Assessment Of Non-calcified Coronary Plaque And Coronary Artery Bypass Grafts Using 64-Slice Computed Tomographic Angiography

PartⅠNoncalcified Coronary Plaques by 64-Slice Computed TomographyBACKGROUNDThe assessment of noncalcified coronary plaques by noninvasive strategies may be important to improve cardiovascular risk stratification.OBJECTIVES1. To investigate characteristics of clearly discernible noncalcified coronary plaques2. To assess may allow for improved cardiovascular risk stratification. by these plaques in CT angiography.3. To investigate the prevalence of clearly discernible noncalcified coronary plaques in a patient population with suspected significant CAD.METHODSPatientsBetween October 2005 through January 2007,161 consecutive patients with an intermediate risk for having CAD were referred to our interdisciplinary cardioradiologic MSCT laboratory. The intermediate risk for having significant CAD was defined as (1) chest pain in the presence of negative stress tests or (2) absence of chest pain but positive stress tests or (3) absence of chest pain and of positive stress tests but intermittent arrhythmias. Excluded were patients with (1) known coronary artery disease, (2) chest pain in combination with positive tests for myocardial ischemia or (3) patients with arrhythmias not allowing ECG-triggering of the MSCT scan.Multi-Slice Spiral Computed TomographyPatients with a heart rate >60 bpm received metoprolol 5-20mg iv. before the MSCT scan(Sensation 64 Cardiac, Siemens Medical Solutions). Coronary vasodilatation was achieved by the administration of nitroglycerin 0.8mg sublingually before the scan to obtain a maximum opacification of the coronary arteries. A native scan without contrast dye was performed to determine the total calcium burden of the coronary tree (sequential scan with 30×0.6 mm collimation, tube current 60mAs at 120 kV). Contrast-enhanced CT angiography data were acquired with the use of a spiral scan with 64×0.6-mm collimation, 330 ms gantry rotation, pitch of 0.2 and tube voltage at 120 kV. 64 overlapping 0.6mm slices per rotation were acquired with the use of a focal spot periodically moving in the longitudinal direction (z-flying focal spot). This sampling scheme results in an improved spatial resolution which is identical to that of a 64 x 0.3mm detector (0.4 x 0.4 x 0.4 mm isotropic resolution). Tube current was modulated according to the ECG, with a maximum current of 850-950 mAs during a time period of approximately 330 ms centered at 375ms before the next R wave and reduction by 80% during the remaining cardiac cycle. In our cardiovascular MSCT research laboratory the estimated effective dose associated with cardiac 64-slice CT angiography was estimated to be 11.0±4.1 mSv. Contrast agent (60-80 mL; 350 mg iodine/mL) was injected intravenously (4.5-5.0 mL/s). Transaxial images were reconstructed using an ECG-gated half-scan reconstruction algorithm (temporal resolution 164 ms) and kernel B30f. In case of a heart rate of >65 beats/min, a bi-segmental reconstruction algorithm is applied that uses data obtained from two consecutive heartbeats, reducing the effective reconstruction interval per heart cycle down to 83 ms, depending on the heart rate. The position of the reconstruction window within the cardiac cycle was individually optimized to minimize motion artifacts.MSCT Image InterpretationVessel wall calcifications were quantified on a separate workstation, based on the standard built-in algorithm using an Agatston score equivalent (ASE) adapted for MSCT. Two reviewers independently evaluated the contrast-enhanced MSCT scans by assessment of the axial slices, of multi-planar reformations and of three thin-slab maximum intensity projections (MIPs). Orientated along the heart axis the thin-slab (5 mm thickness, 1 mm increment) MIPs were reconstructed perpendicular to each other. The coronary artery tree was segmented according to modified American Heart Association classification (14) and the segments were investigated for lumen narrowings. Segments were graded as small (diameter < 1.5mm), normal appearing (stenosis grade 0-24%), slightly narrowed (stenosis grade 25-49%), moderately narrowed (stenosis grade 50-74%) and severely narrowed (stenosis grade≥75%). The presence of noncalcified coronary atherosclerotic plaque, alone or in combination with calcifications, was defined as any discernible structure in the coronary artery wall with a computed tomography density below the contrast-enhanced coronary lumen but above the surrounding connective tissue. For the determination of plaque density values the respective coronary segment was rendered and displayed in orthogonal views (0.6mm thick slices) according to the vessel axis. Measurements were obtained from manually traced regions of interests encompassing the noncalcified plaque proportions. Based on previous studies noncalcified plaque proportions with density values < 70HU were classified as predominantly lipid-rich while plaques with density values≥70 were classified as predominantly fibrous-rich.Statistical AnalysisContinuous variables are expressed as median [interquartile range] and compared by means of Mann-Whitney-U test; discrete variables are expressed as counts or percentages and compared with chi-square or Fisher's exact test (whenever an expected cell value was < 5). Statistical significance was accepted for P<0.05.RESULTSNo coronary calcifications were present in 63(39%) patients, while calcified plaques were determined in 98(61%) patients. Subsequent contrast-enhanced coronary CT angiography revealed the presence of noncalcified plaques in 10(16%) of the 63 patients, who had no coronary calcifications. In these patients, noncalcified plaques were the only manifestation of CAD. In patients with coronary calcifications additional noncalcified plaques were detected in 38(39%) patients, while 60(61%) patients were free of noncalcified plaques by CT angiography. In summary, CAD due to the presence of calcified or noncalcified plaques was detected in a total of 108 patients. Patients without CAD were younger and presented with a lower cardiovascular risk profile, resulting in a lower 10-year risk for a cardiovascular event by the PROCAM-Score. Accordingly, less cardiovascular medications were taken by patients without CAD.Noncalcified plaques, alone or in combination with calcifications, were seen in 48(44%) of 108 patients with CAD (30% of all 161 studied patients). Patients with noncalcified plaques did not differ with respect to most traditional cardiovascular risk factors, including age, sex, body mass index, arterial hypertension, smoking as well as the estimated 10-year cardiovascular risk by the PROCAM-Score. Patients with noncalcified plaques were characterized by a trend of having more diabetes mellitus as well as significantly higher total cholesterol and LDL levels. Furthermore, the inflammatory marker CRP was significantly increased in patients with noncalcified plaques. While there were no differences in the rates of ?-blockers, ACE-inhibitors, diuretics as well as Ca2+-antagonists, the use of statins was significantly lower in patients with noncalcified plaques. The MSCT investigation revealed that patients with noncalcified plaques tend to have less coronary calcifications than patients without noncalcified plaques (Agatson Score Equivalent: 80 [9, 246] vs. 170 [17, 554] for patients with vs. without noncalcified plaques; P=0.12). In fact, noncalcified plaques were the only manifestation of CAD in 10(16%) of 63 patients who had no coronary calcifications in the native scan. Noncalcified coronary plaques were identified in a total of 77 coronary segments (1.6±1.1 segments per patient, range 1-5). 34(44%) segments revealed completely noncalcified plaques while 43(56%) segments had mixed plaques with calcified and noncalcified components. The majority of these plaques resulted in a lumen narrowing of <50% and was predominantly located in the left anterior descending (LAD) artery. According to the density values approximately half of noncalcified plaques were predominantly lipid-rich.Noncalcified coronary plaques were detected in 48 (29.8%) of 161 enrolled patients. Although noncalcified plaques together with coronary calcifications were present in 38 of 161 (23.6%) patients, the prevalence of noncalcified plaques as the only manifestation of CAD was 6.2% (10 of 161 patients). Patients with noncalcified plaques were characterized by significantly higher total cholesterol, low-density lipoprotein, and C-reactive protein levels as well as a trend for more diabetes mellitus. The majority of noncalcified plaques resulted in lumen narrowing of <50%. Of the remaining 113 patients, CAD and coronary calcifications were ruled out in 53 of 161 (32.9%) patients, whereas 60 of 161 (37.3%) patients presented with calcifications in the absence of noncalcified plaque.CONCLUSIONS1. With the use of 64-slice CT, clearly discernible noncalcified atherosclerotic coronary plaques can be detected in a large group of patients with an intermediate risk for having CAD.2. The assessment of these plaques by CT angiography may allow for improved cardiovascular risk stratification.3. 64-slice CT has high Diagnostic Accuracy to CAD, especially high Specificity. PartⅡAssessment of Coronary Artery Bypass Grafts Using 64-Slice Computed Tomographic AngiographyBACKGROUND1. Most of the previous studies with 4- and 16-slice CT only assessed graft patency.2. Due to the limited resolution, the evaluation of anastomoses and peripheral vessels was usually not possible.3. The introduction of 64-slice CT with an increased spatial and temporal resolution may enlargen the diagnostic CT capabilities in the assessment of patients after bypass graft surgery.OBJECTIVETo evaluate the accuracy of 64-slice CT angiography in the detection of stenoses after bypass surgery compared with invasive angiography and regardless of the presence of arrhythmia.METHODSStudy populationIn 138 consecutive patients with a history of CABG and in whom invasive angiography was planned for suspected bypass graft disease, MSCT was performed usually 24 hours prior to catheterization. Exclusion criteria were known contrast dye allergy or severe kidney failure(elevated serum creatinine >1.8mg/dl). Patients with arrhythmias at the time of study inclusion or CT scanning were not excluded.Patient Preparation, MSCT Angiography and Image Interpretationcontrast-enhanced CT angiography data(Sensation 64 Cardiac, Siemens Medical Solutions)were acquired after vasodilation with nitroglycerin and administration of intravenous metoprolol in patients with a heart rate >60bpm. The scanning range included the entire course of venous grafts as well as the most proximal part of internal mammary artery(IMA)grafts at their subclavian origin, if these arterial grafts had been used for bypass surgery. The contrast dye volume(90-205mL; 350mg iodine/ml)was individually adapted to match the scan duration and the selected contrast dye flow rates. In order to minimize motion artifacts due to unwittingly diaphragm movements CT angiograms were acquired in the caudo-cranial direction, if the breath holding period lasted≥15s. In patients with sinus rhythm images were reconstructed in mid-diastole with a sharp kernel B36f, while in patients with arrhythmias the image reconstruction was performed usually in mid-diastole and end-systole. The methods for dose estimation of CT angiography have been described, previously. Two investigators who were aware of the surgical CABG report, but were blinded toward the angiographic results, evaluated all bypass grafts with the use of axial slices and three thin-slab maximum intensity projections. Each graft was classified as either evaluable or not evaluable according to the image quality. Bypass grafts treated with placed stents, were excluded from the analysis. The main analysis was performed on a per-graft basis which considered a bypass graft diseased if there was a lumen narrowing≥50% at any graft location. In the per-patient analysis, patients were classified as positive for significant graft disease if there was a significant stenosis in any bypass graft.Invasive angiography.Conventional invasive angiography which was the standard of reference for the comparison with MSCT results, was performed according to standard techniques. The angiograms were evaluated by two cardiologists blinded to the MSCT results. Quantitative coronary angiography was applied to determine lesion severity of diseased bypass grafts.Statistical AnalysisResults are expressed as counts(or proportions in %)or as mean±SD. The analysis was performed(1)on a per-graft basis, evaluating the most severe lesion in a given bypass graft, and(2)on a per-patient basis, evaluating the presence of any significant bypass narrowing in a given patient. The diagnostic MSCT results in the detection of significant disease in the evaluable segments were expressed as sensitivity, specificity, negative and positive predictive value with their respective 95% confidence interval. In addition, a second per-patient based analysis was performed on an"intention-to-diagnose"basis, in which bypass grafts determined as inconclusive by CT angiography were considered as significantly diseased by MSCT(lumen narrowing≥50%).Categorical variables were compared with chi square analysis. Continuous variables were compared using the Student t test. Subgroup analyses focused on the diagnostic 64-slice CT performance in patients with arrhythmias, in patients with higher heart rates, and between arterial and venous bypass grafts. Statistical significance was accepted for P values < 0.05.RESULTS138 patients with a total of 418 bypass grafts were studied. Twelve bypass grafts with previously placed stents were excluded from the analysis.MSCT Compared With Invasive Angiography for Assessment of Bypass GraftsOverall, 397 of 406 grafts(98%)demonstrated with sufficient image quality for the assessment of bypass grafts by MSCT. In 9 grafts image quality was insufficient due to motion artifacts(8 bypass grafts)or due to numerous metallic clips adjacent to the bypass graft(1 bypass graft). According to invasive angiography, 281(71%)of these bypass grafts were patent and non-stenotic, while 116(29%)presented with either complete occlusion(84 grafts, 21%)or significant stenosis(32 grafts, 8%). All 84(100%)occlusions and 113 of 116(97%)graft occlusions or stenoses were correctly identified by MSCT(Table 2, Figure 1 and 2). One stenosis in the proximal third of a LIMA graft and two very short membranous-like stenoses close to the distal anastomosis site in a venous and a radial artery graft were not identified with MSCT. Of the 406 bypass grafts, arterial and venous bypass grafts were present in 147(36.2%)and 259(63.8%)grafts. The diagnostic accuracy did not differ between arterial and venous grafts.Influence of the Presence of Arrhythmias on MSCT Accuracy for Assessment of Bypass GraftsArrhythmias during scanning were present in 42/138(30%)patients with a total of 131 grafts. The evaluability of bypass grafts in patients with arrhythmias was significantly lower than in patients without arrhythmias(95% vs. 100%, p<0.01). No significant differences were detected for the diagnostic accuracy in evaluable grafts.Influence of Heart Rate on MSCT Accuracy for Assessment of Bypass GraftsThe evaluability of 143 bypass grafts in 50/138(36%)patients with a mean heart rate of≥65 bpm was significantly lower than in patients with heart rates <65 bpm(94% vs. 100%, p<0.01). There were no significant differences the diagnostic accuracy in the assessment of evaluable bypass grafts between patients with heart rates≥65 bpm and <65 bpm.Diagnostic MSCT Accuracy on a Per-Patient Based Analysis.On a per patient based analysis, significant disease in bypass grafts could not be ruled out owing to a limited evaluability of the CT scan in 4/138(3%)patients(motion artefacts in 3 patients, extensive metallic clips in one patient). In evaluable patients the sensitivity, specificity as well as PPV and NPV were 100%(95% CI: 94-100%), 92%(95% CI: 82-97%), 93%(95% CI: 85-97%)and 100%(95% CI: 93-100%), respectively. Including the non-evaluable patients for an"intention-to-diagnose"based analysis, the resulting values for sensitivity, specificity as well as PPV and NPV were 100%(95% CI: 94-100%), 87%(95% CI: 76-93%), 89%(95% CI: 79-94%)and 100%(95% CI: 93-100%), respectively.CONCLUSIONS:1. 64-slice CT angiography is a reliable non-invasive method for the evaluation of bypass patency and stenosis.2. A high diagnostic accuracy was obtained despite the inclusion of patients with arrhythmia.3. Precise assessment of peripheral vessels was possible due to the increased resolution of 64-slice CT angiography.4. A further improve of temporal and spatial resolution is still desirable for the evaluation of patients with extensive motion artefacts and severe calcifications.