Clinical Study On Perioperative Myocardial Protection And VIS/PEDF Predicting Prognosis Of Cardiac And Cerebral Injury In Acute Stanford Type A Aortic Dissection

Background:Acute Stanford type A aortic dissection(ATAAD)is a critical disease in cardiovascular disease.Its mortality and complications(especially cardiac and cerebral complications)are high.Emergency surgery is the main treatment,but because of the long duration of operation and cardiopulmonary bypass,and the need to experience hypothermic circulatory arrest,the heart and brain must experience the process of ischemia-reperfusion,the risk of surgery is high,and there is a higher demand for perioperative cardiac and cerebral protection.del Nido cardioplegia is specially developed for pediatric heart surgery by Professor Pedro del Nido and his team in the United States.Single perfusion can obtain long-term myocardial protection,and the effect is satisfactory.The 2013 survey showed that it is the most commonly used cardioplegia for pediatric heart surgery in the United States,with the use rate as high as 38%.Since 2014,del Nido cardioplegia has been gradually applied to adult heart surgery.Its myocardial protection effect is similar to that of conventional blood cardioplegia,and it has the advantages of simple management and low cost,so it is popular.However,at present,the clinical research of del Nido cardioplegia used in adult heart surgery is mainly limited to the patients with relatively low risk such as coronary artery bypass grafting and valve surgery,and there is no research report of del Nido cardioplegia used in the myocardial protection of ATAAD operation.Therefore,we designed a randomized controlled study to investigate the efficacy and safety of del Nido cardioplegia in the surgical treatment of ATAAD patients.On the other hand,although the treatment of ATAAD has been made progress,the mortality and complication rate are still high,and it is still very difficult to make accurate risk prediction in perioperative period.At present,there is still a lack of a clinically reliable scoring system/biomarker,which can be a good predictor of adverse prognosis such as cardiac and cerebral injury in patients with total arch replacement of ATAAD.Therefore,we studied the value of vasoactive inotropic score(VIS)and the serum level of pigment epithelium derived factor(PEDF)in the prediction of adverse prognosis with cardiac and cerebral injury in patients with total arch replacement of ATAAD.This paper discusses how to simplify the operation process,and predict adverse prognosis in the perioperative period of surgical treatment in ATAAD patients from three aspects of intraoperative intervention,risk score and biomarkers,so as to achieve satisfactory cardiac and cerebral protection effect.Objective:This paper focuses on the perioperative cardiac and cerebral protection in ATAAD patients during surgical treatment,aiming at:1.In the first part,the efficacy and safety of del Nido cardioplegia in the surgical treatment of ATAAD patients were discussed,which provided a reference for the selection of appropriate cardioplegia in clinical ATAAD surgery;2.The second part analyzes the value of perioperative VIS in the prediction of prognosis of cardiac and cerebral injury in patients with total arch replacement of ATAAD;3.The third part analyzes the value of perioperative serum PEDF level in the prediction of prognosis of cardiac and cerebral injury in patients with total arch replacement of ATAAD.Methods:1.Patients were randomly assigned to del Nido cardioplegia(DN)group(n=101)or St.Thomas cardioplegia(STH)group(n=100)according to inclusion and exclusion criteria.Myocardial protection was performed in two groups according to the corresponding cardioplegia perfusion strategy,and primary outcome-cardiac troponin I(c Tn I)plasma content and secondary outcomes were compared between the two groups.Secondary outcomes mainly include:spontaneous rebound rate,operation time,cardiopulmonary bypass time,aortic occlusion time,circulatory arrest time,total cardioplegia perfusion volume,cardioplegia perfusion doses,intensive care unit(ICU)stay time,ventilator assistance time,blood transfusion volume,VIS,major postoperative complications,30-day mortality,etc;2.The patients were divided into adverse prognosis group(n=69)and normal prognosis group(n=132)according to the presence or absence of composite adverse prognosis.Compare the differences of perioperative variables between the two groups,and compare VIS with Euro SCORE II,a commonly used clinical scoring system,and explore the ability of VIS to predict the composite adverse prognosis in patients with total arch replacement of ATAAD,and further discuss the value of VIS in predicting prognosis of postoperative cardiac and cerebral injury;3.The patients were divided into adverse prognosis group(n=46)and normal prognosis group(n=101)according to the presence or absence of composite adverse prognosis.Compare the differences of perioperative variables between the two groups,and compare PEDF with c Tn I and neuron-specific enolase(NSE),which are the classic markers of cardiac and cerebral injury,and explore the ability of predicting composite adverse prognosis in patients with total arch replacement of ATAAD and further discuss the value of PEDF serum content to predict the prognosis of postoperative cardiac and cerebral injury;4.Statistical analysis:The measurement data with normal distribution trend are represented by mean and standard deviation((?)±s),and those without normal distribution trend are represented by median and interquartile spacing.Independent sample t test or nonparametric test are used for group comparison.The counting data are expressed by frequency and percentage,andX~2 test(chi-square test),X~2test of continuity correction or Fisher exact probability test are selected for comparison among groups.Repeated measurement data were analyzed by two factor repeated analysis of variance.The prediction value is evaluated by ROC,and binary logistic regression analysis was used to determine the independent risk factors of adverse prognosis.Special instructions,in the first part,according to the experimental design,plasma c Tn I content(low excellent index)is selected as the primary outcome,and non-inferiority analysis is used.The statistical significance level is taken as one sideα=0.025,β=0.20,and the non-inferiority limit value is 2.4.That is to say,at the significant level of unilateral and 0.025,if the upper limit of 95%confidence interval of the mean value difference of plasma c Tn I between DN group and STH group is not higher than 2.4ng/ml when they enter ICU for 24h,there is statistical significance.SPSS 22.0 software was used for all statistical analysis,which was conducted at the level of bilateral and 0.05 significance(except for special instructions).Results:1.The first part:comparison of primary outcome in this study:the upper limit of 95%confidence interval of the mean difference of plasma c Tn I content between the two groups at the time point of entering ICU for 24 hours is 2.2 ng/ml,which is less than the margin of 2.4 ng/ml,so this study considers that del Nido cardioplegia is not inferior to St.Thomas cardioplegia.In the comparison of secondary outcomes,cardioplegia perfusion doses(2[2,2]vs 2[2,3],P<0.001)and the total cardioplegia perfusion volume(1700[1500,1950]vs 2400[2013,2700],P<0.001)in DN group were lower than those in STH group,with significant difference.The difference between the two groups in operation time,cardiopulmonary bypass time,aortic occlusion time,circulatory arrest time,ICU stay time,ventilator assist time,blood transfusion volume,the incidence of tracheotomy,secondary admission to ICU,acute respiratory insufficiency,permanent neurological dysfunction,renal insufficiency,liver insufficiency was not statistically significant.The30-day mortality in DN group and STH group was 7.92%and 17.00%,respectively.Although the difference was not statistically significant(P=0.051),it showed a trend of reduction in the 30-day mortality in DN group.The incidence of cardiac arrest in DN group was significantly lower than that in STH group(0 vs 10%,P=0.001).ICU48h VIS(3[0,5]vs 5[0,5],P=0.009),24hmax VIS(5[3,8]vs 5[5,10],P=0.011),24hmean VIS(3.2[2.0,6.3]vs 5.0[2.9,6.8],P=0.039)in DN group were significantly lower than those in STH group;2.The second part:in this study,the AUC predicted composite adverse prognosis by VIS at all time points in patients with total arch replacement of ATAAD was greater than0.5(P<0.001),among which the AUC of 24hmax VIS was the largest(0.707),at this time,the best cutoff value of 24hmax VIS was 9 points.Logistic regression analysis showed that24hmax VIS≥9 points was an independent risk factor for composite adverse prognosis after total arch replacement in ATAAD patients(OR 4.643,95%CI:1.806-11.939,P=0.001).At the same time,further subgroup analysis showed that 24hmax VIS could also predict30-day mortality(AUC 0.702),cardiovascular complications(AUC 0.781)and cerebral complications(AUC 0.725);3.The third part:in this study,the levels of serum PEDF in patients with total arch replacement of ATAAD at anesthesia induction were significantly higher than 0.5 in terms of AUC predicted by ROC for the adverse prognosis(composite adverse prognosis 0.706,30-day mortality 0.737,cardiac complications 0.722,cerebral complications 0.745)and had statistical significance.Logistic regression analysis also showed that the levels of serum PEDF at anesthesia induction≥16.99μg/ml was an independent risk factor for composite adverse prognosis after total arch replacement in ATAAD patients((OR 6.131,95%CI:2.014-18.664,P=0.001).The best cut-off values of the levels of serum PEDF for the prediction of composite adverse prognosis,30-day mortality,cardiovascular complications and cerebral complications were 16.99μg/ml、17.18μg/ml、20.94μg/ml、16.99μg/ml,respectively.Among them,the level of serum PEDF at anesthesia induction was more prominent in predicting of cardiovascular complications(sensitivity=53.8%,specificity=91.0%),cerebral complications(sensitivity=74.4%,specificity=69.2%).Conclusions:1.In the first part,our prospective randomized controlled study confirmed that del Nido cardioplegia is safe,simple and feasible in inducing cardiac arrest in patients with ATAAD,and its myocardial protection effect is not inferior to that of classical St.Thomas cardioplegia;2.In the second part,we confirm that 24hmax VIS can predict the adverse prognosis,such as cardiac and cerebral injury after operation in patients with total arch replacement of ATAAD,and 24hmax VIS≥9 points is an independent risk factor for composite adverse prognosis;3.In the third part,we confirmed that the level of serum PEDF at anesthesia induction can predict the adverse prognosis,such as cardiac and cerebral injury after operation in patients with total arch replacement of ATAAD.The level of serum PEDF≥16.99μg/ml at anesthesia induction is an independent risk factor for composite adverse prognosis;4.In this paper,through three parts of research,from the three perspectives of the improvement of myocardial protection,perioperative risk score and perioperative biomarker evaluation,we focus on how to effectively conduct perioperative cardiac and cerebral protection in the perioperative period of surgical treatment of ATAAD patients,which contributes to perioperative cardiac and cerebral protection during the operation of in ATAAD patients.