Multimodality imaging in chronic coronary artery disease
Henneman, M.M.
Citation
Henneman, M. M. (2008, December 18). Multimodality imaging in chronic coronary artery disease. Retrieved from https://hdl.handle.net/1887/13367
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/13367
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Global and regional left ventricular function:
a comparison between gated single photon emission computed tomography, 2D echocardiography and multi-slice computed tomography
Maureen M. Henneman1, Jeroen J. Bax1, Joanne D. Schuijf1, J. Wouter Jukema1, Eduard R.
Holman1, Marcel P. M. Stokkel2, Hildo J. Lamb3, Albert de Roos3, Ernst E. van der Wall1
1Department of Cardiology, 2Department of Nuclear Medicine, and the 3Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
Eur J Nucl Med Mol Imaging 2006;33:1452-60
2
Chapter
Introduction: Global and regional left ventricular (LV) function are important indicators of the cardiac status in patients with coronary artery disease (CAD). Therapy and prognosis are to a large extent dependent on LV function. Multi-slice computed tomography (MSCT) has already earned its place as an imaging modality for non-invasive assessment of the coronary arteries, but since retrospective gating to the patient’s ECG is performed, information on LV function can be derived.
Methods: In 49 patients with known or suspected CAD, coronary angiography with MSCT imaging was performed, in addition to gated SPECT and 2D echocardiography. LV end- diastolic and LV end-systolic volumes and LV ejection fraction was analyzed with dedicated software (Mass, Medis, Leiden, The Netherlands for MSCT; gated SPECT by QGS, Cedars- Sinai Medical Center, Los Angeles, California), and by the biplane Simpson’s rule for 2D echocardiography. Regional wall motion was evaluated according to a 17-segment model and a 3-point score system.
Results: Correlations were fairly good between gated SPECT and MSCT (LVEDV: r=0.65; LVESV:
r=0.63; LVEF: r=0.60), and excellent between 2D echocardiography and MSCT (LVEDV: r=0.92;
LVESV: r=0.93; LVEF: r=0.80). Agreement for regional wall motion was 95% (κ=0.66) between gated SPECT and MSCT, and 96% (κ=0.73) between 2D echocardiography and MSCT.
Conclusions: Global and regional LV function and LV volumes can adequately be assessed with MSCT. Correlations with 2D echocardiography are stronger than with gated SPECT.
Introduction
Left ventricular (LV) systolic function is important for risk stratification in coronary artery disease (CAD).1-3 Cardiac magnetic resonance (CMR) is currently regarded as the gold standard for the evaluation of LV volumes and ejection fraction; however other non-invasive imaging techniques can also be used for the assessment of these parameters. A widely used imaging modality for this purpose is 2D echocardiography as well as gated single photon emission computed tomography (SPECT). Cardiac multi-slice computed tomography (MSCT) is an upcoming technique for non-invasive evaluation of coronary arteries.4-6 Since the MSCT scan is linked to the patient’s electrocardiogram (ECG), retrospective gating is possible. This enables the measurement of LV volumes and ejection fraction, and even the assessment of regional wall motion on the short-axis images. However, extensive validation of 16- and 64-slice MSCT in assessing global and regional LV function and LV volumes has not yet been performed. Although MSCT is currently not regarded as the first choice imaging modality for the evaluation of these parameters because of the relative high radiation burden, it can provide additional information on the cardiac status in addition to non-invasive evaluation of the coronary arteries.
The aim of the present study was to perform an extensive comparison between MSCT, gated SPECT and 2D echocardiography, in assessing global and regional LV function and volumes in patients with known or suspected CAD.
Methods
Patients and study protocol
Forty-nine patients with known or suspected CAD underwent 16-slice MSCT (n=31) or 64-slice MSCT imaging (n=18) to assess coronary artery disease. Patients were selected consecutively, depending on the availability of 2D echocardiography and gated SPECT. We retrospectively analyzed global and regional LV function and LV volumes, and compared these measurements with 2D echocardiography and gated SPECT imaging. The study population consisted of 35 men and 14 women, with a mean age of 62±12 years. Seventeen (35%) patients had a history of previous myocardial infarction. A total of 30 (61%) patients used beta-blocking agents. Clinical characteristics of the study population are summarized in Table 1.
Table 1. Clinical characteristics of the study population (n=49).
Characteristic Age (yrs) Men
History of myocardial infarction Location
Anterior Inferior
Q wave on electrocardiogram PCI
CABG
62±12 35 (71%) 17 (35%)
7 (41%) 10 (59%) 12 (71%) 16 (33%) 7 (14%) PCI=percutaneous coronary intervention; CABG=coronary artery bypass grafting
Patients with (supra-)ventricular arrhythmias were excluded, as well as patients with renal insufficiency (serum creatinine >120 mmol/l) and known allergy to iodine contrast media.
MSCT
Data acquisition, 16-slice MSCT
In 31 patients, MSCT examination was performed with a 16-slice Toshiba Multi-slice Aquilion 16 system (Toshiba Medical Systems, Otawara, Japan). Scan parameters were as follows: collimation was 16x0.5 mm; rotation time 400, 500 or 600 ms, depending on heart rate, and tube current and voltage were 250 mA and 120 kV, respectively. Total contrast dose for the scan varied from 120 to 150 ml, depending on total scan time, with an injection rate of 4 ml/s through the antecubital vein (Xenetix 300, Guerbet, Aulnay S. Bois, France), followed by a saline flush of 40 ml. After a predefined threshold of +100 Hounsfield units (HU) was reached in the region of interest (ROI) placed in the aorta, the helical scan was started automatically. All images were acquired during an inspiratory breath hold, while the electrocardiogram was registrated simultaneously for retrospective gating of the data. With the aid of a segmental reconstruction algorithm, data of 2 or 3 consecutive heart beats were used to generate a single image.
Data acquisition, 64-slice MSCT
In 18 patients, MSCT examination was performed with a 64-slice Toshiba Multi-slice Aquilion 64 system (Toshiba Medical Systems, Otawara, Japan). The scan was performed according to the following parameters: collimation was 64x0.5 mm and rotation time was 400 or 450 ms, depending on heart rate. Tube current and voltage were 300 mA and 120 kV, respectively. Total amount of contrast (Iomeron 400, Altana, Konstanz, Germany) was 80 ml, followed by a saline flush of 40 ml.
After a predefined threshold of +100 HU was reached in the ROI placed in the aorta, the helical scan started automatically. All images were acquired during an inspiratory breath hold, while the ECG was registrated simultaneously for retrospective gating of the data.
For assessment of LV function and LV volumes on both 16- and 64- slice MSCT images, 5.0-mm slices were reconstructed in the short-axis orientation at 20 time points, starting at early systole (0% of cardiac cycle) to end-diastole (95% of cardiac cycle) in steps of 5%. Consequently, images of the 16- and 64-slice MSCT were transferred to a remote workstation with dedicated cardiac function analysis software (CMR Analytical Software System, Medis, Leiden, The Netherlands).
Data analysis
To determine LV function, an independent observer manually outlined endocardial borders on the short-axis cine images. The papillary muscles were regarded as being part of the left ventricular cavity. The LV end-diastolic (LVEDV) and LV end-systolic (LVESV) volumes were calculated and the LV ejection fraction (LVEF) was derived by subtracting the end-systolic volume from the end- diastolic volume and dividing the result by the end-diastolic volume. The regional wall motion
was assessed visually using the short-axis slices, by two observers blinded to all other data using a 17-segment model.7 A 3-point scoring system was used to assign to each segment a wall motion score: 1=normokinesia, 2=hypokinesia, 3=a- or dyskinesia.8
Data on intraobserver variability for MSCT measurements in our institution are 1.7±7.6 ml (LVEDV), 1.0±6.2 ml (LVESV) and -0.93±3.2% (LVEF).
Gated SPECT imaging
Myocardial SPECT imaging with technetium-99m tetrofosmin (500 MBq, injected at rest) was performed using a triple head SPECT camera system (GCA 9300/HG, Toshiba Corp.) equipped with low energy high-resolution collimators. Around the 140-KeV energy peak of technetium-99m tetrofosmin, a 20% window was used. A total of 90 projections (step and shoot mode, 35 seconds per projection, imaging time 23 minutes) were obtained over a 360-degree circular orbit. Data were stored in a 64x64 matrix. LV volumes were calculated from the gated short-axis images using previously validated and commercially available automated software (quantitative gated SPECT, QGS, Cedars-Sinai Medical Center, Los Angeles, California).9 After segmentation of the LV, endo- and epicardial surfaces are estimated and displayed, the LV end-systolic and end-diastolic volumes are calculated and the LV ejection fraction can be derived. Regional wall motion was evaluated using the same 17-segment model and 3-point scale as described above for MSCT.
2D echocardiography
In this patient population, 2D echocardiography was performed as part of clinical protocols.
Patients were imaged in the left lateral decubitus position with a commercially available system (Vingmed Vivid-7, GE-Vingmed, Milwaukee, Wisconsin, USA). Images were acquired using 3.5-MHz transducer at a depth of 16 cm in the parasternal view and apical 2- and 4-chamber views. From the apical 2- and 4-chamber views, the LV volumes were derived and LVEF was calculated using the biplane Simpson’s rule.10 Regional wall motion was assessed using the same 17-segment model and 3-point scoring system as described for MSCT and gated SPECT. Global and regional LV function and LV volumes were assessed by an experienced cardiologist, who was blinded to the results of MSCT and gated SPECT.
Data on intraobserver variability for 2D echo measurements in our institution are 6±9 ml (LVEDV), 4±7 ml (LVESV), and 4±4% (LVEF).
Statistical analysis
Continuous data are expressed as mean±SD. Agreement for LV volumes and global LV function by MSCT and gated SPECT, and MSCT and 2D echocardiography was determined by Pearson’s correlation coefficient and Bland-Altman analysis.11 The 95% limits of agreement were defined as the range of values ±2 SDs from the mean value of differences. Agreement between findings on MSCT, gated SPECT and 2D echocardiography for assessment of regional LV function was calculated and κ values were determined (<0.40 poor agreement, 0.40 to 0.75 fair to good, and >0.75 excellent).12 A P-value <0.05 was considered statistically significant.
Results
Left ventricular end-diastolic volume
On gated SPECT, a mean LVEDV was found of 86±30 ml (range 33 to 171 ml) and 139±35 ml (range 64 to 240 ml) on 2D echocardiography, compared to 137±32 ml (range 71 to 210 ml) on MSCT.
Correlation coefficients for LVEDV were fairly good (r=0.65; P <0.001 for gated SPECT compared with MSCT, Figure 1A) ,and excellent (r=0.92; P <0.001 for 2D echocardiography compared with MSCT, Figure 2A). Bland-Altman analysis showed a mean difference of values of -51 ml for the comparison between gated SPECT and MSCT (95% limits of agreement ranging from -103 to 2 ml, Figure 1B), and a mean difference of values of 2 ml for the comparison between 2D echocardiography and MSCT (95% limits of agreement ranging from -25 to 29 ml, Figure 2B).
A
y=0.6969x + 76.928 r=0.65; P <0.001
0 50 100 150 200 250
0 50 100 150 200
LVEDV SPECT (ml)
LVEDV MSCT (ml)
B
-120 -100 -80 -60 -40 -20 0 20 40
40 90 140 190
Mean LVEDV SPECT - MSCT (ml) Difference in LVEDV SPECT - MSCT (ml)
Figure 1. (A) Linear regression plot shows correlation between left ventricular end-diastolic volume (LVEDV) as measured by MSCT and gated SPECT. (B) Bland-Altman plot of LVEDV shows the difference between each pair plotted against the average value of the same pair, i.e. mean value of differences (solid line) and mean value of differences±2 SDs (dotted lines).
Left ventricular end-systolic volume
On gated SPECT, a mean LVESV was found of 36±21 ml (range 4 to 100 ml) and 63±19 ml (range 28 to 124 ml) on 2D echocardiography, compared to 59±21 ml (range 23 to 119 ml) as assessed on MSCT.
Correlation coefficients for LVESV were fairly good (r=0.63; P <0.001) for gated SPECT compared with MSCT (Figure 3A), and excellent (r=0.93; P <0.001) for 2D echocardiography compared with MSCT (Figure 4A). Bland-Altman analysis showed a mean difference of values of -23 ml for the comparison between gated SPECT and MSCT (95% limits of agreement ranging from -59 to 13 ml, Figure 3B), and a mean difference of values of 4 ml for the comparison between 2D echocardiography and MSCT (95% limits of agreement ranging from -12 to 20 ml, Figure 4B).
A
y=0.8541x + 18.21 r=0.92; P <0.001
0 50 100 150 200 250
0 50 100 150 200 250 300
LVEDV ECHO (ml)
LVEDV MSCT (ml)
B
-30 -20 -10 0 10 20 30 40 50
50 100 150 200 250
Mean LVEDV ECHO - MSCT (ml) Difference in LVEDV ECHO - MSCT (ml)
Figure 2. (A) Linear regression plot shows correlation between left ventricular end-diastolic volume (LVEDV) as measured by MSCT and 2D echocardiography. (B) Bland-Altman plot of LVEDV shows the difference between each pair plotted against the average value of the same pair, i.e. mean value of differences (solid line) and mean value of differences±2 SDs (dotted lines).
A
y=0.6421x + 35.864 r=0.63; P <0.001
0 20 40 60 80 100 120 140
0 20 40 60 80 100 120
LVESV SPECT (ml)
LVESV MSCT (ml)
B
-80 -60 -40 -20 0 20 40 60
0 20 40 60 80 100 120
Mean LVESV SPECT - MSCT (ml) Difference in LVESV SPECT - MSCT (ml)
Figure 3. (A) Linear regression plot shows correlation between left ventricular end-systolic (LVESV) as measured by MSCT and gated SPECT. (B) Bland-Altman plot of LVESV shows the difference between each pair plotted against the average value of the same pair, i.e. mean value of differences (solid line) and mean value of differences±2 SDs (dotted lines).
A
y=1.0095x - 4.414 r=0.93; P <0.001
0 20 40 60 80 100 120 140
0 20 40 60 80 100 120 140
LVESV ECHO (ml)
LVESV MSCT (ml)
B
-20 -15 -10 -5 0 5 10 15 20 25
0 50 100 150
Mean LVESV ECHO - MSCT (ml) Difference in LVESV ECHO - MSCT (ml)
Figure 4. (A) Linear regression plot shows correlation between left ventricular end-systolic (LVESV) as measured by MSCT and 2D echocardiography. (B) Bland-Altman plot of LVESV shows the difference between each pair plotted against the average value of the same pair, i.e. mean value of differences (solid line) and mean value of differences±2 SDs (dotted lines).
Left ventricular ejection fraction
The mean values for LVEF were 62±13% (range 40 to 88%) on gated SPECT, 55±8% (range 32 to 73%) on 2D echocardiography and 58±8% (range 40 to 73%) on MSCT. Correlation coefficients for LVEF were fairly good (r=0.60; P <0.001) for gated SPECT compared with MSCT (Figure 5A), and good (r=0.80; P <0.001) for 2D echocardiography compared with MSCT (Figure 6A). Bland-Altman analysis showed a mean difference of values of 4% for the comparison between gated SPECT and MSCT (95%
limits of agreement ranging from -17 to 24%, Figure 5B), and a mean difference of values of -3% for the comparison between 2D echocardiography and MSCT (95% limits of agreement ranging from -13 to 7%, Figure 6B).
A y=0.3684x + 35.238 r=0.60; P <0.001
0 20 40 60 80
0 20 40 60 80 100
LVEF SPECT (%)
LVEF MSCT (%)
B
-40 -30 -20 -10 0 10 20 30
35 45 55 65 75 85
Mean LVEF SPECT - MSCT (%) Difference in LVEF SPECT - MSCT (%)
Figure 5. (A) Linear regression plot shows correlation between left ventricular ejection fraction (LVEF) as measured by MSCT and gated SPECT. (B) Bland-Altman plot of LVEF shows the difference between each pair plotted against the average value of the same pair, i.e. mean value of differences (solid line) and mean value of differences±2 SDs (dotted lines).
A y=0.7634x + 15.977 r=0.80; P <0.001
0 20 40 60 80
0 20 40 60 80
LVEF ECHO (%)
LVEF MSCT (%)
B
-15 -10 -5 0 5 10
30 40 50 60 70 80
Mean LVEF ECHO - MSCT (%) Difference in LVEF ECHO - MSCT (%)
Figure 6. (A) Linear regression plot shows correlation between left ventricular ejection fraction (LVEF) as measured by MSCT and 2D echocardiography. (B) Bland-Altman plot of LVEF shows the difference between each pair plotted against the average value of the same pair, i.e. mean value of differences (solid line) and mean value of differences±2 SDs (dotted lines).
Regional wall motion
In all 833 segments wall motion analysis was possible. In 71 (9%) segments wall motion abnormalities were observed on gated SPECT: 47 segments displayed hypokinesia, whereas in 24 segments a- or dyskinesia was present. On MSCT, a decreased wall motion was detected in 53 (75%) segments. A good agreement was shown between the two techniques, with 95% of the segments scored identically on both modalities (κ=0.66, Table 2). Agreements for the individual gradings for the regional wall motion (normokinesia, hypokinesia, and a -or dyskinesia) were 98%, 60%, and 54%, respectively.
Table 2. Agreement between MSCT and gated SPECT in the evaluation of wall motion abnormalities (95%, κ statistics 0.66).
MSCT
SPECT 1 2 3 Total
1 749 13 0 762
2 18 28 1 47
3 0 11 13 24
Total 767 52 14 833
1=normokinesia; 2=hypokinesia; 3=akinesia or dyskinesia
On 2D echocardiography, reduced wall motion was observed in 72 (9%) segments: 51 segments displayed hypokinesia, and 21 segments were a- or dyskinetic. MSCT detected correctly a wall motion abnormality in 54 (75%) segments. A good agreement was demonstrated between the 2 techniques, with 96% of the segments scored identically on both modalities (κ=0.73, Table 3).
Table 3. Agreement between MSCT and 2D echocardiography in the evaluation of wall motion abnormalities (96%, κ statistics 0.73).
MSCT
2D echo 1 2 3 Total
1 749 11 1 761
2 15 36 0 51
3 3 5 13 21
Total 767 52 14 833
1=normokinesia; 2=hypokinesia; 3=akinesia or dyskinesia
Agreements for the individual gradings for the regional wall motion were 98% (normokinesia), 71%
(hypokinesia), and 62% (a- or dyskinesia).
Discussion
Several imaging modalities allow assessment of global and regional LV function and LV volumes.
The imaging procedure of MSCT is relatively simple (it is the same scan procedure as is performed for coronary angiography with MSCT, since the radiation burden is too high to justify MSCT imaging solely for evaluation of cardiac function). For reconstruction of the scan in short axis cine-loops, subsequent delineation of the endocardial contours and analysis of LV volumes and regional function, approximately 15 to 20 minutes is needed. The reproducibility of the measurements with MSCT is excellent. Motion artifacts in the scan can potentially blur the endocardial contours, and can thus diminish the reliability of functional measurements. However, with the 64-slice MSCT the imaging time has been reduced to 10 seconds which is a manageable breath hold for almost all patients. In patients with cardiovascular disease, global and regional LV function and LV volumes play a significant role in clinical work up, therapy and prognosis. MSCT imaging in patients will be performed primarily for evaluation of coronary artery disease; in these patients additional information on global and regional left ventricular function and left ventricular volumes can be of incremental value for making diagnosis and deciding on therapeutic strategy. Since MSCT can provide information on these parameters in addition to evaluation of the coronary arteries, it is important to validate assessment of these parameters by MSCT in comparison to more established modalities. The purpose of the present study was to evaluate the performance of MSCT for the assessment of global and regional LV function and LV volumes, and to compare the MSCT findings with measurements on gated SPECT and 2D echocardiography.
Our results show that MSCT and 2D echocardiography correlate very well for assessment of LVEDV, whereas the correlation with gated SPECT for these parameters was less strong. An explanation for this finding could be that a larger part of the LV outflow tract is visible on MSCT and 2D echocardiography and thus included LV analysis, as compared to gated SPECT.13 It is possible that, on gated SPECT, due to lower counts in the basal part of the septum, this part of the LV will be underestimated.
Furthermore, it is known that the diagnostic accuracy of gated SPECT is lower in small hearts.14 This could also contribute to the somewhat lesser correlations observed between gated SPECT and MSCT, as compared to the correlations between 2D echocardiography and MSCT. The fact that 500 MBq of technetium-99m tetrofosmin was used could also have contributed to this finding. In this study the data on evaluation of LVEF appear to be the most homogeneous among the techniques.
Nevertheless, the results of the present study are in line with a previous report of Yamamuro et al.15 The authors compared functional analysis performed with 8-slice MSCT performed with gated SPECT, 2D echocardiography and CMR. In that study, assessment of LVEF with MSCT was more accurate as compared to gated SPECT or 2D echocardiography.
In the present study, agreement for regional wall motion between gated SPECT and MSCT was good (κ=0.66), and even slightly better between 2D echocardiography and MSCT (κ=0.73). These results are in line with previous studies.16-18 However, CMR is currently regarded as gold standard for the assessment of cardiac volumes and function. Mahnken et al.19 compared 16-slice MSCT with CMR for the evaluation of regional wall motion, and demonstrated a good overall agreement of 86.3% (κ=0.79), indicating that MSCT is a suitable imaging modality for the assessment of regional wall motion.
However, several limitations must be mentioned. First, an ongoing issue is the radiation burden of MSCT. For this matter, MSCT is not considered to be the first choice imaging modality for the assessment of global and regional LV function and volumes. Nevertheless, additional information on global and regional LV function is essential in the evaluation of cardiac disease and the present study demonstrated that this information can be derived from the same MSCT data set as used for coronary artery imaging. Second, no comparison with CMR has been performed in the current study. However, gated SPECT and 2D echocardiography are well established imaging modalities for analysis of cardiac function and they are frequently used for this purpose in daily clinical practice.
Therefore, validation against these techniques is important.
Another limitation with regard to the study population is that the study population was relatively small and that only patients with slightly reduced or normal LVEF were included. Last of all, in this study 31 patients underwent 16-slice MSCT, whereas in 18 patients 64-slice MSCT was performed.
Yet, comparison of Bland-Altman analyses between these groups did not show a significant difference for any of the global LV function parameters, nor was there a difference for regional LV function.
Conclusions
In summary, assessment of global and regional LV function and LV volumes can be well performed with MSCT. Correlations between gated SPECT and MSCT, and between 2D echocardiography and MSCT are sufficiently adequate to evaluate cardiac function.
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