• Wensheng Li, Anqing Huang, Hailan Zhu, Xinyue Liu, Xiaohui Huang, Yan Huang, Xiaoyan Cai, Jianhua Lu, and Yuli Huang.
• Shunde Hospital of Southern Medical University, Foshan (Guangdong), China.
• Med. J. Aust. 2020 Oct 1; 213 (8): 374-379.

ObjectiveGut microbiota-produced trimethylamine N-oxide (TMAO) is a risk factor for cardiovascular events. However, conflicting findings regarding the link between plasma TMAO level and prognosis for patients with heart failure have been reported. We examined the association of plasma TMAO concentration with risk of major adverse cardiac events (MACEs) and all-cause mortality in patients with heart failure.Study DesignMeta-analysis of prospective clinical studies.Data SourcesWe searched electronic databases (PubMed, EMBASE) for published prospective studies examining associations between plasma TMAO level and MACEs and all-cause mortality in adults with heart failure.Data SynthesisHazard ratios (HRs) with 95% confidence intervals for associations between TMAO level and outcomes were estimated in random effects models. In seven eligible studies including a total of 6879 patients (median follow-up, 5.0 years) and adjusted for multiple risk factors, higher plasma TMAO level was associated with greater risks of MACEs (TMAO tertile 3 v tertile 1: HR, 1.68; 95% CI, 1.44-1.96; per SD increment: HR, 1.26; 95% CI, 1.18-1.36) and of all-cause mortality (TMAO tertile 3 v tertile 1: HR, 1.67; 95% CI, 1.17-2.38; per SD increment: HR, 1.26; 95% CI, 1.07-1.48). Higher TMAO level was also associated with greater risk of MACEs after adjusting for estimated glomerular filtration rate (eGFR; six studies included); however, the heterogeneity of studies in which risk was adjusted for eGFR was significant (I2  = 76%).ConclusionsElevated plasma TMAO level in patients with heart failure is associated with poorer prognoses. This association is only partially mediated by renal dysfunction.© 2020 AMPCo Pty Ltd.

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