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Coronary Angiography with Flat Panel Digital Detectors Significantly Increases the Sensitivity for Calcium Detection in Relation
July 2005
Coronary calcification is an important process of atherosclerosis and represents advanced coronary disease.1,2 The presence and extent of coronary calcification is an important determinant of the outcome of percutaneous intervention (increases the risk of dissection after balloon dilation, may indicate plaque rotational ablation as initial treatment, or may dissuade from direct stenting).3–6
For these reasons, the detection of calcium is relevant in the evaluation of the coronary arteries. Coronary angiography has been the “gold standard” for diagnosis and interventional treatment of coronary disease, despite its many inherent limitations. Intravascular ultrasound provides transmural images of coronary arteries in vivo, being free of the constraints of angiography, and has been extensively used to evaluate the extent and depth of coronary calcification.7–11
Several studies with IVUS have demonstrated that angiography is relatively specific, but not very sensitive for the detection of coronary calcium deposits. Mintz et al., with a large sample of patients, reported a sensitivity of 48% and a specificity of 89%.9 In this study, calcium was detected in 73% of lesions by IVUS, but only in 38% by angiography. Tuzcu et al. compared angiography and IVUS and observed a sensitivity of 45% and a specificity of 82% for calcium detection.10
A new fluoroscopic imaging modality has emerged recently, providing higher image quality and dose reduction. This technology is based on a FPDD of amorphous silicon, which works by converting X-ray signals into digital images at the point of acquisition. The detector captures information with minimal loss over the full range of typical exposures at a low dose, eliminating some artifacts and distortions associated with conventional image intensifier chains.12 However, there are no studies demonstrating that these theoretical advantages translate into a relevant diagnostic improvement with practical implications.
In this study, we compared IVUS and coronary angiography for detection of calcium, but we used two different fluoroscopic systems, one with a conventional image intensifier chain, and the other with flat-panel digital detector technology.
Methods
Patients. From January 2002 to January 2003, 100 consecutive patients were studied by IVUS and coronary angiography with a conventional system (Advantx™ DLX 3, GE Medical systems). From February 2003 to March 2004, 100 consecutive patients were studied by IVUS and coronary angiography with a flat panel digital detector system (Innova™ 2000, GE Medical systems). The study group was comprised of these 200 patients; the first 100 were studied in 2002, when we only had a conventional fluoroscopy system, and the other 100 were studied in 2003/2004, when the new Innova 2000 FPDD system became available. Therefore, no patient selection for the equipment existed. These 200 patients underwent IVUS examination of target lesions in order to assess severity and other lesional characteristics, and to guide therapeutic intervention when indicated. An informed, written consent was obtained from all patients.
Coronary angiography. Angiograms of the 200 patients were reviewed for calcification by two investigators who were unaware of the IVUS findings. The studies were stored on CD ROM, and were reviewed with the same program on the same computer. The investigators evaluated the presence and extent of calcification, indicating the location of calcium in relation to the lesions, branches and other anatomical data, in order to have matched observations with IVUS studies. The severity of calcification was graded in a semi-quantitative manner: none; mild = barely visible in close examination before contrast injection; moderate = more evident but noted only during the cardiac cycle before contrast injection; severe = noted without cardiac motion before contrast injection, compromising both sides of the arterial lumen.
Intravascular ultrasound. The studies were performed with 20 MHz solid-state, 2.9 Fr Avanar F/X catheters (Volcano Therapeutics Inc., Rancho Cordova, California) interfaced to a dedicated scanner. The catheter was placed distal to the target lesion and pull-back was done to generate images along the length of the vessel. The video loops were stored on CD-ROM, and analysis of the images was performed by one person who was blinded to the angiographic results. Calcium deposit was defined as a highly echogenic area in the plaque generating acoustic shadowing. The presence of calcium was analyzed and reported in the lesion site and reference segments (within 10 mm of lesion borders). Calcification was described by indicating the location in relation to the lesion, branches or other anatomical features, angular extension (degrees of arc of vessel wall exhibiting shadowing) and depth (superficial or deep). For analysis, patients were classified according to the number of quadrants with calcification: no calcium, 1º–90º, 91º–180º, 181º–270º and 271º–360º. This measurement was performed using a protractor placed at the center of the artery. If a target segment contained more than one arc of calcification, the total circumference was recorded.
Statistical analysis. Continuous variables were tested for normal distribution with the Kolmogorov-Smirnov test. Those with normal distribution are expressed as mean ± standard deviation and are compared by t-tests. Those not normally distributed were compared by the Wilcoxon test (paired data) or the Mann-Whitney U-test (unpaired data). Categorical variables are expressed as percentages and compared by chi-square statistics or the Fisher’s exact test, as indicated. The level of significance for hypothesis testing was p Results
The demographics and clinical characteristics of patients included in both groups are presented in Table 1. No significant differences were observed between the groups.
Calcification by angiography. Angiograms using the Advantx system revealed calcium deposits at the target vessel in 32 patients (32%).The calcified lesion was located in the LAD in 59.4% of the patients, in the LCx in 6.2%, in the RCA in 15.6%, and in the LMCA in 18.7%. Calcification was mild in 18 patients, moderate in 13, and severe in 1 case. Angiograms with the Innova system showed calcification at the target vessel in 57 patients (57%). Calcified lesions were found in the LAD in 50.8% of the patients, in the LCx in 10.5%, in the RCA in 22.8%, and in the LMCA in 15.7% of the patients. The degree of calcification was mild in 33 lesions, moderate in 21 lesions, and severe in 3 lesions. In 20 randomized patients from each group, the median radiation dose/area with the Innova system in diagnostic angiography was 51.6 Gy/cm2 (interquartile range 23–67) and 76 Gy/cm2 with the Advantx system (interquartile range 37–107 Gy/cm2) (p = 0.03).
Calcification by ultrasonography. In the CONV group, calcification was reported in 77 cases (77%), and was located in the LAD in 49.3 % of the patients, in the LCx in 18.2%, in the RCA in 20.8%, and in the LMCA in 11.7% of the patients. The calcium deposit was deep in plaque in 25.9% of cases, superficial in 55.8%, and mixed in 18.2%. The classification according to the arc of calcification is described in Table 2. The mean length of target lesion calcium was 3.3 ± 3.74 mm.
In the FPDD group, calcification was observed in 79 cases (79%), and was located in the LAD in 46.8% of the patients, in the RCA in 25.3%, in the LCx in 11.4%, and in the LMCA in 16.45% of the patients. Calcium was superficial in plaque in 53.2%, deep in 29.1%, and mixed in 17.7%. The mean length of target lesion calcium was 3.35 ± 3.8 mm. The extent of calcification in the lesions is presented in Table 2.
Agreement: Angiography versus ultrasound. The overall sensitivity of angiography for calcium detection with the Advantx system was 41.6%, and 72% with the Innova system (p 270º. Specificity was very high and similar, being 91.3% and 90.4% for the CONV and FPDD groups, respectively.
Discussion
The lesion-associated coronary artery calcium increases with the extent and severity of atherosclerosis, and procedures are being developed to detect coronary calcification noninvasively as a screening test for significant coronary disease, and as a prognostic tool.13 Thus, the non-invasive detection of coronary calcium is predictive of future cardiac events, presumably because coronary calcification is a marker for overall atherosclerotic plaque burden.
In coronary angiograms, the detection of calcium in otherwise angiographically normal segments reveals significant disease at that level. Coronary calcification also has important implications in the invasive management of coronary disease. The impact on PCI success is adverse, increasing the rate of dissection and compromising the expansion of the stents implanted.3–6 The presence of calcium should prevent direct stenting and may indicate, in some cases, rotational atheroablation as the first therapeutic approach.14–15
The presence of calcium in non-stenotic left main coronary artery represents disease at this level, and in those with significant stenosis, may portend higher risk when performing angioplasty. Moderate or severe calcification proximal to a diseased bifurcation may dissuade the operator from using such devices as “crushing” stents or bifurcated stent designs. Coronary calcification, thus, offers relevant information regarding diagnosis and interventional treatment.
Coronary calcification: IVUS versus angiography. IVUS has been used to accurately evaluate the extent and depth of calcium deposits in coronary atheroma, and to determine the sensitivity and specificity of angiography for calcium detection.7–11
Several studies comparing angiography with IVUS in the nineties showed that coronary angiography is relatively specific, but has poor sensitivity for detecting mild or moderate calcification, and only moderate sensitivity for extensive lesion calcium. Mintz et al., in a large study, reported a sensitivity of 48% and a specificity of 89%. In this study, calcium was detected by IVUS in 73% of lesions, but only in 38% by angiography.9 The same group demonstrated with IVUS that coronary calcification correlates with plaque burden, but not with the degree of lumen compromise.11 Tuzcu et al. obtained similar results, demonstrating that compared with IVUS, the sensitivity of angiography was 45%, and the specificity was 82% for calcium detection. Calcium was reported in 34% of lesions by angiography and in a 75% of lesions by IVUS.10 The ability of angiography to identify calcium depended on the arcs, lengths and location of the deposits.9–11 The angiographic sensitivity was only 25% for arcs of calcium 270º.9 Superficial calcium was more frequently detected than deep calcium, perhaps because it represents a thicker accumulation — provided that IVUS cannot measure calcium thickness.9–11
Flat panel digital detectors. All of these observations were made with a conventional fluoroscopic system based on image intensifier chains. In recent years, a new fluoroscopic imaging technique has been developed which uses an amorphous silicon flat panel detector to convert X-ray signals into digital images at the point of acquisition. This detector captures information with minimal loss over the full range of typical exposures at a low dose, eliminating some artifacts and distortions associated with conventional image intensifier chains.12
The first flat panel system available on the market was the Innova 2000™ from GE Medical Systems. Taking into consideration all the theoretical advantages of this new X-ray imaging modality and our daily practical observations, we decided to evaluate and compare the diagnosis capability of the flat panel technology for calcium detection, comparing it with the conventional fluoroscopic system and using IVUS as the gold standard.
Patients groups and IVUS findings. In our study, two consecutive series of patients were evaluated for sensitivity and specificity of calcium detection using a conventional angiography system and a flat panel system, compared with IVUS. The patient groups were completely comparable in all characteristics, and no selection bias was possible since these groups corresponded to two consecutive periods, one before and the other after the availability of the Innova 2000 system. The clinical similarity was also confirmed by comparable IVUS findings in both cohorts in relation to calcification. These findings were also similar to those reported by other studies evaluating calcium by IVUS.9,10Angiographic detection of calcium: Conventional versus flat panel. The results with conventional angiography have been comparable to those observed in previous studies performed using similar fluoroscopic systems.9,10 Sensitivity and specificity were in the same range with slight variations consisting in a somehow lower sensitivity and higher specificity, perhaps explained by some observational or X-ray equipment differences in those studies. In our study, sensitivity was 41.6%, compared with 48% and 45% in the previously mentioned studies. According to the authors, the specificity was 91.3%, 89% and 82%.9,10
On the other hand, the results with the Innova 2000 system were remarkably different, demonstrating a significantly higher sensitivity, and a comparable high specificity. The improvement in sensitivity was significant for cases with mild and moderate extension of calcification. The location and length of calcium had no influence on these findings because both groups were similar. These results are in accordance with the theoretical advantages proposed for this technique, and with the empirical observations that we had obtained from our daily clinical practice. Moreover, a previous study evaluating the detection of thoracic calcification with dual-energy chest radiography using a flat panel system, showed an improvement in detection ability.16 It is important to note that this superior performance, as it has been demonstrated in various studies, could be achieved with a lower radiation dose.12 Although the purpose and design of our study did not focus on this aspect, the evaluations performed by the radioprotection unit of our hospital suggested a lower radiation dose in the FPDD group.
Study limitations. An ideal design for this study would require imaging the same series of patients using both fluoroscopic systems, however, this could be ethically controversial and very difficult to accomplish in reality. Therefore, different populations had to be studied using the two angiograpic systems. These two cohorts corresponded to consecutive periods, thus no selection for either of the systems was possible. As was expected the clinical and angiographic profiles of both groups were very similar.
The second limitation could be the sample size which was not very large, but was within the range of other studies.10 The observed differences were statistically significant, however, and we believe they were sufficient to draw meaningful conclusions. Nevertheless, studies conducted with larger samples are warranted.
The third limitation of our study arises from potential observational bias. Although the IVUS investigator was unaware of the angiographic findings, and the angiography investigators were blinded to the IVUS results, the latter could not be blinded to the X-ray imaging systems, since these systems show clear image characteristic differences. Nevertheless, the higher sensitivity obtained with a biased tendency to report more calcium with one system would have been penalized with a lower specificity, but this was not the case.
The final limitation, and perhaps the most important, is the potential inferiority of the Advantx system compared to its more updated model, and to other manufacturers’ conventional fluoroscopic systems. The inclusion of a third group evaluated with one of these sysetms would have strengthened our conclusions, but our facility only has these two systems. The Advantx system has undergone periodic technical updates since 1998, and appropriate component replacements were made on our system to keep it up to date. The previously mentioned studies performed in the late 1990s used other conventional fluoroscopic systems and yielded similar results to those of the Advantx system.
Conclusion
The new fluoroscopic systems based on flat panel digital detectors significantly increase the sensitivity for calcium detection, without detrimental effect on specificity. This advantage is important because it may have a beneficial impact on the diagnosis and therapeutic management of patients with coronary disease.
hemodinamica@humv.es
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