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hs-cTn Assays: A Game Changer?
chest Pain Protocol, continued from page 6
Than added that demonstrating the
value of a structured risk assessment was
a key objective of ASPECT. “A lot of literature
shows that assessments of pre-test
probabilities are done extremely poorly
by clinicians,” he observed. “In general, we
tend to overestimate the risks because we’re
concerned about the possibility of getting
it wrong. We also tend not to agree with
each other in assessing risk. That’s why we
thought some sort of structured risk assessment
was important.”
The Role of High-Sensitivity cTn Assays
While experts agreed that the ASPECT protocol
broke ground by laying out objective
assessment criteria for ACS, several observers
questioned the relevancy of a POC panel
employing CK-MB, myoglobin, and a
contemporary—but not high-sensitivity—
cTnI assay, given that both high-sensitivity
cTnT and cTnI assays with limits of detection
10 times lower than conventional assays
are about to hit the U.S. market (CLN
Feb 2011). In addition, the cTnI assay used
in ASPECT, the Alere Triage CardioProfiler,
is not approved for use in the U.S.
“There’s no question that ASPECT adds
to the argument that myoglobin and CK-
8 CliniCal laboratory news July 2011
MB are no longer necessary,” said Wu. “In
my opinion that conclusion was reached
years ago, even before the advent of the
current generation of troponin assays, but
this reaffirms even more so that labs should
move away from the former two.”
Than explained that in his own clinical
practice, he has not used myoglobin or
CK-MB for at least a decade, but that the
ASPECT investigators specifically wanted
to evaluate a POC biomarker panel. “We
were interested in the point-of-care concept,
but we also felt that by using a slightly
inferior troponin assay, one can say you
can do this with any troponin assay you
like—either point-of-care or central lab—
because even a less-sensitive assay works
just fine,” he explained. “The main message
of the paper was that the combination
of this risk/pre-test probability tool, with
ECG and troponin or combinations of
biomarkers can be used for safe, early discharge
of some patients.
Whether the new high-sensitivity cTn
assays will hinder or harm efforts to speed
emergency department assessment of chest
pain patients remains unclear. Some observers,
like Michael Kontos, MD, argued
that the assays will help quickly identify the
lowest of low-risk patients but contribute
Guidelines for
managing acute coronary
syndrome Patients
Key professional organizations have published guidelines on
the use and interpretation of cardiac biomarkers in aCs.
acc/aha 2007 Guidelines for the management of Patients
with unstable angina/non-sT-elevation myocardial
infarction, J am Coll Cardiol 2007;50:e1–157.
clinical Policy: critical issues in the evaluation and
management of adult Patients with non-sT-segment
elevation acute coronary syndromes,
annals of emergency Medicine 2006;48:270–301.
nacb laboratory medicine Practice Guidelines for
utilization of biochemical markers in acute coronary
syndromes and heart failure, Clin Chem 2007;53:2086–2096.
Testing of low-risk Patients Presenting to the emergency
department with chest Pain: a scientific statement from
the american heart association, Circulation 2010;122;1756–76.
universal definition of myocardial infarction,
J am Coll Cardiol 2007;50:2173–2195.
in other ways to slower emergency department
processing times. “You’ll have the really
low-risk cohort where the troponin will
be so sensitive that once you do the test and
clinical assessment, you’ll essentially be able
to exclude an acute coronary syndrome,”
he said. “But then you’ll have a more intermediate
risk group that will have detectible
troponin levels—not necessarily with serial
changes or highly suggestive of acute
coronary syndrome—but they clearly need
some sort of further evaluation.” Kontos is
associate professor of internal medicine at
Virginia Commonwealth University’s Pauley
Heart Center in Richmond.
While high-sensitivity cTnI and cTnT
assays might pose challenges in understanding
just what very low levels of circulating
cTn mean, Than suggested that
when used with other components of the
ASPECT protocol, the tests still would
bring clarity and speed to emergency department-based
chest pain evaluations.
“There are far more patients who need to
be ruled-out than ruled-in, and the way
I see the high-sensitivity troponin assays
working is that you’ll be able to set a slightly
higher pretest probability to your risk score
because the assay will be more sensitive,” he
said. “This will enable you to incorporate
a broader group of patients in a potential
early rule-out group. There needs to be a
greater awareness of rule-out and the benefits
it can have on the healthcare system.”
A Glimpse of the Future
Most experts agreed that the high-sensitivity
cTnT and cTnI assays eventually would
lead the way towards shorter chest pain assessment
protocols. “Conceptually, this a
great model to consider, and it’s a good first
step in thinking about whether assays will
be able to differentiate chest pain patients
this early in the process. The high-sensitivity
troponin assays will narrow the window,”
predicted Fred Apple, PhD, professor
of laboratory medicine and pathology
at the University of Minnesota School of
Medicine, and medical director of clinical
laboratories at Hennepin County Medical
Center in Minneapolis.
However, Apple cautioned that considerably
more research would be needed
before 2-hour chest pain work-ups become
standard-of-care. “We’ll need a wealth of
more information before we start changing
practice patterns. The high-sensitivity troponin
assays will need to be looked at for
baseline and two hours for every person
who walks in the emergency department
with suspected acute coronary syndrome,
and determine whether an absolute value
or delta change percent is best for patient
triage. This is not ready for primetime just
yet.”
Research efforts that might transform
chest pain assessment standards already are
underway. For example, a team of British
researchers recently reported that patients
with suspected MI who were tested at presentation
and after 90 minutes with a POC
biomarker panel consisting of cTn, CK-
MB, and myoglobin had shorter median,
but not mean, lengths of stay in the emergency
department and were discharged
more frequently without inpatient admission
(Heart 2011;97:190–196).
In addition, Amsterdam and his colleagues
at UC Davis are preparing to
publish results from an accelerated assessment
process for very low risk patients.
“We’ve been investigating a protocol
that involves a clinical assessment,
biomarkers, and ECG with a two-to-four
hour period,” he said. “It’s a minority
of our population, but we’ve found
the patients we’re doing this with to be
very safe with no events at 30-days.”
Than also has initiated a randomized
controlled trial using the ASPECT protocol
but with a central lab-based cTn assay.
“I wouldn’t expect anyone to change their
practice necessarily based on the ASPECT
study, but I might expect them to take more
interest when results from this second study
become available,” he said. “We expect that
we’ll demonstrate that you can send 15
to 20 percent of patients home early and
safely, with an economic benefit in terms of
bed days saved.” CLN