The study, conducted in 96 United States and Canadian hospitals and published in the Oct. 31 issue of the New England Journal of Medicine, shows that the "troponin T" test is a powerful indicator of how injured a heart is, especially when used in patients who don't show clear evidence of trouble from standard electrocardiography (EKG) readings.
The researchers say the study is important because physicians can't easily detect distinct signs of heart disease in some patients who come to the hospital with chest pain. The American Heart Association estimates that in one year as many as 1.5 million Americans will have a heart attack and 500,000 of them will die. Thousands of those who will die will have been prematurely released from the hospital because their heart attack was not diagnosed, the study's authors said.
Troponin T is a regulatory protein that helps heart muscle contract. Once this muscle starts dying, cell membranes break down and internal cellular material, including proteins, are released and are carried away by blood. Authors of the study say that the troponin T test offers a single measurement that can help emergency department physicians and cardiologists more readily determine which heart patients should be referred for more comprehensive diagnostic testing.
"The relationship between the blood level of this protein and the risk of death was a direct one in this study," said Dr. Magnus Ohman, the lead researcher and a cardiologist at the Duke Clinical Research Institute. "The troponin T test is an extremely useful tool that can give physicians additional insight into the extent of a patient's heart disease.
"In the least, it should be used in a hospital's emergency department when other indicators, such as an electrocardiogram, don't show clear evidence of trouble," Ohman said in an interview.
Co-author Dr. Robert Califf, director of the Duke institute, said that while the test may result in increased health care costs, because it will identify those patients who need immediate and aggressive heart care, it "will save more lives."
"We have long needed a way to identify those patients with no telltale signs of possible acute heart disease other than pain," Califf said. "In an emergency department, we need additional tools to help us decide who should receive quicker intervention."
The test was administered to 855 patients in North America, and involved physicians from both small community hospitals and large research centers. The primary researchers were from Duke, The Cleveland Clinic Foundation, The University Of Edmonton in Canada, the University of Maryland Medical System, the Universities of Heidelberg and Hamburg in Germany, and Methodist Hospital-Baylor College of Medicine in Houston.
It was conducted as a sub-study of a larger clinical trial known as GUSTO IIa, and was supported by Ciba-Geigy Corp., Advanced Cardiovascular Systems, and the German pharmaceutical company Boehringer Mannheim, which manufactures the troponin T test. The test, which costs $30, received U.S. Food and Drug Administration approval in 1994.
In the study, the troponin T test was administered within 12 hours of the onset of symptoms in patients, but physicians did not use test results to refine treatment. Rather, the tests were "blinded," that is, they were processed at a lab at the University of Maryland Medical System, and results were not known until all patients in the study had been enrolled.
These results were then compared to indications of heart disease from an EKG, which records the flow of electrical energy through the heart, and from a standard blood test known as CK-MB, which measures creatine kinase, another marker of heart damage. CK-MB must be administered at least twice, once when a patient is first seen, and then several hours later for a comparison reading. All three test measurements were then compared to what treatment the patient received and whether they died.
Specifically, the researchers found:
On admission to the hospital, 36 percent of the patients had elevated troponin T levels. Death within a month was significantly higher in these patients (11.8 percent) than in patients with lower levels of the protein (3.9 percent).
Of the three measurements, troponin T level was the variable most strongly related to 30-day mortality, followed by EKG readings, and then CK-MB test results. The relation between protein level and death rate was "nearly linear and direct," Ohman said.
Patients with a positive troponin T level but with no significant EKG readings were more than three times as likely to die in a month than those patients with low troponin T and negative EKG readings. Specifically, among the patients with no clear evidence of new heart damage, 9.9 percent of those with positive troponin T results died compared to 3 percent of patients with low troponin T.
Duke researchers now are studying a large number of patients with confirmed heart attacks to further determine the ability of troponin T results to signal the need for aggressive treatment. They are researching a newer version of the test, called the CARDIAC T Rapid Assay, as part of a larger, ongoing study of medications to treat acute heart attacks. That clinical trial, known as GUSTO III, has enrolled 10,000 of a projected 15,000 patients internationally.