European Heart Journal Advance Access originally published online on June 15, 2007
European Heart Journal 2007 28(14):1765-1772; doi:10.1093/eurheartj/ehm188
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Comparison of two-dimensional speckle and tissue Doppler strain measurement during dobutamine stress echocardiography: an angiographic correlation
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane Qld 4102, Australia
Received 29 July 2005; revised 4 November 2007; accepted 26 April 2007; online publish-ahead-of-print 15 June 2007.
* Corresponding author. Tel: +61 7 3240 5346; fax: +61 7 3240 5399. E-mail address: tmarwick{at}soms.uq.edu.au
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Abstract |
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Aims: Two-dimensional (2D)-strain derived from speckle-tracking is an alternative to tissue velocity imaging (TVI)-based strain. We compared their feasibility and accuracy in 150 patients undergoing dobutamine stress echocardiography (DSE) and coronary angiography.
Methods and results: 2D- and TVI-strain were obtained in three apical views at rest and peak stress. Peak systolic strain rate (SR), endsystolic strain (
end-sys), and peak strain (peak) were measured off-line at rest and peak stress, and results were compared with wall motion analysis and significant coronary artery disease (CAD 
70% diameter stenosis). Optimal cut-offs were derived from receiver operating characteristic (ROC) curves for sentinel segments. The most feasible method was 2D-strain at rest, and TVI-strain at peak stress. The average peak SR and end-sys at peak stress in segments of patients with significant CAD was less than in segments of patients without CAD (P < 0.0001) and mean PSI at peak stress was higher (P < 0.0001) with both 2D- and TVI-strain. Peak systolic SR at peak stress had the best area under the ROC for both 2D- (AUC 0.67) and TVI-strain (AUC 0.71) for the diagnosis of CAD. The accuracy of WMS (75%) for diagnosis of CAD per patient was similar to 2D-SR (69%) and TVI-SR (74%). The accuracy of 2D-SR and TVI-SR at peak stress was 78 vs. 79% (P = NS) for LAD, 67 vs. 73% (P = NS) for LCX, and 59 vs. 74% (P = 0.008) for RCA disease.
Conclusion: Measurement of speckle tracking strain during DSE is feasible and similar in accuracy to TVI-strain in the anterior, but not in the posterior circulation.
Key Words: Dobutamine stress echo • Ischaemia • Strain rate • Coronary angiography
These authors are to be regarded as joint first authors. 
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Introduction |
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Dobutamine stress echocardiography (DSE) is widely used for assessing the presence, location, and extent of coronary artery disease (CAD), but it remains limited by its subjective interpretation and dependence on both image quality and experience.1–3 The need for a more quantitative method for evaluation of stress echocardiography has provoked the introduction of several imaging methods,4–6 but translation and tethering effects between normal and hypocontractile segments may limit the applicability of these techniques.7 By measuring deformation derived from tissue Doppler velocity (TVI), strain imaging has largely overcome these limitations. However, the routine clinical use of these measurements is constrained by problems that are inherent in the use of Doppler, that relate to signal noise and angle dependency.8,9
Two-dimensional (2D) strain is based on speckle tracking in 2D gray scale images.10–12 Initial studies have shown 2D strain to reliably measure myocardial strain rate (SR) and strain at rest, although the measurements may underestimate tissue velocity-based measurements.11 In this study of the accuracy of interpretive strategies during DSE, we sought to compare the feasibility and diagnostic accuracy of 2D- with TVI-SR and strain with conventional wall motion analysis.
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Methods |
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Study population
We sought to study consecutive patients who underwent both DSE for clinical evaluation of myocardial ischaemia and coronary angiography within 12 months of DSE. These data were entered prospectively into a database, which was sampled over 2 years to examine the association of myocardial deformation responses with the diagnosis of CAD. After exclusion of patients with severely depressed LV function, significant valvular heart disease, left bundle branch block on ECG, and previous coronary artery bypass grafting, we identified the first 150 consecutive patients.
Dobutamine stress
DSE was performed using a standard protocol13 in all patients after obtaining consent. Intravenous dobutamine was initiated at 5 µg/kg/min, and the dose increased every 3 min to 10, 20, 30, and finally 40 µg/kg/min. If 85% of the age-predicted maximal heart rate was not achieved, atropine was given. Standard end-points were used, including conclusion of the protocol, development of severe angina or other intolerable symptoms, development of hypertension (systolic pressure > 230 mmHg), symptomatic hypotension, serious arrhythmia, or extensive ischaemia. Wall motion was assessed by an expert observer. A positive test is defined by a new or worsening wall motion abnormality. In segments with a resting wall motion abnormality, the biphasic response was used to define ischaemia.
Image acquisition
Patients were imaged in the left lateral decubitus position before and during the test, using a commercially available system (Vivid 7 running BT06.0.0 software, General Electric Medical Systems, Milwaukee, Wisconsin). Harmonic images were obtained using a 3.5 MHz transducer in the apical four-chamber, long-axis, and two-chamber views. Two-dimensional gray scale images were obtained at a frame rate of 60–80 frames/s at rest and peak stress, and separate harmonic colour TVI images were saved with a colour frame-rate of 100–140 frames/s (depending on the sector width), in the three standard apical views. These colour TVI images were recorded with digital media using high spatial resolution, at a depth of 16 cm, with pulse repetition frequencies between 500 and 1000 Hz, resulting in aliasing velocities between 16 and 32 cm/s. Three cardiac cycles were saved in digital format onto a magneto-optical disk for off-line analysis (EchoPac BTO6.0.0, GE Medical Systems) by observers blinded to the angiographic findings.
Image analysis
Myocardial strain and SR using both techniques and wall motion score were measured in the same 16 myocardial segments—six (anteroseptal, anterior, anterolateral, posterior, inferior, inferoseptal) at the basal and mid-levels and four (anterior, anterolateral, inferior, inferoseptal) at the apex.14
Measurement of tissue velocity imaging strain
SR data were measured from the slope of the regression line of all the velocity estimates between two points in the middle of each myocardial segment, separated by a distance of 12 mm. Measurements were avoided from walls that were poorly visualized, with aliasing on tissue velocity, or with insonation angles > 30°. The region of interest was tracked manually in each frame, in order to maintain a mid-myocardial position and avoid intra-cavity velocities.
Measurement of two-dimensional strain
The endocardial borders were traced at the end-systolic frame of the 2D images from the three apical views. On the basis of this line, the software then automatically tracked myocardial motion, creating basal-, mid-, and apical regions of interest, in which tracking quality was verified using a scale of 1 to 3 (1, excellent; 2, acceptable; 3, poor). In segments with a tracking score of 3, the observer readjusted the endocardial trace line until a better tracking score was achieved—if this was not attainable, that segment was excluded. Numerical and graphical displays of deformation parameters (reflecting the average value for tracking all of the acoustic markers in each segment) were then automatically generated for all six segments from each view.
SR was obtained from the peak negative value of the TVI or 2D systolic curves (before aortic valve closure) in each segment, at baseline and peak stress (Figure 1). Endsystolic strain (end-sys) was measured at end-systole on the TVI and 2D curves. End-systole on colour tissue Doppler images is marked by a brief colour change at the base of the mitral leaflet and septum on the TVI velocity images, attributed to aortic valve closure. As this is not apparent on the 2D strain images, the first zero-crossing of the velocity curve was used to denote end-systole for 2D strain.15 If further shortening occurred after the end of systole, this was measured as the peak strain (peak). The difference between end-sys and peak was calculated as the post-systolic shortening (PSS), and from this the post-systolic index (PSI) was derived from the equation: PSS/peak. Change (delta) in strain and SR (value at peak stress – value at baseline) were also calculated.
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Angiographic comparison
All patients underwent coronary angiography using the Judkins technique. Significant CAD was defined as > 70% luminal diameter stenosis.
For comparison with the angiographic findings, segments were correlated with the arterial supply as proposed by Geleijnse et al.,13 considering the left anterior descending artery (LAD) to supply anterior, anteroseptal, apical, and midseptal segments, the circumflex (LCX) to supply the anterolateral, and the right coronary artery (RCA) to supply the basal to mid inferior and basal inferoseptum. The posterior wall was assigned depending on the relative size of the left and right coronary arteries.
Reproducibility
Reproducibility was assessed for both 2D and TVI strain. Interobserver variability in the measurement of peak SR and peak systolic strain (end-sys) at both rest and peak stress views were evaluated in 10 randomly selected patients (total 320 segments) by two independent observers. To obtain the intraobserver variability, the same observer who was blinded to the former results, measured peak SR and end-sys at a separate time, at least 2 weeks later. Reproducibility was expressed as 95% limits of agreement.
Statistical analysis
Summary data are expressed as mean ± SD or as a percentage of patients. The statistical package SPSS for Windows (Release 11.0 SPSS Inc., Chicago, IL) was used for basic statistical analysis, with Stata (version 8, Stata Corp, College Station, TX) being used for repeated-measures analyses. Paired t-tests were used for comparison of matched segments in patients with and without CAD. A generalized estimating equation was used to compare the SRI parameters between ischaemic and non-ischaemic segments, adjusting for the correlation between segments within each patient. Bonferroni correction was used to correct for multiple analyses.
The optimal SR and end-sys cut-off values for predicting significant coronary artery stenosis were determined from a receiver operating characteristic (ROC) curves, which accounted for repeated measures (SAS for Windows 9.1, SAS Institute, Cary, NC). The area under the ROC curve (AUC) was used to compare the diagnostic validity, and a z-score was calculated to determine the difference of AUCs.16 The optimal cut-off point was chosen as the whole value giving the best compromise of specificity and sensitivity in an ROC curve based on a randomly selected group of 75 patients, and the reliability of the cut-points was assessed in the remaining 75 patients. Accuracy was calculated as the total number of true positive and true negative tests divided by the total number of patients. A true positive test was defined when an abnormal segment was subtended by a significant coronary artery stenosis. Values for accuracy were compared using a 
2 test.
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Results |
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Patient characteristics
The clinical and echocardiographic features of patients are shown in Table 1. Regional wall motion abnormalities in at least two segments at rest were present in 62 patients because of previous myocardial infarction. The wall motion score at rest and peak stress were 1.3 ± 0.6 and 1.4 ± 0.7, respectively.
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Feasibility and reproducibility
At rest, 2D SR were obtainable in 2100 of 2400 segments (88%), compared with 2042 segments with TVI SR (85%, P = 0.02). Peak stress images could be measured in 1972 segments (82%) with 2D SR, the remainder being compromised by deterioration of 2D image quality. Conventional TVI SR assessment was possible in 2038 at peak stress (85%, P = 0.01). The interobserver and intraobserver limits of agreement of 2D and TVI strain are shown in Table 2.
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Strain rate and strain with or without coronary artery disease
The results for segments in patients with and without CAD are summarized in Table 3. For both 2D and TVI measures, resting SR and
end-sys were less in segments subtended by significantly stenosed coronary arteries, compared with uninvolved segments. At peak stress, the average peak SR, delta SR, and end-sys were less in patients with significant CAD than those without CAD (P < 0.0001). PSI at peak stress, for both 2D and TVI strain, was significantly higher in segments supplied by coronary arteries with significant stenosis compared with uninvolved regions (P < 0.0001). 2D SR and end-sys values at peak stress were significantly higher than those of TVI strain.
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The diagnostic validity of each parameter to predict significant CAD was compared by measuring the AUC. The prediction of significant CAD with peak SR at peak stress provided the largest AUC with both 2D strain (AUC 0.67) and TVI strain (AUC 0.71). These areas were also similar with both 2D strain and TVI-based measurements of
end-sys (0.66 vs. 0.64) and PSI (0.60 vs. 0.63).
Diagnostic accuracy: comparison with visual estimation
To avoid the requirement of measuring waveforms in all segments and to make the technique feasible for routine clinical use, we sought a representative segment of each coronary territory for diagnosis of significant stenosis using ROC curve analysis. In the anterior circulation, the AUCs of the ROC curves for 2D SR at peak stress were mostly similar to those of TVI SR and for both methods, the optimal segment for the LAD was the apical septum (AUC 0.85, 0.87). In the posterior wall there were no significant differences between the AUCs for 2D SR and TVI SR, and the basal posterior segment (optimal AUC by 2DS, second best by TVI) was selected so that performance of the methods in the LCx territory could be compared in the same site. However, in the RCA territory, TVI SR had significantly greater AUCs compared with 2D SR and the mid inferior segment (second best by both) was selected so that performance of the methods in the RCA territory could be compared in the same site (Table 4, Figure 3). By analysis of these marker segments, optimal cut-offs for 2D SR and TVI SR were obtained (Figure 2), and then applied to assess diagnostic accuracy for territory of disease (Figure 3).
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The diagnostic accuracy of 2D SR at peak stress was equivalent to TVI SR (78 vs. 79%, P = NS) in the LAD territory and compared well with WMS accuracy (75%, P = NS). In the RCA territory, however, the diagnostic accuracy of 2D SR at peak stress was significantly lower than TVI SR (59 vs. 74%, P = 0.008) and WMS (59 vs. 73%, P = 0.009). In the LCx territory, 2D SR at peak stress was significantly less accurate than WMS (67 vs. 81%, P = 0.02), secondary to reduced specificity, but not different from TVI strain. The sensitivity, specificity, and diagnostic accuracy for 2D SR and TVI SR at peak stress (single segment model) compared with subjective wall motion scoring per patient yielded no significant differences (Figure 4), with the accuracy for diagnosis of CAD by 2D SR (69%) vs. TVI SR (74%) vs. WMS being 75% (all P = NS).
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To ensure that the optimal cut-offs per sentinel segment were reproducible, we divided the study population into two groups (group 1 and group 2) based on random selection of DbE studies and reassessed the AUCs and cut-offs for the ROC curves in each group (Table 5). There were no significant differences in ROC AUCs for each group compared with the group as a whole, nor for accuracies obtained in the diagnosis of LAD, RCA, and LCx territory CAD by applying the obtained cut-offs.
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Discussion |
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The results of this study indicate that 2D strain is a useful adjunctive method to quantify regional contractile function in the anterior circulation during DSE.
Quantification of dobutamine stress echocardiography
Stress echocardiography is already an established tool for clinical decision making, with an average accuracy of > 80% for detection of significant coronary artery stenosis in large studies. Unfortunately, DbE has important limitations, including endocardial border definition and subjective interpretation of regional wall motion abnormalities.17 Despite improvements, there remain significant differences in the interpretation of DSE among experienced readers.2 Several quantitative imaging methods, including myocardial tissue Doppler velocity or colour kinesis, have been proposed in an attempt to overcome these limitations of visual wall motion scoring.6,18–20 Although these provide some benefit, especially to less expert readers,6,21 these techniques remain limited by translation and tethering effects.
Limited clinical data have been reported with TVI-based measurement of SR and strain during DSE. This approach is independent of overall heart motion, and therefore more site-specific than measurement of Doppler tissue velocities. Consequently, longitudinal systolic strain and SR are more sensitive in detecting regional myocardial ischaemia than tissue velocity.22–24 Voigt et al.24,25 reported that the ratio of PSS to maximal segmental deformation was the best quantitative parameter to detect regional ischaemia. In a group of patients with normal resting function, these authors reported the PSS ratio to have a sensitivity of 82% and specificity of 85%, comparable with that of conventional qualitative visual DSE assessment. End-systole is differently defined with the two methods and may be more difficult to assess with 2DS. Nonetheless, even TVI-based PSS did not prove as useful in our study, perhaps reflecting some differences in patient profile. The optimal parameter in this study was peak SR (AUC 0.71), which had a similar AUC to that of peak SR in the study of Voigt, notwithstanding the use of regional SR to detect significant epicardial coronary stenosis in our study, rather than regional myocardial ischaemia.
Comparison of tissue velocity imaging strain and 2D strain
Although TVI-derived SR and strain are sufficiently robust to quantify DSE, the application of this technique for routine clinical use must overcome several drawbacks. First, TVI-derived SR is sensitive to angulation issues like other Doppler techniques. During acquisition, every effort should be taken to align the tissue direction parallel with the beam direction, although this is technically challenging in the apical segments. The second limitation of TVI-SR is signal noise. In this study, we attempted to optimize the approach to acquisition and processing, including high frame-rate and lateral resolution acquisition, use of an offset distance (strain length) of 12 mm and 40 ms Gaussian filter and tracking of the sample on the gray scale image during post-processing. However, these measures make this technique rather time consuming.26
2D strain has already been described both in vivo and in vitro, and the feasibility of the technique has been confirmed at rest.10–12 Several advantages of 2D strain have become apparent over TVI-based strain. First, the acquisition is less demanding—a sector width and frame rate (70–80 frames/s) can be used that are more consistent with standard imaging. The method is angle independent, as 2D strain allows tracking of natural acoustic speckles which are equally distributed within the whole myocardium,11 so that all three components of deformation (axial, radial, and circumferential) may be measured.27
Discrepancies between strain measurements in the two vascular territories
The diagnostic content of 2D strain was less in the right coronary (AUC = 0.65) and the left circumflex territory (AUC = 0.76) than in the anterior coronary circulation (AUC = 0.85). Similarly, the sensitivity, specificity, and accuracy of 2D strain in the LAD territory (77, 79, and 78%) exceeded these findings in the LCx (71, 66, and 67%) and RCA (65, 56, and 59%). The lower sensitivity for detection of disease in the posterior-lateral circulation may be due to problems with image quality in the inferior, lateral, and posterior walls, evidenced by a higher tracking score compared with the anterior segments (2.2 ± 0.6 vs. 1.9 ± 0.7, P < 0.01). The accuracy of 2D strain during tracking is dependent on the characteristics of the image, and because of its dependence on gray scale image quality, 2D strain seems less reliable in the posterior circulation, with the worst performance in the anterolateral wall (ROC AUC for peak 2D SR 0.59 for the basal anterolateral and 0.66 for the mid anterolateral segments, respectively). In contrast, TVI based strain is less dependent on image quality, and consequently TVI strain accuracy seems to have an advantage in the posterior coronary circulation. The total analysis times of 2D and TVI strain in all segments were 
25 min for each technique and remains time consuming. The use of a sentinel segment may be more feasible in clinical practice.
Quantitative and qualitative dobutamine stress echocardiography analysis
Because the measurement of all 16 segments for the diagnosis of CAD is complicated and of limited feasibility for routine clinical work, we used single ‘sentinel’ segments at the distal end of the perfusion territory of each coronary artery. For both methods, the optimal segment for the LAD was the apical septum (AUC 0.85, 0.87). In the LCX and RCA, different segments gave the highest AUC. In order to compare the same segment, we ranked the AUCs and selected the segment that gave the best overall performance—basal posterior was first on 2DS and second on TVI—with no difference in AUCs, whereas basal lateral was first by TVI but fourth by 2DS and AUCs were different. The optimal RCA segments were again unmatched—we chose the second best by both techniques. This marker segment was used to compare the two strain measurement techniques and wall motion scoring with the presence of significant coronary stenosis. Neither 2D SR nor TVI SR at peak stress (single segment model) added incremental benefit to visual WMS assessment in the diagnosis of significant CAD per patient.
Limitations
The normal approach to wall motion analysis is to acquire each image with a wide enough sector to include both walls in each view. However, TVI strain is optimally obtained with imaging of one wall at a time using narrow sector imaging, which increases temporal resolution without sacrificing spatial resolution and also leads to better alignment of the wall with the Doppler beam. The use of high-resolution, full-sector images rather than narrow sector images may have been a disadvantage for TVI-based strain, although the difference between these approaches is small.28
The clinical application of myocardial deformation methods is subject to signal noise that can make some of the segments uninterpretable. From the standpoint of data analysis, these segments constitute missing data. As there is no evidence that the segmental function influences the ability to interpret the degree of myocardial deformation, we do not believe that exclusion of these missing observations introduces a selection bias into the study. Moreover, there was no strategy that we could rationalize that could overcome this problem of missing data.
Clinical implications
Although TVI-based strain is feasible in the clinical setting, it has limitations in the evaluation of angle-dependent segments. 2D strain is dependent in gray scale image quality, but is more reproducible. Moreover, the 2D strain technique does pose some problems at peak stress, with tracking problems likely secondary to hyperdynamic LV contractility and excessive annular motion in the base, making this technique challenging in the postero-lateral circulation. Despite these limitations, 2D strain is more automated and applicable. A hybrid technique combining TVI and 2D strain may prove optimal.
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Supplementary material |
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Supplementary material is available at European Heart Journal online.
Conflict of interest: The authors' research group receives grant support from General Electric Medical Systems, but unrelated to this study.
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Footnotes |
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These authors are to be regarded as joint first authors. |
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