Prognostic value of the level of gut microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure：a meta-analysis and systematic review

AimsIntestinal microbial metabolite trimethylamine N-oxide (TMAO) is considered to be a key mediator between intestinal microbiota changes and heart failure (HF). Clinical evidences showed that patients with HF had relatively high level of plasma TMAO than those without. However, the relationship between plasma TMAO and the prognostics of patients with HF has not been investigated. This study aims to evaluate the relationship between plasma TMAO and the outcomes of patients with HF. Methods and resultsPubMed, EMBASE, Cochrane Library databases were included for systematic literature search. The included studies were used for the extraction of overall hazard ratios of adverse events data (myocardial infarction, cardiovascular hospitalization, cardiovascular mortality, revascularization and stroke) as well as all-cause mortality data. Cochrans Q test and I2 statistical methods were applied to assess heterogeneity. Selection of random effects model or fixed effects model were according to heterogeneity. Sensitivity analysis and subgroup analysis were used to find the source of heterogeneity. Among the 7 included studies, all studies published all-cause mortality data and 6 provided adverse events. And the results demonstrated that higher level of plasma TMAO (defined according to original studies)was an indicator of risk of all-cause mortality (HR =0.26, 95% CI: 0.20-0.32, I2 = 96.1%,) and risk of adverse events (HR =1.79, 95% CI: 1.37-2.22, I2 = 78.6%). There was no significant publication bias among the included studies (Eggers,P = 0.130;Beggs tests P = 0.452). Further subgroup analysis did not show that study location, follow-up time, or year of publication had any effect on the results. The results of sensitivity analysis do not indicate that any of the included affected the robustness of the results. ConclusionHeart failure patients with higher baseline plasma TMAO is a risk factor for all-cause mortality and adverse events.