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The Value Of P Wave In Predicting Recurrence After Ablation Of Persistent Atrial Fibrillation And Bioinformatics Analysis Of Gene Expression In These Patients

Posted on:2022-02-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:T LiuFull Text:PDF
GTID:1484306554987339Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The exact mechanism of atrial fibrillation is unclear.At present,the understanding of the mechanism of atrial fibrillation has changed from the initial "multi-wavelet theory" to the current "focal drive with fibrillation-like conduction" and "pulmonary vein wave" theory.On the basis of Haissagueeree's "driving" theory and "multi-wavelet reentry" theory,and combined with the results of clinical surgical ablation,a new "pulmonary vein wave" hypothesis is put forward.The hypothesis holds that the pulmonary vein and its surrounding atrial tissue are the key sites for the occurrence and maintenance of atrial fibrillation,and focal rapid ectopic activation originating from the pulmonary vein is easy to form reentrant and fibrillation-like conduction when passing through the vestibule of the pulmonary vein.And then lead to the occurrence and maintenance of atrial fibrillation.Catheter ablation of bilateral pulmonary vein-vestibular electrical isolation has become one of the main treatments for paroxysmal atrial fibrillation.In addition,recent technological advances have extended the indication of catheter ablation to persistent atrial fibrillation.However,the long-term success rate of catheter ablation of persistent atrial fibrillation is not satisfactory.In fact,the ordinary 12-lead ECG is an easy-to-use and inexpensive tool.We will further study whether the P-wave analysis can be used to detect the postoperative recurrence of persistent atrial fibrillation and whether it reflects the changes of atrial electrical structure and anatomical results after operation.It is of great significance for the prediction of the risk of recurrence of atrial fibrillation and the management of postoperative patients,especially for the treatment of patients with persistent atrial fibrillation.MiRNAs plays a variety of roles in atrial fibrillation,including regulating cardiac electrical remodeling and structural remodeling.Different miRNAs expressions were up-regulated or down-regulated in patients with atrial fibrillation.Some studies have suggested that circ RNA acts as a regulator of miRNA levels,so circ RNAs may be a potential biomarker for the occurrence and development of atrial fibrillation.In addition,bioinformatics analysis provides a new perspective for circ RNAs involving atrial fibrillation and lays a foundation for the future study of the potential role of circ RNAs in atrial fibrillation.In this study,we conducted a comprehensive analysis based on the GEO data set to further identify abnormally regulated circ RNA,in atrial fibrillation to explore the mechanism of the genetic level of atrial fibrillation.The biological functions of these differentially expressed genes were further explored through the annotation of gene function and metabolic pathway and the construction of protein interaction network,in order to provide more basic basis for the exploration of molecular biology and pathophysiological pathogenesis of atrial fibrillation.to provide new targets for the development of new diagnostic biomarkers and drug therapy.Part 1 The value of P-wave parameters and Macrua index in predicting recurrence after Catheter Ablation of Persis-tent Atrial FibrillationObjective: To study the value of P wave related parameters(amplitude,duration,dispersion)and Macrua index in predicting the recurrence of early and late atrial fibrillation after catheter ablation.Methods:We reviewed the information of 80 patients with persistent atrial fibrillation who underwent circumferential pulmonary vein-vestibular catheter ablation from 2018 to 2020,and collected 12-lead synchronous body surface electrocardiogram on the same day after operation.the P wave parameters(time limit,amplitude,dispersion)and Macrua index were measured,and the recurrence of atrial fibrillation was observed in early(within 3months)and late(after 3months)to 1 year after operation.The effects of P wave parameters and Macrua index on the recurrence of early and late atrial fibrillation were compared and analyzed,and the difference was statistically significant.Receiver operating characteristic curve(ROC curve)was used to evaluate its value in predicting the recurrence of atrial fibrillation after catheter ablation in patients with persistent atrial fibrillation.Results:During the 3-month follow-up,60 cases(75%)had no recu-rrence of atrial fibrillation and 68 cases(85%)had no recurrence of atrial fibrillation at 12 months.1.P wave amplitude: The amplitude of P wave in lead ?,AVR and V2-V6 in early recurrence group was lower than that in early non-recurrence group,and the amplitude of P wave in ? AVF V2-V6 lead inlate recurrence group was smaller than that in late recurrence group.2.P wave duration: P wave duration in ? lead of early recurrenc group was longer than that of early non-recurrence group,and P wave duration of V1 lead of late recurrence group was longer than that of latenon-recurrence group.3.P wave dispersion(Pd):There was no significant difference in P wave dispersion between early non-recurrent group and recurrent group,late non-recurrent group and recurrent group(early and late),respectively.4.Macrua index: the Macrua index of lead ? in the early recurren-ce group was bigger than that in the early non-recurrence group,and the Macrua index in lead V1 in the late recurrence group was bigger than that in the late non-recurrence group,which was consistent with the change of P wave duration.There was no significant difference between earlyand late recurrence groups.5.ROC curve:Select those with significant differences between the two groups as the X axis.Taking the recurrence of atrial fibrillation as the Y axis,the area under the ROC curve(AUC)was calculated.Of which the area under the ROC curve in ? lead of early recurrence group and ? and AVF lead of late recurrence group was 0.793,0.754 and 0.85,respectively.Summary:1.P wave amplitude: The amplitude of P wave in lead ?,AVR and V2-V6 in the early recurrent group was lower than that in the early non-recurrent group.The amplitude of the P wave in lead ? AVF V2-V6 in the late recurrent group was smaller than that in the late non-recurrentgroup.2.P wave duration: P wave duration in lead ? in early recurrence group was shorter than that in early non-recurrence group,and P wave duration in lead V1 in late recurrence group was smaller than that in late non-recurrence group.3.Macrua index: There was no significant statistical difference betwe-en early and late recurrence groups.4.ROC curve: The area under the ROC curve with the amplitude of P wave in lead ? and AVF as X axis in early recurrent group and late recurrent group was 0.793,0.754 and 0.85 respectively.Part 2 Identification of circular RNA–micro RNA–messenger RNA regulatory network in atrial fibrillation by integrated analysisObjective: Circular RNA(circ RNA)is a noncoding RNA that forms a closed-loop structure,and its abnormal expression may cause disease.We aimed to fifind potential network for circ RNA-related competitive endogenous RNA(ce RNA)in atrial fifibrillation(AF).Methods:The circ RNA,miRNA,and mRNA expression profifiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively.Difffferentially expressed circ RNAs(DEcirc RNAs),difffferentially expressed miRNAs(DEmiRNAs),and difffferentially expressed mRNAs(DEmRNAs)were identifified,followed by the establishment of DEcirc RNA-DEmiRNA-DEmRNA regulatory network.Functional annotation analysis of host gene of DEcirc RNAs and DEmRNAs in ce RNA regulatory network was performed.In vitro experiment and electronic validation were used to validate the expression of DEcirc RNAs,DEmiRNAs,and DEmRNAs.Results:A total of 1611 DEcirc RNAs,51 DEmiRNAs,and 1250 DEmRNAs were identifified in AF.The DEcirc RNA-DEmiRNA-DEmRNA network contained 62 circ RNAs,14 miRNAs,and 728 mRNAs.Among which,two ce RNA regulatory pairs of hsa-circ RNA-100053-hsami R-455-5pTRPV1 and hsa-circ RNA-005843-hsa-mi R-188-5p-SPON1 were identifified.In addition,six miRNA-mRNA regulatory pairs including hsa-mi R-34c-5pINMT,hsa-mi R-1253-DDIT4 L,hsa-mi R-508-5p-SMOC2,hsa-mi R-943-ACTA1,hsa-mi R-338-3p-WIPI1,and hsa-mi R-199a-3p-RAP1GAP2 were also obtained.m TOR was a signifificantly enriched signaling pathway of host gene of DEcirc RNAs.In addition,arrhythmogenic right ventricular cardiomyopathy,dilated cardiomyopathy,and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcirc RNA-DEmiRNADEmRNA regulatory network.The expression validation of hsa-circ RNA-402565,hsa-mi R-34c-5p,hsa-mi R-188-5p,SPON1,DDIT4 L,SMOC2,and WIPI1 was consistent with the integrated analysis.Summary:Based on bioinformatics analysis,we identified two pairs of ce RNA regulatory pairs in patients with persistent atrial fibrillation.They are hsa-circ RNA-100053-hsa-mi R-455-5p-TRPV1 and hsa-circ RNA-005843-hsami R-188-5p-SPON1,respectively.Conclusions:1.P wave duration in lead ?,P wave amplitude in lead ?,AVR and V2-V6 in early recurrence group,P wave duration in lead V1 and P wave amplitude in lead ?,AVF and V2-V6 in late recurrence group had influence on recurrence of atrial fibrillation,among which P wave amplitude in lead ? in early recurrence group and lead ? and AVF in late recurrence group had great influence on recurrence of atrial fibrillation.2.Based on bioinformatics analysis,we identified two pairs of ce RNA regulatory pairs in patients with persistent atrial fibrillation.They are hsa-circ RNA-100053-hsa-mi R-455-5p-TRPV1 and hsa-circ RNA-005843-hsami R-188-5p-SPON1,respectively.
Keywords/Search Tags:Persistent atrial fibrillation, Radiofrequency ablation, 12 lead electrocardiogram, P wave parameterse, Macrua index, Bioinformatics analysis, Differentially expressed genes
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