一站式复合技术治疗冠状动脉多支病变的安全性和有效性研究

【作者】 高培显；

【导师】 胡盛寿；

【作者基本信息】 中国协和医科大学 ， 心血管外科， 2010， 博士

【摘要】 中文摘要(第一部分)：一站式复合技术再血管化治疗冠状动脉多支病变的近中期临床结果目的：一站式复合技术融合了经皮冠状动脉介入治疗(Percutaneous coronary intervention, PCI)和微创冠状动脉旁路移植术(Minimally invasive direct coronary artery bypass, MIDCAB)的优势,在配备有影像学设备的“复合”手术室内对病人实施完全再血管化,并进行实时影像学评价。本研究旨在总结一站式复合技术血运重建治疗冠状动脉多支病变的初步临床经验,并分析一站式复合技术血运重建的安全性和临床应用价值。方法：自2007年6月至2009年12月,连续有104例患者在我院接受一站式复合技术血运重建。冠状动脉病变支数平均2.4支／例。首先经胸骨下端小切口在不停跳状态下行LIMA至LAD旁路移植术,即刻冠状动脉造影证实LIMA-LAD通畅后同期对其它冠状动脉病变靶血管行PCI治疗。对围术期抗凝抗血小板方案进行改良如下：围术期持续应用阿司匹林；MIDCAB术后即刻冠状动脉造影证实血运重建满意后给予负荷剂量波立维300mg,术后予维持剂量75mg／天应用12个月。结果：共有103例(99.0%)患者成功进行一站式复合技术血运重建,1例(1.0%)患者在对第一钝缘支行PCI治疗时,因钝缘支夹层形成且血流动力学不稳定遂在一站式复合手术室内转为体外循环下CABG.术中冠状动脉造影示4例(3.8%)患者LIMA-LAD吻合不满意,立即再次开胸手术矫正。PCI治疗冠状动脉靶病变188处,平均1.8±0.9支／人；其中12处(6.4%)靶病变仅行PTCA,其余病变均置入支架,共置入191枚DES,3枚BMS。PCI即刻造影成功率为98.4%。术后因呼吸衰竭死亡1例(1.0%),急性肺栓塞1例(1.0%),胸腔积液5例(4.9%),出现新发房颤12例(11.5%)。术后30天内无心肌梗死、因出血而再手术、急性肾功能衰竭、脑血管意外或再血管化等发生。术后平均随访15.0±8.5月,随访期间无死亡、心肌梗死或脑血管意外等发生。术后1年30例(29.4%)患者行冠状动脉造影复查,3例(2.9%)行冠状动脉多层螺旋CT检查,所有LIMA桥血管均证实通畅,未发现支架内狭窄或支架内血栓形成。1例(1.0%)患者在术后1年的冠状动脉造影随访时因回旋支近端新发病变而再次接受PCI再血管化。1例(1.0%)患者心绞痛复发,现药物治疗。结论：一站式复合技术再血管化治疗冠状动脉多支病变安全可行。中文摘要(第二部分)：一站式复合技术与非体外循环冠状动脉旁路移植术治疗冠状动脉多支病变的对比研究目的：非体外循环冠状动脉旁路移植术(Off-pump coronary artery bypass, OPCAB)是目前最为常用也是较为成熟的外科血运重建微创术式。本研究旨在比较一站式复合技术与OPCAB治疗冠状动脉多支病变患者的近期临床结果,并评价一站式复合技术治疗冠状动脉多支病变高危患者的临床应用价值。方法：自2007年6月至2008年12月,共有52例患者在我院接受一站式复合技术冠状动脉血运重建。同期360例冠状动脉多支病变患者行单纯OPCAB,应用倾向性评分匹配(Propensity score matching)的统计方法抽取52例OPCAB患者与一站式复合技术组患者进行1：1配对。研究终点是两组患者院内临床结果和随访期间的免于主要心脏或脑血管不良事件(Major adverse cardiac or cerebrovascular events, MACCE)发生的生存率。结果：两组之间患者基线特征无明显差异。两组院内均无MACCE发生,主要并发症发生率之间无显著差异。一站式复合技术组的ICU滞留时间为(33.3±28.4)小时,呼吸机辅助时间为(11.5±6.9)小时,术后平均住院(8.1±1.7)天,均相应的少于OPCAB组(分别为(49.3±39.0)小时,P=0.03；(18.2±18.2)小时,P=0.0003；(9.1±3.1)天,P=0.047)。一站式复合技术组术后失血量为(860±460)mL,显著少于OPCAB组((1108±59)mL,P=0.02),需要输血的比例(34.6%)显著低于OPCAB组(55.8%,P=0.03)。但一站式复合技术再血管化耗时较长,费用高于OPCAB组。平均随访15.4±5.2个月,一站式复合技术组和OPCAB组之间实际生存率分别为100%和94.2%(Log-rank P=0.11),两组免于MACCE发生的生存率分别为96.2%和90.4%(Log-rank P=0.84),两组之间差异均无统计学意义。结论：与OPCAB相比较,一站式复合技术再血管化可减少术后出血量和血液制品的使用,促进术后尽快恢复。近期随访结果显示一站式复合技术可以达到与传统OPCAB相近的临床结果。中文摘要(第三部分)：一站式复合技术与经皮冠状动脉介入治疗冠状动脉多支病变的对比研究目的：PCI是冠状动脉再血管化最为常用的手段。本研究旨在比较一站式复合技术与常规PCI治疗冠状动脉多支病变的近期临床结果,并进一步评价一站式复合技术的临床应用价值。方法：自2007年6月至2008年12月,共有52例患者在我院接受一站式复合技术冠状动脉血运重建。同期399例冠状动脉多支病变患者行PCI治疗,应用倾向性评分匹配(Propensity score matching)的统计方法抽取52例OPCAB患者与一站式复合技术组患者进行1：1配对。研究终点是两组患者院内临床结果和随访期间的免于MACCE发生的生存率。结果：匹配后两组患者的大部分术前基线资料无显著的统计学差异。两组患者院内均无死亡、围术期心肌梗死、脑卒中、支架内血栓或再次再血管化等发生。一站式复合技术组中有6例(11.5%)为无保护左主干病变。一站式复合技术组前降支系统使用的支架数量(复合技术组0.1±0.3枚／人,PCI组1.1±0.4枚／人,P<0.01)、平均置入的支架数(复合技术组1.7±0.9枚／人,PCI组2.6±0.7枚／人,P<0.001)以及置入支架的长度(复合技术组34.0±20.1mm,PCI组42.2±19.9mm,P=0.04)均显著低于PCI组。一站式复合技术组患者的完全再血管化程度(定义为直径在2.25mm以上且狭窄≥70%的靶血管均得到血运重建)为96.2%,显著高于PCI组(67.3%,P=0.0001)。两组支架置入成功率和院内总费用无显著差异。术后平均随访11.2±4.0个月,两组均无死亡、心梗或脑卒中等不良事件发生,一站式复合技术组1例(1.9%)患者因新发病变而再次血管化,1例(1.9%)患者因首次未完全再血管化而再次行PCI。PCI组有6例(11.5%)患者再次住院行PCI治疗。一站式复合技术组免于MACCE的生存率为96.2%,显著高于PCI组(88.0%,Log-rank P=0.001),差异有统计学意义。结论：一站式复合技术再血管化可以安全有效地用于冠状动脉多支病变和无保护左主干病变的治疗。与传统PCI比较,一站式复合技术再血管化可以减少支架的使用数量,提高完全再血管化程度,降低术后近期的MACCE发生率。中文摘要(第四部分)：应用血小板聚集率评价一站式复合技术血运重建改良抗血小板方案的有效性研究目的：一站式复合技术融合了PCI和MIDCAB的优势,可以在配备有影像学设备和心脏外科设备的“复合”手术室内对病人完全再血管化,并进行实时影像学评价。一站式复合技术的出现,为一些具备传统手术高危因素的多支病变患者提供了一种更个性化的治疗选择,但是PCI／支架置入术后必需的抗凝抗血小板治疗与外科术后出血之间的矛盾仍然是该技术临床应用面临的难题。本研究以传统PCI的常规抗凝抗血小板治疗措施为对照,通过评价本研究所采用的抗凝抗血小板策略下围术期血小板活性的变化,评价该抗凝抗血小板治疗措施的有效性。方法：自2008年9月至2009年2月,连续有23例冠状动脉多支病变患者(复合技术组)接受一站式复合技术血运重建,选择同期接受传统PCI／支架置入治疗的20例多支病变患者为对照(PCI组)。PCI组患者围术期常规服用阿司匹林300mg／天,术前给予波立维负荷剂量(300mg),此后予75mg／天维持1年。该改良的抗血小板治疗方案为围术期持续应用阿司匹林；MIDCAB术后即刻冠状动脉造影证实血运重建满意后给予负荷剂量波立维300mg,术后予维持剂量75mg／天应用12个月。分别在术前、术后2小时、术后24小时和72小时取血标本,采用光学法血小板聚集实验(Platelet aggregation test, PAgT)检测血小板活性变化。分别通过花生四烯酸(Arachidonic acid, AA)(终浓度为0.5mmol／L)诱导的PAgT和二磷酸腺苷(Adenosine diphosphate, ADP)(终浓度为10μmol／L)诱导的PAgT反映阿司匹林和波立维的血小板抑制效果。结果：复合技术组术后24小时血小板数量(160×103／μL)显著低于PCI组(207×103／μL,P=0.0018)。PCI组AA和ADP诱导的血小板聚集率在支架置入前后无明显变化。复合技术组术后24小时AA诱导的血小板聚集率为5.4%,显著高于术前基线值(4.4%,P=0.0079),也显著高于同时期PCI组AA诱导的血小板聚集率(3.5%,P=0.0023)。复合技术组术前ADP诱导的血小板聚集率为67.3%,显著高于同时期的PCI组(53.0%,P=0.011),此后逐渐降低,并于术后2小时和24小时达到与PCI组相似的血小板抑制程度。围术期无支架内血栓形成、因出血再次手术或大量出血等不良事件发生,两组30天内均无死亡、心肌梗死或再血管化等发生。结论：本研究的改良抗凝抗血小板方案在围术期持续应用阿司匹林,并在术中PCI之前应用负荷剂量波立维。血小板聚集率变化显示,该方案在术后早期即可达到与常规PCI抗血小板治疗方案相似血小板抑制效果。因此,该改良的抗凝抗血小板方案可安全有效的应用于一站式复合技术血运重建。更多还原

【Abstract】 ABSTRACT (PART ONE): "One-Stop" Hybrid Coronary Revascularization for Multivessel Coronary Artery Disease with a Modified Antiplatelet Protocol:early and mid-term clinical outcomesObjective:"One-stop" hybrid coronary artery revascularization combines minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous coronary intervention (PCI) simultaneously in a single, enhanced operating suite. This study sought to investigate the early and mid-term clinical outcomes of this one-stop hybrid approach with a modified antiplatelet protocol.Materials and Methods:From June 2007 to December 2009,104 consecutive patients were planned to undergo one-stop hybrid coronary revascularization. MIDCAB was first performed to anastomosis the left internal mammary artery (LIMA) to the left anterior descending coronary artery (LAD) through lower partial ministernotomy. LIMA-LAD graft patency was then confirmed by coronary angiography. Catheter-based interventions on non-LAD lesions were then completed in the same setting. The modified antiplatelet regimen included perioperative aspirin; clopidogrel was routinely discontinued 7 days or more before operation, and then administered intraoperatively with a 300-mg loading dose, followed by a maintenance dose of 75 mg/day for 12 months.Results:One-stop hybrid procedure was successfully carried out in 103 (99.0%) patients. Conversion to conventional on-pump coronary artery bypass grafting (CABG) was required in 1 (1.0%) patient. Four major defects (3.8%) were found in the LIMA grafts and were immediately repaired. A total of 188 lesions were treated by PCI, mean number of lesions treated was 1.8±0.9 per patient. Angiographic success of PCI, based on visual analysis, was obtained in 185 of 188 lesions (98.4%). Balloon angiography alone was used in 12 lesions.191 drug-eluting stents (DES) and 3 bare-mental stents (BMS) were implanted. Angiographic success of stents was 100%. There was 1 (1.0%) deaths within 30 days after operation. One patient (1.0%) developed pulmonary thromboembolism, pleural effusion in 5 (4.9%) patients, and transient atrial fibrillation in 12 (11.5%) patients. All the 102 patients survived the follow-up period of 15.0±8.5 months. No deaths, myocardial infarctions, strokes, recurrent angina, severe bleeding, or stent thrombosis occurred. Thirty patients (29.4%) underwent follow-up coronary angiography and 3 patients (2.9%) underwent 64-slice computed tomography. All LITA grafts were confirmed patent. Only one patient (1.0%) underwent repeat revascularization at the 1-year follow-up angiogram.Conclusions:One-stop hybrid coronary revascularization provides a feasible and safe alternative for selected patients with multivessel disease, especially for those at high risk for conventional strategies. ABSTRACT (PART TWO): Comparison of one-stop hybrid coronary revascularization and off-pump coronary artery bypass in the treatment of multivessel coronary artery disease: a propensity score matching analysisObjectives:OPCAB has been widely used as an alternative for the conventional on-pump coronary artery bypass. This study sought to compare the early and short-term clinical outcomes of one-stop hybrid coronary revascularization with those in a matched subset of patients undergoing OPCAB.Materials and Methods:From June 2007 to December 2008,52 consecutive patients underwent planned one-stop hybrid revascularization in our institution. By using propensity score matching method, a matched group of 52 patients were selected from a cohort of 360 patients who underwent conventional OPCAB via median sternotomy in our institution during the same period. We compared the in-hospital clinical outcomes and freedom from major adverse cardiac or cerebrovascular events (MACCEs) at follow-up period.Results:The baseline characteristics were similar between the two groups. Patients in the hybrid group required shorter intubation times ((11.5±6.9) hours versus 18.2±18.2, P=0.03), shorter lengths of stay in ICU ((33.3±28.4) hours versus (49.3±39.0) hours, P=0.003), less stay in hospital after operation ((8.1±1.7) days versus (9.1±3.1) days, P=0.047). Moreover, the one-stop hybrid group also showed significant reduction in total blood loss ((860±460) mL versus (1108±596) mL, P=0.02) and need of blood transfusion (34.6%versus 55.8%, P=0.03) than the OPCAB group. The in-hospital postoperative major complications were of no significant difference between the two groups. During a mean follow-up of 15.4±5.2 months, the hybrid group showed comparable with the OPCAB group in actual survival (100%versus 94.2%, Log-rank P=0.11) and MACCE-freesurvival (96.2%versus 90.4%, Log-rank P=0.84).Conclusions:The one-stop hybrid coronary revascularization shortens patient postoperative recovery, and shows superior in-hospital outcomes and noninferior short-term outcomes compared with OPCAB. ABSTRACT (PART THREE): Comparison of one-stop hybrid coronary revascularization and percutaneous coronary intervention for the treatment of multivessel coronary artery disease: a propensity score matching analysisObjectives:PCI is the most commonly used intervention for coronary artery disease. This study compared one-stop hybrid approach and PCI for treating patients with multivessel or left main coronary artery disease (or both).Materials and Methods:From June 2007 to December 2008,52 consecutive patients underwent planned one-stop hybrid revascularization in our institution. By using propensity score matching method, a matched group of 52 patients were selected from a cohort of 399 patients who underwent conventional PCI in our institution during the same period. We compared the in-hospital clinical outcomes and freedom from MACCE at follow-up period.Results:Most baseline characteristics were similar between the two groups. No MACCE occurred during the in-hospital period. There were 6 patients (11.5%) with both multivessel and left main coronary artery disease in the one-stop hybrid group. Patients in the hybrid group required less stents implantation in left anterior descending (LAD) artery (0.1±0.3 versus 1.1±0.4, P<0.01) and less stents used per patient (1.7±0.9 versus 2.6±0.7, P<0.001), but achieved more complete revascularization (defined as residual restenosis less than 70%in vessels diameter more than 2.25mm) (96.2%versus 67.3%, P=0.0001). Average total stent length was 34.0±20.1 mm in the one-stop hybrid group versus 42.2±19.9 mm in PCI group (P =0.04). There were no significant differences in success rate of stent implantation and total in-hospital costs between this two groups. During a mean follow-up of (11.2±4.0) months, the hybrid group showed higher MACCE-free survival (96.2%versus 88.0%, Log-rank P=0.001) than the PCI group.Conclusions:One-stop hybrid revascularization is a safe and effective alternative for patients with multivessel and/or left main coronary artery disease. Compared with PCI, one-stop hybrid strategy could reduce the number of stent implantation, achieve more complete revascularization and result in greater clinical benefits at short-term follow-up. ABSTRACT (PART FOUR): Evaluation of antiplatelet effects of a modified protocol by platelet aggregation in patients undergoing "one-stop" hybrid coronary revascularizationObjectives:"One-stop" hybrid coronary revascularization has emerged to be a reliable and attractive alternative for selected patients with multivessel coronary artery disease. However, the optimal antiplatelet regimen of the one-stop hybrid procedure still remains controversial. We modified the antiplatelet protocol in order to reduce the risk of perioperative bleeding and maximally inhibit platelet activity. This study sought to investigate whether the inhibition of platelet activity by this modified antiplatelet protocol is comparable with the conventional protocol widely used and recommended in percutaneous coronary interventions (PCI).Materials and Methods:From September 2008 to February 2009,23 patients undergoing one-stop hybrid procedure and 20 patients undergoing conventional PCI with stenting were enrolled in this prospective study. The modified antiplatelet protocol included perioperative use of aspirin; clopidogrel was administered immediately before PCI with a 300-mg loading dose, followed by a maintenance dose of 75 mg/day for 12 months. Blood samples were obtained before the operation and 2 hours, day 1 and day 3 after operation. Platelet aggregation was induced with:1) arachidonic acid (AA) (final concentration 0.5 mmol/L) to assess the efficacy of aspirin; 2) adenosine diphosphate (ADP) (final concentration 10μmol/L) to assess the specific efficacy of clopidogrel.Results:Platelet counts were statistically lower in the hybrid group than in the PCI control group (160×103/μL versus 207×103/μL, P=0.0018) on day 1 after operation. AA-induced platelet aggregation increased significantly in the one-stop hybrid group in comparison with the preoperative baseline values (5.4%versus 4.4%, P=0.0079) and the PCI control group (5.4%versus 3.5%, P=0.0023) on day 1 after operation. ADP-induced platelet aggregation gradually decreased in the hybrid group, and achieved similar platelet inhibition with the PCI group on 2 hours and day 1 after operation. No major adverse clinical events such as death, perioperative myocardial infarction, stent thrombosis, or reoperation for bleeding occurred in both groups within 30 days after procedure.Conclusions:This study demonstrates that our modified antiplatelet therapy can sufficiently inhibit platelet activity similarly as the conventional protocol for PCI early after operation. Thus, this modified protocol, with continuous use of aspirin and intraoperative administration of loading dose clopidogrel, might be a safe and effective antiplatelet strategy for the one-stop hybrid coronary revascularization.更多还原