The American Heart Association's Get With the Guidelines (GWTG)-Stroke programme has changed stroke care delivery in the USA since its establishment in 2003. GWTG is a voluntary registry and continuous quality improvement initiative that collects data on patient characteristics, hospital adherence to guidelines and inpatient outcomes. Implementation of the programme saw increased provision of evidence-based care and improved patient outcomes. This review will describe the development of the programme and discuss the impact on stroke outcomes and transformation of stroke care delivery that followed its implementation.

The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program.

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.

BACKGROUND:The use of endovascular therapy (EVT) in patients with acute ischemic stroke who have large vessel occlusion has rapidly increased in the United States following pivotal trials demonstrating its benefit. Information about the contribution of interhospital transfer in improving access to EVT will help organize regional systems of stroke care. METHODS:We analyzed trends of transfer-in EVT from a cohort of 1 863 693 patients with ischemic stroke admitted to 2143 Get With The Guidelines-Stroke participating hospitals between January 2012 and December 2017. We further examined the association between arrival mode and in-hospital outcomes by using multivariable logistic regression models. RESULTS:Of the 37 260 patients who received EVT at 639 hospitals during the study period, 42.9% (15 975) arrived at the EVT-providing hospital after interhospital transfer. Transfer-in EVT cases increased from 256 in the first quarter 2012 to 1422 in the fourth quarter 2017, with sharply accelerated increases following the fourth quarter 2014 ( P<0.001 for change in linear trend). Transfer-in patients were younger and more likely to be of white race, to arrive during off-hours, and to be treated at comprehensive stroke centers. Transfer-in patients had significantly longer last-known-well-to-EVT initiation time (median, 289 minutes versus 213 minutes; absolute standardized difference, 67.33) but were more likely to have door-to-EVT initiation time of ≤90 minutes (65.6% versus 23.6%; absolute standardized difference, 93.18). In-hospital outcomes were worse for transfer-in patients undergoing EVT in unadjusted and in risk-adjusted models. Although the difference in in-hospital mortality disappeared after adjusting for delay in EVT initiation (14.7% versus 13.4%; adjusted odds ratio, 1.01; 95% CI, 0.92-1.11), transfer-in patients were still more likely to develop symptomatic intracranial hemorrhage (7.0% versus 5.7%; adjusted odds ratio, 1.15; 95% CI, 1.02-1.29) and less likely to have either independent ambulation at discharge (33.1% versus 37.1%; adjusted odds ratio, 0.87; 95% CI, 0.80-0.95) or to be discharged to home (24.3% versus 29.1%; adjusted odds ratio, 0.82; 95% CI, 0.76-0.88). CONCLUSIONS:Interhospital transfer for EVT is increasingly common and is associated with a significant delay in EVT initiation highlighting the need to develop more efficient stroke systems of care. Further evaluation to identify factors that impact EVT outcomes for transfer-in patients is warranted.

Background and Purpose- Optimal blood pressure (BP) management during the early stages of aneurysmal subarachnoid hemorrhage remains uncertain. Observational studies have found worse outcomes in patients with increased hemodynamic variability, suggesting BP optimization as a potential neuroprotective strategy. In this study, we calculated personalized BP targets at which cerebral autoregulation was best preserved. We analyzed how deviation from these limits correlates with functional outcome. Methods- We prospectively enrolled 31 patients with aneurysmal subarachnoid hemorrhage. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation-a surrogate for cerebral blood flow-as well as intracranial pressure (ICP) in response to changes in mean arterial pressure using time-correlation analysis. The resulting autoregulatory indices were used to identify the upper and lower limit of autoregulation. Percent time that mean arterial pressure exceeded limits of autoregulation was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using ordinal multivariate logistic regression. Results- Personalized limits of autoregulation were computed in all patients (age 57.5±13.4, 23F, mean World Federation of Neurological Surgeons 2±1, monitoring time 67.8±50.8 hours). Optimal BP and limits of autoregulation were calculated on average for 89.5±6.7% of the total monitoring period. ICP- and NIRS-derived optimal pressures strongly correlated with one another (P<0.0001). Percent time that mean arterial pressure deviated from limits of autoregulation significantly associated with worse functional outcome at discharge (NIRS, P=0.001; ICP, P=0.004) and 90 days (NIRS, P=0.002; ICP, P=0.003), adjusting separately for age, World Federation of Neurological Surgeons, vasospasm, and delayed cerebral ischemia. Conclusions- Both invasive (ICP) and noninvasive (NIRS) determination of personalized BP targets after aneurysmal subarachnoid hemorrhage is feasible, and these 2 approaches revealed significant collinearity. Furthermore, exceeding individualized limits of autoregulation was associated with poor functional outcomes.

Objective

To determine whether lower socioeconomic status (SES) and longer home to hospital driving time are associated with reductions in tissue plasminogen activator (tPA) administration and timeliness of the treatment.

Methods

We conducted a retrospective observational study using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between January 2015 and March 2017. The study included 118,683 ischemic stroke patients age ≥18 who were transported by emergency medical services to one of 1,489 US hospitals. We defined each patient's SES based on zip code median household income. We calculated the driving time between each patient's home zip code and the hospital where he or she was treated using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA). Outcomes were analyzed using hierarchical multivariable logistic regression models.

Results

SES was not associated with OTA (p = 0.31) or tPA administration (p = 0.47), but was associated with the secondary outcomes of onset-to-treatment time (OTT) (p = 0.0160) and in-hospital mortality (p = 0.0037), with higher SES associated with shorter OTT and lower in-hospital mortality. Driving time was associated with tPA administration (p < 0.001) and OTA (p < 0.0001), with lower odds of tPA (0.83, 0.79-0.88) and longer OTA (1.30, 1.24-1.35) in patients with the longest vs shortest driving time quartiles. Lower SES quintiles were associated with slightly longer driving time quartiles (p = 0.0029), but there was no interaction between the SES and driving time for either OTA (p = 0.1145) or tPA (p = 0.6103).

Conclusions

Longer driving times were associated with lower odds of tPA administration and longer OTA; however, SES did not modify these associations.

Background There is disagreement in the literature about the relationship between strokes and seasonal conditions. We sought to (1) describe seasonal patterns of stroke in the United States, and (2) determine the relationship between weather variables and stroke outcomes. Methods and Results We performed a cross-sectional study using Get With The Guidelines-Stroke data from 896 hospitals across the continental United States. We examined effects of season, climate region, and climate variables on stroke outcomes. We identified 457 638 patients admitted from 2011 to 2015 with ischemic stroke. There was a higher frequency of admissions in winter (116 862 in winter versus 113 689 in spring, 113 569 in summer, and 113 518 in fall; P<0.0001). Winter was associated with higher odds of in-hospital mortality (odds ratio [OR] 1.08 relative to spring, confidence interval [ CI ] 1.04-1.13, P=0.0004) and lower odds of discharge home ( OR 0.92, CI 0.91-0.94, P<0.0001) or independent ambulation at discharge ( OR 0.96, CI 0.94-0.98, P=0.0006). These differences were attenuated after adjusting for climate region and case mix and became inconsistent after controlling for weather variables. Temperature and precipitation were independently associated with outcome after multivariable analysis, with increases in temperature and precipitation associated with lower odds of mortality ( OR 0.95, CI 0.93-0.97, P<0.0001 and OR 0.95, CI 0.90-1.00, P=0.035, respectively). Conclusions Admissions for ischemic stroke were more frequent in the winter. Warmer and wetter weather conditions were independently associated with better outcomes. Further studies should aim to identify sensitive populations and inform public health measures aimed at resource allocation, readiness, and adaptive strategies.

BACKGROUND: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program. METHODS: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications. RESULTS: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event (P<0.01 for all). In patients with acute ischemic stroke, large improvements were observed for anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022), smoking cessation counseling (44.7%-97.8%), dysphagia screening (53.8%-83.5%), thrombolytic treatment for patients arriving by 3.5 hours, treat by 4.5 hours (15.2%-92.9%), door-to-needle time within 60 minutes (19.0%-75.3%), and endovascular door-to-puncture time within 90 minutes (54.7%-62.8%). Similar improvements were also observed for measures relevant to patients with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack. Multivariable analysis showed that there was a sustained increase in odds of receiving each performance measure over time, independent of patient and hospital characteristics for each type of cerebrovascular event. After risk adjustment, there were temporal trends that patients were less likely to be discharged to a skilled nursing facility, and, for ischemic stroke only, more likely to be discharged directly home. CONCLUSIONS: During the first 20 years, Get With The Guidelines-Stroke participation was associated with sustained improvement in evidence-based care and outcomes for patients with stroke and transient ischemic attack in the United States.

Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease-providing an overview of the journey from patch-clamp experiments to phase III trials.

Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days. Results- Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 [95% CI, 1.3-2.7] P=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach. Conclusions- Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.