Trimethylamine N-Oxide Levels Are Associated with Severe Aortic Stenosis and Predict Long-Term Adverse Outcome

Abstract

Objective: Trimethylamine N-oxide (TMAO), a pathological microbial metabolite, is demonstrated to be related to cardiovascular diseases. This study was (1) to investigate the association between TMAO and aortic stenosis and (2) to determine the prognostic value of TMAO for predicting mortality after transcatheter aortic valve replacement (TAVR). Methods: 299 consecutive patients (77 (72–81) years, 58.2% male, Society of Thoracic Surgeons (STS) score 5.8 (4.9–9.3)) with severe aortic stenosis and 711 patients (59 (52–66) years, 51.9% male) without aortic stenosis were included in this retrospective study. A total of 126 pairs of patients were assembled by Propensity Score Matching. The primary outcome was all-cause mortality using survival analyses stratified by TMAO quartiles. Results: Patients with severe aortic stenosis had higher TMAO levels (3.18 (1.77–6.91) μmol/L vs. 1.78 (1.14–2.68) μmol/L, p < 0.001), and TMAO remained significantly higher after adjusting for baseline characteristics. Higher TMAO level was associated with higher 2-year all-cause mortality (19.2% vs. 9.5%, log-rank p = 0.028) and higher late cumulative mortality (34.2% vs. 19.1%, log-rank p = 0.004). In Cox regression multivariate analysis, higher TMAO level remained an independent predictor (hazard ratio 1.788; 95% CI 1.064–3.005, p = 0.028) of all-cause mortality after adjusting for STS score, N-terminal pro b-type natriuretic peptide, and maximum velocity. Conclusions: The TMAO level was higher in aortic stenosis patients. Elevated TMAO was associated with poor adverse outcome after TAVR.