Microbiome-Derived TMAO Exhibits No Protective Effect against GIB in LVAD Patients

Purpose Trimethylamine N-oxide (TMAO) is a novel, gut microbe-derived metabolite that directly contributes to platelet activation and thrombosis, and is associated with increased cardiovascular risk. Gastrointestinal bleeding (GIB) is the most common complication during LVAD support and is related to acquired coagulopathy. We hypothesized that higher levels of TMAO might have a protective effect against the risk of GIB in LVAD patients. Methods We prospectively enrolled 123 heart failure (HF) patients undergoing LVAD surgery at our institution between Jan 2011 and Aug 2016. TMAO was measured in blood at three time points pre- and post-LVAD: baseline (pre-LVAD), 3-6 mo post-LVAD, and >6 mo post-LVAD. Patients were categorized by > median vs ≤median TMAO level. We assessed time to GIB occurrence for each time point separately. Univariable Cox proportional hazard models were constructed, along with multivariable models adjusted for (i) age and sex and (ii) age, sex, and estimated glomerular filtration rate (eGFR). Results Among 123 pts (age 57.5 ± 14.8, 86% male, 59% white), TMAO levels were measured at baseline in 77 pts, 3-6 mo post-LVAD in 54 pts, and >6 mo post-LVAD in 60 pts. Median (IQR) TMAO levels were 7.67 (3.86, 13.80) for pre-LVAD, 5.38 (3.21, 9.82) for 3-6 mo, 5.97 (4.44, 10.78) >6 mo. In univariable analysis, there was no significant difference in time to GIB for above vs below median TMAO levels at all time points. These findings were similar in each of the multivariable models (Table). Conclusion Although TMAO levels have been associated with pro-thrombotic potentials, no association was found between pre- and post-LVAD levels of TMAO and the risk of GIB in our cohort of LVAD patients.