Midregion Prohormone Adrenomedullin and Prognosis in Patients Presenting With Acute Dyspnea: Results From the BACH (Biomarkers in Acute Heart Failure) Trial

doi:10.1016/j.jacc.2011.06.006

Journal of the American College of Cardiology

Volume 58, Issue 10, 30 August 2011, Pages 1057-1067

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Objectives

The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-proADM) in all patients, cardiac and noncardiac, presenting with acute shortness of breath.

Background

The recently published BACH (Biomarkers in Acute Heart Failure) study demonstrated that MR-proADM had superior accuracy for predicting 90-day mortality compared with B-type natriuretic peptide (area under the curve: 0.674 vs. 0.606, respectively, p < 0.001) in acute heart failure.

Methods

The BACH trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. Using this dataset, the prognostic accuracy of MR-proADM was evaluated in all patients enrolled for predicting 90-day mortality with respect to other biomarkers, the added value in addition to clinical variables, as well as the added value of additional measurements during hospital admission.

Results

Compared with B-type natriuretic peptide or troponin, MR-proADM was superior for predicting 90-day all-cause mortality in patients presenting with acute dyspnea (c index = 0.755, p < 0.0001). Furthermore, MR-proADM added significantly to all clinical variables (all adjusted hazard ratios: >3.28), and it was also superior to all other biomarkers. MR-proADM added significantly to the best clinical model (bootstrap-corrected c index increase: 0.775 to 0.807; adjusted standardized hazard ratio: 2.59; 95% confidence interval: 1.91 to 3.50; p < 0.0001). Within the model, MR-proADM was the biggest contributor to the predictive performance, with a net reclassification improvement of 8.9%. Serial evaluation of MR-proADM performed in patients admitted provided a significant added value compared with a model with admission values only (p = 0.0005). More than one-third of patients originally at high risk could be identified by the biomarker evaluation at discharge as low-risk patients.

Conclusions

MR-proADM identifies patients with high 90-day mortality and adds prognostic value to natriuretic peptides in patients presenting with acute shortness of breath. Serial measurement of this biomarker may also prove useful for monitoring, although further studies will be required. (Biomarkers in Acute Heart Failure [BACH]; NCT00537628)

Key Words

adrenomedullin

biomarker

heart failure

Abbreviations and Acronyms

ADM

adrenomedullin

AHF

acute heart failure

BNP

B-type natriuretic peptide

confidence interval

coefficient of variation

emergency department

hazard ratio

IQR

interquartile range

MR-proADM

midregion proadrenomedullin

MR-proANP

midregion pro–atrial natriuretic peptide

NRI

net reclassification improvement

NT-proBNP

N-terminal pro–B-type natriuretic peptide

PCT

procalcitonin

Cited by (0)

: Dr. Maisel has received research support from Roche, Biosite, and Bayer and is a consultant for Biosite. Dr. Mueller has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Novartis Foundation, the Krokus Foundation, Abbott, Biosite, B·R·A·H·M·S, Roche, and the University of Basel. Dr. Peacock is a member of the scientific advisory boards of Abbott, Beckman-Coulter, Biosite, Inverness, Ortho Clinical Diagnostics, and Response Biomedical and has received research grants from Abbott, Biosite, and Inverness. Dr. Richards is a member of the scientific advisory board of Inverness Medical and has received travel support, honoraria, and research grants from Roche Diagnostics and Inverness Medical (Biosite). Dr. Filippatos has received research support from Biosite, B·R·A·H·M·S, and Roche. Dr. Di Somma is a consultant for Biosite. Dr. Ng has received research support from B·R·A·H·M·S. Dr. Daniels has received research grants from Roche Diagnostics and Alere, Inc. Dr. Neath is a consultant for B·R·A·H·M·S USA and Thermo Fisher Scientific. Dr. Christenson has served as a consultant to Siemens Diagnostics, Critical Care Diagnostics, and BG Medicine; and has received research funding from B·R·A·H·M·S. Dr. McCord has received research support from B·R·A·H·M·S. Mr. Hartmann and Dr. Morgenthaler are employees of B·R·A·H·M·S AG, a company that is developing and marketing in vitro diagnostic products, including the midregion proadrenomedullin assay used in this study. Dr. Anker has received honoraria from B·R·A·H·M·S, Abbott, and Biosite and is a consultant for and has received research support from B·R·A·H·M·S. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Steven D. Nissen, MD, served as Guest Editor for this paper.