| Background:During the final stages of cardiovascular disease progression,heart failure manifests in a variety of pathophysiological ways such as inflammation and activation of neuroendocrine system.It is common for heart failure patients to be diagnosed,treated,and managed on a standardized basis,but their rehospitalization rate and mortality rate remain high.The long-term management of heart failure still faces a severe test.Intestinal microorganisms and their metabolites affect the physiological and pathological state of human body all the time.Numerous studies have confirmed that trimethylamine oxide is a metabolite produced by intestinal microorganisms that plays a key role in heart failure development.At present,most clinical studies tend to have a positive correlation between the increase of plasma trimethylamine oxide levels and adverse events of heart failure.It should be noted,however,that some studies have come to the opposite conclusion.Objective:This meta-analysis aims to determine the relationship between plasma trimethylamine oxide levels and heart failure prognosis.Methods:According to the standard process of meta-analysis,we registered in PROSPERO and obtained the registration number:CRD4202384787.Pub Med,Embase,Web of Science,the Cochrane Library,CNKI,Weipu electronic databases,SINOMED and Wanfang Database were systematically searched.The retrieval literature mainly includes prospective studies to explore the relationship between the level of trimethylamine oxide and the prognosis of patients with heart failure.Search terms include trimethylamine oxide,trimethylamine N-oxide,TMAO,heart failure,myocardial failure,left heart failure,right heart failure,cardiac decompensation,congestive heart failure,etc.The search date was from the establishment of the database to November 22,2022.The inclusion criteria of the study included:(1)published articles at home and abroad and the subjects were patients with heart failure;(2)prospective studies;(3)studies reported major adverse cardiovascular events(MACEs),including cardiovascular mortality,myocardial infarction,cardiovascular hospitalization,or all-cause mortality;and(4)the study must report risk ratio(HR)/relative risk(RR)and 95%CI.(5)the follow-up period is more than or equal to 1 year.Exclusion criteria include:(1)repeated inclusion of the study;(2)lack of data on patients with heart failure;(3)follow-up period of less than 1 year;and(4)review articles,case reports,animal trials,systematic reviews,meta-analysis,reviews,editorials or conference abstracts.This meta-analysis was mainly included in a prospective cohort study.Therefore,the Newcastle-Ottawa scale(NOS)was used to evaluate the literature included in this review.Using Stata(14.0 version of Stata Corporation,College Station,TX,USA),a meta-analysis was conducted.Based on the survival data finally included in the literature,the effect HR was summarized and logarithmic conversion was carried out,and the standard error after logarithmic conversion was calculated.The total effect was calculated by Z test,P<0.05 was statistically significant.Heterogeneity is evaluated by I~2 test and Q test.When I~2<50%and Q test P>0.1,it can be considered that there is no heterogeneity.However,due to clinical and methodological heterogeneity,some study designs reported the results of the random effect model when confounding factors were excluded.Even if the heterogeneity is not significant,we will conduct a subgroup analysis of the main results according to different regions,average age,duration of follow-up,type of heart failure and study sample size.When I~2>50%and Q test P<0.05,it is suggested that there is a high degree of heterogeneity.We will select a random effect model for combined analysis,construct a funnel chart.Egger and Begg tests can be used to determine publication bias.If there is publication bias,the publication bias will be corrected by clipping method.After excluding the clinical and methodological heterogeneity,a sensitivity analysis was conducted to determine whether the meta-analysis results were stable.Results:A total of 15 articles(17 studies)involving 17,324 subjects from 2014 to 2022were included after the search.Our meta-analysis shows that patients with heart failure with high plasma TMAO concentration are more prone to major cardiovascular events than those with low plasma TMAO level[HR=1.35,95%CI(1.21-1.51),P<0.05],and higher plasma TMAO levels increased the risk of all-cause death compared with low plasma levels of TMAO[HR=1.39,95%CI(1.29-1.51),P<0.05].Consistent results were also obtained in all subgroups and sensitivity analysis.Conclusions:1.The increase of plasma TMAO level is related to the poor prognosis of patients with heart failure.2.Plasma TMAO levels may be predictive of major adverse cardiovascular events and long-term all-cause mortality in patients with heart failure. |
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