Prognostic value of serial N-terminal pro-B-type natriuretic peptide measurements in adults with congenital heart disease

Background--A single NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement is a strong prognostic factor in adult congenital heart disease. This study investigates NT-proBNP profiles within patients with adult congenital heart disease and relates these to cardiovascular events. Methods and Results--In this prospective cohort, 602 patients with adult congenital heart disease were enrolled at the outpatient clinic (years 2011-2013). NT-proBNP was measured at study inclusion in 595 patients (median age 33 [IQR 25-41] years, 58% male, 90% NYHA I) and at subsequent annual visits. The primary end point was defined as death, heart failure, hospitalization, arrhythmia, thromboembolic event, or cardiac intervention; the secondary end point as death or heart failure. Repeated measurements were analyzed using linear mixed models and joint models. During a median follow-up of 4.4 [IQR 3.8-4.8] years, a total of 2424 repeated measurements were collected. Average NT-proBNP increase was 2.9 pmol/L the year before the primary end point (n=199, 34%) and 18.2 pmol/L before the secondary end point (n=58, 10%), compared with 0.3 pmol/L in patients who remained end point-free (P-value for difference in slope 0.006 and < 0.0