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Öğe Aortic arch atherosclerosis in patients with embolic stroke of undetermined source: an exploratory analysis of the NAVIGATE ESUS trial(LIPPINCOTT WILLIAMS & WILKINS, 2019) Ntaios, George.; Pearce, Lesly A.; Meseguer, Elena.; Endres, Matthias.; Amarenco, Pierre.; Ozturk, Serefnur.; Lang, Wilfried.; Bornstein, Natan M.; Molina, Carlos A.; Pagola, Jorge.; Mundl, Hardi.; Berkowitz, Scott D.; Liu, Yan Yun.; Sen, Souvik.; Connolly, Stuart J.; Hart, Robert G.; NAVIGATE ESUS Investigators.Background and Purpose- Aortic arch atherosclerosis (AAA) is a possible source of embolism in patients with embolic stroke of undetermined source. Previous studies reported high rates of embolic events in patients with AAA, especially those with high-risk AAA. This exploratory analysis of NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) focused on patients with AAA and assessed their characteristics, stroke recurrence rates, and response to treatment. Methods- The detection of AAA and the assessment of its features were based on transesophageal echocardiography that was done in 19% of participants. AAA plaques were considered to have complex features when reported as complex or ulcerated or were >= 4 mm in thickness or had a mobile thrombus present. Results- Among 1382 participants who had transesophageal echocardiography, 397 (29%) had AAA and 112 (8%) had complex AAA. Mean (SD) age (63 [10] versus 67 [9] versus 69 [9]; P<0.001), prevalence of diabetes mellitus (19% versus 26%, versus 32%; P=0.002), and aortic valvulopathy (10 versus 20 versus 20; P<0.001) increased across no versus noncomplex versus complex AAA, respectively. In multivariable analyses, increasing age, diabetes mellitus, aortic valvulopathy, statin use before randomization, chronic infarcts on imaging, and region were independently associated with any AAA versus no AAA and also with complex AAA versus no AAA. Multiterritorial qualifying infarcts rather than single-territory infarcts were observed in 21% with complex AAA versus 17% noncomplex versus 13% no AAA (P=0.07). Annualized rates of ischemic stroke recurrence were 7.2% versus 4.2% versus 5.6% for complex versus noncomplex versus no AAA, respectively. While prevalence of complex AAA increased with increasing risk score, after adjusting for risk score, we did not observe increased risk of recurrent stroke for patients with complex AAA (hazard ratio, 1.1; 95% CI, 0.53-2.4), although the number of outcomes was limited. In patients with complex AAA, 4 strokes occurred among rivaroxaban-assigned patients and 4 strokes among aspirin-assigned patients. Conclusions- Complex AAA is prevalent in embolic stroke of undetermined source patients and is associated with atherosclerotic burden. Whether complex AAA independently increases recurrent stroke risk and whether a non-vitamin-K oral anticoagulant as compared with aspirin may be effective for reducing recurrent stroke requires additional study.Öğe Effect of glyceryl trinitrate on hemodynamics in acute stroke data from the ENOS trial(LIPPINCOTT WILLIAMS & WILKINS, 2019) Appleton, Jason P.; Woodhouse, Lisa J.; Bereczki, Daniel.; Berge, Eivind.; Christensen, Hanne K.; Collins, Ronan.; Gommans, John.; Ntaios, George.; Ozturk, Serefnur.; Szatmari, Szabolcs.; Wardlaw, Joanna M.; Sprigg, Nikola.; Rothwell, Peter M.; Bath, Philip M.Background and Purpose-Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods-Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results-Increased baseline BP (diastolic, variability), heart rate, and rate-pressure product were each associated with unfavorable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in modified Rankin Scale (highest quintile adjusted odds ratio, 1.65; 95% CI, 1.37-1.99), worse cognitive scores (telephone mini-mental state examination: highest quintile adjusted mean difference, -2.03; 95% CI, -2.84 to -1.22), and increased odds of death at day 90 (highest quintile adjusted odds ratio, 1.57; 95% CI, 1.12-2.19). GTN lowered BP and rate-pressure product and increased heart rate at day 1 and reduced between-visit systolic BP variability. Conclusions-Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and rate-pressure product, GTN reduced betweenvisit systolic BP variability. Agents that lower BP variability in acute stroke require further study.Öğe Noncontrast computed tomography signs as predictors of hematoma expansion, clinical outcome, and response to tranexamic acid in acute intracerebral hemorrhage(LIPPINCOTT WILLIAMS & WILKINS, 2020) Law, Zhe Kang.; Ali, Azlinawati.; Krishnan, Kailash.; Bischoff, Adam.; Appleton, Jason P.; Scutt, Polly.; Woodhouse, Lisa.; Pszczolkowski, Stefan.; Cala, Lesley A.; Dineen, Robert A.; England, Timothy J.; Ozturk, Serefnur.; Roffe, Christine.; Bereczki, Daniel.; Ciccone, Alfonso.; Christensen, Hanne.; Ovesen, Christian.; Bath, Philip M.; Sprigg, Nikola.Background and Purpose- Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods- The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome. Results- Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16-2.03]; P=0.003), black hole (aOR, 2.03 [1.34-3.08]; P=0.001), and hypodensities (aOR, 2.06 [1.48-2.89]; P<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10-2.11]; P=0.012), hypodensities (aOR, 1.37 [1.05-1.78]; P=0.019), and island sign (aOR, 2.59 [1.21-5.55]; P=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63-0.94]; P=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (P interaction all >0.05). Conclusions- Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid.Öğe Relationship between race and outcome in asian, black, and caucasian patients with spontaneous intracerebral hemorrhage: data from the virtual international stroke trials archive and efficacy of nitric oxide in stroke trial(SAGE PUBLICATIONS LTD, 2018) Krishnan, Kailash.; Beishon, Lucy.; Berge, Eivind.; Christensen, Hanne.; Dineen, Robert A.; Ozturk, Serefnur.; Sprigg, Nikola.; Wardlaw, Joanna M.; Bath, Philip M.Background and purpose Although poor prognosis after intracerebral hemorrhage relates to risk factors and hematoma characteristics, there is limited evidence for the effect of race-ethnicity. Methods Data from 1011 patients with intracerebral hemorrhage enrolled into hyperacute trials and randomized to control were obtained from the Virtual International Stroke Trials Archive and Efficacy of Nitric Oxide in Stroke Trial. Clinical characteristics and functional outcome were compared among three racial groups - Asians, Blacks, and Caucasians. Results The majority of patients were Caucasian (78.1%) followed by Asians (14.5%) and Blacks (5.5%). At baseline, Caucasians were older and had larger hematoma volumes; Blacks had lower Glasgow Coma Scale and higher systolic blood pressure (all p<0.05). Although the primary outcome of modified Rankin Scale did not differ at 90 days (p=0.14), there were significant differences in mortality (p<0.0001) and quality of life (EQ-5D p<0.0001; EQ-VAS p 0.015). In test of multiple comparisons, Caucasians were more likely to die (p=0.0003) and had worse quality of life (EQ-5D p=0.003; EQ-VAS p<0.0001) as compared to Asians. Conclusion Race-ethnicity appears to explain some of the variation in clinical characteristics and outcomes after acute intracerebral hemorrhage. Factors that explain this variation need to be identified.Öğe Route of feeding as a proxy for dysphagia ater stroke and the effect of transdermal glyceryl trinitrate: data from the efficacy of nitric oxide in stroke randomised controlled trial(SPRINGER, 2018) Woodhouse, Lisa J.; Scutt, Polly.; Hamdy, Shaheen.; Smithard, David G.; Cohen, David L.; Roffe, Christine.; Bereczki, Daniel.; Berge, Eivind.; Bladin, Christopher F.; Caso, Valeria.; Christensen, Hanne K.; Collins, Rónán.; Czlonkowska, Anna.; Silva, Asita de.; Etribi, Anwar.; Laska, Ann-Charlotte.; Ntaios, George.; Ozturk, Serefnur.; Phillips, Stephen J.; Prasad, Kameshwar.; Szatmari, Szabolcs.; Sprigg, Nikola.; Bath, Philip M.at day Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ae6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke.
