【作者】 王学锋；

【导师】 肖颖彬；

【作者基本信息】 第三军医大学 ， 外科学， 2007， 博士

【摘要】 研究背景:心脏瓣膜疾病是常见的心脏疾病,在我国发病率较高。心脏瓣膜置换手术是治疗瓣膜疾病最有效的方法,随着对瓣膜疾病的认识水平、瓣膜置换技术、心肌保护技术、体外循环技术、围手术期并发症防治水平以及瓣膜工艺水平等的提高,心脏瓣膜置换手术的疗效有了显著提高,但对于合并巨大左室的重症心脏瓣膜疾病,手术后早期并发症发生率和死亡率仍明显较高,有关其远期疗效的报道也不尽相同。对于重症心脏瓣膜疾病患者,术中心肌保护仍是心脏外科研究的热点问题,目前在合并主动脉瓣关闭不全的巨大左室心脏瓣膜置换手术中,多采用冠状静脉窦逆行灌注的心肌保护方法,而由于传统观念影响,经冠状动脉直接顺行灌注的心肌保护方法在临床应用甚少。本研究旨在回顾分析巨大左室心脏瓣膜置换手术后早期死亡的危险因素;探讨巨大左室心脏瓣膜置换手术的最佳心肌保护方法;随访分析巨大左室心脏瓣膜置换手术后远期疗效和抗凝治疗情况及其影响因素。研究方法:第一部分为临床回顾性研究,应用Microsoft Access XP数据库和SPSS 10.0统计软件,收集1996年1月至2005年4月我院157例合并巨大左室心脏瓣膜置换手术患者的临床资料。重点分析患者性别、病因、基础病变、手术类型、手术方式、所用瓣膜类型、心肌保护方式、体外循环转流时间、阻断主动脉时问以及手术并发症等因素对手术早期死亡的影响。第二部分为前瞻性研究,探讨采用不同心肌保护方法对2005年5月至2006年10月我院18例合并巨大左室心脏瓣膜置换手术的心肌保护效果。全部选择男性病例,按不同手术类型随机分为两组:冷血冠状动脉间断顺行灌注(顺灌组)和冷血冠状静脉窦逆行灌注(逆灌组),每组9例。观察指标:临床疗效(包括并发症及早期死亡情况、心功能等级、超声检查左室舒张末期直径、左室射血分数和左室缩短指数),肌酸激酶同工酶MB(CKMB),心肌肌钙蛋白I(cTnI),血乳酸含量,心肌氧摄取率等。第三部分为临床前瞻性研究,采用门诊复查、电话随访和信件随访相结合的办法,对我院1996年1月至2005年4月实施巨大左室心脏瓣膜置换手术后早期存活的146例患者进行远期疗效和抗凝治疗情况随访,并分析影响其远期存活率和疗效的危险因素,临床疗效评价指标有:心功能等级、病人对疗效的自我评价、严重不良事件发生情况等。心脏超声检查主要评价左室舒张末期直径、左室射血分数和左室缩短指数等。研究结果:第一部分结果:1、合并巨大左室心脏瓣膜置换手术157例,早期死亡率为7.01%(11/157),明显高于同期非巨大左室心脏瓣膜置换手术组(p＜0.05),后者早期死亡率为1.56%(21/1350)。2、单因素分析结果显示:男性病人、病因为感染性心内膜炎、术前心功能Ⅳ级、左室舒张末期直径≥8.0cm、左室射血分数＜50%或左室缩短指数＜30%、双瓣膜置换、体外循环转流时间＞130分钟、阻断主动脉时间＞90分钟、冠状静脉窦逆行灌注心肌保护组巨大左室心脏瓣膜置换手术后早期死亡率升高,提示上述因素可能是早期死亡的危险因素。3、手术早期死亡原因分析显示,巨大左室心脏瓣膜置换手术后早期死亡原因分别为室颤、低心输出量综合征和多脏器功能衰竭。室颤、心脏骤停死亡6例,占54.54%(6/11),为首位死亡原因。第二部分结果:1、18例巨大左室心脏瓣膜置换手术患者早期死亡2例,顺灌组和逆灌组各1例,其余患者治愈出院。两组患者体外循环转流时间、阻断主动脉时间、术后并发症发生情况、呼吸机辅助时间、住院时间、心功能恢复情况均无明显差异(p＞0.05)。心脏超声检查显示两组左室舒张末期直径均较术前缩小(p＜0.05),而顺灌组术后左室功能恢复更好。2、两组患者阻断主动脉前血清CK-MB和cTnI浓度就比术前1天明显升高(p＜0.05),阻断主动脉后进一步升高,到手术后第1天达到高峰,手术后第3天恢复到阻断主动脉前水平。顺灌组在开放主动脉10分钟和手术后第1天血清CK-MB和cTnI浓度低于逆灌组(p＜0.05)。3、两组患者阻断主动脉40分钟心肌氧摄取率均明显降低,和阻断主动脉前比较差异显著(p＜0.05),两组间比较无差异(p＞0.05)。开放主动脉10分钟心肌氧摄取率有所升高,但仍低于阻断主动脉前(p＜0.05),顺灌组心肌氧摄取率略高于逆灌组,但无统计学差异(p＞0.05)。4、两组患者阻断主动脉后动脉血和冠脉回血乳酸含量均较阻断前明显增加(p＜0.05),顺灌组在开放主动脉10分钟时动脉血和冠脉回血乳酸含量低于逆灌组(p＜0.05)。乳酸摄取率(负值)与乳酸变化趋势基本一致。第三部分结果:1、远期随访125例,失访21例,平均随访3.29年,累计随访412人年。巨大左室心脏瓣膜置换手术后主要并发症有心律失常、心功能衰竭、出血、栓塞和感染性心内膜炎。远期死亡10例,远期死亡率为2.43%病人·年,主要死亡原因为室颤和不明原因猝死。2、远期随访结果显示,巨大左室心脏瓣膜置换手术后91.30%的患者心功能恢复至Ⅰ—Ⅱ级,较术前明显改善(p＜0.05),98.26%的患者自觉手术有效;双瓣膜置换手术后心功能Ⅲ—Ⅳ级比例高于二尖瓣置换组和主动脉瓣置换组(p＜0.05)。心脏超声随访发现远期存活115例患者左室舒张末期直径较术前明显缩小(p＜0.05);左室射血分数和左室缩短指数较术前有明显改善(p＜0.05),双瓣膜置换手术患者左室功能改善不如二尖瓣置换组和主动脉瓣置换组(p＜0.05)。3、单因素分析结果显示男性、术前左室功能低下、双瓣膜置换手术患者巨大左室心脏瓣膜置换手术后远期死亡率较高(p＜0.05)。不定期检测抗凝水平的患者远期抗凝相关并发症发生率较高(p＜0.05)。结论:1、合并巨大左室心脏瓣膜置换手术早期死亡率明显较高,但是其整体疗效仍较为满意。男性患者、感染性心内膜炎、术前心功能差、双瓣膜置换手术、体外循环转流时间和主动脉阻断时间过长等是早期死亡危险因素。早期死亡的原因主要有室颤、低心输出量综合征和多脏器功能衰竭。2、准确把握手术时机,良好的术中心肌保护,熟练而规范的手术处理,积极而合理的并发症防治是提高巨大左室心脏瓣膜置换手术后早期疗效的关键。3、在巨大左室心脏瓣膜置换手术中,相比于冠状静脉窦逆行灌注的心肌保护,采用冠状动脉顺行灌注手术后早期心脏功能恢复较好,心肌损伤减轻,心肌代谢维持较好,是一种方便、可行、效果良好的心肌保护方法。4、合并巨大左室心脏瓣膜置换手术后远期疗效较好。男性病例、双瓣膜置换、术前心功能差是手术后远期死亡的危险因素。远期死亡原因主要有室颤、顽固性心功能衰竭、抗凝出血和感染性心内膜炎。不定期检测抗凝水平的患者远期抗凝相关并发症发生率较高。5、加强术后心功能支持治疗,积极防治术后心律失常,严格定期随访制度有助于降低巨大左室心脏瓣膜置换手术后远期并发症发生率,提高远期疗效。更多还原

【Abstract】 Background:Heart valve disease is common in China and the incidence is very high.Heart valve replacement is the most effective way to treat this disease.As the knowledge of this disease, the surgical technique,myocardial protection technique,extracorporeal circulation,and treatment of the preoperational complications are improved,the outcome of the heart valve replacement has become better.However,the incidence of the complications and the mortality in the early time after operation are still high,and the results about the late efficacy are different.In the severe patients with heart valve disease,the myocardial protection during the operation is still the focus.At present,retrograde cardioplegia via coronary sinus is usually used in the heart valve replacement in patients with aortic insufficiency combined with large left ventricle.Because of the influence of the traditional ideas,the antegrade cardioplegia is used unusually.The present study is to analyze the risk factors of the mortality in the early time after the heart valve replacement in patients with large left ventricle retrospectively,to investigate the best myocardial protective way,to analyze the late efficacy and the anticoagulation through follow-up.Methods:The first part of this study is clinic retrospective research.The SPSS 10.0 statistical software was used in this part.Clinic materials were collected in157 patients with heart valve replacement combined with large left ventricle from January,1996 to April,2005. The sexuality,etiological factors,pathological characters,operation mode,the type of mechanical valve,myocardial protection way,the duration of the extracorporeal circulation, the time of aortic clamping and complications were analyzed for the mortality early after operation.The second part is the prospective study.The efficacy of the different myocardial protection ways was investigated in 18 cases of heart valve replacement combined with large left ventricle.All the patients in this part were male,who were divided into two groups,including the intermittent antegrade cardioplegia group and the retrograde cardioplegia group.There were 9 patients in each group.The observing markers included clinical efficacy（complication and early mortality,NYHA classification,the diameter of the left ventricle at the end of the diastolic phase,the EF and the FS from echo）,CK-MB, cTnI,lactic acid concentration in blood,MVO₂.The last part is also prospective research.146 surviving patients with heart valve replacement combined with large left ventricle from January,1996 to April,2005 were followed up for the late efficacy and anticoagulation with the methods,like reexamination and follow up through telephone or letter.The risk factors affecting the late surviving incidence and the efficacy were analyzed.The evaluation indexes of the clinical efficacy included the NYHA classification,the self-evaluation on the efficacy from the patients,the occurrence of the severe events.The echocardiography was used to detect the diameter of the left ventricle at the end of the diastolic phase,the EF and the FS.Results:The first part:1.The early mortality in 157 patients was 7.01%（11/157）,which was much higher than that in patients（1.56%（21/1350） ） with heart valve replacement and without large left ventricle（p＜0.05）.2.The risk factors for the early death after operation included male,infective endocarditis,NYHAⅣcardiac function,the diameter of the left ventricle at end of the diastolic phase≥8.0cm,EF of the left ventricle＜50%or the FS＜30%,double valve replacement,the time of cardiopulmonary bypass＞130min,the time of aortic clamping＞90min and retrograde cardioplegia.3.The analysis for the cause of the early death showed that ventricular fibrillation,low cardiac output syndrome and MODS were the main causes of the early death in these patients.6 patients died of ventricular fibrillation and heart arrest（54.54%（6/11） ）,which was the capital cause of the early death.The second part:1.2 patients from the two groups died early after heart valve replacement in all the 18 patients with lager left ventricle.The other patients recovered well.There were no significant difference in cardiopulmonary bypass time,the time of aortic clamping, complication after operation,ventilation assisting time,hospital time,recover of cardiac function between the two groups（p＞0.05）.The echo showed that the diameter of the left ventricle at the end of the diastolic phase decreased compared to that before operation （p＜0.05）.The cardiac function of patients in the antegrade cardioplegia group recovered better.2.Serum CK-MB and cTnI levels before aortic clamping were higher than those before operation in the two groups（p＜0.05）.After the clamp,the levels increased further and get to the peak at the first day after operation.At the third day after operation,these two markers returned to the levels before the aortic clamping.The antegrade cardioplegia group had the lower serum concentration of CK-MB and cTnI on the 10^th min after the opening of aorta and the first day after operation,compared to the retrograde cardioplegia group.3.The MVO₂ decreased significantly 40 min after the aortic clamping in the two groups（p＜0.05）.The MVO₂ increased 10min after the opening of the aorta,which was lower than that before the clamping（p＜0.05）.The MVO₂ in the antegrade cardioplegia group was little higher than that in the retrograde cardioplegia group,but the difference was not significant（p＞0.05）.4.The lactic acid concentration in arterial blood and the blood from coronary sinus was much higher after the clamping than before the clamping（p＜0.05）.The lactic acid concentration in the antegrade cardioplegia group was lower than that in the retrograde cardioplegia group at the 10^th min after the opening of the aorta（p＜0.05）.The third part:1.125 patients were successfully followed up in 146 patients.The average follow-up time was 3.29 years.The main complications after heart valve replacement in patients with large left ventricle included arrhythmia and decreasing of the cardiac function,bleeding, embolism and infective endocarditis.10 patients died and the late mortality was 2.43%pt-yr. One of the causes of death was ventricular fibrillation.However,some patients suddenly died of unknown events.2.The results of follow-up showed that 91.30%of all the patients got the better cardiac function（NYHAⅠ-Ⅱ）,compared to that before operation（p＜0.05 ）,98.26%of all the patients thought that the treatment was effective.The proportion of NYHAⅢ-Ⅳcardiac function in the patients with double valve replacement was higher than that in the patients with mitral or aortic valve replacement（p＜0.05）.The echo showed that 115 surviving patients had the smaller left ventricle,compared to that before operation（p＜0.05）.EF and FS were improved significantly,too（p＜0.05）.However,the improvement of cardiac function in patients with double valve replacement was less than that in patients with mitral or aortic valve replacement（p＜0.05）.3.It was found that male patients,dysfunction of left ventricle and double valve replacement led to the higher late mortality（p＜0.05） Irregular monitoring of anticoagulation led to the higher incidence of anticoagulation related complications （p＜0.05）Conclusions:1.The early mortality was high in this group of patients with large left ventricle after heart valve replacement,but the outcome was still satisfactory.The risk factors for the early death after operation included male patients,infective endocarditis,dysfunction of the heart, double valve replacement,and the long duration of cardiopulmonary bypass and aortic clamping.The main causes of the early death included ventricular fibrillation,low cardiac output syndrome and MODS.2.The key measures to improve the early treatment efficacy in patients with large left ventricle after heart valve replacement included the accurate opportunity of operation, satisfactory myocardial protection,proficient surgical skills,active and reasonable prevention and treatment of complications.3.In the patients with large left ventricle and undergoing heart valve replacement,the antegrade cardioplegia through coronary artery could led to the better recovery of cardiac function,the lighter myocardial injury and better maintenance of the myocardiac metabolism,compared to the retrograde cardioplegia through coronary sinus.Therefore, antegrade cardioplegia through coronary artery is a convenient and effective cardioprotective way.4.The late efficacy of this group of patients was fairly satisfactory.The risk factors for the late death included male patients,double valve replacement,dysfunction of the heart before operation.The main causes of the late death included ventricular fibrillation, refractory heart failure,bleeding caused by coagulation,and infective endocarditis. Irregular monitoring of coagulation caused higher incidence of coagulation related complications.5.The active support of the cardiac function after operation,the prevention and cure of arrhythmia,regular follow-up could help lower the incidence of the late complications and improve the late efficacy.更多还原