| Part Ⅰ:Etiology Analysis and clinical Prognosis of Acute cerebral infarction with Atrial FibrillationObjective:To investigate the etiological types of acute cerebral infarction(ACI)complicated with atrial fibrillation(AF),and analyze the influencing factors prompting AFrelated cardiogenic cerebral infarction.To further study the factors of symptomatic intracranial hemorrhage(sICH)and poor clinical prognosis in ACI patients with AF.Methods:ACI patients with AF in The Stroke Center of First Affiliated Hospitial of Soochow University from September 2018 to September 2020 were collected continuously,according to Trial of Org 10172 in Acute Stroke Treatment(TOAST)classification criteria and The Stroke Prevention in Atrial fibrillation(SPAF)study,cerebral infarction was divided into AF-related cardioembolism(CE)and AF unrelated cerebral infarction.The latter included large artery atherosclerosis(LAA),small vessel occlusion(SVO),the stroke of undetermined cause(SUC),and other rare causes(OC).Age,gender and other demographic factors,classic cerebrovascular disease risk factors,history of coronary heart disease,history of peripheral artery disease,history of chronic heart failure,and the National Institutes of Health Stroke Scale(NIHSS)score at admission were collected.Logistic regression analysis indicated that it was the influencing factor of AF-related cardiogenic cerebral infarction.All enrolled patients were followed up for 90 days.The primary endpoint was a 90-day modified Rankin Scale(mRS),with mRS 4-6 defined as a poor outcome and mRS 0-3 as a good outcome.The secondary endpoint was the rate of symptomatic intracranial hemorrhage(sICH)within 90 days.Heidelberg classification criterion was used for sICH.Finally,logistic regression analysis was used to analyze the influencing factors of poor prognosis and sICH.Results:According to the TOAST standard,the screened 388 cases included 281cases of CE type,41 cases of SAO type,23 cases of SUE type,and 16 cases of OC.The differences between CE type and non-CE type in the history of hypertension,diabetes,previous history of peripheral vascular disease,chronic heart failure,admission NIHSS,and N-terminal ProB-type Natriuretic peptide(NT-proBNP)were statistically significant.The non-CE group had more patients with hypertension(73.8%vs.58.8%),diabetes(32.6%vs.16.1%),and peripheral artery disease(12.8%vs.3.4%),but the CE group had a higher NIHSS score(median:13 vs.6).Univariate analysis showed a history of diabetes(OR:0.423,95%CI:0.250-0.717),a history of peripheral vascular disease(OR:0.289,95%CI:0.116-0.718)and fibrinogen(Fbg)(OR:0.778,95%CI:0.620-0.977)were negatively correlated with CE type.NIHSS score at admission(OR:1.213,95%CI:1.072-1.373)and NT-proBNP(OR:1.213,95%CI:1.072-1.373)was positively correlated with CE type.After adjusting for confounding factors in multivariate analysis,Age(OR:0.961,95%CI:0.933-0.962),diabetes mellitus(OR:0.370,95%CI:0.205-0.667),previous history of stroke(OR:0.513,95%CI:0.247-0.961)and previous history of peripheral vascular disease(OR:0.117,95%CI:0.040-0.343)were negatively correlated with CE type,but NIHSS score at admission(OR:1.099,95%CI:1.060-1.140)and NT-proBNP(OR:1.155,95%CI:1.018-1.310)were significantly positively correlated with CE type.For the 90-day short-term prognosis of ACI patients combined with AF,univariate analysis showed age(OR:1.081,95%CI:1.052-1.111),history of hypertension(OR:1.843,95%CI:1.046-3.248),history of ischemic stroke(OR:2.230,95%CI:1.319-3.769),previous history of coronary heart disease(OR:2.076,95%CI:1.205-3.503),history of chronic heart failure(OR:2.662,95%CI:1.608-4.407),CE type(OR:3.385,95%CI:2.0175.680),NIHSS score at admission(OR:1.266,95%CI:1.212-1.323)were positively correlated with poor prognosis.After multifactor adjustment,age(OR:1.062,95%CI:1.025-1.101),history of ischemic stroke(OR:3.998,95%CI:1.811-8.824),CE type(OR:2.686,95%CI:1.260-5.726),NIHSS score on admission(OR:1.312,95%CI:1.239-1.389)were independently positively correlated with poor prognosis,and reperfusion treatment(OR:0.328,95%CI:0.160-0.669)was independently negatively correlated with poor prognosis.In terms of sICH in patients with ACI combined with AF,univariate analysis revealed previous coronary heart disease(OR:4.663,95%CI:2.257-9.632),history of ischemic stroke(OR:2.284,95%CI:1.061-4.915),chronic heart failure(OR:2.187,95%CI:1.0374.613),NIHSS score at admission(OR:1.014,95%CI:1.060-1.150),reperfusion therapy(OR:3.058,95%CI:1.474-6.347)were positively correlated with sICH,after multifactor adjustment,NIHSS score on admission(OR:1.116,95%CI:1.065-1.168),and reperfusion treatment(OR:3.218,95%CI:1.468-7.054)were positively correlated with sICH.Conclusion:In this study,it was found that CE type of stroke was the majority of acute cerebral infarction patients with atrial fibrillation,followed by SAO type,LAA type,and SUE type,OC type.The positive correlation factors for CE were NIHSS score at admission and NT-proBNP,while the negative correlation factors included age,history of diabetes mellitus,history of ischemic stroke.The poor clinical prognosis was independently positively correlated with age,history of ischemic stroke,CE type,NIHSS score on admission,and negatively correlated with reperfusion treatment.Symptomatic intracranial hemorrhage was independently positively correlated with NIHSS score on admission,and reperfusion treatment.Part Ⅱ:clinical prognosis after reperfusion therapy for cerebral infarction associated with atrial fibrillationObjective:This study was designed to analyze the risk factors affecting the poor prognosis and symptomatic intracranial hemorrhage in patients with AF-related cardiogenic cerebral infarction treated by reperfusion therapy at our center.Methods:A prospective single-center cohort study was conducted.152 patients with AF-related ACI in the Stroke Center of First Affiliated Hospitial of Soochow University from September 2018 to September 2020 were continuously collected.The classification criteria of stroke were TOAST.Detailed demographic data,finally looks normal until emergency room time,medical history,clinical manifestations,and vascular risk survey were collected,and interest indicators D-dimer,fibrinogen(Fbg),NT-proBNP,hypersensitive CRP,infarct core volume,ischemic penumbra volume were collected.Follow-up of 90 days,the primary endpoint was a 90-day modified Rankin Scale(mRS),with mRS 4-6 defined as a poor outcome and mRS 0-3 as a good outcome.The secondary endpoint was the rate of sICH within 90 days.Heidelberg’s typing criterion was still used to determine the classification.Results:The poor prognosis group and the good prognosis group were compared in age[77.0(69.5,80.0)vs.71(66.0,76.0)],hypertension(81.2%vs.59.0%),diabetes(27.5%vs.13.3),finally looks normal until emergency room time[220(165,282)vs.181(120,240)],systolic blood pressure[159(146,163.5)vs.146(134,160)],diastolic blood pressure[92(80,102)vs.82(78,92)],admission NIHSS[19.0(14.0,23.0 vs.12.0(6.0,16.0)],D-dimer[2.0(1.4,3.7)vs.1.0(0.57,1.74)],hypersensitive CRP[15.6(13.9,25.6)vs.9.0(4.1,9.0)]and NT-proBNP[1500.0(944.5,2528.0)vs.881.5(600.0,1377.0)],these differences were statistically significant.In terms of CT perfusion,the poor prognosis group had a higher infarct core[49.0(19.5,84.0)vs.8.0(2.0,19.0)]and ischemic penumbra volume[164(107,243)vs.55(17,131)].SICH was higher in the poor prognosis group(31.9%vs.2.4%).Univariate analysis showed that age(OR:1.051,95%CI:1.012-1.092),hypertension(OR:2.989,95%CI:1.419-6.298),diabetes mellitus(OR:2.487,95%CI:1.089-5.679),finally looks normal until emergency room time(OR:1.007,95%CI:1.003-1.011),systolic blood pressure(OR:1.033,95%Cl:1.012-1.055),diastolic blood pressure(OR:1.027,95%CI:1.003-1.052),admission NIHSS(OR:1.244,95%CI:1.155-1.341),D-dimer(OR:1.468,95%CI:1.157-1.861),hypersensitive CRP(OR:1.008,95%CI:1.048-1.130),NT-proBNP(OR:1.261,95%CI:1.096-1.451),infarct core volume(OR:1.058,95%CI:1.036-1.081)and ischemic penumbra volume(OR:1.013,95%CI:1.008-1.018)were positively correlated in poor prognosis group compared with good prognosis group.After multifactor adjustment,independent positive correlation factors affecting poor prognosis of AF-related cerebral infarction included admission NIHSS(OR:1.171,95%CI:1.059-1.296)and infarct core volume(OR:1.043,95%CI:1.013-1.073).The area under ROC curve of combined admission NIHSS,and infarct core volume reached 0.897,indicating the reatively large diagnostic and prediction efficiency.Symptomatic intracranial hemorrhage was associated with older age[79.0(73.0,80.0)vs.72(66.0,78.8)],more history of stroke(29.2%vs.10.9%),higher NIHSS score at admission[21.0(13.8,23.0)vs.14(8.0,18.0)],higher D-dimer[2.6(1.3,4.4)vs.1.2(0.7,2.2)],higher NT-proBNP[1868.5(1025.0,2979.0)vs.1000.0(633.0,1500.0)].In terms of CT perfusion parameters,the poor prognosis group had larger infarct core volume[60.5(12.3,149.5)vs.17.0(4.0,38.8)]and ischemic penumbra[171(130,274)vs.17.0(4.0,38.8)].Univariate analysis showed that the positive correlation factors affecting symptomatic intracranial hemorrhage included age(OR:1.082,95%CI:1.020-1.148),and previous stroke history(OR:3.353,95%CI:1.184-9.492),admission NIHSS(OR:1.174,95%CI:1.0761.282),NT-proBNP(OR:1.177,95%CI:1.046-1.325),infarct core volume(OR:1.013,95%CI:1.006-1.020)and ischemic penumbra volume(OR:1.007,95%CI:1.002-1.012).After multi-factor adjustment,it was found that independent positive correlation factors affecting symptomatic intracranial hemorrhage included age(OR:1.061,95%CI:1.002-2.125)admission NIHSS(OR:1.111,95%CI:1.007-1.225),NT-proBNP(OR:1.165,95%CI:1.011-1.341)and infarct core volume(OR:1.011,95%CI:1.003-1.019).The area under the ROC curve of combined admission NIHSS,NT-proBNP,and infarct core volume reached 0.808,indicating the maximum diagnostic and prediction efficiency.Subgroup analysis of intravenous thrombolytic therapy showed that the independent positive correlation factors affecting sICH after intravenous therapy for AF-related cerebral infarction were NIHSS score on admission(OR:1.267,95%CI:1.059-1.516)and infarct core volume(OR:1.014,95%CI:1.006-1.023).Subgroup analysis of mechanical thrombectomy showed that the independent positive correlation factors affecting the poor prognosis of mechanical thrombectomy for AF related cerebral infarction were age(OR:1.194,95%CI:1.027-1.138)and NIHSS score on admission(OR:1.257,95%CI:1.007-1.065),infarct core volume(OR:1.036,95%CI:1.007-1.065).Conclusions:In this study,it was found that the independent positive correlation factors affecting the poor prognosis of AF-related cerebral infarction after reperfusion treatment included admission NIHSS and NT-proBNP.Combined admission NIHSS score and infarct core volume can effectively predict poor prognosis.Independent positive correlation factors affecting symptomatic intracranial hemorrhage transformation include age,admission NIHSS,NT-probNP,and infarct core volume.Combined admission NIHSS,NT-probNP,and infarct core volume can effectively predict sICH.Part Ⅲ:Analysis of pathological features of emboli in cerebral infarction associated with atrial fibrillationObjective:To analyze and compare the distribution of fibrin/platelets,red blood cells,and white blood cells in the pathological analysis of cerebral infarction emboli associated with atrial fibrillation and atherosclerotic cerebral infarction emboli,and further explore the distribution characteristics of immune-inflammatory cells such as CD4,CD8,and CD68 in the two emboli.Methods:A total of 111 acute infarction patients with mechanical thrombectomy were prospectively collected.47 emboli of AF-related concern origin,10 of atherosclerotic type,and 6 of unknown cause were screened out.The piece with the largest volume of emboli taken out for the first time was selected.The surface blood was washed with normal saline immediately,soaked with 10%formalin,and embedded with paraffin within 24 hours.The wax block was cut with a thickness of 4um,and the part with the largest cross-section containing emboli was selected for HE staining and immunohistochemical staining for CD42b,CD4+,CD8+,and CD68+.Image J software was used to analyze embolus components:fibrin/platelet,red blood cell,white blood cell,CD42b visual field area distribution ratio,and the number of immune-inflammatory cells such as CD4+,CD8+and CD68+visual field(cells/mm2).Statistical analysis was made of the distribution differences of interested embolus components in AF-related cerebral infarction,atherosclerotic cerebral infarction,and unexplained cerebral infarction,and to explore the correlation between the embolus components of interest and the times of extraction,the time from a puncture to opening,and 24 hours of neurological defects.Results:1.The percentage distribution of fibrin/platelet in AF related cardiogenic cerebral infarction、LAA type and unexplained cerebral infarction were as follows:53.0(43.0,60.0)vs.30.0(21.0,32.8)vs.45.0(41.5,51.0).Comparing with large artery atherosclerosis model embolus,fibrin/platelet components in AF-related cerebral infarction were higher;comparing with AF-related cerebral infarction,the distribution of red blood cells in atherosclerotic emboli was higher,41.5(29.8,45.0)vs.16.0(12.0,23.0).Comparing with the large atherosclerotic type,the distribution of white blood cells in AF-related cerebral infarction was higher,9.0(8.0,10.0)vs.6.0(5.0,7.0).The distribution of CD42b was higher in AF-related cerebral infarction,30.0(23.0,40.0)vs.10.5(9.8,17.5).2.Comparing with AF-related cerebral infarction,large atherosclerotic cerebral infarction emboli had higher CD4+distribution:15.0(12.8,18.5)vs.6.0(5.0,8.0),and higher CD8+distribution:11.0(9.8,12.0)vs.3.0(2.0,4.0),higher CD68 distribution:11.0(9.8,12.0)vs.3.0(2.0,4.0);The distribution of CD4+,CD8+,and CD68+in atherosclerotic infarcts was also higher than that in unexplained infarcts.There was no correlation between fibrin/platelet,RBC,WBC,CD4+,CD8+,CD42b,and mRS score of 90 days after mechanical thrombin removal.Fibrin and red blood cells in thromboembolic of atherosclerotic cerebral infarction were distributed separately,while AF-related cardiogenic emboli were concerned about the cross-linked distribution of fibrin and red blood cells.3.There was no correlation between fibrin/platelet,RBC,CD4+,CD8+,and CD42b and the neurological deficit score 24h after thrombectomy.After adjusting age and initial neurological deficit score,only the fibrin/platelet had a weak positive correlation with the neurological deficit 24h after thrombectomy,r=0.262,other components of interest remain irrelevant.Fibrin/platelet,WBC,CD4 were negatively correlated with the time from a puncture to opening,while RBC was positively correlated with PTR time.Conclusion:1.This study found that AF-related cerebral infarction embolus was concerned with the higher distribution of fibrin/platelet and the higher distribution of red blood cells in emboli of atherosclerotic cerebral infarction.The ratio of fibrin/platelet and red blood cells can be used as two possible markers for the classification of causes of cerebral infarction complicated with AF.Fibrin and red blood cells in thromboembolic of atherosclerotic cerebral infarction were distributed separately,while AF-related cardiogenic emboli were concerned about the cross-linked distribution of fibrin and red blood cells.2.Comparing with AF source emboli,there is a higher distribution of CD4+,CD8+,and CD68+in atherosclerotic cerebral infarction emboli,and these three immune inflammatory cells may be potential therapeutic targets in the process of intravenous thrombolysis or mechanical thrombolysis.3.There was a weak positive correlation between the distribution of fibrin/platelets in the embolus and the neurological deficit 24h after thrombus removal.The emboli with a higher distribution of fibrin/platelets,white blood cells,number of CD4+cells had a shorter time from the beginning of puncture to the opening,while the emboli with a higher distribution of red blood cells had a long time from the beginning of puncture to the opening.It is difficult to find an embolic marker that affects the prognosis of stroke. |
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