Trimethylamine N‐oxide and outcomes in patients hospitalized with acute heart failure and preserved ejection fraction

Abstract

Aims Trimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota. Elevated TMAO levels are associated with a poor prognosis in patients with heart failure with reduced ejection fraction. However, the prognostic effect of elevated TMAO levels on heart failure with preserved ejection fraction (HFpEF) remains unclear. Methods and results We consecutively enrolled 146 patients who were hospitalized and discharged from Tottori University Hospital with the primary diagnosis of HFpEF (ejection fraction ≥ 50%). High TMAO levels were defined as those greater than the median value in the patients (20.37 μmol/L). Patients with high TMAO levels had a significantly higher prevalence of prior hospitalization for heart failure and severe renal dysfunction than those with low TMAO levels. They also had a significantly higher acylcarnitine to free carnitine ratio than those with low TMAO levels, which indicated abnormal fatty acid metabolism and relative carnitine deficiency. After adjustment for differences in the patients' background in multivariate analysis, high TMAO levels remained independently associated with a high incidence of the composite endpoints of death due to cardiac causes and hospitalization for heart failure (adjusted hazard ratio, 1.91; 95% confidence interval, 1.01 to 3.62; P < 0.05). There was a significant interaction between TMAO and nutritional status on the primary outcome, and the prognostic effect of TMAO was enhanced in patients with malnutrition. Conclusions Elevated TMAO levels at discharge are associated with an increased risk of post-discharge cardiac events in patients with HFpEF, especially those with the complication of malnutrition.

A systematic review and meta-analysis of the gut microbiota-dependent metabolite trimethylamine N-oxide with the incidence of atrial fibrillation

“…Of these, 79 reports lacked relevant data, and two articles were excluded because of data duplication. Ultimately, four cohort studies (21,(25)(26)(27), one nested casecontrol study (22), and one cross-sectional study (28) were included in our meta-analysis, with a total of 8,837 patients, including 1,668 patients with AF. The flow chart for the study selection is shown in Figure 1.…”

“…Reports in the current meta-analysis mainly investigated the role of TMAO in the bloodstream of patients who had different diseases, including kidney disease (28), acute and chronic heart failure (CHF) (25)(26)(27), and suspected stable angina pectoris (21). Two studies did not directly give the average circulating TMAO concentration of patients (21,22).…”

“…Two studies did not directly give the average circulating TMAO concentration of patients (21,22). Three studies were conducted in Europe (21,22,25), two in Asia (26,27), and one study involved 22 countries (28). In four studies, plasma TMAO was estimated (21,22,25,26), while in one study, serum TMAO was investigated (28), and one study did not specify whether the TMAO was from plasma or serum (27).…”

“…Three studies were conducted in Europe (21,22,25), two in Asia (26,27), and one study involved 22 countries (28). In four studies, plasma TMAO was estimated (21,22,25,26), while in one study, serum TMAO was investigated (28), and one study did not specify whether the TMAO was from plasma or serum (27). The sample sizes of the individual studies ranged from 146 to 4,141.…”

“…The sample sizes of the individual studies ranged from 146 to 4,141. Three studies had a relatively small sample size (<1,200) (22,25,27), while the remaining three studies had a relatively large sample size (>1,200) (21,26,28). The NOS was applied to the cohort and case-control studies to further evaluate the quality of included studies considered to be of medium to high quality.…”