Temporal Course of Plasma Trimethylamine N-Oxide (TMAO) Levels in ST-Elevation Myocardial Infarction

Abstract

The gut metabolite trimethylamine N-oxide (TMAO) at admission has a prognostic value in ST-elevation myocardial infarction (STEMI) patients. However, its sequential changes and relationship with long-term infarct-related outcomes after primary percutaneous coronary intervention (PCI) remain elusive. We delineated the temporal course of TMAO and its relationship with infarct size and left ventricular ejection fraction (LVEF) post-PCI, adjusting for the estimated glomerular filtration rate (eGFR). We measured TMAO levels at admission, 24 h and 4 months post-PCI in 379 STEMI patients. Infarct size and LVEF were determined by cardiac magnetic resonance 4 months after PCI. TMAO levels decreased from admission (4.13 ± 4.37 μM) to 24 h (3.41 ± 5.84 μM, p = 0.001) and increased from 24 h to 4 months (3.70 ± 3.86 μM, p = 0.026). Higher TMAO values at 24 h were correlated to smaller infarct sizes (rho = −0.16, p = 0.024). Larger declines between admission and 4 months suggestively correlated with smaller infarct size, and larger TMAO increases between 24 h and 4 months were associated with larger infarct size (rho = −0.19, p = 0.008 and rho = −0.18, p = 0.019, respectively). Upon eGFR stratification using 90 mL/min/1.73 m2 as a cut-off, significant associations between TMAO and infarct size were only noted in subjects with impaired renal function. In conclusion, TMAO levels in post-PCI STEMI patients are prone to fluctuations, and these fluctuations could be prognostic for infarct size, particularly in patients with impaired renal function.

Alterations in trimethylamine-N-oxide in response to Empagliflozin therapy: a secondary analysis of the EMMY trial

“…Interestingly, the post-MI rise in TMAO levels at each visit in our study was lower than the levels reported in previous study cohorts from the Netherlands, Japan, and China [ 17 – 19 ]. This finding is intriguing and raises the question whether this modest rise in TMAO is clinically significant for increasing the risk of future CVD events.…”

“…Similarly, a decline in TMAO levels from admission (4.13 ± 4.37 μM) to 24 h (3.41 ± 5.84 μM), and an increase from 24 h to 4 months (3.70 ± 3.86 μM) in STEMI patients was reported by another recent study. Also, a decline in TMAO from admission to 4 months was inversely correlated (rho = − 0.16, p = 0.024) with infarct size [ 17 ]. The results of these studies underscore the clinical importance of repeated measurements of TMAO and its different fluctuation patterns during acute and chronic phases of post-ischemic events for predicting future CVD events.…”

“…Furthermore, some studies conducted in patients with acute ischemic events have reported considerable variations in TMAO over time, which may offer a better understanding of the severity and prognosis of these events. For instance, TMAO levels declined within 24 h after myocardial infarction and increased in subsequent months, and its latter values predicted future CVD events better than its acute values [ 17 , 18 ]. Another study showed that changes in TMAO levels following acute myocardial infarction (AMI) were significantly associated with MACE [ 19 ].…”

The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases

“…According to the research, gut microbiota may be an important diagnostic marker for CAD in the future (129). As an active metabolite synthesized by intestinal microbiota, the increased level of TMAO is associated with increased risks of CAD and all-cause mortality (130,131). In addition, Guo et al reported that associations of TMAO with CAD were sex-related (132).…”

Gut Molecules in Cardiometabolic Diseases: The Mechanisms behind the Story

“…The pro-thrombotic activity of TMAO occurs due to the increase in calcium release from intracellular stores and enhancement of the platelet activation and responsiveness to different pro-coagulant factors, and consecutive thrombosis potential [ 134 ] via phosphorylation of ERK1/2/JNK in platelets [ 135 ]. In STEMI patients undergoing PCI, TMAO levels fluctuated during the 4-month follow-up and these changes predicted the infarct size, showing significant association, particularly in patients with impaired renal function, suggesting that TMAO could be involved in the ventricular remodeling [ 136 ].…”