第二军医大学  2014, Vol. 35 Issue (3): 317-320   PDF    
应用自制带侧孔灌注球囊处理经皮冠状动脉介入术中无复流的方法
谭洪文, 张志钢, 白元, 李长永, 许旭东, 张必利, 朱嘉琦, 赵仙先, 吴弘, 秦永文    
第二军医大学长海医院心血管内科, 上海 200433
摘要目的 探讨应用自制带侧孔球囊处理经皮冠状动脉介入术(percutaneous coronary intervention,PCI)过程中无复流(no-reflow,NR)的安全性及有效性。方法 2011年1月至2012年1月在我院行PCI术中发生NR的患者,排除冠状动脉狭窄、夹层、痉挛或血栓。共23例,平均年龄(62.0±13.8)岁,其中急诊ST抬高急性心肌梗死(ST segment elevation myocardial infraction,STEMI)患者14例,择期PCI患者9例;NR发生于前降支11例,右冠状动脉8例,回旋支4例。应用自制带侧孔球囊在发生NR的冠脉内推注硝酸甘油及盐酸替罗非班,观察治疗前后靶血管心肌梗死溶栓试验(thrombolysis in myocardial infarction,TIMI)血流分级情况,STEMI患者术后心电图ST段回落(ST segment resolution,STR)情况,术后3 d心电图ST-T变化情况,住院期间冠状动脉穿孔、夹层、血栓等并发症。术后1个月随访心电图,心脏超声射血分数(left ventricular ejection fraction,LÜEF)及短轴缩短率,术后6个月随访心功能及主要心血管不良事件(major adverse cardiovascular event,MACE)发生率。结果 应用带侧孔球囊冠脉内注射药物后血流TIMI 1级3例,TIMI 2级5例,TIMI 3级15例。14例急诊STEMI患者术后ST段完全回落(≥70%)8例,部分回落(30%~69%)4例,2例无回落(<30%);2例ST段无回落患者中1例术后出现心室电风暴,经治疗后好转出院,1例术后因心包填塞经心胸外科急诊手术发现左室游离壁破裂,抢救无效死亡。9例择期PCI患者术后心电图ST段一过性抬高3例,经保守治疗1周心电图ST段回落,住院期间无冠状动脉穿孔、夹层、血栓发生。22例患者出院后1个月查心脏超声,平均LÜEF为(50.6±14.3)%,短轴缩短率0.36±0.04,心电图提示6例有非特异性ST-T改变。4例STEMI患者因非罪犯血管行PCI治疗时复查造影提示发生NR血管血流TIMI 3级。术后6个月时随访无MACE事件,心功能(NYHA)Ⅰ级18例,Ⅱ级4例。结论 初步研究表明应用自制带侧孔灌注球囊推注药物方法治疗PCI术中NR安全、经济、便捷、有效,但仍需大样本临床研究进行评价。
关键词经皮冠状动脉介入治疗     无复流     治疗    
Self-made side hole balloon for treating no-reflow following percutaneous coronary intervention
TAN Hong-wen, ZHANG Zhi-gang, BAI Yuan, LI Chang-yong, XU Xu-dong, ZHANG Bi-li, ZHU Jia-qi, ZHAO Xian-xian, WU Hong, QIN Yong-wen    
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Abstract: Objective To assess the safety and effectiveness of self-made side hole balloon for treating no-reflow following percutaneous coronary intervention(PCI). Methods Twenty-three patients diagnosed with no-reflow during PCI from Jan. 2012 to Jan. 2013 were enrolled. Residual stenosis, thrombosis,dissection, and spasm of coronary artery were excluded. The mean age of the 23 patients was (62.0±13.8) years old. Of the 23 patients 14 had ST segment elevation myocardial infarction (STEMI), and 9 underwent elective PCI. There were 11 cases with no-reflow in the left anterior descending branch, 8 in the right coronary artery and 4 in the circumflex branch. The drugs (nitroglycerin and tirofiban) were selectively injected into the vessel using self-made side hole balloons. The thrombolysis in myocardial infarction (TIMI) grade before and after procedure,ST segment resolution (STR),ST-T changes for 24 and 72 hours and complications (perforation, dissection,and thrombosis of coronary artery) were observed postoperatively. Patients were followed up by ECG and echocardiogram at 1 month after PCI. Incidence of major adverse cardiovascular events (MACEs) and cardiac function were observed 6 months after PCI. Results After intracoronary administration of drug therapy, TIMI grade-1 flow was found in 3 patients, TIMI grade-2 flow in 5 patients and TIMI grade-3 flow in 15 patients. In patients with STEMI, complete resolution (≥70%) was found in 8 patients,partial resolution (30%-69%) in 4, and no resolution (<30%) in 2. One of the 2 patients with ventricular electrical storm was treated with temporary cardiac pacing and drug therapy and recovered within 1 week; the other one with pericardial tamponade who was treated with emergency surgery repair died. In 9 patients undergoing selected PCI,transient ST segment changes were noted in 3 patients which recovered within 1 week after conservative treatment; with no perforation, dissection,or thrombosis of coronary artery. One month after discharge, echocardiogram of the 22 patients showed a mean left ventricular ejection fraction (LÜEF) of (50.6±14.3)% and a fractional shortening in the short axis view of 0.36±0.04, and ECG showed non-specific changes of ST-T in 6 patients. In 4 patients with STEMI, culprit artery showed TIMI grade-3 by angiography performed during PCI for non-culprit vessel 1 month after primary PCI. At 6 months after primary PCI, there was no MACE; 18 patients were in New York Heart Association Class Ⅰ and 4 in Class Ⅱ. Conclusion Self-made side hole balloon is a safe, economical, effective and convenient method for intracoronary administration of nitroglycerin and tirofiban in treating no-flow during PCI, but the result still needs further verification.
Key words: percutaneous coronary intervention     no-reflow     treatment    

经皮冠状动脉介入术(percutaneous coronary intervention,PCI)过程中的“无复流”(no-reflow,NR)现象是术后发生主要心血管不良事件(major adverse cardiovascular event,MACE)的独立预测因素之一[ 1,2 ]。经导管冠状动脉内注射药物是治疗NR的主要方法之一,目前临床应用较多的是经指引导管、灌注导管或灌注球囊在冠脉内注入药物。近年来我们应用自制带侧孔球囊在PCI术中于冠脉内注射药物,降低了成本并取得了较好的疗效,现将该方法报告如下。

1 资料和方法 1.1 病例资料

2011年1月至2012年1月在我院行PCI治疗术中发生NR的患者。所有患者均为经皮冠状动脉球囊成形术(percutaneous transluminal coronary angioplasty,PTCA)或者植入支架后经冠状动脉造影提示血流明显减慢[心肌梗死溶栓试验(thrombolysis in myocardial infarction,TIMI)血流分级≤2级],或者无血流(TIMI血流分级0级或1级),急性心肌梗死患者根据罪犯血管血栓负荷情况行血栓抽吸术,并且排除冠状动脉狭窄、夹层、痉挛或血栓形成等机械性梗阻存在。共23例患者入选,平均年龄(62.0±13.8)岁,男性15例,女性8例; 合并2型糖尿病10例。其中急诊ST抬高急性心肌梗死(ST segment elevation myocardial infraction,STEMI)患者14例,择期PCI患者9例; NR发生于前降支11例,右冠状动脉8例,回旋支4例。

1.2 治疗方法 1.2.1 制备带侧孔球囊

以压力泵低压力202~404 kPa (2~4 atm)扩张快速交换球囊(1.5 mm×15 mm~2.0 mm×15 mm),球囊膨胀后应用24 G针头在球囊前1/3处制作1~2个侧孔,观察侧孔液体流出是否顺利,轻轻挤压球囊以缩小球囊外径,必要时可利用球囊或支架包装中的保护套对球囊进行塑形以缩小使用过的球囊的外径,增加通过性,冲洗球囊表面。 1.2.2 推送球囊

沿发生NR的血管内导丝推送球囊,透视下将连接压力泵的自制带侧孔球囊送至NR段血管中段。

1.2.3 推注药物

卸下压力泵,球囊尾端连接注射器,轻轻回抽后,推注药物(硝酸甘油100~200 μg,根据血压情况可重复4次; 盐酸替罗非班10 μg/kg)经球囊侧孔至冠状动脉内,约2~5 min后复查造影观察血流恢复情况,血流恢复不明显可继续推送球囊至NR血管中远段再次推注药物。5~10 min后观察经自制带侧孔球囊冠脉内推注药物后发生NR的冠状动脉血流恢复情况,对靶血管血流TIMI 1级或2级的患者征求患者或家属同意后行血管内超声检查排除夹层等机械梗阻。PTCA术后根据靶血管血栓负荷及血流恢复情况植入冠脉内支架,所有患者术后常规抗凝、三联抗血小板(阿司匹林、氯吡格雷、盐酸替罗非班10 μg/kg)治疗。

1.3 效果评价

观察应用经自制侧孔球囊注射药物前后靶血管TIMI血流恢复情况,STEMI患者术后心电图ST段回落(ST segment resolution,STR)情况,择期PCI患者术后3 d心电图ST-T变化情况及住院期间冠状动脉穿孔、夹层、血栓等并发症。出院患者1个月后随访心电图、心脏超声射血分数(left ventricular ejection fraction,LVEF)及短轴缩短率,术后6个月随访心功能情况及MACE发生率。 2 结 果

所有自制带侧孔球囊均通过了经PTCA术的靶血管,经注射药物治疗后复查冠脉造影前向血流TIMI 1级3例(13.0%),2级5例(21.7%),3级15例(65.3%); TIMI血流1~2级的患者中5例行血管内超声检查排除机械性梗阻。14例STEMI患者中,术后心电图ST段完全回落(≥70%)8例(57.1%),部分回落(30%~69%)4例(28.6%),2例(14.3%)无回落(<30%); 2例ST段无回落患者中,1例术后出现心室电风暴,经药物及心脏临时起搏治疗后好转出院,1例术后因心包填塞经心胸外科急诊手术,术中发现左室游离壁破裂,经抢救无效死亡。9例择期PCI患者术后心电图ST段一过性抬高3例(33.3%),经冠心病监护室(CCU)观察及药物治疗后1周复查心电图ST段回落,住院期间患者无冠状动脉穿孔、夹层、血栓发生。

22例出院患者术后1个月查心脏超声平均LVEF为(50.6±14.3)%,短轴缩短率为0.36±0.04,6例患者心电图提示非特异性ST-T改变,4例STEMI患者因对非罪犯血管行PCI治疗时复查造影提示急诊介入手术中发生NR血管前向血流TIMI 3级。术后6个月时随访无MACE事件,心功能(NYHA)Ⅰ级18例(81.8%),Ⅱ级4例。

3 讨 论

PCI术中的NR现象是指虽然心外膜冠状动脉闭塞或狭窄减轻或消除后,缺血心肌组织微循环灌注不足,冠脉造影表现为血流明显减慢 (血流≤TIMI 2级),或者无血流(TIMI血流0级或1级),并且排除冠状动脉残余狭窄、夹层、痉挛或血栓形成等机械性梗阻。由于界定的标准及研究的临床背景的差异,报道的NR现象发生率不尽相同,为5%~50%[ 3,4 ],在急诊PCI以及对大隐静脉桥血管的介入治疗时其发生率更高。本研究中植入支架后的NR现象多发生于急诊手术PTCA术后或支架植入后以高压球囊后扩张后。NR现象起始于心肌缺血期,恶化于再灌注期,至今机制仍不明确。目前认为是多因素导致的微血管功能障碍,主要包括: 缺血损伤,远端微循环栓塞,再灌注损伤以及冠状动脉微循环的易损性[ 5 ]。NR既是心肌继续缺血、梗死面积扩展、左室重构心功能恢复不良和死亡的预测因子,也是心肌和微血管损伤的标志,并且与左室舒张功能不全、恶性心律失常、心脏破裂有密切关系,可使住院病死率和心肌梗死发生率增加5~10倍[ 6 ],远期死亡风险增加1倍[ 1 ]

NR的预防及治疗包括PCI术前、术中及术后的多项综合措施,冠状动脉内注射抗血小板或扩张血管药物仍是PCI术中发生NR后常用的方法[ 7 ],经冠脉内注射药物可提高局部药物浓度,使药物在病变血管直接发生作用,并且能够减少因全身应用扩张血管药物导致血压降低的发生,通常经冠脉内注射药物是经过指引导管直接推注,而当TIMI血流≤2级时为了使药物作用于血流减慢的区域,推荐使用灌注球囊或者灌注导管以保证药物到达远端血管床,国内有使用抽吸导管推注药物的报道[ 8 ],但是PCI术中抽吸导管使用无支架球囊或PTCA球囊频率高。美国心血管造影与介入协会(SCAI)关于NR现象的处理建议中,一线的治疗药物包括腺苷、维拉帕米、硝普钠,而尼卡地平、尼可地尔及地尔硫 因证据不充分而作为二类推荐。应用灌注导管或灌注球囊一方面增加手术费用,另一方面应用灌注球囊在注射药物前需要退出导丝,再次治疗时需要重新置入导丝,增加手术时间及导丝再次进入血管引发并发症的风险(进入夹层或支架外)。此外一些导管室并不常规配备灌注导管及灌注球囊,抽吸导管在择期手术中并非常规应用,并且术中病变血管发生NR时患者常伴有胸闷、胸痛,心动过缓或过速,血压下降等危急情况需要手术医生紧急处理。我们利用PTCA术中用过的预扩张球囊或释放后的支架球囊制作带侧孔的球囊,代替灌注球囊及灌注导管在NR的冠状动脉内推注药物,通过23例患者应用的临床实践观察,该方法简便易行、可操作性强,应用于急诊及择期PCI术中发生的NR情况,操作过程无需退出工作导丝,安全性高。仅有1例因急性前壁心肌梗死 11 h行急诊PCI,术后心包填塞,急诊外科手术证实为左心室游离壁破裂,抢救无效死亡。考虑为梗死时间长,心肌坏死范围广导致心脏破裂,并非手术操作所致。出院后患者随访6个月无MACE发生,心功能无恶化。因此我们认为该方法可提高无复流疗效,降低手术费用,具有一定临床意义。

在使用该方法进行操作时应注意以下几个方面: (1)在球囊自制侧孔时,使用低压力202~404 kPa(2~4 atm)扩张球囊便于操作,在球囊前1/3处制作1~2个侧孔,大小以24 G针头较为合适; (2)冲洗球囊表面后轻轻挤压球囊观察球囊内液体自侧孔流出情况,同时将球囊重新塑形缩小外径以便于输送及通过病变,此时不能回抽压力泵,防止气体进入球囊及其充盈腔内导致气栓; (3)推送球囊时尾端连接压力泵推送,透视下将球囊推送至发生NR的血管远端及中段,卸下压力泵后连接抽好药物的注射器,此时应小心推注防止气体进入; (4)沿球囊推注药物速度应恒定缓慢,不宜过快,防止侧孔注射药物压力过高刺激血管痉挛,同时应密切观察患者有创动脉压。必须强调的是由于自制侧孔球囊无法有效回抽排气,因此在操作过程中应小心操作防止气体进入球囊内导致气栓发生。虽然本组病例中自制的侧孔球囊均可推送至预定注射药物的血管部位,但是由于球囊为再次利用,其外径增加,因此仍有可能无法到达预定部位,此时可在近端注射药物或者采用微导管等其他治疗方法。

PCI术中NR现象是由多种原因导致的一种临床表现,尽管目前公认冠状动脉微循环灌注异常为NR发生的核心机制,但其确切机制仍不明确,其干预应从多个方面多角度进行,包括对于高危患者的识别,术前充分抗血小板、抗凝、抑制炎性因子,术中应用血栓抽吸、远端保护、或者采取缺血后适应等综合治疗措施,术后继续抗血小板及扩张血管药物联合应用,必要时应用主动脉内球囊反搏(intra-aortic ballon pump,IABP)等措施。本文介绍的方法仅为冠脉内注射药物的一种新方法,目前尚未见到与本方法类似的相关文献报道,根据目前临床观察该法安全、有效、便捷、经济,具有一定临床意义,但仍需更多临床病例实践及对照试验证实其疗效。

4 利益冲突

所有作者声明本文不涉及任何利益冲突。

参考文献
[1] Ndrepepa G, Tiroch K, Fusaro M, Keta D, Seyfarth M, Byrne R A, et al.5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction[J].J Am Coll Cardiol, 2010, 55:2383-2389.
[2] Galiuto L, Garramone B, Scar A, Rebuzzi A G, Crea F, La Torre G, et al.The extent of microvascular damage during myocardial contrast echocardiography is superior to other known indexes of post-infarct reperfusion in predicting left ventricular remodeling: Results of the multicenter AMICI study[J].J Am Coll Cardiol, 2008, 51:552-559.
[3] Rezkalla S H, Kloner R A.Coronary no-reflow phenomenon: from the experimental laboratory to the cardiac catheterization laboratory[J].Catheter Cardiovasc Interv, 2008, 72:950-957.
[4] Eeckhout E, Kern M J.The coronary no-reflow phenomenon: a review of mechanisms and therapies[J].Eur Heart J, 2001, 22:729-739.
[5] Niccoli G, Kharbanda R K, Crea F, Banning A P.No-reflow: again prevention is better than treatment[J].Eur Heart J, 2010, 31:2449-2455.
[6] Brosh D, Assali A R, Mager A, Porter A, Hasdai D, Teplitsky I, et al.Effect of no-reflow during primary percutaneous coronary intervention for acute myocardial infarction on six-month mortality[J].Am J Cardiol, 2007, 99:442-445.
[7] Klein L W, Kern M J, Berger P, Sanborn T, Block P, Babb J, et al; Interventional Cardiology Committee of the Society of Cardiac Angiography and Interventions.Society of cardiac angiography and interventions: suggested management of the no-reflow phenomenon in the cardiac catheterization laboratory[J].Catheter Cardiovasc Interv, 2003, 60:194-201.
[8] Zhao Y J, Fu X H, Ma X X, Wang D Y, Dong Q L, Wang Y B, et al.Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for the prevention of the no-reflow phenomenon following primary percutaneous coronary intervention in acute myocardial infarction[J].Exp Ther Med, 2013, 6:479-484.