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CLINICAL STUDY: MYOCARDIAL ISCHEMIA

Strain rate measurement by doppler echocardiography allows improvedassessment of myocardial viability inpatients with depressed left ventricular function

Rainer Hoffmann, MD^*,*, Ertunc Altiok^*, Bernd Nowak, MD, Nicole Heussen, Harald Kühl, MD, Hans-J.ürgen Kaiser, MD, Udalrich Büll, MD and Peter Hanrath, MD, FACC^*

^* Medical Clinic I, University RWTH, Aachen, Germany
Department of Nuclear Medicine, University RWTH, Aachen, Germany
Department of Biomedical Statistics, University Rheinisch Westfälische Technische Hochschule, Aachen, Germany

Manuscript received February 22, 2001; revised manuscript received October 15, 2001, accepted November 1, 2001.

^* Reprint requests and correspondence: Dr. Rainer Hoffmann, Medical Clinic I, University RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
Rhof{at}pcserver.mk1.rwth-aachen.de

	Abstract

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OBJECTIVES: This study sought to evaluate whether objective assessment of the myocardial functional reserve, using strain rate imaging (SRI), allows accurate detection of viable myocardium.

BACKGROUND: Strain rate imaging is a new echocardiographic modality that allows quantitative assessment of segmental myocardial contractility.

METHODS: In 37 patients (age 58 ± 9 years) with ischemic left ventricular dysfunction, myocardial viability was assessed using low-dose (10 µg/kg body weight per min) two-dimensional dobutamine stress echocardiography (DSE), tissue Doppler imaging, SRI and ¹⁸F-fluorodeoxyglucose (¹⁸FDG) positron emission tomography (PET). The peak systolic tissue Doppler velocity and peak systolic myocardial strain rate were determined at baseline and during low-dose dobutamine stress from the apical views.

RESULTS: A total of 192 segments with dyssynergy at rest were classified by ¹⁸FDG PET as viable in 94 and nonviable in 98. An increase of peak systolic strain rate from rest to dobutamine stimulation by more than –0.23 1/s allowed accurate discrimination of viable from nonviable myocardium, as determined by ¹⁸FDG PET with a sensitivity of 83% and a specificity of 84%. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for prediction of nonviable myocardium, as determined by ¹⁸FDG PET using SRI, of 0.89 (95% confidence interval [CI] 0.88 to 0.90), whereas the area under the ROC curve using tissue Doppler imaging was 0.63 (95% CI 0.61 to 0.65).

CONCLUSIONS: The increase in the peak systolic strain rate during low-dose dobutamine stimulation allows accurate discrimination between different myocardial viability states. Strain rate imaging is superior to two-dimensional DSE and tissue Doppler imaging for the assessment of myocardial viability.

Abbreviations and Acronyms   1FDG   CI   confidence interval   DSE   dobutamine stress echocardiography   18FDG   18F-fluorodeoxyglucose   LV   left ventricle or ventricular   PET   positron emission tomography   ROC   receiver operating characteristic   SR   strain rate   SRI   strain rate imaging   99mTc   technetium-99m   TDI   tissue Doppler imaging

	Methods

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Study group.   This study was approved by the local Ethical Committee, and all subjects gave written, informed consent. A total of 37 patients (58 ± 9 years; 29 men) with reduced LV function (ejection fraction 43.5 ± 9.9%) due to a previous myocardial infarction who underwent DSE, TDI, SRI and ¹⁸FDG PET for the evaluation of viable myocardium were included. Coronary angiography and cineventriculography were performed in all patients.

Echocardiography.   Echocardiograms were obtained with a Vivid Five System (GE Vingmed Sound AS, Horton, Norway). Apical long-axis, two- and four-chamber views were acquired. The LV was divided according to the 16-segment model of the American Society of Echocardiography (13).

Dobutamine echocardiography.   Dobutamine infusion was started at 5 µg/kg body weight per min for 5 min, followed by 10 µg/kg per min for another 5 min. Images were acquired continuously on tape and stored digitally at the end of every dose step. The aim was to observe the monophasic response. Each LV segment was scored at rest and during dobutamine stimulation as normokinetic, mildly hypokinetic, severely hypokinetic, akinetic or dyskinetic. Depending on the contractility at rest and at low-dose dobutamine, segments were described as 1) normal: normal contractility or mild hypokinesia at rest and with dobutamine; 2) viable: severely hypokinetic, akinetic or dyskinetic segments at rest, with improvement by at least one grade with dobutamine administration; and 3) nonviable: severe wall motion abnormality at rest, without improvement with dobutamine.

Tissue Doppler imaging.   Color tissue Doppler recordings were obtained at rest and during dobutamine stress using the same apical transducer positions. Digital data were transferred for off-line analysis, applying the software incorporated in the Vivid Five System (GE Vingmed). This allowed determination of the tissue Doppler velocity of a chosen sample volume for each instant during one cardiac cycle. The peak systolic tissue velocity was determined as the maximal positive velocity within 350 ms after the QRS complex. It was evaluated for each segment of the 16-segment model at rest and during dobutamine stimulation, placing the sample volume in the basal part of each segment halfway between the endocardium and epicardium. Autocorrection of sample volume location during systolic contraction accounted for the inward motion of the ventricular wall to keep the sample volume halfway between the endocardium and epicardium. Three consecutive beats were analyzed.

Strain rate imaging.   This type of imaging is an extension of TDI, which determines the velocity gradient between two points along the ultrasound beam. The strain rate (SR) is equivalent to the spatial gradient of velocity. It is characterized by the equation: SR = (v[r] – v[r + r])/r, as described previously (9). An offset of r = 1 cm was used in all studies. Strain rate imaging was performed from the apical long-axis, two- and four-chamber views. This allowed the determination of a baso-apical velocity gradient within each segment. During SRI, the image sector was kept as narrow as possible to achieve the highest possible frame rates. For this purpose, only one wall (septal, lateral, posterior, anterior, inferior and anteroseptal) was imaged at a time. This allowed achievement of frame rates >140/min with real-time display of SR color images and also maintenance of the angle between the Doppler beam and the longitudinal shortening direction of the wall at <30°. Digital data were transferred to customized, dedicated research software (GE Vingmed). This made it possible to determine the SR at any instant during one cardiac cycle. The peak systolic SR was determined as the maximal negative SR within 350 ms after the QRS complex. It was determined for each segment at rest and with dobutamine. Positioning of the sample volume and autocorrection of sample volume location were done as described for TDI. The SR data were averaged from three consecutive beats. Cardiac cycles with disturbance of the rhythm were excluded.

Positron emission tomography.   The PET protocol has been described in detail (14). Technetium-99m (^99mTc)-tetrofosmin was used as marker of myocardial perfusion and ¹⁸FDG as a marker of myocardial metabolism. Myocardial perfusion imaging was performed 60 min after injection of 10 mCi of ^99mTc-tetrofosmin. Acquisition of PET images was performed at the same day of the DSE examination. Static emission scans were acquired 45 to 60 min after injection of 5 mCi of ¹⁸FDG. Reoriented tetrofosmin and ¹⁸FDG data were simultaneously quantified by an automatic count-based algorithm using the 16 segments of the echocardiographic model. Tetrofosmin and ¹⁸FDG uptake in each segment was expressed as a percentage of the region with the maximal tetrofosmin uptake. Depending on ^99mTc tetrofosmin and ¹⁸FDG tracer uptake, myocardial segments were classified into three groups: 1) normal segments, defined by a tetrofosmin uptake >70%; 2) mismatch (viable) segments, defined by a tetrofosmin uptake 70% and a better preserved ¹⁸FDG uptake (¹⁸FDG – tetrofosmin uptake >20%); and 3) intermediate and match segments (nonviable), defined by a concordant reduction of both tracers to 70%.

Coronary angiography and cineventriculography.   The severity of coronary stenosis was determined quantitatively (QuantCor, CASS II, Siemens, Erlangen, Germany). Monoplane planimetry of cineventriculograms was performed to determine the LV ejection fraction.

Statistics.   Data are expressed as the mean value ± SD. To compare segmental TDI data with SR data at rest and during dobutamine, relative to the results of ¹⁸FDG PET, we used a summary statistic. This required a calculation of mean values for viable and nonviable segments, respectively, per patient. Then, the paired Student t test, at the very conservative Bonferroni-adjusted individual significance level (0.05/15; number of comparisons = 15), was performed to compare viable with nonviable segments in 37 patients. The global significance level was set at 0.05. Recently described nonparametric analysis of overall sensitivities and specificities, as well as areas under the receiver operating characteristic (ROC) curves, was applied (15). Analysis of ROC curves was used to assess the optimal cut-off point of the increase in systolic peak SR and of the increase in systolic peak tissue velocity for the detection of myocardial viability.

	Results

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Significant coronary artery stenosis (>50% diameter stenosis) was documented in each patient. Visual assessment of wall motion was possible in 556 (94%) of the 592 segments. A total of 344 segments (62%) demonstrated normal function, and 212 segments were dyssynergic at rest.

¹⁸FDG PET.   Of the 212 dyssynergic segments, 69 segments (32%) were found to have normal perfusion and metabolism and 35 segments (17%) to be viable with depressed perfusion. The combined 104 segments were subsequently compared with 108 segments (51%) with a match or intermediate finding, which were defined as nonviable.

Two-dimensional DSE.   A total of 119 (56%) of 212 segments showing severe dyssynergy at rest did not show improvement in wall motion with dobutamine stimulation and were considered nonviable. There were 93 segments (44%) that were considered viable.

Tissue Doppler imaging.   Analysis of TDI samplings was feasible in 92% of all segments, including 192 of the 212 segments defined as dyssynergic by two-dimensional echocardiography. These 192 dyssynergic segments were divided on the basis of the ¹⁸FDG PET results into 94 segments showing viability and 98 segments showing nonviability. Peak systolic tissue Doppler velocities at rest and during dobutamine stimulation, as well as the increase from rest to dobutamine stimulation for the different viability states, as determined by ¹⁸FDG PET, are given in Table 1. At rest, viable myocardium had a peak systolic tissue Doppler velocity similar to that of nonviable myocardium. During low-dose dobutamine stimulation, the peak systolic tissue Doppler velocity increased significantly for both viable myocardium and nonviable myocardium. The increase in the peak systolic tissue Doppler velocity was not significantly different between viable and nonviable myocardium.

View larger version (78K): [in this window] [in a new window]   Figure 1 Strain rate imaging of the septal wall at rest (upper) and during dobutamine stimulation (lower). The color changes from green to yellow for the mid-anterior segment, indicating an increase of contractility. This segment has been shown to be viable by 18F-fluorodeoxyglucose positron emission tomography.

View larger version (20K): [in this window] [in a new window]   Figure 2 Strain rate tracings at rest (solid line) and during dobutamine stimulation (dotted line) for one cardiac cycle of a hypokinetic segment at rest, shown to be viable by 18FDG PET. There is an increase in the peak systolic strain rate from 1.1 1/s at rest to 2.0 l/s during dobutamine stimulation.

Comparison of echocardiographic techniques for detection of viability.   There was agreement between ¹⁸FDG PET and two-dimensional DSE in the assessment of viability in 66% of segments. This corresponded to a sensitivity and specificity of two-dimensional DSE in the detection of viability, as determined by ¹⁸FDG PET, of 75% and 63%, respectively. For changes in peak systolic tissue velocities and changes in peak systolic SR, ROC curve analysis was used to determine the cut-off value with the highest sensitivity and specificity for the detection of viability using ¹⁸FDG PET as reference. Tissue Doppler imaging agreed in 66% and SRI in 83% of segments with assessment of segmental viability by ¹⁸FDG PET. An increase in peak systolic tissue velocity <1.05 cm/s had a sensitivity of 69% and a specificity of 64% to predict nonviability, as determined by ¹⁸FDG PET. The ROC analysis showed an area under the curve of 0.63 (95% confidence interval [CI] 0.61 to 0.65) for the prediction of nonviable myocardium. An increase in SR below –0.23 (l/s) had a sensitivity of 83% and a specificity of 84% to predict nonviability determined by ¹⁸FDG PET (Fig. 3). The ROC analysis showed an area under the curve of 0.89 (95% CI 0.88 to 0.90) for the prediction of nonviable myocardium. The difference between the ROC areas of SR and TDI was 0.26 (95% CI 0.25 to 0.27). Table 3 shows that SR analysis compared favorably with two-dimensional DSE and TDI for the detection of viability.

View larger version (29K): [in this window] [in a new window]   Figure 3 Plot of increase in strain rate during dobutamine stimulation determined by strain rate imaging and increase in tissue velocities during dobutamine stimulation determined by tissue Doppler imaging for myocardial segments defined as normal or viable and for those defined as nonviable by 18F-fluorodeoxyglucose positron emission tomography.

	Discussion

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Myocardial viability.   Two-dimensional DSE has been used as a widely available and cheap method for assessment of myocardial viability (2,3). However, the method is limited by the subjective evaluation process (4,5). Assessment of myocardial contractility in segments adjacent to infarct-related areas is difficult. Endocardial excursion of a segment may be due to active contraction or passive drawing motion from adjacent segments. Assessment of wall thickening may be challenging, as the epicardial visibility is often low.

Tissue Doppler imaging.   This imaging method has been suggested for quantification of ventricular contractility and objective assessment of stress echocardiograms (6,7,16,17). However, TDI has several limitations. The velocity determined by TDI does not differentiate between active contraction and passive following of tissue. Thus, rotation and translation movements of the whole heart, as well as active contraction of segments adjacent to the analyzed segment, may affect the determined velocity. The point velocity measured by TDI may therefore incorrectly reflect the contractility of the analyzed segment. Analysis of tissue velocities by TDI from apical views is hampered by the fact that the obtained velocities represent a cumulative velocity of all segments apical to the analyzed segment. This results in an increase of tissue velocities from the apex to base (6). Furthermore, the impact of segments located apical to the analyzed segment inhibits the ability to accurately determine whether contractility is depressed at the level of the analyzed segment. Several solutions have been suggested to circumvent these difficulties. Nishino et al. (18) applied M-mode TDI, in combination with dobutamine stimulation, in the post-myocardial infarction setting and reported a high sensitivity for the prediction of reversible dysfunction. They determined a velocity gradient between the endocardium and epicardium both at rest and during dobutamine stress to evaluate the functional reserve. Evaluation of TDI for only the basal segment in the apical views has been described (19). This resulted in the assessment of viability for a whole ventricular wall from the apex to base. Although this approach circumvents the difficulties of the segmental analysis related to the baso-apical tethering, it results in a loss of spatial information on the exact pattern of viability distribution.

Strain rate imaging.   This new imaging method was derived from color tissue Doppler imaging, which has recently been implemented as a real-time modality (8,9). Strain and SR can be determined by an algorithm that calculates spatial differences in tissue velocities between neighboring myocardial regions. Strain is the degree of lengthening or compression between two adjacent points in space. Strain rate equals the rate of regional myocardial deformation. Thus, it is equivalent to the velocity gradient between two points with a small offset (8). The advantage of SR is that it is not affected by global cardiac displacement and the tethering effects of adjacent segments. Urheim et al. (9) demonstrated in an animal model that systolic strain determined by Doppler imaging correlates closely with strain determined by sonomicrometry. In contrast, the relationship between Doppler velocities and regional myocardial function was much looser. Myocardial Doppler velocities of basal nonischemic myocardial segments were found to be reduced in cases of apical ischemia, although regional strain was unchanged. This was explained by the tethering effects. There are limited data on the assessment of strain and SR by Doppler echocardiography in clinical practice. Edvardsen et al. (11) demonstrated in 17 patients that strain analysis is a more accurate marker than TDI for detecting systolic regional myocardial dysfunction induced by coronary occlusion. Götte et al. (12) demonstrated that strain analysis is more accurate than planar wall thickening analysis in the discrimination of dysfunctional from functional myocardium after infarction. The present study related SR measurements obtained at rest and during dobutamine stimulation to myocardial viability determined by ¹⁸FDG PET. The results of this study indicate that changes in SR during dobutamine stimulation allow accurate assessment of myocardial viability. Strain rate imaging was more accurate than TDI for the assessment of myocardial viability. This should be explained by the aforementioned difficulties of point velocities determined by TDI to accurately reflect local myocardial contractility and viability.

Study limitations.   Only low-dose dobutamine stress was applied in this study. Thus, assessment of the biphasic response to evaluate myocardial viability was not possible. However, we thought this was adequate, as previous studies have demonstrated that the monophasic response at a low dose identifies most viable segments or that peak dose sampling does not add incremental value as compared with low-dose sampling (19). The current technology of SRI is characterized by considerable noise in the SR signal. We believe that we could reduce the impact of this limitation by averaging the results of three heartbeats. The mean difference between repeated measurements was much smaller than the mean difference in SR between viable and nonviable regions during dobutamine stimulation, indicating that SR data can be used with sufficient confidence. However, the noise in the SR signal increases with higher heart rates and reduced image quality. The analysis of strain by Doppler echocardiography is very angle-dependent (8,9). Accurate SR data can be expected only if the angle between the ultrasonic beam and LV axis is very small (8). For this reason, we performed SR analysis only for one myocardial wall at a time and requested an angle between the ultrasonic beam and LV axis of <20°. Because of the greater angle between the ultrasonic beam and LV axis for apical segments, determination of SR for apical segments is likely to be less accurate (8). ¹⁸FDG PET was used as the reference standard to evaluate viability. However, although ¹⁸FDG PET is an accurate marker of histologic viability, it has limitations in the prediction of functional recovery after revascularization (20). Future studies will need to show the accuracy of SR results in comparison with two-dimensional DSE and TDI for the prediction of functional improvement after revascularization.

Conclusions.   The increase of peak systolic myocardial SR during low-dose dobutamine stimulation allows accurate assessment of myocardial viability in patients with depressed LV function after myocardial infarction. The method compares favorably with TDI and two-dimensional DSE in the evaluation of myocardial viability and is likely to be an important step in the effort to objectively assess myocardial contractility.

	References

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