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Novel candidate biomarker for heart
failure also strongly predicts risk of death
Better understanding of biomarkers'
significance may allow personalized treatment planning
BOSTON - August 6, 2007 - A potential new biomarker for heart
failure may be more powerful than established measures in identifying
patients at increased risk for death from several causes. In a report
to appear in the Journal of the American College of Cardiology
that has received early online release, an international research
team describes finding that blood levels of a protein called ST2
both indicate the presence of heart failure among patient with shortness
of breath and powerfully predict the risk that a patient will die
during the following year. Improved understanding of how ST2 and
other biomarkers reflect aspects of the heart's hormonal environment
someday may allow clinicians to develop more effective, individualized
treatment plans.
"While we are now able to diagnose heart failure with great
sensitivity using natriuretic peptide tests, we have miles to go
before we can reduce the considerable risk that accompanies that
diagnosis," says James Januzzi Jr., MD, of the MGH
Cardiology Division, who led the study. "It's highly likely
that examining a patient's pattern of several complementary biomarkers
will be superior for predicting risk than using just one. If we
could harness the information these biomarkers yield to better adjust
therapies - in the same way that antibiotics are chosen based on
the organism causing the infection - that would be revolutionary."
A condition in which the heart muscle is damaged and cannot pump
blood efficiently, heart failure is a major cause of cardiac death.
Diagnosis has been a challenge, since the symptoms of heart failure
are similar to those of many other conditions. In recent years studies
from several groups, including collaborators on the current report,
have identified a number of candidate biomarkers for diagnosis.
In 2005, Januzzi and colleagues from the MGH published the
PRIDE study, which showed that a protein called NT-proBNP, one
of the natriuretic peptides, could confirm or rule out a diagnosis
of heart failure in emergency room patients with shortness of breath.
In addition NT-proBNP strongly predicted death among such patients.
Recent smaller studies have suggested that ST2, which appears to
have a role in the inflammatory response, also may be expressed
within the heart in situations involving stress to the cardiac muscle,
including heart failure. To more closely examine ST2's potential
as a heart failure biomarker, the research team analyzed data and
blood samples from the PRIDE study participants, almost 600 individuals
who had come to the MGH Emergency Department with shortness of breath.
In this study, the single largest ST2 analysis to date, the researchers
confirmed ST2 as a novel marker of heart failure, finding the highest
levels among participants with the disorder. More striking, elevated
ST2 levels strongly predicted the risk of death during the year
after the initial hospital visit, even among patients who did not
have heart failure. In fact, ST2 appeared to be a stronger predictor
of death than was NT-proBNP, and a combination of both biomarkers
gave the most accurate prediction for all study participants
"We have confirmed the potential importance of ST2 to predict
risk. What we don't have now is information on how ST2 changes after
adequate heart failure treatment and what that tells us about patients'
response to therapy," Januzzi says. "It's likely that
patterns of multiple biomarkers will help us identify patients with
heart failure who remain at a high risk for death, even though they
appear to be symptomatically improving during treatment. There are
studies underway here at MGH and elsewhere investigating whether
such biomarker 'fingerprints' can guide specific treatment strategies
for heart failure and other cardiovascular diseases." Januzzi
is an associate professor of Medicine at Harvard Medical School
and director of the Cardiac Intensive Care Unit at MGH.
Additional co-authors of the current report are Claudia Chae, MD,
MPH, Aaron Baggish, MD, Michelle O'Donoghue, MD, Rahul Sakhuja,
MD, Annabel Chen, MD, and Kent Lewandrowski, MD, of MGH Cardiology;
Frank Peacock, MD, Cleveland Clinic; Alan Maisel, MD, University
of California, San Diego; Robert Jesse, MD, Virginia Commonwealth
University; Roland van Kimmenade, MD, University Hospital of Maastricht,
The Netherlands; Donald Lloyd-Jones, MD, MSc, Northwestern University
Feinberg School of Medicine; and Alan Wu, PhD, University of California,
San Francisco.
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,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
MGH and Brigham and Women's Hospital are founding members of Partners
HealthCare HealthCare System, a Boston-based integrated health care
delivery system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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