Prognostic Value of Elevated Levels of Intestinal Microbe-Generated Metabolite Trimethylamine-N-Oxide in Patients With Heart Failure

BACKGROUND Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear. OBJECTIVE This study investigated the potential pathophysiologic contributions of intestinal microbiota in HF. METHODS We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over 5-year follow-up in 720 stable subjects with HF. RESULTS Median TMAO level was 5.0 μM, which was higher than in non-HF subjects (3.5 -μM; p < 0.001). There was modest but significant correlation between TMAO and B-type natriuretic peptide (BNP) (r = 0.23; p < 0.001). Higher plasma TMAO level was associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio [HR]: 2.2; 95% confidence interval [CI]: 1.42 to 3.43; p < 0.001), as well as following the addition of estimated glomerular filtration rate to the model (HR: 1.75; 95% CI: 1.07 to 2.86; p < 0.001). CONCLUSION High TMAO levels are observed in patients with HF and elevated TMAO levels portend higher long-term mortality risk independent of traditional risk factors.