Author + information
- Received November 2, 2017
- Revision received January 10, 2018
- Accepted January 14, 2018
- Published online March 12, 2018.
- James L. Januzzi Jr., MDa,b,c,∗ (, )
- Annabel A. Chen-Tournoux, MDd,
- Robert H. Christenson, PhDe,
- Gheorghe Doros, PhDc,f,
- Judd E. Hollander, MDg,
- Phillip D. Levy, MD, MPHh,
- John T. Nagurney, MDi,b,
- Richard M. Nowak, MDj,
- Peter S. Pang, MD, MSk,
- Darshita Patel, MSl,
- W. Franklin Peacock, MDm,
- E. Joy Rivers, PhDl,
- Elizabeth L. Walters, MDn,
- Hanna K. Gaggin, MD, MPHa,b,c,
- on behalf of the ICON-RELOADED Investigators
- aDivision of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- bHarvard Medical School, Boston, Massachusetts
- cBaim Institute for Clinical Research, Boston, Massachusetts
- dDivision of Cardiology, Department of Medicine, Jewish General Hospital, Montreal, Quebec, Canada
- eDepartment of Pathology, University of Maryland School of Medicine, Baltimore, Maryland
- fDepartment of Biostatistics, Boston University, Boston, Massachusetts
- gDepartment of Emergency Medicine, Jefferson University, Philadelphia, Pennsylvania
- hDepartment of Emergency Medicine, Wayne State University, Detroit, Michigan
- iDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts
- jDepartment of Emergency Medicine, Henry Ford Health System, Detroit, Michigan
- kDepartment of Emergency Medicine, Indiana University School of Medicine & Indianapolis EMS, Indianapolis, Indiana
- lRoche Diagnostics, Indianapolis, Indiana
- mDepartment of Emergency Medicine, Baylor College of Medicine, Houston, Texas
- nDepartment of Emergency Medicine, Loma Linda University Medical Center, Loma Linda, California
- ↵∗Address for correspondence:
Dr. James L. Januzzi, Jr., Department of Cardiology, Massachusetts General Hospital, Yawkey 5B, 33 Fruit Street, Boston, Massachusetts 02114.
Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed.
Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting.
Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF.
Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13).
Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.
This study was funded by Roche Diagnostics, Inc. Dr. Januzzi is supported in part by the Hutter Family Professorship; has received grant support from Abbott, Cleveland Heart Labs, Siemens, Singulex, and Prevencio; has received consulting income from Roche Diagnostics, Critical Diagnostics, Sphingotec, Phillips, and Novartis; and has participated in clinical endpoint committees/data or safety monitoring boards for Novartis, Amgen, GE, Janssen, Pfizer, and Boehringer Ingelheim. Dr. Chen-Tournoux has received consulting income from Roche Diagnostics. Dr. Christenson has received grant support from Roche Diagnostics, Siemens Healthcare Diagnostics, Beckman Coulter, Spingotech, Ortho Clinical Diagnostics, and Abbott; and has received consulting income from Roche Diagnostics, Siemens Healthcare Diagnostics, and Becton Dickinson. Dr. Doros has received consulting income from Pfizer, Genzyme, and Sarepta. Dr. Hollander has received support from the Patient-Centered Outcomes Research Institute, National Institutes of Health, Alere, Siemens, Roche, Portola, and Trinity. Dr. Levy has received research support or grants from the Patient-Centered Outcomes Research Institute, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Minority Health and Health Disparities, Amgen, Bristol-Myers Squibb, Novartis, Trevena, Edwards Lifesciences, and Cardiorentis; has ownership interest in Mespere and Carbon Lifeform Innovations; and has served as a consultant for Novartis, Cardiorentis, Trevena, Apex Innovations, Roche Diagnostics, Siemens, Shire, Sciex, and ZS Pharma. Dr. Nagurney has received grant support from Roche Diagnostics, Alere/Biosite, Boehringer Ingelheim, Thermo Fisher, and Nanosphere. Dr. Nowak has received grant support from Roche Diagnostics, Siemens, Abbott, Novartis, and Radiometer; and is a consultant for Roche, Siemens, Abbott, Trinity, and Thermo Fisher. Dr. Pang has received research support or grants from Roche, Novartis, Patient-Centered Outcomes Research Institute, American Heart Association, National Heart, Lung, and Blood Institute, and Agency for Healthcare Research and Quality; and has been a consultant for Bristol-Myers Squibb, Novartis, Trevena, and Roche Diagnostics. Ms. Patel and Dr. Rivers are or have been employees of and representatives of Roche Diagnostics. Dr. Peacock has received grant support from Abbott, Alere, Banyan, Cardiorentis, Janssen, Pfizer, Roche, The Medicines Company, and ZS Pharma; has served as a consultant for Alere, Bayer, Beckman, Cardiorentis, Ischemia Care, Instrument Labs, Janssen, Phillips, Prevencio, The Medicines Company, and ZS Pharma; and has ownership interests in Comprehensive Research Associates LLC and Emergencies in Medicine LLC. Dr. Walters has received investigator funding for this study from Roche Diagnostics. Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation; has received grant support from Roche Diagnostics and Portola; has received consulting income from Roche Diagnostics, Amgen, and Ortho Clinical; and has received research payments for clinical endpoint committees for EchoSense and Radiometer. Lori Daniels, MD, served as Guest Editor for this paper.
- Received November 2, 2017.
- Revision received January 10, 2018.
- Accepted January 14, 2018.
- 2018 The Authors
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