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DOI: 10.1148/radiol.2203001129
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(Radiology. 2001;220:707-711.)
© RSNA, 2001

Cardiac Imaging

Effect of Electrocardiogram Triggering on Reproducibility of Coronary Artery Calcium Scoring1

Songshou Mao, MD, Hamid Bakhsheshi, RT, Bin Lu, MD, Steve C. K. Liu, MD, Ronald J. Oudiz, MD and Matthew J. Budoff, MD

1 From the Harbor-UCLA Research and Education Institute, 1124 W Carson St, RB-2, Torrance, CA 90502. Received June 20, 2000; revision requested August 18; final revision received March 8, 2001; accepted March 16. Address correspondence to M.J.B. (e-mail: mbudoff@rei.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
PURPOSE: To test the hypothesis that computed tomographic (CT) scanning during early rather than middle diastole can significantly reduce the interscan variability of coronary artery calcium (CAC) scores.

MATERIALS AND METHODS: Five hundred thirty-eight patients were initially enrolled; 282 of them were found to have CAC at electron-beam CT and underwent repeat scanning to measure interscan variability with different electrocardiogram (ECG) triggers. Eight patients were excluded owing to respiratory motion; thus, 274 asymptomatic patients were examined. Patients were randomly assigned to different ECG trigger interval groups: 40% (group 1), 50% (group 2), 60% (group 3), and 80% (group 4). Patients in whom more than one-third of sections had greater than 10% ECG trigger variability were classified in the untriggered group (group 5). Interscan variation was compared among all five groups.

RESULTS: Interscan variabilities in CAC groups 1–5 were 11.5%, 15.3%, 20.3%, 17.4%, and 33.1%, respectively, for total calcium area, and 15.0%, 23.3%, 25.6%, 24.0%, and 42.4%, respectively, for total calcium score. CAC score variability was reduced by 34%; and calcium area variability, by 38% in group 1, as compared with the reduced variabilities in group 4 (P < .01 for both measures). Breath holding was adequate in 812 cases, and ECG triggering was correct in 790 of cases.

CONCLUSION: Study results strongly support the use of an ECG trigger of 40% rather than 80% of the R-R interval in electron-beam CT calcium studies.

Index terms: Computed tomography (CT), electron beam, 548.12111, 548.12116, 548.12119 • Coronary vessels, calcification, 54.812 • Coronary vessels, CT, 548.12111, 548.12116, 548.12119 • Coronary vessels, stenosis or obstruction, 548.76, 548.812


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Quantification of coronary artery calcium (CAC) with electron-beam computed tomography (CT) has shown promise as a surrogate marker of coronary atherosclerosis. It is being used increasingly by cardiologists and primary care physicians in clinical practice to assess cardiac risk (1–5). Limited reproducibility, however, reduces the capability of electron-beam CT to enable accurate tracking of the progression of atherosclerosis—that is, coronary calcium. The lower reproducibility of CAC studies is primarily due to cardiac motion artifacts (2,6–8). The most common trigger time used during electron-beam CT scanning is 80% of the R-R interval (6–10). We previously found that coronary motion is at its nadir during early diastole—that is, 30%–50% of the R-R interval (11). The aim of this study was to test the hypothesis that scanning during early diastole (40% of the R-R interval) can significantly reduce the interscan variability of CAC scores, as compared with scanning during middle diastole (80% of the R-R interval), which is currently the most widely used electrocardiogram (ECG) trigger interval.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Study Population
Five hundred thirty-eight patients who were referred by their primary physician for evaluation of CAC originally underwent CT scanning after giving informed consent. The study was approved by the institutional review board and research committee at our institution. The first scan was visually evaluated for the presence of any CAC, and if calcium was found, the patient underwent a second electron-beam CT CAC examination. Two hundred eighty-two asymptomatic patients with CAC at the first scanning (mean age, 52.6 years) were included in this study. Eight patients with substantial respiratory artifacts (with overlap or misregistration of cardiac structures on at least three sections) were excluded, so 274 patients were left.

The 274 patients were randomly assigned to one of four trigger protocols (groups 1–4) on the basis of the day of their CT examination. Patients in whom at least 10% of the images obtained had erroneous triggering on either scan were placed in group 5. All patients seen for CAC evaluation on a given day underwent scanning with the assigned trigger interval. To avoid scheduling bias, the scanning protocol (ie, assigned trigger interval) was given to the technicians at the beginning of each scanning day after all scheduling for that day was complete. Group 1 consisted of 57 patients; group 2, 55 patients; group 3, 60 patients; group 4, 60 patients; and group 5, 42 patients. Group 5 consisted of 12 patients without ECG triggering on one of two scans and 30 patients in whom more than one-third of the sections obtained had at least 10% of the ECG trigger interval change from the assigned trigger time (because of premature beats or improper triggering). We also analyzed the data according to the patient’s assigned treatment group (intention-to-treat analysis); group 5 was excluded from this analysis, in which the original four groups were assessed.

A total of 820 scans were obtained in this study: Two images each were obtained in the 282 patients (564 images) who had CAC at initial scanning, and one scan each was obtained in 256 patients who did not have CAC at initial scanning. These images were evaluated for ECG triggering and scanning times, as well as for the ability of each patient to maintain adequate breath holding during scanning. To assess breath holding, the technologist (H.B.) looked for evidence of breathing during scanning, and the reader (S.M.) evaluated the images for evidence of respiratory motion between scans.

Electron-Beam CT
Electron-beam CT studies were performed by using a CT scanner (C-150XL; Imatron, San Francisco, Calif). Image sections were obtained with the patient in the supine position and no couch angulation. Thirty contiguous images with 3-mm section thickness were obtained, starting 9 mm above the left main coronary artery to the bottom of both ventricles (12). We used a method previously described (13) to identify the starting point for CAC scanning. The scan acquisition time was 100 msec, with the ECG triggered to points during diastole that corresponded to 40% (group 1), 50% (group 2), 60% (group 3), or 80% (group 4) of the R-R interval. Patients held their breath during the entire acquisition time. The technologist evaluated the first scan for evidence of CAC. If CAC was seen on the scan, the patient underwent repeat scanning with the same protocol and the same R-R trigger. The second scan was obtained within a few minutes of the first one. The patient was not taken off the table between scan acquisitions. A field of view of 35 cm was used to reconstruct images in all studies.

CAC Scoring
The reader (S.M.), who had 10 years experience with electron-beam CT, was blinded with regard to all clinical information related to the patient and with regard to the R-R interval used in that study. To avoid bias, the reader randomly evaluated studies with no knowledge of the patient’s identifying information. Each scan was read once by this blinded observer. We used a CT threshold of 130 HU and required a minimum area of 2 mm2 for identification of a calcific lesion. The lesion score was calculated by multiplying the lesion area by an attenuation factor derived from the maximal HU value within this area, as described by Agatston et al (12).

All scoring was performed by using the intrinsic software in the workstation. The attenuation factor was assigned as follows: 1 for lesions with a maximal attenuation of 130–199 HU, 2 for lesions with a maximal attenuation of 200–299 HU, 3 for lesions with a maximal attenuation of 300–399 HU, and 4 for lesions with a maximal attenuation of 400 HU or greater. The total calcium score was determined by summing the individual lesion scores from each of four anatomic sites: left main, left anterior descending, circumflex, and right coronary arteries. Similarly, the total calcium area was measured by summing the individual lesion areas from all epicardial arteries. The prevalence of small (<10-mm2) calcific lesions and their influence on reproducibility were assessed.

Statistical Analyses
The percentage of variation in the CAC area and Agatston score was defined as follows: {[score 1 - score 2]/[(0.5 x score 1) + (0.5 x score 2)]} x 100. Analysis of the mean variation in CAC area and mean score within each of the five subject groups was performed by using a standard two-sample t test for independent samples. Comparisons of means and variations among the four trigger groups were made by using two-way analysis of variance, and posthoc testing was performed by using the Scheffé test for multiple comparisons. An {alpha} level of 5% (.05) was used to determine statistically significant differences.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
The average interscan variability differed significantly among the four groups. The lowest interscan variability was seen in group 1, that of patients with images obtained by using a 40% ECG R-R trigger interval. The interscan variabilities in CAC (by total area) in groups 1–5 were 11.5%, 15.3%, 20.3%, 17.4%, and 33.1%, respectively. The interscan variabilities in total calcium score were 15.0%, 23.3%, 25.6%, 24.0%, and 42.4%, respectively (Table 1). Similarly, the interscan variabilities in CAC score and area for individual lesions were lowest in group 1. The variabilities in CAC score (by percentage of variation and mean score difference) and area within individual lesions for each group are shown in Table 2. There were significant differences in variability of CAC area and Agatston score between group 1 and groups 3–5, both for total patient CAC and individual lesion CAC (P < .05). There were no significant differences between group 1 and group 2 in CAC area measurements (within patients or individual lesions), but the interscan variability in scores was significantly lower in group 1 than in group 2 for both individual lesion scores (31.8% vs 39.8%; P =.04) and total patient scores (15.0% vs 23.3%; P = .01). When group 1 was compared with groups 2–4, there was a significant improvement in variability according to analysis of variance and posthoc Scheffé test results (P = .035). In the intention-to-treat model, in which patients were enrolled in study groups on the basis of their assigned trigger protocol, variabilities were 18.4%, 25.6%, 27.0%, and 25.9% for groups 1–4, respectively.


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  		TABLE 1. Interscan Variability among Patients in Four Trigger Interval Groups

 

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  		TABLE 2. Interscan Variability among Lesions in Four Trigger Interval Groups

 
No significant differences in total or individual CAC areas and CAC scores were found in groups 2–4 (P > .05). The prevalence of small (<10-mm2) calcific lesions was similar in each group (6%–8%) and did not contribute to the variability among the groups assessed in this study. The causes of poor triggering (10 patients in group 5) were premature beats (atrial and ventricular) and other atrial arrhythmias. Incorrect identification of the R-R wave by the ECG-gating software or inadequate ECG triggering occurred in only 30 (3.7%) of the 820 CAC scans (in 282 persons with two scans plus 256 patients with one scan).

We also measured the scanning times and the ability of each patient to maintain adequate breath holding during scanning. The mean scan acquisition time was 27.8 seconds in this study. Substantial breathing during scan acquisition occurred in only eight (1%) of the 820 cases.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Variation in CAC Volume and Agatston Score
The interscan variability in CAC, as quantitated according to volume, area, or score, has been reported by several investigators (6–10,12,14,15). Interobserver and intraobserver reproducibility was consistently reported to be high. In one study (12), the mean error was 2.5%, with an SD of 5% between two observers, and in another study (14), a 2.5%–5.0% intraobserver difference was noted for one observer, who read the scans twice.

A more important limitation of CAC scanning with electron-beam CT is high interscan variability, which can limit longitudinal studies with this modality (6). The interscan reproducibilities of total CAC scores achieved by several investigators by using Agatston scores are summarized in Table 3. Total patient score variability ranged from 13% to 38% (6,8,9, 14,15). Compared with the Agatston scoring method, volumetric methods have yielded smaller variations (6,9); however, the interscan variability still has been too high with 80% triggering used for short-term (<1-year) tracking of coronary calcium scores.


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  		TABLE 3. Interscan Reproducibility of Total Coronary Calcium Scores

 
By excluding the patients with poor ECG triggering from groups 1–4 (placing them in group 5) and excluding the patients with improper breath holding from all five groups, we were able to systematically eliminate inaccurate triggering and improper breath holding as factors differentiating the different ECG trigger times. The differences seen with varying ECG trigger intervals in our study were due to cardiac motion, which occurred most commonly at or near 80% of the R-R interval (atrial systole; Fig 1). The variabilities in patient calcific area were 11.5%–20.3%; in patient Agatston score, 15.0%–25.6%; in individual lesion area, 25.3%–34.6%; and in individual lesion Agatston score, 31.8%–41.8%. These results are similar to previous reports (9) of interscan reproducibility with this modality. It should be noted that in this study, no patient had coronary calcium on the first scan and a score of zero on the second scan.



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  		Figure 1. Sample ECG tracing demonstrates the trigger time relative to a typical cardiac cycle. The most commonly used trigger, 80% of the R-R interval, occurs on or near the P wave during atrial systole. The triggers used in this study included 40%, 50% ({bullet}), and 60% ({blacklozenge}) of the R-R interval.

 
Factors Affecting Interscan Variability
The causes of interscan variability are multifactorial. First, a partial volume effect and a high signal-to-noise ratio can lead to some interscan variability (6–10). We excluded lesions smaller than 2 mm2 (<4 pixels) from scoring to diminish the possible effect of noise. Even when all parameters and clinical factors are ideal, partial voluming can cause some variation (8). When 3-mm-thick scans are used to detect small foci of calcium, the foci may lie completely within the thickness of one section or be partially included in an adjacent section. Decreased section thickness has been demonstrated to be an important factor in reducing volume average effects and in improving spatial resolution (6).

Another area of variability was demonstrated in a previous study (7) in which image noise was shown to be associated with the subject’s chest circumference. The CAC volumetric score, or volume (area), method (6,9) enables one to exclude some of this variability by not including peak attenuation in these scoring equations. Thus, small changes in peak attenuation should not affect the reproducibility of volume measurements. The volume (or area) method also allows the partial volume effect to be minimized. The use of the step function in the Agatston method to quantitate calcium accentuates the partial volume effect, because all of the pixels within a lesion are weighted according to the value of the highest pixel. This highest pixel value has a large influence on score and has the potential to cause variation between two scans (6). Although the volumetric method might have some theoretical advantages over the Agatston method in relation to scoring, the Agatston method is still the most widely used and studied. The methodological reduction of interscan variability by means of changing the ECG trigger proposed in our study should improve both the Agatston and volume CAC scores.

Another source of scan variability is motion artifact from respiratory motion, which leads to diminished scan reproducibility. Respiratory motion can be reduced, and, thus reproducibility can be optimized, in most cases with careful patient instruction in breath holding (6,8). Most electron-beam CT examinations require only 30 seconds of breath holding to complete a CAC study. In our study, 99% of patients were able to adequately hold their breath for this examination.

We believe that a major contributor to CAC variability is coronary artery motion artifact. This is a major limiting factor in obtaining reproducible diagnostic images at coronary artery scanning (6–10,12–15) and three-dimensional coronary artery angiography (16–19) with electron-beam CT and other tomographic cardiac imaging modalities. The finding in our study that 40% ECG triggering can significantly reduce interscan variability is important. This suggests that optimal ECG triggering can reduce longitudinal motion artifacts—that is, smearing of calcium due to cardiac motion (Fig 2). The decreased motion and clearer visualization of the artery (Fig 2b) have implications in other applications in cardiac imaging, including intravenous coronary angiography with electron-beam CT (16–19) and magnetic resonance (MR) imaging (20), and in tracking atherosclerotic burden over time (21–23). Individual variations with different heart rates could not be assessed in this study owing to the limited size of each study group. It is unlikely that certain heart rates are triggered with lower variability at 80% triggering: Previous study results show that the least motion among all heart rates occurs at 30%–50% of the R-R interval (11).



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  		Figure 2a. (a) Series of transverse CT images obtained with an 80% R-R interval trigger, from the most cranial to the caudal position, show cardiac motion artifacts in the left main (large arrow), left anterior descending (arrowhead), and right coronary (small arrows) arteries. The coronary calcium demonstrates longitudinal motion artifacts—that is, smearing of calcium due to cardiac motion. The right coronary artery (small arrows in middle and bottom rows) demonstrates a smeared appearance owing to cardiac motion. (b) Series of transverse CT images obtained in the same patient as in a at the same levels with a 40% R-R interval trigger. The coronary calcium demonstrates many fewer motion artifacts in the left main (large arrow), left anterior descending (arrowhead), and right coronary (small arrows) arteries at all levels. The right coronary artery, which appears as a circle rather than a smear of calcium on these images, has the most marked decrease in motion. This decrease in motion artifacts improved reproducibility and enabled more accurate visualization of the coronary arteries. In a and b, the top row shows the most cranial sections, which demonstrate the left main and proximal left anterior descending arteries; the middle row shows the middle left anterior descending and right coronary arteries; and the bottom row shows the more caudal sections.

 


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  		Figure 2b. (a) Series of transverse CT images obtained with an 80% R-R interval trigger, from the most cranial to the caudal position, show cardiac motion artifacts in the left main (large arrow), left anterior descending (arrowhead), and right coronary (small arrows) arteries. The coronary calcium demonstrates longitudinal motion artifacts—that is, smearing of calcium due to cardiac motion. The right coronary artery (small arrows in middle and bottom rows) demonstrates a smeared appearance owing to cardiac motion. (b) Series of transverse CT images obtained in the same patient as in a at the same levels with a 40% R-R interval trigger. The coronary calcium demonstrates many fewer motion artifacts in the left main (large arrow), left anterior descending (arrowhead), and right coronary (small arrows) arteries at all levels. The right coronary artery, which appears as a circle rather than a smear of calcium on these images, has the most marked decrease in motion. This decrease in motion artifacts improved reproducibility and enabled more accurate visualization of the coronary arteries. In a and b, the top row shows the most cranial sections, which demonstrate the left main and proximal left anterior descending arteries; the middle row shows the middle left anterior descending and right coronary arteries; and the bottom row shows the more caudal sections.

 
Optimal ECG Triggering and Scan Variability
Reduced interscan variability is partly due to advances in electron-beam CT scanners. In earlier studies of electron-beam CT reproducibility, the high interscan variability was due at least in part to the need for two breath holds to cover the coronary anatomy. The ability to scan the entire heart during one breath hold is at least partially responsible for the improved reproducibility, as seen in this study and in that of Callister et al (9). New ECG-gating software (ie, C-150; Imatron) has been released by the manufacturer of the electron-beam CT scanner (Imatron). This updated software has led to improved gating, and more than 95% of heartbeats are gated appropriately at the correct R-R interval (8). These advances minimize errors due to cardiac motion and misregistration errors due to triggering during various phases of the cardiac cycle. In the present study, 30 out of a total of 820 CAC scans had inadequate ECG triggering (>10% variation from the programmed ECG trigger on more than one-third of sections). This 96.3% accuracy is a marked improvement compared with that of the ECG triggering achieved with the original software, which was previously demonstrated to be 70%–80% accurate (8,24).

In conclusion, the reproducibility of electron-beam CT scans and CAC scores is affected by several controllable factors. Reproducibility can be optimized by using newer ECG-gating software, providing patients with proper instruction on breath holding, and using volumetric scoring methods. The, to our knowledge, previously unreported association between electron-beam CT reproducibility and R-R trigger interval also is a controllable factor. Triggering each scan at 40% of the R-R interval to minimize coronary arterial motion can further reduce scan-to-scan variability and improve cardiac CT and MR image quality.


   FOOTNOTES
 
Abbreviations: CAC = coronary artery calcium, ECG = electrocardiogram

Author contributions: Guarantor of integrity of entire study, M.J.B.; study concepts and design, S.C.K.L., S.M.; literature research, M.J.B.; clinical studies, H.B., B.L.; experimental studies, B.L.; data acquisition, H.B., S.M.; data analysis/interpretation, M.J.B.; statistical analysis, R.J.O., S.M.; manuscript preparation, M.J.B.; manuscript definition of intellectual content, M.J.B.; manuscript editing and review, R.J.O., M.J.B.; manuscript final version approval, S.M., H.B., B.L., M.J.B.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 

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Electron Beam CT Versus 16-MDCT on the Variability of Repeated Coronary Artery Calcium Measurements in a Variable Heart Rate Phantom
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R. C. Detrano, M. Anderson, J. Nelson, N. D. Wong, J. J. Carr, M. McNitt-Gray, and D. E. Bild
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Radiology, August 1, 2005; 236(2): 477 - 484.
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J. Horiguchi, H. Yamamoto, Y. Akiyama, N. Hirai, K. Marukawa, H. Fukuda, and K. Ito
Variability of Repeated Coronary Artery Calcium Measurements by 16-MDCT with Retrospective Reconstruction
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T. Schlosser, P. Hunold, A. Schmermund, H. Kuhl, K.-U. Waltering, J. F. Debatin, and J. Barkhausen
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Radiology, November 1, 2004; 233(2): 586 - 589.
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B. Lu, N. Zhuang, S.-S. Mao, J. Child, S. Carson, and M. J. Budoff
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C. Hong, T. K. Pilgram, F. Zhu, and K. T. Bae
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U. J. Schoepf, C. R. Becker, B. M. Ohnesorge, and E. K. Yucel
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Radiology, July 1, 2004; 232(1): 18 - 37.
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J. Horiguchi, H. Yamamoto, Y. Akiyama, K. Marukawa, N. Hirai, and K. Ito
Coronary Artery Calcium Scoring Using 16-MDCT and a Retrospective ECG-Gating Reconstruction Algorithm
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Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 2004; 9(2): 75 - 82.
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W. Stanford, B. H. Thompson, T. L. Burns, S. D. Heery, and M. C. Burr
Coronary Artery Calcium Quantification at Multi-Detector Row Helical CT versus Electron-Beam CT
Radiology, February 1, 2004; 230(2): 397 - 402.
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J. A. Rumberger and L. Kaufman
A Rosetta Stone for Coronary Calcium Risk Stratification: Agatston, Volume, and Mass Scores in 11,490 Individuals
Am. J. Roentgenol., September 1, 2003; 181(3): 743 - 748.
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C. Hong, K. T. Bae, T. K. Pilgram, and F. Zhu
Coronary Artery Calcium Quantification at Multi-Detector Row CT: Influence of Heart Rate and Measurement Methods on Interacquisition Variability—Initial Experience
Radiology, July 1, 2003; 228(1): 95 - 100.
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B. Lu, N. Zhuang, S.-S. Mao, J. Child, S. Carson, H. Bakhsheshi, and M. J. Budoff
EKG-triggered CT Data Acquisition to Reduce Variability in Coronary Arterial Calcium Score
Radiology, September 1, 2002; 224(3): 838 - 844.
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