Bioactive adrenomedullin a prognostic biomarker in patients with mild to moderate dyspnea at the emergency department: an observational study

Abstract

Acute dyspnea with underlying congestion is a leading cause of emergency department (ED) visits with high rates of hospitalization. Adrenomedullin is a vasoactive neuropeptide hormone secreted by the endothelium that mediates vasodilation and maintains vascular integrity. Plasma levels of biologically active adrenomedullin (bio-ADM) predict septic shock and vasopressor need in critically ill patients and are associated with congestion in patients with acute heart failure (HF) but the prognostic value in unselected dyspneic patients at the ED is unknown. The purpose of this study is to test if bio-ADM predicts adverse outcomes when sampled in patients with acute dyspnea at presentation to the ED. In this single-center prospective observational study, we included 1402 patients from the ADYS (Acute DYSpnea at the Emergency Department) cohort in Malmö, Sweden. We fitted logistic regression models adjusted for sex, age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and C-reactive protein (CRP) to associate bio-ADM plasma levels to mortality, hospitalization, intravenous (IV) diuretic treatment and HF diagnosis. Using receiver operating characteristic (ROC) curve analysis we evaluated bio-ADM discrimination for these outcomes compared to a reference model (sex, age, NT-proBNP, creatinine, and CRP). Model performance was compared by performing a likelihood ratio test on the deviances of the models. Bio-ADM (per interquartile range from median) predicts both 90-day mortality [odds ratio (OR): 1.5, 95% confidence interval (CI) 1.2–2.0, p < 0.002] and hospitalization (OR: 1.5, 95% CI 1.2–1.8, p < 0.001) independently of sex, age, NT-proBNP, creatinine, and CRP. Bio-ADM statistically significantly improves the reference model in predicting mortality (added χ2 9.8, p = 0.002) and hospitalization (added χ2 14.1, p = 0.0002), and is associated with IV diuretic treatment and HF diagnosis at discharge. Plasma levels of bio-ADM sampled at ED presentation in acutely dyspneic patients are independently associated with 90-day mortality, hospitalization and indicate the need for decongestive therapy.