Meta-analysis And Mechanism Study Of Traditional Chinese Medicine In The Treatment Of Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction(HFpEF)is a common type of heart failure in clinical practice,which has exerted adverse effects on patients’ quality of life and social and economic burden.There is no effective medical treatment method for HFpEF in modern medicine.Under the guidance of holistic concept and syndrome differentiation,TCM can effectively improve the clinical symptoms and quality of life of HFpEF patients.In recent years,traditional Chinese medicine in the treatment of HFpEF has accumulated certain clinical evidence,but the sample sizes of these related studies are too small,and the evidence is scant.In this study,Meta analysis and data mining were performed on literatures related to traditional Chinese medicine in the treatment of HFpEF in major databases,and network pharmacological analysis was conducted on high-frequency drug use,in order to provide theoretical basis and reference for the treatment of HFpEF with traditional Chinese medicine,and to explore the mechanism of Chinese medicine in the treatment of HFpEF.Objective:1.To objectively evaluate the efficacy of traditional Chinese medicine in the treatment of HFpEF.2.To explore the the rule of medication by analyzing the treatment of HFpEF by traditional Chinese medicine.3.To explore the mechanism of Chinese medicine in the treatment of HFpEF.Methods:1.Meta analysisSearch Wanfang,China CNKI,VIP,CBM,PubMed,Embase and Cochrane Library to collect the clinical trials on the treatment of HFpEF by traditional Chinese medicine.Using Revman 5.3 to perform meta analysis of the included literature.2.Data MiningThe prescription data used in the Meta analysis were input into Excel to analyze the frequency of drugs and drug rules.3.Network pharmacologyA network pharmacological study was carried out on the traditional Chinese medicine with the frequency of use≥10.The effective ingredients and action targets of high-frequency traditional Chinese medicine were searched by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)."Heart failure with preserved ejection fraction" was used as the key word to search for disease targets in GeneCards and DisgeNet databases.The common targets of diseases and drugs were imported into String to construct a protein-protein interaction(PPI)network,and the gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed on the common targets of drugs and diseases using R software.Results:1.Meta analysis30 clinical trials were included in the meta-analysis,including 2600 patients,1313 patients in the experimental group and 1287 patients in the control group.The Meta-analysis results showed that the treatment group exhibited more effectiveness in improving cardiac function[OR=3.20,95%CI(2.30,4.45),P<0.00001],TCM syndromes[OR=3.27,95%CI(2.22,4.83),P<0.00001],6-minute walk distance[MD=46.43,95%CI(30.01,62.85),P<0.00001]and E/A[MD=0.15,95%CI(0.05,0.25),P=0.005].Interms of BNP[MD=-202.80,95%CI(-308.92,-96.67),P=0.0002]and NT-proBNP[MD=-243.71,95%CI(-313.21,-174.21),P<0.00001],LVEDD[MD=-1.01,95%CI(-1.58,-0.44),P=0.0005],LAD[MD=-1.60,95%CI(-2.92,-0.28),P=0.02]and E/E’[MD=-1.71,95%CI(-2.52,-0.90),P<0.0001]in the treatment group were lower than those of the control group.There was no significant difference between the experimental group and the control group in terms of LVEF[MD=0.92,95%CI(-0.16,1.99),P=0.10].2.Data MiningThe 30 literatures included in this study involved 69 traditional Chinese medicine in total.The high-frequency traditional Chinese medicines are Salvia miltiorrhiza,Astragalus membranaceus,Cassia twig,Licorice,Ginseng,Draba nemorosa,Poria,etc.Salvia miltiorrhiza was the most frequently used drug.3.Network pharmacologyA total of 253 active ingredient action targets were retrieved from the high-frequency traditional Chinese medicines.233 HFpEF targets were retrieved,and 41 intersection targets were obtained by intersecting active ingredient action targets and disease targets of HFpEF.KEGG pathway analysis showed that TCM participated in the treatment of HFpEF through TNF signaling pathways,AGE-RAGE signaling pathway of diabetes complications,PI3K-Akt signaling pathway and other pathways.Conclusions:1.Traditional Chinese medicines has better effect in the treatment of HFpEF.2.The traditional Chinese medicines with the frequency of use≥10 are Salvia miltiorrhiza,Astragalus membranaceus,Cassia twig,Licorice,Ginseng,Draba nemorosa,Poria.The result showed that the main treatment of HFpEF was to invigorate qi,activate blood circulation.3.High-frequency traditional Chinese medicine plays a regulatory role on HFpEF mainly through the TNF signaling pathways,AGE-RAGE signaling pathway of diabetes complications and PI3K-Akt signaling pathway,etc.,reflecting the multi-component,multi-target and multi-pathway characteristics of traditional Chinese medicine in the treatment of HFpEF.