Trimethylamine N-Oxide Was Not Associated With 30-Day Left Ventricular Systolic Dysfunction in Patients With a First Anterior ST-Segment Elevation Myocardial Infarction After Primary Revascularization: A Sub-analysis From an Optical Coherence Tomography Registry

Abstract

Objective: Left ventricular systolic dysfunction (LVSD) after ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. Trimethylamine N-oxide (TMAO), a gut metabolite, is linked to cardiovascular diseases but its relationship with LVSD after STEMI remains unclear. The present study therefore aimed to investigate the relationship between TMAO and LVSD at 30 days after a first anterior STEMI.Methods: This was a sub-study from the OCTAMI (Optical Coherence Tomography Examination in Acute Myocardial Infarction) registry. Eligible patients were included in current study if they: (1) presented with a first anterior STEMI; (2) had available baseline TMAO concentration; (3) completed a cardiovascular magnetic resonance examination at 30 days after STEMI. LVSD was defined as left ventricular ejection fraction < 50%. Associations between TMAO and left ventricular ejection fraction, infarct size and left ventricular global strain were examined.Results: In total, 78 patients were included in final analysis. Overall, TMAO was moderately associated with peak cTnI (r = 0.27, p = 0.01), age (r = 0.34, p < 0.01), and estimated glomerular filtration rate (r = −0.30, p < 0.01). At 30-day follow-up, 41 patients were in the LVSD group and 37 in the non-LVSD group. Baseline TMAO levels were not significantly different between the two groups (LVSD vs. non-LVSD: median 1.9 μM, 25−75th percentiles 1.5–3.3 μM vs. median 1.9 μM, 25−75th percentiles 1.5–2.7 μM; p = 0.46). Linear regression analyses showed that TMAO was not associated with left ventricular ejection fraction, infarct size or left ventricular global strain at 30 days (all p > 0.05).Conclusions: TMAO was not significantly correlated with 30-day LVSD in patients with a first anterior STEMI after primary revascularization.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03593928.

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

“…In humans, previous reports showed that TMAO levels were not associated with infarct size as determined by peak admission CK-MB and creatine phosphate values [ 20 , 29 ]. These findings are supported by the recent work of Zhou et al, in which it was shown that baseline TMAO levels did not significantly correlate with infarct size nor with LVEF at 30 days in patients presenting with a first anterior STEMI [ 30 ]. Our work extends these findings as it includes all STEMI patients irrespective of the culprit vessel involved and reports the relationship between TMAO (at and across three distinct timepoints) and infarct-related outcomes (at 4 months).…”

“…Thus, the question that remains in light of our findings and the nature of our post hoc analysis is whether TMAO’s association with infarct-related outcomes is simply confounded by low eGFR. This possibility is supported by the findings of the aforementioned works of Zhou et al, in which TMAO was not shown to be associated with infarct outcomes, and the work of Sonmez and colleagues, in which decreased eGFR (eGFR < 60 mL/min/1.73 m 2 ) was shown to be associated with lower LVEF and greater infarct sizes [ 30 , 37 ]. The lack of significant relationships between TMAO and infarct-related outcomes in our <60 mL/min/1.73 m 2 eGFR group does not necessarily refute the confounding possibility, seeing that such group comprised of only 14 subjects.…”

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

“…In contrast, dietary supplementation of TMAO drastically reduced diastolic dysfunction in heart failure mice models [ 41 ]. Whereas TMAO was not associated with left ventricular systolic dysfunction at 30-day follow-up in patients with STEMI [ 42 ]. These conflicting results in animal and clinical studies accentuate the need for more longitudinal studies on TMAO and various cardiac function parameters in CVD cohorts and the impact of cardiovascular disease modifying drugs on TMAO levels and their predictive potential.…”

Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy

“…Multivariate analysis showed that plasma TMAO was significantly associated with new atherosclerosis and plaque rupture in patients with very late stent thrombosis (VLST) ( 32 ). However, TMAO was not significantly correlated with 30-day left ventricular systolic dysfunction in patients with a first anterior STEMI after primary revascularization ( 33 ).…”