Gut Microbiota-Derived Metabolite and Heart Failure with Reduced Ejection Fraction (HFrEF): Elevated Trimethylamine N-Oxide (TMAO) as a Potential Biomarker.

TMAO levels were significantly elevated in HFrEF patients compared to healthy controls.

• HFrEF patients had serum TMAO of 3.64 µM (IQR 3.00–4.31) versus 1.22 µM (IQR 0.92–2.36) in controls (p < 0.05).
• Forty HFrEF patients and forty-one matched healthy controls were recruited.
• Serum TMAO was quantified using enzyme-linked immunosorbent assay (ELISA).
• Associations were examined using Spearman correlation and regression models.

Elevated TMAO correlated with impaired cardiac structural and functional parameters as well as lower serum albumin.

• Spearman correlation analyses were used to examine associations between TMAO and cardiac and clinical parameters.
• Lower serum albumin was among the clinical parameters associated with elevated TMAO.
• Both structural and functional cardiac parameters showed correlations with TMAO levels in HFrEF patients.

TMAO was independently associated with HFrEF severity in both mildly and moderately reduced ejection fraction groups.

• In the mildly reduced EF group (EF 30–40%), TMAO showed OR 1.83 (95% CI 1.04–3.23, p = 0.036).
• In the moderately reduced EF group (EF 20–30%), TMAO showed OR 2.05 (95% CI 1.18–3.57, p = 0.010).
• These associations were identified via multinomial regression analysis.
• Albumin was also independently associated with HFrEF severity: OR 0.56 (95% CI 0.36–0.89, p = 0.015) in the mildly reduced EF group and OR 0.61 (95% CI 0.39–0.93, p = 0.022) in the moderately reduced EF group.

TMAO demonstrated good discriminative ability for HFrEF that improved substantially when combined with clinical covariates.

• ROC analysis showed TMAO alone had an AUC of 0.853 for discriminating HFrEF.
• When TMAO was combined with clinical covariates, the AUC improved to 0.967.
• These findings support the role of TMAO as a potential biomarker for HFrEF.

The study supports integrating TMAO and albumin as a nutritional marker into HFrEF risk stratification frameworks.

• Gut-derived metabolites, particularly TMAO, have been implicated in the pathophysiology of heart failure.
• The findings suggest that both TMAO and serum albumin may complement existing clinical parameters in risk stratification.
• The study population consisted of 40 HFrEF patients and 41 matched healthy controls.