Current territorial organization for access to revascularization therapies for acute ischemic stroke in the Veneto region (Italy) from 2017 to 2021.

INTRODUCTION: To evaluate the access to treatments with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) in acute ischemic stroke patients admitted to stroke units (SUs) of Veneto region (Italy) according to current "hub-and-spoke" model from 2017 to 2021. PATIENTS AND METHODS: We retrospectively analyzed data on treatments with IVT and/or MT for stroke patients admitted to the 23 SUs (6 Hubs and 17 Spokes) of the 6 macro-areas including 9 local sanitary units (LSUs) and 2 hospitals. RESULTS: We reported 6093 treatments with IVT alone, 1114 with IVT plus MT, and 921 with MT alone. Number of stroke unit (SU) beds/100,000 inhabitants ranges from 2.3 to 2.8, and no difference was found among different macro-areas. Number of treatments/100,000 inhabitants/year ranges from 19 to 34 for IVT alone, from 2 to 7 for IVT plus MT, and from 2 to 5 for MT alone. Number of IVT alone/SU bed/year ranges from 9 to 21 in the Hub and from 6 to 12 in the Spokes. Rate of IVT plus MT in patients directly arrived in the same LSU's Hub ranges from 50 to 81%, likewise the one of MT alone ranges from 49 to 84%. CONCLUSIONS: Treatment target rates of IVT and MT set by Action Plan for Stroke in Europe 2018-2030 has been globally exceeded in the Veneto region. However, the target rate of MT and access revascularization treatments is heterogeneous among different macro-areas. Further efforts should be made to homogenize the current territorial organization.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials.

BACKGROUND: Since its approval, the use of alteplase had been limited to patients aged ≤80 years. AIMS: TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence. METHODS: TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0-2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly. RESULTS: Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69-2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights. CONCLUSIONS: The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.

Factors influencing cognitive performance after 1-year treatment with direct oral anticoagulant in patients with atrial fibrillation and previous ischemic stroke: a pilot study.

Anticoagulant treatment as stroke prevention, particularly direct oral anticoagulant (DOAC), may reduce the risk of dementia in patients with atrial fibrillation (AF). We aimed to assess factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. We recruited 33 ischemic stroke patients who were discharged from Verona Stroke Unit with diagnosis of AF and prescription of treatment with DOAC. For each cognitive test, we estimated the effect of T0 (first session) variables on T1 (1-year session) cognitive performance using ordinal logistic regression fitted to a 1 point-shift from 4 to 0 on ESs. The effect of T0 clinical variables was presented as odds ratio (OR) with 95% confidence interval (CI) after adjustment for T0 total score of the corresponding cognitive test. Sustained AF (OR: 4.259, 95% CI 1.071-16.942) and ischemic heart disease (OR: 6.654, 95% CI 1.329-33.300) showed a significant effect on T1 MoCA Test; congestive heart failure on T1 RAVLT Immediate recall (OR: 9.128, 95% CI 1.055-78.995), T1 RAVLT Delayed recall (OR: 7.134, 95% CI 1.214-52.760), and T1 Trail Making Test (Part A) (OR: 16.989, 95% CI 1.765-163.565); sustained AF (OR: 5.055, 95% CI 1.224-20.878) and hyperlipidemia (OR: 4.764, 95% CI 1.175-19.310) on T1 Digit span forward Test; ischemic heart disease (aOR: 8.460, 95% CI 1.364-52.471) on T1 Stroop Color and Word Test (time); Dabigatran use (aOR: 0.084, 95% CI 0.013-0.544) on FAB; age ≥ 75 years (aOR: 0.058, 95% CI 0.006-0.563) and hyperlipidemia (aOR: 5.809, 95% CI 1.059-31.870) on T1 Phonemic word fluency Test; female sex (aOR: 6.105, 95% CI 1.146-32.519), hyperlipidemia (aOR: 21.099, 95% CI 2.773-160.564), total Modified Fazekas Scale score > 1 (aOR: 78.530, 95% CI 3.131-1969.512) on Semantic word fluency Test. Sustained AF, ischemic heart disease, congestive heart failure, hyperlipidemia, and female sex were the factors influencing cognitive performance after 1-year treatment with DOAC in patients with AF and previous ischemic stroke. Modified Fazekas Scale score in the first session was the only radiological variable that had a significant effect on cognitive performance.

Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation.

BACKGROUND AND PURPOSE: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. METHODS: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. RESULTS: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). CONCLUSIONS: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation.

OBJECTIVE: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed. METHODS: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585). INTERPRETATION: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.

A nomogram to predict unfavourable outcome in patients receiving oral anticoagulants for atrial fibrillation after stroke.

INTRODUCTION: It is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients. PATIENTS AND METHODS: We conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (<65 years, reference; 65--79; or 80), National Institutes of Health Stroke Scale score (0--5 points, reference; 6--15; 16--25; or >25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve. RESULTS: A total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training (n = 1553) and test (n = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852; p = 0.276 for the Hosmer--Lemeshow test). DISCUSSION AND CONCLUSION: Our nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.

Small vessel disease and biomarkers of endothelial dysfunction after ischaemic stroke.

INTRODUCTION: Although pathogenesis of small vessel disease is poorly understood, increasing evidence suggests that endothelial dysfunction may have a relevant role in development and progression of small vessel disease. In this cross-sectional study, we investigated the associations between imaging signs of small vessel disease and blood biomarkers of endothelial dysfunction at two different time points in a population of ischaemic stroke patients. PATIENTS AND METHODS: In stroke patients treated with intravenous thrombolysis, we analysed blood levels of von Willebrand factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and vascular endothelial growth factor. Three reviewers independently assessed small vessel disease features using computed tomography. At baseline and 90 days after the index stroke, we tested the associations between single and combined small vessel disease features and levels of blood biomarkers using linear regression analysis adjusting for age, sex, hypertension, diabetes, smoke. RESULTS: A total of 263 patients were available for the analysis. Mean age (±SD) was 69 (±13) years, 154 (59%) patients were male. We did not find any relation between small vessel disease and endothelial dysfunction at baseline. At 90 days, leukoaraiosis was independently associated with intercellular adhesion molecule-1 (ß = 0.21; p = 0.016) and vascular cell adhesion molecule-1 (ß = 0.22; p = 0.009), and lacunes were associated with vascular endothelial growth factor levels (ß = 0.21; p = 0.009) whereas global small vessel disease burden was associated with vascular endothelial growth factor (ß = 0.26; p = 0.006). DISCUSSION: Leukoaraiosis and lacunes were associated with endothelial dysfunction, which could play a key role in pathogenesis of small vessel disease. CONCLUSIONS: Small vessel disease features and total burden were associated with endothelial dysfunction 90 days after the stroke, whereas there was no relation during the acute phase. Our results suggest that endothelial dysfunction, particularly vascular endothelial growth factor, is involved in pathological process of small vessel disease.

Anticoagulation After Stroke in Patients With Atrial Fibrillation.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.

BACKGROUND: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. PURPOSE: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. METHODS: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. RESULTS: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)). CONCLUSIONS: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation.

OBJECTIVE: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. METHODS: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09). INTERPRETATION: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.

Small Vessel Disease Is Associated with Tissue Inhibitor of Matrix Metalloproteinase-4 After Ischaemic Stroke.

Small vessel disease (SVD) is frequent in aging and stroke patients. Inflammation and remodeling of extracellular matrix have been suggested as concurrent mechanisms of SVD. We investigated the relationship between imaging features of SVD and circulating metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with ischaemic stroke. In patients treated with intravenous thrombolysis, we took blood samples before intravenous thrombolysis and 90 days after the acute stroke and analysed levels of MMPs and TIMPs. We assessed leukoaraiosis, number of lacunes and brain atrophy on pre-treatment CT scan and graded global SVD burden combining such features. We investigated associations between single features, global SVD and MMPs and TIMPs at baseline and at follow-up, retaining univariate statistically significant associations in multivariate linear regression analysis and adjusting for clinical confounders. A total of 255 patients [mean (±SD) = 68.6 (± 12.7) years, 154 (59%) males] were included, 107 (42%) had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. A total of 107 (42%) patients had no signs of SVD; 47 (19%) had from moderate to severe SVD burden. After adjustment, only TIMP-4 proved associations with SVD features. Brain atrophy was associated with baseline TIMP-4 (ß = 0.20;p = 0.019) and leukoaraiosis with 90 days TIMP-4 (ß = 0.19; p = 0.013). Global SVD score was not associated with baseline TIMP-4 levels (ß = 0.10; p = 0.072), whereas was associated with 90 days TIMP-4 levels (ß = 0.21; p = 0.003). Total SVD burden was associated with higher TIMP-4 levels 90 days after stroke, whereas was not during the acute phase. Our results support a biological relationship between SVD grade and TIMP-4.

Intravenous thrombolysis for ischemic stroke in the Veneto region: the gap between eligibility and reality.

Intravenous thrombolysis (IVT) is the treatment of choice for most patients with acute ischemic stroke. According to the recently updated guidelines, IVT should be administered in absence of absolute exclusion criteria. We aimed to assess the proportion of ischemic strokes potentially eligible and actually treated with IVT, and to explore the reasons for not administering IVT. We prospectively collected and analyzed data from 1184 consecutive ischemic stroke patients admitted to the 22 Stroke Units (SUs) of the Veneto region from September 18th to December 10th 2017. Patients were treated with IVT according to the current Italian guidelines. For untreated patients, the reasons for not administering IVT were reported by each center in a predefined model including absolute and/or relative exclusion criteria and other possible reasons. Out of 841 (71%) patients who presented within 4.5 h of stroke onset, 704 (59%) had no other absolute exclusion criteria and were therefore potentially eligible for IVT according to the current guidelines. However, only 323 (27%) patients were eventually treated with IVT. Among 861 (73%) untreated patients, 480 had at least one absolute exclusion criterion, 283 only relative exclusion criteria, 56 only other reasons, and 42 a combination of relative exclusion criteria and other reasons. Our study showed that only 46% (323/704) of the potentially eligible patients were actually treated with IVT in the SUs of the Veneto region. All healthcare professionals involved in the acute stroke pathway should make an effort to bridge this gap between eligibility and reality.

Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

[Prevention of cardioembolic events after intracranial hemorrhage]. / Prevenzione degli eventi cardioembolici dopo emorragia intracranica.

In high thromboembolic risk patients who experienced hemorrhagic stroke, the prevention of cardioembolic events and recurrence of intracranial bleeding should be guaranteed. The consultant cardiologist should carefully identify the most appropriate therapeutic approach for these patients. Among patients with previous hemorrhagic stroke, only few restart oral anticoagulant therapy (OAT) after cerebral bleeding; however, as reported by some registries, it is likely that resuming OAT exerts a favorable effect on the combined outcome of ischemic stroke/systemic embolism/all-cause death. In these patients, several parameters should be evaluated, such as the type of intracranial bleeding, the presence of a previous thromboembolic event, the global thromboembolic risk, as well as the history of a previous OAT. This review deals with a particularly interesting matter, requiring a number of decision-making turning points, i.e. whether it is appropriate or not to start or resume OAT, what drug class and timing choice in such a case, and the potential valuable alternatives to OAT.

The dispersion of myocardial repolarization in ischemic stroke and intracranial hemorrhage.

BACKGROUND: Markers of dispersion of myocardial repolarization have been proposed to identify the patients at higher risk of malignant arrhythmic events. The aim of the present study is to assess a possible association of the electrocardiografic (ECG) markers of the dispersion of repolarization with the type of stroke, involvement of insula, neurological severity (National Institutes of Health Stroke Scale, NIHSS score), and disability (modified Rankin Scale, mRS score) in patients with a cerebrovascular event. METHODS: We conducted a retrospective analysis based on data prospectively collected from consecutive patients with a cerebrovascular event who underwent 12­lead ECG at admission to the Verona Stroke Unit. RESULTS: Of the 63 patients included in the study, 55 had ischemic stroke and 8 intracranial hemorrhage. TpTe (time between the peak and the end of the T wave) and TpTe/QTc (TpTe/corrected time between the start of the Q wave and the end of the T wave) in lead V5 were higher in intracranial hemorrhage than in ischemic stroke (p = 0.03 and p = 0.04, respectively) and QT max (the longest QT calculated in the 12 leads) was higher in patients with involvement of insula (p ≤ 0.01). A correlation was found between QTc max and NIHSS score at admission (p = 0.02), QT max and NIHSS score at discharge (p = 0.05), and QT max and mRS score at discharge (p = 0.02). CONCLUSIONS: TpTe and TpTe/QTc in V5 lead were associated with intracranial hemorrhage and QT max was associated with involvement of insula. The prolongation of QT was correlated with neurological severity and disability.

Introduction of direct oral anticoagulant within 7 days of stroke onset: a nomogram to predict the probability of 3-month modified Rankin Scale score > 2.

In clinical practice, direct oral anticoagulants (DOACs) are often started earlier (≤ 7 days) than in randomized clinical trials after stroke. We aimed to develop a nomogram model incorporating time of DOAC introduction ≤ 7 days of stroke onset in combination with different degrees of stroke radiological/neurological severity at the time of treatment to predict the probability of unfavorable outcome. We conducted a multicenter prospective study including 344 patients who started DOAC 1-7 days after atrial fibrillation-related stroke onset. Computed tomography scan 24-36 h after stroke onset was performed in all patients before starting DOAC. Unfavorable outcome was defined as modified Rankin Scale (mRS) score > 2 at 3 months. Based on multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve (AUC-ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. Onset-to-treatment time for DOAC (OR: 1.21, p = 0.030), NIH Stroke Scale (NIHSS) score at the time of treatment (OR: 1.00 for NIHSS = 0-5; OR: 2.67, p = 0.016 for NIHSS = 6-9; OR: 26.70, p < 0.001 for NIHSS = 10-14; OR: 57.48, p < 0.001 for NIHSS ≥ 15), size infarct (OR: 1.00 for small infarct; OR: 2.26, p = 0.023 for medium infarct; OR: 3.40, p = 0.005 for large infarct), and age ≥ 80 years (OR: 1.96, p = 0.028) remained independent predictors of unfavorable outcome to compose the nomogram. The AUC-ROC of nomogram was 0.858. Calibration was good (p = 2.889 for the Hosmer-Lemeshow test). The combination of onset-to-treatment time of DOAC with stroke radiological/neurological severity at the time of treatment and old age may predict the probability of unfavorable outcome.

Alcohol intake and the risk of intracerebral hemorrhage in the elderly: The MUCH-Italy.

OBJECTIVE: To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding. METHODS: We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH. RESULTS: We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32). CONCLUSIONS: In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH.