David L. Tirschwell

Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke

BACKGROUND Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age. METHODS In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated. RESULTS We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased. CONCLUSIONS In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).

Validating Administrative Data in Stroke Research

Background and Purpose— Research based on administrative data has advantages, including large numbers, consistent data, and low cost. This study was designed to compare different methods of stroke classification using administrative data. Methods— Administrative hospital discharge data and medical record review of 206 patients were used to evaluate 3 algorithms for classifying stroke patients. These algorithms were based on all (algorithm 1), the first 2 (algorithm 2), or the primary (algorithm 3) administrative discharge diagnosis code(s). The diagnoses after review of medical record data were considered the gold standard. Then, using a large administrative data set, we compared patients with a primary discharge diagnosis of stroke with patients with their stroke discharge diagnosis code in a nonprimary position. Results— Compared with the gold standard, algorithm 1 had the highest &kgr; for classifying ischemic stroke, with a sensitivity of 86%, specificity of 95%, positive predictive value of 90%, and &kgr;=0.82. Algorithm 3 had the highest &kgr; values for intracerebral hemorrhage and subarachnoid hemorrhage. For intracerebral hemorrhage, the sensitivity was 85%, specificity was 96%, positive predictive value was 89%, and &kgr;=0.82. For subarachnoid hemorrhage, those values were 90%, 97%, 94%, and 0.88, respectively. Nonprimary position ischemic stroke patients had significantly greater comorbidity and 30-day mortality (odds ratio, 3.2) than primary position ischemic stroke patients. Conclusions— Stroke classification in these administrative data were optimal using all discharge diagnoses for ischemic stroke and primary discharge diagnosis only for intracerebral and subarachnoid hemorrhage. Selecting ischemic stroke patients on the basis of primary discharge diagnosis may bias administrative samples toward more benign, unrepresentative outcomes and should be avoided.

Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies

Background: Withdrawal of support in patients with severe brain injury invariably leads to death. Preconceived notions about futility of care in patients with intracerebral hemorrhage (ICH) may prompt withdrawal of support, and modeling outcome in patient populations in whom withdrawal of support occurs may lead to self-fulfilling prophecies. Methods: Subjects included consecutive patients with supratentorial ICH. Radiographic characteristics of the hemorrhage, clinical variables, and neurologic outcome were assessed. Attitudes about futility of care were examined among members of the departments of neurology and neurologic surgery through a written survey and case presentations. Results: There were 87 patients with supratentorial ICH; overall mortality was 34.5% (30/87). Mortality was 66.7% (18/27) in patients with Glasgow Coma Score ≤8 and ICH volume >60 cm3. Medical support was withdrawn in 76.7% (23/30) of patients who died. Inclusion of a variable to account for the withdrawal of support in a model predicting outcome negated the predictive value of all other variables. Patients undergoing surgical decompression were unlikely to have support withdrawn, and surgery was less likely to be performed in older patients (p < 0.01) and patients with left hemispheric hemorrhage (p = 0.04). Survey results suggested that practitioners tend to be overly pessimistic in prognosticating outcome based upon data available at the time of presentation. Conclusions: The most important prognostic variable in determining outcome after ICH is the level of medical support provided. Withdrawal of support in patients felt likely to have a “poor outcome” biases predictive models and leads to self-fulfilling prophecies. Our data show that individual patients in traditionally “poor outcome” categories can have a reasonable neurologic outcome when treated aggressively.

Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association

Each chapter listed in the Table of Contents (see next page) is a hyperlink to that chapter. The reader clicks the chapter name to access that chapter. Each chapter listed here is a hyperlink. Click on the chapter name to be taken to that chapter. Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA’s My Life Check - Life’s Simple 7 (Figure1), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents …

Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups

Objective: To perform a health maintenance organization–based case-control study to evaluate the association of total and high density lipoprotein (HDL) cholesterol with the risk of stroke subtypes and in patient subgroups. Methods: Cases had a confirmed incident ischemic stroke (n = 1,242) or hemorrhagic stroke (n = 313). Controls (n = 6,455) were identified in a companion myocardial infarction study. Risk of stroke was modeled using logistic regression. Results: The highest total cholesterol quintile was associated with an increased risk of ischemic stroke compared to the lowest quintile (OR = 1.6, 95% CI 1.3 to 2.0) with the strongest subtype associations for atherosclerotic stroke (OR = 3.2) and lacunar stroke (OR = 2.4). The highest HDL cholesterol quintile was associated with a decreased risk of ischemic stroke compared to the lowest quintile (OR = 0.8, CI 0.6 to 1.0). Subgroup analyses suggested that the total cholesterol association was more important for patients < 66 years of age and those with HDL < 50 mg/dL; the HDL association was more important for patients without diabetes or atrial fibrillation. The second through fourth total cholesterol quintiles were associated with a decreased risk of hemorrhagic stroke compared to the lowest quintile (OR = 0.7, CI 0.5 to 1.0). Conclusions: Higher total and lower HDL cholesterol levels were associated with increased risk of ischemic stroke, especially certain stroke subtypes and patient subgroups. The lowest levels of total cholesterol were associated with an increased risk of all hemorrhagic strokes.

Moyamoya disease in Washington State and California

The authors identified 298 diagnoses of moyamoya in California and Washington from hospital discharge databases during the period 1987 to 1998. The incidence was 0.086/100,000 persons. The ethnicity-specific incidence rate ratios compared to whites were 4.6 (95% CI: 3.4 to 6.3) for Asian Americans, 2.2 (95% CI: 1.3 to 2.4) for African Americans, and 0.5 (95% CI: 0.3 to 0.8) for Hispanics. The incidence of moyamoya in Washington and California was lower than reported in Japan, but the rate among U.S. Asians is similar.

Predictive value of somatosensory evoked potentials for awakening from coma.

ObjectivesA systematic review of somatosensory evoked potentials performed early after onset of coma, to predict the likelihood of nonawakening. The pooled results were evaluated for rates of awakening, confidence intervals, and the possibility of rare exceptions. Data SourcesForty-one articles reporting somatosensory evoked potentials in comatose patients and subsequent outcomes, from 1983 to 2000. Study SelectionStudies were included if they reported coma etiology, age group, presence or absence of somatosensory evoked potentials, and coma outcomes. Data ExtractionWe separated patients into four groups: adults with hypoxic-ischemic encephalopathy, adults with intracranial hemorrhage, adults and adolescents with traumatic brain injury, and children and adolescents with any etiologies. Somatosensory evoked potentials were categorized as normal, abnormal, or bilaterally absent. Outcomes were categorized as persistent vegetative state or death vs. awakening. Data SynthesisFor each somatosensory evoked potential result, rates of awakening (95% confidence interval) were calculated: adult hypoxic-ischemic encephalopathy: absent 0% (0%–1%), abnormal 22% (17%–26%), normal 52% (48%–56%); adult intracranial hemorrhage: absent 1% (0%–4%), present 38% (27%–48%); adult-teen traumatic brain injury: absent 5% (2%–7%), abnormal 70% (64%–75%), normal 89% (85%–92%); child-teen: absent 7% (4%–10%), abnormal 69% (61%–77%), normal 86% (80%–92%). ConclusionsSomatosensory evoked potential results predict the likelihood of nonawakening from coma with a high level of certainty. Adults in coma from hypoxic-ischemic encephalopathy with absent somatosensory evoked potential responses have <1% chance of awakening.

Extravasation of Radiographic Contrast Is an Independent Predictor of Death in Primary Intracerebral Hemorrhage

BACKGROUND AND PURPOSE Hematomas that enlarge following presentation with primary intracerebral hemorrhage (ICH) are associated with increased mortality, but the mechanisms of hematoma enlargement are poorly understood. We interpreted the presence of contrast extravasation into the hematoma after CT angiography (CTA) as evidence of ongoing hemorrhage and sought to identify the clinical significance of contrast extravasation as well as factors associated with the risk of extravasation. METHODS We reviewed the clinical records and radiographic studies of all patients with intracranial hemorrhage undergoing CTA from 1994 to 1997. Only patients with primary ICH were included in this study. Univariate and multivariate logistic regression analyses were performed to determine the associations between clinical and radiological variables and the risk of hospital death or contrast extravasation. RESULTS Data were available for 113 patients. Contrast extravasation was seen in 46% of patients at the time of CTA, and the presence of contrast extravasation was associated with increased fatality: 63.5% versus 16.4% in patients without extravasation (P=0.011). There was a trend toward a shorter time (median+/-SD) from symptom onset to CTA in patients with extravasation (4.6+/-19 hours) than in patients with no evidence of extravasation (6.6+/-28 hours; P=0.065). Multivariate analysis revealed that hematoma size (P=0.022), Glasgow Coma Scale (GCS) score (P=0.016), extravasation of contrast (P=0.006), infratentorial ICH (P=0.014), and lack of surgery (P<0.001) were independently associated with hospital death. Variables independently associated with contrast extravasation were hematoma size (P=0.024), MABP >120 mm Hg (P=0.012), and GCS score of </=8 (P<0.005). CONCLUSIONS Contrast extravasation into the hematoma after ICH is associated with increased fatality. The risk of contrast extravasation is increased with extreme hypertension, depressed consciousness, and large hemorrhages. If contrast extravasation represents ongoing hemorrhage, the findings in this study may have implications for therapy of ICH, particularly with regard to blood pressure management.

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.)

Community-based education improves stroke knowledge.

Background and Purpose: Despite advances in stroke therapy, the public remains uninformed about stroke, and few stroke patients present to the hospital in time to receive treatment. Health education campaigns can increase community awareness and may decrease time to hospital presentation among stroke patients. Methods: We conducted a community-based education campaign utilizing television and newspapers to inform the residents of King County, Wash., USA, about stroke and the need to call 911. The effectiveness of the campaign was assessed, using a pretest-posttest design, through telephone interviews with residents of King County. Results: Prior to the education campaign, 59.6% of persons in King County could name a risk factor for stroke, but only 45.2% knew that the brain was the organ of injury. And while 68.2% of persons stated that they would call 911 in the event of stroke, only 38.6% could name a symptom of stroke. The knowledge deficit was greatest among Asian-Americans, men, the less educated and low-income residents. There was a significant increase in stroke knowledge following the education campaign; respondents were 52% (p = 0.005) more likely to know a risk factor for stroke and 35% (p = 0.032) more likely to know a symptom of stroke after the campaign. Conclusions: Baseline knowledge about stroke among the public is poor, but can be increased through public education campaigns.