Trimethylamine N-Oxide as a Biomarker for Left Ventricular Diastolic Dysfunction and Functional Remodeling After STEMI

Abstract

Despite successful primary percutaneous coronary intervention (PPCI), the incidence of heart failure (HF) following ST-elevation myocardial infarction (STEMI) remains high. We investigated using Trimethylamine N-oxide (TMAO), a gut microbiota-derived biomarker, to predict adverse functional left ventricular (LV) remodeling (FLVR) and/or diastolic dysfunction (DD), which are precursors of HF post-STEMI. This prospective, observational study enrolled 204 STEMI patients with multivessel coronary artery disease after PPCI. TMAO level was collected at the baseline and 3 months. An echocardiography was performed at the baseline and at 12 months. The primary endpoints were the number of patients developing Group 4 FLVR or ≥Grade II DD at 12 months. The median age was 65 [57.00, 76.00] and 39.7% were women. The primary endpoints occurred in 47 (23.0%) patients. Three months of TMAO can discriminate patients with/without ≥Grade II LV DD and FLVR Grade 4 with areas under the curve (AUC) of the ROC of 0.72 (95% CI: 0.63–0.81; p < 0.001) and 0.77 (95% CI: 0.63–0.91), respectively. Similar results were shown in the validation cohort of 31 patients. The addition of 3 months of TMAO to traditional risk factors significantly improved the AUCs from 0.675 to 0.736 for ≥Grade II DD and from 0.793 to 0.873 for FLVR Grade 4. In multivariable logistic regression, 3 months of TMAO was independently associated with ≥Grade II DD (OR: 1.29 (1.13–1.50), p < 0.001) and FLVR Grade 4 (OR: 1.28 (1.12–1.47), p < 0.001). Three months of TMAO is strongly associated with LV DD and adverse remodeling after STEMI and may help identifying such patients for early treatment.