-rank p 0.0001).


The authors concluded that NT-proBNP provides prognostic information beyond a conventional risk marker model in patients with ACHD and can reliably exclude the risk of death and heart failure. NT-proBNP, hs-TnT, and GDF-15 identify patients at highest risk of cardiovascular events and may play an important role in the monitoring and management of patients with ACHD.


While cardiac biomarkers have been extensively studied and validated in adults with acquired heart disease, there has been little prospective study of their role in determining prognosis in ACHD. This study assessed three cardiac biomarkers in relation to a composite cardiac endpoint. The study demonstrated both the role of elevated NT-proBNP in identifying high-risk patients, as well as a very reassuring negative predictive value for patients with low NT-proBNP. While the study is limited by a heterogeneous patient population, this is consistent with a real-world population seen at ACHD referral centers. The study suggests a prognostic role for biomarkers in ACHD, particularly in identifying low-risk patients who may not require as frequent follow-up and diagnostic imaging studies.

Keywords: Arrhythmias, Cardiac, Biomarkers, Diagnostic Imaging, Growth Differentiation Factor 15, Heart Defects, Congenital, Heart Failure, Natriuretic Peptide, Brain, Peptide Fragments, Risk Factors, Thromboembolism, Troponin T

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