Biomarker Prediction of 14-Day Mortality in Emergency Department Patients Presenting With the Symptom of Acute Shortness of Breath

Study Objectives Biomarkers predict short term mortality in patients presenting to the emergency department (ED) with acute heart failure (acute heart failure) but none have been analyzed for their ability to forecast 14-day mortality in all patients presenting to the ED with symptoms of acute shortness of breath (shortness of breath). Short term mortality prediction is of particular relevance to the emergency physician as possibly an intervention could be performed to prevent a near-future death. This analysis of the BACH (Biomarkers in Acute Heart Failure) Trial describes the accuracy of several biomarkers for predicting all-cause 14-day mortality in the entire BACH population, irrespective of the final diagnosis.Methods The BACH Trial was a prospective, 15-center, multinational study of patients presenting to the ED with a primary complaint of acute shortness of breath. This data set was analyzed to determine the prognostic accuracy of the presenting c-terminal pro-arginine vasopressin (copeptin), mid-region-pro-adrenomedullin (MR-proADM), natriuretic peptides, and troponin levels in predicting short term mortality for all enrolled patients. Plasma specimens were stored at -70 C and all biomarkers (except troponin) were measured in a core lab at the University of Maryland. Prognostic performance of the biomarkers and relevant clinical variables and routine labs were described based on Cox regression (Chi2, p-value, C index) and receiver operating characteristic curve analysis (AUC).Results BACH enrolled 1641 patients with a mean age of 63.8 ± 16.9 years, 52.3% were males and 66.4% were white, 29.0% black and 3.7% another race. Overall 34.6% were adjudicated to have acute heart failure, 12.2% chronic obstructive pulmonary disease, 7.0% asthma, 6.8% pneumonia, 6.5% chest pain of unknown etiology, 3.7% bronchitis, 3.4% arrhythmia, 2.4% acute coronary syndrome, 2.3% pulmonary embolus, 1.6% influenza and 18.5% with an alternate final diagnosis. There were 43 (2.7%) deaths within 14 days of the ED visit. The AUC for this short term mortality receiver operating characteristic curve was 0.676, 0.727 and .691 for BNP, NT-proBNP and mid-region pro-atrial natriuretic peptide and 0.672, 0.774 and 0.792 for troponin (I or T), MR-proADM and copeptin respectively. Copeptin added significant predictive value to BNP, NT-proBNP and troponin (LR 46.88, 33.97 and 29.12 respectively, all p < 0.00001). MR-proADM also added significant predictive value to BNP, NT-proBNP and troponin (LR 41.9, 26.05 and 24.58 respectively, all p<0.00001). Lastly adding MR-proADM to copetin or copetin to MR-proADM added significant predictive value (LRs 9.38, p < 0.00219 and 15.96, p < 0.00007 respectively).Conclusions The novel biomarkers copeptin and MR-proADM, either alone or in combination, may provide superior short term mortality prediction compared to the natriuretic peptides and troponin in patients presenting to the ED with a primary complaint of shortness of breath, irrespective of the etiology. These results could help risk stratify these symptom specific patients and thus alter their ED management.