Usefulness of the Troponin-Ejection Fraction Product to

Differentiate Stress Cardiomyopathy from ST-Segment Elevation

Myocardial Infarction
Francisco O. Nascimento, MDa,*, Solomon Yang, MDa, Maiteder Larrauri-Reyes, MDa,
Andres M. Pineda, MDa, Vertilio Cornielle, MDa, Orlando Santana, MDa, Todd B. Heimowitz, DOa,
Gregg W. Stone, MDb,c, and Nirat Beohar, MDa
The presentation of stress cardiomyopathy (SC) with nonobstructive coronary artery disease mimics that of ST-segment elevation myocardial infarction (STEMI) due to coronary
occlusion. No single parameter has been successful in differentiating the 2 entities. We thus
sought to develop a noninvasive clinical tool to discriminate between these 2 conditions. We
retrospectively reviewed 59 consecutive cases of SC at our institution from July 2005
through June 2011 and compared those with 60 consecutives cases of angiographically
conrmed STEMI treated with primary percutaneous coronary intervention in the same
period. All patients underwent acute echocardiography, and the peak troponin I level was
determined. The troponin-ejection fraction product (TEFP) was derived by multiplying the
peak troponin I level and the echocardiographically derived left ventricular ejection fraction. Comparing the SC and STEMI groups, the mean left ventricular ejection fraction at
the time of presentation was 30 9% versus 44 11%, respectively (p <0.001), and the peak
troponin I was 7.6 18 versus 102.2 110.3 ng/dl, respectively (p <0.001). The mean TEFP
was thus 182 380 and 4,088 4,244 for the SC and STEMI groups, respectively
(p <0.001). Receiver operating characteristic curve analysis showed that a TEFP value 250
had a sensitivity of 95%, a specicity of 87%, a negative predictive value of 94%, a positive
predictive value of 88%, and an overall accuracy of 91% to differentiate a true STEMI from
SC (C-statistic 0.91 0.02, p <0.001). In conclusion, for patients not undergoing emergent
angiography, the TEFP may be used with high accuracy to differentiate SC with nonobstructive coronary artery disease from true STEMI due to coronary occlusion. 2014
Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:429e433)
The discrimination of the likelihood of stress cardiomyopathy (SC) versus ST-segment elevation myocardial
infarction (STEMI) due to coronary thrombosis is of
particular importance when it involves unstable (i.e., highrisk) patients with critical medical conditions such as severe
sepsis, postoperative shock, respiratory failure, or oncologic
patients during the nadir phase of chemotherapy induction,
in whom cardiac catheterization entails increased risk.1e4
Thus far, no reliable predictor to suggest SC or, more
importantly, to rule out STEMI due to coronary occlusion in
such clinical conditions has been reported.5e9 From experience, we have noticed that patients with SC often have a
signicantly reduced left ventricular ejection fraction
(LVEF), disproportionate to the level of the troponin increase (i.e., the peak troponin level is less than would
otherwise be expected), whereas in the cases of STEMI, the
troponin increase is relatively greater for the moderately
a
Department of Cardiology, The Mount Sinai Heart Institute, Miami Beach,
Florida; bColumbia University Medical Center, New York, New York; and
c
The Cardiovascular Research Foundation, New York, New York. Manuscript
received August 14, 2013; revised manuscript received and accepted October
27, 2013.
See page 432 for disclosure information.
*Corresponding author: Tel: (305) 674-2163; fax: (305) 647-2368.
E-mail address: fonasci@gmail.com (F.O. Nascimento).

0002-9149/13/$ - see front matter 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjcard.2013.10.013

reduced LVEF. The synchronous trend toward a lower value

of peak troponin level and LVEF in SC compared with
STEMI has led us to propose a novel parameter, TEFP,
which is derived from the product of peak troponin I level
and echocardiographically derived acute LVEF. We thus
sought to evaluate the utility of TEFP in distinguishing
between SC and STEMI in critically ill hospitalized patients.
Methods
After obtaining approval from the institutional review
board, we retrospectively reviewed 76 consecutive cases at
our institution (from July 2006 through June 2012) with
acute coronary syndromes, in whom coronary angiography
demonstrated nonobstructive coronary disease and in whom
a diagnosis SC was made. We also reviewed 80 consecutives cases of angiographically conrmed STEMI due to
coronary occlusion during the same period, starting in July
2006. The demographic data, medical history, cardiac biomarkers, 12-lead electrocardiogram, echocardiogram, coronary angiogram, and ventriculogram ndings were
reviewed. All patients from both groups had to have at least
2 samples of troponin I measured 8 to 12 hours apart and
checked within 24 hours from onset of symptoms or electrocardiographic abnormality. The peak troponin I level and
the baseline acute echocardiographically derived LVEF was
www.ajconline.org

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The American Journal of Cardiology (www.ajconline.org)

Figure 1. Flow diagram of patient entry into the study. PCI percutaneous coronary intervention.

Table 1
Patient characteristics and lab values
Characteristic
Age (mean  SD)
Women (%)
Peak troponin I (ng/dl)
LVEF (%)
TEFP

STEMI (n 60)

SC (n 59)

62  16
17 (31)
102.2  110.3
44  11
4,088  4,244

74  27
37 (63)
7.6  18.7
30  9
182  380

<0.001
<0.001
<0.001
<0.001
<0.001

Continuous variables are expressed as mean  SD.

used for the product calculation. An echocardiogram of good

technical quality obtained within 24 hours of syndrome
onset had to be available to be reviewed, to allow the use of
the biplane Simpsons method to assess LVEF. Also, they
had to have a follow-up echocardiography to reassess LVEF
recovery. The peak troponin I level and the echocardiographically derived LVEF was used for the TEFP calculation. A follow-up echocardiogram within 1 month was also
required in all patients with SC to reassess LVEF recovery.
The selected patients with SC satised the Mayo Clinic
criteria2 for the diagnosis of SC as follows: (1) transient
akinesia or dyskinesia in the left ventricular apical and
midventricular segments with regional wall motion abnormalities extending beyond a single epicardial vascular distribution; (2) the absence of obstructive coronary disease or
angiographic evidence of an acute plaque rupture; (3) new
electrocardiographic abnormalities (either ST-segment
elevation or T-wave inversion); and (4) the absence of
recent signicant head trauma, intracranial bleeding, pheochromocytoma, obstructive epicardial coronary artery disease, myocarditis, or hypertrophic cardiomyopathy. We
excluded patients with intermediate obstructive coronary
artery disease (as determined by angiographic evidence of

Figure 2. Distribution plot of peak troponin I level versus ejection fraction

in patients with SC and STEMI. Each mark represents a patient. Patient
with SC are plotted in lled squares, whereas patients with STEMI are
plotted in unlled diamonds. EF ejection fraction.

>50% diameter stenosis in at least one of the epicardial

vessel that was associated with the affected wall motion
abnormality), patients with persistent wall motion abnormalities, and patients without a follow-up echocardiogram
to reassess left ventricular function reversibility of the wall
motion abnormalities. The control group included the

Coronary Artery Disease/TEFP to Diagnose Stress Cardiomyopathy

431

Table 2
Diagnostic performance of troponin-ejection fraction product (TEFP) 250
for discriminating ST-segment elevation myocardial infarction from stress
cardiomyopathy
Parameter
Sensitivity
Specicity
Positive predictive value
Negative predictive value
Overall accuracy

Figure 3. ROC curve of TEFP. The TEFP ROC curve (blue line) showed an
area under the curve (C-statistic) of 0.91  0.02, p value <0.001. Green
line reference.

Probability
0.95
0.87
0.88
0.94
0.91

the operator to have chronic total occlusion or the patients

whose culprit-occluded vessel could not be revascularized
were excluded.
Echocardiograms of all cases of SC and STEMI included
in this study were independently reviewed by 2 different
echocardiographers certied by the National Board of
Echocardiography (F.O.N and O.S), and the LVEF was
calculated using the biplane Simpsons method, from
orthogonal 2-chamber and 4-chamber apical views.10 When
the LVEF differed by >5% between the 2 assessors, the
case was reviewed and a consensus was established.
Continuous variables were analyzed using Student t test
and are presented as mean  1 SD. The categorical data are
presented as percentages and frequencies and were analyzed
using the chi-square test. A p value of <0.05 was considered
to be signicant. The variable analyzed was dened as the
product of the peak troponin level multiplied by the LVEF
(troponin  ejection fraction productTEFP). Corresponding receiver operating characteristic (ROC) curves
were plotted for the TEFP and peak troponin level. Then,
the optimal discriminating threshold of TEFP value was
determined. The sensitivity, specicity, negative predictive
value, positive predictive value, and accuracy were calculated as well. All statistical analyses were performed using
SPSS, version 17 (SPSS Institute, Chicago, Illinois).
Results

Figure 4. The TEFP ROC curve (blue line) showed an area under the curve
of 0.91  0.02 with a p value <0.001. The peak troponin level ROC curve
(green line) showed an area under the curve of 0.81  0.03. The area under
curve of TEFP is signicantly greater than peak troponin level (p <0.01). It
indicates that TEFP is a useful diagnostic parameter to differentiate SC from
STEMI, and it has incremental diagnostic yields than troponin level alone.
Brown line reference.

patients with ST-segment elevation on the electrocardiogram

and whose coronary angiogram showed total occlusion
(Thrombolysis In Myocardial Infarction 0 or 1 ow) of at
least 1 epicardial coronary artery, with Thrombolysis In
Myocardial Infarction 0 or 1 ow in that subtending the
corresponding myocardial territory, and those who underwent
successful primary percutaneous coronary intervention and
revascularization in the same procedure. Patients deemed by

We initially evaluated 76 cases of presumed SC; of

which, 17 were excluded because of not meeting inclusion
criteria or for the presence of at least 1 exclusion criterion.
Therefore, we analyzed 59 consecutive cases of denite SC.
In the STEMI group, 80 consecutive cases were initially
reviewed, but 20 did not satisfy the inclusion and/or
exclusion criteria and were excluded from the analysis
(Figure 1). The nal study population thus consisted of 59
patients with SC and 60 patients with true STEMI.
Patient characteristics are listed in Table 1. The peak
troponin I level was 7.6  18 ng/dl in the SC group, which
is signicantly lower than the 102.2  110.3 ng/dl in the
STEMI group (p <0.001). The SC group had a lower LVEF
than the STEMI group (30  9% vs 44  11%, p <0.001).
After a mean follow-up duration of 10 days, the LVEF of
SC group improved signicantly from 30  9% to 56  9%
(p <0.001). The peak troponin I level (ng/dl) was multiplied
by the echocardiographically derived acute LVEF (%); the
troponin-LVEF product (TEFP) was calculated for the SC
and the STEMI groups and then compared. The mean TEFP

432

The American Journal of Cardiology (www.ajconline.org)

was 182  380 and 4,088  4,244, respectively, for SC and

STEMI groups (p <0.001). A scatter plot (Figure 2) of peak
troponin levels versus LVEF demonstrated the different
distributions of the 2 groups of patients with SC and those
with STEMI. The ROC curves of TEFP (Figure 3) and peak
troponin levels were plotted to determine the optimum cutoff value where to separate the patients with SC and patients
with STEMI. The areas under the ROC curves (C-statistic)
were 0.91  0.02, p <0.001 for TEFP and 0.81  0.03,
p <0.001 for peak troponin level. The comparison between
both ROC curves showed signicant difference in those
parameters (p <0.01; Figure 4). At a TEFP value 250,
STEMI can be discriminated from SC with a sensitivity of
95%, a specicity of 87%, a negative predictive value of
94%, a positive predictive value of 88%, and an overall
accuracy of 91% (Table 2).
Discussion
The principal contribution of our study is the development of the troponin  LVEF product (TEFP), as a simple
clinical tool to accurately distinguish SC from STEMI.
TEFP 250 had 88% positive predictive value to predict
STEMI, with 95% negative predictive value when <250.
This readily available index thus may enhance the likelihood
of accurately discriminating these 2 conditions in critically
ill patients with other serious co-morbidities, in whom immediate cardiac catheterization is not performed. Although
peak troponin level alone also offers some discrimination
value between SC and STEMI, the comparison of the TEFP
and peak troponin level ROC curves indicates that TEFP has
incremental diagnostic yields than troponin alone (p <0.01),
and it is a useful and more accurate diagnostic parameter.
As the clinical presentation of SC in an acutely ill patient
resembles STEMI, coronary angiography is a mandatory
part of the workup to exclude coronary thrombosis and
occlusion.2 Unlike the initial reports in which in such patients with SC had chest pain and ST-segment elevation,
later series described several patients with dyspnea as the
main complaint, whereas others were asymptomatic.10,11 In
addition, the electrocardiographic ndings of SC are
frequently lone T-wave abnormality, which makes the
clinical diagnosis less precise. When the troponin level becomes elevated in patients in whom SC is considered,
coronary angiography becomes unavoidable to exclude
coronary occlusion, regardless of the low range of the peak
troponin level and the echocardiographic demonstration of
apical ballooning with a hyperkinetic base.12e16 We found
that critically ill patients, often unstable with multiple
medical problems other than coronary artery disease, not
infrequently present with those ndings during hospitalization. A coronary angiography is typically performed in these
patients despite its risks as previously there has been no
certain method to discriminate between STEMI and SC, not
even with advanced imaging modalities such as cardiac
magnetic resonance imaging or nuclear scintigraphy.17,18
The TEFP may now be used with high diagnostic accuracy
to discriminate SC from STEMI, potentially avoiding the
risks and costs of cardiac catheterization in such patients.
Note that our proposal is not to defer coronary angiography for patients who present to the emergency department

with an acute chest pain syndrome and ST-segment elevation.

When there is clinical suspicion of STEMI, no time should be
wasted to obtain an echocardiogram or wait for the troponin
level to peak. This type of patient in such clinical presentation
needs emergent cardiac catheterization. However, for critically ill patients with noncardiac co-morbidities who are
already hospitalized and who are found to have troponin level
elevation with low LVEF, the TEFP may be calculated to
assess the likelihood of SC before referring for coronary
angiography. If the TEFP is <250, it is indeed very likely that
the problem is SC rather than STEMI.
The principal limitation of our study is that it is a retrospective analysis from a single institution. SC is a relatively
rare disease, and therefore the sample size was moderate.
A prospective multicenter study should ideally be performed
to conrm our results. We also required the STEMI control
group to have undergone successful primary percutaneous
coronary intervention. This may have led to an underestimation of the peak troponin level in such patients who had
percutaneous coronary intervention performed. As such, the
TEFP may have even greater diagnostic accuracy to
discriminate STEMI from SC in patients not undergoing
coronary angiography than described in the present report.
Disclosures
Dr. Stone is a consultant for Boston Scientic, Minnesota.
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