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心脏淀粉样变(cardiac amyloidosis,CA)是由于不同的前体蛋白异常折叠沉积于心肌细胞间隙中导致的疾病[1-2],伴有心脏功能受损及心脏电传导异常。临床常见的CA分型包括轻链型CA(light chain CA,AL-CA)和转甲状腺素蛋白相关CA(transthyretin-related CA,ATTR-CA),由于AL-CA和ATTR-CA患者的血清生物标志物、治疗方法和预后存在很大差异,因此CA的分型诊断尤为重要。99Tcm-焦磷酸盐(pyrophosphate,PYP)显像可特异性诊断ATTR-CA,随着其临床应用的进展,临床医师对不同采集时间[99Tcm-PYP 注射后1 h(以下简称早期显像)和99Tcm-PYP注射后3 h(以下简称延迟显像)]及不同采集方式(平面显像和断层显像)图像的解读也有了更深入的认识。由于早期平面显像的假阳性率较高,延迟显像心脏血池的清除更好,因此越来越多的研究者建议进行早期断层显像、延迟断层显像和延迟平面显像,以提高诊断的准确率[3-7],但尚需大样本量的研究结果证实。本研究拟比较99Tcm-PYP双时相平面显像和断层显像的各种阳性诊断标准,并通过比较CA不同临床分型(AL-CA和ATTR-CA)的图像特征,评价不同采集时间、采集方式及评分模式在99Tcm-PYP双时相平面显像和断层显像诊断ATTR-CA中的效能。
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由表1可知,157例疑诊CA的患者中,CA 83例(其中ATTR-CA 23例、AL-CA 60例)、非CA 74例。非CA组、AL-CA组和ATTR-CA组患者高血压、活检(心内膜心肌活检、其他组织活检)、血或尿IFE或FLC、左心室壁厚度>12 mm的差异均有统计学意义(均P<0.05);性别、年龄、左心室射血分数<50%的差异均无统计学意义(均P>0.05)。99Tcm-PYP显像阳性患者的血和尿IFE、FLC检测结果均为阴性,经心内膜心肌活检诊断为ATTR-CA(图1)。99Tcm-PYP显像阴性患者的血和尿IFE、FLC检测结果均为阴性,心内膜心肌活检为阴性,非特异性改变,临床诊断为限制型心肌病(图2)。
组别 例数 性别
(男/女)年龄(岁, )$\bar x \pm s $ 高血压(例) 活检(例) 血或尿IFE或
FLC(例)超声心动图(例) 心内膜心肌 其他组织 左心室射血
分数<50%左心室壁
厚度>12 mm非CA组 74 52/22 58.0±17.9 35 21 13 26 34 55 AL-CA组 60 39/21 59.6±11.1 15 36 24 53 31 58 ATTR-CA组 23 17/6 60.2±12.2 3 15 6 14 10 23 合计 157 108/49 58.9±14.8 53 72 43 93 75 136 检验值 − χ2=0.758 F=0.296 χ2=12.538 χ2=17.411 χ2=8.407 χ2=38.863 χ2=0.634 χ2=18.436 P值 − 0.685 0.744a 0.002 <0.001 0.015 <0.001 0.728 <0.001 注: −表示无此项数据;a表示采用Bonferroni校正,P<0.016为差异有统计学意义。CA为心脏淀粉样变;AL-CA为轻链型心脏淀粉样变;ATTR-CA为转甲状腺素蛋白相关心脏淀粉样变;IFE为免疫固定电泳;FLC为游离轻链 表 1 非CA组、AL-CA组、ATTR-CA组患者的一般资料及部分检查结果比较
Table 1. Comparison of general information and partial examination results among non-cardiac amyloidosis (CA) group, light chain cardiac amyloidosis (AL-CA) group, and transthyretin-related cardiac amyloidosis (ATTR-CA) group patients
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由表2可知,3组患者早期平面显像和延迟平面显像的H/CL按从大到小排序均为ATTR-CA组>AL-CA组>非CA组,且ATTR-CA组早期平面显像和延迟平面显像的H/CL均值均>1.5。依据平面显像半定量分析法,早期平面显像非CA组和AL-CA组阳性患者共32例(23.9%,32/134),ATTR-CA组阳性患者21例(91.3%,21/23);延迟平面显像以H/CL≥1.3为阳性标准时,非CA组和AL-CA组阳性患者共56例(41.8%,56/134),ATTR-CA组阳性患者22例(95.7%,22/23);延迟平面显像以H/CL≥1.5为阳性标准时,非CA组和AL-CA组阳性患者共12例(9.0%,12/134),ATTR-CA组阳性患者17例(73.9%,17/23)。依据Perugini法,早期平面显像非CA组和AL-CA组阳性患者共80例(59.7%,80/134),ATTR-CA组阳性患者23例(100%,23/23);延迟平面显像非CA组和AL-CA组阳性患者共11例(8.2%,11/134),ATTR-CA组阳性患者22例(95.7%,22/23)。依据断层显像半定量评分法,早期断层显像非CA组和AL-CA组阳性患者共1例(0.7%,1/134),ATTR-CA组阳性患者18例(78.3%,18/23);延迟断层显像非CA组和AL-CA组阳性患者共2例(1.5%,2/134),ATTR-CA组阳性患者21例(91.3%,21/23)。ATTR-CA组、非CA组、AL-CA组3组之间的早期显像和延迟显像的H/CL、Perugini法及断层显像半定量评分结果的差异均有统计学意义(均P<0.001)。
组别 早期显像 延迟显像 H/CL Perugini法(例) 断层显像半定
量评分(例)H/CL Perugini法(例) 断层显像半定
量评分 (例)$\bar x \pm s $ ≥1.5(例) 0分 1分 2分 3分 0分 1分 2分 $\bar x \pm s $ ≥1.3(例) ≥1.5(例) 0分 1分 2分 3分 0分 1分 2分 非CA组(n=74) 1.33±0.21 15 3 32 38 1 49 25 0 1.23±0.17 25 4 36 32 6 0 71 2 1 AL-CA组(n=60) 1.41±0.18 17 3 16 40 1 21 38 1 1.31±0.15 31 8 13 42 5 0 56 3 1 ATTR-CA组(n=23) 1.94±0.36 21 0 0 9 14 0 5 18 1.74±0.30 22 17 0 1 13 9 1 1 21 检验值 F=64.218 χ2=40.870 χ2=82.932 χ2=126.373 F=65.634 χ2=27.019 χ2=56.386 χ2=114.152 χ2=128.283 P值 <0.001a <0.001 <0.001 <0.001 <0.001a <0.001 <0.001 <0.001 <0.001 注:a表示采用Bonferroni校正,P<0.016为差异有统计学意义。CA为心脏淀粉样变;PYP为焦磷酸盐;AL-CA为轻链型心脏淀粉样变;ATTR-CA为转甲状腺素蛋白相关心脏淀粉样变;H/CL为心脏与对侧肺摄取比值 表 2 非CA组、AL-CA组、ATTR-CA组患者99Tcm-PYP双时相平面显像和断层显像结果
Table 2. Results of 99Tcm-pyrophosphate (PYP) dual-phase planar imaging and tomographic imaging among non-cardiac amyloidosis (CA) group, light chain cardiac amyloidosis (AL-CA) group, and transthyretin-related cardiac amyloidosis (ATTR-CA) group patients
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由表3可知,早期显像和延迟显像的H/CL、Perugini法和断层显像半定量评分诊断ATTR-CA的效能相比,早期平面显像Perugini法诊断ATTR-CA的准确率最低,灵敏度为100%、特异度为40.3%、准确率为49.0%;延迟断层显像半定量评分诊断ATTR-CA的准确率最高,灵敏度为91.3%、特异度为98.5%、准确率为97.5%。对不同采集时相和不同采集方式的诊断方法的诊断结果分别进行两两比较,结果显示,早期断层显像半定量评分与延迟断层显像半定量评分诊断ATTR-CA具有较好的一致性(Kappa值=0.835),诊断效能的差异无统计学意义(χ2=110.883,P=0.219);延迟平面显像 Perugini法与延迟断层显像半定量评分诊断ATTR-CA具有较好的一致性(Kappa值=0.784),诊断效能的差异有统计学意义(χ2=101.258,P=0.004),后者的诊断准确率高;其余不同采集时相和不同采集方式的诊断方法之间的诊断一致性一般或较差(Kappa值为0.135~0.679)。
诊断效能 早期显像 延迟显像 H/CL≥1.5 Perugini法
(≥2分)断层显像半定量
评分(=2分)H/CL Perugini法
(≥2分)断层显像半定量
评分(=2分)≥1.3 ≥1.5 灵敏度 91.3(21/23) 100.0(23/23) 78.3(18/23) 95.7(22/23) 73.9(17/23) 95.7(22/23) 91.3(21/23) 特异度 76.1(102/134) 40.3(54/134) 99.3(133/134) 58.2(78/134) 91.0(122/134) 91.8(123/134) 98.5(132/134) 准确率 78.3(123/157) 49.0(77/157) 96.2(151/157) 63.7(100/157) 88.5(139/157) 92.4(145/157) 97.5(153/157) 注: PYP为焦磷酸盐;H/CL为心脏与对侧肺摄取比值 表 3 99Tcm-PYP双时相平面显像和断层显像诊断转甲状腺素蛋白相关心脏淀粉样变的效能比较(%)
Table 3. Comparison of the efficacy of 99Tcm-pyrophosphate (PYP) dual-phase planar imaging and tomographic imaging in diagnosis of transthyretin-related cardiac amyloidosis (%)
99Tcm-PYP 双时相平面显像和断层显像在诊断转甲状腺素蛋白相关心脏淀粉样变中的临床应用价值
Clinical application value of 99Tcm-PYP dual-phase planar imaging and tomographic imaging in the diagnosis of transthyretin-related cardiac amyloidosis
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摘要:
目的 探讨99Tcm-焦磷酸盐(PYP)双时相平面显像和断层显像在诊断转甲状腺素蛋白相关心脏淀粉样变(ATTR-CA)中的临床应用价值。 方法 回顾性研究2020年3月至2023年1月于中国医学科学院阜外医院临床疑诊心脏淀粉样变(CA)的患者157例,其中男性108例、女性49例,年龄(58.9±14.8)岁,范围10~88岁。患者静脉注射740 MBq 99Tcm-PYP,分别于注射后1 h(以下简称早期显像)、注射后3 h(以下简称延迟显像)行平面显像和断层显像。平面显像采用Perugini法和半定量分析法进行ATTR-CA的阳性诊断,断层显像采用半定量评分法进行ATTR-CA的阳性诊断。以临床分型为分组标准,将所有患者分为轻链型心脏淀粉样变(AL-CA)组、ATTR-CA组、非CA组,比较各组间平面显像Perugini法(≥2分为阳性)、平面显像半定量分析法(心脏与对侧肺摄取比值 ≥1.5为阳性)、断层显像半定量评分法(2分为阳性)的诊断结果差异,分析99Tcm-PYP显像不同采集时相和不同采集方式的影像特征及诊断效能。采用单因素方差分析及Bonferroni检验分析计量资料的组间差异;采用χ2检验或Fisher确切概率法分析计数资料的组间差异;采用Kappa检验分析计数资料的组间一致性并用配对χ2检验(McNemar检验)比较各种诊断方法之间诊断效能的差异。 结果 根据临床诊断,157例疑诊CA的患者中,CA 83例(其中ATTR-CA 23例、AL-CA 60例)、非CA 74例。延迟断层显像半定量评分法对ATTR-CA诊断的灵敏度为91.3%、特异度为98.5%、准确率为97.5%,与其他不同采集时相和不同采集方式的诊断方法相比,准确率最高;而早期平面显像Perugini法诊断的灵敏度为100%、特异度为40.3%、准确率为49.0%,与其他各种诊断方法相比,准确率最低。对各种不同采集时相和不同采集方式的诊断结果进行两两比较,结果显示,早期断层显像半定量评分和延迟断层显像半定量评分诊断ATTR-CA具有较好的一致性(Kappa值=0.835),诊断效能的差异无统计学意义(χ2=110.883,P=0.219);延迟平面显像 Perugini法与延迟断层显像半定量评分对ATTR-CA的诊断具有较好的一致性(Kappa值=0.784),诊断效能的差异有统计学意义(χ2=101.258, P=0.004),后者诊断准确率高;其余各种不同采集时相和不同采集方式的诊断方法之间的诊断一致性一般或较差(Kappa值为0.135~0.679)。 结论 早期平面显像诊断ATTR-CA存在误诊现象,早期断层显像、延迟断层显像、延迟平面显像对ATTR-CA的诊断准确率高。 -
关键词:
- 淀粉样变性 /
- 心肌 /
- 放射性核素显像 /
- 体层摄影术,发射型计算机,单光子 /
- 99m锝焦磷酸盐
Abstract:Objective To explore the clinical application value of 99Tcm-pyrophosphate (PYP) dual-phase planar imaging and tomographic imaging in the diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA). Methods This retrospective study was conducted on 157 patients with suspected cardiac amyloidosis (CA) at Fuwai Hospital, Chinese Academy of Medical Sciences, from March 2020 to January 2023, including 108 males and 49 females, aged (58.9±14.8) years, ranging from 10 to 88 years old. The patients were intravenously injected with 740 MBq 99Tcm-PYP, and planar imaging and tomographic imaging were performed at 1 h (hereinafter referred to as early imaging) and 3 h (hereinafter referred to as delayed imaging) after injection. The Perugini method and semi-quantitative analysis method were used for the positive diagnosis of ATTR-CA in planar imaging, while the semi-quantitative scoring method was used for the positive diagnosis of ATTR-CA in tomographic imaging. Using clinical classification as the grouping criteria, all patients were divided into light chain cardiac amyloidosis (AL-CA) group, ATTR-CA group, and non-CA group. Diagnostic results of the Perugini method in planar imaging (positive for ≥2 points), semi-quantitative analysis method in planar imaging (positive for the uptake ratio of heart to contralateral lung ≥1.5), and semi-quantitative scoring method in tomographic imaging (positive for 2 points) were compared among the groups, and the 99Tcm-PYP imaging characteristics and diagnostic efficacy of different acquisition phases and different acquisition methods were analyzed. One-way analysis of variance and Bonferroni test were used to analyze the intergroup differences in measurement data. The χ2 test or Fisher′s exact probability method was used to analyze intergroup differences in counting data. In addition, the Kappa test was used to analyze the intergroup consistency of counting data, and the paired χ2 test (McNemar test) was used to compare the differences in diagnostic efficiencies among various diagnostic methods. Results According to clinical diagnosis, of the 157 suspected patients with CA, 83 were confirmed to have CA (including 23 cases of ATTR-CA and 60 cases of AL-CA), and 74 cases were identified as non-CA. The sensitivity, specificity, and accuracy of the semi-quantitative scoring method for delayed tomographic imaging in the diagnosis of ATTR-CA were 91.3%, 98.5%, and 97.5%, respectively, compared with other diagnostic methods with different acquisition phases and different acquisition methods, and the accuracy was the highest. On the contrary, the sensitivity, specificity, and accuracy of the Perugini method for early planar imaging were 100%, 40.3%, and 49.0%, respectively, compared with various diagnostic methods, and the accuracy was the lowest. After pairwise comparison of the diagnostic results for various different acquisition phases and methods, early tomographic imaging and delayed tomographic imaging showed good consistency in the semi-quantitative scoring method for the diagnosis of ATTR-CA (Kappa=0.835), but the difference in diagnostic efficacy was not statistically significant (χ2=110.883, P=0.219). The Perugini method of delayed planar imaging and the semi-quantitative scoring method of delayed tomographic imaging also had good consistency in the diagnosis of ATTR-CA (Kappa=0.784), and the difference in diagnostic efficacy was statistically significant (χ2=101.258, P=0.004), with the latter having a higher diagnostic accuracy. Moreover, the diagnostic consistency among other diagnostic methods with different acquisition phases and methods was average or poor (Kappa is 0.135–0.679). Conclusions Misdiagnosis was found in the diagnosis of ATTR-CA using early planar imaging. Early tomographic imaging and delayed tomographic imaging, as well as delayed planar imaging, had high diagnostic accuracy for ATTR-CA. -
表 1 非CA组、AL-CA组、ATTR-CA组患者的一般资料及部分检查结果比较
Table 1. Comparison of general information and partial examination results among non-cardiac amyloidosis (CA) group, light chain cardiac amyloidosis (AL-CA) group, and transthyretin-related cardiac amyloidosis (ATTR-CA) group patients
组别 例数 性别
(男/女)年龄(岁, )$\bar x \pm s $ 高血压(例) 活检(例) 血或尿IFE或
FLC(例)超声心动图(例) 心内膜心肌 其他组织 左心室射血
分数<50%左心室壁
厚度>12 mm非CA组 74 52/22 58.0±17.9 35 21 13 26 34 55 AL-CA组 60 39/21 59.6±11.1 15 36 24 53 31 58 ATTR-CA组 23 17/6 60.2±12.2 3 15 6 14 10 23 合计 157 108/49 58.9±14.8 53 72 43 93 75 136 检验值 − χ2=0.758 F=0.296 χ2=12.538 χ2=17.411 χ2=8.407 χ2=38.863 χ2=0.634 χ2=18.436 P值 − 0.685 0.744a 0.002 <0.001 0.015 <0.001 0.728 <0.001 注: −表示无此项数据;a表示采用Bonferroni校正,P<0.016为差异有统计学意义。CA为心脏淀粉样变;AL-CA为轻链型心脏淀粉样变;ATTR-CA为转甲状腺素蛋白相关心脏淀粉样变;IFE为免疫固定电泳;FLC为游离轻链 表 2 非CA组、AL-CA组、ATTR-CA组患者99Tcm-PYP双时相平面显像和断层显像结果
Table 2. Results of 99Tcm-pyrophosphate (PYP) dual-phase planar imaging and tomographic imaging among non-cardiac amyloidosis (CA) group, light chain cardiac amyloidosis (AL-CA) group, and transthyretin-related cardiac amyloidosis (ATTR-CA) group patients
组别 早期显像 延迟显像 H/CL Perugini法(例) 断层显像半定
量评分(例)H/CL Perugini法(例) 断层显像半定
量评分 (例)$\bar x \pm s $ ≥1.5(例) 0分 1分 2分 3分 0分 1分 2分 $\bar x \pm s $ ≥1.3(例) ≥1.5(例) 0分 1分 2分 3分 0分 1分 2分 非CA组(n=74) 1.33±0.21 15 3 32 38 1 49 25 0 1.23±0.17 25 4 36 32 6 0 71 2 1 AL-CA组(n=60) 1.41±0.18 17 3 16 40 1 21 38 1 1.31±0.15 31 8 13 42 5 0 56 3 1 ATTR-CA组(n=23) 1.94±0.36 21 0 0 9 14 0 5 18 1.74±0.30 22 17 0 1 13 9 1 1 21 检验值 F=64.218 χ2=40.870 χ2=82.932 χ2=126.373 F=65.634 χ2=27.019 χ2=56.386 χ2=114.152 χ2=128.283 P值 <0.001a <0.001 <0.001 <0.001 <0.001a <0.001 <0.001 <0.001 <0.001 注:a表示采用Bonferroni校正,P<0.016为差异有统计学意义。CA为心脏淀粉样变;PYP为焦磷酸盐;AL-CA为轻链型心脏淀粉样变;ATTR-CA为转甲状腺素蛋白相关心脏淀粉样变;H/CL为心脏与对侧肺摄取比值 表 3 99Tcm-PYP双时相平面显像和断层显像诊断转甲状腺素蛋白相关心脏淀粉样变的效能比较(%)
Table 3. Comparison of the efficacy of 99Tcm-pyrophosphate (PYP) dual-phase planar imaging and tomographic imaging in diagnosis of transthyretin-related cardiac amyloidosis (%)
诊断效能 早期显像 延迟显像 H/CL≥1.5 Perugini法
(≥2分)断层显像半定量
评分(=2分)H/CL Perugini法
(≥2分)断层显像半定量
评分(=2分)≥1.3 ≥1.5 灵敏度 91.3(21/23) 100.0(23/23) 78.3(18/23) 95.7(22/23) 73.9(17/23) 95.7(22/23) 91.3(21/23) 特异度 76.1(102/134) 40.3(54/134) 99.3(133/134) 58.2(78/134) 91.0(122/134) 91.8(123/134) 98.5(132/134) 准确率 78.3(123/157) 49.0(77/157) 96.2(151/157) 63.7(100/157) 88.5(139/157) 92.4(145/157) 97.5(153/157) 注: PYP为焦磷酸盐;H/CL为心脏与对侧肺摄取比值 -
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