| Objective:Cardiogenic shock(CS)was associated with significant morbidity and mortality.Venoarterial extracorporeal membrane oxygenation(VA-ECMO)was used increasingly to treat CS,however the mortality was still around 40-75%.Especially in China,the use of VA-ECMO is still at the stage of promotion and development,and the patient population and disease spectrum,as well as the management experience,were very different from those in Europe and the United States,and there are many problems that need to be solved in the selection of the population,device placement,prognosis analysis,operation management and quality control.When the failing heart cannot overcome the afterload generated by ECMO,left ventricular dilatation and refractory pulmonary edema may occur,seriously affecting the prognosis of CS patients.Left heart decompression(LHD)can reduce left heart load,but there is a lack of evidence from high-quality studies to support its efficacy and safety in clinical use and whether it is cardioprotective.Unfortunately,there are no animal models available for preclinical research to identify if ECMO combined with LHD was useful,making it even difficult to investigate the ideal strategy,timing of decompression,and underlying mechanisms.For the reasons above,this study was designed as follows: Chapter 1-to review the experience of VA-ECMO implementation in CS patients at West China Hospital for 8 years and analyze the main risk factors affecting survival;Chapter 2-to evaluate the safety and efficacy of VA-ECMO combined with LHD.To analyze the risk factors affecting the successful weaning from ECMO.Next,to explore the relationship between LHD timing and patient prognosis.Chapter 3-to establish a novel pre-clinical animal model of VA-ECMO combined LHD for CS,and to explore the appropriate decompression pathways,devices and flow rates.Chapter 4-to evaluate whether LHD can have a protective effect on cardiopulmonary function and the related mechanisms based on previous animal model.Next,to identify if decompression timing is associated with cardiopulmonary protection and the role of inflammatory response.Materials and Methods:Chapter 1: a single-center retrospective cohort study.Adult patients undergoing VA-ECMO support for CS at West China Hospital from January 2012 to December 2019 were included,and their demographic characteristics,medical history,preoperative baseline characteristics,outcomes,and complications were collected.The primary study outcome was in-hospital death,and secondary study outcomes were myocardial recovery,successful ECMO weaning,duration of ECMO support,duration of mechanical ventilation,length of hospital stay,costs,and major complications.Chapter 2 is divided into two parts: the first part is a case-control study,in order to study the safety and efficacy of VA-ECMO combined with LHD treatment.36 patients who met the indications for LHD were included.They were divided into LHD(-)and LHD(+)groups according to whether or not LHD was performed,to compare whether LHD could affect patient prognosis.The primary study outcome was inhospital death and secondary study outcomes were myocardial recovery,successful ECMO weaning,duration of ECMO support,duration of mechanical ventilation,length of stay,costs,and major complications.The second part is a retrospective cohort study designed to further analyze the risk factors affecting successful ECMO weaning in patients treated with ECMO and LHD.19 patients were enrolled and retrospectively analyzed to explore the relationship between LHD timing and patient prognosis.The primary study outcome being successful ECMO weaning.Finally,the optimal decompression timing using ROC curves was identified.Chapter 3: six anesthetized Beagle dogs were intubated and then underwent median sternotomy.CS was induced by ligation of left anterior descending artery.1 hour after acute myocardium ischemia,the animals were treated by femoral-femoral VA-ECMO.To better evaluate hemodynamic changes of LHD,we compare different venting flow about 20ml/kg/min and 40ml/kg/min.Chapter 4: 12 Beagle dogs were randomly divided into two groups,one for early decompression(Group E)and one for late decompression(Group L).In group E,peripheral VA-ECMO and LHD was initiated simultaneously 1 hour after coronary ligation at a flow rate of 40 ml/kg/min for 3 hours;in group L,peripheral VA-ECMO and was initiated 1 hour after coronary ligation and then left heart decompression was started 1 hour after ECMO support,so the total LHD duration was 2 hours.The changes in hemodynamics,blood gas analysis,and echocardiography were recorded at the beginning of the coronary ligation experiment(T0),the start of ECMO(in which group E was combined with LHD,while group L was not combined with LHD)(T1),the start of LHD in group L(T2),and the end of the experiment(T3),respectively.The changes in the above indexes were compared at different time points.Myocardial and lung tissue specimens were retained for pathological examination at the end of the experiment.The inflammatory factors of IL-6 and TNF-α were measured in left ventricular myocardium,plasma and lung tissues.Results:Chapter 1: A total of 63 adult patients,aged 50(29-64)years and 65.08% male,were included for statistical analysis.The mean ECMO support was 119.62 ± 84.7 hours.Acute decompensated heart failure(n=31,47.62%)was the main diagnosis for VA-ECMO support.Univariate analysis found that age,extracorporeal cardiopulmonary resuscitation(ECPR),acute ischemic heart disease,vasoactive drug score,APACHE II score,SAVE score,PH,BE,lactate,and partial pressure of oxygen(PO2)were associated with patient prognosis;multifactorial regression analysis suggested that only SAVE score and PO2 were independent predictors of in-hospital death(P=0.015;P=0.004).Lactate was significantly higher at 6,12,24,and 48 hours of VA-ECMO initiation in the death group compared to the survivor group(P=0.001;P=0.01;P=0.004;P=0.004).24 hours after VA-ECMO support initiation,brain natriuretic peptide(BNP)and creatine phosphokinase isoenzyme(CK-MB)levels were significantly higher in the death group compared to the survivor group(P=0.050;P=0.050).In-hospital mortality was 69.84% and the main cause of death was cardiac(n=28,63.64%).66.67%(n=42)of patients were successfully weaned from ECMO,but only 33.33%(n=21)had myocardial recovery.Infection(53.97%,n=34)was the most common complication after VA-ECMO,especially pulmonary infection(n=30,47.62%).LHD was performed in about 1/3(30.16%)of patients,with a higher percentage of LHD in the survivor group than in the death group(42.1% vs.25%).More than half(59.09%,n=26)of the patients died within 1 week of ECMO initiation,with a 5-year survival rate of 84.2%.The findings in this chapter suggest that cardiopulmonary protection is key to improving VA-ECMO outcomes,and LHD may help reduce in-hospital mortality in CS patients undergoing VA-ECMO.Chapter 2: LV dilatation occurred in 57.14%(n=36)of patients on VA-ECMO support and LHD was carried by 30.16%(n=19)of total VA-ECMO patients,with uneventful rate of major complications.Transaortic catheter venting(TACV)was the predominant decompression modality used(n=16).Patients in the LHD(+)group had a trend toward lower mortality(57.89% vs.76.47%),easier successful weaning from ECMO(63.16% vs.52.94%),and easier recovery of myocardial function(47.37% vs.35.29%)than patients in the LHD(-)group.The retrospective cohort study found that high initial APACHE II score(P=0.021),ECPR(P=0.003)and late decompression initiation(P=0.046)were risk factors for successful ECMO weaning in patients with ECMO and LHD(n=19).The ROC analysis identified LHD within 16 hours of VAECMO initiation as the ideal time split point for successful LHD for ECMO weaning.The time point was used to divide patients into an early decompression group(decompression <16 hours from ECMO initiation,n=13)and a late decompression group(decompression ≥16 hours from ECMO initiation,n=6).Patients in the early LHD group had significantly lower in-hospital mortality(38.46 % vs.100 %,P=0.012),significantly higher odds of successful ECMO weaning(84.62 % vs.16.67 %,P=0.004)and myocardial recovery(69.23 % vs.0 %,P=0.005).The results of this chapter suggest that LHD may be able to reduce in-hospital mortality and promote myocardial recovery and successful ECMO weaning.Timing of LHD is associated with patient prognosis,and early decompression,especially within 16 hours of ECMO initiation,significantly improves patient prognosis.Chapter 3: 4 animals survived till the end of the study.The ECMO flow was easily achieved at 100ml/kg/min which was adequate to guarantee cardiopulmonary support.The most appropriate decompression pathway on dogs was directly putting a venting cannula through left ventricular apex.ECMO cannot prevent the increase of left heart filling pressures during acute heart failure.After 30 minutes of decompression,the left atrial pressure and mean pulmonary artery pressure decreased by 41.7% and 34.4 respectively on flow of 40ml/kg/min,but low venting flow of 20ml/kg/min cannot change the hemodynamics significantly.Chapter 4: compared to group L at T2 time point,animals in group E had lower LAP(20.33±4.68 vs.28.17±5.31,P=0.036),lower LVEDP(18.67±3.56 vs.27.33±3.88,P=0.015),lower m PAP(26.50±5.09 vs.40.17±8.8,P=0.012),lower coronary arteriovenous oxygen saturation difference(50.67±3.67 vs.61.83±7.00,P=0.035),combined with smaller left atrial diameter(2.03±0.16 vs.2.61±0.35,P=0.014)and increased coronary perfusion pressure(43.83±6.52 vs.27.50±9.35,P=0.042).The above findings suggest that LHD can reduce left heart filling pressure and pulmonary artery pressure,decrease myocardial oxygen consumption,increase coronary perfusion and thus improve myocardial oxygen supply.Compared to group L at T3 time point,animals in group E had higher MBP(69.35±17.91 vs.59.95±15.39,P=0.047),lower mean pulmonary artery pressure(18.50±2.74 vs.32.17±6.18,P=0.004),higher left ventricular oxygen saturation(91.83±1.94 vs.1.94 vs.84±3.79,P=0.035)and better TAPSE(6.38±1.46 vs.4.03±1.06,P=0.011).Histopathological examination suggested less right ventricular pathological damage(1.28±0.39 vs.1.89±0.49,P=0.028),lower lung tissue wet-to-dry weight ratio(7.46±1.28 vs.10.88±3.06,P=0.023)and lower lung pathology score)in the E group compared to L group(1.17±0.35 vs.2.00±0.47,P=0.046).Also,lower lung tissue IL-6(454.68±34.71 vs.568.65±59.84,P=0.022)and TNF-α(275.61±44.95 vs.383.92±47.63,P<0.001)were found.The above findings suggest that early LHD improves right ventricular systolic function,improves pulmonary oxygenation,and attenuates pathological damage to the right ventricular myocardium and lung.The mechanism of its pulmonary protective effect is related to attenuating the local pulmonary inflammatory response.Conclusion:In this study,we evaluated the current status of VA-ECMO practice in our center.Also,we assessed the safety and efficacy of left heart decompression by combining clinical and animal experiments.We conducted a preliminary animal models of left heart decompression,which was evaluated by decompression pathways,decompression flow,decompression efficacy and decompression timing,as well as their cardiopulmonary protection mechanisms.We found that:(1)the severeness and initial pulmonary impairment before ECMO initiation was closely related to prognosis,and maintenance of cardiopulmonary function during ECMO support is key to reduce mortality.(2)left heart decompression can be safely implemented,and it may improve patient prognosis.Early decompression(within 16 hours of ECMO initiation)can significantly reduce in-hospital mortality.(3)LHD significantly reduces left heart filling pressures and pulmonary artery pressures in during ECMO support.Early LHD may improve prognosis by reducing pulmonary and right heart pathological damage.The pulmonary protective effect was associated with attenuating the level of local inflammatory response in the lung.In conclusion,in patients undergoing VA-ECMO support for cardiogenic shock,enhanced monitoring and maintenance of cardiopulmonary function should be emphasized.Early implementation of left heart decompression can exert significant cardiopulmonary protective effects,so it should be emphasized in future clinical work. |
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