Author + information
- Received February 22, 2001
- Revision received October 15, 2001
- Accepted November 1, 2001
- Published online February 6, 2002.
- ↵*Reprint requests and correspondence:
Dr. Rainer Hoffmann, Medical Clinic I, University RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
- Harald Kühl, MD
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.
The identification of dysfunctional but viable myocardium in patients with depressed left ventricular (LV) function has important therapeutic and prognostic implications (1). Although dobutamine stress echocardiography (DSE) has been demonstrated to be a reliable technique for identification of myocardial viability, 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) remains the reference technique for detection of viable myocardium (2,3). An advantage of PET is the possibility of a quantitative analysis. In contrast, DSE relies on a subjective interpretation of wall motion (4,5). Tissue Doppler imaging (TDI) has been suggested for quantitative analysis of regional myocardial function (6,7). It allows the assessment of local tissue velocities (point velocities). The point velocity of a specific LV region, however, does not differentiate between active contraction and passive drawing motion related to translation and rotation of the whole heart or contraction of adjacent segments. Strain rate imaging (SRI) is a new technique derived from TDI, which allows the determination of velocity gradients between two points in space. The resulting contraction variable is independent of passive tethering effects from other regions and therefore appears promising for quantification of regional myocardial function (8,9). Although the technique has been validated in animal models, there is only little experience in clinical settings (10–12). This study evaluated the use of SRI, in combination with LV stimulation, using dobutamine for the identification of viable myocardium determined by 18FDG PET in patients with significant LV dysfunction.
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.
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 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 + Δr])/Δr, as described previously (9). An offset of Δr = 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.
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 ttest, 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.
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.
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.
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.
Systolic SR sampling
Analysis of SR samplings was possible in 542 segments (92%). Strain rate analysis was possible in the same 192 segments with dyssynergy at rest, as in TDI. Peak systolic SR data at rest and during dobutamine stimulation for the different viability states, as determined by 18FDG PET, are given in Table 2. Peak systolic SR was similar at rest for both viable and nonviable myocardium. During dobutamine stimulation, the peak systolic SR increased significantly for viable myocardium, whereas it remained unchanged for nonviable myocardium (Table 2). Figures 1 and 2⇓⇓show SR images and the analysis of SR curves of a dyssynergic segment found to be viable by 18FDG PET.
In addition, the relationship between SR data and PET results for all LV segments, including segments with normal function, was analyzed. Peak systolic SR at rest was 0.85 ± 0.39 l/s for myocardium defined as normal or viable by PET, and 0.64 ± 0.32 l/s for myocardium defined as nonviable by 18FDG PET (p < 0.001). Repeat analysis of peak systolic SRI data was performed for 30 segments to evaluate the reproducibility of SR data. There was a mean difference of 0.05 ± 0.03 l/s between the first and second analysis.
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 3shows that SR analysis compared favorably with two-dimensional DSE and TDI for the detection of viability.
This study demonstrated that: 1) SRI can be used for assessment of myocardial function in a routine clinical setting; 2) SRI, in combination with dobutamine stimulation, is an accurate means to determine myocardial viability determined by 18FDG PET; and 3) SRI compares favorably with two-dimensional echocardiography and TDI in the determination of myocardial viability determined by 18FDG PET.
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.
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.
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.
- confidence interval
- dobutamine stress echocardiography
- left ventricle or ventricular
- positron emission tomography
- receiver operating characteristic
- strain rate
- strain rate imaging
- tissue Doppler imaging
- Received February 22, 2001.
- Revision received October 15, 2001.
- Accepted November 1, 2001.
- American College of Cardiology
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