"In an analysis of patients from several parts of the world, we showed that this test is greatly valuable in the diagnosis and prognosis of patients with both systolic and diastolic heart failure," says James Januzzi Jr., MD, of the MGH Cardiology Division, the paper's co-lead author. "It's a single blood test that can provide multiple pieces of important information."
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 challenging because its symptoms can overlap those of other conditions. Earlier this year Januzzi and colleagues from the MGH published the PRIDE study, the first prospective American trial measuring NT-proBNP in patients coming to a hospital emergency department with shortness of breath. Other research groups, including collaborators in the current study, have conducted single-site investigations supporting the usefulness of NT-proBNP for confirming a diagnosis of heart failure.
The International Collaborative of NT-proBNP (ICON) Study brought together data from the PRIDE study and similar information from the Christchurch Cardioendocrine Research Group in New Zealand and the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain, with previously unpublished information gathered by researchers from the University Hospital of Maastricht, The Netherlands, led by co-lead author Roland van Kimmenade, MD. Their analysis consisted of information from 1,256 patients, of which 720 had acute heart failure.
As in the earlier studies, NT-proBNP levels were significantly higher in patients found to have heart failure and highest in those with the most severe symptoms. The larger scale of the study permitted more in-depth analysis of data, allowing the establishment of age-specific NT-proBNP levels defining a clear diagnosis of heart failure. The measurement below which heart failure could be ruled out was the same for all age groups.
Analysis of the prospective value of NT-proBNP testing showed that patients who died within a little more than two months after symptom onset had significantly higher blood levels of the protein. In fact, NT-proBNP measurement was the single strongest predictor of death within that time period, and those with the most significantly elevated levels had a five-fold increase in the risk of death.
"Because patients with acute heart failure release such high levels of NT-proBNP, there had been conflicting information about the usefulness of a single measurement for establishing prognosis, but this analysis shows the initial assay to be strongly predictive of short-term outcome," says Januzzi. "Our results underscore this test's exceptional usefulness for diagnosis and for identifying those patients who should have higher levels of monitoring and more aggressive treatment. ICON has set world-wide standards for NT-proBNP testing in patients coming to hospital emergency departments with shortness of breath."
An assistant professor of Medicine at Harvard Medical School, Januzzi adds, "This study was characterized by exceptional collaboration among these four medical centers. The group from New Zealand pioneered the use of this test; the researchers from the Netherlands contributed the largest population of subjects with acute heart failure; and the clinical investigators from Barcelona previously published one of the first analyses of NT-proBNP in the emergency department setting. We are continuing the ICON initiative in several follow-up studies, two of which have been submitted for publication."
Along with van Kimmenade, co-authors of the ICON study are John Lainchbury, MD, and Mark Richards, MD, of Christchurch School of Medicine and Health Sciences in New Zealand; Antoni Bayes-Genis, MD, Jordi Ordonez-Llanos, MD, PhD, and Miguel Santalo-Bel, MD, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; and Yigal Pinto, MD, University Hospital of Maastricht, The Netherlands. The study was supported by a grant from Roche Diagnostics, which manufactures 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 nearly $500 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.