Keywords
Left ventricular dyssynchrony - myocardial infarction - tissue synchronization imaging
INTRODUCTION
Mechanical dyssynchrony is increasingly used to describe the mechanical effects of
asynchronous ventricular contraction and relaxation, which may or may not be associated
with electrical conduction delay.[1] Left ventricular (LV) dyssynchrony is observed in 30–40% of patients with a normal
QRS duration[1] and in a significant number of patients with heart failure (HF) and preserved LV
ejection fraction (LVEF).[2] Coronary artery disease (CAD) is one of the most common causes of HF with preserved
left ventricular ejection fraction (LVEF); however, there are limited results about
mechanical dyssynchrony in patients with CAD with preserved LVEF.[3] Acute myocardial infarction leads to a delayed onset and slower rate of contraction
and relaxation in regional myocardial segments and may cause LV mechanical dyssynchrony
and subsequent clinical HF.[3] Local myocardial conduction and systolic function may be assessed using tissue Doppler
imaging (TDI), strain rate imaging, or tissue synchronization imaging (TSI).[4] Until now, however, evaluation of systolic function of the myocardium has mainly
depended on detection of global function or analyze changes in time and the conduction
function of the heart.[4] Approaches have been developed to investigate local myocardial conduction and systolic
function such as Doppler tissue imaging, strain rate imaging, and especially TSI.[4] We aimed to assess LV dyssynchrony in patients with ST elevation myocardial infarction
(STEMI) using TSI.
MATERIALS AND METHODS
This study included 36 patients that presented with acute STEMI who were recruited
from the coronary care unit at a university hospital. The control group comprised
20 age and sex-matched healthy individuals.
Patients with a wide QRS complex (≥120ms), myocardial diseases (hypertrophic cardiomyopathy,
restrictive cardiomyopathy, or dilated cardiomyopathy), paced rhythm, rheumatic heart
disease with significant valvular lesions, previous open heart surgery, and poor echocardiographic
windows were excluded from the study. Written informed consent for participation was
obtained, and the hospital ethics committee approved the protocol.
All participants in the study were subjected to the following: full history taking,
thorough clinical examination, 12-lead electrocardiography (ECG) and echocardiographic
examination. Transthoracic echocardiographic examination was performed using a commercially
available system (Vivid 9; GE Vingmed Ultrasound AS, Horten, Norway) equipped with
a 1.7–4 MHz phased-array transducer with simultaneous ECG tracing. Echocardiography
was performed within 24h of the admission in the left lateral position, according
to the recommendations of the American Society of Echocardiography.[5]
Conventional echocardiography
M-mode echocardiography
M-mode echocardiography was performed using the parasternal long axis view with the
M-mode cursor perpendicular to the interventricular septum and posterior wall at the
level of the mitral valve tip for measurement of LV end-diastolic diameter (LVEDD),
LV end-systolic diameter (LVESD), interventricular septal thickness in diastole, posterior
wall thickness in diastole, fractional shortening, and LVEF.
Two-dimensional echocardiography
Two-dimensional (2D) echocardiography for assessment of wall motion abnormality and
estimation of EF was performed using Simpson’s method.
Doppler echocardiography
For measurement of peak E (early diastolic) wave velocity, peak A (late diastolic)
wave velocity, and the E/A ratio with pulsed Doppler sample volume, the transmitral
Doppler probe was placed in the middle of the LV inflow tract 1cm below the plane
of the mitral annulus in the apical four-chamber view. Trans-aortic Doppler in the
apical five-chamber and three-chamber views was used for measuring aortic valve opening
and closure.
Tissue strain imaging
The automatically color-coded time to peak myocardial velocity (Ts) was measured using
a 6mm sample volume manually positioned within the 2D TSI image for 12 LV segments.
The 12 segments included 6 basal and 6 mid-wall segments of opposing LV walls in apical
two-, three-, and four-chamber views. At least three consecutive beats on TSI were
stored and the images were analyzed offline using a customized software package (EchoPAC
for PC; GE Vingmed Ultrasound) [Figure 1]. To prevent the TSI system from measuring peak systolic velocities outside the ejection
phase, the event-timing tool was used to manually adjust start and end times of the
aortic valve ejection. Parameters of systolic dyssynchrony were computed using the
software. The parameters included standard deviation (SD) of Ts of the 12 LV segments
(dyssynchrony index), septal-lateral delay, septal-posterior delay, and all segmental
maximum difference. The dyssynchrony index is the most widely used parameter for LV
dyssynchrony, which is defined as a dyssynchrony index >34.4ms on TSI.[6] LV systolic dyssynchrony is defined as septal-lateral delay or septal-posterior
delay ≥2 SDs above the control.[7]
Figure 1: (A) Tissue synchronization imaging (TSI) of the LV in patient with anterior
myocardial Infarction (apical four-chamber view) demonstrating cursor placement for
auto-TSI analysis; the bulls-eye diagram for time to peak velocity measurements showed
LV dyssynchrony as dyssynchrony index was 62 ms. (B) TSI of the LV in control (apical
four-chamber view)
STEMI complications
All patients were followed up for any inhospital post-STEMI complications including
death, cardiogenic shock, pulmonary edema, arrhythmia, stroke, acute kidney injury,
severe mitral regurgitation, ventricular septal rupture, and complete heart block.
Statistical analysis
Statistical analysis was performed using IBM-SPSS (version 20; IBM Corp, Armonk, NY)
software. Mean and SD were computed for all quantitative variables. Student’s t-test
was used to compare quantitative data between the STEMI and healthy control groups,
patients with and without anterior STEMI, and patients with and without STEMI complications.
The chi-square test was used to compare qualitative data. The Pearson correlation
test was used to analyze the TSI parameters correlated with LVEF, LVESD, and LVESD
in the STEMI group. P < 0.05 was considered statistically significant.
RESULTS
Baseline characteristics
The cohort comprised 36 patients presenting with acute STEMI (mean age, 54±10.8 years)
and 20 age and sex-matched healthy volunteers who represented the control group (mean
age, 49.1±7.5). Among the patients in the STEMI group, 41.7% were hypertensive, 33.3%
were diabetic, 33.3% had dyslipidemia, and 55.6% were smokers [Table 1].
Table 1
Demographic data of the studied groups
|
Patients group (N = 36)
|
|
Woman, n (%)
|
8 (22.2%)
|
|
Men, n (%)
|
28 (77.8%)
|
|
Age (years), Mean ± standard deviation
|
54.06 ± 10.81
|
|
Hypertension n (%)
|
15 (41.7%)
|
|
Diabetes mellitus, n (%)
|
12 (33.3%)
|
|
Dyslipidemia, n (%)
|
12 (33.3%)
|
|
Smoking, n (%)
|
20 (55.6%)
|
In the STEMI group, 47% (n = 17) of patients developed post-STEMI complications: 35.2%
(6) had pulmonary edema,11.7% (2) had cardiogenic shock, 11.7% (2) had stroke, 17.6%
(3) had ventricular tachycardia, 17.6% (3) had heart block, and 5.7% (1) had ventricular
septal rupture.
Conventional echocardiographic parameters in the STEMI and control groups
The left atrial (LA) diameters, LVEDD, LVESD, and A-wave velocity were significantly
higher in the STEMI group than in the control group (3.79cm vs. 3.31cm, P = 0.0001; 3.74cm vs. 2.97cm, P = 0.001; and 5.27cm vs. 4.94cm, P = 0.006, respectively). On the other hand, the E/A ratio and LVEF were significantly
lower in the STEMI group (1.01 vs. 1.30, P = 0.002; and 49.03% vs. 68.45%, P = 0.0001, respectively) [Table 2].
Table 2
Drugs
|
A
|
B
|
|
STEMI group (n = 36)
|
Control group (n = 20)
|
P-value
|
Anterior (n = 24)
|
Non-anterior (n = 12)
|
P-value
|
|
LVESD = left ventricle end-systolic diameter, LVEDD= left ventricle end-diastolic
diameter, SD = standard deviation, STEMI = ST elevation myocardial infarction
|
|
Aortic opening (cm), mean ± SD
|
2.69 ± 0.17
|
2.59 ± 0.18
|
0.070
|
3.17 ± 0.37
|
2.98 ± 0.45
|
0.175
|
|
Left atrium (cm), mean ± SD
|
3.79 ± 0.56
|
3.31 ± 0.16
|
<0.0001
|
3.81 ± 0.62
|
3.74 ± 0.43
|
0.724
|
|
LVESD (cm), mean ± SD
|
3.74 ± 0.83
|
2.97 ± 0.75
|
0.001
|
3.67 ± 0.84
|
3.19 ± 0.88
|
0.043
|
|
LVEDD (cm), mean ± SD
|
5.27 ± 0.47
|
4.94 ± 0.31
|
0.006
|
5.28 ± 0.49
|
4.98 ± 0.31
|
0.012
|
|
Ejection fraction (%), mean ± SD
|
49.03 ±10.13
|
68.45 ± 3.68
|
<0.0001
|
46.25 ± 8.19
|
54.58 ± 1 1.64
|
0.018
|
|
E m/s, mean ± SD
|
0.68 ± 0.20
|
0.71 ± 0.1 1
|
0.603
|
0.66 ± 0.20
|
0.73 ± 0.18
|
0.317
|
|
A m/s, mean ± SD
|
0.68 ± 0.17
|
0.57 ± 0.06
|
0.009
|
0.73 ± 0.17
|
0.58 ± 0.12
|
0.020
|
|
E/A, mean ± SD
|
1.01 ± 0.34
|
1.30 ± 0.27
|
0.002
|
0.88 ± 0.29
|
1.53 ± 0.62
|
<0.0001
|
TSI parameters in the STEMI and control groups
Significantly longer septal-lateral and septal-posterior delays were found in the
STEMI group than in the control group (36.36ms vs. −6.0ms, P = 0.036; and 42.7ms vs. 23.94ms, P = 0.042, respectively). In addition, all segment maximum differences and all segment
SD (dyssynchrony index) were found to be significantly higher in the patients with
STEMI than in the controls (131.28ms vs. 95.45ms, P = 0.013; and 44.47ms vs. 26.45ms, P = 0.001, respectively) [Table 3]; [Figure 1].
Table 3
Comparison of tissue synchronization imaging (TSI) parameters in studied groups (A)
and comparison of TSI parameters between patients with anterior myocardial infarction
(MI) and non-anterior MI (B)
|
A
|
B
|
|
STEMI group (n = 36)
|
Control group (n = 20)
|
P-value
|
Anterior (n = 24)
|
Non-anterior (n = 12)
|
P-value
|
|
SD = standard deviation, STEMI = ST elevation myocardial infarction
|
|
Septal lateral delay (ms), Mean ± SD
|
36.36 ± 75.89
|
-6.00 ± 59.98
|
0.036
|
57.21 ± 66.45
|
-5.82 ± 82.87
|
0.022
|
|
Septal post delay (ms), Mean ± SD
|
42.72 ± 35.40
|
23.94 ± 15.19
|
0.042
|
55.75 ± 29.08
|
16.67 ± 33.30
|
0.001
|
|
All segment maximum difference (ms) Mean ± SD
|
131.28 ± 53.73
|
95.45 ± 41.58
|
0.013
|
148.29 ± 54.12
|
97.25 ± 34.13
|
0.005
|
|
All segment SD (ms)
|
44.47 ± 15.82
|
26.45 ± 7.06
|
<0.001
|
47.21 ± 19.03
|
36.91 ± 8.89
|
0.017
|
Conventional echocardiographic parameters in patients with and without anterior STEMI
We found that LVEDD, LVESD, and A-wave velocity were significantly higher in patients
with anterior STEMI (5.28cm vs. 4.98cm, P = 0.012; 3.67cm vs. 3.19cm, P = 0.043; and 0.73 m/s vs. 0.58 m/s, P = 0.020 respectively). However, the LVEF and E/A ratio were significantly lower in
patients with anterior STEMI (46.25% vs. 54.58%, P = 0.018; and 0.88 vs. 1.53, P = 0.0001, respectively). Interestingly, LA dimension and E-wave velocity were not
significantly different (P = 0.724 and P = 0.317, respectively) [Table 2].
TSI parameters in patients with and without anterior STEMI
Septal-lateral and septal-posterior wall delays, all segment maximum difference, and
all segment SD (dyssynchrony index) were significantly higher in patients with anterior
STEMI than in those without (57.21ms vs. −5.82ms, P = 0.022; 55.75ms vs. 16.67ms, P = 0.001; 148.29ms vs. 97.25ms, P = 0.005; and 47.21ms vs. 36.91ms, P = 0.017, respectively) [Table 3].
TSI parameters in patients with and without complicated STEMI
A significant increase in delay between the septal-lateral walls and septal-posterior
walls, all segment maximum difference, and all segment SD (dyssynchrony index) was
observed in patients with complicated STEMI (70.89ms vs. 15.83ms, P = 0.038; 57.44ms vs. 19.06ms, P = 0.040; 138.11ms vs. 100.0ms, P = 0.035; and 45.44ms vs. 32.50ms, P = 0.021, respectively) [Table 4].
Table 4
Comparison of tissue synchronization imaging parameters between complicated patients
and noncomplicated patients
|
Complicated STEMI (n = 17 [47%])
|
Noncomplicated STEMI (n = 19 [53%])
|
Independent t-test
|
|
t
|
P-value
|
|
SD = standard deviation, STEMI = ST elevation myocardial infarction
|
|
Septal lateral delay (ms) Mean ± SD
|
70.89 ± 78.05
|
15.83 ± 74.64
|
2.163
|
0.038
|
|
Septal post delay (ms) Mean ± SD
|
57.44 ± 50.96
|
19.06 ± 56.83
|
-2.134
|
0.040
|
|
All segment maximum difference (ms) Mean ± SD
|
138.1 1 ± 62.38
|
100.00 ± 39.07
|
2.197
|
0.035
|
|
All segment SD (ms) Mean ± SD
|
138.1 1 ± 62.38
|
32.50 ±13.26
|
2.422
|
0.021
|
Correlation between conventional echocardiographic and TSI parameters in STEMI group
Across the entire study population, we found that there was a highly significant negative
correlation between LVEF and TSI parameters, such as septal-lateral wall delay (r = −0.665; P = 0.0001), septal-posterior wall delay (r = −0.978; P = 0.0001), all segments maximum difference (r = −0.557; P = 0.0001), and dyssynchrony index (r = −0.608; P = 0.0001). In contrast, there was a positive correlation between LVESD and septal-lateral
wall delay (r = 0.250; P = 0.001), septal-posterior wall delay (r = 0.068; P = 0.001), all segments maximum difference (r = 0.257; P = 0.001), and dyssynchrony index (r = 0.523; P = 0.001) [Table 5]; [Figure 2].
Figure 2: Correlation chart in STEMI between (A) EF and dyssynchrony index and (B)
LVESD and dyssynchrony index. LVESD = left ventricular end-systolic diameter, STEMI
= ST elevation myocardial infarction
Table 5
Correlation between conventional echocardiographic parameters and tissue synchronization
imaging parameters in ST elevation myocardial infarction patients
|
|
Septal lateral delay (ms)
|
Septal post delay (ms)
|
All segment maximum difference (ms)
|
All segment SD (ms)
|
|
SD = standard deviation, LVEDD = left ventricle end-diastolic diameter, LVESD = left
ventricle end-systolic diameter P < 0.05
|
|
LVEDD (cm)
|
r
|
0.228
|
-0.125
|
0.262
|
0.283
|
|
|
P value
|
0.181
|
0.468
|
0.123
|
0.094
|
|
LVESD (cm)
|
r
|
0.250
|
0.068
|
0.257
|
0.523
|
|
|
P value
|
0.002
|
0.002
|
0.001
|
0.001
|
|
Ejection fraction (%)
|
r
|
-0.665
|
-0.978
|
-0.557
|
-0.608
|
|
|
P value
|
0.0002
|
0.0001
|
0.0001
|
0.0001
|
|
Aortic opening (cm)
|
r
|
0.058
|
0.211
|
0.08
|
0.151
|
|
|
P value
|
0.742
|
0.217
|
0.642
|
0.378
|
|
Left atrium (cm)
|
r
|
0.213
|
0.003
|
-0.11
|
0.222
|
|
|
P value
|
0.220
|
0.984
|
0.525
|
0.193
|
|
E
|
r
|
0.173
|
-0.048
|
0.312
|
0.296
|
|
|
P value
|
0.319
|
0.780
|
0.064
|
0.080
|
|
A
|
r
|
0.441
|
0.180
|
0.166
|
0.201
|
|
|
P value
|
0.008
|
0.293
|
0.334
|
0.239
|
|
E/A
|
r
|
-0.308
|
-0.262
|
-0.114
|
-0.083
|
|
|
P value
|
0.072
|
0.122
|
0.509
|
0.631
|
DISCUSSION
After myocardial infarction (MI), LV global contraction is asynchronous due to the
partial reduction or even the loss of infarct myocardial contractility, which ultimately
results in LV global remodeling and dysfunction. Furthermore, MI occurring in different
segments is associated with variable effects on LV function and clinical prognosis.[7]
Among the various echocardiographic techniques, TDI has gained acceptance by virtue
of the ability to define regional timing and contractility as well as its reproducibility.
Recently, TDI has evolved into another technical modality, TSI. Tissue imaging portrays
regional asynchrony on 2D echocardiography by transforming the timing of regional
peak velocity into color codes. This allows for immediate visual identification of
regional delay in systole by comparing the color mapping of orthogonal walls. In addition,
quantitative measurement of regional delay is possible. However, the ability of TSI
to assess systolic asynchrony and predict a positive response to cardiac resynchronization
therapy has not been explored.[8],[9],[10]
LV mechanical dyssynchrony leads to a decrease in ejection fraction and stroke volume,
an abnormal distribution of wall tension, and increased workload during cardiac contraction.[11],[12],[13] In fact, LV systolic function failure is a grave complication after MI. Thus, an
accurate and detailed assessment of LV remodeling and systolic dyssynchrony carries
significant implications for clinical management and prognosis. LV dyssynchrony includes
both mechanical and electrical dyssynchrony, and the former has been commonly accepted
as a direct indicator of LV systolic dyssynchrony.[9]
In the current study, we found that patients with STEMI had significant LV systolic
dyssynchrony compared to controls. Furthermore, we found that LV dyssynchrony is more
common in patients with anterior STEMI. Ng et al.[14] reported similar results, where LV dyssynchrony was present in a significant proportion
of patients early after acute MI in the absence of congestive HF. In the current study,
LVESD was significantly higher in patients with STEMI than in controls, whereas LVEDD
was not significantly different. Similarly, Mollema et al.[15] found that the incidence of LV dilatation after acute MI was not markedly increased;
however, LVESV was significantly larger in patients who died from a cardiac cause
than in survivors.
LA diameter in our study was significantly larger in the patients with STEMI than
in the controls, which can be explained by the increase in the LA pressure as a result
of post-MI diastolic dysfunction, higher LV filling pressure, and/or mitral regurgitation.[16] Our findings agree with those of Meris et al.[17] who concluded that early LA remodeling and size after MI is an independent predictor
of death or hospitalization for HF in patients with high-risk MI. In addition, they
found that the risk appears to be continuous even in patients with a slightly larger
LA.[17],[18]
The patients with anterior STEMI in our study had a significantly lower LVEF, higher
LV volumes, and frequent LV systolic dyssynchrony than those with a non-anterior STEMI.
Moreover, inhospital complications, especially HF, were more frequent in patients
with anterior STEMI. This may be due to the extensive myocardial necrosis and greater
myocardial damage, which leads to decreased LV systolic dysfunction in anterior MIs.[19]
The findings of our study were consistent with those of Zhang et al.,[20] who found that peak systolic velocity durations were significantly longer in patients
with acute MI, especially those with anterior infarcts. However, their study employed
cardiac magnetic resonance to assess the size and location of the infarction. Of note,
our study showed a significant negative correlation between all TSI parameters and
LVEF. This was in agreement with Zhou et al.[21] who evaluated the relation between LVEF and LV dyssynchrony, and reported that the
LV dyssynchrony occurred more often in patients with cardiac dysfunction after MI,
and was significantly related to LVEF. Furthermore, our study found a significant
positive correlation between all TSI parameters and LVESD, which was consistent with
the results of Mollema et al.[15] and Ng et al.[14]
The clinical implication of our study is to draw attention to the importance of assessment
of LV dyssynchrony in patients with acute myocardial infarction, which necessitates
early aggressive treatment and longer follow-up.
LIMITATIONS OF THE STUDY
Our study is limited by its small sample size. Therefore, larger numbers of patients
with longer follow-ups should be recruited in subsequent studies. Another limitation
is that LV dyssynchrony is affected by other factors, such as hypertension and diabetes
mellitus. However, because numerous patients with STEMI exhibit these risk factors,
we did not exclude them from our study. Further studies focusing on the effect of
ischemia itself on LV dyssynchrony are needed. Finally, we did not study the effect
of percutaneous coronary intervention on LV dyssynchrony.
CONCLUSION
Patients with acute STEMI, particularly anterior infarcts, showed significant LV dyssynchrony,
which is an independent predictor of inhospital complications and is closely related
to the size of the myocardial infarction. Aggressive treatment is highly recommended
in such patients.
