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.
Highlights
Patients experiencing shortness of breath have been reported to account for close to one in ten visits to the emergency department (ED)
Dividing the cohort into quartiles based on biologically active adrenomedullin (bio-ADM) concentration the following was observed: Proportion of females decreased with increasing bio-ADM levels (p < 0.005)
With regard to prevalent disease, there was an increasing proportion of patients with Congestive heart failure (CHF) with higher bio-ADM levels (p-trend < 0.001). This is true for the proportion of prevalent chronic obstructive pulmonary disease (COPD) (p-trend < 0.005) but not for undifferentiated infection at triage (p-trend > 0.9)
Summary
Reports suggest that up to half of these patients get admitted for further in-hospital workup. The reasons behind such high admittance rates range from the fact that undifferentiated dyspnea may be caused by potentially life-threatening conditions while the diagnostic process is often complicated by the presence of several comorbidities, among the elderly [1]. Internal and Emergency Medicine of clinically useful diagnostic tools available to both the most effective treatment to initiate at the ED and decide whether in-patient management for further workup is required. In the differential diagnostic workup for CHF, current practice entails a physical examination, vital signs, electrocardiogram, laboratory tests, and common imaging modalities [2]. The prognostication and preliminary diagnosis of unselected acute dyspnea during the first hour at the ED, which determines the level of care and acute treatment, remains a huge challenge
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