Clinical Study Of Coronary Artery Bypass Grafting On Ischemic Heart Disease And Left Ventricular Dysfunction

Purpose:Ischemic heart disease(IHD)and left ventricular dysfunction(LVD)is the main cause of chronic heart failure.Coronary artery bypass grafting(CABG)is the standard treatment for IHD,and cell transplantation and gene Regenerative medicine technology has become the promising treatment in this field.The main purposes in this research are as follows:1.Retrospectively analysising the timing,risk factors,myocardial protection,advantage comparing with PCI,short-term and long-term efficacy of CABG in the treatment of patients with IHD and LVD;2.Prospectively studying the safety and efficacy of CABG combined with autologous bone marrow mononuclear cells(aBMMNCs)/adenovirus-hepatocyte growth factor(ad-HGF)intra-myocardial injection for treatment of IHD and LVD by randomized controlled trial.Methods1、A database of patients with IHD and LVD(LVEF≦50%)who underwent CABG at the PLA General Hospital from January 2003 to December 2013 was collected.A total of 380 patients were enrolled in the database.Demographic data EuroSCORE risk factors,interval time between myocardial infarction and CABG operation,type of cardioplegia were collected and short-term outcomes(in-hospital mortality and major complications),and long-term outcomes(all-cause death and main adverse events)were recorded as the primary endpoint,(1)multiple regression analysis was used to analyze the risk factors for the short-term and long-term results of CABG for IHD and LVD;(2)the patients were grouped by time interval between myocardial infarction and CABG(within 3 weeks,3 weeks to 3 months,and more than 3 months),and the effects of CABG on the short-term and long-term results were compared among the three groups.(3)586 patients with IHD and LVD who received PCI therapy were selected as the control group,and were 1:1 paired according to preoperative risk factors.The short-term effects of different revascularization strategy were compared and analyzed;(4)comparing the effect of myocardial protection between HTK solution and blood-containing cardioplegia on the patients with IHD and LVD.2、Patients with IHD and LVD were enrolled in this research.Based on the treatment methods,they were divided into cell transplantation+CABG group and isolate CABG group.In the cell transplantation trial,80ml of stermal bone marrow blood was aspirated from the sternum before sternotomy,and density gradient method was used to isolate autologous bone marrow mononuclear cell suspension.Both the treatment group and the control group underwent CABG under cardiopulmonary bypass and arrested heart.The treatment group underwent multiple injections of aBMMNCs in the myocardium around the peri-infarcted region.The rest of the operation was consistent with the control group and was completed as usual.Preoperative/postoperative echocardiography and other indicators were used to evaluate left ventricular fimction.The patients’ short-term and long-term mortality and major adverse events were recorded.The safety and effectiveness of the cell therapy were evaluated.3.Patients with IHD and LVD were enrolled in this study.Based on the treatment methods,they were divided into high concentration ad-HGF(5×109pfyu/person)+CABG group(H group),low concentration ad-HGF(1.5×109pfu/person)+CABG group(L group)and isolate CABG group.All of the groups underwent CABG under cardiopulmonary bypass and arrested heart.The treatment group underwent multiple injections of ad-HGF solution in the myocardium around the peri-infarcted region.The rest of the operation was consistent with the control group and was completed as usual.Preoperative/postoperative echocardiography,MRI,PETCT and other indicators were used to evaluate left ventricular function and sear.The patients’ short-term and long-term mortality and major adverse events were recorded.The effectiveness of ad-HGF were evaluated.Result:1、In addition to operative mortality,delayed extubation,low cardiac output syndrome,malignant ventricular arrhythmia,acute renal insufficiency,and perioperative myocardial infarction were major adverse events in the early postoperative period.Logistic regression analysis showed that the implantation of IABP during perioperative period was a common risk factor for delayed extubation and low cardiac output syndrome,and was also closely related to operative mortality.Multivariate analysis of COX proportional hazard model showed that preoperative LVEF and the use of IABP during perioperative period were risk factors for long-term postoperative survival.2、The incidence of low cardiac output syndrome was significantly higher in the early intervention group than in the other two groups,and there was no significant difference in other postoperative adverse events.The overall 5-year survival rate was 82.8%.The Kaplan-Meier curve showed no significant difference in 5-year survival rates between the three groups(χ2＝0.668,P=0.716).The proportion of patients who were free from all-cause death or re-hospitalization for heart failure were 54.5%,67.2%,and 62.3%,respectively,and there was no statistically significant difference(x2＝0.878,P＝0.645).Multivariate regression analysis showed that preoperative critical status rather than time interval between myocardial infarction and CABG operation was the risk factor for the postoperative long-term survival.3、The number of target vessels treated by the CABG group was significantly higher than that of the PCI group(2.90±0.81 vs.1.67±0.73,P=0.000),and the degree of complete revascularization was also significantly higher than that of the PCI group(94.8%vs.51.8%,P＝0.000).Intra-group comparison showed the postoperative LVEF of the two groups was significantly improved compared with those preoperatively(P=0.000).The LVEDD of the CABG group was significantly decreased postoperatively(P＝0.000),however there was no significant change of LVEDD in PCI group(P＝0.361).Comparing between the two groups,the changing value of LVEDD in CABG group was significantly higher than that in PCI group.However,there was no significant difference in the changing value of LVEF between the two groups(P>0.05).There were no significant differences in operative mortality,severe ventricular arrhythmia,postoperative renal failure,low cardiac output syndrome,respiratory insufficiency,perioperative IABP and cerebrovascular complications(P>0.05)between the groups.4、The number of anastomosis,CPB time,aorta clamping time,pulmonary pressure after reperfusion,and inotropic support after reperfusion were significantly higher in the HTK group than in the blood cardioplegia group,but there was no significant difference in the rate of spontaneous beating after reperfusion between the two groups.There were no significant differences between the two groups in terms of operative mortality and severe perioperative complications.5、33 patients were enrolled in the trial.Among them,17 patients were enrolled in the cell transplantation+CABG group and 16 patients in the control group.The cell transplantation group received an average of 98.5±48.3x106 aBMMNCs per patient.There was no complications such as in-hospital mortality,myocardial infarction,stroke,re-sternotomy for hemaostsis,and renal failure in the whole group.There was no significant difference in the incidence of arrhythmia(atrial fibrillation and ventricular arrhythmia),CPB time,and number of anastomosis between the two groups.The aorta clamping time was longer in the cell transplantation group than in the control group.33 patients completed six-month follow-up.1 patient in the cell transplantation group suffered from sudden death at 10 months after operation,leaving 32 patients completed two-year follow-up.The LVEF in the cell transplantation group was significantly higher than that in the control group at six-month follow-up,but there was no significant difference between the two groups at two-year follow-up.There was no significant difference between LVEDV and LVESV at six-month and two-year follow-up after operation.There were no significant differences between the two groups in terms of NYHA Ⅲ/Ⅳ ratio,6-minute walking distance difference,BNP difference,and MACES event ratio.6.Totally 13 patients were enrolled in the trial and 6 in the H group,2 in the L group and 5 in the control group.There was no complication such as in-hospital mortality,myocardial infarction,stroke,re-stemotomy for hemaostsis,and renal failure in the whole group.Compared with that of the control group,the scar size evaluated by MRI was decreased in the H group at the 3-month follow-up and 6-month follow-up,although it only reached signigicance at the 3-month follow-up(P>0.05).Other parameters have no difference among the groups in both timing.Conclusions1、CABG is a reliable treatment for patients with IHD and LVD.The short-term and long-term results are satisfactory.Low cardiac output syndrome is the main cause of operative mortality.Perioperative use of IABP is a common risk factor for delayed extubation and low cardiac output syndrome,which is also closely associated with operative mortality and long-term survival.High-quality perioperative management is essential to the short-term results.2、Surgical revascularization for patients with STEMI and LVD could be performed on different timing after STEMI with comparable operatively mortality and long-term survival.However,early intervention(within 30 days after STEMI)carried a higher incidence of postoperative low cardiac output syndrome.Meticulous perioperative management was prerequisite to implementation of early surgical revascularization.Preoperative severe condition rather than time interval of CABG after STEMI was the risk factor of long-term survival.3、For patients with complex coronary artery disease and left ventricular dysfunction,CABG and PCI are safe and feasible revascularization treatments.Compared with PCI,CABG is more completely revascularized,and the improvement of left ventricular function is more obvious in the early postoperative period.4、For patients with complex coronary artery disease and left ventricular dysfunction,both HTK and 4:1 blood-containing cardioplegia provide safe and effective myocardial protection.In the cases with prolonged myocardial ischemia,HTK did not increase the incidence of early operative cardiovascular adverse events in patients.5、Intra-myocardial injection of aBMMNC transplantation on arrested heart during CABG is a safe procedure based on a longer period observation.The patients with chronic ischemic heart failure can benefit from aBMMNCs transplantation in the short-term(6 months)demonstrated by improved global LVEF compared with the control group;however,this additional benefit dimed with time as showed by 24-month clinical and echocardiographic follow-up results.6、For patients with IHD and LVD,intra-myocardial injection of 5×109pfu/person ad-HGF on arrested heart during CABG could significantly decrease the scar size at 3 month postoperatively,but couldn’t show beneficial effect on the left ventricle geometry and globle function.