Mid-Region Pro-Hormone Markers for Diagnosis and Prognosis in Acute Dyspnea

• Published in: Journal of the American College of Cardiology Vol. 55; no. 19; pp. 2062 - 2076
• Main Authors: Maisel, Alan, MD, Mueller, Christian, MD, Nowak, Richard, MD, Peacock, W. Frank, MD, Landsberg, Judd W., MD, Ponikowski, Piotr, MD, PhD, Mockel, Martin, MD, Hogan, Christopher, MD, Wu, Alan H.B., PhD, Richards, Mark, MD, PhD, Clopton, Paul, MS, Filippatos, Gerasimos S., MD, Di Somma, Salvatore, MD, Anand, Inder, MD, DPhil (Oxon), Ng, Leong, MD, Daniels, Lori B., MD, MAS, Neath, Sean-Xavier, MD, PhD, Christenson, Robert, PhD, Potocki, Mihael, MD, McCord, James, MD, Terracciano, Garret, BS, Kremastinos, Dimitrios, MD, Hartmann, Oliver, MSc, von Haehling, Stephan, MD, Bergmann, Andreas, PhD, Morgenthaler, Nils G., MD, PhD, Anker, Stefan D., MD, PhD
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.05.2010
• Subjects: acute dyspnea; BACH; Cardiovascular; Internal Medicine; markers; pro-hormone; acute dyspnea; NP; BNP; HR; interquartile range; AUC; NT-proBNP; receiver-operating characteristic; MR-proANP; mid-regional pro-atrial natriuretic peptide; acute heart failure; ED; MR-proADM; CI; ROC; natriuretic peptide; pro-hormone; area under the curve; IQR; emergency department; B-type natriuretic peptide; CV; hazard ratio; BACH; confidence interval; mid-regional pro-adrenomedullin; markers; N-terminal pro–B-type natriuretic peptide; AHF; coefficient of variation
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.02.025

Objectives Our purpose was to assess the diagnostic utility of mid-regional pro–atrial natriuretic peptide (MR-proANP) for the diagnosis of acute heart failure (AHF) and the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with AHF. Background There are some caveats and limitations to natriuretic peptide testing in the acute dyspneic patient. Methods The BACH (Biomarkers in Acute Heart Failure) trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. A noninferiority test of MR-proANP versus B-type natriuretic peptide (BNP) for diagnosis of AHF and a superiority test of MR-proADM versus BNP for 90-day survival were conducted. Other end points were exploratory. Results MR-proANP (≥120 pmol/l) proved noninferior to BNP (≥100 pg/ml) for the diagnosis of AHF (accuracy difference 0.9%). In tests of secondary diagnostic objectives, MR-proANP levels added to the utility of BNP levels in patients with intermediate BNP values and with obesity but not in renal insufficiency, the elderly, or patients with edema. Using cut-off values from receiver-operating characteristic analysis, the accuracy to predict 90-day survival of heart failure patients was 73% (95% confidence interval: 70% to 77%) for MR-proADM and 62% (95% confidence interval: 58% to 66%) for BNP (difference p < 0.001). In adjusted multivariable Cox regression, MR-proADM, but not BNP, carried independent prognostic value (p < 0.001). Results were consistent using NT-proBNP instead of BNP (p < 0.001). None of the biomarkers was able to predict rehospitalization or visits to the emergency department with clinical relevance. Conclusions MR-proANP is as useful as BNP for AHF diagnosis in dyspneic patients and may provide additional clinical utility when BNP is difficult to interpret. MR-proADM identifies patients with high 90-day mortality risk and adds prognostic value to BNP. (Biomarkers in Acute Heart Failure [BACH]; NCT00537628 )