【作者】 姜睿；

【导师】 胡盛寿； 何作祥； 田月琴； 王巍；

【作者基本信息】 中国协和医科大学 ， 心血管外科学， 2008， 博士

【摘要】 冠心病治疗从不同病理基础、不同阶段以及疾病的个体出发，形成了从内科药物治疗、介入治疗到外科手术治疗的全方位治疗原则。在中国越来越多的冠心病患者接受着冠状动脉旁路移植术并从中获益。随着循证医学的发展，如何选择治疗策略，远期疗效成为医生最关注的重点。由于心肌的不可再生性，冠心病的治疗原则都是恢复未死亡心肌(存活心肌)的血液供应，所以各种治疗策略的选择以及再血管化后效果的评判都与一个极其重要的因素——存活心肌直接相关，也就是说存活心肌是决定预后的重要指标。既往关于冠状动脉旁路移植术的危险因素以及存活心肌与预后的研究揭示了一些有意义的结论，但仍有不足之处。如冠脉旁路移植术危险因素分析中都没有从心肌存活的角度参与分析，也没有从心肌存活的角度探讨远期预后。由于心肌存活在冠心病病理生理方面的重要性，我们期待在选择治疗前能够了解更多的心肌存活和预后相关的信息，但是存活心肌是否可以评价再血管化后的远期疗效，选用哪种方式评价预后成为本次研究的主要内容。目的：探讨存活心肌的量和部位与远期心血管不良事件之间的关系。方法：临床资料选自中国医学科学院阜外心血管病医院1999年1月1日至2005年12月31日(以手术日期为准)行CABG术(包括缺血所致二尖瓣的乳头肌功能不全需要同期行二尖瓣成形或置换术以及室壁瘤手术)且术前进行了同位素SPECT存活心肌试验的冠心病患者。排除院内死亡患者后共709人进入本研究。于术后定期对患者进行随访。调阅上述病人核医学资料，以心室17节段对术前心肌灌注和代谢(存活)情况进行半定量评分并进一步得出量化结果，在此基础上计算出整体左心室以及前壁、侧壁、间壁、下后壁、心尖各部位灌注和存活情况。并结合其他潜在危险因素，通过受试者工作特征曲线(ROC曲线)、COX多因素分析等统计手段探寻心肌灌注、存活情况与事先选定的远期心脏不良事件：心因性死亡、再次入院以及复合终点事件之间的关系。结果：平均随访天数为3．43±2．42年。用ROC曲线分别确定同位素整体存活评分对术后远期心源性死亡、再入院及复合终点事件预测的相应界值分别为15分、9分和13分。通过确定的界值将患者分组，经Kaplam-Meier曲线分析界值上下两组的远期事件发生有显著差异，并通过了Log-rank方法的验证。同位素以整体灌注/存活为观察点COX多元分析表明：同位素整体存活总评分与远期心源性死亡、远期再入院以及复合终点事件均有相关性，总存活分值越高，发生上述事件的可能性越大，是独立的危险预测因子。同位素整体存活百分比也是远期心源性死亡和复合终点事件的独立保护性因子，但和再入院有相关性的保护因子是总灌注百分比。同位素以5节段为观察点COX多元分析表明：左心室心尖、侧壁心肌的存活情况是远期心源性死亡的独立保护性因子；左心室侧壁灌注情况、前壁和侧壁的心肌存活情况是远期再入院的独立保护性因子；左心室前壁、侧壁的存活心肌的情况是复合终点事件的独立保护性因子。同位素以3支血管支配区域为观察点COX多元分析表明：前降支支配区、回旋支支配区的存活心肌情况是远期心源性死亡、远期再入院的独立保护性因子；回旋支支配区域的心肌存活情况同时还是复合终点事件的独立保护性因子。结论：1通过引入核医学中关于心肌存活的指标，结合其他相关因素，以左心室整体同位素灌注/代谢(存活)的情况出发，我们发现核素左心室存活心肌总评分对远期心源性死亡、再入院、复合终点事件有良好的区分性，评分分值越高，远期发生心脏不良事件的几率越大。同时我们找到了上述评分预测不同远期事件的界值，当评分超过该界值，该患者远期预后欠佳(整体存活总分15分、9分、13分分别是预测远期心源性死亡、再入院、复合终点事件的界值)。将总体存活和灌注情况协同其他相关因素引入COX回归方程，整体存活情况和存活总分仍与远期不良心脏事件相关。2通过引入核医学中关于心肌存活的指标，结合其他相关因素，以左心室各节段同位素灌注/代谢的情况为着眼点发现左心室前壁和心尖部(大体等同于前降支支配区)、侧壁亦是回旋支支配区域的存活心肌情况是影响远期预后的重要的独立相关因素。对于前壁部分心梗的患者，注重前壁即前降支再血管化的同时，亦应该重视侧壁的再血管化，这对于远期预后有重要意义。心尖对维持左心室的几何构型和生物力学有着重要意义，心尖部存活心肌少的病人远期心脏事件发生几率高。更多还原

【Abstract】 Therapy of coronary heart disease is performed on the basis ofthe individuals of different pathological bases,stages and diseases,forming an all-round therapeutic principle of from the medical drugtherapy,interventional therapy to the surgical therapy.More andmore patients with the coronary heart disease in China receivedand benefited from the coronary artery bypass graft (CABG).Withthe developments in evidence-based medicine,how to select thetherapeutic strategy and the long-term efficacy became the focalpoints to which doctors paid most attention.Due to thenon-reproducibility of heart muscle,the therapeutic principle isalways to recover the blood supply of non-dead (survived) cardiacmuscle.Therefore,the selection of various therapeutic strategiesand the evaluation on the effect after revascularization arecorrelated directly with a very important factor (survived muscle),that is,the survived cardiac muscle is an important index fordeciding the prognosis.Previous studies on the risk factors of CABG and on the survived cardiac muscle and prognosis revealed some meaningfulconclusions but were still insufficient.For instance,the analyses onthe risk factors of CABG were not performed,and did not explorethe long-term prognosis,from the myocardial survival.Due to theimportance of myocardial survival in the pathophysiology ofcoronary heart disease,we look forward to being able to knowmore information about myocardial survival and prognosis prior tothe selection of therapy.However,whether the myocardial survivalcan evaluate the long-term efficacy after revascularization andwhich method will be adopted to assess the prognosis become themajor goals of this study.Objective:To explore the relationship between the volume andposition of myocardial viability and the long-term cardiovascularadverse event.Method:Clinical data were selected from thecoronary-heart-disease patients with CABG operation and theisotopic SPECT test of survived muscle prior to the operation in theFuwai Cardiovascular Hospital,the Chinese Academy of MedicalScience from 01/01/99 to 12/31/05 (in accordance with the date ofsurgery).Total 709 patients were included in this study afterremoving the dead patients in the hospital.Regular follow-up inpatients was performed following operation.Investigate the nuclearmedicine documents of the patients above,make the semiquantitative scores of myocardial perfusion and metabolism(survival) prior to operation by the 17-segment method of ventricle,and further obtain the quantified results,based on which calculationwas carried out for the perfusion and survival in the respectivepositions of whole left ventricle and its anterior wall,lateral wall,partition,inferoposterior wall and cardiac apex.In combination withother potential risk factors,the statistical tools,e.g.the receiveroperating characteristic (ROC) curve,the COX multifactor analysis,etc.,were used to explore the relationship between the myocardialperfusion and survival and the long-term cardiac adverse events(cardiogenic death,readmission,and the combined end events)selected in advance.Results:The mean duration of follow-up was3.43±2.42 years.Using the ROC curve,the critical values ofisotopic overall survival score were determined to be 15,9 and 13,respectively,for the long-term cardiogenic death,readmission andthe combined end events after operation.Patients were groupedaccording to the determined critical value.A significant difference inthe incidence of long-term event in the two groups above and underthe critical value was revealed by analysis based on theKaplam-Meier curve,and verified by the Log-rank method.TheCOX multivariate analysis using the isotopic overallperfusion/survival as the observation point indicated that the total score of isotopic overall survival was correlated with the long-termcardiogenic death,the long-term readmission and the combinedend event,with more possible occurrence of the above eventswhen higher in the total survival scores,and was an independentpredictive factor.The isotopic overall survival percentage was alsoan independent protective factor of long-term cardiogenic deathand the combined end event,but the protective factor correlatedwith readmission was the total perfusion percentage.The COXmultivariate analysis using the isotopic 5 segment as theobservation point indicated that the cardiac apex of left ventricleand the heart muscle in lateral wall were the independent protectivefactors of long-term cardiogenic death,the perfusion in the lateralwall of left ventricle and the myocardial survival of anterior andlateral walls were the independent protective factors of long-termreadmission,and the myocardial survival of anterior and lateralwalls of left ventricle were the independent protective factors of thecombined end events.The COX multivariate analysis using thecontrol area of three vessels as the observation point indicated thatthe survived cardiac muscles in the control areas of anteriordescending branch and circumflex branch were the independentprotective factors for the long-term cardiogenic death andreadmission,and meanwhile the myocardial survival in the control area of circumflex branch was also an independent protectivefactor for the combined end events.Conclusion:1) Through theintroduction of the myocardial survival index in the nuclearmedicine,in combination with other related factors,from theisotopic overall perfusion/metabolism (survival) of ventricle,wefound that the total scores on the survived cardiac muscle of the leftventricle with nuclide have the good distinguish ability for thelong-term cardiogenic death,readmission and the combined endevents,with the higher incidence of long-term cardiac adverseevents when higher in the score.Furthermore,the critical value ofthe above scores for predicting different long-term events wasrevealed.When the score of one patient exceeds the critical value,the patient will have a not-good-enough long-term prognosis (thetotal overall-survival scores of 15,9 and 13 are the critical valuesfor predicting the long-term cardiogenic death,readmission and thecombined end events,respectively).After the overall survival andperfusion,together with other related factors,are introduced intothe COX regression equation,the overall survival and the totalscore of survival are still correlated with the long-term cardiacadverse events.2) Through the introduction of the myocardialsurvival index in the nuclear medicine,in combination with otherrelated factors,with the isotopic perfusion/metabolism in each segment of left ventricle as the observation point,it was found thatthe survived muscles in the anterior wall,cardiac apex (roughlyequivalent to the anterior descending branch) and lateral wall of leftventricle and the circumflex branch were the important independentrelated factors influencing the long-term prognosis.With respect tothe patients with myocardial infarction in the anterior wall,moreattentions are paid to the revascularization of anterior wall (i.e.anterior descending branch),and meanwhile should also be paid tothe revascularization of lateral wall,which has an importantsignificance for the long-term prognosis.The cardiac apex has theimportant significances for maintaining the geometricalconfiguration and biomechanics of left ventricle.There is a higherincidence rate of long-term cardiac events in the patients withsmaller survived cardiac muscle in the cardiac apex.更多还原