CARDIOLOGY/EXPERT CLINICAL MANAGEMENT
Managing Troponin Testing
Judd E. Hollander, MD*
*Corresponding Author. E-mail: judd.hollander@jefferson.edu, Twitter: @juddhollander.
0196-0644/$-see front matter
Copyright © 2016 by the American College of Emergency Physicians.
http://dx.doi.org/10.1016/j.annemergmed.2016.05.023
[Ann Emerg Med. 2016;-:1-5.]
Editor’s Note: The Expert Clinical Management series
consists of shorter, practical review articles focused on the
optimal approach to a specific sign, symptom, disease,
procedure, technology, or other emergency department
challenge. These articles—typically solicited from
recognized experts in the subject area—will summarize the
best available evidence relating to the topic while including
practical recommendations where the evidence is
incomplete or conflicting.
INTRODUCTION
Troponin is released in myocardial injury whether or not
the injury is caused by acute myocardial infarction (Figure 1).
There are 4 main categories of disease that might result in
acute myocardial injury. Acute myocardial infarction can
occur because of obstruction to flow through the coronary
vessels (type I acute myocardial infarction) or through supply-
demand mismatch, as might occur in profound anemia with
decreased oxygen-carrying capacity (type II acute myocardial
infarction). Nonischemic cardiac conditions, as well as
noncardiac disorders, also cause myocardial injury.
There are no “false-positive” troponin elevations; all reflect
myocardial injury and all portend a worse prognosis than for
otherwise similar patients without a troponin elevation. This
has been shown for patients with heart failure,1 renal failure,2
gastrointestinal bleeding,3 sepsis,4 respiratory disease,5
pulmonary embolism,6 subarachnoid hemorrhagic, or
stroke.7,8 An elevated troponin level even indicates a worse
prognosis in asymptomatic people without known
cardiovascular disease.9-11 The higher the troponin, the worse
the prognosis, regardless of the cause of the elevation1,12; thus,
the mantra that “any troponin is worse than no troponin and
more troponin is worse than less troponin.”
LABORATORY MEDICINE 101 FOR EMERGENCY
PHYSICIANS
Troponin levels generally begin to increase within 2 to
4 hours; most acute myocardial infarction patients can be
Volume -, no. - : - 2016
identified within 6 to 9 hours after the onset of pain.
Troponin assays, used in the United States, are becoming
increasingly sensitive, with measurable troponin values
(those within the normal range but above the lower limit of
detection) now detectable in 20% to 50% of patients with
the standard contemporary assays (also known as sensitive
or moderately sensitive assays). Troponin assays currently
used in Europe and pending approval in the United States
measure troponin levels above the lower limit of detection
in 50% or more of patients (these are referred to as high-
sensitivity assays).
It is important to verify that your laboratory defines
abnormal values by the 99th percentile of a normal
population, rather than the former 95% threshold, and that
your assay demonstrates no greater than a 10% to 20%
coefficient of variation at this upper limit of normal. The
strategies discussed in this article assume compliance with
these important benchmarks. Although all troponin I and
T assays differ, their interpretation is similar; therefore, in
this article I will simply refer to them all as troponins.
APPROACH TO INTERPRETING TROPONIN
VALUES
A general approach to troponin interpretation is
outlined in Figure 2. Emergency physicians are faced with
interpretation of troponin results in 3 different scenarios:
the test was ordered specifically to exclude an acute
coronary syndrome, as part of a panel for some other
condition, or through standing orders, and after clinical
evaluation the clinician would not have ordered the test.
When Acute Coronary Syndrome Is the Primary
Concern
A troponin elevation in the presence of a compatible
history or ECG evidence of ischemia indicates an acute
myocardial infarction. The third universal definition of
myocardial infarction requires a combination of an increase
or decrease in cardiac biomarkers, with at least 1 value
above the 99% percentile of the upper reference limit and a
Annals of Emergency Medicine 1
Managing Troponin Testing
Figure 1. Some cardiac and noncardiac causes of troponin
elevation in the absence of thrombotic occlusion.
history concerning for acute ischemia, new significant ECG
changes, including ST- or T-wave changes, left bundle
branch block, pathologic Q waves, evidence of regional wall
motion abnormality, loss of viable myocardium, or
detection of thrombus.13
In a patient with an acute coronary syndrome,
verification of a troponin elevation will prompt specific
therapies such as enoxaparin, glycoprotein IIb and IIIa
receptor antagonists, and percutaneous coronary
intervention.12,14 When it is not clear whether a troponin
elevation reflects acute or chronic myocardial injury, a
2 Annals of Emergency Medicine
Hollander
repeated value 1 to 3 hours later (D value) can be helpful
because it will increase with acute injury.
The exclusion of acute myocardial infarction such that a
patient can be discharged requires reducing the likelihood
of a serious cause to an acceptable threshold, typically
considered to be less than a 1% to 2% likelihood of adverse
events.15 Traditionally, this required serial troponin values
during 12 or more hours. Multiple studies now show that
myocardial infarction can be ruled out within a shorter
timeframe, using D values (the absolute change in troponin
values taken 1 to 3 hours apart).
The European Society for Cardiology (ESC)14
recommends a rapid rule-out protocol at 0 and 3 hours,
using high-sensitivity cardiac troponin tests. They endorse
an even more rapid rule-out and rule-in protocol at 0 and 1
hours with a few selected high-sensitivity assays.14 The
International Federation of Clinical Chemistry
recommends D values 3 hours apart.16 This strategy works
with some of the contemporary moderate-sensitivity assays
used currently in the United States and the high-sensitivity
assays used in Europe. The use of an absolute rather than
relative difference between values appears superior.17,18
The optimal absolute difference required to identify acute
myocardial infarction depends on the specific assay being
used and the interval between values.
Several large clinical studies support this approach.19-26
Using several different assays, Reichlin et al19 and Keller
et al20 found very high sensitivities (>90%) at presentation
that approached 100% by 3 hours. Performance
characteristics at 3 hours were similar between standard
contemporary and high-sensitivity troponins.21 Point-of-
care assays currently do not share these performance
characteristics.22
Contemporary troponin assays (those with moderate
sensitivity) alone do not reduce the miss rate to less than
1%, but combining troponin testing with some features of
the clinical presentation achieves that goal. Two large trials,
ASPECT and ADAPT,23,24 found that a combination of a
nonischemic ECG, 2 troponins 2 hours apart, and a TIMI
score of 0 had a 0.3% to 0.9% prevalence of 30-day adverse
events rates (including acute myocardial infarction). The
TRAPID trial, using high-sensitivity troponins 1 hour
apart, had a 0.9% misdiagnosis rate in the 63% of patients
without acute myocardial infarction.25 These studies have
limitations because they did not use the test results to
discharge the patients and few patients presented shortly
after symptom onset, when the performance of the assays is
less well defined.27
An additional useful feature is the duration of chest pain.
Although not well defined, there is some duration of chest
pain that is long enough that the patient either has had an
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Hollander Managing Troponin Testing

Troponin Obtained

ACS 1o Concern ACS Not 1o Concern

Assess Symptom Medical Condition In retrospect,

Onset and Duration That Can Impact would not have
Heart * ordered troponin

Multiple Short 1 or more Single Prolonged

Episodes Intermediate Episode Troponin Troponin Troponin
Length Positive Negative Positive
Episodes

Repeat; Treat 1o Treat 1o

Troponin Troponin Troponin Treat Concern Concern;
Negative Positive Negative presenting Repeat and/or
condition; refer for long
Consider term risk
NSTEMI strati ication ‡
Repeat and Treat ACS Repeat in 2-3
perform hours or
testing to rule discharge
out ischemia
or CAD †

Figure 2. Approach to evaluation of patients who had a troponin test ordered in the emergency department. *Examples include but are not
limited to hypertension, kidney disease, and pulmonary embolism. †Examples include myocardial perfusion imaging and coronary computed
tomographic angiography. ‡Long-term risk stratification depends on specific conditions being evaluated. ACS, Acute coronary syndrome;
NSTEMI, non-ST-elevation myocardial infarction; CAD, coronary artery disease.

acute myocardial infarction or the symptoms are not due to days ago). Stable serial measurements 2 to 3 hours apart
ischemia, making unstable angina no longer a concern. indicate chronic myocardial injury.12,14,16 With
Thus, a single negative troponin-level result can exclude nonischemic acute injury and chronic myocardial injury,
acute myocardial infarction when obtained more than 6 to there is no evidence that any specific additional treatment
9 hours after the onset of prolonged chest pain.12,14 The
ESC guidelines use 6 hours as the timeframe for a single 100 potential ACS patients
high-sensitivity troponin test.14 The American College of
Cardiology/American Heart Association guidelines
recommend that troponin be measured at presentation and
3 to 6 hours after symptom onset.12 If the patient has an 35 Discharged 65 Admitted
intermediate to high risk presentation (Figure 3), 1 more
value is recommended 3 hours later (6 to 9 hours after
symptom onset). Low-risk patients do not require further
troponin testing. 50 Obs/Adm 15 Cards

94% Sens; 80% Spec

WHEN THE PRIMARY CONCERN IS NOT AN 44
8
ACUTE CORONARY SYNDROME
A negative troponin level result in a patient without 16-17 trop + 14-15 trop +
concern for acute coronary syndrome does not need to be 69 Discharged non ACS ACS
repeated. When elevated, however, it indicates acute or
Figure 3. Effect of high-sensitivity troponin testing on ED
chronic myocardial injury (Figure 1), with the former disposition decision. Obs, Observation; Adm, admission; Cards,
usually confirmed by an increasing pattern (although a cardiology; Sens, sensitivity; Spec, specificity; Trop, troponin; þ,
declining pattern can be observed if the injury occurred positive.

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Managing Troponin Testing
Figure 4. Approach to interpretation of positive troponin values.
beyond that indicated for the primary condition affects
mortality, so treat according to the underlying condition
(eg, heart failure, myocarditis) and recognize the higher risk
for complications.
When it is not clear that a troponin elevation reflects
chronic myocardial injury, a repeated troponin level
measurement in 2 to 3 hours will help exclude acute
myocardial injury. Despite their worse prognosis, patients
with chronic troponin elevation do not require hospitalization
for this laboratory value alone. They should, however, be
carefully assessed for known causes of troponin elevation
associated with adverse short-term outcomes (eg, heart failure,
renal failure, cardiomyopathy).
INCORPORATING TROPONIN INTO YOUR
PRACTICE
Troponin levels, when used correctly, can more rapidly
identify both the high- and low-risk patients presenting
with potential acute coronary syndrome (Figure 4). With
older less sensitive troponin assays, all elevations were
thought to be diagnostic of acute myocardial infarction, but
with the more sensitive assays that is no longer the case.
The following model28 (Figure 3) illustrates the beneficial
effect of an assay with 94% sensitivity and 80% specificity
on ED disposition. Assume that for every 100 patients
presenting to the ED with a potential acute coronary
syndrome, 65 are admitted (15 to cardiology [the acute
coronary syndrome patients], 50 to observation or
hospitalists) and 35 are discharged to home. Use of the
assay with these performance characteristics would nearly
4 Annals of Emergency Medicine
Hollander
double the discharge rate from 35 to 69 patients while
maintaining a miss rate of approximately 1%, improving
efficiency, and decreasing costs. However, only 14 of the
31 patients with a troponin elevation would have an acute
myocardial infarction. If all 31 of these patients were
admitted to cardiologists for investigation of myocardial
ischemia, most would have false-positive results; they
would not have acute myocardial infarction and would not
benefit from catheterization and percutaneous coronary
interventions. This decreases efficiency and increases costs.
Approaching these patients, understanding that they have
myocardial injury but not necessarily an acute myocardial
infarction will help allocate resources optimally. A single
troponin elevation does not distinguish acute from chronic
injury. When injury is acute, it does not distinguish acute
myocardial infarction from other causes. When injury is
from acute myocardial infarction, it does sort out whether the
patient has type I versus type II, and finally, it does not
inform whether the patient has underlying coronary disease.
Thus, the increased efficiency that comes with being able to
increase discharge rates needs to be coupled with a thoughtful
approach that does not reflexively admit all patients with
small troponin elevations to cardiologists, without sorting
through which ones might have a cardiac problem.
In summary, troponin is released in the setting of
myocardial injury. The challenge is to distinguish acute
from chronic myocardial injury. Serial troponin values
recorded 2 to 3 hours apart will make this distinction. We
must then distinguish acute myocardial infarction from
other causes of acute myocardial injury because the
treatments differ. It is also important to remember that any
troponin is worse than no troponin and more troponin is
worse than less troponin.
Supervising editor: Steven M. Green, MD
Author affiliations: From the Department of Emergency Medicine,
Sidney Kimmel Medical College at Thomas Jefferson University,
Philadelphia, PA.
Funding and support: By Annals policy, all authors are required to
disclose any and all commercial, financial, and other relationships
in any way related to the subject of this article as per ICMJE conflict
of interest guidelines (see www.icmje.org). The author has stated
that no such relationships exist and provided the following details:
The author reports receiving grants from Alere, Siemens, Trinity,
and Roche and consulting for Radiometer and Janssen.
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