Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study

Abstract

To externally validate the prognostic impact of copeptin, either alone or integrated in risk stratification models, in pulmonary embolism (PE), we performed a analysis of 843 normotensive PE patients prospectively included in three European cohorts.Within the first 30 days, 21 patients (2.5%, 95% CI 1.5-3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7-2.5) died due to PE. Patients with copeptin ≥24 pmol·L had a 6.3-fold increased risk for an adverse outcome (95% CI 2.6-15.5, p<0.001) and a 7.6-fold increased risk for PE-related death (95% CI 2.3-25.6, p=0.001). Risk classification according to the 2014 European Society of Cardiology (ESC) guideline algorithm identified 248 intermediate-high-risk patients (29.4%) with 5.6% (95% CI 3.1-9.3) at risk of adverse outcomes. A stepwise biomarker-based risk assessment strategy (based on high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and copeptin) identified 123 intermediate-high-risk patients (14.6%) with 8.9% (95% CI 4.5-15.4) at risk of adverse outcomes. The identification of patients at higher risk was even better when copeptin was measured on top of the 2014 ESC algorithm in intermediate-high-risk patients (adverse outcome OR 11.1, 95% CI 4.6-27.1, p<0.001; and PE-related death OR 13.5, 95% CI 4.2-43.6, p<0.001; highest risk group all other risk groups). This identified 85 patients (10.1%) with 12.9% (95% CI 6.6-22.0) at risk of adverse outcomes and 8.2% (95% CI 3.4-16.2) at risk of PE-related deaths.Copeptin improves risk stratification of normotensive PE patients, especially when identifying patients with an increased risk of an adverse outcome.

Prognostic value of copeptin in patients with acute pulmonary thromboembolism

“…In terms of life threatening conditions, such as severe sepsis, septic shock, hemorrhagic shock and ischemic stroke, copeptin increases to concentrations above 100 pmol/L . The cut‐off of serum copeptin level was 24 pmol/L for prognostic value in PE patients in two study, and also as 7.8 ng/mL in our study . In addition, the cut‐off value of copeptin level was 4.84 ng/dL for the diagnostic predictor in another study .…”

“…In this study, copeptin was used with a predefined cut‐off value of 24 pmol/L, which resulted in a satisfactory prognostic performance. It was also associated with 6.3 times higher risk for an adverse outcome and with 7.6 times higher risk for PE‐related death . In another study conducted by Maisel et al, it was reported that high concentrations of copeptin were related to increased 90‐day mortality in heart failure and copeptin was a significant predictor of 90‐day mortality .…”

“…Following stress, copeptin levels in the blood rise rapidly and they become normalized within several hours . This condition may reflect a novel pathophysiological axis of PE severity by indicating the systemic response to impaired hemodynamics because of RV failure . To rapidly identify the patients with very low risks of mortality, who represent approximately one‐third of the whole population, it is suggested to utilize the PESI score.…”

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)

“…In a single-centre derivation study investigating 268 normotensive PE patients, copeptin levels ⩾24 pmol/L were associated with a 5.4-fold (95% CI 1.7-17.6) increased risk of an adverse outcome [216]. These results were confirmed in 843 normotensive PE patients prospectively included in three European cohorts [217].…”

Prognostic Value of Elevated Copeptin and High-Sensitivity Cardiac Troponin T in Patients with and without Acute Coronary Syndrome: The ConTrACS Study

“…Given the paucity of existing evidence the interpretation of these non-diagnostic constellations remains unclear and may cause improper conclusions among physicians [9]. In contrast to cTn, the release of copeptin is unspecific and may be stimulated by numerous acute clinical pathologies, including acute heart failure, pulmonary embolism, and sepsis [10][11][12][13]. Previously, elevated copeptin values in patients with suspected ACS but also non-ACS conditions were found to confer incremental prognostic information beyond an increased hs-cTn [10,14].…”