Risk stratification of normotensive pulmonary embolism: prognostic impact of copeptin

The prognostic value of copeptin, the C-terminal fragment of the precursor protein of vasopressin which is released upon stress, and hypotension in pulmonary embolism is unknown, especially if combined with biomarkers reflecting different pathophysiological axes such as myocardial injury (high-sensitivity troponin T (hsTnT)) and stretch (N-terminal pro-brain natriuretic peptide (NT-proBNP)). We prospectively studied 268 normotensive pulmonary embolism patients included in a single-centre cohort study. Patients with an adverse 30-day outcome (5.6%) had higher copeptin levels than patients with a favourable course (median (interquartile range) 51.8 (21.6-90.8) versus 13.2 (5.9-39.3) pmol.L-1; p=0.020). Patients with copeptin levels above the calculated optimal cut-off value of 24 pmol.L-1 had a 5.4-fold increased risk for an adverse outcome (95% CI 1.68-17.58; p=0.005). We developed a strategy for risk stratification based on biomarkers. None of 141 patients (52.6%) with hsTnT <14 pg.mL(-1) or NT-proBNP <600 pg.mL(-1) had an adverse outcome (low risk). Copeptin >= 24 pmol.L-1 stratified patients with elevated hsTnT and NT-proBNP as intermediate-low and intermediate-high risk (5.6% and 20.0% adverse outcome, respectively). Compared to the algorithm proposed by the 2014 European Society of Cardiology guideline, more patients were classified as low risk (52.8% versus 17.5%, p<0.001) and more patients in the intermediate-high risk group had an adverse outcome (20.0% versus 11.6%). Copeptin might be helpful for risk stratification of normotensive patients with pulmonary embolism, especially if integrated into a biomarker-based algorithm.