Effects Of Extracorporeal Cardiac Shock Wave On SDF-1 Expression And EPCs Proliferation In Peripheral Blood Of Patients With Chronic Coronary Syndrome

Objective:Chronic coronary syndrome(CCS)can benefit most patients after treatment with drugs,percutaneous coronary intervention(PCI),coronary artery bypass graft(CABG).However,CCS patients are often accompanied by microvascular disease.The effect of improving myocardial ischemia is poor.Extracorporeal cardiac shock wave(CSWT)is a new technology that can promote myocardial microvascular regeneration and improve myocardial ischemia.Studies have found that stromal cell-derived factor-1(SDF-1)can increase the number of endothelial progenitor cells(EPCs)and enhance their angiogenesis.This study aims to explore the correlation between myocardial ischemia and improvement of cardiac function and SDF-1 and EPCs in patients with CCS after CSWT treatment,so as to reveal the mechanism of CSWT promoting angiogenesis.Methods:A total of 46 patients(38 males and 8 females)with CCS diagnosed and treated in the Department of Cardiology or Cardiac surgery of the first affiliated Hospital of Kunming Medical University from December 2018 to August 2020 were prospectively collected.Moderate and severe coronary artery stenosis was indicated by coronary angiography(CAG)or coronary artery CT angiography(CCTA).Under regular medication or PCI or CABG treatment,there were still clinical manifestations of myocardial ischemia,such as chest tightness,chest pain,shortness of breath,poor activity endurance and so on.46 patients were divided into CSWT treatment group and control group.Patients in CSWT group were treated with CSWT 9 times a month while receiving standard medication.The patients in control group only accepted standard medical treatment.Imaging evaluation,clinical status evaluation and blood biochemical determination were performed in all patients in groups at 0,1 and 6 months respectively.Imaging evaluation included cardiac structure and function and global longitudinal myocardial strain(GLS)by echocardiography,99Tcm methoxyisobutyl isonitrile myocardial perfusion imaging(MPI)to identify viable myocardium and locate myocardial ischemic segments.Clinical status evaluation included New York Heart function Association(NYHA),Canadian Cardiovascular Association(CCS)angina pectoris score,Seattle angina questionnaire(SAQ)score,Minnesota Heart failure score,SF-36 heart failure,6min Walking Test(6MWT)and nitrate dosage.Blood biochemical assays include ELISA double-antibody sandwich method to detect the level of SDF-1 in peripheral blood,and flow cytometry to detect the number of EPCs in peripheral blood.Result:1.The completion of follow-up:23 patients in CSWT group completed 9 times shock wave treatments with 48 segments,and all patients completed follow-up.2 patients were re-admitted to hospital for other reasons(1 case of gout and 1 case of rectal cancer with gastrointestinal bleeding).Admission was not related to CSWT.23 patients in control group were not treated with CSWT,4 patients lost follow-up and the rate of missing follow-up was 8%.patient in the control group was hospitalized again because of severe chest tightness and chest pain at 1 month follow-up.Coronary angiography showed that LCX stenosis was 80%,and a stent was implanted again.2 Evaluation of imaging:there was no significant difference in LVEDD and LVEF within and between groups at 0 month and 1 month(P>0.05).In 1 month,GLS in CSWT group was not significantly improved compared with that in 0 month,and there was no difference compared with the control group in the same period.While in 6 months,the absolute value of GLS in CSWT group was significantly higher than that of 0 month,but not significantly higher than that of 1 month,and significantly improved in 0 and 1 month compared with control group.At 6 months,MPI in rest and load state of CSWT group was improved as compared with that of 0 month(P<0.05).In control group,there was no significant difference in above-mentioned indexes within and between groups at 0,1 and 6 months(P>0.05).3 Evaluation of clinical situation:at 1 and 6 months,NYHA grade,CCS angina pectoris grade and nitrate dosage decreased,while SAQ score increased significantly in CSWT group,and the above-mentioned indexes were still significantly improved at 6 months after follow-up(P<0.05).And also significantly improved compared with control group except nitrates dosage at 1 month.At 6 month,the nitrate dosage was significantly lower than that of control group(P<0.05).At 1 month,the SF-36 score in CSWT was not significantly higher than that of 0 month,and no significant improvement compared with control group(P>0.05).But at 6 month,it was significantly better than that of 0 and 1 month in CSWT group,whereas no significant improvement compared with control group at the same time(P>0.05)·At 1 month,the 6MWT of CSWT group was not significantly higher than that of 0 month,and also no significant improvement compared with that of control group(P>0.05).At 6 months,6MWT of CSWT group was not significantly better than that of 1 month,but significantly better than that of 0 month,and significantly better than that of control group at the same time(P<0.05),At 1 and 6 months,there was no significant difference in quality of life within and between groups scored by SF-36.4 Evaluation of blood indexes:the number of EPCs colonies in 0,1 and 6 months in CSWT group increased with the passage of time.There was significant difference between 0 and 1 month,0 and 6 months(P<0.05),but no significant difference between 1 and 6 months(P>0.05).In 1 month,the number of EPCs colonies in the CSWT group was 0.255%higher than that of control group without statistical significancy(P>0.05)In 6 months,the number of EPCs colonies in CSWT group was 0.249%higher than that of control group,but no significant difference(P>0.05).SDF-1 in CSWT group showed an upward trend in 0,1 and 6 months,there was no significant difference between 0 and 1 month,but was significant difference between 0 and 6 months,1 and 6 months(P<0.05).There was no significant difference in SDF-1 between CSWT group and control group at 1 and 6 months(P>0.05).5 Correlation analysis:the number of EPCs colonies in peripheral blood was positively correlated with SDF-1 in 0,1 and 6 months.There was a negative correlation between EPCs and CCS angina pectoris grade(r=0.297,p=0.013),but no correlation between EPCs and NYHA cardiac function(r=0.004,p=0.976),SAQ score(r=0.232,p=0.055),6MWT(r=0.085,p=0.487),and GLS(r=0.235,p=0.052).The level of SDF-1 was positively correlated with EPC,but no correlation with other indexes.Conclusion:1.CSWT is a safe and non-invasive revascularization therapy on patients with CCS who still have obvious symptoms after routine treatment.It has a positive effect at 6 months follow-up,including improving myocardial perfusion,cardiac function and quality of life.2.One of the mechanisms of angiogenesis induced by CSWT may be related to EPCs and SDF-1.The proliferation of EPCs up-regulated by the expression of SDF-1 after CSWT promote the establishment of collateral circulation of ischemic myocardium.