"We found that testing with the NT-proBNP assay was an extremely accurate way to identify or exclude heart failure in patients with shortness of breath," says James Januzzi Jr., MD, of the MGH Cardiology Division, the paper's lead author. "Importantly, we also found that the very best results came from combining the results of this very sensitive and specific blood test with the logic and wisdom of a good emergency physician, which gave the optimal balance between biologic data and clinical judgement."
Congestive heart failure, which occurs when an impaired heart muscle cannot pump blood efficiently, is a growing health problem and major cause of cardiac death. The diagnosis of heart failure may be difficult to make because its typical symptoms can overlap with those of other conditions. Missing a heart failure diagnosis can put patients at high risk of serious problems, including death, but overdiagnosis may lead patients to receive unnecessary treatment.
"To date, the way physicians have traditionally evaluated potential heart failure patients has been rather random, with some receiving a physical examination and medical history while others also get expensive and time-consuming procedures," Januzzi says. "Having a widely-available, accurate, and cost-effective diagnostic method would be of extraordinary value."
Proteins called natriuretic peptides are produced when the cardiac muscle is under stress. The role of testing for these proteins in several forms of cardiovascular disease has been the subject of intense recent study. In 2002, the newest generation of natriuretic peptide assays became available, and soon thereafter the current investigation – called the PRIDE study – was launched to determine the usefulness of a test for NT-proBNP in evaluating emergency patients. At the time of its launch, the PRIDE study was the first prospective American trial of NT-proBNP and the largest such study to study the test in patients with shortness of breath.
About 600 patients who came to the MGH Emergency Department with shortness of breath were enrolled in the study. In addition to standard evaluation of symptoms, a blood sample was drawn for NT-proBNP measurement. After the emergency assessment was completed, the attending physicians were asked to estimate the likelihood that the patients' symptoms were caused by heart failure, based on all available information except the NT-proBNP assay. For patients admitted to the hospital, the entire record of their stay was included in the study data. Sixty days after the original emergency visit, the researchers followed up with each patient, contacting them personally and reviewing their records to identify any subsequent clinical events. Participation in the study in no way changed the care or treatment the patients received.
To determine the diagnoses for this study, cardiologists not involved in the patients' care reviewed all the participants' relevant hospital records from the initial emergency visit through the 60-day follow up. In assigning the final diagnosis – either acute heart failure or some other cause for shortness of breath – these physicians also did not have access to the NT-proBNP results.
When they reviewed NT-proBNP levels, the researchers found that the protein's concentrations were significantly higher in patients eventually diagnosed with heart failure and highest in those with most severe symptoms. For identifying heart failure in these emergency patients, the test alone was significantly more accurate than was the physicians' original likelihood assessment, but a combination of NT-proBNP levels and physician judgement produced the most accurate method of diagnosis.
"We also identified specific NT-proBNP levels above which the diagnosis of heart failure is clear and below which the symptoms are definitely not cardiac-related," Januzzi says. "So we've shown that this test not only can confidently exclude the presence of congestive heart failure, which other studies have examined, but can confirm that diagnosis as well. NT-proBNP performed exceptionally well and confirms the value of the natriuretic peptide class of cardiac biomarkers as a whole. We believe NT-proBNP testing should now become a routine component of evaluation for patients with shortness of breath in emergency department settings." Januzzi is an assistant professor of Medicine at Harvard Medical School.
Co-authors of the study – all from the MGH – are Carlos Camargo, MD, PhD; Saif Anwaruddin, MD; Aaron Baggish, MD; Annabel Chen, MD; Daniel Krauser, MD; Roderick Tung, MD; Renee Cameron, MS; Tobias Nagurney, MD; Claudia Chae, MD, MPH; Donald Lloyd-Jones, MD, ScM; David Brown, MD; Stacy Foran-Melanson, MD, PhD; Patrick Sluss, MD, PhD; Elizabeth Lee-Lewandrowski, PhD, MPH; and Kent Lewandrowski, MD. The study was supported by a grant from Roche Diagnostics, which manufacturers the NT-proBNP assay studied.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $450 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.