| Background and purpose:In recent years,a large number of studies have found that the deubiquitinase BRCC36 is closely related to the repair and antagonism of ventricular remodeling after myocardial injury.This study aimed to investigate whether BRCC36 concentrations in plasma are associated with the occurrence and severity of heart failure.Methods:From October 2020 to August 2021,a total of 98 patients with heart failure who were hospitalized in the department of cardiology of affiliated hospital of Yangzhou University and 81 healthy patients during the same period were selected to participate in this study.According to the New York Heart Association（NYHA）cardiac function classification,the subjects were divided into 4 groups:control group,cardiac function class Ⅰ-Ⅱ group,cardiac function class Ⅲ group,and cardiac function class Ⅳ group.In addition,subjects were divided into three groups according to echocardiographic ejection fraction results:control group,heart failure with preserved ejection fraction（HFpHF）group（EF≥50%）,and heart failure with reduced ejection fraction（HFrEF）group（EF<50%）.Blood samples were collected from all subjects on admission or the next morning,as well as blood samples from 25 patients in the heart failure group on the day of discharge after standard treatment.The supernatant was obtained by centrifugation and stored in a-80° refrigerator.The general baseline data（including age,gender,BMI,underlying diseases and comorbidities,blood routine and blood biochemical indicators,myocardial injury markers,coagulation function,NT-proBNP,etc.）.Echocardiography was performed,and left ventricular end-diastolic volume（LVEDV）,left ventricular end-systolic volume（LVESV）,and left ventricular ejection fraction（LVEF）,left ventricular fractional shortening（LVFS）were recorded.All samples were quantified by enzyme-linked immunosorbent assay（ELISA）using a commercial off-the-shelf kit.SPSS.26 software was used for analyzing BRCC36 concentrations and other clinical data among all groups to determine whether there were differences and correlations.Logistic binary regression analysis was used to evaluate which factors were independently associated with heart failure;in addition,the receiver operating curve（ROC）was used to evaluate the diagnostic value and severity of BRCC36 in heart failure.Result:1.A total of 179 patients were included in this study,and 204 BRCC36 blood samples were tested,of which 25 were pre-discharge review samples in the heart failure group.All subjects were divided into control group and heart failure group according to whether they had heart failure or not;the concentration of BRCC36 in the heart failure group was significantly lower than that in the control group（P<0.05）,and the age in the heart failure group was significantly higher than that in the control group（P<0.05）,the incidence of hypertension,diabetes,coronary heart disease,arrhythmia and valvular disease in the heart failure group was higher than that in the control group（P<0.05）.The levels of CRP,ALT,Cr,BUN,D-dimer,NT-proBNP,LVEDV and LVESV in the heart failure group were significantly higher than those in the control group（P<0.05）,while PLT,ALB,TC,TG,HDL-C,LDL-C,LVEF and LVFS levels were lower than those in the control group（P<0.05）.2.All patients with heart failure were divided into three groups according to the NYHA cardiac function classification:cardiac function class Ⅰ-Ⅱ group,cardiac function class Ⅲgroup,and cardiac function class Ⅳ group.Comparison between the groups showed that the concentration of BRCC36 in the cardiac function class Ⅳ group was lower than those in the cardiac function grade Ⅰ-Ⅱ group（P<0.05）,and the rest indicators including HDL-C,LVEDV,LVESV,LVFS,LVEF and NT-proBNP were statistically different（P<0.05）.3.The heart failure group was divided into the HFpEF group and HFrEF group according to the EF value of cardiac color Doppler ultrasound with 50%as the cut-off point.Among them,the BRCC36 value in the HFrEF group was significantly lower than that in the HFpEF group（P<0.05）,and there were significant differences among the other groups including the prevalence of arrhythmia and cardiomyopathy,LVEDV,LVESV,LVFS,LVEF and NT-proBNP,the difference was statistically significant（P<0.05）.4.The results of Spearman correlation analysis and multiple linear regression analysis showed that BRCC36 concentration was negatively correlated with cardiac function classification（rs=-0.448）,RDW（r=-0.261）,Cr（r=-0.309）,D-dimer（r=-0.340）,LVEDV（r=-0.346）,LVESV（r=-0.287）and NT-proBNP（r=-0.460）（P<0.001）.With PLT（r=0.215）,TC（r=0.306）,HDL-C（r=0.239）,LDL-C（r=0.249）,ALB（r=0.374）,FS（r=0.203）and EF（r=0.310）was positively correlated（P<0.001）,among them,there was a moderate correlation with cardiac function class and NT-proBNP,others were weakly correlated.Factors related to BRCC36 were included as independent variables into the multiple linear regression model,and BRCC36 was used as the dependent variable.The rusult is that the concentration of BRCC36 decreased with the increase of NT-proBNP（β=-0.546,P<0.05）and RDW（β=-0.188,P<0.05）,and with the decrease of LVFS（β=0.335,P<0.05）.5.Binary Logistic regression analysis showed that BRCC36,ALB,Cr,ALT and CRP were independently associated with heart failure,among which BRCC36[OR=0.180,95%CI（0.098-0.333）]and ALB[OR=0.586,95%CI]（0.396-0.867）]are protective factor for heart failure,while Cr[OR=1.266,95%CI（1.056-1.517）],ALT[OR=1.315,95%CI（1.035-1.672）]and CRP[OR=1.789,95%CI（0.098-2.694）]were independent risk factor for heart failure.6.The area under the curve（AUC）of the ROC curve by BRCC36 concentration used to predict the occurrence of heart failure is 0.745,the best cutoff value is 1.65ng/ml,the sensitivity and specificity are 65.4%and 79.6%,respectively.The AUC of the ROC used to assess the severity of heart failure and predict different types of heart failure was 0.633,the best cut-off value was 1.50ng/ml,and the sensitivity and specificity were 56.8%and 70.4%;The area under the curve of ROC curve drawed to evaluate the severity of heart failure and predict different types of heart failure by NT-proBNP was 0.707,the best cut-off value was 4907pg/ml,and the sensitivity and specificity were 68.5%and 70.5%.7.Taking the EF value as the gold standard,using the cut-off point value obtained from the ROC curve as the diagnostic cut-off point,a four-table table was drawn to calculate the value of BRCC36 and NT-proBNP in assessing the severity of heart failure respectively,where the sensitivity and specificity were related to the ROC curve.The results were basically the same.The positive predictive value of BRCC36 in assessing the severity of heart failure was 69.8%,the negative predictive value was 56.4%,the positive likelihood ratio was 1.88,the negative likelihood ratio was 0.63,and the accuracy was 62.2%;NT-proThe positive predictive value of BNP in assessing the severity of heart failure was 74.0%,the negative predictive value was 64.6%,the positive likelihood ratio was 2.32,the negative likelihood ratio was 0.45,and the accuracy was 69.4%;combined BRCC36 and NT-proBNP to assess heart failure The sensitivity and specificity of the severity of aging were 77.8%and 72.7%,the positive predictive value was 77.8%,the negative predictive value was 72.7%,the positive likelihood ratio was 2.85,the negative likelihood ratio was 0.31,and the accuracy was 75.5%.8.The area under the ROC curve of BRCC36 for diagnosing HFpEF was 0.698,the best cut-off value was 2.01ng/ml,and the sensitivity and specificity were 48.1%and 95.5%,respectively;the area under the ROC curve of BRCC36 for diagnosing HFrEF was 0.783,The optimal cut-off value was 1.64ng/ml,and the sensitivity and specificity were 65.4%and 85.2%,respectively.9.The 25 patients sourced from the heart failure group had no significant difference in the BRCC36 concentration on the day of discharge after 7-10 days of standard treatment compared with that on admission（P>0.05）.Conclusion:1.The concentration of BRCC36 in the plasma of patients with heart failure is lower than that of healthy people,which is negatively correlated with the severity of the disease,and the concentration of BRCC36 decreases with the decrease of cardiac function;2.Plasma BRCC36 concentration has diagnostic value for different types of heart failure;3.The value of BRCC36 for assessing the severity of heart failure is slightly lower than that of NT-proBNP,and the combination of BRCC36 and NT-proBNP can greatly improve the value of assessing the severity of heart failure;4.The concentration of BRCC36 in the plasma of patients with heart failure did not change significantly before and after short-term standardized treatment;5.BRCC36,as an influencing factor of heart failure,can be used to diagnose heart failure and assess its severity. |
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