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Novel candidate biomarker for heart failure also strongly predicts risk of death

August 07, 2007

Better understanding of biomarkers' significance may allow personalized treatment planning

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.

Massachusetts General Hospital