| Late outcomes and prognostic factors for patients with ST-segment elevation myocardial infarction who completed primary coronary intervention within 90 minutesObjective Recently,domestic and foreign guidelines suggested that the first medical contact to device(FMC-to-device)time?90 mins in percutaneous coronary intervention(PCI)capable hospital when treating ST-segment elevation myocardial infarction(STEMI)patients undergoing primary PCI(PPCI).But data is scarce regarding whether further reduction in FMC-to-device time into 60mins has a beneficial effect on long-term clinical outcomes,and the factors influence the total ischemic time in these patients have been poorly studied.At present,a large amount of research work demonstrated that off-hours and self-transportation are two independent risk factors for high mortality rate and prolonged the FMC-to-device time of patients undergoing PPCI.It is considered that the high mortality rate of PPCI during off-hours and self-transportation may be due to the long FMC-to-device delay.Therefore,this study only included patients who completed PPCI within 90 minutes,so as to eliminate the influence of excessively long FMC-to-device as much as possible.We aimed to investigate:1.Whether further shortening FMC-to-device time into 60mins has a beneficial effect on late clinical outcomes,2.Whether off-hours PPCI still affected the late outcomes and which prehospital and in-hospital key time interval contributed to the prolonged FMC-to-device time,3,Whether EMS-transportation still affected the late outcomes of PPCI and which prehospital and in-hospital key time interval contributed to the prolonged FMC-to-device time.Methods This multicenter retrospective study included 670 STEMI patients who underwent successful PPCI and had an FMC-to-device time<90 mins from 19 chest pain centers in Beijing from January 2018 to December 2018.According to the FMC-to-device time,the patients were divided into the long-time group(FMC-to-device>60 minutes)and the short-time group(FMC-to-device?60 minutes);According to the hospitalization time,the patients were divided into the on-hours group and the off-hours group;According to the mode of admission,the patients were divided into the(emergency medical services,EMS)transportation group and the self-transportation group.And Baseline characteristics,clinical data and key time intervals during treatment were collected from the Quality Control&Improvement Center of Cardiovascular Intervention of Beijing by the "Heart and Brain Green Channel"(HBGC)app.Patients were followed up for an average of 24 months in order to acquire the information of major adverse cardiovascular events(MACEs),which defined as all-cause death,reinfarction,or target vessel revascularization.Results1.Overall,the median age of the patients was 58.8 years,and 19.9%were female.Of these,441 patients(65.8%)in the long-time group and 229 patients(34.2%)in the short-time group.The median FMC2B was 69 mins in all patients,77 mins in the long time group and 50 mins in the short time group(p<0.01).Although symptom-to-FMC in the long-time group was significantly shorter than that in the short-time group(95 min vs.110 min,P=0.017),the total ischemia time was still significantly longer(173 min vs.160 min,P=0.024).Compared with the long-time group,the patients in the short-time group were more likely to arrive at the hospital during on-hours(52.4%vs.39.9%,P=0.002)and by EMS-transportation(48.5%vs.36.3%,P=0.002).Multiple logistic regression analysis showed that off-hours(OR=0.591,95%CI 0.426?0.821,P=0.002)and self-transportation(OR=0.610,95%CI 0.437?0.850,P=0.004)were independently associated with FMC-to-device>60mins.During an average follow-up period of 24 months,a total of 64 patients experienced the MACEs,50 in the long-time group and 14 in the short-time group.The incidence of MACEs in short-time group was significantly lower than that in long-time group(6.1%vs.11.3%,P=0.031).Kaplan-Meier curves showed that MACE was more frequently observed in the long-time group than in the short-time group(p=0.031).Multivariate Cox regression models indicated that FMC2B<60min(OR 0.529,95%CI 0.291-0.959,P=0.036),age(OR=1.052,95%CI 1.027-1.078,P<0.001)and heart rate(OR=1.019,95%CI 1.005-1.033,P=0.006)were significantly associated with increased risk of MACEs(OR 0.529,95%CI 0.291-0.959,P=0.036)after controlling for confounding factors.And off-hours admission(OR=1.071,95%CI 0.649-1.767,P=0788)and self-transportation(OR=1.326,95%CI 0.811-2.286,P=0.242)was not a predictor of 2-year MACEs.2.There are 296 patients(44.2%)underwent PPCI during on-hours and 374 patients(55.8%)during off-hours.Compared with the on-hours group,the off-hours group had a longer FMC-to-device time(71 min vs 65 min,P<0.001)and activation-to-arrival time(22min vs 16min,P<0.001),and fewer patients had an FMC-to-device time ?60 min(29.1%vs 40.7%,P=0.002).However,there were no differences in symptom-to-device time,symptom-to-FMC time,FMC-to-ECG time,ECG-to-activation time,arrive to device time between the two groups(P>0.05).During the mean follow-up period of 24 months,a total of 64 participants experienced MACEs(9.6%),with 28(9.5%)in the on-hours group and 36(9.6%)in the off-hours group(p>0.05).Similarly,the Kaplan-Meier curves showed that the risks of MACEs,all-cause death,reinfarction and target vessel revascularization(TVR)were not statistically significant between the two groups3.There are 271 patients(40.4%)in EMS-transportation group and 399 patients(59.6%)in self-transportation group.Compared with the EMS-transportation group,the self-transportation group had a longer FMC-to-device time(70 min vs 65 min,P<0.001)and ECG-to-activation time(22min vs 15min,P<0.001),and fewer patients had an FMC-to-device time ?60 min(29.6%vs 41.0%,P=0.002).However,there were no differences in symptom-to-device time,symptom-to-FMC time,FMC-to-ECG time,activation-to-arrive time,arrive-to-device time between the two groups(P>0.05).During the mean follow-up period of 24 months,a total of 64 participants experienced MACEs(9.6%),with 24(8.9%)in the EMS-transportation group and 40(10.0%)in the self-transportation group(P=0.613).Similarly,the Kaplan-Meier curves showed that the risks of a MACEs,all-cause death,reinfarction and TVR were not statistically significant between the two groups(P>0.05).Conclusions1.STEMI patients undergoing PPCI with FMC-to-device time ?90mins,further shortening FMC-to-device time into 60 mins was associated with a reduced incidence of 2-year MACEs.2.STEMI patients who underwent PPCI within 90 mins,off-hours admission was safe,with no difference in the risk of 2-year MACEs compared with those with on-hours admission.Effective measures should be taken to shorten the time delay between the activation-to-arrival of the catheter lab.3.STEMI patients who underwent PPCI within 90 mins,self-transportation was safe,with no difference in the risk of 2-year MACEs compared with those by EMS-transportation.Effective measures should be taken to shorten the diagnosis delay(ECG-to-activation time)in patients who arrived by self-transportation.Effect and mechanism of LCZ696 on proliferation of hypoxic endothelial cellsObjective:Studies have shown that Sacubitril/valsartan(LCZ696)significantly improves endothelium-dependent vasodilation in patients with hypoxia.Meanwhile,peroxisomal proliferation-activated receptor(PPARy)may be involved in the anti-hypoxia of endothelial cells by regulating the angiotensin receptor.However,the changes of endothelial cells' metabolic function under hypoxia have not been fully studied.The purpose of this study was to investigate the effect of LCZ696 on endothelial cell proliferation in hypoxic environment in vitro and its possible mechanism.Methods:1.Endothelial cells were cultured under the condition of normal oxygen and hypoxia for growth count and cell proliferation were detected by two-dimensional clone formation.2.The effect of LCZ696 on the proliferation of endothelial cells under hypoxia condition was detected after LCZ696 treatment.3.The expression of PPAR-yin the vascular endothelial cells before and after LCZ696 treatment were detected by Western Blot.Results:1.Under hypoxia condition,the proliferation of vascular endothelial cells was significantly decreased compared with normal culture cells,and the ability of clone formation was significantly decreased.2.LCZ696 treatment can improve the growth count and clone formation ability of vascular endothelial cells under hypoxia condition.3.The increase of PPARy expression in endothelial cells under hypoxia was detected by Western Blot,and LCZ696 treatment could re-normal the expression of PPARy in endothelial cells under hypoxia.Conclusion:LCZ696 can improve endothelial cell proliferation under hypoxia in vitro.PPARy was upregulated in vascular endothelial cells under hypoxia environment,and its normal expression was restored after the intervention of LCZ696,suggesting that the protection of vascular endothelial cell function under hypoxia by LCZ696 may be related to the regulation of PPARy. |
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