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Thrombus Burden And Pathological Characteristics Of Culprit Coronary Lesions In Acute Myocardial Infarctio

Posted on:2024-04-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:J Y ZhouFull Text:PDF
GTID:1524306938974869Subject:Internal Medicine
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Background:A substantial group of patients with ST-segment elevation myocardial infarction(STEMI)suffer from sustained myocardial ischemia despite successful primary percutaneous coronary intervention(PPCI).In previous studies,coronary thrombus fragments and plaque debris have been linked to distal embolization and microvascular obstruction(MVO).This study aims to investigate optical coherence tomography(OCT)based quantitative assessment of coronary residual thrombus burden before stenting and its potential impact on ventricular function and deformation in STEMI patients.Methods:This is a sub-analysis of the OCTAMI registry(Optical Coherence Tomography Examination in Acute Myocardial Infarction).The OCTAMI registry is a prospective study enrolling consecutive patients with STEMI for OCT-based assessment of coronary culprit lesion.Participation in this sub-study required a diagnosis of first-ever anterior wall myocardial infarction and informed consent to a cardiac magnetic resonance(CMR)follow-up.In OCT image analysis,thrombus was defined as an irregular mass floating in the lumen or adjacent to the luminal surface.Residual thrombus burden before stenting was assessed based on lumen area and thrombus area measured by planimetry per frame.OCT-derived residual thrombus burden indexs included:1)total thrombus-to-lumen volume ratio(TTR):total residual thrombus volume and total vessel lumen volume over 30 mm target length were measured,respectively,and their ratio was reported as TTR.2)Maximal thrombus-to-lumen area ratio(MTR):per frame thrombus to lumen area ratio was calculated and the maximum within 30 mm target length was reported as MTR.3)minimal flow area(MFA):flow area was calculated by subtracting residual thrombus area(if any)from lumen area per frame and the minimum was reported as MFA.CMR followup was scheduled at 30 days post STEMI.The primary outcomes were CMR-derived parameters including left ventricular ejection fraction(LVEF),infarct size,MVO,and left ventricular global strains in radial(GRS),circumferential(GCS),longitudinal(GLS)directions.Associations between each residual thrombus burden index and each component of primary outcomes were tested in univariable linear regression analysis and then validated in multivariable models.Covariables for multivariable regression model for each outcome included those with two-sided p value<0.1 in univariable analysis and those with clinical importance,namely age and sex.Receiver operator characteristic(ROC)curves were drawn to determine the cutoff value and diagnostic accuracy of OCT-derived residual thrombus burden indexes for predicting LV dysfunction(defined as LVEF<50%)at 30-day follow-up.Results:From March 2017 to March 2019,forty-two patients with first-ever anterior STEMI were eligible for this study.The median days from the index procedure to CMR follow-up was 33 days with inter-quarter range of 30 to 37days.The average age was 54 years old and 88.1%(37/42)were male.In OCT examination,59.5%(25/42)patients presented with plaque rupture.In residual thrombus burden assessment,the median of TTR,MFA,and MTR were 0.9%,1.02 mm2,and 31.3%,accordingly.In CMR strain analysis,the average LV global peak strains of the entire group were 23.3%,-14.6%,and-12.1%in radial,circumferential,and longitudinal directions,respectively.MTR was significantly associated with LVEF(per 10%,adjusted β=-1.96,95%confidential interval[CI]-3.66 to-0.26),MVO(per 10%,adjusted β=0.07,95%CI 0.01 to 0.13),GRS(per 10%,adjustedβ=-1.26,95%CI-2.28 to-0.23),and GCS(per 10%,adjusted β=0.53,95%CI 0.01 to 1.06).However,it was not related to GLS(per 10%,adjusted β=0.29,95%CI-0.85 to 1.43)or infarct size(per 10%,adjusted β=0.07,95%CI-0.40 to 0.55).The optimal threshold value of MTR was 33.7%for predicting LVEF<50%at 30-day follow-up,with a sensitivity of 75%and a specificity of 77%.In patients with preserved LVEF ≥40%,MTR>33%was an independent predictor for impaired LV global peak strains.However,TTR and MFA did not show significant correlation with LV dysfunction at 30 days.Conclusion:Larger residual thrombus burden was associated with worse left ventricular global peak strains in radial and circumferential directions and more MVO at 30-day follow-up in patients with STEMI after revascularization.Among OCT-derived indexes of residual thrombus burden,MTR but neither TTR nor MFA had a predictive value for shortterm LV dysfunction and MVO.Background:ST-segment elevation myocardial infarction(STEMI)is due in great measure to epicardial coronary artery thrombotic occlusion secondary to plaque instability.Previous pathological and intravascular imaging studies reported that plaque rupture and plaque erosion are the two most frequently observed vulnerable plaque types for culprit lesions in STEMI.Despite extensive studies on morphologic characteristics of vulnerable plaques,it remains unclear what are the initial steps for thrombus formation or mechanisms governing thrombus propagation or degeneration.Recent studies showed that inflammation not only plays a role in the pathogenesis of atherosclerosis but also provides microenvironment encompassing pro-inflammatory and pro-thrombotic factors.Among different types of white blood cells recruited to vulnerable atherosclerotic plaque,neutrophils have drawn more and more attentions due to its unique microstructureneutrophil extracellular traps(NETs).NETs have been reported to be associated with a number of pathophysiological processes such as thrombosis initiation,amplification of inflammation,and hypo-fibrinolysis.This study aims to investigate the association between NETs in aspirated coronary thrombus and risk profile of patients with STEMI.Methods:This is a sub-analysis of the OCTAMI registry(Optical Coherence Tomography Examination in Acute Myocardial Infarction).The OCTAMI registry is a prospective study enrolling consecutive patients with STEMI for OCT-based assessment of coronary culprit lesion.Thrombus aspiration was carried out at the discretion of operators and current study enrolled all patients who underwent thrombus aspiration with retrieved materials qualified for analysis.All participants enrolled in OCTAMI registry from March 2017 to November 2018 were screened for eligibility of this study.NET s in thrombus were identified by immunofluorescence as the co-localization of anti-histone H3,myeloperoxidase and DNA.NETs level was assessed using a semi-quantitative score.Patient-oriented composite endpoint(POCE)included all-cause death,myocardial infarction,stroke,any revascularization,and re-admission for heart failure.Results:Between March 2017 and November 2019,a total of 381 patients enrolled in the OCTAMI registry received aspiration thrombectomy,among whom solid materials were successfully retrieved in 123 of them.Nineteen more patients were excluded due to OCT failure(4 patients),no pre-intervention OCT images(2 patients),coronary embolism(1 patient),pre-intervention thrombolysis(2 patients),in-stent lesions(10 patients).Finally,104 patients were included in the final analysis.According to semi-quantitative NETs score,seventeen patients were graded as score 0,twenty-seven with score 1,thirty-five with score 2,and twenty-five with score 3.Thereafter,patients were divided into two groups:44 in the low NETs group(NETs score 0 and 1)and 60 in the high NETs group(NETs score 2 and 3).The two groups were comparable in age,sex,and comorbidities but the high NETs group presented with significantly higher level of high-sensitivity C reactive protein than the low NETs group(median 9.3 mg/L vs 5.2 mg/L,p=0.036).Although the majority of assessed culprit plaque morphologic characteristics did not differ significantly between groups,the lipid arc was smaller(maximal lipid arc 320°vs 360°,p=0.012)and the flow area was larger(median 1.85mm2 vs 1.65mm2,p=0.041)in the high NETs group.No significant difference of POCE was observed between groups in patientoriented composite endpoint.Conclusion:Increased NETs in aspirated coronary thrombus from culprit lesion are associated with elevated systemic inflammation level but less severe atherosclerosis burden at culprit lesion in STEMI.Background:Stent thrombosis(ST)remains a rare but severe complication after percutaneous coronary intervention(PCI).Moreover,patients with ST-segment elevation myocardial infarction(STEMI)due to ST have a higher risk of cardiovascular ischemic adverse events comparing with those having de novo coronary artery disease.Ticagrelor,a potent and reversible anti-platelet P2Y12 inhibitor,has been recommended by current guidelines over clopidogrel for patients with acute coronary syndrome(ACS),whilst there is limited data regarding its effectiveness in patients with ST.Therefore,this study aims to compare the efficiency of ticagrelor versus clopidogrel on top of aspirin as dual antiplatelet therapy in patients with late or very late ST(LST/VLST)after successful primary PCI(PPCI).Methods:This is a retrospective observational study.Patients with ACS who were admitted underwent PPCI between 1 January 2010 and 31 December 2017 were screened for eligibility for current study.Major inclusive criterium was angiographically definite LST/VLST.The primary outcome was major adverse cardiovascular events(MACE),defined as a composite of death,myocardial infarction,ischemic stroke,and revascularization.Safety outcome included bleeding events of all Bleeding Academic Research Consortium(BARC)types.Cumulative incidence of outcomes was analyzed using Kaplan-Meier curve and log-rank test was applied for comparison between groups.Multivariable Cox proportional hazard ratio models were constructed to compare the efficiency and safety outcomes between ticagrelor group and clopidogrel group.Propensity score matching analysis was applied to balance baseline characteristics between groups and to adjust for potential confounders.Results:A total of 4538 patients continuously admitted for ACS were screened for angiographically definite LST/VLST.Two-hundred and forty-one patients were included in the final analysis and were grouped according to dual anti-platelet therapy strategy at discharge,namely aspirin plus ticagrelor(n=81)or aspirin plus clopidogrel(n=160).After propensity score matching,65 pairs were obtained.The incidence of MACE in the ticagrelor group was significantly lower compared with that in the clopidogrel group(9.3%vs 21.5%,log-rank p=0.048).However,no significant between-group difference was observed in individual components of MACE,including death,myocardial infarction,ischemic stroke,and revascularization.Conclusions:After successful PPCI for ACS due to angiographically definite LST/VLST,patients who received ticagrelor had a significant lower rate of MACE compared with those who received clopidogrel.
Keywords/Search Tags:ST-segment elevation myocardial infarction, thrombus, optical coherence tomography, cardiac magnetic resonance, feature-tracking strain, inflammation, thrombosis, pathological stain, stent thrombosis, ticagrelor, clopidogrel, dual anti-platelet therapy
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