Copyright © 2007, The European Society of Cardiology
Application of tissue Doppler to interpretation of exercise echocardiography: Diagnostics of ischemia localization in patients with ischemic heart disease
Almazov Research Institute of Cardiology, 15, Parkhomenko Street, 194156 Saint-Petersburg, Russia
Received 24 April 2006; received in revised form 29 June 2006; accepted after revision 11 August 2006.
* Corresponding author. Tel.: +7 8123798472. zag_angel{at}yahoo.com
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Abstract |
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Development of optimal methods for the objective non-invasive diagnosis of coronary artery disease remains a challenge for imaging techniques in stress tests.
Aim: The aim of this study was to obtain quantitative diagnostic criteria TDI which could detect significant coronary artery disease during exercise echocardiography.
Methods and results: We evaluated regional systolic and diastolic myocardial functions of 123 patients by pulsed wave tissue Doppler imaging (TDI) in eight segments of left ventricle during exercise stress testing. Diagnostic criteria were obtained by comparing TDI and coronary angiography data. Best cut-points of velocity parameters allowed developing two diagnostic models for the detection of left anterior descending (LAD) and circumflex (LCx) artery diseases. The accuracy of the TDI diagnostic model for LAD-disease was 86.2% and for LCx-disease 78.3%. There were no criteria for the detection of RCA disease in this study.
Conclusion: So TDI is a very accurate method for the detection of LAD- and LCx-disease during exercise stress echocardiography.
Keywords: Tissue Doppler imaging; Exercise echocardiography; Quantitative stress echocardiography
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Introduction |
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Exercise stress echocardiography is an accurate physiological non-invasive technique for evaluating coronary artery disease, with high sensitivities and specificities (80–85%).1 But this is correct only for experts.2 The subjective interpretation of this type of test makes the accuracy dependent on the experience of the observer, and also poses problems of concordance between experts. Tissue Doppler imaging (TDI) may provide objective quantitative information. Some investigators have demonstrated high feasibility and reproducibility for measurements of myocardial systolic velocities obtained during dobutamine stress by pulsed wave Doppler.3,4 The MYDISE Study (MYocardial Doppler In Stress Echocardiography) also acquired TDI data during dobutamine stress echocardiography.5 They obtained three models for the detection of coronary artery lesions with several variables which included maximal systolic velocity, peak heart rate and gender. When they used only velocity parameters the highest sensitivities and specificities that could be obtained were 63% and 60%, respectively, for left anterior descending artery (LAD) disease, 69% and 67% for left circumflex artery (LCx) and right coronary artery (RCA) diseases, respectively. Unfortunately there is no agreement on quantitative methods or diagnostic criteria for exercise echocardiography. The purpose of this study was to obtain quantitative diagnostic criteria TDI which could detect significant coronary artery disease during exercise echocardiography.
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Methods |
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Patients
The study population of 106 patients underwent exercise stress echocardiography for the assessment of known or suspected coronary artery disease and also came to coronary angiography. The characteristics of the patients are listed in Table 1. Inclusion criterion was significant lesions of the coronary arteries by coronary angiography. Patients with severe valvular lesions, complex atrial or ventricular arrhythmias, or previous revascularization were excluded from the study. However, patients with poor image quality, left ventricular hypertrophy, and left ventricular dysfunction were included. Additionally 17 patients were included in this study as a control group who had not significant lesion of the coronary arteries. These patients underwent exercise stress echocardiography with tissue Doppler analysis after coronary angiography.
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The mean age and sex distribution were similar in the basal group (group 1) and control group (group 2).
Exercise echocardiography with tissue Doppler analysis
Patients were imaged in the left lateral decubitus position before the cycle test using a commercially available system (Hewlett Pacard Sonos 2000). Images were obtained using a 2.5-MHz transducer in the long-, short-axis parasternal views and the four-, two-chamber apical views. Pulsed wave tissue Doppler sampling velocity profiles were recorded during rest. A sample with a fixed length of 3mm was used. Digital storage of single cardiac cycle loops triggering to the QRS complex was saved to magneto-optical disk for visual assessment (off-line analysis). Eight myocardial segment Doppler data (basal and mid-septum, basal and mid-lateral, inferior and anterior walls) were stored on tape for quantitative analysis. Apical segments were not interrogated because previous work6 has shown myocardial Doppler velocity in these regions to be too low to accurately identify ischemia. Then patients underwent cycle ergometry test. The initial power output was 50W, followed by increases of 25W every 2min until standard end points were reached.7 ECG and arterial pressure monitoring were used during the test. Echocardiographic images resembling rest images were obtained within 180s after the patients stopped exercising. The rest and stress images were compared side by side in a cineloop display. Regional left ventricular function was assessed by an expert reader using a standardized 16-segment model. All the tissue Doppler data were analyzed after tests by sonographers blinded to the clinical profile, visual wall motion analysis, and angiographic data of the patients. The following tissue measurements within each interrogated segment were obtained at rest and post-stress: maximum systolic velocity of ejection phase (Smax), mean systolic velocity of ejection phase (Smean), systolic time–velocity integral (TVIm), diastolic early filling velocity (Em), and diastolic late filling velocity (Am). Delta amplitudinis of post-stress and rest maximum systolic velocities (
Smax), mean systolic velocities (Smean), systolic time–velocity integrals (TVIm), diastolic early filling velocities (Em), and diastolic late filling velocities (Am) were calculated. Em/Am ratio at rest and post-stress, Em/Am ratio defined as difference post-stress Em/Am ratio and rest Em/Am, were also calculated. Cardiac cycles with extrasystolic, postextrasystolic beats, or any disturbance of the rhythm were excluded.
Left ventricular wall segments were assigned to vascular territories according to the following schema: left anterior descending artery (LAD) – basal and mid-anteroseptum, mid-septum, all of the apex, basal and mid-anterior walls; left circumflex artery (LCx) – basal and mid-lateral and posterior walls; right coronary artery (RCA) – basal and mid-inferior walls and basal septum.
Left ventricle mass and index of left ventricle mass were additionally measured in patients.
Comparison with coronary angiography
Angiography was considered the reference standard for the detection of coronary artery disease and was performed within 6 months after stress echocardiography qualitatively by an independent angiographer. Significant coronary artery stenosis was identified in the presence of a 
50% reduction in lumen diameter. To determine cut-points of all tissue Doppler parameters the study population was divided into consecutive subgroups according to the absence or presence of significant LAD, LCx, RCA narrowings. The sensitivity, specificity, and accuracy of tissue Doppler assessment (in each patient) within each vascular territory were derived by cross-tabulation against the regional results of coronary angiography. The defined cut-points were applied to tissue Doppler assessment of each segment.
Statistical analysis
Continuous variables were described by means and standard deviations and categorical data were expressed by percentages. For multiple comparisons ANOVA was performed. Comparison of proportions was performed with the Chi-square test and the Fisher's exact tests. Multivariate technique "Classification Trees" with CART-style, Bartlett's Chi-square test, and FACT-style was used for calculation of tissue Doppler cut-points. The "Classification Trees" is a method of discriminant analysis that provides the classification of each case based on predictor variables. This module of "STATISTICA 6.0" determines boundary values of quantitative independent variables that predict membership in the classes of the categorical dependent variables. A comparison between the predictive data and the true values of the categorical dependent variables allowed to compute accuracy, sensitivity and specificity of the tissue Doppler analysis. Significance was determined as P<0.05.
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Results |
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Exercise stress echocardiography
The hemodynamic responses to exercise stress are summarized in Table 2. In group 1 symptoms suggestive of myocardial ischemia were reported in 62 patients (58.5%); ST-depression was in 39 patients (31.7%).
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Coronary angiography
Of the 123 patients in the study, 17 patients (13.8%) had no significant disease, 24 patients (19.5%) had single-vessel disease, 41 patients (33.3%) had two-vessel disease, and 41 (33.3%) had three-vessel disease. Among those with significant disease, the LAD was involved in 88 patients (71.5%), the LCx was stenosed in 69 patients (56.1%), and the RCA was involved in 72 patients (58.5%).
Tissue Doppler velocities
Of the 1968 segments available for assessment, 1797 segments (91%) had adequate waveforms for the assessment of tissue Doppler velocities also taking into account data obtained before 180s after stopping exercise. Parameters of nine mid-anterior segments and five basal anterior segments (1.4% of all the post-stress segment data) were obtained after 180s and were excluded from the analysis. During the statistical analysis group 1 was divided into two subgroups: patients with significant LAD stenosis (LAD+) and patients with no significant LAD stenosis, but with LCx or/and RCA stenosis (LAD–). Also group 1 was divided into two other subgroups: patients with significant LCx stenosis (LCx+) and patients with no significant LCx stenosis, but with LAD or/and RCA stenosis (LCx–). Finally group 1 was divided into two other subgroups: patients with significant RCA stenosis (RCA+), and patients with no significant RCA stenosis, but with LAD or/and LCx stenosis (RCA–). All obtained parameters were compared in subgroups and with corresponding parameters in the control group. All the subgroups had similar exercise capacity, peak heart rate and peak systolic blood pressure.
Table 3 shows the velocity parameters which differed in the subgroups. There were no parameters which differed in the subgroup RCA+ in comparison with the subgroup RCA–.
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Using "Classification Trees" the velocity cut-points were obtained. The following velocity parameters were the best discriminators between patients with normal and stenosed LAD: post-stress mean systolic velocity in basal anterior wall segment (cut-point 4.9cm/s), post-stress time–velocity integral in basal anterior wall segment (cut-point 1.36cm), and delta mean systolic velocities in mid-septum segment (cut-point 0.39cm/s). The highest accuracy was obtained if two or three above-mentioned parameters were less or equal than cut-point values. The following velocity parameters were the best discriminators between patients with normal and stenosed LCx: post-stress mean systolic velocity (cut-point 3.1cm/s), post-stress time–velocity integral (cut-point 1.14cm), and delta time–velocity integral in mid-lateral segment (cut-point 0.26cm). Also the highest accuracy was obtained if two or three of the above-mentioned parameters were less or equal than cut-point values.
Detailed analysis of the subgroups revealed that after excluding patients with scar of LAD territory (previous myocardial infarction) the subgroups LAD+ and LAD– had significant differences as before. Patients of the LAD+ subgroup had lower mean values of post-stress maximum systolic velocity, delta maximum systolic velocity, delta mean systolic velocity in mid-septum; delta mean systolic velocity, delta time–velocity integral in basal anterior wall segment; delta mean systolic velocity, delta time–velocity integral in mid-anterior wall segment. The subgroups LCx+ and LCx– also had significant differences after excluding patients with scar of LCx territory. The LCx+ subgroup had lower mean values of time–velocity integral in basal lateral wall segment, delta time–velocity integral in mid-lateral wall segment.
The patients of the LAD+ subgroup with previous myocardial infarction had lower mean values of rest maximum systolic velocity, rest mean systolic velocity, rest time–velocity integral in mid-septum; post-stress mean systolic velocity, post-stress time–velocity integral, post-stress diastolic early filling velocity in basal anterior wall segment than the patients of the LAD+ subgroup without previous myocardial infarction. The velocity parameters of the LCx+ subgroup patients with previous myocardial infarction did not differ from the velocity parameters of the patients without previous myocardial infarction.
Comparison with coronary angiography
Fig. 1 shows the sensitivity, specificity, and accuracy of visual wall motion analysis for the detection of coronary artery disease in each vascular territory. Fig. 2 shows the sensitivity, specificity, and accuracy of tissue Doppler diagnostic models for the detection of LAD and LCx lesions.
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Discussion |
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Interpretation of stress echocardiography depends on the experience of the observer. It requires significant training.2 Tissue Doppler analysis offers a practical approach to quantification of exercise echocardiography for facilitation and objectivity of the assessment. Indeed, echocardiographers have less accuracy of visual wall motion analysis then experts in stress echocardiography, but they can perform Tissue Doppler analysis with high quality without long training. Sometimes application of the diagnostic models with several Doppler parameters possibly will be helpful to improve the assessment of stress echocardiography not only for novices, but also for experts. It is especially important in situations of poor image quality, subtle wall motion abnormalities and in case of boundary lesion. The latter situation requires particularly objective assessment.
Previous studies have shown the possibility of using parameters of tissue Doppler for interpretation of stress echocardiography.4,5,8 However, these studies referred to dobutamine echocardiography and they could not be applied to exercise echocardiography as Doppler velocities had greater amplitudes at the peak of the dobutamine test than during the exercise test.9 Although if a patient is able to exercise, then exercise, rather than pharmacological stress, is accepted as the best stress agent because it is physiologic, relatively inexpensive, safer,10 and it provides more reliable ST segment responses and physiologic data regarding exercise capacity.4,6 Other earlier studies used tissue Doppler during exercise echocardiography, but they did not obtain high-accuracy diagnostic criteria for the detection of coronary artery disease.6
We did not compare the quantitative data and the qualitative interpretation of stress echocardiography as we considered that it was not quite correct because accuracy of visual assessment varied widely (really from 65% to 98%) depending on individual experience and level of proficiency of stress echo laboratory. On the other hand, it was shown in the multicentre, multinational MYDISE study that tissue Doppler data had high reproducibility3 and minor interobserver variability. So the comparison between our qualitative subjective interpretation and the quantitative tissue Doppler data reflects the situation for our laboratory and will not be correct for other laboratories.
Offered diagnostic models involve parameters of two segments for diagnosis of LAD-disease and of a segment for diagnosis of LCx-disease that leads to a decrease in time consumption to some extent as compared with full pulsed wave Doppler analysis.
There were no criteria for the detection of RCA disease in our study. Other studies discovered velocity characteristics which can help to recognize RCA lesion.4,8 Perhaps it connects with different sensitivities of the used techniques.
The patients in the control group had accountably higher exercise capacity, peak heart rate and peak systolic blood pressure that skewed the differences between basal and control groups' tissue Doppler indices. But the main goal of this study was to find differences between the subgroups with and without significant lesions of each coronary artery. And these subgroups had similar capacity, peak heart rate and peak systolic blood pressure.
In our investigation we analyzed systolic and diastolic velocity parameters. The systolic velocities were better predictors of coronary artery stenoses than the diastolic ones. The data are in close agreement with an experimental study.11 The reason for the poor correlation between diastolic parameters and coronary lesions might be related to the initial changes of diastolic function in the majority of the cases as a result of hypertrophy of the left ventricle.
Study limitations
Used method is based on pulsed wave Doppler which has a number of shortcomings. First, the motion of adjacent normal muscle may influence on an abnormal segment increasing its velocity, and conversely, an ischemic or scarred segment may lower velocity of a normal segment.12 Second, translation and rotation of the heart and tilt angle may alter velocity parameters. Application of strain rate will probably solve the problem. Although at present some authors report that strain rate imaging is marked as angle dependency, more so than for other Doppler modalities.13
Another limitation is the time lag of up to 6 months between stress echocardiography and angiography.
Furthermore, the major drawback in clinical application of pulsed wave Doppler for stress echocardiography is time consumption. The required analysis time for all the eight segments per patient is approximately 30min. But offered parameters of two segments for diagnosis LAD-disease and of a segment for diagnosis LCx-disease can be analyzed approximately in 10min.
The difficulty in quantifying the apical segment is another disadvantage of the method.14 Our results suggest that lack of apical data may be compensated by sensitivity of tissue Doppler to abnormal mid-septum and basal anterior wall. We did not obtain diagnostic criteria for recognizing RCA stenosis. The inability to evaluate the apex and the RCA blood supply zone with the offered method may appropriately lead to a hybrid approach of wall motion scoring and tissue Doppler analysis in the eventual clinical application of the technique.
The results of this study cannot be extrapolated directly to myocardial velocities measured by pulsed wave tissue Doppler during exercise, since such velocities are about 20% higher than "off-line" measurement.5,15
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References |
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- Fraser A.G., Payne N., Madler C.F., Janerot-Sjoberg B., Lind B., Grocott-Mason R.M., et al. Feasibility and reproducibility of off-line tissue Doppler measurements of regional myocardial function during dobutamine stress echocardiography. Eur J Echocardiogr (2003) 4:43–53.[CrossRef][Medline]
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[Abstract/Free Full Text] - Gorcsan J. III, Deswal A., Mankad S., Mandarino W.A., Mahler C.M., Yamazaki N., et al. Quantification of the myocardial response to low-dose dobutamine using tissue Doppler echocardiographic measures of velocity gradient. Am J Cardiol (1998) 81:615–623.[CrossRef][Web of Science][Medline]
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