【作者】 姜朝晖；

【导师】 杨向军； J(？)rge Hausleiter；

【作者基本信息】 苏州大学 ， 内科学， 2007， 博士

【摘要】 第一部分64层MSCT检测患者冠状动脉非钙化斑块目的1、应用64层螺旋CT评价患者是否存在冠状动脉钙化斑块,非钙化斑块和/或冠脉狭窄。2、结合临床特征,评估冠状动脉非钙化斑块对心血管疾病预后的意义。3、判断冠状动脉钙化非斑块在入选人群中的发生率。方法1、研究对象:选取在2005年10月到2007年1月之间,连续在德国心脏中心就诊符合入选条件的患者,共161例。2、研究对象的是有显著的CAD中等危险因素:(1)有胸痛或者呼吸困难症状但是ECG负荷试验阴性;(2)无胸痛症状但是ECG负荷试验阳性或;(3)无胸痛症状,ECG负荷试验阳性但是有间歇性的心律失常。3、研究对象的除外标准是(1)已知的冠状动脉疾病,(2)胸痛症状合并有心肌缺血的试验阳性;(3)患者存在心律失常,不适于ECG门控MSCT扫描。4、CT扫描器:西门子Sensation 64 CT机型(Sensation 64 Cardiac, Siemens Medical Solutions)。5、扫描参数如下:层数×准直器宽度64×0.6 mm,球管电流60mAs,电压120 kV,机架旋转时间330 ms,螺距0.2。机架每旋转一周可以获取64层的数据,每层厚度0.6mm,同时增加周期性的z-轴飞聚焦技术。6、统计学分析非连续性的变量用百分数表示,采取卡方检验或者Fisher’s精确概率法比较差异。P<0.05提示有显著性的统计学意义。结果1冠状动脉钙化和非钙化斑块的分布161例患者进行了冠状动脉MSCT成像。108例CAD患者中有48例(44%)有冠状动脉非钙化斑块,38例既有非钙化斑块又合并有冠状动脉钙化。63例(39%)患者没有检测到冠状动脉钙化,在这63例患者中10例(16%)患者冠状动脉MSCT显影观察到了非钙化斑块,而且这些非钙化斑块是这些患者患有冠状动脉粥样硬化的唯一表现。98(61%)例患者有钙化斑块,其中有38例(39%)患者同时检测到非钙化斑块,其他60例(61%)患者的冠状动脉MSCT显影检查中未见非钙化斑块;108例CAD患者有冠状动脉非钙化斑或同时合并有冠状动脉钙化,占全部161例入选研究的患者的30%。2、有非钙化斑块和无非钙化斑块患者的临床特征非钙化斑块和那些传统的心血管疾病危险因素,例如年龄,性别,体重指数,血压,吸烟,同时都用于PROCAM积分法估计10年内的心血管疾病危险。有非钙化斑块的患者有很强的糖尿病患病倾向,同时存在显著增高的总胆固醇和LDL水平,而且炎症标记物CRP水平也显著的增高。根据斑块的密度值,大约半数的非钙化斑块是明显富含脂质的斑块。有非钙化斑块的入选患者在使用?受体阻断剂、ACEI、利尿剂和钙拮抗剂等方面没有差异,而使用的他叮类则显著地较低。MSCT检查提示,有非钙化斑块患者的冠状动脉钙化程度比没有非钙化斑块患者的钙化程度要轻些,但是两组比较未见显著性差异(ASE: 80 [9, 246] vs. 170 [17, 554];有非钙化斑块患者vs.没有非钙化斑块患者,P=0.12)。3、64层MSCT对冠脉狭窄的诊断将64层MSCT和冠脉造影QCA结果按同一冠状动脉节段一对一的分析。共分析了冠状动脉节段257段,其敏感性根据狭窄程度有所不同,我们分析了狭窄程度是<50%,>50%和>75%的3个亚组的情况,在冠状动脉近段和中段,结果敏感性分别是80%、75%和88%;在冠状动脉远端敏感性分别是76%、67%和80%;汇总全部节段汇总分析,敏感性分别是79%、73%和80%;特异性无论在冠状动脉近段和中段或者远端,还是汇总全部节段汇总分析都是达97%到了97%。结论1、有CAD中等危险程度的患者,64层MSCT可以检测到冠状动脉非钙化粥样硬化斑块。2、应用无创性的CT造影评估冠状动脉非钙化斑块对冠心病危险分层有着重要的帮助。3、64层MSCT对冠脉狭窄的诊断有很高的准确性,尤其是特异性更高,提示64层MSCT对于冠心病的筛选有着很大的价值。第二部分64层螺旋CT评估患者冠状动脉旁路移植血管目的1、评价64层螺旋CT血管造影对冠状动脉旁路移植血管的诊断价值。2、伴有心律失常的患者中的诊断价值。3、评价在实际临床工作中的非选择的病例,更为准确的评价64层螺旋CT血管造影的诊断价值。方法1、研究对象:在2006年2月到2007年2月,连续入选的138例CABG术后患者,因疑诊冠状动脉旁路移植血管病变就诊。2、研究对象的排除标准是:已知的造影剂过敏或严重的肾功能衰竭( Scr >1.8mg/dl)。在CT扫描过程中伴有心律失常的患者也被纳入研究观察内。3、西门子Sensation 64 CT机型(Sensation 64 Cardiac, Siemens Medical Solutions)。4、扫描参数如下:层数×准直器宽度64×0.6 mm,球管电流60mAs,电压120 kV,机架旋转时间330 ms,螺距0.2。机架每旋转一周可以获取64层的数据,每层厚度0.6mm,同时增加周期性的z-轴飞聚焦技术。5、有创性血管造影用冠状动脉定量分析(QCA)判断冠状动脉及旁路移植血管病变的狭窄程度,其结果由两位不知晓MSCT血管造影结果的心脏病专家评价。采取离线的自动边缘监测系统分析数字造影图像,在本中心的QCA中心实验室进行。6、统计学分析计数资料用百分数(%)表示,计量资料用均数±标准差(mean±SD)表示。MSCT的诊断结果用敏感性,特异性,阳性预测值和阴性预测值和相应的95%可信区间来表示。MSCT血管造影提示血管内腔狭窄≥50%表明冠状动脉旁路移植血管有明显的病变。绝对变量用卡方检验;连续性变量用t检验。P<0.05提示有显著性的统计学意义。结果1. 138例患者共418支冠状动脉旁路移植血管。其中12支因为在以前植入过血管内金属支架而排除在外,406支血管纳入统计分析,移植血管可评价率是98% (397/406)。2、MSCT评估冠状动脉旁路移植血管敏感性,特异性,阳性预测值、阴性预测值和诊断准确率分别是:97% (113/116),97%(273/281)、93%(113/121)和99% (273/276),诊断准确率97%;对于完全闭塞的血管敏感性,特异性,阳性预测值、阴性预测值和诊断准确率都是100%;加上排除在外的血管汇总分析的敏感性是90%。3、MSCT评估静脉旁路移植血管敏感性,特异性,阳性预测值、阴性预测值和诊断准确率分别是:98% (253/259)、98% (88/89)、96%(160/164)、96%(88/92)和99%(160/161),诊断准确率98%(248/253)。4、MSCT评估动脉旁路移植血管敏感性,特异性,阳性预测值、阴性预测值和诊断准确率分别是:98% (144/147)、93% (25/27)、97%(113/117)、86%(25/29)、98%(113/115)诊断准确率是96%(138/144)。5、根据每例患者分析MSCT对冠状动脉旁路移植血管的评估选择可评价的图像分析,MSCT诊断的敏感性,特异性,阳性预测值和阴性预测值分别是100%(95% CI: 94-100%)、92%(95% CI: 82-97%)、93%(95% CI: 85-97%)和100%(95% CI: 93-100%)。如果包括图像不可评价的患者做一个汇总诊断分析,其敏感性,特异性,阳性预测值和阴性预测值分别是100%(95% CI: 94-100%),87%(95% CI: 76-93%),89%(95% CI: 79-94%)和100%(95% CI: 93-100%)。6、MSCT对周围冠状动脉的评估MSCT诊断显著狭窄的敏感性、特异性、阳性预测值和阴性预测值分别是87%、96%、57%和99%,诊断准确率是94%;如果把不可评价的周围冠状动脉包括在内作汇总分析,MSCT诊断显著狭窄的敏感性、特异性、阳性预测值和阴性预测值分别是94%、74%、30%和99%。7、心律失常对准确性的影响扫描过程中有42例(30%)患者出现心律失常,涉及到共131支血管。在伴有心律失常患者中,可评价的冠状动脉旁路移植血管数目明显低于无心律失常的患者(95% vs. 100%,p<0.01)。但是,在可评价血管中,诊断的准确性没有因为心律失常而降低。8、心率对准确性的影响心率<65bpm的患者的移植血管的可评价比例为100%(275 /275)。而50例(36%)平均心率≥65bpm的患者的移植血管的可评价比例是94%(135/143),两者之间有显著性差异,p<0.01。在可评价的冠状动脉旁路移植血管中,无论患者的心率≥65bpm或者<65bpm,诊断准确性无显著的差异。9、体重指数对准确性的影响MSCT对BMI超过30kg/m2的这些肥胖患者诊断的敏感性、特异性、阳性预测值和阴性预测值分别94%、100%、100%和98% ,而对BMI<30kg/m2的患者的敏感性、特异性、阳性预测值和阴性预测值分别99%、96%、91%和99%。结论1. 64层CT血管造影术是评价患者冠状动脉旁路移植血管是否通畅的较可靠的无创性手段2.诊断冠状动脉旁路移植血管有很高的准确性,在伴有心律失常的患者中也同样有很高的准确性。3.由于64层CT分辨率的增加,同时也能够准确的评价旁路移植血管相应的周围冠状动脉。4.如果进一步改进CT的时间和空间分辨率,对于评价运动伪像较多的和血管钙化严重的病例会有很大的帮助。更多还原

【Abstract】 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.更多还原