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 <0.001, respectively). In patients with elevated baseline NT‐proBNP (>14 pmol/L, n=315, 53%), repeated measurements were associated with the primary end point (HR per 2‐fold higher value 2.08; 95% CI 1.31–3.87; P<0.001) and secondary end point (HR 2.47; 95% CI 1.13–5.70; P=0.017), when adjusted for the baseline measurement. CONCLUSIONS: NT‐proBNP increased before the occurrence of events, especially in patients who died or developed heart failure. Serial NT‐proBNP measurements could be of additional prognostic value in the annual follow‐up of patients with adult congenitive heart disease with an elevated NT‐proBNP.