SIGNIFICANCE OF NATIVE AND ALLOGRAFT CAD

Early Assessment of Strain Echocardiography Can

Accurately Exclude Significant Coronary Artery
Stenosis in Suspected NonST-Segment Elevation
Acute Coronary Syndrome
Thomas Dahlslett, MD, Sigve Karlsen, MD, Bjrnar Grenne, MD, PhD, Christian Eek, MD, PhD,
Benthe Sjli, MD, PhD, Helge Skulstad, MD, PhD, Otto A. Smiseth, MD, PhD, Thor Edvardsen, MD, PhD,
and Harald Brunvand, MD, PhD, Arendal, Trondheim, and Oslo, Norway

Background: Many patients with suspected nonST-segment elevation acute coronary syndrome (NSTE-
ACS) do not have significant coronary artery disease. The current diagnostic approach of repeated electrocar-
diography and cardiac biomarker assessment requires observation for >6 to 12 hours. This strategy places a
heavy burden on hospital facilities. The objective of this study was to investigate whether myocardial strain
assessment by echocardiography could exclude significant coronary artery stenosis in patients presenting
with suspected NSTE-ACS.

Methods: Sixty-four patients presenting to the emergency department with suspected NSTE-ACS without
known coronary artery disease, inconclusive electrocardiographic findings, and normal cardiac biomarkers
at arrival were enrolled. Twelve-lead electrocardiography, troponin T assay, and echocardiography were per-
formed at arrival, and all patients underwent coronary angiography. Significant coronary stenosis was defined
as >50% luminal narrowing. Global myocardial peak systolic longitudinal strain was measured using speckle-
tracking echocardiography. Left ventricular ejection fraction and wall motion score index were calculated.

Results: No significant stenosis in any coronary artery was found in 35 patients (55%). Global peak systolic lon-
gitudinal strain was superior to conventional echocardiographic parameters in distinguishing patients with and
without significant coronary artery stenosis (area under the curve, 0.87). Sensitivity and specificity were calcu-
lated as 0.93 and 0.78, respectively, and positive predictive value and negative predictive value as 0.74 and
0.92, respectively. Feasibility of the strain measurements was excellent, with 97% of segments analyzed.

Conclusions: Myocardial strain by echocardiography may facilitate the exclusion of significant coronary artery
stenosis among patients presenting with suspected NSTE-ACS with inconclusive electrocardiographic find-
ings and normal cardiac biomarkers. (J Am Soc Echocardiogr 2014;27:512-9.)

Keywords: Acute coronary syndrome, Speckle-tracking, Myocardial strain, Echocardiography, Emergency

department

Symptoms suggestive of acute coronary syndrome account for up to a
quarter of acute hospital admissions in the Western world.1 However,
most patients presenting with chest pain and suspected acute coro-
nary syndrome do not have significant coronary artery disease.2
From the Srlandet Hospital, Arendal, Norway (T.D., S.K., B.G., B.S., H.B.); St.
Olavs Hospital, Trondheim, Norway (B.G.); and Oslo University Hospital,
Rikshospitalet, Oslo, Norway (C.E., H.S., O.A.S., T.E.).
This study was funded by the Norwegian Health Association, South-Eastern
Norway Regional Health Authority, and Srlandet Hospital (Arendal, Norway).
Reprint requests: Harald Brunvand, MD, PhD, Srlandet Hospital Arendal,
Department of Medicine, Postboks 783, Stoa, 4809 Arendal, Norway (E-mail:
harald.brunvand@sshf.no).
0894-7317/$36.00
Copyright 2014 by the American Society of Echocardiography.
http://dx.doi.org/10.1016/j.echo.2014.01.019
512
Diagnostic protocols to rule out coronary artery disease are based
on risk factors, multiple electrocardiographic (ECG) assessments,
repeated cardiac biomarker assessments, noninvasive stress testing,
and, if indicated, invasive coronary angiography.3 This approach is
resource intensive and time-consuming and places a heavy burden
on overcrowded emergency departments. To cope with these chal-
lenges and facilitate early discharge of patients with low or intermedi-
ate likelihood of coronary artery disease, accelerated diagnostic
protocols based on clinical scoring, imaging, and high-sensitivity bio-
markers have been proposed.4,5 However, these have not yet
gained wide clinical acceptance. To improve the identification of
patients without significant coronary artery stenosis, more robust
diagnostic methods are needed.
Myocardial strain by speckle-tracking echocardiography is a tech-
nique based on widely available two-dimensional grayscale echocar-
diography, enabling the accurate evaluation of global and regional
myocardial function, and it has been shown to be sensitive to
Journal of the American Society of Echocardiography Dahlslett et al 513
Volume 27 Number 5

Abbreviations
abnormalities caused by
ischemia and necrosis.6 Strain
cTnT = Cardiac troponin T echocardiography can be per-
ECG = Electrocardiographic formed bedside in the emer-
gency setting at low cost and
ER = Emergency room has been demonstrated to iden-
GRACE = Global Registry of tify high-risk patients with
Acute Coronary Events nonST-segment elevation acute
coronary syndrome (NSTE-
LV = Left ventricular
ACS) in this setting.7 However,
LVEF = Left ventricular even low-grade ischemia might
ejection fraction cause deterioration of myocar-
NSTE-ACS = NonST- dial function and can be de-
segment elevation acute tected by myocardial strain
coronary syndrome imaging.8 We therefore hypothe-
sized that strain echocardiogra-
ROC = Receiver operating phy might be used to identify
characteristic
patients admitted with suspected
WMSI = Wall motion score NSTE-ACS and without signifi-
index cant coronary artery disease.
The aim of our study was to
evaluate the ability of myocardial strain by echocardiography to
predict significant coronary artery disease among patients presenting
to the emergency department with suspected NSTE-ACS with incon-
clusive ECG findings and normal initial biomarkers.
room (ER) using a Vivid 7 scanner (GE Vingmed Ultrasound AS,
Horten, Norway) and stored digitally. Three consecutive cycles
from three apical image planes were recorded using two-
dimensional grayscale echocardiography. Echocardiographic record-
ings were analyzed by a single observer blinded to patient data, using
commercially available software (EchoPAC version 112; GE Vingmed
Ultrasound AS). Peak systolic strain was defined as the maximum
value of peak negative strain (myocardial shortening) or peak positive
strain (myocardial lengthening) during systole (Figure 1). The end of
systole was defined by the aortic valve closure signal by Doppler
flow. Global peak systolic longitudinal strain by speckle-tracking echo-
cardiography was calculated in a 16-segment left ventricular (LV)
model as the average segmental value on the basis of three apical
imaging planes. LV ejection fraction (LVEF) was calculated using
Simpsons biplane method.
Territorial strain was calculated as the average of peak systolic strain
values in segments belonging to the theoretical perfusion territory of
each major coronary artery on the basis of a modified 16-segment
model described by Cerqueira et al.7,12 The lowest absolute
territorial strain value for each patient was assessed as a marker for
identification of significant coronary stenosis.
Wall motion score was visually assessed in a 16-segment model as
follows: 1 = normal, 2 = hypokinetic, 3 = akinetic, and 4 = dyski-
netic.13 Wall motion score index (WMSI) was calculated by averaging
all analyzed segments.

METHODS Coronary Angiography

Study Population
Sixty-four patients with suspected NSTE-ACS without known coronary
artery disease, inconclusive ECG findings, and normal cardiac
biomarkers at admission were enrolled at Srlandet Hospital Arendal.
Patients admitted with suspected NSTE-ACS were enrolled if the
following criteria were met: (1) acute anginal pain lasting >10 min, (2)
episode of chest pain within the past 3 days, and (3) indication for
coronary angiography according to current guidelines.9 Exclusion
criteria were: (1) age < 18 years, (2) QRS duration > 0.12 sec, (3) severe
valve dysfunction as defined in the European Society of Cardiology
guidelines for the management of valvular heart disease,10 (4) atrial
fibrillation with heart rate > 100 beats/min or other continuous
arrhythmia, (5) known coronary artery disease, (6) severe mental disor-
der, (7) abnormal initial cardiac troponin T (cTnT), (8) abnormal ECG
findings, and (9) short life expectancy of extracardiac reason.
Abnormal cTnT was defined as >30 ng/L. Abnormal ECG findings
were defined as a >1-mm ST-segment deviation in any lead or symmet-
ric T-wave inversion in two or more consecutive leads at admission.
All patients were evaluated and treated according to current guide-
lines. The regional committee for medical research and ethics approved
the research protocol. All participants gave written informed consent.
The Global Registry of Acute Coronary Events (GRACE) risk
score, which has been shown to have good ability to assess risk for
death in patients presenting with acute coronary syndrome,11 was
calculated on the basis of age, heart rate, systolic blood pressure,
Killip class, cardiac arrest, ST-segment deviation, serum creatinine
level, and cardiac biomarker status from data collected on admission.
Echocardiography
Echocardiographic examinations were performed a median of 1.7
hours (interquartile range, 4.5 hours) after arrival in the emergency
Coronary angiography (Figure 1) was performed in all patients a me-
dian of 26 hours (interquartile range, 22 hours) after admission.
Experienced operators unaware of all clinical data retrospectively
analyzed the angiograms. Significant and high-grade coronary artery
stenoses were defined as luminal narrowing $50% and $75% in
any epicardial coronary artery, respectively. Total occlusion was
defined as Thrombolysis In Myocardial Infarction flow grade 0 or 1.
Statistical Analysis
Continuous data are expressed as mean 6 SD or as median (inter-
quartile range). Comparisons between group means were analyzed
using Students t test, the Mann-Whitney U test, or Fishers exact
test as appropriate. Categorical data are presented as number
(percentage).
We analyzed the diagnostic performance of echocardiographic pa-
rameters and GRACE score by calculating the area under the receiver
operating characteristics (ROC) curves. ROC curve analyses were
undertaken using DeLong, DeLong, and Clarke-Pearson comparison
in MedCalc version 12.6.0 (MedCalc Software, Mariakerke,
Belgium). All other statistical analyses were performed using SPSS
version 20 (SPSS, Inc, Chicago, IL). To evaluate the diagnostic perfor-
mance of the studied parameters, patients were randomly divided in a
1:1 fashion into a derived cohort and a test cohort, each consisting of
32 patients. Optimal cutoff values were calculated in the derived
cohort and then applied to the test cohort, producing sensitivity, spec-
ificity, negative predictive value, and positive predictive value for the
studied parameters. An optimal cutoff from the pooled cohort con-
sisting of all 64 patients was also calculated to provide a more accurate
cutoff value for future studies. The optimal cutoffs were defined as the
values of the ROC curves that were closest to the upper left corner.
The reliability of the optimal cutoff values was validated using
514 Dahlslett et al Journal of the American Society of Echocardiography
May 2014

Figure 1 (Left) Coronary angiogram of the right coronary artery with (arrow) and without significant coronary artery stenosis. (Right)
Corresponding strain curves from the inferior wall. Aortic valve closure (AVC) is marked with a vertical green line. Peak systolic
longitudinal strain is the point with the highest absolute value of the curve before AVC.

bootstrap resampling (1,000 iterations), and 95% confidence inter- Table 1 Clinical characteristics in the pooled cohort
vals on the basis of bootstrap percentiles are presented. consisting of all 64 patients
Intraobserver and interobserver variability was analyzed by
repeating the strain measurements in the echocardiographic examina- Significant (>50%) coronary artery stenosis
tions of 10 randomly selected patients. Intraclass correlation coeffi-
Variable No (n = 35) Yes (n = 29) P
cients for both intraobserver and interobserver variability were
obtained using a two-way mixed model. Patient characteristics
Age (y) 54 6 12 56 6 12 .45
Women/men 13/22 7/22 .26
Cardiac medications
RESULTS on admission
Aspirin 3 (9%) 5 (17%) .71
Clinical and Angiographic Data
b-blockers 2 (6%) 7 (24%) .07
Of the 64 patients who had normal initial cTnTand inconclusive ECG Statins 5 (14%) 6 (21%) .53
findings, 35 (55%) did not have significant coronary artery stenosis Clopidogrel 0 (0%) 0 (0%)
and 29 (45%) had significant coronary artery stenosis by coronary ACE inhibitors or ARBs 1 (3%) 0 (0%)
angiography. Baseline and clinical data for patients with and without Hypertension 4 (11%) 11 (38%) .02
significant coronary artery stenosis are presented in Table 1. Time Hypercholesterolemia 10 (29%) 11 (38%) .43
from onset of symptoms to arrival in the ER, time from arrival in Current smoker 11 (31%) 17 (59%) .03
the ER to echocardiographic examination, and time from arrival in Diabetes 4 (11%) 4 (14%) 1.00
the ER to coronary angiography did not differ significantly between Family history of CAD 24 (69%) 14 (58%) .10
the two groups, although there was a trend toward a shorter time GRACE risk score 89 6 22 105 6 29 .02
from arrival in the ER to coronary angiography in patients with signif-
icant coronary artery stenosis. ACE, Angiotensin-converting enzyme; ARB, angiotensin receptor
In the group with significant coronary artery stenosis, four patients blocker; CAD, coronary artery disease.
had 50% stenosis, one patient had 75% stenosis, 15 patients had 90% Data are expressed as mean 6 SD or as number (percentage). P
values are from unpaired t tests or Fishers exact tests.
stenosis, and nine patients had total occlusions in one or more coro-
nary arteries. Fifteen of these patients had elevated troponins in the
second test, indicating nonST-segment elevation myocardial infarc-
tion, whereas 14 were diagnosed with unstable angina pectoris. In (Table 2). Distributions of studied parameters are presented in
the group without significant coronary artery stenosis, none of the Figure 2.
35 patients had elevated troponins in the second test, and all were In a ROC analysis of the pooled cohort consisting of all 64 patients,
given a final diagnosis of noncoronary chest pain. all studied parameters had areas under the curve significantly larger
than 0.5 for prediction of both significant and high-grade coronary ar-
tery stenosis (Table 3). Global peak systolic longitudinal strain was
Echocardiographic Parameters significantly better than LVEF, GRACE score, and WMSI in discrimi-
Global peak systolic longitudinal strain, territorial longitudinal strain, nating between significant and nonsignificant coronary artery stenosis
LVEF, and WMSI measured at admission differed significantly be- (P < .05 for all tests using DeLong, DeLong, and Clarke-Pearson com-
tween patients with and without significant coronary artery stenosis parison). ROC curves for ruling out significant coronary artery
Journal of the American Society of Echocardiography Dahlslett et al 515
Volume 27 Number 5

Table 2 Clinical and echocardiographic findings in the Earlier echocardiographic studies focused on how to detect patients
pooled cohort consisting of all 64 patients with coronary disease.14 In contrast, this study was designed to describe
how an accurate assessment of myocardial strain might exclude signif-
Significant coronary artery icant coronary artery disease. A number of patients admitted to hospi-
stenosis (>50%) tals with suspected NSTE-ACS have inconclusive ECG findings and
Variable No (n = 35) Yes (n = 29) P normal troponins. However, some of these patients still have significant
coronary artery disease in need of further treatment. Therefore, it is of
Clinical data importance to separate patients without significant coronary artery ste-
Time (h) from onset of 10 (21) 6 (10) .45 nosis from those with significant coronary artery stenosis. We found
symptoms to arrival in ER that the use of global myocardial strain by echocardiography in the
Time (h) from arrival in ER to 2 (8.7) 1.3 (3.5) .36 ER, in addition to electrocardiography and initial troponin values,
echocardiography
may improve the early identification of patients without significant cor-
Time (h) from arrival in ER to 27 (26) 23 (16) .07
onary artery disease after arrival to the ER. Global myocardial strain was
coronary angiography
calculated by averaging peak systolic longitudinal strain values from a
Echocardiographic data
LVEF (%) 58 6 9 52 6 8 .01
16-segment model. These results may have important clinical implica-
tions and might reduce the need for hospitalization and further exam-
WMSI 1.00 (0.00) 1.13 (0.25) <.001
Territorial strain (%) 20 6 3 15 6 4 <.001 inations. In particular, many unnecessary invasive coronary
Global peak systolic strain (%) 21 6 3 16 6 4 <.001
angiographic procedures may be avoided.
Even in patients with unstable angina pectoris, in whom ischemia is
Data are expressed as median (interquartile range) or as mean 6 SD. not of sufficient severity or duration to produce myocardial necrosis,
P values are from unpaired t tests, Mann-Whitney U tests, or Fishers myocardial systolic function is probably acutely affected.15,16
exact tests. Echocardiography is easily accessible in the acute setting of
suspected acute coronary syndrome, and it has previously been
stenosis are illustrated in Figure 3. The optimal cutoff value of global reported that normal results on conventional rest echocardiography
peak systolic longitudinal strain for ruling out significant coronary ar- are an indicator of low clinical risk among patients with chest pain
tery stenosis was 20%. A 95% confidence interval for the optimal and nonischemic ECG findings.17 However, it has been questioned
cutoff value ( 19% to 21%) was estimated by performing boot- whether WMSI has sufficient sensitivity for the detection of subtle
strapping analysis (1,000 iterations). Optimal cutoff values for all stud- regional wall motion abnormalities to safely rule out significant coro-
ied parameters for ruling out both significant and high-grade coronary nary artery disease among patients with unstable angina, in whom
artery stenosis are given in Table 3. cardiac markers are negative.17-19 This study confirms that neither
To test the ability of global peak systolic longitudinal strain to distin- WMSI nor LVEF had sufficient accuracy to exclude coronary artery
guish between patients with and without significant coronary artery ste- stenosis in this patient group.
nosis, we performed a separate ROC analysis on a random sample (a There are a number of reasons why strain may perform better than
derived cohort automatically selected by SPSS) with 50% of the pa- traditional echocardiographic parameters. In coronary ischemia,
tients (n = 32, 15 of whom had significant coronary artery stenosis) regional wall motion abnormalities precede both ECG findings and
and found an optimal cutoff value of 21% (area under the curve, symptoms.20-22 Moreover, subendocardial fibers are the first to
0.90; 95% confidence interval, 0.740.99). This value was applied become ischemic.23 The subendocardial fibers are oriented mainly in
on the test cohort containing the remaining 50% of the patients (n = the longitudinal oblique direction, suggesting that ischemia in the suben-
32, 14 of whom had significant coronary artery stenosis) and identified docardial layer mostly affects LV longitudinal function.24 Conventional
13 of the 14 patients with significant coronary artery stenosis, resulting echocardiographic parameters, such as LVEF and WMSI, are based on
in sensitivity and specificity levels of 0.93 and 0.78, respectively, and ventricular volume change and visual assessment of moving endocar-
positive predictive value and negative predictive value of 0.74 and dium, respectively. Subtle ischemia affecting LV longitudinal function
0.92, respectively. The accuracy of global peak systolic longitudinal may not be detected by these methods, because the preserved
strain in distinguishing between patients with and without significant circumferential function in the nonischemic midwall and subepicar-
coronary artery stenosis was calculated as 78%. One patient in the dium opposes sufficient decrease in LVEF and inward motion. By
test cohort with significant coronary artery stenosis had a global peak computerized tracking of the movement of individual speckles in the
longitudinal strain value better than the statistical optimal cutoff value. myocardium, longitudinal strain by speckle-tracking echocardiography
This patient had a 50% stenosis in the circumflex coronary artery. has the ability to perceive subtle changes in LV function caused by
Feasibility of the strain measurements was excellent, with 97% of ischemia. Global strain measures actual deformation in the myocar-
segments analyzed. Reproducibility was evaluated in 10 randomly dium rather than wall motion or volume changes secondary to myocar-
selected patients. Intraclass correlations for intraobserver variability dial deformation. As shown previously, strain echocardiography is more
and interobserver variability were 0.94 and 0.92, respectively. accurate in describing LV function than LVEF and WMSI25 and has
better reproducibility, especially in patients with mildly reduced LV
function. A normal global strain measurement may therefore better
DISCUSSION separate patients without significant coronary artery disease from those
with slightly depressed regional function as a result of ischemia caused
To our knowledge, this study is the first to evaluate myocardial strain by significant coronary artery disease.
by speckle-tracking as an early method to identify patients without In our study, we found that global longitudinal strain was superior to
significant coronary artery stenosis in a population with suspected LVEF, WMSI, and GRACE score as a method to separate patients with
NSTE-ACS with inconclusive ECG findings and normal initial cardiac from those without significant coronary artery disease. Although not
biomarkers. statistically significant, there was also a tendency toward global
516 Dahlslett et al Journal of the American Society of Echocardiography
May 2014

Figure 2 Distribution of studied parameters in the pooled cohort containing all 64 patients. Round and square dots represents
patients without and with significant coronary artery stenosis, respectively. Lines show median 6 interquartile range for WMSI
and mean 6 SD for other parameters.

longitudinal strains being superior to territorial strain in separating the
two patients groups. This was somewhat surprising because ischemic
heart disease most commonly presents with regional LV dysfunction.
Intuitively, measuring strain in the territory of the ischemia should be
more accurate, as such a measure would be less affected by the noni-
schemic territories with normokinesis or even hyperkinesis. However,
there are several possible explanations of these findings. Territorial
strain in this study was based on anatomic perfusion territories
described by Cerqueira et al.,12 and these anatomic territories may
not necessarily apply to the actual perfusion territory of an individual
patient, because of both misalignment of image planes and individual
variations in the perfusion territory of the coronary arteries. The
affected territory may thus be split between two or three of the studied
territories. Most important, territorial strain values are based on only
five or six segments, making territorial strain a much less robust param-
eter than global strain, which is calculated on the basis of 16 segments.
Using the optimal cutoff value of global strain estimated from the
derived cohort, one patient with significant coronary stenosis in the
test cohort was falsely classified as normal. This patient had a 50%
stenosis of the circumflex coronary artery, which may not have
caused sufficient ischemia to produce a detectable wall motion defect
in the left ventricle.
Journal of the American Society of Echocardiography
Volume 27 Number 5
Table 3 ROC analyses with AUCs and optimal cutoff values of GRACE score and echocardiographic parameters in the pooled
cohort consisting of all 64 patients
Rule out significant stenosis ($50%)
GRACE risk score
LVEF
WMSI
Territorial longitudinal strain
Global peak systolic longitudinal strain
Rule out high-grade stenosis ($75%)
GRACE risk score
LVEF
WMSI
Territorial longitudinal strain
Global peak systolic longitudinal strain
AUC, Area under the curve; CI, confidence interval.
Ninety-five percent CIs for optimal cutoff values were estimated by performing bootstrapping analysis (1,000 iterations).
*P < .05 versus AUC of 0.5.
Figure 3 ROC curve analysis for the exclusion of significant
coronary artery stenosis in patients presenting with suspected
NSTE-ACS without known coronary artery disease and with
normal initial troponin T and inconclusive ECG findings. AUC,
Area under the curve. *AUC significantly larger (P < .05) compared
with AUCs for LVEF, WMSI, and GRACE score (DeLong, DeLong,
and Clarke-Pearson comparison). The AUCs for all parameters
were significantly larger than 0.5 (P < .05).
Recently, studies using latest generation high-sensitivity cTnT
assays have demonstrated that acute myocardial infarction can be
ruled out in about a quarter of patients presenting with suspected
acute coronary syndrome on the basis of enzymes measured at
admission.5 However, cardiac enzymes are markers of necrosis, and
consequently, patients with unstable angina may not be recognized.
Our study shows that using results from cTnT measured on admission
and myocardial strain by speckle-tracking can increase diagnostic
precision and more safely rule out significant coronary artery stenosis
in patients presenting to the ER with suspected NSTE-ACS.
Dahlslett et al 517
AUC (95% CI) Optimal cutoff point (95% CI)
0.68 (0.55 to 0.79)* 88 (69 to 112)
0.68 (0.55 to 0.79)* 52% (42% to 61%)
0.74 (0.62 to 0.84)* 1.09 (1.00 to 1.10)
0.83 (0.72 to 0.91)* 18% ( 21% to 18%)
0.87 (0.77 to 0.94)* 20% ( 21% to 19%)
0.64 (0.51 to 0.76)* 75 (48 to 75)
0.65 (0.52 to 0.77)* 63% (49% to 65%)
0.75 (0.63 to 0.85)* 1.09 (1.00 to 1.09)
0.86 (0.75 to 0.93)* 18% ( 20% to 18%)
0.89 (0.79 to 0.96)* 20% ( 21% to 20%)
It has also recently been shown that using a combined strategy with
initial cardiac proteins, electrocardiography, and computed tomographic
coronary angiography may enable safe and early discharge of patients
with suspected NSTE-ACS.26,27 However, computed tomographic
angiography may cause an increase in downstream testing and
radiation exposure, with no decrease in the overall cost of care.26
Echocardiography is widely available, can be performed at low cost,
and adds valuable information to possible differential diagnosis.
Previous studies have demonstrated that acute coronary occlusion
in patients with suspected NSTE-ACS may be early recognized by
echocardiography.7 The present study indicates that early echocardi-
ography may also facilitate the exclusion of significant coronary artery
stenosis. Potentially, prolonged hospitalization and unnecessary
invasive procedures may be avoided, thus reducing cost and risk for
complications.
Limitations
Our study assessed only patients without known coronary artery
disease. Myocardial strain often remain depressed in patients with
former myocardial infarctions, even after successful revascularization,
so ruling out new coronary artery stenosis may be more challenging in
this population.
Echocardiography is user dependent, and the echocardiographic
examinations in this study were recorded with speckle-tracking anal-
ysis in mind. Great care was therefore taken to achieve the best
possible image quality. The speckle-tracking analysis had excellent
interobserver and intraobserver reproducibility, but we did not assess
the variation between the two echocardiographic examinations in this
patient group and setting.
In this study, patients were examined mainly in the ER during or
just after an episode of chest pain. We may speculate that a high
natural adrenergic state may have contributed to the relatively high
absolute strain values reported in our study, but the results of strain
analysis are also known to vary among ultrasound vendors, machines,
and even software versions.28 The population used in the analysis was
relatively small, and thus confidence intervals were wide, but the
contrast between conventional echocardiographic methods and
strain echocardiography were large and the significance levels high.
Optimal cutoff values should be interpreted with care, as there still
518 Dahlslett et al
are no industry standards for strain. Larger multicenter and multiven-
dor studies are needed to evaluate more exact test characteristics.
Even if strain by speckle-tracking may be far better than conven-
tional echocardiographic methods in identifying patients without
significant coronary stenosis, patients with significant coronary ste-
nosis may still be falsely classified as not having significant coronary
stenosis. However, these patients are likely to have low risk and
could probably safely be handled as outpatients.29 In contrast,
some patients may be classified with patients who have significant
coronary stenosis on the basis of symptoms and reduced global lon-
gitudinal strain, but in whom the myocardial dysfunction is caused
by other disease, such as nonischemic cardiomyopathies, acute
myocarditis, and significant valve disease. Our data do not support
the hypothesis that global longitudinal strain can discriminate
reduced global longitudinal strain caused by significant coronary
disease from reduced global longitudinal strain caused by other dis-
eases. Thus, a measurement of global longitudinal strain in this
setting is primarily a method to aid the exclusion of significant cor-
onary artery disease. Patients with significantly reduced LV function
must be managed using other diagnostic methods to clarify the
absence or presence of coronary artery disease.
Patients with severe valvular dysfunction were excluded from the
study because of concern that it would influence loading conditions
and LV function and thus global longitudinal strain values.30 As a result,
strain would not be able to distinguish between LV dysfunction due to
coronary artery disease and ischemia or dysfunction due to severe
valvular disease. Therefore, patients with severe valvular disease are
not suitable for exclusion of coronary artery disease by strain in the ER.
Performing bedside echocardiography with strain analysis in patients
with chest pain may be a challenge in the ER because of limited time
and resources. Reorganization may be necessary, especially after hours.
Early education of residents in basic echocardiography may be needed.
Patients with chest pain and inconclusive ECG findings should undergo
echocardiographic examinations with strain analysis as early as possible,
both to facilitate early exclusion of significant coronary disease and to
establish possible life-threatening conditions such as myocardial infarc-
tion, aortic dissection, or pulmonary embolism.31 We believe that add-
ing early echocardiographic examination with strain analysis may
facilitate safe exclusion of significant coronary disease and thus lead
to early discharge and overall cost savings.
CONCLUSIONS
The present study demonstrates that myocardial strain by speckle-
tracking may be superior to conventional echocardiographic
parameters in excluding significant coronary artery stenosis in patients
with suspected NSTE-ACS, inconclusive ECG findings, and normal
cardiac biomarkers. A combined strategy with electrocardiography,
a single set of cardiac proteins, and measurement of myocardial strain
by speckle-tracking echocardiography may aid clinicians in excluding
significant coronary artery stenosis and thereby allow early discharge.
Future multicenter and multivendor studies are needed to evaluate
more exact test characteristics.
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