Cerebrospinal Creatine Kinase BB Isoenzyme: A Biomarker for Predicting Outcome After Cardiac Arrest.

BACKGROUND: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. METHODS: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). RESULTS: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. CONCLUSIONS: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Whole-Genome Sequencing Association Analyses of Stroke and Its Subtypes in Ancestrally Diverse Populations From Trans-Omics for Precision Medicine Project.

BACKGROUND AND PURPOSE: Stroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Precision Medicine (TOPMed) Program, we aimed to identify novel variants, especially low-frequency or ancestry-specific variants, associated with all stroke, ischemic stroke and its subtypes (large artery, cardioembolic, and small vessel), and hemorrhagic stroke and its subtypes (intracerebral and subarachnoid). METHODS: Whole-genome sequencing data were available for 6833 stroke cases and 27 116 controls, including 22 315 European, 7877 Black, 2616 Hispanic/Latino, 850 Asian, 54 Native American, and 237 other ancestry participants. In TOPMed, we performed single variant association analysis examining 40 million common variants and aggregated association analysis focusing on rare variants. We also combined TOPMed European populations with over 28 000 additional European participants from the UK BioBank genome-wide array data through meta-analysis. RESULTS: In the single variant association analysis in TOPMed, we identified one novel locus 13q33 for large artery at whole-genome-wide significance (P<5.00×10-9) and 4 novel loci at genome-wide significance (P<5.00×10-8), all of which need confirmation in independent studies. Lead variants in all 5 loci are low-frequency but are more common in non-European populations. An aggregation of synonymous rare variants within the gene C6orf26 demonstrated suggestive evidence of association for hemorrhagic stroke (P<3.11×10-6). By meta-analyzing European ancestry samples in TOPMed and UK BioBank, we replicated several previously reported stroke loci including PITX2, HDAC9, ZFHX3, and LRCH1. CONCLUSIONS: We represent the first association analysis for stroke and its subtypes using whole-genome sequencing data from ancestrally diverse populations. While our findings suggest the potential benefits of combining whole-genome sequencing data with populations of diverse genetic backgrounds to identify possible low-frequency or ancestry-specific variants, they also highlight the need to increase genome coverage and sample sizes.

Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2020 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association's 2020 Impact Goals. RESULTS: Each of the 26 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Clinical Performance Measures for Stroke Rehabilitation: Performance Measures From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released the adult stroke rehabilitation and recovery guidelines in 2016. A working group of stroke rehabilitation experts reviewed these guidelines and identified a subset of recommendations that were deemed suitable for creating performance measures. These 13 performance measures are reported here and contain inclusion and exclusion criteria to allow calculation of rates of compliance in a variety of settings ranging from acute hospital care to postacute care and care in the home and outpatient setting.

HIV Viremia and Risk of Stroke Among People Living with HIV Who Are Using Antiretroviral Therapy.

BACKGROUND: Rates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined. METHODS: Between 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States. We considered three parameterizations of viral load (VL) including (1) baseline (most recent VL before study entry), (2) time-updated, and (3) cumulative VL (copy-days/mL of virus). We used Cox proportional hazards models to estimate hazard ratios (HRs) for stroke risk comparing the 75th percentile ("high VL") to the 25th percentile ("low VL") of baseline and time-updated VL. We used marginal structural Cox models, with most models adjusted for traditional stroke risk factors, to estimate HRs for stroke associated with cumulative VL. RESULTS: Among 15,974 people living with HIV, 139 experienced a stroke (113 ischemic; 18 hemorrhagic; eight were unknown type) over a median follow-up of 4.2 years. Median baseline VL was 38 copies/mL (interquartile interval: 24, 3,420). High baseline VL was associated with increased risk of both ischemic (HR: 1.3; 95% CI = 0.96-1.7) and hemorrhagic stroke (HR: 3.1; 95% CI = 1.6-5.9). In time-updated models, high VL was also associated with an increased risk of any stroke (HR: 1.8; 95% CI = 1.4-2.3). We observed no association between cumulative VL and stroke risk. CONCLUSIONS: Our findings are consistent with the hypothesis that elevated HIV VL may increase stroke risk, regardless of previous VL levels.

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

OBJECTIVE: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH. METHODS: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses. RESULTS: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10-100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively. INTERPRETATION: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.

Association of Type 2 Diabetes Mellitus and Glycemic Control With Intracranial Plaque Characteristics in Patients With Acute Ischemic Stroke.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has shown to be associated with carotid plaque vulnerability. However, the impact of T2DM on intracranial artery atherosclerosis is not well-understood. PURPOSE: To evaluate the association of diabetes and glycemic control with intracranial atherosclerotic plaque characteristics identified by three-dimensional contrast enhanced MR vessel wall imaging in patients after acute ischemic stroke. STUDY TYPE: Prospective. POPULATION: Two hundred and eighty-eight symptomatic patients with acute ischemic stroke due to intracranial atherosclerotic plaque. FIELD STRENGTH/SEQUENCE: T1 WI volume isotropic turbo spin-echo acquisition sequence at 3.0 T. ASSESSMENT: Clinical profiles, blood biomarkers, the number of intracranial plaques, plaque enhanced score, and the features (location, luminal stenotic rate, intraplaque hemorrhage, length, burden, enhancement grade, and ratio) of culprit plaque (defined as the most stenotic lesion ipsilateral to the ischemic event) and nonculprit plaque were analyzed by three radiologists. STATISTICAL TESTS: Analysis of variance (ANOVA), Shapiro-Wilk normality test, Levene's test, ANOVA with Bonferroni post-hoc test, Kruskal Wallis H test with subsequent pairwise comparisons, chi-square with Bonferroni post-hoc test, generalized linear regression, Pearson correlation test, Kendall's W and intra-class correlation coefficient. RESULTS: Two hundred and twenty-five participants (age 60 ± 10 years, 58.7% male) with 958 intracranial plaques were included. More intracranial plaques were found in the T2DM group than the non-T2DM group (4.80 ± 2.22 vs. 3.60 ± 1.78, P < 0.05). Patients with poorly-controlled T2DM exhibited higher culprit plaque enhancement ratio than patients with well-controlled T2DM and non-T2DM (2.32 ± 0.61 vs. 1.60 ± 0.62 and 1.39 ± 0.39; respectively, P < 0.05). After adjusting for other clinical variables, T2DM was independently associated with increased intracranial plaque number (ß = 0.269, P < 0.05), and HbA1c level was independently associated with culprit plaque enhancement ratio (ß = 0.641, P < 0.05) in multivariate analysis. DATA CONCLUSION: T2DM is associated with an increased intracranial plaque number. Higher HbA1c is associated with stronger plaque enhancement. 3D contrast enhanced MR vessel wall imaging may help better understand the association of T2DM and glycemic control with intracranial plaque. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

Medical and Surgical Management of Left Ventricular Assist Device-Associated Intracranial Hemorrhage.

OBJECTIVES: Management of left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH) is complicated by the competing concerns of hematoma expansion and the risk of thrombosis. Strategies include reversal or withholding of anticoagulation (AC) and neurosurgical (NSG) interventions. The consequences of these decisions can significantly impact both short- and long-term survival. Currently no guidelines exist. We reviewed medical and NSG practices following LVAD-associated ICH and analyzed outcomes. MATERIALS AND METHODS: Retrospective analysis of data collected between 2012-2018 was performed. Survival probability following ICH was calculated using the Kaplan-Meier method. RESULTS: Out of 283 patients, 32 (11%) had 34 ICHs: 16 intraparenchymal (IPH, 47%), 4 subdural (SDH, 12%), and 14 subarachnoid (SAH, 41%). IPH tended to occur sooner (median 138 [IQR 48 - 258] days post-LVAD placement) and be more neurologically devastating (mean GCS 11.4 [4.4]). Antithrombotics were reversed in 27 (79%); 1 thrombotic event occurred while off AC. Following resumption, re-hemorrhage occurred in 7 (25%), a median of 13 days (IQR 8-30) post-ICH. Five underwent NSG intervention and 6 (18%) went on to receive heart transplant. Overall, 30-day mortality was 26% (38% in IPH, 0% in SDH, and 29% in SAH), but rose to 44% at 6 months. CONCLUSION: ICH is a common post-LVAD complication with high short- and long-term mortality, though ICH subtypes may not be equally devastating. Despite this, some may benefit from neurosurgical intervention and do well following cardiac transplant. Anticoagulation is frequently reversed after ICH. Resumption however should be approached cautiously in patients with LVADs given their possible baseline coagulopathy.

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

BACKGROUND: Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. METHODS: In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. RESULTS: We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group. CONCLUSIONS: Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270 .).

Genome-wide association study of cerebral small vessel disease reveals established and novel loci.

Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 × 10-8] at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS.

Challenges of Thrombolysis in a Developing Country: Characteristics and Outcomes in Peru.

BACKGROUND: The availability of intravenous tissue plasminogen activator (IV-tPA) remains limited worldwide, especially in low-income countries, where the burden of disability due to ischemic stroke is the highest. AIMS: To evaluate outcomes and safety of IV-tPA at the only Peruvian reference institute for neurologic diseases. METHODS: We conducted a prospective, observational study of stroke patients who received IV-tPA between 2009 and 2016. We assessed characteristics associated with good outcome (modified Rankine scale 0-2) at 3 months using a multivariate regression model; and factors correlated with clinical improvement (delta National Institute of Health Stroke Scale (NIHSS)) using linear regression. RESULTS: Only 1.98% (39/1,1962) of patients presenting with ischemic stroke received IV-tPA. Nearly half (41%) were younger than 60 years, 56.4 % were men, and most strokes were cardioembolic (46.2%). The majority (64.1%) were treated within 3-4.5 hours. The median NIHSS on admission and discharge was 9 and 4, respectively; 42.1% of patients had an mRS of 0-1 at 3 months. Three patients (7.7%) developed hemorrhagic conversion, and 1 patient died (2.6%). Patients with good outcomes had lower pretreatment systolic blood pressure (138.9 versus 158.1 mm Hg, P < .007), fewer complications during hospitalization (5 versus 9 events, P < .001), shorter hospital stay (14 versus 21 days, P < .03) and, paradoxically, longer last known well -to-door times (148.3 versus 105 minutes, P < .0022). Clinical improvement was associated with shorter door-to-tPA times and obesity. CONCLUSIONS: Our findings indicate that IV-tPA has similar safety and outcomes compared to developed countries. All internal metrics (door-to-tPA, door-to-CT, and CT-to-tPA time) improved over time, highlighting areas for future implementation science studies to further expedite the administration of IV-tPA.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Increased Blood Pressure Variability Contributes to Worse Outcome After Intracerebral Hemorrhage.

Background and Purpose- Increased systolic blood pressure variability (BPV) is associated with worse outcome after acute ischemic stroke and may also have a negative impact after intracerebral hemorrhage. We sought to determine whether increased BPV was detrimental in the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial. Methods- The primary outcome of our study was a 3-month follow-up modified Rankin Scale of 3 to 6, and the secondary outcome was a utility-weighted modified Rankin Scale. We calculated blood pressure mean and variability using systolic blood pressure from the acute period (2-24 hours postrandomization) and subacute period (days 2, 3, and 7). Results- The acute period included 913 patients and the subacute included 877. For 5 different statistical measures of systolic BPV, there was a consistent association between increased BPV and worse neurological outcome in both the acute and subacute periods. This association was not found for systolic blood pressure mean. Conclusions- In this secondary analysis of ATACH-2, we show that increased systolic BPV is associated with worse long-term neurological outcome. Additional research is needed to find techniques that allow early identification of patients with an expected elevation of BPV and to study pharmacological or protocol-based approaches to minimize BPV.

2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations for clinicians caring for adult patients with acute arterial ischemic stroke in a single document. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 guidelines and subsequent updates. METHODS: Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. The members of the writing group unanimously approved all recommendations except when relations with industry precluded members voting. Prerelease review of the draft guideline was performed by 4 expert peer reviewers and by the members of the Stroke Council's Scientific Statements Oversight Committee and Stroke Council Leadership Committee. These guidelines use the American College of Cardiology/American Heart Association 2015 Class of Recommendations and Levels of Evidence and the new American Heart Association guidelines format. RESULTS: These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. CONCLUSIONS: These guidelines are based on the best evidence currently available. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. METHODS: We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10-8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. RESULTS: The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: a genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: ß, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: ß, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). CONCLUSIONS: We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.

Minority Patients are Less Likely to Undergo Withdrawal of Care After Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Prior studies of patients in the intensive care unit have suggested racial/ethnic variation in end-of-life decision making. We sought to evaluate whether race/ethnicity modifies the implementation of comfort measures only status (CMOs) in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). METHODS: We analyzed data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a prospective cohort study specifically designed to enroll equal numbers of white, black, and Hispanic subjects. ICH patients aged ≥ 18 years were enrolled in ERICH at 42 hospitals in the USA from 2010 to 2015. Univariate and multivariate logistic regression analyses were implemented to evaluate the association between race/ethnicity and CMOs after adjustment for potential confounders. RESULTS: A total of 2705 ICH cases (912 black, 893 Hispanic, 900 white) were included in this study (mean age 62 [SD 14], female sex 1119 [41%]). CMOs patients comprised 276 (10%) of the entire cohort; of these, 64 (7%) were black, 79 (9%) Hispanic, and 133 (15%) white (univariate p < 0.001). In multivariate analysis, compared to whites, blacks were half as likely to be made CMOs (OR 0.50, 95% CI 0.34-0.75; p = 0.001), and no statistically significant difference was observed for Hispanics. All three racial/ethnic groups had similar mortality rates at discharge (whites 12%, blacks 9%, and Hispanics 10%; p = 0.108). Other factors independently associated with CMOs included age (p < 0.001), premorbid modified Rankin Scale (p < 0.001), dementia (p = 0.008), admission Glasgow Coma Scale (p = 0.009), hematoma volume (p < 0.001), intraventricular hematoma volume (p < 0.001), lobar (p = 0.032) and brainstem (p < 0.001) location and endotracheal intubation (p < 0.001). CONCLUSIONS: In ICH, black patients are less likely than white patients to have CMOs. However, in-hospital mortality is similar across all racial/ethnic groups. Further investigation is warranted to better understand the causes and implications of racial disparities in CMO decisions.

Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society.

The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease is the leading cause of death and major disability in adults ≥75 years of age; however, despite the large impact of cardiovascular disease on quality of life, morbidity, and mortality in older adults, patients aged ≥75 years have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older patients with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in a nursing home or assisted living facility. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older patients typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision making, and recommend future research to close existing knowledge gaps. To achieve these objectives, we conducted a detailed review of current American College of Cardiology/American Heart Association and American Stroke Association guidelines to identify content and recommendations that explicitly targeted older patients. We found that there is a pervasive lack of evidence to guide clinical decision making in older patients with cardiovascular disease, as well as a paucity of data on the impact of diagnostic and therapeutic interventions on key outcomes that are particularly important to older patients, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older patients representative of those seen in clinical practice and that incorporate relevant outcomes important to older patients in the study design. The results of these studies will provide the foundation for future evidence-based guidelines applicable to older patients, thereby enhancing patient-centered evidence-based care of older people with cardiovascular disease in the United States and around the world.

Palliative Care for Hospitalized Patients With Stroke: Results From the 2010 to 2012 National Inpatient Sample.

BACKGROUND AND PURPOSE: Substantial variability exists in the use of life-prolonging treatments for patients with stroke, especially near the end of life. This study explores patterns of palliative care utilization and death in hospitalized patients with stroke across the United States. METHODS: Using the 2010 to 2012 nationwide inpatient sample databases, we included all patients discharged with stroke identified by International Classification of Diseases-Ninth Revision codes. Strokes were subclassified as ischemic, intracerebral, and subarachnoid hemorrhage. We compared demographics, comorbidities, procedures, and outcomes between patients with and without a palliative care encounter (PCE) as defined by the International Classification of Diseases-Ninth Revision code V66.7. Pearson χ2 test was used for categorical variables. Multivariate logistic regression was used to account for hospital, regional, payer, and medical severity factors to predict PCE use and death. RESULTS: Among 395 411 patients with stroke, PCE was used in 6.2% with an increasing trend over time (P<0.05). We found a wide range in PCE use with higher rates in patients with older age, hemorrhagic stroke types, women, and white race (all P<0.001). Smaller and for-profit hospitals saw lower rates. Overall, 9.2% of hospitalized patients with stroke died, and PCE was significantly associated with death. Length of stay in decedents was shorter for patients who received PCE. CONCLUSIONS: Palliative care use is increasing nationally for patients with stroke, especially in larger hospitals. Persistent disparities in PCE use and mortality exist in regards to age, sex, race, region, and hospital characteristics. Given the variations in PCE use, especially at the end of life, the use of mortality rates as a hospital quality measure is questioned.