Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials.

BACKGROUND: Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement. OBJECTIVE: To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality. METHODS: Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated. RESULTS: Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively). CONCLUSIONS: In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. METHODS: In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. RESULTS: Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. CONCLUSIONS: Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME.

OBJECTIVE: Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile. METHODS: Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI). RESULTS: A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6 ml (interquartile range= 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13 ml. INTERPRETATION: Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies.

Automated Communication Tools and Computer-Based Medication Reconciliation to Decrease Hospital Discharge Medication Errors.

This study sought to determine the effects of automated primary care physician (PCP) communication and patient safety tools, including computerized discharge medication reconciliation, on discharge medication errors and posthospitalization patient outcomes, using a pre-post quasi-experimental study design, in hospitalized medical patients with ≥2 comorbidities and ≥5 chronic medications, at a single center. The primary outcome was discharge medication errors, compared before and after rollout of these tools. Secondary outcomes were 30-day rehospitalization, emergency department visit, and PCP follow-up visit rates. This study found that discharge medication errors were lower post intervention (odds ratio = 0.57; 95% confidence interval = 0.44-0.74; P < .001). Clinically important errors, with the potential for serious or life-threatening harm, and 30-day patient outcomes were not significantly different between study periods. Thus, automated health system-based communication and patient safety tools, including computerized discharge medication reconciliation, decreased hospital discharge medication errors in medically complex patients.

The Value of Quality Improvement Process in the Detection and Correction of Common Errors in Echocardiographic Hemodynamic Parameters in a Busy Echocardiography Laboratory.

BACKGROUND: Accurate assessment of cardiac structures, ventricular function, and hemodynamics is essential for any echocardiographic laboratory. Quality improvement (QI) processes described by the American Society of Echocardiography (ASE) and the Intersocietal Commission (IAC) should be instrumental in reaching this goal. METHODS: All patients undergoing transthoracic echocardiogram (TTE) followed by cardiac catheterization within 24 hours at Christiana Care Health System in 2011 and 2012 were identified, with 126 and 133 cases, respectively. Hemodynamic parameters of diastolic function and pulmonary artery systolic pressure (PASP) on TTE correlated poorly with catheterization in 2011. An educational process was developed and implemented at quarterly QI meetings based on ASE and IAC recommendations to target frequently encountered errors and provide methods for improved performance. The hemodynamic parameters were then reexamined in 2012 postintervention. RESULTS: Following the QI process, there was significant improvement in the correlation between invasive and echocardiographic hemodynamic measurements in both systolic and diastolic function, and PASP. This reflected in significant better correlations between echo and cath LVEF [R = 0.88, ICC = 0.87 vs. R = 0.85, ICC = 0.85; P < 0.001], average E/E' and of left ventricle end-diastolic pressure (LVEDP) [R = 0.62 vs. R = 0.09, P = 0.006] and a better correlation for PASP [R = 0.77, ICC = 0.77 vs. R = 0.30, ICC = 0.31; P = 0.05] in 2012 compared to 2011. CONCLUSION: The QI process, as recommended by ASE and IAC, can allow for identification as well as rectification of quality issues in a large regional academic medical center hospital.

Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.

BACKGROUND: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. METHODS: We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). RESULTS: The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). CONCLUSIONS: In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

Impact of telemedicine implementation in thrombolytic use for acute ischemic stroke: the University of Pittsburgh Medical Center telestroke network experience.

BACKGROUND: Intravenous thrombolysis is the only therapy for acute ischemic stroke that is approved by the US Food and Drug Association. The use of telemedicine in stroke makes it possible to bring the expertise of academic stroke centers to underserved areas, potentially increasing the quality of stroke care. METHODS: All consecutive admissions for stroke were reviewed for 1 year before telemedicine implementation and for variable periods thereafter. A retrospective review identified 2588 admissions for acute stroke between March 2005 and December 2008 at 12 hospitals participating in a telestroke network, including 919 patients before telemedicine was available and 1669 patients after telemedicine was available. The primary outcome measure was the rate of intravenous tissue plasminogen activator (IV tPA) use before and after telemedicine implementation. RESULTS: One hundred thirty-nine patients received IV tPA in both study phases, with 26 (2.8%) patients treated before starting telemedicine and 113 (6.8%) after starting telemedicine (P < .001). Incorrect treatment decisions occurred 7 times (0.39%), with 2 (0.2%) pretelemedicine and 5 (0.3%) posttelemedicine (P = .70). Arrivals within 3 hours from symptom onset were more frequent in the posttelemedicine compared to the pretelemedicine phases (55 [6%] vs 159 [9.5%]; P = .002). Among the patients treated with IV tPA, symptomatic intracranial hemorrhage occurred in 2 patients (1 [10.7%] pretelemedicine vs 1 [1.8%] posttelemedicine; P = .34). CONCLUSIONS: Telestroke implementation was associated with an increased rate of thrombolytic use in remote hospitals within the telemedicine network.

Use of an abnormal laboratory value-drug combination alert to detect drug-induced thrombocytopenia in critically Ill patients.

PURPOSE: The aim of this study was to assess the performance of a commercially available clinical decision support system (CDSS) drug-laboratory result alert in detecting drug-induced thrombocytopenia in critically ill patients. MATERIALS AND METHODS: Adult patients admitted to the medical and cardiac intensive care unit during an 8-week period and identified by 1 of 3 signals in the CDSS, TheraDoc, were eligible. Alerts were generated when the patient had a low platelet count and was ordered a potentially causal drug. Patients were evaluated in real time for the occurrence of an adverse drug reaction using 3 causality instruments. Positive predictive values were calculated for the alert. RESULTS: Sixty-four patients with a mean age of 54 years met the inclusion criteria, generating 350 alerts. Positive predictive values were 0.36, 0.83, and 0.40 for signals 1, 2, and 3, respectively. Overall, there were 137 adverse drug reactions identified in the 350 alerts, with heparin, vancomycin, and famotidine as the 3 most common potential causes. CONCLUSIONS: A commercial CDSS drug-laboratory alert is effective at identifying drug-induced thrombocytopenia in the intensive care unit and may improve patient safety. Compared with previous studies, the combination alert performs better than alerts based exclusively on laboratory values and should be considered to reduce alert fatigue.

Endovascular treatment of tandem extracranial/intracranial anterior circulation occlusions: preliminary single-center experience.

BACKGROUND AND PURPOSE: Acute ischemic stroke due to tandem occlusions of the extracranial internal carotid artery and intracranial arteries has a poor natural history. We aimed to evaluate our single-center experience with endovascular treatment of this unique stroke population. METHODS: Consecutive patients with tandem occlusions of the internal carotid artery origin and an intracranial artery (ie, internal carotid artery terminus, M1 middle cerebral artery, or M2 middle cerebral artery) were studied retrospectively. Treatment consisted of proximal revascularization with angioplasty and stenting followed by intracranial intervention. Endpoints were recanalization of both extracranial and intracranial vessels (Thrombolysis In Myocardial Ischemia ≥2), parenchymal hematoma, and good clinical outcome (modified Rankin Scale ≤2) at 3 months. RESULTS: We identified 77 patients with tandem occlusions. Recanalization occurred in 58 cases (75.3%) and parenchymal hematoma occurred in 8 cases (10.4%). Distal embolization occurred in 3 cases (3.9%). In 18 of 77 patients (23.4%), distal (ie, intracranial) recanalization was observed after proximal recanalization, obviating the need for distal intervention. Good clinical outcomes were achieved in 32 patients (41.6%). In multivariate analysis, Thrombolysis In Myocardial Ischemia ≥2 recanalization, baseline National Institutes of Health Stroke Scale score, baseline Alberta Stroke Programme Early CT score, and age were significantly associated with good outcome. CONCLUSIONS: Endovascular therapy of tandem occlusions using extracranial internal carotid artery revascularization as the first step is technically feasible, has a high recanalization rate, and results in an acceptable rate of good clinical outcome. Future randomized, prospective studies should clarify the role of this approach.

Survival and neurologic recovery in patients with ST-segment elevation myocardial infarction resuscitated from cardiac arrest.

OBJECTIVES: We examined outcomes of patients resuscitated from cardiac arrest owing to ST-segment elevation myocardial infarction (STEMI) and predictors of survival and neurologic recovery. BACKGROUND: Immediately after resuscitation from cardiac arrest owing to STEMI, many patients show signs of neurologic impairment, and benefits of percutaneous coronary intervention and subsequent prognosis are not well defined. METHODS: Between January 1, 2002, and December 31, 2006, we retrospectively identified consecutive patients resuscitated from cardiac arrest, regardless of time to return of spontaneous circulation (ROSC) and neurologic status, and reviewed the outcomes of those who had STEMI. Mortality and neurologic recovery at discharge and long-term mortality were assessed by individual chart review for those who underwent emergent angiography. RESULTS: Our study population consisted of 98 patients; 64% survived to discharge, and 92% had a full neurologic recovery. Predictors of survival were shorter time to ROSC, younger age, neurologic status post-resuscitation (alert or minimally responsive), and male sex. Predictors of neurologic recovery included shorter time to ROSC, neurologic status post-resuscitation (alert or minimally responsive), and younger age. Ninety-six percent of patients who were alert post-resuscitation survived. Ninety-three percent of patients who were minimally responsive post-resuscitation survived. Fifty-nine patients were unresponsive post-resuscitation, with 44% survival, of whom 88% had full neurologic recovery. In the unresponsive group, unwitnessed arrest, prolonged ROSC, and older age were associated with increased risk of death, and older age and prolonged ROSC predicted poor neurologic recovery. CONCLUSIONS: When resuscitated patients with STEMI are being evaluated in the emergency department, serious consideration should be given to emergent angiography and revascularization, regardless of neurologic status.

Left ventricular functional recovery with percutaneous, transvascular direct myocardial delivery of bone marrow-derived cells.

BACKGROUND: The potential for cellular cardiomyoplasty to provide functional left ventricular recovery in the chronically injured heart remains unclear. METHODS: Yorkshire swine (n = 10; 35-50 kg) had anterolateral myocardial infarction (MI) induced by coil embolization of the left anterior descending artery. Approximately 5 weeks post-MI, a composite, intravascular ultrasound-guided catheter system (TransAccess) was used to deliver an autologous, labeled, bone marrow-derived cell sub-population (approximately 3 x 10(8) cells) or saline control (approximately 50 injections/arm) through coronary veins directly into infarct and peri-infarct myocardium. Two months post-transplant, the animals had blinded endocardial and epicardial left ventricular electrical scar mapping and biventricular electrical stimulation. Coronary angiography and quantitative biplane ventriculography were performed at baseline, transplant, and sacrifice time-points. RESULTS: Robust, viable, predominantly desmin-negative cell grafts were demonstrated post-mortem in all treatment animals. Baseline and pre-transplant global and regional wall motion was similar between groups. The cell treatment group demonstrated functional recovery with a left ventricular ejection fraction of 38.1% at the time of transplant increasing to 48.5% (p = 0.005) at sacrifice, whereas the control arm was unchanged (38.0% vs 34.3%, respectively; p = NS). The regional improvement corresponded with a reduction in percentage of hypokinetic (52.1%-42.9%, p = 0.002) and percentage of akinetic (24.8%-17.7%, p = 0.04) segments in the cell-treated animals. Epicardial scar area was not different (37 cm2 vs 23 cm2, p = 0.37) between groups. CONCLUSIONS: Percutaneous, transvascular, direct intramyocardial bone marrow cell transplantation is safe and feasible in chronically infarcted tissue. In this pilot study, cell therapy improved overall left ventricular systolic function by recruiting previously hypokinetic or akinetic myocardial tissue.