Detecting acute coronary syndrome when seconds count
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
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
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
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.