Evaluation Of Left Ventricular Function And CircRNA Regulation In Cirrhotic Cardiomyopathy Before And After Liver Transplantation

Objective:To evaluate the left ventricular structure and function change and the improvement after liver transplantation in patients with CCM by conventional echocardiography and three-dimensional speckle tracking imaging（3D-STI）,to explore the regulatory effect of circ RNA on cirrhotic cardiomyopathy（CCM）and the possibility of differentially expressed circ RNA as a potential therapeutic target for CCM.Methods:From January 2021 to June 2022,100 patients with liver cirrhosis（LC）in the Affiliated Hospital of Qingdao University were enrolled:35 cirrhosis cardiomyopathy[LC-CCM（+）],65 liver cirrhosis non-cardiomyopathy[LC-CCM（-）],according to the diagnosis criteria of systolic dysfunction and/or diastolic dysfunction according to the2020 CCM guidelines.And 50 healthy volunteers were selected as the controls.In the LC-CCM（+）group,16 patients with CCM who underwent liver transplantation were selected,and the data was performed again at 1 month after liver transplantation.Left atrial anterior and posterior diameter（LAD）,left ventricular end-diastolic diameter（LVDd）,left ventricular end-systolic diameter（LVDs）,interventricular septum thickness（IVST）,left ventricular posterior wall thickness（LVPWT）,early peak diastolic flow rate（E）,late peak diastolic flow rate（A）early peak diastolic velocity（e’）and left ventricular ejection fraction（LVEF）were measured by conventional echocardiography.Left ventricular global longitudinal strain（GLS）,global radial strain（GRS）,global circumcircular strain（GCS）,left ventricular maximum volume(LVV_max)and left ventricular minimum volume(LVV_min)were measured by 3D-STI.Mosteller formula was used to calculate the body surface area（BSA）,and the left ventricular maximum volume index(LVVI_max)and left ventricular minimum volume index(LVVI_min)were calculated after correction of BSA,and the differences between groups were compared.Four CCM patients who had undergone liver transplantation were selected.Gene sequencing technology was used to detect the circ RNA expression profile of patients with CCM before and after liver transplantation and predicted the differential circ RNA target genes.Results:（1）Compared with the control group,LAD,LVDd,LVDs,IVST and LVPWT were increased in LC-CCM（+）group and LC-CCM（-）group.Compared with the control group,A were increased in LC-CCM（+）group.Compared with the control group and LC-CCM（-）group,e’was decreased in LC-CCM（+）group.Compared with the control group,the E/e’of LC-CCM（+）group and LC-CCM（-）group increased.Compared with LC-CCM（-）group,the E/e’of LC-CCM（+）group increased（P<0.05）.（2）Compared with the control group,GLS,GRS and GCS were decreased and LVV_max,LVV_min,LVVI_max,LVVI_minwere increased in LC-CCM（+）group and LC-CCM（-）group.Compared with LC-CCM（-）group,GLS,GRS and GCS were decreased and LVVI_minwere increased in LC-CCM（+）group（P<0.05）.（3）Compared with those before liver transplantation,LAD,LVDd,LVDs,IVST,LVPWT,A,LVV_max,LVV_min,LVVI_min,LVVI_maxdecreased,E,E/A,e’,GLS,GRS,GCS increased after liver transplantation（P<0.05）.（4）Compared with those before liver transplantation,a total of 1495 circ RNAs were dysregulated after liver transplantation in 4 CCM patients undergoing liver transplantation,of which 176 were upregulated and 1319 were downregulated（P<0.05）.The Real Time Quantitative PCR（q RT-PCR）results showed that circ-ASAP1,circ-N4BP2L2,circ-EXOC6B were significantly downregulated（P<0.05）,which were consistent with the RNA sequencing data,and circ-ASAP1 had the most significant difference.Bioinformatics analysis suggested that m TOR and MAPK signaling pathways might be involved in the pathogenesis of CCM.By constructing a circ RNA-mi RNA-m RNA interaction network,hsa-mi R-197-3p,hsa-mi R-483-3p,and hsa-mi R-885-3p,particularly key mi RNA（hsa-mi R-483-3p）,were found to be the major potential genes involved in CCM regulation.Conclusions:1.Conventional echocardiography and 3D-STI showed that CCM patients had changes in left ventricular structure and function,including left ventricular enlargement,increased ventricular wall thickness,and decreased systolic and diastolic functions.2.The above changes were improved after liver transplantation.3.Circ RNA plays a crucial regulatory role in the occurrence of CCM before and after liver transplantation,and their potential biological function might be the key to diagnosis and treatment.