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Chapter 6
Relation between global left ventricular
longitudinal strain assessed with novel
automated function imaging and biplane left
ventricular ejection fraction in patients with
coronary artery disease
Victoria Delgado, MD, Sjoerd A. Mollema, MD, Claudia Ypenburg, MD, Laurens F. Tops,
MD, Ernst E. Van der Wall, MD, PhD, Martin J. Schalij, MD, PhD, Jeroen J. Bax, MD, PhD
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
J Am Soc Echocardiogr 2008;21:1244-1250
Abstract
Objective: Automated function imaging (AFI) is a novel algorithm based on speckle-tracking
imaging that can be used for assessment of global longitudinal strain of the left ventricle. The
purpose of this study was to evaluate the relation between global longitudinal peak systolic
strain (GLPSS Avg) assessed by AFI and left ventricular (LV) ejection fraction (LVEF).
Methods: The study population consisted of 222 consecutive patients with coronary artery
disease (99 patients with acute ST-segment elevation myocardial infarction (STEMI) and 123
patients with advanced ischemic heart failure) and 20 age-matched control patients. LVEF was
calculated by Simpson’s rule. The GLPSS Avg was obtained by AFI.
Results: In the overall study group (65 ± 10 years, 77% men) mean GLPSS Avg was 11.1 ± 4.8%
and mean LVEF was 37 ± 14%. Linear regression analysis showed a good correlation between
GLPSS Avg and biplane LVEF for the overall study population (r=0.83; p<0.001). However, in
patients with STEMI and patients with heart failure the correlation was less strong (r=0.42 and
r=0.62, respectively).
Conclusion: Systolic global longitudinal strain assessed by AFI was linearly related to biplane
LVEF. In patients with STEMI or heart failure, less strong correlations were observed, suggesting
Chapter 6
that these two parameters reflect different aspects of systolic LV function.
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Introduction
Left ventricular ejection fraction (LVEF) is a strong prognostic parameter in patients with heart
disease and is an important component in the prognostic work-up of patients with coronary
artery disease (1-3). For the echocardiographic quantification of systolic left ventricular (LV)
function, biplane measurement of LVEF on standard 2-dimensional (2D) images using the
Simpson’s rule is currently the method of preference (4). Recently, automated function imaging
tracking imaging, by assessment of global LV longitudinal strain (5). This imaging technique
is able to discriminate between active and passive myocardial motion and enables the angleindependent quantification of myocardial deformation in two dimensions.
Data concerning the relation between global LV longitudinal systolic strain with AFI and
biplane LVEF as markers of systolic LV function are scarce (6). The purpose of the present study
was to evaluate the relation between global LV longitudinal systolic strain assessed by AFI and
biplane LVEF in a large cohort of patients with coronary artery disease with varying LVEF, ranging from mild to severely depressed.
Methods
Study population and protocol
During a 1-year period, a total of 222 patients with coronary artery disease referred for 2D echocardiography were included. The overall study group consisted of patients who underwent
clinically indicated echocardiography in the acute setting of ST-segment elevation myocardial
infarction (STEMI patients, n=99) or chronic ischemic heart failure (n=123).
During 2D echocardiography, biplane LV volumes and LVEF were measured and global LV
longitudinal strain using AFI was assessed. In the STEMI patients, echocardiography was performed within 48 hours of admission. The heart failure patients underwent echocardiography
as part of the routine clinical evaluation.
Data of the patients with coronary artery disease were compared with a group of agematched controls (n=20) selected from an echocardiographic database (7). The control group
comprised patients referred for echocardiography with atypical chest pain, palpitations or
syncope without murmur. In particular, only patients without structural heart disease and
normal LV systolic function and dimensions were selected. Furthermore, subjects who were
referred for echocardiographic evaluation of known valvular disease, murmur, or heart failure
were excluded.
Relation between global left ventricular longitudinal strain assessed with novel AFI and biplane LVEF in patients with coronary artery disease
(AFI) was introduced as a novel method to reflect systolic LV function, based on 2D speckle-
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Echocardiography
2D Echocardiography was performed with the patient in the left lateral decubitus position using
a commercially available system (Vivid 7, General Electric Vingmed, Milwaukee, Wisconsin, USA)
equipped with a 3.5-MHz transducer. Standard 2D images triggered to the QRS complex, were
saved in cine-loop format. LV end-systolic and end-diastolic volumes were assessed and LVEF
was calculated from the apical 4- and 2-chamber views using the Simpson’s rule (8).
Global left ventricular longitudinal strain analysis
Global LV longitudinal strain was quantified using AFI, which provides a new imaging technique
based on 2D strain imaging (6). The software analyzes motion by tracking speckles (natural
acoustic markers) in the ultrasonic image in two dimensions. The frame-to-frame changes of
the speckles are used to derive motion and velocity. For this purpose, one single cardiac cycle
is needed from each apical view (apical long axis, 4- and 2-chamber views).
First, the end-systolic frame is defined in the apical long-axis view. The closure of the aortic
valve is marked and the software measures the time interval between R wave and aortic valve
closure. This interval is used as a reference for the 4- and 2-chamber view loops. After defining the mitral annulus and the LV apex with 3 index points at the end-systolic frame in each
apical view, the automated algorithm traces 3 concentric lines on the endocardial border, the
mid-myocardial layer and epicardial border, including the entire myocardial wall. The tracking
algorithm follows the endocardium from this single frame throughout the cardiac cycle, and
allows for a further manual adjustment of the region of interest to ensure that all myocardial
regions are included throughout the cardiac cycle. The left ventricle is divided in 6 segments in
each apical view and the tracking quality is validated for each segment. Then, the myocardial
motion is analyzed by speckle-tracking within the region of interest.
Finally, the automated algorithm, using a 17-segment model, provides the peak systolic
longitudinal strain for each LV segment in a “bull‘s eye” plot, with the average value of peak systolic longitudinal strain for each view and the averaged global longitudinal peak systolic strain
(GLPSS Avg) for the complete left ventricle. In general, longitudinal strain values are presented
as negative values; a larger negative value indicates a larger extent of longitudinal strain. For
the purpose of the present study, the global strain values are presented as positive values.
Mean frame rate of the obtained images was 70 fps (range 40-100 fps). For global LV longitudinal strain analysis, digital cine-loops were off-line processed using commercially available
software (EchoPac 6.1, GE Medical Systems, Horten, Norway).
Chapter 6
Statistical analysis
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Continuous data were presented as mean values ± SD and comparisons among groups were
performed using the one-way analysis of variance test with Bonferroni post-hoc study. Categorical data were presented as percentages and were compared using the c2-test. Global
longitudinal strain was correlated with LVEF by linear regression analysis.
Reproducibility of GLPSS Avg values measured with AFI was analyzed with repeated measurements of global LV longitudinal strain by one experienced observer at two different time
points and by a second experienced observer in 25 randomly selected patients (5 controls, 10
STEMI patients and 10 heart failure patients). Intra- and inter-observer agreement for global
LV longitudinal strain measurements were evaluated by Bland-Altman analysis. Furthermore,
intra-class correlation coefficients were used as indicators of reproducibility.
All statistical analyses were performed with SPSS software (version 12.0, SPSS Inc., Chicago,
Results
Study population
The overall study group comprised 222 coronary artery disease patients (66 ± 10 years, 177
men [80%]) and 20 controls (64 ± 13 years, 11 men [55%]). The clinical characteristics for the
overall study population and for each subgroup are summarized in Table 1.
The group of patients with STEMI comprised 99 patients (65 ± 9 years, 76 men [76%]). Primary percutaneous coronary intervention was performed in all patients. Mean peak levels of
creatine phosphokinase and troponin T were 2369 ± 1801 U/L and 6 ± 5 μg/L, respectively. The
123 patients with chronic ischemic heart failure (67 ± 10 years, 101 men [82%]) were in stable
clinical conditions and received optimal medical treatment at maximum dosages tolerated.
The control group comprised 20 patients with no evidence of structural heart disease at the
echocardiographic studies.
Table 1. Clinical characteristics of the study population
STEMI
(n=99)
Heart
failure
(n=123)
p value
Overall
(n=242)
Controls
(n=20)
Age (yrs)
65 ± 10
64 ± 13
65 ± 9
67 ± 10
0.3
Male, n (%)
188 (77)
11 (55)
76 (76)
101 (82)
0.02
Hypertension, n (%)
79 (33)
6 (30)
37 (37)
36 (29)
0.4
Smoking, n (%)
94 (39)
1 (5)
57 (57)
36 (29)
<0.001
Hypercholesterolemia, n (%)
46 (19)
2 (10)
18 (18)
26 (21)
0.5
Diabetes mellitus, n (%)
37 (15)
3 (15)
15 (15)
19 (15)
0.9
Positive family history, n (%)
68 (28)
3 (15)
38 (38)
27 (22)
0.01
Peripheral vascular disease, n (%)
41 (17)
2 (10)
26 (26)
13 (11)
0.4
Drug therapy, n (%)
Beta-blockers
Ca-antagonists
ACE-inhibitors/ARBs
Diuretics
176 (70)
11 (4)
195 (79)
117 (48)
6 (30)
1 (5)
3 (15)
2 (10)
91 (92)
4 (4)
91 (92)
10 (10)
79 (64)
6 (5)
101 (82)
105 (85)
<0.001
0.9
<0.001
<0.001
ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; STEMI: ST-segment elevation
myocardial infarction.
Relation between global left ventricular longitudinal strain assessed with novel AFI and biplane LVEF in patients with coronary artery disease
Illinois). A p value <0.05 was considered statistically significant.
101
Echocardiography
The echocardiographic characteristics of the study population are shown in Table 2. Differences
in LV volumes differed significantly between the 3 subgroups. Mean LV end-systolic volume
(LVESV) and end-diastolic volume (LVEDV) were largest in patients with heart failure (173 ± 68
ml and 226 ± 78 ml, respectively; p<0.0001). In STEMI patients, mean LVESV was 68 ± 21 ml and
mean LVEDV measured 128 ± 34 ml. In control patients, LV volumes were smallest with a mean
LVESV of 36 ± 12 ml and a mean LVEDV of 86 ± 22 ml. In addition, heart failure patients had
significantly lower LVEF than the other groups of patients (24 ± 7% versus 47 ± 7% for STEMI
patients and 58 ± 6% for control patients; p<0.0001).
Table 2. Echocardiographic characteristics of the study population
Overall
(n=242)
Controls
(n=20)
STEMI
(n=99)
Heart failure
(n=123)
p value
LVESV (ml)
118 ± 75
36 ± 12
68 ± 21
173 ± 68
<0.0001
LVEDV (ml)
175 ± 80
86 ± 22
128 ± 34
226 ± 78
<0.0001
LVEF (%)
GLPSS Avg (%)
37 ± 14
58 ± 6
47± 7
24 ± 7
<0.0001
11.1 ± 4.8
18.3 ± 1.7
14.0 ± 3.4
7.6 ± 3.0
<0.0001
GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF: left ventricular ejection fraction;
LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; STEMI: STsegment elevation myocardial infarction.
Global left ventricular longitudinal peak systolic strain
The AFI algorithm was able to provide GLPSS Avg in all patients (Table 2). Control patients
showed the highest mean GLPSS Avg being 18.3 ± 1.7% (p<0.0001 versus STEMI and heart
Chapter 6
failure patients) (Figure 1). The patients with STEMI showed a mean GLPSS Avg of 14.0 ± 3.4%.
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Figure 1. Average GLPSS Avg values for each group of patients are displayed in a box-plot figure. In
control patients, the highest GLPSS Avg was demonstrated. In patients with STEMI, GLPSS Avg was lower,
whereas patients with heart failure had the lowest GLPSS Avg. ANOVA: analysis of variance; GLPSS Avg:
averaged global longitudinal peak systolic strain; STEMI: ST-segment elevation myocardial infarction.
Patients with heart failure had a mean GLPSS Avg of 7.6 ± 3.0%. In Figure 2, examples of strain
curves and bull’s-eye plots, providing peak systolic longitudinal strain for all LV segments, are
Relation between global left ventricular longitudinal strain assessed with novel AFI and biplane LVEF in patients with coronary artery disease
demonstrated for the 3 patient groups.
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Figure 2. Longitudinal strain curves and bull’s-eye plots showing segmental peak systolic longitudinal strain of
representative patients from each patient group (panel A: control; panel B: STEMI; panel C: chronic ischemic heart
failure). As conventionally accepted, LV segments with normal strain (highest values of GLPSS) are presented
in red and those LV segments with abnormal strain (lowest values of GLPSS) are presented in blue. The bull’s
eye plot of the control patient shows high and homogeneous peak systolic longitudinal strain for the entire left
ventricle. In the patient with STEMI, decreased peak systolic longitudinal strain is observed in the inferoseptal
LV segments consistent with the region of infarction and the culprit coronary artery (right coronary artery). The
bull’s eye plot of the patient with heart failure shows a globally reduced peak systolic longitudinal strain. GLPSS:
global longitudinal peak systolic strain; LV: left ventricular; STEMI: ST-segment elevation myocardial infarction.
The intra-observer agreement for GLPSS Avg measurements was good, with an average difference of -0.3 ± 0.6% (mean ± 2SD) between repeated measurements. The intra-class correlation coefficient for intra-observer comparisons was 0.95. Similarly, agreement of measurements
made by two different observers was good, with an average difference of -0.2 ± 2.6% (mean ±
2SD) and an intra-class correlation coefficient of 0.92.
Linear regression analysis demonstrated a good correlation between GLPSS Avg and LVEF
for the overall study population (y=0.28x+0.88; r=0.83; p<0.001) (Figure 3).
In the group of patients with STEMI, a moderate correlation between GLPSS Avg and LVEF
Chapter 6
was observed (r=0.42) (Figure 4, panel A). Similarly, in the subgroup of patients with ischemic
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heart failure patients a moderate correlation between these two parameters was obtained
(r=0.62) (Figure 4, panel B).
25
Figure 3. Relation between GLPSS Avg and LVEF presented for the overall
Figure 3. Relation
between GLPSS Avg and LVEF presented for the overall study population (▲ = controls;
GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF: left
○ = STEMI; ● = heart failure). GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF: left
ventricular
ejection
fraction;
STEMI:elevation
ST segment
elevation
myocardial infarction.
ventricular ejection
fraction;
STEMI:
ST-segment
myocardial
infarction.
Figure 4. Relation between GLPSS Avg and LVEF presented for patient subgroups: STEMI patients (panel
A) and heart failure patients (panel B). GLPSS Avg: averaged global longitudinal peak systolic strain; LVEF:
left ventricular ejection fraction; STEMI: ST-segment elevation myocardial infarction.
Discussion
The main findings of the present study can be summarized as follows: 1) assessment of global LV
longitudinal strain with AFI can be applied in a heterogeneous study population with coronary
artery disease to evaluate global systolic LV function, 2) assessment of global LV longitudinal
Relation between global left ventricular longitudinal strain assessed with novel AFI and biplane LVEF in patients with coronary artery disease
study population (▲ = controls; ○ = STEMI; ● = heart failure).
105
strain using AFI is highly reproducible, and 3) a good relation is observed between global LV
longitudinal strain assessed with AFI, and biplane LVEF.
Relevance of systolic left ventricular function in patients with coronary artery disease
In several studies, a strong relation has been demonstrated between systolic LV function and
prognosis in a number of different clinical conditions (2,9,10). Particularly in patients with coronary artery disease, LVEF is the strongest predictor of long-term survival (11-13). In patients
with stable angina, the annual mortality rate exceeds 3% for those patients with LVEF <35%
(10,14). In addition, Bennet et al., evaluating 94,558 patients with high-risk non-ST-elevation
acute coronary syndrome enrolled in the CRUSADE trial, found a significantly higher adjusted
mortality in patients with LVEF <40% than in those patients with preserved LVEF (adjusted OR
2.76, 95% CI 2.48-3.07) (3,15). Furthermore, in several large clinical trials evaluating different
therapeutic strategies (e.g. renin-angiotensin-aldosteron inhibitors or implantable cardioverterdefibrillators) LVEF was used for the selection of patients (16-18).
Because of its wide availability and safety, 2D echocardiography is the most frequently used
imaging modality for the quantification of systolic LV function. Several echocardiographic
parameters have been used to evaluate systolic LV function: LVEF, wall motion score index and
mitral annular peak systolic velocity assessed with tissue Doppler imaging (4,19,20). However,
biplane LVEF quantified using the Simpson’s rule is the most widely used parameter in epidemiological and clinical trials (4).
Relation between LVEF and global left ventricular longitudinal strain
Although LVEF constitutes a simple method to study systolic LV function accurately and with
high reproducibility, this parameter does not always reflect the actual extent of myocardial
damage after infarction. Therefore, in patients with extensive myocardial infarction, the presence of regional hyperkinesis may result in almost normal LVEF, thereby affecting the prognostic value of this parameter (21). Consequently, the assessment of regional LV function has been
proposed as a more sensitive method to detect systolic LV dysfunction. Thus, wall motion score
index, a semi-quantitative method to assess regional myocardial function using 2D echocardiography, has been demonstrated to provide incremental predictive value for morbidity and
mortality as compared to biplane LVEF (22). However, this approach is based on a subjective
visual assessment of regional wall motion.
In contrast, strain and strain rate imaging measure the magnitude and rate of regional myo-
Chapter 6
cardial deformation, respectively. Both imaging methods enable the differentiation between
106
those myocardial segments with an active contraction and those that are tethered by other
segments (23). The AFI algorithm is a novel method based on 2D strain imaging that enables
the quantification of myocardial strain simultaneously in different LV segments with ultrasound
beam angle-independency by tracking acoustic pixels equally distributed within the myocardial
wall. As applied to apical views, this method allows for the measurement of regional myocardial
shortening and, subsequently, enables the calculation of global LV longitudinal strain as the
average of the 17-segment longitudinal peak systolic strain values.
In the present study, a broad spectrum of patients with coronary artery disease was studied
including patients with acute myocardial infarction and patients with chronic ischemic heart
failure. Biplane LVEF was measured in all patients and used as a reference parameter to assess
the clinical usefulness of a novel algorithm, global LV longitudinal strain quantified using AFI,
to study global systolic LV function. The mean global LV longitudinal strain was linearly related
Several previous studies have demonstrated a good correlation between global LV longitudinal strain measured with speckle-tracking imaging and wall motion score index (5,6). Reisner
et al. found significant lower values for average global longitudinal strain in 27 consecutive
patients with myocardial infarction as compared to control patients (14.7 ± 5.1% versus 24.1
± 2.9%; p<0.0001) (5). Furthermore, the authors demonstrated a good correlation between
global longitudinal strain and wall motion score index (r=0.68; p<0.0001).
Of note, the present study is the first to relate a global value for LV longitudinal strain with
biplane LVEF. Between these two parameters, a good relation was observed in a heterogeneous
study population with coronary artery disease.
In addition, measurement of global LV longitudinal strain was feasible in all patients. No
patient had to be excluded due to poor image quality. The intra-observer and inter-observer
variability were studied and good agreement was noticed. Therefore, measurement of global LV
longitudinal strain using AFI provides reproducible assessment of systolic LV function. Ideally,
an independent measurement of LV longitudinal strain by another technique would be desirable to evaluate the accuracy of the novel AFI method based on speckle-tracking imaging. This
was not available in the current study, but previous work validated speckle-tracking-derived
strain against sonomicrometry and tagged magnetic resonance (24).
Although the correlation between the GLPSS Avg and biplane LVEF was good in the overall
population, in patients with coronary artery disease (STEMI or chronic heart failure) the correlation was less strong. This observation suggests that the 2 parameters are not identical, but
rather reflect different aspects of systolic LV function.
Finally, outcome data of coronary artery disease patients were not systematically recorded
and therefore, the prognostic value of GLPSS Avg could not be determined in the present study.
Conclusions
Global LV longitudinal strain assessed with AFI is linearly related to biplane LVEF. AFI allows
reproducible quantification of systolic LV function. In patients with ischemic heart disease, a
less strong correlation between GLPSS Avg and biplane LVEF was observed, suggesting that
Relation between global left ventricular longitudinal strain assessed with novel AFI and biplane LVEF in patients with coronary artery disease
to biplane LVEF in the overall population.
107
these two parameters reflect different aspects of LV systolic function. In this perspective, addi-
Chapter 6
tional studies are needed to evaluate the clinical implications.
108
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