Association Of Cerebral Small Vessel Disease With Hemorrhagic Transformation In Patients With Acute Ischemic Stroke Treated With Rt-PA

Objective:The effect of cerebral small vessel disease(c SVD)on the outcome in patients with ischemic stroke undergoing intravenous thrombolysis remains not fully understood.The purpose of this study was to investigate the association between baseline individual c SVD marker and total c SVD burden and intracranial hemorrhagic transformation(HT)in patients with acute ischemic stroke who received intravenous thrombolysis with recombinant tissue-plasminogen activator(rt-PA).Methods:We included two retrospective acute ischemic stroke cohorts(Fujian Medical University Union Hospital and Longyan First Hospital)in this study.We semi-quantitatively assessed the individual marker of c SVD(lacune,white matter hyperintensities [WMH],microbleeds [CMB],and basal ganglia enlarged perivascular spaces [BG-EPVS])based on a well-validated scale.We quantified the total c SVD burden using a comprehensive score(0-4).Our primary outcome was cerebral hemorrhagic transformation(HT)after intravenous thrombolysis.The patients were divided into two groups(HT versus non-HT).We compared the differences in baseline demographics,clinical characteritics,individual c SVD markers and total c SVD burden between the two groups.We constructed a binary logistic regression model to examine the associations between individual c SVD markers as well as total c SVD burden and HT.ROC(Receiver Operating Characteristic)curve analysis was used to evaluate the predictive value of total c SVD burden for HT after thrombolysis.Results:1.We included 241 patients with acute ischemic stroke(65.98±11.51 years,163[67.6%] males)receiving rt-PA intravenous thrombolytic therapy in Fujian Medical University Union Hospital from January 1st,2013 to December 31 st,2020 and in the First Hospital of Longyan City from January 1st,2016 to December 31 st,2020.A total of 47(19.5%)patients underwent cerebral HT after thrombolytic therapy.2.Patients with and without HT were significantly different in age(P=0.014),having a history of atrial fibrillation(P<0.001),receiving endovascular thrombectomy(P<0.001),baseline NIHSS score(P<0.001),>10 BG-EPVS(P=0.007),and ≥1 CMB(P<0.001),the total c SVD burden(P<0.001).3.Univariate logistic regressional analysis showed that age(OR:1.039,95%CI:1.008-1.071,P=0.015),atrial fibrillation(OR:4.516,95%CI: 2.306-8.843,P<0.001),combined endovascular thrombectomy(OR:9.864,95%CI: 3.837-25.359,P<0.001),baseline NIHSS score(OR:1.150,95%CI: 1.086-1.218,P<0.001),c SVD burden(per point increase,OR:2.235,95%CI: 1.568-3.186,P<0.001),>10 BG-EPVS(OR:2.562,95%CI: 1.274-5.151,P=0.008),≥1 CMB(OR:5.291,95% CI: 2.675-10.463,P<0.001)were significantly related to HT.4.The significant variables in univariate analysis were included with each c SVD marker and c SVD total burden into multivariate logical regression analysis showed that c SVD total burden score(per point increase,adjusted OR:2.391,95%CI: 1.560-3.666,P<0.001),>10 BG-EPVS(adjusted OR:3.322,95%CI: 1.449-7.616,P<0.005),≥1CMB(adjusted OR:5.027,95%CI: 2.268-11.143,P<0.001)were significantly correlated with hemorrhagic transformation.5.ROC curve analysis showed that a cut-off value with 7.5 using a combined baseline NIHSS and total c SVD score had the best predictive value for HT(AUC 0.804[95%CI 0.744-0.864],P<0.001).The cut-off value with 1.5 of total c SVD score(AUC0.714[95%CI 0.628-0.799],P<0.001)can be better predicted HT.In addition,The cut-off value of the baseline NIHSS score of 5.5 was the best(AUC 0.776[95%CI0.709-0.843],P<0.001)for predicting HT.The comprehensive NIHSS score and total c SVD score had a better predictive performance for HT than NIHSS score alone(P=0.0006).Conclusions:1.>10 BG-EPVS,≥1 CMB,and the total c SVD burden were independent risk factors for cerebral hemorrhagic transformation in patients with acute ischemic stroke treated with rt-PA.2.Compared to NIHSS score alone,a combined NIHSS and c SVD score had better performance in predicting HT.