# Gut Microbiota-Derived Trimethylamine N-Oxide and NT-proBNP in Heart Failure: A Critical Review of Diagnostic and Prognostic Value

## TL;DR

This paper reviews how TMAO, a gut microbiota product, can help predict heart failure outcomes and complements existing biomarkers like NT-proBNP.

## Contribution

The paper introduces TMAO as a novel metabolic-inflammation biomarker that improves long-term heart failure risk prediction.

## Key findings

- TMAO is an independent predictor of cardiovascular events and mortality in heart failure patients.
- Combining TMAO with NT-proBNP improves risk prediction in patients with comorbidities like diabetes and kidney disease.
- TMAO reflects gut-heart axis dysfunction and offers insights into intestinal barrier integrity in heart failure.

## Abstract

Objective: The study aims to evaluate the diagnostic and prognostic efficacy of gut-derived trimethylamine N-oxide (TMAO) as a molecular biomarker for heart failure (HF) in comparison to the N-terminal pro-B-type natriuretic peptide. Background: The clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is frequently affected by non-cardiac physiological variables, including adiposity, advanced age, and renal clearance rates. Consequently, there is a compelling need for additional biomarkers. This analysis investigates TMAO as a critical mediator within the gut–heart axis, reflecting systemic inflammation and myocardial fibrosis secondary to intestinal dysbiosis. Methods: A comprehensive literature search was conducted using PubMed. Keywords such as “trimethylamine N-oxide”, “heart failure”, “heart failure with preserved ejection fraction” and “N-terminal pro-B-type natriuretic peptide” were used. The inclusion criteria comprised original research and literature reviews describing the pathophysiological mechanisms and clinical utility of TMAO in the context of HF diagnosis and prognosis. Results: The analyzed literature suggests that TMAO functions as an independent predictor of major adverse cardiovascular events, correlating with all-cause mortality and rehospitalization risk across all HF phenotypes. Furthermore, data indicate that using TMAO alongside NT-proBNP measurements may predict patient risk more accurately, particularly in patients where natriuretic peptide interpretation is traditionally obscured by comorbidities such as diabetes mellitus and chronic kidney disease. Conclusions: Although NT-proBNP remains the gold standard for acute diagnosis, TMAO provides significant value for long-term clinical management. By serving as a metabolic–inflammatory indicator, TMAO complements standard diagnostic panels, offering deeper insights into the prognostic trajectory and the underlying intestinal barrier integrity of patients with HF.