Tissue Mitral Annular Displacement in Patients With Myocardial Infarction　― Comparison With Global Longitudinal Strain ―

Abstract

Background: Global longitudinal strain (GLS) can predict prognosis after myocardial infarction (MI). Tissue mitral annular displacement (TMAD) is another index of longitudinal left ventricular deformity, and is less dependent on image quality than GLS. We investigated the relationship between TMAD and GLS, and their ability to predict outcomes after MI.

Methods and Results: GLS and TMAD were measured on echocardiograms 2 weeks after MI in 246 consecutive patients (median age 62 years, 85.7% male). TMAD was measured from apical 4- and 2-chamber views (TMAD_4ch and TMAD_2ch, respectively), and a mean value (TMAD_av) was calculated. TMAD_4ch, TMAD_2ch, and GLS were successfully measured in 240 (97.5%), 210 (85.3%) and 214 patients (87.0%), respectively. All TMAD parameters were significantly correlated with GLS (R=0.71–0.75) and left ventricular ejection fraction (LVEF; R=0.48–0.53). TMAD parameters were weakly correlated with peak creatine kinase (CK; R=0.20) and CK-MB (R=0.21–0.25). GLS and TMAD_av were significantly associated with LVEF after 6 months (R=0.48–0.53) and all-cause mortality during the follow-up period (median 1,242 days). TMAD_av discriminated patients with higher all-cause mortality when patients were divided into 3 groups, namely upper 25%, middle range, and lower 25% of TMAD_av (P=0.041, log-rank test). GLS detected high-risk patients using 15.0% as a cut-off value.

Conclusions: TMAD could be a simple and reliable alternative to GLS for predicting outcomes in patients with MI.

Left ventricular (LV) systolic function is a major determinant of prognosis in patients with myocardial infarction (MI). LV ejection fraction (LVEF) is associated with morbidity and mortality after MI,^1,2 and guidelines recommend its measurement in patients with ST-elevation myocardial infarction (STEMI).^3,4 However, LVEF measured on 2-dimensional (2D) echocardiography (2DE) has limited reliability.^5,6 Longitudinal myocardial strain measured by 2D speckle tracking echocardiography (2DSTE) is a new index of longitudinal deformity of the LV. Global longitudinal strain (GLS), an average of segmental longitudinal strain, is an index of LV systolic function that is less dependent on the operator and more reproducible than LVEF.^7,8 GLS is well associated with infarct size^9–11 and microvascular obstruction after primary percutaneous coronary intervention (PCI),^12,13 and has better predictive value than LVEF,^14,15 in patients with MI. GLS also detects small systolic dysfunction¹⁶ and is associated with prognosis,¹⁴ even in patients showing normal to moderately reduced LVEF after MI.

However, some technical issues may limit the use of GLS in daily practice. Standard 3 apical images (apical long axis, 4-chamber, and 2-chamber views) are required to assess GLS, which may be time-consuming in a busy clinical situation. The accuracy of GLS is affected by the quality of all apical images, and suboptimal images could lead to inconclusive studies.^17,18

For patients with suboptimal image quality, alternative indices of longitudinal LV deformity that are less dependent on image quality are recommended.¹⁹ Mitral annular plane systolic excursion (MAPSE), longitudinal movement of the mitral annular plane assessed by M-mode echocardiography, is one such index.²⁰ MAPSE is well correlated with GLS not only in healthy populations,^21,22 but also in patients with a history of MI.²³ However, MAPSE is dependent on the insonation angle, which may lead to inaccurate measurement. Tissue mitral annular displacement (TMAD) is a unique echocardiography technique that assesses longitudinal displacement of the mitral annulus using 2DSTE.^24,25 TMAD is well correlated with LVEF,^24,25 and is considered a rapid and accurate index of longitudinal LV contraction. TMAD is similar to MAPSE but is not angle dependent, and semiautomatic measurement yields low intra- and interobserver variability.²⁴ TMAD could be less dependent on image quality than GLS because the mitral annulus is an easily detectable, echo-dense structure. TMAD could be obtained using an image only from an apical 4- or 2-chamber view, which would make it less time-consuming than GLS. Conversely, TMAD may be affected by local wall motion abnormality, and its feasibility in patients showing asynergy after MI has not been fully elucidated. In the present study we investigated whether TMAD could be an alternative to GLS in patients with MI, particularly for the prediction of functional and clinical outcomes.

Methods

Study Population

In all, 422 consecutive patients with acute MI admitted to Sakurabashi Watanabe Hospital between January 2007 and September 2012 were registered in the prospective multicenter Osaka Acute Coronary Insufficiency Study (OACIS) Registry (University Hospital Medical Information Network [UMIN] Clinical Trials Registry ID: UMIN000004575). Diagnostic criteria of acute MI in the OACIS Registry have been reported elsewhere.^26,27 Briefly, ≥2 of the following criteria were required for diagnosis: (1) a clinical history of central chest pressure, pain, or tightness lasting >30 min; (2) ST segment elevation >0.1 mV in at least 1 standard or 2 precordial leads; and (3) an increase in serum creatinine kinase (CK) to more than twice the normal laboratory value. Of these 422 patients, 290 patients who underwent echocardiography 2 weeks after the onset of MI using an iE33 (Philips Healthcare, Andover MA, USA) were enrolled in the present study. Patients were excluded if: (1) primary PCI for an occluded or stenosed culprit vessel was not attempted during the acute phase of MI; (2) they had an arrhythmia disturbing GLS and TMAD measurement, such as atrial fibrillation and multiple extra beats; (3) they underwent incomplete echocardiographic study or their images were not stored; and (4) they had poor image quality that rendered the images unsuitable for analysis.

All clinical and laboratory data were obtained from the OACIS Registry data and from the medical records of Sakurabashi Watanabe Hospital. Estimated glomerular filtration rate (GFR) was determined at the time of hospital admission and discharge using the Modification of Diet in Renal Disease (MDRD) equation modified for the Japanese population.²⁸ Information on subsequent clinical events up to 5 years was gathered by investigators by visiting outpatient clinics or by verbal or written blinded review of the circumstances surrounding each death.

This study was conducted in accordance with the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Sakurabashi Watanabe Hospital (Reference no. 17-32). One of the investigators obtained informed consent from each patient before they were included in the study.

Echocardiography Examinations

Standard 2D echocardiography was performed with an iE33 at 2 weeks and 6 months after the onset of MI. An experienced echocardiographer blinded to the clinical data analyzed stored images using Q-station software (Philips Healthcare). LVEF was measured using the Auto-EF function on the Q-station, which automatically detects the LV endocardial border and measured LVEF from apical 4- and 2-chamber view images based on Simpson’s rule. All parameters were measured in duplicate and averaged.

Segmental longitudinal strain was measured using stored images from apical long axis, 4-chamber, and 2-chamber views.¹⁹ The end-systolic frame was defined in the apical long-axis view and aortic valve closure was identified. The closure of the aortic valve was marked, and the Q-station software measured the time between the R-wave and aortic valve closure, which was used as a reference for the other view loops. We manually defined the mitral annulus and left ventricular apex with 3 index points at the end-systolic frame in each apical image. The Q-station software automatically traced 3 concentric lines on the endocardial border, mid-myocardial layer, and epicardial border, and followed the endocardium from this single frame throughout the cardiac cycle. If the automated tracking was inappropriate by visual assessment, we manually adjusted the region of interest (ROI). The LV in each apical image was divided into 6 segments, and the tracking quality for each segment was validated by the operator. The software measured the percentage wall lengthening and shortening and calculated peak systolic longitudinal strain for each segment, and the results of all 3 planes were combined into a single bull’s eye plot based on a 17-segment model. GLS was automatically calculated as an averaged value of peak longitudinal strain in all segments. GLS was expressed in terms of absolute values in the present study.²⁹

TMAD was measured on the same apical 2- and 4-chamber images using Q-station software. We placed 2 ROIs on the mitral annulus and 1 on the apex. The movement of each annular ROI towards the apex was automatically measured during a cardiac cycle by the software. The displacement of the mid-portion of the mitral annulus was determined and indexed by LV length as TMAD. TMAD obtained from apical 4- and 2-chamber images was designated as TMAD_4ch and TMAD_2ch, respectively, and their the mean value (TMAD_av) was calculated.

Data Reproducibility

Intra- and interobserver agreements in TMAD_4ch, TMAD_2ch, and GLS were evaluated by measuring these parameters in 10 randomly selected cases twice by the same observer or by 2 independent observers, respectively. Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated. As shown in Table 1, the measurement of all these parameters showed excellent intraobserver agreement. GLS also had excellent interobserver agreement, and TMAD_4ch and TMAD_2ch showed good interobserver agreement.

Table 1. Intra- and Interobserver Agreements of Tissue Mitral Annular Displacement and Global Longitudinal Strain Measurements

	Intraobserver agreement		Interobserver agreement
	ICC	95% CI	ICC	95% CI
TMAD4ch	0.97	0.90–0.99	0.85	0.45–0.96
TMAD2ch	0.97	0.90–0.99	0.75	0.26–0.93
GLS	0.96	0.87–0.99	0.97	0.89–0.99

Intraclass correlation coefficients (ICC) were calculated using values measured twice by the same observer (intraobserver agreement) and by 2 independent observers (interobserver agreement) in 10 randomly selected cases. CI, confidence interval; GLS, global longitudinal strain; TMAD_4ch and TMAD_2ch, tissue mitral annular displacement measured on images from apical 4- and 2- chamber views, respectively.

Statistical Analysis

Continuous variables are expressed as the median with interquartile range (IQR) and categorical variables are expressed as absolute frequencies or relative percentages. Comparisons were made using 1-way analysis of variance (ANOVA) for continuous variables, and the significance of differences was calculated using Tukey’s honestly significant difference (HSD) test for factor analysis. Categorical variables were compared using Fisher’s exact test. Correlation coefficients were compared using Z scores produced by Fisher’s r to z transformation. To determine the ability of each echocardiographic parameter to predict all-cause mortality, a Cox proportional hazard model was constructed including age, sex, risk factors, and each parameter. Event-free survival was analyzed using the Kaplan-Meier method with the log-rank test for group comparisons. Cut-off values of indices used for the Kaplan-Meier analysis in all study patients were arbitrarily determined.

All statistical analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) with the graphical user interface EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan).

Results

Patient Characteristics

Of the 290 patients enrolled in the present study, 43 were excluded because of incomplete echocardiography study (n=33), poor image quality (n=8), and arrhythmia (n=2). The final study group consisted of 246 patients (median age 62 years [IQR 54–71 years], 85.7% male). The clinical characteristics of the patients are presented in Table 2; 171 (69.5%) patients had a history of hypertension, 190 (77.2%) had dyslipidemia, 96 (39.0%) had diabetes, 40 (16.3%) had prior MI, and 155 (63.0%) were smokers. Emergency coronary angiography was performed in all patients, and primary PCI was performed in 242 (98.4%). Anterior MI was observed in 82 (33.3%) patients, and 215 (87.3%) patients showed STEMI. Median CK and CK-MB concentrations were 2,038 IU/L (IQR 938–4,045 IU/L) and 136 IU/L (IQR 67–269 IU/L), respectively. Peak CK ≥5,000 IU/L was observed in 43 (17.5%) patients, whereas 66 (26.8%) patients had CK ≤1,000 IU/L.

Table 2. Patient Characteristics

Age (years)	62 [54–71]
Male sex	211 (85.7)
BMI (kg/m2)	24.1 [22.3–26.4]
Hypertension	171 (69.5)
Dyslipidemia	190 (77.2)
Diabetes	96 (39.0)
Smoking	155 (63.0)
History of prior MI	40 (16.3)
STEMI	215 (87.3)
Anterior AMI	82 (33.3)
eGFR (mL/min/1.73 m2)
At admission	66.4 [52.3–82.0]
At discharge	61.7 [49.1–73.8]
Peak CK (IU/L)	2,038 [938–4,045]
Peak CK-MB (IU/L)	136 [67–269]
Medication at discharge
Antiplatelet agents	240 (97.6)
β-blockers	173 (70.3)
ACEI	134 (54.4)
ARBs	89 (36.2)
CCBs	39 (15.9)
Diuretics	38 (15.4)
Statins	178 (72.4)

Data are given as n (%) or the median [interquartile range]. ACEI, angiotensin-converting enzyme inhibitor; AMI, acute myocardial infarction; ARBs, angiotensin receptor blockers; BMI, body mass index; CCBs, calcium channel blockers; CK creatine kinase; CK-MB, creatine kinase myocardial band; eGFR estimated glomerular filtration rate; MI, myocardial infarction; STEMI, ST-elevation myocardial infarction.

Measurement of GLS and TMAD

Figure 1 shows representative images in 2 patients with inferior wall MI. In Case A (57 years old, male), peak longitudinal strain was well preserved in each LV segment 2 weeks after MI (Figure 1, Upper left) and GLS was calculated to be 19.5%. TMAD_4ch was calculated to be 12.2% (Figure 1, Upper right) and LVEF was measured as 63%. In Case B (39 years old, male), peak longitudinal strain was widely impaired within the inferior lesion, and GLS was reduced to 12.2% (Figure 1, Lower left). TMAD_4ch was reduced to 9.6% (Figure 1, Lower right) and LVEF was 44.5%.

Figure 1.

Representative images in patients with inferior myocardial infarction (MI). Longitudinal strain and tissue mitral annular displacement measured from apical 4-chamber views (TMAD_4ch) from 2 patients with inferior MI. (Left) Segmental peak longitudinal strain values are shown on a bull’s eye plot. (Right) The movement of regions of interest (ROIs) on both sides of the mitral annulus towards the apex during systole was traced, and the movement of the midpoint of annular ROIs was indexed by left ventricle (LV) length to calculate TMAD. In Case A, global longitudinal strain (GLS) was 19.5% and TMAD_4ch was 12.2%; in Case B, reductions were seen in both GLS (12.2%) and TMAD_4ch (9.6%). ANT, anterior; INF, inferior; LAT, lateral; SEPT, septum.

TMAD_4ch and TMAD_2ch were successfully measured in 240 (97.5%) and 210 (85.3%) patients, respectively, within 2 min. The main reason for unsuccessful TMAD measurement was drift of the apical ROI during a cardiac cycle. GLS was correctly measured in 214 (87.0%) patients. The major reason for unsuccessful GLS measurement was inappropriate image quality for proper speckle tracking in some of the LV segments. A significant difference was observed in the rate of successful measurement among the 3 indices (P<0.0001). Median values for TMAD_4ch, TMAD_2ch, and TMAD_av in the study group were 12.6% (IQR 10.1–14.9%), 12.4% (IQR 10.0–14.6%), and 12.7% (IQR 10.7–14.6%), respectively. GLS was 17.4% (IQR 14.2–19.2%) and LVEF was 55.3% (IQR 49.8–60.8%).

There were significant correlations among TMAD parameters; R=0.72 (95% CI 0.65–0.78) between TMAD_4ch and TMAD_2ch, R=0.93 (95% CI 0.91–0.95) between TMAD_4ch and TMAD_av, and R=0.92 (95% CI 0.90–0.94) between TMAD_2ch and TMAD_av (Figure 2, Upper panels). TMAD parameters were significantly correlated with GLS (R=0.71; 95% CI 0.63–0.76), and there were correlations between TMAD_4ch and GLS (R=0.71; 95% CI 0.64–0.77), TMAD_2ch and GLS (R=0.75; 95% CI 0.69–0.81), and TMAD_av and GLS (Figure 2, Middle panels). There were no significant differences in the correlation coefficients between GLS and TMAD parameters. All these correlations were statistically significant (P<0.0001). Although the correlation coefficient between TMAD_av and GLS tended to be better in 81 patients with impaired GLS (<16%; R=0.66) than in 129 patients with preserved GLS (≥16%; R=0.48), the difference did not reach statistical difference (P=0.052).

Figure 2.

Correlations among tissue mitral annular displacement (TMAD) and other echocardiographic parameters. (Upper) There were good correlations among TMAD parameters (TMAD measured apical 4- and 2-chamber views [TMAD_4ch and TMAD_2ch, respectively], mean TMAD [TMAD_av]). All TMAD parameters showed good correlations with global longitudinal strain (GLS; Middle) and moderate correlations with left ventricular ejection fraction (LVEF; Lower). R values are given on each plot, with 95% confidence intervals in parentheses.

Because TMAD parameters may be differently affected by the location of the MI, we investigated its effects on correlations between TMAD parameters and GLS. Both TMAD_4ch and GLS were reliably measured in 213 patients, and there was no difference in correlation coefficients between 69 patients (32.4%) with anterior wall MI (R=0.72) and those with inferior/posterior MI (R=0.66; P=0.38). TMAD_2ch and GLS were also measured in 210 patients, and there was no difference in the correlation coefficients between the 2 groups (anterior wall MI [n=66], R=0.74; inferior/posterior MI [n=144], R=0.67; P=0.36). There was also no difference in the correlation coefficients for TMAD_av and GLS between the anterior wall MI (n=66; R=0.77) and inferior/posterior MI (n=144; R=0.73) groups (P=0.56).

TMAD parameters were also moderately correlated (P<0.0001) with LVEF (R=0.49; 95% CI 0.37–0.58), and there were correlations between TMAD_4ch and LVEF (R=0.48; 95% CI 0.36–0.58), TMAD_2ch and LVEF (R=0.53; 95% CI 0.41–0.62), and TMAD_av and LVEF (Figure 2, Lower panels). The correlation between each TMAD parameter and GLS was better than that between TMAD and LVEF (TMAD_4ch, P=0.004; TMAD_2ch, P=0.004; TMAD_av, P=0.002). There was a good correlation between GLS and LVEF (R=0.75; 95% CI 0.69–0.81; P<0.0001).

Association Between Echocardiographic Indices and Peak CK/CK-MB and Functional Outcomes

We investigated the correlation between echocardiographic indices and peak CK and CK-MB. As indicated in Table 3, there were weak but significant correlations between TMAD parameters and peak CK and CK-MB values. GLS and LVEF were also weakly correlated with peak CK and CK-MB values (Table 3).

Table 3. Correlation Between Echocardiography and Enzyme Parameters

	Peak CK		Peak CK-MB
	R (95% CI)	P value	R (95% CI)	P value
TMAD4ch	0.20 (0.07, −0.31)	0.002	0.21 (0.09, 0.33)	0.001
TMAD2ch	0.20 (0.07, 0.33)	0.003	0.25 (0.12, 0.37)	0.0003
TMADav	0.20 (−0.06, 0.33)	0.004	0.24 (0.10, 0.36)	0.0006
GLS	0.26 (0.12, 0.37)	0.0002	0.26 (0.13, 0.38)	0.0001
LVEF	0.18 (0.05, 0.30)	0.006	0.24 (0.12, 0.36)	0.0002

LVEF, left ventricular ejection fraction; TMAD_av, mean value of TMAD_4ch and TMAD_2ch. Other abbreviations as in Tables 1,2.

Figure 3 shows the relationship between LVEF at 6 months and echocardiographic indices at baseline. There were significant correlations between LVEF at 6 months and TMAD_4ch (R=0.49; 95% CI 0.37–0.58), TMAD_2ch (R=0.48; 95% CI 0.36–0.58), and TMAD_av (R=0.53; 95% CI 0.41–0.62). LVEF at 6 months was also correlated with GLS (R=0.52; 95% CI 0.41–0.62) and baseline LVEF (R=0.56; 95% CI 0.46–0.65). All these correlations were statistically significant (P<0.0001). There was no difference in the correlation coefficients between GLS and LVEF at 6 months and between TMAD_av and LVEF (P=1.00).

Figure 3.

Correlations among echocardiographic parameters and left ventricular ejection fraction (LVEF) at 6 months after myocardial infarction. (Upper) There were significant correlations between LVEF at 6 months and all tissue mitral annular displacement (TMAD) parameters. There were also significant correlations between LVEF at 6 months and global longitudinal strain (GLS; Lower left) and LVEF at 2 weeks (Lower right). R values are given on each plot, with 95% confidence intervals in parentheses.

Echocardiographic Indices and Mortality After MI

To compare the predictive value of TMAD parameters with that of GLS for all-cause mortality, we selected 204 patients in whom GLS, TMAD_4ch, and TMAD_2ch were all successfully measured. Age (median 62 years [IQR 54–71 years]), sex (86.3% male), and other clinical parameters did not differ significantly between the 204 selected patients and the original study cohort. The 204 selected patients were followed-up for median of 735 days (IQR 358–1,346 days), and 6 patients (2.9%) died during the follow-up period (their characteristics are summarized in Supplementary Table 1). Cox hazard proportional model analysis for each parameter indicated that GLS (P=0.029; hazard ratio [HR] per unit 1.30; 95% CI 1.03–1.64) or TMAD_av (P=0.033; HR per unit 0.74; 95% CI 0.57–0.98) were significant predictors for all-cause mortality (Table 4). LVEF (P=0.11), TMAD_4ch (P=0.08), and TMAD_2ch (P=0.059) were not selected as independent predictors of all-cause mortality.

Table 4. Cox Proportional Hazard Models for Prediction of All-Cause Death

	Coefficient	Hazard ratio	95% CI		P value
			Upper	Lower
Model 1 including TMADav
Age	0.072	1.074	0.960	1.202	0.21
Male sex	1.699	5.468	0.338	88.460	0.23
Diabetes	−1.407	0.245	0.021	2,823	0.26
Hypertension	0.178	0.00006	0.000000	–	1.0
Dyslipidemia	0.672	1.957	0.266	14,400	0.51
Anterior MI	−0.185	0.0000009	0.00000	–	1.0
TMADav	−0.297	0.743	0.565	0.977	0.033
Model 2 including GLS
Age	0.075	1.078	0.964	1.206	0.19
Male sex	2.016	7.508	0.458	123.200	0.16
Diabetes	−1.525	0.218	0.018	2.582	0.23
Hypertension	0.179	0.00006	0.000000	–	1.0
Dyslipidemia	0.621	1.861	0.244	14,170	0.55
Anterior MI	−0.183	0.0000001	0.00000	–	1.0
GLS	0.260	1.297	1.028	1.638	0.029

CI, confidence interval; GLS, global longitudinal strain; MI, myocardial infarction; TMAD_av, mean value of tissue mitral annular displacement measured on images from apical 4- and 2-chamber views.

Patients were divided into 3 groups based on the IQR of TMAD_av: the upper 25% (Q1; >14.7%), middle range (Q2–3; 10.7–14.7%), and lower 25% (Q4; <10.7%). Kaplan-Maier curves showed the patients with the lowest TMAD_av had higher mortality during the follow-up period than the other groups (P=0.041, log-rank test; Figure 4A). There were no differences in clinical background among the groups, except for age and peak CK/CK-MB (Supplementary Table 2). A similar analysis based on the IQR of GLS (i.e., Q1, >19.2%; Q2–3, 14.5–19.2%; and Q4, <14.5%) revealed no significant associations with mortality (P=0.058, Figure 4C). Conversely, patients with GLS ≤15.0% had higher mortality than those with GLS >15.0% (P=0.042; Figure 4D). In addition, mortality was higher among patients with TMAD_av ≤8.0% than >8.0% (P=0.023; Figure 4B).

Figure 4.

Kaplan-Meier curves for all-cause death in patients with myocardial infarction. All-cause mortality during the follow-up period (median 735 days) was analyzed among 204 patients in whom global longitudinal strain (GLS) and tissue mitral annular displacement from apical 4- and 2-chamber views (TMAD_4ch and TMAD_2ch, respectively) were all measured. (A) Kaplan-Meier curves among patients divided according to quartiles of mean TMAD (TMAD_av): upper 25% (Q1; >14.7%), middle range (Q2–3; 10.7–14.7%), and lower 25% (Q4; <10.7%). Patients in Q1 had higher mortality than those in the other groups (P=0.041, log-rank test). (B) Kaplan-Meier curves among patients divided into 2 groups based on TMAD_av. Mortality was higher for patients with TMAD_av ≤8.0% than >8.0% (P=0.023). (C) Dividing patients into groups based on the interquartile range of GLS (Q1 [>19.2%], Q2–3 [14.5 to 19.2%], and Q4 [<14.5%]) revealed no significantly associations with mortality (P=0.058). (D) GLS was associated with all-cause mortality when patients were divided into 2 groups using 15.0% as a cut-off value.

Discussion

In the present study, we measured TMAD and GLS in 246 consecutive patients 2 weeks after MI. All TMAD parameters (TMAD_4ch, TMAD_2ch, and TMAD_av) showed good correlation with GLS. TMAD parameters and GLS were significantly correlated with LVEF. All these echocardiographic indices were significantly correlated with peak CK and CK-MB values, as well as with LVEF measured 6 months later. GLS and TMAD_av were associated with all-cause mortality during the follow-up period (median 1,242 days). Kaplan-Meier curve analysis demonstrated that TMAD_av significantly discriminated patients with higher all-cause mortality when patients were divided into 3 groups into the upper 25% (>14.7%), middle range (10.7–14.7%), and lower 25% (<10.7%) of TMAD_av (P=0.041, log-rank test). In addition, mortality was higher in patients with GLS ≤15.0% than >15.0% (P=0.042). These results indicate the possibility of using TMAD as an alternative index to GLS in patients with MI.

TMAD and GLS in Patients With MI

Although TMAD can be interpreted as the volume change during systole and it was correlated with LVEF, its correlation with GLS was significantly better than with LVEF. The LV wall has complex myocardial fiber orientation with longitudinal and circumferential fibers showing a continuous variation in angulations. TMAD and GLS represent the shortening of longitudinal fibers, whereas LVEF reflects all the radial, circumferential, and longitudinal contractions. Thus, TMAD and GLS, representative of LV longitudinal deformity, could have different clinical implications from LVEF.

Infarct size is a major determinant of functional and clinical outcomes after MI.^30,31 Although the present study demonstrated that TMAD parameters and GLS were significantly correlated with peak CK/CK-MB values, their correlation with CK/CK-MB was only modest (Table 3). The correlation of LVEF with CK/CK-MB was no better than that of TMAD or GLS with CK/CK-MB. However, these echocardiographic indices were well correlated with LVEF after 6 months (TMAD parameters, R=0.48–0.53, GLS, R=0.52; LVEF at 2 weeks, R=0.56). CK and CK-MB are surrogate markers of infarct size and have only a weak relationship with infarct size determined by¹⁸ F-fluorodeoxyglucose positron emission tomography³² or by cardiac magnetic resonance imaging (CMR).³³ GLS is reported to be correlated with infarct size measured by CMR.^9,11 TMAD may represent infarct size better than CK/CK-MB and GLS.

The present study had a limited number of patients, and these patients only had modest infarct size and very low mortality, which made it difficult to construct a Cox hazard model including all the echocardiographic parameters and to determine cut-off values using proper statistical methods instead of assigning arbitrary values. Moreover, the number of deaths during the follow-up period was too small to exclude the possibility that the results regarding all-cause death may be just coincidental. Thus, the present results may be inconclusive about the prognostic value of TMAD_av and GLS. This may also explain why LVEF was not associated with mortality, in contrast with findings in prior studies.^1,2

In the presence of asynergy segments, movement of the mitral annulus may be observed differently on each image plane, and TMAD parameters may be affected by the location of the infarct area. TMAD_4ch and TMAD_2ch showed excellent correlation in the present study, and both showed similar correlations with GLS. They also showed similar correlations with CK/CK-MB and LVEF at 6 months, and the correlations were not better for TMAD_av. One of the advantages of TMAD is that it can be obtained from a single image plane. TMAD_av may have better ability to predict all-cause mortality than TMAD_4ch and TMAD_2ch, but it may reduce this advantage. The other advantage of TMAD is that it is less dependent on image quality than GLS. GLS could not be measured in 13% of patients in the present study, mostly because of insufficient image quality in some myocardial segments, whereas TMAD_4ch was correctly measured in almost all patients (97.5%). TMAD_2ch was assessed in only 85.3% of patients. The lateral part of the mitral annulus may be hard to visualize from an apical 2-chamber view in some patients. TMAD_4ch may be the most suitable of the TMAD parameters for clinical practice, whereas TMAD_2ch and TMAD_av should be used based on the purpose of their assessment and depending on the conditions of patients.

TMAD also has some limitations compared with GLS. TMAD does not assess segmental deformation as strain analysis by 2DSTE. TMAD may be affected by some conditions that do not affect GLS, including LV curvature, right ventricle dysfunction, mitral valve disease, and mitral ring calcification. In the presence of pericardial effusion, TMAD may be incorrect because of a mobile apex. Even though strain measurement by 2DSTE is somehow vendor dependent, the vender-independent normal range of GLS is determined as 20±2%.⁷ TMAD is measured only by machines from a single vendor (Philips), and its normal range has still not been determined.

Study Limitations

The present study was conducted as a single-center retrospective study with a limited number of patients; therefore, the results must be interpreted carefully. Many patients had only a small infarct size and good prognosis, which may have resulted in an underestimation of the prognostic value of echocardiographic indices. As a multicenter registration study, the OACIS collected only mortality as prognostic data. We could not analyze the association between echocardiographic parameters and other major cardiovascular events, such as MI, heart failure hospitalization, and stroke. We only evaluated all-cause mortality in the present study, with the cause of death not specified, and the prognostic value for cardiovascular death or events was not investigated. It should be noted that the present study could not determine superiority between TMAD and GLS with regard to prognostic value. Even though GLS and TMAD could be successfully measured in most patients, TMAD_2av and GLS could not be obtained in approximately 15% of study subjects. We only selected patients in whom all of GLS, TMAD_4ch, and TMAD_2ch were obtained for the analysis of mortality, which excluded 17% of potential study patients. Even though this is not large proportion, the exclusions may have affected the results of the present study somehow.

Despite these limitations, the findings of the present study suggest that TMAD has the potential to be an easy and less image-dependent alternative modality to GLS for risk stratification of patients with MI. Unfortunately, TMAD is less frequently used than GLS. To make this useful modality more widely used in clinical situations, a prospective multicenter study should be performed to evaluate the feasibility and potential of TMAD.

Acknowledgments

The authors would like to thank M. Ueda and sonographers in Sakurabashi Watanabe Hospital for collecting echocardiographic data.

Sources of Funding

This study did not receive any specific funding.

Disclosures

Katsuomi Iwakura has received remuneration from Boehringer Ingelheim, AstraZeneca, Ono Pharmaceutical, and Eli Lilly. Yasuhiko Sakata is a member of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to declare.

IRB Information

This study was approved by the Ethics Committee of Sakurabashi Watanabe Hospital (Reference no. 17-32).

Supplementary Files

Please find supplementary file(s);

http://dx.doi.org/10.1253/circrep.CR-21-0076

References

• 1.   Solomon SD, Skali H, Anavekar NS, Bourgoun M, Barvik S, Ghali JK, et al. Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction. Circulation 2005; 111: 3411–3419.
• 2.   Halkin A, Singh M, Nikolsky E, Grines CL, Tcheng JE, Garcia E, et al. Prediction of mortality after primary percutaneous coronary intervention for acute myocardial infarction: The CADILLAC risk score. J Am Coll Cardiol 2005; 45: 1397–1405.
• 3.   Anderson JL. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127: 362–425.
• 4.   Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2018; 39: 119–177.
• 5.   Jenkins C, Bricknell K, Hanekom L, Marwick TH. Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimensional echocardiography. J Am Coll Cardiol 2004; 44: 878–886.
• 6.   Bellenger NG, Burgess MI, Ray SG, Lahiri A, Coats AJS, Cleland JGF, et al. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance: Are they interchangeable? Eur Heart J 2000; 21: 1387–1396.
• 7.   Farsalinos KE, Daraban AM, Ünlü S, Thomas JD, Badano LP, Voigt JU. Head-to-head comparison of global longitudinal strain measurements among nine different vendors: The EACVI/ASE Inter-Vendor Comparison Study. J Am Soc Echocardiogr 2015; 28: 1171–1181.
• 8.   Macron L, Lairez O, Nahum J, Berry M, Deal L, Deux JF, et al. Impact of acoustic window on accuracy of longitudinal global strain: A comparison study to cardiac magnetic resonance. Eur J Echocardiogr 2011; 12: 394–399.
• 9.   Gjesdal O, Helle-Valle T, Hopp E, Lunde K, Vartdal T, Aakhus S, et al. 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, 2 p following 196.
• 10.   Munk K, Andersen NH, Nielsen SS, Bibby BM, Bøtker HE, Nielsen TT, et al. Global longitudinal strain by speckle tracking for infarct size estimation. Eur J Echocardiogr 2011; 12: 156–165.
• 11.   Diao KY, Yang ZG, Ma M, He Y, Zhao Q, Liu X, et al. The diagnostic value of global longitudinal strain (GLS) on myocardial infarction size by echocardiography: A systematic review and meta-analysis. Sci Rep 2017; 7: 1–8.
• 12.   Bière L, Donal E, Terrien G, Kervio G, Willoteaux S, Furber A, et al. Longitudinal strain is a marker of microvascular obstruction and infarct size in patients with acute ST-segment elevation myocardial infarction. PLoS One 2014; 9: 1–9.
• 13.   Huttin O, Zhang L, Lemarié J, Mandry D, Juillière Y, Lemoine S, et al. Global and regional myocardial deformation mechanics of microvascular obstruction in acute myocardial infarction: A three dimensional speckle-tracking imaging study. Int J Cardiovasc Imaging 2015; 31: 1337–1346.
• 14.   Ersbøll M, Valeur N, Mogensen UM, Andersen MJ, Møller JE, Velazquez EJ, et al. Prediction of all-cause mortality and heart failure admissions from global left ventricular longitudinal strain in patients with acute myocardial infarction and preserved left ventricular ejection fraction. J Am Coll Cardiol 2013; 61: 2365–2373.
• 15.   Antoni ML, Mollema SA, Delgado V, Atary JZ, Borleffs CJW, Boersma E, et al. Prognostic importance of strain and strain rate after acute myocardial infarction. Eur Heart J 2010; 31: 1640–1647.
• 16.   Cimino S, Canali E, Petronilli V, Cicogna F, De Luca L, Francone M, et al. Global and regional longitudinal strain assessed by two-dimensional speckle tracking echocardiography identifies early myocardial dysfunction and transmural extent of myocardial scar in patients with acute ST elevation myocardial infarction and relatively. Eur Heart J Cardiovasc Imaging 2013; 14: 805–811.
• 17.   Shiran A, Blondheim DS, Shimoni S, Jabarren M, Rosenmann D, Sagie A, et al. Effect of image quality on accuracy of two-dimensional strain echocardiography for diagnosing ischemic chest pain: A 2DSPER multicenter trial substudy. Int J Cardiovasc Imaging 2019; 35: 617–625.
• 18.   Rösner A, Barbosa D, Aarsæther E, Kjønås D, Schirmer H, D’Hooge J. The influence of frame rate on two-dimensional speckle-tracking strain measurements: A study on silico-simulated models and images recorded in patients. Eur Heart J Cardiovasc Imaging 2015; 16: 1137–1147.
• 19.   Lang RM, Badano LP, Victor MA, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28: 1–39.
• 20.   Hensel KO, Roskopf M, Wilke L, Heusch A. Intraobserver and interobserver reproducibility of M-mode and B-mode acquired mitral annular plane systolic excursion (MAPSE) and its dependency on echocardiographic image quality in children. PLoS One 2018; 13: e0196614.
• 21.   Terada T, Mori K, Inoue M, Yasunobu H. Mitral annular plane systolic excursion/left ventricular length (MAPSE/L) as a simple index for assessing left ventricular longitudinal function in children. Echocardiography 2016; 33: 1703–1709.
• 22.   Støylen A, Mølmen HE, Dalen H. Relation between mitral annular plane systolic excursion and global longitudinal strain in normal subjects: The HUNT study. Echocardiography 2018; 35: 603–610.
• 23.   Gjesdal O, Vartdal T, Hopp E, Lunde K, Brunvand H, Smith HJ, et al. Left ventricle longitudinal deformation assessment by mitral annulus displacement or global longitudinal strain in chronic ischemic heart disease: Are they interchangeable? J Am Soc Echocardiogr 2009; 22: 823–830.
• 24.   DeCara JM, Toledo E, Salgo IS, Lammertin G, Weinert L, Lang RM. Evaluation of left ventricular systolic function using automated angle-independent motion tracking of mitral annular displacement. J Am Soc Echocardiogr 2005; 18: 1266–1269.
• 25.   Tsang W, Ahmad H, Patel AR, Sugeng L, Salgo IS, Weinert L, et al. Rapid estimation of left ventricular function using echocardiographic speckle-tracking of mitral annular displacement. J Am Soc Echocardiogr 2010; 23: 511–515.
• 26.   Kojima T, Hikoso S, Nakatani D, Suna S, Dohi T, Mizuno H, et al. Impact of hyperglycemia on long-term outcome in patients with ST-segment elevation myocardial infarction. Am J Cardiol 2020; 125: 851–859.
• 27.   Matsumoto S, Nakatani D, Sakata Y, Suna S, Shimizu M, Usami M, et al. Elevated serum heart-type fatty acid-binding protein in the convalescent stage predicts long-term outcome in patients surviving acute myocardial infarction. Circ J 2013; 77: 1026–1032.
• 28.   Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: 982–992.
• 29.   Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, et al. Definitions for a common standard for 2D speckle tracking echocardiography: Consensus document of the EACVI/ASE/industry task force to standardize deformation imaging. J Am Soc Echocardiogr 2015; 28: 183–193.
• 30.   Kwong RY, Chan AK, Brown KA, Chan CW, Reynolds HG, Tsang S, et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation 2006; 113: 2733–2743.
• 31.   Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 1998; 97: 765–772.
• 32.   Kunze KP, Dirschinger RJ, Kossmann H, Hanus F, Ibrahim T, Laugwitz KL, et al. Quantitative cardiovascular magnetic resonance: Extracellular volume, native T₁ and ¹⁸F-FDG PET/CMR imaging in patients after revascularized myocardial infarction and association with markers of myocardial damage and systemic inflammation. J Cardiovasc Magn Reson 2018; 20: 1–11.
• 33.   Tiller C, Reindl M, Holzknecht M, Klapfer M, Beck A, Henninger B, et al. Biomarker assessment for early infarct size estimation in ST-elevation myocardial infarction. Eur J Intern Med 2019; 64: 57–62.