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

Figures

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  Figure A1. Temporal relationship between TMAO levels sampled at baseline, 3 months, and 12 months. TMAO = Trimethylamine N-oxide.

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  Figure A2. (A) ROC curve analysis of predicting group 4 FLVR with TMAO at 3 months in the validation cohort. ROC = receiver operating characteristic, FLVR = functional left ventricular remodeling, AUC = area under the ROC curve. (B) ROC curve analysis of predicting grade II or III diastolic dysfunction with TMAO at 3 months in the validation cohort.

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  Figure A3. Incidence of clinical events in 3-month TMAO quartile. LVEF = left ventricular ejection fraction, MI = myocardial infarction, MACCE = major adverse cardiovascular and cerebrovascular events defined as the composite of all-cause death, any MI, any revascularization, both ischemic and hemorrhagic strokes, and hospitalization for heart failure.

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  Figure A4. Cumulative event curve of heart failure hospitalization grouped by the four quartiles of TMAO levels at 3 months.

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  Figure 1. Study flow chart. Selection process and patient enrolment flow chart. STEMI = ST-segment elevation myocardial infarction, PCI = percutaneous coronary intervention, CABG = coronary artery bypass graft surgery.

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  Figure 2. Correlation analysis of TMAO levels and echocardiographic parameters. E/A, early-to-late diastolic filling velocity; average e’, averaged diastolic myocardium velocity at the septal and lateral side of the mitral annulus; E/e’, the ratio between early mitral inflow velocity and mitral annular early diastolic velocity; LV, left ventricular; LVEDV, LV end-diastolic volume; LVEF, LV ejection fraction; LAVI, left atrium volume index; and TRpV, tricuspid regurgitation peak velocity. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001.

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  Figure 3. (A) Restricted cubic spline curve for the association between 3-month TMAO level and the log odds of group 4 FLVR at 12 months. (B) Restricted cubic spline curve for the association between 3-month TMAO level and the log odds of grade II or III DD at 12 months.

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  Scheme 1. Central illustration: Heart failure and gut dysbiosis can mutually potentiate each other (left upper panel). The mechanism with which Trimethylamine N-oxide (TMAO) induces cardiac dysfunction was demonstrated in the right upper panel. The ROC curve analysis of predicting ≥ grade II left ventricular diastolic dysfunction (LVDD) with baseline echocardiographic parameters and biomarkers and the ROC curve analysis of predicting group 4 functional left ventricular remodeling (FLVR) with baseline echocardiographic parameters and biomarkers are shown in the lower left and the lower right panel, respectively. AUC = area under the ROC curve, CRP = C-reactive protein, BNP = brain natriuretic peptide.

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  Figure 4. (A) ROC curve analysis of predicting group 4 FLVR with traditional risk factors and models with biomarkers. (B) ROC curve analysis of predicting grade II or III DD with traditional risk factors and models with biomarkers. Traditional risk factors: age, gender, hypertension, diabetes, hyperlipidemia, and smoking. Model 1: traditional risk factors + hs-CRP and BNP level at 3 months, Model 2: Model 1 + 3 months of TMAO.

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  Figure 5. Cumulative event curve of TMAO quartiles and incidence of MACCE at 1 year. MACCE = major adverse cerebral and cardiovascular events.