Pathobiology Of Acute Myocardial Infarction Based On Imaging Features Of Coronary Plaque

Background The gut microbial metabolite trimethylamine N-oxide(TMAO)promotes atherosclerosis and cardiovascular diseases.TMAO levels are associated with the coronary atherosclerotic burden in patients with stable coronary artery disease.However,the relationship between TMAO levels and the coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction(STEMI)is unknown.Methods We prospectively enrolled 2 cohorts in this study,including 335 patients with STEMI and 53 healthy controls.The coronary atherosclerotic burden was quantified by the number of diseased coronary arteries and the SYNTAX score.Fasting plasma TMAO was measured by stable isotope dilution liquid chromatography tandem mass spectrometry.Results The median TMAO levels in patients with STEMI and healthy controls were 2.18(interquartile range[IQR]:1.34 to 3.90)?M and 1.23[IQR:0.84 to 2.42]?M,respectively.Of the 335 patients with STEMI,TMAO levels were significantly higher in the multivessel disease group than in the single-vessel disease group(p<0.001)and in the group with intermediate-high SYNTAX scores(SYNTAX score?23)than in the group with low SYNTAX scores(SYNTAX score?22)(p<0.001).Based on the ordinal logistic regression analysis adjusted for traditional risk factors,elevated TMAO levels predicted both a high SYNTAX score(adjusted odds ratio[OR]:1.16;95%confidence interval[CI]:1.06 to 1.29;p=0.001)and the presence of multivessel disease(adjusted OR:1.15;95%CI:1.01 to 1.32;p=0.035).Conclusion In conclusion,plasma TMAO levels are associated with a high coronary atherosclerotic burden in patients with STEMI.Background Previous studies showed trimethylamine N-oxide(TMAO)has proatherogenic effects and notably ST-segment elevation myocardial infarction(STEMI)patients with plaque rupture had significantly higher plasma TMAO values than those with plaque erosion,and the TMAO levels were similar between patients with plaque erosion and healthy controls,which implying TMAO participates in the occurrence of plaque rupture,but not plaque erosion.This study aims to explore the relations between plasma TMAO and coronary culprit plaque inflammation and vulnerable characterizations assessed by optical coherence tomography(OCT)in AMI patients exhibiting plaque rupture.Methods We consecutively enrolled 90 patients with AMI undergoing primary percutaneous coronary intervention and exhibiting plaque rupture at the site of the culprit stenosis identified by OCT.Demographic data,risk factors,procedural and OCT data,previous medical history and perioperative laboratory findings were collected in all patients.Plasma TMAO levels were measured using stable isotope dilution liquid chromatography tandem mass spectrometry.All patients were divided into two groups(high TMAO group and low TMAO group)according to the median plasma TMAO level.We compare the clinical baseline characteristics and the microstructural characteristics of culprit plaques assessed by OCT between these two groups of patients,and plaque inflammation was qualified by the presence of macrophage infiltration and quantified by macrophage density.Results The frequency of diabetes mellitus and the glycated hemoglobin levels were significantly higher in the high TMAO group(48.9%vs.26.7%,P=0.050;(7.0±1.7)%vs.(6.3±1.5)%,P=0.040;respectively).The culprit plaques in the high TMAO group exhibited a thinner fibrous cap thickness[60(60,100)?m]vs.90(70,110)?m,P=0.013],higher frequency of thin-cap fibroatheroma(55.6%vs.15.6%,P<0.001),microvessel(24.4%vs.4.4%,P=0.014)and macrophage infiltration(72.0%vs.28.0%,P<0.001)compared with the low TMAO group.Fifty(55.6%)patients had macrophage infiltration at the site of the plaque rupture.Patients with macrophage infiltration had higher TMAO levels than those without[4.14(3.14-6.52)?M versus 2.40(1.78-3.08)?M,P<0.001].Moreover,TMAO levels were significantly positively associated with macrophage density(Pearson's correlation coefficient:r=0.542,P<0.001).Furthermore,multivariate regression analysis after adjustment for confounding factors showed that TMAO remained independently correlated with plaque inflammation(adjusted odds ratio:3.32,95%CI,1.77 to 6.23;P<0.001).Conclusions Plasma TMAO is significantly correlated with plaque inflammation and plaque vulnerability in STEMI patients exhibiting plaque rupture,providing new insights for optimizing the current risk stratifications and clinical treatments of patients with STEMI and plaque rupture.Background Healed plaque is a hallmark of previous regional plaque rupture or erosion.We hypothesized that the plasma level of trimethylamine N-oxide(TMAO)is related to healed culprit plaque in ST-segment elevation myocardial infarction(STEMI)patients.Methods A prospective cohort of 206 patients with STEMI who were examined by optical coherence tomography(OCT)was enrolled in our study.After exclusion,156 patients were finally enrolled and categorized into healed plaque(n=54)and non-healed plaque(n=102)groups.Plasma TMAO levels were detected by stable isotope dilution liquid chromatography tandem mass spectrometry.Results Increased age and low body mass index were more common in patients with healed plaques than in patients without healed plaques.Through OCT observation,plaque rupture(81.5%vs.45.1%,p<0.001),thin cap fibroatheroma and macrophages(42.6%vs.20.6%,p=0.004,70.4%vs.26.5%,p<0.001,respectively)were more frequently seen in patients with healed plaques than in patients without healed plaques.The TMAO level in patients with healed plaques was significantly higher than that in patients without healed plaques(3.9 ?M[2.6-5.1]vs.1.8 ?M[1.0-2.7],p<0.001).Furthermore,the ROC analysis showed that TMAO can be used as a potential biomarker to predict healed plaque presence with a cutoff value of 2.9 ?M(AUC=0.810,sensitivity:72.2%,specificity:81.4%).Conclusions Healed plaque in STEMI patients is associated with a high level of plaque vulnerability and inflammation.A high level of plasma TMAO can be a useful biomarker to differentiate STEMI patients with healed culprit plaques.Background Diabetes mellitus(DM)or pre-diabetes status is closely associated with features of vulnerable coronary lesions in patients with stable coronary heart disease or acute coronary syndrome.However,the association between duration of diabetes and the morphologies and features of vulnerable plaques has not been fully investigated in patients with acute myocardial infarction(AMI).Methods We enrolled a total of 279 patients who presented with AMI between March 2017 and March 2019 and underwent pre-intervention optical coherence tomography imaging of culprit lesions.Patients with DM were divided into two subgroups:a Short-DM group with DM duration of<10 years and a Long-DM group with DM duration of?10 years.Baseline clinical data and culprit-plaque characteristics were compared between patients without DM(the Non-DM group),those in the Short-DM group,and those in the Long-DM group.Results Patients with DM represented 34.1%of the study population(95 patients).The Short-and Long-DM groups included 64(67.4%)and 31 patients(32.6%),respectively.Glycated hemoglobin A1c(HbA1c)levels were significantly higher in the Long-DM group than the Non-or Short-DM groups(8.4%[Long-DM]versus 5.7%[Non-DM]and 7.6%[Short-DM],P<0.001).In addition,the highest prevalence of lipid-rich plaques,thin-cap fibroatheroma(TCFA),and plaque ruptures of culprit lesions were observed in the Long-DM group(lipid-rich plaques:80.6%[Long-DM]versus 52.2%[Non-DM]and 62.5%[Short-DM],P=0.007;TCFA:41.9%[Long-DM]versus 19.6%[Non-DM]and 31.3%[Short-DM],P=0.012;plaque rupture:74.2%[Long-DM]versus 46.7%[Non-DM]and 48.4%[Short-DM],P=0.017).The frequency of calcification was significantly higher among patients with DM than among those without(62.1%versus 46.2%,P=0.016);however,no significant differences were found between the DM subgroups(61.3%[Long-DM]versus 62.5%[Short-DM],P=0.999).Conclusions Increased duration of DM combined with higher HbAlc levels influences culprit-plaque characteristics in patients with DM who suffer AMI.These findings might account for the higher risks of cardiac death in DM patients with long disease duration.Background Previous studies reported that pre-infarction angina(PIA)played a crucial role in restricting infarct size,improving cardiac function and reducing mortality in patients suffered acute myocardial infarction(AMI).This study aims to identify morphological characteristics of the culprit plaque by optical coherence tomography(OCT)associated with PIA in patients with ST-segment elevation myocardial infarction(STEMI).Methods A total of 279 STEMI patients between March 2017 and March 2019 who underwent intravascular OCT of culprit lesion were included.Patients were divided into two groups according to whether exhibiting PIA:the PIA group and the non-PIA group.Baseline clinical data and culprit-plaque characteristics were compared between these two groups.Results Of the total patients,153(54.8%)presented with PIA.No differences were observed in clinical and angiographic data between two groups,except STEMI onset with exertion was significantly less common in PIA group(24.2%versus 40.5%,P=0.004).Moreover,patients with PIA exhibited a significantly lower incidence of plaque rupture(40.5%versus 61.9%,P<0.001)and lipid-rich plaques(48.4%versus 69.0%,P=0.001)in culprit lesions.The prevalence of thin-cap fibroatheroma(TCFA)was lower in PIA group,presenting a thicker fibrous cap thickness,although statistically significant differences were not observed(20.3%versus 30.2%,P=0.070;129.1±92.0?m versus 111.4 ± P=0.088;respectively).Multivariate logistic regression analysis indicated that PIA was an independent negative predictor for plaque rupture(odds ratio:0.44,95%confidence interval:0.27-0.72,P=0.001).Conclusions Compared with patients without PIA,STEMI patients with PIA showed a significantly lower prevalence of plaque rupture and lipid-rich plaques in culprit lesion,implying different mechanisms of STEMI attack in these two groups.