doi: 10.1161/CIRCIMAGING.108.784900
Original Articles |
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
From the Departments of Cardiology (O.G., T.H.-V., K.L., T.V., S.A., H.I., T.E.) and Radiology (E.H., H.-J.S.), Rikshospitalet University Hospital, University of Oslo, Oslo, Norway.
Correspondence to Thor Edvardsen, MD, PhD, Department of Cardiology, Rikshospitalet University Hospital, N-0027 Oslo, Norway. E-mail thor.edvardsen{at}klinmed.uio.no
Received April 14, 2008; accepted September 23, 2008.
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Abstract |
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Background— The objective of the study was to evaluate the ability of established and new parameters of global systolic left ventricle function to estimate myocardial infarct size.
Increasing infarct extent is associated with impaired prognosis in chronic ischemic heart disease. Systolic myocardial deformation is a complex 3D process that is mainly influenced by the amount and transmural distribution of viable myocardium. Speckle-tracking echocardiography (2D-STE) enables deformation assessment along the 3 main cardiac axes independent of insonation angle.
Methods and Results— Global longitudinal, circumferential, and radial strain and left ventricle twist by 2D-STE, global longitudinal strain rate and strain by tissue Doppler imaging, and left ventricle ejection fraction and wall motion score index were assessed in 40 patients 8.5±5.4 months after a first myocardial infarct and compared with global myocardial infarct mass assessed by contrast-enhanced MRI. Longitudinal and circumferential strain by 2D-STE and longitudinal strain and strain rate by tissue Doppler imaging significantly separated medium-sized infarcts from small or large infarcts at the global level (P<0.05). All deformation indices correlated significantly with global infarct mass (P<0.01). Circumferential and longitudinal strains by 2D-STE demonstrated the best ability to identify medium-sized global myocardial infarcts.
Conclusions— Circumferential and longitudinal strains by 2D-STE correlate with myocardial infarct mass and significantly differentiate among large, medium, and small myocardial infarcts.
Key Words: infarction • MRI • myocardial contraction • tissue Doppler echocardiography • speckle-tracking echocardiography
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Introduction |
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Mortality after acute myocardial infarction (MI) is closely related to infarct size and location.1,2 Clinical improvement from revascularization therapy depends on the transmural distribution of necrosis, infarct size, and location.3,4 Risk stratification therefore requires reliable and feasible clinical tools to measure the exact extent and location of myocardial necrosis.
Clinical Perspective see p 189
Quantification of MI size by contrast-enhanced MRI (CE-MRI) has been validated,5 predicts cardiovascular events,1 and is considered the "gold standard" for infarct assessment. MRI examinations, however, are time consuming and expensive, and the availability of scanners are limited. Feasible techniques for the evaluation of myocardial viability are strongly needed.
Echocardiographic assessment of left ventricular ejection fraction (LVEF) is easily available and feasible but is basically a measure of global LV function. Evaluation of regional function by analyzes of endocardial motion or local wall thinning and thickening characteristics require well-trained personnel.
Strain and strain rate (SR) are clinical indices of regional myocardial deformation6–9 and have been introduced and validated using tagged MRI and sonomicrometry.10–12 To eliminate the problem of angle dependency of Doppler-derived analyses, strain measurement based on 2D speckle-tracking echocardiography (2D-STE) has been developed.13–16 2D-STE enables regional deformation assessment in circumferential, longitudinal, and radial directions,17–20 and furthermore, the ability to assess LV rotation and twist.13 Recently, global longitudinal strain based on the average of regional deformations have been shown to predict infarct size better than LVEF,18,20 but global deformation in the other directions have not been examined. There is a need to clarify whether any global deformation parameter is superior in the evaluation of the failing LV function in ischemic heart disease.
In the present study, we tested the ability of new and established echocardiographic indices of global LV function to estimate myocardial infarct mass assessed by CE-MRI.
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Methods |
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Patient Population
Forty patients (age, 58±10 years; 9 women) previously treated with percutaneous coronary intervention (PCI) because of acute ST-segment elevation MI were included in the study. Patients with contraindications to MRI were excluded, but no patients were excluded because of impaired echocardiographic image quality. The clinical data are presented in Table 1, and the infarct characteristics are shown in Table 2. Patients were examined with CE-MRI and echocardiography 8.5±5.4 months after the index MI. The echocardiographic study was typically performed within 4 hours of the MRI. Patients were hemodynamically stable during the studies. All study subjects were in sinus rhythm and had a QRS width <120 ms. None had significant valvular dysfunction as defined by echocardiography. The study was approved by the Regional Committee for Medical Research Ethics (REK Sør, Oslo, Norway), and all subjects gave written informed consent.
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MRI
MRI was performed using 1.5-T units (Magnetom Vision Plus or Magnetom Sonata, Siemens, Erlangen, Germany) and a phased array body coil. Late enhancement images were obtained 10 to 20 minutes after intravenous injection of 0.1 or 0.2 mmol/kg gadopentetate dimeglumine (Magnevist, Schering, Berlin, Germany) in multiple short-axis slices covering the LV (slice thickness, 7 mm; interslice gap, 3 mm; Figure 1). A breath-hold segmented magnetization-prepared turbo gradient echo sequence was used with an inversion time of 210 to 260 ms.
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The LV myocardium was manually divided into 16 segments,21 and the infarcted as well as the total myocardial area of each segment was drawn (PACS, Sectra, Sweden). Areas with pixel intensities more than 2 SDs above the mean pixel intensity of normal myocardium of the same slice were considered infarcted.3,22 The total myocardial volume and the absolute and relative infarct volumes were calculated for each segment. The myocardial and infarct masses were converted from volume by multiplying by 1.05 g/mL,23 and the global infarct mass was calculated as the sum of all segmental values for each patient.20 Patients were divided into groups depending on the global infarct mass: small infarcts of <30 g, medium-sized infarcts of 30 to 50 g, and large myocardial infarcts of
50 g.1
The transmural infarct extent of each segment was assessed. Subendocardial infarct was defined as transmural infarct extent <50% of the segmental myocardial area, whereas transmural infarct was defined when 50% was involved.3
Echocardiography
Images were obtained in the left lateral decubitus position. The study examinations were performed with a Vivid 7 scanner (GE Vingmed Ultrasound, Horten, Norway), using a phased-array transducer. Three consecutive heart cycles from the 3 standard apical views (4-chamber, 2-chamber, and long axis) and 3 short-axis views (basal, midventricular, and apical levels) were obtained by conventional 2D grayscale echocardiography, as well as tissue Doppler imaging (TDI) for the 3 standard apical views, using a narrow sector angle with the ventricular wall parallel to the ultrasound beam. The average frame rate was 62±23 s–1 for long axis, 68±21 s–1 for short axis, and 115±21 s–1 for TDI analyses. The digital loops were stored and analyzed by EchoPac software (EchoPac 6.0, GE Vingmed Ultrasound). LVEF was assessed by the modified Simpson rule. A 16-segment LV model21 was used for strain, SR, and wall motion score in this study.
Myocardial Deformation
Segmental longitudinal strain was assessed by 2D-STE in apical 4-chamber, 2-chamber, and apical long-axis projections, and circumferential and radial strain were assessed in 3 short-axis views (basal, midventricular and apical). The endocardial borders were manually traced in end systole, and adjusted if the automatic tracking was considered suboptimal by visual or automated assessment. Segmental strain was automatically calculated as the average strain within each segment. End systole was defined as aortic valve closure in apical long-axis view. Peak systolic strain, postsystolic strain, and maximal strain was assessed, and postsystolic shortening index was calculated as postsystolic strain divided by maximal strain.24
Peak systolic longitudinal strain and SR were measured by TDI from the standard LV apical projections. The region of interest was set to 12x6 mm, and representative segmental traces were manually detected from the basal part of each segment. All global deformation indices were calculated as the average of the observed segmental values.
Twist
Rotation was analyzed by 2D-STE in basal and apical short-axes views. Peak systolic twist was calculated as the difference in maximal rotation between the 2 levels.13
Wall Motion Score Index
Wall motion was visually assessed according to the American Society of Echocardiography25 by an experienced observer. The observer evaluated image quality, and segments were discarded if the quality were found insufficient for analysis. Wall motion score index (WMSI) was calculated for each patient as the average of analyzed segmental values.
Statistical Analysis
The data were analyzed using standard statistical software (SPSS version 14, SPSS Inc, Chicago, Ill). Continuous variables are expressed as mean±SD, when otherwise is not stated. Differences between the groups were analyzed with 1-way ANOVA at the global level. Differences between the segmental groups were analyzed with a mixed-effects linear model, and adjusted for correlations both within patients and within regions. Bonferroni correction was applied for all post hoc tests.
Associations of global infarct mass with global values were analyzed by linear regression (stepwise). The 4 longitudinal deformation parameters (longitudinal strain by TDI or 2D-STE, SR, and postsystolic shortening index) are internally dependant and were tested separately first. Only the ones who significantly contributed to the model (2D-STE strain only) were included in the final model.
Receiver-operating characteristic (ROC) curves were constructed, and areas under curves were measured. Sensitivities and specificities for all global deformation indices were determined for ability to identify medium-sized myocardial infarct, because infarct size has been proved to predict prognosis.1 For all statistical comparisons, P<0.05 was considered significant.
Statement of Responsibility
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.
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Results |
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Feasibility
Infarct mass was analyzed in all (640) LV segments by CE-MRI. By 2D-STE, the feasibility of longitudinal strain analyses was 93% of the LV segments, 81% for circumferential strain, and 73% for radial strain. Feasibility was 96% for longitudinal strain and 95% for SR analyses by TDI. WMS was analyzed in 98% of the segments. Segments were excluded because of reverberations, valvular interference, tracking difficulties, or poor image quality. LVEF, WMSI, twist, and global deformation parameters were analyzed in all patients.
MRI
Infarct characteristics are displayed in Table 2. The average infarct mass was 34±27 g (19±13% of LV mass). By CE-MRI, 19 of the patients had small MI, 13 patients had medium-sized MI, and 8 patients had large MI. The total number of infarcted LV segments per patient was 7.9±4.1 when averaged over all patients, and 2.6±2.6 of these segments were transmurally infarcted.
2D-STE and TDI
Global longitudinal and circumferential strain by speckle-tracking techniques were able to differentiate among the 3 infarct sizes (P<0.01; Table 3), and examples of MRI images and global strain curves from representative patients with medium and large MI are displayed (Figures 1 and 2
). Global longitudinal strain and SR by TDI also distinguished significantly among 3 different sizes of LV infarct mass (P<0.05). Global radial strain and postsystolic shortening index separated large MI from medium or small MI (P<0.01) but failed to separate the smallest infarct groups.
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All global strain and SR indices correlated significantly (P<0.01) with infarct mass (Figure 3) but with a lower correlation coefficient for radial strain and postsystolic shortening index. Global longitudinal strain assessed by speckle tracking and TDI were strongly related (r=0.91; P<0.01).
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ROC analysis was performed for all global indices to identify sensitivities and specificities for the detection of medium-sized MI (Figure 4). The sensitivity and specificity was generally good for all 2D-STE strain parameters. By visual comparison, 2D-STE longitudinal and circumferential strain seems somewhat better than radial strain to detect medium-sized MI.
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At the segmental level, all strain directions by 2D-STE as well as the TDI indices separated significantly between the different levels of infarct transmurality (Table 4; P<0.01). Using ROC analysis, longitudinal strain by 2D-STE revealed the highest sensitivity and specificity for detection of transmural segmental MI.
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LVEF, WMS, and LV Twist
WMSI failed to separate small from medium MI (P=0.14) but could differentiate large MI both from small and medium MI (P<0.01). LVEF and LV twist separated significantly (P<0.01) between small and large infarct. Correlations to global infarct mass were significant both for LVEF, WMSI, and LV twist (P<0.01; Figure 3). By visual assessment, ROC analysis showed reduced sensitivity and specificity for detecting the smallest infarctions compared with the strain techniques (Figure 4).
Multivariate Analyses
In a multivariate regression model only longitudinal and circumferential strain by speckle-tracking echocardiography contributed significantly to the description of the global infarct size (Table 5). Including both circumferential and longitudinal strain in the model increased the correlation coefficient to 0.88 with a constant of 144±10.
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Discussion |
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A number of echocardiographic indices have been introduced during the last 2 decades for assessment of segmental myocardial function. Myocardial strain has demonstrated to be superior compared with myocardial velocity parameters by TDI.8 The recent development of STE permits assessment of global myocardial deformation independently of insonation angle.
The present study is the first to describe and directly compare global myocardial deformation parameters and to test their ability to quantify global myocardial infarct mass. Global shortening strains by 2D-STE and TDI were excellent markers of global infarct mass as assessed by CE-MRI and could clearly separate small, middle, and large MI. Radial strain and the traditional parameters LVEF and WMSI, however, displayed inferior ability to identify the smallest infarcts. The global strain methods are probably the best available tools for assessment of global infarct size in the clinical setting.
3D Deformation
Myocardial motion is complex. Myocardial fibers orientation gradually shifts from a counterclockwise oblique longitudinal direction in the endocardial layer, to near circumferential in the midmyocardial layer, and clockwise oblique longitudinal in the subepicardial layer.26 Three main deformation patterns form perpendicular axes in a local heart coordinate system:27 longitudinal shortening, circumferential shortening, and radial thickening. In addition, shear strains and LV twist caused by deformation variation within the myocardial wall have been described by MRI.28
A close relationship between infarct transmurality by CE-MRI and segmental circumferential or radial strain has previously been demonstrated.17 Similar relations have been found for longitudinal strain in acute18 as well as in chronic ischemic heart disease.20 Global strain has been introduced as an index of global LV function,29 but correlations with global infarct mass have previously only been assessed for global longitudinal strain.
In the present study, global longitudinal and circumferential strains both displayed excellent correlations with infarct mass and ability to correctly classify the amount of MI mass. Radial strain correlated less well with infarct mass. The shortening deformation in systole normally occurs along the longitudinal and circumferential axes. Systolic radial thickening, on the contrary, is because of a combination of myocyte thickening and shearing forces of the oblique fiber layers in the subendocardium.30
The feasibility of radial strain was low in the present study. One explanation for this observation is the presence of fewer speckles in the radial direction. The distance from epicardium to endocardium along the radial direction is approximately 1 cm, whereas the typical distance for a segment along the circumferential and longitudinal directions are 2.5 and 3 cm, respectively. Therefore, more speckles are found in circumferential and longitudinal sample volumes compared with the radial. Moreover, there is also a great transmural gradient of radial strain in the normal myocardium.7 Longitudinal deformation is principally parallel to the beam direction, whereas circumferential and radial deformation takes place in a mixture of directions relative to the beam direction.
2D-STE versus TDI
The correlation to global infarct mass was better for global longitudinal strain by 2D-STE than by TDI. This is in accordance with the results of Cho et al.15 In their study, segmental strain analyses by 2D-STE displayed superior ability to differentiate normal and dysfunctional segments when compared with strain by TDI. Strain analyses by 2D-STE is less angle dependent, and regional strain by 2D-STE is an average of strain from the whole segment. Strain by TDI, on the contrary, is measured in smaller regions of interest within the segment and is, thus, more prone to variation.
In the present study, correlation with infarct mass was similar for global SR and strain by 2D-STE, and the sensitivities and specificities for identification of MI where excellent by both methods. SR was not analyzed by 2D-STE in the present study because the frame rate of 2D-STE is still not sufficiently high for reliable SR-analyses.
SR by Doppler and strain by 2D-STE seems to be equally good techniques for detecting MI in chronic ischemic heart disease, but reliable deformation assessment by TDI is generally limited to the longitudinal direction.
Infarct Size
The experienced cardiologist can easily identify large myocardial infarcts by visual analysis of echocardiograms, but identification of small MI might be challenging. In the present study, all global deformation indices were excellent markers of large myocardial infarct. Identification of medium-sized infarcts was superior for circumferential and longitudinal strain by 2D-STE. Postsystolic shortening did not provide additional information when compared with peak systolic strain.
WMSI correlated to a lesser extent with myocardial infarct mass and was unable to differentiate between the smallest infarct sizes in the present study. Wall motion score has only one level for description of segmental hypokinesia. Thus, segmental hypokinesia includes a range of myocardial infarct transmurality levels. Deformation analyses, on the contrary, are performed along a continuous scale and display the potential to better distinguish between the levels of dysfunction. This might explain why strain measurement is better to identify the smallest infarcts.
Whereas LV twist is a good index of global LV systolic deformation, LVEF reflects the relative LV volume reduction. Both indices are dependant on function in several myocardial segments. Therefore, impairment of these indices requires decreased function in several LV-segments, which might not be present in patients with relatively limited myocardial scar. In the present study, these indices were unable to distinguish between small and medium-sized MI. Ischemic injury is associated with a regional reduction in myocardial contraction. Deformation assessment by strain or SR measurements, therefore, has a theoretical advantage in describing global LV function in ischemic heart disease.
Infarct Transmurality
Revascularization was in average performed 4 hours after initiation of symptoms in the present study. This relatively late reperfusion might explain the large infarcts with a central transmural infarct surrounded by a zone of spared epicardium (Figure 1).31 In the present study, all indices of segmental myocardial function significantly separated among noninfarcted, subendocardial infracted, and transmural infarcted segments. This is in accordance with previously published results.9,17,18,20,32,33
Study Limitations
All indices of LV function are load dependent and should be interpreted with care when there are changes in loading conditions.10 However, we examined our patients in a stable condition, verifying the clinical usefulness of the method under this circumstance.
2D-STE measurements have the advantage of being relatively angle independent. It is, however, like all echocardiographic methods, dependent on image quality. Global strain is the sum of strain values in all analyzed segments divided by the number of analyzed segments. When the image quality generally is low and many LV-segments are discarded, the global strain value might be misjudged. In the present study, all efforts were made to obtain high-quality images. Strain values were obtained in 73% to 93% of the segments, demonstrating that the 2D-STE technique is feasible in most patients.
Myocardial deformation is a complex 3D process that is a composite of regional elastic properties as well as intrinsic and extrinsic forces. Echocardiographic deformation analyses do not, at the present time, provide information on shear strains or transmural strain gradients, and this must be considered when interpreting echocardiographic strain measurements.
The frame rate of grayscale images is still not sufficiently high for reliable SR analyses, longitudinal SR was therefore analyzed by TDI.
In the present study, only 3 echocardiographic LV short-axis slices were recorded, compared with 8 to 11 short-axis slices by MRI. Comparison to infarct mass assessed from the whole LV by MRI is therefore a difficult task and might represent a problem when assessing the smallest myocardial infarcts.
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Conclusions |
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Global strain by 2D-STE assessed from circumferential and longitudinal directions correlated well with global infarct mass by CE-MRI and could separate among small, medium, and large myocardial infarcts. Global longitudinal or circumferential strain adds incremental and accurate information regarding myocardial infarct mass when compared with LVEF or WMSI analyses. The present study demonstrates that global strain has the potential to become a clinical bedside tool to quantify global function in regional LV disease. There is a need for studies designed to evaluate the deformation indices’ ability to predict prognosis in ischemic heart diseases.
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Acknowledgments |
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We appreciate the help from A.H. Pripp, MS, PhD, at the Department of Research Services, Biostatistics Unit, Rikshospitalet University Hospital.
Sources of Funding
Drs Gjesdal, Helle-Valle, Lunde, and Vartdal are recipients of research fellowships from the Norwegian Council on Cardiovascular Diseases, Oslo, Norway.
Disclosures
None.
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References |
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The online-only Data Supplement is available at http://circimaging.ahajournals.org/cgi/content/full/1/3/189/DC1.
Related Article
Circ Cardiovasc Imaging 2008 1: 189-196.
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