Download Strain Echocardiography and Wall Motion Score Index Predicts Final

Strain Echocardiography and Wall Motion Score Index
Predicts Final Infarct Size in Patients With
Non–ST-Segment–Elevation Myocardial Infarction
Christian Eek, MD; Bjørnar Grenne, MD; Harald Brunvand, MD, PhD; Svend Aakhus, MD, PhD;
Knut Endresen, MD, PhD; Per K. Hol, MD, PhD; Hans-Jørgen Smith, MD, PhD;
Otto A. Smiseth, MD, PhD; Thor Edvardsen, MD, PhD; Helge Skulstad, MD, PhD
Downloaded from http://circimaging.ahajournals.org/ by guest on May 6, 2017
Background—Infarct size is a strong predictor of mortality and major adverse cardiovascular events after myocardial
infarction. Acute reperfusion therapy limits infarct size and improves survival, but its use has been confined to patients
with ST-segment– elevation myocardial infarction. The purpose of this study was to assess the relationship between
echocardiographic parameters of left ventricular (LV) systolic function obtained before revascularization and final
infarct size in patients with non–ST-segment– elevation myocardial infarction, as well as the ability of these parameters
to identify patients with substantial infarction.
Methods and Results—Sixty-one patients with non–ST-segment– elevation myocardial infarction were examined by
echocardiography immediately before revascularization, 2.1⫾0.6 days after hospitalization. LV systolic function was
assessed by ejection fraction, wall motion score index, and circumferential, longitudinal, and radial strain in a
16-segment LV model. Global strain represents average segmental strain values. Infarct size was assessed after 9⫾3
months by late-enhancement MRI, as a percentage of total LV myocardial volume. A good correlation was found
between infarct size and wall motion score index (r⫽0.74, P⬍0.001) and global longitudinal strain (r⫽0.68, P⬍0.001).
Global longitudinal strain ⬎⫺13.8% and wall motion score index ⬎1.30 accurately identified patients with substantial
infarction (ⱖ12% of myocardium, n⫽13; area under the receiver operator curve, 0.95 and 0.92, respectively).
Conclusions—Echocardiographic parameters of LV systolic function correlate to infarct size in patients with non–STsegment– elevation myocardial infarction. Global longitudinal strain and wall motion score index are both excellent
parameters to identify patients with substantial myocardial infarction, who may benefit from urgent reperfusion therapy. (Circ
Cardiovasc Imaging. 2010;3:187-194.)
Key Words: myocardial infarction 䡲 echocardiography 䡲 MRI 䡲 myocardial contraction
I
nfarct size is a strong predictor of mortality and major
adverse cardiovascular events after myocardial infarction
(MI).1 Reperfusion therapy by thrombolysis or percutaneous
coronary intervention (PCI) salvages viable myocardium and
preserves left ventricular (LV) function by reduction of
infarct size.2 This strategy has improved clinical outcome
after MI but is generally confined to patients with STsegment– elevation MI (STEMI). ST-segment elevation in the
ECG has high specificity but suboptimal sensitivity for
detection of MI and acute coronary occlusion3 and has
demonstrated only modest correlation to infarct size.4 A
number of patients with non–ST-segment– elevation MI
(NSTEMI) have substantial infarction,5,6 but these patients
rarely fulfill criteria for acute reperfusion therapy. In current
clinical practice, no instant method for early assessment of
final infarct size in patients with NSTEMI exists.
Clinical Perspective on p 194
Acute coronary occlusion is followed by rapid changes in
LV systolic function that can be quantified by echocardiography.7 In STEMI patients, echocardiographic parameters of
LV systolic function are demonstrated to correlate to infarct
size, both in the acute and chronic phases.8,9 Strain echocardiography is an accurate and validated measure of regional
systolic LV function10,11 that has demonstrated excellent
ability to differentiate between different levels of infarct
size.8 Recently, strain echocardiography has been validated
as a prognostic indicator.12,13 Contrast-enhanced MRI
(CE-MRI) is considered the gold standard for assessment of
final infarct size.14 We assessed the ability of strain echocardiography and established indices of LV systolic function to
predict final infarct size and specifically the ability to stratify
Received September 18, 2009; accepted January 4, 2010.
From the Department of Cardiology (C.E., S.A., K.E., O.A.S., T.E., H.S.), the Department of Radiology (H.-J.S.), and The Interventional Centre
(P.K.H.), Rikshospitalet, Oslo University Hospital, Oslo, Norway; the Faculty of Medicine (C.E., B.G., H.-J.S., O.A.S., T.E.), University of Oslo, Oslo,
Norway; and the Department of Medicine (B.G., H.B.), Sørlandet Hospital HF, Arendal, Norway.
Correspondence to Helge Skulstad, MD, PhD, Department of Cardiology, Rikshospitalet University Hospital, 0027 Oslo, Norway. E-mail
[email protected]
© 2010 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
187
DOI: 10.1161/CIRCIMAGING.109.910521
188
Circ Cardiovasc Imaging
March 2010
patients with regard to substantial as opposed to minor
myocardial necrosis.
Methods
This study was conducted in a single tertiary coronary care center.
Consecutive patients with documented NSTEMI on whom coronary
angiography was planned within 3 days of index admission were
prospectively enrolled from May 2007 to June 2008. All patients
were enrolled and examined immediately on arrival at the
invasive center.
Patients
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The study population comprises 61 patients with a diagnosis of
NSTEMI confirmed at the referring hospital by elevated troponin I or
troponin T above the 99% percentile. Blood samples acquired
immediately before coronary angiography were available in 56
patients (92%), and all subsequent reports of troponin T refer to this
sample. Time from hospital admission to coronary angiography was
2.1⫾0.6 days (range, 1 to 3 days). Exclusion criteria were prior MI;
evidence of STEMI (ST-elevation ⬎0.1 mV (0.2 mV in precordial
leads V1–V3) in 2 or more contiguous leads on any ECG during
index admission; bundle-branch block with QRS ⬎120 ms; severe
valvular disease; previous heart surgery; extensive comorbidity with
short life expectancy; atrial fibrillation with heart rate ⬎100; and any
condition interfering with the patient’s ability to comply and contraindications to MRI. All patients were considered clinically and
hemodynamically stable during index admission, and none were
referred for urgent coronary intervention. The study was approved by
the regional ethics committee, and all patients gave written
informed consent.
CE-MRI
Final infarct size was quantified by MRI at follow-up 9⫾3 months
after inclusion, using a 1.5-T unit (Magnetom Sonata, Siemens,
Erlangen, Germany) on 29 patients and a 3-T unit (Philips Medical
Systems, Best, The Netherlands) on 32 patients. Late-enhancement
images were obtained 10 to 20 minutes after intravenous injection of
0.1 to 0.2 mmol/kg gadopentetate dimeglumine (Magnevist, Schering, Berlin, Germany) in multiple short-axis slices covering the
entire LV. Typical image parameters were slice thickness, 8 mm;
gap, 2 mm; and inversion time, 270 ms. On each short-axis image,
total myocardial area as well as area of infarcted myocardium was
manually drawn (PACS, Sectra, Sweden). Final infarct size was
calculated as infarct volume as a percentage of total myocardial
volume. Segmental transmurality was calculated in a 16-segment LV
model as infarct volume divided by myocardial volume per segment,
and segments with ⱖ50% contrast enhancement were judged transmurally infarcted.16 Both short- and long-term mortality rates have
been demonstrated to be increased in patients with infarct size
ⱖ12%.1,17 Therefore, patients were dichotomized by infarct size
using 12% as cutoff. Figure 1 is an illustration of MRI images and
strain values from 1 patient.
Coronary Angiography
Coronary angiography was performed by standard (Judkins) technique, using digital image acquisition and storage. Revascularization
was not part of the study protocol and was performed on clinical
indication. Compliant to current guidelines, complete revascularization was attempted. All analyses were performed in retrospect by a
single experienced invasive cardiologist, blinded to the results of the
other imaging studies.
Echocardiography
Statistical Analyses
Echocardiographic examinations were performed with a Vivid 7
scanner (GE Vingmed, Horten, Norway), using a phased array
transducer. The patients were examined immediately before coronary angiography. Three consecutive cycles in 3 apical planes
(4-chamber, 2-chamber, and long axis) and 3 short-axis planes
(mitral valve, papillary muscle, and apical) were obtained by
conventional 2D gray-scale echocardiography, using second harmonic imaging. Loops were digitally stored and later analyzed
off-line using Echo-Pac version 7.0.0. (GE Vingmed). All examinations were performed by 1 operator. LV ejection fraction (LVEF)
was calculated from 4-chamber and 2-chamber images, using the
modified Simpson rule. Wall motion score was assessed in a
16-segment model.15 Segmental wall motion was judged by an
experienced cardiologist as normal⫽1, hypokinetic⫽2, akinetic⫽3,
and dyskinetic⫽4. Wall motion score index (WMSI) represents the
average value of analyzed segments.
Continuous variables are presented as mean⫾SD or median (interquartile range [IQR]). The relationship between infarct size and
echocardiographic parameters were analyzed by bivariate correlation. Differences between groups were analyzed with the Student t
test, Mann–Whitney U test, or Kruskal-Wallis test. Categorical
variables are presented as numbers (percentage) and were analyzed
by ␹2 test or Fisher exact test. We used receiver operator analysis
(ROC) curves to identify the cutoff for optimal sensitivity and
specificity to detect infarct size ⱖ12% of total LV myocardial
volume.17 Area under the curve (AUC), negative predictive value,
positive predictive value, and accuracy (overall fraction correct) are
reported. The AUC is a measure of discriminating power and
represents the probability of the model to assign a higher probability
to a correct case than to an incorrect case for all possible pairs of
cases.
To assess the value of the potential combined use of echocardiographic parameters, a logistic regression model (enter) was used.
LVEF and WMSI are conventional parameters of LV systolic
function and were entered as covariates along with the strain
parameter that demonstrated the best correlation to infarct size. The
predicted probabilities from this model were used to calculate the
AUC (equivalent to the c-statistic) of the combination of variables.
Interobserver variability and intraobserver variability were calculated by intraclass correlation coefficient in 16 randomly selected
patients. Comparison between ROC curves was performed according
to the method described by Hanley and McNeil,18 using dedicated
software (MedCalc Software version 10.3.1.0, Mariakerke, Belgium). All other statistical analyses were performed on SPSS version
13 (SPSS Inc, Chicago, Ill). The authors had full access to the data
and take responsibility for its integrity. All authors have read and
agree to the manuscript as written.
Strain Analyses
Longitudinal, circumferential, and radial strain was measured by
speckle tracking echocardiography in a 16-segment LV model.10,15
Peak negative systolic strain, which represents the maximum systolic
longitudinal or circumferential shortening, was noted for each
segment. For radial strain, the peak positive systolic value was used.
As a measure of global systolic function, values of all segments were
averaged to obtain global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS). Torsion was
assessed as the difference in rotation between the basal and apical
planes. All echocardiographic and strain analyses were performed
separately and blinded to other patient data.
ECG
For ST-segment analyses, the ECG obtained in the emergency room
at referring hospital was used. Evidence of ischemia was defined as
any ST-deviation ⬎0.5 mm or symmetrical T-wave inversion
⬎3 mm in 2 or more contiguous leads (10 mm/mV). The sum of all
ST-segment deviations exceeding 0.5 mm was recorded.
Results
Patient characteristics, risk factors, and medications are listed
in Table 1.
Eek et al
Echocardiography in NSTEMI
189
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Figure 1. MRI and strain echocardiography. A, Short-axis MRI images from base (upper left) to apex (lower right). B, 16-segment bull’s
eye plot of segmental longitudinal strain values. Myocardial regions with impaired systolic function clearly correspond to regions with
late enhancement. In this patient, coronary angiography revealed occlusion of a large intermediate branch. Infarct size was calculated
to 17.6% of total LV myocardial volume. GLS was ⫺12.3%; LVEF, 46%; GCS, ⫺18.6%; and WMSI, 1.38.
Feasibility and Reproducibility
No patients were excluded because of suboptimal image
quality on echocardiography. Longitudinal strain values
could be obtained in 960 (98.4%), circumferential strain
values in 877 (90.0%), radial strain in 864 (89%), and WMS
in 973 (99.7%) of all LV segments. LVEF could be calculated
in all patients and LV torsion in 60 patients (98%). Intraclass
correlation coefficients for interobserver and intraobserver
variability of GLS were 0.94 and 0.96, respectively.
Angiographic Findings and Revascularization
Table 1. Patient Characteristics, Risk Factors, and
Medical Treatment
Characteristic
Infarct Size ⬍12% Infarct Size ⱖ12%
(n⫽48)
(n⫽13)
P Value
Age, y
57.8⫾7.2
57.2⫾13.6
0.81
BMI, kg/m2
27.2⫾3.0
28.5⫾3.2
0.20
Male sex
37 (77)
11 (85)
0.72
Current smoker
20 (42)
7 (54)
0.43
Hypercholesterolemia
18 (38)
2 (15)
0.19
Hypertension
19 (40)
5 (39)
1.00
Diabetes mellitus
6 (13)
1 (8)
1.00
History of CAD
3 (6)
0 (0)
1.00
Aspirin
48 (100)
13 (100)
1.00
Clopidogrel
48 (100)
13 (100)
1.00
1.00
Risk factors
Medication
LMWH
47 (98)
13 (100)
␤-blocker
35 (73)
10 (77)
1.00
Statin
44 (92)
12 (92)
1.00
1 (2)
0 (0)
1.00
14 (29)
3 (23)
1.00
1 (2)
0 (0)
1.00
Warfarin
ACE inhibitor or ARB
GpIIbIIIa inhibitor
Data are presented as mean⫾SD or n (%). Hypercholesteremia was defined
as use of statins or cholesterol⬎240 mg/dL. Hypertension was defined as use
of antihypertensive medication. BMI indicates body mass index; CAD, coronary
artery disease; LMWH, low-molecular-weight heparin; ACE, angiotensinconverting enzyme, ARB, angiotensin receptor blocker; GpIIbIIIa, glycoprotein IIbIIIa.
All patients underwent coronary angiography. Significant
stenosis was found in 54 patients (89%). Of these, 15 (28%)
underwent surgical revascularization and 37 (69%) underwent PCI. Stents were used in 33 (89%) of PCI patients, and
TIMI 3 flow in all attempted vessels was achieved in 32
(97%). Three patients who underwent PCI of the culprit
lesion in addition had significant lesions in other vessels that
were not amenable to PCI because of small vessel diameter.
Between revascularization and follow-up, 1 patient had reinfarction with minimal enzyme release (troponin T, 0.18 ␮g/L)
in the same vessel as was initially treated.
Infarct Size and Transmurality by CE-MRI
The distribution of infarct size is demonstrated in Figure 2.
Median infarct size was 5.4% (IQR, 1.7% to 11.4%) of total
LV myocardial volume. Thirteen patients (21%) had infarct
size ⱖ12%, and 13 patients (21%) had no visible late
enhancement on CE-MRI (infarct size, 0%). Thirty patients
(49%) had final infarct size ⬍5% of total LV mass. Of 976
analyzed segments, evidence of infarction by late enhancement was seen in 249 (26%). Of these, 199 (80%) demonstrated subendocardial and 50 (20%) transmural infarction.
Echocardiography and Infarct Size
A significant correlation was found between all parameters of
LV systolic function and final infarct size (Figure 3). Importantly, the echocardiographic parameters of LV systolic
function were able to discriminate between patients with final
infarct size ⬍12% or ⱖ12% (Table 2). To further elucidate
whether the relationship between myocardial systolic func-
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March 2010
Figure 2. Infarct size. Bar graph demonstrating
the distribution of final infarct size.
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tion and final MI size is time-dependent, we dichotomized
patients into those arriving early (day 1, n⫽9) and those
arriving late (days 2 to 3, n⫽52). For patients arriving early,
the correlation between myocardial systolic function and final
infarct size was excellent (GLS, r⫽0.94, P⬍0.001; WMSI,
r⫽0.88, P⫽0.002). For patients arriving late, the correlation
was good (GLS, r⫽0.65, P⬍0.001; WMSI, r⫽0.72,
P⬍0.001).
Among strain parameters, GLS demonstrated the closest
correlation to infarct size and was therefore entered as a
covariate in the logistic regression model, along with LVEF
and WMSI. Details are reported in Tables 3 and 4. WMSI and
GLS remained significant predictors, LVEF did not. ROC
analysis (Figure 4 and Table 5) demonstrate that GLS and
WMSI had excellent ability to identify patients with infarct
size ⱖ12%, superior to that of GCS, GRS, LVEF, and
torsion. Interestingly, the AUC from the logistic regression
model (AUC, 0.98; 95% confidence interval, 0.90 to 1.00)
was not significantly different compared with WMSI or
GLS alone. None of the predictor variables were affected
by age or sex.
LV systolic function was reassessed by GLS at follow-up.
A persistent impairment was found in patients with infarct
size ⱖ12% compared with those with smaller infarcts (GLS,
14.1⫾2.0% versus 17.5⫾2.2%; P⬍0.001). A small but significant improvement of systolic function was observed, as
mean change in GLS was ⫺1.0⫾1.9% (P⬍0.001 by paired
Student t test). The observed change in GLS did not correlate
to final infarct size (r⫽⫺0.1, P⫽0.47).
Angiographic Findings and Infarct Size
Infarct size was similar in patients with single-vessel versus
multivessel disease (6.3% [IQR, 2.5% to 14.7%] versus 6.0%
[IQR, 2.1% to 12.0%]; P⫽0.86). However, infarct size was
dependent on patency of the infarct related artery (IRA). In
patients with an occluded IRA, median infarct size was 8.3%
Figure 3. Scatterplots of infarct size by
CE-MRI and echocardiographic parameters of LV systolic function. Dashed lines
indicate the cutoff value to identify infarct
size ⱖ12% (Table 5). Pearson correlation
coefficients are reported in the figure.
Rank correlations were similar (WMSI–
Spearman ␳⫽0.65, P⬍0.001; GLS–Spearman ␳⫽0.59, P⬍0.001).
Eek et al
Table 2.
Echocardiographic Findings by Infarct Size
Infarct Size ⬍12%
(n⫽48)
LVEF, %
Infarct Size ⱖ12%
(n⫽13)
57.5⫾7.7
48.5⫾9.3
Table 4.
191
Classification Table
Predicted Infarct ⱖ12%
P Value
0.001
1.08 (1.0–1.21)
1.44(1.28–1.50)
⬍0.001
GLS, %
⫺16.9⫾2.2
⫺12.6⫾1.7
⬍0.001
GCS, %
⫺22.1⫾3.8
⫺18.2⫾5.5
0.030
WMSI
Echocardiography in NSTEMI
GRS, %
35.0⫾13.2
27.6⫾8.3
0.018
Torsion, degrees
13.2⫾6.7
10.2⫾8.2
0.173
EDV, mL
112⫾25
121⫾27
0.226
ESV, mL
48⫾14
62⫾22
0.031
Data are presented as mean⫾SD or median (IQR). EDV indicates end-diastolic
volume; ESV, end-systolic volume.
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(IQR, 4.2% to 17.5%) versus 3.5% (IQR, 0.0% to 8.0%) in
patients with a patent IRA (P⫽0.004). Occlusion of the IRA
was found in 9 of 13 patients (69%) with infarct size ⱖ12%.
Infarct size was not significantly different dependent on
coronary territory (Table 6), but, numerically, smaller infarcts
were found in the right coronary artery (RCA) territory.
Choice of surgical versus percutaneous revascularization was
not significantly associated with final infarct size.
ECG, Troponin T, and Clinical Findings Versus
Infarct Size
Twenty-two patients (36%) had evidence of ischemia on the
ECG, as defined above. Compared with patients without
ischemic changes, these had larger infarcts (7.3% [IQR, 4.4%
to 17.5%] versus 3.2% [IQR, 0% to 10.4%], P⫽0.008).
However, ischemic ECG changes were found in only 7 of 13
patients (54%) with infarct size ⱖ12%, and prevalence of
ischemic ECG findings was not statistically different from
patients with smaller infarcts (54% versus 31%, P⫽0.19).
The sum of ST-segment deviations did not correlate to infarct
size (r⫽0.15, P⫽0.26). Serum levels of troponin T obtained
immediately before coronary angiography correlated significantly to infarct size (r⫽0.64, P⬍0.001) and could identify
patients with infarct size ⱖ12% with sensitivity 63% and
specificity 91%, using 1.4 ng/mL as cutoff. No significant
differences were found in clinical parameters listed in Table
7, nor in risk factors or medication listed in Table 1.
0
1
47
1
2
11
Observed
0
Infarct ⱖ12%
1
infarct size in NSTEMI patients. We found a significant
correlation between echocardiographic parameters of LV
systolic function and final infarct size. Because acute coronary occlusion is accompanied by very rapid alterations in
myocardial systolic function,7 the method may be applicable
even in the very early phase in the development of MI. This
has important clinical implications because it may provide a
means for early identification of patients who have substantial infarction. Current guidelines recommend acute reperfusion therapy only in clinically unstable NSTEMI patients.19
This strategy may be inadequate in the subgroup of NSTEMI
patients who have substantial infarction. These patients have
a high prevalence of total occlusions and are likely to benefit
from acute reperfusion therapy, as it may reduce infarct size
and salvage viable myocardium. Importantly, in current
clinical practice, echocardiography is the only bedside, noninvasive method to identify these patients.
Infarct Size and Prognosis
Final infarct size is a strong predictor of mortality and major
adverse cardiovascular events.1,17,20,21 Current reperfusion
therapy is highly effective, and the relative reduction of
infarct size achieved is typically 40% by thrombolysis and
60% by primary PCI.22 The reduced mortality rate observed
in the reperfusion era is largely attributable to reduction of
final infarct size.2 A treatment that results in a 3% to 5%
absolute reduction of infarct size is associated with improved
survival and reduction of clinical events.20 Previous studies
Discussion
Our study demonstrates the use of a noninvasive imaging
modality applied before revascularization to predict final
Table 3.
Logistic Regression Model for Infarct Size >12%
Variable
Coefficient
Estimate
Wald ␹ 2
P
Intercept
⫺1.07
Odds Ratio (95% CI)
0.009
0.92
LVEF*
0.04
0.23
0.64
1.04 (0.89–1.22)
WMSI†
1.27
5.23
0.02
3.55 (1.20–10.47)
GLS*
1.26
6.46
0.01
3.51 (1.33–9.25)
*Odds ratio for each 1 percentage point increase.
†Odds ratio for each 0.1 point increase. AUC for entire model, 0.98 (95% CI,
0.90 to 1.00). Nagelkerke R2⫽0.80. Correlation between covariates: GLS
versus LVEF, r⫽0.47; WMSI versus LVEF, r⫽0.71; WMSI versus GLS, r⫽0.65.
All P⬍0.001.
Figure 4. ROC analysis set to identify infarct size ⱖ12% of total
LV myocardial volume.
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Table 5.
March 2010
ROC Analysis of Echocardiographic Parameters for Identification of Infarct Size >12%
Cutoff
Sensitivity, %
Specificity, %
AUC
NPV
PPV
51%
69
79
0.80 (0.68 – 0.89)
0.91
0.47
0.77
1.30
77
92
0.93* (0.83–0.98)
0.94
0.71
0.89
GLS
⫺13.8%
85
96
0.95* (0.86–0.99)
0.96
0.85
0.93
GCS
⫺19.2%
62
81
0.71 (0.58–0.82)
0.89
0.47
0.77
GRS
27.4%
69
69
0.68 (0.53–0.83)
0.89
0.38
0.69
7.2
54
75
0.64 (0.46–0.82)
0.85
0.37
0.70
LVEF
WMSI
Torsion
Accuracy
The AUC is reported with 95% CIs. NPV indicates negative predictive value; PPV, positive predictive value.
*P⬍0.02 versus LVEF, GCS, GRS, and torsion. The cutoff values that give the largest sum of sensitivity and specificity are reported.
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have demonstrated increased mortality rate to be associated
with infarct size ⱖ12%.1,17 In addition, 1 large trial found
12% to be median infarct size in STEMI patients treated by
acute reperfusion.17 Hence, we chose 12% as cutoff to
identify patients at increased risk in our study.
systolic function largely persists despite revascularization. As
the observed improvement of myocardial systolic function
did not correlate to infarct size, stunning and hibernation were
evenly distributed between different levels of infarct size and
are not likely to have confounded our results.
Infarct Size in NSTEMI Patients
Prediction of Infarct Size by Echocardiography
Since the introduction of more sensitive biochemical markers
of myocardial necrosis, an increasing number of patients with
non–ST-segment elevation acute coronary syndrome are diagnosed with MI.23 Hence, the NSTEMI population comprises a large number of patients with only minimal myocardial necrosis, leaving “typical” infarct size in this group
relatively small. Accordingly, in our study, 13 patients (21%)
had no visible area with late enhancement, and 30 patients
(49%) had small infarcts (⬍5% of total LV volume).
It is important to recognize that the difference between
STEMI and NSTEMI by definition is electrophysiological
and not pathophysiological. As this and other studies show, a
subgroup of NSTEMI patients have substantial infarction,5,6
and there is a significant overlap in final infarct size between
STEMI and NSTEMI patients.6 Even patients with a normal
ECG my develop large infarctions.5 The latter corresponds to
our findings, as only 7 of 13 patients (54%) with infarct size
ⱖ12% had any evidence of ischemia in the ECG.
As several factors affect LV systolic function in the acute
ischemic setting, no absolute relationship between final
infarct size and LV systolic function can be expected. In the
present study, we demonstrate correlation coefficients of 0.74
and 0.68 for WMSI and GLS, respectively. Hence, variability
in infarct size can explain approximately 50% of the observed
variability in LV systolic function assessed by GLS or
WMSI. Stunning, hibernation, ongoing ischemia without
necrosis, and differences in loading conditions are likely to
account for much of the remaining variability. The relatively
small improvement in LV systolic function from baseline to
follow-up may indicate that stunning or hibernation do not
play major roles and that the observed reduction in LV
In the present study, WMSI and GLS were independent
predictors of infarct size ⱖ12% by logistic regression analysis (Table 3). However, the discriminating power of both
parameters used alone was excellent, and the combined use did
not significantly increase power. WMSI is an established parameter of LV systolic function, validated as a prognostic indicator
after MI.24 However, it is semiquantitative, experiencedependent, and based on subjective interpretation of myocardial
motion. Longitudinal strain by speckle tracking echocardiography is a relatively new parameter that has not yet reached
widespread use in clinical practice. The reported values of GLS
were substantially lower compared with those previously reported in healthy individuals (GLS⫽⫺21.7⫾1.6%).25 It can be
calculated using commercially available dedicated software
from several vendors. The calculation is semiautomatic; it
provides an objective measure of segmental systolic shortening
on a linear scale and has also previously demonstrated excellent
feasibility and reproducibility.26 Recently, it has also been
shown to be superior to LVEF and WMSI for prediction of
mortality.13
As previously demonstrated by others, circumferential
strain is less accurate than longitudinal strain in predicting
subendocardial infarction.27 In NSTEMI, the infarction is
predominantly subendocardial, and 80% of infarcted seg-
Systolic blood pressure,
mm Hg
144⫾26
141⫾28
0.75
Table 6.
Diastolic blood pressure,
mm Hg
81⫾16
77⫾16
0.42
69⫾11
0.17
Infarct Size by Infarct Location
LAD Territory
(n⫽15)
Infarct size, %
10.4 (2.6 –15.9)
LCx Territory
(n⫽16)
9.2 (3.7–16.5)
RCA Territory
(n⫽21)
4.4 (1.7– 8.6)
P Value
0.21
The infarct-related artery could be identified in 52 patients. Data are
presented as median (IQR). LAD indicates left anterior descending coronary
artery; LCx, left circumflex artery; RCA, right coronary artery.
Table 7. Clinical and ECG Findings With Respect to
Infarct Size
Characteristic
Heart rate, beats/min
Recurrent chest pain
Infarct Size ⬍12% Infarct Size ⱖ12%
(n⫽48)
(n⫽13)
P Value
64⫾10
6 (13)
1 (8)
1.00
Ischemic ECG
15 (31)
7 (54)
0.19
Sum of ST-deviation, mm
0.0 (0.0–1.0)
Values are mean⫾SD, median (IQR) or n (%).
1.0 (0.0–2.5)
0.18
Eek et al
Echocardiography in NSTEMI
193
ments were subendocardial in our study. Subendocardial
layers of the myocardium contain predominantly longitudinal
fibers, which may explain why longitudinal strain was more
accurate. Second, longitudinal strain tracks motion parallel to
the ultrasound beam, where resolution is optimal, in contrast
to circumferential and radial strain, where motion is tracked
in all directions. In addition, circumferential strain and radial
strain are calculated from short-axis images, where image
planes are not well standardized, and there is considerable
through plane motion in basal parts of the heart. The reason
why circumferential and radial strains were less accurate may
therefore partly be caused by methodological reasons.
applied in the emergency room. We do not know how well
our discrimination model will fit new data. Nevertheless,
because 2 different methods (GLS and WMSI), assessed by 2
different observers, both demonstrated excellent discrimination, it is unlikely that this is a chance finding. Prior MI was
an exclusion criterion in this study. Distinguishing between
acute and chronic MI is difficult and was not the aim of this
study. However, echocardiography may still be of great value
for patients with chronic MI. Development of new areas with
reduced systolic function might indicate high risk and lend
support to choice of an aggressive treatment strategy.
Diagnostic Tools for Early Assessment of
Infarct Size
Echocardiographic parameters of LV systolic function obtained before revascularization correlate to final infarct size
in NSTEMI patients. Our findings demonstrate that patients
with a potential for substantial myocardial damage may be
identified with high accuracy. Because echocardiography is
easily performed in the emergency room, it may serve as a
tool for selection of NSTEMI patients who should be considered for urgent revascularization to limit infarct size.
Conclusion
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After acute occlusion of a coronary artery, the time window
for myocardial salvage is narrow. Therefore, a tool to predict
infarct size should be based on information that can be
obtained in the emergency room. Recent data suggest that
24% of all NSTEMI patients have total occlusion of the
infarct-related artery, and the urgent need to identify patients
who have substantial infarction has recently been pointed
out.28 In the present study, clinical characteristics and ECG
were unable to identify patients with substantial infarction.
Biochemical markers of myocardial necrosis have demonstrated significant correlation to final infarct size in this and
numerous other studies. However, due to the slow release of
these biomarkers, only peak values or values from a sample
taken at a fixed time point minimum 12 hours after onset of
chest pain have been validated.20 Elevated biochemical markers from a very early sample obtained in the emergency room
are certainly evidence of myocardial necrosis, but not the
extent of such, and are not likely to be useful in identification
of patients with substantial infarction. Myocardial systolic
function, on the other hand, is dependent on a continuous
blood supply and deteriorates within seconds of acute coronary occlusion,7 even before the onset of necrosis. Hence, an
important advantage of echocardiography is that it can
identify patients with developing substantial infarction at a
time point when intervention can still achieve significant
myocardial salvage. In our study, a stronger relationship
between final infarct size and myocardial systolic function
was found in patients arriving early, compared with those
arriving late. This indicates that the association is present at
an early stage during development of MI. ST-segment deviations in the ECG, when present, also appear rapidly after
onset of ischemia. However, in our study neither the presence
nor magnitude of ST-segment deviation was able to identify
patients with substantial infarction.
Limitations
Echocardiography was not performed in the emergency room,
but on arrival at the invasive center 1 to 3 days later.
However, as acute coronary occlusion is accompanied by
very rapid alterations in myocardial systolic function,7 similar
findings can be expected even at a very early stage. Nevertheless, infarct expansion and edema developing during the
first hours may be accompanied by alterations in systolic
function, and our model requires prospective validation
Sources of Funding
Drs Eek and Grenne are recipients of research fellowships from
the Norwegian Foundation for Health and Rehabilitation (Oslo,
Norway).
Disclosures
None.
References
1. Burns RJ, Gibbons RJ, Yi Q, Roberts RS, Miller TD, Schaer GL,
Anderson JL, Yusuf S. The relationships of left ventricular ejection
fraction, end-systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by
thrombolysis. J Am Coll Cardiol. 2002;39:30 –36.
2. White HD, Van de Werf FJ. Thrombolysis for acute myocardial
infarction. Circulation. 1998;97:1632–1646.
3. Perron A, Lim T, Pahlm-Webb U, Wagner GS, Pahlm O. Maximal
increase in sensitivity with minimal loss of specificity for diagnosis of
acute coronary occlusion achieved by sequentially adding leads from the
24-lead electrocardiogram to the orderly sequenced 12-lead electrocardiogram. J Electrocardiol. 2007;40:463– 469.
4. Christian TF, Gibbons RJ, Clements IP, Berger PB, Selvester RH,
Wagner GS. Estimates of myocardium at risk and collateral flow in acute
myocardial infarction using electrocardiographic indexes with comparison to radionuclide and angiographic measures. J Am Coll Cardiol.
1995;26:388 –393.
5. Kontos MC, Kurdziel KA, Ornato JP, Schmidt KL, Jesse RL, Tatum JL.
A nonischemic electrocardiogram does not always predict a small myocardial infarction: results with acute myocardial perfusion imaging. Am
Heart J. 2001;141:360 –366.
6. Martin TN, Groenning BA, Murray HM, Steedman T, Foster JE, Elliot
AT, Dargie HJ, Selvester RH, Pahlm O, Wagner GS. ST-segment
deviation analysis of the admission 12-lead electrocardiogram as an aid to
early diagnosis of acute myocardial infarction with a cardiac magnetic
resonance imaging gold standard. J Am Coll Cardiol. 2007;50:
1021–1028.
7. Theroux P, Franklin D, Ross J Jr, Kemper WS. Regional myocardial
function during acute coronary artery occlusion and its modification by
pharmacologic agents in the dog. Circ Res. 1974;35:896 –908.
8. Gjesdal O, Helle-Valle T, Hopp E, Lunde K, Vartdal T, Aakhus S, Smith
HJ, Ihlen H, Edvardsen T. Noninvasive separation of large, medium, and
small myocardial infarcts in survivors of reperfused ST-elevation myocardial infarction: a comprehensive tissue Doppler and speckle-tracking
echocardiography study. Circ Cardiovasc Imaging. 2008;1:189 –196.
9. Vartdal T, Brunvand H, Pettersen E, Smith HJ, Lyseggen E, Helle-Valle
T, Skulstad H, Ihlen H, Edvardsen T. Early prediction of infarct size by
194
10.
11.
12.
13.
14.
15.
Downloaded from http://circimaging.ahajournals.org/ by guest on May 6, 2017
16.
17.
18.
19.
Circ Cardiovasc Imaging
March 2010
strain Doppler echocardiography after coronary reperfusion. J Am Coll
Cardiol. 2007;49:1715–1721.
Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen
E, Stoylen A, Ihlen H, Lima JA, Smiseth OA, Slordahl SA. Noninvasive
myocardial strain measurement by speckle tracking echocardiography:
validation against sonomicrometry and tagged magnetic resonance
imaging. J Am Coll Cardiol. 2006;47:789 –793.
Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial
strain by Doppler echocardiography. Validation of a new method to
quantify regional myocardial function. Circulation. 2000;102:
1158 –1164.
Cho GY, Marwick TH, Kim HS, Kim MK, Hong KS, Oh DJ. Global
2-dimensional strain as a new prognosticator in patients with heart failure.
J Am Coll Cardiol. 2009;54:618 – 624.
Stanton T, Leano R, Marwick T. Prediction of all-cause mortality from
global longitudinal speckle strain: comparison with ejection fraction and
wall motion scoring. Circ Cardiovasc Imaging. 2009;2:356 –364.
Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy
J, Finn JP, Klocke FJ, Judd RM. Relationship of MRI delayed contrast
enhancement to irreversible injury, infarct age, and contractile function.
Circulation. 1999;100:1992–2002.
Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey
WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. Standardized
myocardial segmentation and nomenclature for tomographic imaging of
the heart: a statement for healthcare professionals from the Cardiac
Imaging Committee of the Council on Clinical Cardiology of the
American Heart Association. Circulation. 2002;105:539 –542.
Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ,
Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance
imaging to identify reversible myocardial dysfunction. N Engl J Med.
2000;343:1445–1453.
Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ,
Gibbons RJ. Infarct size after acute myocardial infarction measured by
quantitative tomographic 99mTc sestamibi imaging predicts subsequent
mortality. Circulation. 1995;92:334 –341.
Hanley JA, McNeil BJ. A method of comparing the areas under receiver
operating characteristic curves derived from the same cases. Radiology.
1983;148:839 – 843.
Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey
DE Jr, Chavey WE, Fesmire FM, Hochman JS, Levin TN, Lincoff AM,
20.
21.
22.
23.
24.
25.
26.
27.
28.
Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs
AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW,
Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA 2007 guidelines
for the management of patients with unstable angina/non ST-elevation
myocardial infarction. Circulation. 2007;116:e148 – e304.
Gibbons RJ, Valeti US, Araoz PA, Jaffe AS. The quantification of infarct
size. J Am Coll Cardiol. 2004;44:1533–1542.
Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA,
Schulman SP, Blumenthal RS, Lima JA. Prognostic significance of
microvascular obstruction by magnetic resonance imaging in patients
with acute myocardial infarction. Circulation. 1998;97:765–772.
Kastrati A, Mehilli J, Dirschinger J, Schricke U, Neverve J, Pache J,
Martinoff S, Neumann FJ, Nekolla S, Blasini R, Seyfarth M, Schwaiger
M, Schomig A. Myocardial salvage after coronary stenting plus
abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial. Lancet. 2002;359:920 –925.
Roger VL, Killian JM, Weston SA, Jaffe AS, Kors J, Santrach PJ,
Tunstall-Pedoe H, Jacobsen SJ. Redefinition of myocardial infarction:
prospective evaluation in the community. Circulation. 2006;114:
790 –797.
Moller JE, Hillis GS, Oh JK, Reeder GS, Gersh BJ, Pellikka PA. Wall
motion score index and ejection fraction for risk stratification after acute
myocardial infarction. Am Heart J. 2006;151:419 – 425.
Gjesdal O, Hopp E, Vartdal T, Lunde K, Helle-Valle T, Aakhus S, Smith
HJ, Ihlen H, Edvardsen T. Global longitudinal strain measured by twodimensional speckle tracking echocardiography is closely related to myocardial infarct size in chronic ischaemic heart disease. Clin Sci (Lond).
2007;113:287–296.
Sjøli B, Ørn S, Grenne B, Ihlen H, Edvardsen T, Brunvand H. Diagnostic
capability and reproducibility of strain by Doppler and by Speckle
tracking in patients with acute myocardial infarction. J Am Coll Cardiol
Img. 2009;2:24 –33.
Chan J, Hanekom L, Wong C, Leano R, Cho GY, Marwick TH. Differentiation of subendocardial and transmural infarction using twodimensional strain rate imaging to assess short-axis and long-axis myocardial function. J Am Coll Cardiol. 2006;48:2026 –2033.
Dixon WC, Wang TY, Dai D, Shunk KA, Peterson ED, Roe MT.
Anatomic distribution of the culprit lesion in patients with non-STsegment elevation myocardial infarction undergoing percutaneous
coronary intervention: findings from the National Cardiovascular Data
Registry. J Am Coll Cardiol. 2008;52:1347–1348.
CLINICAL PERSPECTIVE
Infarct size is a strong prognostic indicator after myocardial infarction. In patients with ST-segment elevation myocardial
infarction, reperfusion therapy is effective in reducing infarct size and has improved survival. However, a proportion of
non–ST-segment– elevation myocardial infarction patients also experience substantial myocardial infarction, but these
patients are rarely eligible for acute reperfusion therapy. Severe myocardial ischemia and necrosis is not always reflected
in ST segment elevation, and these patients often do not reveal clinical signs of instability. Hence, there is a need for other
modalities to identify these patients. Abundant evidence has demonstrated that myocardial ischemia causes rapid
deterioration of myocardial systolic function. Echocardiography is a fast and available tool for estimation of myocardial
systolic function. Left ventricular ejection fraction and wall motion score index are conventional parameters used to
estimate left ventricular systolic function. Recently, strain measurement by speckle tracking has emerged as a new
modality. The present study demonstrates that non–ST-segment– elevation myocardial infarction patients with substantial
myocardial infarction can be identified by echocardiographic parameters of left ventricular systolic function. Global
longitudinal strain and wall motion score index both demonstrate excellent discriminating power. Echocardiography and
particularly strain echocardiography may facilitate the evaluation of interventions that impact outcomes in patients with
non–ST-segment– elevation myocardial infarction.
Strain Echocardiography and Wall Motion Score Index Predicts Final Infarct Size in
Patients With Non−ST-Segment−Elevation Myocardial Infarction
Christian Eek, Bjørnar Grenne, Harald Brunvand, Svend Aakhus, Knut Endresen, Per K. Hol,
Hans-Jørgen Smith, Otto A. Smiseth, Thor Edvardsen and Helge Skulstad
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Circ Cardiovasc Imaging. 2010;3:187-194; originally published online January 14, 2010;
doi: 10.1161/CIRCIMAGING.109.910521
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