BACKGROUND:
The number of patients with adult congenital heart disease (ACHD) is rapidly increasing. In order to optimize patient management, there is a great need to accurately identify high-risk patients. Still, no biomarker has been firmly established as a clinically useful prognostic tool in this group. We studied the association of 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 ACHD.
METHODS:
Clinically stable patients with ACHD who routinely visited the outpatient clinic between April 2011 and April 2013 underwent clinical assessment, electrocardiography, echocardiography and biomarker measurement (NT-proBNP, hs-TnT and GDF-15) at the time of study inclusion. Patients were prospectively followed for the occurrence of cardiovascular events (death, heart failure, hospitalization, arrhythmia, thromboembolic events, and re-intervention). Survival curves were derived by the Kaplan-Meier method and Cox regression was performed to investigate the relation between biomarkers and events with adjustment for multiple clinical and echocardiographic variables.
RESULTS:
In total, 595 patients were included (median age 33 [IQR 25-41] years, 58% male, 90% New York Heart Association class I). Patients were followed during a median of 42 [IQR 37-46] months. Of the three evaluated biomarkers, NT-proBNP in the upper quartile (>33.3 pmol/L) was most strongly associated with cardiovascular events (n=165, adjusted HR=9.05 [3.24-25.3], P<0.001) and with death or heart failure (n=50, adjusted HR 16.0 [2.04-126], P<0.001). When NT-proBNP was analyzed as a continuous variable, similar findings were retrieved. The cumulative proportion of patients with death and heart failure was only 1% in the lowest two NT-proBNP quartiles. In patients with elevated NT-proBNP (>14 pmol/L), 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).
CONCLUSIONS:
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. Elevated levels of NT-proBNP, hs-TnT and GDF-15 identify patients at highest risk of cardiovascular events. These biomarkers therefore may play an important role in the monitoring and management of patients with ACHD.

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doi.org/10.1161/CIRCULATIONAHA.116.023255, hdl.handle.net/1765/94875
Circulation (Baltimore)

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/early/2016/11/03/CIRCULATIONAHA.116.023255 ;
Data Supplement (unedited) at: http://circ.ahajournals.org/content/suppl/2016/11/03/CIRCULATIONAHA.116.023255.DC1.html


Baggen, V., van den Bosch, A., Eindhoven, J., Schut, A.-R., Cuypers, J., Witsenburg, M., … Roos-Hesselink, J. (2017). Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease. Circulation (Baltimore), 135(3), 264–279. doi:10.1161/CIRCULATIONAHA.116.023255