Syed F. Ali

Temporal Trends in Patient Characteristics and Treatment With Intravenous Thrombolysis Among Acute Ischemic Stroke Patients at Get With the Guidelines–Stroke Hospitals

BACKGROUND Substantial efforts over the past decade have increased rates of intravenous tissue plasminogen activator (tPA) use in the United States. We sought to determine changes in patient characteristics and rates of tPA use over time among hospitalized acute ischemic stroke (AIS) patients. METHODS AND RESULTS We analyzed all AIS patients (n=1 093 895) and those arriving ≤ 2 hours and treated with tPA ≤ 3 hours after onset (n=50 798) from 2003 to 2011 in the American Heart Associations Get with the Guideline-Stroke (GWTG-Stroke). Categorical data were analyzed by Pearson χ(2) and continuous data by Wilcoxon test. Intravenous tPA use ≤ 3 hours after onset increased from 4.0% to 7.0% in all AIS admissions and 42.6% to 77.0% in AIS patients arriving ≤ 2 hours and fully eligible for tPA (P<0.001). In univariate analysis, tPA use increased over time, especially in those aged >85 years, nonwhite, and with milder strokes (National Institutes of Health Stroke Scale 0-4). Door-to-image time (median 24 versus 20 minutes) and door-to-tPA time (median 81 versus 72 minutes) also improved, with ≈65% of tPA-treated patients getting brain imaging ≤ 25 minutes after arrival. Multivariable analysis showed that with each additional calendar year, the odds that an eligible patient would receive tPA increased by 1.37-fold, adjusting for other covariates. CONCLUSIONS The frequency of IV tPA use among all AIS patients, regardless of contraindications, nearly doubled from 2003 to 2011. Treatment with tPA has expanded to include more patients with mild deficits, nonwhite race/ethnicity, and oldest old age.

Paradoxical Association of Smoking With In‐Hospital Mortality Among Patients Admitted With Acute Ischemic Stroke

Background Compared to those who never smoked, a paradoxical effect of smoking on reducing mortality in patients admitted with myocardial ischemia has been reported. We sought to determine if this effect was present in patients hospitalized with ischemic stroke. Methods and Results Using the local Get with the Guidelines‐Stroke registry, we analyzed 4305 consecutively admitted ischemic stroke patients (March 2002–December 2011). The sample was divided into smokers versus nonsmokers. The main outcome of interest was the overall inpatient mortality. Compared to nonsmokers, tobacco smokers were younger, more frequently male and presented with fewer stroke risk factors such as hypertension, hyperlipidemia, diabetes, coronary artery disease, and atrial fibrillation. Smokers also had a lower average NIH Stroke Scale (NIHSS) and fewer received tissue plasminogen activator (tPA). Patients in both groups had similar adherence to early antithrombotics, dysphagia screening prior to oral intake, and deep vein thrombosis (DVT) prophylaxis. Smoking was associated with lower all‐cause in‐hospital mortality (6.6% versus 12.4%; unadjusted OR 0.46; CI [0.34 to 0.63]; P<0.001). In multivariable analysis, adjusted for age, gender, ethnicity, hypertension, diabetes mellitus, hyperlipidemia, CAD, atrial fibrillation, NIHSS, and tPA, smoking remained independently associated with lower mortality (adjusted OR 0.64; CI [0.42 to 0.96]; P=0.03). Conclusions Similar to myocardial ischemia, smoking was independently associated with lower inpatient mortality in acute ischemic stroke. This effect may be due to tobacco‐induced changes in cerebrovascular vasoreactivity, or may be due in part to residual confounding. Larger, multicenter studies are needed to confirm the finding and the effect on 30‐day and 1‐year mortality.

Improving Door-to-Needle Times A Single Center Validation of the Target Stroke Hypothesis

Background and Purpose— National guidelines recommend imaging within 25 minutes of emergency department arrival and intravenous tissue-type plasminogen activator within 60 minutes of emergency department arrival for patients with acute stroke. In 2007, we implemented a new institutional acute stroke care model to include 10 best practices and evaluated the effect of this intervention on improving door-to-computed tomography (CT) and door-to-needle (DTN) times at our hospital. Methods— We compared patients who presented directly to our hospital with acute ischemic stroke in the preintervention (2003–2006) and postintervention (2008–2011) periods. We did not include 2007, the year that the new protocol was established. Predictors of DTN ⩽60 minutes before and after the intervention were assessed using &khgr;2 for categorical variables, and t test and Wilcoxon signed-rank test for continuous variables. Results— Among 2595 patients with acute stroke, 284 (11%) received intravenous tissue-type plasminogen activator. For patients arriving within an intravenous tissue-type plasminogen activator window, door-to-CT <25 improved from 26.7% pre intervention to 52.3% post intervention (P<0.001). Similarly, the percentage of patients with DTN <60 doubled from 32.4% to 70.3% (P<0.001). Patients with DTN ⩽60 did not differ significantly with respect to demographics, comorbidities, or National Institutes of Health Stroke Scale score in comparison with those treated after 60 minutes. Conclusions— Door-to-CT and DTN times improved dramatically after applying 10 best practices, all of which were later incorporated into the Target Stroke Guidelines created by the American Heart Association. The only factor that significantly affected DTN60 was the intervention itself, indicating that these best practices can result in improved DTN times.

The TeleStroke Mimic (TM)-Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network

Background Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England–based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver‐operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM‐Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM‐Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision‐support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time‐critical telestroke evaluations.

Characteristics and Outcomes Among Patients Transferred to a Regional Comprehensive Stroke Center for Tertiary Care

Background and Purpose— Many patients are transferred to comprehensive stroke centers for advanced acute ischemic stroke care, especially after intravenous tissue plasminogen activator. We sought to determine differences in the baseline characteristics and outcomes between patients with acute ischemic stroke presenting directly to our academic stroke center’s front door versus transfers-in from another acute care hospital. Methods— Using our institutional Get With The Guidelines (GWTG)-Stroke registry, we analyzed all 3660 consecutively admitted patients with acute ischemic stroke (January 2005–June 2012). Univariate and multivariable models explored differences in front door versus transfer-in patients. Results— Fifty percent of all patients with acute ischemic stroke were transfer-in. Compared with front door patients, transfer-in were younger (67±16 versus 71±15 years; P<0.001), had worse median initial National Institutes of Health Stroke Scale score (7.0 versus 4.0; P<0.001), more often had limb weakness (35% versus 27%; P<0.001) or aphasia (16% versus 11%; P<0.001), and received intravenous tissue plasminogen activator (29% versus 13%; P<0.001). Despite a trend toward higher in-hospital mortality in transfer-in patients, the difference was not statistically significant (13% versus 11%; P=0.08) between the 2 groups. Transfer-in patients had a longer hospital length of stay (5 versus 4 days; P<0.001) and were more often discharged to inpatient rehabilitation (48% versus 34%; P<0.001). Independent predictors of in-hospital mortality were increasing age (odds ratio [OR], 1.38 per decade [1.23–1.55]; P<0.001), atrial fibrillation (OR, 1.47 [1.12–1.93]; P=0.006), coronary artery disease (OR, 2.02 [1.53–2.67]; P<0.001), and initial National Institutes of Health Stroke Scale (OR, 1.20 per point [1.18–1.23]; P<0.001). Transfer status was not independently associated with in-hospital mortality (OR, 0.99 [0.76–1.29]; P=0.928). Conclusions— Despite having more severe strokes on arrival at our hospital, transfer-in patients had similar in-hospital mortality versus front door patients and were more likely to be discharged to rehabilitation. These outcomes lend support to the concept of regionalized stroke care and concentrating patients who are more disabled at more advanced stroke care centers.

Baseline Predictors of Poor Outcome in Patients Too Good to Treat With Intravenous Thrombolysis

Background and Purpose— Several studies have reported poor outcomes in patients too good to treat with intravenous thrombolysis because of mild or rapidly improving symptoms. We sought to determine baseline clinical and imaging predictors of poor outcome in these patients. Methods— Among 3950 consecutive stroke admissions (2009–2015) in our local Get With the Guidelines–Stroke database, 632 patients presented ⩽4.5 hours and did not receive tissue-type plasminogen activator, with 380 of 632 (60.1%) being too good to treat. Univariate and multivariable analyses explored the clinical and imaging features associated with poor outcome (defined as not being discharged to home) in these 380 cases. Results— Among these 380 cases, only 68% were discharged home; the other 25% to inpatient rehabilitation, 4% to a skilled nursing facility, and 3% expired or were discharged to hospice. Patients with poor outcome were older, were more often Hispanic, had more vascular risk factors, and had higher median National Institutes of Health Stroke Scale. Imaging characteristics associated with poor outcomes included large or multifocal infarction and poor collaterals. In multivariable analysis, only age, initial National Institutes of Health Stroke Scale, and infarct location were independently associated with poor outcome. Conclusions— Approximately one third of patients deemed too good for intravenous tissue-type plasminogen activator are unable to be discharged directly to home. Given the current safety profile of intravenous tissue-type plasminogen activator, our results suggest that the concept of being too good to treat should be re-examined with an emphasis on the features associated with poor outcome identified in our study. If replicated, these findings could be incorporated into tissue-type plasminogen activator decision-making algorithms.

Smoking Paradox in Patients Hospitalized With Coronary Artery Disease or Acute Ischemic Stroke Findings From Get With The Guidelines

Background—Smoking is a potent risk factor for coronary artery disease (CAD) and acute ischemic stroke (AIS), but there are numerous reports of lower in-hospital mortality among smokers versus nonsmokers hospitalized for these events. Methods and Results—We analyzed all consecutive patients hospitalized with a first index CAD (n=158 054) or AIS (n=899 295) event in Get With The Guidelines from 2002 to 2012; 20.4% of AIS and 30.4% of patients with CAD were past-year smokers. Multivariable models and age-stratified analyses were used to estimate the adjusted odds ratio of in-hospital mortality in smokers versus nonsmokers. Smokers were younger, more often male, with fewer vascular risk factors, and were more likely to be admitted to hospitals that were large, academic, or in the South. In-hospital mortality was significantly lower among smokers in both CAD (2.7% versus 5.2%; P<0.0001) and AIS (3.5% versus 5.8%; P<0.0001). The difference between unadjusted and adjusted odds ratios for smoking (0.57 versus 0.86 in CAD; 0.56 versus 0.86 in AIS) indicates the presence of substantial confounding by age and other covariates, but a significant association of past-year smoking remained. Conclusions—Among patients hospitalized with CAD and AIS, smoking is a risk factor for early age of onset, even among those with few vascular risk factors. The persistent association with lower in-hospital mortality after adjusted and stratified analyses probably represents residual unmeasured confounding, although a biological effect of smoking cannot be excluded. Further clinical and prospective population-based studies are needed to explore variables that contribute to outcomes in these patients.

Validating the telestroke mimic score a prediction rule for identifying stroke mimics evaluated over telestroke networks

Background and Purpose— Up to 30% of acute stroke evaluations are deemed stroke mimics, and these are common in telestroke as well. We recently published a risk prediction score for use during telestroke encounters to differentiate stroke mimics from ischemic cerebrovascular disease derived and validated in the Partners TeleStroke Network. Using data from 3 distinct US and European telestroke networks, we sought to externally validate the TeleStroke Mimic (TM) score in a broader population. Methods— We evaluated the TM score in 1930 telestroke consults from the University of Utah, Georgia Regents University, and the German TeleMedical Project for Integrative Stroke Care Network. We report the area under the curve in receiver-operating characteristic curve analysis with 95% confidence interval for our previously derived TM score in which lower TM scores correspond with a higher likelihood of being a stroke mimic. Results— Based on final diagnosis at the end of the telestroke consultation, there were 630 of 1930 (32.6%) stroke mimics in the external validation cohort. All 6 variables included in the score were significantly different between patients with ischemic cerebrovascular disease versus stroke mimics. The TM score performed well (area under curve, 0.72; 95% confidence interval, 0.70–0.73; P<0.001), similar to our prior external validation in the Partners National Telestroke Network. Conclusions— The TM score’s ability to predict the presence of a stroke mimic during telestroke consultation in these diverse cohorts was similar to its performance in our original cohort. Predictive decision-support tools like the TM score may help highlight key clinical differences between mimics and patients with stroke during complex, time-critical telestroke evaluations.