Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease
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.
- troponin T
- growth-differentiation factor-15 follow-up studies
- adult congenital heart disease
- Received April 29, 2016.
- Revision received October 6, 2016.
- Accepted October 19, 2016.