冠状动脉轻中度狭窄病变的结构及生物机械和功能特性的临床研究
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摘要
研究背景 急性冠状动脉综合征是由于不稳定斑块破裂诱发血栓形成所致。60%-70%的冠心病患者发生急性冠状动脉综合征前仅有轻中度血管狭窄(造影直径狭窄率20%-60%)。因此,阻止不稳定的轻中度狭窄病变的发展对预防急性心血管事件尤为重要。
病理学研究发现不稳定斑块具有以下几个组织学特征:较大的斑块但相对大的管腔,大的脂核,伴有炎症细胞浸润的薄的纤维帽,和较多的新生血管。此外,生物机械力是触发不稳定斑块破裂的重要因素。生物机械力包括斑块内部的压力与外部张力,后者包括切变力、环周力及局部管壁的张力,外部张力在触发斑块破裂中起重要作用。我们推测轻中度狭窄斑块易于破裂不仅与其固有的结构特性有关,而且与局部冠状动脉的生物机械特性有关,但关于这方面的研究还有限。主要原因是受常用的研究方法即冠状动脉造影(CAG)的限制,CAG只能显示血管长轴的管腔投影影像,对管壁结构提供的信息有限。血管内超声显像(IVUS)是近年来应用于临床诊断冠状动脉病变的一种新手段,不仅能够显示管壁的形态、结构而且准确测量管腔及斑块面积。因此,我们可以利用IVUS在体研究轻中度狭窄病变血管壁的生物机械特性、斑块的结构及行为。
对冠状动脉中度狭窄病变的患者应当采取何种治疗方案使其受益最大,往往让医生难以决定。CAG与IVUS主要提供冠状动脉解剖上的狭窄程度,对于狭窄病变有无功能意义提供的信息有限,而后者对临床决策非常重要。心肌血流储备(FFRmyo)是反映狭窄病变生理功能的特异性指标,已被发达国家许多心脏中心采用,但在我国此项工作才刚刚起步。由于目前FFRmyo测定费用昂贵,如能利用CAG、IVUS测定的指标评估狭窄病变的功能意义将有助于节省费用和缩短手术时间。
研究目的:1)通过IVUS检测冠状动脉轻中度狭窄病变斑块的结构特性与生物机械特性,探讨这些因素对斑块稳定性的影响;2)探讨CAG显示的造影剂排空滞缓的机制;3)评估轻中度狭窄病变的功能意义,以FFRmyo<0.75为界限值,探讨CAG与IVUS检测指标对狭窄病变功能意义的判断价值。
研究方法 1)20例CAG示造影剂排空滞缓和62例冠状动脉轻中度狭窄(直径狭窄率20%-60%)的患者进行了IVUS检查,同时记录冠状动脉口的压力,分析病变及参照血管段的狭窄程度、斑块特征及血管重构类型,计算病变冠状动脉的生物机械特性(膨胀性与硬度)及斑块行为(斑块面积在心动周期的变化)。依据IVUS检测指标将轻中度狭窄患者分为不稳定型斑块组与稳定型斑块组。比较两组间病变冠状动脉的生物机械特性与斑块行为的差异。2)冠状动脉内注射硝酸甘油前后连续记录IVUS图像,分析管腔面积在注射前后的变化。在偏心病变,分别测量管壁的正常部分与斑块部分周长的变化。3)应用引导导管及压力导丝记录病变近端与远端的压力,冠状动脉内注射腺苷诱发充血相,冠状动脉病变远端的平均压除以近端的平均压计算心肌血流储备分数(FFRmyo)。直线回归分析CAG、IVUS检测指标与FFRmyo之间的相关性;以FFRmyo<0.75为界限值,采用受试者工作特征(ROC)曲线选择CAG、IVUS测量指标的最佳截断点。
研究结果 1)与冠状动脉造影重度狭窄患者比较,轻中度狭窄者软斑块、薄纤维帽、斑块破裂及正重构多见,分别为58%、66%、28%和52%(均p<0.01)。2)造影剂排空滞缓者存在较小的粥样斑块(面积狭窄率19.48%±5.23%),正重构多见(87%)。3)轻中度狭窄患者中具有不稳定斑块特征者较具有稳定斑块特征者冠状动脉膨胀性增大(2.1±0.3 vs.1.2±0.2 mmHg-1, p<0.01),但均低于造影正常的冠状动脉。稳定斑块者病变冠状动脉硬度β增大(8.1±1.3 vs. 29.4±7.2, p<0.01);两组病变斑块面积在收缩期均增加,但不稳定斑块者斑块面积的变化较稳定斑块者大(0.52±0.22 mm2 vs. 0.24±0.19 mm2, p<0.01)。4)冠状动脉内注射硝酸甘油50s时,正常血管横切面积显著增加(32%±6%),病变血管对硝酸甘油诱导的血管扩张反应减弱,但不稳定斑块组血管扩张程度较稳定斑块者大(11%±4% vs.4%±2%,p<0.01);偏心型斑块者,正常部分的管壁周长较斑块部分管壁周长增加的程度大(14%±5% vs.4%±2%,p<0.01)。5)与正常冠状动脉者比较,轻中度狭窄者FFRmyo降低(0.83±0.15 vs. 0.97±0.02, p<0.01),14处病变(30%)低于界限值(FFRmyo<0.75)。根据ROC分析,判断狭窄病变FFRmyo<0.75的最佳截断点,CAG直径狭窄率≥50%,灵敏度=64%,特异性=84%;最小管腔直径≤1.5mm,灵敏度=69%,特异性=90%。IVUS面积狭窄率≥65%,灵敏度=100%,特异性=72%;最小管腔面积≤4mm2,灵敏度=93%,特异性=77%。
研究结论 1)冠状动脉轻中度狭窄者多数具有软的偏心斑块,薄纤维帽与正重构,这些结构特性导致了斑块的不稳定:2)造影剂排空滞缓冠状动脉段的结构特征是小的粥样斑块与正重构,是冠状动脉粥样硬化的早期表现,但具有病变不稳定的结构特点;
3)轻中度狭窄病变中具有不稳定斑块特征的冠状动脉血管膨胀性与斑块膨胀性增大,及偏心病变的正常管壁部分与斑块部分扩张程度不一致,可能影响斑块易损区的张力,增加不稳定斑块的脆弱性;4)冠状动脉中度狭窄患者心肌血流储备功能下降,部分病变(30%)低于界限值(FFRmyo<0.75)。CAG直径狭窄率≥50%及最小管腔直径≤1.5mm,IVUS面积狭窄率≥65%,最小管腔面积≤4
Background Acute coronary syndromes are thought to result from atherosclerotic plaque disruption and intramural thrombus formation. In nearly 60%-70% of all patients presenting with acute ischemic syndromes, a coronary angiogram performed weeks or months before the acute events had shown the culprit lesion site to have mildly stenosis (diameter stenosis between 20%-60%). Therefore, it is probably important for preventing the acute cardiovascular events to stabilize vulnerable plaque in mildly stenosis.
Pathologic studies have demonstrated that ruptured plaques have been shown to have several histomorphologic features including a large plaque, a large lipid core, a thin fibrous cap with inflammatory cell infiltration and more neovascularity. In addition, plaque disruption is triggered by intrinsic plaque changes, such as increased pressure in atheroma and by extrinsic stress. Prior investigators have suggested that several kinds of stress, including shear stress and circumferential and localized wall stress, play an important role in plaque disruption. Therefore, we presume that the plaque vulnerability of mildly lesions will be related to its intrinsic structural features and biomechanical characteristics. However, very little is known about their relationship between structural features and plaque vulnerability and about effect of biomechanical characteristics and plaque behavior on vulnerable plaque. It is well known that coronary angiography (CAG) can not accurately determine lesion morphology because it only shows the silhouette of the contrast materiel passing through the stenotic lesions. In recent years, intravascular ultrasound (IVUS) has evolved as a valuable adjunct to angiography. IVUS allows precise tomographic measurement of lumen area and plaque size, distribution and, to some extent, composition. Therefore, IVUS provide us likelihood for study on structural features and biomechanics characteristics in angiographic mildly stenosis in vivo.
Clinical decision making in patients with intermediate coronary stenosis(40%-60% diameter stenosis) is still challenging. CAG and IVUS are often used to evaluate coronary stenosis severity, but provide a little information in assessment of the functional significance
of the lesion. The later is essential in clinic decision making. Myocardial fractional flow reserve (FFRmyo) is a special index of the functional severity of coronary stenosis. Although the application of FFRmyo to assess intermediate coronary lesion is widely performed in some centers in developed countries, its use in China was lagged. Because it is relatively expensive to measure FFRmyo, it will be beneficial to save the expenses and to short operation time if CAG and IVUS criteria could be clinically used as tools to discriminate functional significant of intermediate stenosis.
Objective The purposes of present study are as follow: 1) to investigate the vulnerable mechanism of mildly lesion by evaluating the effect of structure and biomechanical characteristics on plaque; 2) to investigate the structural characteristics of angiographic contrast materiel drain-lagged segments; 3) to assess the functional significance of the mildly lesion and to find the relation between FFRmyo and CAG indexes (percent diameter stenosis and minimal lumen diameter) and IVUS indexes (percent area stenosis and minimal lumen cross-sectional area) of lesion severity.
Methods 1) In 20 patients of angiographic contrast materiel drain-lagged and in 62 patients of angiographic mildly coronary stenosis (diameter stenosis 20%-60%), IVUS imaging (2.9F catheter, 30-MHz transducer) was performed and intracoronary pressure was recorded. The characteristics of the plaques and reference segments were analyzed and the biomechanical properties (distensibility index and stiffness) of coronary artery were calculated and the plaque behavior during cardiac cycle was determined. The plaques were classified as either unstable plaques group or stable plaques group by IVUS image. The difference of biomechanical properties and plaque
病理学研究发现不稳定斑块具有以下几个组织学特征:较大的斑块但相对大的管腔,大的脂核,伴有炎症细胞浸润的薄的纤维帽,和较多的新生血管。此外,生物机械力是触发不稳定斑块破裂的重要因素。生物机械力包括斑块内部的压力与外部张力,后者包括切变力、环周力及局部管壁的张力,外部张力在触发斑块破裂中起重要作用。我们推测轻中度狭窄斑块易于破裂不仅与其固有的结构特性有关,而且与局部冠状动脉的生物机械特性有关,但关于这方面的研究还有限。主要原因是受常用的研究方法即冠状动脉造影(CAG)的限制,CAG只能显示血管长轴的管腔投影影像,对管壁结构提供的信息有限。血管内超声显像(IVUS)是近年来应用于临床诊断冠状动脉病变的一种新手段,不仅能够显示管壁的形态、结构而且准确测量管腔及斑块面积。因此,我们可以利用IVUS在体研究轻中度狭窄病变血管壁的生物机械特性、斑块的结构及行为。
对冠状动脉中度狭窄病变的患者应当采取何种治疗方案使其受益最大,往往让医生难以决定。CAG与IVUS主要提供冠状动脉解剖上的狭窄程度,对于狭窄病变有无功能意义提供的信息有限,而后者对临床决策非常重要。心肌血流储备(FFRmyo)是反映狭窄病变生理功能的特异性指标,已被发达国家许多心脏中心采用,但在我国此项工作才刚刚起步。由于目前FFRmyo测定费用昂贵,如能利用CAG、IVUS测定的指标评估狭窄病变的功能意义将有助于节省费用和缩短手术时间。
研究目的:1)通过IVUS检测冠状动脉轻中度狭窄病变斑块的结构特性与生物机械特性,探讨这些因素对斑块稳定性的影响;2)探讨CAG显示的造影剂排空滞缓的机制;3)评估轻中度狭窄病变的功能意义,以FFRmyo<0.75为界限值,探讨CAG与IVUS检测指标对狭窄病变功能意义的判断价值。
研究方法 1)20例CAG示造影剂排空滞缓和62例冠状动脉轻中度狭窄(直径狭窄率20%-60%)的患者进行了IVUS检查,同时记录冠状动脉口的压力,分析病变及参照血管段的狭窄程度、斑块特征及血管重构类型,计算病变冠状动脉的生物机械特性(膨胀性与硬度)及斑块行为(斑块面积在心动周期的变化)。依据IVUS检测指标将轻中度狭窄患者分为不稳定型斑块组与稳定型斑块组。比较两组间病变冠状动脉的生物机械特性与斑块行为的差异。2)冠状动脉内注射硝酸甘油前后连续记录IVUS图像,分析管腔面积在注射前后的变化。在偏心病变,分别测量管壁的正常部分与斑块部分周长的变化。3)应用引导导管及压力导丝记录病变近端与远端的压力,冠状动脉内注射腺苷诱发充血相,冠状动脉病变远端的平均压除以近端的平均压计算心肌血流储备分数(FFRmyo)。直线回归分析CAG、IVUS检测指标与FFRmyo之间的相关性;以FFRmyo<0.75为界限值,采用受试者工作特征(ROC)曲线选择CAG、IVUS测量指标的最佳截断点。
研究结果 1)与冠状动脉造影重度狭窄患者比较,轻中度狭窄者软斑块、薄纤维帽、斑块破裂及正重构多见,分别为58%、66%、28%和52%(均p<0.01)。2)造影剂排空滞缓者存在较小的粥样斑块(面积狭窄率19.48%±5.23%),正重构多见(87%)。3)轻中度狭窄患者中具有不稳定斑块特征者较具有稳定斑块特征者冠状动脉膨胀性增大(2.1±0.3 vs.1.2±0.2 mmHg-1, p<0.01),但均低于造影正常的冠状动脉。稳定斑块者病变冠状动脉硬度β增大(8.1±1.3 vs. 29.4±7.2, p<0.01);两组病变斑块面积在收缩期均增加,但不稳定斑块者斑块面积的变化较稳定斑块者大(0.52±0.22 mm2 vs. 0.24±0.19 mm2, p<0.01)。4)冠状动脉内注射硝酸甘油50s时,正常血管横切面积显著增加(32%±6%),病变血管对硝酸甘油诱导的血管扩张反应减弱,但不稳定斑块组血管扩张程度较稳定斑块者大(11%±4% vs.4%±2%,p<0.01);偏心型斑块者,正常部分的管壁周长较斑块部分管壁周长增加的程度大(14%±5% vs.4%±2%,p<0.01)。5)与正常冠状动脉者比较,轻中度狭窄者FFRmyo降低(0.83±0.15 vs. 0.97±0.02, p<0.01),14处病变(30%)低于界限值(FFRmyo<0.75)。根据ROC分析,判断狭窄病变FFRmyo<0.75的最佳截断点,CAG直径狭窄率≥50%,灵敏度=64%,特异性=84%;最小管腔直径≤1.5mm,灵敏度=69%,特异性=90%。IVUS面积狭窄率≥65%,灵敏度=100%,特异性=72%;最小管腔面积≤4mm2,灵敏度=93%,特异性=77%。
研究结论 1)冠状动脉轻中度狭窄者多数具有软的偏心斑块,薄纤维帽与正重构,这些结构特性导致了斑块的不稳定:2)造影剂排空滞缓冠状动脉段的结构特征是小的粥样斑块与正重构,是冠状动脉粥样硬化的早期表现,但具有病变不稳定的结构特点;
3)轻中度狭窄病变中具有不稳定斑块特征的冠状动脉血管膨胀性与斑块膨胀性增大,及偏心病变的正常管壁部分与斑块部分扩张程度不一致,可能影响斑块易损区的张力,增加不稳定斑块的脆弱性;4)冠状动脉中度狭窄患者心肌血流储备功能下降,部分病变(30%)低于界限值(FFRmyo<0.75)。CAG直径狭窄率≥50%及最小管腔直径≤1.5mm,IVUS面积狭窄率≥65%,最小管腔面积≤4
Background Acute coronary syndromes are thought to result from atherosclerotic plaque disruption and intramural thrombus formation. In nearly 60%-70% of all patients presenting with acute ischemic syndromes, a coronary angiogram performed weeks or months before the acute events had shown the culprit lesion site to have mildly stenosis (diameter stenosis between 20%-60%). Therefore, it is probably important for preventing the acute cardiovascular events to stabilize vulnerable plaque in mildly stenosis.
Pathologic studies have demonstrated that ruptured plaques have been shown to have several histomorphologic features including a large plaque, a large lipid core, a thin fibrous cap with inflammatory cell infiltration and more neovascularity. In addition, plaque disruption is triggered by intrinsic plaque changes, such as increased pressure in atheroma and by extrinsic stress. Prior investigators have suggested that several kinds of stress, including shear stress and circumferential and localized wall stress, play an important role in plaque disruption. Therefore, we presume that the plaque vulnerability of mildly lesions will be related to its intrinsic structural features and biomechanical characteristics. However, very little is known about their relationship between structural features and plaque vulnerability and about effect of biomechanical characteristics and plaque behavior on vulnerable plaque. It is well known that coronary angiography (CAG) can not accurately determine lesion morphology because it only shows the silhouette of the contrast materiel passing through the stenotic lesions. In recent years, intravascular ultrasound (IVUS) has evolved as a valuable adjunct to angiography. IVUS allows precise tomographic measurement of lumen area and plaque size, distribution and, to some extent, composition. Therefore, IVUS provide us likelihood for study on structural features and biomechanics characteristics in angiographic mildly stenosis in vivo.
Clinical decision making in patients with intermediate coronary stenosis(40%-60% diameter stenosis) is still challenging. CAG and IVUS are often used to evaluate coronary stenosis severity, but provide a little information in assessment of the functional significance
of the lesion. The later is essential in clinic decision making. Myocardial fractional flow reserve (FFRmyo) is a special index of the functional severity of coronary stenosis. Although the application of FFRmyo to assess intermediate coronary lesion is widely performed in some centers in developed countries, its use in China was lagged. Because it is relatively expensive to measure FFRmyo, it will be beneficial to save the expenses and to short operation time if CAG and IVUS criteria could be clinically used as tools to discriminate functional significant of intermediate stenosis.
Objective The purposes of present study are as follow: 1) to investigate the vulnerable mechanism of mildly lesion by evaluating the effect of structure and biomechanical characteristics on plaque; 2) to investigate the structural characteristics of angiographic contrast materiel drain-lagged segments; 3) to assess the functional significance of the mildly lesion and to find the relation between FFRmyo and CAG indexes (percent diameter stenosis and minimal lumen diameter) and IVUS indexes (percent area stenosis and minimal lumen cross-sectional area) of lesion severity.
Methods 1) In 20 patients of angiographic contrast materiel drain-lagged and in 62 patients of angiographic mildly coronary stenosis (diameter stenosis 20%-60%), IVUS imaging (2.9F catheter, 30-MHz transducer) was performed and intracoronary pressure was recorded. The characteristics of the plaques and reference segments were analyzed and the biomechanical properties (distensibility index and stiffness) of coronary artery were calculated and the plaque behavior during cardiac cycle was determined. The plaques were classified as either unstable plaques group or stable plaques group by IVUS image. The difference of biomechanical properties and plaque
引文
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