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大量循证医学证据表明,核素心肌灌注显像(myocardial perfusion imaging,MPI)在冠心病的诊断、危险分层、存活心肌检测、治疗决策制定、疗效评价、预后评估以及其他多种心脏疾病的诊治中具有重要的临床价值[1]。其中负荷MPI目前被广泛用于临床。目前临床应用的负荷药物有潘生丁、腺苷和多巴酚丁胺等,但都有不同的局限性。前两者不宜应用于慢性阻塞性肺部疾病及Ⅱ度和Ⅲ度房室传导阻滞患者,后者不宜用于高血压患者。瑞加诺生(regadenoson,商品名为Lexiscan)是选择性的腺苷A2A受体激动剂,不仅可以扩张冠状动脉,而且操作方法简单,仅一次静脉推注;较少引起房室传导阻滞和支气管收缩,所以将成为临床较安全的心脏负荷试验药物[2]。本研究比较瑞加诺生注射液与腺苷注射液作为负荷药物行MPI,评价其诊断冠心病的有效性及安全性。
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瑞加诺生组和腺苷组受试者的冠状动脉血管数目分别为51支和75支,2组一般资料的比较,差异均无统计学意义(表1)。17名瑞加诺生组受试者CAG阳性的有10支(19.6%,10/51),其中狭窄≥50%且<75%、狭窄≥75%的患者均为5支(50%);25名腺苷组受试者CAG阳性的有14支(18.7%,14/75),其中狭窄≥50%且<75%、狭窄≥75%的患者分别为6支(42.9%)、8支(57.1%)。瑞加诺生组与腺苷组CAG阳性率及狭窄程度的比较,差异均无统计学意义(Fisher's确切概率法,均P>0.05)。
组别 男性/
女性(例)年龄
(岁)身高
(cm)体重
(kg)体重指数
(kg/cm2)收缩压
(mm Hg)舒张压
(mm Hg)心率
(次/min)高血压
[例(%)]糖尿病
[例(%)]高血脂
[例(%)]腺苷组(n=25) 12/13 56.32±7.34 165.68±6.55 69.08±10.13 25.12±2.92 137.04±16.15 84.04±11.17 64.28±9.42 18(72.00) 5(20.00) 11(44.00) 瑞加诺生组(n=17) 8/9 59.83±7.88 165.56±9.03 67.22±8.33 24.54±2.67 131.67±11.72 80.83±9.76 63.39±11.51 12(70.59) 7(41.12) 7(41.12) 检验值 −0.228a −1.503b 0.052b 0.638b 0.670b 1.201b 0.978b −1.286b −0.371a −1.346a −0.228a P值 0.820 0.141 0.961 0.527 0.506 0.237 0.334 0.206 0.710 0.178 0.740 注:表中,1 mm Hg=0.133 kPa。a为Wilcoxon Z秩和检验;b为t检验 表 1 2组疑似冠心病的受试者的临床资料比较
Table 1. Comparison of clinical characteristics between two groups of subjects with coronary disease
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典型病例的瑞加诺生负荷MPI图见图1,显像结果为前壁心尖段及间壁可逆性缺血,CAG显像结果为左前降及近段长病变,最窄处80%~90%狭窄。17名受试者51支血管中,CAG诊断冠状动脉正常41支、异常10支;MPI诊断正常39支、异常12支(表2),2种诊断方法结果的比较,差异无统计学意义(McNemar检验,P=0.727)。以CAG为标准,瑞加诺生组负荷MPI诊断冠心病的灵敏度为70.00%(7/10)、特异度为87.80%(36/41)、阳性预测值为58.33%(7/12),阴性预测值为92.31%(36/39)、准确率为84.31%(43/51)。瑞加诺生负荷MPI与CAG诊断一致性分析,结果显示存在中度一致性(κ=0.537,P<0.001)。
图 1 冠心病患者(女性,62岁)的瑞加诺生负荷心肌灌注显像图
Figure 1. Myocardial perfusion imaging diagram of regadenoson stress in corouary disease patient(female, 62 years old)
CAG 瑞加诺生组(n=17) 腺苷组(n=25) 阳性 阴性 合计 阳性 阴性 合计 阳性 7 3 10 10 4 14 阴性 5 36 41 8 53 61 合计 12 39 51 18 57 75 注:表中,2组分别与CAG诊断结果的比较,差异均无统计学意义(McNemar检验,P=0.727、0.388)。MPI:心肌灌注显像;CAG:冠状动脉血管造影 表 2 2组疑似冠心病受试者的MPI与CAG诊断结果的比 较(例)
Table 2. Comparing the results of myocardial perfusion imaging and coronary angiography of two groups of subjects with suspected coronary disease (case)
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典型病例的腺苷负荷MPI图见图2,显像结果为心尖、前壁的心尖段及间壁可逆性缺血,CAG显像结果为左前降支近段可见80%狭窄。25名受试者75支血管中,CAG诊断冠状动脉正常61支、异常14支;MPI诊断正常57支、异常18支(表2),2种诊断方法结果的比较差异无统计学意义(McNemar检验,P=0.388)。以CAG为标准,腺苷组负荷MPI诊断冠心病的灵敏度为71.43%(10/14)、特异度为86.89%(53/61)、阳性预测值为55.56%(10/18)、阴性预测值为92.98%(53/57)、准确率为84.00%(63/75)。腺苷负荷MPI与CAG诊断一致性分析,结果显示存在中度一致性(κ=0.525,P<0.001)。
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以CAG为标准,2种诊断方法的灵敏度、特异度、阳性预测值、阴性预测值和准确率的比较差异均无统计学意义(Fisher's确切概率法,均P=1.00)。
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本试验共发生38例次与研究药物有关的不良反应,主要表现为心悸、胸闷、头晕、胸痛和恶心等。部分受试者同时出现多种不良反应,多数发生在开始用药后1~2 min,症状较轻微,一般停药后很快自行缓解,无需干预,瑞加诺生组与腺苷组均未见严重不良反应。2组药物综合不良反应比较,差异无统计学意义(Fisher's确切概率法,P>0.05)。但瑞加诺生组的不良反应较少见静息脸红、胸痛、呼吸困难和恶心,而腹部不适、头晕头痛较多。其中,2组的比较只有腹部不适的差异有统计学意义(Fisher's确切概率法,P=0.044)(表3)。
组别 总不良反应 脸红 胸痛、胸闷 呼吸困难 头晕、头痛 恶心 腹部不适 心悸 瑞加诺生组(n=17) 74.47 5.88 35.29 23.53 58.82 5.88 35.29 23.53 腺苷组(n=25) 84.00 12.00 48.00 32.00 44.00 20.00 4.00 16.00 Pa值 0.694 0.635 0.530 0.731 0.530 0.374 0.044 0.694 注:表中,a:检验方法为Fisher's确切概率法,无检验值 表 3 2组疑似冠心病受试者药物不良反应发生率的比较(%)
Table 3. Comparison of adverse incidence of two groups of subjects with suspected coronary disease (%)
瑞加诺生负荷心肌灌注显像诊断冠心病的初步临床研究
Regadenoson stress myocardial perfusion imaging for detecting coronary artery disease
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摘要:
目的 探讨瑞加诺生注射液作为负荷药物行核素心肌灌注显像(MPI)诊断冠心病的有效性及安全性。 方法 选取2017年9月至2018年10月于山西医科大学第一医院住院的疑似冠心病的42名受试者进行回顾性研究。采用完全随机法将受试者分为2组:瑞加诺生组[男性8名、女性9名,年龄(59.83±7.88)岁]和腺苷组[男性12名、女性13名,年龄(56.32±7.34)岁],分别行瑞加诺生和腺苷注射液的静息MPI后再行负荷MPI,之后2周内所有受试者均行冠状动脉血管造影(CAG)检查。以CAG结果为标准,分析2组MPI诊断冠心病的效能并观察不良反应。计量资料的组间比较采用两独立样本t检验、配对t检验或方差分析、Wilcoxon Z秩和检验;计数资料的组间比较采用McNemar检验或Fisher's确切概率法;瑞加诺生和腺苷的MPI检查方法的一致性比较采用Kappa检验。 结果 2组一般资料、CAG阳性率及狭窄程度的比较,差异均无统计学意义(t=−1.503~1.201,Z=−1.346~−0.228,Fisher's确切概率法,均P>0.05)。瑞加诺生负荷MPI诊断冠心病的灵敏度为70.00%(7/10)、特异度为87.80%(36/41)、阳性预测值为58.33%(7/12)、阴性预测值为92.31%(36/39)、准确率为84.31%(43/51);腺苷负荷MPI诊断冠心病的灵敏度为71.43%(10/14)、特异度为86.89%(53/61)、阳性预测值为55.56%(10/18)、阴性预测值为92.98%(53/57)、准确率为84.00%(63/75),2种MPI方法诊断效能的各项指标的比较差异均无统计学意义(Fisher's确切概率法,均P=1.00),其分别与CAG结果比较,均存在中度一致性(κ=0.537、0.525,均P<0.001)。药物不良反应为轻微和暂时的,2组间在脸红、胸痛和胸闷、呼吸困难、头晕和头痛、恶心、心悸等不良反应的比较,差异均无统计学意义(Fisher's确切概率法,均P>0.05),只有腹部不适的差异有统计学意义(Fisher's确切概率法,P=0.044)。 结论 瑞加诺生作为心脏负荷试验药物用于MPI诊断冠心病,与腺苷注射液比较具有相似的有效性及安全性。 Abstract:Objective To investigate the efficacy and safety of regadenoson injection as cardiac stress medicine. It was compared with adenosine injection by using radionuclide myocardial perfusion imaging (MPI) to diagnose coronary disease. Coronary angiography (CAG) was the standard used for this study. Methods Forty-two subjects with suspected coronary heart disease who were admitted in the First Hospital of Shanxi Medical University from September 2017 to October 2018 were retrospectively analyzed. All subjects were randomly divided into two groups, namely, regadenoson group (8 males; 9 females; age: 59.83±7.88 years old) and adenosine group (12 males; 13 females; age: 56.32±7.34 years old). All subjects underwent rest MPI and stress MPI. Regadenoson and adenosine were injected as medicines. All subjects underwent CAG within 2 weeks. The diagnostic efficacy of regadenoson and adenosine were compared with the results of CAG, which was defined as the gold standard. Adverse reactions were also observed for the two drugs. Two sample t-test, paired t-test or analysis of variance, and Wilcoxon Z rank sum test were used to compare measurement data. Two sample McNemar test or Fisher's exact test were used to measure data. Kappa test was used to test the consistency of the two groups. Results There were no statistically significant difference between the two groups of general data, the positive rate and the degree of stenosis (t=−1.503−1.201, Z=−1.346−−0.228, Fisher's exact test, all P>0.05). With the results of CAG as the gold standard, the diagnosis sensitivity of regadenoson MPI was 70.00% (7/10), specificity was 87.80% (36/41), positive predictive value was 58.33% (7/12), negative predictive value was 92.31% (36/39), and accuracy was 84.31% (41/51). The sensitivity of adenosine MPI was 71.43% (10/14), specificity was 86.89% (53/61), positive predictive value was 55.56% (10/18), negative predictive value was 92.98% (53/57), and accuracy was 84.00% (63/75). No obvious statistically significant difference for each value was found between the two drugs (Fisher's exact test, all P=1.00). The consistency was moderate between the two groups of drugs and CAG (κ=0.537, 0.525, respectively, both P<0.001). The side effects were mild and transient. No obvious statistically significant difference (Fisher's exact test, all P>0.05) was found between the two groups in terms of adverse reactions, such as blushing, chest pain, chest tightness, dyspnea, dizziness, headache, nausea, and palpitation. Statistically significant difference was only found for abdominal discomfort (Fisher's exact test, P=0.044). Conclusion Regadenoson injection is similar in terms of efficacy and safety when compared with the injection drug load of adenosine according to the results of myocardial perfusion imaging. -
Key words:
- Coronary disease /
- Myocardial perfusion imaging /
- Regadenoson /
- Adenosine /
- Coronary angiography
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表 1 2组疑似冠心病的受试者的临床资料比较
Table 1. Comparison of clinical characteristics between two groups of subjects with coronary disease
组别 男性/
女性(例)年龄
(岁)身高
(cm)体重
(kg)体重指数
(kg/cm2)收缩压
(mm Hg)舒张压
(mm Hg)心率
(次/min)高血压
[例(%)]糖尿病
[例(%)]高血脂
[例(%)]腺苷组(n=25) 12/13 56.32±7.34 165.68±6.55 69.08±10.13 25.12±2.92 137.04±16.15 84.04±11.17 64.28±9.42 18(72.00) 5(20.00) 11(44.00) 瑞加诺生组(n=17) 8/9 59.83±7.88 165.56±9.03 67.22±8.33 24.54±2.67 131.67±11.72 80.83±9.76 63.39±11.51 12(70.59) 7(41.12) 7(41.12) 检验值 −0.228a −1.503b 0.052b 0.638b 0.670b 1.201b 0.978b −1.286b −0.371a −1.346a −0.228a P值 0.820 0.141 0.961 0.527 0.506 0.237 0.334 0.206 0.710 0.178 0.740 注:表中,1 mm Hg=0.133 kPa。a为Wilcoxon Z秩和检验;b为t检验 表 2 2组疑似冠心病受试者的MPI与CAG诊断结果的比 较(例)
Table 2. Comparing the results of myocardial perfusion imaging and coronary angiography of two groups of subjects with suspected coronary disease (case)
CAG 瑞加诺生组(n=17) 腺苷组(n=25) 阳性 阴性 合计 阳性 阴性 合计 阳性 7 3 10 10 4 14 阴性 5 36 41 8 53 61 合计 12 39 51 18 57 75 注:表中,2组分别与CAG诊断结果的比较,差异均无统计学意义(McNemar检验,P=0.727、0.388)。MPI:心肌灌注显像;CAG:冠状动脉血管造影 表 3 2组疑似冠心病受试者药物不良反应发生率的比较(%)
Table 3. Comparison of adverse incidence of two groups of subjects with suspected coronary disease (%)
组别 总不良反应 脸红 胸痛、胸闷 呼吸困难 头晕、头痛 恶心 腹部不适 心悸 瑞加诺生组(n=17) 74.47 5.88 35.29 23.53 58.82 5.88 35.29 23.53 腺苷组(n=25) 84.00 12.00 48.00 32.00 44.00 20.00 4.00 16.00 Pa值 0.694 0.635 0.530 0.731 0.530 0.374 0.044 0.694 注:表中,a:检验方法为Fisher's确切概率法,无检验值 -
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