Chun-jian Li1, Jie-qi Li2, Xiao-fang Liang1, Xiao-xiang Li2, Jian-guo Cui1, Zhi-jian Yang1, Qing Guo3,Ke-jiang Cao1, Jun Huang11. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing 210029, China2. Department of Cardiology, The Affiliated Hospital of Guiyang Medical College, 28 Guiyi Street, Guiyang 550004, China3. Population Health Research Institute, MacMaster University, 237 Barton Street East, Hamilton, ON L8L 2X2, CanadaCorrespondence to Chun-jian LiTel +86-25-83718836, ext 6018Fax +86-25-83674380E-mail lijay@njmu.edu.cn Key Words Point-of-care test; Heart-type fatty-acid binding protein ; Acute myocardial infarction; DiagnosisAbstractAim: To investigate the efficacies of point-of-care test of heart-type fatty-acid binding protein (H-FABP) and its combinations with the conventional biomarkers in the diagnosis of early AMI. Methods: 227 patients suspected of AMI were consecutively recruited in two centers. Biomarkers including H-FABP, myoglobin (MYO), creatine kinase-myocardial band (CK-MB) and cardiac troponin T (cTnT) were determined simultaneously at admission. AMI was defined according to the universal definition of myocardial infarction. Chi-Square test was adopted for the analysis. Results: In patients presenting within 12h of symptom onset, the sensitivity of H-FABP[93.0%(95%CI: 86.6%-96.9%)] was significantly higher than that of initial CK-MB [67.5%(95%CI:58.1%-76.0% ),p<0.0001], cTnT [69.3%(95%CI:60.0%- 77.6%), p <0.0001] and MYO [68.6%(95%CI:54.1%-80.9%), p <0.05]. The negative predictive value of H-FABP [92.8% (95%CI:86.3%-96.8%)] was significantly higher than that of initial CK-MB [74.7% (95%CI:66.8%-81.5%), p <0.001] and cTnT [75.9% (95%CI: 68.1%-82.6%), p<0.001]. The sensitivity of H-FABP+cTnT combination [94.7% (95%CI: 88.9%-98.0% )] was significantly higher than that of admission cTnT [69.3%(95%CI: 60.0%-77.6%),p<0.0001], CK-MB+cTnT [75.4% (95%CI:66.5%-83.0%), p<0.0001] and MYO+CK-MB+cTnT [74.5% (95%CI:60.4%-85.7%), p <0.05]. The negative predictive value of H-FABP+cTnT [94.5% (95%CI:88.4%-98.0%] was significantly higher than that of initial cTnT [75.9% (95%CI:68.1%-82.6%), p <0.001] and CK-MB+cTnT [79.1%(95%CI: 71.2%-85.6%), p <0.001]. Subgroup analysis showed that the superiorities of both the sensitivities and the negative predictive values of H-FABP and H-FABP+cTnT combination occurred only in patients who presented within 6h of the symptom onset. Conclusions: Point-of-care test of H-FABP can be used as a valuable biomarker to exclude an early-stage AMI. Combining H-FABP and cTnT provides the best performance for early AMI diagnosis.IntroductionAcute myocardial infarction (AMI) is a primary life-threatening cardiac disease, early and correct diagnosis is of great importance to enable immediate and intensified treatment which consequently reduces mortality[1,2,3]. Unfortunately, at least one-fifth of AMIs are clinically unrecognized because of absence of chest discomfort or atypical ECG changes [4]. Thus, early AMI diagnosis relies crucially on the biochemical markers in these cases. Heart-type fatty acid-binding protein (H-FABP) is a small cytoplasmic protein which is abundantly expressed in human heart[5]. It was first shown to be released from injured myocardium in 1988, after which its application as a biochemical marker has been investigated[6,7]. Recently, the point-of-care immunochromatographic assay of H-FABP has been created to achieve a rapid determination of the whole blood H-FABP level. However, researches have shown inconsistent performances of H-FABP rapid penal test in the diagnosis of AMI. So the priority of H-FABP is worthy of further investigation. We conducted this study in two centers to determine the value of the point-of-care test of H-FABP alone and in combination with cTnT in early AMI diagnosis, and hypothesized that, 1) H-FABP is superior to the conventional biomarkers in the diagnosis of early AMI; 2) Combining H-FABP and cTnT can improve the performance of single cTnT and is superior to other regular combinations. Materials and methodsStudy subjects This study was conducted in two centers simultaneously in accordance with the Declaration of Helsinki and was approved by the local ethics board. Patients presenting chest pain more than 30 min and less than 12 h suspected of AMI were enrolled consecutively in the study. Patients’ symptoms and past medical history were documented at admission using a pre-defined protocol. Diagnostic criteria The standard diagnosis was made after critical review of all the clinical pictures and relevant information by a senior cardiologist. AMI was defined as detection of initial or 12h cTnT ≥ 0.1ng/ml together with evidence of myocardial ischemia with at least one of the following: i) Symptoms of ischemia; ii) ECG changes indicative of new ischemia (new ST-T changes or new left bundle branch block [LBBB]);iii) Development of pathological Q waves in the ECG; iv) Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality[1]. Diagnostic outcomes were first categorized into the following groups: i) ST-elevation myocardial infarction (STEMI); ii) non-ST-elevation myocardial infarction (NSTEMI); iii) unstable angina (UA); iv) chronic angina (CA); and v) non-cardiac chest pain (NCCP) [1,2,8]. The first two groups were later integrated into AMI group, and the last three into non-myocardial infarction (NMI) group.Determinations of H-FABP and other biomarkers Initial blood samples were collected from every subject upon hospital admission for the determinations of H-FABP and other biomarkers. A point-of-care H-FABP kit, using a rapid immunochromatographic method, was applied to qualitatively determine the H-FABP levels in whole blood samples with a cut-off level at 7ng/ml. The test was interpreted within 10 min after the blood was applied into the sample slot of the test strip, and the results were judged as positive or negative by different types of the color changes. Trained medical staff, blinded to the standard diagnosis, was qualified to perform the H-FABP test. The package of H-FABP kit (20Test/kit, Pattern number: HFABPM20, Batch No: 20070620) was supplied by Wuhan EasyDiagnosis Biomedicine Co., Ltd (Wuhang, China) (Figure 1). MYO, CK-MB and cTnT were determined from the initial blood samples using the immunofluorescence method, dry chemistry analysis and the enzyme-linked immunosorbent assay (ELISA) with cut-off levels of 46 ng/ml, 25U/L and 0.1ng/ml respectively. Any results that were no less than the cut-off levels were defined as positive results. Conversely, those being less than the cut-off levels were defined as negative results. Regarding the combinations, positive results were defined as positive of any component markers, while negative results were defined as negative of all the component markers. cTnT was re-determined at least 12h from the onset of the chest pain to fulfill a final diagnosis.Statistics All the data were analyzed in MacMaster University, Canada. SAS 9.1 analysis software was used for the statistics, data were expressed as mean ± SD. Student’s t test and Chi-Square were used to compare the differences of the basic characteristics between AMI and NMI groups. Chi-Square test was also adopted to analyze the differences of the sensitivity, specificity, positive and negative predictive values. Fisher’s exact test was used when any cell in the square was less than five. The level of significance was set at 0.05.ResultsPatient characteristics 227 patients, 163 male and 64 female, average age 64.5 ± 11.6 years, were recruited in the period from Jan 2008 to Aug 2008. According to the diagnostic criteria, 114 patients were defined as AMI; 27 patients as UA; 20 patients as CA; and 66 patients as NCCP. Compared with the NMI patients, AMI patients were older, more likely to be male, more likely to have previous coronary artery disease, and more likely to have a heart function of New York class III and IV (Table 1). The average symptom-to-sample time (from symptom onset to initial blood sampling) of total AMI patients was 4.96 ± 3.08 h (median 4h), in which 38 (33.3%) patients were admitted within 3 h (2.03 ± 0.80h; median 2h), 44(38.6%) patients between 3 to 6 h (4.44 ± 0.68h; median 4.25h), and 32 (28.1%) patients between 6 to12 h (9.16 ± 2.01h; median 9h) of symptom onset. Superiorities of H-FABP and its combinations H-FABP, CK-MB and cTnT were measured in all the 227 subjects. The sensitivity of H-FABP[93.0% (95%CI: 86.6%-96.9%)] was significantly higher than that of initial CK-MB [67.5% (95%CI: 58.1%-76.0% ), p <0.0001] and cTnT [69.3%(95%CI: 60.0%-77.6%), p <0.0001]. Similarly, the negative predictive value of H-FABP [92.8% (95%CI: 86.3%-96.8%)] was significantly higher than that of initial CK-MB [74.7% (95%CI:66.8%-81.5%), p <0.001] and cTnT [75.9% (95%CI: 68.1%-82.6%), p <0.001]. The sensitivity of H-FABP + cTnT combination [94.7% (95%CI:88.9%-98.0% )] was significantly higher than that of admission cTnT [69.3% (95%CI: 60.0%-77.6%), p <0.0001] and CK-MB + cTnT [75.4% (95%CI: 66.5%-83.0%), p <0.0001]. The negative predictive value of H-FABP + cTnT [94.5% (95%CI: 88.4%-98.0%] was also significantly higher than that of initial cTnT [75.9% (95%CI: 68.1%-82.6%), p <0.001] and CK-MB + cTnT [79.1% (95%CI: 71.2%-85.6%), p <0.001]. The sensitivity and negative predictive values of H-FABP, H-FABP + cTnT, H-FABP + CK-MB + cTnT had no significant difference. Also, the specificities and the positive predictive values of H-FABP, CK-MB, cTnT, H-FABP + cTnT, H-FABP + CK-MB + cTnT and CK-MB + cTnT had no statistical difference (Figure 2, Figure,3).Performances of the biomarkers in different time windows We separated the patients into 3 subgroups by symptom-to-sample time as: i) ≦3 h; ii) >3 h, ≦6h (3-6 h); and iii) >6 h, ≦12 h (6-12 h). The sensitivities of H-FABP of the three time windows were 84.2% (95%CI: 68.7%-94.0%), 95.5% (95%CI: 84.5%-99.4%) and 100% (95%CI: 89.1%-100.0%) respectively, and the negative predictive values were 86.0% (95%CI: 72.1%-94.7%), 94.3% (95%CI: 80.8%-99.3%),and 100% (95%CI: 89.4%-100.0%) respectively. The sensitivity and negative predictive value of H-FABP were both significantly higher than that of initial CK-MB and cTnT within 3-6h of symptom onset, which were more significantly higher when patients presented within 3h of the chest pain. Conversely, neither of them reached significant difference when patients presented 6-12h of the symptom onset. H-FABP + cTnT exhibited the same superiorities over initial cTnT and CK-MB + cTnT within 3h or 3-6h of the symptom onset. The sensitivities and negative predictive values of all the single and combined biomarkers increased by time and reached 100% within 6-12 h of symptom onset. No differences of the specificities or positive predictive values among single biomarkers or the combinations were found within the same subgroup (Figure 4). Performances of H-FABP, MYO and the associated combinations Additional detection of MYO were performed in one center, where 51 AMI patients and 53 non-AMI patients were included. The sensitivity of H-FABP was significantly higher than that of MYO [86.3% (95%CI: 73.7%-94.3%) vs 68.6%(95%CI: 54.1%-80.9%); p = 0.0330]. The sensitivity of H-FABP + cTnT was significantly higher than that of MYO + CK-MB + cTnT [90.2%(95%CI: 78.6%-96.7%) vs 74.5%(95%CI: 60.4%-85.7%); p = 0.0377] (Figure 2, Figure 3). On the other hand, the negative predictive value of H-FABP was better than MYO[86.5%(95%CI: 74.2%-94.4%) vs 73.8%(95%CI: 60.9%-84.2%); p = 0.093], The negative predictive value of H-FABP + cTnT was better than MYO + CK-MB + cTnT [90.0%(95%CI: 78.2%-96.7%) vs 77.2%(95%CI: 64.2%- 87.3%); p = 0.077] (Figure 2, Figure 3). In the subgroups separated by different symptom to sample time, H-FABP presented better sensitivity and negative predictive value than MYO in patients admitted within 3h or 3-6h. H-FABP + cTnT showed the same superiority over MYO + CK-MB + cTnT in 3h and 3-6h of the symptom onset, although the differences were not statistically significant. The sensitivities and the negative predictive values of H-FABP, MYO and the two combinations all reached 100% at 6-12h of the incidence (Figure 5).The specificities and the positive predictive values among H-FABP, MYO, H-FABP + cTnT and MYO + CK-MB + cTnT did not show significant difference in the total subjects or within each subgroup.DiscussionThis study was conducted in two cardiac centers simultaneously, which disclosed that the performance of point-of-care test of H-FABP was superior to that of CK-MB, cTnT and MYO by providing higher sensitivity and negative predictive values specifically in early stage of AMI (≦6 h of the symptom onset). In the mean time, H-FABP+cTnT combination showed significantly higher sensitivity and negative predictive values than that of single cTnT and the regular combinations including CK-MB+cTnT and MYO+CK-MB+cTnT.Currently used biomarkers such as CK-MB and cTnT are both myocardial construction proteins and have higher cardiac specificity, which have being referred as key cardiac biomarkers for AMI diagnosis[1]. However, neither of them can identify AMI until more than 4 hours after onset of the chest pain in most cases[9,10]. MYO is more sensitive in the early phase of AMI, but its specificity is not satisfying [9]. Thus H-FABP would act as a fewer available cardiac biomarker with superior performance in the diagnosis of early-stage AMI.The superior performance of H-FABP may be attributed to the following two factors: i) smaller molecular weight: H-FABP is a small cytoplasmic protein, which has a very low molecular weight of 15kDa, while the molecular weight of MYO,CK-MB and cTnT are 18,80 and 37 kDa respectively[11,12,13]. ii) steeper tissue-to-plasma gradient: The myocardial content of H-FABP (0.52 mg/g wet wt) is 4.5 fold lower than that of myoglobin (2.35 mg/g wet wt), yet the basic plasma level of H-FABP (2.8 μg/L) is 10-fold lower than the later (30 μg/L) [14,15]. So H-FABP tissue-to-plasma gradient is at least two-fold steeper than that of myoglobin. This characteristic, along with the higher permeability of the endothelial barrier for small proteins, enable H-FABP to exhibit an early and significant release after myocardial necrosis and make it more easily being detected, thus endue H-FABP with a superior capability for early AMI diagnosis.However, it has been noted that H-FABP isoform is produced not only in cardiomyocytes but also, to a lesser extent, in skeletal muscle, distal tubular cells of the kidney, specific parts of the brain, lactating mammary glands and the placenta[16]. In the clinical studies, serum H-FABP level is also elevated under heart failure, hypertension, aortic valve regurgitation, renal dysfunction and muscular exercise [17,18,19,20]. Our study demonstrated that H-FABP had a specificity that was slightly lower than CK-MB and cTnT, and was not superior to MYO in any time period within 12h after onset of the symptoms. Besides, the positive predictive value of H-FABP did not show superiority to MYO, CK-MB or cTnT. Therefore, multiple physiological and pathological factors should be considered while the point-of-care test of H-FABP is applied in AMI diagnosis. The multi-marker concept was put forward recently in diagnosing AMI, predicting disease risk and evaluating patient outcomes[21,22]. Mion et al used an automated protein biochip microarray system, which allowed a simultaneous determination of six biomarkers, and found that H-FABP + cTnI combination presented the highest sensitivity (83.3%) and specificity (92.2%), and favored it as the most effective “two marker strategy” of the five combinations determined in the study[23]. We investigated the performances of different combinations including H-FABP + cTnT , CK-MB + cTnT, MYO + CK-MB + cTnT and H-FABP + CK-MB + cTnT in this study. As a result, the H-FABP + cTnT significantly improved the sensitivity and negative predictive value of single cTnT, and exhibited the highest sensitivity and negative predictive value as compared with CK-MB + cTnT and MYO + CK-MB + cTnT in early phase of AMI (≦6h). Tri-marker test of H-FABP + CK-MB + cTnT did not improve the sensitivity and negative predictive value of H-FABP + cTnT. Although the specificity and the positive predictive value of H-FABP + cTnT were not superior to that of other combinations, it was not inferior to that of any single cardiac marker or combination. These findings suggested that H-FABP + cTnT is currently the most effective combination for the diagnosis of early AMI. One limitation of this study was that we only assessed the performance of H-FABP from single measurement on the participants, sequential measurements were not performed, so the performances of H-FABP in different time windows were evaluated from different subjects, while not a dynamic investigation of the same population. In conclusion, our study demonstrated that the point-of-care test of H-FABP is a more sensitive test for the AMI diagnosis compared with conventional cardiac markers, which can be used as a valuable biomarker to exclude an early-stage AMI (within 6h after onset of the symptoms). Combining H-FABP and cTnT provides the best performance for early AMI diagnosis.AcknowledgmentsWe thank the staff of the coronary heart disease ward of the First Affiliated Hospital of Nanjing Medical University, and those of the Affiliated Hospital of Guiyang Medical College for helping us to collect the blood samples and the related data. We also thank the laboratory personnel for the assistance of analyzing the serum levels of MYO, CK-MB and cTnT. Author ContributionChun-jian Li, Zhi-jian Yang, ,Ke-jiang Cao, Jun Huang designed research; Chun-jian Li, Jie-qi Li, Xiao-fang Liang, Xiao-xiang Li, Jian-guo Cui performed research; Chun-jian Li, Qing Guo analyzed data; Chun-jian Li wrote the paper. References1. Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. J Am Coll Cardiol 2007; 50: 2173-2195. 2. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, et al. 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李春坚 王晖朱铁兵 杨志健 曹克将[摘要] 目的 探讨应用磁导航引导进行冠状动脉介入治疗的有效性和安全性。方法 入选在磁导航室经冠状动脉造影确诊并符合介入治疗适应证的冠状动脉病变。经股动脉或桡动脉径路,采用磁导航引导进行冠状动脉介入治疗,记录靶病变特征、手术过程、X线暴露时间、X线暴露量和相关并发症。用Stata 9.2软件进行数据分析。结果 自2006年4月至2008年6月共入选冠心病患者121例,治疗靶血管病变138处,其中A型病变30处、B1型病变50处、B2型病变36 处、C型病变22处(包括闭塞病变7处)。靶病变平均狭窄程度(85.3±10.0)%、平均长度(21.1±10.0)mm。在磁导航引导下,磁导丝通过病变134处,病变通过率为97.1%。磁导丝置入过程中X线暴露时间(55.9±35.4)s、X线暴露量(98.0±86.1)mGy/ (490.0±422.2)uGym2、对比剂用量(8.0±5.4)ml。在磁导丝通过的靶病变中共置入支架164枚。未发生与磁导航系统相关的并发症。磁导丝未能通过的靶病变共4处,其中2处为慢性完全闭塞(CTO)病变,另2处为伴有钙化的次全闭塞病变。结论 将磁导航系统应用于常规的冠状动脉介入治疗是可行的,磁导丝病变通过率高,安全性好。CTO病变和伴有钙化的次全闭塞病变不适宜应用磁导航系统进行介入治疗。[关键词] 冠状动脉粥样硬化性心脏病;介入治疗;磁导航Clinical analysis of 121 coronary artery interventions guided by the magnetic navigation systemLI Chun-jian,WANG Hui, ZHU Tie-bing, YANG Zhi-jian, CAO Ke-jiangDepartment of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, ChinaCorresponding author: LI Chun-jian, Email: lijay@njmu.edu.cn[Abstract] Objective To investigate the efficacy and safety of the magnetic navigation system used in the real world coronary artery intervention. Methods All the lesions detected by the coronary artery angiography in the magnetic navigation catheter lab that met the criteria of coronary artery intervention were included and treated by percutaneous coronary intervention(PCI) under the guidance of the magnetic navigation system. The characteristic of the target lesion, process of the procedure, time and dose of the X-ray exposure, and the complication of the procedure were recorded. Stata 9.2 software was used to perform the statistical analysis. Results 121 patients were recruited during the period from April 2006 to Jun 2008, in which 138 target lesions were intervened by PCI. Among all the included lesions, 30 were classified as type A, 50 as type B1, 36 as type B2, 22 as type C (including seven total occlusions). The average stenosis of the target lesions was (85.3±10.0)%, average length was 21.1±10.0mm. Under the guidance of the magnetic navigation system, 134 target lesions were passed by the magnetic guide-wires, the lesion passing ratio was 97.1%. The X-ray exposure time, X-ray dosage and the contrast volume used during the period of the wire placement were 55.9±35.4 seconds, 98.0±86.1mGy/490.0±422.2 uGym2 and 8.0±5.4 ml, respectively. 164 stents were deployed in the vessels after the magnetic wires being successfully placed. No complications associated with the magnetic navigation system were found. Magnetic guide-wires failed to pass four target lesions, two of which were chronic total occlusions (CTOs), and another two were calcified subtotal occlusions. Conclusions It is feasible to adopt the magnetic navigation system in the real-world coronary artery intervention. The magnetic guide-wire has a high lesion-passing ratio, and an excellent procedure safety. The CTOs and calcified subtotal occlusions are not ideal lesions for the magnetic navigation system.[Key words] Coronary artery disease; Interventional therapy; Magnetic navigation近30年来,随着各种新的介入器械和设备逐步应用到临床,冠状动脉介入治疗技术日趋成熟。而与此同时,尝试用介入方法进行治疗的冠状动脉病变也趋向复杂,如分叉病变、高度扭曲病变和慢性闭塞病变等,应用常规介入方法对上述病变进行治疗更为困难。磁导航系统(magnetic navigation system,MNS)是近年发明并已应用于临床的新型介入导航系统。研究显示,在冠状动脉复杂病变的模型中,利用磁导航引导,可显著降低手术时间和X线暴露量[1]。本研究旨在探讨在真实(Real world)的冠状动脉介入实践中,应用磁导航引导的有效性和安全性。资料与方法1.入选受试者:自2006年4月至2008年6月,根据入选和排队标准,连续入选在磁导航室接受经皮冠状动脉介入治疗(PCI)的冠心病患者121例,其中男性100例,女性21例,平均年龄(63±10)岁。入选标准:(1)冠状动脉造影显示至少有一个冠状动脉和(或)其主要分支直径狭窄大于70%。(2)符合国内、外PCI指南中PCI适应证[2-3]。排除标准:(1)不适宜暴露于强磁场的患者:体内置入心脏起搏器或置入式心脏复律除颤器(ICD)者;体内植有金属假体,如人工心脏金属瓣膜、金属假肢或关节者。(2)急性冠脉综合征。本研究经南京医科大学第一附属医院伦理委员会批准,术前获取所有受试者的知情同意。2.冠状动脉造影及靶血管三维重建:采用Seldinger 法进行股动脉或桡动脉穿刺,常规行左、右冠状动脉造影。用冠状动脉影像分析软件(QCA)测量靶病变的长度及直径狭窄。按照ACC/AHA分类法将靶病变分为A、B1、B2、C四型[4]。通过系统携带软件将靶血管影像从血管造影系统转入磁导航系统(Niobe II MNS,Stereotaxis Inc.,USA),选择投照角度相差大于30度的两张X线影像,在导航系统中通过计算机软件进行三维血管重建(图1)。3.导航模式及导航过程:磁导航软件系统具有二维、三维、牛眼(Bull's eye)、血管内(Intra-vascular)和导航球(Navisphere)等多种导航模式(图2)。本研究以三维导航模式为主,必要时调整至二维、牛眼、血管内或导航球导航模式。4.经皮冠状动脉血管成形术(PTCA):据冠状动脉走向及靶病变特征选用指引导管和磁导丝。在导丝被推送出指引导管前,将导航磁体由“存留位”转向“导航位”,并将初始导航方向设定与靶血管起始方向一致。在导丝被推送出指引导管后,选用适当的导航模式,据重建后的靶血管走向和实时X线影像间断调整磁场方向,使磁场导向始终与靶血管走向一致,逐步推送导丝直到其行进至靶血管末端(图3)。记录选用的导航模式、磁导丝类型、导丝通过病变情况及其由靶血管起始部行进至靶血管末端的X线暴露时间和X线暴露量。随访患者至出院,记录术后病情及各种相关并发症。5.统计学分析:采用EpiData 3.1进行数据管理,用Stata 9.2统计软件进行数据分析。结 果1. 靶病变情况:在入选的121例受试者中,共有138处靶病变接受了PCI治疗,靶病变的基本情况见表1。2. PCI:在磁导航引导下,经股动脉径路介入干预靶病变130处,经桡动脉径路介入干预靶病变8处。单次PCI干预同一患者1支靶血管106例、2支靶血管13例、3支靶血管2例。在所有入选的138处靶病变中,磁导丝首次尝试成功通过病变132处,更换磁导丝再次尝试通过病变2处,最终磁导丝成功通过病变134处,未能通过病变4处,总病变通过率97.1%;导丝置入过程中的X线暴露时间(55.9±35.4)s、X线暴露量(98.0±86.1)mGy/(490.0±422.2) uGym2、对比剂用量(8.0±5.4)ml。8例经桡动脉径路进行PCI的靶病变均治疗成功,磁导丝首次病变通过率100%;导丝置入过程中的X线暴露时间(65.5±47.7)s、X线暴露量(139.0±149.2)mGy /767.7 ±758.8uGym2、对比剂用量(13.0±12.4)ml。15例患者在同次手术中接受了2处或3处靶血管的PCI,磁导丝成功通过靶病变30处,病变通过率93.8%。在所有成功放置磁导丝的病变中共置入支架164枚,术后靶血管TIMI血流Ⅲ级者132处(98.5%)、Ⅱ级2处(1.5%)。研究中选用Cronus软导丝56根(40.6%)、Cronus中等硬度导丝63根(45.7%)、Titan软导丝18根(13.0%)、Titan强支撑导丝1根(0.7%)。有128处(92.8%)病变采用了三维导航、102(73.9%)处病变采用了二维导航、9(6.5%)处病变采用了血管内(Intravascular)导航、6(4.3%)处病变采用了牛眼(Bull’s eye)导航、3(2.2%)处病变采用了导航球导航。磁导丝未能通过4处病变,其中2处为LCX伴有钙化的慢性闭塞(CTO)病变,另2处分别为LCX(病变节段血管扭曲)和RCA(病变远段血管扭曲)伴钙化的慢性次全闭塞病变。上述病变均在更换普通导丝后,采用常规介入方法治疗成功。其中2例由Cronus软导丝分别更换为Asahi Neo’s 软导丝和Miracle 3导丝,另2例分别由Titan软导丝和Cronus中等硬度导丝更换为PT2 TM (LS)导丝。3. 手术安全性:本研究未发生与应用磁导丝相关的冠状动脉夹层或穿孔等并发症。受试者在术后住院期间无心肌梗死或死亡发生。1例患者术后次日出现背部持续性酸涨感(与术前心绞痛性质、部位不同),复查心电图未见动态变化,术后3日出院。出院后随访18个月,患者仍有不同程度的背部酸涨感,呈持续性,与活动无关,在服用活血化瘀类中药后自感症状好转,因对日常生活无显著影响,故未再进一步就诊。术后与穿刺相关的并发症共8例次,其中7例为穿刺局部皮下瘀斑,1例为穿刺部位皮下血肿,经相应处理均好转出院。讨 论本研究在国内初次报道将磁导航系统应用于PCI的结果。主要发现包括:(1)在真实的冠状动脉介入实践中,磁导丝的病变通过率达97.1%;(2)利用磁导航引导,经桡动脉径路行PCI或同次手术进行多个冠状动脉PCI是可行的;(3)CTO病变和伴有钙化的次全闭塞病变不适宜应用磁导航系统进行PCI;(4)应用磁导航引导进行冠状动脉PCI相对安全。目前相关研究在国外也仅有少量报道。Atmakuri等[5]对预计用常规介入方法难于甚至不能完成的复杂冠状动脉病变应用磁导航引导进行了PCI。在入选的59例患者中,磁导丝2次尝试总病变通过率为85%,导丝置入时间10.5min,手术成功率79%。Tsuchida等[6]在排除了直径狭窄大于80%和完全闭塞的病变后,对21处简单病变进行了介入干预,结果磁导丝的病变通过率为90%,导丝置入过程中X线暴露时间105 s, X线暴露量215 Gym2,对比剂用量13 ml。与上述研究相比,本研究入选了在磁导航室接受PCI的所有病变,样本量相对较大,因而结果可更客观地反映磁导航系统在真实的冠状动脉介入实践中的有效性和安全性。入选本研究的138处靶病变平均狭窄程度(85.3±10.0)%,病变复杂程度介于上述两项研究之间。磁导丝的总病变通过率、导丝置入过程中的X线暴露时间、X线暴露量、对比剂用量等参数均优于上述两项研究结果。Kiemeneij等[7]认为应用磁导航系统进行冠状动脉PCI存在明显的学习曲线,其研究结果显示,在利用磁导航引导完成160例PCI后,磁导丝置入过程中X线暴露时间由入门阶段的109 s减至47 s。相比之下,本中心的研究结果已跨越了学习曲线的上升阶段。本研究应用磁导航系统引导对经股动脉和桡动脉两种不同径路的PCI均进行了尝试。实践表明,经股动脉PCI时应用磁导航系统较为方便。经桡动脉径路进行PCI时,因手术操作位于患者上肢,将磁体移至“导航位”稍有不便,但只要注意无菌防护,将两磁体“头部”用无菌单覆盖,应用磁导航引导经桡动脉进行PCI也是完全可行的。本研究还发现,在患者能耐受的前提下,应用磁导航引导对同一患者在同次PCI中进行2支、3支冠状动脉血管的干预也是可行的。此时,需要在冠状动脉造影完成后,对多支血管分别进行三维重建,然后依次应用重建后的三维血管模型引导进行PCI。磁导丝是在应用磁导航系统时所需的一种特制导丝,其顶端有2-3mm金管包裹的钕铁硼磁铁。与普通导丝比较,磁导丝有其独特的优点,在置入磁导丝前,术者无需对其预先塑形,在置入导丝过程中,其顶端保持竖直(或30度弯曲)状态,故在通过竖直的冠状动脉节段时,导丝不易进入分支血管,而在通过扭曲的冠状动脉节段时,术者可改变磁场方向,任意调整磁导丝顶端的方向,使其顺利通过扭曲的血管或病变。相比之下,在使用普通导丝前,术者均需预先对其进行塑形,而塑形后顶端弯曲的导丝行进在竖直的血管时容易进入周边分支,当行进至扭曲的血管节段时,亦常因预先塑形的弯曲程度不理想而需取出导丝重新塑形。研究显示,应用磁导航系统进行冠状动脉PCI可能会减少导丝置入过程中的X线暴露时间,减低X线暴露量[1]。本研究术后部分患者出现了与穿刺相关的并发症,包括皮下瘀血、局部血肿等。但未发现与磁导丝或磁导航系统确切相关的并发症。研究中磁导丝未能通过的4处靶病变为CTO病变或伴有钙化的次全闭塞病变。Kiemeneij等[7]的研究亦发现,在磁导丝未能通过的35处病变中25处为CTO病变,提示上述病变不适宜应用磁导航系统进行PCI。本研究发现,磁导丝难于通过上述病变除了与病变本身较为复杂有关外,尚存在以下原因:(1)应用磁导航系统进行冠状动脉PCI尚处起步阶段,具备不同性能的磁导丝种类尚不完善。(2)应用磁导航系统进行三维重建所生成的血管模型与真实血管的解剖位置尚难于100%的完全重合,因而在极高度狭窄病变的导航过程中可能会出现一些偏差。(3)磁导丝顶端有一长度为2~3 mm的金管包裹小磁体,由于这段磁体的顺应性较低,在CTO病变或伴有钙化的次全闭塞病变中的通过能力可能要低于普通导丝。因此,改善磁导丝顶端金属磁体的顺应性,减少磁体长度,增加磁导丝品种,提高重建血管三维模型的精准性是磁导航系统函待解决的主要问题。磁导航系统给心血管PCI带来了一种全新的操作模式。在磁导航系统引导下进行冠状动脉PCI是可行的,磁导丝的病变通过率高、安全性好。参 考 文 献[1] Ramcharitar S, Patterson MS, van Geuns RJ, et al. 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