Analysis Of Clinical Characteristics And Diagnostic Value Of CircACSL1 In Children With Fulminant Myocarditis

BackgroundMyocarditis is an inflammatory disease of the myocardium that is mild in most patients.The most severe form of myocarditis is fulminant myocarditis(FM),which usually presents with hemodynamic disturbances early in the course of the disease and has a mortality rate of 48%in pediatric patients.The clinical presentation of fulminant myocarditis is heterogeneous,especially in pediatric patients,who may present with fever,vomiting,diarrhea,malaise,or mild chest pain early in the course of the disease,with some children showing signs of viral infection in the days prior to the onset of the disease.Therefore,in clinical practice,history taking is particularly important.In addition,peripheral blood markers of myocardial injury,electrocardiogram,chest X-ray,and echocardiogram are also important diagnostic bases.In patients with fulminant myocarditis,peripheral blood leukocytes,CRP,PCT and other infection markers and myocardial injury markers such as HS-TnT and CK-MB are elevated to varying degrees,and large heart shadow and reduced left ventricular ejection fraction are also common manifestations of fulminant myocarditis.The treatment of fulminant myocarditis is a comprehensive life-support-based regimen,which is a combination of mechanical circulatory support devices and immune system modulation.The most important of these treatments is extracorporeal membrane oxygenation(ECMO).Early application of ECMO can greatly improve survival in pediatric patients with fulminant myocarditis.Left ventricular ejection fraction(LVEF)has been shown in several studies to have predictive value for the prognosis of patients with fulminant myocarditis.Objective:In this study,we will analyze the clinical characteristics of a group of patients with fulminant myocarditis through clinical data and look for risk factors for fulminant myocarditis in children requiring ECMO support therapy and in-hospital mortality.Methods:Thirty-three children with fulminant myocarditis who were hospitalized in the Department of Pediatric Cardiology or the Department of Pediatric Intensive Care Medicine of Shandong First Medical University from August 2019 to December 2022 were retrospectively collected and divided into ECMO-treated and non-ECMO-treated groups according to treatment measures,and into survival and in-hospital death groups according to outcome,and the differences in their clinical data were compared separately,and the factors that differed in the two groups were subjected to logistic regression analysis to find independent risk factors for ECMO treatment and in-hospital death,and their predictive value was assessed by ROC curves.Results:1.The median age of the 33 children with fulminant myocarditis was 10 years,the median length of stay was 17 days,and there was no significant difference by gender.There were 8 deaths,with a mortality rate of 24%,and 6 deaths in the ECMO-treated group.In all patients with fulminant myocarditis,most of them started with non-specific symptoms such as fever,vomiting and abdominal pain.2.IL-6 in laboratory tests was higher in the ECMO-treated group than in the nonECMO-treated group,and the incidence of ventricular tachycardia,pleural effusion and invasive ventilator use were higher than in the non-ECMO-treated group.LVEF was lower in the ECMO-treated group than in the non-ECMO-treated group,and all differences were statistically significant.3.LVEF was an independent risk factor for the need of ECMO treatment in FM patients,with a cut-off value of 33.5%,a sensitivity of 93.3%,and a specificity of 88.2%,the area under the curve of the ROC curve was 0.9588,p<0.0001.4.The length of stay and LVEF in the inhospital death group were lower than those in the survivor group,and the percentage of WBC,PCT,IL-6,NT-proBNP and invasive ventilator application in laboratory tests were higher than those in the survivor group,and the differences were statistically significant.5.LVEF was an independent risk factor for in-hospital death in FM patients with a cutoff value of 29.5%,sensitivity of 85.7%and specificity of 80%.the area under the curve of ROC curve was 0.8714,p=0.003.Concusions:Left ventricular ejection fraction can have good predictive value as an independent risk factor for patients with fulminant myocarditis requiring ECMO therapy and in-hospital death.Fulminant myocarditis(FM)is a rare but serious type of myocarditis.It is characterized by rapid onset,rapid progression,and high mortality rate,and can usually result in serious complications such as cardiogenic shock and heart failure within a short period of time,which can be life-threatening.The clinical symptoms of FM in children are atypical and may manifest as fever,vomiting,abdominal pain,and malaise,which are often misdiagnosed as respiratory or digestive system diseases.Due to the invasive nature and low sensitivity of endomyocardial myocardial biopsy,it is less commonly used in clinical practice.Therefore,the current diagnosis of fulminant myocarditis still relies on clinical diagnosis,which requires a comprehensive medical history,markers of myocardial injury,electrocardiogram,chest Xray and echocardiogram to make a comprehensive judgment.Therefore,there is an urgent need for the emergence of low-cost,highly specific serological biomarkers.Non-coding RNAs(ncRNAs)are transcriptionally active but not protein-coding RNAs in the human genome that have important regulatory functions.ncRNAs have been identified as key regulators of the cardiovascular system for diagnosis and therapy.Some ncRNAs in blood change in different disease states and are well stabilized in the peripheral circulation,thus having great potential in the diagnosis of fulminant myocarditis.However,current studies of non-coding RNAs in the diagnosis of fulminant myocarditis in children are still limited.Objective:We selected ncRNAs that have been studied mechanistically but not clinically validated by our group in the early stage and some ncRNA molecules that have been confirmed to be involved in the occurrence and development of myocarditis in previous literature reports but not systematically validated,and clinically validated them to select ncRNAs with potential as biomarkers of fulminant myocarditis,analyze their expression characteristics in fulminant myocarditis,and assess their diagnostic value.Methods:Thirty-three cases of fulminant myocarditis,30 cases of dilated cardiomyopathy(DCM)initially diagnosed and hospitalized at the Department of Pediatric Cardiology or the Department of Pediatric Intensive Care Medicine of Shandong First Medical University from August 2019 to December 2022,were retrospectively collected.In addition,there were 32 healthy children who were seen in the Department of Pediatric Health Care.The baseline clinical characteristics of each group of patients were analyzed.qRT-PCR was used to analyze the differential expression of ncRNA of fulminant myocarditis compared with dilated cardiomyopathy and healthy controls,and the diagnostic value was evaluated by applying the receiver operating characteristic(ROC)curve.The correlation with clinical indices of myocarditis and the trend of change in the course of the disease were analyzed.Results:1.LVEF of patients in the fulminant myocarditis group was significantly lower than that of healthy controls,and HS-cTn T and NT-proBNP were significantly higher than those of healthy controls,and the differences were statistically significant.2.A total of four ncRNA molecules were screened and the candidate ncRNA molecules were initially validated,and the results showed that lncRNA NONHSAT177112.1,lncRNA NONHSAT253897.1,circHIPK3 were not significantly different between the fulminant myocarditis group and the healthy control group,and circACSL1 in the fulminant myocarditis group The expression of circACSL1 was significantly higher in the fulminant myocarditis group than in the healthy control group,with a p-value of 0.0382.circACSL1 was selected as the target molecule.3.The expression of circACSL1 in children with fulminant myocarditis was significantly higher than that in the dilated cardiomyopathy group(p=0.01)and the healthy control group(p<0.0001).The expression in the DCM group was not statistically different from that in the healthy control group.4.circACSL1 was significantly higher in the acute phase of fulminant myocarditis than in the recovery phase,with a statistical difference between the two groups(p=0.026)5.circACSL1 had good diagnostic value in fulminant myocarditis,and the area under the curve of ROC curve was 0.9044,p<0.0001.6.The expression of circACSL1 did not correlate with infection index,and showed a moderate negative correlation with LVEF(r=-0.5066,p=0.0031),a strong positive correlation with HS-TnT(r=0.8596,p<0.0001),and a moderate positive correlation with NT-proBNP(r=0.6283,p<0.0001).7.The expression of circACSL1 in peripheral blood of patients with fulminant myocarditis gradually decreased within 1 week of admission,which was opposite to the trend of LVEF and approximately the same as that of HS-TnT and NT-proBNP.Concusions:1.CircACSL1 can be used to differentiate fulminant myocarditis from dilated cardiomyopathy,and has a high diagnostic value for fulminant myocarditis in children.CircACSL1 expression was significantly altered during the course of myocarditis and correlated significantly with the recovery of left ventricular function.3.CircACSL1 is expected to be a powerful indicator for the diagnosis,treatment and disease monitoring of childhood fulminant myocarditis.