College of American Pathologists
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Detecting acute coronary syndrome when seconds count

July 2003
Paul Karr

A multi-marker cardiac test kit has just been unveiled in the U.S. market.

The Food and Drug Administration approved in March the Triage Cardio Profiler, a four-substance test panel that can spot or rule out acute coronary syndromes using small blood samples within 15 minutes.

The panel was developed by San Diego-based Biosite. Its Triage Profiler is the first quick test to combine a set of reliable cardiac necrosis markers with an additional neurohormonal marker that can tip off ER physicians to the lurking problem of congestive heart failure.

“By combining all four tests on one cartridge, this test helps physicians quickly elucidate which diagnostic and treatment pathway you send a patient down,” says Robert Christenson, PhD, a professor of pathology and medical and research technology and director of rapid response laboratories at the University of Maryland School of Medicine in Baltimore.

The test panel is compact enough to use at the point of care, and results of the four assays are delivered within 15 minutes.

“This is a nice platform. It’s going to make a difference because it’s quick and accurate,” says W. Frank Peacock, MD, director of emergency department clinical operations at the Cleveland Clinic, who is part of a survey of cardiac blood-test analysis results at U.S. hospitals. The survey has found the “door-to-brain” time—that is, the time between patient arrival in the ER and availability of the blood test results to ER physicians—typically averages about 2.5 hours. “With the Triage Profiler, you can have a result in less than an hour,” he says.

To use the system, users first add about six drops of a patient’s blood or plasma sample to a plastic device roughly the size of a tongue depressor, and then plug the device into the front of an analyzer similar in size to a desktop telephone.

The plastic device uses so-called microcapillary technology to survey blood chemistry. Arrays of tiny capillaries move the patient sample through a series of antibody-based protein binding sites, each geared to detect a particular substance released when heart function is impaired or heart tissue begins to die. When the antibodies detect creatinine kinase, myoglobin, troponin I, or B-type natriuretic peptide, a binding process occurs with a fluorescent tag. The analyzer detects and records the quantitative level of the substance, which can then be compared to normal levels of those chemicals.

“Normally to do this you need a big laboratory analyzer, with pumps and pipette heads moving fluids around,” says Biosite CEO Kim Blickenstaff. “We’re trying to make these very complex binding diagnostics as simple as glucose tests have now become. Glucose testing once used to be done only in reference labs.”

During a myocardial infarction, myoglobin is one of the first substances released into the blood. “Elevated myoglobin gives you the early hunch,” says Dr. Christenson, “and high troponin levels confirm it.”

In a summary of seven clinical trials and 19 cohort studies, collected by Paul Heidenreich, MD, et al, in the Journal of the American College of Cardiology (2001; 38: 478-485), the short-term odds of patient mortality increased three to eight times if troponin levels were elevated. The Triage Profiler panel’s new troponin marker has a detection limit of 0.05 ng/mL.

“If there were a drug that performed as well in the therapeutic world as troponin does as a predictor of death or recurrent myocardial infarction, it would probably cost a thousand dollars a dose,” Dr. Christenson says. “It’s a fantastic marker; if it’s elevated and a patient has the symptoms, you’re certain of the diagnosis. In my mind there are very few clinical pathology tests, perhaps only pregnancy and glucose tests, that have as high a diagnostic reliability as troponin.”

The three protein assays are useful as a way to identify lower-risk patients who are probably not experiencing heart attacks, say emergency physicians. The fourth diagnostic on the panel—for the hormone known as B-type natriuretic peptide, or BNP—represents an important wrinkle in the Triage Profiler: It’s the only FDA-approved BNP test now on the market, and ER physicians can use it for double duty—as an independent marker to risk-stratify MI and ACS patients and to diagnose heart failure. That’s because elevated BNP levels are proving to be a remarkably strong indicator for diminishing left ventricular function.

The ventricles release BNP hormone when the heart over-stretches (from hypertension, for example), and the resulting fluid overload impairs pumping function in a chronic, gradually worsening manner. BNP is a kind of defense against this overload; it relaxes blood vessels and causes sodium and water to be excreted, temporarily easing the fluid and pressure. Thus, a test for BNP can catch heart failure in process. As reported by David Morrow, MD, et al, in the Journal of the American College of Cardiology (2003;41:1264–1272), researchers have determined that blood BNP levels greater than 80 pg/mL correlate strongly with increased risk of congestive heart failure within 30 days of the test. On average, there is a fivefold increase in risk compared with patients whose blood levels do not rise above the 80 pg/mL threshold.

“Before the BNP test, physicians would look at signs and symptoms and use chest x-rays. They were perhaps 60 percent specific in determining whether shortness of breath was CHF or not,” says Biosite’s Blickenstaff. “Now we are bringing that level to 85 percent or 90 percent with this test. That’s a huge improvement in detection.”

The Cardiac Profiler’s BNP component could also eventually serve as a checkup for heart failure patients showing no symptoms at all of declining heart health. Company officials say future plans for the kit might include such portable applications as ambulance or physician-office versions if they prove practical and cost-effective and receive the appropriate FDA approval.

“Chest pain or shortness of breath can be caused by so many things—asthma, allergy, indigestion, and so on—but a heart attack is so important and the consequences so dire that you need to know if it’s happening right away,” says Dr. Christenson. “These tests help you prove it, or prove otherwise. If the troponin and myoglobin levels are low after appropriate specimen timing, it can’t be cell death and heart attack; if the BNP levels are, for example, 40, it can’t be heart failure. By combining BNP with the other markers, it becomes a very valuable test, particularly in the troponin-negative ACS patient.”

In this cohort, he says, the evidence shows that over the six months after the index event, patients with BNP>80 are at sixfold higher risk of death, and 3.5-fold higher risk of a combined outcome of death or MI. Thus, “BNP helps to independently refine risk stratification,” he says, “and the idea of pulling all these together in one panel is very rational.”

Paul Karr is a writer in North Bergen, NJ.