Microbiota‐dependent metabolite trimethylamine‐N‐oxide is associated with disease severity and survival of patients with chronic heart failure

Nov 11, 2014Journal of internal medicine

Gut bacteria-related compound trimethylamine-N-oxide linked to disease severity and survival in chronic heart failure patients

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Abstract

Plasma levels of TMAO were significantly elevated in patients with chronic heart failure compared to control subjects.

TMAO levels were higher in patients with New York Heart Association (NYHA) classes III and IV.
Patients with ischaemic heart failure exhibited the highest TMAO levels, followed by those with stable coronary artery disease and nonischaemic heart failure.
TMAO, unlike its precursors choline and betaine, was associated with reduced transplant-free survival.
Approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant over 5.2 years of follow-up.
Findings suggest a possible link between TMAO levels and adverse outcomes in chronic heart failure.

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OBJECTIVES: Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF.

DESIGN: Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant-free survival in the patients with HF were explored.

RESULTS: Plasma levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant-free survival: approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 2.24, 95% confidence interval 1.28-3.92, P = 0.005).

CONCLUSIONS: TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.

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Microbiota‐dependent metabolite trimethylamine‐N‐oxide is associated with disease severity and survival of patients with chronic heart failure

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